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"abstract": "Reactive arthritis is a rare complication of Clostridium difficile enterocolitis, especially in children. We review the 6 pediatric cases published in the English and non-English literature and discuss their clinical presentation, outcome, treatment, and pathophysiology. We also report the seventh case of Clostridium difficile reactive arthritis in a 6-year-old boy who was treated with amoxicillin-clavulanate for 10 days because of an upper respiratory infection. After the antibiotic course, the child developed at the same time diarrhea with positive stool culture for Clostridium difficile and an asymmetric polyarthritis. Nonsteroidal anti-inflammatory drugs and metronidazole completely resolved the pain, joint swelling, and diarrhea. After twelve months of follow-up there has been no recurrence. This report confirms the self-limiting course of Clostridium difficile reactive arthritis. Clostridium difficile testing in children with gastrointestinal symptoms and acute onset of joint pain should be always considered.",
"affiliations": "Department of Pediatrics, Santa Maria delle Croci Hospital, 48121 Ravenna, Italy.;Department of Pediatrics, Santa Maria delle Croci Hospital, 48121 Ravenna, Italy.;Department of Pediatrics, Santa Maria delle Croci Hospital, 48121 Ravenna, Italy.;Department of Pediatrics, Santa Maria delle Croci Hospital, 48121 Ravenna, Italy.",
"authors": "Cappella|Michela|M|;Pugliese|Fabrizio|F|;Zucchini|Andrea|A|;Marchetti|Federico|F|",
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"fulltext": "\n==== Front\nCase Rep PediatrCase Rep PediatrCRIPECase Reports in Pediatrics2090-68032090-6811Hindawi Publishing Corporation 10.1155/2016/1591753Case Report\nClostridium difficile Enterocolitis and Reactive Arthritis: A Case Report and Review of the Literature Cappella Michela Pugliese Fabrizio Zucchini Andrea Marchetti Federico \n*\nDepartment of Pediatrics, Santa Maria delle Croci Hospital, 48121 Ravenna, Italy*Federico Marchetti: federico.marchetti@ausl.ra.itAcademic Editor: Ashraf T. Soliman\n\n2016 14 4 2016 2016 15917537 2 2016 3 4 2016 Copyright © 2016 Michela Cappella et al.2016This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Reactive arthritis is a rare complication of Clostridium difficile enterocolitis, especially in children. We review the 6 pediatric cases published in the English and non-English literature and discuss their clinical presentation, outcome, treatment, and pathophysiology. We also report the seventh case of Clostridium difficile reactive arthritis in a 6-year-old boy who was treated with amoxicillin-clavulanate for 10 days because of an upper respiratory infection. After the antibiotic course, the child developed at the same time diarrhea with positive stool culture for Clostridium difficile and an asymmetric polyarthritis. Nonsteroidal anti-inflammatory drugs and metronidazole completely resolved the pain, joint swelling, and diarrhea. After twelve months of follow-up there has been no recurrence. This report confirms the self-limiting course of Clostridium difficile reactive arthritis. Clostridium difficile testing in children with gastrointestinal symptoms and acute onset of joint pain should be always considered.\n==== Body\n1. Introduction\nReactive arthritis (ReA) is an aseptic acute inflammatory arthritis which develops after an extra-articular infection triggered by arthritogenic bacteria, more frequently from Salmonella, Shigella, Yersinia, and Campylobacter. It is often associated with the human leucocyte antigen- (HLA-) B27 and usually considered in adult classification as a subtype of spondyloarthropathies. The criteria currently used to diagnose ReA are those of the 1995 Berlin Third International Workshop: (1) the presence of a predominantly lower limb asymmetrical oligoarthritis and (2) clinical laboratory evidence of a preceding infection [1].\n\nA particular type of ReA has been described in connection with Clostridium difficile (CD) colitis. Although Clostridium difficile ReA is largely described in adults, there are few pediatric case reports probably due to CD asymptomatic colonization in newborns and infants. However, the incidence of CD among hospitalized children has increased in the last few years [2]. To the best of our knowledge, only six cases have been reported in the pediatric population [3–7]. We report the seventh pediatric case of ReA following CD enterocolitis.\n\n2. Case Report\nA 6-year-old boy was admitted to our department because of pain in the right knee and both ankles started five days before admission. Three weeks earlier he had completed a 10-day course of oral amoxicillin-clavulanate. Off antibiotics, he developed watery diarrhea and abdominal pains.\n\nOn admission the child presented with a profuse diarrhea; his left knee and both ankles were swollen, warm, and painful with significant limitation of motion. He could neither stand nor walk because of severe pain. All his other joints were normal. He had no fever. The remaining general examination was unremarkable; in particular he had no rash, mucositis, pharyngitis, urethritis, or conjunctivitis. Initial investigations showed a normal white cells count with a mild increase of C-reactive protein (39 mg/L, normal range 0–5 mg/L) and of the erythrocyte sedimentation rate (30 mm/h; normal range < 20 mm/h); electrolytes were normal. Haemoglobin concentration, platelet count, and fibrinogen were all in the normal range, as antistreptolysin-O (ASO) level (90 KUI/L; normal value < 200 KUI/L).\n\nThree days later the arthritis slowly resolved spontaneously in the left knee and ankles but appeared in the right shoulder and homolateral hip with a migratory pattern. This polyarthritis was accompanied, at that time, with unremitting and not elevated fever (38°C at the maximum). Ultrasonography showed a mild effusion in the right knee, ankles, and right hip joint. X-rays were normal. Both synovial fluid and blood cultures were negative. Tests for immunoglobulin and complement were normal. Autoantibodies (e.g., rheumatoid factor and antinuclear antibodies) were absent and HLA-B27 antigen was negative. Eyes did not show any sign of iridocyclitis on the slit lamp. A cardiac evaluation, including echocardiogram, ruled out any evidence of carditis. Serological tests for arthritis related infections (such as group A Streptococcus, Borrelia, Cytomegalovirus, Epstein-Barr-Virus, andParvovirus B19) were also negative.\n\nOur patient's diarrhea, which started following antibiotics, gradually resolved during his hospital stay. Stool cultures for enteric pathogens (such as Salmonella, Shigella, Yersinia, Campylobacter, and common viral agent) were negative but CD and CD toxin A and toxin B were detected by ELISA technique. Fecal calprotectin was not increased.\n\nGiven positive stool cultures for CD and the polyarthritis, our patient was started on oral naproxen (15 mg/kg for three times a day) for three weeks and metronidazole therapy (7.5 mg/kg every eight hours) for ten days.\n\nOver that period, diarrhea and the polyarthritis rapidly improved. After three weeks of naproxen therapy his symptoms completely resolved. Joint pain abated, the mobility recuperated, and no other joint involvement was noted. Inflammatory parameters turn out to be negative, within seven days after starting treatment. Stool culture after 4 weeks was negative. Fecal calprotectin remained negative.\n\nOur little patient was clinically followed up for 12 months. By then he had completely recovered.\n\n3. Discussion\nReA is a nonseptic acute inflammatory arthritis occurring after an intercurrent infection in which the causative organism is outside from the joint. The most frequent causes of ReA are intestinal and genital bacterial infections. ReA is typically characterized by asymmetrical oligo or polyarthritis predominantly in the lower limbs large joints (knee, ankle, and hip) [8, 9]. Symptoms of ReA present themselves approximately from 2 to 4 weeks following infection. The classic triad of arthritis, urethritis, and conjunctivitis, known as Reiter syndrome, is relatively uncommon and the term has been frequently used in the pediatric rheumatology literature in the past [9].\n\nSeveral patients present a migratory pattern of polyarticular arthritis, but a few have monoarticular or oligoarticular arthritis. Acute arthritis is characterized by severe pain and sometimes erythema over the affected joints but some children may show only light or moderate joint pain and swelling. Enthesitis or tenosynovitis may occur alone or with arthritis. Extra-articular symptoms included systemic signs such as fever, weight loss, fatigue, and skin, eyes, and mucous membranes disease (erythema nodosum, urethritis, conjunctivitis, iridocyclitis, or acute anterior uveitis) [2]. There is a strong association with HLA-B27 antigen and the frequency and severity of joint pain after intestinal or genitourinary infections are higher in HLA-B27 positive patients [9].\n\nReA can occur at any age, most frequently in young children after enteric infections (Salmonella, Shigella, Yersinia enterocolitica, and Campylobacter jejuni), pharyngitis caused by group A Streptococcus, or more rarely a genitourinary tract infection (Chlamydia trachomatis).\n\nCD is Gram-positive bacillus, spore-forming, obligate anaerobic bacteria and it is the most common cause of antimicrobial-associated diarrhea and colitis after a period of antibiotic therapy [2]. The major risk factor for CD infection in childhood is antibiotic exposure, especially to cephalosporins, broad-spectrum penicillins including amoxicillin, clindamycin, and fluoroquinolones [10]. Infection with toxin-producing strains of CD generally leads to a spectrum of disease ranging from mild, self-limited diarrhea to explosive, watery diarrhea with occult blood or mucous to pseudomembranous colitis.\n\nCD infections are generally more severe in certain populations, including patients receiving chemotherapy or with chronic gastrointestinal diseases [2]. According to the review by Jacobs et al. [10], 35 cases of ReA following CD enterocolitis were documented in adults. The characteristics of CD-associated ReA appeared to be similar both in adults and in children. For the diagnosis of ReaA following CD enterocolitis the criteria established by Putterman and Rubinow [11] may be applied to children. These criteria include the following:Appearance of arthritis together with or following the onset of diarrhea and/or colitis.\n\nDiarrhea appearing some time after a course of systemic antimicrobial therapy.\n\nMicrobiologic proof of CD involvement (either positive stool culture or assay for toxin).\n\nNo reasonable alternative diagnosis for arthritis or diarrhea (i.e., no other identified infectious agent).\n\nIn order to perform a diagnosis of ReA associated with CD enterocolitis, a history of diarrhea after a course of antibiotic or the exclusion of other causes of gastroenteritis or noninfectious arthritis is essential.\n\nOur case fulfills the above criteria by Putterman and Rubinow [11]. Microbiologic confirmation was given by the positive stool culture and CD toxin evidence, together with the absence of other enterobacterial infections.\n\nIn addition, antibiotic therapy was previously administered in our patient. There was no evidence of antecedent group A streptococcal infection (ASO title was not raised) and our case did not meet the modified Jones criteria, therefore excluding the diagnosis of acute rheumatic fever or poststreptococcal reactive arthritis. An inflammatory bowel disease (IBD) was considered as it is frequently associated with CD colonization but the dosage of fecal calprotectin, which has a high negative predictive value for IBD, was negative [12]. Moreover, the gradual improvement of colitis allowed the exclusion of IBD. Postinfective arthritis was ruled out because of the negative serological investigation and the polyarticular involvement with migratory patterns.\n\nA literature search of MEDLINE, Google Scholar, and Cochrane Reviews computerized databases using the keywords “Clostridium difficile”, “arthritis”, and “child” to identify all papers reporting CD enterocolitis-associated reactive arthritis in childhood was performed. In addition, the search was extended to all relevant articles in the reference lists. No year or language restriction was applied to our search. Two reviewers performed a first stage selection of the total identified studies based on the following inclusion and exclusion criteria (using the abstract or the full text article when required).\n\nAll published papers were included in the present review only if they met the following inclusion criteria: (1) appearance of acute arthritis and/or tenosynovitis between 4 weeks before and 12 weeks after the onset of diarrhea and/or colitis; (2) diarrhea appearing some time after a course of systemic antimicrobial therapy; (3) microbiologic proof of CD involvement (either positive stool culture or assay for toxin); (4) no reasonable alternative diagnosis for arthritis or diarrhea (i.e., no other identified infectious agent); (5) negative synovial fluid cultures (if obtained); and (6) age of patient between 1 and 18 years.\n\nSix reports (5 papers) [3–7] met our review's inclusion criteria and their full texts were analysed. Table 1 shows details regarding these reports on CD ReA in childhood. Cron and Gordon [3] described the first case in 1997 in the USA, and the second one was from the USA as well [4]; thereafter three children in France [5, 6] and one child in the UK [7] were diagnosed with CD ReA. The median age was 6.5 years (range 2.5–11) and there was no age difference between males and females. Arthritis was most often migratory and polyarticular, involving large joints in all cases. CD stool culture was positive in all of them. Only the cases reported by Löffler et al. [5] illustrated that CD-associated colitis was not preceded by antibiotic course but it may be explained by a transient colonization of toxicogenic CD. The duration of the arthritis may be variable. Usually the arthritis resolved from one to four weeks with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Only in the one case described by Löffler et al. [5] symptoms may persist for more than one year.\n\nIn agreement with the other reports, our case confirms the good outcome of ReA following CD infection with a self-limiting course (3 weeks). Only one case documented a child who developed an acute abdomen and underwent a laparotomy for presumed peritonitis [7].\n\nThe treatment of ReA following CD infection included the discontinuation of antimicrobial agents and the use of oral NSAIDs coupled with metronidazole therapy for 7–10 days in children and adolescents with mild-to-moderate colitis or vancomycin in more severe diseases. All of previous cases were treated with vancomycin or metronidazole; only the case described by Finger and Neubauer [4] was resolved with only ibuprofen.\n\n4. Conclusion\nThe CD infection should be suspected in children presenting with an acute inflammatory arthritis following an episode of diarrhea especially when stool culture for common enteric bacterial infection turns out to be negative and the patient has received antibiotic therapy before the onset of diarrhea. Therefore, we suggest performing tests for CD toxin in children with these characteristics because CD infection associated with ReA can be unrecognized.\n\nAbbreviations\nReA:Reactive arthritis\n\nCD:\n Clostridium difficile\n\n\nNSAIDs:Nonsteroidal anti-inflammatory drugs.\n\nCompeting Interests\nThe authors declare that they have no competing interests.\n\nAuthors' Contributions\nMichela Cappella is responsible for study design, data collection, data interpretation, paper preparation, and literature review and contributed to the diagnosis. Fabrizio Pugliese and Andrea Zucchini are responsible for data collection and data interpretation, contributed to the diagnosis, and provided clinical assistance. Federico Marchetti performed study design, data collection, and data interpretation and contributed to the diagnosis and paper preparation. All authors approved the final version of the paper.\n\nTable 1 Case reports in the literature on Clostridium difficile enterocolitis-associated reactive arthritis in children.\n\nAuthors/articles\t Cron and Gordon 1997 [3]\t Löffler et al. 2004 [5]\t Durand and Miller [7]\t Finger and Neubauer 1997 [4]\t Dacheux et al. 2012 [6]\t\n\nAge\n\t\n2,5\n\t\n11\n\t\n6\n\t\n10\n\t\n3\n\t\n7\n\t\nSex\tM\tM\tF\tF\tM\tM\t\nPrevious antibiotic therapy\tAmoxicillin \tLincomycin\tND\tErythromycin and penicillin V\tCefixime\t Amoxicillin-clavulanate\t\nJoints involved\tLeft knee and shoulder\tLeft and right ankles; right knee; both hips; both elbows; left wrist\tBoth knees, both elbows, and both hips\tLeft hips\tRight hip, shoulder, and knee\tTwelve joints\t\nSymptoms associated\t \tSkin nodules\t \tAseptic peritonitis\t \t \t\nTreatment \tVancomycin\tVancomycin\tVancomycin\tMetronidazole\tIbuprofen\tMetronidazole\t\nDisease's duration (days)\t25\t588\t14\t7\t7\t7\n==== Refs\n1 Kingsley G. Sieper J. Third international workshop on reactive arthritis. An overview Annals of the Rheumatic Diseases 1996 55 8 564 584 8815821 \n2 Schutze G. E. Willoughby R. E. Committee on Infectious Diseases American Academy of Pediatrics Clostridium difficile infection in infants and children Pediatrics 2013 131 1 196 200 23277317 \n3 Cron R. Q. Gordon P. V. Reactive arthritis to Clostridium difficile in a child Western Journal of Medicine 1997 166 6 419 421 2-s2.0-0030984762 9217461 \n4 Finger D. R. Neubauer J. V. Reactive arthritis following Clostridium difficile colitis in a 3-year-old patient Journal of Clinical Rheumatology 1997 3 2 102 104 10.1097/00124743-199704000-00007 2-s2.0-0030923094 19078131 \n5 Löffler H. A. Pron B. Mouy R. Wulffraat N. M. Prieur A.-M. \nClostridium difficile -associated reactive arthritis in two children Joint Bone Spine 2004 71 1 60 62 10.1016/s1297-319x(03)00056-3 2-s2.0-0842267163 14769523 \n6 Dacheux C. Pruvost I. Herbaux B. Nectoux E. Clostridium difficile reactive arthritis in a 7-year-old child Archives de Pediatrie 2012 19 6 607 611 10.1016/j.arcped.2012.03.011 2-s2.0-84861483480 22542720 \n7 Durand C. L. Miller P. F. Severe clostridium difficile colitis and reactive arthritis in a ten-year-old child Pediatric Infectious Disease Journal 2009 28 8 750 751 10.1097/INF.0b013e31819bdaa3 2-s2.0-68649104798 19633524 \n8 Burgos-Vargas R. Vazquez-Mellado J. Cassidy J. T. Petty R. E. Reactive arthritis Textbook of Pediatric Rheumatology 2010 6th Philadelphia, Pa, USA Elsevier Saunders 591 599 \n9 Wiström J. Norrby S. R. Myhre E. B. Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study Journal of Antimicrobial Chemotherapy 2001 47 1 43 50 2-s2.0-0035180464 11152430 \n10 Jacobs A. Barnard K. Fishel R. Gradon J. D. Extracolonic manifestations of Clostridium difficile infections: Presentation of 2 cases and review of the literature Medicine 2001 80 2 88 101 10.1097/00005792-200103000-00002 2-s2.0-0035074089 11307591 \n11 Putterman C. Rubinow A. Reactive arthritis associated with Clostridium difficile pseudomembranous colitis Seminars in Arthritis and Rheumatism 1993 22 6 420 426 10.1016/s0049-0172(05)80033-2 2-s2.0-0027174578 8342048 \n12 Ananthakrishnan A. N. Issa M. Binion D. G. \nClostridium difficile and inflammatory bowel disease Gastroenterology Clinics of North America 2009 38 4 711 728 10.1016/j.gtc.2009.07.003 2-s2.0-70350759934 19913210\n\n",
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{
"abstract": "Lithium intoxication might be lethal particularly in elderly persons who have multiple drugs. We present an aged bipolar patient with lithium intoxication probably caused by the interaction between fluvoxamine and azilsartan. Fluvoxamine inhibits many cytochrome P450 enzyme (CYP) including CYP2C9, which metabolizes azilsartan. Thus, azilsartan could cause more negative effects for sodium reabsorption at renal tubules when co-administered with fluvoxamine, resulted in a decrease in lithium excretion.",
"affiliations": "Dr. Nagamine is with the Sunlight Brain Research Center in Yamaguchi, Japan.",
"authors": "Nagamine|Takahiko|T|",
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"country": "United States",
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"issue": "17(4-6)",
"journal": "Innovations in clinical neuroscience",
"keywords": "drug interaction; elderly; lithium intoxication",
"medline_ta": "Innov Clin Neurosci",
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"nlm_unique_id": "101549695",
"other_id": null,
"pages": "45-46",
"pmc": null,
"pmid": "32802593",
"pubdate": "2020-04-01",
"publication_types": "D002363:Case Reports",
"references": "15086664;26936045;27222761;18399712;22467847;27216792;28437764",
"title": "Lithium Intoxication in the Elderly: A Possible Interaction between Azilsartan, Fluvoxamine, and Lithium.",
"title_normalized": "lithium intoxication in the elderly a possible interaction between azilsartan fluvoxamine and lithium"
} | [
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"medicinalproduct": "LITHIUM."
}
],
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"reaction": [
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "23.1",
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},
{
"reactionmeddrapt": "Toxicity to various agents",
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}
],
"summary": null
},
"primarysource": {
"literaturereference": "NAGAMINE T. LITHIUM INTOXICATION IN THE ELDERLY: A POSSIBLE INTERACTION BETWEEN AZILSARTAN, FLUVOXAMINE, AND LITHIUM. INNOV CLIN NEUROSCI. 2020?17(4-6):45-46",
"literaturereference_normalized": "lithium intoxication in the elderly a possible interaction between azilsartan fluvoxamine and lithium",
"qualification": "1",
"reportercountry": "JP"
},
"primarysourcecountry": "JP",
"receiptdate": "20201026",
"receivedate": "20201026",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18428912,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
},
{
"companynumb": "JP-TEVA-2020-JP-1843729",
"fulfillexpeditecriteria": "1",
"occurcountry": "JP",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUVOXAMINE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75893",
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},
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"activesubstancename": "LITHIUM CARBONATE"
},
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"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "LITHIUM CARBONATE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "AZILSARTAN KAMEDOXOMIL"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
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"drugcharacterization": "3",
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"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
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"drugrecurrence": null,
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"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZILSARTAN"
}
],
"patientagegroup": "6",
"patientonsetage": "82",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Myoclonus",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Tremor",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Renal impairment",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Somnolence",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Altered state of consciousness",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Disorientation",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NAGAMINE T. LITHIUM INTOXICATION IN THE ELDERLY: A POSSIBLE INTERACTION BETWEEN AZILSARTAN, FLUVOXAMINE, AND LITHIUM. INNOV-CLIN-NEUROSCI 2020?17(4):45-46.",
"literaturereference_normalized": "lithium intoxication in the elderly a possible interaction between azilsartan fluvoxamine and lithium",
"qualification": "1",
"reportercountry": "JP"
},
"primarysourcecountry": "JP",
"receiptdate": "20201103",
"receivedate": "20201103",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18457221,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
}
] |
{
"abstract": "Purpose Ado-trastuzumab emtansine (T-DM1) is currently approved for treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (MBC) who previously received trastuzumab and a taxane. However, there are no data on the activity of T-DM1 in patients who received prior pertuzumab, which is now included as standard first-line therapy. The goal of this study was to assess the efficacy of T-DM1 in routine clinical practice in a contemporary patient population that received both prior trastuzumab and pertuzumab. Patients and Methods We identified all patients with HER2-positive MBC who received T-DM1 after trastuzumab and pertuzumab between March 1, 2013, and July 15, 2015, via electronic pharmacy records and departmental databases at three institutions: MD Anderson Cancer Center, Smilow Cancer Hospital at Yale, and The James Cancer Hospital at the Ohio State University. We reviewed medical records of each case to confirm treatment sequencing and outcome. Results Of patients, 82 were identified and 78 were available for outcome analysis; 32% received T-DM1 as first- and second-line line therapy, and 48% received it as fourth-line treatment or later. Rate of prolonged duration on therapy, defined as duration on therapy ≥ 6 months, was 30.8% (95% CI, 20.6% to 41.1%), and tumor response rate was 17.9% (95% CI, 9.4% to 26.4%). Median duration on therapy was 4.0 months (95% CI, 2.7 to 5.1; range, 0 to 22.5 months). T-DM1 was discontinued for disease progression in 84% of patients and for toxicity in 10%. Conclusion Tumor response rates were lower than in prior reports of trastuzumab-resistant, HER2-positive MBC, but one third of patients received therapy with T-DM1 for ≥ 6 months, which suggests a clinically relevant benefit in patients who received prior pertuzumab.",
"affiliations": "Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.;Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.;Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.;Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.;Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.;Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.;Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.;Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.;Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.;Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.;Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.",
"authors": "Dzimitrowicz|Hannah|H|;Berger|Michael|M|;Vargo|Craig|C|;Hood|Annette|A|;Abdelghany|Osama|O|;Raghavendra|Akshara Singareeka|AS|;Tripathy|Debu|D|;Valero|Vicente|V|;Hatzis|Christos|C|;Pusztai|Lajos|L|;Murthy|Rashmi|R|",
"chemical_list": "D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008453:Maytansine; C508053:ERBB2 protein, human; D018719:Receptor, ErbB-2; C485206:pertuzumab; D000068878:Trastuzumab; D000080044:Ado-Trastuzumab Emtansine",
"country": "United States",
"delete": false,
"doi": "10.1200/JCO.2016.67.3624",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0732-183X",
"issue": "34(29)",
"journal": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
"keywords": null,
"medline_ta": "J Clin Oncol",
"mesh_terms": "D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001943:Breast Neoplasms; D018450:Disease Progression; D006801:Humans; D008453:Maytansine; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Receptor, ErbB-2; D066066:Response Evaluation Criteria in Solid Tumors; D019233:Retreatment; D012189:Retrospective Studies; D000068878:Trastuzumab",
"nlm_unique_id": "8309333",
"other_id": null,
"pages": "3511-3517",
"pmc": null,
"pmid": "27298406",
"pubdate": "2016-10-10",
"publication_types": "D016428:Journal Article",
"references": "23801166;23020162;16236737;14770426;22153890;22649126;16236738;19010901;23704196;22149875;24793816;19097774;21172893;24677057;24879797;11248153;24706168;23829891;17192538;24101045;23382472;20404251;24210572",
"title": "T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab.",
"title_normalized": "t dm1 activity in metastatic human epidermal growth factor receptor 2 positive breast cancers that received prior therapy with trastuzumab and pertuzumab"
} | [
{
"companynumb": "US-ROCHE-1773313",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ADO-TRASTUZUMAB EMTANSINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
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"drugindication": "HER-2 POSITIVE BREAST CANCER",
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"medicinalproduct": "TRASTUZUMAB EMTANSINE"
}
],
"patientagegroup": null,
"patientonsetage": null,
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"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Thrombocytopenia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Ejection fraction decreased",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Fatigue",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Decreased appetite",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Fall",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Arthralgia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Transaminases increased",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Neuralgia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Serum sickness-like reaction",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": ", BERGER M, VARGO C, HOOD A, ABDELGHANY O, RAGHAVENDRA A, TRIPATHY D, VALERO V, HATZIS C, PUSZTAI L AND MURTHY R. T-DM1 ACTIVITY IN METASTATIC HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2-POSITIVE BREAST CANCERS THAT RECEIVED PRIOR THERAPY WITH TRASTUZUMAB AND PERTUZUMAB. JOURNAL OF CLINICAL ONOLOGY 2016 OCT 10;34 (29):3511-3517.",
"literaturereference_normalized": "t dm1 activity in metastatic human epidermal growth factor receptor 2 positive breast cancers that received prior therapy with trastuzumab and pertuzumab",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20161021",
"receivedate": "20160909",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 12727204,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20170207"
}
] |
{
"abstract": "BACKGROUND\nTo describe the possible role of oxaliplatin in worsening pre-existing interstitial lung disease.\n\n\nMETHODS\nAfter we encountered a patient with an interstitial lung disease who experienced a fatal progression of his pulmonary disease associated with oxaliplatin therapy, a computer-aided search was conducted to identify other similar patients. Twenty-six patients with various lung diseases who had received oxaliplatin therapy at Mayo Clinic in Rochester, MN from January 2000 to December 2006 were identified. Three of these patients had radiologic evidence of interstitial lung disease before undergoing oxaliplatin therapy. We examined the medical records and imaging studies of these three patients to further define their clinical presentation, radiological and functional characteristics, and clinical outcome.\n\n\nRESULTS\nAll three patients experienced symptomatic and radiologic worsening of their interstitial lung disease following oxaliplatin administration. One of these patients died from refractory respiratory failure; the remaining two patients stabilized after the discontinuation of oxaliplatin therapy and have since shown modest improvement in pulmonary symptoms and lung function. There were no other potential causes identified for the unexpected progression of their lung disease other than the temporal relationship to oxaliplatin therapy.\n\n\nCONCLUSIONS\nTreatment with oxaliplatin, in the setting of a pre-existing interstitial lung disease, may be associated with respiratory deterioration. It is unknown whether this is mediated by acceleration of the underlying parenchymal disease or by a superimposed acute lung injury caused by oxaliplatin.",
"affiliations": "Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. wilcox.bradley@mayo.edu",
"authors": "Wilcox|Brad E|BE|;Ryu|Jay H|JH|;Kalra|Sanjay|S|",
"chemical_list": "D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin",
"country": "England",
"delete": false,
"doi": "10.1016/j.rmed.2007.09.001",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0954-6111",
"issue": "102(2)",
"journal": "Respiratory medicine",
"keywords": null,
"medline_ta": "Respir Med",
"mesh_terms": "D000368:Aged; D000970:Antineoplastic Agents; D015179:Colorectal Neoplasms; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial; D008297:Male; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D012129:Respiratory Function Tests; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome",
"nlm_unique_id": "8908438",
"other_id": null,
"pages": "273-9",
"pmc": null,
"pmid": "17945475",
"pubdate": "2008-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Exacerbation of pre-existing interstitial lung disease after oxaliplatin therapy: a report of three cases.",
"title_normalized": "exacerbation of pre existing interstitial lung disease after oxaliplatin therapy a report of three cases"
} | [
{
"companynumb": "US-CIPLA LTD.-2018US17230",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "GEMCITABINE\\GEMCITABINE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
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"drugrecurreadministration": null,
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"medicinalproduct": "GEMCITABINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARBOPLATIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "077861",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBOPLATIN."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Fibrosis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Dyspnoea",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WILCOX BE, RYU JH AND KALRA S. EXACERBATION OF PRE?EXISTING INTERSTITIAL LUNG DISEASE AFTER OXALIPLATIN THERAPY: A REPORT OF THREE CASES. RESPIRATORY MEDICINE. 2008?102:273?279",
"literaturereference_normalized": "exacerbation of pre existing interstitial lung disease after oxaliplatin therapy a report of three cases",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180706",
"receivedate": "20180509",
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},
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"safetyreportid": 14868530,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
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{
"abstract": "Many patients with intentional drug overdose (IDO) are admitted to a medium (MC) or intensive care unit (IC) without ever requiring MC/IC related interventions. The objective of this study was to develop a decision tool, using parameters readily available in the emergency room (ER) for patients with an IDO, to identify patients requiring admission to a monitoring unit.\n\n\n\nRetrospective cohort study among cases of IDO with drugs having potentially acute effects on neurological, circulatory or ventilatory function, admitted to the MC/IC unit between 2007 and 2013. A decision tool was developed, using 6 criteria, representing intubation, breathing, oxygenation, cardiac conduction, blood pressure, and consciousness. Cases were labeled as 'high acuity' if one or more criteria were present.\n\n\n\nAmong 255 cases of IDO that met the inclusion criteria, 197 were identified as \"high acuity\". Only 70 of 255 cases underwent one or more MC/IC related interventions, of which 67 were identified as 'high acuity by the decision tool (sensitivity 95.7%).\n\n\n\nIn a population of patients with intentional drug overdose with agents having potentially acute effect on vital functions, 95.7% of MC/IC interventions could be predicted by clinical assessment, supplemented with electrocardiogram and blood gas analysis, in the ER.",
"affiliations": "Intensive Care Unit, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE Deventer, The Netherlands. Electronic address: h.vandenoever@dz.nl.;Intensive Care Unit, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE Deventer, The Netherlands. Electronic address: mirjavandam@gmail.com.;Teaching Hospital Deventer, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE Deventer, The Netherlands. Electronic address: e.vantriet@dz.nl.;Department of Clinical Pharmacy, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE Deventer, The Netherlands; Department of Pharmacotherapy, -Epidemiology and -Economics, University Groningen, Antonius Deusinglaan 1, 9713AV, Groningen, The Netherlands. Electronic address: f.jansman@dz.nl.",
"authors": "van den Oever|Huub L A|HLA|;van Dam|Mirja|M|;van 't Riet|Esther|E|;Jansman|Frank G A|FGA|",
"chemical_list": null,
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"doi": "10.1016/j.jcrc.2016.09.020",
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"issn_linking": "0883-9441",
"issue": "37()",
"journal": "Journal of critical care",
"keywords": "Admission avoidance; Clinical management; Deliberate self; Drug overdose; Medium care; Triage",
"medline_ta": "J Crit Care",
"mesh_terms": "D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003422:Critical Care; D020000:Decision Support Systems, Clinical; D062787:Drug Overdose; D005260:Female; D006301:Health Services Needs and Demand; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010343:Patient Admission; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013406:Suicide, Attempted; D014218:Triage; D055815:Young Adult",
"nlm_unique_id": "8610642",
"other_id": null,
"pages": "156-161",
"pmc": null,
"pmid": "27744235",
"pubdate": "2017-02",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Clinical parameters that predict the need for medium or intensive care admission in intentional drug overdose patients: A retrospective cohort study.",
"title_normalized": "clinical parameters that predict the need for medium or intensive care admission in intentional drug overdose patients a retrospective cohort study"
} | [
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{
"abstract": "Infection, thrombosis, and catheter dislodgment are well-recognized potential complications of chronic intravenous prostanoid therapy for pulmonary arterial hypertension. As long-term outcomes of pulmonary hypertension patients improve, novel adverse events are likely to arise. We describe the sudden development of unexplained hypotension and lightheadedness in a patient receiving intravenous epoprostenol for several years, ultimately determined to be due to an unusual catheter complication, not previously described in this population.",
"affiliations": "1 6797 Pulmonary Diseases and Critical Care Medicine, University of North Carolina , Chapel Hill, NC, USA.;2 Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.;3 Central Line Service, Beth Israel Deaconess Medical Center, Boston, MA, USA.",
"authors": "LeVarge|Barbara L|BL|;Law|Anica C|AC|;Murphy|Blanche|B|",
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"fulltext": "\n==== Front\nPulm CircPulm CircPULsppulPulmonary Circulation2045-89322045-8940SAGE Publications Sage UK: London, England 10.1177/204589321774805410.1177_2045893217748054Case ReportOccult catheter rupture causing episodic symptoms in a patient treated with epoprostenol LeVarge Barbara L. 1Law Anica C. 2Murphy Blanche 31 6797Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill, NC, USA2 Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA3 Central Line Service, Beth Israel Deaconess Medical Center, Boston, MA, USABarbara L. LeVarge, Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, 130 Mason Farm Road, Chapel Hill, NC 27599, USA. Email: barbara_levarge@med.unc.edu18 12 2017 Jan-Mar 2018 8 1 20458932177480542 8 2017 21 11 2017 © The Author(s) 20172017SAGE Publications Ltd, or Pulmonary Vascular Research Institute, unless otherwise noted. Manuscript content on this site is licensed under Creative Commons LicensesCreative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Infection, thrombosis, and catheter dislodgment are well-recognized potential complications of chronic intravenous prostanoid therapy for pulmonary arterial hypertension. As long-term outcomes of pulmonary hypertension patients improve, novel adverse events are likely to arise. We describe the sudden development of unexplained hypotension and lightheadedness in a patient receiving intravenous epoprostenol for several years, ultimately determined to be due to an unusual catheter complication, not previously described in this population.\n\npulmonary arterial hypertensionepoprostenolcatheter rupturecover-dateJanuary-March 2018\n==== Body\nCase report\nA 61-year-old woman with idiopathic pulmonary arterial hypertension (PAH) managed with intravenous epoprostenol and oral tadalafil was seen for evaluation of recurrent episodes of lightheadedness, nausea, and flushing. Episodes first began one month before current presentation when she noted severe lightheadedness and palpitations upon waking in the morning, leading her to call 911. On evaluation by emergency medical services, her systolic blood pressure was in the 50 s with heart rate in the 80 s in sinus rhythm. She received 500 mL normal saline and was brought to the emergency department. Blood pressure on arrival was 113/67 and she felt markedly improved. She was admitted overnight for observation and telemetry monitoring with no further events. Her episode was attributed to vasovagal symptoms and she was discharged home. Following this event, she had numerous recurrent episodes of more mild, sudden onset lightheadedness, flushing, palpitations, and nausea. Symptoms would last for 5–15 min and then resolve.\n\nThere had been no recent changes to her PAH medications, mixing practices, or pump settings. Epoprostenol was infused at 48 ng/kg/min (concentration = 45,000 ng/mL, 77 mL/24 h) using the CADD-Legacy Ambulatory Infusion Pump and a single lumen 9.6 French tunneled silicone catheter, placed in the right subclavian position eight years earlier. There were no recent pump alarms and episodes did not respond to changing out her existing pumps to new ones. Inspections of the catheter, connections, and exit site were unremarkable. There were no fevers or infectious signs or symptoms. A right heart catheterization was planned to further evaluate her symptoms.\n\nOn the day of her planned catheterization procedure, the patient was preparing to change her epoprostenol cartridge and tubing when she noticed a focal area of “ballooning” of her tunneled catheter adjacent to the clamp. With gentle compression of this area, the dilated area collapsed with immediate reproduction of symptoms of lightheadedness and flushing. She presented to the emergency room for further evaluation. A catheter repair was performed with resection of the dysfunctional portion of the catheter and replacement with a new end segment. The patient did very well after catheter repair with complete resolution of symptomatic episodes. The dysfunctional catheter segment was further explored with injection of various volumes of fluid while clamped, revealing a focal aneurysmal segment (Fig. 1).\nFig. 1. The resected segment of the patient’s tunneled catheter, injected with the indicated amounts of fluid against a closed clamp. This maneuver unmasked an aneurysmal segment of the catheter and the cause of the patient’s episodes.\n\n\n\nDiscussion\nThe focal dilatation of catheter, occurring just upstream of our patient’s clamp, likely developed secondary to clamp-site damage and stenosis. In the setting of stenosis and upstream increase in intraluminal pressure, the walls of the catheter weaken and dilate, essentially representing a contained partial rupture. As her infusion pump continued to deliver medication uninterrupted, no pump alarms activated despite the fact that the patient experienced several minutes of low or absent drug delivery, with epoprostenol accumulating within the aneurysmal segment. In this case, the elasticity of the catheter was preserved, allowing spontaneous or induced contraction with bolus of the prostanoid, leading to symptoms as described. The external catheter further returned to its normal appearance, with routine inspection of the catheter unrevealing. Though her episodes were suggestive of excess prostanoid, it was challenging to determine the etiology until the aneurysmal segment was visualized.\n\nWe would expect this type of catheter complication to be more common with increasing age and use of the catheter. Intravenous epoprostenol and treprostinil have been approved in the United States for PAH since 1995 and 2004, respectively. Many PAH patients on these therapies are surviving 5–10 years or more.1,2 Our patient, for example, had been treated with epoprostenol for more than 15 years at the time of this event, and her current catheter had been in place for eight years. A tunneled central catheter (TCC) for intravenous prostanoid is considered “permanent” and there are no guidelines for (or against) routine replacement; in practice, catheter replacement is only done in situations of infection or malfunction. In other populations using long-term TCCs, guidelines do not recommend routine scheduled catheter replacement.3–5\n\nSeveral studies detail infectious complications for PAH patients receiving intravenous prostanoids, with event rates in the range of 0.03–0.36 per 1000 catheter-days.1,6–8 However, much less attention has been paid to non-infectious catheter-related complications in this population. Mechanical complications have been noted as relatively unusual events in the controlled trials,9,10 with few case reports otherwise describing non-infectious catheter-related adverse events.11\n\nPermanent TCCs are used for a variety of more common indications, including chronic hemodialysis as well as administration of chemotherapy or parenteral nutrition. In a large study of home infusion catheters, catheter dysfunction preventing normal use occurred at a rate of 0.29 per 1000 catheter-days in those with TCCs; the majority of these events were non-thrombotic. This is compared to the observed infection rate of 0.70 per 1000 catheter-days in these same patients.12 Other studies in varied populations with TCCs have found mechanical complications (e.g. dislodgment, occlusion, rupture) to be at least as common as infectious complications.13–15 An investigation involving 584 patients receiving parenteral nutrition studied 99 patients with mechanical complications of a TCC; 65% of mechanical complications were classified as catheter rupture, described by the authors as “balloon-like” expansion of the external catheter, most often near the clip.16 Other data supports that catheter rupture is more likely in silicone (vs. polyurethane) catheters, similar to those used in most intravenous prostanoid patients.17,18\n\nThe short half-life (t1/2) of prostanoids, in particular epoprostenol (t1/2 = 2–6 minutes), necessitates continuous delivery via ambulatory infusion pump. This short t1/2 also means that small errors in dosing can have large effects. In this case, we estimate that the patient was inadvertently bolused 1–1.5 mL of epoprostenol with her current presentation, and possibly much more during her previous hypotensive episode. Depending on rate and concentration, even this small bolus can be substantial. For our patient, this provided her with a bolus dose that was intended to be given over 20 min. The pharmacokinetics and/or lack of vasoactive side effects of most TCC infusions would not create such dramatic symptoms should a similar catheter malfunction occur. It is even likely that a comparable bolus of treprostinil, with longer t1/2, could go unnoticed. Thus, this type of catheter damage may certainly be under-recognized. In the systolic heart failure population, chronic dobutamine infusion could in theory have the same risk with a similar type of malfunction; however, these patients have worse survival and are less likely to be using a catheter for a long duration.19\n\nIn summary, mechanical catheter complications of chronic intravenous prostanoid therapy, though poorly described in the PAH literature, must be recognized by those caring for PAH patients. As PAH patients enjoy improved survival in the modern treatment era, such events will become more common, particularly for those with older tunneled catheters. While routine replacement of older catheters likely leads to more harm than benefit, close inspection or provocation of the external catheter may reveal surreptitious mechanical problems in symptomatic patients.\n\nAcknowledgments\nWritten consent for case report and image publication was provided by our patient.\n\nConflict of interest\nThe author(s) declare that there is no conflict of interest.\n\nFunding\nThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\n==== Refs\nReferences\n1 Sitbon O Humbert M Nunes H et al. \nLong-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival . J Am Coll Cardiol \n2002 ; 40 : 780 –788 .12204511 \n2 Yamamoto K Takeda Y Takeda Y et al. \nLong-term survival of patients with pulmonary arterial hypertension recovering to World Health Organization functional class I or II: a historical comparison between intravenous epoprostenol and oral agents . BMC Res Notes \n2014 ; 7 : 359 .24920465 \n3 Pittiruti M Hamilton H Biffi R et al. \nESPEN Guidelines on Parenteral Nutrition: central venous catheters (access, care, diagnosis and therapy of complications) . Clin Nutr \n2009 ; 28 : 365 –377 .19464090 \n4 Fluck R Kumwenda M \nRenal Association Clinical Practice Guideline on vascular access for haemodialysis . Nephron Clin Pract \n2011 ; 118 (Suppl 1 ): c225 –240 .\n5 National Kidney Foundation . KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for 2006 Updates: hemodialysis adequacy, peritoneal dialysis adequacy and vascular access . Am J Kidney Dis \n2006 ; 48 : S1 –S322 .17045862 \n6 McLaughlin VV Shillington A Rich S \nSurvival in primary pulmonary hypertension: the impact of epoprostenol therapy . Circulation \n2002 ; 106 : 1477 –1482 .12234951 \n7 Kitterman N Poms A Miller DP et al. \nBloodstream infections in patients with pulmonary arterial hypertension treated with intravenous prostanoids: insights from the REVEAL REGISTRY® . Mayo Clin Proc \n2012 ; 87 : 825 –834 .22883740 \n8 Nagai T Kohsaka S Anzai T et al. \nLow incidence of catheter-related complications in patients with advanced pulmonary arterial hypertension undergoing continuous epoprostenol infusion . Chest \n2012 ; 141 : 272 –273 .22215838 \n9 Barst RJ Rubin LJ Long WA et al. \nA comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension . N Engl J Med \n1996 ; 334 : 296 –301 .8532025 \n10 Badesch DB Tapson VF McGoon MD et al. \nContinuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial . Ann Intern Med \n2000 ; 132 : 425 –434 .10733441 \n11 Malaczynska-Rajpold K Kurzyna M Koteja A et al. \nThe “bouncing” catheter . Cardiol J \n2016 ; 23 : 552 –553 .27723062 \n12 Moureau N Poole S Murdock MA et al. \nCentral venous catheters in home infusion care: outcomes analysis in 50,470 patients . J Vasc Interv Radiol \n2002 ; 13 : 1009 –1016 .12397122 \n13 Cesaro S Cavaliere M Pegoraro A et al. \nA comprehensive approach to the prevention of central venous catheter complications: results of 10-year prospective surveillance in pediatric hematology-oncology patients . Ann Hematol \n2016 ; 95 : 817 –825 .26961934 \n14 Cotogni P Pittiruti M Barbero C et al. \nCatheter-related complications in cancer patients on home parenteral nutrition: a prospective study of over 51,000 catheter days . JPEN J Parenter Enteral Nutr \n2013 ; 37 : 375 –383 .23002096 \n15 O’Neill VJ Jeffrey Evans TR Preston J et al. \nA retrospective analysis of Hickman line-associated complications in patients with solid tumours undergoing infusional chemotherapy . Acta Oncol \n1999 ; 38 : 1103 –1107 .10665770 \n16 Blasiak R Lawinski M Majewska K et al. \nDamage of central catheters in home parenteral nutrition patients . Pol Przegl Chir \n2015 ; 87 : 579 –586 .26816406 \n17 Seckold T Walker S Dwyer T \nA comparison of silicone and polyurethane PICC lines and postinsertion complication rates: a systematic review . J Vasc Access \n2015 ; 16 : 167 –177 .25634150 \n18 Wildgruber M Lueg C Borgmeyer S et al. \nPolyurethane versus silicone catheters for central venous port devices implanted at the forearm . Eur J Cancer \n2016 ; 59 : 113 –124 .27023050 \n19 Gorodeski EZ Chu EC Reese JR et al. \nPrognosis on chronic dobutamine or milrinone infusions for stage D heart failure . Circ Heart Fail \n2009 ; 2 : 320 –324 .19808355\n\n",
"fulltext_license": "CC BY-NC",
"issn_linking": "2045-8932",
"issue": "8(1)",
"journal": "Pulmonary circulation",
"keywords": "catheter rupture; epoprostenol; pulmonary arterial hypertension",
"medline_ta": "Pulm Circ",
"mesh_terms": null,
"nlm_unique_id": "101557243",
"other_id": null,
"pages": "2045893217748054",
"pmc": null,
"pmid": "29249170",
"pubdate": "2018",
"publication_types": "D002363:Case Reports",
"references": "23002096;12234951;8532025;27723062;26961934;21555898;19808355;22883740;10665770;25634150;12397122;24920465;27023050;26816406;12204511;10733441;22215838;19464090",
"title": "Occult catheter rupture causing episodic symptoms in a patient treated with epoprostenol.",
"title_normalized": "occult catheter rupture causing episodic symptoms in a patient treated with epoprostenol"
} | [
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"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Hypotension",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
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"reactionmeddrapt": "Flushing",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
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"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Palpitations",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
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},
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"literaturereference": "LEVARGE BL, LAW AC, MURPHY B. OCCULT CATHETER RUPTURE CAUSING EPISODIC SYMPTOMS IN A PATIENT TREATED WITH EPOPROSTENOL. PULM-CIRC 2018?8(1):1-3.",
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},
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},
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{
"abstract": "BACKGROUND\nThere has been no previous prospective examination of the homogeneity of chronic non-cancer pain (CNCP) patients in risk factors for non-adherent opioid use.\n\n\nOBJECTIVE\nTo identify whether latent risk classes exist among people with CNCP that predict non-adherence with prescribed opioids.\n\n\nMETHODS\nProspective cohort study.\n\n\nMETHODS\nThe Pain and Opioids IN Treatment prospective cohort comprises 1,514 people in Australia prescribed pharmaceutical opioids for CNCP interviewed 3 months apart. Risk factors were assessed in wave 1, and non-adherent behaviors in the 3 months prior to wave 1 and wave 2. Latent class analysis was used to examine groups with differing risk profiles. Logistic regression was used to examine predictors of non-adherence.\n\n\nRESULTS\nA 4-class model was selected with classes described as: 1) Poor Physical Functioning group (27%); 2) Poor Coping/Physical Functioning group (35%); 3) Substance Use Problems group (14%); and 4) Multiple Comorbid Problems group (25%). The latter 2 groups had an increased risk of requesting increased opioid doses, early script renewals, using diverted medication, dose stock-piling, and unsanctioned dose alteration at wave 2.\n\n\nCONCLUSIONS\nRisk factor onset prior to non-adherent behavior cannot be determined.\n\n\nCONCLUSIONS\nClusters of CNCP patients with distinct risk profiles for non-adherence exist. Each group was identified by at least one risk factor but the likelihood of non-adherent opioid use was higher in groups with particular clusters of multiple risk factors. Not all those with risk factors display non-adherence, emphasising the need for strategies to reduce risk for those patients displaying particular clusters of risks.",
"affiliations": "School of Medicine (Psychology), University of Tasmania, Hobart, Tasmania, Australia.;School of Medicine (Psychology), University of Tasmania, Hobart, Tasmania, Australia; National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia.;National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia.;National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia.;National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia Drug and Alcohol Services South Eastern Sydney Local Health District.;School of Population Health, University of Queensland, Queensland, Australia.;National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia.;School of Medicine (Psychology), University of Tasmania, Hobart, Tasmania, Australia.",
"authors": "Peacock|Amy|A|;Degenhardt|Louisa|L|;Campbell|Gabriella|G|;Larance|Briony|B|;Nielsen|Suzanne|S|;Hall|Wayne|W|;Mattick|Richard P|RP|;Bruno|Raimondo|R|",
"chemical_list": "D000701:Analgesics, Opioid",
"country": "United States",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1533-3159",
"issue": "19(3)",
"journal": "Pain physician",
"keywords": null,
"medline_ta": "Pain Physician",
"mesh_terms": "D000223:Adaptation, Psychological; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid; D001315:Australia; D059350:Chronic Pain; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D019966:Substance-Related Disorders",
"nlm_unique_id": "100954394",
"other_id": null,
"pages": "E421-34",
"pmc": null,
"pmid": "27008298",
"pubdate": "2016-03",
"publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "A Typology of Predictive Risk Factors for Non-Adherent Medication-Related Behaviors among Chronic Non-Cancer Pain Patients Prescribed Opioids: A Cohort Study.",
"title_normalized": "a typology of predictive risk factors for non adherent medication related behaviors among chronic non cancer pain patients prescribed opioids a cohort study"
} | [
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}
],
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"reaction": [
{
"reactionmeddrapt": "Treatment noncompliance",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug abuse",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug diversion",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Product use issue",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
}
],
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},
"primarysource": {
"literaturereference": "PEACOCK A, DEGENHARDT L, CAMPBELL G, LARANCE B, NIELSEN S, HALL W, ET AL. A TYPOLOGY OF PREDICTIVE RISK FACTORS FOR NON-ADHERENT MEDICATION-RELATED BEHAVIORS AMONG CHRONIC NON-CANCER PAIN PATIENTS PRESCRIBED OPIOIDS: A COHORT STUDY. PAIN PHYSICIAN 2016;19(3):E421-E434.",
"literaturereference_normalized": "a typology of predictive risk factors for non adherent medication related behaviors among chronic non cancer pain patients prescribed opioids a cohort study",
"qualification": "1",
"reportercountry": "AU"
},
"primarysourcecountry": "AU",
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},
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"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
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"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160815"
}
] |
{
"abstract": "OBJECTIVE\nTo report a case of acute cholestatic hepatitis associated with the selective cyclooxygenase-2 inhibitor celecoxib.\n\n\nMETHODS\nA 41-year-old white man was hospitalized for jaundice after 2 doses of celecoxib 200 mg for pain associated with right-knee trauma. Laboratory workup showed hyperbilirubinemia, mildly elevated serum transaminase concentrations, and cholestasis. Abdominal imaging showed no dilation of the biliary tree. Histology showed cholestasis, with bile plugs in dilated bile canaliculi and a mild portal infiltrate that are highly suggestive of drug-induced cholestasis.\n\n\nCONCLUSIONS\nThis is the fourth report in the English-language literature describing cholestatic hepatitis temporally related to celecoxib use, the second supported by histologic findings typical of drug-induced cholestasis, and the first in a patient who denied use of alcoholic beverages and was taking no other drugs or herbal products at the time of the reaction. The Naranjo probability scale indicated that celecoxib was a probable cause of acute cholestatic hepatitis in this patient.\n\n\nCONCLUSIONS\nCholestatic hepatitis is a well-recognized adverse effect of several drugs. Although celecoxib is considered to have a very low potential for hepatic toxicity, well-documented reports of adverse reactions can contribute significantly to the definition of more accurate safety profiles for new drugs introduced into clinical practice.",
"affiliations": "Department of Internal Medicine, Catholic University of Sacred Heart, Rome, Italy. agrieco@rm.unicatt.it",
"authors": "Grieco|Antonio|A|;Miele|Luca|L|;Giorgi|Andrea|A|;Civello|Ignazio M|IM|;Gasbarrini|Giovanni|G|",
"chemical_list": "D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013449:Sulfonamides; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000068579:Celecoxib",
"country": "United States",
"delete": false,
"doi": "10.1345/aph.1C110",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1060-0280",
"issue": "36(12)",
"journal": "The Annals of pharmacotherapy",
"keywords": null,
"medline_ta": "Ann Pharmacother",
"mesh_terms": "D000208:Acute Disease; D000328:Adult; D000410:Alanine Transaminase; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001219:Aspartate Aminotransferases; D000068579:Celecoxib; D056486:Chemical and Drug Induced Liver Injury; D002779:Cholestasis; D006801:Humans; D006932:Hyperbilirubinemia; D008297:Male; D011720:Pyrazoles; D013449:Sulfonamides; D005723:gamma-Glutamyltransferase",
"nlm_unique_id": "9203131",
"other_id": null,
"pages": "1887-9",
"pmc": null,
"pmid": "12452750",
"pubdate": "2002-12",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Acute cholestatic hepatitis associated with celecoxib.",
"title_normalized": "acute cholestatic hepatitis associated with celecoxib"
} | [
{
"companynumb": "JP-PFIZER INC-2019417987",
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{
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"activesubstance": {
"activesubstancename": "CELECOXIB"
},
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"drugdosagetext": "200 MG, DAILY",
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],
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"patientonsetage": "41",
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"reaction": [
{
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"reactionmeddraversionpt": "22.1",
"reactionoutcome": "1"
},
{
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"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "GRIECO, A.. ACUTE CHOLESTATIC HEPATITIS ASSOCIATED WITH CELECOXIB. THE ANNALS PHARMACOTHERAPY. 2002?36:1887-1889",
"literaturereference_normalized": "acute cholestatic hepatitis associated with celecoxib",
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},
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{
"abstract": "Prostate cancer is the second leading cause of cancer-related death in men in most Western countries. In this report, we present 2 cases of metastatic castration-resistant prostate cancer and chronic kidney disease. Both patients underwent and developed clinical resistance to androgen-deprivation therapy. Subsequently, the patients were treated with the conventional chemotherapeutic approach, which resulted in the worsening of renal function and performance status. Therefore, we opted for treatment with abiraterone acetate, and the patients exhibited improvements in renal function with good response of the disease.",
"affiliations": "From the Medical Oncology Unit, Policlinico Umberto I Hospital, University of Rome, Roma (EF); Pharmacology Unit (AIF); and Medical Oncology Unit, University of Siena, Siena, Italy (RP, LL, GR).",
"authors": "Francini|Edoardo|E|;Petrioli|Roberto|R|;Fiaschi|Anna Ida|AI|;Laera|Letizia|L|;Roviello|Giandomenico|G|",
"chemical_list": "D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; C089740:abiraterone",
"country": "United States",
"delete": false,
"doi": "10.1097/MD.0000000000000163",
"fulltext": "\n==== Front\nMedicine (Baltimore)Medicine (Baltimore)MEDIMedicine0025-79741536-5964Wolters Kluwer Health 2550105810.1097/MD.0000000000000163001635700ArticleClinical Case ReportEffects of Abiraterone Acetate on Chronic Kidney Disease in 2 Patients With Metastatic Castration-resistant Prostate Cancer Francini Edoardo MDPetrioli Roberto MDFiaschi Anna Ida PharmaDLaera Letizia MDRoviello Giandomenico MDCao. Chun-Xia From the Medical Oncology Unit, Policlinico Umberto I Hospital, University of Rome, Roma (EF); Pharmacology Unit (AIF); and Medical Oncology Unit, University of Siena, Siena, Italy (RP, LL, GR).Correspondence: Dr Giandomenico Roviello, Oncology Unit, Siena 53100, Italy (e-mail: giandomenicoroviello@hotmail.it).12 2014 12 12 2014 93 27 e16324 8 2014 9 9 2014 9 9 2014 Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins2014This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0Abstract\nProstate cancer is the second leading cause of cancer-related death in men in most Western countries. In this report, we present 2 cases of metastatic castration-resistant prostate cancer and chronic kidney disease. Both patients underwent and developed clinical resistance to androgen-deprivation therapy. Subsequently, the patients were treated with the conventional chemotherapeutic approach, which resulted in the worsening of renal function and performance status. Therefore, we opted for treatment with abiraterone acetate, and the patients exhibited improvements in renal function with good response of the disease.\n\nOPEN-ACCESSTRUE\n==== Body\nINTRODUCTION\nAbiraterone acetate (AA) is a novel irreversible inhibitor of CYP17 that was approved by the Food and Drug Administration (FDA) on April 28, 2011 in combination with prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC), which was previously treated with docetaxel. The approval of this agent was based on a multinational randomized, double-blind, placebo-controlled, phase III trial that involved 1195 patients with docetaxel-refractory CRPC.1 This study demonstrated a median overall survival in the AA arm of 14.8 months compared with 10.9 months in the placebo arm (hazard ratio: 0.646, 95% confidence interval: 0.54–0.77; P = 0.0001). Furthermore, in 2013, AA was approved by regulatory agencies in the United States and Europe for chemotherapy-naive mCRPC. This approval followed positive results from a phase III COU-AA-302 trial in which 1088 chemotherapy-naive men with metastatic CRPC who were treated with AA/prednisone exhibited prolonged overall survival compared with those treated with a regimen of placebo/prednisone.2 More recently, the prespecified interim analysis of the efficacy and safety outcomes in the COU-AA-302 study revealed median overall survivals of 35.3 months on AA versus 30.1 months on placebo.3\n\nWithin the histories of patients with prostate cancer, the development of a chronic kidney disease (CKD) is not uncommon. In this report, we describe 2 patients with mCRPC and CKD who were treated with AA and experienced improvements in renal function, dramatic declines in prostate-specific antigen (PSA) levels, improvements in performance status, and reductions in bone pain.\n\nCASE REPORT 1\nIn 2002, a 76-year-old man presented with a PSA level of 15 ng/mL. His physical examination was normal, and a digital rectal examination revealed a slightly enlarged prostate. Biopsies revealed a prostate cancer with no evidence of distant metastases and a Gleason score of 7 (4 + 3). Given the patient's advanced age, surgery was excluded. Moreover, the patient refused to undergo radiotherapy; therefore, he was treated with leuprolide and oral bicalutamide.\n\nFollow-up visits were scheduled every 3 months that included serial physical examination, routine blood evaluations that included serum PSA determinations at regular intervals (every 2–3 months) and radiological assessments every 6 to 12 months or as clinically indicated.\n\nIn January 2010, an episode of hematuria, urinary retention, and bilateral hydronephrosis with acute renal failure (creatinine 6.39 mg/dL) occurred, and a percutaneous ureterostomy was performed. However, although the episode of acute kidney failure was resolved, the patient presented with CKD in subsequent tests (creatinine 2.0 mg/dL, creatinine clearance 35 mL/min). Stage 3B CKD was diagnosed and required observation and control of blood pressure and other risk factors.\n\nIn May 2010, the patient reported low-grade, constant back pain. A radionuclide scintigraphy revealed several areas suggestive of metastatic bone disease (ie, the right parietal bone, lumbar spine, sternum, ribs, pelvis, and right femur), and a serum PSA determination revealed a level of 210 ng/mL.\n\nTherefore, the patient began chemotherapy with estramustine phosphate 560 mg per os daily and zoledronic acid intravenously every 28 days. Laboratory data revealed the following values: haemoglobin level 11.8 g/mL, hematocrit 38.5%, white blood cell count (WBC) 4200 cells/mm3, platelets 179,000 cells/mL, blood urea nitrogen 69 mg/dL, creatinine 2.6 mg/dL, and creatinine clearance 26.92 mL/min (stage 4 CKD). Due to age of the patient, the normality of the electrolytes, and the low urea value, renal replacement was not considered. Abdomen CT revealed the presence of a bilateral percutaneous ureterostomy with reduction of both kidneys, particularly the left, and the CT also revealed the presence of multiple osteosclerotic lesions in the lumbar spine and pelvis.\n\nFollow-up visits that included determination of the serum PSA were scheduled every 2 months. These evaluations revealed a progressive increase in PSA to 421 ng/mL (Figure 1); therefore, in July 2011, the patient received a second line of chemotherapy with docetaxel 40 mg/m2 intravenous infusion on days 1, 8, 15, 22, and 29 in a 6-week cycle.\n\nFIGURE 1 Trend of creatinine clearance and PSA during docetaxel and abiraterone acetate therapy.\n\nOver the first 3 months, the PSA exhibited a small decrease to 339.7 ng/mL; after 6 months of treatment, the PSA went down to 243.7 ng/mL, but the laboratory data revealed a worsening of renal function with a blood urea nitrogen level of 60 mg/dL, a creatinine level of 3.5 mg/dL, and a creatinine clearance of 19.64 mL/min (stage 4 CKD). Furthermore, the patient reported a partial resolution of the back pain. In contrast, the patient experienced considerable toxicity with side effects including neutropenia, anemia, thrombocytopenia, fatigue, nail changes, dry eyes, which were grades I or II in most of the examinations, and a worsening of performance status. Treatment with docetaxel was discontinued, and, due to the toxicity, a hormonal approach with oral AA was undertaken (1000 mg die, administered as four 250-mg tablets and prednisone 10 mg die in 2 daily dosings).\n\nSix months after beginning the new treatment, the PSA exhibited a substantial reduction (48.57 ng/mL; Figure 1), an improvement in renal function was observed (blood urea nitrogen 45 mg/dL, creatinine 2.1 mg/dL, and creatinine clearance 32.14 mL/min [stage 3B CKD]), electrolytes were normal, and the patient reported a reduction in bone pain with a decrease in analgesic consumption and an improvement in performance status. The treatment was well-tolerated without considerable side effects.\n\nCurrently, the patient is continuing treatment, his PSA level is 24.5 ng/mL (28 months without an increase in PSA), his creatinine is 2 mg/dL, and his creatinine clearance is 33.13 mL/min (stage 3B CKD).\n\nCASE REPORT 2\nIn November 2004, a 59-year-old man presented with a PSA of 13.7 ng/mL and a Gleason 7 (3 + 4) prostate adenocarcinoma. He underwent radical prostatectomy, and extensive perineural invasion and an extracapsular extension of the tumor were found. Subsequently, he was treated with radiation therapy and androgen-deprivation therapy consisting of leuprolide and oral bicalutamide.\n\nFollow-up visits were scheduled every 3 months with serial physical examinations, routine blood evaluations, which included serum PSA determinations at regular intervals (every 2 to 3 months), and radiological assessments every 6 to 12 months or as clinically indicated.\n\nIn October 2009, his PSA increased to 53.45 ng/mL, and an abdominal magnetic resonance imaging identified metastases to the pelvic lymph nodes. From 2010 through 2011, the patient received docetaxel and epirubicin (11 cycles) followed by weekly navelbine per os for 6 months. In November 2011, there was a substantial increase in the PSA value (72.68 ng/mL; Figure 2), and the patient underwent docetaxel rechallenge with weekly docetaxel alone for 4 months.\n\nFIGURE 2 Trend of creatinine clearance and PSA during docetaxel and abiraterone acetate therapy.\n\nDuring the first cycle of docetaxel rechallenge, an episode of urinary retention and bilateral hydronephrosis with acute renal failure (creatinine 7.34 mg/dL) occurred, and a percutaneous ureterostomy was performed. When the episode of acute kidney failure was resolved, laboratory tests revealed CDK with a creatinine level of 2.6 md/dL and a creatinine clearance of 24.62 mL/min. A stage 4 CDK was diagnosed and required observation and control of blood pressure and other risk factors. Other options were not considerate due to the age of the patient and the normality of the electrolytes and urea.\n\nIn March 2012, the PSA value decreased to 29.78 ng/mL; however, laboratory data revealed a partial improvement in renal function with a blood urea nitrogen level of 83 mg/dL, a creatinine level of 3.1 mg/dL, and a creatinine clearance of 20.32 mL/min (stage 4 CDK). Moreover, the patient began to suffer from the side effects of chemotherapy; therefore, some cycles were delayed due to toxicity.\n\nSubsequently, he began AA (1000 mg die, administered as four 250-mg tablets and prednisone 10 mg die in 2 daily dosing). His PSA exhibited a substantial reduction (4.91 ng/mL; Figure 2), improvements in renal function were observed (blood urea nitrogen 57 mg/dL, creatinine 1.7 mg/dL, creatinine clearance 37.06 mL/min, stage 3B CKD), his electrolyte levels were normal, and the treatment was well tolerated without considerable side effects. Currently, the patient is continuing treatment, his PSA level is 0.1 ng/mL (24 months without an increase in PSA), his creatinine is 1.6 mg/dL, and his creatinine clearance is 38.16 mL/min (stage 3B CKD).\n\nDISCUSSION\nUntil recently, patients who had progressed following docetaxel treatment had very limited options that included mitoxantrone, which was the first cytotoxic agent to be approved for the palliative treatment of men with CRPC.4 Other agents have been tested, but most studies have reported no objective responses or responses of <15%,5 and unfortunately, all of these agents have provided short-term clinical responses that are associated with a considerable toxicities. Moreover, the antifungal agent ketoconazole, which is used as an inhibitor of the activities of several enzymes involved in androgen synthesis such as CYP17 and CYP11, has been investigated.6 However, ketoconazole lacks specificity for the CYP17 family of enzymes, which unfortunately leads to significant toxicities (eg, hepatotoxicity, gastrointestinal toxicity, and adrenal insufficiency).6\n\nIn the past 3 years, several new agents with different mechanisms of action have been developed for the treatment of prostate cancer1,2,7,9–12 with the goal of prolonging the overall survival of CRPC patients. Sipuleucel-T has been found to improve the overall survival of asymptomatic or mildly symptomatic men, most of whom had not received chemotherapy.7 However, sipuleucel-T has primarily been used in the United States and has been used less in Europe.8 Cabazitaxel was approved by the FDA for the treatment of patients with mCRPC who have previously been treated with docetaxel chemotherapy.9\n\nUnfortunately, treatment with cabazitaxel is not without toxicity; indeed, severe neutropenia is common (89%), and 18% of patients discontinue the drug due to adverse events.9 Radium-223 has been reported to have a favorable safety profile with minimal myelotoxicity10; nevertheless, reports on the efficacy of radium-223 are recent, and at the time of this report, radium-223 was not commercially available. Rather, based on a systemic hormonal approach, AA and enzalutamide were approved for the treatment of patients with mCRPC following docetaxel treatment.1,2–11 Although enzalutamide exhibits a favorable toxicity profile,11,12 it could not be used for our patients because it is not yet commercially available; therefore, we opted for treatment with AA and excluded further lines of chemotherapy with cabazitaxel.\n\nSince the first phase II studies of AA,13 it has been clear that the blockade of cytochrome CYP17 is associated with increased mineralocorticoid levels that result in some adverse events, the most common of which are hypokalemia, fluid retention, and hypertension; however, these toxicities are largely abrogated by the co-administration of low-dose glucocorticoids.\n\nAs illustrated by the 2 cases reported herein before, the patients continued to respond to treatment with docetaxel, but their laboratory data revealed worsening of their renal function that prevented the continuation of treatment with this chemotherapeutic agent. Conversely, after initiating AA, their renal functions exhibited improvements (Figures 1 and 2) without significant toxicity. Notably, in our patients, AA exhibited its efficacy via substantial PSA responses that were sustained over time. Indeed, after 28 and 24 months, the patient's PSAs did not increase. These durations are longer than the time to PSA progression and the overall median survival of patients who were treated with AA in the trial by de Bono (10.2 and 14.8 months, respectively). Interestingly, our patients also exhibited longer times to PSA progression than the median time of the patients in the COU-AA-302 trial (11.1 months). Therefore, the prognoses were better for our cases. However, it is difficult to explain the reasons for the prolonged survivals observed in our cases and whether the CDK played a role. To date, both patients are still receiving AA treatment.\n\nCONCLUSIONS\nRecent studies showed that systemic hormone therapy is a well-tolerated option by the patients with CRPC. AA is one of the emerging novel therapies for advanced prostate cancer that employs a systemic hormonal approach.\n\nAbbreviations: AA = abiraterone acetate, CKD = chronic kidney disease, FDA = Food and Drug Administration, mCRPC = metastatic castration-resistant prostate cancer, PSA = prostate-specific antigen, WBC = white blood cell count.\n\nEthical approval was obtained from the ethics committee of the University of Siena. Written informed consent was obtained from the patients for publication of these case reports.\n\nThe authors have no conflicts of interest to disclose.\n==== Refs\nREFERENCES\n1. de Bono JS Logothetis CJ Molina A \nAbiraterone and increased survival in metastatic prostate cancer . N Engl J Med \n2011 ; 364 :1995 –2005 .21612468 \n2. Ryan CJ Smith MR de Bono JS \nAbiraterone in metastatic prostate cancer without previous chemotherapy . N Engl J Med \n2013 ; 368 :138 –148 .23228172 \n3. Rathkopf DE Smith MR de Bono JS \nUpdated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302) . Eur Urol \n2014 ; Mar 6. pii: S0302-2838(14)00185-7. doi: 10.1016/j.eururo.2014.02.056 .\n4. Tannock IF Osoba D Stockler MR \nChemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points . J Clin Oncol \n1996 ; 14 :1756 –1764 .8656243 \n5. Garmey EG Sartor O Halabi S \nSecond-line chemotherapy for advanced hormone-refractory prostate cancer . Clin Adv Hematol Oncol \n2008 ; 6 :118 –122 .127-32 .18347563 \n6. Vasaitis T Bruno R Njar V \nCYP17 inhibitors for prostate cancer therapy . J Steroid Biochem Mol Biol \n2011 ; 125 :23 –31 .21092758 \n7. Kantoff PW Higano CS Shore ND \nIMPACT Study Investigators . Sipuleucel-T immunotherapy for castration-resistant prostate cancer . N Engl J Med \n2010 ; 363 :411 –422 .doi: 10.1056/NEJMoa1001294 .20818862 \n8. Di Lorenzo G Buonerba C Kantoff PW \nImmunotherapy for the treatment of prostate cancer . Nat Rev Clin Oncol \n2011 ; 8 :551 –561 .21606971 \n9. de Bono JS Oudard S Ozguroglu M \nPrednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial . Lancet \n2010 ; 376 :1147 –1154 .20888992 \n10. Parker C Nilsson S Heinrich D \nAlpha emitter radium-223 and survival in metastatic prostate cancer . N Engl J Med \n2013 ; 369 :213 –223 .23863050 \n11. Scher HI Fizazi K Saad F \nAFFIRM Investigators . Increased survival with enzalutamide in prostate cancer after chemotherapy . N Engl J Med \n2012 ; 367 :1187 –1197 .22894553 \n12. Beer TM Armstrong AJ Rathkopf DE \nthe PREVAIL Investigators . Enzalutamide in Metastatic Prostate Cancer before Chemotherapy . N Engl J Med \n2014 ; 371 :24 –33 .\n13. Attard G Reid AH A’Hern R \nSelective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer . J Clin Oncol \n2009 ; 27 :3742 –3748 .19470933\n\n",
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{
"abstract": "A previously healthy 32-year-old woman developed cyclical mood swings after being prescribed cabergoline for a pituitary microprolactinoma. These mood swings persisted for over 2 years, at which point she developed an acute manic episode with psychotic features and was admitted to a psychiatry unit. Cabergoline was discontinued and replaced with aripiprazole 10 mg/day. Her manic episode quickly resolved, and she was discharged within 6 days of admission. The aripiprazole suppressed her prolactin levels for over 18 months of follow-up, even after the dose was lowered to 2 mg/day. There was no significant change in tumor size over 15 months, treatment was well tolerated and the woman remained psychiatrically stable.\n\n\nCONCLUSIONS\nDopamine agonists such as cabergoline, which are a standard treatment for microprolactinomas, can have serious adverse effects such as psychosis or valvular heart disease.Aripiprazole is a well-tolerated atypical antipsychotic that, unlike other antipsychotics, is a partial dopamine agonist capable of suppressing prolactin levels.Adjunctive, low-dose aripiprazole has been utilized to reverse risperidone-induced hyperprolactinemia.This case report demonstrates how aripiprazole monotherapy, in doses ranging from 2 to 10 mg/day, was effective in suppressing prolactin in a woman with a microprolactinoma who developed psychiatric side effects from cabergoline.",
"affiliations": "Alberta Hospital Edmonton, Addiction and Mental Health Program, Alberta Health Services , 17480 Fort Road, Post Office Box 307, Edmonton, Alberta , Canada T5J 2J7.",
"authors": "Burback|Lisa|L|",
"chemical_list": null,
"country": "England",
"delete": false,
"doi": "10.1530/EDM-15-0100",
"fulltext": "\n==== Front\nEndocrinol Diabetes Metab Case RepEndocrinol Diabetes Metab Case RepedmEDM Case ReportsEndocrinology, Diabetes & Metabolism Case Reports2052-0573Bioscientifica Ltd Bristol EDM15010010.1530/EDM-15-0100Novel TreatmentManagement of a microprolactinoma with aripiprazole in a woman with cabergoline-induced mania Aripiprazole for microprolactinomaBurback Lisa Alberta Hospital Edmonton, Addiction and Mental Health Program, Alberta Health Services, 17480 Fort Road, Post Office Box 307, Edmonton, Alberta, Canada T5J 2J7Correspondence should be addressed to L Burback Email: lisa.burback@albertahealthservices.ca6 10 2015 2015 2015 15010026 9 2015 6 10 2015 © 2015 The authors2015This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.Summary\nA previously healthy 32-year-old woman developed cyclical mood swings after being prescribed cabergoline for a pituitary microprolactinoma. These mood swings persisted for over 2 years, at which point she developed an acute manic episode with psychotic features and was admitted to a psychiatry unit. Cabergoline was discontinued and replaced with aripiprazole 10 mg/day. Her manic episode quickly resolved, and she was discharged within 6 days of admission. The aripiprazole suppressed her prolactin levels for over 18 months of follow-up, even after the dose was lowered to 2 mg/day. There was no significant change in tumor size over 15 months and treatment was well tolerated. However, after 9 months of taking 2 mg aripiprazole, she developed brief manic symptoms, and the dose was returned to 10 mg daily, with good effect.\n\nLearning points\n\nDopamine agonists such as cabergoline, which are a standard treatment for microprolactinomas, can have serious adverse effects such as psychosis or valvular heart disease.\n\nAripiprazole is a well-tolerated atypical antipsychotic that, unlike other antipsychotics, is a partial dopamine agonist capable of suppressing prolactin levels.\n\nAdjunctive, low-dose aripiprazole has been utilized to reverse risperidone-induced hyperprolactinemia.\n\nThis case report demonstrates how aripiprazole monotherapy, in doses ranging from 2 to 10 mg/day, was effective in suppressing prolactin in a woman with a microprolactinoma who developed psychiatric side effects from cabergoline.\n==== Body\nBackground\nMicroprolactinomas are often treated with dopamine agonists, which can have serious medical and psychiatric adverse effects, including psychosis, impulse control disorders, dyskinesia, pulmonary fibrosis and valvular heart disease. Aripiprazole, a well-tolerated partial dopamine agonist, is an atypical antipsychotic that can reduce prolactin levels. Even small doses have been used adjunctively to treat antipsychotic-induced hyperprolactinemia. However, aripiprazole has not been evaluated for the general treatment of hyperprolactinemia in patients with microprolactinomas. Nor has it been studied for the treatment of hyperprolactinemia in patients without psychiatric illness. This case report illustrates its successful use in suppressing prolactin in a patient with no previous psychiatric history who developed severe psychiatric side effects from cabergoline. Aripiprazole may be a novel and well tolerated therapy for the treatment of hyperprolactinemia due to microprolactinomas. Further research is warranted.\n\nCase presentation\nA 32-year-old, otherwise healthy woman with no previous psychiatric history developed mania after treatment with cabergoline for a microprolactinoma. She was a professional woman, and was married with two young children. She had a remote history of migraine, was a non-smoker and had no history of substance abuse. The family history was positive for depression, possible bipolar disorder and alcohol dependence.\n\nAt the time of her diagnosis, she reported a 1-year history of frontal headaches and galactorrhea, and 2 years of amenorrhea, starting after the birth of her second child. Her first prolactin level was 48.1 μg/l (reference <25 μg/l) at the time of referral to endocrinology, ∼7 months before her diagnosis. (See Table 1 for the results of endocrine laboratory investigations.) A pituitary MRI revealed an ‘8×4 mm heterogeneous lesion with a fluid level’ suggestive of a microprolactinoma with subacute hemorrhage (Figs 1 and 2).\n\nTable 1 Endocrine laboratory results\n\n\nTests\n\t\nTime of referral\n\na\n\n\t\nDiagnosis\n\nb\n\n\t\n2 months\n\nc\n\n\t\n3 months\n\nc\n\n\t\n6 months\n\nc\n\n\t\n1 year\n\nc\n\n\t\n18 months\n\nc\n\n\t\n27 months\n\nc\n\n(psychiatric admission)\n\t\n39 months\n\nc\n\n\t\nReference range and units\n\t\nProlactin\t48.1\t\n44.5\n\t\n26.3\n\t10.2\t8.3\t9.7\t6.5\t6.2\t10.5\t<25.0 μg/l\t\nBeta HCG\nd\n\n\t<1.0\t\n0.3\n\t\t\t\t\t\t<5\t\t<5.0 U/l\t\nFSH\ne\n\n\t7.3\t8.5\t3.8\t5.8\t7.2\t3.6\t5.2\t\t\tFollicular/luteal: <7.0 U/l\t\n\t\t\t\t\t\t\t\t\t\tMidcycle: 4.0–15.0 U/l\t\nLH\nf\n\n\t3.9\t3.3\t7.1\t8.5\t6.2\t7.9\t13.9\t\t\tFollicular/luteal: <15.0 U/l\t\n\t\t\t\t\t\t\t\t\t\tMidcycle: 30.0–100.0 U/l\t\nEstradiol\t143\t304\t384\t415\t239\t616\t1752\t\t\tFollicular: 70–680 pmol/l\t\n\t\t\t\t\t\t\t\t\t\tMidcycle: 550–1950 pmol/l\t\n\t\t\t\t\t\t\t\t\t\tLuteal: 200–780 pmol/l\t\nIGF1\ng\n\n\t\t306\t\t\t\t246\t\t\t\t115–430 μg/l\t\nMorning cortisol\t\t189 & 159\t\t\t\t331\t\t\t182\t120–620 nmol/l\t\nTSH\nh\n\n\t2.15\t1.47\t\t\t\t1.25\t\t2.10\t3.44\t0.2–4.0 mU/l\t\nFree T4\n\ni\n\n\t\t11.2\t\t\t\t12.7\t\t22.6\t\t9.0–23.0 pmol/l\t\nFree T3\n\nj\n\n\t\t4.9\t\t\t\t4.7\t\t6.0\t\t3.5–6.5 pmol/l\t\na Time of referral to endocrinologist, ∼7 months before diagnosis.\n\nb Time of diagnosis by endocrinologist.\n\nc Months after diagnosis.\n\nd Human chorionic gonadotropin.\n\ne Follicle-stimulating hormone.\n\nf Luteinizing hormone.\n\ng Insulin-like growth factor-1.\n\nh Thyroid-stimulating hormone.\n\ni Thyroxine.\n\nj Triiodothyronine.\n\nFigure 1 Sagital MRI image of pituitary microprolactinoma.\n\nFigure 2 Coronal T2 MRI image of patient's microprolactinoma.\n\nShe was prescribed cabergoline 0.25 mg orally per week. Two months later, her prolactin level was 26.3 μg/l (reference <25 μg/l) so the dose was increased to 0.25 mg twice weekly. At her 6-month appointment, she complained of ‘mood changes,’ especially depressed mood in the 2 weeks prior to her menses. Therefore, cabergoline was reduced to 0.25 mg weekly. Her prolactin levels remained suppressed, and repeat MRIs 6 and 18 months after diagnosis showed no change.\n\nHowever, she continued to have cyclical mood fluctuations. She would experience 2 weeks of normal mood, followed by a week of depressed mood with hypersomnia, anorexia and fatigue, and then a week of hypomanic symptoms. During her hypomanic phase, she reported a decreased need for sleep, increased energy, racing thoughts, distractibility, over-talkativeness and feeling like she was ‘strong and capable.’\n\nIn the week before hospitalization, she rapidly developed mania with pressured speech, agitation, labile affect, a decreased need for sleep and grandiose, religious and persecutory delusions. She described seeing Jesus in a white shadow and hearing ringing sounds that she believed were an announcement of His coming. She believed she could predict the future and talk to Jesus. She thought her husband was ‘the Antichrist’ who might harm their two children. She was admitted to psychiatry, and cabergoline was discontinued.\n\nInvestigation\nLaboratory investigations at the time of admission revealed a prolactin level of 6.2 μg/l (reference <25 μg/l). See Table 1 for results of other endocrine laboratory investigations. In addition, calcium was 2.44 mmol/l (reference 2.10–2.60 mmol/l), random glucose 5.4 mmol/l (reference 3.3–11.0 mmol/l), sodium 140 mmol/l (reference 133–146 mmol/l), potassium 4.0 mmol/l (reference 3.3–4.8 mmol/l), creatinine 68 μmol/l (reference 50–105umol/l), vitamin B12 640 pmol/l (reference >150 pmol/l), ferritin 66 μg/l (reference 12–300 μg/l) and folate was >40 nmol/l (reference <10 nmol/l for deficiency). C-reactive protein was undetectable, and a complete blood count, urinalysis and a urine drug screen were unremarkable.\n\nTreatment\nIn the emergency department, the patient briefly received oral clonazepam and olanzapine to reduce agitation. However, this was quickly switched to aripiprazole 10 mg orally per day as monotherapy. The rationale was that aripiprazole is a partial dopamine agonist that can suppress prolactin. Other antipsychotic treatments block dopamine receptors and can cause hyperprolactinemia to varying degrees. It was hoped that aripiprazole would treat her manic symptoms while also suppressing her prolactin levels, avoiding the need for a full dopamine agonist such as cabergoline. The manic symptoms quickly resolved, and she was discharged home 6 days after admission. Given the rapid improvement in her symptoms after cabergoline was discontinued, she was diagnosed with a cabergoline-induced bipolar disorder.\n\nOutcome and follow-up\nAfter discharge from hospital, she was instructed to keep a mood diary that included mood, neurovegetative function and her menstrual cycle. During the next few months, there was no evidence of premenstrual dysphoric disorder, clinical depression or hypomania. However, she did report generalized anxiety in reaction to her manic episode. She was treated with escitalopram 10 mg orally daily, with excellent effect.\n\nFollow-up investigations related to her microprolactinoma revealed stability. Prolactin was 11.4 μg/l (reference <25 μg/l) 2 months after discharge. A follow up MRI 3 months post discharge, which was 2.5 years after the microprolactinoma diagnosis, showed a slight reduction in tumor size to ‘6 mm in maximal dimension,’ which was ‘more heterogeneous and less conspicuous when compared to the previous study.’\n\nAfter a few months of escitalopram treatment, she felt emotionally blunted and fatigued. Therefore, escitalopram was weaned and discontinued, without sequelae. She continued aripiprazole 10 mg daily, which was eventually weaned to a final dose of 2 mg/day. Laboratory investigations at 1 year post-discharge revealed a prolactin level of 10.5 μg/l (reference <25 μg/l), with normal TSH and cortisol (Table 1). A follow-up MRI 15 months after her discharge reported a 6 mm pituitary lesion, which was considered essentially unchanged. She remained medically and psychiatrically stable, with no further signs or symptoms of hyperprolactinemia, for 18 months of follow-up after her hospitalization. Then suddenly after 9 months of taking aripiprazole 2 mg daily, she developed 4 days of manic symptoms, and her dose was increased to 10 mg per day, which restored euthymia.\n\nDiscussion\nMicroprolactinomas are often treated with ergot-derived dopamine agonists such as cabergoline or bromocriptine. These drugs activate D2 receptors in the pituitary gland, which inhibits adenyl cyclase activity and results in reduced gene transcription and prolactin secretion. However, dopamine agonists also affect other dopamine, serotonin and adrenergic receptors, which can lead to adverse effects. Stimulation of D1 receptors can cause postural hypotension or dyskinesia (1, 2). Mesocortical and mesolimbic D2 and D3 receptors are thought to be involved in mood and behavior, and dopamine agonists can trigger psychosis or mania (1, 2, 3). Impulse control disorders (ICDs), including problem gambling, hypersexuality, compulsive eating and compulsive shopping, may be mediated by D3 receptors in the mesolimbic system (2, 3). However, problem gambling has also been linked to D2 and D4 receptors (2). Noronha published a relevant review, which includes cases of ICDs that developed during treatment with dopamine agonists prescribed for prolactinomas (3). D4 stimulation has also been associated with ‘sudden onset sleep’ or ‘sleep attacks (2).’\n\nErgot-derived dopamine agonists also influence various serotonin receptor subtypes. Retroperitoneal and pulmonary fibrosis and valvular heart disease may be related to stimulatory effects on 5-HT1B and 5-HT2B receptors. Valvulopathy is thought to be partly due to 5-HT2B-induced mitogenesis in cardiac cells, leading to an overgrowth of tissue (2). Dopamine agonists may also cause hallucinations via stimulatory effects on 5HT2A and 5HT2C receptors. Kvernmo published a review of dopamine agonist receptor binding properties, which details the differences between them (2). In contrast aripiprazole blocks 5HT2A receptors.\n\nPatients who develop mania or psychosis as a consequence of dopamine agonists receive the diagnosis of a substance-induced mood disorder or substance-induced psychosis. However, it is possible that some of these patients have an underlying psychiatric illness that was triggered by the dopamine agonist. In this case, the patient did not have a psychiatric history prior to cabergoline therapy. However, there was a family history of bipolar disorder. Regardless, the manic episode resolved very quickly after initial cabergoline was discontinued, giving support to the diagnosis of cabergoline-induced bipolar disorder.\n\nHowever, the patient developed four days of manic symptoms nine months after her aripiprazole dose was reduced to 2 mg/day. There have been case reports of aripiprazole causing mania in susceptible people, possibly due to partial dopamine agonism in combination with 5-HT1A agonism and 5-HT2A antagonism (4). However this is rare, and her family history points to an underlying bipolar disorder that was triggered by cabergoline. The dose was increased to 10 mg/day, which is considered a mood-stabilizing dose.\n\nPsychosis usually requires antipsychotic medications, most of which raise prolactin levels and possibly promote tumor growth (1). It is theorized that antipsychotics raise prolactin by blocking dopamine, which ordinarily suppresses prolactin levels. A comprehensive review of the impact of various antipsychotics on prolactin can be found elsewhere (5). In contrast to most antipsychotics, aripiprazole is a partial dopamine agonist, especially at low doses. It has been shown to reduce prolactin levels in patients with and without hyperprolactinemia (5, 6).\n\nSeveral studies have examined the use of aripiprazole augmentation in patients with risperidone-induced hyperprolactinemia (7, 8, 9, 10). In one study, 16 female patients with schizophrenia and risperidone-induced hyperprolactinemia received aripiprazole, which was increased from 3 to 12 mg/day, in 3 mg increments over 2- to 4-week intervals. Aripiprazole reduced prolactin levels at all four doses trialed, with a plateau effect at 6 mg/day (7). This is in keeping with the theory that aripiprazole exhibits more dopamine agonism at lower doses than at higher doses.\n\nLi et al. conducted a meta-analysis of five randomized controlled trials investigating the safety and efficacy of aripiprazole for antipsychotic induced hyperprolactinemia. Trials utilized aripiprazole in doses ranging from 2 to 30 mg/day. Aripiprazole was superior to placebo with respect to prolactin normalization (risk difference 0.76; 95% CI 0.67–0.85; P<0.00001). A secondary analysis of patients receiving only 5 mg/day was similar (risk difference 0.74; 95% CI 0.62–0.87; P<0.00001). There was no overall difference in adverse events or discontinuation rates between aripiprazole and placebo groups. Sedation, insomnia and headache were more frequent for doses >15 mg/day. The authors suggested that low-dose aripiprazole 5 mg/day may be optimal (8).\n\nHowever, this is controversial. A randomized, double blind trial of 119 schizophrenia patients with risperidone-induced hyperprolactinemia investigated the dose response relationship between aripiprazole and prolactin levels. Risperidone-treated patients were randomized to either placebo or aripiprazole 5, 10 or 20 mg/day for 8 weeks. All three aripiprazole doses reduced prolactin within 2 weeks. In contrast to the previous studies, the effect on prolactin was greater in the 10 mg- and 20 mg/day groups, relative to the 5 mg/day group (9). In a case series, Lozano reported that an average dose of 17 mg/day was effective in reducing risperidone-induced hyperprolactinemia (10).\n\nReports also raise the possibility of prolactin deficiency in aripiprazole-treated patients (10). Lozano suggested, based on a study of 161 outpatients taking various atypical antipsychotics with or without aripiprazole, that the odds of a prolactin level of <3 μg/l was 0.81 in patients receiving aripiprazole (n=20) and 0.029 for those without aripiprazole (n=141). Authors concluded that patients receiving at least 17 mg daily had a high likelihood of prolactin deficiency (odds ratio, 28; 95% CI, 7.42–105.78; P<0.001), which could cause infertility, menstrual disorders, decreased testosterone and oligospermia (10). Interestingly, there are also reports of aripiprazole causing hyperprolactinemia, especially at higher doses (1, 5, 11).\n\nAripiprazole has been used to treat psychosis in patients with established primary psychotic illnesses and comorbid microprolactinomas, often in combination with a dopamine agonist (1, 6). Chen et al. also reported on a woman with established bipolar disorder and comorbid microprolactinoma who developed mania and was treated with aripiprazole monotherapy. In her case, when the dose was lowered from 30 to 5 mg/day, prolactin levels fell more dramatically and the hyperprolactinemia symptoms abated (12). This supports the idea that lower doses are more prodopaminergic.\n\nSome authors have suggested that aripiprazole may be the treatment of choice for patients with comorbid microprolactinoma and psychosis (5, 6). However, adding or switching to aripiprazole may cause worsening of psychotic symptoms, agitation or activation in patients with established schizophrenia or schizoaffective disorder. In a systematic review of reported cases, a higher risk was associated with severe or treatment-resistant psychotic illness, higher doses of antipsychotics, use of conventional neuroleptics, and longer illness course. This may be due to aripiprazole's weaker antipsychotic effect, partial dopamine agonism, or the higher affinity for the D2 receptor. Alternatively, it could be related to dopamine upregulation in the context of long-term, high-potency neuroleptic use in severely ill patients (13).\n\nTo this author's knowledge, this is the first reported case of aripiprazole monotherapy for the treatment of microprolactinoma in a patient without a prior psychiatric history. In her case, cabergoline caused mood cycling and eventually a severe manic episode. Aripiprazole, in doses ranging from 2 to 10 mg daily, successfully suppressed her prolactin levels over 18 months, and tumor size remained stable over 15 months of follow-up. Given the serious side effects of dopamine agonists, the relative safety of low-dose aripiprazole, and the short list of treatment options, it should be investigated as a general treatment option for hyperprolactinemia due to microprolactinoma.\n\nPatient consent\nConsent was obtained from the patient described.\n\nDeclaration of interest\nThe author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.\n\nFunding\nThis research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.\n==== Refs\nReferences\n1 \n\nAli \nS \n, \nKlahr \nK \n & \nFreudenreich \nO \n. 2015 \nManagement of psychosis associated with a prolactinoma: case and review of the literature . Psychosomatics \n51 \n2010 \n370 –376 . 10.1016/S0033-3182(10)70718-0 \n20833935 \n2 \n\nKvernmo \nT \n, \nHouben \nJ \n & \nSylte \nI \n. 2008 \nReceptor-binding and pharmacokinetic properties of dopaminergic agonists . Current Topics in Medicinal Chemistry \n8 \n1049 –1067 . 10.2174/156802608785161457 \n18691132 \n3 \n\nNoronha \nS \n, \nStokes \nV \n, \nKaravitaki \nN \n & \nGrossman \nA \n. 2010 \nTreating prolactinomas with dopamine agonists: always worth the gamble? . Endocrine \nIn press \n10.1007/s12020-015-0727-2 \n\n4 \n\nDonohue \nA \n\nFirst Manic Episode in a 55-Year-Old Man After Initiation of Aripiprazole . Psychiatry \n7 \n37 –39 .\n5 \n\nPeuskens \nJ \n, \nPani \nL \n, \nDetraux \nJ \n & \nDe Hert \nM \n. 2014 \nThe effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review . CNS Drugs \n28 \n421 –453 . 10.1007/s40263-014-0157-3 \n24677189 \n6 \n\nHoffer \nZS \n, \nRoth \nRL \n & \nMathews \nM \n. 2009 \nEvidence for the partial dopamine-receptor agonist aripiprazole as a first-line treatment of psychosis in patients with iatrogenic or tumorigenic hyperprolactinemia . Psychosomatics \n50 \n317 –324 . 10.1176/appi.psy.50.4.317 \n19687170 \n7 \n\nYasui-Furukori \nN \n, \nFurukori \nH \n, \nSugawara \nN \n, \nFujii \nA \n & \nKaneko \nS \n. 2010 \nDose-dependent effects of adjunctive treatment with aripiprazole on hyperprolactinemia induced by risperidone in female patients with schizophrenia . Journal of Clinical Psychopharmacology \n30 \n596 –599 . 10.1097/JCP.0b013e3181ee832d \n20814333 \n8 \n\nLi \nX \n, \nTang \nY \n & \nWang \nC \n. 2013 \nAdjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia: meta-analysis of randomized controlled trials . PLoS ONE \n8 \ne70179 \n10.1371/journal.pone.0070179 \n23936389 \n9 \n\nChen \nJX \n, \nSu \nYA \n, \nBian \nQT \n, \nWei \nLH \n, \nZhang \nRZ \n, \nLiu \nYH \n, \nCorrell \nC \n, \nSoares \nJC \n, \nYang \nFD \n, \nWang \nSL \n\n\n2015 \nAdjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: a randomized, double-blind, placebo-controlled, dose-response study . Psychoneuroendocrinology \n58 \n130 –140 . 10.1016/j.psyneuen.2015.04.011 \n25981348 \n10 \n\nLozano \nR \n, \nMarin \nR \n & \nSantacruz \nMJ \n. 2014 \nProlactin deficiency by aripiprazole . Journal of Clinical Psychopharmacology \n34 \n539 –540 . 10.1097/JCP.0000000000000151 \n24911440 \n11 \n\nSaraf \nG \n, \nBehere \nRV \n, \nVenkatasubramanian \nG \n, \nRao \nNP \n, \nVarambally \nS \n & \nGangadhar \nBN \n. 2014 \nHyperprolactinemia with aripiprazole: understanding the paradox . American Journal of Therapeutics \n21 \ne80 –e81 . 10.1097/MJT.0b013e3182456de7 \n22357167 \n12 \n\nChen \nS \n & \nHsiao \nY \n. 2010 \nTreatment with aripiprazole for hyperprolactinemia induced by pituitary microadenoma in a bipolar I disorder patient . Journal of Clinical Psychopharmacology \n30 \n78 –80 . 10.1097/JCP.0b013e3181ca3c85 \n20075655 \n13 \n\nTakeuchi \nH \n & \nRemington \nG \n. 2013 \nA systematic review of reported cases involving psychotic symptoms worsened by aripiprazole in schizophrenia or schizoaffective disorder . Psychopharmacology \n228 \n175 –185 . 10.1007/s00213-013-3154-1 \n23736279\n\n",
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"title": "Management of a microprolactinoma with aripiprazole in a woman with cabergoline-induced mania.",
"title_normalized": "management of a microprolactinoma with aripiprazole in a woman with cabergoline induced mania"
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"abstract": "OBJECTIVE\nThe aim of this study was to evaluate the safety and efficacy of osimertinib for elderly patients, since the data remain limited.\n\n\nMETHODS\nA total of 77 patients with advanced non-small cell lung cancer (NSCLC) harboring the epidermal growth factor receptor (EGFR) T790M mutation and treated with osimertinib were reviewed. Efficacy and safety indicators, such as EGFR-tyrosine kinase inhibitor (TKI)-related adverse events (AEs) and osimertinib-associated hematotoxicity, were evaluated in elderly patients (elderly group, EG; age, ≥75 years) by comparing them with younger patients (non-EG; aged <75 years). The frequency of AEs associated with osimertinib was compared with the initial EGFR-TKI treatment before osimertinib administration in the same patient cohort.\n\n\nRESULTS\nOf the total 77 patients, 18 (23%) were assigned to the EG, whereas 59 (77%) were assigned to the non-EG. There were no significant differences in overall response rate and progression-free survival between the two groups. Regarding the safety of osimertinib, the EG had significantly more grade ≥2 paronychia than the non-EG (16.6% vs. 1.6%, p=0.04). Additionally, the maximum grade of EGFR-TKI-related AEs associated with osimertinib in the EG was significantly lower than that of the initial EGFR-TKI treatment (p=0.03).\n\n\nCONCLUSIONS\nOsimertinib is a safe and effective treatment option for elderly patients with advanced NSCLC who harbor the EGFR mutation.",
"affiliations": "Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.;Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.;Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan t.yoshida@aichi-cc.jp.;Department of Nursing, Aichi Cancer Center Hospital, Nagoya, Japan.;Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.;Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.;Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.;Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.;Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.;Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.;Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.;Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.",
"authors": "Furuta|Hiromi|H|;Uemura|Takehiro|T|;Yoshida|Tatsuya|T|;Kobara|Makiko|M|;Yamaguchi|Teppei|T|;Watanabe|Naohiro|N|;Shimizu|Junichi|J|;Horio|Yoshitsugu|Y|;Kuroda|Hiroaki|H|;Sakao|Yukinori|Y|;Yatabe|Yasushi|Y|;Hida|Toyoaki|T|",
"chemical_list": "D000178:Acrylamides; D000814:Aniline Compounds; D010879:Piperazines; D047428:Protein Kinase Inhibitors; C000596361:osimertinib; C512478:EGFR protein, human; D066246:ErbB Receptors",
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"issue": "38(9)",
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"keywords": "EGFR-TKIs-related adverse events; NSCLC; Osimertinib; hematotoxicity",
"medline_ta": "Anticancer Res",
"mesh_terms": "D000178:Acrylamides; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000814:Aniline Compounds; D002289:Carcinoma, Non-Small-Cell Lung; D018572:Disease-Free Survival; D066246:ErbB Receptors; D005260:Female; D006801:Humans; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D012189:Retrospective Studies; D016896:Treatment Outcome",
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"title": "Efficacy and Safety Data of Osimertinib in Elderly Patients with NSCLC Who Harbor the EGFR T790M Mutation After Failure of Initial EGFR-TKI Treatment.",
"title_normalized": "efficacy and safety data of osimertinib in elderly patients with nsclc who harbor the egfr t790m mutation after failure of initial egfr tki treatment"
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"literaturereference": "YOSHIDA T, FURUTA H, UEMURA T, KOBARA M, YAMAGUCHI T, WATANABE N, ET AL. EFFICACY AND SAFETY DATA OF OSIMERTINIB IN ELDERLY PATIENTS WITH NSCLC WHO HARBOR THE EGFR T790M MUTATION AFTER FAILURE OF INITIAL EGFR?TKI TREATMENT. ANTICANCER RESEARCH. 2018?38:9:5231?5237.",
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"abstract": "Immune reconstitution inflammatory syndrome associated with dermatophytoses (tinea-IRIS) may cause considerable morbidity. Yet, it has been scarcely reported and is rarely considered in the differential diagnosis of HIV associated cutaneous lesions in Africa. If identified, it responds well to antifungals combined with steroids. We present two cases of suspected tinea-immune reconstitution inflammatory syndrome from a large HIV clinic in rural Tanzania.\n\n\n\nA first case was a 33 years-old female newly diagnosed HIV patient with CD4 count of 4 cells/μL (0 %), normal complete blood count, liver and renal function tests was started on co-formulated tenofovir/emtricitabine/efavirenz and prophylactic cotrimoxazole. Two weeks later she presented with exaggerated inflammatory hyperpigmented skin plaques with central desquamation, active borders and scratch lesions on the face, trunk and lower limbs. Tinea-IRIS was suspected and fluconazole (150 mg daily) and prednisolone (1 mg/Kg/day tapered down after 1 week) were given. Her symptoms subsided completely after 8 weeks of treatment, and her next CD4 counts had increased to 134 cells/μL (11 %). The second case was a 35 years-old female newly diagnosed with HIV. She had 1 CD4 cell/μL (0 %), haemoglobin 9.8 g/dl, and normal renal and liver function tests. Esophageal candidiasis and normocytic-normochromic anaemia were diagnosed. She received fluconazole, prophylactic cotrimoxazole and tenofovir/emtricitabine/efavirenz. Seven weeks later she presented with inflammatory skin plaques with elevated margins and central hyperpigmentation on the trunk, face and limbs in the frame of a good general recovery and increased CD4 counts (188 cells/μL, 6 %). Tinea-IRIS was suspected and treated with griseofulvin 500 mg daily and prednisolone 1 mg/Kg tapered down after 1 week, with total resolution of symptoms in 2 weeks.\n\n\n\nThe two cases had advanced immunosuppression and developed de-novo exaggerated manifestation of inflammatory lesions compatible with tinea corporis and tinea facies in temporal association with antiretroviral treatment initiation and good immunological response. This is compatible with unmasking tinea-IRIS, and reminds African clinicians about the importance of considering this entity in the differential diagnosis of patients with skin lesions developing after antiretroviral treatment initiation.",
"affiliations": "Chronic Diseases Clinic of Ifakara, Ifakara Health Institute, P. O Box 53, Ifakara, Tanzania. hmapesi@ihi.or.tz.;University Hospital Son Espases, Palma de Mallorca, Spain.;University of Basel, Basel, Switzerland.;University of Basel, Basel, Switzerland.;Chronic Diseases Clinic of Ifakara, Ifakara Health Institute, P. O Box 53, Ifakara, Tanzania. emili.letang@unibas.ch.",
"authors": "Mapesi|Herry|H|0000-0001-7753-464X;Ramírez|Adrià|A|;Tanner|Marcel|M|;Hatz|Christoph|C|;Letang|Emilio|E|;|||",
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"fulltext": "\n==== Front\nBMC Infect DisBMC Infect. DisBMC Infectious Diseases1471-2334BioMed Central London 182410.1186/s12879-016-1824-4Case ReportImmune reconstitution inflammatory syndrome associated with dermatophytoses in two HIV-1 positive patients in rural Tanzania: a case report http://orcid.org/0000-0001-7753-464XMapesi Herry +255717340426hmapesi@ihi.or.tz 123Ramírez Adrià adriatix@gmail.com 4Tanner Marcel marcel.tanner@unibas.ch 23Hatz Christoph christoph.hatz@unibas.ch 23Letang Emilio +255 787 736 169emili.letang@unibas.ch 1235the KIULARCO Study GroupAsantiel Aschola Battegay Manuel Chale Adolphina Faini Diana Felger Ingrid Francis Gideon Furrer Hansjakob Gamell Anna Glass Tracy Hatz Christoph Hwaya Specioza Kasuga Bryson Kimera Namvua Kisunga Yassin Klimkait Thomas Letang Emilio Luhombero Antonia Luwanda Lameck B. Mapesi Herry Mbwile Leticia Mkulila Mengi Mkumbo Julius Mkusa Margareth Mnzava Dorcus K. Mossad Germana Mpundunga Dolores Mtandanguo Athumani Mwamelo Kim D. Myeya Selerine Nahota Sanula Ndaki Regina Ngulukila Agatha Ntamatungiro Alex John Samson Leila Sikalengo George Tanner Marcel Vanobberghen Fiona Kalinjuma Aneth V. Weisser Maja 1 Chronic Diseases Clinic of Ifakara, Ifakara Health Institute, P. O Box 53, Ifakara, Tanzania 2 University of Basel, Basel, Switzerland 3 Chronic Diseases Clinic of Ifakara, Swiss Tropical & Public Health Institute (Swiss TPH), Ifakara Health Institute (IHI), Ifakara branch, P.O. Box 53, Ifakara, Tanzania 4 University Hospital Son Espases, Palma de Mallorca, Spain 5 ISGLOBAL, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain 20 9 2016 20 9 2016 2016 16 49513 2 2016 9 9 2016 © The Author(s). 2016\nOpen AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background\nImmune reconstitution inflammatory syndrome associated with dermatophytoses (tinea-IRIS) may cause considerable morbidity. Yet, it has been scarcely reported and is rarely considered in the differential diagnosis of HIV associated cutaneous lesions in Africa. If identified, it responds well to antifungals combined with steroids. We present two cases of suspected tinea-immune reconstitution inflammatory syndrome from a large HIV clinic in rural Tanzania.\n\nCases presentation\nA first case was a 33 years-old female newly diagnosed HIV patient with CD4 count of 4 cells/μL (0 %), normal complete blood count, liver and renal function tests was started on co-formulated tenofovir/emtricitabine/efavirenz and prophylactic cotrimoxazole. Two weeks later she presented with exaggerated inflammatory hyperpigmented skin plaques with central desquamation, active borders and scratch lesions on the face, trunk and lower limbs. Tinea-IRIS was suspected and fluconazole (150 mg daily) and prednisolone (1 mg/Kg/day tapered down after 1 week) were given. Her symptoms subsided completely after 8 weeks of treatment, and her next CD4 counts had increased to 134 cells/μL (11 %). The second case was a 35 years-old female newly diagnosed with HIV. She had 1 CD4 cell/μL (0 %), haemoglobin 9.8 g/dl, and normal renal and liver function tests. Esophageal candidiasis and normocytic-normochromic anaemia were diagnosed. She received fluconazole, prophylactic cotrimoxazole and tenofovir/emtricitabine/efavirenz. Seven weeks later she presented with inflammatory skin plaques with elevated margins and central hyperpigmentation on the trunk, face and limbs in the frame of a good general recovery and increased CD4 counts (188 cells/μL, 6 %). Tinea-IRIS was suspected and treated with griseofulvin 500 mg daily and prednisolone 1 mg/Kg tapered down after 1 week, with total resolution of symptoms in 2 weeks.\n\nConclusion\nThe two cases had advanced immunosuppression and developed de-novo exaggerated manifestation of inflammatory lesions compatible with tinea corporis and tinea facies in temporal association with antiretroviral treatment initiation and good immunological response. This is compatible with unmasking tinea-IRIS, and reminds African clinicians about the importance of considering this entity in the differential diagnosis of patients with skin lesions developing after antiretroviral treatment initiation.\n\nKeywords\nHIVImmune reconstitution inflammatory syndromeCase reportissue-copyright-statement© The Author(s) 2016\n==== Body\nBackground\nImmune reconstitution inflammatory syndrome asociated with dermatophytoses (tinea-IRIS) may cause considerable morbidity given the high prevalence of fungal skin infections, especially in HIV/AIDS patients with late presentation. Despite having been reported to be associated with 52–78 % of cutaneous associated IRIS [1], it has been scarcely reported and is rarely considered in the differential diagnosis of HIV-associated cutaneous lesions in Sub-Saharan Africa (SSA). If identified, it responds well to antifungals combined with steroids [2]. We present two photographically documented cases of suspected tinea-IRIS in HIV-individuals in rural Tanzania. The two patients developed the lesions two and 7 weeks respectively after starting antiretroviral treatment (ART). They were treated with fluconazole and griseofulvin respectively combined with oral prednisolone. The symptoms resolved after 8 and 2 weeks in both patients respectively.\n\nCase I presentation\nA 33 years-old Tanzanian woman presented to the HIV clinic suffering from skin itching for 3 months prior to the visit. She tested positive for HIV and she was enrolled in care. At the baseline physical examination she had pruritic papular eruptions (PPE) involving both upper and lower limbs. Other systems and the vital signs were unremarkable.\n\nInvestigations\nHer baseline investigations showed CD4 count of 4 cells/μL (0 %), with normal complete blood count (CBC), liver function test (LFT) and estimated glomerular filtration rate (eGFR). She had negative Cryptococcal plasma antigen (CRAG) and Venereal Disease Research Laboratory (VDRL) test. She also had negative Hepatitis B surface antigen (HBsAg) and negative screening test for cervical cancer screening.\n\nTreatment\nShe was started ART on day four after enrollment into care in our HIV-Clinic on co-formulated tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg/efavirenz 600 mg (TDF/FTC/EFV) with prophylactic cotrimoxazole, 960 mg once daily. She was also prescribed symptomatic treatment for PPE, receiving cetirizine 5 mg once daily for 1 week.\n\nOutcome and follow-Up\nTwo weeks after initiating ART she returned to the HIV-clinic with an exaggerated inflammatory manifestation, including hyperpigmented skin plaques with central desquamation and active borders on the face, trunk and lower limbs. The lesions were itching and surrounded by scratchy lesions (Fig. 1). Tinea-IRIS was suspected and fluconazole (150 mg daily), prednisolone (1 mg/kg for 1 weeks tapered down during the second week) and cetirizine 5 mg once daily for 1 week were given. Her symptoms subsided after 8 weeks of antifungal treatment (Fig. 1). Her CD4 count after 2 months on ART increased to 134 cells/μL (11 %) (Table 1).Fig. 1 Pictures of the case I before and after treatment. Picture a shows exaggerated inflammatory manifestation, including hyperpigmented skin plaques with central desquamation and active borders. The lesions were itching in nature surrounded by scratchy lesions on the face, trunk and lower limbs. Picture b shows improvement after 8 weeks treatment with fluconazole, prednisolone and cetirizine\n\nTable 1 Summary of clinical presentation, treatment and outcome of both patients\n\nPatient\tInitial Diagnosis\tBaseline CD4 Counts (cells/μL)\tInitial Treatment\tTime to IRIS (weeks)\tClinical Presentation\tEvent CD4 counts (cells/μL)\tIRIS Treatment\tOutcome\tTime to Response (weeks)\t\nCASE I\tHIV WHO stage II\nPPE\t4\tTDF/FTC/EFV Cotrimoxazole prophylaxis Cetirizine\t2\tInflammatory lesions on upper limbs, face and trunk\t134a\n\tFluconazole Prednisolone Cetrizine\tComplete response\t8\t\nCASE II\tHIV WHO Stage IV\nCAP\nEsophageal candidiasis\t1\tTDF/FTC/EFV Amoxicillin Fluconazole Cotrimoxazole prophylaxis\t7\tInflammatory lesions on upper limbs, face and trunk\t188\tGriseofulvin, Prednisolone Cetrizine\tComplete response\t2\t\n\nCAP community acquired pneumonia, IRIS, immune reconstitution inflammatory syndrome, PPE papular pruritic eruption, TDF/FTC/EFV tenofovirdisoproxilfumarate / emtricitabine / efavirenz\n\n\naCD4 measured 6 weeks after the event\n\n\n\nCase II presentation\nA 35 years-old newly HIV-diagnosed female presented to the HIV clinic complaining of generalized body itching associated with intermittent papular rashes involving both lower limbs, which had started 1 month prior to the visit. She also had difficult in swallowing and dry cough for 1 week. She reported experienced night sweats, weight loss and chest pain for the last months. On physical examination she had oral thrush, PPE involving both lower limbs and bronchial breath sounds on auscultation. Other systems explorations were normal.\n\nInvestigations\nHer baseline CD4 count was of 1 cell/μL (0 %). Her CBC showed normocytic normochromic anemia (haemoglobin 9.8 g/dl, MCV 86 femtoliter, MCH 28 picograms/cell) with an otherwise unremarkable CBC and normal LFT and eGFR. She had negative CRAG, VDRL, HBsAg and cervical cancer screening. Her chest radiograph showed alveolo-interstitial opacities involving the left lower lobe and a diagnosis of community acquired pneumonia (CAP) was reached. Sputum smears were negative for Acid Fast Bacilli and Xpert MTB/RIF on sputum was negative as well.\n\nTreatment\nShe received fluconazole 150 mg once daily for 21 days for oropharyngeal and suspected esophageal candidiasis, amoxicillin 1 g three times daily during week one for CAP, prophylaxis with cotrimoxazole 960 mg once daily and 400 mg of ferric ammonium citrate / 3 mg of folic acid daily for 1 month for anemia. She started ART 3 days later with TDF/FTC/EFV.\n\nOutcome and follow-up\nSeven weeks after ART initiation she started to experience skin rashes in both upper limbs, which rapidly involved the neck, trunk and the face (Fig. 2). The lesions clinically progressed to inflammatory skin plaques with elevated margins and central hyperpigmentation on the trunk, face and limbs in the frame of a good general recovery and increased CD4 count and percentage (188 cells/μL - 6 %). Tinea-IRIS was suspected and treated with griseofulvin 500 mg once daily with prednisolone 1 mg/kg for 1 week tapered down during the second week and cetirizine 5 mg once daily for 1 week. At the end of the second week of antifungal and steroid treatment, there was total resolution of the lesions (Fig. 2) (Table 1).Fig. 2 Pictures of the case II before and after treatment. Picture a shows inflammatory skin plaques with elevated margins and central hyperpigmentation on the trunk, face and limbs 7 weeks after ART initiation. Picture b shows improvement after 2 weeks treatment with griseofulvin, prednisolone and cetirizine\n\n\n\nDiscussion\nThe occurrence of PPE in adult African patients has been observed as highly predictive of HIV infection [3] and has been correlated with low CD4+ cell count (<200 cells/l). Differential diagnosis of PPE includes tinea, a fungal infection which involves the keratinized epidermis, nails, and hair caused by common opportunistic pathogens associated with HIV.\n\nNo comprehensive studies on dermatophyte infections have been conducted on HIV-individuals in low-income countries (LIC), where more than 90 % of the global HIV-infected population resides. Prevalence of tinea infestation among people living with HIV (PLHIV) is likely to be high and to occur in all HIV-infected patients at one point of their lives [4]. Three types of dermatophytes account for the majority of infections: Epidermophyton, Trichophyton, and Microsporum. The most common dermatophytes affecting PLHIV includes Trichophyton rubrum, which is known to be the most prevalent, followed by Trichophyton mentagrophytes, Trichophyton tonsurans, Candida albicans, and Epidermophyton floccosum [5]. The infection in PLHIV has been associated with the degree of immunosuppression, being more frequent with low CD4 count like in our two patients. The clinical presentation range from being asymptomatic to disseminated disease affecting all four extremities.\n\nTinea, also known as ring worm, is the term representing a variety of skin mycoses and its diagnosis could be confirmed by potassium hydroxide (KOH) examination of scrapings from material taken from the active border of the lesions. This is a very simple laboratory examination which should be made widely available in resource limited settings. A fungal culture on Sabouraud’s medium can also be used to confirm the diagnosis, although it is slower. Although the etiological diagnosis relies on microbiological techniques, in rural settings of LIC diagnosis is mostly based on clinical judgment.\n\nThe availability of ART in SSA has significantly improved the quality of life for PLHIV. However, despite the fact that ART usually causes viral load suppression and restores patient’s immunity, in some patients the restored immune response is immunopathological and causes the immune reconstitution inflammatory syndrome (IRIS) [6]. IRIS occurs when immunity is restored especially in the first months of effective ART. In a prospective cohort study conducted among HIV patients in South Africa, 10.4 % of patients initiating ART developed IRIS [7]. Mucocutaneous manifestations of IRIS have been poorly documented. A study conducted in Mozambique showed 26.5 % of patients developed IRIS after a median time of 62 days from ART initiation with 53 % of them having mucocutaneous manifestations. Tinea accounted for 47 % of all mucocutaneous IRIS cases [8]. In another study conducted in Brazil, 10–25 % of unselected patients starting ART developed IRIS with 52–78 % of these patients presenting with cutaneous features [1, 9]. Tinea-IRIS lesions can be visible on patient’s skin, and despite not being associated with mortality can cause a decrease in the quality of life [10]. Moreover, it requires a high index of suspicion to be treated.\n\nIn this report, we present two HIV infected patients whom we suspected to develop tinea-IRIS after starting ART. The first case developed tinea-IRIS 2 weeks after starting ART and was successfully treated with fluconazole and prednisolone. The second case presented with suspected tinea-IRIS 7 weeks after starting ART. With the evidence of increase in resistance to fluconazole after a prolonged exposure and the fact that she was treated for esophageal candidiasis with fluconazole for 3 weeks, she was treated with oral griseofulvin and prednisolone and her symptoms subsided completely after 2 weeks of treatment. Although highly suggestive of IRIS due to the temporal association with ART initiation and the concomitant immune reconstitution, de novo dermatophyte infection cannot be ruled out in this case [11]. We treated both patients with two locally available antifungals which have shown to be effective against tinea infection and can be combined with steroids [2].\n\nConclusion\nTo our knowledge these are the first two cases with tinea-IRIS to be reported in Tanzania. The two cases presented had advanced immunosuppression and developed de-novo exaggerated inflammatory lesions compatible with tinea corporis and facies in temporal association with ART initiation and good immunological response. This is compatible with unmasking tinea-IRIS, and reminds African clinicians about the importance of considering this entity in the differential diagnosis of patients with skin lesions developing after ART initiation, as fungal skin infestation is likely to be widely prevalent. Close follow-up is warranted in late presenters to timely identify and treat IRIS. In LIC like Tanzania where there are 4,993 estimated cases of serious fungal infections per 100,000 person/year, clinical judgment, appropriate microbiological tests and laboratory trained technicians are vital [12]. Additionally, since treatment with readily available in LIC antifungals such as fluconazole and griseofulvin combined with predinisolone have been proved to be effective, early diagnosis and treatment is paramount to reduce the associated morbidity, as shown by these two cases.\n\nAbbreviations\nCAPCommunity acquired pneumonia\n\nCBCCompete blood count\n\nCRAGCryptococcal plasma antigen\n\neGFREstimated glomerular filtration rate\n\nHBsAgHepatitis B surface antigen\n\nHIVHuman immunodeficiency virus\n\nIRISImmune reconstitution inflammatory syndrome\n\nKOHPotassium hydroxide\n\nLFTLiver function test\n\nLICLow-income countries\n\nMCHMean corpuscular hemoglobin\n\nMCVMean corpuscular volume\n\nPLHIVPeople living with HIV\n\nPPEPruritic papular eruptions\n\nSSASub-Saharan Africa\n\nTDF/FTC/EFVtenofovir/emtricitabine/efavirenz\n\nTinea-IRISTinea-immune reconstitution inflammatory syndrome\n\nVDRLVenereal disease research laboratory\n\nAcknowledgements\nWe would like to acknowledge the contribution made by Nora Tan from Stanford University in reviewing the manuscript. We would like to acknowledge the contributions from all members of Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) study group. The KIULARCO and the Chronic Diseases Clinic of Ifakara (CDCI) receive financial support from the Government of the Canton of Basel, Switzerland, the Swiss Tropical and Public Health Institute, the Ifakara Health Institute, the Government of Tanzania, and USAID through TUNAJALI-Deloitte. The members of the KIULARCO Study Group are: Aschola Asantiel, Manuel Battegay, AdolphinaChale, Diana Faini, Ingrid Felger, Gideon Francis, Hansjakob Furrer, Anna Gamell, Tracy Glass, Christoph Hatz, Specioza Hwaya, Bryson Kasuga, Namvua Kimera, Yassin Kisunga, Thomas Klimkait, Emilio Letang, Antonia Luhombero, Lameck B Luwanda, Herry Mapesi, Leticia Mbwile, Mengi Mkulila, Julius Mkumbo, Margareth Mkusa, Dorcus K Mnzava, Germana Mossad, Dolores Mpundunga, Athumani Mtandanguo, Kim D Mwamelo, Selerine Myeya, Sanula Nahota, Regina Ndaki, Agatha Ngulukila, Alex John Ntamatungiro, Leila Samson, George Sikalengo, Marcel Tanner, Fiona Vanobberghen, Aneth V Kalinjuma and Maja Weisser.\n\nFunding\nNo additional funds was required for this case report.\n\nAvailability of data and materials\nData can be found in the electronic databases of KIULARCO.\n\nAuthors contribution\nHM and EL were involved in the clinical management of both patients. HM, AR and EL wrote the manuscript. MT, CH, and EL contributed to draft the manuscript. All authors read and approved the final version of the manuscript.\n\nAuthors’ information\nHM is a medical doctor working at the chronic diseases clinic of Ifakara (CDCI) and currently a pursuing a Masters of Epidemiology at Swiss Tropical and Public Health Institute and University of Basel, Basel, Switzerland. AR is a resident of internal medicine at University Hospital Son Espases, Palma de Mallorca, Spain. MT is the former director of the Swiss Tropical and Public Health Institute of Basel, Switzerland. CH is the Chief medical officer and head of the Medical Services and Diagnostic at the Swiss Tropical and Public Health Institute of Basel, Switzerland and Head of Social-and Preventive Medicine Institute at the University Zürich. EL is an internal medicine specialist and the Head of the Chronic Diseases Clinic of Ifakara.\n\nCompeting interest\nThe authors declare that they have no competing interests.\n\nEthics and consent to participate\nBoth patients had given their written informed consent to participate in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). The KIULARCO study received ethical approval from the Ifakara Health Institute Institutional Review Board, the National Institute for Medical Research of Tanzania, the Tanzanian Commission of Science and Technology, and the Ethics Committee of the University and State of Basel.\n\nConsent for publication\nWritten informed consent was obtained from both patients for publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor of this journal.\n==== Refs\nReferences\n1. Osei-Sekyere B Karstaedt AS Immune reconstitution inflammatory syndrome involving the skin Clin Exp Dermatol 2010 35 5 477 81 10.1111/j.1365-2230.2009.03620.x 19874370 \n2. Ansari S, Hedayati MT, Zomorodian K, Pakshir K, Badali H, Rafiei A, et al. Molecular characterization and in vitro antifungal susceptibility of 316 clinical isolates of dermatophytes in Iran. Mycopathologia. 2015;14.\n3. Colebunders R Mann JM Francis H Bila K Izaley L Kakonde N Generalized papular pruritic eruption in African patients with human immunodeficiency virus infection AIDS Lond Engl 1987 1 2 117 21 \n4. Coldiron BM Bergstresser PR Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus Arch Dermatol 1989 125 3 357 61 10.1001/archderm.1989.01670150047004 2522293 \n5. Rodwell GEJ Bayles CL Towersey L Aly R The prevalence of dermatophyte infection in patients infected with human immunodeficiency virus Int J Dermatol 2008 47 4 339 43 10.1111/j.1365-4632.2008.03416.x 18377595 \n6. French MA Price P Stone SF Immune restoration disease after antiretroviral therapy AIDS Lond Engl 2004 18 12 1615 27 10.1097/01.aids.0000131375.21070.06 \n7. Murdoch DM Venter WDF Feldman C Van Rie A Incidence and risk factors for the immune reconstitution inflammatory syndrome in HIV patients in South Africa: a prospective study AIDS Lond Engl 2008 22 5 601 10 10.1097/QAD.0b013e3282f4a607 \n8. Letang E, Miro JM, Nhampossa T, Ayala E, Gascon J, Menendez C, et al. Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome in a Rural Area of Mozambique. PLoS ONE [Internet]. 2011 Feb 28 [cited 2014 Sep 8];6(2). Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046140/\n9. da Silva BCM Paula CR Auler ME Ruiz da S L Dos Santos JI Yoshioka MCN Dermatophytosis and immunovirological status of HIV-infected and AIDS patients from Sao Paulo city, Brazil Mycoses 2014 57 6 371 6 24417711 \n10. Singh F Rudikoff D HIV-associated pruritus: etiology and management Am J Clin Dermatol 2003 4 3 177 88 10.2165/00128071-200304030-00004 12627993 \n11. Hryncewicz-Gwóźdź A Kalinowska K Plomer-Niezgoda E Bielecki J Jagielski T Increase in resistance to fluconazole and itraconazole in Trichophyton rubrum clinical isolates by sequential passages in vitro under drug pressure Mycopathologia 2013 176 1–2 49 55 10.1007/s11046-013-9655-y 23595653 \n12. Faini D Maokola W Furrer H Hatz C Battegay M Tanner M Burden of serious fungal infections in Tanzania Mycoses 2015 58 Suppl 5 70 9 10.1111/myc.12390 26449510\n\n",
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"mesh_terms": "D000225:Adenine; D000328:Adult; D000349:Africa; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D003521:Cyclopropanes; D003841:Deoxycytidine; D005260:Female; D015658:HIV Infections; D015497:HIV-1; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome; D008297:Male; D063065:Organophosphonates; D013636:Tanzania; D014005:Tinea",
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"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "12627993;15280772;3130077;26369643;26449510;18317001;2522293;21386993;19874370;23595653;24417711;18377595",
"title": "Immune reconstitution inflammatory syndrome associated with dermatophytoses in two HIV-1 positive patients in rural Tanzania: a case report.",
"title_normalized": "immune reconstitution inflammatory syndrome associated with dermatophytoses in two hiv 1 positive patients in rural tanzania a case report"
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{
"reactionmeddrapt": "Tinea infection",
"reactionmeddraversionpt": "21.0",
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},
{
"reactionmeddrapt": "Immune reconstitution inflammatory syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
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],
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},
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"literaturereference": "MAPESI H, LETANG E, RAMIREZ A, TANNER M, HATZ C.. IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME ASSOCIATED WITH DERMATOPHYTOSES IN TWO HIV?1 POSITIVE PATIENTS IN RURAL TANZANIA: A CASE REPORT. BMC INFECTIOUS DISEASES. 2016?16:495:1 TO 5",
"literaturereference_normalized": "immune reconstitution inflammatory syndrome associated with dermatophytoses in two hiv 1 positive patients in rural tanzania a case report",
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{
"abstract": "This study compares the efficacy and tolerability of olanzapine versus risperidone among patients with schizophrenia who are established in outpatient psychiatric care and entering supported employment. A multicenter, randomized, double-blind trial was conducted among 107 outpatients with schizophrenia, who were cross-titrated to flexible dose risperidone or olanzapine over 2 weeks. Clinical endpoints included time to hospitalization and persistence on assigned medication. Weight, laboratory tests, psychopathology, neurologic side effects, social adjustment and role functioning were assessed at 3-6 month intervals. Data were analyzed first by randomized treatment, and then reassessed controlling for prior medication treatment. The proportion of patients on assigned medication at 18 months was 30.9% for risperidone and 37.3% for olanzapine. Mean doses were 6.4 ± 3.2 mg daily for risperidone, and 17.0 ± 5.0 mg daily for olanzapine. The groups did not differ significantly in time to medication discontinuation, first hospitalization or first employment. There were few differences in psychopathology, laboratory, or neurological assessments between groups at 18 months. Patients randomized to olanzapine gained modestly more weight. Controlling for pre-randomization medication suggested improvement in some aspects of psychopathology from switching medications; however, switching from olanzapine to risperidone was associated with more hospitalizations. Risperidone and olanzapine have similar efficacy and tolerability in patients with schizophrenia who are participating in supported employment. Randomization to olanzapine was associated with more weight gain, but randomization from olanzapine to risperidone appeared to be associated with a greater likelihood of hospitalization. Careful monitoring of metabolic effects and participation in supported employment may have contributed to minimal weight gain and metabolic effects.",
"affiliations": "Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, United States. Electronic address: dnoordsy@stanford.edu.;Semel Institute for Neuroscience at UCLA, Los Angeles, CA, United States; VA Greater Los Angeles, Los Angeles, CA, United States.;Semel Institute for Neuroscience at UCLA, Los Angeles, CA, United States; Department of Biostatistics, UCLA School of Public Health, Los Angeles, CA, United States.;Southern New Hampshire University, United States.;Semel Institute for Neuroscience at UCLA, Los Angeles, CA, United States; VA Greater Los Angeles, Los Angeles, CA, United States.",
"authors": "Noordsy|Douglas L|DL|;Glynn|Shirley M|SM|;Sugar|Catherine A|CA|;O'Keefe|Christopher D|CD|;Marder|Stephen R|SR|",
"chemical_list": "D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine",
"country": "England",
"delete": false,
"doi": "10.1016/j.jpsychires.2017.09.008",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0022-3956",
"issue": "95()",
"journal": "Journal of psychiatric research",
"keywords": "Antipsychotic medication; BMI; Schizophrenia; Supported employment",
"medline_ta": "J Psychiatr Res",
"mesh_terms": "D000328:Adult; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D004311:Double-Blind Method; D016832:Employment, Supported; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D017063:Outcome Assessment, Health Care; D018967:Risperidone; D012559:Schizophrenia; D015430:Weight Gain",
"nlm_unique_id": "0376331",
"other_id": null,
"pages": "299-307",
"pmc": null,
"pmid": "28942217",
"pubdate": "2017-12",
"publication_types": "D003160:Comparative Study; D016428:Journal Article; D016448:Multicenter Study; D016449:Randomized Controlled Trial",
"references": "17151159;24129841;7212946;9812110;17606657;24506576;27703755;15285957;2574607;15538607;12042192;28146614;28242107;15863797;19542525;16460134;16172203;3998720;28142387;17548746;12927005;10724130;28219485;18374841;8013215;6474101;2336066;16585435;16585434;27799019;11229989;4917967;14399272;19398192;24491908;16215191;26481174;22121860",
"title": "Risperidone versus olanzapine among patients with schizophrenia participating in supported employment: Eighteen-month outcomes.",
"title_normalized": "risperidone versus olanzapine among patients with schizophrenia participating in supported employment eighteen month outcomes"
} | [
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},
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{
"abstract": "Statin intolerance, primarily myalgia, is not uncommon in patients treated for elevated low-density lipoprotein cholesterol. Nonstatin drugs, such as ezetimibe, can spare patients from statin exposure, while still reducing low-density lipoprotein cholesterol. Ezetimibe is generally very well tolerated, although gastrointestinal and musculoskeletal symptoms have been occasionally reported. We describe an extremely rare case of an ezetimibe-associated liver injury who required protracted treatment with prednisone and azathioprine. Ezetimibe-associated liver injury should be suspected with development of hepatic abnormalities concurrent with the timing of ezetimibe treatment and in the absence of other possible precipitating factors.",
"affiliations": "Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.;Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.;Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.;Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.",
"authors": "Kanagalingam|Tharsan|T|;Lazarte|Julieta|J|;Wong|David K H|DKH|;Hegele|Robert A|RA|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1016/j.cjco.2020.09.018",
"fulltext": "\n==== Front\nCJC Open\nCJC Open\nCJC Open\n2589-790X Elsevier \n\nS2589-790X(20)30152-9\n10.1016/j.cjco.2020.09.018\nCase Report\nLiver Injury Associated With Ezetimibe Monotherapy\nKanagalingam Tharsan MSca Lazarte Julieta MScabc Wong David K.H. MDd Hegele Robert A. MD, FRCPC, FACPhegele@robarts.caabc∗ a Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada\nb Department Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada\nc Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada\nd Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada\n∗ Corresponding author: Dr Robert A. Hegele, Robarts Research Institute, Western University, 4288A-1151 Richmond St North, London, Ontario N6A 5B7, Canada. Tel.: +1-519-931-5271; fax: +1-519-931-5218. hegele@robarts.ca\n28 9 2020 \n2 2021 \n28 9 2020 \n3 2 195 197\n28 8 2020 23 9 2020 © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc.2020Canadian Cardiovascular SocietyThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Statin intolerance, primarily myalgia, is not uncommon in patients treated for elevated low-density lipoprotein cholesterol. Nonstatin drugs, such as ezetimibe, can spare patients from statin exposure, while still reducing low-density lipoprotein cholesterol. Ezetimibe is generally very well tolerated, although gastrointestinal and musculoskeletal symptoms have been occasionally reported. We describe an extremely rare case of an ezetimibe-associated liver injury who required protracted treatment with prednisone and azathioprine. Ezetimibe-associated liver injury should be suspected with development of hepatic abnormalities concurrent with the timing of ezetimibe treatment and in the absence of other possible precipitating factors.\n\nRésumé\nL’intolérance aux statines, se manifestant principalement par une myalgie, n’est pas rare chez les patients traités pour des taux élevés de cholestérol à lipoprotéines à basse densité (LDL). Des médicaments n’appartenant pas à la classe des statines, comme l’ézétimibe, permettent d’éviter l’exposition aux statines chez les patients, tout en réduisant le taux le cholestérol LDL. L’ézétimibe est généralement bien toléré, bien que des symptômes gastro-intestinaux et musculosquelettiques aient été signalés à l’occasion. Nous décrivons un cas extrêmement rare de lésion hépatique associée à l’ézétimibe ayant nécessité un traitement prolongé par la prednisone et l’azathioprine. Il faut soupçonner une lésion hépatique liée à l’ézétimibe lors de la survenue d’anomalies hépatiques pendant le traitement par l’ézétimibe en l’absence d’autres facteurs déclencheurs.\n==== Body\nStatins are the cornerstone therapy to reduce low-density lipoprotein (LDL) cholesterol levels and its associated risk of atherosclerotic cardiovascular disease.1 However, statin intolerance, primarily statin-associated muscle symptoms affect 2.5%-5% of patients.2 Nonstatin drugs are thus essential to spare affected patients from statin exposure, while still reducing LDL cholesterol.1 Treatment guidelines endorse the use of both ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) as safe and effective second-line LDL-lowering treatments to consider in response to statin intolerance.1 Ezetimibe lowers LDL cholesterol by blocking sterol uptake via the Niemann-Pick C1-like 1 protein (NPC1L1) in the upper small intestine.3 It has been available in Canada since 2003. Ezetimibe is generally very well tolerated, although gastrointestinal and musculoskeletal symptoms have been reported in approximately 0.1%-2% of patients.4, 5, 6, 7 Although no cases of ezetimibe-induced liver injury were observed in randomized clinical trials, there are a few case reports of this complication.4, 5, 6, 7 We describe an extremely rare case of an ezetimibe-associated liver injury.\n\nCase Report\nA 59-year-old asymptomatic man of European descent was referred to the lipid clinic with high LDL cholesterol levels. His medical history was positive only for appendectomy and he was not taking any medication including neither natural health products nor supplements. He had no history of the use of either alcohol or recreational drugs. His family history was positive for dyslipidemia in 2 brothers, one of whom died of a myocardial infarction at age 67. The patient’s father and mother each also died from sudden cardiac events at ages 62 and 80, respectively. On physical examination, his height was 180 cm, weight was 81.5 kg, body mass index (BMI) was 25.2 kg/m2, supine blood pressure was 104/60 mm Hg, and radial pulse was 75 beats/min. No physical stigmata of familial hypercholesterolemia were detected, that is, no xanthomas, xanthelasmas, or corneal arcus. There was no hepatosplenomegaly, and cardiovascular examination was normal.\n\nHis lipid profile showed total cholesterol, triglyceride, high-density lipoprotein cholesterol, and LDL cholesterol of 5.62, 1.12, 1.02, and 4.09 mmol/L, respectively. His apolipoprotein B level was 1.41 g/L (target < 0.8 g/L) and lipoprotein (a) was normal at < 10 mg/dL.1 His 2008 Framingham 10-year risk of cardiovascular disease was 11.2%.1 Baseline liver enzymes included alanine transaminase (ALT) 54 U/L (normal < 46 U/L), aspartate transaminase (AST) 33 U/L (normal < 37 U/L), bilirubin 10.2 μmol/L (normal 3.4-17.1 μmol/L), and alkaline phosphatase (ALP) 68 U/L (normal 40-129 U/L). Creatine kinase was 94 U/L (normal < 190 U/L). His mean carotid intima medial thickness was at the 50th percentile for age and sex. Targeted DNA sequencing found no pathogenic familial hypercholesterolemia mutation but showed a high polygenic score for LDL cholesterol (unweighted 15/20, or the 92nd percentile). His clinical and biochemical pictures were thus consistent with polygenic hypercholesterolemia, with a positive family history of early atherosclerotic cardiovascular disease and intermediate Framingham cardiovascular risk.\n\nThe patient was prescribed atorvastatin 20 mg daily but discontinued this treatment after 8 weeks because of severe myalgia, with normal creatine kinase at 103 U/L. After discussion, his preference was to avoid another statin and instead to try the PCSK9 inhibitor alirocumab 75 mg subcutaneously biweekly. As monotherapy, this treatment effectively reduced his plasma LDL cholesterol level to 1.41 mmol/L (55 mg/dL) within 8 weeks with no adverse effects (Fig. 1). Unfortunately, after 18 months, the patient's medical insurer declined to continue coverage of alirocumab therapy until a 3-month trial of ezetimibe 10 mg daily had been completed.Figure 1 Timeline showing liver function tests. Periods of medication (doses described in text) are shown with the horizontal lines. Azathioprine was still taken at the time of last assessment. ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate aminotransferase.\n\n\n\nWithin a month of starting ezetimibe therapy, the patient began to experience progressive and eventually debilitating frontal headaches, which led him to discontinue the medication within 8 weeks. After stopping ezetimibe, his headaches abated, but his health continued to deteriorate. One month after ezetimibe therapy had been stopped, he presented to the emergency department with anorexia, right upper quadrant abdominal pain radiating to the back, profound pruritus with no obvious rash, diarrhoea, debilitating sleeping difficulties, and new-onset arthralgia. His BMI had decreased to 23.4 kg/m2. His liver was palpable 4 cm below the right costal margin. ALT, AST, and ALP were 300, 129, and 1344 U/L, respectively. Bilirubin and international normalized ratio were normal at 14 μmol/L and 1.0, respectively. Viral serology was negative for hepatitis A, B, and C, and HIV. The antinuclear antibody test was positive. There were no other contributing factors that may have precipitated acute liver injury after ezetimibe discontinuation.\n\nA trial of ursodiol and cholestyramine resulted in no significant improvement in pruritus. He was prescribed hydromorphone for pain. A month later, his BMI was further reduced to 22.8 kg/m2. ALT, AST, and ALP were 300, 158, and 1600 U/L, respectively. Fibroscan of the liver was 12.9 kPa, which was consistent with fibrosis and/or severe inflammation. A liver biopsy showed active parenchymal inflammation and bile duct injury, but without fibrosis. A causal relationship was assessed using the Roussel Uclaf Causality Assessment Method causality scale,8 which is a well-established and commonly used tool to determine causality in cases of suspected drug-induced liver injury, by quantitatively assessing factors such as age, time of onset, liver function, drug use, and other comorbidities. In this case, ezetimibe-induced liver injury was determined as being probable for this patient with a score of 8. He was prescribed prednisone 40 mg daily and azathioprine 100 mg daily. Within 1 month, his ALT, AST, ALP, and bilirubin each decreased by > 50%. Prednisone was gradually tapered and stopped after a total of 7 months, but azathioprine was maintained (Fig. 1). After stopping prednisone, his BMI was 24.7 kg/m2 and his liver function tests had returned to the normal range. He restarted alirocumab 75 mg daily subcutaneously biweekly. Six months after stopping prednisone, on azathioprine 100 mg daily and alirocumab, his total cholesterol, triglyceride, high-density lipoprotein and LDL cholesterol were 3.63, 1.51, 0.86 and 2.08, respectively. His ALT, AST, and ALP were 12, 10, and 91 U/L, respectively, whereas total bilirubin was 7.0 μmol/L. He felt improved overall, although he still reported fatigue with exertion.\n\nDiscussion\nWe report a patient with severe ezetimibe-induced liver injury lasting several months after discontinuation of the medication. Suggestive features include the development of hepatic abnormalities in relation to the timing of ezetimibe treatment, and the absence of other possible precipitating agents and causes of acute liver injury. He remained symptomatic for more than 7 weeks after discontinuation of ezetimibe and in the acute stage of illness was at high risk for liver failure. Despite the severe ALP elevation, liver biopsy showed active parenchymal inflammation. Ursodiol was initially used because of the early predominance of the ALP elevation, but inflammation observed on liver biopsy led to switch to prednisone plus azathioprine. He required prednisone for a total of 7 months together with ongoing azathioprine before biochemical and clinical resolution, and has now returned close to his baseline state of health.\n\nEzetimibe is a useful second-line therapy for hypercholesterolemia that produces a modest reduction in LDL cholesterol compared with statin therapy.3 Severe side effects are very rare, particularly when the drug is used as monotherapy in patients with statin intolerance.2,3 Most previous published cases of ezetimibe-induced liver injury have been reported in combination with a statin.4,5 Indeed, the drug label warns of possible liver enzyme elevation when ezetimibe is prescribed in combination with a statin, but with no mention of such effects when used as monotherapy. Only 2 case reports describe liver injury when ezetimibe was used as monotherapy, but both subjects had other medical conditions such as treated hypertension.6,7 In contrast, our subject was on ezetimibe monotherapy solely, without any other medication or underlying condition except for hypercholesterolemia.\n\nIt remains unclear how ezetimibe induced the liver injury observed here. Ezetimibe does not interact with cytochrome P450 system or liver enzymes.3 However, ezetimibe circulates enterohepatically and likely blocks sterol absorption from hepatocytes via the inhibition of hepatic NPC1L1.3 Thus, there is some plausible connection to the liver as a site of action. This unique patient's history illustrates an extremely rare but potentially life-threatening hazard of ezetimibe monotherapy.Novel Teaching Points\n• Although very rare, ezetimibe-associated liver injury is a potentially serious complication.\n\n• With hepatic inflammation due to ezetimibe, discontinue treatment and consider systemic steroids and anti-inflammatory agents, with weekly monitoring of liver function tests (ALT, AST, ALP, total bilirubin).\n\n• Inhibitors of PCSK9 may be safe and effective alternatives to consider for LDL lowering in certain patients intolerant to statins and ezetimibe.\n\n\n\n\n\nAcknowledgements\nWe gratefully acknowledge the written consent, support, and cooperation of the patient in preparation of this report.\n\nFunding Sources\nJ.L. is supported by the Canadian Institutes of Health Research (Doctoral Research Award) and the Schulich School of Medicine and Dentistry (Cobban Student Award in Heart and Stroke Research). RAH is supported by the Jacob J. Wolfe Distinguished Medical Research Chair, the Edith Schulich Vinet Research Chair in Human Genetics, and the Martha G. Blackburn Chair in Cardiovascular Research. R.A.H. has also received operating grants from the Canadian Institutes of Health Research (Foundation award), the Heart and Stroke Foundation of Ontario (G-18-0022147).\n\nDisclosures\nR.A.H. reports consulting fees from Acasti, Aegerion, Akcea/Ionis, Amgen, HLS Therapeutics Novartis, Regeneron, and Sanofi. The rest of the authors have no conflicts of interest to disclose.\n\nEthics Statement: The research reported has adhered to ethical guidelines (Western University protocol 0379).\n\nSee page 197 for disclosure information.\n==== Refs\nReferences\n1 Anderson T.J. Grégoire J. Pearson G.J. 2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult Can J Cardiol 32 2016 1263 1282 27712954 \n2 Mancini G.B. Baker S. Bergeron J. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Consensus Working Group Update (2016) Can J Cardiol 32 Suppl 2016 S35 65 27342697 \n3 Phan B.A. Dayspring T.D. Toth P.P. Ezetimibe therapy: mechanism of action and clinical update Vasc Health Risk Manag 8 2012 415 427 22910633 \n4 Stolk M.F. Becx M.C. Kuypers K.C. Seldenrijk C.A. Severe hepatic side effects of ezetimibe Clin Gastroenterol Hepatol 4 2006 908 911 16797241 \n5 Ellingsen S.B. Nordmo E. Lappegard K.T. Recurrence and severe worsening of hepatotoxicity after reintroduction of atorvastatin in combination with ezetimibe Clin Med Insights Case Rep 10 2017 1179547617731375 \n6 Liu Q. Tobias H. Petrovic L.M. Drug-induced liver injury associated with ezetimibe therapy Dig Dis Sci 52 2007 602 605 17219067 \n7 Castellote J. Ariza J. Rota R. Girbau A. Xiol X. Serious drug-induced liver disease secondary to ezetimibe World J Gastroenterol 14 2008 5098 5099 18763297 \n8 Danan G. Teschke R. RUCAM in drug and herb induced liver injury: the update Int J Mol Sci 17 2015 14\n\n",
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"abstract": "Polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative age-related macular degeneration among Asian individuals. To our knowledge, there are no large randomized clinical trials to evaluate intravitreal ranibizumab, with and without verteporfin photodynamic therapy (vPDT), for the treatment of PCV.\n\n\n\nTo compare the efficacy and safety of combination therapy of ranibizumab and vPDT with ranibizumab monotherapy in PCV.\n\n\n\nA double-masked, multicenter randomized clinical trial of 322 Asian participants with symptomatic macular PCV confirmed by the Central Reading Center using indocyanine green angiography was conducted between August 7, 2013, and March 2, 2017.\n\n\n\nParticipants were randomized 1:1 to ranibizumab, 0.5 mg, and vPDT (n = 168; combination therapy group) or ranibizumab, 0.5 mg, and sham PDT (n = 154; monotherapy group). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT/sham PDT on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.\n\n\n\nStep 1 assessed whether combination therapy was noninferior (5-letter margin) to monotherapy for change in best-corrected visual acuity from baseline and superior in complete polyp regression. If noninferiority was established, step 2 assessed whether combination therapy was superior to monotherapy measured by best-corrected visual acuity change at month 12.\n\n\n\nBaseline demographics of the 322 participants were comparable between the treatment groups. Mean (SD) age of the patients was 68.1 (8.8) years, and overall, 69.9% of the patients were men. At baseline, the overall mean best-corrected visual acuity and mean central subfield thickness were 61.1 letters and 413.3 μm, respectively. At 12 months, mean improvement from baseline was 8.3 letters with combination therapy vs 5.1 letters with monotherapy (mean difference, 3.2 letters; 95% CI, 0.4-6.1), indicating that combination therapy met the predefined criterion for noninferiority as well as being superior to monotherapy (P = .01). Combination therapy was also superior to monotherapy in achieving complete polyp regression at month 12 (69.3% vs 34.7%; P < .001). Over 12 months, the combination therapy group received a median of 4.0 ranibizumab injections compared with 7.0 in the monotherapy group. Vitreous hemorrhage was the only ocular serious adverse event (combination therapy group, 1 [0.6%]; monotherapy group, 3 [2.0%]).\n\n\n\nAfter 12 months, combination therapy of ranibizumab plus vPDT was not only noninferior but also superior to ranibizumab monotherapy in best-corrected visual acuity and superior in complete polyp regression while requiring fewer injections. Combination therapy should be considered for eyes with PCV.\n\n\n\nclinicaltrials.gov Identifier: NCT01846273.",
"affiliations": "Eye and Retina Surgeons, Camden Medical Centre, Singapore, Singapore.;Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.;Department of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, Japan.;Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, National University of Singapore, Singapore.;Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan.;Department of Ophthalmology, Rajavithi Hospital, Bangkok, Thailand.;Fundus Image Reading Centre, National Healthcare Group Eye Institute, Singapore.;Novartis Pharma AG, Basel, Switzerland.;Novartis Pharma AG, Basel, Switzerland.;Fundus Image Reading Centre, National Healthcare Group Eye Institute, Singapore.;Department of Ophthalmology, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.",
"authors": "Koh|Adrian|A|;Lai|Timothy Y Y|TYY|;Takahashi|Kanji|K|;Wong|Tien Y|TY|;Chen|Lee-Jen|LJ|;Ruamviboonsuk|Paisan|P|;Tan|Colin S|CS|;Feller|Chrystel|C|;Margaron|Philippe|P|;Lim|Tock H|TH|;Lee|Won Ki|WK|;|||",
"chemical_list": "D020533:Angiogenesis Inhibitors; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D000069579:Ranibizumab",
"country": "United States",
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"mesh_terms": "D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors; D002829:Choroid; D015862:Choroid Diseases; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006801:Humans; D007275:Injections, Intravenous; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D017319:Photosensitizing Agents; D011127:Polyps; D011166:Porphyrins; D000069579:Ranibizumab; D012189:Retrospective Studies; D016896:Treatment Outcome; D000077362:Verteporfin",
"nlm_unique_id": "101589539",
"other_id": null,
"pages": "1206-1213",
"pmc": null,
"pmid": "28983556",
"pubdate": "2017-11-01",
"publication_types": "D017429:Clinical Trial, Phase IV; D016428:Journal Article; D016448:Multicenter Study; D016449:Randomized Controlled Trial; D013485:Research Support, Non-U.S. Gov't",
"references": "25343244;27094371;19563374;24653824;17660987;26102436;26558226;22426346;22127224;1693009;22922845;11934327;25758601;24280967;17709578;27142805;25072645;19715154;21386762;23455233;25830698;17460589;20075967;21146223;19854291;27237048;20532141;23876867;18626733;28120909",
"title": "Efficacy and Safety of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: A Randomized Clinical Trial.",
"title_normalized": "efficacy and safety of ranibizumab with or without verteporfin photodynamic therapy for polypoidal choroidal vasculopathy a randomized clinical trial"
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}
],
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}
},
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"literaturereference": "TAKAHASHI K, KOH A, LAI TYY. EFFICACY AND SAFETY OF RANIBIZUMAB WITH OR WITHOUT VERTEPORFIN PHOTODYNAMIC THERAPY FOR POLYPOIDAL CHOROIDAL VASCULOPATHY: A RANDOMIZED CLINICAL TRIAL. JAMA OPHTHALMOLOGY 2017;:-.",
"literaturereference_normalized": "efficacy and safety of ranibizumab with or without verteporfin photodynamic therapy for polypoidal choroidal vasculopathy a randomized clinical trial",
"qualification": "1",
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{
"abstract": "A 74-year-old female patient with end-stage renal disease, undergoing periodic hemodialysis, was hospitalized due to infection by multidrug-resistant Acinetobacter baumannii after hip replacement surgery. She was treated with tigecycline, a glycylcycline agent. Subsequently she developed coagulation disorders as substantiated by increased international normalized ratio (INR), prolonged partial thromboplastin time (aPTT), and severe hypofibrinogenemia, followed by transaminasemia, cholestasis, and anemia. Ultrasonography and computed tomography revealed no underlying pathological entities. Tigecycline was discontinued and the patient underwent daily hemodialysis and received multiple fresh frozen plasma transfusions. Additionally, she was treated with colistin. Her clinical and laboratory status improved. We suggest that patients treated with tigecycline should be monitored for changes in INR, aPTT, and fibrinogen levels to avoid severe, life-threatening coagulation disturbances.",
"affiliations": "From the 1 Nephrological Department, General Hospital of Pella , Edessa , Greece.",
"authors": "Sabanis|Nikolaos|N|;Paschou|Eleni|E|;Gavriilaki|Eleni|E|;Kalaitzoglou|Asterios|A|;Vasileiou|Sotirios|S|",
"chemical_list": "D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline; D003091:Colistin",
"country": "England",
"delete": false,
"doi": "10.3109/23744235.2015.1043942",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "2374-4243",
"issue": "47(10)",
"journal": "Infectious diseases (London, England)",
"keywords": "Hypofibrinogenemia; acinetobacteur baumannii; adverse event; coagulation disorder; hemodialysis; tigecycline",
"medline_ta": "Infect Dis (Lond)",
"mesh_terms": "D000151:Acinetobacter Infections; D040981:Acinetobacter baumannii; D000368:Aged; D000900:Anti-Bacterial Agents; D001778:Blood Coagulation Disorders; D003091:Colistin; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D007676:Kidney Failure, Chronic; D008911:Minocycline; D010314:Partial Thromboplastin Time; D006435:Renal Dialysis; D000078304:Tigecycline",
"nlm_unique_id": "101650235",
"other_id": null,
"pages": "743-6",
"pmc": null,
"pmid": "25951751",
"pubdate": "2015",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Hypofibrinogenemia induced by tigecycline: a potentially life-threatening coagulation disorder.",
"title_normalized": "hypofibrinogenemia induced by tigecycline a potentially life threatening coagulation disorder"
} | [
{
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"literaturereference": "SABANIS, N.. HYPOFIBRINOGENEMIA INDUCED BY TIGECYCLINE: A POTENTIALLY LIFE-THREATENING COAGULATION DISORDER. INFECTIOUS DISEASES. 2015?47 (10):10.3109/23744235.2015.1043942",
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"qualification": "3",
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{
"abstract": "Percutaneous transvenous mitral commisurotomy (PTMC) is a frequently used minimally invasive procedure for patients with symptomatic mitral stenosis. However, it is not without complications. Few complications which are distinctive to the procedure are thromboembolism, left-to-right shunts, mitral regurgitation, cardiac tamponade and complete heart block. We present the case of a 32-year-old female patient scheduled for a PTMC, who had multiple complications during the procedure. She developed cardiac tamponade for which pericardiocentesis and autotransfusion was done. Subsequently she exhibited epileptiform activity for which there was a diagnostic dilemma due to the presence of multiple confounding factors. However, she had a complete recovery without any residual sequelae at the time of discharge.",
"affiliations": "Department of Cardiac Anaesthesiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India.;Department of Cardiac Anaesthesiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India.;Department of Cardiac Anaesthesiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India.",
"authors": "Balaji|Rohini Mayur|RM|;Dhananjaya|Manasa|M|;Thimmarayappa|Ashwini|A|",
"chemical_list": null,
"country": "India",
"delete": false,
"doi": "10.4103/aca.ACA_54_18",
"fulltext": "\n==== Front\nAnn Card AnaesthAnn Card AnaesthACAAnnals of Cardiac Anaesthesia0971-97840974-5181Wolters Kluwer - Medknow India 31274497ACA-22-31810.4103/aca.ACA_54_18Case ReportTroubleshooting for Epileptiform Activity during Percutaneous Transvenous Mitral Commisurotomy Balaji Rohini Mayur Dhananjaya Manasa Thimmarayappa Ashwini Department of Cardiac Anaesthesiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, IndiaAddress for correspondence: Dr. Ashwini Thimmarayappa, 395, 14th Main, 1st Block, 3rd Stage, Basaveshwaranagar, Bengaluru - 560 079, Karnataka, India. E-mail: rohinimayur.b@gmail.comJul-Sep 2019 22 3 318 320 Copyright: © 2019 Annals of Cardiac Anaesthesia2019This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.Percutaneous transvenous mitral commisurotomy (PTMC) is a frequently used minimally invasive procedure for patients with symptomatic mitral stenosis. However, it is not without complications. Few complications which are distinctive to the procedure are thromboembolism, left-to-right shunts, mitral regurgitation, cardiac tamponade and complete heart block. We present the case of a 32-year-old female patient scheduled for a PTMC, who had multiple complications during the procedure. She developed cardiac tamponade for which pericardiocentesis and autotransfusion was done. Subsequently she exhibited epileptiform activity for which there was a diagnostic dilemma due to the presence of multiple confounding factors. However, she had a complete recovery without any residual sequelae at the time of discharge.\n\nCardioemboliepileptiform activityfentanyllocal anesthetic systemic toxicitypercutaneous transvenous mitral commisurotomy\n==== Body\nIntroduction\nRheumatic heart disease (RHD) contributes largely to the burden of valvular heart diseases in the Indian subcontinent with prevalence rates varying from 4.54 to 6/1000 population.[1] Mitral stenosis (MS) is probably one of the most common valvular pathologies to occur as a sequelae of RHD.[2] Inoue et al. described percutaneous transmitral commissurotomy (PTMC) as a modality of treatment for mitral stenosis. PTMC can be associated with complications like thromboembolism, left-to-right shunts, mitral regurgitation, cardiac tamponade and complete heart block.[34]\n\nWe present the combined occurrence of cardiac tamponade and epileptiform activity during PTMC in a 32-year-old female patient.\n\nThe cause for the seizures proved to be a diagnostic dilemma.\n\nCase Report\nOur patient was a 32-year-old female, 149 cm in height, weighing 36 kg with severe symptomatic MS. She did not have any comorbidities and her past history was insignificant. The transthoracic echocardigraphy (TTE) examination prior to the procedure revealed critical MS (mitral valve orifice area of 0.6 cm2) with thickened leaflets, submitral fusion, mitral valve gradient of 26/13, pulmonary artery systolic pressure of 59 mmHg and a suspected clot in the roof of the left atrium (LA). In order to confirm the findings, a transesophageal echocardiography (TEE) examination was performed. This confirmed the diagnosis of critical MS, but ruled out the presence of a clot in the LA. Instead, the TEE exam documented grade 3 spontaneous echo contrast in the LA.\n\nIn view of the above mentioned findings, she was scheduled to undergo a high risk PTMC. Her preoperative blood investigations were unremarkable except for a hemoglobin level of 10.5 g%.\n\nHer baseline vitals were as follows - blood pressure (BP) - 122/76 mmHg, Pulse Rate (PR) - 101 beats per minute (bpm), room air saturation (SpO2) - 98%. She had an 18G peripheral intravenous (IV) catheter in situ in the left upper limb.\n\nRight femoral venous and arterial access were secured using Seldinger's technique under local anesthesia – 10 ml 1% lignocaine was used for infiltration. 8F sheaths were inserted through both the vascular punctures. Mullin's sheath and Brockenbrough needle were used for transseptal puncture during which the patient developed hypotension (74/40 mmHg) and bradycardia (38 bpm). Diminished movement of the left cardiac border was visualized on fluoroscopy simultaneously and hence a diagnosis of cardiac tamponade was made. Injection atropine 0.6 mg was administered IV and second large bore peripheral IV cannula was inserted. Oxygen was supplemented via facemask. A 7F pigtail catheter was immediately inserted using echo and fluoroscopy guidance into the pericardial sac and autotransfusion was started. Poststabilization, her vitals were BP – 140/80 mmHg, PR– 110 bpm, SpO2 –100%. A blood gas sample revealed all parameters to be within normal limits except for the hemoglobin which was 8.5 g%. The right-sided sheaths were kept in situ and the procedure was resumed by inserting a second Mullin's sheath through a left femoral venous access after infiltrating 10 ml 1% plain lignocaine.\n\nDuring manipulation of the second Mullin's sheath, the patient complained of severe pain over the left lower limb catheterisation site, for which, IV fentanyl 40 mcg was administered. Following this, she developed altered sensorium associated with tonic posturing and jaw clenching. As there was no response to IV midazolam 2 mg, IV propofol 30 mg was administered which terminated the episode. Simultaneously her respiration was assisted with bag and mask. Her vitals remained stable except for tachycardia (147 bpm) and post ictal confusion.\n\nPTMC was resumed and the procedure was completed without any further complications. Postprocedure, she was shifted to the recovery room where she recovered completely within half an hour. Rest of the hospital stay was uneventful and the patient did not have any residual neurological deficit at the time of discharge.\n\nDiscussion\nThe peak incidence of rheumatic MS has been known to occur between 30 and 39 years of age with nearly two-thirds (65.9%) of the patients being females.[1] PTMC is recommended for symptomatic patients with severe MS and favorable valve morphology as determined by Wilkin's score.[5] It was first used by Inoue in 1982 to provide immediate symptomatic and hemodynamic improvement.[6]\n\nPTMC, like any other procedure, is not bereft of complications. Bleeding, thromboembolic events, seizures, development of mitral regurgitation, residual atrial septal defect, perforation of cardiac chambers, cardiac tamponade[346] are few of the reported complications.\n\nDuring the course of the procedure, our patient developed cardiac tamponade. The incidence of tamponade during PTMC varies from 0% to 9%.[7] The tamponade was immediately diagnosed and treated. Although our patient did not require any inotropic support or surgical intervention, there have been individual and case series reports where patients have required the same, contributing to increased morbidity and mortality.[37]\n\nAn additional dose of local anesthetic was infiltrated to secure the second femoral access. Fentanyl was also administered as the patient complained of pain following which she exhibited epileptiform activity. The differential diagnoses considered for the etiology of the epileptiform activity were cardiogenic embolic phenomena, local anesthetic neurotoxicty and fentanyl induced seizures.\n\nAlthough cerebral angiography was considered on table to rule out cardioemboli, it was not done since the presenting feature was predominant epileptiform activity without any associated focal neurological deficits. Arboix and Alió in their review on cardioembolic strokes[8] state that although there is no gold standard to provide a diagnosis, 79.7% of such embolic events are associated with sudden onset of focal neurological deficits. They also state that emboli arising from the cardiac chambers are often large and hence more likely to cause severe stroke, disability and death with a low frequency of symptom free hospital discharge.\n\nThe second possible differential diagnosis considered was local anesthetic systemic toxicity (LAST), as a result of either intravascular injection or higher cumulative dose. Direct intravascular injection leading to LAST may not have any premonitory symptoms and the patient can directly develop seizure activity that may progress to cardiac excitation (tachycardia, ventricular arrhythmias).[9] After exhibiting epileptiform activity, the patient developed tachycardia (147 bpm). This pattern correlated with the described pattern of initial neurotoxicity followed by cardiotoxicity in LAST following intravascular injection.\n\nEpileptiform activity has also been described after the administration of opioids including fentanyl.[1011] Since the occurrence of seizures concurred with the administration of fentanyl, opioid-induced seizure was a possibility. Postulates proposed to explain the neuronal excitation are dose dependent selective stimulation of κ and μ opioid receptors, decreased GABA mediated interneuronal inhibition of pyramidal neurons and inhibition of hyperpolarization activated potassium currents.[11] There also have been case reports describing the potentiation of epileptiform activity due to lignocaine by fentanyl.[12] Since the administration of fentanyl and lignocaine concurred in our patient, the potentiation could have led to development of seizures.\n\nConclusion\nSeizures during PTMC is not an uncommon occurrence. Both anesthetic and procedural factors must be considered during development of complications. Caution should be exercised while using local anesthetic, even if it is for surface infiltration, especially when used in conjunction with fentanyl.\n\nDeclaration of patient consent\nThe authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.\n\nFinancial support and sponsorship\nNil.\n\nConflicts of interest\nThere are no conflicts of interest.\n==== Refs\n1 Manjunath CN Srinivas P Ravindranath KS Dhanalakshmi C Incidence and patterns of valvular heart disease in a tertiary care high-volume cardiac center: A single center experience Indian Heart J 2014 66 320 6 24973838 \n2 Lock JE Khalilullah M Shrivastava S Bahl V Keane JF Percutaneous catheter commissurotomy in rheumatic mitral stenosis N Engl J Med 1985 313 1515 8 4069160 \n3 Varma PK Theodore S Neema PK Ramachandran P Sivadasanpillai H Nair KK Emergency surgery after percutaneous transmitral commissurotomy: Operative versus echocardiographic findings, mechanisms of complications, and outcomes J Thorac Cardiovasc Surg 2005 130 772 6 16153927 \n4 Shankarappa RK Agrawal N Patra S Karur S Nanjappa MC An unusual percutaneous transmitral commissurotomy: A collection of four rare occurrences! J Cardiovasc Dis Res 2013 4 191 4 24396260 \n5 Nishimura RA Otto CM Bonow RO Carabello BA Erwin JP 3rd Guyton RA 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines J Am Coll Cardiol 2014 63 e57 185 24603191 \n6 Nobuyoshi M Hamasaki N Kimura T Nosaka H Yokoi H Yasumoto H Indications, complications, and short-term clinical outcome of percutaneous transvenous mitral commissurotomy Circulation 1989 80 782 92 2791243 \n7 Koujalgi RI Anandan PK Basappa H Manjunath CN Stitch in time saves nine-Cardiac tamponade during percutaneous transvenous mitral commissurotomy (PTMC) – Stitching phenomenon Int J Cardiovasc Cerebrovasc Dis 2015 3 11 3 \n8 Arboix A Alió J Cardioembolic stroke: Clinical features, specific cardiac disorders and prognosis Curr Cardiol Rev 2010 6 150 61 21804774 \n9 Neal JM Bernards CM Butterworth JF Di Grigorio G Drasner K Hetjmanek MR ASRA practice advisory on local anesthetic systemic toxicity Regional Anesth Pain Med 2010 35 152 61 \n10 Modica PA Tempelhoff R White PF Pro – And anticonvulsant effects of anesthetics (Part I) Anesth Analg 1990 70 303 15 2407150 \n11 Zuleta-Alarcon A Castellon-Larios K Moran KR Soghomonyan S Kurnutala LN Bergese SD Anesthesia-related perioperative seizures: Pathophysiology, predisposing factors and practical recommendations Austin J Anesth Analg 2014 2 1026 \n12 Hsieh XX Hsu YC Cherng CH Lin CC Huang GS Lin SL Grand mal seizure induced by low-dose fentanyl and lidocaine in a young child Acta Anaesthesiol Taiwan 2015 53 105 8 26108757\n\n",
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"issue": "22(3)",
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"keywords": "Cardioemboli; epileptiform activity; fentanyl; local anesthetic systemic toxicity; percutaneous transvenous mitral commisurotomy",
"medline_ta": "Ann Card Anaesth",
"mesh_terms": "D000328:Adult; D001804:Blood Transfusion, Autologous; D006348:Cardiac Surgical Procedures; D004827:Epilepsy; D005260:Female; D006801:Humans; D007431:Intraoperative Complications; D019060:Minimally Invasive Surgical Procedures; D008946:Mitral Valve Stenosis; D020519:Pericardiocentesis; D016896:Treatment Outcome",
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"pages": "318-320",
"pmc": null,
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"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "16153927;24973838;20216033;24603191;2791243;26108757;2407150;21804774;4069160;24396260",
"title": "Troubleshooting for epileptiform activity during percutaneous transvenous mitral commisurotomy.",
"title_normalized": "troubleshooting for epileptiform activity during percutaneous transvenous mitral commisurotomy"
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{
"abstract": "BACKGROUND\nSeveral cases of folliculotropic mycosis fungoides, associated with immunosuppressive therapy, including calcineurin inhibitors, have been reported in solid organ transplant patients. We have encountered 3 patients on immunosuppressive therapy who developed follicular eruptions with folliculocentric infiltrates of nonatypical lymphocytes.\n\n\nOBJECTIVE\nTo characterize these follicular eruptions and review the literature.\n\n\nMETHODS\nThree patients, aged 7-15 years, who were treated with systemic immunosuppressive therapy developed follicular eruptions characterized histopathologically by folliculocentric lymphocytic infiltrates. These were studied clinically, histopathologically, immunophenotypically, and molecularly for T-cell receptor (TCR) gene rearrangement.\n\n\nRESULTS\nAll 3 cases were characterized histopathologically by folliculocentric infiltrates of nonatypical CD3 T lymphocytes with variable follicular exocytosis. Two cases also showed follicular mucinosis. Marked reduction in CD7 staining, and marked predominance of CD4 cells over CD8 cells was observed in all 3 cases. The TCR gene rearrangement studies were monoclonal in 2 cases. Oral calcineurin inhibitors (2 cyclosporine A and 1 tacrolimus) were part of the therapeutic regimen in all 3 patients. Their cessation along with local corticosteroid creams in 2 patients, and phototherapy with oral acitretin in one patient, was associated with complete clinical remission.\n\n\nCONCLUSIONS\nPatients undergoing systemic immunosuppressive therapy that includes calcineurin inhibitors might develop follicular eruption with some immunophenotypical variations and a monoclonal TCR gene rearrangement but lack sufficient cytomorphological features of folliculotropic mycosis fungoides. Altering the immunosuppressive agent including calcineurin inhibitors may result in regression of the eruptions.",
"affiliations": "Department of Dermatology, Rambam Health Care Campus, Haifa, Israel.;Department of Dermatology, Rambam Health Care Campus, Haifa, Israel.;Department of Dermatology, Rambam Health Care Campus, Haifa, Israel.;Department of Hematology, Rambam Health Care Campus, Haifa, Israel.;The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.;The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.;Department of Dermatology, Rambam Health Care Campus, Haifa, Israel.",
"authors": "Avitan-Hersh|Emily|E|;Dias-Polak|David|D|;Ramon|Michal|M|;Sahar|Dvora|D|;Magen|Daniella|D|;Pollack|Shirley|S|;Bergman|Reuven|R|",
"chemical_list": "D007166:Immunosuppressive Agents",
"country": "United States",
"delete": false,
"doi": "10.1097/DAD.0000000000001547",
"fulltext": null,
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"issn_linking": "0193-1091",
"issue": "42(7)",
"journal": "The American Journal of dermatopathology",
"keywords": null,
"medline_ta": "Am J Dermatopathol",
"mesh_terms": "D000293:Adolescent; D002648:Child; D005076:Exanthema; D006801:Humans; D007049:Iatrogenic Disease; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents; D008297:Male",
"nlm_unique_id": "7911005",
"other_id": null,
"pages": "498-505",
"pmc": null,
"pmid": "31789839",
"pubdate": "2020-07",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": null,
"title": "Follicular Eruption With Folliculotropic Lymphocytic Infiltrates Associated With Iatrogenic Immunosuppression: Report and Study of 3 Cases, and Review of the Literature.",
"title_normalized": "follicular eruption with folliculotropic lymphocytic infiltrates associated with iatrogenic immunosuppression report and study of 3 cases and review of the literature"
} | [
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"literaturereference": "HERSH E, POLAK D, RAMON M, SAHAR D, MAGEN D, POLLACK S, ET. AL. FOLLICULAR ERUPTION WITH FOLLICULOTROPIC LYMPHOCYTIC INFILTRATES ASSOCIATED WITH IATROGENIC IMMUNOSUPPRESSION: REPORT AND STUDY OF 3 CASES, AND REVIEW OF THE LITERATURE. AM J DERMATOPATHOL 2019?00:1-8",
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"medicinalproduct": "CYCLOSPORINE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
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"drugadministrationroute": "065",
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"drugindication": "ALLOGENIC BONE MARROW TRANSPLANTATION THERAPY",
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"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
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"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
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"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "4",
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"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
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"drugindication": "ALLOGENIC BONE MARROW TRANSPLANTATION THERAPY",
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"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CYCLOSPORINE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "050574",
"drugbatchnumb": null,
"drugcharacterization": "1",
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"drugdosagetext": "UNK",
"drugenddate": null,
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"drugindication": "ALLOGENIC BONE MARROW TRANSPLANTATION THERAPY",
"drugintervaldosagedefinition": null,
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"medicinalproduct": "CYCLOSPORINE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
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"drugcumulativedosageunit": null,
"drugdosageform": null,
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"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
}
],
"patientagegroup": null,
"patientonsetage": "15",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Cutaneous T-cell lymphoma",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "AVITAN?HERSH E, DIAS?POLAK D, RAMON M, SAHAR D, MAGEN D, POLLACK S, ET AL.. FOLLICULAR ERUPTION WITH FOLLICULOTROPIC LYMPHOCYTIC INFILTRATES ASSOCIATED WITH IATROGENIC IMMUNOSUPPRESSION: REPORT AND STUDY OF 3 CASES, AND REVIEW OF THE LITERATURE. AMERICAN JOURNAL OF DERMATOPATHOLOGY. 2020?42(7):498?505",
"literaturereference_normalized": "follicular eruption with folliculotropic lymphocytic infiltrates associated with iatrogenic immunosuppression report and study of 3 cases and review of the literature",
"qualification": "3",
"reportercountry": "IL"
},
"primarysourcecountry": "IL",
"receiptdate": "20210413",
"receivedate": "20210413",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19130671,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
}
] |
{
"abstract": "A follow-up blood count was performed on a 74-year-old woman diagnosed with colitis due to cytomegalovirus and under treatment with valganciclovir. The automated complete blood count revealed an abnormal white blood cells (WBC) scattergram together with WBC alert flags. The peripheral blood smear showed neutrophils with markedly hyposegmented nuclei or bilobed nuclei and very condensed chromatin or clumping chromatin all consistent with Pelger-Huët anomaly (PHA). We checked previous blood counts, ruling out an inherited PHA. We assessed the haematological, infectious and iatrogenic aetiologies for an acquired PHA. Once the valganciclovir treatment was completed and the drug was withdrawn, without changing the rest of the treatment, the morphological abnormalities of neutrophils were completely resolved. We conclude therefore that the acquired PHA presented by our patient is probably related to valganciclovir treatment.",
"affiliations": "Clinical Laboratory, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain melva.nieto@salud.madrid.org.;Clinical Laboratory, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain.",
"authors": "Nieto-Borrajo|Elva|E|http://orcid.org/0000-0002-0984-1485;Bermejo-Rodriguez|Alfredo|A|",
"chemical_list": "D000998:Antiviral Agents; D000077562:Valganciclovir",
"country": "England",
"delete": false,
"doi": "10.1136/bcr-2019-230958",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1757-790X",
"issue": "12(10)",
"journal": "BMJ case reports",
"keywords": "drugs: infectious diseases; haematology (including blood transfusion)",
"medline_ta": "BMJ Case Rep",
"mesh_terms": "D000368:Aged; D000998:Antiviral Agents; D003092:Colitis; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections; D005260:Female; D006801:Humans; D010381:Pelger-Huet Anomaly; D000077562:Valganciclovir",
"nlm_unique_id": "101526291",
"other_id": null,
"pages": null,
"pmc": null,
"pmid": "31611226",
"pubdate": "2019-10-13",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "28092888;19021122;29765286;22338047;20552303;26333345;16003243;21228370",
"title": "Acquired Pelger-Huët anomaly in a patient treated with valganciclovir.",
"title_normalized": "acquired pelger hu t anomaly in a patient treated with valganciclovir"
} | [
{
"companynumb": "ES-CIPLA LTD.-2019ES07329",
"fulfillexpeditecriteria": "1",
"occurcountry": "ES",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "VALGANCICLOVIR"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "209672",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CYTOMEGALOVIRUS COLITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VALGANCICLOVIR."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Neutrophil Pelger-Huet anomaly present",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NIETO-BORRAJO E, BERMEJO-RODRIGUEZ A. ACQUIRED PELGER-HU?T ANOMALY IN A PATIENT TREATED WITH VALGANCICLOVIR. BMJ CASE REP. 2019?12 (10):156 TO 157",
"literaturereference_normalized": "acquired pelger hu t anomaly in a patient treated with valganciclovir",
"qualification": "3",
"reportercountry": "ES"
},
"primarysourcecountry": "ES",
"receiptdate": "20191108",
"receivedate": "20191108",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17007669,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200122"
}
] |
{
"abstract": "BACKGROUND\nOwing to efficacy and tolerability, abiraterone acetate (AA) is a leading treatment for men with metastatic castration-resistant prostate cancer. Increased serum concentrations of AA, such as by taking AA with food, may lead to the inhibition of additional enzymes in the androgen synthesis pathway implicated in castration-resistant prostate cancer progression.\n\n\nMETHODS\nMedical records of men with metastatic castration-resistant prostate cancer (mCRPC) who received AA between 1 April 2011 and 31 December 2013 were retrospectively reviewed. The primary outcome was the percent of men with a rising PSA on AA who experienced any PSA decline within 3 months after changing the administration of AA from without food to with food. Secondary outcomes were median time on AA therapy in men who received AA therapy without food versus those that switched administration from without food to with food at PSA progression, and the percent of men who experienced any decline in serum testosterone concentration, and the rate of adverse events observed while taking AA with food.\n\n\nRESULTS\nNineteen men who switched AA administration from without food to with food and 41 patients who administered AA without food only were included in the study. Of those patients who took AA with food at PSA progression, a PSA decline was observed in 3 of the 19 (16%) men, including 3 of the 14 men who had an initial response to AA (21%). Testosterone declined in five out of seven patients from pre-food levels. The median time on AA therapy was increased by nearly 100 days in patients who switched AA administration from without food to with food. No increases in toxicity were observed.\n\n\nCONCLUSIONS\nSome men with mCRPC may benefit from taking AA with food. Further prospective comparative studies are needed to determine if changing AA administration is beneficial.",
"affiliations": "Department of Pharmacy, Duke University Hospital, Durham, NC, USA.;Department of Pharmacy, Duke University Hospital, Durham, NC, USA.;Division of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute, Durham, NC, USA.;Division of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute, Durham, NC, USA.;Division of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute, Durham, NC, USA.",
"authors": "Stover|J T|JT|;Moore|R A|RA|;Davis|K|K|;Harrison|M R|MR|;Armstrong|A J|AJ|",
"chemical_list": "D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate",
"country": "England",
"delete": false,
"doi": "10.1038/pcan.2015.7",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1365-7852",
"issue": "18(2)",
"journal": "Prostate cancer and prostatic diseases",
"keywords": null,
"medline_ta": "Prostate Cancer Prostatic Dis",
"mesh_terms": "D000069501:Abiraterone Acetate; D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen; D064129:Prostatic Neoplasms, Castration-Resistant; D016896:Treatment Outcome",
"nlm_unique_id": "9815755",
"other_id": null,
"pages": "161-6",
"pmc": null,
"pmid": "25777155",
"pubdate": "2015-06",
"publication_types": "D016428:Journal Article",
"references": "22753664;21632851;15150570;23585511;16278481;23849416;24859991;25053178;21680543;14607214;25184630;23576708;20159814;18645193;23993097;21612468;23228172;24399786;24074764;20159824",
"title": "Reversal of PSA progression on abiraterone acetate through the administration with food in men with metastatic castration-resistant prostate cancer.",
"title_normalized": "reversal of psa progression on abiraterone acetate through the administration with food in men with metastatic castration resistant prostate cancer"
} | [
{
"companynumb": "US-JNJFOC-20150515113",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROSTATE CANCER METASTATIC",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ABIRATERONE ACETATE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "202379",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": null,
"drugenddate": "20131231",
"drugenddateformat": "102",
"drugindication": "PROSTATE CANCER METASTATIC",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "20110401",
"drugstartdateformat": "102",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ABIRATERONE ACETATE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FINASTERIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
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"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FINASTERIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DUTASTERIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
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"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DUTASTERIDE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Wrong technique in product usage process",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hypokalaemia",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hypertension",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Fatigue",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Blood creatinine increased",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Prostatic specific antigen increased",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Blood testosterone decreased",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Aspartate aminotransferase increased",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hot flush",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Alanine aminotransferase increased",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "JT S, RA M, K D, MR H, AJ A. REVERSAL OF PSA PROGRESSION ON ABIRATERONE ACETATE THROUGH THE ADMINISTRATION WITH FOOD IN MEN WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER. PROSTATE CANCER + PROSTATIC DISEASES 2015;18 (2):161-6.",
"literaturereference_normalized": "reversal of psa progression on abiraterone acetate through the administration with food in men with metastatic castration resistant prostate cancer",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20150805",
"receivedate": "20150805",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11341471,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20151125"
}
] |
{
"abstract": "A 76-year-old woman from a tuberculosis (TB) endemic region with chronic myelomonocytic leukemia (CMML) on Azacitidine presented with a non-productive cough. A CT scan of the chest revealed a lobulated opacity in the right upper lobe and antibiotic therapy was initiated for a potential bacterial pneumonia. However, a high suspicion for pulmonary TB remained given her nation of origin, immunosuppression, and imaging findings. Three sputum and bronchoalveolar lavage (BAL) acid-fast bacilli (AFB) smears with PCR testing for Mycobacterium tuberculosis were negative, as were examinations for other potential fungal or bacterial etiologies of the patient's symptoms and imaging findings. While awaiting final TB culture results from BAL, her CMML underwent a transformation to acute myeloid leukemia (AML). Given the urgent need for initiation of chemotherapy, empiric treatment for TB was commenced while awaiting the final TB culture. Within 48-hours of initiating therapy for TB, the patient's fevers subsided. One week after discharge our team was notified of a positive M. tuberculosis culture from BAL. We suspect that our patient had a latent TB infection which reactivated due to her CMML. This case highlights the importance of maintaining a high clinical suspicion for TB in high-risk patients, even in the case of initially negative laboratory examinations. Further, it demonstrates the importance of screening and treating latent TB in patients with leukemias.",
"affiliations": "Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, USA.;Emergency Medicine, University of Michigan, Ann Arbor, USA.;Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, USA.;Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, USA.",
"authors": "Pescatore|Jay|J|;Cohen|Ashley|A|;Moturi|Krishna|K|;Hernandez-Acosta|Ruben|R|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.7759/cureus.15491",
"fulltext": "\n==== Front\nCureus\nCureus\n2168-8184\nCureus\n2168-8184\nCureus Palo Alto (CA)\n\n10.7759/cureus.15491\nInfectious Disease\nPulmonology\nHematology\nReactivation of Pulmonary Tuberculosis During Treatment of Chronic Myelomonocytic Leukemia\nMuacevic Alexander\nAdler John R\nPescatore Jay 1\nCohen Ashley 2\nMoturi Krishna 1\nHernandez-Acosta Ruben 1\n1 Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, USA\n2 Emergency Medicine, University of Michigan, Ann Arbor, USA\nJay Pescatore jay.mark.pescatore@gmail.com\n7 6 2021\n6 2021\n13 6 e154917 6 2021\nCopyright © 2021, Pescatore et al.\n2021\nPescatore et al.\nhttps://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.\nThis article is available from https://www.cureus.com/articles/58715-reactivation-of-pulmonary-tuberculosis-during-treatment-of-chronic-myelomonocytic-leukemia\nA 76-year-old woman from a tuberculosis (TB) endemic region with chronic myelomonocytic leukemia (CMML) on Azacitidine presented with a non-productive cough. A CT scan of the chest revealed a lobulated opacity in the right upper lobe and antibiotic therapy was initiated for a potential bacterial pneumonia. However, a high suspicion for pulmonary TB remained given her nation of origin, immunosuppression, and imaging findings. Three sputum and bronchoalveolar lavage (BAL) acid-fast bacilli (AFB) smears with PCR testing for Mycobacterium tuberculosis were negative, as were examinations for other potential fungal or bacterial etiologies of the patient’s symptoms and imaging findings. While awaiting final TB culture results from BAL, her CMML underwent a transformation to acute myeloid leukemia (AML). Given the urgent need for initiation of chemotherapy, empiric treatment for TB was commenced while awaiting the final TB culture. Within 48-hours of initiating therapy for TB, the patient’s fevers subsided. One week after discharge our team was notified of a positive M. tuberculosis culture from BAL. We suspect that our patient had a latent TB infection which reactivated due to her CMML. This case highlights the importance of maintaining a high clinical suspicion for TB in high-risk patients, even in the case of initially negative laboratory examinations. Further, it demonstrates the importance of screening and treating latent TB in patients with leukemias.\n\nactive pulmonary tuberculosis\nchronic myelomonocytic leukemia\nlatent tuberculosis infection\ntuberculosis/ transmission\ntuberculosis testing\nmicrobiology\ninfection microbiology\nThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\nIntroduction\n\nActive tuberculosis (TB) most often results from the reactivation of a prior latent infection. Populations of individuals including those with HIV, solid organ transplant history, chronic renal failure, or diabetes have been identified by both the Centers for Disease Control (CDC) and American Thoracic Society (ATS) as at high risk for developing active TB [1].\n\nThis case highlights the importance of awareness of the increased risk for reactivation TB in patients with myelodysplastic syndrome/myeloproliferative disorder (MDS/MPD), particularly those from TB-endemic regions. It also demonstrates the importance of screening and treatment of latent TB in patients with leukemia. Further, it reinforces the importance of clinical judgement in cases where confirmatory exam results may take prolonged periods of time to result.\n\nThis case report has been presented at the 2020 national CHEST conference (https://journal.chestnet.org/article/S0012-3692(20)32659-3/fulltext). \n\nCase presentation\n\nA 76-year-old woman with a four-month history of chronic myelomonocytic leukemia (CMML) being treated with Azacitidine presented to the emergency department with a chief complaint of a non-productive cough for one month. She endorsed 10 days of recurrent fevers, pleuritic chest pain, and night sweats. She also reported a 10 lb weight loss which she had attributed to a decreased appetite from chemotherapy. She denied any recent travel history but did mention that her husband was treated for latent TB 10 years prior.\n\nOn the initial examination, the patient was tachycardic, afebrile, and otherwise hemodynamically stable. Other than a mild leukocytosis to 12.5 k/µL, laboratory examinations were unremarkable. A chest CT scan revealed a new lobulated opacity of the right upper lobe as well as new mediastinal, supraclavicular, and upper abdominal lymphadenopathy (Figure 1). This was as compared to CT imaging performed at the time of her initial CMML diagnosis four months earlier.\n\nFigure 1 Cross-sectional CT Chest of Right Upper Lobe Opacity\n\nThe patient was admitted and empirically started on vancomycin and meropenem for hospital-acquired pneumonia. Given her history of TB exposure, current immunosuppression, and the radiologic findings, a high suspicion for TB remained. However, early in her hospitalization, three acid-fast bacilli (AFB) smears with nucleic-acid amplification testing (NAAT-PCR) for Mycobacterium tuberculosis were negative. Throughout the hospital course and despite treatment with broad-spectrum antibiotics the patient continued to have a persistent fever with an oral temperature maximum of 38.7 °C and at least one reading of 37.9 °C or higher daily during the first eight days of admission. This prompted further infectious diseases work-up, with a particular focus on fungal infections which might have mimicked the presentation of TB. Such examinations included serum galactomannan, beta-D-glucan, cryptococcal antigen, urinary Legionella, Blastomyces, and Histoplasma antigens, all of which were negative. A QuantiFERON Gold (IFN-gamma release assay) was positive. Given the patient’s continued symptoms, negative infectious diseases work-up, and unresponsiveness to antibiotic therapy, TB was still suspected. The patient continued to have only scant sputum production despite induction attempts; therefore, a bronchoscopy was planned in order to obtain bronchoalveolar lavage (BAL) in hopes of better targeting her therapies. BAL from the patient’s right upper lobe tested negative for fungal antigens and were culture-negative for bacteria or fungi. The AFB smear and PCR from the BAL were also negative, but formal BAL TB cultures were ordered.\n\nDiscussion\n\nPatients with hematologic malignancies are considered a high-risk group for having active TB, most notably lymphoma and myelodysplastic syndrome/myeloproliferative disorder (MDS/MPN) [2]. In a large population-based cohort study patients with MDS, MPN, or lymphoma were found to have the greatest risk for TB in comparison to patients with other malignancies [2]. This increased susceptibility to TB is either a direct consequence of immunosuppression from the malignancy, secondary to therapy, or a combination of both. The malignancy-related decrease in T cells, especially CD4 type, directly results in immunosuppression. Therapy with corticosteroids, fludarabine, or hematopoietic stem cell transplantation may also play a significant role in further suppression of T cell function [3]. Case reports of platinum-based chemotherapeutic agents and radiation therapy have also been reported to cause immunosuppression allowing for reactivation of TB [4].\n\nWe suspect that our patient from a TB-endemic region with a known exposure to latent TB had latent TB infection herself which was subsequently reactivated. We propose that the reactivation in this patient was primarily the result of her CMML, classified as an overlap of MDS/MPN. It is also possible that the patient’s treatment with the antimetabolite therapy Azacitidine, through further immunosuppression and dampening of T-cell responses, contributed to her risk for reactivation as well. Although Azacitidine has been reported to cause pneumonitis [5], no incidents of TB have been reported in prior case reviews [6,7]. It is possible, however, that Azacitidine, in causing a dose-dependent loss of T-cell populations, could increase the risk for reactivation of TB [8].\n\nConclusions\n\nIn this case, a high index of clinical suspicion for tuberculosis, despite negative AFB smears and NAAT-PCR, allowed for the timely treatment of the patient. This case highlights the importance of an awareness of the increased risk for TB reactivation in patients with MDS/MPN, particularly those from TB-endemic regions. It also demonstrates the importance of screening for and treatment of latent TB in patients with leukemias. Further, it reinforces the importance of clinical judgement in cases where confirmatory examination results may take prolonged periods of time.\n\nHuman Ethics\n\nThe authors have declared that no competing interests exist.\n\nConsent was obtained or waived by all participants in this study\n==== Refs\nReferences\n\n1 Targeted tuberculin testing and treatment of latent tuberculosis infection 42021 American Thoracic Society & Centers for Disease Control and Prevention 2000 http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4906a1.htm\n2 The risk of tuberculosis in cancer patients is greatest in lymphoma and myelodysplastic syndrome/myeloproliferative neoplasm: a large population-based cohort study Leuk Lymphoma Ganzel C Silverman B Chemtob D Ben Shoham A Wiener-Well Y 720 725 60 2019 http://doi.org/10.1080/10428194.2018.1499904 30188229\n3 Risk factors for and attributable mortality from tuberculosis in patients with hematologic malignances Haematologica Silva FA Matos JO de Q Mello FC Nucci M 1110 1115 90 2005 https://pubmed.ncbi.nlm.nih.gov/16079111/ 16079111\n4 Reactivation of pulmonary tuberculosis during cancer treatment Int J Mycobacteriol Jacobs RE Gu P Chachoua A 337 340 4 2015 http://doi.org/10.1016/j.ijmyco.2015.05.015 26964818\n5 How to diagnose early 5-Azacytidine-induced pneumonitis: a case report Drug Saf Case Rep Misra SC Gabriel L Nacoulma E Dine G Guarino V 4 4 2017 http://doi.org/10.1007/s40800-017-0047-y 28217822\n6 Treatment of chronic myelomonocytic leukemia with 5-Azacitidine: a case series and literature review Leuk Res Thorpe M Montalvão A Pierdomenico F Moita F Almeida A 1071 1073 36 2012 https://doi.org/10.1016/j.leukres.2012.04.024 22607959\n7 Activity of azacitidine in chronic myelomonocytic leukemia Cancer Costa R Abdulhaq H Haq B 2690 2696 117 2011 http://doi.org/10.1002/cncr.25759 21656746\n8 5-azacytidine promotes an inhibitory T-cell phenotype and impairs immune mediated antileukemic activity Mediators Inflamm Stübig T Badbaran A Luetkens T 418292 2014 2014 http://doi.org/10.1155/2014/418292 24757283\n\n",
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"literaturereference": "GLAUSER M, PAYMAN V. FALLING FOR HER PSYCHIATRIST: AN UNUSUAL CAUSE OF FALLS IN THE ELDERLY. INT PSYCHOGERIATR. 2016;28(4):695-6.",
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{
"abstract": "We encountered two patients with hepatocellular carcinoma (HCC) who showed rapid progression of liver failure during sorafenib treatment. One had portal vein tumor thrombus (PVTT) and the other developed portal vein thrombosis (PVT) during the treatment, and both of them experienced the elevation of serum lactate dehydrogenase (LDH) concentration during the administration of sorafenib. Their clinical courses indicate that the liver failure might have been caused by sorafenib-induced liver hypoxia, being amplified in the circumstances with reduced portal flow. To our best knowledge, all the reported patients who achieved complete remission (CR) during sorafenib monotherapy had a condition that could decrease portal blood flow. We hypothesized that pathogenesis of disease may be similar in HCC patients who achieve CR and those who experience liver failure while on sorafenib. Sorafenib treatment of patients with HCC and deteriorated portal flow may be a double-edged sword.",
"affiliations": "Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.",
"authors": "Yamasaki|Akihiro|A|;Umeno|Narihiro|N|;Harada|Shigeru|S|;Tanaka|Kosuke|K|;Kato|Masaki|M|;Kotoh|Kazuhiro|K|",
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"country": "China",
"delete": false,
"doi": "10.21037/jgo.2015.10.07",
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"issn_linking": "2078-6891",
"issue": "7(3)",
"journal": "Journal of gastrointestinal oncology",
"keywords": "Sorafenib; hepatocellular carcinoma (HCC); liver failure",
"medline_ta": "J Gastrointest Oncol",
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"nlm_unique_id": "101557751",
"other_id": null,
"pages": "E36-40",
"pmc": null,
"pmid": "27284486",
"pubdate": "2016-06",
"publication_types": "D002363:Case Reports",
"references": "20479781;23914915;17071608;19247201;24348819;19789317;20809183;20309643;21347197;18650514;21457447;23525021;23857091;24552144;21633647;19095497;22563643;23556056;24621095;22687270;21829024;21241463;21263091;19944333;23902251;23426789",
"title": "Deteriorated portal flow may cause liver failure in patients with hepatocellular carcinoma being treated with sorafenib.",
"title_normalized": "deteriorated portal flow may cause liver failure in patients with hepatocellular carcinoma being treated with sorafenib"
} | [
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{
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{
"abstract": "No major complications have been associated with the ultrasound-guided continuous adductor canal block (cACB). We present a case of iatrogenic pseudoaneurysm in a branch of the superficial femoral artery in a 44-year-old patient after a cACB for knee surgery. Both anesthesia and surgery were completed uneventfully. The postoperative day 3 examination showed a complete quadricep impairment and a large hematoma in a medial-anterior part of the thigh, and laboratory tests reported hemoglobin = 7.2 g dL. The computed tomography scan revealed the pseudoaneurysm (16 × 16 × 18 mm) that was successfully embolized after selective catheterization. The patient was discharged regularly on postoperative day 12.",
"affiliations": "From the *Istituto Ortopedico G. Pini, Milan, Italy; †Università dell'Insubria di Varese, Varese, Italy; and ‡Università degli studi di Milano, Milano, Italy.",
"authors": "Cappelleri|Gianluca|G|;Molinari|Pietro|P|;Stanco|Antonella|A|",
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"mesh_terms": "D000328:Adult; D017541:Aneurysm, False; D001340:Autonomic Nerve Block; D005263:Femoral Artery; D006801:Humans; D007049:Iatrogenic Disease; D008297:Male",
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"pages": "200-202",
"pmc": null,
"pmid": "27552243",
"pubdate": "2016-11-01",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Iatrogenic Pseudoaneurysm After Continuous Adductor Canal Block.",
"title_normalized": "iatrogenic pseudoaneurysm after continuous adductor canal block"
} | [
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{
"abstract": "We report the case of an eradicated multiresistant Serratia marcescens prosthetic hip joint infection. It is estimated that enteric Gram-negative organisms account for approximately 8% of prosthetic joint infections. However, the evolving multiresistant strains of organisms being encountered in hospital acquired infections is making eradication increasingly difficult. We describe n our surgical and microbiological approach to this in a complex case.",
"affiliations": "Sheffield Teaching Hospitals NHS Foundation Trust, UK.",
"authors": "Cannon|T A|TA|;Partridge|D G|DG|;Boden|R A|RA|;Townsend|R|R|;Stockley|I|I|",
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"medline_ta": "Ann R Coll Surg Engl",
"mesh_terms": "D000900:Anti-Bacterial Agents; D019644:Arthroplasty, Replacement, Hip; D002939:Ciprofloxacin; D005839:Gentamicins; D006801:Humans; D008297:Male; D008875:Middle Aged; D016459:Prosthesis-Related Infections; D016868:Serratia Infections; D012706:Serratia marcescens",
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"pmid": "25350172",
"pubdate": "2014-11",
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"title": "Case report of a successfully treated gentamicin and ciprofloxacin resistant Serratia marcescens prosthetic joint infection.",
"title_normalized": "case report of a successfully treated gentamicin and ciprofloxacin resistant serratia marcescens prosthetic joint infection"
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] |
{
"abstract": "BACKGROUND\nSpontaneous spinal subdural hematoma (SSDH) is a rare but disabling condition, accounting for only 4.1% of all intraspinal hematomas. Risk factors include arteriovenous malformations, coagulopathy, therapeutic anticoagulation, underlying neoplasms, or following spinal puncture. Vitamin K antagonists, antiplatelet agents, and heparinoids have been associated with SSDHs in prior reports. To the best of our knowledge, no cases have reported this association with the factor Xa inhibitor, rivaroxaban, and SSDHs.\n\n\nMETHODS\nWe report the case of a 69-year-old Honduran man with a 5-year history of symptomatic palpitations due to non-valvular atrial fibrillation. He was initially refractory to pharmacologic therapy. He underwent cardioversion in February 2014. After cardioversion, he remained asymptomatic on flecainide. He was anticoagulated on rivaroxaban 20 mg daily without incident since early 2013 until presentation in August 2014. He presented with sudden onset of excruciating upper and lower back pain after minimal movement. This was immediately followed by bilateral lower extremity paresis rapidly progressing to paraplegia with bowel and bladder dysfunction over 15 minutes. Magnetic resonance imaging demonstrated an acute spinal subdural hematoma extending from T3 inferiorly to the conus medullaris. Six months after undergoing cervical and lumbar drainage procedures, he has not recovered bowel, bladder, or lower extremity neurologic function.\n\n\nCONCLUSIONS\nNon-traumatic spontaneous spinal subdural hematoma is a rare neurological emergency that may occur during the use of rivaroxaban in patients with non-valvular atrial fibrillation. Physicians should suspect SSDH in patients on rivaroxaban with acute onset of severe back pain and neurologic symptoms to improve the odds of a favorable outcome.",
"affiliations": "Department of Internal Medicine, University of Miami/Jackson Memorial Hospital, Miami, FL, USA.;Department of Internal Medicine, University of Miami/Jackson Memorial Hospital, Miami, FL, USA.;Department of Internal Medicine, University of Miami/Jackson Memorial Hospital, Miami, FL, USA.;Department of Internal Medicine, University of Miami/Jackson Memorial Hospital, Miami, FL, USA.",
"authors": "Castillo|Jessica M|JM|;Afanador|Hayley F|HF|;Manjarrez|Efren|E|;Morales|Ximena A|XA|",
"chemical_list": "D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban",
"country": "United States",
"delete": false,
"doi": "10.12659/AJCR.893320",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1941-5923",
"issue": "16()",
"journal": "The American journal of case reports",
"keywords": null,
"medline_ta": "Am J Case Rep",
"mesh_terms": "D000368:Aged; D001281:Atrial Fibrillation; D065427:Factor Xa Inhibitors; D046649:Hematoma, Subdural, Spinal; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D000069552:Rivaroxaban",
"nlm_unique_id": "101489566",
"other_id": null,
"pages": "377-81",
"pmc": null,
"pmid": "26090890",
"pubdate": "2015-06-19",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "10419371;10507957;11725255;12520314;13244833;15347012;18894192;19717844;19762550;21830957;21870978;21874549;21945405;23988138;24055744;24251359;29252220",
"title": "Non-Traumatic Spontaneous Spinal Subdural Hematoma in a Patient with Non-Valvular Atrial Fibrillation During Treatment with Rivaroxaban.",
"title_normalized": "non traumatic spontaneous spinal subdural hematoma in a patient with non valvular atrial fibrillation during treatment with rivaroxaban"
} | [
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},
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"drugenddate": "20140731",
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"drugindication": "ANTICOAGULANT THERAPY",
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],
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"reaction": [
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"reactionmeddrapt": "Spinal subdural haematoma",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "3"
},
{
"reactionmeddrapt": "Spinal cord haemorrhage",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Myelitis transverse",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Spinal cord compression",
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},
{
"reactionmeddrapt": "Spinal subarachnoid haemorrhage",
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}
],
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"abstract": "Objective: Differential diagnosis of neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) or mimics can be challenging, especially in patients with atypical presentations and negative serostatus for aquaporin-4 antibodies (AQP4-Ab). This brief research report describes magnetic resonance imaging (MRI) findings focusing on quantitative apparent diffusion coefficient (ADC) histogram analysis as a potential tool to differentiate NMOSD from MS. Methods: Longitudinal MRI data obtained during routine clinical examinations were retrospectively analyzed in a patient with histologically determined cerebral NMOSD, a patient with an acute tumefactive MS lesion, and a patient with ischemic stroke. Histogram analyses of ADC maps were evaluated. Results: A patient diagnosed with MS experienced a severe rebound after fingolimod withdrawal and a single daclizumab injection. Cerebral NMOSD manifestation was confirmed by brain biopsy. However, the patient did not fulfill consensus criteria for NMOSD and was AQP4-Ab negative. Comparison of ADC histogram analyses of this patient with those from a patient with MS and one with ischemic stroke revealed differential ADC characteristics: namely a more pronounced and prolonged ADC leftward shift in inflammatory than in ischemic pathology, even more accentuated in NMOSD versus MS. Conclusion: ADC map histograms and ADC threshold values for different conditions may be useful for differentiation of large inflammatory brain lesions and further studies are merited.",
"affiliations": "Department of Diagnostic and Interventional Neuroradiology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.;Department of Diagnostic and Interventional Neuroradiology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.;Department of Diagnostic and Interventional Neuroradiology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.;Department of Neurology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.;Institute of Clinical Chemistry, Inselspital, University Hospital and University of Bern, Bern, Switzerland.;Department of Neurology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.;Department of Neurology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.;Department of Diagnostic and Interventional Neuroradiology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.;Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.;Department of Neurology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.;Department of Neurology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.",
"authors": "Wagner|Franca|F|;Grunder|Lorenz|L|;Hakim|Arsany|A|;Kamber|Nicole|N|;Horn|Michael P|MP|;Muellner|Julia|J|;Hoepner|Robert|R|;Wiest|Roland|R|;Metz|Imke|I|;Chan|Andrew|A|;Salmen|Anke|A|",
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"doi": "10.3389/fneur.2018.00782",
"fulltext": "\n==== Front\nFront NeurolFront NeurolFront. Neurol.Frontiers in Neurology1664-2295Frontiers Media S.A. 10.3389/fneur.2018.00782NeurologyBrief Research ReportRebound After Fingolimod and a Single Daclizumab Injection in a Patient Retrospectively Diagnosed With NMO Spectrum Disorder—MRI Apparent Diffusion Coefficient Maps in Differential Diagnosis of Demyelinating CNS Disorders Wagner Franca 1*†Grunder Lorenz 1†Hakim Arsany 1Kamber Nicole 2Horn Michael P. 3Muellner Julia 2Hoepner Robert 2Wiest Roland 1Metz Imke 4Chan Andrew 2Salmen Anke 21Department of Diagnostic and Interventional Neuroradiology, Inselspital, University Hospital and University of Bern, Bern, Switzerland2Department of Neurology, Inselspital, University Hospital and University of Bern, Bern, Switzerland3Institute of Clinical Chemistry, Inselspital, University Hospital and University of Bern, Bern, Switzerland4Institute of Neuropathology, University Medical Center Göttingen, Göttingen, GermanyEdited by: Jorge Matias-Guiu, Complutense University of Madrid, Spain\n\nReviewed by: Bonaventura Casanova, Hospital Universitari i Politècnic La Fe, Spain; Ester Moral, Hospital de Sant Joan Despí Moisès Broggi, Spain\n\n*Correspondence: Franca Wagner franca.wagner@insel.chThis article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Neurology\n\n†These authors have contributed equally to this work\n\n27 9 2018 2018 9 78207 7 2018 30 8 2018 Copyright © 2018 Wagner, Grunder, Hakim, Kamber, Horn, Muellner, Hoepner, Wiest, Metz, Chan and Salmen.2018Wagner, Grunder, Hakim, Kamber, Horn, Muellner, Hoepner, Wiest, Metz, Chan and SalmenThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Objective: Differential diagnosis of neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) or mimics can be challenging, especially in patients with atypical presentations and negative serostatus for aquaporin-4 antibodies (AQP4-Ab). This brief research report describes magnetic resonance imaging (MRI) findings focusing on quantitative apparent diffusion coefficient (ADC) histogram analysis as a potential tool to differentiate NMOSD from MS.\n\nMethods: Longitudinal MRI data obtained during routine clinical examinations were retrospectively analyzed in a patient with histologically determined cerebral NMOSD, a patient with an acute tumefactive MS lesion, and a patient with ischemic stroke. Histogram analyses of ADC maps were evaluated.\n\nResults: A patient diagnosed with MS experienced a severe rebound after fingolimod withdrawal and a single daclizumab injection. Cerebral NMOSD manifestation was confirmed by brain biopsy. However, the patient did not fulfill consensus criteria for NMOSD and was AQP4-Ab negative. Comparison of ADC histogram analyses of this patient with those from a patient with MS and one with ischemic stroke revealed differential ADC characteristics: namely a more pronounced and prolonged ADC leftward shift in inflammatory than in ischemic pathology, even more accentuated in NMOSD versus MS.\n\nConclusion: ADC map histograms and ADC threshold values for different conditions may be useful for differentiation of large inflammatory brain lesions and further studies are merited.\n\nMRIADChistogram analysisMSmultiple sclerosisneuromyelitis opticaNMOSD\n==== Body\nIntroduction\nNeuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory disorders of the central nervous system (CNS) that can have clinical and radiological overlaps. Differential diagnosis can be challenging, especially in patients with NMOSD who test negative for aquaporin-4 antibodies (AQP4-Ab, up to 20%) (1–3). This is a matter of high clinical relevance as MS drugs may not only lack efficacy in patients with NMOSD but might even be harmful (4–7). Additional objective markers that distinguish AQP4-Ab-negative NMOSD from MS are thus needed.\n\nWe report on a patient treated for relapsing–remitting MS (RRMS) who experienced a severe rebound of an inflammatory CNS disorder after cessation of fingolimod and overlapping initiation of daclizumab. In this patient with negative serum AQP4-Ab and anti-myelin-oligodendrocyte-glycoprotein (MOG-)Ab, brain biopsy revealed neuropathological characteristics of NMOSD.\n\nAcute demyelinating CNS lesions are described as exhibiting restricted diffusion (8). Nevertheless, routine magnetic resonance imaging (MRI) including diffusion-weighted sequences cannot differentiate between acute inflammatory and ischemic entities. Therefore, textural analysis methods in MRI are receiving increased attention. We discuss the potential use of quantitative apparent diffusion coefficient (ADC) histogram analysis on cranial MRI as a diagnostic tool that may aid in differentiation between MS and NMOSD.\n\nMethods\nThe local ethics committee (Kantonale Ethikkommission Bern, Switzerland, KEK-BE reg. no. 2016-02035, 2017-01369) gave approval for access to and use of the patient data for retrospective clinical research. All data presented were obtained during routine clinical investigations and retrospectively analyzed in a pseudonymized fashion.\n\nA retrospective case analysis of an NMOSD patient followed the clinical evolution, paraclinical findings, and MRI results. A longitudinal case study using quantitative MRI analysis was performed to compare the NMOSD patient with an RRMS patient during relapse, and a patient with acute ischemic stroke.\n\nThe routine clinical MRI protocol for MS included the following non-contrast sequences: diffusion-weighted imaging, 3D T1w MP-RAGE and 3D T2w GRE. After contrast application, PD/T2w, axial T1w SE, and 3D T1w MP-RAGE were acquired. ADC maps were evaluated longitudinally (b = 0, b = 1,000 s/mm2, monoexponential ADC calculation) on a pixel-by-pixel basis for the diffusion-restricted area and used for histogram analysis (9). For the analysis of the ADC maps, we used commercially available software for automated and multivendor postprocessing (Olea Sphere®, version number 3.0-SP11). The lesion voxels collected from the contoured regions of interest (ROIs) provided histograms from which dispersion parameters were computed (9). For all measurements, we used the ADCs provided by the imaging system, with a reference value for water of 2.3 × 10−9 m2/s.\n\nEach MRI examination generated multiple sections with abnormal ROIs. Skewness and kurtosis derived from the histograms reflected the shape of each histogram. Kurtosis is a measure of the peak of the histogram. It is zero if there is a Gaussian distribution, positive if it has a sharp peak, and negative if it has a flat plateau. Skewness is a measurement of the histogram asymmetry. It is zero when the majority of the data are concentrated in the midline, positive if the majority of data are concentrated to the left of the mean, and negative if the majority of data are concentrated to the right of the mean.\n\nResults\nClinical findings\nOur patient was diagnosed with RRMS in 2002 after a severe first relapse with hemiparesis on the right side. She was treated with interferon-beta from 2003 until 2015. Owing to insufficient clinical response and continuing relapse activity, as well as side effects, her treatment was switched to fingolimod in 2015. Relapse phenotypes were described by the patient as having included optic neuritis (right) and coordination problems with the right hand. During fingolimod treatment, ongoing MRI activity was detected. In 2016, the fingolimod dosage was reduced due to lymphopenia (0.5 mg, 5 times a week). Since the lymphopenia did not resolve, fingolimod was finally stopped in March 2017 (last documented lymphocyte value 0.38 G/l) and daclizumab was started at the end of April 2017 (documented normalization of lymphocyte count to 1.37 G/l). Only 7 days after the first administration of daclizumab, severe progressive neurological deterioration occurred. The patient initially showed quadrant anopsia (lower right quadrant), which progressed rapidly despite early initiation of high-dose steroids. When she was referred to our hospital only 2 days later, the patient showed hemiplegia with neglect and hemianopsia (right), global aphasia, dysphagia and reduced consciousness (EDSS 9.5).\n\nOver the course of 15 days, the five MR brain scans of our patient conducted within this period revealed markedly progressive T2/FLAIR-hyperintense signal alterations in the left hemisphere from the frontoparietal region to the occipital lobe with increasing patchy contrast enhancement in the confluent lesion.\n\nLaboratory findings\nCSF analysis demonstrated 25 cells/μl with lympho-monocytic pleocytosis and presence of CSF-specific oligoclonal bands (OCB). Highly sensitive polymerase chain reaction (PCR) detected neither JC virus DNA nor HSV or VZV DNA. The results of serological screening for infectious agents were negative (hepatitis B/C, HIV, Borrelia burgdorferi, Treponema pallidum, Mycobacterium tuberculosis). Differential screening tests for vasculitis and connectivitis were negative. Repeated testing for AQP4-Ab (cell-based assay: IIFT, Euroimmun AG, Lübeck, Germany) was negative. Retrospective testing of the first plasma exchange (PLEX) specimen was negative for AQP4-Ab and MOG-Ab. All tests were performed after admission to our hospital following a previous pulsed steroid treatment at another location.\n\nBrain biopsy\nBrain biopsy was performed due to further deterioration despite two high-dose steroid pulses and seven sessions of plasma exchange, presenting with a seizure of focal onset. The biopsy showed an inflammatory demyelinating lesion (Supplementary Material). The inflammatory infiltrate consisted of numerous macrophages with macrophage-derived foam cells, and a CD8+-dominated T cell infiltrate. The demyelination was patchy. Strikingly, the lesion showed astropathic changes with a reduction of astrocytes and AQP4 loss within the lesion areas. These changes are typical for NMOSD, but not for MS. Also typical for NMOSD, was loss of oligodendrocytes. CD20-positive B-cells were found in perivascular compartments. Complement or immunoglobulin (Ig) deposits around vessels or eosinophils within lesions—changes observed especially in early active NMOSD lesions—were not present (10). The brain biopsy showed no evidence for progressive multifocal leukoencephalopathy or lymphoma.\n\nClinical evolution\nThe patient initially received acyclovir as a co-treatment; and sequentially high-dose pulsed steroids and PLEX. Beginning clinical remission was noted. Follow-up MRI 1 month later showed that the lesion extent had decreased. With the help of extensive rehabilitation therapy, the patient further improved (last documented EDSS 5.0). Long-term treatment with rituximab was initiated 8 weeks after symptom onset (total dosage 1,500 mg) and the patient exhibited clinical and radiological stability at the time of writing (after approximately 6 months of follow-up).\n\nADC histogram: differences between entities\nHead MRI on admission (before biopsy) indicated a large FLAIR hyperintense and diffusion-restricted periventricular white matter lesion located in the parietal, occipital and frontal lobe with faint contrast enhancement in the anterior portion of the lesion (Figure 1A). Spinal MRI showed a non-enhancing T2-hyperintense lesion at the C3–4 level, which had been noted on previous scans, and two focal non-enhancing lesions in the conus medullaris.\n\nFigure 1 MRI in the acute phase of NMOSD (A), tumefactive MS (B), and ischemic stroke (C). (A–C): Apparent diffusion coefficient (ADC) map (left), transverse FLAIR-attenuated inversion recovery weighted scan (middle), transverse contrast-enhanced T1 weighted scan (right) for the NMOSD patient (A), the patient with tumefactive MS (B) and the patient with ischemic stroke (C). In (B) the contrast enhancement in basal ganglia on the left corresponds to a developmental venous anomaly.\n\nTo detect potential differences in MRI features between patients with NMOSD, MS, and ischemic stroke, we compared longitudinal MRI data from our NMOSD patient, acquired in the acute phase (day 3 from symptom onset; Figure 1A), with an RRMS patient who had an acute tumefactive MS lesion (Figure 1B) and a patient who had had an acute ischemic stroke (Figure 1C).\n\nIn the patient with histopathological features of NMOSD, the ADC maps showed restricted periventricular diffusion in the frontal, parietal and occipital lobe with corresponding signal abnormalities on FLAIR-weighted imaging and mild focal contrast enhancement. Similarly, in the RRMS patient with a tumefactive MS lesion, there was a periventricular ADC restriction in the frontal, parietal, and occipital lobe and in the splenium. This, again, was associated with corresponding signal abnormalities on FLAIR-weighted imaging and diffuse focal contrast enhancement. Quantitative ADC maps for the patient with acute ischemic stroke showed restricted periventricular diffusion in the caudate nucleus and in the frontal lobe, and signal abnormalities on FLAIR-weighted imaging, but no contrast enhancement. The signal characteristics of FLAIR and ADC were similar and thus could not be used to differentiate between the entities.\n\nAll three patients underwent several follow-up MRIs with anatomic and diffusion-weighted sequences. The mean ROI-based ADC values, skewness and kurtosis were determined from the MRIs from the patients with brain lesions and ischemic stroke, respectively (see Supplementary Material). ADC values were reduced in NMOSD, MS and ischemic stroke, with a corresponding skewness of the ADC histograms when compared with normal tissue (normal white matter ADC values range from 670 to 800*10−6mm2/s). (11) In this one-to-one, days-after-onset comparison and follow-up, the leftward shift in the NMOSD patient was more distinct and prolonged than those seen in the MS and ischemic stroke patients (Figures 2A–C). Skewness in the patient with ischemic stroke was markedly less pronounced than in those with MS and NMOSD.\n\nFigure 2 ROI mean ADC signal intensity of NMOSD (A), tumefactive MS (B), and ischemic stroke (C). Mean ADC values of abnormal ROIs in NMOSD (2A), MS (2B) and ischemic stroke (2C) at the time of initial MR and at follow-up; with histogram analysis for comparison.\n\nDiscussion\nWe describe a patient with histopathological changes typical of NMOSD with clear astrocytopathy and AQP4 loss. However, this patient did not fulfill the diagnostic consensus criteria for NMOSD, (2) meeting only one clinical core criterion (cerebral manifestation), and showing absence of longitudinal extensive transverse myelitis (LETM) or clear optic neuritis, and AQP4-Ab negativity.\n\nThe classical structural pattern of NMOSD is extensive lesions, particularly in the spinal cord (presenting as LETM) and the optic nerve. However, revised diagnostic criteria emphasize other sites of inflammation such as the area postrema, brainstem, and diencephalon, as well as cerebral manifestations (2).\n\nIn retrospect, the history of optic neuritis—described by the patient, but not distinctly mentioned in her previous medical records—might have led NMOSD to be considered earlier. However, optic neuritis is a very common symptom in MS too, and only now is MRI able to demonstrate different patterns of optic neuritis in MS versus NMOSD (2). An imaging-based differential diagnosis with older scans would thus have been be highly unlikely.\n\nThe patient was seronegative for both AQP4-Ab and MOG-Ab assessed in a cell-based assay. Up to 20% of NMOSD patients are seronegative (3). As immunomodulatory treatments including steroids may influence these results, we cannot exclude false-negative findings (12). This reflects a common clinical dilemma as the diagnostic process often runs in parallel with already administered acute treatments.\n\nIn this case, the additional diagnostic findings, especially the CSF results showing lympho-monocytic pleocytosis and presence of CSF-specific OCB, did not help in differentiating NMOSD from MS. For OCB, frequencies up to 30% in NMOSD patients have been reported (3).\n\nInterestingly, in our patient's previous MRI scans, brain pathology before the current attack was not highly suggestive of long-standing MS. Scans over the 15-years disease course demonstrated only a few rather unspecific lesions, except for one larger lesion adjacent to the left ventricle. The overall lesion burden was thus low. The spinal cord had focal, non-LETM lesions. This is usually considered as being MS-specific; however, short transverse myelitis is also a common phenomenon in NMOSD and has been found to delay diagnosis and treatment of NMOSD (13).\n\nNMOSD with cerebral pathology was only differentiated from MS, after 15 years of disease course, by brain biopsy. Even so, not all the described features of NMOSD were found in the biopsy material (10). This again might have been influenced by both the timing of the biopsy and previous administration of acute treatments including steroids and plasma exchange. Eosinophilic infiltration and complement or Ig deposition as markers of early active lesions were thus not detectable. However, the pattern of extensive macrophage infiltration, loss of AQP4, astrocytes and oligodendrocytes, together with perivascular B-cell infiltration was highly suggestive.\n\nThe lack of typical LETM or clear optic neuritis and negative AQP4-Ab together with the suboptimal response to treatment with interferon-beta and fingolimod may never have led to consideration of NMOSD, as this is also seen in MS. However, after cessation of fingolimod, severe disease exacerbation was noted. This rebound phenomenon has recently been described in MS patients, (14–16) but also as a potentially severe phenomenon in patients with NMOSD (6). In our patient, rebound occurred sooner than reported in the literature. Early re-initiation of therapy, within 1 month, with a highly active compound, daclizumab, could not prevent fingolimod-associated rebound. As there is no information on IL-2 receptor blockade in NMOSD patients, it is not known whether daclizumab might have propagated the rebound. Given the short latency between the first and only injection of daclizumab and symptom onset, causality seemed unlikely. However, in light of the recent withdrawal from the market of daclizumab following eight cases of serious inflammatory brain disorders, (17) this possibility might need to be reconsidered once further information on these cases becomes available.\n\nAnatomical MRI findings of brain lesions can be typical of both NMOSD and MS (18). In particular, for intracranial NMOSD manifestation, cases with occipital lesions similar to our patient have been reported (19, 20). Involvement of the splenium in an “arch bridge pattern” as seen in the MS patient is actually more prevalent in NMOSD patients (18). Lesion enhancement in seronegative NMOSD patients is more prevalent than in seropositive ones, complicating both radiological and clinical differential diagnosis of large inflammatory brain lesions (21, 22). While asymptomatic or post-acute NMOSD brain lesions typically show high intensity on both DWI and ADC, there is a lack of literature about DWI and ADC imaging characteristics of symptomatic NMOSD brain lesions (23).\n\nWe compared the MRI characteristics of our patient to MRIs from patients with MS and ischemic stroke. NMOSD lesions display a loss of astrocytes (20, 24) as was evident in the biopsy material from our patient, which is atypical for MS. However, in anatomical MRI, this is not well represented. Quantitative and longitudinal MR analysis may further aid in this respect (9, 25).\n\nSkewness and kurtosis are relatively simple parameters that describe texture heterogeneity. Computer-aided texture analysis shows promise as a method for lesion characterization. It assesses and quantifies lesion characteristics using pixel values and/or their distribution within target lesions, providing a more detailed and reproducible quantitative assessment than is possible from visual analysis by human observers.\n\nIn our case comparison, a difference in ADC map histograms was detected. Skewness in ischemic stroke is markedly less pronounced than in MS and NMOSD. The texture parameter skewness may help to distinguish between these diseases. The difference can be summarized as a more pronounced and prolonged skewness in inflammatory brain pathology than in stroke and seems to be even more pronounced and prolonged in NMOSD than in MS. It is important to bear in mind that these are only observations in single patients and confirmation from larger studies is necessary.\n\nHowever, in several tumor studies, texture analysis with different imaging modalities has been shown to reflect tumor heterogeneity and was reported to be able to distinguish between multiple features—including imaging parameters, pathological subtypes, and genetic profiles—in various types of tumors (26–28). Therefore, in oncological imaging, textural analysis methods are already well established. Tumor heterogeneity can be caused by variations in cellularity, angiogenesis, extracellular matrix, or necrosis (29). Thus, quantification of ADC map histograms and definition of ADC threshold values for different diseases might represent a prospective, useful noninvasive imaging tool for differentiation of large inflammatory brain lesions. This should be further evaluated in future studies. Earlier differentiation could allow patients to be selected sooner and directed more quickly to the most appropriate treatment.\n\nConclusion\nADC map histograms and ADC threshold values for different conditions may be useful for differentiation of large inflammatory brain lesions and further studies are merited.\n\nAuthor contributions\nFW and AS collected all the references, wrote the main clinical part of the brief research report and contributed to the study design. FW, AC, and RW supervised the report. RH, JM, and NK were responsible for correction, and also contributed to the background clinical knowledge of our case. LG and AH contributed to the histogram analysis data collection. IM was in response for the histopathological statement. MH was in response for the laboratory findings and analysis.\n\nConflict of interest statement\nFW received a research grant from the Swiss MS Society, none related to the submitted work. RH received research and/or travel grants from Novartis, Biogen Idec and the Swiss MS Society and speaker's honoraria from Biogen, Novartis, Merk and Almirall, none related to this work. IM reports personal fees from BiogenIdec, Bayer Healthcare, TEVA, Serono, Novartis, Genzyme, and Roche as well as a grant from BiogenIdec, none related to the submitted work. AC received personal compensation for activities with Bayer, Biogen, Genzyme, Merck, Novartis, Roche, and Teva and research support from the Swiss National Science Foundation (SNF, No. 310030_172952), Genzyme and UCB. He serves on the editorial board of Clinical and Translational Neuroscience and the Journal of International Medical Research. AS received speaker's honoraria and/or travel compensation for activities with Almirall Hermal GmbH, Biogen, Merck, Novartis, Roche and Sanofi Genzyme, none related to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\n\nWe would like to thank Susan Kaplan for the language check of the manuscript.\n\nFunding. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\n\nSupplementary material\nThe Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2018.00782/full#supplementary-material\n\nClick here for additional data file.\n\n Click here for additional data file.\n\n Click here for additional data file.\n\n Click here for additional data file.\n\n Click here for additional data file.\n\n Click here for additional data file.\n\n Click here for additional data file.\n\n Click here for additional data file.\n\n Abbreviations\nADCapparent diffusion coefficient\n\nCNScentral nervous system\n\nCSFcerebrospinal fluid\n\nDWIdiffusion-weighted imaging\n\nLETMlongitudinal extensive transverse myelitis\n\nMSmultiple sclerosis\n\nNMOneuromyelitis optica\n\nNMOSDneuromyelitis optica spectrum disorder\n\nOCBoligoclonal bands\n\nPCRpolymerase chain reaction\n\nPLEXplasma exchange\n\nROIregion of interest.\n==== Refs\nReferences\n1. Thompson AJ Banwell BL Barkhof F Carroll WM Coetzee T Comi G . Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria . Lancet Neurol . (2017 ) 17 :162 –173 . 10.1016/S1474-4422(17)30470-2 29275977 \n2. Wingerchuk DM Banwell B Bennett JL Cabre P Carroll W Chitnis T . International consensus diagnostic criteria for neuromyelitis optica spectrum disorders . Neurology . (2015 ) 85 :177 –89 . 10.1212/WNL.0000000000001729 26092914 \n3. Hinson SR Lennon VA Pittock SJ . Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders . Handb Clin Neurol . (2016 ) 133 :377 –403 . 10.1016/B978-0-444-63432-0.00021-9 27112688 \n4. Gelfand JM Cotter J Klingman J Huang EJ Cree BAC . Massive CNS monocytic infiltration at autopsy in an alemtuzumab-treated patient with NMO . Neurol Neuroimmunol Neuroinflamm . (2014 ) 1 :e34 . 10.1212/NXI.0000000000000034 25340086 \n5. Kleiter I Hellwig K Berthele A Kümpfel T Linker RA Hartung HP . Failure of natalizumab to prevent relapses in neuromyelitis optica . Arch Neurol . (2012 ) 69 :239 –45 . 10.1001/archneurol.2011.216 22332191 \n6. Min JH Kim BJ Lee KH . Development of extensive brain lesions following fingolimod (FTY720) treatment in a patient with neuromyelitis optica spectrum disorder . Mult Scler . (2012 ) 18 :113 –5 . 10.1177/1352458511431973 22146605 \n7. Palace J Leite MI Nairne A Vincent A . Interferon Beta treatment in neuromyelitis optica: increase in relapses and aquaporin 4 antibody titers . Arch Neurol . (2010 ) 67 :1016 –7 . 10.1001/archneurol.2010.188 20697055 \n8. Balashov KE Lindzen E . Acute demyelinating lesions with restricted diffusion in multiple sclerosis . Mult Scler . (2012 ) 18 :1745 –53 . 10.1177/1352458512445407 22523157 \n9. Pope WB Kim HJ Huo J Alger J Brown MS Gjertson D . Recurrent glioblastoma multiforme: ADC histogram analysis predicts response to bevacizumab treatment . Radiology (2009 ) 252 :182 –9 . 10.1148/radiol.2521081534 19561256 \n10. Lucchinetti CF Mandler RN McGavern D Bruck W Gleich G Ransohoff RM . A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica . Brain (2002 ) 125 (Pt 7 ):1450 –61 . 10.1093/brain/awf151 12076996 \n11. Helenius J Soinne L Perkio J Salonen O Kangasmäki A Kaste M . Diffusion-weighted MR imaging in normal human brains in various age groups . AJNR Am J Neuroradiol . (2002 ) 23 :194 –9 . 11847041 \n12. Jiao Y Fryer JP Lennon VA Jenkins SM Quek AML Smith CY . Updated estimate of Aqp4-Igg serostatus and disability outcome in neuromyelitis optica . Neurology (2013 ) 81 :1197 –204 . 10.1212/WNL.0b013e3182a6cb5c 23997151 \n13. Flanagan EP Weinshenker BG Krecke KN Lennon VA Lucchinetti CF McKeon A . Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders . JAMA Neurol. (2015 ) 72 :81 –7 . 10.1001/jamaneurol.2014.2137 25384099 \n14. Berger B Baumgartner A Rauer S Mader I Luetzen N Farenkopf U . Severe disease reactivation in four patients with relapsing-remitting multiple sclerosis after fingolimod cessation . J Neuroimmunol . (2015 ) 282 :118 –22 . 10.1016/j.jneuroim.2015.03.022 25903738 \n15. Faissner S Hoepner R Lukas C Chan A Gold R Ellrichmann G . Tumefactive multiple sclerosis lesions in two patients after cessation of fingolimod treatment . Ther Adv Neurol Disord . (2015 ) 8 :233 –8 . 10.1177/1756285615594575 26557898 \n16. Hatcher SE Waubant E Nourbakhsh B Crabtree-Hartman E Graves JS . Rebound syndrome in patients with multiple sclerosis after cessation of fingolimod treatment . JAMA Neurol . (2016 ) 73 :790 –4 . 10.1001/jamaneurol.2016.0826 27135594 \n17. EMA Available online at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2018/03/news_detail_002917.jsp&mid=WC0b01ac058004d5c1 2018 (Accessed March 07, 2018).\n18. Kim HJ Paul F Lana-Peixoto MA Tenembaum S Asgari N Palace J . MRI characteristics of neuromyelitis optica spectrum disorder: an international update . Neurology (2015 ) 84 :1165 –73 . 10.1212/WNL.0000000000001367 25695963 \n19. Magana SM Matiello M Pittock SJ McKeon A Lennon VA Rabinstein AA . Posterior reversible encephalopathy syndrome in neuromyelitis optica spectrum disorders . Neurology (2009 ) 72 :712 –7 . 10.1212/01.wnl.0000343001.36493.ae 19237699 \n20. Lee DH Metz I Berthele A Stadelmann C Brück W Linker RA Gold R . Supraspinal demyelinating lesions in neuromyelitis optica display a typical astrocyte pathology . Neuropathol Appl Neurobiol . (2010 ) 36 :685 –7 . 10.1111/j.1365-2990.2010.01105.x 20618839 \n21. Eichel R Meiner Z Abramsky O Gotkine M \nAcute disseminating encephalomyelitis in neuromyelitis optica: closing the floodgates . Arch Neurol . 2008 :267 –71 . 10.1001/archneurol.2007.59 \n22. Jurynczyk M Weinshenker B Akman-Demir G Asgari N Barnes D Boggild M . 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(2013 ) 82 :e537 –43 . 10.1016/j.ejrad.2013.06.024 23910996 \n27. Miles KA Ganeshan B Rodriguez-Justo M Goh VJ Ziauddin Z Engledow A . Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer . J Nucl Med . (2014 ) 55 :386 –91 . 10.2967/jnumed.113.120485 24516257 \n28. Weiss GJ Ganeshan B Miles KA Campbell DH Cheung PY Frank S . Noninvasive image texture analysis differentiates K-ras mutation from pan-wildtype NSCLC and is prognostic . PLoS ONE (2014 ) 9 :e100244 . 10.1371/journal.pone.0100244 24987838 \n29. Ng F Ganeshan B Kozarski R Miles KA Goh V . Assessment of primary colorectal cancer heterogeneity by using whole-tumor texture analysis: contrast-enhanced CT texture as a biomarker of 5-year survival . Radiology (2013 ) 266 :177 –84 . 10.1148/radiol.12120254 23151829\n\n",
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"authors": "Orfali|Nina|N|;Jhanwar|Yuliya|Y|;Koo|Calvin|C|;Pasciolla|Michelle|M|;Baldo|Maria|M|;Cuvilly|Edwidge|E|;Furman|Richard|R|;Gergis|Usama|U|;Greenberg|June|J|;Guarneri|Danielle|D|;Hsu|Jing-Mei|JM|;Leonard|John P|JP|;Mark|Tomer|T|;Mayer|Sebastian|S|;Maignan|Kathleen|K|;Martin|Peter|P|;Opong|Adomah|A|;Pearse|Roger|R|;Phillips|Adrienne|A|;Rossi|Adriana|A|;Ruan|Jia|J|;Rutherford|Sarah C|SC|;Ryan|Jessy|J|;Suhu|Grace|G|;Van Besien|Koen|K|;Shore|Tsiporah|T|",
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"journal": "Leukemia & lymphoma",
"keywords": "Lymphoma; bendamustine; hematopoietic stem cell transplantation",
"medline_ta": "Leuk Lymphoma",
"mesh_terms": "D000971:Antineoplastic Combined Chemotherapy Protocols; D006801:Humans; D008223:Lymphoma; D016879:Salvage Therapy; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous",
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"title": "Sequential intensive chemotherapy followed by autologous or allogeneic transplantation for refractory lymphoma.",
"title_normalized": "sequential intensive chemotherapy followed by autologous or allogeneic transplantation for refractory lymphoma"
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"drugenddateformat": null,
"drugindication": "Peripheral T-cell lymphoma unspecified",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
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"drugtreatmentdurationunit": null,
"medicinalproduct": "CISPLATIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARMUSTINE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "300 MG/M2, CYCLIC(DAY-6)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Peripheral T-cell lymphoma unspecified",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "300",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARMUSTINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MELPHALAN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "140 MG/M2, CYCLIC(DAY -1)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Peripheral T-cell lymphoma unspecified",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
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"drugrecurrence": null,
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"drugstructuredosageunit": "009",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "MELPHALAN"
},
{
"actiondrug": "5",
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"activesubstancename": "MELPHALAN"
},
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"drugauthorizationnumb": null,
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"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
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"drugdosagetext": "UNK",
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"medicinalproduct": "MELPHALAN"
},
{
"actiondrug": "5",
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"activesubstancename": "BENDAMUSTINE"
},
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"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
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"drugdosageform": null,
"drugdosagetext": "200 MG, DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Peripheral T-cell lymphoma unspecified",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
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"drugrecurrence": null,
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"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BENDAMUSTINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ROMIDEPSIN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Peripheral T-cell lymphoma unspecified",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ROMIDEPSIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4.5 MG/KG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4.5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "THYMOGLOBULIN"
}
],
"patientagegroup": null,
"patientonsetage": "48",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Second primary malignancy",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Post transplant lymphoproliferative disorder",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Epstein-Barr virus infection reactivation",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Orfali, N.. Sequential intensive chemotherapy followed by autologous or allogeneic transplantation for refractory lymphoma. Leukemia and Lymphoma. 2021;10.1080/10428194.2021.1881516",
"literaturereference_normalized": "sequential intensive chemotherapy followed by autologous or allogeneic transplantation for refractory lymphoma",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20211118",
"receivedate": "20210308",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 18982582,
"safetyreportversion": 3,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 1,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
}
] |
{
"abstract": "Praziquantel (PZQ) has been commonly used to treat diverse parasitic infections for over thirty years. Many studies have confirmed its efficacy for the treatment of cysticercosis and the side effects. We reported a rare case of a 56-year-old Chinese man with cerebral cysticercosis. He had experienced acute pancytopenia two times following PZQ treatment (40 mg/kg per day for five days) and gradually recovered after PZQ withdrawal, which was an adverse effect of PZQ that was not previously reported in the literatures. It is suggested that medical observation and dynamic monitoring of PBC should be maintained throughout the entire PZQ therapy course until two weeks after the drug withdrawal, especially in elderly people and those receiving increasing dosages.",
"affiliations": "Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, No 600 Tianhe Road, Guangzhou, 510630, China. Electronic address: yeqzhang@163.com.;Department of Emergency, The Third Affiliated of Sun Yat-Sen University, No 600# Tianhe Road, Guangzhou, 510630, China. Electronic address: fuyongmei1973@163.com.;Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, No 600 Tianhe Road, Guangzhou, 510630, China. Electronic address: dhong@mail.sysu.edu.com.;Department of Gastroenterology, The Seventh Affiliated Hospital of Sun Yat-Sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen, 518107, China. Electronic address: Sophia_soso@live.cn.;Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, No 600 Tianhe Road, Guangzhou, 510630, China. Electronic address: Laijing@mail.sysu.edu.cn.",
"authors": "Zhang|Yeqiong|Y|;Fu|Yongmei|Y|;Deng|Hong|H|;Li|Qianhui|Q|;Lai|Jing|J|",
"chemical_list": "D011223:Praziquantel",
"country": "Netherlands",
"delete": false,
"doi": "10.1016/j.jiac.2020.06.001",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1341-321X",
"issue": "26(10)",
"journal": "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy",
"keywords": "Adverse effect; Cysticercosis; Pancytopenia; Praziquantel",
"medline_ta": "J Infect Chemother",
"mesh_terms": "D000368:Aged; D003551:Cysticercosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D020019:Neurocysticercosis; D010198:Pancytopenia; D011223:Praziquantel",
"nlm_unique_id": "9608375",
"other_id": null,
"pages": "1082-1085",
"pmc": null,
"pmid": "32600852",
"pubdate": "2020-10",
"publication_types": "D002363:Case Reports",
"references": null,
"title": "Acute pancytopenia due to praziquantel treatment for cerebral cysticercosis: A rare case report.",
"title_normalized": "acute pancytopenia due to praziquantel treatment for cerebral cysticercosis a rare case report"
} | [
{
"companynumb": "CN-BAYER-2020-143283",
"fulfillexpeditecriteria": "1",
"occurcountry": "CN",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PRAZIQUANTEL"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "018714",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FILM-COATED TABLET",
"drugdosagetext": "20 MG, QD",
"drugenddate": "201104",
"drugenddateformat": "610",
"drugindication": "NEUROCYSTICERCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": "201104",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PRAZIQUANTEL."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PRAZIQUANTEL"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "018714",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FILM-COATED TABLET",
"drugdosagetext": "20 MG, QD, PATIENT WAS PRESCRIBED THE SAME COURSES INTERMITTENTLY FOR TEN MORE TIMES",
"drugenddate": "201312",
"drugenddateformat": "610",
"drugindication": "NEUROCYSTICERCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": "201104",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PRAZIQUANTEL."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PRAZIQUANTEL"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "018714",
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"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FILM-COATED TABLET",
"drugdosagetext": "40 MG, QD",
"drugenddate": "201806",
"drugenddateformat": "610",
"drugindication": "NEUROCYSTICERCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": "201806",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "40",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PRAZIQUANTEL."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PRAZIQUANTEL"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "018714",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FILM-COATED TABLET",
"drugdosagetext": "40 MG, QD",
"drugenddate": "201812",
"drugenddateformat": "610",
"drugindication": "NEUROCYSTICERCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": "201812",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "40",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PRAZIQUANTEL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ALBENDAZOLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "20 MG, QD, AND TWELVE SAME",
"drugenddate": "201801",
"drugenddateformat": "610",
"drugindication": "NEUROCYSTICERCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": "201402",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ALBENDAZOLE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PRAZIQUANTEL"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "018714",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FILM-COATED TABLET",
"drugdosagetext": "20 MG, QD, AND TWELVE SAME",
"drugenddate": "201801",
"drugenddateformat": "610",
"drugindication": "NEUROCYSTICERCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": "201402",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PRAZIQUANTEL."
}
],
"patientagegroup": "5",
"patientonsetage": "56",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Pancytopenia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Pancytopenia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Contraindicated product administered",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Seizure",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 201806"
}
},
"primarysource": {
"literaturereference": "YEQIONG ZHANG, YONGMEI FU, HONG DENG, QIANHUI LI, JING LAI. ACUTE PANCYTOPENIA DUE TO PRAZIQUANTEL TREATMENT FOR CEREBRAL CYSTICERCOSIS: A RARE CASE REPORT. JOURNAL OF INFECTION AND CHEMOTHERAPY. 2020?XX:XX?XX",
"literaturereference_normalized": "acute pancytopenia due to praziquantel treatment for cerebral cysticercosis a rare case report",
"qualification": "3",
"reportercountry": "CN"
},
"primarysourcecountry": "CN",
"receiptdate": "20200909",
"receivedate": "20200724",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18067931,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20201103"
}
] |
{
"abstract": "BACKGROUND\nPosterior reversible encephalopathy syndrome (PRES) has only rarely been reported in patients with multiple sclerosis (MS).\n\n\nMETHODS\nCase report of a patient with relapsing remitting (RR) MS patient on interferon (INF) treatment, who developed posterior fossa PRES.\n\n\nRESULTS\nA 46-year-old male diagnosed with RR MS in 2010 was placed on INF beta-1a therapy. He remained in clinical remission for seven years. He then presented with headache of one month duration and worsening upper extremity ataxia. Cranial MRI revealed two new enhancing cerebellar lesions (one with tumefactive features). Within the next 10 days the patient developed severe holocephalic headache, vomiting, altered consciousness and gait instability. Urgent brain MRI revealed diffuse hyperintense lesions in T2WI and FLAIR sequences in bilateral cerebellar hemispheres and the right thalamus, with marked swelling, increased diffusivity indicative of vasogenic edema and patchy-nodular enhancement, while smaller lesions were also found in posterior temporal, parietal and occipital lobes. Severely elevated blood pressure was noted. Treatment with hypertonic agents, esmolol drip and IV steroids was instituted, resulting in remarkable improvement within the next several days. Repeat MRI showed almost complete resolution of the cerebellar lesions. Interferon beta was discontinued and blood pressure remained well controlled.\n\n\nCONCLUSIONS\nPatients with RR MS on IFN beta therapy can develop PRES via the combination of hypertension and endothelial dysfunction by IFN, even when stable on this treatment. Neurologists should be keen to differentiate the appearance of PRES lesions from those of fulminant MS relapse, opportunistic infections or malignancy.",
"affiliations": "Department of Neurology, University Hospital of Heraklion, Crete, Greece. Electronic address: vasmast@yahoo.com.;Department of Neurology, University Hospital of Heraklion, Crete, Greece.;Department of Radiology-MRI Unit, School of Medicine, University of Crete, Crete, Greece.;Department of Neurology, University Hospital of Heraklion, Crete, Greece; Department of Neurology, School of Medicine, University of Crete, Crete, Greece; Department of Neurology & Comprehensive Stroke Center, Henry Ford Hospital, Detroit, MI, United States.",
"authors": "Mastorodemos|Vasileios C|VC|;Ioannidis|Stefanos G|SG|;Papadaki|Efrosini Z|EZ|;Mitsias|Panayiotis D|PD|",
"chemical_list": "D007372:Interferons",
"country": "Netherlands",
"delete": false,
"doi": "10.1016/j.msard.2020.102356",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "2211-0348",
"issue": "45()",
"journal": "Multiple sclerosis and related disorders",
"keywords": "Interferon beta; Multiple sclerosis; Posterior reversible encephalopathy syndrome",
"medline_ta": "Mult Scler Relat Disord",
"mesh_terms": "D006801:Humans; D007167:Immunotherapy; D015994:Incidence; D007372:Interferons; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis; D054038:Posterior Leukoencephalopathy Syndrome",
"nlm_unique_id": "101580247",
"other_id": null,
"pages": "102356",
"pmc": null,
"pmid": "32659736",
"pubdate": "2020-10",
"publication_types": "D002363:Case Reports",
"references": null,
"title": "Posterior Reversible Encephalopathy Syndrome, Multiple Sclerosis and interferon therapy: Association, co-incidence or convoluted interplay?",
"title_normalized": "posterior reversible encephalopathy syndrome multiple sclerosis and interferon therapy association co incidence or convoluted interplay"
} | [
{
"companynumb": "GR-EMD SERONO-9176557",
"fulfillexpeditecriteria": "1",
"occurcountry": "GR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VENLAFAXINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
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"medicinalproduct": "VENLAFAXINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "BUPROPION"
},
"drugadditional": null,
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"drugcharacterization": "2",
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"drugdosagetext": null,
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"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
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"drugtreatmentdurationunit": null,
"medicinalproduct": "BUPROPION."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "INTERFERON BETA-1A"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "103780",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RELAPSING-REMITTING MULTIPLE SCLEROSIS",
"drugintervaldosagedefinition": null,
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"literaturereference": "MASTORODEMOSA V, IOANNIDISA S, PAPADAKIB E, MITSIASA P. POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME, MULTIPLE SCLEROSIS AND INTERFERON THERAPY: ASSOCIATION, CO?INCIDENCE OR CONVOLUTED INTERPLAY?.. MULTIPLE SCLEROSIS AND RELATED DISORDERS. 45?45.",
"literaturereference_normalized": "posterior reversible encephalopathy syndrome multiple sclerosis and interferon therapy association co incidence or convoluted interplay",
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},
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{
"abstract": "BACKGROUND\nSodium-glucose cotransporter 2 (SGLT2) inhibition has been shown to reduce cardiovascular mortality and preserve kidney function in patients with type 2 diabetes. Kidney transplant recipients with diabetes demonstrate increased risk and accelerated progression of micro- and macrovascular complications and may specifically benefit from SGLT2 inhibition. However, potential concerns of SGLT2 inhibition include volume depletion and urinary tract infections.\n\n\nOBJECTIVE\nWe report data on the use of SGLT2 inhibitors in a case series of ten patients with diabetes after kidney transplantation in order to analyze efficacy, safety, and the effect on renal function.\n\n\nMETHODS\nPatients with a stable allograft function and no history of recurrent urinary tract infections were eligible. The SGLT2 inhibitor empagliflozin was given as add-on to preexisting antidiabetic treatment with initial dose reduction of the latter.\n\n\nRESULTS\nMedian estimated glomerular filtration rate at baseline was 57 mL/min/1.73 m2 and remained stable throughout the follow-up of 12.0 (5.3-12.0) months. Median HbA1c decreased from 7.3 to 7.1%. The rate of urinary tract infections and other side effects was low.\n\n\nCONCLUSIONS\nSGLT2 inhibition is feasible and well tolerated in selected kidney transplant recipients with diabetes. Whether SGLT2 inhibition is able to reduce cardiovascular mortality and improve allograft survival in these patients has to be addressed in further studies.",
"affiliations": "Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University of Tübingen, Tübingen, Germany.;Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University of Tübingen, Tübingen, Germany.;Department of General, Visceral and Transplant Surgery, University of Tübingen, Tübingen, Germany.;Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University of Tübingen, Tübingen, Germany.;Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University of Tübingen, Tübingen, Germany.;Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University of Tübingen, Tübingen, Germany, martina.guthoff@med.uni-tuebingen.de.",
"authors": "Mahling|Moritz|M|;Schork|Anja|A|;Nadalin|Silvio|S|;Fritsche|Andreas|A|;Heyne|Nils|N|;Guthoff|Martina|M|",
"chemical_list": "D051297:Sodium-Glucose Transporter 2",
"country": "Switzerland",
"delete": false,
"doi": "10.1159/000501854",
"fulltext": null,
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"issn_linking": "1420-4096",
"issue": "44(5)",
"journal": "Kidney & blood pressure research",
"keywords": "Diabetes mellitus; Empagliflozin; Kidney transplantation; Renal and cardiovascular endpoints; Sodium-glucose cotransporter 2 inhibition",
"medline_ta": "Kidney Blood Press Res",
"mesh_terms": "D000368:Aged; D003924:Diabetes Mellitus, Type 2; D006801:Humans; D016030:Kidney Transplantation; D008875:Middle Aged; D011446:Prospective Studies; D051297:Sodium-Glucose Transporter 2",
"nlm_unique_id": "9610505",
"other_id": null,
"pages": "984-992",
"pmc": null,
"pmid": "31437852",
"pubdate": "2019",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Sodium-Glucose Cotransporter 2 (SGLT2) Inhibition in Kidney Transplant Recipients with Diabetes Mellitus.",
"title_normalized": "sodium glucose cotransporter 2 sglt2 inhibition in kidney transplant recipients with diabetes mellitus"
} | [
{
"companynumb": "DE-B.I. PHARMACEUTICALS,INC./RIDGEFIELD-2019-BI-101274",
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{
"actiondrug": "5",
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},
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"reactionmeddrapt": "Respiratory tract infection",
"reactionmeddraversionpt": "22.0",
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{
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"literaturereference": "GUTHOFF M, MAHLING M, SCHORK A, NADALIN S, FRITSCHE A, HEYNE N, ETAL. SODIUM-GLUCOSE COTRANSPORTER 2 (SGLT2) INHIBITION IN KIDNEY TRANSPLANT RECIPIENTS WITH DIABETES MELLITUS. KIDNEY AND BLOOD PRESSURE RESEARCH. 2019?.",
"literaturereference_normalized": "sodium glucose cotransporter 2 sglt2 inhibition in kidney transplant recipients with diabetes mellitus",
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{
"abstract": "We report a case of fulminant Acanthamoeba castellanii encephalitis in a patient with chronic lymphocytic leukemia treated with ibrutinib. The unusually rapid neurologic decline and fatal outcome observed are probably related to alterations in immunologic function associated with inhibition of Bruton tyrosine kinase.",
"affiliations": "University of Vermont Medical Center, Burlington, Vermont, USA.;Brigham and Women's Hospital, Boston, Massachusetts, USA.;Brigham and Women's Hospital, Boston, Massachusetts, USA.",
"authors": "Crothers|Jessica W|JW|0000-0003-4594-5051;Hsu|Liangge|L|;Marty|Francisco M|FM|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1093/ofid/ofaa025",
"fulltext": "\n==== Front\nOpen Forum Infect DisOpen Forum Infect DisofidOpen Forum Infectious Diseases2328-8957Oxford University Press US 10.1093/ofid/ofaa025ofaa025Brief ReportFulminant Acanthamoeba castellanii Encephalitis in an Ibrutinib-Treated Patient http://orcid.org/0000-0003-4594-5051Crothers Jessica W 1Hsu Liangge 2Marty Francisco M 21 \nUniversity of Vermont Medical Center, Burlington, Vermont, USA2 \nBrigham and Women’s Hospital, Boston, Massachusetts, USACorrespondence: Jessica Crothers, MD, Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, 111 Colchester Ave, Burlington, VT 05401 (jessica.crothers@uvmhealth.org).2 2020 20 1 2020 20 1 2020 7 2 ofaa02502 12 2019 17 1 2020 16 1 2019 10 2 2020 © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.2020This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.comAbstract\nWe report a case of fulminant Acanthamoeba castellanii encephalitis in a patient with chronic lymphocytic leukemia treated with ibrutinib. The unusually rapid neurologic decline and fatal outcome observed are probably related to alterations in immunologic function associated with inhibition of Bruton tyrosine kinase.\n\nAcanthamoeba castellaniiamoebaNaegleriaencephalitisibrutinib\n==== Body\nA 70-year-old man on treatment with ibrutinib for chronic lymphocytic leukemia (CLL) presented to an outside hospital with fever (40.3°C), malaise, weakness, and confusion in August 2018. His medical history was notable for interstitial lung disease and splenectomy. He was treated with ceftriazone and azithromycin for presumed pneumonia but developed confusion followed by seizures a day later. Brain magnetic resonance imaging (MRI) demonstrated a 3.4-cm irregular enhancing lesion in the left occipital lobe. Empirical treatment was changed to vancomycin, cefepime, and metronidazole, and the patient was transferred to our institution 4 days later. Upon arrival, the patient was nonresponsive. Head computed tomography demonstrated vasogenic edema surrounding the occipital lesion, but no hemorrhages or midline shift to explain his coma (Figure 1). On physical exam, his heart rate was 92 bpm, blood pressure 126/60 mmHg, temperature 37.8°C, and oxygen saturation 93%. He was unable to answer questions or follow commands and had only minimal withdrawal from painful stimuli.\n\nFigure 1. Multiple axial T2 (A, B, C) and postcontrast (D, E, F) images show numerous lesions at the left pons, bilateral cerebellum (A, D), right anterior temporal and left occipital lobes (B, E), and right splenium (C, F) associated with dark T2 rim, edema, and mild amorphous enhancement.\n\nHis family reported that he had been well until 4 days before presentation, when he developed drenching night sweats and confusion, followed by visual disturbances, including loss of color vision, and then he lost the ability to care for himself, becoming noninteractive and unable to recognize others. He previously worked as a carpenter and had not traveled recently. Of note, the patient had cats and had cleaned his Koi pond filters, spraying them with a hose 3 days before developing symptoms.\n\nUpon admission, the patient’s antimicrobial regimen included vancomycin, cefepime, metronidazole, and liposomal amphotericin B, which was later changed to isavuconazole. Laboratory testing included a leukocyte count of 16 200 cells/µL with 70.8% neutrophils; hematocrit, 40.2%; platelets, 124 K/µL; galactomannan, 0.04; 1-3-Beta D glucan, <31 pg/mL; serum cryptococcal antigen, negative; anaplasma, babesia, and Lyme polymerase chain reaction (PCR), negative; blood cultures, negative; HIV testing, negative; toxoplasma IgG and IgM, negative; toxoplasma PCR, negative; JC virus (John Cunningham or Human polyomavirus 2 virus), negative. Lumbar puncture was performed (opening pressure, 29 cm2 H20; glucose, 98; protein, 111; nucleated cells, 53; lymphocytes, 59%; monocytes, 18%; neutrophils, 16%; atypical lymphocytes, 5%). Initial cerebrospinal fluid (CSF) testing was extensive and unremarkable.\n\nThe patient declined, becoming comatose with decorticate posturing. Repeat MRI imaging in preparation for neurosurgical intervention revealed multiple new contiguous and noncontiguous areas of supra- and infratentorial involvement with hemorrhagic transformation. Surgery was not performed. The patient expired 10 days after initial presentation; autopsy was declined.\n\nGiven the patient’s history of freshwater exposure from spraying Koi pond filters, a CSF sample was sent to the Centers for Disease Control and Prevention Free-Living and Intestinal Amebas Laboratory for molecular testing. The sample was initially reported as negative for Naegleria fowleri, Balamuthia mandrillaris, and Acanthameoba spp. by PCR, but retesting as part of the laboratory’s internal assessment practices revealed inconsistent low-level positivity with atypical PCR products (2 sequences at 430 bp and 330 bp instead of 1 longer product). This prompted further evaluation by Sanger sequencing, which identified Acanthamoeba castellanii genotype I. No trophozoites were seen on CSF Gram stain or cytology.\n\nAmebiasis of the CNS represents a critical yet often challenging clinical diagnosis. Caused by free-living amoebas, including Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri, case fatality of amebic encephalitis approaches 100%. Primary amoebic meningoencephalitis (PAM) usually occurs when N. fowleri gains access to the brain via the olfactory bulb. Death is rapid, and patients, who are commonly young and healthy with a history of fresh water exposure in summer months, present with frontal lobe lesions and grossly abnormal CSF findings [1, 2]. Acanthamoeba spp. typically cause subacute infections, termed granulomatous amoebic encephalitis (GAE), in older, immunocompromised patients, who present with vague neurologic symptoms for weeks to months with progressive CNS disease and death. Free-living amoebas, including Acanthamoeba, are widely distributed in the environment, and many healthy individuals have serologic evidence of exposure [3, 4]. Exposure can occur by inhalation or by direct inoculation into the cornea, sinonasal mucosa, or skin. Ensuing disease varies according to host immunologic status, route of exposure, and strain virulence. CNS invasion occurs hematogenously or by direct extension through the nasal epithelium. Mucosal IgA antibodies appear to play an important role in initial host defense, followed by complement activation and antibody-mediated recognition of the organisms by phagocytic cells [5]. Well-developed granulomata are not observed in immunocompromised patients, who instead develop multifocal lesions with severe hemorrhagic necrosis filled by numerous trophozoites.\n\nAlthough it is difficult to establish the exact timing of this patient’s infection, his lack of previous symptoms and potential exposure to contaminated water via spraying of Koi pond filters suggest inhalation of amoebae, with a fulminant clinical course in the spectrum of PAM despite the identification of Acanthamoeba castellanii. The use of molecular sequencing in this case highlights the need for multimodal approaches in the diagnosis of CNS infections. Likely due to a low level of potentially degraded DNA in the CSF, this case was initially negative by targeted multiplex TaqMan real-time PCR, a technique that requires 180 bp of nonamplified DNA [6]. Sanger sequencing, however, was able to provide species-level identification of the causative organisms. Sanger sequencing is based on the selective incorporation of chain-termination dideoxynucleotides by DNA polymerase and does not rely on primer binding, making it a more sensitive technique capable of picking up small fragments of DNA that might not bind strongly and consistently to a particular PCR primer. Sanger sequencing also has the advantage over newer, next-generation short-read technologies of creating longer sequence reads (>500 bp) for improved species identification.\n\nTo our knowledge, this is the second case of amebic encephalitis reported in the literature in a patient taking ibrutinib, highlighting the potentially unique risk of infection in patients taking Bruton kinase inhibitors [7]. We hypothesize that ibrutinib-mediated alterations of immunologic function resulted in uncontrolled amoebic proliferation, CNS invasion, and unusually rapid clinical deterioration [8, 9] There have been several reports of fungal diseases in patients receiving ibrutinib, including invasive aspergillosis, cryptococcosis, and pneumocystosis [10], suggesting that off-target effects of ibrutinib may be additive, altering the T cell–macrophage axis in addition to B-cell function. The propensity of these invasive diseases to be neurotropic in patients receiving ibrutinib [11, 12] remains to be elucidated.\n\nAcknowledgments\nWe have no formal acknowledgments for the completion of this work.\n\n\n\nFinancial support. This work was not supported by extramural funding.\n\n\nPotential conflicts of interest. J.W.C., no conflict; L.H., no conflict; F.M.M., no conflict. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.\n==== Refs\nReferences\n1. \nOng TYY , Khan NA , Siddiqui R \nBrain-eating amoebae: predilection sites in the brain and disease outcome . J Clin Microbiol 2017 ; 55 :1989 –97 .28404683 \n2. \nVisvesvara GS , Moura H , Schuster FL \nPathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea . FEMS Immunol Med Microbiol 2007 ; 50 :1 –26 .17428307 \n3. \nCursons RT , Brown TJ , Keys EA , et al. \nImmunity to pathogenic free-living amoebae: role of humoral antibody . Infect Immun 1980 ; 29 :401 –7 .7216418 \n4. \nLares-Jiménez LF , Borquez-Román MA , Alfaro-Sifuentes R , et al. \nDetection of serum antibodies in children and adolescents against Balamuthia mandrillaris, Naegleria fowleri and Acanthamoeba T4 . Exp Parasitol 2018 ; 189 :28 –33 .29673623 \n5. \nAlizadeh H , Apte S , El-Agha MS , et al. \nTear IgA and serum IgG antibodies against Acanthamoeba in patients with Acanthamoeba keratitis . Cornea 2001 ; 20 :622 –7 .11473164 \n6. \nQvarnstrom Y , Visvesvara GS , Sriram R , da Silva AJ \nMultiplex real-time PCR assay for simultaneous detection of Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri . J Clin Microbiol 2006 ; 44 :3589 –95 .17021087 \n7. \nVoshtina E , Huang H , Raj R , Atallah E \nAmebic encephalitis in a patient with chronic lymphocytic leukemia on ibrutinib therapy . Case Rep Hematol 2018 ; 2018 :6514604 .30155323 \n8. \nŁanocha-Arendarczyk N , Kolasa-Wołosiuk A , Wojciechowska-Koszko I , et al. \nChanges in the immune system in experimental acanthamoebiasis in immunocompetent and immunosuppressed hosts . Parasit Vectors 2018 ; 11 :517 .30236160 \n9. \nMarciano-Cabral F , Cabral GA \nThe immune response to Naegleria fowleri amebae and pathogenesis of infection . FEMS Immunol Med Microbiol 2007 ; 51 :243 –59 .17894804 \n10. \nChamilos G , Lionakis MS , Kontoyiannis DP \nCall for action: invasive fungal infections associated with ibrutinib and other small molecule kinase inhibitors targeting immune signaling pathways . Clin Infect Dis 2018 ; 66 :140 –8 .29029010 \n11. \nGhez D , Calleja A , Protin C , et al ; French Innovative Leukemia Organization (FILO) CLL group \nEarly-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib . Blood 2018 ; 131 :1955 –9 .29437588 \n12. \nLionakis MS , Dunleavy K , Roschewski M , et al. \nInhibition of B cell receptor signaling by ibrutinib in primary CNS lymphoma . Cancer Cell 2017 ; 31 :833 –843.e5 .28552327\n\n",
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"keywords": "Acanthamoeba castellanii; Naegleria; amoeba; encephalitis; ibrutinib",
"medline_ta": "Open Forum Infect Dis",
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"title": "Fulminant Acanthamoeba castellanii Encephalitis in an Ibrutinib-Treated Patient.",
"title_normalized": "fulminant acanthamoeba castellanii encephalitis in an ibrutinib treated patient"
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"literaturereference": "CROTHERS JW, HSU L, MARTY FM. FULMINANT ACANTHAMOEBA CASTELLANII ENCEPHALITIS IN AN IBRUTINIB-TREATED PATIENT. OPEN FORUM INFECT DIS. 2020?7(2):OFAA025",
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"abstract": "Stroke caused by acute occlusion of basilar artery (AOBA) produces high risk of death. In eligible patients, thrombolysis significantly reduces mortality and disability rate. In most hospitals, thrombolysis is limited to intravenous (IV) route of recombinant tissue plasminogen activator, without any therapeutic alternative in cases of treatment failure. We report a case of cardioembolic AOBA, not responsive to a conventional regimen of IV recombinant tissue plasminogen activator. A sequential combination of IV tenecteplase (0.4 mg/kg) led to a complete recanalization of basilar artery, with a very good clinical outcome. The potential for a combination of two successive IV regimens should be evaluated in AOBA.",
"affiliations": "Department of Neurology, University Hospital of Fort-de-France, Martinique, the French West Indies. didier.smadja@chu-fortdefrance.fr",
"authors": "Smadja|Didier|D|;Olindo|Stéphane|S|;Saint-Vil|Martine|M|;Chausson|Nicolas|N|",
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"abstract": "We report a case of placental infection leading to preterm delivery in a mother diagnosed with septicemia and pneumonia due to Burkholderia pseudomallei in pregnancy. Placental infection occurred despite prolonged ceftazidime therapy.",
"affiliations": "Microbiology Department, PathWest Laboratories, Perth, Australia.;Division of Obstetrics and Gynaecology, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia.;Neonatology Critical Care Unit, King Edward Memorial Hospital, Perth, Australia.;Infectious Diseases Department, Fiona Stanley Hospital, Perth, Australia.;Microbiology Department, PathWest Laboratories, Perth, Australia.;Global and Tropical Health Division, Menzies School of Health Research and Infectious Diseases Department, Royal Darwin Hospital, Darwin, Australia.",
"authors": "Porter|Michelle C|MC|;Pennell|Craig E|CE|;Woods|Patricia|P|;Dyer|John|J|;Merritt|Adam J|AJ|;Currie|Bart J|BJ|",
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"issue": "98(3)",
"journal": "The American journal of tropical medicine and hygiene",
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"medline_ta": "Am J Trop Med Hyg",
"mesh_terms": "D000328:Adult; D000900:Anti-Bacterial Agents; D001315:Australia; D016957:Burkholderia pseudomallei; D002821:Chorioamnionitis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008554:Melioidosis; D010920:Placenta; D011247:Pregnancy; D047928:Premature Birth; D018805:Sepsis; D013785:Thailand; D014195:Travel; D000076082:Travel-Related Illness; D016896:Treatment Outcome",
"nlm_unique_id": "0370507",
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"pages": "797-799",
"pmc": null,
"pmid": "29363450",
"pubdate": "2018-03",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "10674644;11302149;25811783;27438887;18256414;15626961;25228703;28599008;3355451;12767750;25758020;16515111;22970946;25205706;22739573",
"title": "Case Report: Chorioamnionitis and Premature Delivery due to Burkholderia pseudomallei Infection in Pregnancy.",
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] |
{
"abstract": "Ticagrelor and atorvastatin are commonly used medications in the management of acute coronary syndrome and percutaneous intervention. This is a report of a patient case of a potential drug interaction leading to the use of alternative therapy.\nA 58-year-old male presented for cardiac catheterization following an abnormal stress test. He underwent placement of a drug-eluting stent and was started on ticagrelor. Three months later, he was noted to have elevated creatine kinase (CK), thought to be related to a potential drug-drug interaction between ticagrelor and atorvastatin. Ticagrelor was discontinued and he was successfully transitioned to clopidogrel. CK returned to normal within weeks of this change.\nPharmacokinetic studies have demonstrated a potential interaction between ticagrelor and atorvastatin but have not been deemed clinically significant. To date, only one other case report has been published discussing this interaction and consideration of alternative therapy. This case report is unique, with ticagrelor being the only new medication added prior to the abnormal CK finding.\nA probable drug-drug interaction occurred with concomitant ticagrelor and atorvastatin. While this interaction may not always be clinically significant, it is reasonable to consider in patients who present with signs and symptoms of adverse effects.",
"affiliations": "1 Department of Pharmacy, WakeMed Health & Hospitals, Raleigh, NC, USA.",
"authors": "Beavers|Janna C|JC|",
"chemical_list": "D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D000069059:Atorvastatin; D000077144:Clopidogrel; D003402:Creatine Kinase; D000077486:Ticagrelor",
"country": "United States",
"delete": false,
"doi": "10.1177/0897190017740282",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0897-1900",
"issue": "32(1)",
"journal": "Journal of pharmacy practice",
"keywords": "adverse drug reaction; atorvastatin; creatine kinase; drug interaction; ticagrelor",
"medline_ta": "J Pharm Pract",
"mesh_terms": "D000069059:Atorvastatin; D006328:Cardiac Catheterization; D000077144:Clopidogrel; D003402:Creatine Kinase; D004347:Drug Interactions; D054855:Drug-Eluting Stents; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors; D000077486:Ticagrelor",
"nlm_unique_id": "8900945",
"other_id": null,
"pages": "106-108",
"pmc": null,
"pmid": "29096571",
"pubdate": "2019-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Elevated Creatine Kinase due to Potential Drug Interaction With Ticagrelor and Atorvastatin.",
"title_normalized": "elevated creatine kinase due to potential drug interaction with ticagrelor and atorvastatin"
} | [
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},
{
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{
"abstract": "OBJECTIVE\nTo identify the prevalence of and risk factors for inadvertent hypothermia after procedures performed with procedural sedation and analgesia in a cardiac catheterization laboratory.\n\n\nMETHODS\nA single-center, prospective observational study.\n\n\nMETHODS\nA tertiary-care private hospital in Australia.\n\n\nMETHODS\n399 patients undergoing elective procedures with procedural sedation and analgesia were included. Propofol infusions were used when an anesthesiologist was present. Otherwise, bolus doses of either midazolam or fentanyl or a combination of these medications was used.\n\n\nMETHODS\nNone\n\n\nRESULTS\nHypothermia was defined as a temperature<36.0°C. Multivariate logistic regression was used to identify risk factors. Hypothermia was present after 23.3% (n = 93; 95% confidence interval [CI] 19.2%-27.4%) of 399 procedures. Sedative regimens with the highest prevalence of hypothermia were any regimen that included propofol (n = 35; 40.2%; 95% CI 29.9%-50.5%) and the use of fentanyl combined with midazolam (n = 23; 20.3%; 95% CI 12.9%-27.7%). Difference in mean temperature from pre-procedure to post-procedure was -0.27°C (standard deviation 0.45). Receiving propofol (odds ratio [OR] 4.6 95% CI 2.5-8.6), percutaneous coronary intervention (OR 3.2; 95% CI 1.7-5.9), body mass index<25 (OR 2.5; 95% CI 1.4-4.4) and being hypothermic prior to the procedure (OR 4.9; 95% CI 2.3-10.8) were independent predictors of post-procedural hypothermia.\n\n\nCONCLUSIONS\nA moderate prevalence of hypothermia was observed. The small absolute change in temperature observed may not be a clinically important amount. More research is needed to increase confidence in the authors' estimates of hypothermia in sedated patients and its impact on clinical outcomes.",
"affiliations": "Institute of Health and Biomedical Innovation, Queensland University Technology, Kelvin Grove, QLD, Australia. Electronic address: aaron.conway@qut.edu.au.;Cardiac Catheter Laboratories, Princess Alexandra Hospital, Wooloongabba, QLD, Australia.;Coffs Harbour Health Campus and Rural Clinical School, Coffs Harbour, NSW, Australia.",
"authors": "Conway|Aaron|A|;Kennedy|Wendy|W|;Sutherland|Joanna|J|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1053-0770",
"issue": "29(5)",
"journal": "Journal of cardiothoracic and vascular anesthesia",
"keywords": "cardiac catheterization laboratory; conscious sedation; deep sedation; hypothermia; monitoring; risk factors; temperature",
"medline_ta": "J Cardiothorac Vasc Anesth",
"mesh_terms": "D000368:Aged; D000698:Analgesia; D001831:Body Temperature; D006328:Cardiac Catheterization; D016292:Conscious Sedation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007035:Hypothermia; D007755:Laboratories, Hospital; D008297:Male; D009517:New South Wales; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors",
"nlm_unique_id": "9110208",
"other_id": null,
"pages": "1285-90",
"pmc": null,
"pmid": "26384630",
"pubdate": "2015-10",
"publication_types": "D016428:Journal Article; D064888:Observational Study; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Inadvertent Hypothermia After Procedural Sedation and Analgesia in a Cardiac Catheterization Laboratory: A Prospective Observational Study.",
"title_normalized": "inadvertent hypothermia after procedural sedation and analgesia in a cardiac catheterization laboratory a prospective observational study"
} | [
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"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIDAZOLAM-CLARIS"
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hypothermia",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CONWAY A, KENNEDY W, SUTHERLAND J. INADVERTENT HYPOTHERMIA AFTER PROCEDURAL SEDATION AND ANALGESIA IN A CARDIAC CATHETERIZATION LABORATORY: A PROSPECTIVE OBSERVATIONAL STUDY. JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA. 2015 OCT;29(5):1285-1290.",
"literaturereference_normalized": "inadvertent hypothermia after procedural sedation and analgesia in a cardiac catheterization laboratory a prospective observational study",
"qualification": "3",
"reportercountry": "AU"
},
"primarysourcecountry": "AU",
"receiptdate": "20171219",
"receivedate": "20171219",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 14306303,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180321"
}
] |
{
"abstract": "BACKGROUND\nOccupational toxic epidermal necrolysis (TEN) related to Dalbergia cochinchinensis has seldom been reported in the past. Its clinical characteristic needs to be investigated. This study reports eight cases of such disease in China.\n\n\nMETHODS\nEight patients with occupational TEN admitted from 2003 to 2012 were retrospectively analyzed and compared with 15 patients admitted with TEN caused by drugs as controls. Patients all received combination therapy of corticosteroid and intravenous immunoglobulin. The times for bullous ceasing, tapering of corticosteroid, and total hospitalization were compared between the two groups of patients. SCORTEN, a severity-of-illness scoring system for TEN prognosis, was applied to evaluate clinical outcome.\n\n\nRESULTS\nThe three time measurements in occupational TEN were longer than those in control, and the differences were statistically significant (P = 0.0023, 0.026, 0.0017), which means the total dose of corticosteroid needed in occupational TEN was higher than that in the control. There were no deaths in the two groups, although expected deaths were 0.612 and 0.836, respectively.\n\n\nCONCLUSIONS\nOccupational TEN has a longer progression than TEN caused by drugs, and there is more difficulty in its treatment. Clinicians should pay attention to this disease. However, its mechanism and target therapy remain unclear.",
"affiliations": "Affiliated Huashan Hospital, Fudan University, Shanghai, China.;Affiliated Huashan Hospital, Fudan University, Shanghai, China.;Affiliated Huashan Hospital, Fudan University, Shanghai, China.;Affiliated Huashan Hospital, Fudan University, Shanghai, China.;Affiliated Huashan Hospital, Fudan University, Shanghai, China.;Affiliated Huashan Hospital, Fudan University, Shanghai, China.;Affiliated Huashan Hospital, Fudan University, Shanghai, China.",
"authors": "Yang|Yongsheng|Y|;Zhang|Zhen|Z|;Lu|Xiaonian|X|;Zhu|Xiaohua|X|;Huang|Qiong|Q|;Liang|Jun|J|;Xu|Jinhua|J|",
"chemical_list": "D005938:Glucocorticoids; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D008775:Methylprednisolone",
"country": "England",
"delete": false,
"doi": "10.1111/ijd.12784",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0011-9059",
"issue": "54(12)",
"journal": "International journal of dermatology",
"keywords": null,
"medline_ta": "Int J Dermatol",
"mesh_terms": "D000328:Adult; D016022:Case-Control Studies; D035782:Dalbergia; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007374:Interior Design and Furnishings; D008297:Male; D066192:Manufacturing Industry; D008775:Methylprednisolone; D008875:Middle Aged; D009784:Occupational Diseases; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013262:Stevens-Johnson Syndrome; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult",
"nlm_unique_id": "0243704",
"other_id": null,
"pages": "1435-41",
"pmc": null,
"pmid": "25944249",
"pubdate": "2015-12",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Occupational toxic epidermal necrolysis associated with dalbergia cochinchinensis: a retrospective comparative study of eight cases in China.",
"title_normalized": "occupational toxic epidermal necrolysis associated with dalbergia cochinchinensis a retrospective comparative study of eight cases in china"
} | [
{
"companynumb": "CN-MYLANLABS-2016M1002176",
"fulfillexpeditecriteria": "1",
"occurcountry": "CN",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DIPYRIDAMOLE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075769",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIPYRIDAMOLE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxic epidermal necrolysis",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "YANG Y, ZHANG Z, LU X, ZHU X, HUANG Q, LIANG J, ET AL. OCCUPATIONAL TOXIC EPIDERMAL NECROLYSIS ASSOCIATED WITH DALBERGIA COCHINCHINENSIS: A RETROSPECTIVE COMPARATIVE STUDY OF EIGHT CASES IN CHINA. INT-J-DERMATOL 2015?54(12):1435-1441.",
"literaturereference_normalized": "occupational toxic epidermal necrolysis associated with dalbergia cochinchinensis a retrospective comparative study of eight cases in china",
"qualification": "3",
"reportercountry": "CN"
},
"primarysourcecountry": "CN",
"receiptdate": "20160119",
"receivedate": "20160119",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11928442,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20160526"
},
{
"companynumb": "CN-LUPIN PHARMACEUTICALS INC.-2016-00389",
"fulfillexpeditecriteria": "2",
"occurcountry": "CN",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "078154",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
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"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVETIRACETAM."
}
],
"patientagegroup": null,
"patientonsetage": "20",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxic epidermal necrolysis",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "XU J, LIANG J, HUANG Q, LU X, ZHU X, YANG Y, ZHANG Z. OCCUPATIONAL TOXIC EPIDERMAL NECROLYSIS ASSOCIATED WITH DALBERGIA COCHINCHINENSIS: A RETROSPECTIVE COMPARATIVE STUDY OF EIGHT CASES IN CHINA. INT-J-DERMATOL. 2015;54(12):1435-1441.",
"literaturereference_normalized": "occupational toxic epidermal necrolysis associated with dalbergia cochinchinensis a retrospective comparative study of eight cases in china",
"qualification": "1",
"reportercountry": "CN"
},
"primarysourcecountry": "CN",
"receiptdate": "20160802",
"receivedate": "20160802",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 12616895,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20161109"
}
] |
{
"abstract": "OBJECTIVE\nTramadol is a weak opioid used as a step 2 analgesic, approved in France for moderate to severe pain. After dextropropoxyphene withdrawal, a national pharmacovigilance follow-up of tramadol was decided by the French Drug Agency.\n\n\nMETHODS\nAll Serious Adverse Drug Reactions (SADR) notified with tramadol to the French PharmacoVigilance Centres (CRPV) and pharmaceutical companies between August 1(st), 2010 and July 31(th), 2011 were analyzed.\n\n\nRESULTS\nDuring the study period, 296 cases of SADR were notified to CRPV and 59 to pharmaceutical companies. Apart from opiate-related SADR, tramadol induced serotoninergic SADR, including seizures or serotoninergic syndromes. Several « unlabelled » SADR were also identified: some of them, like hyponatremia or hypoglycemia, are poorly known by health professionals. Other were never published: peripheral edema or pancreatitis.\n\n\nCONCLUSIONS\nThis study shows that besides well-known opioid or serotoninergic ADR, tramadol can also induce 2 other relatively unknown ADR: hypoglycemia and hyponatremia.",
"affiliations": "Laboratoire de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, et Centre Midi-Pyrénées d'Évaluation et d'Information sur la Pharmacodépendance-Addictovigilance, Université de Toulouse, Faculté de Médecine, Centre hospitalier universitaire, Toulouse, France. dabadie@cict.fr",
"authors": "Abadie|Delphine|D|;Durrieu|Geneviève|G|;Roussin|Anne|A|;Montastruc|Jean-Louis|JL|;|||",
"chemical_list": "D000701:Analgesics, Opioid; D014147:Tramadol",
"country": "France",
"delete": false,
"doi": "10.2515/therapie/2013021",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0040-5957",
"issue": "68(2)",
"journal": "Therapie",
"keywords": null,
"medline_ta": "Therapie",
"mesh_terms": "D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000701:Analgesics, Opioid; D004345:Drug Industry; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005602:France; D006801:Humans; D007003:Hypoglycemia; D007010:Hyponatremia; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D014147:Tramadol",
"nlm_unique_id": "0420544",
"other_id": null,
"pages": "77-84",
"pmc": null,
"pmid": "23773348",
"pubdate": "2013",
"publication_types": "D004740:English Abstract; D016428:Journal Article",
"references": null,
"title": "\"Serious\" adverse drug reactions with tramadol: a 2010-2011 pharmacovigilance survey in France.",
"title_normalized": "serious adverse drug reactions with tramadol a 2010 2011 pharmacovigilance survey in france"
} | [
{
"companynumb": "PHHY2013FR145514",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "TRAMADOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075968",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "112.5 MG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "1",
"drugrecurrence": [
{
"drugrecuraction": "Oedema peripheral"
}
],
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "112.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRAMADOL"
}
],
"patientagegroup": null,
"patientonsetage": "70",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Weight increased",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Oedema peripheral",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ABADIE D, DURRIEU G, ROUSSIN A, MONTASTRUC JL.. ^SERIOUS^ ADVERSE DRUG REACTIONS WITH TRAMADOL: A 2010-2011 PHARMACOVIGILANCE SURVEY IN FRANCE.. THERAPIE. 2013;68(2):77-84",
"literaturereference_normalized": "serious adverse drug reactions with tramadol a 2010 2011 pharmacovigilance survey in france",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20150521",
"receivedate": "20131218",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9771234,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150821"
},
{
"companynumb": "PHHY2013FR145515",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TRAMADOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075968",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "2 DF, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "FACIAL NEURALGIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "032",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRAMADOL"
}
],
"patientagegroup": null,
"patientonsetage": "46",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Malaise",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ABADIE D, DURRIEU G, ROUSSIN A, MONTASTRUC JL.. ^SERIOUS^ ADVERSE DRUG REACTIONS WITH TRAMADOL: A 2010-2011 PHARMACOVIGILANCE SURVEY IN FRANCE.. THERAPIE. 2013;68(2):77-84",
"literaturereference_normalized": "serious adverse drug reactions with tramadol a 2010 2011 pharmacovigilance survey in france",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20150521",
"receivedate": "20131218",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9771237,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150821"
},
{
"companynumb": "FR-ZYDUS-002478",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TRIMEBUTINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "IN TOTAL",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
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"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIMEBUTINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TIAPROFENIC ACID"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "IN TOTAL",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TIAPROFENIC ACID"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TRAMADOL"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "090404",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "IN TOTAL",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRAMADOL."
}
],
"patientagegroup": "5",
"patientonsetage": "20",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Altered state of consciousness",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Vomiting",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hallucination",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Somnolence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Dyspepsia",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Intentional overdose",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Confusional state",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Psychiatric symptom",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Gastrointestinal disorder",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Completed suicide",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Suicidal ideation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Dizziness",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Seizure",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Neurological symptom",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Coma",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Nausea",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ABADIE D, ET AL. SERIOUS ADVERSE DRUG REACTIONS WITH TRAMADOL: A 2010-2011 PHARMACOVIGILANCE SURVEY IN FRANCE. THERAPIE 2013 MAR?68(2):77-84.",
"literaturereference_normalized": "serious adverse drug reactions with tramadol a 2010 2011 pharmacovigilance survey in france",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20190109",
"receivedate": "20140124",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9850917,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
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{
"abstract": "We present a case of a young woman diagnosed with complex regional pain syndrome (CRPS) who underwent spinal cord stimulator (SCS) implantation. She had 2 successful pregnancies following implantation.\n\n\n\nWe evaluated the electronic medical records of the patient following SCS implantation and while pregnant with her second and third children. A phone interview was conducted after her third pregnancy to discuss her experience with SCS use during and after pregnancy.\n\n\n\nPhysical medicine and rehabilitation pain management clinic and obstetrician clinic, affiliated with the Medical College of Wisconsin in Milwaukee, Wisconsin.\n\n\n\nA 26-year-old woman with history of CRPS type I.\n\n\n\nThis 26-year-old woman was diagnosed with CRPS type I after left knee surgery. All conservative treatments had failed prior to her undergoing SCS implantation after the birth of her first child. SCS implantation brought near complete resolution of her symptoms. When she became pregnant with her second child, she turned off her SCS. Her CRPS symptoms intensified, but she had a normal pregnancy. She turned the SCS back on postpartum and elected to continue its use throughout her third pregnancy. She had a normal pregnancy, and her CRPS symptoms were well controlled. The patient and her children are currently healthy. Her SCS remains functional and effective.\n\n\n\nBoth an SCS and many medications used for pain management in CRPS could cause harm to both mother and fetus in pregnancy. Further research must be done to determine the safety and efficacy of SCS use in pregnancy.",
"affiliations": "Department of Physical Medicine and Rehabilitation, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A.;Department of Physical Medicine and Rehabilitation, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A.",
"authors": "Jozwiak|Meagan J|MJ|0000-0001-8802-7299;Wu|Hong|H|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1111/papr.12825",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1530-7085",
"issue": "20(1)",
"journal": "Pain practice : the official journal of World Institute of Pain",
"keywords": "complex regional pain syndrome type I; spinal cord stimulation",
"medline_ta": "Pain Pract",
"mesh_terms": "D000328:Adult; D005260:Female; D006801:Humans; D059408:Pain Management; D011247:Pregnancy; D011248:Pregnancy Complications; D012019:Reflex Sympathetic Dystrophy; D062187:Spinal Cord Stimulation",
"nlm_unique_id": "101130835",
"other_id": null,
"pages": "88-94",
"pmc": null,
"pmid": "31357254",
"pubdate": "2020-01",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Complex Regional Pain Syndrome Management: An Evaluation of the Risks and Benefits of Spinal Cord Stimulator Use in Pregnancy.",
"title_normalized": "complex regional pain syndrome management an evaluation of the risks and benefits of spinal cord stimulator use in pregnancy"
} | [
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}
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{
"reactionmeddrapt": "Maternal exposure during pregnancy",
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],
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},
"primarysource": {
"literaturereference": "JOZWIAK MJ, WU H.. COMPLEX REGIONAL PAIN SYNDROME MANAGEMENT: AN EVALUATION OF THE RISKS AND BENEFITS OF SPINAL CORD STIMULATOR USE IN PREGNANCY. PAIN PRACTICE. 2020?20(1):88-94",
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] |
{
"abstract": "BACKGROUND\nCalcific uraemic arteriolopathy (calciphylaxis) is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis. It mainly affects patients with end-stage renal disease (ESRD) on haemodialysis, but may rarely occur in the absence of ESRD in conditions such as primary hyperparathyroidism, malignancy, alcoholic liver disease and connective tissue disease.\n\n\nMETHODS\nWe reviewed the records of all patients diagnosed with calciphylaxis while on renal replacement therapy at Tygerberg Hospital, Cape Town, South Africa, between 1990 and 2014, to describe its presentation, course and final outcome.\n\n\nRESULTS\nNineteen patients developed calciphylaxis over this period. Their median age was 34 years and 13 (68.4%) were female. Fifteen (78.9%) had received a kidney transplant. All patients had painful skin lesions that rapidly progressed to infarction. Small-vessel calcification was seen on skin biopsy in 13 patients. Twelve patients had hyperparathyroidism. Several of the transplanted patients had been treated for graft rejection in the year preceding the diagnosis. Treatment consisted of good wound care and efforts to normalise serum calcium and phosphate levels. Five patients received an urgent parathyroidectomy. The outcome was fatal in 17 patients, with sepsis being the main cause of death.\n\n\nCONCLUSIONS\nIn our patients, calciphylaxis carried a worse prognosis than previously reported internationally. It should always be considered in the differential diagnosis of painful skin lesions in the dialysis or transplant patient.",
"affiliations": "Division of Nephrology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa. mrd@sun.ac.za.",
"authors": "Sebastian|S|S|;Jordaan|H F|HF|;Schneider|J W|JW|;Moosa|M R|MR|;Davids|M R|MR|",
"chemical_list": null,
"country": "South Africa",
"delete": false,
"doi": "10.7196/SAMJ.2017.v107i2.11058",
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"issue": "107(2)",
"journal": "South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde",
"keywords": null,
"medline_ta": "S Afr Med J",
"mesh_terms": null,
"nlm_unique_id": "0404520",
"other_id": null,
"pages": "140-144",
"pmc": null,
"pmid": "28220742",
"pubdate": "2017-01-30",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Calcific uraemic arteriolopathy (calciphylaxis) in patients on renal replacement therapy.",
"title_normalized": "calcific uraemic arteriolopathy calciphylaxis in patients on renal replacement therapy"
} | [
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{
"abstract": "Propofol is a hypnotic agent for induction and maintainance of general anaesthesia and it is used for sedation of critically ill intensive care patients. As a rare adverse effect propofol can cause acute pancreatitis. We report a case of post-operative pancreatitis in an otherwise healthy 62-year-old male who was anaesthezised with propofol during an otherwise uncomplicated surgery for thyroid carcinoma. Other common causes could be excluded. Since this is a possible lethal complication in post-operative patients, medical doctors should be aware of this adverse effect.",
"affiliations": "Øre-, Næse-, Halskirurgisk Afdeling, Aalborg Universitetshospital, Hobrovej 18-22, 9100 Aalborg. karoline.lange@rn.dk.",
"authors": "Lange|Karoline|K|;Rostgaard-Knudsen|Martin|M|;Rasmussen|Bodil Steen|BS|",
"chemical_list": "D018686:Anesthetics, Intravenous; D015742:Propofol",
"country": "Denmark",
"delete": false,
"doi": null,
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"issn_linking": "0041-5782",
"issue": "176(21)",
"journal": "Ugeskrift for laeger",
"keywords": null,
"medline_ta": "Ugeskr Laeger",
"mesh_terms": "D018686:Anesthetics, Intravenous; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis; D011183:Postoperative Complications; D015742:Propofol; D013964:Thyroid Neoplasms",
"nlm_unique_id": "0141730",
"other_id": null,
"pages": null,
"pmc": null,
"pmid": "25351903",
"pubdate": "2014-05-19",
"publication_types": "D002363:Case Reports",
"references": null,
"title": "Propofol-induced pancreatitis after surgery for thyroid carcinoma.",
"title_normalized": "propofol induced pancreatitis after surgery for thyroid carcinoma"
} | [
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"abstract": "Metastatic colorectal cancer represents a striking example of clonal heterogeneity and tumour evolution, which generates acquired resistance to therapy. Once hard to perform, the study of clonal heterogeneity is now significantly aided by the use of liquid biopsies.\nWe herein report a case of a patient with colorectal cancer and serial development of multiple metastases which were all resected and genotyped. A rare point mutation was identified in the primary tumour (but not in any of the organ metastatic sites), as well as in the first and the last out of three consecutive liquid biopsies. The review of the literature offered some insight in the evolution of the patient's tumour and general directions on how to interpret liquid biopsy results.\nThis patient case emphasises the need for large prospective studies designed to bridge liquid biopsy data with useful clinical endpoints, in order to optimally integrate this revolutionary tool in everyday practice.",
"affiliations": "Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.;Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.;Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.;Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece.;Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece.;GeneKor Medical SA, Athens, Greece.;GeneKor Medical SA, Athens, Greece.;Haematology Laboratory, Ioannina University Hospital, Ioannina, Greece.;Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.",
"authors": "Kastrisiou|Myrto|M|;Zarkavelis|George|G|;Kampletsas|Eleftherios|E|;Panopoulou|Eleni|E|;Goussia|Anna|A|;Nasioulas|George|G|;Papadopoulou|Eirini|E|;Tsaousi|Christina|C|;Pentheroudakis|George|G|",
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"fulltext": "\n==== Front\nESMO OpenESMO OpenesmoopenesmoopenESMO Open2059-7029BMJ Publishing Group BMA House, Tavistock Square, London, WC1H 9JR 29942663esmoopen-2018-00032910.1136/esmoopen-2018-000329Original Research1506Clonal evolution of colorectal cancer in a patient with serially resected metastases and liquid biopsies: a case report and discussion of the literature Kastrisiou Myrto 12Zarkavelis George 12Kampletsas Eleftherios 1Panopoulou Eleni 3Goussia Anna 3Nasioulas George 4Papadopoulou Eirini 4Tsaousi Christina 5Pentheroudakis George 12\n1 \nSociety for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece\n\n2 \nMedical Oncology, Medical School, University of Ioannina, Ioannina, Greece\n\n3 \nDepartment of Pathology, Medical School, University of Ioannina, Ioannina, Greece\n\n4 \nGeneKor Medical SA, Athens, Greece\n\n5 \nHaematology Laboratory, Ioannina University Hospital, Ioannina, Greece\nCorrespondence to Dr George Pentheroudakis; gpenther@otenet.gr2018 9 6 2018 3 4 e00032907 2 2018 02 4 2018 03 4 2018 © European Society for Medical Oncology (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.2018This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Background\nMetastatic colorectal cancer represents a striking example of clonal heterogeneity and tumour evolution, which generates acquired resistance to therapy. Once hard to perform, the study of clonal heterogeneity is now significantly aided by the use of liquid biopsies.\n\nMethod\nWe herein report a case of a patient with colorectal cancer and serial development of multiple metastases which were all resected and genotyped. A rare point mutation was identified in the primary tumour (but not in any of the organ metastatic sites), as well as in the first and the last out of three consecutive liquid biopsies. The review of the literature offered some insight in the evolution of the patient’s tumour and general directions on how to interpret liquid biopsy results.\n\nConclusions\nThis patient case emphasises the need for large prospective studies designed to bridge liquid biopsy data with useful clinical endpoints, in order to optimally integrate this revolutionary tool in everyday practice.\n\ncolorectal cancerclonal heterogeneitystk11liquid biopsiesspecial-featureunlocked\n==== Body\nKey questions\nWhat is already known about this subject?\nCancer is highly heterogeneous in both space and time, due to emergence of new clones with different metastatic potential throughout the course of the disease.\n\nTumour heterogeneity is bidirectionally related to resistance to treatment through evolutionary selective pressure.\n\nThe mutated gene described herein has been associated with a number of solid tumours, although rarely in somatic colorectal neoplasms.\n\nWhat does this study add?\nThis is a rare case of serially resected metastases which were tested for cancer-related mutations.\n\nOur data offer insight in tumour evolution, also giving a hint of how administration of targeted agents may interfere with it.\n\nThe specific nucleotide substitution we describe has never been reported in any type of neoplasia.\n\nHow might this impact on clinical practice?\nReporting rare cases is the only way to gain experience in how to deal with them.\n\nThis case report also highlights the lack of evidence on actionability of markers studied by liquid biopsies and the need to prospectively validate their clinical utility.\n\nIntroduction\nClonal heterogeneity and clonal evolution, both very common features of colorectal neoplasia, refer to the emergence of distinct, subclonal tumour populations with differing genotypic abnormalities, either spontaneously or as a result of administered therapies that eliminate some vulnerable, and favour the growth of resistant, tumour cells. Conventionally, tumour clonal heterogeneity was difficult to study, as this required repeated biopsies associated with cost, morbidity and sampling errors. The technological breakthrough of liquid biopsies offered promise in this setting. ‘Liquid biopsy’ refers to the detection and characterisation of circulating cell-free nucleic acids (or cell-free DNA (cfDNA)) from peripheral venous blood. The characterisation of a DNA fragment as tumour derived (circulating tumour DNA (ctDNA)) is mainly based on the identification of a known genetic alteration or methylation pattern specific to the tumour and/or absent from normal tissue, by use of different techniques. The sensitivity of liquid biopsy depends on the abundance of tumour nucleic acids as represented by disease stage or overall tumour load. Here, we present a case of a patient with metastatic colorectal cancer (CRC) for whom multiple metastases and plasma were available throughout the disease course, thus enabling us to monitor cancer evolution.\n\nCase report\nA 44-year-old male patient presented to the emergency department of our University Hospital complaining of tenesmus and perineal pain in March 2012. He was an active smoker (60 pack-years) and his medical history consisting of hypertension and allergic rhinitis. His family history was significant and included a paternal grandmother with gynaecological cancer and three paternal aunts with undefined neoplasias.\n\nRectosigmoidoscopy revealed two synchronous ulcerated lesions, extending 5 and 12 cm from the dentate line, respectively. A CT scan of the chest, abdomen and pelvis showed a hepatic metastasis in liver segment VI and subcentimetre lung nodules in the right upper and lower lobes, respectively, biopsied as non-malignant. The patient underwent rectosigmoidectomy by abdominoperineal resection. Pathology of the surgical specimens revealed adenocarcinoma in both sites and confirmed R0 resection. The two lesions were sized 4.4×2.5 cm and 2.1×2.1 cm; 18 out of the 27 excised lymph nodes were positive for carcinomatous metastasis. The tumour was therefore staged as IIIC (T3N2bMx) multicentric rectal adenocarcinoma and was found to be wild type in extended RAS testing (KRAS and NRAS exons 2, 3, 4 by Illumina MiSeq PCR platform) and microsatellite stable (by tumour PCR testing of the Bethesda panel of five dinucleotide repeats).\n\nThe patient was started on capecitabine-based concurrent external beam chemoradiotherapy (total dose 50.4 Gy in 19 fractions) followed by five cycles of chemotherapy (capecitabine orally at 1000 mg/m2 twice daily on days 1–14 and oxaliplatin intravenously at 130 mg/m2 on day 1 every 3 weeks, or CAPOX), which were well tolerated. In December 2012, he underwent resection of liver segment VI, which confirmed the synchronous metastasis, upstaging the carcinoma to stage IV disease. Four additional 3-week treatment courses of CAPOX with panitumumab (at 8 mg/kg body weight) were administered, with no CT evidence of residual disease. The patient was followed up for 6 months and subsequently quit the follow-up programme on his own volition.\n\nIn April 2016, CT and positron-emission tomography (PET)/CT depicted a 3×2.3 cm mass in the right lower pulmonary lobe, two paratracheal and one subcarinal lymph nodes (with maximal diameters at 2.0 and 2.3 cm, respectively) and a 12 mm right supraclavicular node. Recurrence was confirmed with resection of the supraclavicular lymph node, followed by lung lobectomy and resection of mediastinal nodes by an attending thoracic surgeon. The supraclavicular node and the lung deposit were positive for adenocarcinoma, with an immunohistochemical profile compatible with the known primary (cytokeratin 20 positive, CDX2 positive, cytokeratin 7 negative, thyroid transcription factor-1 negative, Napsin A negative). In September 2016, due to balance and gait problems, a brain CT and MRI revealed an enhancing right cerebellar 3.2×3×3 cm metastasis, managed with right suboccipital craniectomy followed by brain radiotherapy. Histology confirmed the presence of metastasis with morphology and immunophenotype consistent with gastrointestinal origin (figure 1).\n\nFigure 1 Infiltration of the cerebral cortex from a moderately differentiated adenocarcinoma (H&E ×100).\n\nRestaging CT scans of the abdomen and thorax showed no visible remaining disease. Before proceeding with further systemic therapy and in view of occurrence of multiple distant relapses which had been resected, we opted for study of clonal heterogeneity of the patient’s malignancy in the context of a research protocol. Additionally, we needed to design a targeted therapeutic strategy. Next Generation Sequencing of 50 cancer-related genes was thus applied in all resected neoplastic material available (figure 2). The resected primary tumour was confirmed to be all RAS wild type; it, however, harboured a point mutation on the STK11 gene exon 6 (STK11 c.759C>A). The mutation was somatic and tumour specific, as it was not present in germ line DNA isolated from peripheral blood white blood cells at baseline. The other metastatic sites (from the liver, supraclavicular lymph node, lung and brain) tested negative for mutations in all the examined genes, including STK11.\n\nFigure 2 Tested genes per site of neoplastic material or cell-free DNA that was subjected to next-generation sequencing. Μutated genes are depicted in dark.\n\nChemotherapy (intravenous infusions of irinotecan at 180 mg/m2, leucovorin at 400 mg/m2, 5-fluorouracil at 400 mg/m2 on day 1, then at 4800 mg/m2 over 2 days, FOLFIRI) plus panitumumab (intravenously at 480 mg/kg on day 1) every 2 weeks were initiated in order to eradicate potential micrometastatic disease and a peripheral venous blood sample was drawn in November 2016 before the initiation of systemic therapy. Peripheral blood cfDNA in November 2016 yielded the presence of the STK11 mutation that was detected in the primary tumour resected in March 2012. A repeat cfDNA sample was drawn in February 2017 (after one cycle of FOLFIRI/panitumumab) with no evidence of any mutation. In the patient’s last follow-up visit in October 2017 (4 months after the completion of 11 cycles of FOLFIRI/panitumumab), he was clinically and radiologically disease free. During the same visit, a third cfDNA sample was acquired, in which the STK11 mutation was again identified. The clonal make-up of the malignancy over time is summarised in figure 3.\n\nFigure 3 Mutational evolution of the tumour in the various sites over time. CAPOX, capecitabine/oxaliplatin; FOLFIRI, folinic acid/5-fluorouracil/irinotecan; met, metastasis; res’d, resected; SCLN, subclavicular lymph node.\n\nDiscussion\nThe gene that was found mutated in our patient (STK11, also called LKB1) encodes a serine/threonine kinase that coordinates cell growth, polarity, motility and metabolism.1 STK11 is a well-established tumour suppressor and a promoter of apoptosis1 whose actions are partly mediated by AMPK.2 Besides its function against tumour growth, it appears to be required for normal development in utero. Germ line mutations in the STK11 gene are frequently associated with Peutz-Jeghers syndrome and related neoplasias, while somatic mutations have been reported in various malignancies among which non-small cell lung carcinoma, cervical cancers and cutaneous melanomas.1 2\n\n\n\nSTK11 is only rarely mutated in somatic CRC (in 5/653 or 0.8%).3 Of note, the specific single nucleotide substitution in the STK11 gene we discovered, namely, c.759C>A (p.Y253), is previously unreported in any type of neoplasia; however, the importance of this case lies elsewhere. It is unique in the sense that all four metastatic sites were resected and genetically analysed—a strategy difficult to implement in clinical practice which, however, may offer exceptional insight in the spatiotemporal genetic evolution of the tumour.\n\n\nRAS mutation status being more than 90% concordant between primary tumour and metastases,4 5 ‘private’ mutations are rare (accounting for 18 out of 434 mutations in tumour tissue samples from 69 patients),5 often associated with more than one independent primaries.4 Synchronous primary CRCs occur in 3.4%–6.2% of patients with CRC, with 9/13 pairs of synchronous primary CRCs exhibiting discordant KRAS mutational profiles.4 Interestingly, our patient harboured two distinct rectal primaries. It is thus possible that the metastases originated from the STK11-wild type rectal primary, whereas cfDNA harbouring the STK11 mutation originated from the other, supposedly STK11-mutated rectal primary. The fact that the patient’s mutation was ‘primary specific’ is an even rarer finding. This could be a result of onsite heterogeneity and associated random sampling error (as genetic analysis of the metastases was performed on block sections rather than the whole of the surgical specimens), although the examination of more than one metastatic sites weakens this hypothesis. Finally, one could hypothesise that the absence of the STK11 mutation from the metastatic tissue is owing to the administered treatment, as a direct result of the lowered tumour burden achieved by therapy. KRAS-mutant allele levels have also been reported to gradually drop following anti-estimated glomerular filtration rate (EGFR) therapy withdrawal.6 7 However, the effect of EGFR inhibitors on malignant clonal evolution5 mainly refers to the emergence of de novo mutations8 9 rather than the evanescence of existing ones.\n\nIn our patient case, the true clinically relevant question lies in the appearance, disappearance and subsequent reappearance of the STK11 mutation in the bloodstream. The use of ctDNA for the detection of KRAS mutations in patients with CRC is associated with high specificity (0.96 and 0.9810 11 in two recent meta-analyses), the detection of a mutation being impossible outside the context of residual disease12 and trustworthy for diagnosing recurrence, while negative results cannot assure the complete elimination of tumour cells. In light of this data, the identification of the STK11 mutation in the patient’s circulation points to an occult niche of tumour cells shedding mutant DNA.\n\nIn conclusion, liquid biopsies are rapidly being integrated as useful adjuncts in clinical practice. Among their various emerging applications, they illustrate molecular heterogeneity over time and space, track tumour dynamics, spontaneous and therapy induced and help monitor response to therapy and minimal residual disease.13 However, only rationally designed prospective studies that couple liquid biopsy data to clinically relevant endpoints will identify the clinical utility and actionableness of this powerful tool, along with its contribution to studying clonal heterogeneity.\n\nContributors: MK, GZ, EK and GP had full access to all of the data of the case and take the responsibility for the integrity and interpretation of the data. AG kindly provided and edited Figure 1. MK performed the literature search, designed and edited the text, Figures 2 and 3 and their legends. GP conceived and finally reviewed the manuscript. All the authors contributed to the writing of the manuscript.\n\nFunding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.\n\nCompeting interests: GN and EP are employees of GeneKor Medical SA, Athens, Greece.\n\nPatient consent: Obtained.\n\nProvenance and peer review: Not commissioned; externally peer reviewed.\n==== Refs\nReferences\n1. \nLiu Y , Marks K , Cowley GS , et al \nMetabolic and functional genomic studies identify deoxythymidylate kinase as a target in LKB1-mutant lung cancer . Cancer Discov \n2013 ;3 :870 –9 . 10.1158/2159-8290.CD-13-0015 \n23715154 \n2. \nHardie DG , Alessi DR \nLKB1 and AMPK and the cancer-metabolism link – ten years after . BMC Biol \n2013 ;11 :36 \n10.1186/1741-7007-11-36 \n23587167 \n3. \nMalapelle U , Pisapia P , Sgariglia R , et al \nLess frequently mutated genes in colorectal cancer: evidences from next-generation sequencing of 653 routine cases . J Clin Pathol \n2016 ;69 :767 –71 . 10.1136/jclinpath-2015-203403 \n26797410 \n4. \nVakiani E , Janakiraman M , Shen R , et al \nComparative genomic analysis of primary versus metastatic colorectal carcinomas . J Clin Oncol \n2012 ;30 :2956 –62 . 10.1200/JCO.2011.38.2994 \n22665543 \n5. \nBrannon AR , Vakiani E , Sylvester BE , et al \nComparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions . Genome Biol \n2014 ;15 :454 \n10.1186/s13059-014-0454-7 \n25164765 \n6. \nTrojan J , Klein-Scory S , Koch C , et al \nClinical application of liquid biopsy in targeted therapy of metastatic colorectal cancer . Case Rep Oncol Med \n2017 ;2017 :1 –3 . 10.1155/2017/6139634 \n\n7. \nSiravegna G , Mussolin B , Buscarino M , et al \nClonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients . Nat Med \n2015 ;21 :827 \n10.1038/nm0715-827b \n\n8. \nMohan S , Heitzer E , Ulz P , et al \nChanges in colorectal carcinoma genomes under anti-EGFR therapy identified by whole-genome plasma DNA sequencing . PLoS Genet \n2014 ;10 :e1004271\n10.1371/journal.pgen.1004271 \n24676216 \n9. \nKovaleva V , Geissler AL , Lutz L , et al \nSpatio-temporal mutation profiles of case-matched colorectal carcinomas and their metastases reveal unique de novo mutations in metachronous lung metastases by targeted next generation sequencing . Mol Cancer \n2016 ;15 :63 \n10.1186/s12943-016-0549-8 \n27756406 \n10. \nHao YX , Fu Q , Guo YY , et al \nEffectiveness of circulating tumor DNA for detection of KRAS gene mutations in colorectal cancer patients: a meta-analysis . Onco Targets Ther \n2017 ;10 :945 –53 . 10.2147/OTT.S123954 \n28243130 \n11. \nTang M , Deng Z , Li B , et al \nCirculating tumor DNA is effective for detection of KRAS mutation in colorectal cancer: a meta-analysis . Int J Biol Markers \n2017 ;32 :421 –7 . 10.5301/ijbm.5000295 \n\n12. \nDiehl F , Schmidt K , Choti MA , et al \nCirculating mutant DNA to assess tumor dynamics . Nat Med \n2008 ;14 :985 –90 . 10.1038/nm.1789 \n18670422 \n13. \nDiaz LA , Bardelli A \nLiquid biopsies: genotyping circulating tumor DNA . J Clin Oncol \n2014 ;32 :579 –86 . 10.1200/JCO.2012.45.2011 \n24449238\n\n",
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"title": "Clonal evolution of colorectal cancer in a patient with serially resected metastases and liquid biopsies: a case report and discussion of the literature.",
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},
{
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},
{
"reactionmeddrapt": "Colorectal cancer metastatic",
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"reactionoutcome": "6"
},
{
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"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 201301"
}
},
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"literaturereference": "ZARKAVELIS G. CLONAL EVOLUTION OF COLORECTAL CANCER IN A PATIENT WITH SERIALLY RESECTED METASTASES AND LIQUID BIOPSIES: A CASE REPORT AND DISCUSSION OF THE LITERATURE. BMJ. 2018?3(4):E000329 (1-4)",
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"transmissiondate": "20200409"
}
] |
{
"abstract": "We report a rare case of adenoviral pneumonia in a previously healthy pregnant woman at 26(+4) weeks' gestation. She presented with persistent high fever, cough for 5 days, and developed progressive dyspnea with hypoxemic respiratory failure and bilateral pulmonary infiltrates with pleural effusions. Aggressive supportive care and timely obstetrical management saved the mother and prevented preterm delivery and fetal anomaly.",
"affiliations": "Department of Pulmonary and Critical Care Medicine, Peking University First Hospital, Beijing, China.;Department of Pulmonary and Critical Care Medicine, Peking University First Hospital, Beijing, China.;Department of Pulmonary and Critical Care Medicine, Peking University First Hospital, Beijing, China.;Laboratory of Virology, Capital Institute of Pediatrics, Beijing, China.;Laboratory of Virology, Capital Institute of Pediatrics, Beijing, China.;Department of Pulmonary and Critical Care Medicine, Peking University First Hospital, Beijing, China. quechengli@hotmail.com.",
"authors": "Liao|Ji-Ping|JP|;Wang|Guang-Fa|GF|;Jin|Zhe|Z|;Qian|Yuan|Y|;Deng|Jie|J|;Que|Cheng-Li|CL|",
"chemical_list": null,
"country": "Australia",
"delete": false,
"doi": "10.1111/jog.13036",
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"issn_linking": "1341-8076",
"issue": "42(9)",
"journal": "The journal of obstetrics and gynaecology research",
"keywords": "adenovirus; immunocompetent; pneumonia; pregnancy",
"medline_ta": "J Obstet Gynaecol Res",
"mesh_terms": "D000256:Adenoviridae; D000328:Adult; D005260:Female; D005865:Gestational Age; D006801:Humans; D008168:Lung; D011024:Pneumonia, Viral; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011256:Pregnancy Outcome; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome",
"nlm_unique_id": "9612761",
"other_id": null,
"pages": "1194-7",
"pmc": null,
"pmid": "27325617",
"pubdate": "2016-09",
"publication_types": "D002363:Case Reports",
"references": "15270922;15295381;22608839;25112957;10868146;23021691;21345415;24897084;27325617;21502080;21640231;17573440;21900872;21718493",
"title": "Severe pneumonia caused by adenovirus 7 in pregnant woman: Case report and review of the literature.",
"title_normalized": "severe pneumonia caused by adenovirus 7 in pregnant woman case report and review of the literature"
} | [
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}
],
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"reaction": [
{
"reactionmeddrapt": "Foetal exposure during pregnancy",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Respiratory distress",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
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"reactionmeddraversionpt": "19.1",
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}
],
"summary": null
},
"primarysource": {
"literaturereference": "LIAO J-P, WANG G-F, JIN Z, QIAN Y, DENG J, QUE C-L. SEVERE PNEUMONIA CAUSED BY ADENOVIRUS 7 IN PREGNANT WOMAN: CASE REPORT AND REVIEW OF THE LITERATURE. J-OBSTET-GYNAECOL-RES 2016;42(9):1194-1197.",
"literaturereference_normalized": "severe pneumonia caused by adenovirus 7 in pregnant woman case report and review of the literature",
"qualification": "3",
"reportercountry": "CN"
},
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"receiptdate": "20161013",
"receivedate": "20161013",
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},
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},
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"seriousnesscongenitalanomali": null,
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}
] |
{
"abstract": "BACKGROUND\nThe prognosis of locally advanced Gastric Cancer following surgical therapy alone is poor. Peritoneum represents a preferential site of dissemination in such neoplasm. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used in association with cytoreductive surgery (CRS) in the treatment of GC peritoneal carcinomatosis (PC). Aim of our preliminary experience is reporting our data on prophylactic HIPEC (P-HIPEC) in patients with GC at high risk of developing PC.\n\n\nMETHODS\nEleven patients underwent P-HIPEC at our General and Emergency Surgery Department. All the patients were affected of high risk GC: serosa invasive tumors (T4), conventional cytology-positive or quantitative PCR detection of CEA mRNA on peritoneal lavage. Seven subtotal and four total gastrectomies with D2 or D2+ were performed. All the anastomoses were made before HIPEC. The procedure was carried out for 60 minutes with Mytomicin C and Cisplatin in all patients. Post-operative monitoring in Intensive Care Unit least for 24-48 hours. Oral nutrition was started precociously (day 5) also according with bowel movements and stool/gas passage. Follow-up took place in all patients at 1 month from surgery then every 6 months for 2 years and every 12 months for the following years.\n\n\nRESULTS\nIn four patients a neoadjuvant treatment was scheduled due to T or N stage at pre-operative evaluation. Gastric resection was guided on tumor location while the choice of performing a D2 or D2 + lymphadenectomy was up to preoperative imaging and intra-operative nodal status. No intra-operative complications were recorded. Median operation time was 398 minutes. In our series we recorded 20 adverse events. Median number for each patient was 1 adverse effect (range 0-2). Eight patients experienced a surgical adverse effect (G2-G3) that did not require any surgical treatment. Only one patient with duodenal stump dehiscence and intra-abdominal sepsis (G4-G5) underwent re-operation and died for severe hemorrhagic pancreatitis. Another patient died for ARDS. Per-operative mortality was 18%. Both patients were older then 70 years old. Median hospital stay was 14 days. Median follow-up was 15.9 months. Median survival was 29.6 months and median DFS was 20 months. Only one patient developed a peritoneal recurrence at 12 months and died for disease progression. Seven patients are still alive and disease free at last follow-up. One patient affected of variable immunodeficiency died at 9 months for pulmonary sepsis without any sign of local recurrence.\n\n\nCONCLUSIONS\nPeritoneal dissemination appears to be a strong determinant in defining GC patients prognosis. Even after curative resection, peritoneal recurrence develops in about 60% of the patients with T3 and T4 tumors, and up to 40% of resected gastric cancer patients die as a direct result of peritoneal dissemination. Clinical trials showed that surgery plus HIPEC was associated with a significant improvement in survival compared to surgery alone in patients affected of GC with resectable PC. At present day there are not studies evaluating the role of P-HIPEC in patients at high risk of developing PC. The rationale of P-HIPEC is based on the concept that positive peritoneal lavage is considered an M1 (stage IV) similarly to macroscopic PC by the 7th TNM classification. Also analogous is the median survival of this 2 groups of patients. Detection of peritoneal micrometastases with cytologic examination has been considered a major method to predict peritoneal recurrences; the sensitivity of this assay is low. Recently, molecular approaches using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) technique has made possible the increase in the sensitivity. We can conclude, although the preliminary experience, that prophylactic HIPEC in locally advanced gastric cancer is feasible, increasing median survival compared to surgery alone. For sure this procedure need to be performed in the highly specialized centres strongly respecting the eligibility criteria.",
"affiliations": null,
"authors": "Graziosi|Luigina|L|;Cantarella|Francesco|F|;Mingrone|Elvira|E|;Gunnellini|Marco|M|;Cavazzoni|Emanuel|E|;Liberati|Marina|M|;Donini|Annibale|A|",
"chemical_list": null,
"country": "Italy",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0003-469X",
"issue": "84(5)",
"journal": "Annali italiani di chirurgia",
"keywords": null,
"medline_ta": "Ann Ital Chir",
"mesh_terms": "D000230:Adenocarcinoma; D000328:Adult; D000368:Aged; D018890:Chemoprevention; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms; D013274:Stomach Neoplasms",
"nlm_unique_id": "0372343",
"other_id": null,
"pages": "551-6",
"pmc": null,
"pmid": "24140896",
"pubdate": "2013",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Preliminary results of prophylactic HIPEC in patients with locally advanced gastric cancer.",
"title_normalized": "preliminary results of prophylactic hipec in patients with locally advanced gastric cancer"
} | [
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],
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},
{
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"reactionoutcome": "6"
},
{
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},
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"literaturereference": "GRAZIOSI L, CANTARELLA F, MINGRONE E, GUNNELLINI M, CAVAZZONI E, LIBERATI M, DONINI A. PRELIMINARY RESULTS OF PROPHYLACTIC HIPEC IN PATIENTS WITH LOCALLY ADVANCED GASTRIC CANCER. ANN ITAL CHIR. 2013 SEP-OCT;84(5):551-6.",
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},
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},
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},
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"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
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"transmissiondate": "20150821"
},
{
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{
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},
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"medicinalproduct": "CISPLATIN."
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}
],
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"patientsex": "2",
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"reaction": [
{
"reactionmeddrapt": "Hepatotoxicity",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
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"reactionoutcome": "6"
}
],
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},
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"literaturereference": "GRAZIOSI L, CANTARELLA F, MINGRONE E, GUNNELLINI M, CAVAZZONI E, LIBERATI M, DONINI A. PRELIMINARY RESULTS OF PROPHYLACTIC HIPEC IN PATIENTS WITH LOCALLY ADVANCED GASTRIC CANCER. ANN ITAL CHIR. 2013 SEP-OCT;84(5):551-6.",
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},
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"receiptdate": "20150526",
"receivedate": "20150526",
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] |
{
"abstract": "The objective of this study was to collect the data of medication errors by the self-report of doctors and nurses in critically ill surgical patients.\n\n\n\nAll data were collected from THAI-SICU database in nine medical schools in Thailand during a\nperiod of 22 months. The occurrence and medication error related factors were recorded.\n\n\n\nFrom 4,652 admissions, there were only 10 cases of medication error. Of these, there were only 7 cases of complete self-report medication error, and all of them had no critical side effects. Most cases were of receiving wrong doses of medicine especially overdosing. The medicine preparers, administrators and the error detectors were mostly nurses. For immediate outcomes, two cases were reported of low blood pressure and one case was reported of lowering self-conscious. For longterm outcomes, there were two cases of prolonged ICU stays. Regarding the contributing factors, the most frequent problem found was communication. The most important factor minimizing incidents was to increase proper care. As to suggested corrective strategies, it was found that improved supervision was most needed.\n\n\n\nReporting of medication errors by a self-report of doctors and nurses is low in this cohort, which might result from occurrences not being reported. The wrong dose is the most common occurrence and the communication is the most related factor.",
"affiliations": null,
"authors": "Thawitsri|Thammasak|T|;Chittawatanarat|Kaweesak|K|;Chaiwat|Onuma|O|;Charuluxananan|Somrat|S|",
"chemical_list": null,
"country": "Thailand",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0125-2208",
"issue": "99 Suppl 6()",
"journal": "Journal of the Medical Association of Thailand = Chotmaihet thangphaet",
"keywords": null,
"medline_ta": "J Med Assoc Thai",
"mesh_terms": "D016638:Critical Illness; D003625:Data Collection; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D015994:Incidence; D008508:Medication Errors; D011446:Prospective Studies; D012307:Risk Factors; D013785:Thailand",
"nlm_unique_id": "7507216",
"other_id": null,
"pages": "S69-S73",
"pmc": null,
"pmid": "29906085",
"pubdate": "2016-11",
"publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Self-Reporting of Medication Errors in Critically Ill Surgical Patients in the THAI-SICU Study.",
"title_normalized": "self reporting of medication errors in critically ill surgical patients in the thai sicu study"
} | [
{
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"activesubstance": {
"activesubstancename": "VALPROATE SODIUM"
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}
],
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"reaction": [
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"reactionmeddrapt": "Drug dispensing error",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Somnolence",
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"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 20110819"
}
},
"primarysource": {
"literaturereference": "THAWITSRI T, CHITTAWATANARAT K, CHAIWAT O, CHARULUXANANAN S. SELF-REPORTING OF MEDICATION ERRORS IN CRITICALLY ILL SURGICAL PATIENTS IN THE THAI-SICU STUDY. JOURNAL OF THE MEDICAL ASSOCIATION OF THAILAND. 2016;99 (6):S69-S73.",
"literaturereference_normalized": "self reporting of medication errors in critically ill surgical patients in the thai sicu study",
"qualification": "3",
"reportercountry": "COUNTRY NOT SPECIFIED"
},
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}
] |
{
"abstract": ": Cancer is associated with a prothrombotic or hypercoagulable state. Intracoronary thrombosis is a rare and potentially life-threatening complication in cancer patients. We describe a rare case of large nonocclusive intracoronary thrombosis successfully treated by means of medical therapy.",
"affiliations": "Division of Cardiology, Ospedale San Paolo, Dipartimento di Scienze della Salute, University of Milan, Milan, Italy.",
"authors": "Centola|Marco|M|;Lucreziotti|Stefano|S|;Cazzaniga|Sara|S|;Salerno-Uriarte|Diego|D|;Sponzilli|Carlo|C|;Carugo|Stefano|S|",
"chemical_list": "D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D015251:Epirubicin; D002945:Cisplatin",
"country": "United States",
"delete": false,
"doi": "10.2459/JCM.0000000000000444",
"fulltext": null,
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"issn_linking": "1558-2027",
"issue": "17 Suppl 2()",
"journal": "Journal of cardiovascular medicine (Hagerstown, Md.)",
"keywords": null,
"medline_ta": "J Cardiovasc Med (Hagerstown)",
"mesh_terms": "D000368:Aged; D000925:Anticoagulants; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms; D002945:Cisplatin; D017023:Coronary Angiography; D003328:Coronary Thrombosis; D004359:Drug Therapy, Combination; D015251:Epirubicin; D005260:Female; D005343:Fibrinolytic Agents; D006801:Humans; D010975:Platelet Aggregation Inhibitors; D016896:Treatment Outcome",
"nlm_unique_id": "101259752",
"other_id": null,
"pages": "e241-e243",
"pmc": null,
"pmid": "27606783",
"pubdate": "2016-12",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "A rare case of large intracoronary thrombosis in advanced breast cancer patient treated with epirubicin and cisplatin.",
"title_normalized": "a rare case of large intracoronary thrombosis in advanced breast cancer patient treated with epirubicin and cisplatin"
} | [
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"medicinalproduct": "CISPLATIN (MANUFACTURER UNKNOWN)"
},
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}
],
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"patientonsetage": "71",
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"reaction": [
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},
{
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],
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},
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"literaturereference": "CENTOLA M,LUCREZIOTTI S,CAZZANIGA S,SALERNO-URIARTE D,SPONZILLI C,CARUGO S. A RARE CASE OF LARGE INTRACORONARY THROMBOSIS IN ADVANCED BREAST CANCER PATIENT TREATED WITH EPIRUBICIN AND CISPLATIN.. J CARDIOVASC-MED-(HAGERSTOWN) 2016?241-243.",
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},
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},
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"medicinalproduct": "CISPLATIN."
}
],
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"patientonsetage": "71",
"patientonsetageunit": "801",
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"reaction": [
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"reactionmeddrapt": "Acute coronary syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Coronary artery thrombosis",
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"reactionoutcome": "1"
}
],
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},
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"literaturereference": "CENTOLA M, LUCREZIOTTI S, CAZZANIGA S, SALERNO-URIARTE D, SPONZILLI C, CARUGO S. A RARE CASE OF LARGE INTRACORONARY THROMBOSIS IN ADVANCED BREAST CANCER PATIENT TREATED WITH EPIRUBICIN AND CISPLATIN. J-CARDIOVASC-MED-(HAGERSTOWN) 2016?17 (SUPPL. 2):E241-E243.",
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},
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},
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},
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"medicinalproduct": "CISPLATIN."
}
],
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"abstract": "Acute esophageal necrosis (AEN) has been rarely described and has poorly understood pathophysiology although it is thought to be related to mucosal defense barrier disruption. We report a case of AEN in a 71-year-old patient with clinical signs of gastric outlet obstruction along with anemia and sepsis in the setting of a recent kidney transplant. After failing standard supportive measures, tacrolimus was switched to cyclosporin with overall rapid improvement of AEN and concomitant duodenal ulcerations. This case underscores a possible rare adverse effect of a commonly used immunosuppressant agent that, to our knowledge, has not been specifically reported.",
"affiliations": "Division of Gastroenterology, Loyola University Medical Center, Maywood, IL.;Division of Gastroenterology, Loyola University Medical Center, Maywood, IL.",
"authors": "Wanta|Kaitlin|K|;Abegunde|Ayokunle T|AT|",
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"fulltext": "\n==== Front\nACG Case Rep J\nACG Case Rep J\nACGCRJ\nACGCRJ\nAC9\nACG Case Reports Journal\n2326-3253 Wolters Kluwer Maryland, MD \n\nACGCR-19-0188\n10.14309/crj.0000000000000396\n00031\nCase Report\nEsophagus\nTacrolimus-Induced Acute Esophageal Necrosis\nWanta Kaitlin DO1 Abegunde Ayokunle T. MD, MSc, MRCGP, FACP1 1 Division of Gastroenterology, Loyola University Medical Center, Maywood, IL\nCorrespondence: Ayokunle T. Abegunde, MD, MSc, MRCGP, FACP (Ayokunle.Abegunde@lumc.edu).\n6 2020 \n25 6 2020 \n7 6 e0039614 4 2019 09 8 2019 © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.2020This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.ABSTRACT\nAcute esophageal necrosis (AEN) has been rarely described and has poorly understood pathophysiology although it is thought to be related to mucosal defense barrier disruption. We report a case of AEN in a 71-year-old patient with clinical signs of gastric outlet obstruction along with anemia and sepsis in the setting of a recent kidney transplant. After failing standard supportive measures, tacrolimus was switched to cyclosporin with overall rapid improvement of AEN and concomitant duodenal ulcerations. This case underscores a possible rare adverse effect of a commonly used immunosuppressant agent that, to our knowledge, has not been specifically reported.\n\nOPEN-ACCESSTRUE\n==== Body\nINTRODUCTION\nAcute esophageal necrosis (AEN) with duodenal ulceration is incredibly rare. Although the pathophysiology is not entirely understood, spontaneous resolution is typically seen within 1–2 weeks with supportive care.1 Tacrolimus is a commonly used immunosuppressant agent in the post-transplant setting and has previously been documented to cause stomatitis. In one case report, esophageal and ileal ulceration occurred. However, tacrolimus has not previously been found to induce or contribute to AEN.2\n\nCASE REPORT\nA 71-year-old man with coronary artery disease and type 2 diabetes complicated by end-stage renal disease presented with intractable nausea, emesis, poor oral intake, and generalized weakness 10 days postoperatively from an uncomplicated renal transplant. Immediately postoperatively, the patient was initiated on tacrolimus, mycophenolate, sulfamethoxazole/trimethoprim, acyclovir, and a 1-week course of prednisone. There was no nonsteroidal anti-inflammatory drug use. On presentation, the patient had transient volume responsive hypotension and hypothermia, which resolved in less than 24 hours. Laboratory evaluation revealed hyperglycemia (glucose 308 mg/dL), leukocytosis (white blood cell count 28.7 K/UL), hypoalbuminemia (albumin 2.2 mg/dL), a lactate of 8.8 mm/L, and a supratherapeutic tacrolimus trough of 15.8 ng/mL which had been previously therapeutic. His renal function was unchanged from 4 days earlier.\n\nA computed tomography scan revealed a markedly distended stomach and thickened distal esophagus (Figure 1). A nasogastric tube was placed for 48 hours for gastric decompression and he was started on piperacillin-tazobactam. An infectious workup was unrevealing. Although both the trend in lactate and leukocytosis serially improved, he developed acute on chronic anemia with a hemoglobin of 6.2 mg/dL (baseline 10 mg/dL) with melena. Esophagogastroduodenoscopy (EGD) on postoperative day (POD) 13 showed pan circumferential necrosis and black pigmentation from the upper esophageal sphincter to the gastroesophageal junction with poor luminal distension, a normal stomach, and numerous clean-based duodenal ulcers extending from the bulb to the second portion (Figure 2). By comparison, an EGD from 2 months earlier showed a small duodenal adenoma but was otherwise unremarkable with gastric biopsies that were negative for Helicobacter pylori. He was placed on a liquid diet, high-dose oral proton pump inhibitor (PPI), and sucralfate slurry but continued to be transfusion-dependent with ongoing melena and new dysphagia. On POD 24, an EGD showed progression of proximal luminal narrowing requiring an ultrathin endoscope to traverse the esophagus and no improvement in duodenal ulceration or esophageal necrosis. Esophageal biopsies showed granulation tissue and necrotic debris consistent with ulceration; immunostains were negative for a viral etiology. Fasting serum gastrin level was 151 pg/mL on PPI. The lack of endoscopic healing with an otherwise improved clinical picture prompted a search for an alternative cause.\n\nFigure 1. Computed tomography without contrast showing (A) gastric distention and (B) thickened distal esophagus.\n\nFigure 2. Esophagogastroduodenoscopy showing (A) the esophagus with ulceration and necrosis throughout and (B) duodenum with numerous clean-based ulcers.\n\nA single case reported a distal esophageal and ileal ulcer in a postheart transplant patient who failed to improve with standard medical therapy, however, rapidly and completely healed on switching from tacrolimus to cyclosporin. On POD 25, the patient was transitioned from tacrolimus to cyclosporin, kept nil per os, and started on total parental nutrition. One week later, his hemoglobin stabilized. Repeat EGD on POD 32 showed marked improvement in esophageal necrosis with residual edema and friability along with nearly completely healed duodenal ulcers (Figure 3). Improvement was most pronounced in the middle and distal third of the esophagus. There was persistent luminal narrowing in the proximal esophagus. The patient was advanced to a full liquid diet and maintained on PPI. He underwent a surgical gastrostomy tube and was transitioned off total parental nutrition. Six weeks later, serial EGDs were performed for a 4-mm diameter stricture measuring 6 cm in length using Savary dilation starting at 18Fr and ultimately increased to 36Fr by the third dilation EGD.\n\nFigure 3. Follow-up images 1 week after discontinuing tacrolimus of (A) the esophagus and (B) duodenum.\n\nDISCUSSION\nThis case describes a rare adverse effect of a commonly used immunosuppressant, tacrolimus, and highlights the importance of pharmacovigilance in post-transplant patients. Although rare gastrointestinal side effects have been reported with calcineurin inhibitors, to our knowledge, this is the first reported case of tacrolimus-induced AEN. The pathogenesis of AEN in this patient was likely multifactorial. The patient shared many of the known risk factors for AEN, including advanced age, male gender, vascular disease, renal insufficiency, diabetes, and malnourishment.3 Renal transplant literature has also described the risk of peptic ulcer disease postoperatively.4 Although the pathophysiology is not entirely elucidated, the underlying mechanism is likely related to impaired mucosal defense barriers, hypoperfusion, and gastric content reflux. It is not uncommon to have gastric sparing or duodenal ulceration in AEN, as seen in this patient, although duodenal involvement does portend a poorer prognosis specifically related to the risk of stricture, which can be 25%. A case report has documented AEN in an ill postrenal transplant patient although the resolution was seen with supportive care.5 Unlike expected endoscopic improvement in AEN in 1–2 weeks, our patient failed to respond to standard medical therapy. However, after discontinuation of tacrolimus, there was a rapid improvement in both esophageal and duodenal pathology, suggesting at minimum an adverse drug reaction as a contributor to the evolution and persistence of AEN. Although this patient did manifest as a typical presentation of a rare syndrome, what is notable is the unique impact of tacrolimus on AEN.\n\nDISCLOSURES\nAuthor contributions: K. Wanta wrote the manuscript and is the article guarantor. AT Abegunde edited the manuscript.\n\nFinancial disclosure: None to report.\n\nInformed consent was obtained for this case report.\n==== Refs\nREFERENCES\n1. Gurvitis GE Shapsis A Lau N Gualteri N Robilotti JG \nAcute esophageal necrosis: A rare syndrome\n. J Gastroenterol. \n2007 ;42 (1 ):29 –38\n.\n2. Pan D Shaye O Kobashigawa JA \nTacrolimus-associated diffuse gastrointestinal ulcerations and pathergy: Case report\n. Transpl Proc. \n2017 ;49 (1 ):216 –7\n.\n3. Gurvitis GE Cherian K Shami MN \nBlack esophagus: New insights and multicenter international experience in 2014\n. Dig Dis Sci. \n2015 ;60 (2 ):444 –53\n.25297468 \n4. Steger AC Timoney AS Griffen S Salme RR Williams G \nThe influence of immunosuppression on peptic ulceration following renal transplantation and the role of endoscopy\n. Nephro Dial Transpl. \n1990 ;5 (4 ):289 –92\n.\n5. Mealiea D Greenhouse D Velez M Moses P Marroguin CE \nAcute esophageal necrosis in an immunosuppressed kidney transplant recipient: A case report\n. Transpl Proc. \n2018 ;50 (10 ):3966 –72\n.\n\n",
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"issn_linking": "2326-3253",
"issue": "7(6)",
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] |
{
"abstract": "BACKGROUND\nWe describe a heart transplant patient with painful periostitis and exostoses who was receiving long-term therapy with voriconazole, which is a fluoride-containing medication. Elevated plasma and bone fluoride levels were identified. Discontinuation of voriconazole therapy led to improvement in pain and reduced fluoride and alkaline phosphatase levels.\n\n\nMETHODS\nTo determine whether voriconazole is a cause of fluoride excess, we measured plasma fluoride levels in 10 adult post-transplant patients who had received voriconazole for at least 6 months and 10 post-transplant patients who did not receive voriconazole. To assess the effect of renal insufficiency on fluoride levels in subjects receiving voriconazole, half were recruited on the basis of a serum creatinine level of ≥1.4 mg/dL on their most recent measurement, whereas the other 5 subjects receiving voriconazole had serum creatinine levels <1.4 mg/dL. All control subjects had serum creatinine levels of ≥1.4 mg/dL. Patients were excluded from the study if they received a fluorinated pharmaceutical other than voriconazole.\n\n\nRESULTS\nAll subjects who received voriconazole had elevated plasma fluoride levels, and no subjects in the control group had elevated levels (14.32 μmol/L ± 6.41 vs 2.54 ± 0.67 μmol/L; P<.001). Renal function was not predictive of fluoride levels. Plasma fluoride levels remained significantly higher in the voriconazole group after adjusting for calcineurin inhibitor levels and doses. Half of the voriconazole group subjects had evidence of periostitis, including exostoses in 2 patients. Discontinuation of voriconazole therapy in patients with periostitis resulted in improvement of pain and a reduction in alkaline phosphatase and fluoride levels.\n\n\nCONCLUSIONS\nVoriconazole is associated with painful periostitis, exostoses, and fluoride excess in post-transplant patients with long-term voriconazole use.",
"affiliations": "Department of Internal Medicine, Division of Endocrinology, Diabetes, Nutrition, and Metabolism, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA. wermers.robert@mayo.edu",
"authors": "Wermers|Robert A|RA|;Cooper|Kay|K|;Razonable|Raymund R|RR|;Deziel|Paul J|PJ|;Whitford|Gary M|GM|;Kremers|Walter K|WK|;Moyer|Thomas P|TP|",
"chemical_list": "D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D000469:Alkaline Phosphatase; D065819:Voriconazole; D005459:Fluorides",
"country": "United States",
"delete": false,
"doi": "10.1093/cid/ciq188",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1058-4838",
"issue": "52(5)",
"journal": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America",
"keywords": null,
"medline_ta": "Clin Infect Dis",
"mesh_terms": "D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase; D000935:Antifungal Agents; D005096:Exostoses; D005260:Female; D005459:Fluorides; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010522:Periostitis; D010949:Plasma; D011743:Pyrimidines; D014180:Transplantation; D014230:Triazoles; D065819:Voriconazole",
"nlm_unique_id": "9203213",
"other_id": null,
"pages": "604-11",
"pmc": null,
"pmid": "21239842",
"pubdate": "2011-03-01",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Fluoride excess and periostitis in transplant patients receiving long-term voriconazole therapy.",
"title_normalized": "fluoride excess and periostitis in transplant patients receiving long term voriconazole therapy"
} | [
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"abstract": "Collagenous gastroenteritis is a rare disease that is known to be associated with the drug olmesartan, an angiotensin II receptor antagonist used to treat hypertension. It is characterized histologically by increased subepithelial collagen deposition with associated inflammation and epithelial injury. Endoscopically, the mucosa appears inflamed and friable and may be nodular or atrophic. We report a case of acute gastric bleeding on direct mucosal contact during endoscopy in a patient with olmesartan-associated collagenous gastroduodenitis to raise awareness of this potential endoscopic complication.",
"affiliations": "Orange Pathology Associates, PC, Department of Pathology, Orange Regional Medical Center, 707 East Main St., Middletown, NY 10940, USA.;Horizon Family Medical Group, Department of Gastroenterology, Orange Regional Medical Center, 707 East Main St., Middletown, NY 10940, USA.",
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"fulltext": "\n==== Front\nCase Rep Gastrointest MedCase Rep Gastrointest MedCRIGMCase Reports in Gastrointestinal Medicine2090-65282090-6536Hindawi 10.1155/2018/3295204Case ReportAcute Gastrointestinal Bleeding in Olmesartan-Associated Collagenous Gastroduodenitis: A Potential Endoscopic Complication http://orcid.org/0000-0001-6605-0199Hudacko Rachel rhudacko@gmail.com\n1\nSiegel Lance \n2\n\n1Orange Pathology Associates, PC, Department of Pathology, Orange Regional Medical Center, 707 East Main St., Middletown, NY 10940, USA\n2Horizon Family Medical Group, Department of Gastroenterology, Orange Regional Medical Center, 707 East Main St., Middletown, NY 10940, USAAcademic Editor: Chia-Tung Shun\n\n2018 14 3 2018 2018 32952043 11 2017 12 2 2018 Copyright © 2018 Rachel Hudacko and Lance Siegel.2018This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Collagenous gastroenteritis is a rare disease that is known to be associated with the drug olmesartan, an angiotensin II receptor antagonist used to treat hypertension. It is characterized histologically by increased subepithelial collagen deposition with associated inflammation and epithelial injury. Endoscopically, the mucosa appears inflamed and friable and may be nodular or atrophic. We report a case of acute gastric bleeding on direct mucosal contact during endoscopy in a patient with olmesartan-associated collagenous gastroduodenitis to raise awareness of this potential endoscopic complication.\n==== Body\n1. Introduction\nCollagenous gastroenteritis is a pattern of injury that is characterized histologically by subepithelial collagen deposition >10 μm in thickness with associated mucosal inflammation and epithelial injury [1]. The collagen bands are usually irregular, often entrap small capillaries, and can be highlighted with a trichrome stain. It is a rare disorder that may involve the stomach (collagenous gastritis) and/or small bowel (collagenous enteritis/sprue) and may occasionally coexist with the more common entity, collagenous colitis. The etiology of collagenous gastroenteritis is unknown but is suspected to be immune-mediated and may be associated with certain medications including the antihypertensive drug olmesartan, an angiotensin II receptor antagonist [2]. Several reports in the literature describe cases of olmesartan-associated collagenous duodenitis/sprue [3–5] with fewer reports of olmesartan-associated collagenous gastritis [3, 6] and only rare reports involving both the stomach and small bowel [3]. We herein report a case of olmesartan-associated collagenous gastroduodenitis that was complicated by acute gastrointestinal bleeding during endoscopy.\n\n2. Case Presentation\nA 64-year-old woman presented to the gastroenterologist with abdominal pain, unintentional 10 pound weight loss over 3 months, and reflux symptoms. Pertinent medical history included hypertension treated with olmesartan 20 mg once a day for the past 7 years, hyperlipidemia treated with simvastatin, gastroesophageal reflux disease treated with pantoprazole 20 mg twice a day, and osteoporosis treated with denosumab injections every 6 months. Esophagogastroduodenoscopy (EGD) performed in the office showed granular mucosa in the proximal duodenum and nodular mucosa in the stomach with numerous linear ulcers. On withdrawal of the scope from the duodenum, a large amount of fresh blood was noted in the stomach with clotted blood near the cardia. The bleeding was believed to be due to either the underlying gastric ulcers or a Mallory Weiss tear. The patient was transferred to the emergency department for further evaluation.\n\nOn admission, the hemoglobin and hematocrit were normal, and an emergent EGD was performed. The gastric fundus and body appeared atrophic with friable and severely inflamed mucosa and multiple linear ulcers without active bleeding (Figure 1). The antral mucosa appeared erythematous. Biopsies of the stomach and duodenum were performed. The biopsies of the antrum and body showed increased subepithelial collagen deposition confirmed on a trichrome stain, chronic inflammation in the lamina propria, surface epithelial regenerative changes, and erosions, consistent with collagenous gastritis (Figure 2). The gastric body mucosa was atrophic with near-total loss of parietal cells. Immunostain for H. pylori organisms was negative, and a Congo red stain for amyloid was negative. The biopsies of the duodenum showed partial villous atrophy and increased subepithelial collagen deposition confirmed on a trichrome stain, consistent with collagenous duodenitis/sprue (Figure 3). The patient was started on high dose acid suppression with pantoprazole 40 mg twice a day, and the olmesartan was discontinued.\n\nFollow-up EGD 7 weeks later showed somewhat atrophic gastric mucosa with few residual linear areas of erythema and complete resolution of the ulcers, inflammation, and mucosal friability (Figure 4). The duodenal mucosa appeared normal. Colonoscopy was unremarkable. Repeat biopsies showed marked improvement of the collagenous gastritis with resolution of the epithelial injury and only rare residual foci of subepithelial collagen. A mild nonspecific chronic inactive gastritis remained present. The biopsies from the duodenum and left colon showed normal mucosa without evidence of collagenous duodenitis or collagenous colitis.\n\n3. Brief Discussion\nOlmesartan-associated collagenous gastroenteritis is a rare entity that may be immune-mediated in nature. The length of time of olmesartan use before onset of symptoms varies from less than 1 month to 11 years [7]. When the stomach is solely involved, symptoms include dyspepsia, anemia due to bleeding, weight loss, and diarrhea. When the small intestine is involved, the most common symptoms are watery diarrhea and weight loss due to malabsorption [2]. The characteristic endoscopic finding of collagenous gastritis is nodular mucosa. Other findings include erythema, mucosal friability, erosions, ulcers, and atrophy [2, 6]. The endoscopic findings in the small bowel are nonspecific and include pale mucosa, mucosal thickening, and scalloping [2, 4].\n\nThe diagnostic histologic feature of collagenous gastroenteritis is band-like layer of subepithelial collagen deposition that is at least 10 μm in thickness and is associated with a chronic inflammatory infiltrate and surface epithelial injury [1]. The deposits can be patchy and irregular and often entrap superficial dilated capillaries [2]. Bleeding results from surface epithelial injury and sloughing which exposes these capillaries.\n\nThe majority of cases of olmesartan-associated collagenous gastroenteritis reported in the literature resolved after cessation of the drug [7]. One study reported complete clinical and pathologic resolution of collagenous duodenitis after treatment with the immunosuppressive drugs FK-506 and rapamycin [8]. Our patient had a complete clinical response and near-complete pathologic response at 7-week follow-up after discontinuation of olmesartan.\n\nIn summary, we report a case of acute gastric bleeding during endoscopy due to olmesartan-associated collagenous gastroduodenitis. The mechanism of bleeding in this disease is the presence of abnormal subepithelial collagen causing mucosal fragility. Bleeding may be spontaneous and chronic with associated anemia or may be acute and caused by direct contact with instruments during endoscopy, as was believed to be the reason for the acute bleed in this case. Although rare, it is important for endoscopists to be aware of this potential endoscopic complication in patients taking olmesartan.\n\nConflicts of Interest\nThere are no conflicts of interest or funding sources.\n\nFigure 1 Endoscopic photos of the body of the stomach show diffusely nodular mucosa (a) with deep linear ulcers (arrows) and severe inflammation and hemorrhage (b).\n\nFigure 2 20x magnification: (a) hematoxylin and eosin-stained section of the gastric body shows a thick, markedly irregular pink band of subepithelial collagen deposition with complete surface erosion. The mucosa is inflamed and atrophic with loss of parietal cells. Arrows indicate entrapped capillaries. (b) Trichrome stain highlights the collagen blue.\n\nFigure 3 20x magnification: (a) hematoxylin and eosin-stained section of the duodenum shows villous shortening/partial atrophy with increased subepithelial collagen deposition (pink). (b) Trichrome stain highlights the collagen blue. Arrows indicate entrapped capillaries.\n\nFigure 4 Endoscopic photos of the body of the stomach 7 weeks after cessation of olmesartan show atrophic mucosa with few residual areas of erythema (arrow) and complete resolution of the ulcers.\n==== Refs\n1 Colletti R. B. Trainer T. D. Collagenous gastritis Gastroenterology 1989 97 6 1552 1555 2-s2.0-0024389094 10.1016/0016-5085(89)90403-4 2583419 \n2 Nielsen O. H. Riis L. B. Danese S. Bojesen R. D. Soendergaard C. Proximal collagenous gastroenteritides: clinical management: a systematic review Annals of Medicine 2014 46 5 311 317 10.3109/07853890.2014.899102 2-s2.0-84905506705 24716737 \n3 Rubio-Tapia A. Herman M. L. Ludvigsson J. F. Severe spruelike enteropathy associated with olmesartan Mayo Clinic Proceedings 2012 87 8 732 738 2-s2.0-84866370242 10.1016/j.mayocp.2012.06.003 22728033 \n4 Nielsen J. A. Steephen A. Lewin M. Angiotensin-II inhibitor (olmesartan)-induced collagenous sprue with resolution following discontinuation of drug World Journal of Gastroenterology 2013 19 40 6928 6930 2-s2.0-84887012347 10.3748/wjg.v19.i40.6928 24187471 \n5 Desruisseaux C. Bensoussan M. Désilets E. Adding water to the mill: olmesartan-induced collagenous sprue—a case report and brief literature review Canadian Journal of Gastroenterology and Hepatology 2016 2016 2 4837270 10.1155/2016/4837270 2-s2.0-84971473467 \n6 Ma C. Park J. Y. Montgomery E. A. A comparative clinicopathologic study of collagenous gastritis in children and adults: The same disorder with associated immune-mediated diseases The American Journal of Surgical Pathology 2015 39 6 802 812 2-s2.0-84929897264 10.1097/PAS.0000000000000441 25871617 \n7 Burbure N. Lebwohl B. Arguelles-Grande C. Green P. H. R. Bhagat G. Lagana S. Olmesartan-associated sprue-like enteropathy: A systematic review with emphasis on histopathology Human Pathology 2016 50 127 134 2-s2.0-84960962888 10.1016/j.humpath.2015.12.001 26997446 \n8 Scialom S. Malamut G. Meresse B. Gastrointestinal disorder associated with olmesartan mimics autoimmune enteropathy PLoS ONE 2015 10 6, article e0125024 10.1371/journal.pone.0125024 2-s2.0-84939176524\n\n",
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"abstract": "With resurgence of multidrug resistance (MDR) bacteria and no new novel broad-spectrum antibiotic in research pipeline, usage of older generation antibiotics, once discarded due to their toxicity profile are becoming popular again. Often these drugs are the only option left in managing MDR bacteria-related sepsis. Colistin is one of such antibiotic which is often used in recent times after decades of its avoidance due to its diverse toxicity profile. In this case report, we present a rare myasthenic syndrome like neuromuscular complication developed in a patient after receiving colistin for treatment of MDR Klebsiella-related urosepsis.",
"affiliations": "Department of Nephrology, ILS Hospital, Dum Dum, Kolkata, West Bengal, India.;Department of Nephrology, ILS Hospital, Dum Dum, Kolkata, West Bengal, India.",
"authors": "Sengupta|Pratim|P|;Biswas|Sumanta|S|",
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"mesh_terms": "D000900:Anti-Bacterial Agents; D003091:Colistin; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic; D007710:Klebsiella Infections; D008875:Middle Aged; D018908:Muscle Weakness; D009469:Neuromuscular Junction; D020511:Neuromuscular Junction Diseases; D020127:Recovery of Function; D013577:Syndrome; D016896:Treatment Outcome; D014552:Urinary Tract Infections",
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}
],
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},
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] |
{
"abstract": "The Impella manufacturer has changed its recommendation for the diluent of the heparinized purge solution from 20% dextrose (D20) to 5% dextrose (D5). This reduced viscosity may result in increased purge solution infusion rates and unfractionated heparin (UFH) exposure. Increased UFH exposure could potentially cause increased bleeding events and may necessitate reduction in UFH concentration in the purge solution. Our objective was to evaluate anticoagulation for patients on Impella pumps receiving heparinized purge solution with D20 or D5 diluents.\nThis retrospective cohort analysis evaluated patients requiring Impella support outside of the cardiac catheterization lab. The primary outcome evaluated the number of patients with at least one supratherapeutic activated partial thromboplastin time (aPTT) while receiving heparinized purge solution alone without systemic UFH. Secondary outcomes included heparin concentration changes made to the purge solution, bleeding, and thrombotic events.\nTwelve patients received Impella support for an average of 37 hours (range, 10.8-89.6). Four patients received D20 and 8 patients received D5 purge solution. Five patients had at least one supratherapeutic aPTT while receiving heparinized purge solution alone without additional systemic UFH. All 5 patients were in the D5 group. Of these 5 patients, 3 required purge heparin concentration decreases and 3 had bleeding events. No patients had pump thrombosis.\nD5 purge solution with heparin 50 units/mL may increase the risk of supratherapeutic aPTTs, leading to increased bleeding. Decreasing heparin to 25 units/mL as a standard in purge solution may decrease these risks; however, protection against thrombosis remains unknown.",
"affiliations": "1 Department of Pharmaceutical Care, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.;2 Department of Pharmacy Services, Carilion Roanoke Memorial Hospital, Roanoke, VA, USA.",
"authors": "Dietrich|Jenna N|JN|https://orcid.org/0000-0001-8090-1949;Kazmi|Hasan|H|https://orcid.org/0000-0003-0049-1228",
"chemical_list": "D000925:Anticoagulants; D006493:Heparin; D005947:Glucose",
"country": "United States",
"delete": false,
"doi": "10.1177/0897190018757148",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0897-1900",
"issue": "32(4)",
"journal": "Journal of pharmacy practice",
"keywords": "Impella; anticoagulation; heparin; left ventricular assist device; purge solution",
"medline_ta": "J Pharm Pract",
"mesh_terms": "D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants; D015331:Cohort Studies; D005260:Female; D005947:Glucose; D006353:Heart-Assist Devices; D006470:Hemorrhage; D006493:Heparin; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D012189:Retrospective Studies; D013927:Thrombosis",
"nlm_unique_id": "8900945",
"other_id": null,
"pages": "464-469",
"pmc": null,
"pmid": "29439593",
"pubdate": "2019-08",
"publication_types": "D003160:Comparative Study; D016428:Journal Article",
"references": null,
"title": "Bleeding Risks in Patients on Percutaneous Ventricular Assist Devices Receiving Two Different Dextrose Concentrations of Heparinized Purge Solution: A Case Series.",
"title_normalized": "bleeding risks in patients on percutaneous ventricular assist devices receiving two different dextrose concentrations of heparinized purge solution a case series"
} | [
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"drugdosageform": "SOLUTION FOR INJECTION",
"drugdosagetext": "UNK (PURGE SOLUTION)",
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"drugindication": "ACUTE MYOCARDIAL INFARCTION",
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"medicinalproduct": "HEPARIN SODIUM."
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{
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}
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{
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],
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{
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}
],
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"reactionmeddraversionpt": "21.0",
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},
{
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"reactionoutcome": "6"
}
],
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"abstract": "This study investigated the efficacy of imatinib based therapy with intensified consolidation therapy in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) to prevent early relapse. We conducted a phase II trial of imatinib-combined chemotherapy for newly diagnosed BCR-ABL-positive ALL in adults. Sixty-eight patients were included in the trial between October 2008 and December 2010. The median age was 49 years, with 28 patients >55 years of age. Sixty-five patients achieved CR (95.6%). The estimated 2-year event-free survival (EFS) and overall survival (OS) were 62.3% and 67.4%, respectively. Allogeneic stem cell transplantation (allo-SCT) at initial CR was performed in 43 patients. Thirty-five of 39 patients <55 years and 8 of 26 patients >55 years underwent allo-SCT at first CR. The 3-year OS in patients <55 years receiving allo-SCT at first CR, patients >55 years receiving allo-SCT at first CR, patients <55 years not receiving allo-SCT at first CR, and patients >55 years not receiving allo-SCT at first CR were 80.4%, 41.1%, 32.5%, and 52.0%, respectively (P = 0.058). The three-year EFS in each group was 76.7%, 53.6%, not reached, and 26.4%, respectively (P = 0.150). A high CR rate was observed with imatinib-based chemotherapy allowing allo-SCT in a high proportion of patients, particularly those <55 years. Moreover, intensified consolidation therapy reduced early relapse rates following induction therapy and resulted in improved OS and EFS rates following allo-SCT. This trial was registered with the UMIN (000001226).",
"affiliations": "Department of Hematology, Yokohama City University Medical Center, Yokohama, Japan.;Department of Hematology, Fujita Health University Hospital, Toyoake, Japan.;Tokyo Metropolitan Health and Medical Treatment Corporation Tama-Hokubu Medical Center, Tokyo, Japan.;Department of Hematology/Oncology, Kurashiki Central Hospital, Kurashiki, Japan.;Department of Hematology, Seichokai Fuchu Hospital, Osaka, Japan.;Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan.;Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.;Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.;Division of Hematology and Oncology, Toyohashi Municipal Hospital, Toyohashi, Japan.;Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan.;Department of Hemato-Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.;Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.;Institute of Liberal Arts and Science, Kanazawa University, Kanazawa, Japan.;Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.;Oncology Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.;Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.;National Hospital Organization Nagoya Medical Center, Nagoya, Japan.",
"authors": "Fujisawa|Shin|S|http://orcid.org/0000-0003-2028-0209;Mizuta|Shuichi|S|;Akiyama|Hideki|H|;Ueda|Yasunori|Y|;Aoyama|Yasutaka|Y|;Hatta|Yoshihiro|Y|;Kakihana|Kazuhiko|K|;Dobashi|Nobuaki|N|;Sugiura|Isamu|I|;Onishi|Yasushi|Y|;Maeda|Tomoya|T|;Imai|Kiyotoshi|K|;Ohtake|Shigeki|S|;Miyazaki|Yasushi|Y|;Ohnishi|Kazunori|K|;Matsuo|Keitaro|K|;Naoe|Tomoki|T|",
"chemical_list": "D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl",
"country": "United States",
"delete": false,
"doi": "10.1002/ajh.24653",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0361-8609",
"issue": "92(4)",
"journal": "American journal of hematology",
"keywords": null,
"medline_ta": "Am J Hematol",
"mesh_terms": "D000293:Adolescent; D000328:Adult; D060830:Consolidation Chemotherapy; D005260:Female; D016044:Fusion Proteins, bcr-abl; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult",
"nlm_unique_id": "7610369",
"other_id": null,
"pages": "367-374",
"pmc": null,
"pmid": "28103625",
"pubdate": "2017-04",
"publication_types": "D017427:Clinical Trial, Phase II; D016428:Journal Article",
"references": null,
"title": "Phase II study of imatinib-based chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia.",
"title_normalized": "phase ii study of imatinib based chemotherapy for newly diagnosed bcr abl positive acute lymphoblastic leukemia"
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"abstract": "Solid organ transplant recipients have an elevated incidence of thyroid cancer. We evaluated a wide range of potential risk factors in a cohort of 229 300 U.S. solid organ transplant recipients linked with 15 stage/regional cancer registries (1987-2012). Incidence rate ratios (IRRs) were adjusted for age, sex, race/ethnicity, transplanted organ, year of transplantation, and time since transplantation. Hazard ratios (HRs) for death and/or graft failure were adjusted for age, sex, race/ethnicity, transplanted organ, and year of transplantation. After transplantation, 356 thyroid cancers were diagnosed. Thyroid cancer incidence was 2.50-fold higher in transplant recipients than the general population (95% confidence interval [CI] 2.25-2.77). Among recipients of different organs, kidney recipients had the highest incidence of thyroid cancer (IRR = 1.26, 95% CI 1.03-1.53). Elevated thyroid cancer incidence was associated with cholestatic liver disease/cirrhosis as an indication for liver transplantation (IRR = 1.69, 95% CI 1.09-2.63), hypertensive nephrosclerosis as an indication for kidney transplantation (IRR = 1.41, 95% CI 1.03-1.94), and longer prior dialysis among kidney recipients (5+ vs. <1 year, IRR = 1.92, 95% CI 1.32-2.80; p-trend <0.01). Posttransplantation diagnosis of thyroid cancer was associated with modestly increased risk of death (HR = 1.33, 95% CI 1.02-1.73). Overall, our results suggest that end-stage organ disease and longer duration of dialysis may contribute to higher thyroid cancer incidence in transplant recipients.",
"affiliations": "Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.;Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.;Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.;University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI.;Department of Epidemiology, University of Iowa, Iowa City, IA.;Cancer Epidemiology Services, New Jersey Department of Health, Trenton, NJ.;Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.",
"authors": "Kitahara|C M|CM|;Yanik|E L|EL|http://orcid.org/0000-0002-5835-0201;Ladenson|P W|PW|;Hernandez|B Y|BY|;Lynch|C F|CF|;Pawlish|K S|KS|;Engels|E A|EA|",
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"doi": "10.1111/ajt.14310",
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"issue": "17(11)",
"journal": "American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons",
"keywords": "cancer/malignancy/neoplasia: risk factors; clinical research/practice; epidemiology; immunosuppression/immune modulation; kidney transplantation/nephrology; organ transplantation in general; translational research/science",
"medline_ta": "Am J Transplant",
"mesh_terms": "D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D011379:Prognosis; D012042:Registries; D006435:Renal Dialysis; D012307:Risk Factors; D013964:Thyroid Neoplasms; D066027:Transplant Recipients; D014481:United States",
"nlm_unique_id": "100968638",
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"pages": "2911-2921",
"pmc": null,
"pmid": "28397388",
"pubdate": "2017-11",
"publication_types": "D016428:Journal Article",
"references": "26746479;25011453;10616827;22045767;20150194;16868053;25340595;8641223;26756356;23464511;16684987;19563337;19951937;10408483;19942714;26731613;26563384;15223891;25284703;7871153;24257690;26462967;19240234;17617273;25575645;18766448;24824312;9569948;27418023;28054345;18160464;23057816;26270022;17179459;23759880;9777744;17913661;15698444;22569239",
"title": "Risk of Thyroid Cancer Among Solid Organ Transplant Recipients.",
"title_normalized": "risk of thyroid cancer among solid organ transplant recipients"
} | [
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"literaturereference": "KITAHARA C, YANIK E, LADENSON P, HERNANDEZ B, LYNCH C, PAWLISH K AND ENGELS E. RISK OF THYROID CANCER AMONG SOLID ORGAN TRANSPLANT RECIPIENTS. AMERICAN JOURNAL OF TRANSPLANTATION 2017 NOV;17 (11):2911-2921.",
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"abstract": "The occurrence of collagenous colitis (CC) in patients with pre-existing inflammatory bowel diseases (IBD) is rare, with only seven cases reported in the past. Herein, we report two IBD cases who developed CC after successful treatment of their IBD with two different tumor necrosis factor (TNF)-α inhibitors, which have been previously reported to successfully treat refractory CC. This report highlights the need to do random biopsies of the colon for CC diagnosis in IBD patients with symptoms of diarrhea after complete mucosal healing. The report also reviews plausible mechanisms as to how CC may develop, including the role of multiple medications.",
"affiliations": "Graduate College, Rush University, Chicago, IL, USA.;Graduate College, Rush University, Chicago, IL, USA.;Department of Pathology, Rush University, Chicago, IL, USA.;Department of Medicine, Division of Gastroenterology and Nutrition, Rush University, Chicago, IL, USA.",
"authors": "Saad|Rahoma E|RE|;Shobar|Rima M|RM|;Jakate|Shriram|S|;Mutlu|Ece A|EA|",
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"fulltext": "\n==== Front\nGastroenterol Rep (Oxf)Gastroenterol Rep (Oxf)gastroGastroenterology Report2052-0034Oxford University Press 10.1093/gastro/gox026gox026Case ReportDevelopment of collagenous colitis in inflammatory bowel disease: two case reports and a review of the literature Saad Rahoma E 1Shobar Rima M 1Jakate Shriram 2Mutlu Ece A 31 Graduate College, Rush University, Chicago, IL, USA2 Department of Pathology, Rush University, Chicago, IL, USA3 Department of Medicine, Division of Gastroenterology and Nutrition, Rush University, Chicago, IL, USACorresponding author. Clinical Research Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Rush University, 1725 W. Harrison, Suite 206, Chicago, IL 60612, USA. Tel: +1–312–563–3880; Fax: +1–312–563–3883; Email: ece_mutlu@rush.edu6 2019 19 7 2017 19 7 2017 7 3 218 222 27 12 2016 27 4 2017 08 5 2017 © The Author(s) 2017. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University2017This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comAbstract\nThe occurrence of collagenous colitis (CC) in patients with pre-existing inflammatory bowel diseases (IBD) is rare, with only seven cases reported in the past. Herein, we report two IBD cases who developed CC after successful treatment of their IBD with two different tumor necrosis factor (TNF)-α inhibitors, which have been previously reported to successfully treat refractory CC. This report highlights the need to do random biopsies of the colon for CC diagnosis in IBD patients with symptoms of diarrhea after complete mucosal healing. The report also reviews plausible mechanisms as to how CC may develop, including the role of multiple medications.\n\nCollagenous colitisinflammatory bowel diseasetumor necrosis factor-αinhibitorsinfliximabadalimumab\n==== Body\nIntroduction\nCollagenous colitis (CC) and lymphocytic colitis (LC) represent the two main types of microscopic colitis (MC). Patients with CC mostly present with chronic intermittent watery diarrhea [1]. CC mainly affects middle-aged women at an age of approximately 55–63.8 years, with a female-to-male ratio of 3–6.8:1 [1,2]. Macroscopically, during colonoscopy, a patient with CC has normal-appearing colonic mucosa, although some abnormal changes have been reported in the literature, including edema, erythema, abnormal vasculature pattern and diffuse mucosal cloudiness [1,3]. CC is typically diagnosed after microscopic examination, showing a thickened sub-epithelial collagen band ≥10 μm in colorectal biopsies [4]. Surface epithelial damage with inflammatory cell infiltration in both surface epithelium and lamina propria is also present [5].\n\nThe cause of CC and its association with other diseases are still unclear. Chutkan et al. in 2000 reported a family of mother, daughter and son who have CC, ulcerative colitis (UC) and Crohn’s disease (CD), respectively, suggesting that CC and inflammatory bowel diseases (IBD) could be related or have a common genetic predisposition [6], but some studies have failed to find any significant association between CC and IBD [2], and yet others have reported the co-occurrence of CC and IBD. In most of the latter studies reporting co-occurrence of the two disease entities, CC was followed by the eventual development of clinical and pathological IBD [7–13]. There are also two reported cases of simultaneous occurrence of CC and IBD [14,15].\n\nHere, we report two cases of IBD who have developed CC years after the onset of IBD in two patients who were in clinical remission. Interestingly, both cases had been successfully treated with tumor necrosis factor (TNF)-α inhibitors. In this report, we also review the seven published cases of CC that developed after pre-existing IBD [16–21]. Our report highlights two important issues: CC development occurs most often in patients who are clinically and endoscopically in remission necessitating random mucosal biopsies during endoscopy before symptoms can be attributed to irritable bowel syndrome (IBS); and CC can develop while the patient is in remission on TNF-α inhibitors, which have been used to treat refractory CC.\n\nCase 1\nA 49-year-old white female was diagnosed in 2004 with UC that involved her entire colon (i.e. pan-colitis) at the age of 39. Her symptoms of UC were intermittent bloody diarrhea, fecal urgency, fatigue and abdominal cramping with bowel movements. She was tried on mesalamine which did not control her symptoms; azathioprine and 6-mercaptopurine which gave her abdominal pain and resulted in pancreatitis; and infliximab to which she had a severe infusion reaction. She was then started on adalimumab in March 2008 (before the FDA approval of adalimumab for UC in the US) to which she clinically responded well. She had undergone multiple colonoscopies with surveillance biopsies in 2006, 2009 and 2010. None of these showed any evidence of CC. In 2011, colonoscopy showed minimal to no active disease, presence of multiple pseudo-polyps and no evidence of CC. Her past medical history included diabetes, Hashimoto’s thyroiditis, anxiety, hyperlipidemia, gastroesophageal reflux disease and multiple drug allergies. Her medications at the time of CC diagnosis were adalimumab, rabeprazole, levothyroxine, pravastatin, glimepiride, metformin, ramipril, cetirizine, aspirin (81 mg daily) and multivitamins. She denied any history of smoking and she rarely drank any alcohol.\n\nIn 2013, the patient presented to the clinic with complaints of chronic intermittent diarrhea and abdominal pain for the past 3–4 months and she reported that this was very different from what she usually experiences with UC flares. Specifically, she denied any weight loss and blood in the stool. Her physical examination was unremarkable. Her laboratory studies revealed a normal complete blood count (CBC), CMP, erythrocyte sedimentation rate (ESR) and C-reaction protein (CRP). Her transglutaminase Ab (IgA), gliadin Ab (IgG and IgA) and endomysial Ab (IgA) were negative for celiac disease. Her anti-nuclear antibodies (ANA) were also normal. Stool for culture, ova and parasites, and C. difficile toxin were negative. A repeat colonoscopy showed a few 1–4 mm ulcerations around the ileocecal valve and in the sigmoid, and large pseudo-polyps in the left colon, as before. The rest of the colonic mucosa appeared normal, but was scarred and stiff. Histopathology of the surveillance colonic biopsies revealed a new-onset CC, with a thickened sub-epithelial collagen band of > 12 μm to > 15 μm (Figure 1). She was started on cholestyramine and budesonide with resolution of her symptoms of CC. The patient was then maintained on cholestyramine long term to control her CC. A repeat colonoscopy was performed in 2015 for colon cancer surveillance and there was resolution of the histological changes of CC but mildly active patchy histological UC with mild erythema and granularity of the mucosa.\n\n\nFigure 1. (A) Low-power microphotograph showing colonic mucosa with diffuse chronic colitis and thickened subsurface collagen band (H&E stain, ×100). (B) Trichrome stain showing thickened collagen band (>15 μm).\n\nCase 2\nA 61-year-old white Hispanic female with symptoms of CD for 10 years was diagnosed with CD (involving her esophagus, stomach, ileum and colon). She was started on infliximab with great improvement in her disease. She additionally had a past medical history of diabetes, hypothyroidism, diverticulosis and gastroesophageal reflux disease. In addition to infliximab, her medications included levothyroxine, sitagliptin phosphate, metformin, pravastatin, lansoprazole and vitamin D. She actively smoked cigarettes and rarely drank any alcohol. While she was on infliximab, the patient developed dysphagia and an esophagogastroduodenoscopy (EGD) was performed revealing candida esophagitis, which was successfully treated with fluconazole. A year after the start of infliximab in 2014, she presented with an unintentional weight loss of more than 2 kg, fatigue, abdominal pain and chronic intermittent diarrhea with some rectal bleeding. The patient’s laboratory studies revealed a normal CBC, CMP, ESR and CRP. Stool for culture, ova and parasites, and C. difficile toxin PCR were negative for any evidence of infection. She had an EGD with small bowel biopsies that was also negative for celiac disease or other pathology. A surveillance colonoscopy was performed and showed few scattered aphthous ulcerations in the distal terminal ileum and complete mucosal healing of her colon. Histopathology of the colonic biopsies showed inactive CD and a diffuse mild chronic colitis with a thickened collagen band (>25 μm) throughout the colon that is consistent with CC (Figure 2). She was started on cholestyramine and her symptoms of CC completely resolved. She was then maintained on cholestyramine long term to control her CC. Also, in the meantime, the dose of infliximab was reduced in the patient due to recurrent candida esophagitis. A repeat colonoscopy was performed in 2016 for colon cancer surveillance and there was resolution of the histological changes of CC and the CD was inactive in the terminal ileum and colon with complete mucosal healing and inactive colitis on random biopsies.\n\n\nFigure 2. (A) Medium-power microphotograph showing diffuse chronic colitis, thickened collagen band and surface denudation (H&E stain, ×200). (B) Trichrome stain showing thickened collagen band (>25 μm).\n\nDiscussion\nCC has been linked with IBD, but development of CC after the IBD diagnosis is rare. CC has not been reported to occur in IBD patients in remission or those on TNF-α inhibitors. In fact, TNF-α inhibitors have been reported to successfully treat six out of seven cases of CC that were refractory to treatment [22–24]. Herein, we report two patients who developed CC following successful treatment of their IBD with TNF-α inhibitors, namely infliximab and adalimumab. This finding highlights the importance of taking random biopsies of the colon even if the mucosa appears normal endoscopically in IBD patients. We also highlight that CC in patients with existing IBD can be temporary.\n\nThere are seven IBD cases that have been previously reported to develop CC subsequently to their IBD diagnosis and these are shown in Table 1 along with the features and characteristics related to each case, and the two cases from this report are also included in the table. It is important to note that seven out of the nine cases of CC emergence after IBD development occurred in the cases which were in remission. Of the two remaining active cases, one had active perianal disease and the left colon looked otherwise normal [20]. The other had active terminal ileitis and systemic amyloidosis, and the colon also looked normal [17]. These features highlight an important need to keep CC in the differential diagnosis of persistent diarrhea in IBD patients, and to take random mucosal biopsies of the normal-looking colon before symptoms are attributed to IBS or other causes, even after successful treatment. Other causes of diarrhea in IBD have been getting more notice in the context of clinical trials. Until recently, randomized clinical trials of IBD (and especially those in CD) enrolled subjects with persistent diarrhea and symptoms such as abdominal pain and general wellbeing used in composite symptom indices; yet, a significant portion of the patients in such clinical trials had no appreciable endoscopic evidence of inflammation, necessitating a recent recommendation to add objective measures such as CRP/colonoscopy/magnetic resonance elastography to the inclusion criteria of active IBD subjects [25]. This fact points out the importance of looking for additional causes of diarrhea in IBD patients other than the IBD itself, and implies how often the problem of diarrhea in IBD is misinterpreted as active disease. This also highlights a need for literature such as our case report documenting such additional causes of diarrhea in IBD patients and the need for random biopsies of the colon regardless of endoscopic appearances.\n\nTable 1. Cases in the literature reported to develop CC after an established diagnosis of IBD\n\n\tAge at CC diagnosis (years)/gender\tIBD type\tPart of GI tract involved\tDuration of IBD before CC diagnosis (years)\tIBD medication at CC diagnosis\tDuration of TNFα inhibitor before onset of CC (months)\tActive vs remission at CC diagnosis\tOther medications\tAssociated diseases\tMedications used to treat CC\tOutcome of CC\tReference\t\nCase 1\t49/Female\tUC\tEntire colon\t10\tAdalimumab\t66\tRemission\tRabeprazole, levothyroxine, glimepiride, metformin, ramipril, cetirizine, aspirin\tDiabetes, Hashimoto’s thyroiditis, anxiety, GERD and multiple drug allergies\tCholestyramine and budesonide\tComplete resolution\tThis report\t\nCase 2\t60/Female\tCD\tEsophagus, stomach, ileum and colon\t2\tInfliximab\t12\tRemission\tLevothyroxine, sitagliptin phosphate/ metformin hydrochloride, pravastatin, lanzoprazole\tDiabetes, hypothyroidism, diverticulosis and GERD\tCholestyramine\tComplete resolution\tThis report\t\nCase 3\t35/Male\tCD\tTerminal ileum\tNR\tNo medications\tNA\tActive\tIndomethacin, ACEI, ARB, IV antibiotics, steroids\tNephrotic syndrome, Amyloidosis\tNR\tNR\t[17]\t\nCase 4\t79/Female\tUC\tNR\t14\tMesalamine\tNA\tRemission\tNR\tNR\tMesalamine\tComplete resolution\t[16]\t\nCase 5\t59/Female\tUC\tLeft side of the colon\t13\tMesalamine\tNA\tRemission\tIbuprofen (no association with CC symptoms)\tNR\tBismuth\tComplete resolution\t[16]\t\nCase 6\t59/Female\tCD\tPerianal\tNR\tInfliximab\tNR\tActive\tMood stabilizers (in the past)\tDepression, h/o acute steroid psychosis\tBismuth subsalicylate and imodium\tComplete resolution\t[20]\t\nCase 7\t63/Male\tUC\tLeft side of the colon\t8\tMesalamine\tNA\tRemission\tNR\tNR\tNR\tNR\t[18]\t\nCase 8\t57/Female\tUC\tEntire colon\t5\tMesalamine and prednisolone\tNA\tRemission\tACEI, Adriamycin, Cyclophosphamide, Etoposide, Melphalan\tSystemic Amyloidosis, autologous stem-cell transplantation\tNR\tNR\t[19]\t\nCase 9\t70/Female\tCD\tEntire colon\t5\tNo medications\tNA\tRemission\tNR\tIDDM, Grave’s disease, atrophic gastritis\tNR\tNR\t[21]\t\nNR, not reported; NA, not applicable; GI, gastrointestinal; IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn’s disease; CC, collagenous colitis; TNFαIs, tumor necrosis factor-α inhibitors; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; GERD, gastroesophageal reflux disease; IDDM, insulin-dependent diabetes mellitus.\n\nWhy and how CC develops in existing IBD patients is not known. Two patients shown in Table 1 had systemic amyloidosis, suggesting an aberrant immune response as an etiology. Interestingly, however, before the addition of the two cases in this report, six out of the seven previously reported patients were on minimal treatment with mesalamines or were on no medications. There is only one case of CC occurring in a patient with CD who had been successfully treated (also with a TNF-α inhibitor) [20]. This patient had colonic disease in remission, but had active perianal disease with a fistula, when CC developed. The noted collagen deposition in this case was most prominent distally and in the perianal area, which clinically and endoscopicaly looked abnomal, and this led to biopsies of the area and the CC diagnosis. Contrary to this previous case with active perianal disease, both of our cases were in complete clinical remission and had endoscopic colonic healing at the time of development of CC. The temporary occurrence of CC in our IBD patients could suggest some kind of aberrant or exaggerated healing response as a result of an imbalance between inflammatory pathways vs mucosal healing pathways, tipping the balance toward protracted healing. This conjecture fits with the clinical course of disease in our two cases. In Case 1 reported here, interestingly enough, we note disappearance of the CC after reappearance of mild UC. In Case 2, a dose reduction in infliximab treatment corresponds with the disappearance of CC.\n\nAmong the proposed theories that initiate the processes leading up to the altered collagen balance seen in CC are immune dysregulation/autoimmunity [2,26]; atypical responses to luminal toxins such as those from bacteria in susceptible patients [27–31] (which also is thought to account for improvement of CC with cholestyramine [32]); and drug idiosyncrasy. The two cases that we report here have preceding autoimmune thyroid disease and diabetes mellitus in addition to IBD, which could have contributed to CC development. In our two cases, despite a response to cholestyramine, we noted no evidence of infectious agents in stool studies. Among the previous medications that have been reported in association with CC and were used in both of our patients are non-steroidal anti-inflammatory drugs (NSAIDs) [33,34], proton pump inhibitors (PPIs) [3,35–37] and statins [34,38,39]. Even though we noted no temporal relationship between the use of these medications and CC onset in our patients, a careful medication history in IBD patients is needed, and it is certainly plausible that one or more of these agents could have led to the development of CC in our two IBD patients.\n\nIn conclusion, our cases highlight that CC development in IBD patients could occur despite successful treatment either due to an exaggerated healing response or due to the effects of multiple medications associated with CC; and highlight the need for random biopsies of the colon in IBD patients with new-onset diarrhea after successful treatment, especially in those cases with complete mucosal healing, before symptoms are attributed to IBS. The evidence presented herein is hypothesis-generating, proposing a need for further studies looking at the association between complete mucosal healing and subsequent CC development and its mechanisms.\n\nAcknowledgements\nR.E.S. and R.S. acquired and analysed the data and reviewed the literature and wrote the manuscript; S.J. provided the pathology images; E.A.M. conceived the report, wrote and revised the manuscript. A written waiver was provided by Rush University Institutional Review Board. Informed consent to participate is not required for case reports per Rush University Institutional Review Board, if fewer than three cases are being reported.\n\nConflict of interest\nNone declared.\n==== Refs\nReferences\n1 \nBohr J , Tysk C , Eriksson S \net al\nCollagenous colitis: a retrospective study of clinical presentation and treatment in 163 patients . Gut 1996 ;39 :846 –51 .9038667 \n2 \nKao KT , Pedraza BA , McClune AC \net al\nMicroscopic colitis: a large retrospective analysis from a health maintenance organization experience . World J Gastroenterol 2009 ;15 :3122 –7 .19575491 \n3 \nChiba M , Sugawara T , Tozawa H \net al\nLansoprazole-associated collagenous colitis: diffuse mucosal cloudiness mimicking ulcerative colitis . World J Gastroenterol 2009 ;15 :2166 –9 .19418592 \n4 \nLee E , Schiller LR , Vendrell D \net al\nSubepithelial collagen table thickness in colon specimens from patients with microscopic colitis and collagenous colitis . Gastroenterology 1992 ;103 :1790 –6 .1451972 \n5 \nJessurun J , Yardley JH , Giardiello FM \net al\nChronic colitis with thickening of the subepithelial collagen layer (collagenous colitis): histopathologic findings in 15 patients . Hum Pathol 1987 ;18 :839 –48 .3610134 \n6 \nChutkan R , Sternthal M , Janowitz HD. \nA family with collagenous colitis, ulcerative colitis, and Crohn’s disease . Am J Gastroenterol 2000 ;95 :3640 –1 .11151908 \n7 \nGoldstein NS , Gyorfi T. \nFocal lymphocytic colitis and collagenous colitis: patterns of Crohn’s colitis? \nAm J Surg Pathol \n1999 ;23 :1075 –81 .10478667 \n8 \nPokorny CS , Kneale KL , Henderson CJ. \nProgression of collagenous colitis to ulcerative colitis . J Clin Gastroenterol 2001 ;32 :435 –8 .11319318 \n9 \nAqel B , Bishop M , Krishna M \net al\nCollagenous colitis evolving into ulcerative colitis: a case report and review of the literature . Dig Dis Sci 2003 ;48 :2323 –7 .14714620 \n10 \nO’Beirne JP , Ireland A. \nProgression of collagenous colitis to Crohn’s disease . Eur J Gastroenterol Hepatol 2005 ;17 :573 –5 .15827449 \n11 \nSmith P , Bishop P , Whorwell PJ. \nCollagenous colitis, ulcerative colitis, coeliac disease and hyperparathyroidism in one patient: implications for the management of collagenous colitis . Eur J Gastroenterol Hepatol 2005 ;17 :1239 –42 .16215438 \n12 \nFreeman HJ , Berean KW , Nimmo M. \nEvolution of collagenous colitis into severe and extensive ulcerative colitis . Can J Gastroenterol 2007 ;21 :315 –18 .17505568 \n13 \nGiardiello FM , Jackson FW , Lazenby AJ. \nMetachronous occurrence of collagenous colitis and ulcerative colitis . Gut 1991 ;32 :447 –9 .2026344 \n14 \nChandratre S , Bramble MG , Cooke WM \net al\nSimultaneous occurrence of collagenous colitis and Crohn’s disease . Digestion 1987 ;36 :55 –60 .3556805 \n15 \nNojgaard C , Nielsen PL , Rumessen JJ. \nSynchronous onset of collagenous colitis and Crohn disease . Ugeskrift for laeger 2002 ;164 :2299 –2300 .11989182 \n16 \nJegadeesan R , Liu X , Pagadala MR \net al\nMicroscopic colitis: is it a spectrum of inflammatory bowel disease? \nWorld J Gastroenterol \n2013 ;19 :4252 –6 .23864791 \n17 \nBlackmur JP , Chapman FA , Bellamy CO \net al\nAnti-TNF-alpha therapy for renal amyloid as a complication of Crohn’s disease . QJM 2014 ;107 :57 –9 .23681221 \n18 \nHaque M , Florin T. \nProgression of ulcerative colitis to collagenous colitis: chance, evolution or association? \nInflamm Bowel Dis \n2007 ;13 :1321 .17567868 \n19 \nJanczewska I , Mejhert M , Hast R \net al\nPrimary AL-amyloidosis, ulcerative colitis and collagenous colitis in a 57-year-old woman: a case study . Scand J Gastroenterol 2004 ;39 :1306 –9 .15743012 \n20 \nMalik TA , Peter S , Jhala N \net al\nCrohn’s colitis with perianal disease complicated by collagenous colitis: discourse on management options . Digestion 2010 ;81 :142 –4 .20090331 \n21 \nSeguenot D , Marteau P , Lavergne A \net al\n[Collagen colitis after Crohn’s disease: a fortuitous association?] . Gastroenterol Clin Biol 1990 ;14 :891 –2 .2276574 \n22 \nPola S , Fahmy M , Evans E \net al\nSuccessful use of infliximab in the treatment of corticosteroid dependent collagenous colitis . Am J Gastroenterol 2013 ;108 :857 –8 .23644970 \n23 \nMunch A , Ignatova S , Strom M. \nAdalimumab in budesonide and methotrexate refractory collagenous colitis . Scand J Gastroenterol 2012 ;47 :59 –63 .22149977 \n24 \nEsteve M , Mahadevan U , Sainz E \net al\nEfficacy of anti-TNF therapies in refractory severe microscopic colitis . J Crohn Colitis 2011 ;5 :612 –18 .\n25 \nD’Haens G , Feagan B , Colombel JF \net al\nChallenges to the design, execution, and analysis of randomized controlled trials for inflammatory bowel disease . Gastroenterology 2012 ;143 :1461 –9 .23000597 \n26 \nVigren L , Tysk C , Strom M \net al\nCeliac disease and other autoimmune diseases in patients with collagenous colitis . Scand J Gastroenterol 2013 ;48 :944 –50 .23800241 \n27 \nJarnerot G , Tysk C , Bohr J \net al\nCollagenous colitis and fecal stream diversion . Gastroenterology 1995 ;109 :449 –55 .7615194 \n28 \nKhan MA , Brunt EM , Longo WE \net al\nPersistent Clostridium difficile colitis: a possible etiology for the development of collagenous colitis . Dig Dis Sci 2000 ;45 :998 –1001 .10795766 \n29 \nVesoulis Z , Lozanski G , Loiudice T. \nSynchronous occurrence of collagenous colitis and pseudomembranous colitis . Can J Gastroenterol 2000 ;14 :353 –8 .10799091 \n30 \nBohr J , Nordfelth R , Jarnerot G \net al\nYersinia species in collagenous colitis: a serologic study . Scand J Gastroenterol 2002 ;37 :711 –14 .12126251 \n31 \nMakinen M , Niemela S , Lehtola J \net al\nCollagenous colitis and Yersinia enterocolitica infection . Dig Dis Sci 1998 ;43 :1341 –6 .9635629 \n32 \nAndersen T , Andersen JR , Tvede M \net al\nCollagenous colitis: are bacterial cytotoxins responsible? \nAm J Gastroenterol \n1993 ;88 :375 –7 .8438843 \n33 \nRiddell RH , Tanaka M , Mazzoleni G. \nNon-steroidal anti-inflammatory drugs as a possible cause of collagenous colitis: a case-control study . Gut 1992 ;33 :683 –6 .1612488 \n34 \nFernandez-Banares F , Esteve M , Espinos JC \net al\nDrug consumption and the risk of microscopic colitis . Am J Gastroenterol 2007 ;102 :324 –30 .17100977 \n35 \nChande N , Driman DK. \nMicroscopic colitis associated with lansoprazole: report of two cases and a review of the literature . Scand J Gastroenterol 2007 ;42 :530 –3 .17454866 \n36 \nKitagawa T , Sato K , Yokouchi Y \net al\nA case of lansoprazole-associated collagenous colitis with longitudinal ulcer . J Gastrointest Liver Dis 2013 ;22 :9 .\n37 \nThomson RD , Lestina LS , Bensen SP \net al\nLansoprazole-associated microscopic colitis: a case series . Am J Gastroenterol 2002 ;97 :2908 –13 .12425567 \n38 \nBonderup OK , Fenger-Gron M , Wigh T \net al\nDrug exposure and risk of microscopic colitis: a nationwide Danish case-control study with 5751 cases . Inflamm Bowel Dis 2014 ;20 :1702 –7 .25153503 \n39 \nPascua MF , Kedia P , Weiner MG \net al\nMicroscopic colitis and medication use . Clin Med Insights Gastroenterol 2010 ;2010 :11 –19 .20640056\n\n",
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{
"abstract": "BACKGROUND\nTreatment nonadherence in people with schizophrenia is associated with relapse and homelessness. Building on the usefulness of long-acting medication and our work in psychosocial interventions to enhance adherence, we conducted a prospective uncontrolled trial of customized adherence enhancement (CAE) plus long-acting injectable antipsychotic (LAI) using haloperidol decanoate in 30 homeless or recently homeless individuals with DSM-IV-defined schizophrenia or schizoaffective disorder.\n\n\nMETHODS\nParticipants received monthly CAE and LAI (CAE-L) for 6 months. Primary outcomes were adherence, as measured by the Tablets Routine Questionnaire, and housing status. Secondary outcomes included psychiatric symptoms, functioning, side effects, and hospitalizations. The study was conducted from July 2010 to December 2012.\n\n\nRESULTS\nThe mean age of participants was 41.8 years (SD = 8.6); they were mainly minorities (90%, n = 27 African-American) and mainly single/never married (70%, n = 21). Most (97%, n = 29) had past or current substance abuse and had been incarcerated (97%, n = 29). Ten individuals (33%) terminated the study prematurely. CAE-L was associated with good adherence to LAI (at 6 months, 76%) and dramatic improvement in oral medication adherence, which changed from missing 46% of medication at study enrollment to missing only 10% at study end (P = .03). There were significant improvements in psychiatric symptoms (P < .001) and functioning (P < .001). Akathisia was a major side effect with LAI.\n\n\nCONCLUSIONS\nWhile interpretation of findings must be tempered by the methodological limitations, CAE-L appears to be associated with improved adherence, symptoms, and functioning in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder. Additional research is needed on effective and practical approaches to improving health outcomes for homeless people with serious mental illness.\n\n\nBACKGROUND\nClinicalTrials.gov identifier: NCT01152697.",
"affiliations": "Departments of Psychiatry and Neurology, University Hospitals of Cleveland, 11100 Euclid Ave, Cleveland, OH martha.sajatovic@uhhospitals.org.",
"authors": "Sajatovic|Martha|M|;Levin|Jennifer|J|;Ramirez|Luis F|LF|;Hahn|David Y|DY|;Tatsuoka|Curtis|C|;Bialko|Christopher S|CS|;Cassidy|Kristin A|KA|;Fuentes-Casiano|Edna|E|;Williams|Tiffany D|TD|",
"chemical_list": "D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; C033563:haloperidol decanoate; D006220:Haloperidol",
"country": "United States",
"delete": false,
"doi": "10.4088/JCP.12m08331",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0160-6689",
"issue": "74(12)",
"journal": "The Journal of clinical psychiatry",
"keywords": null,
"medline_ta": "J Clin Psychiatry",
"mesh_terms": "D000328:Adult; D017109:Akathisia, Drug-Induced; D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D005260:Female; D006220:Haloperidol; D006703:Homeless Persons; D006760:Hospitalization; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D055118:Medication Adherence; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011580:Psychological Techniques; D011618:Psychotic Disorders; D012559:Schizophrenia; D012565:Schizophrenic Psychology; D016896:Treatment Outcome; D014481:United States",
"nlm_unique_id": "7801243",
"other_id": null,
"pages": "1249-55",
"pmc": null,
"pmid": "24434094",
"pubdate": "2013-12",
"publication_types": "D016430:Clinical Trial; D016428:Journal Article; D052061:Research Support, N.I.H., Extramural; D013485:Research Support, Non-U.S. Gov't",
"references": "21497222;7416910;12059843;1939930;2761036;22548902;9366000;12359668;15056516;17766564;1707323;17998265;18384445;9881538;20690885;2147193;7351540;17107245;22966436;19176415;4917967;3616518;2188483;15677603;9286194;22302337;12019661;2574607;7901897;22929875;11167312;18093962;14680415;4009158;10782554;3945130;16079372;7916523",
"title": "Prospective trial of customized adherence enhancement plus long-acting injectable antipsychotic medication in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder.",
"title_normalized": "prospective trial of customized adherence enhancement plus long acting injectable antipsychotic medication in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder"
} | [
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{
"abstract": "Acute myopathy occurred in a 49-year-old woman hospitalized in the intensive care unit for status asthmaticus. She was given high-dose intravenous steroid therapy and intubated. Pancuronium bromide was used for prolonged curarization. Flaccid quadriplegia developed with preservation of the deep tendon reflexes. Muscle biopsy showed a myogenic process with disorganized myofibrils and selective loss of thick myosin filaments. This mainly myogenic process would result from the toxic effect of corticosteroids favored by prolonged curarization although the effect of other factors still remains unknown.",
"affiliations": "Service de Neurologie, CHU Timone, Marseille.",
"authors": "Sangla|I|I|;Pouget|J|J|;Pellissier|J F|JF|;Serratrice|G|G|",
"chemical_list": "D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D009465:Neuromuscular Agents; D011239:Prednisolone; D001507:Beclomethasone; D000420:Albuterol",
"country": "France",
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"issn_linking": "0755-4982",
"issue": "25(7)",
"journal": "Presse medicale (Paris, France : 1983)",
"keywords": null,
"medline_ta": "Presse Med",
"mesh_terms": "D000208:Acute Disease; D000287:Administration, Topical; D000420:Albuterol; D000893:Anti-Inflammatory Agents; D001507:Beclomethasone; D003422:Critical Care; D004359:Drug Therapy, Combination; D004630:Emergencies; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D008875:Middle Aged; D009135:Muscular Diseases; D009465:Neuromuscular Agents; D011239:Prednisolone; D013224:Status Asthmaticus",
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"pages": "284-6",
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"pubdate": "1996-02-24",
"publication_types": "D002363:Case Reports; D004740:English Abstract; D016428:Journal Article",
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"title": "Acute myopathy in an asthmatic patient treated with corticoids and muscle relaxants in the intensive care unit.",
"title_normalized": "acute myopathy in an asthmatic patient treated with corticoids and muscle relaxants in the intensive care unit"
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{
"abstract": "We report a case of a 27-year old woman with persistent fever and pancytopenia who had multiple episodes of a hemophagocytic lymphohistiocytosis (HLH) like condition. The criterion for HLH was satisfied; primary cytomegalovirus (CMV) infection was identified as the cause. Further examination revealed a GATA binding protein 2 mutation. Reports of GATAs deficiency presenting with HLH after primary CMV infection is very limited. As early recognition and diagnosis will improve patients' outcomes, internists and infectious disease specialists should be aware of this disease.",
"affiliations": "Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.;Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.;Department of General Internal Medicine, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.;Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.;Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan. Electronic address: kayokohayakawa@gmail.com.;Department of Pediatrics, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.;Department of Pediatrics, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.;Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.",
"authors": "Suzuki|Tetsuya|T|;Takaya|Saho|S|;Kunimatsu|Junwa|J|;Kutsuna|Satoshi|S|;Hayakawa|Kayoko|K|;Shibata|Hirofumi|H|;Yasumi|Takahiro|T|;Ohmagari|Norio|N|",
"chemical_list": "D000914:Antibodies, Viral; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D002097:C-Reactive Protein",
"country": "Netherlands",
"delete": false,
"doi": "10.1016/j.jiac.2019.07.002",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1341-321X",
"issue": "26(2)",
"journal": "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy",
"keywords": "B lymphocytopenia; GATA binding protein 2; Hemophagcytic lymphohistiocytosis; Monocytopenia; NK lymphocytopenia; Primary cytomegalovirus infection",
"medline_ta": "J Infect Chemother",
"mesh_terms": "D000328:Adult; D000914:Antibodies, Viral; D001706:Biopsy; D001856:Bone Marrow Examination; D002097:C-Reactive Protein; D003586:Cytomegalovirus Infections; D005260:Female; D050989:GATA2 Transcription Factor; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic; D009154:Mutation",
"nlm_unique_id": "9608375",
"other_id": null,
"pages": "252-256",
"pmc": null,
"pmid": "31350183",
"pubdate": "2020-02",
"publication_types": "D002363:Case Reports",
"references": null,
"title": "GATA2 mutation underlies hemophagocytic lymphohistiocytosis in an adult with primary cytomegalovirus infection.",
"title_normalized": "gata2 mutation underlies hemophagocytic lymphohistiocytosis in an adult with primary cytomegalovirus infection"
} | [
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{
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{
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},
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},
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}
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"literaturereference": "Suzuki T, Takaya S, Kunimatsu J, Kutsuna S, Hayakawa K, Shibata H, et al. GATA2 mutation underlies hemophagocytic lymphohistiocytosis in an adult with primary cytomegalovirus infection. J-Infect-Chemother 2020;26(2):252-256.. 2020;26(2):252-256",
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},
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},
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"seriousnesslifethreatening": 2,
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"transmissiondate": "20220423"
}
] |
{
"abstract": "Hematopoietic toxicity from Zidovudine (AZT) is fairly common, resulting in a requirement for red cell transfusions in up to 25% of patients. Reversible agranulocytosis occurred following approximately 1 week of AZT therapy in a man with AIDS. He recovered from the episode without incident. There was no evidence for underlying bone marrow dysfunction or an adverse drug reaction. Careful monitoring of AZT therapy continues to be of great importance.",
"affiliations": "Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68105.",
"authors": "Goldsmith|J C|JC|;Irvine|W|W|",
"chemical_list": "D015215:Zidovudine",
"country": "United States",
"delete": false,
"doi": "10.1002/ajh.2830300416",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0361-8609",
"issue": "30(4)",
"journal": "American journal of hematology",
"keywords": null,
"medline_ta": "Am J Hematol",
"mesh_terms": "D000163:Acquired Immunodeficiency Syndrome; D000328:Adult; D000380:Agranulocytosis; D001706:Biopsy; D001853:Bone Marrow; D006801:Humans; D008297:Male; D015215:Zidovudine",
"nlm_unique_id": "7610369",
"other_id": null,
"pages": "263-4",
"pmc": null,
"pmid": "2929589",
"pubdate": "1989-04",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Reversible agranulocytosis related to azidothymidine therapy.",
"title_normalized": "reversible agranulocytosis related to azidothymidine therapy"
} | [
{
"companynumb": "US-RANBAXY-2013US-65771",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
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{
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"medicinalproduct": "ZIDOVUDINE."
},
{
"actiondrug": "1",
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"activesubstancename": "ACETAMINOPHEN"
},
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"drugdosagetext": "UNK",
"drugenddate": "198711",
"drugenddateformat": "610",
"drugindication": "PYREXIA",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETAMINOPHEN."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "BLEOMYCIN SULFATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
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"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": "19871026",
"drugenddateformat": "102",
"drugindication": "FACE OEDEMA",
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"drugstartdate": "19870910",
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"medicinalproduct": "BLEOMYCIN"
}
],
"patientagegroup": null,
"patientonsetage": "27",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Agranulocytosis",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Mycobacterium avium complex infection",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Respiratory failure",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Thrombocytopenia",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "GOLDSMITH JC, IRVINE W. REVERSIBLE AGRANULOCYTOSIS RELATED TO AZIDOTHYMIDINE THERAPY. AM J HEMATOL. 1989;APR;30(4):263-4",
"literaturereference_normalized": "reversible agranulocytosis related to azidothymidine therapy",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20160511",
"receivedate": "20160511",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12353928,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
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"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
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"transmissiondate": "20160815"
}
] |
{
"abstract": "The FDA has recently endorsed metformin use in patients with T2D and stage 3 CKD (CKD3). However, metformin safety in elderly individuals is unknown. The aim of this study was to identify frequency and risk factors of lactic acid (LA) elevation in ambulatory elderly male US veterans with stable diabetic CKD3 treated with metformin. We studied 92 patients with non-diabetic CKD3 (Group1), diabetic CKD3 not on metformin (Group2) and diabetic CKD3 on metformin (Group 3). Mean LA levels were similar at 1.3 ± 0.3 and 1.3 ± 0.4 mmol/L in Groups 1 and 2, respectively; while, LA was significantly higher in Group 3 (2.1 ± 1.0 mmol/L, P < .001). Only 1 patient in each Groups 1 (4%) and 2 (4%) had hyperlactatemia (LA > 2.0 mmol/L), as compared with 17 (42.5%) patients in Group 3 (P < .05). No differences in age, BMI, eGFR, metformin dosage, and HbA1c were seen in Group 3 patients with and without hyperlactatemia. In the multivariate logistic regression analyses, metformin use was the only factor significantly associated with hyperlactatemia (adjusted OR 25.48, P < .005). In conclusion, metformin therapy is associated with increased risk of hyperlactatemia in elderly men with diabetic CKD3.",
"affiliations": "Nephrology Section, Stratton VA Medical Center, Albany, NY, United States of America; Department of Medicine, Albany Medical College, Albany, NY, United States of America.;Department of Medicine, Albany Medical College, Albany, NY, United States of America.;Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States of America.;Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States of America; Nephrology Section, Memphis VA Medical Center, Memphis, TN, United States of America.;Endocrinology Section, Stratton VA Medical Center, Albany, NY, United States of America; Department of Medicine, Albany Medical College, Albany, NY, United States of America. Electronic address: aidar.gosmanov@va.gov.",
"authors": "Gosmanova|Elvira O|EO|;Shahzad|Sheikh R|SR|;Sumida|Keiichi|K|;Kovesdy|Csaba P|CP|;Gosmanov|Aidar R|AR|",
"chemical_list": "D019344:Lactic Acid; D008687:Metformin",
"country": "United States",
"delete": false,
"doi": "10.1016/j.jdiacomp.2019.107474",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1056-8727",
"issue": "34(1)",
"journal": "Journal of diabetes and its complications",
"keywords": "Chronic kidney disease; Lactate; Metformin",
"medline_ta": "J Diabetes Complications",
"mesh_terms": "D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2; D003928:Diabetic Nephropathies; D018450:Disease Progression; D006801:Humans; D065906:Hyperlactatemia; D019344:Lactic Acid; D008297:Male; D008687:Metformin; D051436:Renal Insufficiency, Chronic; D014481:United States; D014728:Veterans",
"nlm_unique_id": "9204583",
"other_id": null,
"pages": "107474",
"pmc": null,
"pmid": "31677983",
"pubdate": "2020-01",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Metformin is associated with increase in lactate level in elderly patients with type 2 diabetes and CKD stage 3: A case-control study.",
"title_normalized": "metformin is associated with increase in lactate level in elderly patients with type 2 diabetes and ckd stage 3 a case control study"
} | [
{
"companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2022R1-334861",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "075967",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diabetes mellitus",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
}
],
"patientagegroup": "6",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Lactic acidosis",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Metabolic acidosis",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Gosmanova EO, Shahzad SR, Sumida K, Kovesdy CP, Gosmanov AR. Metformin is associated with increase in lactate level in elderly patients with type 2 diabetes and CKD stage 3: A case-control study. J Diabetes Complicat. 2020;34 (1):107474",
"literaturereference_normalized": "metformin is associated with increase in lactate level in elderly patients with type 2 diabetes and ckd stage 3 a case control study",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20220428",
"receivedate": "20220428",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 20761379,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220721"
}
] |
{
"abstract": "BACKGROUND\nGiven the widespread use of immune checkpoint inhibitors (ICIs), newer immune related adverse events (irAEs) have come to light, including flare-ups of preexisting autoimmune disorders (AIDs) and delayed immune-related events. We aimed to identify the frequency and severity of new IRAEs, including AID flares in cancer patients treated with ICIs at our institution. We also studied the tolerability of ICIs upon rechallenge in patients with irAEs and hospital admissions due to irAEs in a community setting in rural Maine.\n\n\nMETHODS\nWe conducted a retrospective chart review analysis of all patients with cancer who received anti-PDL1/PDL1 inhibitors nivolumab, pembrolizumab, atezolizumab, and durvalumab at our tertiary care center from November 2015 to March 2019. Demographic data, cancer type and stage, irAEs, hospital admissions due to irAEs, and drug treatment information was extracted.\n\n\nRESULTS\nWe included 465 patients who received ICIs, 115 (out of 465 25%) developed new irAEs. Preexisting AID were identified in 47 (out of 465) (10%), AID flares were observed in 12 patients (25% of 47). 17 (out of 47 36%) were on immunosuppression for underlying AID, 5 (out of 17, 29%) developed flares. Overall, 148 (32% of 465) irAEs occurred, as some patients had multiple toxicities. Majority were treated for Lung cancer (63%), followed by melanoma and genitourinary cancers. Due to irAE severity, treatment was permanently discontinued in 15% (out of 465) patients. Hospital admissions due to irAEs were required for 34 patients (7.3% of 465). ICI rechallenge was performed in 27 patients (6% of 465), and majority tolerated well.\n\n\nCONCLUSIONS\nOur study shows that ICIs were generally well tolerated and can be used safely even in patients with preexisting AIDs; it is encouraging to see majority tolerated rechallenge with ICIs well.",
"affiliations": "Department of Internal Medicine, Eastern Maine Medical Center, Kelley 6, 489 State Street, Bangor, ME, 04401, USA. vb0818@outlook.com.;Department of Internal Medicine, Eastern Maine Medical Center, Kelley 6, 489 State Street, Bangor, ME, 04401, USA.;Department of Hematology Oncology, Northern Light Cancer Institute, 33 Whiting Hill Lane, Brewer, ME, 04412, USA.",
"authors": "Bhatlapenumarthi|Vineel|V|;Patwari|Anannya|A|http://orcid.org/0000-0003-0902-6912;Harb|Antoine J|AJ|",
"chemical_list": "D000082082:Immune Checkpoint Inhibitors",
"country": "Germany",
"delete": false,
"doi": "10.1007/s00432-021-03610-w",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0171-5216",
"issue": "147(9)",
"journal": "Journal of cancer research and clinical oncology",
"keywords": "Anti-PD1/PDL1 inhibitors; Delayed immune-related events; Hospital admissions due to irAEs; Immune checkpoint inhibitors; Immune-related adverse events; Preexisting autoimmune disorders; Rechallenge with ICIs",
"medline_ta": "J Cancer Res Clin Oncol",
"mesh_terms": "D000368:Aged; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000082082:Immune Checkpoint Inhibitors; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009369:Neoplasms; D011379:Prognosis; D019233:Retreatment; D012189:Retrospective Studies; D015996:Survival Rate",
"nlm_unique_id": "7902060",
"other_id": null,
"pages": "2789-2800",
"pmc": null,
"pmid": "33774736",
"pubdate": "2021-09",
"publication_types": "D016428:Journal Article",
"references": "29297009;32978897;31386608;26412456;26028407;12538684;27566797;28652812;30796151;31269983;29658430;29545095;31911324;29357948;28214654;29917046;32194150;29658845;26712084;3549297;26633184;31200356;28945858;29746230;5719487;29562145;30698276;30190787;29045547;5697162;29951303;27979383;29991499;30104155;31169866;21204754;27660709;28889792",
"title": "Immune-related adverse events and immune checkpoint inhibitor tolerance on rechallenge in patients with irAEs: a single-center experience.",
"title_normalized": "immune related adverse events and immune checkpoint inhibitor tolerance on rechallenge in patients with iraes a single center experience"
} | [
{
"companynumb": "US-BRISTOL-MYERS SQUIBB COMPANY-BMS-2021-036165",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "NIVOLUMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "125554",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 WEEKS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NON-SMALL CELL LUNG CANCER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
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"medicinalproduct": "NIVOLUMAB"
}
],
"patientagegroup": null,
"patientonsetage": "64",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Immune-mediated lung disease",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Immune-mediated hepatitis",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BHATLAPENUMARTHI V, PATWARI A, HARB AJ. IMMUNE?RELATED ADVERSE EVENTS AND IMMUNE CHECKPOINT INHIBITOR TOLERANCE ON RECHALLENGE IN PATIENTS WITH IRAES: A SINGLE?CENTER EXPERIENCE. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY. 2021?1?12",
"literaturereference_normalized": "immune related adverse events and immune checkpoint inhibitor tolerance on rechallenge in patients with iraes a single center experience",
"qualification": "3",
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},
"primarysourcecountry": "US",
"receiptdate": "20210419",
"receivedate": "20210419",
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},
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},
"serious": 1,
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"seriousnessother": 1,
"transmissiondate": "20210717"
},
{
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{
"actiondrug": "1",
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},
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"drugdosagetext": "4 WEEKS",
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"drugindication": "RENAL CELL CARCINOMA",
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"drugrecurreadministration": "3",
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"medicinalproduct": "NIVOLUMAB"
}
],
"patientagegroup": null,
"patientonsetage": "60",
"patientonsetageunit": "801",
"patientsex": "1",
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"reaction": [
{
"reactionmeddrapt": "Immune-mediated arthritis",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BHATLAPENUMARTHI V, PATWARI A, HARB AJ. IMMUNE?RELATED ADVERSE EVENTS AND IMMUNE CHECKPOINT INHIBITOR TOLERANCE ON RECHALLENGE IN PATIENTS WITH IRAES: A SINGLE?CENTER EXPERIENCE. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY. 2021?1?12",
"literaturereference_normalized": "immune related adverse events and immune checkpoint inhibitor tolerance on rechallenge in patients with iraes a single center experience",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210421",
"receivedate": "20210421",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19160444,
"safetyreportversion": 1,
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"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
},
{
"companynumb": "US-BRISTOL-MYERS SQUIBB COMPANY-BMS-2021-036166",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "NIVOLUMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "125554",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 WEEKS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SMALL CELL LUNG CANCER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
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"medicinalproduct": "NIVOLUMAB"
}
],
"patientagegroup": null,
"patientonsetage": "76",
"patientonsetageunit": "801",
"patientsex": "1",
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"reaction": [
{
"reactionmeddrapt": "Immune-mediated lung disease",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Intentional product use issue",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
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"literaturereference_normalized": "immune related adverse events and immune checkpoint inhibitor tolerance on rechallenge in patients with iraes a single center experience",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210419",
"receivedate": "20210419",
"receiver": {
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"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19156144,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
},
{
"companynumb": "US-BRISTOL-MYERS SQUIBB COMPANY-BMS-2021-036180",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "NIVOLUMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "125554",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 WEEKS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MALIGNANT MELANOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
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"drugtreatmentdurationunit": null,
"medicinalproduct": "NIVOLUMAB"
}
],
"patientagegroup": null,
"patientonsetage": "59",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Immune-mediated uveitis",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BHATLAPENUMARTHI V, PATWARI A, HARB AJ. IMMUNE?RELATED ADVERSE EVENTS AND IMMUNE CHECKPOINT INHIBITOR TOLERANCE ON RECHALLENGE IN PATIENTS WITH IRAES: A SINGLE?CENTER EXPERIENCE. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY. 2021?1?12",
"literaturereference_normalized": "immune related adverse events and immune checkpoint inhibitor tolerance on rechallenge in patients with iraes a single center experience",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210420",
"receivedate": "20210420",
"receiver": {
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"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19162644,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
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"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
},
{
"companynumb": "US-BRISTOL-MYERS SQUIBB COMPANY-BMS-2021-035593",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "NIVOLUMAB"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "125554",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
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"drugindication": "MALIGNANT MELANOMA",
"drugintervaldosagedefinition": null,
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"medicinalproduct": "NIVOLUMAB"
}
],
"patientagegroup": null,
"patientonsetage": "66",
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"patientsex": "2",
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"reaction": [
{
"reactionmeddrapt": "Immune-mediated enterocolitis",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
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"literaturereference_normalized": "immune related adverse events and immune checkpoint inhibitor tolerance on rechallenge in patients with iraes a single center experience",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210420",
"receivedate": "20210420",
"receiver": {
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"receivertype": "6"
},
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"safetyreportversion": 1,
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"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
},
{
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"fulfillexpeditecriteria": "1",
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"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PEMBROLIZUMAB"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "125514",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "POWDER FOR INJECTION",
"drugdosagetext": "EVERY 3 WEEKS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MALIGNANT NEOPLASM OF THYMUS",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "3",
"drugrecurreadministration": "2",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "KEYTRUDA"
}
],
"patientagegroup": null,
"patientonsetage": "57",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
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"abstract": "BACKGROUND\nWithholding live-attenuated vaccines in patients using interleukin (IL)-1 or IL-6 blocking agents is recommended by guidelines for both pediatric and adult rheumatic diseases, since there is a risk of infection in an immune suppressed host. However, this has never been studied. This retrospective, multicenter survey aimed to evaluate the safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade.\n\n\nMETHODS\nWe contacted physicians involved in the treatment of autoinflammatory diseases to investigate potential cases. Patients were included if a live-attenuated vaccine had been administered while they were on IL-1 or IL-6 blockade.\n\n\nRESULTS\nSeventeen patients were included in this survey (7 systemic juvenile idiopathic arthritis (sJIA), 5 cryopyrin associated periodic syndrome (CAPS), 4 mevalonate kinase deficiency (MKD) and 1 familial Mediterranean fever (FMF). Three patients experienced an adverse event, of which two were serious adverse events (a varicella zoster infection after varicella zoster booster vaccination, and a pneumonia after MMR booster). One additional patient had diarrhea after oral polio vaccine. Further, seven patients experienced a flare of their disease, which were generally mild. Eight patients did not experience an adverse event or a flare.\n\n\nCONCLUSIONS\nWe have described a case series of seventeen patients who received a live-attenuated vaccine while using IL-1 or IL-6 blocking medication. The findings of this survey are not a reason to adapt the existing guidelines. Prospective trials are needed in order to acquire more evidence about the safety and efficacy before considering adaptation of guidelines.",
"affiliations": "Department of General Pediatrics, University Medical Center Utrecht, Room KE 04 133 1, PO-Box 85090, 3508, AB Utrecht, The Netherlands.;Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.;University College Medical School, National Amyloidosis Center, Royal Free Campus, London, UK.;Department of Pediatric Rheumatology, Cerrahpasa Medical School-Istanbul University, Istanbul, Turkey.;Inflammatory Disease section, National Human Genome Research Institute, Bethesda, MA, USA.;Institute of Pediatrics, Università Cattolica Sacro Cuore, Rome, Italy.;Division of Immunology, Boston Children's Hospital, Boston, MA, USA.;Division of Immunology, Boston Children's Hospital, Boston, MA, USA.;Department of Pediatric Rheumatology, University Medical Center Utrecht, Utrecht, the Netherlands.;Department of Pediatric Rheumatology, University Medical Center Utrecht, Utrecht, the Netherlands.;Department of General Pediatrics, University Medical Center Utrecht, Room KE 04 133 1, PO-Box 85090, 3508, AB Utrecht, The Netherlands. J.Frenkel@umcutrecht.nl.",
"authors": "Jeyaratnam|Jerold|J|;Ter Haar|Nienke M|NM|;Lachmann|Helen J|HJ|;Kasapcopur|Ozgur|O|;Ombrello|Amanda K|AK|;Rigante|Donato|D|;Dedeoglu|Fatma|F|;Baris|Ezgi H|EH|;Vastert|Sebastiaan J|SJ|;Wulffraat|Nico M|NM|;Frenkel|Joost|J|",
"chemical_list": "D007166:Immunosuppressive Agents; D007375:Interleukin-1; D015850:Interleukin-6; D014613:Vaccines, Attenuated",
"country": "England",
"delete": false,
"doi": "10.1186/s12969-018-0235-z",
"fulltext": "\n==== Front\nPediatr Rheumatol Online JPediatr Rheumatol Online JPediatric Rheumatology Online Journal1546-0096BioMed Central London 23510.1186/s12969-018-0235-zResearch ArticleThe safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade: an international survey Jeyaratnam Jerold J.Jeyaratnam@umcutrecht.nl 1ter Haar Nienke M. N.M.terhaar-2@umcutrecht.nl 2Lachmann Helen J. h.lachmann@ucl.ac.uk 3Kasapcopur Ozgur ozgurkasapcopur@hotmail.com 4Ombrello Amanda K. Amanda.ombrello@nih.gov 5Rigante Donato drigante@gmail.com 6Dedeoglu Fatma Fatma.Dedeoglu@childrens.harvard.edu 7Baris Ezgi H. HaticeEzgi.Baris@childrens.harvard.edu 7Vastert Sebastiaan J. B.Vastert@umcutrecht.nl 8Wulffraat Nico M. N.Wulffraat@umcutrecht.nl 8Frenkel Joost 0031-88-7554194J.Frenkel@umcutrecht.nl 11 0000000090126352grid.7692.aDepartment of General Pediatrics, University Medical Center Utrecht, Room KE 04 133 1, PO-Box 85090, 3508, AB Utrecht, The Netherlands 2 0000000090126352grid.7692.aLaboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands 3 0000000121901201grid.83440.3bUniversity College Medical School, National Amyloidosis Center, Royal Free Campus, London, UK 4 0000 0001 2166 6619grid.9601.eDepartment of Pediatric Rheumatology, Cerrahpasa Medical School-Istanbul University, Istanbul, Turkey 5 0000 0001 2233 9230grid.280128.1Inflammatory Disease section, National Human Genome Research Institute, Bethesda, MA USA 6 0000 0001 0941 3192grid.8142.fInstitute of Pediatrics, Università Cattolica Sacro Cuore, Rome, Italy 7 0000 0004 0378 8438grid.2515.3Division of Immunology, Boston Children’s Hospital, Boston, MA USA 8 0000000090126352grid.7692.aDepartment of Pediatric Rheumatology, University Medical Center Utrecht, Utrecht, the Netherlands 21 3 2018 21 3 2018 2018 16 193 1 2018 5 3 2018 © The Author(s). 2018Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background\nWithholding live-attenuated vaccines in patients using interleukin (IL)-1 or IL-6 blocking agents is recommended by guidelines for both pediatric and adult rheumatic diseases, since there is a risk of infection in an immune suppressed host. However, this has never been studied. This retrospective, multicenter survey aimed to evaluate the safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade.\n\nMethods\nWe contacted physicians involved in the treatment of autoinflammatory diseases to investigate potential cases. Patients were included if a live-attenuated vaccine had been administered while they were on IL-1 or IL-6 blockade.\n\nResults\nSeventeen patients were included in this survey (7 systemic juvenile idiopathic arthritis (sJIA), 5 cryopyrin associated periodic syndrome (CAPS), 4 mevalonate kinase deficiency (MKD) and 1 familial Mediterranean fever (FMF). Three patients experienced an adverse event, of which two were serious adverse events (a varicella zoster infection after varicella zoster booster vaccination, and a pneumonia after MMR booster). One additional patient had diarrhea after oral polio vaccine. Further, seven patients experienced a flare of their disease, which were generally mild. Eight patients did not experience an adverse event or a flare.\n\nConclusion\nWe have described a case series of seventeen patients who received a live-attenuated vaccine while using IL-1 or IL-6 blocking medication. The findings of this survey are not a reason to adapt the existing guidelines. Prospective trials are needed in order to acquire more evidence about the safety and efficacy before considering adaptation of guidelines.\n\nKeywords\nAutoinflammatory diseasesLive-attenuated vaccinesBiologicalsIL-1 blockadeIL-6 blockadeissue-copyright-statement© The Author(s) 2018\n==== Body\nBackground\nVaccines have contributed greatly to public health, protecting children and adults from serious infectious diseases [1]. Besides inactivated vaccines there are several live-attenuated vaccines.\n\nAutoinflammatory diseases, such as systemic juvenile idiopathic arthritis (sJIA), familial Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), cryopyrin associated periodic syndrome (CAPS) and tumor necrosis factor (TNF)-receptor associated periodic syndrome (TRAPS) exhibit systemic inflammation or organ specific inflammation caused by dysregulation of the innate immune system. Interleukin (IL)-1 blockade (anakinra, canakinumab and rilonacept) and IL-6 blockade (tocilizumab) have greatly improved the outcome of these patients [2]. However, patients with autoinflammatory diseases potentially face long-term or lifelong immunosuppression thus raising the dilemma if and when vaccinations could be given.\n\nAlthough vaccination is generally considered safe in the healthy population, existing guidelines for both pediatric and adult rheumatic diseases recommend to withhold live-attenuated vaccines in patients using IL-1 or IL-6 blocking agents, because of lack of safety data and the (theoretical) risk of introducing infection in an immune suppressed host [3–5]. On the other hand, patients with autoinflammatory diseases might especially benefit from protection against infectious diseases, as the immunosuppressive therapy renders them more susceptible to infections [6, 7]. In clinical practice, vaccination can be considered on a case-to-case basis weighing the risk of natural infection versus the risk of vaccination, e.g. measles mumps and rubella (MMR) vaccination during measles outbreaks or yellow fever vaccine before travelling to endemic regions.\n\nIn this retrospective survey, we aimed to evaluate the safety and efficacy of live-attenuated vaccines in patients using IL-1 or IL-6 blockade.\n\nMethods\nVia the Paediatric Rheumatology European Society and the International Society for Systemic Auto Inflammatory Diseases pediatric and adult rheumatologists and immunologists were contacted by e-mail in January 2016 in order to recruit potential cases. A reminder was sent up to three times, if no response was obtained. Patients were included if they had received a live-attenuated vaccine while using IL-1 blockade or IL-6 blockade.\n\nEthical approval was obtained by the institutional ethical committee in accordance with local ethical regulations; the survey was conducted in accordance with the ethical principles of the declaration of Helsinki. Written informed consent was obtained from the patient or the legal guardians in case of minors according to local requirements. Demographic and clinical data were collected by local physicians and were anonymized. Adverse events were categorized as adverse events and serious adverse events. Serious adverse events were defined as events leading to death, life-threatening events, events leading to hospitalization, prolonged hospitalization and events leading to severe and/or permanent disability [8]. A flare was defined as the presence of any symptoms of the disease, e.g. fever, rash, abdominal pain and diarrhea.\n\nResults\nIn total 85 physicians from 23 countries were contacted. In total, seventeen patients were included: 7 sJIA, 5 CAPS, 4 MKD and 1 FMF. The median age at vaccination was 9 years (1–58 years), 11 patients were female. Most patients received a booster vaccine for MMR, but patients also received varicella zoster, yellow fever and oral polio vaccines. Patient characteristics are listed in Table 1. The patients are discussed in more detail below.Table 1 Characteristics of all vaccinated patients\n\nPt\tGender\tAge (y)\tCountry\tDisease\tDisease activity\tBiological\tOther DMARDs\tVaccination\tAdverse events\tFlare\t\n1\tFemale\t7\tUSA\tsJIA\tInactive\tAnakinra 4 mg/kg/day\tPrednisone (0.12 mg/kg/day) Methotrexate Leflunomide Thalidomide\tVaricella zoster (booster)\tVaricella zoster infection\t–\t\n2\tFemale\t1\tTurkey\tsJIA\tInactive\tCanakinumab 4 mg/kg/2 months\tPrednisone (5 mg/day) Methotrexate\tMMR booster\tPneumonia\tYes\t\n3\tMale\t2\tTurkey\tsJIA\tInactive\tTocilizumab 12 mg/kg/monthly\tPrednisone (2.5 mg/day)\tOral polio vaccine\tDiarrhea\t–\t\n4\tMale\t12\tUSA\tMKD\tInactive\tAnakinraa 100 mg/day (STOP 3-4D-1D)\t–\tVaricella zoster (booster)\t–\tYes\t\n5\tMale\t9\tUSA\tMKD\tInactive\tAnakinraa 150 mg during flare (STOP 2D-1D)\t–\tVaricella zoster (booster)\t–\tYes\t\n6\tFemale\t4\tUSA\tMKD\tPartially active\tCanakinumaba 4 mg/kg/6 weeks (STOP 3 M–3 M)\t\tVaricella zoster (first vaccine) and MMR first vaccine\t–\tYes\t\n7\tFemale\t2\tTurkey\tFMF\tInactive\tCanakinumab 4 mg/kg/monthly\tPrednisone (2.5 mg/day) Colchicine\tMMR booster\t–\tYes\t\n8\tFemale\t9\tNetherlands\tsJIA\tInactive\tAnakinraa 1.7 mg/kg/2 days (STOP 2D-3D)\tMethotrexate\tMMR booster\t–\tYes\t\n9\tMale\t3\tNetherlands\tsJIA\tInactive\tTocilizumab 132 mg/14 days)\tPrednisone (2.5 mg/day)\tVaricella zoster (first vaccine)\t–\tYes\t\n10\tMale\t12\tItaly\tCAPS\tInactive\tAnakinraa 1.5 mg/kg/day (STOP 3D-14D)\tMethylprednisolone (0.06 mg/kg/day)\tMMR booster\t–\t–\t\n11\tFemale\t12\tItaly\tMKD\tPartially active\tAnakinraa 1.4 mg/kg/day (STOP 3D-28D)\t–\tMMR booster\t–\t–\t\n12\tFemale\t9\tNetherlands\tsJIA\tInactive\tAnakinra 40 mg/3 days\t–\tMMR booster\t–\t–\t\n13\tMale\t9\tNetherlands\tsJIA\tInactive\tTocilizumab 8 mg/kg/2 weeks\tMethotrexate\tMMR booster\t–\t–\t\n14\tFemale\t58\tUnited Kingdom\tCAPS\tInactive\tAnakinraa 100 mg/day (STOP 3D-3D)\t–\tYellow fever (first vaccine)\t–\t–\t\n15\tFemale\t28\tUnited Kingdom\tCAPS\tInactive\tAnakinraa 100 mg/day (STOP 3D-3D)\t–\tYellow fever (first vaccine)\t–\t–\t\n16\tFemale\t26\tUnited Kingdom\tCAPS\tInactive\tAnakinraa 100 mg/day (STOP 3D-3D)\t–\tYellow fever (first vaccine)\t–\t–\t\n17\tFemale\t44\tUnited Kingdom\tCAPS\tInactive\tCanakinumab (150 mg/2 months)\t–\tYellow fever (first vaccine)\t–\t–\t\naBiological stopped prior to vaccination and restarted after vaccination. The period of discontinuation before and after vaccination is indicated in brackets.\n\nD days before or after vaccination, M months before or after vaccination\n\n\n\nAdverse events\nThree patients reported an adverse event after vaccination, of whom two were categorized as severe due to the need for hospitalization.\n\nPatient 1 was a seven-year-old girl with sJIA, who was treated with multiple immunosuppressive agents at the same time, including prednisone, methotrexate (MTX), thalidomide, leflunomide and anakinra. Sixteen days after she received a varicella zoster booster vaccination, she developed vesicles on her trunk and a few on her scalp and extremities. The diagnosis of varicella zoster infection was made on the clinical phenotype; the virus could not be isolated. Because of suspected varicella in an immunocompromised host, she was admitted to hospital for 4 days and was discharged with a 10-day course of intravenous acyclovir. As there was no known exposure to other varicella cases, the infection in this child was considered to be caused by the vaccination itself.\n\nPatient 2 suffered from sJIA and was treated with canakinumab. She was accidentally vaccinated with MMR booster by the vaccination campaign in Turkey. One week after vaccination she was diagnosed with pneumonia, which was confirmed by X-ray. As it was considered to be a bacterial pneumonia, treatment with cefuroxime axetil was started. The patient was hospitalized for 5 days. Besides the pneumonia, she had a sJIA flare with fever and rash during the same period. This flare was treated with low-dose prednisone with good response. The impression of the physicians in charge was that this was a flare of her sJIA. Although extremely unlikely, the coincidence of fever, rash and pneumonia could also be ascribed to measles, introduced by vaccination.\n\nThe last patient (patient 3) with an adverse event was a sJIA patient treated with tocilizumab. One week after vaccination with oral polio vaccine, the patient experienced diarrhea, which was treated with oral fluid replacements, co-trimoxazol and probiotics. This adverse event was thought to be caused by the vaccine, especially since other family members did not suffer from diarrhea.\n\nFlares\nIn total seven patients reported a flare of their disease after vaccination. A MKD patient (patient 4) received 100 mg anakinra daily, which was stopped 3–4 days before booster vaccination with varicella zoster and restarted 1 day after vaccination. He experienced fever after vaccination. Since the fever was thought to be caused by a flare, the patient was treated with the normal dose of anakinra. Patient 5 used anakinra (150 mg) during MKD flares only, since the disease was relatively quiescent. The days before and after vaccination with varicella zoster, anakinra was not administered. After vaccination he experienced fever, which was treated with anakinra. Patient 6 was 4 years old when she received her first MMR and varicella zoster vaccines. Her disease was incompletely controlled under treatment with canakinumab 4 mg/kg every 6 weeks. Canakinumab was stopped 3 months before and restarted 3 months after vaccination. Before vaccination she experienced low grade fevers every week. After vaccination she had a mild flare with fever, vomiting, diarrhea and headache. This flare was treated with acetaminophen and ibuprofen. Patient 7 was treated with canakinumab due to colchicine resistant FMF. Besides FMF, she also suffered from inflammatory bowel disease. The vaccination with MMR booster was administered accidentally by the primary health service in Turkey. Due to this vaccination the next dose of canakinumab was withheld; the following dose was given 2 months after vaccination. One week after vaccination the patient had an FMF attack with fever and abdominal pain, which led to hospitalization. During hospitalization she was treated with low-dose prednisone (2.5 mg/day) and colchicine (0.5 mg/day) with good response. After 8 days she was discharged in good condition.\n\nIn another patient (patient 8) who suffered from sJIA, anakinra was stopped 2 days before and restarted 3 days after vaccination. After MMR booster vaccination she experienced a mild flare with some exanthema, but without fever, which was probably due to the stop of anakinra. This flare did not require any additional treatment.\n\nPatient 9 was a young boy with Down syndrome and sJIA complicated by macrophage activation syndrome. He was initiated on tocilizumab treatment at a very young age, before experiencing varicella zoster infection; therefore, he was vaccinated with a first varicella zoster vaccine, in order to acquire immunity in a controlled setting. After vaccination he suffered from a mild flare with subfebrile temperature, exanthema and malaise. After this flare, the physician and parents decided not to repeat varicella vaccination.\n\nPatients without flares or adverse events\nEight patients did not experience a flare or an adverse event. Patient 10 suffered from Chronic Infantile Neurological Cutaneous Articular (CINCA) syndrome, the most severe form of CAPS, which was treated with anakinra. At the age of 12 years he received MMR vaccination as a routine administration of the booster vaccine. Treatment with anakinra was stopped 3 days before vaccination and restarted 2 weeks afterwards. He did not have any adverse events. Patient 11 who had MKD was in partial remission at the time of vaccination. The treatment of anakinra was stopped 3 days before vaccination and restarted 4 weeks afterwards. The last two patients were Dutch sJIA patients with inactive disease on anakinra (patient 12) or tocilizumab and MTX (patient 13). They received the MMR booster vaccine through the national vaccination program, and reported no symptoms afterwards. Patients 14–16 concerned a mother and two daughters all suffering from CAPS, which was treated with anakinra. In order to be protected against yellow fever during travel, they were all vaccinated without any problems. The three of them suspended anakinra for 3 days prior and 3 days after vaccination. The last patient (patient 17) was treated with canakinumab and received a yellow fever vaccination. The vaccine was given 8 weeks after the last dose and the next dose was given 3 weeks after vaccination.\n\nDiscussion\nThis survey describes the safety of live-attenuated vaccine in a case series of patients using IL-1 or IL-6 blocking medication. The seventeen patients in our series reported three adverse events, of which two were categorized as severe, and seven flares, while eight patients did not report any complaints after vaccination. Although adverse events occurred soon after vaccination, coincidence cannot be ruled out. Flares were associated with discontinuation of IL-1 blockade before vaccination in four of the seven patients.\n\nThe retrospective design of this survey comes with a number of limitations. Due to this design, information on antibody titers is lacking as these are not routinely measured after vaccination. Therefore, we cannot draw any conclusions about the vaccine efficacy. Further, the small number of patients and the variety in diseases, age, medication and vaccines hampers conclusions on the safety of live-attenuated vaccines in general. Immunological characterization of patients before or after vaccination was not possible due to the retrospective design. The small number and the heterogeneity of the group precluded statistical analysis. The small number of patients included, however, reflects the reluctance of physicians to administer live-attenuated vaccines to patients using these biologicals.\n\nA substantial number of patients in this series were vaccinated inadvertently through national vaccination programs, which has also led to a lack of follow-up data since patients were not monitored by their physician during and after vaccination. Live-attenuated vaccines cannot be considered entirely safe in patients using IL-1 or IL-6 blockade since up to three patients experienced an adverse event, while seven patients experienced a flare to some extent. This should be taken into consideration before administering live-attenuated vaccines in patients using IL-1 or IL-6 blockade.\n\nAt least one adverse event was considered to be caused by the micro-organism of the vaccine (patient 2, varicella). However, rash and in particular vesicles are also seen in 3% of healthy children after vaccination with varicella zoster vaccine [9]. Thus, the reported vesicles after vaccination might also be explained by a common vaccination reaction. In the two other patients with an adverse event it cannot be established with certainty that vaccination led to the symptoms of these patients, as pneumonia and diarrhea are common infections in childhood.\n\nIn our series, three of four MKD patients reported a flare after vaccination. It is already known that vaccination is a well-known trigger of fever episodes in MKD [10]. However, in these three patients the biological was stopped around the vaccination, as was the case in a child with another disorder who flared. The discontinuation might have contributed to the flares as well. Further, fever and rash are also quite common symptoms after vaccination in healthy children and adults. For example, fever is noted in 10–15% of children receiving varicella zoster vaccine [9]. After MMR vaccination 17% of healthy children and adults reported fever and 5% mentioned a rash [11].\n\nSeveral studies have described the safety and efficacy of inactivated vaccines in patients using IL-1 blocking agents [12–15]. Two studies on canakinumab showed no difference in antibody titers between groups on canakinumab and subjects not on canakinumab [12, 13]. A study on anakinra also did not show a significant difference in antibody responses [14].\n\nThe data on disease flares and adverse events after vaccination are conflicting. In the phase-III trial of canakinumab in 109 CAPS patients, fifteen patients received influenza vaccination, five patients pneumococcal vaccination and one patient received MMR vaccine [16]. None of these patients reported an adverse event. Also in the study of 17 CAPS patients on canakinumab, no flares were described. Adverse events included predominantly upper respiratory tract infections. However, a recent study showed that CAPS patients treated with canakinumab reacted severely after pneumococcal vaccination [17]. Twelve of 18 patients who received pneumococcal immunizations developed vaccine reactions (fever, swelling, erythema, pain), usually within hours after vaccination. Reactions lasted up to 3 weeks. In two patients pneumococcal vaccination triggered CAPS reactivation with systemic inflammation.\n\nConclusions\nIn conclusion, we have described a retrospective case series of seventeen patients who received live-attenuated vaccines while using IL-1 or IL-6 blocking medication. The current data are insufficient to draw any conclusions about the safety of these vaccines in patients using IL-1/IL-6 blockade. Therefore, more safety and efficacy data are needed before considering adaptation of guidelines. Until that time, physicians should still balance the risk of natural infection versus the risk of vaccination, including disease flares and other adverse events, for each individual patient.\n\nAcknowledgements\nNot applicable\n\nFunding\nThis study did not receive any funding.\n\nAvailability of data and materials\nThe dataset used for this study are available from the corresponding author on reasonable request.\n\nAuthors’ contributions\nAll authors made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data. JJ, NMtH and JF were involved in drafting the manuscript. All authors read and approved the final manuscript.\n\nEthics approval and consent to participate\nEthical approval was obtained by the institutional ethical committee in accordance with local ethical regulations; the study was conducted in accordance with the ethical principles of the declaration of Helsinki. Written informed consent was obtained from the patient or the legal guardians in case of minors according to local requirements.\n\nConsent for publication\nNot applicable\n\nCompeting interests\nThe authors declare that they have no competing interests.\n\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n1. John M, Davey S. State of the world’s vaccines and immunization. Third. Executive summary 2009. URL: http://apps.who.int/iris/bitstream/10665/70114/1/WHO_IVB_09.10_eng.pdf Accessed 27 Nov 2015.\n2. ter Haar N Lachmann H Özen S Woo P Uziel Y Modesto C Treatment of autoinflammatory diseases: results from the Eurofever registry and a literature review Ann Rheum Dis 2013 72 5 678 685 10.1136/annrheumdis-2011-201268 22753383 \n3. Heijstek MW Ott de Bruin LM Bijl M Borrow R van der Klis F Kone-Paut I EULAR recommendations for vaccination in paediatric patients with rheumatic diseases Ann Rheum Dis 2011 70 10 1704 1712 10.1136/ard.2011.150193 21813547 \n4. van Assen S Agmon-Levin N Elkayam O Cervera R Doran MF Dougados M EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases Ann Rheum Dis 2011 70 3 414 422 10.1136/ard.2010.137216 21131643 \n5. ter Haar NM Oswald M Jeyaratnam J Anton J Barron KS Brogan PA Recommendations for the management of autoinflammatory diseases Ann Rheum Dis 2015 74 9 1636 1644 10.1136/annrheumdis-2015-207546 26109736 \n6. Doran MF Crowson CS Pond GR O'Fallon WM Gabriel SE Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study Arthritis Rheum 2002 46 9 2287 2293 10.1002/art.10524 12355475 \n7. Fessler BJ Infectious diseases in systemic lupus erythematosus: risk factors, management and prophylaxis Best Pract Res Clin Rheumatol 2002 16 281 91.4 10.1053/berh.2001.0226 12041954 \n8. Bankowski Z Bruppacher R Crusius I Gallagher J Kremer G Venulet J Reporting adverse drug reactions 1999 Geneva Councel for International Organizations of Medical Scientists \n9. CDC Prevention of varicella updated recommendations of the advisory committee on immunization practices (ACIP) MMWR 1999 48 RR06 1 5 \n10. Ter Haar NM Jeyaratnam J Lachmann HJ Simon A Brogan PA Doglio M The phenotype and genotype of mevalonate kinase deficiency: a series of 114 cases from the Eurofever registry Arthritis Rheum 2016 68 11 2795 2805 10.1002/art.39763 \n11. CDC Understanding MMR vaccine safety 2013 \n12. Chioato A Noseda E Felix SD Stevens M Del Giudice G Fitoussi S Influenza and meningococcal vaccinations are effective in healthy subjects treated with the interleukin-1 beta-blocking antibody canakinumab: results of an open-label, parallel group, randomized, single-center study Clin Vaccine Immunol 2010 17 12 1952 1957 10.1128/CVI.00175-10 20962212 \n13. Brogan P Hofer M Kuemmerle-Deschner J Efficacy, safety, and post-vaccination antibody titer data in children with CAPS treated with Canakinumab Pediatr Rheumatol 2015 13 Suppl 1 P1 10.1186/1546-0096-13-S1-P1 \n14. Quartier P Allantaz F Cimaz R Pillet P Messiaen C Bardin C A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial) Ann Rheum Dis 2011 70 5 747 754 10.1136/ard.2010.134254 21173013 \n15. Heijstek MW Kamphuis S Armbrust W Swart J Gorter S de Vries LD Effects of the live attenuated measles-mumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis: a randomized trial JAMA 2013 309 23 2449 2456 10.1001/jama.2013.6768 23780457 \n16. Kuemmerle-Deschner JB Hachulla E Cartwright R Hawkins PN Tran TA Bader-Meunier B Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes Ann Rheum Dis 2011 70 12 2095 2102 10.1136/ard.2011.152728 21859692 \n17. Jaeger VK, Hoffman HM, van der Poll T, Tilson H, Seibert J, Speziale A, et al. Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study. Rheumatology (Oxford) 2017;56(9):1484–91.\n\n",
"fulltext_license": "CC BY",
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"medline_ta": "Pediatr Rheumatol Online J",
"mesh_terms": "D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D056660:Hereditary Autoinflammatory Diseases; D006801:Humans; D007166:Immunosuppressive Agents; D007223:Infant; D007375:Interleukin-1; D015850:Interleukin-6; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D014613:Vaccines, Attenuated; D055815:Young Adult",
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{
"abstract": "Due to the lack of therapeutic options for patients with progressive multifocal leukoencephalopathy-associated immune reconstitution inflammatory syndrome (PML-associated IRIS), maraviroc has generated expectations among the medical community. However, we report a patient with advanced HIV infection, who developed PML-associated IRIS and had a fatal outcome despite the addition of maraviroc to suppressive ART. Future studies are required to define the therapeutic role of maraviroc in PML-associated IRIS and differentiate individuals who may benefit from maraviroc from those who may develop neurological deterioration.",
"affiliations": "Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Colonia Sección XVI, 14080 México, DF, Mexico.;Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Colonia Sección XVI, 14080 México, DF, Mexico.;Servicio de Patología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, 14080 México, DF, Mexico.;Servicio Clínico 4, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, 14080 México, DF, Mexico.;Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Colonia Sección XVI, 14080 México, DF, Mexico.;Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Colonia Sección XVI, 14080 México, DF, Mexico.",
"authors": "Rodríguez|Mónica|M|;Silva-Sánchez|Fernando Antonio|FA|;Luna-Rivero|César|C|;Vega-Barrientos|Ricardo|R|;Alvarado-de la Barrera|Claudia|C|;Reyes-Terán|Gustavo|G|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1155/2014/381480",
"fulltext": "\n==== Front\nCase Rep MedCase Rep MedCRIMCase Reports in Medicine1687-96271687-9635Hindawi Publishing Corporation 10.1155/2014/381480Case ReportMaraviroc Failed to Control Progressive Multifocal Leukoencephalopathy-Associated IRIS in a Patient with Advanced HIV Infection Rodríguez Mónica \n1\nSilva-Sánchez Fernando Antonio \n1\nLuna-Rivero César \n2\nVega-Barrientos Ricardo \n3\nAlvarado-de la Barrera Claudia \n1\nReyes-Terán Gustavo \n1\n\n*\n1Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Colonia Sección XVI, 14080 México, DF, Mexico2Servicio de Patología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, 14080 México, DF, Mexico3Servicio Clínico 4, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, 14080 México, DF, Mexico*Gustavo Reyes-Terán: gustavo.reyesteran@gmail.comAcademic Editor: Bruno Megarbane\n\n2014 23 12 2014 2014 38148023 9 2014 11 12 2014 Copyright © 2014 Mónica Rodríguez et al.2014This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Due to the lack of therapeutic options for patients with progressive multifocal leukoencephalopathy-associated immune reconstitution inflammatory syndrome (PML-associated IRIS), maraviroc has generated expectations among the medical community. However, we report a patient with advanced HIV infection, who developed PML-associated IRIS and had a fatal outcome despite the addition of maraviroc to suppressive ART. Future studies are required to define the therapeutic role of maraviroc in PML-associated IRIS and differentiate individuals who may benefit from maraviroc from those who may develop neurological deterioration.\n==== Body\n1. Introduction\nProgressive multifocal leukoencephalopathy (PML) remains an incurable and often fatal disease, for which HIV infection is the most frequent immunodeficiency setting [1]. There is no specific treatment, but reversal of immunosuppression by antiretroviral therapy (ART) leads to clinical stabilization in 50–60% of PML patients [2]. Considering that beneficial effects of the CCR5 antagonist maraviroc were reported in two patients with PML-associated immune reconstitution inflammatory syndrome (IRIS)—the first with HIV infection [3] and the second with multiple sclerosis [4]—here we describe a patient with advanced HIV infection, who developed PML-associated IRIS and had a fatal outcome despite the addition of maraviroc to suppressive ART.\n\n2. Case Presentation\nA 55-year-old Mexican individual presented to our institution with a 3-year history of HIV-1 infection and virologic failure after ART interruption (125697 HIV RNA copies/mL, 5.1 log10). Patient informed consent for tests performed for clinical purposes using routine techniques was obtained. Three months before admission, he had initiated ART consisting of abacavir, tenofovir, emtricitabine, and atazanavir/ritonavir. After 1 month on ART, he suffered from fever and productive cough. One week before admission, he also had diarrhea and abdominal pain. On admission, he had a CD4 T cell count of 7 cells/μL and <40 HIV RNA copies/mL, and the neurological examination showed no abnormalities. Chest computed tomography (CT) revealed bronchiectasis and consolidation at right basal segments, pericardial and bilateral pleural effusion, hepatosplenomegaly, biliary lithiasis, and free fluid in the abdominal cavity. Cultures of bronchoalveolar lavage, blood, rectal biopsy, and feces were positive for Mycobacterium avium complex (MAC). MAC-associated IRIS was diagnosed [5], and oral ethambutol, clarithromycin, and azithromycin were prescribed. During hospitalization he developed neurological impairments including visual anosognosia (Anton-Babinski syndrome), afferent pupillary defect, apraxia (of gait, dressing, and eating), right hemiparesis, generalized tonic-clonic seizures, and cognitive deterioration. The CT and magnetic resonance imaging (MRI) of the brain revealed hypointensity on T1 and hyperintensity on T2 and FLAIR images in the subcortical white matter. The lesions had a bilateral, parietal-temporal, occipital, and internal capsule distribution characteristic of PML (Figure 1(a)). MR spectroscopy revealed reduced N-acetylaspartate, increased lipids, and generalized cortical and subcortical atrophy. Cerebrospinal fluid (CSF) was acellular; biochemistry was normal; and cultures were negative for mycobacterial, fungal, parasitic, and conventional bacterial agents. HIV RNA was undetectable in CSF, but JC virus DNA was 822.5 copies/mL (2.91 log10). The patient was diagnosed with PML-associated IRIS [5], so maraviroc 300 mg twice daily and dexamethasone 8 mg every 8 hours for 3 days were added to ART. The patient had a rapid clinical deterioration and died 21 days after maraviroc initiation with a JC virus DNA load of 612.5 copies/mL (2.78 log10). Premortem MRI revealed lesions in subcortical white matter (Figure 1(b)). Autopsy findings included zones of demyelination, enlarged oligodendrocytes with hyperchromatic nuclei and bizarre astrocytes, and brainstem lesions (particularly in medulla oblongata) (Figure 1(c)). Despite the fact that autopsy revealed the presence of MAC in lungs, kidney, and other organs, there was no evidence of septic shock or multiple organic failure. Instead, brainstem demyelination was considered related to subsequent respiratory failure and death.\n\n3. Discussion\nIn contrast with the beneficial effects of maraviroc previously reported in two patients with PML-associated IRIS [3, 4], our patient experienced neurological deterioration. One possible explanation for these contrasting results is that the efficacy of maraviroc could be affected by the degree of immunocompromise and the stage of PML disease. That is, maraviroc efficacy may be probably higher if administered on earlier stages of HIV and JC virus disease. Alternatively, the clinical deterioration of our patient may be related to the immunomodulatory properties of maraviroc. By blocking the CCR5 chemokine receptor, maraviroc inhibits innate and adaptive immune responses, which may actually aggravate the immunocompromised condition of HIV-infected patients. In fact, a complete loss-of-function mutation in CCR5 is associated with symptomatic neuroinflammatory disease for West Nile and tick-borne encephalitis flavivirus infections [6, 7]. By consequence, the possibility that administration of CCR5 inhibitors may increase the risk of opportunistic infections and malignancies in HIV-infected individuals should be considered [8]. In addition, corticosteroids are commonly used in the management of PML-associated IRIS, but their potentially negative effects on the JC virus-specific response may have contributed adversely [9].\n\nA higher proportion of CD8+ T cells coexpressing CCR5 and CXCR3 was found in CSF of patients with cryptococcosis-associated IRIS compared with blood at ART initiation [10]. Thus, CCR5+ T cells have been indirectly implicated in IRIS pathophysiology, and maraviroc is expected to have a beneficial effect on different clinical manifestations of IRIS by interfering with the traffic of effector lymphocytes to sites of opportunistic infection. However, since patients with IRIS usually have low CD4 T cell counts, aggravation of immunodeficiency may have fatal consequences in this particular group. Therefore, close clinical and immunologic monitoring of clinical trials exploring the efficacy of maraviroc in patients with IRIS is mandatory. Future studies are required for identification of patients with IRIS who may benefit from maraviroc.\n\nAcknowledgment\nThis work was supported by the Comisión de Equidad y Género de la Honorable Cámara de Diputados de la LXI Legislatura de México.\n\nConflict of Interests\nThe authors declare that there is no conflict of interests regarding the publication of this paper.\n\nFigure 1 Sequential MRI of the brain and myelin stain. Axial FLAIR images show hyperintensity in patches of subcortical white matter localized in parietal and occipital lobes (a). Premortem axial FLAIR images show increased lesions in bilateral frontal lobes without mass effect after treatment with maraviroc (b). Kluver-Barrera stain (10x) for myelin revealed brainstem zones of demyelination and enlarged oligodendrocytes with hyperchromatic nuclei and bizarre astrocytes (c).\n==== Refs\n1 Tavazzi E. White M. K. Khalili K. Progressive multifocal leukoencephalopathy: clinical and molecular aspects Reviews in Medical Virology 2012 22 1 18 32 10.1002/rmv.710 2-s2.0-84855666303 21936015 \n2 Cinque P. Koralnik I. J. Gerevini S. Miro J. M. Price R. W. Progressive multifocal leukoencephalopathy in HIV-1 infection The Lancet Infectious Diseases 2009 9 10 625 636 10.1016/s1473-3099(09)70226-9 2-s2.0-70349188237 19778765 \n3 Martin-Blondel G. Cuzin L. Delobel P. Cuvinciuc V. Dumas H. Alvarez M. Massip P. Marchou B. Is maraviroc beneficial in paradoxical progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome management? AIDS 2009 23 18 2545 2546 10.1097/qad.0b013e32833365f4 2-s2.0-72949121695 19907215 \n4 Giacomini P. S. Rozenberg A. Metz I. Araujo D. Arbour N. Bar-Or A. Maraviroc and JC virus–associated immune reconstitution inflammatory syndrome The New England Journal of Medicine 2014 370 5 486 488 10.1056/nejmc1304828 24476450 \n5 International Network for the Study of HIV-Associated IRIS General case definition, 2014, http://www.inshi.umn.edu/definitions/General_IRIS/home.html \n6 Lim J. K. McDermott D. H. Lisco A. CCR5 deficiency is a risk factor for early clinical manifestations of west nile virus infection but not for viral transmission The Journal of Infectious Diseases 2010 201 2 178 185 10.1086/649426 2-s2.0-75649111972 20025530 \n7 Kindberg E. Mickiene A. Ax C. Åkerlind B. Vene S. Lindquist L. Lundkvist Å. Svensson L. A deletion in the chemokine receptor 5 (CCR5) gene is associated with tickborne encephalitis Journal of Infectious Diseases 2008 197 2 266 269 10.1086/524709 2-s2.0-39149127314 18179389 \n8 Lederman M. M. Penn-Nicholson A. Cho M. Mosier D. Biology of CCR5 and Its Role in HIV Infection and Treatment Journal of the American Medical Association 2006 296 7 815 826 10.1001/jama.296.7.815 16905787 \n9 Antoniol C. Jilek S. Schluep M. Mercier N. Canales M. Le Goff G. Campiche C. Pantaleo G. Du Pasquier R. A. Impairment of JCV-specific T-cell response by corticotherapy: effect on PML-IRIS management Neurology 2012 79 23 2258 2264 10.1212/wnl.0b013e3182768983 2-s2.0-84871296357 23175722 \n10 Chang C. C. Omarjee S. Lim A. Spelman T. Gosnell B. I. Carr W. H. Elliott J. H. Moosa M.-Y. S. Ndung'u T. French M. A. Lewin S. R. Chemokine levels and chemokine receptor expression in the blood and the cerebrospinal fluid of HIV-infected patientswith cryptococcal meningitis and cryptococcosis—associated immune reconstitution inflammatory syndrome Journal of Infectious Diseases 2013 208 10 1604 1612 10.1093/infdis/jit388 2-s2.0-84888589746 23908492\n\n",
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{
"abstract": "OBJECTIVE\nSince 1997, strong incentives have been introduced worldwide to improve access to safe and effective medicines addressing the therapeutic needs of children. ACE inhibitors, the most prescribed antihypertensive drugs in the paediatric population, are one of the prototype drugs targeted by the legislation initiatives. Our purpose in assembling this review is to evaluate and describe the current evidence for the efficacy and safety profile of ACE inhibitors in the paediatric population.\n\n\nMETHODS\nThe authors made a descriptive review of the literature from 1980 to 2015 using the following search terms: hypertension, child, paediatric, ACE (inhibitors), renin-angiotensin aldosterone system, captopril, lisinopril, enalapril, ramipril and fosinopril.\n\n\nRESULTS\nA total of 16 studies evaluating efficacy and safety of ACE inhibitors were included in this review. The included studies demonstrate that ACE inhibitors have the potency to decrease the systolic and/or diastolic blood pressure with an overall favourable safety profile in a short-term period. More importantly, the incentives resulted in an improvement of the overall availability of paediatric labelling, dosing and safety information for ACE inhibitors. However, they failed to fulfil several of paediatric needs: absence of long-term safety data on growth and maturation, absence of commercially available child-friendly formulations and incomplete evaluation of the entire paediatric hypertension population.\n\n\nCONCLUSIONS\nAdditional efforts are needed to close the gap between the availability of drugs that are labelled and indicated for paediatric use and the actual drug usage in children, especially in young children, neonates and children with severe hypertension, renal transplantation or severe renal impairment.",
"affiliations": "Department of Paediatrics and Medical Genetics, Faculty of Medicine and Health Science, Ghent University, Ghent, Belgium.;Paediatric Nephrology, Ghent University Hospital, Ghent, Belgium.;Department of Paediatrics and Medical Genetics, Faculty of Medicine and Health Science, Ghent University, Ghent, Belgium.",
"authors": "Snauwaert|Evelien|E|http://orcid.org/0000-0003-2660-7460;Vande Walle|Johan|J|;De Bruyne|Pauline|P|",
"chemical_list": "D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents",
"country": "England",
"delete": false,
"doi": "10.1136/archdischild-2016-310582",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0003-9888",
"issue": "102(1)",
"journal": "Archives of disease in childhood",
"keywords": "Hypertension; Pharmacology; angiotensin-converting enzyme inhibitor; child",
"medline_ta": "Arch Dis Child",
"mesh_terms": "D000293:Adolescent; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002648:Child; D002675:Child, Preschool; D006801:Humans; D006973:Hypertension; D007223:Infant; D007231:Infant, Newborn; D016896:Treatment Outcome",
"nlm_unique_id": "0372434",
"other_id": null,
"pages": "63-71",
"pmc": null,
"pmid": "27682140",
"pubdate": "2017-01",
"publication_types": "D016428:Journal Article; D016454:Review",
"references": null,
"title": "Therapeutic efficacy and safety of ACE inhibitors in the hypertensive paediatric population: a review.",
"title_normalized": "therapeutic efficacy and safety of ace inhibitors in the hypertensive paediatric population a review"
} | [
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{
"abstract": "The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. E-mail Dr. Mancano michael.mancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.",
"affiliations": "Temple University School of Pharmacy, Philadelphia, PA, USA.;Temple University School of Pharmacy, Philadelphia, PA, USA.;Temple University School of Pharmacy, Philadelphia, PA, USA.",
"authors": "Mancano|Michael A|MA|;Bulow|Jacqueline Emily Von|JEV|;Ro|Myungsun|M|",
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"issue": "53(6)",
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"pages": "371-375",
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"pmid": "30559522",
"pubdate": "2018-12",
"publication_types": "D016428:Journal Article",
"references": "27612321;27993797;28649876;29257789;29420358;29424801",
"title": "ISMP Adverse Drug Reactions: Lithium-Induced Cardiomyopathy Fixed Drug Eruption Due to Cetirizine, Levocetirizine, and Hydroxyzine Nivolumab-Induced Myasthenia Gravis Nivolumab-Induced Cholangitic Liver Disease Torsade de Pointes Caused by Psychiatric Polypharmacy Trichotillomania Associated With Aripiprazole.",
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}
],
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"reactionoutcome": "2"
},
{
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"reactionoutcome": "2"
},
{
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}
],
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},
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"literaturereference_normalized": "ismp adverse drug reactions lithium induced cardiomyopathy fixed drug eruption due to cetirizine levocetirizine and hydroxyzine nivolumab induced myasthenia gravis nivolumab induced cholangitic liver disease torsade de pointes caused by psychiatric polypharmacy trichotillomania associated with aripiprazole",
"qualification": "2",
"reportercountry": "US"
},
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"receivedate": "20181019",
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},
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},
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"literaturereference": "MANCANO MA, BULOW JEV, RO M. ISMP ADVERSE DRUG REACTIONS: LITHIUM-INDUCED CARDIOMYOPATHY FIXED DRUG ERUPTION DUE TO CETIRIZINE, LEVOCETIRIZINE, AND HYDROXYZINE NIVOLUMAB-INDUCED MYASTHENIA GRAVIS NIVOLUMAB-INDUCED CHOLANGITIC LIVER DISEASE TORSADE DE POINTES CAUSED BY PSYCHIATRIC POLYPHARMACY TRICHOTILLOMANIA ASSOCIATED WITH ARIPIPRAZOLE. HOSPITAL PHARMACY. 2018?1-5",
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}
] |
{
"abstract": "OBJECTIVE\nPatients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemia require chronic blood transfusions which can lead to iron overload and subsequent excess iron-mediated complications. Intensive iron chelation with deferasirox could remove excess iron and can alleviate these events; however, the long-term safety and efficacy in Chinese population are not clearly characterized. This study examined the long-term efficacy and safety of deferasirox in a real-world setting in Taiwan.\n\n\nMETHODS\nThis observational, non-interventional, single-arm, multi-center, phase IV study was designed to collect the safety and clinical information about patients who were treated with deferasirox according to investigator's judgment and in accordance with the general clinical practice.\n\n\nRESULTS\nFrom 2009 to 2011, patients with MDS (N = 38), AA (N = 23), and other rare anemias (N = 18) were enrolled. The mean deferasirox exposure was 17.7 ± 4.02 mg/kg/day. The most common drug-related AEs were skin disorders (32.9%) and gastrointestinal disorders (30.4%), while grade 3-4 AEs were rare (5.1%). In the overall patient population, deferasirox effectively decreased serum ferritin levels at 1 year (P = 0.0154) and 3 years (P = 0.0424) from the baseline. Upon the use of deferasirox, 32.9% patients showed erythroid response and 16.7% patients had platelet response.\n\n\nCONCLUSIONS\nFor patients with MDS, AA, and other rare anemias, the AEs observed in this 3-year surveillance study with deferasirox were mostly mild or moderate. In addition, the hematological response rate was higher than that in the EPIC study, which primarily enrolled Caucasian patients.",
"affiliations": "a Department of Internal Medicine , National Taiwan University Hospital , Taipei , Taiwan.;b Division of Hematology and Oncology , Mackay Memorial Hospital , Taipei , Taiwan.;c Division of Transfusion Medicine, Department of Medicine , Taipei Veterans General Hospital , Taipei , Taiwan.;d Department of Pediatrics , Taichung Veterans General Hospital , Taichung , Taiwan.;e Division of Hematology/Oncology , Tri-Service General Hospital , Taipei , Taiwan.;f Division of Hematology/Oncology, Department of Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan.;g Department of Internal Medicine , Changhua Christian Hospital , Changhua , Taiwan.;h Department of Internal Medicine , Chia-Yi Christian Hospital , Chiayi , Taiwan.;i Department of Medicine , China Medical University Hospital , Taichung , Taiwan.;j Department of Internal Medicine , National Cheng Kung University Hospital , Tainan , Taiwan.;k Department of Internal Medicine , Chung Shan Medical University Hospital , Taichung , Taiwan.",
"authors": "Ko|Bor-Sheng|BS|;Chang|Ming-Chih|MC|;Chiou|Tzeon-Jye|TJ|;Chang|Te-Kau|TK|;Chen|Yeu-Chin|YC|;Lin|Sheng-Fung|SF|;Chang|Cheng-Shyong|CS|;Lu|Yin-Che|YC|;Yeh|Su-Peng|SP|;Chen|Tsai-Yun|TY|;Hwang|Wei-Shou|WS|",
"chemical_list": "D000077588:Deferasirox",
"country": "England",
"delete": false,
"doi": "10.1080/16078454.2018.1557860",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1024-5332",
"issue": "24(1)",
"journal": "Hematology (Amsterdam, Netherlands)",
"keywords": "Adverse events; aplastic anemia; deferasirox; erythroid response; iron chelation; myelodysplastic syndrome",
"medline_ta": "Hematology",
"mesh_terms": "D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic; D000077588:Deferasirox; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases; D006801:Humans; D019190:Iron Overload; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes; D012871:Skin Diseases; D013624:Taiwan",
"nlm_unique_id": "9708388",
"other_id": null,
"pages": "247-254",
"pmc": null,
"pmid": "30558522",
"pubdate": "2019-12",
"publication_types": "D017429:Clinical Trial, Phase IV; D016428:Journal Article; D016448:Multicenter Study; D064888:Observational Study",
"references": null,
"title": "Long-term safety and efficacy of deferasirox in patients with myelodysplastic syndrome, aplastic anemia and other rare anemia in Taiwan.",
"title_normalized": "long term safety and efficacy of deferasirox in patients with myelodysplastic syndrome aplastic anemia and other rare anemia in taiwan"
} | [
{
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"patient": {
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"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DEFERASIROX"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "021882",
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"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KO BS, CHANG CM, CHIOU TJ, CHANG TK, CHANG TK, CHEN YC ET.AL. LONG-TERM SAFETY AND EFFICACY OF DEFERASIROX IN PATIENTS WITH MYELODYSPLASTIC SYNDROME, APLASTIC ANEMIA AND OTHER RARE ANEMIA IN TAIWAN. HEMATOLOGY. 2019?24:247?254",
"literaturereference_normalized": "long term safety and efficacy of deferasirox in patients with myelodysplastic syndrome aplastic anemia and other rare anemia in taiwan",
"qualification": "1",
"reportercountry": "TW"
},
"primarysourcecountry": "TW",
"receiptdate": "20190111",
"receivedate": "20190111",
"receiver": {
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},
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}
] |
{
"abstract": "Primary diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare tumors, recently recognized as a unique entity based on their unique pathologic and clinical characteristics. We report three cases of DLGNT and compare their clinical characteristics and presentation with other reported cases, and with primary leptomeningeal gliomatosis. Because their prognosis is better than that of diffuse leptomeningeal gliomatosis, and pathologic diagnosis may be difficult, clinicians should consider this diagnosis in patients who present with new neurological symptoms, hydrocephalus and diffuse leptomeningeal enhancement on MRI. Further studies are required to better understand the unique biological characteristics of these tumors and to improve therapy.",
"affiliations": "Division of Pediatric Oncology, Children's Hospital of Orange County, California, USA.;Department of Pathology, Children's Hospital Los Angeles, California, USA.;Department of Radiology, Children's Hospital Los Angeles, California, USA.;The Alabama Center for Childhood Cancer and Blood Disorders at Children's of Alabama, University of Alabama at Birmingham, USA.;Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Hospital Los Angeles, California, USA.;Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Hospital Los Angeles, California, USA.",
"authors": "Abongwa|Chenue|C|;Cotter|Jennifer|J|;Tamrazi|Benita|B|;Dhall|Girish|G|;Davidson|Tom|T|;Margol|Ashley|A|",
"chemical_list": null,
"country": "England",
"delete": false,
"doi": "10.1080/08880018.2019.1711270",
"fulltext": null,
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"issn_linking": "0888-0018",
"issue": "37(3)",
"journal": "Pediatric hematology and oncology",
"keywords": "Astrocytoma; glial; glioneuronal; hydrocephalus; leptomeningeal",
"medline_ta": "Pediatr Hematol Oncol",
"mesh_terms": "D001932:Brain Neoplasms; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008577:Meningeal Neoplasms",
"nlm_unique_id": "8700164",
"other_id": null,
"pages": "248-258",
"pmc": null,
"pmid": "31951480",
"pubdate": "2020-04",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review; D059040:Video-Audio Media",
"references": null,
"title": "Primary diffuse leptomeningeal glioneuronal tumors of the central nervous system: Report of three cases and review of literature.",
"title_normalized": "primary diffuse leptomeningeal glioneuronal tumors of the central nervous system report of three cases and review of literature"
} | [
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{
"abstract": "Adenoviral infections of immunocompetent patients usually present as self-limiting pharyngitis, gastroenteritis, urocystitis, or conjunctivitis. In immunosuppressed patients, development of the illness can be severe, even life-threatening or fatal, and therapeutical intervention is difficult. Previous case reports of adenoviral infections after kidney transplantation have described a symptomatology of hemorrhagic cystitis, fever, renal dysfunction, and rarely fatal systemic dissemination. Here we report on a 46-year-old female renal transplant recipient suffering from adenoviral serotype 35 nephritis of the donor organ 29 days after transplantation. In this case, the main symptoms of the adenoviral infection were high fever and progressive renal failure of the transplanted organ. At the peak of the clinical symptoms, owing to histological and immunohistochemical evaluations of a kidney biopsy, we were able to establish the diagnosis in time so that adequate therapy could be employed. Immunosuppression was reduced and modified, and a self-limiting course of the infection was observed, followed by significant improvement of graft function. Subsequent to histological diagnosis, adenoviral particles were isolated from urine and identified as adenovirus serotype 35. Adenoviral nephritis of the transplanted organ should be considered in the differential diagnosis of persistent anuria after kidney transplantation. Our case highlights the importance of applying all possible diagnostic techniques, including histological evaluation of renal biopsies.",
"affiliations": "Institute of Pathology, University of Bonn, Bonn, Germany. Nicolaus.Friedrichs@ukb.uni-bonn.de",
"authors": "Friedrichs|Nicolaus|N|;Eis-Hubinger|Anna-Maria|AM|;Heim|Albert|A|;Platen|Eva|E|;Zhou|Hui|H|;Buettner|Reinhard|R|",
"chemical_list": "D004279:DNA, Viral; D009173:Mycophenolic Acid",
"country": "Germany",
"delete": false,
"doi": "10.1078/0344-0338-00463",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0344-0338",
"issue": "199(8)",
"journal": "Pathology, research and practice",
"keywords": null,
"medline_ta": "Pathol Res Pract",
"mesh_terms": "D000208:Acute Disease; D000256:Adenoviridae; D000258:Adenovirus Infections, Human; D004279:DNA, Viral; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007124:Immunoenzyme Techniques; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation; D008875:Middle Aged; D009173:Mycophenolic Acid; D009393:Nephritis; D016133:Polymerase Chain Reaction; D012703:Serotyping; D016896:Treatment Outcome",
"nlm_unique_id": "7806109",
"other_id": null,
"pages": "565-70",
"pmc": null,
"pmid": "14533942",
"pubdate": "2003",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Acute adenoviral infection of a graft by serotype 35 following renal transplantation.",
"title_normalized": "acute adenoviral infection of a graft by serotype 35 following renal transplantation"
} | [
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"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Kidney transplant rejection",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "1"
},
{
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"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Nephritis",
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"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Anuria",
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"reactionoutcome": "2"
},
{
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{
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"reactionoutcome": "2"
},
{
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},
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"literaturereference": "FRIEDRICHS N, EIS-HUBINGER A, HEIM A, PLATEN E, ZHOU H, BUETTNER R. ACUTE ADENOVIRAL INFECTION OF A GRAFT BY SEROTYPE 35 FOLLOWING RENAL TRANSPLANTATION. PATHOLOGY RESEARCH AND PRACTICE. 2003;199:565-70",
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},
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},
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}
] |
{
"abstract": "We reviewed the 24 week outcomes of HIV-infected patients from our hospital who had their ART switched to dolutegravir monotherapy on an individual clinical basis.\n\n\n\nRetrospective hospital database assessment of virally suppressed patients in whom the treating physician had switched to 50 mg of dolutegravir once daily due to one or more of the following reasons: antiretroviral-related adverse effects; comorbidities; risk of interactions; or archived resistance. Patients had ≥24 weeks of follow-up. Population, virological and immunological responses and safety and tolerability are described.\n\n\n\nThirty-three (22 on PIs, of whom 18 had ritonavir-boosted PI monotherapy) patients were identified: median (IQR) age of 56 (50-62) years, 55% women, median (IQR) of 19 (17-23) years of known HIV infection, 39% prior AIDS events, median (IQR) of 8 (4-13) years with undetectable plasma HIV-1 RNA and median (IQR) CD4 cell count of 596 (420-843) cells/mm(3). Twenty-five (76%) patients had antiretroviral-related adverse effects, 32 (97%) patients had comorbidities, 28 (85%) patients had risk of interactions and 16 (48%) patients had archived resistance. One patient with suboptimal adherence had low-level virological failure through weeks 4-24. HIV RNA genotypic resistance tests detected no integrase mutations at weeks 4 and 24, but 118R was detected in 7% of the integrated HIV DNA at 24 weeks. Patients had significant median decreases in triglycerides (-117 mg/dL), total cholesterol (-36 mg/dL), the total cholesterol/HDL cholesterol ratio (-0.7) and high-sensitivity C-reactive protein (-0.05 mg/dL) (P ≤ 0.007), although the Chronic Kidney Disease Epidemiology Collaboration equation also decreased (-7.1 mL/min) (P < 0.0001).\n\n\n\nThese data suggest the efficacy of dolutegravir monotherapy as a maintenance strategy to be further confirmed in randomized clinical trials.",
"affiliations": "Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.;Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.;Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.;Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.;Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.;Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.;Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.;Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.;Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.;Hospital Universitario San Cecilio, Granada, Spain.;Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.;Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain esteban@fundsoriano.es.",
"authors": "Rojas|Jhon|J|;Blanco|José L|JL|;Marcos|María A|MA|;Lonca|Montserrat|M|;Tricas|Amparo|A|;Moreno|Laura|L|;Gonzalez-Cordon|Ana|A|;Torres|Berta|B|;Mallolas|Josep|J|;Garcia|Federico|F|;Gatell|Jose M|JM|;Martinez|Esteban|E|",
"chemical_list": "D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; C562325:dolutegravir",
"country": "England",
"delete": false,
"doi": "10.1093/jac/dkw078",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0305-7453",
"issue": "71(7)",
"journal": "The Journal of antimicrobial chemotherapy",
"keywords": null,
"medline_ta": "J Antimicrob Chemother",
"mesh_terms": "D005260:Female; D015658:HIV Infections; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012189:Retrospective Studies; D000072230:Sustained Virologic Response; D016896:Treatment Outcome",
"nlm_unique_id": "7513617",
"other_id": null,
"pages": "1975-81",
"pmc": null,
"pmid": "27021341",
"pubdate": "2016-07",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Dolutegravir monotherapy in HIV-infected patients with sustained viral suppression.",
"title_normalized": "dolutegravir monotherapy in hiv infected patients with sustained viral suppression"
} | [
{
"companynumb": "ES-JNJFOC-20160822220",
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{
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"activesubstancename": "RILPIVIRINE"
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],
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},
{
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{
"actiondrug": "1",
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},
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],
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"reaction": [
{
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}
],
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"qualification": "1",
"reportercountry": "ES"
},
"primarysourcecountry": "ES",
"receiptdate": "20160830",
"receivedate": "20160830",
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},
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"sendertype": "2"
},
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"seriousnesscongenitalanomali": null,
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"transmissiondate": "20161109"
}
] |
{
"abstract": "Iatrogenic Kaposi sarcomas (KS) in organ transplant recipients are often treated by switching immunosuppressive therapy to an mTOR inhibitor, such as sirolimus or everolimus, as these have immunosuppressive as well as anti-tumor effects. We report on an 80-year-old male patient who developed a disseminated cutaneous KS during therapy with prednisone and azathioprine for myasthenia gravis. After discontinuation of azathioprine therapy and despite continuing therapy with cortisone, the KS progressed and autoantibody levels against the nicotinic acetylcholine receptor increased. During the administration of everolimus, a long-term near-complete remission of KS and a decrease in autoantibodies took place. This case study illustrates that even in non-organ transplant patients with iatrogenic KS, switching to immunosuppressive therapy using an mTOR inhibitor can be beneficial.",
"affiliations": "Klinik für Dermatologie, Allergologie und Venerologie, Hauttumorzentrum Hannover, Medizinische Hochschule Hannover, Deutschland. krengel.sina@mh-hannover.de",
"authors": "Krengel|S|S|;Satzger|I|I|;Alter|M|M|;Kapp|A|A|;Gutzmer|R|R|",
"chemical_list": "D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus",
"country": "Germany",
"delete": false,
"doi": "10.1007/s00105-011-2274-y",
"fulltext": null,
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"issn_linking": "0017-8470",
"issue": "63(7)",
"journal": "Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete",
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"abstract": "Renal medullary carcinoma (RMC) is a rare but aggressive malignancy affecting young individuals with sickle cell trait. Renal medullary carcinoma commonly presents with advanced or metastatic disease and is associated with a rapidly progressive clinical course and an extremely short overall survival measured in weeks to few months. Due to the rarity of RMC, there is no proven effective therapy and patients are often treated with platinum-based chemotherapy. We report near-complete radiological and pathological response in a patient treated with dose-dense MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy. The patient underwent consolidation nephrectomy and retroperitoneal lymph node dissection and had a 16-month progression-free survival, one of the longest reported in patients with RMC.",
"affiliations": "Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.;Division of General Internal Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.;Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.;Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.;Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.;Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.;Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.;Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.;Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.",
"authors": "Amjad|Ali Imran|AI|;Ali|Hira|H|;Appleman|Leonard J|LJ|;Maranchie|Jodi|J|0000-0002-8534-9468;Jackman|Stephen|S|0000-0001-6049-0038;Parwani|Anil|A|;Dhir|Rajiv|R|;Roy|Somak|S|;Parikh|Rahul A|RA|",
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"fulltext": "\n==== Front\nCase Rep Oncol MedCase Rep Oncol MedCRIONMCase Reports in Oncological Medicine2090-67062090-6714Hindawi Publishing Corporation 10.1155/2014/615895Case ReportRenal Medullary Carcinoma: Case Report of an Aggressive Malignancy with Near-Complete Response to Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Chemotherapy Amjad Ali Imran \n1\nAli Hira \n2\nAppleman Leonard J. \n1\nhttp://orcid.org/0000-0002-8534-9468Maranchie Jodi \n3\nhttp://orcid.org/0000-0001-6049-0038Jackman Stephen \n3\nParwani Anil \n4\nDhir Rajiv \n4\nRoy Somak \n4\nParikh Rahul A. \n1\n*1Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA2Division of General Internal Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA3Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA4Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA*Rahul A. Parikh: parikhr@upmc.eduAcademic Editor: Jose I. Mayordomo\n\n2014 19 8 2014 2014 61589516 6 2014 5 8 2014 Copyright © 2014 Ali Imran Amjad et al.2014This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Renal medullary carcinoma (RMC) is a rare but aggressive malignancy affecting young individuals with sickle cell trait. Renal medullary carcinoma commonly presents with advanced or metastatic disease and is associated with a rapidly progressive clinical course and an extremely short overall survival measured in weeks to few months. Due to the rarity of RMC, there is no proven effective therapy and patients are often treated with platinum-based chemotherapy. We report near-complete radiological and pathological response in a patient treated with dose-dense MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy. The patient underwent consolidation nephrectomy and retroperitoneal lymph node dissection and had a 16-month progression-free survival, one of the longest reported in patients with RMC.\n==== Body\n1. Background\nRenal medullary carcinoma (RMC) was initially described in 1995 in a retrospective study of 34 patients collected over 22 years at the Armed Forces Institute of Pathology. Thirty-three of the 34 patients had sickle cell trait or sickle cell disease; the mean tumor size at diagnosis was 7 cm and median survival following surgery was 12 weeks (range 3–52 weeks) [1]. In a second smaller retrospective analysis with 6 patients, median age at diagnosis was 24.5 years and time from diagnosis to death was 3 months (range 1–7 months) [2]. Karyotyping was performed in 4 patients and revealed chromosome 11 monosomy in all 4 patients and chromosome 3 abnormalities in 2 patients [2]. A retrospective study performed in Brazil, a country with a high incidence of sickle cell trait, identified seven patients with mean age of 22 years (8–69 years) and tumor size ranging from 4 to 12 cm. In this retrospective analysis, survival of patients with advanced RMC ranged from 4 days to 9 months [3]. A number of other case reports and series have described the role of surgery, chemotherapy, immunotherapy, or radiation in the treatment of RMC and found rapid progression despite these therapies [3–6]. Rathmell and Monk initially reported the use of high-dose intensity MVAC chemotherapy in a case-series of three patients with RMC [7]. They noted a significant improvement in both palliation and survival with the use of this regimen. In the current paper, we describe a young 23-year-old subject with sickle cell trait, diagnosed with diffusely metastatic RMC. In spite of having advanced disease, she achieved an excellent response to aggressive cytotoxic chemotherapy with a progression-free survival (PFS) of 16 months.\n\n2. Case Presentation\nA twenty-three-year-old African-American female with sickle cell trait presented to the emergency room with periumbilical and right-sided back pain associated with poor appetite and ten-pound weight loss over 4 months. She denied gross hematuria, dysuria, or additional urinary symptoms. She was a previously healthy nonsmoker with paternal family history of sickle cell trait. Physical examination was pertinent for fullness in the right flank and left supraclavicular lymphadenopathy. Laboratory findings revealed hemoglobin of 11.3 g/dL, platelet count of 269,000 per mm3, and normal LDH of 147 IU/L. Computed tomography (CT) scan of the neck, chest, abdomen, and pelvis demonstrated a 12 cm heterogeneous right renal mass (Figure 1(a)) with retrocaval, aortocaval, and paraaortic lymphadenopathy. In addition, there were bilateral pulmonary nodules (largest in right upper lobe measuring 1.8 × 1.4 cm), left pleural-based nodules (largest at the level of diaphragmatic pleura measuring 2.6 × 1.9 cm), and right hilar (2.5 × 2.2 cm), left supraclavicular, and bilateral cervical lymphadenopathy. MRI of the brain showed no evidence for intracranial metastasis.\n\nBiopsy of left supraclavicular lymph node revealed high-grade renal medullary carcinoma with prominent lymphovascular tumor emboli. The tumor cells were eosinophilic, containing large nuclei and focally prominent nucleoli with brisk mitotic activity. The neoplastic cells stained positive for AE1/AE3, cytokeratin CAM 5.2, epithelial membrane antigen (EMA), E-cadherin, cytokeratin 7, and cytokeratin 19 on immunohistochemical analyses (Figure 2). The cells stained weakly positive for c-Kit and negative for cytokeratin 20, S100 protein, carbonic anhydrase IX, mucicarmine, and CD10. Cytogenetic studies performed on the lymph node isolated a clone of cells with duplication of the long arm of chromosome 1 (resulting in partial trisomy 1q) and a derivative chromosome 22 with chromatin material of unknown origin attached to the long arm (resulting in partial monosomy 22q). Fluorescence in situ hybridization (FISH) for transcription factor E3 (TFE) gene translocation was negative.\n\nTreatment was initiated with dose-dense (dd) MVAC consisting of methotrexate 30 mg/m2 on day 1 followed by vinblastine 3 mg/m2, doxorubicin 30 mg/m2, and cisplatin 70 mg/m2 on day 2 of a 14-day cycle as described for metastatic urothelial carcinomas [8]. She received growth factor support with pegfilgastrim on day 3 to reduce the risk of neutropenic fevers. Treatment with four cycles of dd-MVAC was associated with a significant reduction in size of renal mass from 9.3 cm to 5.9 cm with areas of necrosis on a CT scan of chest, abdomen, and pelvis (Figure 1(b)). There was near-complete resolution of right upper lobe and left lower lobe parenchymal lung nodules and retroperitoneal lymphadenopathy. Multiple pleural-based nodules in the left hemithorax and right hilar lymph node decreased. Two additional cycles of dd-MVAC were administered and a follow-up CT scan showed continued improvement in size of renal mass to 4.4 cm, improvement in retroperitoneal, hilar lymphadenopathy, and parenchymal lung lesions. The subject developed grade I renal insufficiency and grade II chemotherapy-induced nausea and vomiting (CINV) for which the cisplatin dose was reduced by 25% after the initial two cycles. Overall, she tolerated six cycles of dd-MVAC extremely well, with no hospitalizations.\n\nAfter achieving an excellent partial response to neoadjuvant chemotherapy, the patient underwent right radical nephrectomy with complete, bilateral retroperitoneal lymph node dissection without complications. Pathology revealed a gross tumor resection size of 6.2 cm. Viable carcinoma comprised approximately 2–4% of the tumor volume showing neoplastic cells with rhabdoid features in a background of extensive fibrosis and chronic interstitial inflammation. All surgical margins were negative for tumor. Two of 11 lymph nodes (one paracaval and one preaortic from the level of the aortic bifurcation) were involved with carcinoma (0.7 cm in greatest dimension) with no extracapsular extension. Pathologic TNM stage was assessed as pT1b N1 M1. Immunohistochemistry revealed a complete loss of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) expression. Subsequently, she underwent video assisted thoracoscopy and wedge resection of right lower lung lobe. Pathology showed inflammatory changes with no evidence of residual malignancy.\n\nFollow-up imaging in the form of CT chest, abdomen, and pelvis was obtained every four months and at one year from diagnosis she showed no recurrence of disease. At 16 months from initial diagnosis, she developed shortness of breath and restaging scans showed disease recurrence with hepatic, pulmonary lesions and bilateral pleural effusions. She had a rapidly progressive decline after relapse and died without receiving any further therapy.\n\n3. Discussion\nRenal medullary carcinoma (RMC) is a rare form of aggressive kidney cancer (comprising <1% of all kidney cancers) and is exclusively restricted to patients with sickle cell trait or disease. It typically presents in young patients (male : female ratio 2 : 1) and follows an extremely aggressive clinical course with a poor outcome. We report a patient presenting with widely metastatic disease, with bulky renal primary and involvement of lung, pleura, and mediastinal and retroperitoneal lymph nodes. The patient had an excellent response to dose-dense MVAC regimen (methotrexate, vinblastine, doxorubicin, and cisplatin). After completion of six cycles of chemotherapy there was near-complete radiographic response and pathologic response at the primary 12 cm renal mass and surrounding lymph nodes. The patient eventually developed hepatic and pulmonary disease recurrence with a progression-free survival of 16 months.\n\nPatients with RMC have an aggressive course and with cytotoxic regimens, survival is only weeks to a few months. Most patients respond to initial platinum-based chemotherapy but responses are rarely durable. The mechanism of this acquired resistance to cytotoxic chemotherapy is not clearly understood. The MVAC chemotherapy regimen, approved for use in advanced or metastatic transitional cell carcinoma of urinary bladder, has been previously utilized in RMC. Rathmell and Monk treated three patients with dose-dense MVAC and demonstrated partial responses with one patient achieving a 90% response by RECIST criteria after six cycles of chemotherapy. That patient relapsed and died at 12 months from initial diagnosis [7]. Walsh and colleagues reported a complete pathologic response to a combination of paclitaxel, gemcitabine with carboplatin in an 11-year-old patient with diffusely metastatic disease (lung, bone, and liver) [13]. This patient was diagnosed with left supraclavicular node biopsy and underwent neoadjuvant chemotherapy prior to resection of primary tumor and pulmonary metastasis. However, the patient had early relapse with leptomeningeal disease and died 24 months after initial diagnosis [13]. Very few other case reports of complete radiological responses have been described (Table 1). Pirich and colleagues initially reported a 12-year-old with sickle cell trait with a 6-month PFS to MVAC and an overall survival of 15 months [14].\n\nA number of genetic abnormalities with potential pathophysiologic or therapeutic implications have been recently described in RMC. Translocation t(9; 22) involving bcr-abl has been described; however use of imatinib has not yielded any meaningful responses [9, 10]. Rearrangement of the ALK gene with translocation of the ALK receptor tyrosine kinase to a cytoskeleton protein vinculin has been described in a t(2; 10) bearing RMC [15]. In a recent study, RMC tumor specimens were noted to have an absence of SMARCB1/INI1 by immunohistochemistry. This correlates with loss of heterozygosity at the SMARCB1/INI1 gene locus on chromosome 22 [16, 17]. Of note, our patient also demonstrated a loss of SMARCB1/INI1 expression by immunohistochemistry, with karyotyping revealing partial monosomy of chromosome 22q. SMARCB1 is a tumor suppressor gene, which plays a role in chromatin remodeling, cell cycle control, and regulation of cytoskeletal dynamics [18–20]. It is not entirely clear how this gene may play a role in the pathogenesis of RMC. Prior reports have noted increased expression of hypoxia inducible factor (HIF), vascular endothelial growth factor (VEGF), and TP53 in RMC [21]. Limited data on gene expression profiling of RMC using cDNA has shown resemblance to transitional cell carcinoma of the urinary bladder, which is supported with the rationale of treating these patients with MVAC, a regimen utilized commonly in transitional cell carcinomas of the bladder [22]. Whole-genome expression analysis in a patient who had complete remission for 9 months after second-line doxorubicin-based therapy showed high expression of topoisomerase II [23]. This expression profile may explain the unusual chemosensitivity of this patient to topoisomerase II inhibitor-based therapy. In the era of next generation sequencing, it is worth exploring whether sequencing this rare form of cancer will identify any driver-mutations, which can be targeted for therapeutic benefit.\n\n4. Conclusion\nIn summary, we observed an excellent clinical and radiologic response in our patient with diffusely metastatic RMC with a PFS of 16 months on treatment with dd-MVAC followed by consolidation surgery. Thus, aggressive intervention of platinum-based chemotherapy can achieve prolonged responses with significant palliation of symptoms and should be strongly considered.\n\nAbbreviations\nRMC:Renal medullary carcinoma\n\nLDH:Lactate dehydrogenase\n\nEMA:Epithelial membrane antigen\n\nFISH:Fluorescence in situ hybridization\n\nMVAC:Methotrexate, vinblastine, doxorubicin, and cisplatin\n\nSMARCB1/INI-1:SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1\n\nRECIST:Response evaluation criteria in solid tumors.\n\nConsent\nWritten informed consent was obtained from the patient's spouse for publication of this case report and the accompanying figures. A copy of the written consent is available for review.\n\nConflict of Interests\nThe authors declare no conflict of interests.\n\nFigure 1 (a) CT scan of abdomen showing necrotic right-sided tumor replacing the kidney. (b) CT scan after chemotherapy.\n\nFigure 2 Supraclavicular lymph node (20x) with immunohistochemistry for CAM 5.2 and EMA.\n\nTable 1 Case reports of complete radiological responses, regimens used, and survival of patients with renal medullary carcinoma.\n\nCase report\tRegimen described\tSurvival\t\nStahlschmidt et al. (1999) [9]\tMVAC\t11.2 months \t\nSimpson et al. (2005) [10]\tMVAC\t11.2 months\t\nStrouse et al. (2005) [11]\tCisplatin, gemcitabine, and paclitaxel \t10 months and 11 months (n = 2)\t\nRonnen et al. (2006) [12]\tBortezomib\tAlive with no evidence of disease at 27 months \t\nWalsh et al. (2010) [13]\tCarboplatin, gemcitabine, and paclitaxel\t24 months\n==== Refs\n1 Davis CJ Jr. Mostofi FK Sesterhenn IA Renal medullary carcinoma: the seventh sickle cell nephropathy American Journal of Surgical Pathology 1995 19 1 1 11 2-s2.0-0028833027 7528470 \n2 Avery RA Harris JE Davis CJ Jr. Borgaonkar DS Byrd JC Weiss RB Renal medullary carcinoma: clinical and therapeutic aspects of a newly described tumor Cancer 1996 78 1 128 132 8646708 \n3 Watanabe IC Billis A Guimarães MS Renal medullary carcinoma: report of seven cases from Brazil Modern Pathology 2007 20 9 914 920 2-s2.0-34547954957 17643096 \n4 Coogan CL McKiel CF Jr. Flanagan MJ Bormes TP Matkov TG Renal medullary carcinoma in patients with sickle cell trait Urology 1998 51 6 1049 1050 2-s2.0-0032100519 9609653 \n5 Noguera-Irizarry WG Hibshoosh H Papadopoulos KP Renal medullary carcinoma: case report and review of the literature The American Journal of Clinical Oncology: Cancer Clinical Trials 2003 26 5 489 492 2-s2.0-0141926515 \n6 Hakimi AA Koi PT Milhoua PM Renal medullary carcinoma: the Bronx experience Urology 2007 70 5 878 882 2-s2.0-36549034353 18068443 \n7 Rathmell WK Monk JP High-dose-intensity mvac for advanced renal medullary carcinoma: report\nof three cases and literature review Urology 2008 72 3 659 663 2-s2.0-50549095129 18649931 \n8 Sternberg CN de Mulder PHM Schornagel JH Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: european organization for research and treatment of cancer protocol no. 30924 Journal of Clinical Oncology 2001 19 10 2638 2646 2-s2.0-0035873915 11352955 \n9 Stahlschmidt J Cullinane C Roberts P Picton SV Renal medullary carcinoma: prolonged remission with chemotherapy, immunohistochemical characterisation and evidence of bcr/abl rearrangement Medical and Pediatric Oncology 1999 33 6 551 557 10573578 \n10 Simpson L He X Pins M Renal medullary carcinoma and ABL gene amplification Journal of Urology 2005 173 6 1883 1888 2-s2.0-18744377728 15879768 \n11 Strouse JJ Spevak M Mack AK Arceci RJ Small D Loeb DM Significant responses to platinum-based chemotherapy in renal medullary carcinoma Pediatric Blood & Cancer 2005 44 4 407 411 2-s2.0-14644422605 15602719 \n12 Ronnen EA Kondagunta GV Motzer RJ Medullary renal cell carcinoma and response to therapy with bortezomib Journal of Clinical Oncology 2006 24 9, article e14 2-s2.0-33645461448 \n13 Walsh A Kelly DR Vaid YN Hilliard LM Friedman GK Complete response to carboplatin, gemcitabine, and paclitaxel in a patient with advanced metastatic renal medullary carcinoma Pediatric Blood and Cancer 2010 55 6 1217 1220 2-s2.0-77958537003 20979179 \n14 Pirich LM Chou P Walterhouse DO Prolonged survival of a patient with sickle cell trait and metastatic renal medullary carcinoma Journal of Pediatric Hematology/Oncology 1999 21 1 67 69 2-s2.0-0033063652 10029817 \n15 Mariño-Enríquez A Ou W Weldon CB Fletcher JA Pérez-Atayde AR ALK rearrangement in sickle cell trait-associated renal medullary carcinoma Genes Chromosomes and Cancer 2011 50 3 146 153 2-s2.0-78650963448 21213368 \n16 Liu Q Galli S Srinivasan R Linehan WM Tsokos M Merino MJ Renal medullary carcinoma: molecular, immunohistochemistry, and morphologic correlation The American Journal of Surgical Pathology 2013 37 3 368 374 2-s2.0-84873999421 23348212 \n17 Calderaro J Moroch J Pierron G SMARCB1/INI1 inactivation in renal medullary carcinoma Histopathology 2012 61 3 428 435 2-s2.0-84865374130 22686875 \n18 Klochendler-Yeivin A Picarsky E Yaniv M Increased DNA damage sensitivity and apoptosis in cells lacking the Snf5/Ini1 subunit of the SWI/SNF chromatin remodeling complex Molecular and Cellular Biology 2006 26 7 2661 2674 2-s2.0-33645228528 16537910 \n19 Medjkane S Novikov E Versteege I Delattre O The tumor suppressor hSNF5/INI1 modulates cell growth and actin cytoskeleton organization Cancer Research 2004 64 10 3406 3413 2-s2.0-2442649307 15150092 \n20 Versteege I Medjkane S Rouillard D Delattre O A key role of the hSNF5/INI1 tumour suppressor in the control of the G1-S transition of the cell cycle Oncogene 2002 21 42 6403 6412 2-s2.0-0037136674 12226744 \n21 Swartz MA Karth J Schneider DT Rodriguez R Beckwith JB Perlman EJ Renal medullary carcinoma: clinical, pathologic, immunohistochemical, and genetic analysis with pathogenetic implications Urology 2002 60 6 1083 1089 2-s2.0-0036897914 12475675 \n22 Yang XJ Sugimura J Tretiakova MS Gene expression profiling of renal medullary carcinoma: potential clinical relevance Cancer 2004 100 5 976 985 2-s2.0-10744231407 14983493 \n23 Schaeffer EM Guzzo TJ Furge KA Renal medullary carcinoma: Molecular, pathological and clinical evidence for treatment with topoisomerase-inhibiting therapy BJU International 2010 106 1 62 65 2-s2.0-77953206989 20002663\n\n",
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{
"abstract": "The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV- tumours, EBV+ DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV+ DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy-related immunosuppression can transform either CLL cells or non-tumoural B lymphocytes into EBV+ DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2-/- IL2γc-/- mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV+ B-cell clones from 95% of CLL and 64% of MBL patients samples, but not from healthy donors. Eventually, these cells generated monoclonal tumours (mostly CLL-unrelated but also CLL-related), recapitulating the principal features of EBV+ DLBCL in patients. Accordingly, clonally related and unrelated EBV+ DLBCL xenografts showed indistinguishable cellular, virological and molecular features, and synergistically responded to combined inhibition of EBV replication with ganciclovir and B-cell receptor signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by EBV in CLL patients receiving immunosuppressive therapies, and provides the scientific rationale for testing ganciclovir and ibrutinib in EBV+ DLBCL. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.",
"affiliations": "Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;Department of Haematology, University Hospital, and Institute of Molecular and Cellular Biology of Cancer, CIBERONC, University of Salamanca, Salamanca, Spain.;Department of Haematology, Clinica Universidad de Navarra, CIBERONC, University of Navarra, Pamplona, Spain.;KU Leuven, Translational Cell and Tissue Research, Department of Pathology, UZ Leuven, Leuven, Belgium.;Haematopathology Section, Hospital Clinic, Institut d'Investigacions Biomediques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.;Department of Haematology, University Hospital, and Institute of Molecular and Cellular Biology of Cancer, CIBERONC, University of Salamanca, Salamanca, Spain.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;Haematopathology Section, Hospital Clinic, Institut d'Investigacions Biomediques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;Division of Haematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.;Division of Haematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.;Department of Pathology, Hospital Universitario and Instituto de Formacion e Investigacion Marques de Valdecilla, Santander, Spain.;Department of Pathology, Hospital Universitario and Instituto de Formacion e Investigacion Marques de Valdecilla, Santander, Spain.;Department of Haematology, University Hospital, and Institute of Molecular and Cellular Biology of Cancer, CIBERONC, University of Salamanca, Salamanca, Spain.;Department of Haematology, University Hospital, and Institute of Molecular and Cellular Biology of Cancer, CIBERONC, University of Salamanca, Salamanca, Spain.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;Department of Genetics, School of Medicine, University of Navarra, Pamplona, Spain.;Bio-informatics Unit, Department of Genomics and Proteomics, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain.;Department of Haematology, Hospital San Pedro, Logroño, Spain.;Department of Haematology, Hospital San Pedro, Logroño, Spain.;Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Haematology, University Hospital, and Institute of Molecular and Cellular Biology of Cancer, CIBERONC, University of Salamanca, Salamanca, Spain.;Cancer Research Centre, Institute for Biomedical Research of Salamanca and Department of Medicine and Cytometry Service, CIBERONC, University of Salamanca, Salamanca, Spain.;Medical Clinic II, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany.;Department of Haematology, University Hospital, and Institute of Molecular and Cellular Biology of Cancer, CIBERONC, University of Salamanca, Salamanca, Spain.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.;KU Leuven, Translational Cell and Tissue Research, Department of Pathology, UZ Leuven, Leuven, Belgium.;KU Leuven, Translational Cell and Tissue Research, Department of Pathology, UZ Leuven, Leuven, Belgium.;Department of Haematology, University Hospital, and Institute of Molecular and Cellular Biology of Cancer, CIBERONC, University of Salamanca, Salamanca, Spain.;Division of Haematological Oncology, Centre for Applied Medical Research (CIMA), CIBERONC, University of Navarra, Pamplona, Spain.",
"authors": "García-Barchino|Maria J|MJ|;Sarasquete|Maria E|ME|;Panizo|Carlos|C|;Morscio|Julie|J|;Martinez|Antonio|A|;Alcoceba|Miguel|M|;Fresquet|Vicente|V|;Gonzalez-Farre|Blanca|B|;Paiva|Bruno|B|;Young|Ken H|KH|;Robles|Eloy F|EF|;Roa|Sergio|S|;Celay|Jon|J|;Larrayoz|Marta|M|;Rossi|Davide|D|;Gaidano|Gianluca|G|;Montes-Moreno|Santiago|S|;Piris|Miguel A|MA|;Balanzategui|Ana|A|;Jimenez|Cristina|C|;Rodriguez|Idoia|I|;Calasanz|Maria J|MJ|;Larrayoz|Maria J|MJ|;Segura|Victor|V|;Garcia-Muñoz|Ricardo|R|;Rabasa|Maria P|MP|;Yi|Shuhua|S|;Li|Jianyong|J|;Zhang|Mingzhi|M|;Xu-Monette|Zijun Y|ZY|;Puig-Moron|Noemi|N|;Orfao|Alberto|A|;Böttcher|Sebastian|S|;Hernandez-Rivas|Jesus M|JM|;Miguel|Jesus San|JS|;Prosper|Felipe|F|;Tousseyn|Thomas|T|;Sagaert|Xavier|X|;Gonzalez|Marcos|M|;Martinez-Climent|Jose A|JA|",
"chemical_list": "D007166:Immunosuppressive Agents",
"country": "England",
"delete": false,
"doi": "10.1002/path.5060",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0022-3417",
"issue": "245(1)",
"journal": "The Journal of pathology",
"keywords": "EBV; Richter transformation; therapy-related immunosuppression",
"medline_ta": "J Pathol",
"mesh_terms": "D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D002471:Cell Transformation, Neoplastic; D020031:Epstein-Barr Virus Infections; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007166:Immunosuppressive Agents; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D016403:Lymphoma, Large B-Cell, Diffuse; D008297:Male; D008875:Middle Aged",
"nlm_unique_id": "0204634",
"other_id": null,
"pages": "61-73",
"pmc": null,
"pmid": "29464716",
"pubdate": "2018-05",
"publication_types": "D016428:Journal Article; D052061:Research Support, N.I.H., Extramural; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Richter transformation driven by Epstein-Barr virus reactivation during therapy-related immunosuppression in chronic lymphocytic leukaemia.",
"title_normalized": "richter transformation driven by epstein barr virus reactivation during therapy related immunosuppression in chronic lymphocytic leukaemia"
} | [
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"abstract": "Esophageal submucosal hematoma is a rare complication after endovascular surgery. We report a case of an esophageal submucosal hematoma which may have been caused by rigorous cough during extubation.\nA 75-year-old woman underwent endovascular treatment for unruptured cerebral aneurysm under general anesthesia. The patient received aspirin and clopidogrel before surgery and heparin during surgery. Activated clotting time was 316 s at the end of surgery. Protamine was not administered and continuous infusion of argatroban was started after surgery. She had a rigorous cough during removal of the tracheal tube and reported retrosternal discomfort postoperatively. She developed hemorrhagic shock after massive hematemesis. A diagnosis of esophageal submucosal hematoma was made by endoscopic examination and computed tomography. Hemostasis was achieved by compression with a Sengstaken-Blakemore tube and endoscopic cauterization. Blood pressure was recovered by blood transfusion. Endoscopic examination performed 7 days after surgery showed that esophageal submucosal hematoma had almost disappeared and slough had adhered to the mucosal laceration. The patient showed good recovery and was discharged 21 days after surgery.\nCareful extubation and postoperative observation are required in patients receiving antiplatelet and anticoagulant therapy.",
"affiliations": "1Department of Anesthesiology, Tokyo Women's Medical University, Tokyo, 162-8666 Japan.;1Department of Anesthesiology, Tokyo Women's Medical University, Tokyo, 162-8666 Japan.;1Department of Anesthesiology, Tokyo Women's Medical University, Tokyo, 162-8666 Japan.;1Department of Anesthesiology, Tokyo Women's Medical University, Tokyo, 162-8666 Japan.;1Department of Anesthesiology, Tokyo Women's Medical University, Tokyo, 162-8666 Japan.;2Department of Neurosurgery, Tokyo Women's Medical University, Tokyo, 162-8666 Japan.;2Department of Neurosurgery, Tokyo Women's Medical University, Tokyo, 162-8666 Japan.",
"authors": "Ito|Sachiko|S|;Iwata|Shihoko|S|;Kondo|Izumi|I|;Iwade|Motoyo|M|;Ozaki|Makoto|M|0000-0001-7841-6661;Ishikawa|Tatsuya|T|;Kawamata|Takakazu|T|",
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"country": "Germany",
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"doi": "10.1186/s40981-017-0124-3",
"fulltext": "\n==== Front\nJA Clin RepJA Clin RepJA Clinical Reports2363-9024Springer Berlin Heidelberg Berlin/Heidelberg 2945709812410.1186/s40981-017-0124-3Case ReportEsophageal submucosal hematoma developed after endovascular surgery for unruptured cerebral aneurysm under general anesthesia: a case report Ito Sachiko sachi-i@rj9.so-net.ne.jp 1Iwata Shihoko shk_wt_0204@ybb.ne.jp 1Kondo Izumi mimizu@ga2.so-net.ne.jp 1Iwade Motoyo miwade@mrj.biglobe.ne.jp 1http://orcid.org/0000-0001-7841-6661Ozaki Makoto +81-3-3353-8111morton@live.jp 1Ishikawa Tatsuya tishikawa@twmu.ac.jp 2Kawamata Takakazu tkawamata@nij.twmu.ac.jp 21 0000 0001 0720 6587grid.410818.4Department of Anesthesiology, Tokyo Women’s Medical University, Tokyo, 162-8666 Japan 2 0000 0001 0720 6587grid.410818.4Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, 162-8666 Japan 3 10 2017 3 10 2017 12 2017 3 5423 8 2017 26 9 2017 © The Author(s) 2017\nOpen AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background\nEsophageal submucosal hematoma is a rare complication after endovascular surgery. We report a case of an esophageal submucosal hematoma which may have been caused by rigorous cough during extubation.\n\nCase presentation\nA 75-year-old woman underwent endovascular treatment for unruptured cerebral aneurysm under general anesthesia. The patient received aspirin and clopidogrel before surgery and heparin during surgery. Activated clotting time was 316 s at the end of surgery. Protamine was not administered and continuous infusion of argatroban was started after surgery. She had a rigorous cough during removal of the tracheal tube and reported retrosternal discomfort postoperatively. She developed hemorrhagic shock after massive hematemesis. A diagnosis of esophageal submucosal hematoma was made by endoscopic examination and computed tomography. Hemostasis was achieved by compression with a Sengstaken-Blakemore tube and endoscopic cauterization. Blood pressure was recovered by blood transfusion. Endoscopic examination performed 7 days after surgery showed that esophageal submucosal hematoma had almost disappeared and slough had adhered to the mucosal laceration. The patient showed good recovery and was discharged 21 days after surgery.\n\nConclusions\nCareful extubation and postoperative observation are required in patients receiving antiplatelet and anticoagulant therapy.\n\nKeywords\nEsophageal submucosal hematomaCoil embolizationCerebral aneurysmAntiplatelet and anticoagulant therapiesCough during tracheal extubationissue-copyright-statement© The Author(s) 2017\n==== Body\nBackground\nEsophageal submucosal hematoma is a rare condition [1]. Previous reports showed that it may develop after endovascular surgery, which requires postoperative anticoagulation therapy. Chest pain is the most frequent complaint [2], which often misleads a diagnosis such as ischemic heart disease and aortic dissection. We report a case who had hematemesis and developed hemorrhagic shock after endovascular surgery for unruptured cerebral aneurysm under general anesthesia. Prompt endoscopic examination enabled early diagnosis and successful treatment. We discuss the causes of and potential preventive strategies for esophageal submucosal hematoma as well as important reminders at the time of onset and diagnosis and postoperative management. We obtained written informed consent from the patient to publish this case report.\n\nCase presentation\nA 75-year-old woman (154 cm, 49 kg) underwent coil embolization of an unruptured cerebral aneurysm under general anesthesia. Her medical history and preoperative complications were unremarkable. Preoperative laboratory data were within normal limits, with no coagulation abnormalities. Aspirin 200 mg and clopidogrel 300 mg, and aspirin 100 mg and clopidogrel 75 mg were administered orally on the day before, and in the morning of the day of surgery, respectively.\n\nGeneral anesthesia was induced with target-controlled infusion of propofol and remifentanil 0.5 μg/kg/min. After infusion of rocuronium 50 mg, tracheal intubation was performed uneventfully, followed by smooth insertion of a nasogastric tube, which was left open to room air until the completion of surgery, and there was no spontaneous reflux of gastric contents. Anesthesia was maintained with target-controlled infusion of propofol and remifentanil 0.1 μg/kg/min with an inhalational oxygen concentration of 37% under standard monitoring as well as direct radial artery pressure monitoring. Blood pressure and heart rate were stable with continuous infusion of phenylephrine 0.4–0.5 mg/h.\n\nHeparin 400 units were intravenously administered at the beginning of surgery, followed by 500 units during surgery. Activated clotting time (ACT) was 141, 238, 275, and 316 s before and 5 and 40 min after starting surgery, at the end of surgery. Protamine was not administered. Continuous infusion of argatroban 0.8 μg/kg/min was started on completion of surgery.\n\nFentanyl 100 μg was administered 10 min before surgery completion, and continuous infusion of propofol, remifentanil, and phenylephrine was discontinued at the completion of surgery. The patient started to wake 5 min after the completion of surgery, and her systolic blood pressure increased to 160 mmHg and pulse rate to 90 bpm. The nasogastric tube was removed without applying negative pressure after aspirating a small amount of gastric fluid not containing apparent blood components. Sputum was seen in the tracheal tube, which was suctioned. Following this, the patient had a stronger cough. The tracheal tube was removed 12 min after the completion of surgery after confirming recovery of consciousness. After extubation, there was no nausea, vomiting, or strong cough. The patient was stable with a blood pressure of 140/60 mmHg and pulse rate of around 90 bpm, and returned to the ICU 20 min after extubation. Total operative time was 75 min, and total anesthesia time was 130 min.\n\nThe patient started to complain of retrosternal discomfort 24 min after return to the ICU. At that time, her blood pressure was 140/60 mmHg and pulse rate was around 90 bpm. The patient started to complain of nausea 48 min after returning to the ICU. Her systolic blood pressure decreased to 70 mmHg 51 min after returning to the ICU, and the patient had a hematemesis of approximately 200 g of fresh blood. And, the ACT was 280 s. An upper gastrointestinal endoscope was inserted immediately to identify the bleeding point and achieve hemostasis, which showed submucosal thickening extending from the midesophagus to the esophagogastric junction, which was due to the submucosal hematoma (Fig. 1a: endoscopic image). At the esophagogastric junction, the esophageal mucosa was being displaced into the gastric cavity by the submucosal hematoma (Fig. 1b: endoscopic image). There was a bleeding laceration in part of the mucosa, for which pressure hemostasis was performed with a Sengstaken-Blakemore tube. Continuous infusion of argatroban was discontinued and protamine was administered, and the ACT decreased to 126 s. During the endoscopic examination, the submucosal hematoma was extending toward the oral side, and it became a hematoma extending from the esophagogastric junction to the oral cavity at the end of the endoscopic procedure. The hematemesis continued, and the amount of bleeding reached 900 g, and the level of hemoglobin decreased to 7.5 g/dL. A plain computed tomography (CT) was performed to assess the extent of the hematoma, which showed dilatation of the entire esophagus and the soft tissue shadow filled on the dorsal side that was ventrally displacing the lumen (Fig. 2a: CT sagittal section). These findings, along with the endoscopy results, were consistent with the diagnosis of esophageal submucosal hematoma. An isodense area suggesting hematoma was also observed in the gastric cavity. In addition, the dilated cervical esophagus was displacing the trachea (Fig. 2b: CT cross-section). Considering that the patient would have a greater risk of aspirating blood into the trachea if the hematoma ruptured, therefore, we performed tracheal intubation. Observation during the tracheal intubation showed edema at the arytenoid region. After compression with the Sengstaken-Blakemore tube for 1 h, hemostasis was achieved by cauterizing some parts of the mucosal laceration at the esophagogastric junction using the upper gastrointestinal endoscope. Up to this point, the patient was given fluid resuscitation for the decreased blood pressure due to the hemorrhage and was transfused with 10 units of red blood cells and 2 units of fresh frozen plasma.Fig. 1 Upper gastrointestinal endoscopy images immediately after hematemesis. a A longitudinal extension of reddish or wine-colored mucosal thickening (asterisk), obstructing the esophagus, is seen from the midesophagus to the esophagogastric junction. b The submucosal hematoma (two asterisks) is displacing the esophageal mucosa (asterisk) toward the gastric cavity at the esophagogastric junction. A part of the displaced mucosa has a laceration with bleeding\n\n\nFig. 2 Cervical and thoracic CT images after insertion of Sengstaken-Blakemore tube. a Sagittal section: the soft tissue shadow is filled and dilatation can be seen in the posterior wall over the entire length of the esophagus (red arrows), ventrally displacing the lumen. b Cross-section: the cervical esophagus is dilated, displacing the trachea toward the left side\n\n\n\n\nThe patient was fasted and started on omeprazole 40 mg/day; antiplatelet therapy was discontinued. Upper gastrointestinal endoscopy performed on the day after surgery confirmed the absence of expansion of the hematoma or recurrent bleeding. Neck and thoracic plain CT performed 4 days after surgery showed reduced dilatation of the esophagus and improvement in displacement of the trachea, and thus the tracheal tube was removed 5 days after surgery. Upper gastrointestinal endoscopy performed 7 days after surgery showed that the esophageal submucosal hematoma had almost disappeared and the slough had adhered to the mucosal laceration at the esophagogastric junction (Fig. 3). Oral intake was resumed on the same day. The patient showed good recovery and was discharged 21 days after surgery. The patient did not develop thrombotic complications until discharge, although she did not receive antiplatelet or anticoagulant therapy.Fig. 3 Upper gastrointestinal endoscopy image 7 days after surgery. The esophageal submucosal had almost disappeared, and the slough had adhered to the mucosal laceration at the esophagogastric junction\n\n\n\n\nEsophageal submucosal hematoma is a rare condition in the spectrum of esophageal injury including Mallory-Weiss syndrome and Boerhaave syndrome [3]. These conditions are similar in that they are induced by a sudden increase in esophageal pressure. While Mallory-Weiss syndrome and Boerhaave syndrome are usually associated with vomiting, patients with esophageal submucosal hematoma do not always present with vomiting [3, 4]. Classification of the causes of esophageal submucosal hematoma into idiopathic (spontaneous) and traumatic has originally reported by Freeman AH [2]. The idiopathic causes of esophageal submucosal hematoma include a sudden increase in the esophageal pressure not only by vomiting or vomiting reflex but also by coughing and sneezing. Sometimes, the causes are unknown [3–5]. The traumatic causes of esophageal submucosal hematoma include direct or blunt injury caused by medical apparatus inserted into the esophagus [6], insertion of gastric tube [7], and accidental swallowing of foreign objects. Most reported cases with esophageal submucosal hematoma were of patients receiving antiplatelet drugs or who had abnormal coagulation [6–8]. Therefore, bleeding tendency is a contributing factor to the aggravation of esophageal submucosal hematoma [5].\n\nIn the present case, the patient had a stronger cough during the period from the time when the patient woke up from general anesthesia to the time of extubation of the tracheal tube, especially when we suctioned sputum from the tracheal tube. We considered that an increased abdominal pressure due to the cough led to elevated esophageal pressure that could be a cause of the esophageal submucosal dissection or esophageal mucosal injury. During the upper gastrointestinal endoscopic examination performed immediately after hematemesis, the submucosal hematoma was observed to be extending toward the upper esophagus with repeated hematemesis, suggesting that the elevated esophageal pressure was the primary cause of the esophageal submucosal hematoma and its expansion in the present case. Although cough is a rare cause of esophageal submucosal hematoma, Cao et al. reported a case of esophageal submucosal hematoma occurring after persistent coughing for 1 week in a patient with viral bronchitis [5].\n\nThe nasogastric tube was inserted into the stomach after introducing general anesthesia and left open to room air. Direct damage to the mucosa by the nasogastric tube was considered unlikely, because the tube had been inserted into the stomach without resistance and that bloody secretion had not been aspirated from the tube before extubation. Fujimoto et al. reported a case of esophageal submucosal hematoma possibly caused by gastric tube removal with sustained negative pressure [7]. In the present case, aspiration was performed only once before extubation. However, if the tube had been placed around the esophagogastric junction, mucosal injury due to aspiration might have caused the submucosal hematoma.\n\nIn general, when performing coil embolization for an unruptured cerebral aneurysm, antiplatelet therapy is started preoperatively and anticoagulant therapy is started intraoperatively to prevent thrombotic complications [9, 10], However, as there are no established guidelines for preventive treatment, the methods vary between institutions and according to morphology of aneurysms. In our department of neurosurgery, we use two antiplatelet drugs in combination, we administer heparin during surgery to maintain an ACT of 200 s or longer, and we perform continuous infusion of argatroban for 48 h after surgery as anticoagulant therapy. We compared the use of anticoagulant therapy in the present case with that in two previously reported cases of esophageal submucosal hematoma after coil embolization for unruptured cerebral aneurysm [7]. Regarding antiplatelet drugs, one patient used aspirin [7], while the other used aspirin and clopidogrel in the same combination [1] as was used in the present case. Regarding anticoagulant therapy, the initial dose of heparin and ACT during surgery were similar in the three cases; however, the ACT at the completion of surgery was longer in the present case (316 s) than in the other two cases (239 and 265 s, respectively), and the continuous infusion of argatroban was performed only in the present case. Therefore, relatively intensive antithrombotic therapy performed in the present case was considered to have an influence on the occurrence of extensive submucosal hematoma of the esophagus and subsequent massive hematemesis with hemorrhagic shock.\n\nHematemesis, as a symptom of esophageal submucosal hematoma, results from rupture of the most vulnerable part of the mucosa due to expansion of the hematoma [6]. The bleeding point in the present case was the lower part of the esophagus. Anatomically, the mucosa of the lower part of the esophagus is prone to injury under the influence of intrathoracic or esophageal pressure [5]. In the present case, it was considered that the mucosa of the lower part of the esophagus became fragile and ruptured due to an increased pressure by coughing at the time of extubation. In esophageal submucosal hematoma, the amount of hematemesis is usually small. Shim et al. reported that, among 119 patients with esophageal submucosal hematoma reported since 1968, 11 had more than 500 g hematemesis with hypotension or bleeding that required transfusion of at least 4 units [4].\n\nThe present study suggests that coughing at the time of extubation can be a cause of esophageal submucosal hematoma or mucosal rupture. Therefore, clinicians should be very careful about the risk of esophageal submucosal hematoma, especially when treating patients receiving antiplatelet or anticoagulant therapy under general anesthesia. We retrospectively considered that we could have reduced cough if we had suctioned the sputum in the tracheal tube under deep anesthesia. In addition, the use of nasogastric tube should be carefully considered, because its insertion and removal is associated with risk.\n\nConclusions\nThe prognosis of esophageal submucosal hematoma is good. However, patients receiving antiplatelet or anticoagulant therapy have a risk of massive bleeding that requires urgent treatment. Clinicians should be aware of the risk of esophageal submucosal hematoma in postoperative management of patients undergoing coil embolization for cerebral aneurysm.\n\nAbbreviations\nACTActivated clotting time\n\nCTComputed tomography\n\nAcknowledgements\nNone\n\nFunding\nThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\n\nAvailability of data and materials\nThe datasets supporting the conclusions of this article are included within the article.\n\nAuthors’ contributions\nSI and MO wrote the paper. IK, MI, MO, TI, and TK revised the paper. All authors read and approved the final manuscript.\n\nEthics approval and consent to participate\nWritten informed consent was obtained from the patient for publication of this case report and accompanying images.\n\nCompeting interests\nThe authors declare that they have no competing interests.\n\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n1. Yoshihara T Yamane F Kanazawa R Kohyama S Ochiai I Uemiya N Spontaneous esophageal submucosal hematoma following coil embolization for unruptured cerebral aneurysm: a case report JNET 2013 7 40 45 10.5797/jnet.7.40 \n2. Hiller N Zagal I Hadas-Halpern I Spontaneous intramural hematoma of the esophagus Am J Gastroenterol 1999 94 2282 2284 10.1111/j.1572-0241.1999.01314.x 10445563 \n3. Shim J Jang JY Hwangbo Y Dong SH Oh JH Kim HJ Recurrent massive bleeding due to dissecting intramural hematoma of the esophagus: treatment with therapeutic angiography World J Gastroenterol 2009 15 5232 5235 10.3748/wjg.15.5232 19891027 \n4. Yamashita K Okuda H Fukushima H Arimura Y Endo T Imai K A case of intramural esophageal hematoma: complication of anticoagulation with heparin Gastrointest Endosc 2000 52 559 561 10.1067/mge.2000.108664 11023585 \n5. Cao DT Reny JL Lanthier N Frossard JL Intramural hematoma of the esophagus Case Rep Gastroenterol 2012 6 510 517 10.1159/000341808 23730267 \n6. Jeong ES Kim MJ Yoo SH Kim DH Jung JS Koo NH Intramural hematoma of the esophagus after endoscopic pinch biopsy Clin Endosc 2012 45 417 420 10.5946/ce.2012.45.4.417 23251891 \n7. Fujimoto Y Shirozu K Shirozu N Akiyoshi K Nishimura A Kawasaki S Esophageal submucosal hematoma possibly caused by gastric tube insertion under general anesthesia A A Case Rep 2016 7 169 171 10.1213/XAA.0000000000000376 27467902 \n8. Jalihal A Jamaludin AZ Sawkarakumar S Chong VH Intramural hematoma of the esophagus: a rare cause of chest pain Am J Emerg Med 2008 26 843 e1 e2 \n9. Qureshi AI Luft AR Sharma M Guterman LR Hopkins LN Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: part II-clinical aspects and recommendations Neurosurgery 2000 46 1360 1375 10.1097/00006123-200006000-00014 10834641 \n10. Yamada NK Cross DT Pilgram TK Moran CJ Derdeyn CP Dacey RG Jr Effect of antiplatelet therapy on thromboembolic complications of elective coil embolization of cerebral aneurysms AJNR Am J Neuroradiol 2007 28 1778 1782 10.3174/ajnr.A0641 17885244\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2363-9024",
"issue": "3(1)",
"journal": "JA clinical reports",
"keywords": "Antiplatelet and anticoagulant therapies; Cerebral aneurysm; Coil embolization; Cough during tracheal extubation; Esophageal submucosal hematoma",
"medline_ta": "JA Clin Rep",
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"pmid": "29457098",
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"publication_types": "D016428:Journal Article",
"references": "18774068;10834641;11023585;27467902;19891027;23730267;17885244;23251891;10445563",
"title": "Esophageal submucosal hematoma developed after endovascular surgery for unruptured cerebral aneurysm under general anesthesia: a case report.",
"title_normalized": "esophageal submucosal hematoma developed after endovascular surgery for unruptured cerebral aneurysm under general anesthesia a case report"
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{
"abstract": "Fibrosing cholestatic hepatitis (FCH) is a classical but rare and severe form of recurrent hepatitis C virus (HCV) after liver transplantation. Classical anti-HCV therapy, that is pegylated-interferon (peg-interferon) and ribavirin, has been shown to have limited efficacy in treating FCH. Herein, we report on the first case of successful use of peg-interferon, ribavirin, plus sofosbuvir to treat HCV-induced FCH in a combined liver-kidney transplant patient. Antiviral therapy was given for 24 weeks. HCV clearance occurred within 4 weeks after starting therapy and was maintained until 4 weeks after the end of therapy. Antiviral tolerance was good. We conclude that the use of sofosbuvir-based anti-HCV therapy can be successfully used to treat FCH after a liver or combined kidney-liver transplantation.",
"affiliations": "Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.",
"authors": "Delabaudière|Cyrielle|C|;Lavayssière|Laurence|L|;Dörr|Gaëlle|G|;Muscari|Fabrice|F|;Danjoux|Marie|M|;Sallusto|Federico|F|;Peron|Jean Marie|JM|;Bureau|Christophe|C|;Rostaing|Lionel|L|;Izopet|Jacques|J|;Kamar|Nassim|N|",
"chemical_list": "D000998:Antiviral Agents; D004338:Drug Combinations; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D014542:Uridine Monophosphate; C100416:peginterferon alfa-2a; D000069474:Sofosbuvir",
"country": "England",
"delete": false,
"doi": "10.1111/tri.12428",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0934-0874",
"issue": "28(2)",
"journal": "Transplant international : official journal of the European Society for Organ Transplantation",
"keywords": "fibrosing cholestatic hepatitis; hepatitis C virus; kidney transplantation; liver transplantation; sofosbuvir",
"medline_ta": "Transpl Int",
"mesh_terms": "D000368:Aged; D000998:Antiviral Agents; D004338:Drug Combinations; D006526:Hepatitis C; D006801:Humans; D016898:Interferon-alpha; D016030:Kidney Transplantation; D016031:Liver Transplantation; D008297:Male; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin; D000069474:Sofosbuvir; D014542:Uridine Monophosphate",
"nlm_unique_id": "8908516",
"other_id": null,
"pages": "255-8",
"pmc": null,
"pmid": "25159822",
"pubdate": "2015-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Successful treatment of fibrosing cholestatic hepatitis with pegylated interferon, ribavirin and sofosbuvir after a combined kidney-liver transplantation.",
"title_normalized": "successful treatment of fibrosing cholestatic hepatitis with pegylated interferon ribavirin and sofosbuvir after a combined kidney liver transplantation"
} | [
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"abstract": "Cytomegalovirus retinitis (CMVR) commonly affects immunocompromised individuals, including acquired immunodeficiency syndrome (AIDS), post-organ transplant recipients and allogeneic stem cell transplant recipients. CMVR occurring in the acute lymphoblastic leukemia (ALL) maintenance phase of chemotherapy is rare and has been described in the literature as isolated case reports or case series. We report a case of unilateral CMVR in a pediatric patient during maintenance phase therapy for ALL. A 14-year-old boy known case of T-cell ALL with CNS2a status, was treated according to the Children's Oncology Group (COG) AALL0434 protocol. Induction therapy consisted of the standard high-risk four drugs, in addition to intrathecal methotrexate. At week 166 of maintenance therapy, the child presented with painless progressive loss of vision in the right eye for one week. The best-corrected visual acuity (BCVA) of the right eye was 6/36 and the left eye was 6/6. Dilated fundus examination of the right eye showed multiple large yellow-white cloudy chorioretinal lesions with areas of intraretinal hemorrhages in the macula, and overlaying focal vitritis. Optical coherence tomography (OCT) of the right eye showed macular edema and mild subretinal fluid. Cytomegalovirus polymerase chain reaction of the blood was detected with high quantitative value. A diagnosis of CMVR was made and an induction doses of intravenous ganciclovir was followed by maintenance doses of oral valganciclovir. Our case suggests that pediatric patients with ALL in the maintenance phase are considered immunocompromised and that physicians should be aware of CMVR incidence in such group. Early diagnosis and prompt treatment are important to preserve vision and prevent future visual morbidity.",
"affiliations": "Department of Ophthalmology, King Abdulaziz University, Jeddah, SAU.;Department of Ophthalmology - Vitreoretinal Surgery, King Abdulaziz Medical City, Jeddah, SAU.;Department of Pediatrics, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, SAU.",
"authors": "Mandura|Rahaf A|RA|;Talat|Karim|K|;Jastaniah|Wasil|W|",
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"fulltext": "\n==== Front\nCureus\nCureus\n2168-8184\nCureus\n2168-8184\nCureus Palo Alto (CA)\n\n10.7759/cureus.15246\nOphthalmology\nPediatrics\nInfectious Disease\nUnilateral Cytomegalovirus Retinitis in a Child With Acute Lymphoblastic Leukemia While on Maintenance Chemotherapy\nMuacevic Alexander\nAdler John R\nMandura Rahaf A 1\nTalat Karim 2\nJastaniah Wasil 3\n1 Department of Ophthalmology, King Abdulaziz University, Jeddah, SAU\n2 Department of Ophthalmology - Vitreoretinal Surgery, King Abdulaziz Medical City, Jeddah, SAU\n3 Department of Pediatrics, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, SAU\nRahaf A. Mandura dr.mandura@gmail.com\n26 5 2021\n5 2021\n13 5 e1524625 5 2021\nCopyright © 2021, Mandura et al.\n2021\nMandura et al.\nhttps://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.\nThis article is available from https://www.cureus.com/articles/58132-unilateral-cytomegalovirus-retinitis-in-a-child-with-acute-lymphoblastic-leukemia-while-on-maintenance-chemotherapy\nCytomegalovirus retinitis (CMVR) commonly affects immunocompromised individuals, including acquired immunodeficiency syndrome (AIDS), post-organ transplant recipients and allogeneic stem cell transplant recipients. CMVR occurring in the acute lymphoblastic leukemia (ALL) maintenance phase of chemotherapy is rare and has been described in the literature as isolated case reports or case series. We report a case of unilateral CMVR in a pediatric patient during maintenance phase therapy for ALL. A 14-year-old boy known case of T-cell ALL with CNS2a status, was treated according to the Children’s Oncology Group (COG) AALL0434 protocol. Induction therapy consisted of the standard high-risk four drugs, in addition to intrathecal methotrexate. At week 166 of maintenance therapy, the child presented with painless progressive loss of vision in the right eye for one week. The best-corrected visual acuity (BCVA) of the right eye was 6/36 and the left eye was 6/6. Dilated fundus examination of the right eye showed multiple large yellow-white cloudy chorioretinal lesions with areas of intraretinal hemorrhages in the macula, and overlaying focal vitritis. Optical coherence tomography (OCT) of the right eye showed macular edema and mild subretinal fluid. Cytomegalovirus polymerase chain reaction of the blood was detected with high quantitative value. A diagnosis of CMVR was made and an induction doses of intravenous ganciclovir was followed by maintenance doses of oral valganciclovir. Our case suggests that pediatric patients with ALL in the maintenance phase are considered immunocompromised and that physicians should be aware of CMVR incidence in such group. Early diagnosis and prompt treatment are important to preserve vision and prevent future visual morbidity.\n\ncytomegalovirus\ncytomegalovirus retinitis\nacute lymphoblastic leukemia\npediatric\nall\nhematology\nThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\nIntroduction\n\nCytomegalovirus (CMV) is a type 5 herpes virus causing an asymptomatic or minimally symptomatic illness in immunocompetent individuals [1]. Furthermore, it is considered a common opportunistic intraocular infection in acquired immune deficiency syndrome (AIDS) secondary to the depressed cell-mediated immunity when CD4 counts decline to less than 100/μL [2]. It can also occur in patients who received a solid organ or hematopoietic stem cell transplant [1]. Cytomegalovirus retinitis (CMVR) due to CMV infection is very destructive and can cause full-thickness retinal inflammation, hemorrhage, and necrosis which can eventually result in serious complications such as retinal detachment and vision loss [3]. CMVR starts by affecting the vascular endothelial cells. Later, it affects the retinal pigment epithelium. After such manifestations occur, the virus' final cytopathic effect is subsequent retinal necrosis [4]. Acute lymphoblastic leukemia (ALL) patients undergoing maintenance chemotherapy rarely develop CMVR and are usually described as isolated case reports or case series in the literature [5-9]. We describe a case of unilateral CMVR in a pediatric patient during his maintenance phase therapy for ALL.\n\nCase presentation\n\nA 14-year-old boy who is a known case of T-cell acute ALL with CNS2a status presented with painless progressive loss of vision in the right eye for one week. Regarding his ALL history, he initially presented with leukocytosis of 572 x 109/L and flow cytometry confirmed T-cell immunophenotype. He had no clinical symptoms or signs of neurological involvement and his vision was intact. However, he had evidence of blasts with low white blood cells on cyto-spin in his cerebrospinal fluid; thus, his central nervous system (CNS) involvement was categorized as CNS2a. Leukemia cytogenetics showed 46XY, del(6)(q21q23). He was treated according to the Children’s Oncology Group (COG) AALL0434 protocol [10]. Induction therapy consisted of the high-risk four-drug induction and intrathecal therapy. In addition, two extra intrathecal methotrexate doses were given during induction due to his CNS2a status. End-of-induction minimal residual disease (MRD) showed 6% bone marrow blasts and at the end-of-consolidation, his MRD was negative with <0.01% blasts. After completing the intensive phase therapy, he was started on maintenance therapy, which consisted of 12-week cycles of monthly vincristine, dexamethasone pulse therapy, daily oral 6-mercaptopurine and weekly oral methotrexate [10]. He tolerated therapy relatively well until week 166 of maintenance therapy when a painless progressive loss of vision in the right eye started. Prior ocular history was unremarkable with no previous ocular disease while his past medical history was significant for varicella-zoster reactivation at the left thoracic dermatome during week 154 of maintenance therapy and was treated with intravenous acyclovir for 10 days with complete resolution. On ocular exam, the best-corrected visual acuity (BCVA) of the right eye was 6/36 and the left eye was 6/6. Intraocular pressure measured by tonopen was 17 mmHg in the right eye and 15 mmHg in the left eye. Anterior segment examination was normal and anterior chambers were quiet in both eyes without evidence of keratic precipitates or anterior uveitis. Dilated fundus examination of the right eye showed multiple large yellow-white cloudy inflammatory chorioretinal lesions with granular appearance and active borders, the largest lesion measuring around three disc diameters which was located in the macular area extending to the center of the fovea centering around the major retinal arterial vasculature in the posterior pole and surrounding the optic disc. It was associated with significant full-thickness retinal necrosis, intraretinal hemorrhages, perivascular sheathing (perivasculitis) along the arcades, cotton wool spots (soft exudates) and mild focal vitritis overlying the whitish active lesions. No associated retinal breaks or rhegmatogenous retinal detachment were noted (Figure 1). Optical coherence tomography (OCT) of the right eye showed the necrotizing retina appeared swollen as compared to the surrounding areas with the presence of macular edema, mild subretinal fluid accumulation, disturbance of foveal architecture, hyperreflective intraretinal deposits and clumps of hyperreflective material in the posterior vitreous consistent with vitreous cells and debris (Figure 2) while the left eye was normal.\n\nFigure 1 Fundus photo of the right eye showing CMV retinitis with retinal necrosis, intraretinal hemorrhages in the macula area, and focal overlying vitritis.\n\nCMV: cytomegalovirus.\n\nFigure 2 Optical coherence tomography of the right eye showing macular edema and subretinal fluid.\n\nBlood test for CMV polymerase chain reaction (PCR) was performed, and CMV DNA was detected with the highest quantitative level of 409,000 copies/ml and a CD4 count of 2.5 cell/mm. The patient was diagnosed with probable right eye CMVR with no evidence of any other organ involvement based on the clinical and laboratory findings. The maintenance chemotherapy was discontinued, and anti-CMV therapy was started in the form of high induction doses of daily intravenous infusion of ganciclovir 10 mg/kg for four weeks with weekly CMV PCR test. After the patient showed good response from the systemic therapy, no further intravitreal therapy was warranted. On examination, BCVA of the right eye improved to 6/30, and the left eye was 6/6. Dilated fundus examination showed improvement with some resolution of the active retinitis and retinal hemorrhages. CMV PCR was repeated and showed a decreased quantitative level of 8,814 copies/ml.\n\nOn the second week's visit, BCVA of the right eye reached 6/9, and dilated fundus examination showed marked improvement and reduced size of retinitis lesions. Also, there was a considerable replacement of the retinal necrosis with thin whitish fibrous membrane and glial sheets and resolution of the focal vitritis with no sign of disease activity. CMV PCR dropped down to 622 copies/ml and OCT showed clear macula with complete resolution of subretinal fluid. On the subsequent days, the patient was kept on the maintenance doses of oral valganciclovir 900 mg twice daily, which was continued for eight months until complete resolution of symptoms was achieved along with three consecutive negative readings of CMV PCR. The patient resumed and completed chemotherapy therapy a few months later and has been in clinical remission for two years.\n\nDiscussion\n\nCMV viremia occurs in 13.6% of patients with lymphoid malignancies who did not receive stem cell transplantation [11]. CMVR is reported more frequently in children with AIDS than in other immunosuppressive conditions [12]. CMVR is characterized by spreading hematogenously to the retina, which happens after the systemic reactivation of latent infection [13]. An experienced ophthalmologist establishes the diagnosis of CMRV based on typical retina changes. Ocular pathophysiology of CMVR appears as full-thickness necrotizing retinitis. Furthermore, it appears as a fluffy, yellow-white retinal lesions, while intraretinal hemorrhage with little inflammation to the vitreous is an unpredictable sign found in the disease [14]. ALL patients developing CMVR happens mostly during maintenance chemotherapy. This maintenance phase is the most common period in the whole pediatric lymphoblastic group to develop CMV infection [15]. This finding could be due to the immunosuppressive chemotherapeutic agents used in this phase. It is hypothesized that the addition of dexamethasone and vincristine to methotrexate and 6-mercaptopurine may increase the risk of CMVR substantially [7]. The prevalence of CMV reactivation during the maintenance phase is often high and is caused by these drugs due to the development of lymphopenia [7].\n\nWe have treated our patient with intravenous ganciclovir for four weeks, followed by oral valganciclovir. The treatment was well tolerated by the patient without adverse effects and showed a good response resulting in a successful resolution of the CMVR, consistent with the literature [5-9]. The disadvantage of intravenous ganciclovir includes decreased bioavailability in ocular tissues in comparison to intravitreal ganciclovir and a significant relapse rate [12]. However, our patient was followed up for two years and no recurrence has been reported. In addition, systemic ganciclovir has the advantage of limiting the spread of CMV infection to the other eye and we believe that this prevention would not be possible if we considered intravitreal ganciclovir as a sole treatment.\n\nConclusions\n\nCMVR is a tremendous visual threat in immunocompromised patients. Chemotherapy-related immunosuppression in pediatric patients with ALL happens in the maintenance phase of chemotherapy with chances of developing CMVR, making it important to have such a diagnosis in mind when seeing patients with ALL. A careful and vigilant approach to such cases is crucial as early diagnosis and prompt treatment are important to preserve vision and prevent visual morbidity.\n\nHuman Ethics\n\nThe authors have declared that no competing interests exist.\n\nConsent was obtained or waived by all participants in this study. King Abdulaziz Medical City issued approval NA. Both the patient and the guardian provided a written consent for the approval of publishing this case as long as the personal data stays anonymous.\n==== Refs\nReferences\n\n1 Cytomegalovirus Gupta M Shorman M Treasure Island, FL StatPearls 2017 https://www.ncbi.nlm.nih.gov/books/NBK459185/\n2 Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy - an update Indian J Ophthalmol Sudharshan S Nair N Curi A Banker A Kempen JH 1787 1798 68 2020 32823395\n3 Cytomegalovirus retinitis in HIV and non-HIV individuals Microorganisms Munro M Yadavalli T Fonteh C Arfeen S Lobo-Chan AM 8 2019\n4 Cytomegalovirus and the eye Eye Carmichael A 237 240 26 2012 22173076\n5 A case of cytomegalovirus retinitis during maintenance chemotherapy for acute leukemia Pediatr Inf Vaccine Ahn B Song S Han MS 198 204 27 2020\n6 Bilateral cytomegalovirus retinitis in a child with acute lymphoblastic leukemia while on maintenance chemotherapy Pediatr Hematol Oncol J Dedania VS Bhatnagar P Santos RP Kanwar VS 35 37 1 2016\n7 Cytomegalovirus retinitis as an adverse immunological effect of pulses of vincristine and dexamethasone in maintenance therapy for childhood acute lymphoblastic leukemia Pediatr Blood Cancer Moritake H Kamimura S Kojima H 329 331 60 2013 22976937\n8 Cytomegalovirus retinitis in an ALL child on exclusive chemotherapy treated successfully with intravitreal ganciclovir alone J Pediatr Hematol Oncol Singh R Singh R Trehan A Jain R Bhalekar S 0 9 35 2013\n9 Cytomegalovirus retinitis during chemotherapy with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone J Clin Oncol Libby E Movva S Quintana D Abdul-Jaleel M Das A 0 2 28 2010\n10 Early vs. late MRD response- and risk-based treatment intensification of childhood acute lymphoblastic leukemia: a prospective pilot study from Saudi Arabia Exp Hematol Oncol Jastaniah W Elimam N Abdalla K 29 7 2018 30479872\n11 Who is the patient at risk of CMV recurrence: a review of the current scientific evidence with a focus on hematopoietic cell transplantation Infect Dis Ther Styczynski J 1 16 7 2018\n12 Cytomegalovirus retinitis in an ALL child during maintenance therapy treated successfully with intravenous ganciclovir Case Rep Ophthalmol Med Celiker H Karaaslan A Kepenekli Kadayifci E Atici S Soysal A Kazokoglu H Koc A 294238 2014 2014 25161790\n13 Cytomegalovirus retinitis in three pediatric cases with acute lymphoblastic leukemia: case series and review of the literature Jpn J Infect Dis Demir SÖ Çeliker H Karaaslan A 534 538 69 2016 26567834\n14 Cytomegalovirus disease in children with acute lymphoblastic leukemia Pediatr Hematol Oncol Jain R Trehan A Mishra B Singh R Saud B Bansal D 239 247 33 2016 27285991\n15 Thread: Cytomegalovirus (CMV) Retinitis: 36 year-old Indian male with HIV and decreasing visual acuity case 52021 Date J Muthialu A Folk JC 2006 https://www.meduweb.com/showthread.php/27942-Cytomegalovirus-(CMV)-Retinitis-36-year-old-Indian-male-with-HIV-and-decreasing-visual-acuity-case\n\n",
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"abstract": "Infectious complications are a very common and prominent cause of both morbidity and mortality in patients with systemic lupus erythematosus. We present a patient who developed a paravertebral primary tuberculous muscle abscess after aggressive treatment with corticosteroids and immunosuppressive agents.",
"affiliations": "Rheumatology Unit, Hospital NS Aranzazu, San Sebastian, Spain.",
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"title": "Primary tuberculous muscle abscess in a patient with systemic lupus erythematosus.",
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"abstract": "To report the long-term outcomes of three patients with infectious keratitis treated with riboflavin photodynamic antimicrobial therapy (PDAT).\nCase series reporting three patients with infectious keratitis unresponsive to standard medical treatment who underwent riboflavin photodynamic antimicrobial therapy (PDAT) as an adjunct therapy. One male and two female patients were treated, the median age of presentation was 58 years (range, 29-79 years). The organisms isolated and treated were Pseudomonas aeruginosa, Mycobacterium chenolae, and Curvularia spp. Different risk factors to develop corneal infection ulcers were identified, including corneal abrasion in a contact lens user, history of penetrating keratoplasty with chronic use of topical corticosteroids, and organic trauma. The median follow-up was 47 months (range 37-54 months), and there were no complications secondary to riboflavin PDAT treatment. Two cases underwent optical penetrating keratoplasty after infection was resolved and ocular surface was quiet for at least 3 years.\nRiboflavin PDAT can be used as an adjunct treatment in infectious keratitis to strengthen the corneal collagen fibers, delay keratolysis, and allow more time for antimicrobials to work and this way prevent a corneal perforation.",
"affiliations": "Anne Bates Leach Eye Hospital, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.;Ophthalmic Biophysics Center, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.;Anne Bates Leach Eye Hospital, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.;Ophthalmic Biophysics Center, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.;Ophthalmic Biophysics Center, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.;Anne Bates Leach Eye Hospital, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.;Anne Bates Leach Eye Hospital, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.;Anne Bates Leach Eye Hospital, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.;Anne Bates Leach Eye Hospital, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.;Anne Bates Leach Eye Hospital, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.;Anne Bates Leach Eye Hospital, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.",
"authors": "Martinez|Jaime D|JD|;Arboleda|Alejandro|A|;Naranjo|Andrea|A|;Aguilar|Mariela C|MC|;Durkee|Heather|H|;Monsalve|Pedro|P|;Dubovy|Sander R|SR|;Donaldson|Kendall E|KE|;Miller|Darlene|D|;Amescua|Guillermo|G|;Parel|Jean-Marie|JM|",
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"fulltext": "\n==== Front\nAm J Ophthalmol Case RepAm J Ophthalmol Case RepAmerican Journal of Ophthalmology Case Reports2451-9936Elsevier S2451-9936(18)30256-110.1016/j.ajoc.2019.100481100481Case ReportLong-term outcomes of riboflavin photodynamic antimicrobial therapy as a treatment for infectious keratitis Martinez Jaime D. ab1Arboleda Alejandro b1Naranjo Andrea abAguilar Mariela C. bDurkee Heather bMonsalve Pedro aeDubovy Sander R. adeDonaldson Kendall E. aMiller Darlene acAmescua Guillermo gamescua@med.miami.eduab∗Parel Jean-Marie abfa Anne Bates Leach Eye Hospital, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USAb Ophthalmic Biophysics Center, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USAc Ocular Microbiology Laboratory, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USAd Florida Lions Ocular Pathology Laboratory, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USAe Department of Pathology, University of Miami, University of Miami Miller School of Medicine, Miami, FL, USAf University of Liege Sart-Tillman CHU Dept. of Ophthalmology, Liege, Belgium∗ Corresponding author. Anne Bates Leach Eye Hospital Bascom Palmer Eye Institute University of Miami Miller School of Medicine, 900 NW 17th Street, Miami, FL, 33136. gamescua@med.miami.edu1 These authors contributed equally to this study.\n\n01 6 2019 9 2019 01 6 2019 15 10048119 6 2018 25 1 2019 29 5 2019 © 2019 The Authors2019This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Purpose\nTo report the long-term outcomes of three patients with infectious keratitis treated with riboflavin photodynamic antimicrobial therapy (PDAT).\n\nObservations\nCase series reporting three patients with infectious keratitis unresponsive to standard medical treatment who underwent riboflavin photodynamic antimicrobial therapy (PDAT) as an adjunct therapy. One male and two female patients were treated, the median age of presentation was 58 years (range, 29–79 years). The organisms isolated and treated were Pseudomonas aeruginosa, Mycobacterium chenolae, and Curvularia spp. Different risk factors to develop corneal infection ulcers were identified, including corneal abrasion in a contact lens user, history of penetrating keratoplasty with chronic use of topical corticosteroids, and organic trauma. The median follow-up was 47 months (range 37–54 months), and there were no complications secondary to riboflavin PDAT treatment. Two cases underwent optical penetrating keratoplasty after infection was resolved and ocular surface was quiet for at least 3 years.\n\nConclusions and importance\nRiboflavin PDAT can be used as an adjunct treatment in infectious keratitis to strengthen the corneal collagen fibers, delay keratolysis, and allow more time for antimicrobials to work and this way prevent a corneal perforation.\n\nKeywords\nCorneal infectious keratitisPhotodynamic antimicrobial therapyCrosslinkingRiboflavin\n==== Body\n1 Introduction\nEven with proper medical management, some cases of infectious keratitis can progress to a corneal perforation. In some of these cases, a therapeutic corneal transplant is required. However, performing a corneal transplant on an infected and inflamed ocular surface increases the risk of graft failure or graft rejection.1\n\nCorneal crosslinking with riboflavin and ultraviolet-A (UV-A) light has been established as a first-line treatment to prevent the progression of keratoconus or corneal ectasias by strengthening the corneal collagen fibers.2 It was later proposed as a treatment for infectious keratitis unresponsive to medical treatment and was described in the literature as photoactivated chromophore (PACK-CXL)3,4 or riboflavin Photodynamic Antimicrobial Therapy (PDAT).5,6 Bamdad et al. reported a randomized control trial in which the group treated with PACK-CXL had a shorter course of medical treatment and decreased need for therapeutic corneal transplantation.7 A few articles have reported the use of riboflavin CXL as an adjunct therapy for Pseudomonas keratitis4,8, 9, 10 and Mycobacterium keratitis,11,12 but none have reported its utility in treating Curvularia spp.\n\nWe present three cases of infectious keratitis that presented to Bascom Palmer Eye Institute and were treated with riboflavin PDAT. Informed consent was obtained, and the procedure was performed following a modified Dresden protocol.2 Under topical anesthesia, corneal ulcer scraping was performed 1–2 mm around the corneal epithelial defect. One drop of 0.1% riboflavin in 20% dextran solution was applied to the cornea every 3 minutes for a total of 30 minutes. A custom-made shield was placed over the limbal area for protection and the cornea was irradiated for 30 minutes with a custom-made ultraviolet-A (UV-A) light source for a radiant exposure of 5.4 J/cm2. (Fig. 1). The light source, previously described by Halili et al., who conducted in vitro experiments with multiple organisms, contains twenty-four 375nm LEDs and emits a power density of 3 mW/cm2.6Fig. 1 Custom-built riboflavin PDAT system (A) UVA light delivery unit on stand (1: height adjustment; 2: Battery power and cooling system) (B) Laptop to adjust and monitor irradiation timing and center light source over the patient eye (LS: LED light source; LC: Light source controller; GN: goose neck clamp to adjust source over patient eye) (C) Metal corneoscleral well filled with 0.1% riboflavin.\n\nFig. 1\n\n2 Findings\n2.1 Case 1\nA 29-year-old female was referred to our institution with a corneal ulcer secondary to a corneal abrasion while removing a soft contact lens from her right eye. Corneal ulcer cultures came back positive for Pseudomonas aeruginosa with S-/U+ genotype which did not respond to standard medical treatment for 15 days (Table 1 and Fig. 2A). The patient underwent riboflavin PDAT with placement of an amniotic membrane (Ambiodisk, Costa Mesa, CA, USA) and bandage contact lens following the procedure. Topical moxifloxacin with Doxycycline and Vitamin C was continued, while the patient started tapering prednisolone acetate.Table 1 Summary of patients with infectious keratitis who underwent riboflavin photodynamic antimicrobial therapy. All patients underwent a single PDAT session.\n\nTable 1Case #\tOrganism\tTreatment (Time on Tx prior RB PDAT)\tTime to Clinical Resolution (weeks)\tComplication\tSurgical Treatment (time post PDAT)\tTime FU (months)\nComment\t\n1\tPseudomonas aeruginosa\t0.5% Moxifloxacin\n14 mg/ml Fortified tobramycin\nDoxycycline PO 100 mg BID (15 days)\t8\tNone\tPK (12 m)\t54\nCorneal graft clear\t\n2\tMycobacterium chenolae\t5% Amikacin 2% Clarithromycin\n0.5% Moxifloxacin (7 days)\t4\tNone\tNone\t36\nCornea clear\t\n3\tCurvularia spp.\t5% Natamycin\n200 mg Fluconazole tablets,\n0.5% Moxifloxacin (15 days)\t10\tNone\tPK (31 m)\t41\nCorneal graft clear\t\nPK: penetrating keratoplasty; RB PDAT: riboflavin photodynamic antimicrobial therapy; FU: follow-up.\n\nFig. 2 Case 1. (A) Slit-lamp photograph of the right eye with corneal melting inferiorly and thinning. (B) two weeks after riboflavin PDAT, presenting with central corneal infiltrate shrinkage more than 50% and increased peripheral corneal neovascularization. (C) One year after riboflavin PDAT, no corneal infiltration or diffuse corneal scarring were observed. (D) Optical penetrating keratoplasty (OPK) was done one year after PDAT. (E) No organisms identified on gram stained section of cornea. Brown and Hopps gram stain, 400X. (F) OPK remains clear on last follow-up. . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)\n\nFig. 2\n\nThe patient significantly improved after 2 weeks of riboflavin PDAT (Fig. 2 B). Two months after PDAT, antibiotic treatment was suspended. One year after PDAT, the best corrected visual acuity (BCVA) was 20/800, and examination revealed a vascularized and opacified cornea with complete epithelialization and quiet conjunctiva without hyperemia (Fig. 2C). Fifteen months after riboflavin PDAT treatment, we proceeded with an optical penetrating keratoplasty (PK) followed by amniotic membrane placement without complications (Fig. 2D and E). Four years and 6 months after the riboflavin PDAT procedure, BCVA was 20/30, IOP was 20 mmHg, and the corneal graft remained clear without signs of rejection or infection. (Fig. 2F).\n\n2.2 Case 2\nA 79-year-old female patient with history of PK secondary to Fuchs corneal dystrophy 13 years prior, presented with left eye progressive infectious keratitis in the left eye presumed to be secondary to a loose suture. Corneal ulcer cultures came back positive for Mycobacterium chenolae sensitive to Clarithromycin and with intermediate sensitivity to Amikacin (Table 1 and Fig. 3A). There was no improvement in the following 7 days on standard medical treatment and the decision to undergo riboflavin PDAT was made due to the presence of progressive keratolysis. After PDAT, she was started on 0.5% Cyclosporine drops 4 times a day. Nine days after PDAT, the BCVA was 20/200, there was decreased conjunctival hyperemia, and the epithelial defect had healed (Fig. 3B). Three years after riboflavin PDAT, the patient continued on acetate prednisolone eye drops once a day, her BCVA was 20/40 and IOP was19 mmHg. Slit-lamp examination showed a quiet conjunctiva, clear corneal graft and IOL in place (Fig. 3C).Fig. 3 Case 2. (A) Slit-lamp photograph of the left eye. Corneal infiltrate of 1 mm at 3–4 o'clock with corneal epithelial defect. (B) Nine days after riboflavin PDAT, corneal melting stopped, and epithelium healed. (C) Four weeks after riboflavin PDAT, no evidence of infiltrate, corneal scar at 3–4 o'clock. (D) Corneal graft remains clear on last follow-up.\n\nFig. 3\n\n2.3 Case 3\nA 58-year-old male presented with a corneal ulcer in the right eye caused by injury while cutting a tree branch. Corneal ulcer cultures came back positive for Curvularia spp. The patient was started on Natamycin every hour and 0.5% Moxifloxacin every 4 hours (Table 1 and Fig. 4 A). After 15 days without clinical improvement and due to rapid progression of the stromal necrosis, the patient underwent riboflavin PDAT. After treatment, the medication regimen was: Natamycin eye drops every 2 hours, 200 mg Fluconazole tablets twice a day, Cyclosporine-A eye drops 4 times a day, Atropine once a day, and Moxifloxacin (Fig. 4B). After 2 months, the corneal infiltrate disappeared, but evidence of deep stromal neovascularization was found (Fig. 4C). Topical and systemic antifungal medications were discontinued. Six months after riboflavin PDAT, the patient's visual acuity was 20/800 with moderate corneal scarring in the visual axis, a cataract, and iris synechiae (Fig. 4D). Finally, the patient underwent cataract surgery and intraocular lens placement without complications. Four months after surgery, BCVA was 20/70, but the patient complained of severe glare. An optical PK and pupilloplasty was performed (Fig. 4 E, and F). Three years and 5 months after riboflavin PDAT, BCVA was 20/70, IOP was 16 mmHg, and the corneal graft remained clear with no signs of rejection or infection.Fig. 4 Case 3. (A) Slit-lamp photograph of the right eye. Initial presentation: central corneal epithelial defect and dense inferior paracentral corneal infiltrate. (B) Four weeks after riboflavin PDAT, corneal infiltrate decreased and began developing central neovascularization with 1 mm hypopyon. (C) After 2 months, healed cornea with no infiltrate or corneal epithelial defect. (D) Six months after riboflavin PDAT, right eye revealed corneal scarring.(E) No organism identified on Gomori Methenamine-Silver Nitrate stain (GMS) stained section of cornea 400 X. (F) OPK remains clear on last follow-up.\n\nFig. 4\n\n3 Discussion\nInfectious keratitis is a challenging disease, where the causative organisms may display unpredictable behavior and resistance to standard medical treatment. Furthermore, complications that arise from the resistance to topical antimicrobials can lead to devastating consequences.4 The patients in this study exhibited risk factors of infectious keratitis: contact lens use, prior corneal surgery, and prolonged steroid use.13,14,15\n\nOver the last decade, attempts have been made to treat refractory cases of infectious keratitis with new medications and technologies, one such being PACK-CXL. Both in vitro and in vivo studies have shown microbial inhibition of Pseudomonas aeruginosa,16, 17, 18\nMycobacterium chenolae,12 and filamentous fungi with CXL treatment.19\n\nCurvularia spp. is a rare cause of fungal keratitis in the United States, however, there has been an increase of in the number of cases reported in our institution.20 In the case reported, the patient progressed to stromal necrosis despite compliance to standard medical treatment. Other cases have either responded to standard medical treatment, required a therapeutic penetrating keratoplasty, or have been treated for endophthalmitis.\n\nStudies have shown that the adjunct effect of antibiotics and CXL is greater in treating infections than antibiotics alone or CXL alone.17 The patients in our study may be benefitting from this finding, and the marked improvement after PDAT may be due to the synergistic effect of the light therapy and medications. Given the aggressive nature of the microorganisms and the advanced stage of the infections, adjunct treatment was offered to the patients to provide the most effective treatment.\n\nStudies by Said et al. and Kasetsuwan et al., showed that PACK-CXL reduced late complications such as corneal perforation or recurrence of infection compared to antibiotic treatment alone.4,21 Moreover, Bamdad et al. demonstrated a faster recovery of epithelial defect and infiltrates with PACK-CXL.7 Zamani et al. reported 8 patients diagnosed with Pseudomonas aeruginosa keratitis who did not respond to standard antimicrobial treatment; however, after riboflavin CXL treatment, all patients had substantial improvement.22 This is similar to our cases, in which patients continued to worsen despite standard medical treatment until riboflavin PDAT was performed. Shortly after PDAT, patients improved both subjectively and objectively, reporting less pain and appearing better on slit lamp exam. Our presented cases have a significant longer follow up after riboflavin PDAT compared to reported cases in the literature.\n\nAll three patients treated with riboflavin PDAT had a good long-term outcome with no complications. A potential explanation for this may be increased resistance of corneal tissue to enzymatic digestion following PDAT. This enhances corneal strength, delays corneal melting, and allows time for the antimicrobials to take effect.23 Further studies should be performed to better understand the changes of tissues following PDAT.\n\nIn summary, the cases presented highlight the use of riboflavin PDAT as an adjunct treatment for infectious keratitis, with good long-term outcome. Even in the setting of thin corneas, this treatment can help prevent a perforation that would normally result in a therapeutic corneal transplant. Although results are encouraging, and the patients presented had favorable outcomes, we understand the limitations of a retrospective study. Prospective controlled clinical trials are needed to confirm the effectiveness of Riboflavin PDAT in severe cases of infectious keratitis.\n\n4 Patient consent\nThe project was deemed to meet criteria for a case series by the University of Miami Institutional Review Boards (IRB). Therefore, no IRB submission was required prior to reviewing the cases. The study was conducted in accordance with the principles of the Declaration of Helsinki. Patients in this series provided signed voluntary and informed consent to the described treatment. Patients in this series displayed appropriate capacity to provide consent. Patients understood the risks, benefits, and alternatives for the riboflavin photodynamic antimicrobial therapy and understood they were entitled to withdraw previous consent at any time during the treatment.\n\nConsent to publish the case series was not obtained from the patients. The case series does not contain any identifying information.\n\nFunding\nSupported in part by Edward D. and Janet K. Robson Foundation (Tulsa, OK). Florida Lions Eye Bank and the Beauty of Sight Foundation (Miami, FL), Drs. K. R. Olsen and M. E. Hildebrandt, Drs. Raksha Urs, and Aaron Hurtado, NIH Center Grant P30EY14801, Research to Prevent Blindness, Henri and Flore Lesieur Foundation (Chicago, IL) (J.-M. Parel). Research to Prevent Blindness, the Pan-American Association of Ophthalmology and Retina Research Foundation (J. D. Martinez).\n\nConflicts of interest\nNone of the authors have financial disclosures.\n\nAuthorship\nAll authors attest that they meet the current ICMJE criteria for Authorship.\n\nAcknowledgments\nThe authors of this study would like to thank Jennifer Phu for her help preparing the patients and coordinating the treatments. Cynthia Maza from the Florida Lions Ocular Pathology laboratory for helping with histopathology. Harry W. Flynn, MD for following patients, Cornelis Rowaan, BS, Alex Gonzalez, BA, and Wiliam Lee of the Ophthalmic Biophysics Center for participating to the design, development, and construction of the UVA irradiation source,Xiao-Yi Zhou MD and Cynthia Maza, from the Florida Lions Ocular Pathology laboratory for helping with histopathology.\n==== Refs\nReferences\n1 Hossain P. Emergency corneal grafting in the UK: a 6-year analysis of the UK Transplant Registry Br J Ophthalmol 102 1 2018 26 30 28495906 \n2 Wollensak G. Spoerl E. Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus Am J Ophthalmol 135 5 2003 620 627 12719068 \n3 Price M.O. Price F.W. Jr. Corneal cross-linking in the treatment of corneal ulcers Curr Opin Ophthalmol 27 3 2016 250 255 26730652 \n4 Said D.G. Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the treatment of advanced infectious keratitis with corneal melting Ophthalmology 121 7 2014 1377 1382 24576886 \n5 Arboleda A. Assessment of rose bengal versus riboflavin photodynamic therapy for inhibition of fungal keratitis isolates Am J Ophthalmol 158 1 2014 64 70 e2 24792103 \n6 Halili F. Rose bengal- and riboflavin-mediated photodynamic therapy to inhibit methicillin-resistant Staphylococcus aureus keratitis isolates Am J Ophthalmol 166 2016 194 202 27016125 \n7 Bamdad S. Malekhosseini H. Khosravi A. Ultraviolet A/riboflavin collagen cross-linking for treatment of moderate bacterial corneal ulcers Cornea 34 4 2015 402 406 25710507 \n8 Price M.O. Photoactivated riboflavin treatment of infectious keratitis using collagen cross-linking technology J Refract Surg 28 10 2012 706 713 23062001 \n9 Shetty R. Collagen crosslinking in the management of advanced non-resolving microbial keratitis Br J Ophthalmol 98 8 2014 1033 1035 24711659 \n10 Mattila J.S. Treatment of Pseudomonas aeruginosa keratitis with combined corneal cross-linking and human amniotic membrane transplantation Acta Ophthalmol 91 5 2013 e410 e411 23844860 \n11 Alio J.L. Corneal cross linking and infectious keratitis: a systematic review with a meta-analysis of reported cases J Ophthalmic Inflamm Infect 3 1 2013 47 23718849 \n12 Iseli H.P. Ultraviolet A/riboflavin corneal cross-linking for infectious keratitis associated with corneal melts Cornea 27 5 2008 590 594 18520510 \n13 Augustin D.K. Role of defensins in corneal epithelial barrier function against Pseudomonas aeruginosa traversal Infect Immun 79 2 2011 595 605 21115716 \n14 Martinez J.D. Bilateral Mycobacterium chelonae keratitis after phacoemulsification cataract surgery Case Rep Ophthalmol Med 2017 2017 6413160 29234549 \n15 Wilhelmus K.R. Jones D.B. Curvularia keratitis Trans Am Ophthalmol Soc 99 2001 111 130 discussion 130-2 11797300 \n16 Makdoumi K. Evaluation of antibacterial efficacy of photo-activated riboflavin using ultraviolet light (UVA) Graefes Arch Clin Exp Ophthalmol 248 2 2010 207 212 19921518 \n17 Cosar C.B. Microbiologic, pharmacokinetic, and clinical effects of corneal collagen cross-linking on experimentally induced Pseudomonas keratitis in rabbits Cornea 34 10 2015 1276 1280 26226468 \n18 Schrier A. In vitro antimicrobial efficacy of riboflavin and ultraviolet light on Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa J Refract Surg 25 9 2009 S799 S802 19772254 \n19 Alshehri J.M. Evaluation of corneal cross-linking for treatment of fungal keratitis: using confocal laser scanning microscopy on an ex vivo human corneal model Investig Ophthalmol Vis Sci 57 14 2016 6367 6373 27898982 \n20 Ashvini Reddy A.R. Miller Darlene Flynn Harry Smiddy William Lara Wilfredo Albini Thomas The incidence of Curvularia keratitis and A case series of Curvularia endophthalmitis Investig Ophthalmol Vis Sci 54 15 2013 1102 \n21 Kasetsuwan N. Reinprayoon U. Satitpitakul V. Photoactivated chromophore for moderate to severe infectious keratitis as an adjunct therapy: a randomized controlled trial Am J Ophthalmol 165 2016 94 99 26949133 \n22 Zamani M. Panahi-Bazaz M. Assadi M. Corneal collagen cross-linking for treatment of non-healing corneal ulcers J Ophthalmic Vis Res 10 1 2015 16 20 26005547 \n23 Sachdev G.S. Sachdev M. Recent advances in corneal collagen cross-linking Indian J Ophthalmol 65 9 2017 787 796 28905820\n\n",
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{
"abstract": "Alternaria spp. infections are rare, but organ transplant recipients and immunosuppressed patients are particularly at risk of developing cutaneous alternariosis. Although cutaneous alternariosis is well-defined, instances of disseminated infection are exceedingly rare. We report a case of disseminated Alternaria infection in an immunocompromised patient from a primary focus of ungual phaeohyphomycosis.",
"affiliations": "Division of Dermatology, University of Louisville, Louisville, KY. cindy.owen@louisville.edu.",
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"medline_ta": "Dermatol Online J",
"mesh_terms": "D000528:Alternaria; D060487:Alternariosis; D000671:Amputation; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D016867:Immunocompromised Host; D008875:Middle Aged; D014034:Toes",
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"title": "Onset of disseminated cutaneous nodules following toe amputation in heart transplant patient.",
"title_normalized": "onset of disseminated cutaneous nodules following toe amputation in heart transplant patient"
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"abstract": "Caffeine is a known inhibitor of Clozapine metabolism mediated by inhibition of CYP1A2. Hitherto, the effects of caffeine on Clozapine levels have always been modest, as have the clinical manifestations of toxicity resulting from their interaction. We present a case of severe toxicity associated with the co-consumption of caffeine and Clozapine culminating in life-threatening complications requiring management in Intensive Care.\n\n\n\nA 34 year old male with a history of chronic schizophrenia, who had been managed stably on 400 mg Clozapine for the previous 5 years, changed his dietary behaviour and began consuming caffeine-containing energy drinks over the course of 3 weeks. The total daily dose of caffeine was estimated as 600 mg/day (four cans of Red Bull). He subsequently presented to the Emergency Department with life-threatening Clozapine toxicity, resulting in a decreased level of consciousness, severe metabolic acidosis, acute respiratory failure, raised inflammatory markers and acute renal failure attributed to interstitial nephritis. Maximum recorded Clozapine level was 1796 ng/ml.\n\n\n\nThis case describes the interaction between a common caffeine-containing beverage and a commonly prescribed antipsychotic medication, associated with severe adverse effects. We call for clinical and scientific attention to the possible interaction between these substances and draw attention to the implications for prescribing practices and patient counselling.",
"affiliations": "Westmead Hospital Intensive Care Unit, Sydney, Australia. alex.yartsev@health.nsw.gov.au.;Westmead Hospital Intensive Care Unit, Sydney, Australia.",
"authors": "Yartsev|Alex|A|0000-0003-2901-496X;Peisah|Carmelle|C|",
"chemical_list": "D014150:Antipsychotic Agents; D002110:Caffeine; D003024:Clozapine",
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"fulltext": "\n==== Front\nBMC Psychiatry\nBMC Psychiatry\nBMC Psychiatry\n1471-244X\nBioMed Central London\n\n3199\n10.1186/s12888-021-03199-x\nCase Report\nCaffeine-clozapine interaction associated with severe toxicity and multiorgan system failure: a case report\nhttp://orcid.org/0000-0003-2901-496X\nYartsev Alex alex.yartsev@health.nsw.gov.au\n\n1\nPeisah Carmelle 12\n1 grid.413252.3 0000 0001 0180 6477 Westmead Hospital Intensive Care Unit, Sydney, Australia\n2 grid.1005.4 0000 0004 4902 0432 University New South Wales, Sydney, Australia\n13 4 2021\n13 4 2021\n2021\n21 19223 11 2020\n5 4 2021\n© The Author(s) 2021\nhttps://creativecommons.org/licenses/by/4.0/ Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nBackground\n\nCaffeine is a known inhibitor of Clozapine metabolism mediated by inhibition of CYP1A2. Hitherto, the effects of caffeine on Clozapine levels have always been modest, as have the clinical manifestations of toxicity resulting from their interaction. We present a case of severe toxicity associated with the co-consumption of caffeine and Clozapine culminating in life-threatening complications requiring management in Intensive Care.\n\nCase presentation\n\nA 34 year old male with a history of chronic schizophrenia, who had been managed stably on 400 mg Clozapine for the previous 5 years, changed his dietary behaviour and began consuming caffeine-containing energy drinks over the course of 3 weeks. The total daily dose of caffeine was estimated as 600 mg/day (four cans of Red Bull). He subsequently presented to the Emergency Department with life-threatening Clozapine toxicity, resulting in a decreased level of consciousness, severe metabolic acidosis, acute respiratory failure, raised inflammatory markers and acute renal failure attributed to interstitial nephritis. Maximum recorded Clozapine level was 1796 ng/ml.\n\nConclusions\n\nThis case describes the interaction between a common caffeine-containing beverage and a commonly prescribed antipsychotic medication, associated with severe adverse effects. We call for clinical and scientific attention to the possible interaction between these substances and draw attention to the implications for prescribing practices and patient counselling.\n\nKeywords\n\nClozapine\nCaffeine\nInteraction\nMultiorgan system failure\nCase report\nissue-copyright-statement© The Author(s) 2021\n==== Body\nBackground\n\nClozapine is a commonly prescribed medication indicated for the management of treatment-resistant schizophrenia, with a worldwide pattern of increasing use [1–3]. Clozapine is a dibenzazepine derivative which is metabolised predominantly by the liver, the two principal metabolites being desmethylClozapine and Clozapine N-oxide. The demethylation of Clozapine which produces desmethylClozapine is performed by CYP1A2 [4]. Caffeine inhibits the metabolism of Clozapine, probably by inhibition of CYP1A2. The effect of caffeine on Clozapine levels in studies of healthy volunteers has always been modest. For example, serum Clozapine levels increased by only 19% following co-administration of Clozapine (12.5 mg) and caffeine (100 mg) in healthy young adults [5, 6]. Further, the clinical manifestations of toxicity resulting from the interaction of Clozapine and caffeine hitherto described have been similarly relatively mild and have included stiffness, abrupt onset of arousal and exacerbation of psychosis, all of which were easily reversible [6, 7]. However, significant interindividual variability exists in pharmacokinetics of commonly used antipsychotics8. The aforementioned case studies report a Clozapine dose of 200 mg and a caffeine dose of 425-850 mg/day in one scenario [7] and a Clozapine dose of 550 mg with a caffeine intake of 200 mg/d the other [6]. We are unaware of any previous reports of severe, life-threatening interactions between caffeine and Clozapine. We present a case of a patient with chronic schizophrenia managed with a stable long-term dose of Clozapine who presented with severe Clozapine toxicity culminating in multisystem organ failure due to a change in caffeine intake. While this severe adverse interaction is unusual, consumption of high energy drinks is part of a raft of poor nutritional habits often associated with serious mental illness such as schizophrenia both in a chronic state [8–10], as well as a manifestation of relapse [11, 12]. Hence, the importance of shedding light on this case.\n\nCase presentation\n\nA 35 year-old male was brought to the emergency department by ambulance after being found unconscious in his home.\n\nHistory of presenting complaint\n\nHe was last seen to be alert twenty-four hours prior. On the day of his presentation, his carer found him sitting slumped against the wall on the floor, obtunded and tachypnoeic. The ambulance officers made a note of “energy drinks spread over living room table” in his home. At triage in the emergency department, his respiratory rate was 50, heart rate 110, non-invasive systolic blood pressure 129 mmHg. Glasgow coma score (GCS) was initially scored as 14 (E = 4 V = 4 M = 6) and the blood sugar level (BSL) was 32.5 mmol/L. A tympanic temperature of 38.0 C was recorded. Arterial blood gas analysis revealed a profound metabolic acidosis with pH of 6.91, PaCO2 44 mmHg, HCO3− 10, lactate of 6.2, and an anion gap of 26 mmol/L. Point-of-care testing revealed a serum ketone level of 3.0. Given the raised BSL and decreased level of consciousness, a provisional diagnosis of hyperosmolar hyperglycaemic syndrome with diabetic ketoacidosis was made. Shortly after triage, the patient’s level of consciousness deteriorated, with a GCS score of 6 (E = 1 V = 1 M = 4). He was intubated and transferred to the Intensive Care Unit (ICU). A urine drug screen was obtained prior to the intubation, and was negative for all tested substances (amphetamine, cannabis, cocaine, MDMA, benzodiazepines and opiates).\n\nProgress during ICU admission\n\nOver the subsequent 2 days of his stay in the ICU, the patient remained unconscious with minimal sedation, and dependent on mechanical ventilation. He required modest ventilator support and his fraction of inspired oxygen (FiO2) was weaned to 0.3 within the first twenty-four hours.\n\nHe remained stable haemodynamically, and did not require any vasoactive agents to support his blood pressure. During the first 2 days of ICU admission he remained febrile and a significant inflammatory marker rise was observed, with a CRP of 520 mg/L and a procalcitonin of 13.21 μg/L, rising at maximum over his course of stay to 40.77 μg/L. As septic shock was suspected, empiric antimicrobial therapy with meropenem (1 g every 8 h) was commenced. He underwent a computed tomography scan (CT) of the head, chest, abdomen and pelvis, which did not reveal any foci of infection. Specifically, no structural abnormality of the kidneys was detected, nor any changes in the lungs which might have been associated with aspiration pneumonia. Blood cultures and urine cultures did not yield any pathogenic organisms, and COVID-19 PCR was negative. Meropenem was ceased on the third day of admission, as there remained no clinical features of infection.\n\nAs the patient had become anuric and was developing clinically significant fluid overload, a vas cath was placed and continuous renal replacement therapy was commenced (continuous veno-venous haemodiafiltration, CVVHDF). As the serum Clozapine level taken on admission to the emergency department had now became available (1796 ng/ml), Clozapine-induced interstitial nephritis was raised as a possibility, and a trial of intravenous methylprednisolone was commenced empirically (as the patient’s morbidly obese body habitus did not lend itself to a safe renal biopsy). Methylprednisolone (250 mg daily) was used for a total duration of 5 days.\n\nAfter day three of ICU admission, the patient had regained consciousness, and was able to obey simple commands. Having been commenced on olanzapine earlier in the admission for agitation, this was weaned and ceased and aripiprazole (5 mg daily) commenced via NGT (ie prior to extubation) chosen for its safest use in renal failure and in hyperglycaemia. This was well-tolerated and continued for the remainder of his admission.\n\nAfter fluid removal by haemofiltration the patient was extubated on Day 4 of ICU admission, with no further respiratory sequelae. At this stage, the Clozapine level had decreased to 926 μg/L. (see Fig. 1). Fig. 1 “Clozapine level and NorClozapine level”. Solid line: Clozapine level. Dashed line: norClozapine level\n\nPast medical and surgical history\n\nThe patient had a background history of morbid obesity (weight = 142 kg; BMI 48.9 kg/m2), childhood asthma, gastro-oesophageal reflux disease, hypercholesterolaemia and impaired glucose tolerance. His regular medications consisted of Clozapine 400 mg nocte, esomeprazole 20 mg mane, atorvastatin 10 mg nocte, and metformin 500 mg nocte. He was a lifelong non-smoker, and consumed alcohol every day (4 beers, or approximately 60 g of ethanol per day) until the week prior to presentation (see below).\n\nPast psychiatric history\n\nThe patient was commenced on Clozapine (400 mg nocte) 2 years prior to these events, following a prolonged inpatient admission to a mental health facility during which several other agents were trialled unsuccessfully. His psychiatrist confirmed that on Clozapine the patient had remained stable with no relapses and regular clinic attendance. Clozapine levels in the community had been within the normal therapeutic range.\n\nPrior to presentation he had been living alone and working as a cleaner up until the COVID pandemic. He was relatively independent in activities of daily living, although received assistance weekly with grocery shopping from a support worker. He self- administered medications and Clozapine levels had been stable during outpatient therapy, as had been his haematological indices on regular screening, with the exception of mildly reduced lymphocytes at times (with preservation of neutrophil levels). These historical data suggest that this patient was not suffering from any cardiovascular or immunological complications of Clozapine therapy which might otherwise explain his presentation and multi-organ system failure.\n\nMental status examination\n\nUpon review of his mental status following extubation, the patient was appropriate with euthymic mood and bright, reactive affect. There was no evidence of active psychotic symptoms (i.e. no thought disorder, no perceptual abnormalities nor abnormalities of content) or delirium. He denied any suicidal ideation either cross-sectionally or prior to presentation, and rather reported usual compliance with his medication in the weeks leading up to his presentation. He demonstrated good insight and judgement, including help seeking and wanting to remain on psychotropics. According to his own account, during the week before admission, he had decreased his intake of alcohol to zero, while increasing his intake of energy drinks to achieve weight loss with his daily consumption of caffeine fluctuating between 150 and 450 mg/day (between two and six 250 ml cans of Red Bull per day, with a caffeine concentration of 30 mg/100 ml).\n\nProgress and outcome\n\nThe patient was discharged from the ICU after ten days. Methylprednisolone had transitioned to oral prednisolone, the dose of which was weaned gradually over 3 weeks, and ceased. Other complications of his stay included a left lower limb DVT and HITS, which had required intravenous bivalirudin as a bridge to warfarin therapy. His renal function remained impaired following discharge from the ICU, and renormalised only after fourteen days. He was discharged home after a total hospital stay of twenty-seven days. On consultation with the patient and his regular psychiatrist, aripiprazole was continued instead of Clozapine as his regular therapy.\n\nDiscussion and conclusions\n\nThis case describes significant morbidity associated with Clozapine toxicity, which most likely resulted from the interaction between Clozapine and caffeine in an otherwise stable patient with chronic schizophrenia.\n\nClozapine is a known cause of acute interstitial nephritis [13], which manifests as acute kidney injury characterised by the histological finding of inflammatory oedema in the tubulointerstitium of the kidney. Although it is usually described in association with fever, skin rash, and eosinophilia, in reality only a minority of patients demonstrate these “classic” features [14]. Case reports of Clozapine-induced acute interstitial nephritis generally describe renal impairment of subacute onset in stable patients undergoing outpatient treatment [13]. Only one case of Clozapine-induced nephritis required intermittent haemodialysis [15].\n\nClozapine use per se is also a known cause of elevated inflammatory markers and fever, although this phenomenon is usually associated with Clozapine-induced myocarditis. The presence of CRP elevation in association with Clozapine therapy and without myocarditis is also known from case reports [16, 17] where a modest CRP elevation was observed (55.4–122 mg/L). However, in this case, the patient remained febrile for forty-eight hours with temperatures exceeding 39.0 C and had a CRP value of 520 mg/L, more consistent with sepsis. Similarly, a modestly elevated procalcitonin has been reported in association with Clozapine use [18] although in this case, procalcitonin levels were in a range usually associated with severe septic shock. Nothwithstanding this, the only positive peripheral blood culture was collected at the time of his admission to the ED, and had grown S.epidermitis, which was dismissed as a contaminant.\n\nThe other manifestation of severe Clozapine toxicity illustrated here was hyperosmolar hyperglycaemic syndrome with diabetic ketoacidosis, to which the patient was likely prone given his pre-existing metabolic syndrome and Clozapine use [19, 20]. These pre-existing conditions distinguish patients with schizophrenia on long-term antipsychotics such as Clozapine from healthy young adults – upon whom some of the drug interaction studies have been based – and go towards explaining the severity of the toxicity seen in this case.\n\nThe risk of drug interaction – not only involving therapeutic drugs but also recreational agents such as caffeine - must be taken into account when prescribing antipsychotic agents to patients with schizophrenia. This is all the more so because the consumption of caffeinated beverages- whether it be in the form of energy drinks, diet drinks or coffee - is almost ubiquitous and often perceived as harmless by patients. Moreover, the desire to lose weight – the driver in this case - is a natural and desirable response to the weight gain associated with antipsychotic drug use. However, the question remains: how much is “significant amounts of caffeine?” For example, Ellison and Dufresne suggested that caffeine can appreciably inhibit CYP1A2 with the equivalent of three cups of coffee per day [21], or approximately 3 mg/kg of caffeine. More conservatively, de Leon referred to “dramatic changes in caffeine intake” by more than one cup of coffee or two cans of caffeinated soda [22]. By removing caffeine (on average 162 mg/day) from the diet of patients who were receiving Clozapine monotherapy (271 +/− 102 mg/day) and neither alcohol nor any other medication, Carillo et al. [23] were able to reduce Clozapine levels by 46% (from 486 to 306 ng/mL). Given the interindividual variability in pharmacokinetics [24] there is no definitive answer, other than to arm the patient with the information and risks.\n\nThis case of severe Clozapine toxicity may not be attributed entirely to the interaction between Clozapine and caffeine. Clozapine is a substrate for multiple CYP450 enzymes, which include CYP2D6 and CYP3A4 as well as the CYP1A2 pathway affected by caffeine [4]. The patient was also regularly prescribed atorvastatin (10 mg nocte) which is known to inhibit CYP3A4 [25], esomeprazole (20 mg mane) which is not known to inhibit CYP450 enzymes [26] but which may compete with Clozapine as a substrate for CYP3A4, and metformin which does not undergo hepatic metabolism. The doses of these regular medications had remained unchanged for at least 12 months prior to this presentation, during which time the patient had stable Clozapine levels, which makes it unlikely that an atorvastatin-Clozapine interaction had contributed significantly to this sudden onset of severe toxicity. Esomeprazole, by acting as a competitive substrate for CYP3A4, may have contributed to Clozapine toxicity by eliminating this alternative pathway of metabolism, when clearance by the CYP1A2 pathway became unavailable. The patient had also been drinking up to 4 standard drinks of alcohol per day up util 1 week prior to his presentation. Ethyl alcohol is a known inducer of CYP3A4 [27], and the withdrawal of this effect (resulting in reduced CYP3A4 activity) could have contributed to decreased Clozapine clearance by increasing the reliance on the CYP1A2 pathway, which is inhibited by caffeine.\n\nPatient education regarding the potential for drug interaction with specific enquiry into caffeine consumption should form a routine part of psychiatric clinical practice. The severity of the manifestations of Clozapine toxicity resulting from co-consumption of significant amounts of caffeine behoves us to warn our patients of this potential for serious harm from these interactions. Caffeine is not worth dying for.\n\nAbbreviations\n\nICU Intensive Care Unit\n\nGCS Glasgow Coma Scale\n\nBSL Blood Sugar Level\n\nSBE Standard Base Excess\n\nCVVHDF Continuous Veno-Venous HaemoDiaFiltration\n\nNGT NasoGastric Tube\n\nHITS Heparin-Induced Thrombocytopenia Syndrome\n\nDVT Deep Venous Thrombosis\n\nAcknowledgements\n\nThe authors acknowledge the contribution of Ms. Angela Netluch (Clinical Pharmacist) for her contribution to the care of this patient, for identifying the drug interaction, and for her assistance with the manuscript.\n\nAuthors’ contributions\n\nAY was the primary ICU consultant treating the patient, was corresponding author of the manuscript, and wrote the manuscript. CP was one of the consultant psychiatrists involved in his care and contributed to the writing of the manuscript. All authors have read and approved the manuscript.\n\nFunding\n\nThe authors received no funding to support this publication.\n\nAvailability of data and materials\n\nPatient data supporting the results reported in the article can be obtained from the corresponding author by email.\n\nDeclarations\n\nEthics approval and consent to participate\n\nThe patient has given his written consent for the publication of de-identified case information regarding his medical condition and its management\n\nConsent for publication\n\nThe patient has given his written consent for the publication of de-identified case information regarding his medical condition and its management\n\nCompeting interests\n\nThe authors declare that they have no competing interests\n\nPublisher’s Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n\n1. Xu SW Dong M Zhang Q Yang SY Chen LY Sim K He YL Chiu HF Sartorius N Tan CH Chong MY Clozapine prescription pattern in patients with schizophrenia in Asia: the REAP survey (2016) Psychiatry Res 2020 287 112271 10.1016/j.psychres.2019.02.056 30885383\n2. Bachmann CJ Aagaard L Bernardo M Brandt L Cartabia M Clavenna A Coma Fusté A Furu K Garuoliené K Hoffmann F Hollingworth S International trends in clozapine use: a study in 17 countries Acta Psychiatr Scand 2017 136 1 37 51 10.1111/acps.12742 28502099\n3. Siskind DJ Harris M Phillipou A Morgan VA Waterreus A Galletly C Carr VJ Harvey C Castle D Clozapine users in Australia: their characteristics and experiences of care based on data from the 2010 National Survey of high impact psychosis Epidemiol Psychiatric Sci 2017 26 3 325 337 10.1017/S2045796016000305\n4. Pirmohamed M Williams D Madden S Templeton E Park BK Metabolism and bioactivation of clozapine by human liver in vitro J Pharmacol Exp Ther 1995 272 3 984 990 7891353\n5. Hägg S Spigset O Mjörndal T Dahlqvist R Effect of caffeine on clozapine pharmacokinetics in healthy volunteers Br J Clin Pharmacol 2000 49 1 59 63 10.1046/j.1365-2125.2000.00111.x 10606838\n6. Odom-White A de Leon J Clozapine levels and caffeine J Clin Psychiatry 1996 57 4 175 176 8601555\n7. Vainer JL Chouinard G Interaction between caffeine and clozapine J Clin Psychopharmacol 1994 14 4 284 285 10.1097/00004714-199408000-00014 7962690\n8. Bogomolova S Zarnowiecki D Wilson A Fielder A Procter N Itsiopoulos C O'Dea K Strachan J Ballestrin M Champion A Parletta N Dietary intervention for people with mental illness in South Australia Health Promot Int 2018 33 1 71 83 10.1093/heapro/daw055 27476869\n9. Rihs M Muller C Baumann P Caffeine consumption in hospitalized psychiatric patients Eur Arch Psychiatry Clin Neurosci 1996 246 2 83 92 10.1007/BF02274898 9063913\n10. Kruger A Chronic psychiatric patients’ use of caffeine: pharmacological effects and mechanisms Psychol Rep 1996 78 3 915 923 10.2466/pr0.1996.78.3.915 8711047\n11. Cerimele JM Stern AP Jutras-Aswad D Psychosis following excessive ingestion of energy drinks in a patient with schizophrenia Am J Psychiatry 2010 167 3 353 10.1176/appi.ajp.2009.09101456 20194494\n12. Menkes DB Transient psychotic relapse temporally related to ingestion of an \"energy drink\" Med J Aust 2011 194 4 206 10.5694/j.1326-5377.2011.tb03777.x 21401467\n13. Chan SY Cheung CY Chan PT Chau KF Clozapine-induced acute interstitial nephritis Hong Kong Med J 2015 21 4 372 374 10.12809/hkmj144312 26238137\n14. Clarkson MR Giblin L O'Connell FP O'Kelly P Walshe JJ Conlon P O'Meara Y Dormon A Campbell E Donohoe J Acute interstitial nephritis: clinical features and response to corticosteroid therapy Nephrol Dial Transplant 2004 19 11 2778 2783 10.1093/ndt/gfh485 15340098\n15. Elias TJ Bannister KM Clarkson AR Faull D Faull RJ Clozapine-induced acute interstitial nephritis Lancet 1999 354 9185 1180 1181 10.1016/S0140-6736(99)01508-1 10513719\n16. Davey P Gee S Shergill SS Inflammatory response to clozapine in the absence of myocarditis: case report BJPsych open 2016 2 3 244 246 10.1192/bjpo.bp.116.003228 27703781\n17. Štuhec M Clozapine-induced elevated C-reactive protein and fever mimic infection Gen Hosp Psychiatry 2013 35 6 680 6e5 24199788\n18. Duarte TA, Godinho FD, Ferreira AL, Simões do Couto F, Martins PT. Clozapine-Induced Procalcitonin Elevation. Prim Care Companion CNS Disord. 2017;19(3).\n19. Cohen D Correll CU Second-Generation Antipsychotic-Associated Diabetes Mellitus and Diabetic Ketoacidosis: Mechanisms, Predictors, and Screening Need (ASCP Corner) J Clin Psychiatry 2009 70 5 765 10.4088/JCP.09ac05255 19552870\n20. Henderson DC Cagliero E Gray C Nasrallah RA Hayden DL Schoenfeld DA Goff DC Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: a five-year naturalistic study Am J Psychiatr 2000 157 6 975 981 10.1176/appi.ajp.157.6.975 10831479\n21. Ellison JC Dufresne RL A review of the clinical utility of serum clozapine and norClozapine levels Mental Health Clinician 2015 5 2 68 73 10.9740/mhc.2015.03.068\n22. de Leon J Psychopharmacology: atypical antipsychotic dosing: the effect of smoking and caffeine Psychiatr Serv 2004 55 5 491 493 10.1176/appi.ps.55.5.491 15128955\n23. Carrillo JA Herraiz AG Ramos SI Benitez J Effects of caffeine withdrawal from the diet on the metabolism of clozapine in schizophrenic patients J Clin Psychopharmacol 1998 18 4 311 316 10.1097/00004714-199808000-00011 9690697\n24. Jovanović M Vučićević K Miljković B Understanding variability in the pharmacokinetics of atypical antipsychotics–focus on clozapine, olanzapine and aripiprazole population models Drug Metab Rev 2020 52 1 1 8 10.1080/03602532.2020.1717517 32008418\n25. Hukkanen J Puurunen J Hyötyläinen T Savolainen MJ Ruokonen A Morin-Papunen L Orešič M Piltonen T Tapanainen JS The effect of atorvastatin treatment on serum oxysterol concentrations and cytochrome P450 3A4 activity Br J Clin Pharmacol 2015 80 3 473 479 10.1111/bcp.12701 26095142\n26. Andersson T Hassan-Alin M Hasselgren G Röhss K Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole Clin Pharmacokinet 2001 40 7 523 537 10.2165/00003088-200140070-00004 11510629\n27. Feierman DE Melinkov Z Nanji AA Induction of CYP3A by ethanol in multiple in vitro and in vivo models Alcohol Clin Exp Res 2003 27 6 981 988 10.1111/j.1530-0277.2003.tb04424.x 12824820\n\n",
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"issn_linking": "1471-244X",
"issue": "21(1)",
"journal": "BMC psychiatry",
"keywords": "Caffeine; Case report; Clozapine; Interaction; Multiorgan system failure",
"medline_ta": "BMC Psychiatry",
"mesh_terms": "D000328:Adult; D014150:Antipsychotic Agents; D002110:Caffeine; D003024:Clozapine; D006801:Humans; D008297:Male; D012559:Schizophrenia",
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"pages": "192",
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"pubdate": "2021-04-13",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "21401467;19552870;11510629;15340098;24199788;27703781;10513719;7962690;7891353;9690697;27426892;12824820;30885383;32008418;28636813;28502099;10831479;26095142;20194494;9063913;8711047;27476869;15128955;8601555;26238137;10606838",
"title": "Caffeine-clozapine interaction associated with severe toxicity and multiorgan system failure: a case report.",
"title_normalized": "caffeine clozapine interaction associated with severe toxicity and multiorgan system failure a case report"
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{
"abstract": "Acute myeloid leukemia (AML) with FUS-ERG has a poor prognosis regardless of allo-hematopoietic stem cell transplantation (HSCT). Maintenance therapy such as azacitidine after allo-HSCT for AML with FUS-ERG may be clinically meaningful.",
"affiliations": "Department of Pediatrics St. Marianna University School of Medicine Kanagawa Japan.;Department of Pediatrics St. Marianna University School of Medicine Kanagawa Japan.;Department of Pediatrics St. Marianna University School of Medicine Kanagawa Japan.;Department of Pediatrics St. Marianna University School of Medicine Kanagawa Japan.;Department of Pediatrics St. Marianna University School of Medicine Kanagawa Japan.;Department of Pediatrics St. Marianna University School of Medicine Kanagawa Japan.",
"authors": "Keino|Dai|D|https://orcid.org/0000-0003-0312-1636;Mori|Takashi|T|;Morimoto|Mizuho|M|;Kondo|Kensuke|K|;Mori|Tetsuya|T|;Kinoshita|Akitoshi|A|",
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"fulltext": "\n==== Front\nClin Case RepClin Case Rep10.1002/(ISSN)2050-0904CCR3Clinical Case Reports2050-0904John Wiley and Sons Inc. Hoboken 10.1002/ccr3.2461CCR32461Case ReportCase ReportsSalvage therapy with azacitidine for pediatric acute myeloid leukemia with t(16;21)(p11;q22)/FUS‐ERG and early relapse after allogeneic blood stem cell transplantation: A case report KEINO et al.Keino Dai https://orcid.org/0000-0003-0312-1636\n1\nd2keino@marianna-u.ac.jp Mori Takashi \n1\nMorimoto Mizuho \n1\nKondo Kensuke \n1\nMori Tetsuya \n1\nKinoshita Akitoshi \n1\n\n1 \nDepartment of Pediatrics\nSt. Marianna University School of Medicine\nKanagawa\nJapan\n* Correspondence\n\nDai Keino, Department of Pediatrics, St. Marianna University School of Medicine, 2‐16‐1 Sugao Miyamae‐ku, Kawasaki, Kanagawa 216‐8511, Japan.\n\nEmail: d2keino@marianna-u.ac.jp\n27 9 2019 11 2019 7 11 10.1002/ccr3.v7.112149 2152 15 6 2019 05 8 2019 22 8 2019 © 2019 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Abstract\nAcute myeloid leukemia (AML) with FUS‐ERG has a poor prognosis regardless of allo‐hematopoietic stem cell transplantation (HSCT). Maintenance therapy such as azacitidine after allo‐HSCT for AML with FUS‐ERG may be clinically meaningful.\n\nAcute myeloid leukemia (AML) with FUS‐ERG has a poor prognosis regardless of allo‐hematopoietic stem cell transplantation (HSCT). Maintenance therapy such as azacitidine after allo‐HSCT for AML with FUS‐ERG may be clinically meaningful.\n\n\nacute myeloid leukemiaallogeneic hematopoietic stem cell transplantationazacitidineFUS‐ERGsalvage therapyt(16;21)(p11;q22) source-schema-version-number2.0component-idccr32461cover-dateNovember 2019details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_NLMPMC version:5.7.2 mode:remove_FC converted:26.11.2019\n\n\nKeino \nD \n, \nMori \nT \n, \nMorimoto \nM \n, \nKondo \nK \n, \nMori \nT \n, \nKinoshita \nA \n. Salvage therapy with azacitidine for pediatric acute myeloid leukemia with t(16;21)(p11;q22)/FUS‐ERG and early relapse after allogeneic blood stem cell transplantation: A case report . Clin Case Rep . 2019 ;7 :2149 –2152 . 10.1002/ccr3.2461\n==== Body\n1 INTRODUCTION\nWe report a case of pediatric relapse AML with FUS‐ERG after allo‐hematopoietic stem cell transplantation who received salvage therapy with azacitidine (AZA). Our patient was able to achieve 2nd CR by AZA for approximately 8 months. We suggested that AZA may be a salvage therapy for AML with FUS‐ERG.\n\nThe t(16;21)(p11;q22) is a nonrandom chromosomal translocation that occurs in acute myeloid leukemia (AML), myelodysplastic syndrome that evolves into AML, blast crisis of chronic myelogenous leukemia, and rare cases of Ewing's tumors.1 This translocation leads to the production of the FUS‐ERG fusion transcript.2 The incidence of AML with FUS‐ERG is estimated to be 1% of all de novo and secondary cases of AML.3 AML with FUS‐ERG is reportedly associated with a poor prognosis and high rate of relapse.4, 5\n\n\nAML with FUS‐ERG was defined as a high‐risk cytogenetic abnormality because it has been included in the high‐risk criteria in Japanese nationwide clinical trials for pediatric AML since 1999,6, 7 and the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) trial AML‐05 allocated FUS‐ERG‐positive AML to allogeneic hematopoietic stem cell transplantation (allo‐HSCT) as treatment for achieving the first complete remission (CR).6, 8\n\n\nHere, we describe the clinical course of a patient who received salvage therapy with azacitidine (AZA) for pediatric AML with t(16;21)(p11;q22)/FUS‐ERG and experienced early relapse after the first CR with allo‐HSCT.\n\n2 CASE REPORT\nA previously healthy 10‐year‐old boy was admitted to our hospital because of a fever. The physical examination showed petechial hemorrhage of the precordia and leg, but it did not indicate hepatosplenomegaly or lymphadenopathy. Results of the laboratory examination indicated leucocytosis, anemia, and thrombocytopenia. The following findings were observed: white blood cell count, 127,000/µL; neutrophil count, 2.0%; blast cell count, 94.5%; hemoglobin level, 9.3 g/dL; and platelet count, 1.7 × 104/µL. Lactate dehydrogenase and transaminase levels were 2371 IU/L and within normal range, respectively. The bone marrow (BM) examination revealed hypercellular BM. The nucleated cell count was 26.4 × 104/μL with a blast cell count of 71.8% (Figure 1A,B). The result of the peroxidase staining was negative, that of α‐naphthyl butyrate esterase staining was positive, that of naphthol AS‐D chloroacetate esterase staining was negative, and that of sodium fluoride staining was positive. As examined by flow cytometry, the immunophenotype of the blast cells showed positivity for cytoplasmic‐myeloperoxidase (42.9%), CD11b (75.1%), CD13 (95.9%), CD33 (99.2%), CD34 (98.0%), CD38 (35.9%), CD56 (96.2%), CD58 (70.6%), CD64 (43.1%), CD99 (93.4%), and CD117 (86.8%). Chromosomal banding of BM cells revealed 46,XY,del(6)(q21),t(16;21)(p11.2;q22),der(17)t(1;17)(q12;q25)[20]. The patient was negative for FLT3‐ITD, and the quantitative determination of FUS‐ERG‐messenger RNA (mRNA) in BM was 1,608,400 copies/μg RNA. The diagnosis of AML with t(16;21)(p11;q22)/FUS‐ERG and M5a according to the French‐American‐British classification was made based on the BM examination.\n\nFigure 1 Bone marrow specimen (Wright‐Giemsa stain). A, ×400 and (B) ×1000: Leukemic cells are observed\n\nAccording to the AML‐05 protocol of the JPLSG,8 two courses of induction chemotherapy were administered, but CR was not achieved. The chemotherapy (granulocyte colony‐stimulating factor 5 μg/kg/d on days 1‐6, idarubicin 10 mg/m2/d on days 2‐4, fludarabine 30 mg/m2/d on days 2‐6, cytarabine 2 g/m2/d on days 2‐6) that included gemtuzumab ozogamicin (3 mg/m2/d on day 7) led to CR, which was followed by peripheral blood stem cell transplantation (PBSCT) from a human leukocyte antigen (HLA)‐matched sibling donor at 11 years of age. Sibling donor was sister. The conditioning regimen consisted of melphalan (L‐PAM) (90 mg/m2/d daily for 2 days) and buslfan (4 mg/kg/d daily for 4 days). Graft‐versus‐host disease (GVHD) prophylaxis was performed with short‐course methotrexate (MTX) and cyclosporine. BM engraftment was achieved 12 days after PBSCT, but veno‐occlusive disease (VOD) and infective endocarditis developed 20 and 68 days after PBSCT, respectively. Although GVHD prophylaxis had been discontinued because of VOD, he did not have acute GVHD.\n\nAt 145 days, the BM examination revealed the presence of blast cells (3%), 46,XY,del(6)(q21),t(16;21)(p11.2;q22),der(17)t(1;17)(q12;q25)[1]/46,XX[19] in the chromosome banding, and an increased expression of WT1‐mRNA (8,000 copies/μg RNA). He was diagnosed as having a cytogenetic relapse after PBSCT. At 156 days, AZA was administered (100 mg/m2/d for 5 days, every 28 days).9 After two courses of AZA were administered, CR was achieved a second time and chromosomal banding of BM cells revealed 46,XX[16]. The quantitative determination of WT1‐mRNA in peripheral blood was significantly reduced to 140 copies/μg RNA after three courses of AZA. For approximately 8 months, eight courses of AZA were administered, but he was diagnosed as having relapse in the BM and central nervous system (CNS) a second time. The hematotoxicity of AZA was neutropenia of Grades III‐IV and febrile neutropenia.\n\nAlthough low‐dose Ara‐C and aclarubicin with concomitant use of a granulocyte colony‐stimulating factor regimen and triple intrathecal therapy (TIT) consisted of cytarabine (30 mg), methotrexate (12 mg), and hydrocortisone (25 mg) were administered, a third CR was not achieved. TIT was performed a total of 7×, and cerebrospinal fluid test revealed that the leukemia cells were negative. He underwent cranial irradiation (14 Gy) and subsequently received a reduced‐intensity conditioning regimen consisting of fludarabine (30 mg/m2/d for 4 days), cytarabine (2 g/m2/d for 4 days), L‐PAM (60 mg/m2/d for 3 days), and low‐dose total body irradiation (4 Gy) with HLA‐matched cord blood transplantation (CBT). GVHD prophylaxis was performed with short‐course methotrexate (MTX) and tacrolimus. Thrombotic microangiopathy developed 9 days after CBT, and primary graft failure (GF) was diagnosed 20 days after CBT. Therefore, he underwent PBSCT with an HLA‐matched sibling donor without conditioning regimen 20 days after CBT because of GF.\n\nAlthough BM engraftment was achieved, he died of septic shock due to Klebsiella pneumoniae at approximately 3 months after CBT. According to the autopsy results, the presence of leukemic cells was not confirmed.\n\n3 DISCUSSION\nThe CD56 antigen is expressed in natural killer/T‐cell lymphoma, multiple myeloma, and AML. Expression of the CD56 antigen in AML with FUS‐ERG was reported to be associated with failure of CR, early relapse, and an unfavorable prognosis.3 CD56 was highly expressed in our patient's leukemic cells. Further, he did not achieve CR after the administration of two courses of induction chemotherapy according to the AML‐05 protocol, and he experienced early recurrence after PBSCT.\n\nNoort et al reported that no difference in the incidence of relapse could be observed between the MRD‐positive and MRD‐negative AML patients with FUS‐ERG.5 And the outcomes of allo‐HSCT for AML with FUS‐ERG have been reported in Japan.10 Despite all patients receiving allo‐HSCT, 12 achieved their first CR, and 12 of 14 patients eventually died (nine died of AML relapse and three died of transplant‐related toxicities). This fact indicates that allo‐HSCT is not a curative option for AML with FUS‐ERG and that a novel therapeutic approach is needed to improve patients’ outcomes. Considering that AZA was effective in our patient, epigenetic drugs may become a novel therapy option.\n\nLow‐dose AZA maintenance therapy after allo‐HSCT has been reported in patients with AML and myelodysplastic syndrome.11, 12 AZA after allo‐HSCT can induce a CD8+ T‐cell response to tumor antigens, raising the possibility that it may have the potential to augment a graft‐versus‐leukemia (GVL) response.13\n\n\nIt has been reported that a high expression of ERG is linked with an unfavorable prognosis in a subgroup of leukemic patients with AML and acute T‐lymphoblastic leukemia.14 It has also been reported that several accompanying mutation in epigenetic regulators (DNMT3A, ASXL1, BCOR) by targeted NGS approach in AML with FUS‐ERG cases.15\nERG‐positive prostate cancer cells have been reported to induce epigenetic activation of Tudor domain‐containing protein 1, and histone deacetylase inhibitors induce apoptosis and affect the acetylation status of p53.16, 17\n\n\nWe administered AZA for pediatric AML with FUS‐ERG that early relapse occurred after the first CR with allo‐HSCT. The patient was able to maintain CR a second time for approximately 8 months. Although AZA was administered after relapse in our patient, we expected an epigenetic and GVL effect. Our patient may have showed CR because we administered AZA when there were few leukemic cells such as the cytogenetic relapse. Platzbecker et al reported that pre‐emptive therapy with AZA can prevent or substantially delay hematological relapse in measurable residual disease (MRD)‐positive patients with MDS or AML who are at high risk of relapse.18 Therefore, it may be clinically meaningful to administer AZA as maintenance therapy immediately after allo‐HSCT for AML with FUS‐ERG.\n\nHe developed recurrence in the BM and CNS during AZA therapy. Thus, concurrent treatment for recurrence in the BM and CNS was necessary, and we suggested the use of the TIT during administration of AZA.\n\nIn conclusion, expression of the CD56 antigen in AML with FUS‐ERG is associated with a poor prognosis, and achieving CR with allo‐HSCT is difficult. A novel therapeutic approach is needed for this clinical condition, and we suggest epigenetic therapy such as AZA as maintenance therapy after allo‐HSCT for AML with FUS‐ERG.\n\nCONFLICT OF INTEREST\nAll authors declare no conflicts of interest relevant to this article.\n\nAUTHOR CONTRIBUTIONS\nDai Keino: conceptualized and designed the study, drafted the initial manuscript, and approved the final manuscript. Takashi Mori, Mizuho Morimoto, Kensuke Kondo, and Tetsuya Mori: performed the initial analyses, and reviewed and revised the manuscript. Akitoshi Kinoshita: designed the data collection instruments, coordinated and supervised data collection, and critically reviewed the manuscript. All authors approved the final manuscript and agreed to be accountable for all aspects of the work.\n==== Refs\nREFERENCES\n1 \n\nHuret \nJL \n. t(16;21)(p11;q22) . Atlas Genet Cytogenet Oncol Haematol . 2005 ;9 :36 ‐38 .\n2 \n\nMorgan \nR \n, \nRiske \nCB \n, \nMeloni \nA \n, et al. t(16;21)(p11.2;q22): A recurrent primary rearrangement in ANLL . Cancer Genet Cytogenet . 1991 ;53 (1 ):83 ‐90 .2036642 \n3 \n\nJekarl \nDW \n, \nKim \nM \n, \nLim \nJ \n, et al. CD56 antigen expression and hemophagocytosis of leukemic cells in acute myeloid leukemia with t(16;21)(p11;q22) . Int J Hematol . 2010 ;92 :306 ‐313 .20694842 \n4 \n\nKong \nXT \n, \nIda \nK \n, \nIchikawa \nH \n, et al. Consistent detection of TLS/FUS‐ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript . Blood . 1997 ;90 :1192 ‐1199 .9242552 \n5 \n\nNoort \nS \n, \nZimmermann \nRD \n, et al. Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I‐NFM Study Group . Blood . 2018 ;132 :1584 ‐1592 .30150206 \n6 \n\nTaga \nT \n, \nTomizawa \nD \n, \nTakahashi \nH \n, \nAdachi \nS \n. Acute myeloid leukemia in children: current status and future directions . Pediatr Int . 2016 ;58 :71 ‐80 .26645706 \n7 \n\nTsukimoto \nI \n, \nTawa \nA \n, \nHoribe \nK \n, et al. Risk‐stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: the AML99 trial from the Japanese childhood AML cooperative study group . J Clin Oncol . 2009 ;27 :4007 ‐4013 .19620491 \n8 \n\nTomizawa \nD \n, \nTawa \nA \n, \nWatanabe \nT \n, et al. Excess treatment reduction including anthracyclines results in higher incidence of relapse in core binding factor acute myeloid leukemia in children . Leukemia . 2013 ;27 :2413 ‐2416 .23677335 \n9 \n\nSchroeder \nT \n, \nForbel \nJ \n, \nCadeddu \nR‐P \n, et al. Salvage therapy with azacitidine increases regulatory T cells in peripheral blood of patients with AML or MDS and early relapse after allogeneic blood stem cell transplantation . Leukeima . 2013 ;27 :1910 ‐1952 .\n10 \n\nTomizawa \nD \n, \nYoshida \nM \n, \nKondo \nT \n, et al. Allogeneic hematopoietic stem cell transplantation for children and adolescents with high‐risk cytogenetic AML: distinctly poor outcomes of FUS‐ERG‐positive cases . Bone marrow transplant . 2019 ;54 :168 ‐172 .29959437 \n11 \n\nTamura \nA \n, \nIshida \nT \n, \nSaito \nA \n, et al. Low‐dose azacitidine maintenance therapy after allogeneic stem cell transplantation for high‐risk pediatric acute myeloid leukemia . Pediatric Blood Cancer . 2018 ;65 :e27284.29893458 \n12 \n\nLima \nMD \n, \nGiralt \nS \n, \nThall \nPF \n, et al. Maintenance therapy with low‐dose azacitidine after allogeneic hematopoietic stem cell transplantation for relapsed aml or mds: a dose and schedule finding study . Cancer . 2010 ;116 :5420 ‐5431 .20672358 \n13 \n\nMohty \nM \n, \nChevallier \nP \n. Azacitidine after allo‐SCT: the good without the bad? \nBlood . 2012 ;119 :3199 ‐3200 .22493216 \n14 \n\nSotoca \nAM \n, \nPrange \nKH \n, \nReijnders \nB \n, et al. The oncofusion protein FUS–ERG targets key hematopoietic regulators and modulates the all‐trans retinoic acid signaling pathway in t(16;21) acute myeloid leukemia . Oncogene . 2015 ;35 :1965 ‐1975 .26148230 \n15 \n\nZerkalenkova \nE \n, \nPanfyorova \nA \n, \nKazakova \nA \n, et al. Molecular characteristic of acute leukemias with t(16;21)/FUS‐ERG\n . Ann Hematol . 2018 ;97 :977 ‐988 .29427188 \n16 \n\nFortson \nWS \n, \nKayarthodi \nS \n, \nFujimura \nY \n, et al. Histone deacetylase inhibitors, valproic acid and trichostatin‐A induce apoptosis and affect acetylation status of p53 in ERG‐positive prostate cancer cells . Int J Oncol . 2011 ;39 :111 ‐119 .21519790 \n17 \n\nKacprzyk \nLA \n, \nLaible \nM \n, \nAndrasiuk \nT \n, et al. ERG induces epigenetic activation of Tudor domain‐containing protein 1 (TDRD1) in ERG rearrangement‐positive prostate cancer . PLoS ONE . 2013 ;8 :e59976.23555854 \n18 \n\nPlatzbecker \nU \n, \nMiddeke \nJM \n, \nSockel \nK \n, et al. Measurable residual disease‐guided treatment with azacitidine to prevent hematological relapse in patients with myelodysplastic syndrome and acute myeloid leukemia (RELAZA2): an open‐label, multicentre, phase 2 trial . Lancet Oncol . 2018 ;19 :1668 ‐1679 .30442503\n\n",
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"keywords": "FUS‐ERG; acute myeloid leukemia; allogeneic hematopoietic stem cell transplantation; azacitidine; salvage therapy; t(16;21)(p11;q22)",
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"title": "Salvage therapy with azacitidine for pediatric acute myeloid leukemia with t(16;21)(p11;q22)/FUS-ERG and early relapse after allogeneic blood stem cell transplantation: A case report.",
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"medicinalproduct": "CICLOSPORIN"
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{
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},
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"drugdosagetext": "ON DAY 7",
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"medicinalproduct": "GEMTUZUMAB"
},
{
"actiondrug": "5",
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"activesubstancename": "BUSULFAN"
},
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"drugdosagetext": "FOR 4 DAYS",
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"medicinalproduct": "BUSULFAN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CYTARABINE"
},
"drugadditional": "3",
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"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
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"drugdosagetext": "2 G/M2/D ON DAYS 2-6",
"drugenddate": null,
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"drugindication": "ACUTE MYELOID LEUKAEMIA",
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"medicinalproduct": "CYTARABINE/CYTARABINE HYDROCHLORIDE/CYTARABINE OCFOSFATE"
}
],
"patientagegroup": null,
"patientonsetage": "10",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Venoocclusive disease",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KEINO D, MORI T, MORIMOTO M, KONDO K, MORI T, KINOSHITA A. SALVAGE THERAPY WITH AZACITIDINE FOR PEDIATRIC ACUTE MYELOID LEUKEMIA WITH T(16?21)(P11?Q22)/FUS-ERG AND EARLY RELAPSE AFTER ALLOGENEIC BLOOD STEM CELL TRANSPLANTATION: A CASE REPORT. CLIN CASE REP. 2019 SEP 27?7(11):2149-2152.",
"literaturereference_normalized": "salvage therapy with azacitidine for pediatric acute myeloid leukemia with t 16 21 p11 q22 fus erg and early relapse after allogeneic blood stem cell transplantation a case report",
"qualification": "3",
"reportercountry": "JP"
},
"primarysourcecountry": "JP",
"receiptdate": "20191217",
"receivedate": "20191217",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17163240,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20200122"
}
] |
{
"abstract": "In the early 1990s, attention was drawn to the migration of immune cells into the central nervous system via the blood-brain barrier. The literature showed that lymphocytes binding to the endothelium were successfully inhibited by an antibody against α4β1 integrin. These biological findings resulted in the development of a humanized antibody to α4 integrin - natalizumab (NTZ) - to treat multiple sclerosis (MS). Here, we provide a systematic review and meta-analysis on the efficacy and safety of natalizumab, trying to answer the question whether its use may be recommended both in adult and in pediatric age groups as standard MS treatment. Our results highlight the improvement of clinical and radiological findings in treated patients (p < 0.005), confirming NTZ efficacy. Nevertheless, if NTZ is shown to be efficient, further studies should be performed to evaluate its safety and to target the MS profile that could benefit from this treatment.",
"affiliations": "a General Paediatrics Operative Unit , Policlinico-Vittorio-Emanuele University Hospital, University of Catania , Catania , Italy.;b Tehran University of Medical Sciences , Tehran , Iran.;b Tehran University of Medical Sciences , Tehran , Iran.;c Department of Statistics , La Sapienza University of Rome , Rome , Italy.;a General Paediatrics Operative Unit , Policlinico-Vittorio-Emanuele University Hospital, University of Catania , Catania , Italy.;d Paediatric Department, Paediatric Nephrology Operative Unit , Sapienza University of Rome , Rome , Italy.;a General Paediatrics Operative Unit , Policlinico-Vittorio-Emanuele University Hospital, University of Catania , Catania , Italy.",
"authors": "Vitaliti|Giovanna|G|;Matin|Nassim|N|;Tabatabaie|Omidreza|O|;Di Traglia|Mario|M|;Pavone|Piero|P|;Lubrano|Riccardo|R|;Falsaperla|Raffaele|R|",
"chemical_list": "D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab",
"country": "England",
"delete": false,
"doi": "10.1586/14737175.2015.1102061",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1473-7175",
"issue": "15(11)",
"journal": "Expert review of neurotherapeutics",
"keywords": "efficacy; meta-analysis; multiple sclerosis; natalizumab; safety",
"medline_ta": "Expert Rev Neurother",
"mesh_terms": "D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002985:Clinical Protocols; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal; D009103:Multiple Sclerosis; D000069442:Natalizumab",
"nlm_unique_id": "101129944",
"other_id": null,
"pages": "1321-41",
"pmc": null,
"pmid": "26513633",
"pubdate": "2015",
"publication_types": "D016428:Journal Article; D017418:Meta-Analysis; D016454:Review; D000078182:Systematic Review",
"references": null,
"title": "Natalizumab in multiple sclerosis: discontinuation, progressive multifocal leukoencephalopathy and possible use in children.",
"title_normalized": "natalizumab in multiple sclerosis discontinuation progressive multifocal leukoencephalopathy and possible use in children"
} | [
{
"companynumb": "SE-BIOGENIDEC-2011BI003184",
"fulfillexpeditecriteria": "1",
"occurcountry": "SE",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "NATALIZUMAB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "125104",
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"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
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"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": "20080508",
"drugenddateformat": "102",
"drugindication": "MULTIPLE SCLEROSIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
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"drugstartdate": "20071129",
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"medicinalproduct": "TYSABRI"
}
],
"patientagegroup": null,
"patientonsetage": "61",
"patientonsetageunit": "801",
"patientsex": "2",
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"reaction": [
{
"reactionmeddrapt": "Drug specific antibody present",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Multiple sclerosis",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "VITALITI G, MATIN N, TABATABAIE O, DI TRAGLIA M, PAVONE P, LUBRANO R, FALSAPERLA R. NATALIZUMAB IN MULTIPLE SCLEROSIS: DISCONTINUATION, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY AND POSSIBLE USE IN CHILDREN. EXPERT REVIEW OF NEUROTHERAPHEUTICS. 2015? DOI: 10.1586/14737175.2015.1102061",
"literaturereference_normalized": "natalizumab in multiple sclerosis discontinuation progressive multifocal leukoencephalopathy and possible use in children",
"qualification": "1",
"reportercountry": "IT"
},
"primarysourcecountry": "SE",
"receiptdate": "20151119",
"receivedate": "20110208",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 7803957,
"safetyreportversion": 3,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20160305"
},
{
"companynumb": "SE-BIOGENIDEC-2009BI002622",
"fulfillexpeditecriteria": "1",
"occurcountry": "SE",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "NATALIZUMAB"
},
"drugadditional": null,
"drugadministrationroute": "042",
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"drugcharacterization": "1",
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"drugdosageform": "INTRAVENOUS INFUSION",
"drugdosagetext": null,
"drugenddate": "200808",
"drugenddateformat": "610",
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": "802",
"drugintervaldosageunitnumb": "1",
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"drugstartdate": "200805",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "TYSABRI"
}
],
"patientagegroup": null,
"patientonsetage": "22",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Multiple sclerosis relapse",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Drug ineffective",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 200809"
}
},
"primarysource": {
"literaturereference": "VITALITI G, MATIN N, TABATABAIE O, DI TRAGLIA M, PAVONE P, LUBRANO R, ET AL. NATALIZUMAB IN MULTIPLE SCLEROSIS: DISCONTINUATION, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY AND POSSIBLE USE IN CHILDREN. EXPERT REVIEW OF NEUROTHERAPEUTICS 2015? DOI: 10.1586/14737175.2015.1102061",
"literaturereference_normalized": "natalizumab in multiple sclerosis discontinuation progressive multifocal leukoencephalopathy and possible use in children",
"qualification": "1",
"reportercountry": "IT"
},
"primarysourcecountry": "SE",
"receiptdate": "20151119",
"receivedate": "20090209",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 6904392,
"safetyreportversion": 5,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160305"
}
] |
{
"abstract": "Little is known about mechanisms of resistance to poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and platinum chemotherapy in patients with metastatic breast cancer and BRCA1/2 mutations. Further investigation of resistance in clinical cohorts may point to strategies to prevent or overcome treatment failure.\n\n\n\nWe obtained tumor biopsies from metastatic breast cancer patients with BRCA1/2 deficiency before and after acquired resistance to PARPi or platinum chemotherapy. Whole exome sequencing was carried out on each tumor, germline DNA, and circulating tumor DNA. Tumors underwent RNA sequencing, and immunohistochemical staining for RAD51 foci on tumor sections was carried out for functional assessment of intact homologous recombination (HR).\n\n\n\nPre- and post-resistance tumor samples were sequenced from eight patients (four with BRCA1 and four with BRCA2 mutation; four treated with PARPi and four with platinum). Following disease progression on DNA-damaging therapy, four patients (50%) acquired at least one somatic reversion alteration likely to result in functional BRCA1/2 protein detected by tumor or circulating tumor DNA sequencing. Two patients with germline BRCA1 deficiency acquired genomic alterations anticipated to restore HR through increased DNA end resection: loss of TP53BP1 in one patient and amplification of MRE11A in another. RAD51 foci were acquired post-resistance in all patients with genomic reversion, consistent with reconstitution of HR. All patients whose tumors demonstrated RAD51 foci post-resistance were intrinsically resistant to subsequent lines of DNA-damaging therapy.\n\n\n\nGenomic reversion in BRCA1/2 was the most commonly observed mechanism of resistance, occurring in four of eight patients. Novel sequence alterations leading to increased DNA end resection were seen in two patients, and may be targetable for therapeutic benefit. The presence of RAD51 foci by immunohistochemistry was consistent with BRCA1/2 protein functional status from genomic data and predicted response to later DNA-damaging therapy, supporting RAD51 focus formation as a clinically useful biomarker.",
"affiliations": "Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Department of Medicine, Brigham and Women's Hospital, Boston, USA; Broad Institute of MIT and Harvard, Cambridge, USA; Harvard Medical School, Boston, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, USA.;Broad Institute of MIT and Harvard, Cambridge, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, USA.;Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Boston, USA.;Broad Institute of MIT and Harvard, Cambridge, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, USA.;Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Boston, USA.;Broad Institute of MIT and Harvard, Cambridge, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, USA.;Broad Institute of MIT and Harvard, Cambridge, USA; Harvard Medical School, Boston, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Boston, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; University of Massachusetts Medical School, Worcester, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.;Broad Institute of MIT and Harvard, Cambridge, USA.;Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, USA.;City of Hope Comprehensive Cancer Center, Duarte, USA.;Harvard Medical School, Boston, USA; Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, USA.;Yale Cancer Center, New Haven, USA.;Broad Institute of MIT and Harvard, Cambridge, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Department of Medicine, Brigham and Women's Hospital, Boston, USA; Harvard Medical School, Boston, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Department of Medicine, Brigham and Women's Hospital, Boston, USA; Harvard Medical School, Boston, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Department of Medicine, Brigham and Women's Hospital, Boston, USA; Harvard Medical School, Boston, USA.;Harvard Medical School, Boston, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Boston, USA; Department of Radiation Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Department of Medicine, Brigham and Women's Hospital, Boston, USA; Harvard Medical School, Boston, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Department of Medicine, Brigham and Women's Hospital, Boston, USA; Harvard Medical School, Boston, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Department of Medicine, Brigham and Women's Hospital, Boston, USA; Harvard Medical School, Boston, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Boston, USA.;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Department of Medicine, Brigham and Women's Hospital, Boston, USA; Broad Institute of MIT and Harvard, Cambridge, USA; Harvard Medical School, Boston, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, USA. Electronic address: nikhil_wagle@dfci.harvard.edu.",
"authors": "Waks|A G|AG|;Cohen|O|O|;Kochupurakkal|B|B|;Kim|D|D|;Dunn|C E|CE|;Buendia Buendia|J|J|;Wander|S|S|;Helvie|K|K|;Lloyd|M R|MR|;Marini|L|L|;Hughes|M E|ME|;Freeman|S S|SS|;Ivy|S P|SP|;Geradts|J|J|;Isakoff|S|S|;LoRusso|P|P|;Adalsteinsson|V A|VA|;Tolaney|S M|SM|;Matulonis|U|U|;Krop|I E|IE|;D'Andrea|A D|AD|;Winer|E P|EP|;Lin|N U|NU|;Shapiro|G I|GI|;Wagle|N|N|",
"chemical_list": "D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D010984:Platinum",
"country": "England",
"delete": false,
"doi": "10.1016/j.annonc.2020.02.008",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0923-7534",
"issue": "31(5)",
"journal": "Annals of oncology : official journal of the European Society for Medical Oncology",
"keywords": "BRCA1; BRCA2; PARP inhibitor; breast cancer; platinum",
"medline_ta": "Ann Oncol",
"mesh_terms": "D019313:BRCA1 Protein; D024682:BRCA2 Protein; D001943:Breast Neoplasms; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms; D010984:Platinum; D000067856:Poly(ADP-ribose) Polymerase Inhibitors",
"nlm_unique_id": "9007735",
"other_id": null,
"pages": "590-598",
"pmc": null,
"pmid": "32245699",
"pubdate": "2020-05",
"publication_types": "D016428:Journal Article; D052061:Research Support, N.I.H., Extramural; D013485:Research Support, Non-U.S. Gov't; D013486:Research Support, U.S. Gov't, Non-P.H.S.",
"references": "27197267;29635390;29109393;31409614;29713086;30464262;29093439;29617664;30213835;28588062;16731627;18264088;30377213;27993796;20362325;27443740;28765325;26017449;24085845;28414925;28242626;28450425;28578601;21205303;26463832;29755131;28450426;18264087;29669011;20453858",
"title": "Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer.",
"title_normalized": "reversion and non reversion mechanisms of resistance to parp inhibitor or platinum chemotherapy in brca1 2 mutant metastatic breast cancer"
} | [
{
"companynumb": "US-TEVA-2020-US-1245365",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PACLITAXEL"
},
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"medicinalproduct": "PACLITAXEL."
},
{
"actiondrug": "5",
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"activesubstancename": "CARBOPLATIN"
},
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"drugindication": "BREAST CANCER METASTATIC",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBOPLATIN."
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug resistance",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WAKS AG, COHEN O, KOCHUPURAKKAL B, KIM D, DUNN CE, BUENDIA BUENDIA J, ET AL. REVERSION AND NON-REVERSION MECHANISMS OF RESISTANCE TO PARP INHIBITOR OR PLATINUM CHEMOTHERAPY IN BRCA1/2-MUTANT METASTATIC BREAST CANCER. ANN-ONCOL 2020?31(5):590-598.",
"literaturereference_normalized": "reversion and non reversion mechanisms of resistance to parp inhibitor or platinum chemotherapy in brca1 2 mutant metastatic breast cancer",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20200608",
"receivedate": "20200608",
"receiver": {
"receiverorganization": "FDA",
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},
"reporttype": "2",
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"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200714"
},
{
"companynumb": "US-TEVA-2020-US-1245368",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
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{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CARBOPLATIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
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"drugindication": "BREAST CANCER METASTATIC",
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"abstract": "We report a case of problematic spontaneous orgasms during sleep in a 57-year-old woman who also complained of hypnic jerks and symptoms of exploding head syndrome. To our knowledge, this is the first case report in the English language literature of problematic spontaneous orgasms during sleep. She had a complex medical and psychiatric history, and was taking oxycontin, venlafaxine, amitriptyline, and lurasidone. Prolonged video electroencephalogram monitoring did not record any ictal or interictal electroencephalogram discharges, and nocturnal video polysomnography monitoring did not record any behavioral or orgasmic event. Periodic limb movement index was zero events/h. Severe central sleep apnea was detected with apnea-hypopnea index = 130 events/h, but she could not tolerate positive airway pressure titration. Sleep architecture was disturbed, with 96.4% of sleep spent in stage N2 sleep. Bedtime clonazepam therapy (1.5 mg) was effective in suppressing the sleep-related orgasms and hypnic jerks.",
"affiliations": "Minnesota Regional Sleep Disorders Center, Department of Neurology, Hennepin County Medical Center, Minneapolis, Minnesota.;Minnesota Regional Sleep Disorders Center, Department of Psychiatry, Hennepin County Medical Center, Minneapolis, Minnesota.",
"authors": "Irfan|Muna|M|;Schenck|Carlos H|CH|",
"chemical_list": "D002998:Clonazepam",
"country": "United States",
"delete": false,
"doi": "10.5664/jcsm.6902",
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"issn_linking": "1550-9389",
"issue": "14(1)",
"journal": "Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine",
"keywords": "NREM parasomnia; abnormal sexual behaviors in sleep; sexsomnia; sexual parasomnia; sleep sex; sleep-related orgasm",
"medline_ta": "J Clin Sleep Med",
"mesh_terms": "D002998:Clonazepam; D005260:Female; D006801:Humans; D008875:Middle Aged; D009948:Orgasm; D020447:Parasomnias; D017286:Polysomnography; D020182:Sleep Apnea, Central",
"nlm_unique_id": "101231977",
"other_id": null,
"pages": "141-144",
"pmc": null,
"pmid": "29246268",
"pubdate": "2018-01-15",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "17580590;27656267;21493137;28095975;15817520;28364495",
"title": "Sleep-Related Orgasms in a 57-Year-Old Woman: A Case Report.",
"title_normalized": "sleep related orgasms in a 57 year old woman a case report"
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"abstract": "SCN8A encodes Nav1.6, one of the main voltage-gated sodium channel subunits in the brain, and SCN8A mutations lead to epileptic encephalopathy. Particular mutations render the mutant channel more susceptible to inhibition by phenytoin. Yet, the potentially severe side effects of phenytoin maintenance therapy, especially cognitive impairment, are undesirable in these already cognitively impaired patients. We describe a 5-year-old patient with SCN8A encephalopathy in whom phenytoin proved successful as emergency treatment to prevent clustering of seizures and status epilepticus, thus hospital stays. The ketogenic diet, levetiracetam, zonisamide, topiramate, and phenytoin maintenance therapy resulted in adverse reactions not previously documented in SCN8A encephalopathy.",
"affiliations": "Department of Neurology Academic Center for Epileptology Kempenhaeghe and Maastricht UMC+Heeze the Netherlands.;Department of Neurology Academic Center for Epileptology Kempenhaeghe and Maastricht UMC+Heeze the Netherlands.;Department of Neurology Radboud University Medical Center Nijmegen the Netherlands.;Department of Neurology Radboud University Medical Center Nijmegen the Netherlands.;Department of Human Genetics Radboud University Medical Center Donders Institute for Brain, Cognition and Behavior Nijmegen the Netherlands.;Department of Neurology Academic Center for Epileptology Kempenhaeghe and Maastricht UMC+Heeze the Netherlands.",
"authors": "Braakman|Hilde M|HM|;Verhoeven|Judith S|JS|;Erasmus|Corrie E|CE|;Haaxma|Charlotte A|CA|;Willemsen|Marjolein H|MH|;Schelhaas|H Jurgen|HJ|",
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"fulltext": "\n==== Front\nEpilepsia OpenEpilepsia Open10.1002/(ISSN)2470-9239EPI4Epilepsia Open2470-9239John Wiley and Sons Inc. Hoboken 10.1002/epi4.12059EPI412059Short Research ArticleShort Research ArticlePhenytoin as a last‐resort treatment in SCN8A encephalopathy H.M. Braakman et al.Braakman Hilde M. braakmanh@kempenhaeghe.nl \n1\n*Verhoeven Judith S. \n1\nErasmus Corrie E. \n2\nHaaxma Charlotte A. \n2\nWillemsen Marjolein H. \n3\n\n4\nSchelhaas H. Jurgen \n1\n\n1 \nDepartment of Neurology\nAcademic Center for Epileptology\nKempenhaeghe and Maastricht UMC+\nHeeze\nthe Netherlands\n\n2 \nDepartment of Neurology\nRadboud University Medical Center\nNijmegen\nthe Netherlands\n\n3 \nDepartment of Human Genetics\nRadboud University Medical Center\nDonders Institute for Brain, Cognition and Behavior\nNijmegen\nthe Netherlands\n\n4 \nDepartment of Human Genetics\nMaastricht University Medical Center+\nMaastricht\nthe Netherlands\n* Address correspondence to Hilde M. Braakman, Department of Neurology, Academic Center for Epileptology, Kempenhaeghe and Maastricht UMC+, Sterkselseweg 65, 5591 VE Heeze, the Netherlands. E‐mail: braakmanh@kempenhaeghe.nl16 5 2017 9 2017 2 3 10.1111/epi4.2017.2.issue-3343 344 02 4 2017 © 2017 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.Summary\n\nSCN8A encodes Nav1.6, one of the main voltage‐gated sodium channel subunits in the brain, and SCN8A mutations lead to epileptic encephalopathy. Particular mutations render the mutant channel more susceptible to inhibition by phenytoin. Yet, the potentially severe side effects of phenytoin maintenance therapy, especially cognitive impairment, are undesirable in these already cognitively impaired patients. We describe a 5‐year‐old patient with SCN8A encephalopathy in whom phenytoin proved successful as emergency treatment to prevent clustering of seizures and status epilepticus, thus hospital stays. The ketogenic diet, levetiracetam, zonisamide, topiramate, and phenytoin maintenance therapy resulted in adverse reactions not previously documented in SCN8A encephalopathy.\n\nSCN8APhenytoinEpileptic encephalopathy source-schema-version-number2.0component-idepi412059cover-dateSeptember 2017details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.3 mode:remove_FC converted:21.03.2018\n==== Body\nSCN8A encodes Nav1.6, one of the main voltage‐gated sodium channel subunits in the brain, which plays an important role in action potential propagation and spread.1\nSCN8A mutations have been described in patients with epileptic encephalopathy, with seizure onset before the age of 18 months, intellectual disability, and developmental delay.2, 3 Seizure type, neurodevelopment, and disease severity vary between patients with SCN8A encephalopathy,2 likely because distinct mutations in SCN8A confer different effects on Nav1.6 function.4\n\n\nRecently, Barker et al.5 showed that the SCN8A mutation p.Ile1327Val is a gain‐of‐function mutation, resulting in increased seizure susceptibility and rendering the mutant channel more susceptible to inhibition by phenytoin. Hence, phenytoin may be efficacious in SCN8A encephalopathy. The efficacy of phenytoin in SCN8A encephalopathy has previously been observed.3 Phenytoin is a sodium channel blocker and binds at a receptor site in the pore of sodium channels, decreases the sodium influx, and thereby decreases the excitability of the neuron. The reason that phenytoin could be an important treatment option in patients with SCN8A‐related epilepsy is that it is primarily expected to block the increased sodium current through the mutated Nav1.6, but not to affect the function of other voltage‐gated sodium channels not affected by the SCN8A mutation. Given the fact that phenytoin is one of the few sodium channel blockers targeting only the sodium channel and no other molecular targets in the brain, this might explain the observed response to phenytoin treatment in SCN8A encephalopathy patients, in contrast with the response to treatment with other sodium channel blockers.3\n\n\nIn a patient with the SCN8A mutation p.Val233Ile, identified by whole exome sequencing performed as described previously,6 we have observed (1) efficacy of both intravenous and oral phenytoin as an emergency treatment to prevent seizure escalation instead of maintenance therapy and (2) undocumented adverse reactions to a ketogenic diet, levetiracetam, zonisamide, and topiramate.\n\nCase Report\nThe patient is a 5‐year‐old boy with hypotonia from birth, who had his first tonic‐clonic seizure at the age of 4 months. The seizure frequency progressed over 1 year, to four seizures a day. The seizure semiology was always similar and there were no provocative factors such as fever. During this period, his psychomotor development stagnated. A DNA diagnostic test of the SCN1A gene revealed no mutation. Initial treatment with valproic acid and phenobarbital resulted in seizure freedom for 1 year and resumption of psychomotor development. Then, seizures recurred monthly and built up to a status epilepticus once every 2 to 3 months, requiring admission to the intensive care unit (ICU) and benzodiazepine therapy. After every status epilepticus, psychomotor skills deteriorated, including temporary loss of speech. Phenobarbital was switched to lamotrigine and clobazam, without any effect on seizure frequency. Sequential neuropsychological assessments revealed a decrease in total IQ scores from 83 (verbal IQ 88, performance IQ 83) to 63 (verbal IQ 66, performance IQ 70).\n\nKetogenic diet was started but had to be halted because of severe nausea and vomiting, fatigue, increased seizure frequency, and encephalopathy. All improved immediately after cessation of the diet. Seizure frequency decreased to six per year, but all led to epileptic status with ICU admittance. Benzodiazepines were no longer effective, but there was a consistently good response to intravenous phenytoin administration.\n\nAddition of levetiracetam, zonisamide, and later topiramate to maintenance therapy resulted in rapid deterioration, with encephalopathy, ataxia, and dysarthria and recurrent status epilepticus. The encephalopathy, ataxia, and dysarthria quickly disappeared after withdrawal of all three drugs.\n\nWhen a seizure occurred, administration of oral phenytoin at home or, if oral phenytoin treatment failed, intravenous administration at the emergency department, both in a dosage of 10 mg/kg, prevented clustering of seizures and status epilepticus. With oxcarbazepine, valproic acid, lamotrigine, and clobazam maintenance therapy, seizure frequency decreased to once weekly. Because of the success of phenytoin as rescue medication, it was tried as maintenance therapy. Unfortunately, this chronic use of phenytoin, even at a 2 mg/kg/day dose, resulted in severe side effects, including ataxia, dysarthria, and somnolence, and therefore had to be withdrawn.\n\nIn search of successful maintenance therapy, we have recently initiated the new sodium channel blocker lacosamide. At a 2 mg/kg/day dose, he is already more alert but still has weekly seizures for which he uses oral phenytoin (10 mg/kg) at home to prevent clustering of seizures, thus status epilepticus and hospital stays. After a seizure, he experiences 1–2 days of deterioration of his motor skills and temporary loss of speech followed by dysarthria. Currently, he walks without assistance, is able to climb, jump, and cycle with only a slight ataxia and hypotonia, and attends a school for special education.\n\nDiscussion\nThis case demonstrates a favorable response to phenytoin in status epilepticus as well as in the prevention thereof in a patient with a SCN8A mutation. The use of phenytoin and oxcarbazepine is counterintuitive in Dravet‐like syndromes, because patients with classic Dravet syndrome based on SCN1A gene mutations deteriorate when treated with these drugs.7, 8 Phenytoin could be an important treatment option in patients with SCN8A mutation‐related epilepsy because it is primarily expected to block the increased sodium current through the mutated Nav1.6, but not to affect the function of other voltage‐gated sodium channels not affected by the SCN8A mutation.3 Therefore, the diagnosis of SCN8A mutation is important for rational treatment decisions.\n\nThe potentially severe side effects of phenytoin, especially cognitive impairment, are undesirable in patients with SCN8A encephalopathy who already suffer from a delay in cognitive development. Yet, this case demonstrates that there may be merit in using phenytoin as an emergency treatment.\n\nDisclosure\nNone of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.\n\n\nHilde M. Braakman is a pediatric neurologist at the Academic Center for Epileptology.\n==== Refs\nReferences\n1 \n\nOliva \nM \n, \nBerkovic \nSF \n, \nPetrou \nS \n. Sodium channels and the neurobiology of epilepsy . Epilepsia \n2012 ;53 :1849 –1859 .22905747 \n2 \n\nLarsen \nJ \n, \nCarvill \nGL \n, \nGardella \nE \n, et al. The phenotypic spectrum of SCN8A encephalopathy . Neurology \n2015 ;84 :480 –489 .25568300 \n3 \n\nBoerma \nRS \n, \nBraun \nKP \n, \nvan de Broek \nMPH \n, et al. Remarkable phenytoin sensitivity in 4 children with SCN8A‐related epilepsy: a molecular neuropharmacological approach . Neurotherapeutics \n2016 ;13 :192 –197 .26252990 \n4 \n\nde Kovel \nCG \n, \nMeisler \nMH \n, \nBrilstra \nEH \n, et al. Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy . Epilepsy Res \n2014 ;108 :1511 –1518 .25239001 \n5 \n\nBarker \nBS \n, \nOttolini \nM \n, \nWagnon \nJL \n, et al. The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin . Epilepsia \n2016 ;57 :1458 –1466 .27375106 \n6 \n\nNeveling \nK \n, \nFeenstra \nI \n, \nGilissen \nC \n, et al. A post‐hoc comparison of the utility of Sanger sequencing and exome sequencing for the diagnosis of heterogeneous diseases . Hum Mutat \n2013 ;34 :1721 –1726 .24123792 \n7 \n\nMeisler \nMH \n, \nHelman \nG \n, \nHammer \nMF \n, et al. SCN8A encephalopathy: research progress and prospects . Epilepsia \n2016 ;57 :1027 –1035 .27270488 \n8 \n\nDelgado‐Escueta \nAV \n, \nBourgeois \nBF \n. Debate: does genetic information in humans help us to treat patients? PRO—genetic information in humans helps us treat patients. CON—genetic information does not help at all . Epilepsia \n2008 ;49 :13 –24 .\n\n",
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"reactionmeddrapt": "Encephalopathy",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
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"reactionmeddrapt": "Status epilepticus",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
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"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
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"reactionmeddrapt": "Ataxia",
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"literaturereference": "BRAAKMAN H, VERHOEVEN J, ERASMUS C, HAAXMA C, WILLEMSEN M, SCHELHAAS H. PHENYTOIN AS A LAST-RESORT TREATMENT IN SCN8A ENCEPHALOPATHY. EPILEPSIA OPEN. 2017 MAY 16?2(3):343-344.",
"literaturereference_normalized": "phenytoin as a last resort treatment in scn8a encephalopathy",
"qualification": "3",
"reportercountry": "NL"
},
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"receiptdate": "20180411",
"receivedate": "20180411",
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},
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"senderorganization": "FDA-Public Use",
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"transmissiondate": "20180711"
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{
"abstract": "Oromandibular dystonia (OMD) causes involuntary movements of masticatory and lingual muscles impairing eating, speaking, and swallowing. Treatment options are limited. The objective of this study was to determine the safety and efficacy of abobotulinumtoxinA (aboBoNTA) in OMD. A dose-finding study (phase 1) followed by a single session, prospective, single-blind trial (phase 2) was carried out. OMD subjects were evaluated at baseline, 6 and 12 weeks. Muscles injected were tailored to individual symptoms using EMG guidance, but the aboBoNTA dose for each muscle was pre-specified based on phase 1 results. Evaluations were Global Dystonia Rating Scale (GDS), Unified Dystonia Rating Scale (UDRS), Clinical Global Impression (CGI) improvement and severity, and quality of life (OMDQ-25). Adverse events were monitored. The lowest dosage in phase 1 resulted in adverse effects in two of three patients and thus was used in phase 2. In phase 2, adverse effects were observed in 50% of subjects including dysphagia, voice change, and soft palate weakness. Most were mild. Significant improvement was seen in quality of life (OMDQ-25), speech (BFMq21), and change in GDS, UDRS, CGI severity assessed by the unblinded investigator, but not in blinded video ratings. We conclude that aboBoNTA therapy in this study was associated with improved quality of life and was generally well tolerated in OMD, but occurrence of dysphagia dictated the importance of using low genioglossus dosing. Face to face assessment appears to be more sensitive than video assessment for change in OMD severity. Consideration of the disability in OMD places constraints on traditional placebo-control trial design. Development of novel trial designs is warranted.",
"affiliations": "Department of Neurology, Emory University, Atlanta, GA, USA.;Department of Neurology, Emory University, Atlanta, GA, USA.;Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.;Department of Neurology, Emory University, Atlanta, GA, USA.;Department of Neurology, Emory University, Atlanta, GA, USA.;Department of Neurology, Emory University, Atlanta, GA, USA.;Department of Neurology, Emory University, Atlanta, GA, USA. sfactor@emory.edu.",
"authors": "Scorr|Laura M|LM|;Silver|Michael R|MR|;Hanfelt|John|J|;Sperin|Elaine|E|;Freeman|Alan|A|;Jinnah|H A|HA|;Factor|Stewart A|SA|",
"chemical_list": "D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A; C542869:abobotulinumtoxinA",
"country": "United States",
"delete": false,
"doi": "10.1007/s13311-018-0620-9",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1878-7479",
"issue": "15(2)",
"journal": "Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics",
"keywords": "AbobotulinumtoxinA; Clinical trial; Dystonia; Oromandibular dystonia; Quality of life",
"medline_ta": "Neurotherapeutics",
"mesh_terms": "D000368:Aged; D019274:Botulinum Toxins, Type A; D004421:Dystonia; D020821:Dystonic Disorders; D005260:Female; D006801:Humans; D008297:Male; D008410:Masticatory Muscles; D008875:Middle Aged; D009465:Neuromuscular Agents; D010865:Pilot Projects; D011446:Prospective Studies; D016037:Single-Blind Method; D016896:Treatment Outcome",
"nlm_unique_id": "101290381",
"other_id": null,
"pages": "452-458",
"pmc": null,
"pmid": "29542022",
"pubdate": "2018-04",
"publication_types": "D016430:Clinical Trial; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": "11296046;17156419;27776922;27647704;21108749;26788329;14610144;23440162;10644785;24282121;23868503;16417594;3966004;26365917;2325686;24122897;21328222;25476727;27278063;16271495;12621634;9160072;2916831;17089393;7845401;10599789;23649720;3264051;21496604;19855255;17588237;26866500;20494607;21348790;23380701;2899953;24847442;3561773",
"title": "Pilot Single-Blind Trial of AbobotulinumtoxinA in Oromandibular Dystonia.",
"title_normalized": "pilot single blind trial of abobotulinumtoxina in oromandibular dystonia"
} | [
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"companynumb": "US-IPSEN BIOPHARMACEUTICALS, INC.-2016-09173",
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},
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"medicinalproduct": "DYSPORT"
},
{
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"drugdosageform": "POWDER FOR SOLUTION FOR INJECTION",
"drugdosagetext": "NOT REPORTED",
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"drugindication": "OROMANDIBULAR DYSTONIA",
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"medicinalproduct": "DYSPORT"
}
],
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"reaction": [
{
"reactionmeddrapt": "Weight decreased",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Feeding disorder",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Palatal disorder",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Dry mouth",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Cough",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Dysphagia",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Dysphonia",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Throat tightness",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drooling",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Mastication disorder",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Influenza like illness",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "FACTOR S, SILVER M, HANFELT J, SPERIN E, SCORR L, FREEMAN A, JINAH H. PILOT SINGLE-BLIND TRIAL OF ABOBOTULINUMTOXINA IN OROMANDIBULAR DYSTONIA. NEUROTHERAPEUTICS. 2018?15(2):452-458. DOI:10.1007/S13311-018-0620-9",
"literaturereference_normalized": "pilot single blind trial of abobotulinumtoxina in oromandibular dystonia",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190408",
"receivedate": "20190408",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 16168404,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
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"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20190711"
}
] |
{
"abstract": "The risks of osteoporosis and breast cancer are increasing in elderly women. Bisphosphonates and denosumab are recommended for treatment of osteoporosis. They have different and overlapping pharmacodynamics and previous studies have shown conflicting results regarding their risk association with breast cancer. We intend to further look into this issue through a comparative study. Electronic health records of 91,626 women older than 50 years with no previous history of malignancy and no nonbreast cancer during follow-up were retrieved from southern California and retrospectively analyzed using univariate, bivariate, and log-rank tests. Medication use, breast cancer risk, and associated demographic and clinical history were assessed. Over an average of 3.6 years follow-up, the breast cancer relative risks (RRs) counted after 365 days of latency are 1.12 (95% confidence interval [CI]: 0.64-1.97) for denosumab ever users and 0.37 (95% CI: 0.21-0.66) for bisphosphonates ever users, when covariates are comparable. The significant difference is supported by the Log-rank test (p = 0.0004). Excluding statins coprescribers, the breast cancer RR is 1.31 (0.71, 2.43) in denosumab group and 0.26 (0.11, 0.62) in bisphosphonates group. There is a reduced RR in statins ever users (0.47, 95% CI: 0.38-0.58), and the breast cancer risk difference is not significant between concomitant denosumab/statins and bisphosphonates/statins ever users with RR 0.65 (0.16, 2.58) versus 0.55 (0.26, 1.16), p = 0.692. Our data support an association of lower breast cancer risk with bisphosphonates use in elderly women. We did not observe a lower breast cancer risk in denosumab group; however, our data revealed a potential lower breast cancer risk in denosumab users with concurrent statins use and this requires further study.",
"affiliations": "Department of Mathematics, California State University-Dominguez Hills, Carson, California, USA.;Pathology Associates of Anaheim, Anaheim Regional Medical Center, Anaheim, California, USA.;University of California at Los Angeles, Clinical and Translational Science Institute, Los Angeles, California, USA.;University of California at Los Angeles, Clinical and Translational Science Institute, Los Angeles, California, USA.;University of California at Los Angeles, Clinical and Translational Science Institute, Los Angeles, California, USA.",
"authors": "Stanoyevitch|Alexander|A|;Zhang|Lei|L|https://orcid.org/0000-0002-0422-6862;Sanz|Javier|J|;Follett|Robert W|RW|;Bell|Douglas S|DS|https://orcid.org/0000-0002-5063-8294",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1089/whr.2020.0120",
"fulltext": "\n==== Front\nWomens Health Rep (New Rochelle)\nWomens Health Rep (New Rochelle)\nwhr\nWomen's Health Reports\n2688-4844\nMary Ann Liebert, Inc., publishers 140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA\n\n10.1089/whr.2020.0120\n10.1089/whr.2020.0120\nOriginal Article\nAssociation of Antiosteoporotic Medication Bisphosphonates and Denosumab with Primary Breast Cancer: An Electronic Health Record Cohort Study\nStanoyevitch, et al.; Women's Health Reports 2021, 2.1\nStanoyevitch Alexander 1 †\nZhang Lei 2 † https://orcid.org/0000-0002-0422-6862\n\nSanz Javier 3\nFollett Robert W. 3\nBell Douglas S. 3 https://orcid.org/0000-0002-5063-8294\n\n1 Department of Mathematics, California State University-Dominguez Hills, Carson, California, USA.\n2 Pathology Associates of Anaheim, Anaheim Regional Medical Center, Anaheim, California, USA.\n3 University of California at Los Angeles, Clinical and Translational Science Institute, Los Angeles, California, USA.\n† Contribute equally to this paper.\n\n*Address correspondence to: Lei Zhang, MD, PhD, Pathology Associates of Anaheim, Anaheim Regional Medical Center, Anaheim, CA 92801-2804, USA, lei_248@hotmail.com\nThe initial study on identification of cancer cases in electronic health system using ICD and SNOMED codes has been presented as an abstract at The USCAP 106th Annual Meeting, March 4th–10th, 2017 in San Antonio, TX. Poster No. 211. Abstract publication #:1612. The Supplementary Figure S1 is the reprint of that abstract.\n\niORCID ID (https://orcid.org/0000-0002-0422-6862).\n\niiORCID ID (https://orcid.org/0000-0002-5063-8294).\n\n16 8 2021 August 2021\n2021\n16 8 2021 August 2021\n2 1 316324\n14 7 2021 Accepted July 14, 2021\n© Alexander Stanoyevitch et al., 2021; Published by Mary Ann Liebert, Inc.\n2021\nAlexander Stanoyevitch et al.,\nhttps://creativecommons.org/licenses/by/4.0/ This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\n\nBackground: The risks of osteoporosis and breast cancer are increasing in elderly women. Bisphosphonates and denosumab are recommended for treatment of osteoporosis. They have different and overlapping pharmacodynamics and previous studies have shown conflicting results regarding their risk association with breast cancer. We intend to further look into this issue through a comparative study.\n\nMethods: Electronic health records of 91,626 women older than 50 years with no previous history of malignancy and no nonbreast cancer during follow-up were retrieved from southern California and retrospectively analyzed using univariate, bivariate, and log-rank tests. Medication use, breast cancer risk, and associated demographic and clinical history were assessed.\n\nResults: Over an average of 3.6 years follow-up, the breast cancer relative risks (RRs) counted after 365 days of latency are 1.12 (95% confidence interval [CI]: 0.64–1.97) for denosumab ever users and 0.37 (95% CI: 0.21–0.66) for bisphosphonates ever users, when covariates are comparable. The significant difference is supported by the Log-rank test (p = 0.0004). Excluding statins coprescribers, the breast cancer RR is 1.31 (0.71, 2.43) in denosumab group and 0.26 (0.11, 0.62) in bisphosphonates group. There is a reduced RR in statins ever users (0.47, 95% CI: 0.38–0.58), and the breast cancer risk difference is not significant between concomitant denosumab/statins and bisphosphonates/statins ever users with RR 0.65 (0.16, 2.58) versus 0.55 (0.26, 1.16), p = 0.692.\n\nConclusions: Our data support an association of lower breast cancer risk with bisphosphonates use in elderly women. We did not observe a lower breast cancer risk in denosumab group; however, our data revealed a potential lower breast cancer risk in denosumab users with concurrent statins use and this requires further study.\n\nbisphosphonates\nbreast cancer\ndenosumab\nosteoporosis\nstatins\n==== Body\npmcIntroduction\n\nBoth osteoporotic fracture and cancer can be a devastating personal and social economic burden, and the risks for both are increasing when the modern life expectancy is growing over the age of 80 years. Seventy-one percent of osteoporotic fractures occur in women, while breast cancer is the most common tumor all over the world.1,2 The effects of antiosteoporosis medication on breast cancer are a debate and a concern.\n\nCurrently, bisphosphonates (Alendronate, risedronate, and zoledronic acid) and denosumab are recommended by United States Preventive Services Task Force (USPSTF) to treat osteoporosis in postmenopausal women younger or older than 65 years.1\n\nThe antiosteoporotic effects of bisphosphonates and denosumab are different: denosumab is more effective and faster in improving bone mass density; but effects of bisphosphonates continue for years after drug discontinuation because they are imbedded in the bone, while denosumab discontinuation fully and rapidly reverse its effects on bone markers and bone mineral density. Denosumab is contraindicated in severe infection, but is preferred in patients with renal failure.3–5\n\nEpidemiological studies have also shown that bisphosphonates are associated with variable nonadverse, for example, protective or no related risk toward female breast cancer.6–15 A recent study suggests a potential protective effect of denosumab ever use on breast cancer risk in a cohort of older women previously treated with bisphosphonates.16 It is not clear whether this protective effect is due to lingering effects of previous bisphosphonates use. Denosumab is active in body for only 6 months compared to years of lingering effects from bisphosphonates. This may lead to a speculation that denosumab has no effect on breast cancer in women who took and discontinued it. However, drug side effects may not occur until long time after stopping the medication and cancer can be related to radiation exposure events, which have lasted only minutes. A comparative study of denosumab and bisphosphonates might be helpful addressing this question. An initial epidemiological study based on the Nurses' Health Study (NHS) cohort did not show protective effects of statins on breast cancer, when antiosteoporosis therapy was not considered in either medication or control groups.17\n\nCancer risk reduction using pharmacological means is an attractive modern preventive approach that supplements the classical behavioral prevention recommendations. Studying commonly used drugs such as bisphosphonates and statins as candidate cancer chemopreventive agents has the advantage of usually having a low-risk profile and is associated with much clinical experience.\n\nThe osteoporosis risk increases after menopause, which is on average by age of 51, and this is also the early starting age antiosteoporosis medications are provided. We set the start of our observation time as age 50 and older.\n\nThe potential different effects of bisphosphonates and denosumab on breast cancer have not been compared yet. How possibly the drug interaction of antiosteoporosis with statins could further modify breast cancer risk is unknown. Knowledge of these may help decisions on individualized medication best beneficial to patients. We aim to investigate those questions using a cohort, including females 50 years of age or older.\n\nMaterials and Methods\n\nPopulation\n\nThis study was approved by the Research Ethics Board of University of California at Los Angeles (UCLA), IRB#16-000581. Inclusion criteria: female and age 50 or older at their first visit, with at least two ambulatory encounters in 1 year. Exclusion criteria: previous diagnosis of cancer in the first encounter and cancer diagnosis other than breast cancer during follow-up.\n\nData retrieval\n\nThe clinical data were retrieved from electronic health record (EHR) Epic. A 3.6-year duration of chronological clinical information was extracted from the Clarity data base, which has been daily transferred from the Epic application (Chronicles). The requested data output for this project is in nine CSV (comma-separated values) format files, including parameters of ICD, SNOMED diagnoses, laboratories, medications, family history, allergies, vital signs, and demographic information. The medications include prescriptions linked to pharmacy fill-up or in-house administration. All HIPAA (Health Insurance Portability and Accountability Act) identifiers have been stripped from the data sets. These data sets were linked using unique encoded identifiers.\n\nAnalytics\n\nStudy groups\n\nIn addition to denosumab and bisphosphonates, we also examined possible interactions with two other popular drug classes: hormones and statins. The patients were separated into two mutually exclusive groups, medication group and control group:\n\nMedication group\n\nIt includes (1) denosumab, (2) bisphosphonates (Alendronate, Risedronate, Zoledronic, Pamidronate, and Ibandronate), (3) statins (Simvastatin, Atorvastatin, Rosuvastatin, Fluvastatin, Pitavastatin, Lovastatin, and Pravastatin), and (4) hormones (used by women to reduce menopausal symptoms, including patch, tablets or vaginal ring of estradiol, estrogen, and Norethindrone Acetate-Ethinyl Estradiol).\n\nControl group definition\n\nHospital visitors who have never been prescribed bisphosphonates, denosumab, statins, or hormones.\n\nBreast cancer identification\n\nICD-9 (174.9, V10.3) and ICD-10 (C50, Z85.3) codes, which are authoritative tools for disease identification, besides their association with claims and reimbursement, are used to identify breast cancer patients (see Supplementary Fig. S1 for initial validation study).\n\nBreast cancer patients definitions\n\n(1) Patients who were diagnosed with breast cancer 365 days or later after they were first prescribed any of these four medication groups; (2) patients in the control group who were diagnosed with breast cancer at least 365 days after the first encounter. The following situations are excluded from counting of breast cancer cases to focus on primary breast cancer study, and to exclude situations when denosumab/bisphosphonates are used to treat bone metastatic tumor or myeloma: (1) patients exposed to denosumab or bisphosphonates who have cancer diagnoses other than breast type; (2) patients with breast cancer diagnosis before denosumab or bisphosphonates administration.\n\nCovariates\n\nWe examined controlling our comparisons against the following relevant covariates: age, body mass index (BMI), blood pressure (BP), hyperlipidemia, diabetes status, breast cancer family history, and alcohol ever use. Those parameters are extracted from either ICD-diagnosis codes or laboratory measurements or encounter documentation.\n\nStatistical analysis\n\nAll data analyses and application of inclusion and exclusion criteria were performed using the R statistical software package (with R Studio).\n\nThe univariate and bivariate analyses include a Kaplan-Meier plot and its associated log-rank test, relative risks (RRs), confidence intervals (CIs), and Fisher's exact test, and p values (one or two-tail, significance level: p < 0.01) were provided whenever feasible.\n\nFor each patient in the medication group, we computed the last date of any of the four drugs that they took and added that number to 365 to determine the threshold after which a breast cancer diagnosis gets counted.\n\nResults\n\nFormation of study cohort\n\nThe UCLA health system has around 180 primary and specialty care practices in southern California. There are 285,254 patients who are aged 50 years or older at their first visit on or after date of January 01, 2012. The visit types include all encounters documented in the Epic EHR, including ambulatory (outpatient clinics, physician offices, same day/ambulatory surgery centers, urgent care facilities, and other same-day ambulatory hospital encounters), emergency, emergency to inpatient, and inpatient, etc. 205,952 patients who are older than 50, with at least two ambulatory encounters in 1 year from January 1st, 2012 to July 1st, 2016 in UCLA electronic health system were first sorted out. After excluding male patients and patients who have had previous diagnosis of cancer in first encounter and cancer diagnosis other than breast cancer during follow-up, our cohort includes 92,207 female patients. Excluding patients with cancers other than breast, a total of 91,626 patients enter final analysis (Fig. 1).\n\nFIG. 1. Diagram of cohort formation. UCLA, University of California at Los Angeles.\n\nDifferential breast cancer risk between denosumab and bisphosphonates group\n\nThe duration of denosumab and bisphosphonates use in our cohort is mostly around 1–2 years. The number of patients taking the medications and prescription dosage are summarized in Supplementary Table S1.\n\nExcluding the first-year latency, the absolute breast cancer risk in denosumab ever use group is 1.54% (12/778), compared to 0.52% (12/2326) in bisphosphonates, with RR of 1.12 (95% CI: 0.64–1.97) versus 0.37 (95% CI: 0.21–0.66). The accumulative risk is statistically significant (p = 0.0085) [Table 1]. The breast cancer distribution in follow-up time of 3 years as shown by Kaplan-Meier plot and log-rank test is also significant between the two groups (p = 0.0004) (Fig. 2). The covariates between the two groups are comparable (Table 2, a concise summary in Supplementary Table S2).\n\nFIG. 2. Breast cancer free diagnosis in bisphosphonates and denosumab users, Kaplan-Meier plot and log-rank test.\n\nTable 1. Comparison of Breast Cancer Risks Among Different Medication Groups\n\n \tBreast cancer risk & 95% CI\tBreast cancer RRa (95% CI)\tp-(RR of denosumab ≠ bisphosphonates)\t\nMedication ever users\t\n Denosumab\t1.54% (12/778)\n0.68%, 2.41%\t1.12 (0.64–1.97)\t0.0085\t\n Bisphosphonates\t0.52% (12/2326)\n0.22%, 0.81%\t0.37 (0.21–0.66)\t\n Statins\t0.65% (99/15,287)\n0.52%, 0.78%\t0.47 (0.38–0.58)\t \t\n Hormone (for postmenopausal symptoms)\t0.26% (20/7631)\n0.15%, 0.38%\t0.19 (0.12–0.30)\t \t\nComedication ever users\t\n Denosumab+statins\t0.89% (2/224)\n0.24%, 3.90%\t0.65 (0.16–2.58)\t0.6920\t\n Bisphosphonates+statins\t0.76% (7/919)\n0.37%, 1.56%\t0.55 (0.26–1.16)\t\nSingle medication ever users\t\n Denosumab\t1.81% (10/554)\n0.99%, 3.30%\t1.31 (0.71–2.43)\t0.0023\t\n Bisphosphonates\t0.36% (5/1407)\n0.15%, 0.84%\t0.26 (0.11–0.62)\t\nControl\t1.38% (1032/74,867)\n1.30%, 1.47%\t1\t \t\na RRs are comparisons to control population.\n\nCI, confidence interval; RR, relative risk.\n\nTable 2. Stratified Breast Cancer Risk in Different Medication Groups\n\n \tDenosumab N = 778\tBisphosphonates N = 2326\tStatins N = 15,287\tHormone N = 7631\tControl N = 74,867\t\nAge of first encounter (first quarter, median, mean, third quarter)\t62, 68, 69.47, 78\t61, 67, 68.59, 76\t60, 67, 68.23, 75\t55, 60, 61.9, 67\t56, 63, 64.47, 71\t\nFamily history of breast cancer (%, n)\t15% (119)\t12% (273)\t9% (1441)\t14% (1052)\t7% (5187)\t\nAlcohol ever use (%, n)\t\n Yes\t33% (254)\t29% (666)\t31% (4708)\t45% (3446)\t29% (21,815)\t\n No\t46% (356)\t48% (1128)\t44% (6659)\t31% (2372)\t33% (24,469)\t\n Not asked or missing data\t21% (168)\t23% (532)\t25% (3920)\t24% (1813)\t38% (28,583)\t\nBMI\t\n Mean\t24.99\t24.91\t27.88\t25.15\t26.54\t\n >30\t15%\t14%\t14%\t15%\t24%\t\n Breast cancer absolute risk\t1.00%\t0.00%\t0.68%\t0.33%\t2.34%\t\n <25\t51%\t59%\t36%\t57%\t47%\t\n Breast cancer absolute risk\t1.50%\t1.13%\t0.71%\t0.20%\t2.35%\t\n RR (95% CI)a\t0.638 (0.28–1.44)\t0.489 (0.27–0.85)\t0.301 (0.21–0.44)\t0.088 (0.04–0.19)\t1.000\t\nBP\t\n Mean (systolic/diastolic)\t127/73\t128/72\t130/73\t125/73\t128/74\t\n Hypertension (>140/>90) (%)\t26%\t29%\t33%\t21%\t31%\t\n Breast cancer absolute risk\t2.87%\t0.97%\t0.84%\t0.47%\t2.87%\t\n Normal (<120/<80) (%)\t42%\t42%\t36%\t51%\t43%\t\n Breast cancer absolute risk\t1.92%\t0.93%\t0.77%\t0.27%\t1.83%\t\n RR (95% CI)a\t1.052 (0.47–2.38)\t0.509 (0.24–1.08)\t0.420 (0.29–0.61)\t0.145 (0.07–0.29)\t1.000\t\nDiabetes\t\n Diabetes diagnosis (%)\t10%\t9%\t15%\t6%\t15%\t\n Breast cancer absolute risk\t1.92%\t0%\t0.92%\t0.47%\t1.35%\t\n No-diabetic diagnosis\t90%\t91%\t85%\t94%\t85%\t\n Breast cancer absolute risk\t1.57%\t0.85%\t0.60%\t0.25%\t1.38%\t\n RR (95% CI)a\t1.136 (0.62–2.07)\t0.618 (0.39–0.99)\t0.435 (0.35–0.55)\t0.181 (0.11–0.29)\t1.000\t\nLipid panel\t \t \t \t \t \t\n Hyperlipidemia documented (%)\t23%\t23%\t38%b\t18%\t5%c\t\n Breast cancer absolute risk\t1.11%\t1.90%\t0.90%\t0.22%\t2.51%\t\n No hyperlipidemia documented\t\n breast cancer absolute risk\t1.68%\t0.44%\t0.49%\t0.27%\t1.32%\t\n RR (95% CI)a\t1.268 (0.68–2.38)\t0.337 (0.17–0.68)\t0.370 (0.17–0.68)\t0.205 (0.13–0.33)\t1.000\t\na RRs are for strata with normal value, compared to control population.\n\nb Statins are not only indicated for hyperlipidemia situation, but also recommended to optimize lipid levels in diabetes even if those patients may not qualify for the diagnosis of hyperlipidemia.\n\nc The low number is largely due to removal of statin treatment group from the control.\n\nBMI, body mass index; BP, blood pressure; RR, relative risk.\n\nAmong denosumab and bisphosphonates ever users, only 84 (84/3020 = 2.8%) patients have taken both medications during follow-up. Moreover, excluding statins coprescribers, the breast cancer RR is still significantly different between denosumab group and bisphosphonates group [1.31 (0.71, 2.43) vs. 0.26 (0.11, 0.62), p = 0.0023] [Table 1].\n\nParadoxically lower breast cancer risk in hyperlipidemic stratification in denosumab group\n\nWe next examine whether this risk difference between denosumab and bisphosphonates continues to hold in the stratifications of risk factors reflexing general health and physical activity.\n\nOf note, in the medication groups of denosumab, bisphosphonates, statins, and hormones, 3218 women out of 26,022 have taken more than one type of the four medications, accounting for 12% (3218/26,022) of the aforementioned medication prescribers. The control group is hospital or office visitors (n = 74,867) who have never been prescribed bisphosphonates, denosumab, statins, or hormones.\n\nOur data analyses showed that denosumab and control groups have similar breast cancer risk (1.54% vs. 1.38%, p = 0.6965); the breast cancer risks in bisphosphonates (0.52%), statins (0.65%), and hormone (0.26%) groups are significantly lower than control (p = 0.0004, <0.0002, <0.0002) [Table 1]. The differences of breast cancer risk hold constant in stratifications of BMI, BP, and diabetes status [Table 2]. In blood lipid level stratification, however, the breast cancer risk is paradoxically lower in denosumab group (1.11%, 2/181) compared to that in bisphosphonates group (1.90%, 10/526) in hyperlipidemic patients, although the risks in normal lipid group are the opposite (higher in denosumab 1.68%, lower in bisphosphonates 0.44%) [Table 2]. This has raised a concern that lipid lowering medications such as statins may confound breast cancer risk in denosumab users.\n\nJoint use of statins is associated with lower breast cancer risk in the denosumab group but not in the bisphosphonates group\n\nThe concurrent statins use is 29% (224/778) in denosumab groups and 40% (919/2326) in bisphosphonates group (p < 0.001%). When we looked at the breast cancer risk in joint medication users, we found that joint denosumab and statin use showed a lower breast cancer RR compared to denosumab ever use (0.65, 95% CI: 0.16–2.58 vs. 1.12, 95% CI: 0.64–1.97), but the association is not statistically significant. The wide 95% CI (0.16–2.58) observed in joint denosumab and statin users is due to few (n = 2) cancer cases observed. In contrast, joint use of bisphosphonates and statins show a breast cancer RR slightly higher than single medication ever use, but not statistically significant (0.55, 95% CI: 0.26–1.16 vs. 0.55, 95% CI: 0.26–1.16) [Table 1].\n\nOther findings\n\nThe hormone group in this cohort is characterized by lowest proportions of hyperlipidemia, diabetes, hypertension, and highest proportion of lean body figure (BMI less than 25) compared to other groups. This is associated with lowest breast cancer risk among all the groups despite that this group has a higher incidence of breast cancer family history.\n\nOf note, the proportion of hyperlipidemia is low in the control. This is largely due to removal of statin treatment group from the control. In addition, only 38% of patients in statins group have a diagnosis of hyperlipidemia, this is because statins are not only indicated for hyperlipidemia situation, but also recommended to optimize lipid levels in diabetes even if those patients may not qualify for the diagnosis of hyperlipidemia.18\n\nMissing data\n\nThe numbers of missing data vary among categories. Alcohol ever use category has the highest frequency of missing data (up to 25%). Nonetheless, there is no significant difference of missing data among the four medication groups and control group. Missing data were excluded from analysis.\n\nDiscussion\n\nRationale of medication grouping and covariates selections using data from EHRs\n\nBoth denosumab and bisphosphonates are approved by FDA to treat bone metastatic solid tumors or hematopoietic tumor myeloma involving bone. Those clinical scenarios are excluded from this study by excluding any patients with malignant diagnosis in first encounter, and any cancer diagnosis other than breast carcinoma during follow-up, and applying at least 365-day waiting time in medication groups for breast cancer case counting (any breast cancer cases diagnosed 365 days before medication or within 365 days after first encounter were dropped off from analysis).\n\nDenosumab is administrated subcutaneously every 6 months. Bisphosphonates are administered at variable interval of daily, weekly, quarterly, or yearly regime. The half life of bisphosphonates is up to years and denosumab still has a detectable serum level 9 months or later. The optimal duration of antiosteoporosis treatment has not been established. On the contrary, the reported timing of bisphosphonates use associated with breast cancer reduction has a wide variation: some found that the effect existed only after at least 1 year7,9; others said that deduction was not duration dependent6; some indicated that it was present only among women with <2 years of use12; others suggested that it was more marked with increasing duration of use.8 The only denosumab and breast cancer association report studied women who filled a first prescription for denosumab (denosumab ever use).16 In our cohort, the average duration for both denosumab and bisphosphonates use is around 1–2 years and the dosage is shown in Supplementary Table S1. It is uncertain whether various dosages are responsible to the confusing results regarding the estimated effect of bisphosphonates according to the timing of use. Because of the lingering effect of bisphosphonates and low-frequency standard administration regime for denosumab, we classify the antiosteoporosis therapy as two category dichotomous binary data, for example, with or without treatment.\n\nHormone treatment is required for menopausal symptom control in some patients due to decreased endogenous estrogen level. The hormone treatment may indicate both decreased risk for breast cancer (lower endogenous hormone level) and increased risk (supplemental hormone). Hormone users are a highly selected group. We therefore separate this group from our control.\n\nWell-accepted breast cancer risks include age, family history, imbalanced estrogen level, adiposity (BMI), and alcohol ever use.2,19 Smoking might have an initiation role in breast cancer, although no causal relationship is suggested.2 Moreover, diabetes status, which has not been mentioned as a risk factor for breast cancer in World Health Organization (WHO) Classification of Tumors of the Breast, has been reported to be associated with breast cancer.20,21 We included those in our covariate analysis. We compared parameters of BP and lipidemia, which are related to general health and physical activity. The covariate analysis showed that there is no significant biomedical difference between the denosumab and bisphosphonates ever use groups.\n\nComparison of our results with other studies\n\nThere were nine large studies evaluating bisphosphonates use and primary breast cancer risk in different geographic area and in various populations before this study. Three case control studies6–8 and two cohort studies9,11 suggest protective role of bisphosphonates toward breast cancer, and the other four studies10,12–14 did not prove significant protective effect, although no adverse effect is identified. The pooled results of those data15 showed that bisphosphonates were associated with 12% decrease risk of primary breast cancer (RR: 0.88; 95% CI: 0.83–0.94). Our study favors an association of significantly decreased breast cancer risk with bisphosphonates use.\n\nThe most recent large French cohort study10 observed a decrease in breast cancer risk associated with bisphosphonates use restricted to the year after treatment initiation (RR: 0.56; 95% CI: 0.36–0.87). This is close to our finding which also showed breast cancer RR 0.37 (95% CI: 0.21–0.66) in bisphosphonates ever use patients. Per meta-analysis,15 the observed association of primary breast cancer risk with long-term use (≥1 year) of bisphosphonates seemed to be more robust and stronger than that of short-term use (<1 year) (RR: 0.75; 95% CI: 0.66–0.84; and 0.90; 95% CI: 0.84–0.97; respectively). However, the only randomized control trials showed that 3–4 years of bisphosphonate treatment did not decrease the risk of invasive breast carcinoma in postmenopausal women.14 It is noted that this randomized control study was not initially designed to study breast cancer outcome. Future large randomized control studies are required to verify this concern.\n\nDifferent from bisphosphonates whose cancer association has been studied for a decade, there is only one article recently published addressing the relationship between denosumab and breast cancer risk. This first case-control study showed that in a cohort of older women previously treated with bisphosphonates, denosumab use was associated with a 13% decreased breast cancer risk (Hazard Ratio = 0.87; 95% CI: 0.76–1.00).16 There was no relationship between increasing number of denosumab doses and breast cancer risk (p-trend = 0.15).16 Our cohort study, which has a similar length of follow-up to the former study but with a bisphosphonates and denosumab comedication rate of 2.8% (84/3020 = 2.8%), did not come to the same conclusion. We showed that breast cancer risk in denosumab users is not significantly different from the control, although our study demonstrated association of lower breast cancer risk with bisphosphonates.\n\nThe initial epidemiological study on statins and breast cancer association is from the NHS cohort.17 It showed no associated risk of breast invasive carcinoma in statins users, but the comedication analysis did not include bisphosphonates use. All the cohort and case-control studies, which focused on the relationship of bisphosphonates and breast cancer, did not separate statins use from control group either.6–14 In our study, statins are associated with similar breast cancer protective effect as bisphosphonates. This is in consistence with published preclinical research.22–24 It is possible that the comparable breast cancer protective effect of bisphosphonates or statins might be masked when the control group has comedication of either of these two drugs.\n\nWe also showed that comedication of denosumab and statins is associated with lower cancer risk compared to denosumab ever use group, although the cancer cases (events) are less than 5, and statistical significance is hard to evaluate [Table 1]. Plans are underway for our acquiring even larger medical records data sets to further investigate such concepts.\n\nThis healthier biomedical status in the hormone group (lowest proportions of hyperlipidemia, diabetes, hypertension, and highest proportion of lean body figure) may explain the lowest breast cancer risk among all the groups, despite this group has a higher incidence of breast cancer family history. The absence of increased breast cancer risk may also be related to low dose and formulation of supplementary hormone in this group of patients. There is a great discrepancy on breast cancer risk and postmenopausal hormone use.2 In a contemporary observational cohort study, more than 100,000 women aged 50 to 71 were followed prospectively for 15 years. It showed that long-term hormonal contraceptive use reduced ovarian and endometrial cancer risks by 40% and 34%, respectively, with no increase in breast cancer risk regardless of family history.19\n\nPreclinical studies on effects of bisphosphonates, denosumab, and statins toward breast cancer risk\n\nBisphosphonates and denosumab are both antiresorption drugs inhibiting the osteoclasts activity, but with different binding sites in the bone. Bisphosphonates bind to bone mineral matrix hydroxyapatite at the surface of bone and especially within the resorption lacunae, occupying the site of resorption performed by activated osteoclasts, where they could be internalized by the active osteoclasts and inhibit the intracellular mevalonate pathway, leading to impaired function and apoptosis of osteoclasts. Denosumab is a newer monoclonal antibody first approved by FDA for treatment of postmenopausal osteoporosis in June 2010. It suppresses bone resorption by binding to receptor activator of nuclear factor kappa-B ligand (RANKL), preventing it from binding to its receptor on cell surfaces of not only osteoclasts but also osteoclasts precursors and decreasing osteoclast formation, activity, and survival.3\n\nThe pharmaceutical effects of bisphosphonates are mediated by estrogen related receptor α (ERRα).25 ERRα plays roles in osteoporosis and breast cancer development. ERRα transcriptional activity is enhanced by cholesterol and suppressed by statins and bisphosphonates.22 Meanwhile, the epigenetic impacts of statin and bisphosphonates on DNA methylation, histone deacetylation, and microRNAs occurring in normal cells could be both cancer preventing and promoting.23 RANKL/RANK/OPG system (receptor activator of nuclear factor/RANK ligand/osteoprotegerin) is not only critical for the regulation of osteoclast differentiation/activation and calcium release from the skeleton, but also can be regarded as a major downstream mediator of progesterone-driven mammary epithelial cells proliferation, potentially contributing to breast cancer initiation and progression.24 The regulatory network is summarized in Supplementary Figure S2.\n\nThe preclinical studies suggest possible protective role of bisphosphonates on breast cancer. The preclinical studies also suggest a potential synergistic effect between denosumab and statins on breast cancer reduction as well.\n\nLimitation\n\nOne might speculate that the antiosteoporosis medication group might have lower estrogen level than control. One of the factors leading to osteoporosis is plummet of estrogen at age 50 years and older. The estrogen level is mostly affected by age and positively related to BMI or obesity. Those two factors show no significant difference between the antiosteoporosis medication and control groups in our study. These may partially solve the indication bias concern. Preclinical studies (as summarized in Supplementary Fig. S2) suggest some antiestrogen effects of those antiosteoporosis medications, and this could explain the breast cancer risk reduction observed in this cohort study. A randomized control trial is optimal; however, this might be prevented by logistical and financial challenges.\n\nThe electronic health system records individualized personal care, in compliance with standard patient care. It enables us to analyze potential drug interaction among antiosteoporosis drugs, statins, and exogenous hormones in the real world. Although EHR has a strength of medication prescription retrievability, it also carries limitation of efficient and reliable documentation of other clinical information. Age at menarche and breastfeeding history are missing in majority of our EHRs. T-score of Dual-energy X-ray absorptiometry is absent for majority patients. Osteoporosis risk assessment FRAX score is not uniformly used and documented in EHR.\n\nIt is natural to ask whether the breast cancer patients in each medication subgroup have different prognosis. Breast cancer prognosis is currently stratified into eight groups based on anatomic characters, including T (tumor), N (nodes), M (metastasis), and biological types, including estrogen/progesterone receptor, and HER2 (Human Epidermal Growth Factor Receptor 2) status according to American Joint Committee on Cancer (AJCC) 8th edition.26 Furthermore, categorization based on genome, RNA, or protein expression profiles are also applied.26 Such complex stratifications require large number of breast cancer cases for testing of prognosis difference across each subgroup. This question may be addressed in future large-scale studies.\n\nConclusion\n\nThis is the first study to compare the risk of primary breast cancer between bisphosphonates and denosumab users head-to-head. The results, if supported by further studies could be potentially helpful for clinical decision when breast cancer is a concern and patients are treated for osteoporosis with or without comorbidity of hyperlipidemia.\n\nOur data support an association of lower breast cancer risk with bisphosphonates use in elderly women. We did not observe a lower breast cancer risk in denosumab group; however, our data revealed a potential lower breast cancer risk in denosumab users with concurrent statins use and this requires further study.\n\nAvailability of Data and Materials\n\nThe data of this study are available from the Clinical and Translational Science Institute, UCLA. HIPPA restrictions apply.\n\nEthics Declarations\n\nThis study was approved by the Research Ethics Board of University of California at Los Angeles.\n\nSupplementary Material\n\nSupplemental data\n\nSupplemental data\n\nSupplemental data\n\nSupplemental data\n\nAcknowledgment\n\nWe are grateful to the reviewers for their insightful comments which led to improvement in the article. We thank Marianne Zachariah from CTSI, UCLA for consulting.\n\nAuthors' Contributions\n\nData analysis—A.S. and L.Z.; data extraction—J.S. and R.F.; study design—L.Z. and D.B.; article preparation—L.Z., A.S., and D.B.; and D.B. oversees the project.\n\nAuthor Disclosure Statement\n\nNo competing financial interests exist.\n\nFunding Information\n\nThis research was partially supported by NIH National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR001881.\n\nSupplementary Material\n\nSupplementary Figure S1\n\nSupplementary Figure S2\n\nSupplementary Table S1\n\nSupplementary Table S2\n\nCite this article as: Stanoyevitch A, Zhang L, Sanz J, Follett R, Bell D (2021) Association of antiosteoporotic medication bisphosphonates and denosumab with primary breast cancer: an electronic health record cohort study, Women's Health Report 2:1, 316–324, DOI: 10.1089/whr.2020.0120.\n\nAbbreviations Used\n\n95% CI 95% confidence interval\n\nAJCC American Joint Committee on Cancer\n\nBMI body mass index\n\nCSV comma-separated values\n\nEHR electronic health record\n\nERRα estrogen-related receptor α\n\nFDA Food and Drug Administration\n\nHER2 Human Epidermal Growth Factor Receptor 2\n\nHIPPA Health Insurance Portability and Accountability Act\n\nICD International Classification of Diseases\n\nNHS Nurses' Health Study\n\nNM tumor nodes metastasis\n\nOPG osteoprotegerin\n\nRANK receptor activator of nuclear factor kappa-B\n\nRANKL receptor activator of nuclear factor kappa-B ligand\n\nRR relative risk\n\nSNOMED Systematized Nomenclature of Human Medicine\n\nUCLA University of California at Los Angeles\n\nWHO World Health Organization\n==== Refs\nReferences\n\n1. US Preventive Services TaskForces, CurrySJ, KristAH, et al. Screening for osteoporosis to prevent fractures: US preventive services task force recommendation statement. JAMA 2018;319 :2521–2531 29946735\n2. RakhaEA, AllisonKH, EllisIO, et al. Invasive breast carcinoma: General overview. In: WHO Classification of Tumors of the Breast. Lyon: IARC, 2019:83–84.\n3. AnastasilakisAD, PolyzosSA, MakrasP. Therapy of endocrine disease: Denosumab vs. bisphosphonates for the treatment of postmenopausal osteoporosis. Eur J Endocrinol 2018;179 :R31–R45 29691303\n4. KimSY, OkHG, BirkenmaierC, et al. Can denosumab be a substitute, competitor, or complement to bisphosphonates? Korean J Pain 2017;30 :86–92 28416991\n5. SingerA, GrauerA. Denosumab for the management of postmenopausal osteoporosis. Postgrad Med 2010;122 :176–187\n6. VinogradovaY, CouplandC, Hippisley-CoxJ. Exposure to bisphosphonates and risk of common non-gastrointestinal cancers: Series of nested case-control studies using two primary-care databases. Br J Cancer 2013;109 :795–806 23868009\n7. RennertG, PinchevM, RennertHS. Use of bisphosphonates and risk of postmenopausal breast cancer. J Clin Oncol 2010;28 :3577–3581 20567021\n8. NewcombPA, Trentham-DietzA, HamptonJM. Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk. Br J Cancer 2010;102 :799–802 20160722\n9. VestergaardP, FischerL, MeleM, MosekildeL, ChristiansenP. Use of bisphosphonates and risk of breast cancer. Calcif Tissue Int 2011;88 :255–262 21253712\n10. FournierA, MesrineS, GelotA, et al. Use of bisphosphonates and risk of breast cancer in a French cohort of postmenopausal women. J Clin Oncol 2017;35 :3230–3239 28708471\n11. CardwellCR, AbnetCC, VealP, et al. Exposure to oral bisphosphonates and risk of cancer. Int J Cancer 2012;131 :E717–E725 22161552\n12. ChlebowskiRT, ChenZ, CauleyJA, et al. Oral bisphosphonate use and breast cancer incidence in postmenopausal women. J Clin Oncol 2010;28 :3582–3590 20567009\n13. ChiangCH, HuangCC, ChanWL, et al. Oral alendronate use and risk of cancer in postmenopausal women with osteoporosis: A nationwide study. J Bone Miner Res 2012;27 :1951–1958 22532232\n14. HueTF, CummingsSR, CauleyJA, et al. Effect of bisphosphonate use on risk of postmenopausal breast cancer: Results from the randomized clinical trials of alendronate and zoledronic Acid. JAMA Intern Med 2014;174 :1550–1557 25111880\n15. LiuY, ZhangX, SunH, et al. Bisphosphonates and primary breast cancer risk: An updated systematic review and meta-analysis involving 963,995 women. Clin Epidemiol 2019;11 :593–603 31410067\n16. GiannakeasV, CadaretteSM, BanJK, et al. Denosumab and breast cancer risk in postmenopausal women: A population-based cohort study. Br J Cancer 2018;119 :1421–1427 30420611\n17. BorgquistS, TamimiRM, ChenWY, et al. Statin use and breast cancer risk in the nurses' health study. Cancer Epidemiol Biomarkers Prev 2016;25 :201–206 26762806\n18. EldorR, RazI. American diabetes association indications for statins in diabetes: Is there evidence? Diabetes Care 2009;32 (suppl 2 ):S384–S391 19875586\n19. MichelsKA, PfeifferRM, BrintonLA, TrabertB. Modification of the associations between duration of oral contraceptive use and ovarian, endometrial, breast, and colorectal cancers. JAMA Oncol 2018;4 :516–521 29346467\n20. LarssonSC, MantzorosCS, WolkA. Diabetes mellitus and risk of breast cancer: A meta-analysis. Int J Cancer 2007;121 :856–862 17397032\n21. HardefeldtPJ, EdirimanneS, EslickGD. Diabetes increases the risk of breast cancer: A meta-analysis. Endocr Relat Cancer 2012;19 :793–803 23035011\n22. CasaburiI, ChimentoA, De LucaA, et al. Cholesterol as an endogenous ERRα agonist: A new perspective to cancer treatment. Front Endocrinol (Lausanne). 2018;9 :525 , eCollection. 30254608\n23. KarlicH, ThalerR, GernerC, et al. Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells. Cancer Genet 2015;208 :241–252 25978957\n24. InfanteM, FabiA, CognettiF, et al. RANKL/RANK/OPG system beyond bone remodeling: Involvement in breast cancer and clinical perspectives. J Exp Clin Cancer Res 2019;38 :12 30621730\n25. WeiW, SchwaidAG, WangX, et al. Ligand Activation of ERRα by cholesterol mediates statin and bisphosphonate effects. Cell Metab 2016;23 :479–491 26777690\n26. Updated breast chapter of the AJCC cancer staging manual. Available at:https://cancerstaging.org/About/news/Pages/UpdatedBreast-Chapter-for-8th-Edition.aspx Accessed 729, 2021\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2688-4844",
"issue": "2(1)",
"journal": "Women's health reports (New Rochelle, N.Y.)",
"keywords": "bisphosphonates; breast cancer; denosumab; osteoporosis; statins",
"medline_ta": "Womens Health Rep (New Rochelle)",
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"nlm_unique_id": "101768931",
"other_id": null,
"pages": "316-324",
"pmc": null,
"pmid": "34476414",
"pubdate": "2021",
"publication_types": "D016428:Journal Article",
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"title": "Association of Antiosteoporotic Medication Bisphosphonates and Denosumab with Primary Breast Cancer: An Electronic Health Record Cohort Study.",
"title_normalized": "association of antiosteoporotic medication bisphosphonates and denosumab with primary breast cancer an electronic health record cohort study"
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{
"abstract": "BACKGROUND\nNafcillin and cefazolin are considered first-line therapy for most infections with methicillin-susceptible Staphylococcus aureus (MSSA), and recent studies have suggested similar clinical efficacy. Limited data are available on the comparative tolerability of these agents.\n\n\nMETHODS\nIn this retrospective cohort analysis of patients treated with either nafcillin or cefazolin for MSSA infection in the outpatient parenteral antimicrobial therapy clinic at Massachusetts General Hospital from 2007 to 2011, the frequency of premature antimicrobial discontinuation (PAD) and drug-emergent events (DEEs) was calculated.\n\n\nRESULTS\nThree hundred sixty-six and 119 patients were treated with nafcillin or cefazolin, respectively. The median anticipated duration of therapy was comparable at 28 (interquartile range [IQR], 16-37) and 29 (IQR, 24-39) days, respectively, for those treated with nafcillin and cefazolin. Fewer patients completed the prespecified treatment course with nafcillin than with cefazolin (PAD rate, 33.8% vs 6.7%; P < .0001). The hazard ratio for PAD in the nafcillin vs cefazolin groups was 2.81 (95% confidence interval [CI], 1.26-3.68). More patients in the nafcillin group developed rash (13.9% vs 4.2%; P = .002), renal dysfunction (11.4% vs 3.3%; P = .006), and liver function abnormalities (8.1% vs 1.6%; P = .01). Overall rates of DEEs per 1000 patient-days were 16.9 (95% CI, 10.4-27.3) and 4.8 (95% CI, 1.1-10.2), respectively. In 9 cases of nafcillin discontinuation, treatment was changed to cefazolin; all 9 completed treatment with no further observed DEEs.\n\n\nCONCLUSIONS\nNafcillin treatment was associated with higher rates of both PAD as well as DEEs compared with cefazolin treatment. This difference in tolerability, in addition to efficacy and cost, should be considered when decisions for outpatient parenteral MSSA treatment are made.",
"affiliations": "Division of Infectious Diseases, Massachusetts General Hospital Harvard Medical School Division of Infectious Diseases, Boston Children's Hospital.;Division of Infectious Diseases, Massachusetts General Hospital Harvard Medical School Infection Control Unit, Massachusetts General Hospital, Boston, Massachusetts.;Division of Infectious Diseases, Massachusetts General Hospital Harvard Medical School Infection Control Unit, Massachusetts General Hospital, Boston, Massachusetts.;Division of Infectious Diseases, Massachusetts General Hospital Harvard Medical School.",
"authors": "Youngster|Ilan|I|;Shenoy|Erica S|ES|;Hooper|David C|DC|;Nelson|Sandra B|SB|",
"chemical_list": "D000900:Anti-Bacterial Agents; D009254:Nafcillin; D002437:Cefazolin; D008712:Methicillin",
"country": "United States",
"delete": false,
"doi": "10.1093/cid/ciu301",
"fulltext": null,
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"issn_linking": "1058-4838",
"issue": "59(3)",
"journal": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America",
"keywords": "MSSA; OPAT; cefazolin; nafcillin; tolerability",
"medline_ta": "Clin Infect Dis",
"mesh_terms": "D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents; D002437:Cefazolin; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008404:Massachusetts; D008712:Methicillin; D008875:Middle Aged; D009254:Nafcillin; D010045:Outpatients; D012189:Retrospective Studies; D013203:Staphylococcal Infections; D013211:Staphylococcus aureus",
"nlm_unique_id": "9203213",
"other_id": null,
"pages": "369-75",
"pmc": null,
"pmid": "24785233",
"pubdate": "2014-08-01",
"publication_types": "D003160:Comparative Study; D016428:Journal Article; D052061:Research Support, N.I.H., Extramural",
"references": "23532865;20211890;15956145;21073629;20731577;626493;21825299;17065930;16231249;22011388;16004164;24637693;576284;16466894;22445493;19374582;4744022;4791486;15227610;11168180;19487449;20721835;15937778;23223583;19767623;17493182;21371655",
"title": "Comparative evaluation of the tolerability of cefazolin and nafcillin for treatment of methicillin-susceptible Staphylococcus aureus infections in the outpatient setting.",
"title_normalized": "comparative evaluation of the tolerability of cefazolin and nafcillin for treatment of methicillin susceptible staphylococcus aureus infections in the outpatient setting"
} | [
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{
"abstract": "Nonresponse of neovascular age-related macular degeneration (nAMD) to anti-vascular endothelial growth factor (anti-VEGF) therapy can often be attributed to misdiagnosis, and pathologies mimicking AMD might require different therapeutic concepts. In the following, we want to outline a case of presumed nAMD which revealed to be pachychoroid neovasculopathy (PNV) and was successfully treated by the addition of spironolactone. A 67-year-old female patient was referred for nonresponse of nAMD on her left eye after 29 intravitreal injections of aflibercept with no complete resolution of subretinal fluid. On fundoscopy, both maculae presented with pigment epithelium alterations, while the left eye showed subretinal fluid on optical coherence tomography (OCT) with an associated pigment epithelium detachment, which revealed to contain a neovascular network on OCT angiography. There was faint leakage on fluorescence (FAG) and indocyanine green angiography (ICGA) and some focal vascular dilation of the neovascular network on ICGA. Due to the absence of Drusen on any eye, a thick choroid, and the presence of a gravitational tract on blue autofluorescence (BAF), chronic central serous chorioretinopathy with a choroidal neovascularization, defined as PNV in the pachychoroid disease was diagnosed. Upon the addition of spironolactone to anti-VEGF treatment, choroidal thickness significantly decreased, and subretinal fluid resolution was observed and maintained for the first time. In conclusion, PNV should be ruled out in cases of presumed nAMD nonresponding to anti-VEGF. In these cases, a combination therapy of anti-VEGF and mineralocorticoid antagonists can facilitate fluid resorption.",
"affiliations": "Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.;Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.;Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.;Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.",
"authors": "Keidel|Leonie F|LF|;Schworm|Benedikt|B|;Priglinger|Siegfried G|SG|;Siedlecki|Jakob|J|",
"chemical_list": null,
"country": "Switzerland",
"delete": false,
"doi": "10.1159/000510828",
"fulltext": "\n==== Front\nCase Rep Ophthalmol\nCase Rep Ophthalmol\nCOP\nCase Reports in Ophthalmology\n1663-2699\nS. Karger AG Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com\n\n10.1159/000510828\ncop-0012-0116\nCase Report\nPachychoroid Neovasculopathy Disguising as Age-Related Macular Degeneration Treated by Spironolactone and Anti-VEGF Combination Therapy\nKeidel Leonie F.\nSchworm Benedikt\nPriglinger Siegfried G.\nSiedlecki Jakob\nDepartment of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany\nJan-Apr 2021\n9 4 2021\n9 4 2021\n12 1 116123\n29 6 2020\n12 8 2020\n2021\nCopyright © 2021 by S. Karger AG, Basel\n2021\nhttps://creativecommons.org/licenses/by-nc/4.0/ This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.\nNonresponse of neovascular age-related macular degeneration (nAMD) to anti-vascular endothelial growth factor (anti-VEGF) therapy can often be attributed to misdiagnosis, and pathologies mimicking AMD might require different therapeutic concepts. In the following, we want to outline a case of presumed nAMD which revealed to be pachychoroid neovasculopathy (PNV) and was successfully treated by the addition of spironolactone. A 67-year-old female patient was referred for nonresponse of nAMD on her left eye after 29 intravitreal injections of aflibercept with no complete resolution of subretinal fluid. On fundoscopy, both maculae presented with pigment epithelium alterations, while the left eye showed subretinal fluid on optical coherence tomography (OCT) with an associated pigment epithelium detachment, which revealed to contain a neovascular network on OCT angiography. There was faint leakage on fluorescence (FAG) and indocyanine green angiography (ICGA) and some focal vascular dilation of the neovascular network on ICGA. Due to the absence of Drusen on any eye, a thick choroid, and the presence of a gravitational tract on blue autofluorescence (BAF), chronic central serous chorioretinopathy with a choroidal neovascularization, defined as PNV in the pachychoroid disease was diagnosed. Upon the addition of spironolactone to anti-VEGF treatment, choroidal thickness significantly decreased, and subretinal fluid resolution was observed and maintained for the first time. In conclusion, PNV should be ruled out in cases of presumed nAMD nonresponding to anti-VEGF. In these cases, a combination therapy of anti-VEGF and mineralocorticoid antagonists can facilitate fluid resorption.\n\nKeywords\n\nCentral serous chorioretinopathy\nAge-related macular degeneration\nSpironolactone\nChoroid\nTomography\nOptical coherence\n==== Body\nIntroduction\n\nNonresponse of neovascular age-related macular degeneration (nAMD) to intravitreal vascular endothelial growth factor (VEGF) inhibition affects approximately 5–10% of eyes and is attributable to misdiagnosis in almost 50% of cases [1]. Therefore, cases of primarily supposed neovascular AMD should be reevaluated for correct diagnosis, if anti-VEGF therapy proves to be nonefficient [1, 2].\n\nThe recently established pachychoroid spectrum of macular disorders has been shown to represent an important differential diagnosis to nAMD [3]. Pachychoroid is defined as subfoveal diffuse or focal increase in choroidal thickness (>300 µm) on optical coherence tomography (OCT), which is typically associated with abnormally dilated Haller layer vessels (pachyvessels) and an attenuation of the inner choroid (Sattler's layer and choriocapillaris) [3]. Long-term anti-VEGF treatment may induce choroidal thinning of the former above norm thickened choroid [4]. Symptomatic pachychoroid means the presence of either pachychoroidal pigment epitheliopathies, central serous chorioretinopathy (CSC), pachychoroid neovasculopathy (PNV) or pachychoroid aneurysmal type 1 choroidal neovascularization (CNV) (formerly polypoidal choroidal vasculopathy) (PAT1). CSC is present, when a serous retinal detachment with or without serous pigment epithelial detachment (PED), could be visualized. Typical changes like an RPE leakage and delayed choroidal filling in fluorescein and indocyanine green angiography (ICGA) must have been detectable. In 25% of eyes with CSC a PNV, a CNV formation, atop of a thickened choroid develops. It can be visualized on OCT and confirmed by fluorescein and ICGA with evidence of RPE atrophy, diffuse late leakage, and a late staining plaque on ICGA. Changes are considered a PAT1 when RPE detachments associated with choroidal polypoidals were present on OCT and ICGA showed the typical branching vascular network appearance with terminal aneurysmal dilatations.\n\nAlthough nAMD and the pachychoroid disease spectrum feature completely contrary etiopathologies − a pachychoroid due to faulty choroidal autoregulation versus degenerative retinal pigment epithelium and choroidal atrophy in AMD, the distinction between both entities can sometimes be difficult [3]. This is especially true in older patients showing chronic courses of pachychoroid disease and in cases complicated by CNV and PAT1 [5, 6].\n\nIn the following, we would like to outline a case of presumed neovascular AMD with nonresolving subretinal fluid refractory to anti-VEGF, which revealed to be a pachychoroid spectrum disorder complicated by CNV on multimodal imaging. In addition to continued anti-VEGF therapy, we report on the therapeutic addition of the mineralocorticoid antagonist spironolactone, which was used to reduce choroidal thickness and successfully eliminate subretinal fluid previously unresponsive to anti-VEGF.\n\nCase Report\n\nA 67-year-old patient with a history of chronic foveal PED and subretinal fluid on the left eye interpreted as neovascular AMD ex domo was referred to our clinic due to nonresponse to anti-VEGF therapy. On her left eye, 29 monthly aflibercept (Bayer AG, Leverkusen, Germany) injections had been performed for 29 months prior to presentation without achieving complete resolution of subretinal fluid. During the course of the illness, there had never been any signs of intraretinal fluid on OCT. She stated that the onset of first visual symptoms had been at the age of 40 without any medical treatment until commencement of anti-VEGF. Her right eye had a history of foveal pigment alteration, which over the course of the past years had developed a shallow PED and transient subretinal fluid, which showed complete resolution of subretinal fluid after 1 intravitreal injection of ranibizumab (Lucentis, Novartis Pharma, Basel, Switzerland) 22 months before presentation.\n\nHer best-corrected visual acuity was 20/80 on the left eye and 20/32 on the right eye, respectively. Except from a beginning corticonuclear cataract, there were no pathological findings on anterior segment examination on both eyes. Intraocular pressure was normal. There was no family history of any kind of retinal pathology. Medical history included arterial hypertension, hypothyroidism, arthritis, and psoriasis. Medication consisted of ramipril 2.5 mg, bisoprolol 2.5 mg, torasemide 10 mg, and L-Thyroxine 0.1 mg.\n\nOn fundoscopy, both maculae presented with pigment epithelium alterations, while the left macula was slightly prominent. In the following, multimodal imaging including (enhanced depth, EDI) spectral-domain OCT (SD-OCT), near-infrared (NIR) imaging, blue autofluorescence (BAF) confocal laser scanning ophthalmology, fluorescein (FAG), and indocyanine green angiography (ICGA) were performed, all using Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany). Additionally, OCT angiography (OCT-A) was performed using Angioplex on the Cirrus 5000 OCT (Carl Zeiss Meditec AG, Jena, Germany).\n\nOn NIR and SD-OCT, the right eye presented with pigment epithelium mottling and a shallow PED, which showed a type 1 CNV on OCT-A without leakage on FAG/ICGA and OCT-A. Multifocal choroidal hyperpermeability was seen on ICGA. On EDI SD-OCT, choroidal thickness was 371 μm subfoveally.\n\nOn NIR and SD-OCT, the left eye presented with a serous neurosensory detachment of the fovea with elongated photoreceptors and an underlying shallow, irregular, vascularized PED (shown in Fig. 1a). Mean subfoveal choroidal thickness was 266 μm (shown in Fig. 1a). An ill-defined gravitational tract of 4,322 μm diameter horizontally and 4,844 μm vertically was seen on BAF (shown in Fig. 1b). The presence of a CNV type 1 was confirmed on FAG/ICGA and OCT-A (shown in Fig. 2). Only faint leakage was observed from the CNV.\n\nDue to the absence of Drusen on any eye, the findings of multimodal imaging and the nonresponse to anti-VEGF, chronic CSC complicated by a secondary CNV − or, as suggested by the new pachychoroid terminology, PNV − was suspected. As some focal vascular dilations of the neovascular network were visible on ICGA of the left eye, inactive polyps after long-term anti-VEGF therapy as part of a PAT1 cannot be excluded. We did not see nodular flow in either en face or cross-sectional OCT-A scans to confirm active PAT1 [7].\n\nAll possible further options, including photodynamic therapy, were discussed with the patient, who preferred a temporary cessation of anti-VEGF therapy and the start of off-label spironolactone 25 mg BID. Within 6 weeks, subfoveal fluid significantly diminished by 51% from 108 to 55 μm (shown in Fig. 3b) and by 90% to 12 μm after 12 weeks (shown in Fig. 3c). The same applied for choroidal thickness, which decreased from 366 μm by 19% to 295 μm at 6 weeks and by 27% to 267 μm at 12 weeks. Simultaneously to the reduction in subretinal fluid and choroidal thickness, at week 6 the PED was noted to grow on the nasal and temporal CNV borders in the parafoveal region, partially penetrating the retinal pigment epithelium, defining conversion into a type 2 CNV (shown in Fig. 3b). Until the next follow-up after 12 weeks (shown in Fig. 3c), CNV growth and RPE penetration continued, along with newly diagnosed subretinal hyper-reflective material atop the type II CNV borders (shown in Fig. 3c). FAG and OCT-A confirmed the diagnosis of a type II CNV.\n\nTwelve weeks after stopping anti-VEGF and commencing spironolactone, spironolactone was stopped and aflibercept administered again. As a consequence, the type 2 segments of the CNV regressed below the RPE, the PED returned to its original configuration, and subretinal fluid disappeared (shown in Fig. 3d). After 3 further injections, subfoveal choroidal thickness had additionally decreased by 20% to 214 μm, resulting in a total reduction by 42% from 366 μm at baseline. Due to long-standing disease, the inner foveal thickness remained thinned at 75 μm. Final visual acuity was 20/50.\n\nDiscussion\n\nSince the introduction of OCT, the diagnosis of CSC has been mainly based on the presence of foveal subretinal fluid causing neurosensory detachment [3]. Nowadays, enhanced depth OCT imaging, however, allows for additional visualization of the choroid, and a multitude of diseases, including CSC, have been shown to feature overlapping, characteristic alterations of the choroidal vascular architecture [3]. As introduced by Warrow and colleagues [8], the term pachychoroid is increasingly being used to summarize this set of newly characterized macular disorders, which all feature choroidal thickening and hyperperfusion, but can be defined as single entities − or 1 disease in different stages − by the type and amount of other macular tissues affected by the choroidal malfunction (e.g., retinal pigment epithelium, outer retina, and CNV).\n\nThe pachychoroid spectrum is increasingly recognized as a frequent cause of misdiagnosis in AMD. Theoretically, the presence of Drusen is a certain pathognomonic finding of AMD, which in return should exclude the diagnosis of AMD in their absence. However, Drusen can regress upon the formation of CNV or macular atrophy caused by either disorder; type 2 CNV can lead to such severe fibrovascular disruption of the retina that Drusen as underlying cause of the CNV can be obscured; and type 1 CNV caused by pachychoroid diseases can mimic Drusen [9]. In 2012, Fung and colleagues [2] already reported about the phenotypical similarity of type 1 CNV in chronic CSC and neovascular AMD. In more recent reports on macular morphology in the CATT trials, Jaffe and colleagues [8] noted that the presence of subfoveal fluid was a consistent biomarker of good visual acuity in neovascular AMD throughout years 1–5 under anti-VEGF therapy, and recently hypothesized that this might be partly caused by associated pachychoroid disease providing better long-term prognosis than classic neovascular AMD. In contrast to nAMD, in the pachychoroid disease spectrum, CNV is thought to be caused by an increased choroidal perfusion leading to stress in the endothelial cells of the choriocapillaris and resulting in extracellular remodeling (arteriogenesis). As a next step, arteriogenesis-derived vessels may evolve above the destructed RPE cells and form a type I CNV. As recently suggested by Lupidi et al. [10] the loss of the adaptation of choroidal vascular resistance to hemodynamic stress may lead to an increased choroidal blood flow and stress to the RPE cells in patients with hyperactivity of the sympathetic system. The patient's elevated blood pressure may, therefore, contribute to the development of PNV in this case [10]. Thus, the pathogenetic process leading to and maintaining the CNV is dependent on VEGF and might as well be affected by a dysregulation of choroidal vessels [11].\n\nIn the present case, we report on the first successful combination therapy of intravitreal anti-VEGF and oral off-label spironolactone for pachychoroid-associated CNV mimicking neovascular AMD. In spite of the marked disease chronicity and a long previous therapy of 29 intravitreal anti-VEGF injections, the addition of spironolactone for the first time allowed for a complete resolution of the previously recalcitrant subretinal fluid.\n\nSpironolactone and eplerenone, both glucocorticoid-mineralocorticoid inhibitors, have been recently established as efficient off-label therapies for CSC [12]. Both facilitate subretinal fluid resolution and induce choroidal thinning by competitive inhibition of glucocorticoid signaling which is pathologically increased in CSC due to high endogenous (“stress-related”) or exogenous glucocorticoid levels, which, due to the biochemical similarity of glucocorticoid and mineralocorticoid receptors, can activate mineralocorticoid signaling [12]. In turn, an overactivation of mineralocorticoid signaling has been shown to induce angiogenesis and choroidal thickening, while the mineralocorticoid aldosterone has been shown to induce choroidal thickening secondary to an upregulation of a vasodilatory potassium channel only present in the choroid [4].\n\nBoth in pachychoroid disorders and AMD, the role of subretinal fluid, especially when subfoveal, is complex and not fully elucidated. Commonly, disease activity of uncomplicated CSC is defined by subretinal fluid presence, and patients with nonresolving fluid are at high risk of vision-threatening retinal atrophy in the long-term [5]. In neovascular AMD, however, eyes with subretinal fluid have been shown to present better visual acuity than eyes with completely dry maculae, and subretinal fluid is being discussed as a biomarker protective of geographic atrophy [13]. In the case of CNV complicating pachychoroid disorders, for example, CSC or PNV, the case is even more complex, as subretinal fluid can both derive from CNV leakage (due to less aggressive CNV activity often faint to hardly discernible) or pachychoroid activity. For these reasons, at the moment no clear recommendations as to whether or not to completely dry maculae affected by pachychoroid maculopathies or neovascular AMD can be given from a long-term perspective.\n\nInterestingly, the commencement of spironolactone and the withdrawal of anti-VEGF treatment showed a marked change in CNV morphology. CNV in pachychoroid disorders, namely CSC and PNV, is almost exclusively type 1 lesions [3]. In our case, the appearance of subretinal hyper-reflective material above the RPE was noted 6 weeks after the therapeutic intervention, not proving, but indicative of a type 2 CNV conversion. It is unclear whether this is due to the withdrawal of anti-VEGF, leading to CNV regrowth, or the influence of spironolactone on the vasculature. Theoretically, thinning of the Haller layer induced by mineralocorticoid inhibition should improve choriocapillaris perfusion and thus reduce choroidal ischemia which is hypothesized to be a driving factor in pachychoroid disease. As recently reported by Jung et al. [14], long anti-VEGF treatment, however, causes a cumulative reduction of subfoveal choroidal thickness that is greater in Aflibercept than in ranibizumab treated eyes. For this reason, the influence of spironolactone on choroidal thickness in our pre-treated case should be expected to be lower than in a treatment-naïve eye. Mechanistically, the vascular stimulus of the mineralocorticoid antagonist might have caused an inhibition of the type 1 CNV component below the RPE, while residual VEGF-levels in the vitreous body might have led to supra-RPE growth. A limitation regarding multimodal imaging was the fact, that at the time of CNV conversion into a type II CNV, only OCT-B scans were performed. An angiography to fully confirm type II CNV will be performed during the follow-up.\n\nConclusion\n\nPachychoroid disease should be considered in eyes with presumed AMD not adequately responding to anti-VEGF therapy. On OCT, measurements of subfoveal choroidal thickness and the absence of Drusen (especially on the often less affected partner eye) are easily recognizable guiding features. Spironolactone might represent a valuable additional therapy targeting choroidal malfunction in these cases and should be further examined as an adjunct therapy in randomized, controlled trials.\n\nStatement of Ethics\n\nThis case report was approved by the IRB and the patient provided written consent for these data to be published.\n\nConflict of Interest Statement\n\nLeonie Keidel received previous travel expenses from Roche Pharma. Jakob Siedlecki received income from honoraria as a lecturer from Novartis Pharma GmbH (Nürnberg, Germany), Pharm-Allergan GmbH (Frankfurt am Main, Germany), Carl Zeiss Meditec AG (Jena, Germany), and Oculentis OSD Medical GmbH (Berlin, Germany). Jakob Siedlecki received personal consultation fees from Bayer Pharma AG (Berlin, Germany). Jakob Siedlecki received travel reimbursement from Roche AG (Grenzach-Wyhlen, Germany). Benedikt Schworm received previous speaker fees and travel expenses from Novartis Pharma GmbH and Topcon Corporation. Siegfried Priglinger received previous speaker fees and/or travel expenses from Novartis Pharma GmbH, Oertli AG, Bayer AG, Alcon Pharma. GmbH and Pharm-Allergan GmbH.\n\nFunding Sources\n\nNo funding or grant support.\n\nAuthor Contributions\n\nLeonie Keidel authored the article, created the figures, and examined the patient. Jakob Siedlecki authored the article, created the figures, and examined the patient. Benedikt Schworm examined the patient and proofread. Siegfried Priglinger proofread.\n\nPatient Consent\n\nWritten consent to publish personal information and case details has been obtained from the patient. All research and measurements followed the tenets of the Declaration of Helsinki.\n\nAuthorship\n\nAll authors attest that they meet the current ICMJE criteria for authorship.\n\nFig. 1 Multimodal imaging specifically for diseases of the pachychoroid disease spectrum. On EDI-OCT (a) thinning in sattler's and choriocapillaris layer, pathologically dilated veins in the Haller's layer and increased choroidal thickening can be visualized. b BAF reveals a shallow hyper-reflectivity inferior to the fovea, indicating the presence of former subretinal fluid accumulation forming a gravitational tract (arrowhead ∆). OCT, optical coherence tomography; BAF, blue autofluorescence.\n\nFig. 2 Vessel imaging. On fluorescein angiography (a–c), only faint late leakage and mostly staining can be visualized. On ICG (d–f) and even better on OCT-A (g), the borders of the type 1 CNV can be visualized. OCT, optical coherence tomography; OCT-A, OCT angiography; ICG, indocyanine green angiography.\n\nFig. 3 Time course of central retinal thickness, subretinal fluid accumulation, and structural PED changes on OCT. a OCT on the day of presentation (after 29 aflibercept injections) shows a serous detachment of the fovea with elongated photoreceptors and an underlying shallow PED. b OCT 6 weeks after spironolactone administration shows a decrease in subfoveal fluid by 51%. PED growth was noted on the nasal and temporal CNV borders in the parafoveal region. c OCT 12 weeks after spironolactone administration shows a further decrease in subfoveal fluid by 90%, while further CNV growth at the PED borders can be noted, partially penetrating the retinal pigment epithelium with deposition of SHRM (*) atop the now type II CNV borders. d OCT 17 weeks after spironolactone administration and 5 weeks after a further anti-VEGF (aflibercept) injection, a complete resolution of subretinal fluid is achieved. anti-VEGF, anti-vascular endothelial growth factor; PED, pigment epithelium detachment; OCT, optical coherence tomography; SHRM, subretinal hyper-reflective material.\n==== Refs\nReferences\n\n1 Yang S Zhao J Sun X Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review Drug Des Devel Ther 2016 6 10 1857 67\n2 Fung AT Yannuzzi LA Freund KB Type 1 (sub-retinal pigment epithelial) neovascularization in central serous chorioretinopathy masquerading as neovascular age-related macular degeneration Retina 2012 10 32 (9) 1829 37 22850219\n3 Cheung CM Lee WK Koizumi H Dansingani K Lai TY Freund KB Pachychoroid disease Eye (Lond) 2019 1 33 (1) 14 33 29995841\n4 Padrón-Pérez N Arias L Rubio M Lorenzo D García-Bru P Català-Mora J Changes in Choroidal Thickness After Intravitreal Injection of Anti-Vascular Endothelial Growth Factor in Pachychoroid Neovasculopathy Invest Ophthalmol Vis Sci 2018 2 59 (2) 1119 24 29490349\n5 Mrejen S Balaratnasingam C Kaden TR Bottini A Dansingani K Bhavsar KV Long-term Visual Outcomes and Causes of Vision Loss in Chronic Central Serous Chorioretinopathy Ophthalmology 2019 4 126 (4) 576 88 30659849\n6 Dansingani KK Gal-Or O Sadda SR Yannuzzi LA Freund KB Understanding aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy): a lesson in the taxonomy of ‘expanded spectra’ - a review Clin Exp Ophthalmol 2018 3 46 (2) 189 200 29178419\n7 Cheung CM Yanagi Y Akiba M Tan A Mathur R Chan CM Improved Detection and Diagnosis of Polypoidal Choroidal Vasculopathy Using a Combination of Optical Coherence Tomography and Optical Coherence Tomography Angiography Retina 2019 9 39 (9) 1655 63 29927796\n8 Warrow DJ Hoang QV Freund KB Pachychoroid pigment epitheliopathy Retina 2013 9 33 (8) 1659 72 23751942\n9 Querques G Souied EH Vascularized Drusen: Slowly Progressive Type 1 Neovascularization Mimicking Drusenoid Retinal Pigment Epithelium Elevation Retina 2015 12 35 (12) 2433 9 26418449\n10 Lupidi M Fruttini D Eandi CM Nicolò M Cabral D Tito S Chronic Neovascular Central Serous Chorioretinopathy: A Stress/Rest Optical Coherence Tomography Angiography Study Am J Ophthalmol 2020 3 211 63 75 31715159\n11 Cheung CMG Lee WK Koizumi H Dansingani K Lai TYY Freund KB Pachychoroid disease Eye 2019 33 (1) 14 33 29995841\n12 Bousquet E Beydoun T Rothschild PR Bergin C Zhao M Batista R Spironolactone for Nonresolving Central Serous Chorioretinopathy: A Randomized Controlled Crossover Study Retina 2015 12 35 (12) 2505 15 26017871\n13 Jaffe GJ Ying GS Toth CA Daniel E Grunwald JE Martin DF Comparison of Age-related Macular Degeneration Treatments Trials Research Group Macular Morphology and Visual Acuity in Year Five of the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology 2019 2 126 (2) 252 60 30189282\n14 Jung BJ Kim JY Lee JH Baek J Lee K Lee WK Intravitreal aflibercept and ranibizumab for pachychoroid neovasculopathy Sci Rep 2019 2 9 (1) 2055 30765771\n\n",
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"issue": "12(1)",
"journal": "Case reports in ophthalmology",
"keywords": "Age-related macular degeneration; Central serous chorioretinopathy; Choroid; Optical coherence; Spironolactone; Tomography",
"medline_ta": "Case Rep Ophthalmol",
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"title": "Pachychoroid Neovasculopathy Disguising as Age-Related Macular Degeneration Treated by Spironolactone and Anti-VEGF Combination Therapy.",
"title_normalized": "pachychoroid neovasculopathy disguising as age related macular degeneration treated by spironolactone and anti vegf combination therapy"
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"literaturereference": "KEIDEL LF, SCHWORM B, PRIGLINGER SG, SIEDLECKI J. PACHYCHOROID NEOVASCULOPATHY DISGUISING AS AGE?RELATED MACULAR DEGENERATION TREATED BY SPIRONOLACTONE AND ANTI?VEGF COMBINATION THERAPY. CASE REP OPHTHALMOL. 2021?12:116?123",
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{
"abstract": "Methotrexate (MTX) is a commonly used anti-metabolite agent. Increased risk of lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA) has been documented with the prolonged use of immunosuppressive medications such as MTX. This is thought to be the result of immune dysregulation and/or chronic immune stimulation. Most cases of LPDs regress following withdrawal of the offending immunosuppressive agent. We present an interesting and rare case of CD30 and EBV positive CD8 primary cutaneous anaplastic large cell lymphoma (PC-ALCL) in a 66-year-old African American woman. Patient had been on MTX for rheumatoid arthritis (RA) which was stopped after the patient was evaluated at our institution. Patient had an incredible response to stopping immunosuppression with spontaneous regression of skin lesions and disappearance of clonal malignant cell population as evidenced on serial biopsy specimens. Primary cutaneous CD30+ LPDs constitute about 30% of the primary cutaneous T-cell lymphomas (CTLs) and includes entities such as lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (PC-ALCL) and other CD30+ borderline LPDs. Histopathological criteria in addition to CD30 positivity is important for identification of these conditions. Treatment options include \"wait and see\", phototherapy, radiotherapy, topical agents, systemic therapy and surgical resection. Prognosis is excellent and most cases resolve spontaneously on withdrawal of immunosuppression. Refractory cases may require aggressive local treatment or systemic therapy. Brentuximab Vedontin, an anti-CD30 antibody drug conjugate (ADC), may provide additional therapeutic option in refractory cases.",
"affiliations": "Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center Louisville, Kentucky, USA.;Department of Pathology, University of Louisville Health Sciences Center Louisville, Kentucky, USA.;Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center Louisville, Kentucky, USA.;Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center Louisville, Kentucky, USA.;Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center Louisville, Kentucky, USA.",
"authors": "Claudino|Wederson M|WM|;Gibson|Bradley|B|;Tse|William|W|;Krem|Maxwell|M|;Grewal|Jaspreet|J|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": null,
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"issn_linking": "2160-1992",
"issue": "6(1)",
"journal": "American journal of blood research",
"keywords": "Methotrexate; lymphoproliferative disorders",
"medline_ta": "Am J Blood Res",
"mesh_terms": null,
"nlm_unique_id": "101569577",
"other_id": null,
"pages": "1-5",
"pmc": null,
"pmid": "27335685",
"pubdate": "2016",
"publication_types": "D002363:Case Reports",
"references": "26433852;16508929;11090048;22508770;15692063;26485239;23868906;9826579;20669794;10408349;23031074;26518172;18299492;24805861;26510126;26261247;26195435",
"title": "Methotrexate-associated primary cutaneous CD30-positive cutaneous T-cell lymphoproliferative disorder: a case illustration and a brief review.",
"title_normalized": "methotrexate associated primary cutaneous cd30 positive cutaneous t cell lymphoproliferative disorder a case illustration and a brief review"
} | [
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"literaturereference": "CLAUDINO WM, GIBSON B, TSE W, KRE M, GREWAL J.. METHOTREXATE-ASSOCIATED PRIMARY CUTANEOUS CD30-POSITIVE CUTANEOUS T-CELL LYMPHOPROLIFERATIVE DISORDER: A CASE ILLUSTRATION AND A BRIEF REVIEW. AMERICAN JOURNAL OF BLOOD RESEARCH. 2016;6(1):1-5",
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{
"abstract": "This report describes a 40-year-old man suffering from Well's syndrome (recurrent granulomatous dermatitis with eosinophilia) who presented an anterior myocardial infarction complicated by shock and 3rd degree A-V block. The patient died within 12 hours of admission to the hospital. At autopsy, both main coronary arteries showed proximal aneurysms occluded by thrombi. On light microscopy, the aneurysmatic coronary walls were infiltrated by numerous eosinophils, lymphocytes and plasma cells. Similar cellulitis, mainly perivascular, was found in kidneys and anterior mediastinum. Because the patient had been treated with large doses of diclofenac and piroxicam owing to painful arthralgias, the Authors discuss the possible allergic pathogenesis of the vasculitis.",
"affiliations": "Ospedale S. Carlo Borromeo, Milano.",
"authors": "Casazza|F|F|;Fiorista|F|F|;Boeri|R|R|",
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"issue": "19(10)",
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"keywords": null,
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"mesh_terms": "D000328:Adult; D003323:Coronary Aneurysm; D003872:Dermatitis; D004562:Electrocardiography; D004802:Eosinophilia; D006099:Granuloma; D006801:Humans; D008297:Male; D009203:Myocardial Infarction; D013577:Syndrome; D014657:Vasculitis",
"nlm_unique_id": "1270331",
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"pubdate": "1989-10",
"publication_types": "D002363:Case Reports; D004740:English Abstract; D016428:Journal Article",
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"title": "Well's syndrome with eosinophilic vasculitis, coronary aneurysms and myocardial infarction.",
"title_normalized": "well s syndrome with eosinophilic vasculitis coronary aneurysms and myocardial infarction"
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"reaction": [
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"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hypersensitivity vasculitis",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
},
{
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}
],
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{
"abstract": "Carotid stenting is being increasingly used for revascularization of the moderate to severe carotid stenosis and thus its complications are increasingly being recognized. We report a rare complication of induced by iodine contrast in a patient undergoing carotid stenting. s. A 51 year old man after the second stenting developed multiple small infarcts in spite of the distal device. He also had painful parotid swelling which improved within a week. One should be aware of iodine parotitis s in the patients undergoing iodinated contrast study.",
"affiliations": "Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.",
"authors": "Kohat|A K|AK|;Jayantee|K|K|;Phadke|R V|RV|;Muthu|R|R|;Singh|V|V|;Misra|U K|UK|",
"chemical_list": "D000700:Analgesics; D003287:Contrast Media; D017613:Iodine Compounds",
"country": "India",
"delete": false,
"doi": "10.4103/0022-3859.128820",
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"issn_linking": "0022-3859",
"issue": "60(1)",
"journal": "Journal of postgraduate medicine",
"keywords": null,
"medline_ta": "J Postgrad Med",
"mesh_terms": "D000700:Analgesics; D002339:Carotid Arteries; D016893:Carotid Stenosis; D003287:Contrast Media; D006801:Humans; D017613:Iodine Compounds; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D010309:Parotitis; D015607:Stents; D016896:Treatment Outcome",
"nlm_unique_id": "2985196R",
"other_id": null,
"pages": "75-6",
"pmc": null,
"pmid": "24625945",
"pubdate": "2014",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Beware of parotitis induced by iodine-containing contrast media.",
"title_normalized": "beware of parotitis induced by iodine containing contrast media"
} | [
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],
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{
"abstract": "Pneumatosis intestinalis is the presence of gas in the bowel wall and is divided into two categories: life-threatening pneumatosis intestinalis and benign pneumatosis intestinalis. Pneumatosis cystoides intestinalis is a rare condition characterized by gas-filled cysts in submucosa and subserosa. The pathogenesis is unclear, although some causes have been theorized. The presenting clinical findings may be very heterogeneous. Intestinal pneumatosis may lead to various complications. Distinguishing between pneumatosis cystoides intestinalis and life-threatening pneumatosis intestinalis may be challenging, although computed tomography scan allows the detection of additional findings that may suggest an underlying, potentially worrisome cause of pneumatosis intestinalis. To correctly manage the patients affected with this disease is important to differentiate the two types of pneumatosis. The patients with pneumatosis cystoides intestinalis are usually treated conservatively; the surgical treatment is reserved for complications. We described a case of a patient with pneumatosis cystoides intestinalis and gastric perforation. The medical history of the patient revealed a breast cancer treated with mastectomy and chemotherapy; the patient did not report a history of gastrointestinal disease. The abdomen CT showed abscess formation at the level of the antro-pylorus, linear pneumatosis in the gastric wall, and free abdominal air. Multiple small air bubbles was observed in intestinal wall. The intestinal wall was not thickened with normal contrast mucosal enhancement. CT examination showed neither mesenteric stranding nor portal venous gas embolism. The findings of the surgery were gastric perforated peptic ulcer and benign pneumatosis intestinalis.",
"affiliations": "Department of Emergency Radiology, S. Camillo Hospital, Circonvallazione Gianicolense 87, 00152, Rome, Italy. mdipietropaolo@scamilloforlanini.rm.it.;Department of Emergency Radiology, S. Camillo Hospital, Circonvallazione Gianicolense 87, 00152, Rome, Italy.;Department of Emergency Radiology, S. Camillo Hospital, Circonvallazione Gianicolense 87, 00152, Rome, Italy.;Department of Emergency Radiology, S. Camillo Hospital, Circonvallazione Gianicolense 87, 00152, Rome, Italy.;Department of Radiology, Careggi University Hospital, L. go Giovanni Alessandro Brambilla 3, 50134, Florence, Italy.",
"authors": "Di Pietropaolo|Marco|M|;Trinci|Margherita|M|;Giangregorio|Carlo|C|;Galluzzo|Michele|M|;Miele|Vittorio|V|",
"chemical_list": null,
"country": "Japan",
"delete": false,
"doi": "10.1007/s12328-019-00999-3",
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"issn_linking": "1865-7265",
"issue": "13(1)",
"journal": "Clinical journal of gastroenterology",
"keywords": "Bowel; CT; Pneumatosis cystoides intestinalis; Pneumatosis intestinalis",
"medline_ta": "Clin J Gastroenterol",
"mesh_terms": "D018784:Abdominal Abscess; D000368:Aged; D005260:Female; D006801:Humans; D010439:Peptic Ulcer Perforation; D011006:Pneumatosis Cystoides Intestinalis; D013276:Stomach Ulcer; D014057:Tomography, X-Ray Computed",
"nlm_unique_id": "101477246",
"other_id": null,
"pages": "31-36",
"pmc": null,
"pmid": "31161540",
"pubdate": "2020-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": "26099089;17515383;17387535;19710000;16547739;10874196;25360035;10525806;9530294;15933634;19541582;23617487;26183630;21180047;10398791;1587203;23984156;12511155;1439012;25802792;24797647;29954324;22767661;26179526;9641654;6632343;4120645;7528091;23946603;11907358;4365449;18563296;17443004;7787331;11684828;18932291;12074039",
"title": "Pneumatosis cystoides intestinalis: case report and review of literature.",
"title_normalized": "pneumatosis cystoides intestinalis case report and review of literature"
} | [
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{
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}
],
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},
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"literaturereference": "DI PIETROPAOLO M, TRINCI M, GIANGREGORIO C, GALLUZZO M, MIELE V. PNEUMATOSIS CYSTOIDES INTESTINALIS: CASE REPORT AND REVIEW OF LITERATURE. CLIN-J-GASTROENTEROL 2020?13(1):31-36.",
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}
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}
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"literaturereference": "PIETROPAOLO, M.. PNEUMATOSIS CYSTOIDES INTESTINALIS: CASE REPORT AND REVIEW OF LITERATURE. CLINICAL JOURNAL OF GASTROENTEROLOGY. 2020?13 (1):10.1007/S12328-019-00999-3",
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}
] |
{
"abstract": "Immune-related adverse events (irAEs) induced by checkpoint inhibitors are well known. Since fatal outcomes have been reported early detection and adequate management are crucial. In particular, colitis is frequently observed and can result in intestinal perforation. This is the first report of an autoimmune colitis that was treated according to algorithms but became resistant due to a CMV reactivation. The 32-y-old male patient with metastatic melanoma treated within an anti-PD-1/ipilimumab combination study developed severe immune-mediated colitis (CTCAE grade 3) with up to 18 watery stools per day starting 2 weeks after treatment initiation. After improving upon therapy with immunosuppressive treatment (high dose steroids and infliximab) combined with parenteral nutrition diarrhea again exacerbated. Additionally, the patient had asymptomatic grade 3 CTCAE amylase and lipase elevation. Colitis was monitored by weekly endoscopies and colon biopsies were analyzed histologically with CMV staining, multi-epitope ligand cartography (MELC) and qRT-PCR for inflammatory genes. In the course, CMV reactivation was detected in the colon and treated with antiviral medication in parallel to a reduction of corticosteroids. Subsequently, symptoms improved. The patient showed a complete response for 2 y now including regression of bone metastases. CMV reactivation under checkpoint inhibitor therapy in combination with immunosuppressive treatment for autoimmune side effects has to be considered in these patients and if present treated. Potentially, CMV reactivation is underdiagnosed. Treatment algorithms should include CMV diagnostics.",
"affiliations": "Department of Dermatology, University Hospital Erlangen , Ulmenweg 18 , Erlangen, Germany.;Department of Gastroenterology, Pneumology and Endocrinology, University Hospital Erlangen , Ulmenweg 18 , Erlangen, Germany.;Department of Medicine 3, University Hospital Erlangen , Ulmenweg 18 , Erlangen, Germany.;Department of Dermatology, University Hospital Erlangen , Ulmenweg 18 , Erlangen, Germany.;Institute of Pathology, University Hospital Erlangen , Krankenhausstraße 8-10 , Erlangen, Germany.;Department of Dermatology, University Hospital Erlangen , Ulmenweg 18 , Erlangen, Germany.;Department of Dermatology, University Hospital Erlangen , Ulmenweg 18 , Erlangen, Germany.;Department of Surgery, University Hospital Erlangen , Krankenhausstraße 12 , Erlangen, Germany.;Department of Dermatology, University Hospital Erlangen , Ulmenweg 18 , Erlangen, Germany.;Department of Gastroenterology, Pneumology and Endocrinology, University Hospital Erlangen , Ulmenweg 18 , Erlangen, Germany.;Department of Surgery, University Hospital Erlangen , Krankenhausstraße 12 , Erlangen, Germany.;Department of Dermatology, University Hospital Erlangen , Ulmenweg 18 , Erlangen, Germany.",
"authors": "Lankes|Katharina|K|;Hundorfean|Gheorghe|G|;Harrer|Thomas|T|;Pommer|Ansgar J|AJ|;Agaimy|Abbas|A|;Angelovska|Irena|I|;Tajmir-Riahi|Azadeh|A|;Göhl|Jonas|J|;Schuler|Gerold|G|;Neurath|Markus F|MF|;Hohenberger|Werner|W|;Heinzerling|Lucie|L|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1080/2162402X.2015.1128611",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "2162-4011",
"issue": "5(6)",
"journal": "Oncoimmunology",
"keywords": "Autoimmune colitis; CMV; immune-related adverse event irAE; immunotherapy; ipilimumab; multi epitope ligand cartography MELC; nivolumab; side effect management; virus reactivation",
"medline_ta": "Oncoimmunology",
"mesh_terms": null,
"nlm_unique_id": "101570526",
"other_id": null,
"pages": "e1128611",
"pmc": null,
"pmid": "27471608",
"pubdate": "2016-06",
"publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": "23724867;18390726;23690418;17982122;16710025;22551308;23632354;22614989;22030452;23421934;21090563;27085692;21467163;20525992;10896913;24264989;23724846;21639810;19507029;19104936;24944464;26371282;25609166;16087944;25962110;25628259;1916687;23583336;26027431;23341990;7308713;10383813",
"title": "Anti-TNF-refractory colitis after checkpoint inhibitor therapy: Possible role of CMV-mediated immunopathogenesis.",
"title_normalized": "anti tnf refractory colitis after checkpoint inhibitor therapy possible role of cmv mediated immunopathogenesis"
} | [
{
"companynumb": "DE-JNJFOC-20160801411",
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{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "INFLIXIMAB"
},
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"drugindication": "AUTOIMMUNE COLITIS",
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}
],
"patientagegroup": "5",
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"reaction": [
{
"reactionmeddrapt": "Cytomegalovirus infection",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "LANKES K, HUNDORFEAN G, HARRER T, POMMER AJ, AGAIMY A, ANGELOVSKA I, ET AL. ANTI-TNF-REFRACTORY COLITIS AFTER CHECKPOINT INHIBITOR THERAPY: POSSIBLE ROLE OF CMV-MEDIATED IMMUNOPATHOGENESIS. ONCOIMMUNOLOGY 2016;5 (6):E1128611 (1-7).",
"literaturereference_normalized": "anti tnf refractory colitis after checkpoint inhibitor therapy possible role of cmv mediated immunopathogenesis",
"qualification": "3",
"reportercountry": "DE"
},
"primarysourcecountry": "DE",
"receiptdate": "20160810",
"receivedate": "20160810",
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},
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"safetyreportversion": 1,
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},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
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"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20161109"
}
] |
{
"abstract": "Prevotella dentalis is a Gram-negative anaerobic rod involved in various human diseases, especially oral infections. We report a rare case of a pleural effusion due to this microorganism in an elderly patient. An 88-year-old man with chronic respiratory disease presented with a left pleural effusion for more than 1 month. Culture of drained pleural fluid resulted in isolation of P. dentalis. Resistance to penicillin and moxifloxacin was documented. Treatment with drainage and clindamycin was established, but the patient developed cognitive impairment and died after a worsening of his general condition.",
"affiliations": "Department of Microbiology, University Hospital Virgen de las Nieves, Granada, Spain. Electronic address: fernando.cobo.sspa@juntadeandalucia.es.;Department of Microbiology, University Hospital Virgen de las Nieves, Granada, Spain.;Department of Microbiology, University Hospital Virgen de las Nieves, Granada, Spain.;Department of Microbiology, University Hospital Virgen de las Nieves, Granada, Spain.;Department of Medicine, University of Granada, Granada, Spain.;Department of Microbiology, University Hospital Virgen de las Nieves, Granada, Spain.",
"authors": "Cobo|Fernando|F|;Calatrava|Elizabeth|E|;Rodríguez-Granger|Javier|J|;Sampedro|Antonio|A|;Aliaga-Martínez|Luis|L|;Navarro-Marí|José María|JM|",
"chemical_list": "D000900:Anti-Bacterial Agents; D002981:Clindamycin",
"country": "England",
"delete": false,
"doi": "10.1016/j.anaerobe.2018.09.004",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1075-9964",
"issue": "54()",
"journal": "Anaerobe",
"keywords": "Anaerobe; Antimicrobials; Drainage; P. dentalis; Pleural effusion",
"medline_ta": "Anaerobe",
"mesh_terms": "D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents; D016866:Bacteroidaceae Infections; D002981:Clindamycin; D006801:Humans; D008297:Male; D010996:Pleural Effusion; D018720:Prevotella",
"nlm_unique_id": "9505216",
"other_id": null,
"pages": "144-145",
"pmc": null,
"pmid": "30244150",
"pubdate": "2018-12",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "A rare case of pleural effusion due to Prevotella dentalis.",
"title_normalized": "a rare case of pleural effusion due to prevotella dentalis"
} | [
{
"companynumb": "ES-PFIZER INC-2018453172",
"fulfillexpeditecriteria": "1",
"occurcountry": "ES",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN HYDROCHLORIDE"
},
"drugadditional": null,
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"drugauthorizationnumb": "050162",
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"drugdosageform": "CAPSULE, HARD",
"drugdosagetext": "UNK",
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"drugindication": "PLEURAL EFFUSION",
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}
],
"patientagegroup": null,
"patientonsetage": "88",
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"reaction": [
{
"reactionmeddrapt": "General physical health deterioration",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cognitive disorder",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "COBO, F.. A RARE CASE OF PLEURAL EFFUSION DUE TO PREVOTELLA DENTALIS. ANAEROBE. 2018?54:144-145",
"literaturereference_normalized": "a rare case of pleural effusion due to prevotella dentalis",
"qualification": "3",
"reportercountry": "ES"
},
"primarysourcecountry": "ES",
"receiptdate": "20181107",
"receivedate": "20181107",
"receiver": {
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"receivertype": "6"
},
"reporttype": "1",
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"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20190205"
},
{
"companynumb": "ES-MICRO LABS LIMITED-ML2019-00113",
"fulfillexpeditecriteria": "1",
"occurcountry": "ES",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "207402",
"drugbatchnumb": "UNKNOWN",
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"medicinalproduct": "CLINDAMYCIN."
},
{
"actiondrug": "6",
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"activesubstancename": "CEFDITOREN"
},
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"drugtreatmentdurationunit": null,
"medicinalproduct": "CEFDITOREN"
}
],
"patientagegroup": null,
"patientonsetage": "88",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug ineffective",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pathogen resistance",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "COBO F, CALATRAVA E, RODRIGUEZ-GRANGER J, SAMPEDRO A, ALIAGA-MARTINEZ L, NAVARRO-MARI J. A RARE CASE OF PLEURAL EFFUSION DUE TO PREVOTELLA DENTALIS. ANAEROBE. 2018?54:144-145.",
"literaturereference_normalized": "a rare case of pleural effusion due to prevotella dentalis",
"qualification": "3",
"reportercountry": "ES"
},
"primarysourcecountry": "ES",
"receiptdate": "20190202",
"receivedate": "20190202",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15902753,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
}
] |
{
"abstract": "BACKGROUND\nPharmacotherapy is often impeded by adverse drug reactions (ADRs). Among these ADRs cutaneous reactions are the major class being easily identified and reported. If not noted early it has potential to develop into serious lesions.\n\n\nOBJECTIVE\nTo evaluate the clinical patterns of various drug induced cutaneous reactions. Setting A Teaching hospital in India. Methods All suspected cutaneous reactions to systemic drugs which were submitted to the ADR monitoring centre during a 6-month period (March 2014-August 2014) were analysed. Causality relationship, severity assessment and preventability assessment was also done.\n\n\nRESULTS\nOut of 134 cutaneous ADRs, 56 % occurred in females, majority of cases were found in the age group of 41-50 years. The most common type of ADR was maculopapular rash (46.3 %) and majorly implicated drug class was antibiotics (51.3 %). Most (72.3 %) were mild. Polypharmacy and multiple comorbid conditions were important predisposing factors. Over half of the cases (58 %) were not preventable.\n\n\nCONCLUSIONS\nCutaneous adverse reaction patterns and their causes vary as the result of changing use of drugs. In India, antibiotics are responsible for the majority of the cutaneous adverse drug reactions, and maculopapular rash is the side effect that is most reported.",
"affiliations": "Department of Pharmacology, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi, 110062, India.;DGHS, CDSCO (HQ), FDA Bhawan, Kotla Road, New Delhi, 110002, India.;HIMSR, Jamia Hamdard, New Delhi, India.;Department of Medicine and Preventive Cardiology, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi, 110062, India. shridhar.dwivedi@gmail.com.",
"authors": "Chopra|Deepti|D|;Sharma|Vibha|V|;Kapoor|Rohan|R|;Dwivedi|Shridhar|S|",
"chemical_list": "D000900:Anti-Bacterial Agents",
"country": "Netherlands",
"delete": false,
"doi": "10.1007/s11096-015-0161-9",
"fulltext": null,
"fulltext_license": null,
"issn_linking": null,
"issue": "37(6)",
"journal": "International journal of clinical pharmacy",
"keywords": "ADR; Causality; Cutaneous reactions India; Maculopapular rash; Pharmacovigilance India",
"medline_ta": "Int J Clin Pharm",
"mesh_terms": "D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000900:Anti-Bacterial Agents; D015984:Causality; D015897:Comorbidity; D003875:Drug Eruptions; D016903:Drug Monitoring; D005260:Female; D006784:Hospitals, Teaching; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010267:Parapsoriasis; D019338:Polypharmacy; D012867:Skin",
"nlm_unique_id": "101554912",
"other_id": null,
"pages": "996-9",
"pmc": null,
"pmid": "26238222",
"pubdate": "2015-12",
"publication_types": "D016428:Journal Article; D064888:Observational Study",
"references": "9715291;11895622;20618508;11871633;23372206;18312492;1524068;7249508;23776774;23679909",
"title": "An observational study of cutaneous adverse drug reactions in a teaching hospital.",
"title_normalized": "an observational study of cutaneous adverse drug reactions in a teaching hospital"
} | [
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"medicinalproduct": "BUDESONIDE."
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{
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"activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM"
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"medicinalproduct": "ASPIRIN."
},
{
"actiondrug": "5",
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"activesubstancename": "AMOXICILLIN"
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"medicinalproduct": "AMOXICILLIN."
},
{
"actiondrug": "5",
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"activesubstancename": "RABEPRAZOLE"
},
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"medicinalproduct": "RABEPRAZOLE"
}
],
"patientagegroup": "5",
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"reaction": [
{
"reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Rash maculo-papular",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Sunburn",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Photosensitivity reaction",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Conjunctival haemorrhage",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Angioedema",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Flushing",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Urticaria",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Mouth ulceration",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Acne",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Fixed drug eruption",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Rash pustular",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Gingival hypertrophy",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Stevens-Johnson syndrome",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pruritus",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CHOPRA D, SHARMA V, KAPOOR R, DWIVEDI S. AN OBSERVATIONAL STUDY OF CUTANEOUS ADVERSE DRUG REACTIONS IN A TEACHING HOSPITAL. INTERNATIONAL JOURNAL OF CLINICAL PHARMACY 01-DEC-2015;37(6):996-99.",
"literaturereference_normalized": "an observational study of cutaneous adverse drug reactions in a teaching hospital",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": "IN",
"receiptdate": "20160812",
"receivedate": "20160812",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12648685,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20161109"
}
] |
{
"abstract": "BACKGROUND\nClinical practice guidelines for appropriate nonsteroidal anti-inflammatory drug (NSAID) utilisation focus on preventing NSAID-related gastrointestinal (GI), cardiovascular (CV), congestive heart failure (CHF) and renal adverse events. We compared concordance of NSAID prescriptions with clinical practice guideline recommendations in Quebec, pre and post rofecoxib withdrawal from market.\n\n\nMETHODS\nData were obtained from the Quebec Health Insurance Agency (RAMQ). All prescriptions for celecoxib and traditional NSAIDs (tNSAIDs) dispensed to patients ≥50 years of age were evaluated for concordance with clinical practice guidelines. Prescriptions were stratified by time period (pre and post rofecoxib withdrawal) and, GI, CV, CHF and renal risk factors at the dispensing date. Gastro-protective agent (GPA) co-prescriptions were also evaluated.\n\n\nRESULTS\nWe assessed 1,966,793 celecoxib and 1,743,481 tNSAIDs prescriptions. Of celecoxib prescriptions, 87.2% and 86.5% were appropriate in the post- and pre-periods, respectively, compared to 72.6% and 70.1% of tNSAIDs prescriptions, respectively. In logistic regression, 'appropriateness' of celecoxib prescriptions increased with age, rheumatoid arthritis and osteoarthritis (OA), and was higher in the post- versus pre-period (odds ratio 1.22, 95% confidence interval 1.18-1.26); it was lower in women and in patients with higher income. 'Appropriateness' of tNSAID prescriptions decreased in the post-period (0.92, 0.89-0.95), was lower in older persons and those with OA, and higher in women and in higher income patients. Of tNSAID prescriptions that should have received a GPA co-prescription, only 45.6% did.\n\n\nCONCLUSIONS\nConcordance with guideline recommendations increased for celecoxib and decreased for tNSAIDs after rofecoxib withdrawal; GPA co-prescription with tNSAIDs remained suboptimal.",
"affiliations": "Department of Medicine, McGill University, Montreal, Quebec, Canada; Research Institute, McGill University Health Centre, Montreal, Quebec, Canada. elham.rahme@mcgill.ca",
"authors": "Rahme|Elham|E|;Roussy|Jean-Pascal|JP|;Lafrance|Jean-Philippe|JP|;Nedjar|Hacene|H|;Morin|Suzanne|S|",
"chemical_list": "D000894:Anti-Inflammatory Agents, Non-Steroidal; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D000068579:Celecoxib",
"country": "England",
"delete": false,
"doi": "10.1002/pds.2339",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1053-8569",
"issue": "21(4)",
"journal": "Pharmacoepidemiology and drug safety",
"keywords": null,
"medline_ta": "Pharmacoepidemiol Drug Saf",
"mesh_terms": "D000367:Age Factors; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000068579:Celecoxib; D016208:Databases, Factual; D005260:Female; D019983:Guideline Adherence; D006801:Humans; D007783:Lactones; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D010818:Practice Patterns, Physicians'; D011720:Pyrazoles; D011792:Quebec; D012307:Risk Factors; D056737:Safety-Based Drug Withdrawals; D012737:Sex Factors; D012959:Socioeconomic Factors; D013449:Sulfonamides; D013450:Sulfones; D013997:Time Factors",
"nlm_unique_id": "9208369",
"other_id": null,
"pages": "420-7",
"pmc": null,
"pmid": "22223535",
"pubdate": "2012-04",
"publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Concordance with guideline recommendations: previous and more recent nonsteroidal anti-inflammatory drug prescriptions in Quebec, Canada.",
"title_normalized": "concordance with guideline recommendations previous and more recent nonsteroidal anti inflammatory drug prescriptions in quebec canada"
} | [
{
"companynumb": "CA-JNJFOC-20161207894",
"fulfillexpeditecriteria": "1",
"occurcountry": "CA",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "IBUPROFEN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "019012",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
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"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IBUPROFEN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "IBUPROFEN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "019012",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
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"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
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"drugstartdateformat": null,
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"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IBUPROFEN."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Renal disorder",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Cardiac failure congestive",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Cardiovascular disorder",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Gastrointestinal disorder",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "RAHME E, ROUSSY J, LAFRANCE J, NEDJAR H, MORIN S. CONCORDANCE WITH GUIDELINE RECOMMENDATIONS: PREVIOUS AND MORE RECENT NONSTEROIDAL ANTI-INFLAMMATORY DRUG PRESCRIPTIONS IN QUEBEC, CANADA. PHARMACOEPIDEMIOLOGY AND DRUG SAFETY APR-2012;21 (4):420-427.",
"literaturereference_normalized": "concordance with guideline recommendations previous and more recent nonsteroidal anti inflammatory drug prescriptions in quebec canada",
"qualification": "3",
"reportercountry": "CA"
},
"primarysourcecountry": "CA",
"receiptdate": "20161215",
"receivedate": "20161215",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13030030,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170207"
}
] |
{
"abstract": "The management of cesarean section in kyphoscoliotic patient is challenging. The respiratory changes and increased metabolic demands due to pregnancy may compromise the limited respiratory reserves in such patients. Presence of other comorbidities like malaria and respiratory tract infection will further compromise the effective oxygenation. We report a case of kyphoscoliosis along with malaria and acute respiratory distress syndrome for urgent cesarean section.",
"affiliations": "Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, New Delhi, India.;Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, New Delhi, India.;Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, New Delhi, India.;Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, New Delhi, India.;Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, New Delhi, India.;Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, New Delhi, India.",
"authors": "Pandey|Ravindra Kr|RK|;Batra|Meenu M|MM|;Darlong|Vanlal|V|;Garg|Rakesh|R|;Punj|Jyotsna|J|;Kumar|Sri|S|",
"chemical_list": null,
"country": "India",
"delete": false,
"doi": "10.4103/0970-9185.169090",
"fulltext": "\n==== Front\nJ Anaesthesiol Clin PharmacolJ Anaesthesiol Clin PharmacolJOACPJournal of Anaesthesiology, Clinical Pharmacology0970-91852231-2730Medknow Publications & Media Pvt Ltd India JOACP-31-55810.4103/0970-9185.169090Case ReportAnesthetic management of parturient with thoracic kyphoscoliosis, malaria and acute respiratory distress syndrome for urgent cesarean section Pandey Ravindra Kr Batra Meenu M Darlong Vanlal Garg Rakesh Punj Jyotsna Kumar Sri Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, New Delhi, IndiaAddress for correspondence: Dr. Ravindra Kr Pandey, Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India. E-mail: ravindrapandey1972@gmail.comOct-Dec 2015 31 4 558 559 Copyright: © Journal of Anaesthesiology Clinical Pharmacology2015This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.The management of cesarean section in kyphoscoliotic patient is challenging. The respiratory changes and increased metabolic demands due to pregnancy may compromise the limited respiratory reserves in such patients. Presence of other comorbidities like malaria and respiratory tract infection will further compromise the effective oxygenation. We report a case of kyphoscoliosis along with malaria and acute respiratory distress syndrome for urgent cesarean section.\n\nCesarean sectionkyphoscoliosismalariarespiratory tract infection\n==== Body\nIntroduction\nKyphoscoliosis occurs due to disruption of balance between structural and dynamic components or neuromuscular elements of the spine. The respiratory system is compromised, and its severity depends on the severity of the kyphoscoliosis and concomitant respiratory disease.\n\nCase Report\nA 27-year-old, 45 kg female, G1P0L0A0, was admitted at 29 weeks of gestation with complaints of moderate grade fever associated with chills and rigors since 3 weeks, followed by development of cough and difficulty in breathing.\n\nHer past history revealed gradually progressing thoracic kyphoscoliosis following poliomyelitis diagnosed at the age of 4 months. On admission, the patient was diagnosed to have signs and symptoms of ARDS with bilateral lung infiltrates in chest X-ray. Hemogram, renal and liver functions revealed no abnormality except for a total protein of 4.5 gm%, positive peripheral smear for malaria parasite (Plasmodium falciparum) and total leukocyte count of 14,700/mm3. Pulmonary function test revealed a restrictive lung disease (forced vital capacity [FVC], forced expiratory volume [FEV1] and FEV1/FVC were 67%, 58% and 110%, respectively). Other causes of fever such as typhoid, hepatitis, urinary tract infection and cholangitis were ruled out.\n\nShe was admitted to Intensive Care Unit (ICU) and ARDS was managed with intravenous antibiotics cefotaxim 1 g 8 hourly, levofloxacin 500 mg once in 24 h, amikacin 500 mg 12 hourly and metronidazole 500 mg 8 hourly. She also received oral artesunate. She was administered oxygen by face mask (5-6 L/min), steam inhalation, nebulization and chest physiotherapy. There was gradual worsening of her respiratory condition, subsequently leading to desaturation (SpO2 77%) with a respiratory rate (RR) of 50-60 breaths/min, and crepts on auscultation of her right chest. Her arterial blood gas (ABG) analysis revealed PO2-64 mmHg, PCO2-26 mmHg, SpO2 of 88% for which noninvasive continuous positive airway pressure (CPAP) of 5 cmH2O was applied with a FiO2 of 40%. This led to an improvement of her respiratory condition; SpO2 rose to 99% and the RR settled to 20-22 breaths/min. Repeat ABG revealed PO2-96 mmHg, PCO2-34 mmHg and SpO2 99%. She continued to remain on noninvasive CPAP for first 4 days, maintaining hemodynamics and was managed with intravenous antibiotic, steroids and nebulization with bronchodilators. In the ICU she developed hyponatremia (Na+ 128 meq/L) and hypoprotenemia (total proteins 4.5 g/dL and albumin 1.8 g/dL). Hypoproteinemia was managed with albumin (20% 100 mL daily for 5 days) and hyponatremia with 0.9% normal saline administration.\n\nDuring her ICU stay, fetal well-being was also monitored. She was administered intramuscular betamethasone (12 mg, 2 doses 24 h apart) for fetal lung maturity. Tocolytics were also prescribed for occasional uterine contractions (nifedipine 5-10 mg when required). On day 5th of her ICU stay, she had respiratory distress (RR-26-28 breaths/min) and started having labor pains. On examination, patient had uterine contractions and passage of meconium stained liquor per vaginum. This was followed by deterioration of her respiratory condition and desaturation (SpO2 of 73%) even on the support of noninvasive CPAP of 5 cmH2O. Her ABG revealed PO2-52 mmHg, PCO2-45 mmHg and SpO2 of 82%. Fetal Doppler revealed fetal heart rate of 110 beats/min. In view of such critical condition, emergency lower segment cesarean section (LSCS) was planned. In the ICU emergent rapid sequence induction using thiopentone (200 mg) and succinylcholine (75 mg) was performed, followed by tracheal intubation. Patient was then shifted to the operating room in left lateral position with an endotracheal tube in situ on Bain's circuit and with manual assisted ventilation. During the surgery, patient remained hemodynamically stable with systolic blood pressure ranging 110-140 mmHg, diastolic blood pressure ranging 60-80 mmHg and heart rate ranging from 60 to 80 beats/min. She sustained blood loss of 600 mL that was replaced with balanced salt solution and 1 unit of packed red blood cells. A low birth weight (1181 g) female baby was delivered with an APGAR score of 7 and 8 at 1 and 5 min respectively. Baby was shifted to neonatal ICU for further management. In view of her poor lung condition, residual neuromuscular blockade was not reversed, and patient was shifted back to ICU. The lung condition further deteriorated, and ABG revealed-pH 7.321, PaO2 59 mmHg, PaCO2 46 mmHg, HCO3 20 meq/L. The ventilatory management was done as per ARDS management guidelines. Her bronchial alveolar lavage cultures grew acinetobacter and urine culture revealed Escherichia coli that were managed with appropriate intravenous antibiotics. During this period in ICU, she required sedation with midazolam and morphine as well as intermittent neuromuscular blockade and inotropic support (noradrenalin 5-8 mg/kg). Over next 4 days, her lung condition and ABG improved with the gradual increase in PaO2 of 65 mmHg to 202 mmHg and PaO2/FiO2 ratio of 81.25-505. This led to gradual weaning of the patient off the ventilator and finally tracheal extubation 10 days later.\n\nDiscussion\nAnesthetic management of the parturient with thoracic kyphoscoliosis, malaria and ARDS for emergency LSCS is challenging.\n\nPregnant patients with pulmonary compromise (kyphoscoliosis and ARDS in this case) may not tolerate increased metabolic demand generated by the fetus, placenta, and gravid uterus due to limited respiratory reserves.[1] Labor pains result in marked hyperventilation causing a fall in PaCO2 and respiratory alkalosis causing cerebral and uteroplacental vasoconstriction.[12] This reduces the release of oxygen from hemoglobin that not only compromises maternal tissue oxygenation, but also has a deleterious effect on fetal oxygen transfer.\n\nThe presence of kyphoscolisos in parturient may further leads to ventilation/perfusion mismatch and marked dyspnea. It can also interfere with provision of labor analgesia or regional anesthesia for cesarean section.[3]\n\nThe risk of development of ARDS in a parturient is higher than in the nonpregnant population.[4] Golden hour “right decision at right time” is paramount in the management of such cases.\n\nWe conclude that parturient with associated respiratory comorbidities needs timely management for a better outcome not only of the mother, but also of the fetus.\n\nSource of Support: Nil\n\nConflicts of Interest: None declared.\n==== Refs\n1 Bobrowski RA Pulmonary physiology in pregnancy Clin Obstet Gynecol 2010 53 285 300 20436304 \n2 Das B Acid base disorders Indian J Anaesth 2003 47 373 9 \n3 Moran DH Johnson MD Continuous spinal anesthesia with combined hyperbaric and isobaric bupivacaine in a patient with scoliosis Anesth Analg 1990 70 445 7 2316886 \n4 Cole DE Taylor TL McCullough DM Shoff CT Derdak S Acute respiratory distress syndrome in pregnancy Crit Care Med 2005 33 S269 78 16215347\n\n",
"fulltext_license": "CC BY-NC-SA",
"issn_linking": "0970-9185",
"issue": "31(4)",
"journal": "Journal of anaesthesiology, clinical pharmacology",
"keywords": "Cesarean section; kyphoscoliosis; malaria; respiratory tract infection",
"medline_ta": "J Anaesthesiol Clin Pharmacol",
"mesh_terms": null,
"nlm_unique_id": "9516972",
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"pages": "558-9",
"pmc": null,
"pmid": "26702219",
"pubdate": "2015",
"publication_types": "D002363:Case Reports",
"references": "16215347;20436304;2316886",
"title": "Anesthetic management of parturient with thoracic kyphoscoliosis, malaria and acute respiratory distress syndrome for urgent cesarean section.",
"title_normalized": "anesthetic management of parturient with thoracic kyphoscoliosis malaria and acute respiratory distress syndrome for urgent cesarean section"
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"abstract": "Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a class of medications used for glycemic control in type II diabetes mellitus. Their mechanism of action involves preventing resorption of glucose at the proximal kidney, thereby promoting glucosuria and weight loss. However, they have also been found to be associated with euglycemic diabetic ketoacidosis (euDKA). This case describes a 25-year-old male with a history of type II diabetes on metformin, sitagliptin, and dapagliflozin who was admitted with his third episode of pancreatitis secondary to hypertriglyceridemia. His home oral glycemic agents were continued as inpatient. Despite tight euglycemic control, the patient developed profound metabolic acidosis and was found to have an elevated beta-hydroxybutyrate level and normal lactic acid level. He was admitted into the intensive care unit and started on an insulin drip, and after resolution of his acidosis he was transitioned to basal insulin successfully. He was discharged with an insulin regimen while his oral glycemic agents were discontinued indefinitely. SGLT-2 inhibitors are associated with euDKA, most likely as a result of their non-insulin-dependent glucose clearance, hyperglucagonemia, and decreased ketone clearance. The aim of this case report is to inform the physician about the possibility of euDKA in a patient with type II diabetes on a SGLT-2 inhibitor presenting with an acute illness.",
"affiliations": "Western Michigan University Homer Stryker M.D. School of Medicine, USA.;Western Michigan University Homer Stryker M.D. School of Medicine, USA.;Western Michigan University Homer Stryker M.D. School of Medicine, USA.",
"authors": "Badwal|Karun|K|0000-0002-5090-8434;Tariq|Tooba|T|;Peirce|Diane|D|",
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"fulltext": "\n==== Front\nCase Rep EndocrinolCase Rep EndocrinolCRIECase Reports in Endocrinology2090-65012090-651XHindawi 10.1155/2018/6450563Case ReportDapagliflozin-Associated Euglycemic Diabetic Ketoacidosis in a Patient Presenting with Acute Pancreatitis http://orcid.org/0000-0002-5090-8434Badwal Karun karun.badwal@med.wmich.eduTariq Tooba Peirce Diane Western Michigan University Homer Stryker M.D. School of Medicine, USAAcademic Editor: Osamu Isozaki\n\n2018 7 8 2018 2018 64505631 5 2018 11 7 2018 Copyright © 2018 Karun Badwal et al.2018This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a class of medications used for glycemic control in type II diabetes mellitus. Their mechanism of action involves preventing resorption of glucose at the proximal kidney, thereby promoting glucosuria and weight loss. However, they have also been found to be associated with euglycemic diabetic ketoacidosis (euDKA). This case describes a 25-year-old male with a history of type II diabetes on metformin, sitagliptin, and dapagliflozin who was admitted with his third episode of pancreatitis secondary to hypertriglyceridemia. His home oral glycemic agents were continued as inpatient. Despite tight euglycemic control, the patient developed profound metabolic acidosis and was found to have an elevated beta-hydroxybutyrate level and normal lactic acid level. He was admitted into the intensive care unit and started on an insulin drip, and after resolution of his acidosis he was transitioned to basal insulin successfully. He was discharged with an insulin regimen while his oral glycemic agents were discontinued indefinitely. SGLT-2 inhibitors are associated with euDKA, most likely as a result of their non-insulin-dependent glucose clearance, hyperglucagonemia, and decreased ketone clearance. The aim of this case report is to inform the physician about the possibility of euDKA in a patient with type II diabetes on a SGLT-2 inhibitor presenting with an acute illness.\n==== Body\n1. Introduction\nSodium-glucose cotransporter 2 inhibitors are a novel class of medications used for glycemic control in type II diabetes mellitus. They exert their effect by inhibiting SGLT-2 receptors in the kidney which are responsible for the resorption of glucose. This promotes glucosuria and in turn also decreases blood glucose levels [1].\n\nThis mechanism leads to the added benefit of weight loss by caloric loss in the urine, removing the energy source that drives excess adipose tissue formation resulting in improved insulin sensitivity [2, 3]. As dietary modifications and exercise are the mainstay of treatment in type II diabetes, SGLT-2 inhibitors can be used as monotherapy or as an adjunctive to other classes of oral glycemic agents. Common adverse effects reported in the literature are an increased incidence of genitourinary tract infections and orthostatic hypotension as a result of increased urinary frequency and volume. Recently, postmarketing surveillance has revealed an increased incidence of diabetic ketoacidosis in patients taking SGLT-2 inhibitor medications [4].\n\nThis case will illustrate a unique example of euglycemic diabetic ketoacidosis in a type II diabetic patient on a SGLT-2 inhibitor presenting with acute pancreatitis secondary to hypertriglyceridemia.\n\n2. Case Presentation\nThe patient is a 25-year-old gentleman who presented with a one-day history of abdominal pain, nausea, and emesis. He has had two episodes of pancreatitis in the past secondary to hypertriglyceridemia, with the last episode occurring three years ago. He also has type II diabetes controlled with dapagliflozin (SGLT-2 inhibitor), sitagliptin, and metformin. In the emergency department, the patient's initial labs showed a WBC of 23,000 cells/µL, lipase of 2,530U/L, triglyceride level above 5,000mg/dL, bicarbonate 23mEq/L, and glucose 285mg/dL. His initial urinalysis and chest X-ray were unremarkable. A CT scan of his abdomen and pelvis with contrast was performed showing a large amount of peripancreatic inflammatory change consistent with acute pancreatitis (Figure 1). There was no evidence of cholelithiasis or cholecystitis, and the bile duct diameter was within normal limits. Based on these laboratory findings and imaging results, it was concluded that the patient had acute pancreatitis secondary to elevated triglycerides. He was admitted to the inpatient service and dapagliflozin, sitagliptin, and metformin were continued.\n\nThe patient was transitioned from nothing by mouth status on admission to a full-liquid diet on day 3 of hospital stay. By day 5, the lipase level trended down to 158U/L. His blood sugar remained consistently between 120mg/dl and 220mg/dl since admission. Despite maintaining tight euglycemic control, the patient developed profound metabolic acidosis with a gradual downward trend of his bicarbonate level from 23mEq/L to 5mEq/L and a high anion gap of 32 by day 5. This was accompanied by the acute development of tachypnea and tachycardia with a heart rate up to 130bpm. He was immediately started on an IV infusion drip of sodium bicarbonate. The beta-hydroxybutyrate level was 6.06mmol/L with a blood sugar of 161mg/dL and a lactic acid level of 1.5mmol/L. An arterial blood gas revealed a pH of 7.14 and pCO2 of 13mmHg. Although metformin was also continued, the normal lactic acid and elevated beta-hydroxybutyrate supported the diagnosis of DKA. It was concluded that the acidosis was secondary to diabetic ketosis induced by dapagliflozin. All oral glycemic agents were immediately discontinued, and he was transferred to the intensive care unit where he was started on an insulin drip. The nephrology service was consulted and by their recommendations the patient also underwent plasma exchange therapy for hypertriglyceridemia.\n\nAfter being stabilized in the intensive care unit over the course of 24 hours, he was transferred to the general medical floor on an insulin drip and was transitioned to basal insulin. His diet was cautiously advanced in the setting of acute pancreatitis. Mealtime insulin coverage was added as the patient increased his oral intake. His blood sugars continued to remain well controlled between 120mg/dl and 200mg/dl while his insulin regimen was optimized according to his oral intake. He was discharged on an insulin regimen with insulin detemir and insulin lispro with the recommendation to stop all oral glycemic agents.\n\n3. Discussion\nSGLT receptors are a family of sodium glucose cotransporters that are primarily located at the brush border of the proximal convoluted tubules in the kidney [5]. SGLT-2 receptors are a high capacity, low affinity transporter that utilizes the sodium gradient to drive the reabsorption of approximately 90% of the filtered glucose in the S1 segment of the proximal renal tubule. The remaining glucose is reabsorbed by SGLT-1 receptors, which are placed more distally in the S3 segment of the proximal tubule and have a higher affinity but lower capacity for glucose [6]. The SGLT-2 inhibitor class of medications specifically inhibit the SGLT-2 transporters and therefore prevent the reabsorption of the majority of filtered glucose [4, 7, 8]. An added benefit of SGLT-2 inhibitors is the induction of modest weight loss by caloric loss of glucose in the urine leading to decreased visceral and subcutaneous adipose tissue and thereby further improving insulin sensitivity [2]. Finally, some of these agents have also been shown to have cardiovascular mortality benefits [9].\n\nCanagliflozin, dapagliflozin, and empagliflozin are the three SGLT-2 inhibitors currently approved by the FDA for treatment of type II diabetes. However, since the approval of canagliflozin in March 2013, more than 70 cases of DKA have been reported. In May 2015, the FDA issued a warning about the risk of ketoacidosis with the use of SGLT-2 inhibitors [10–12]. Since then, further studies have investigated the incidence of SGLT-2 inhibitor-associated DKA. One study looking at the FDA Adverse Effect Reporting System database identified 7836 patients taking a SGLT-2 inhibitor, out of which 51 patients developed DKA with metabolic data. Of those 51 patients, 20 patients were type I diabetics, 25 patients were type II diabetics, and 6 patients were an unspecified type of diabetes. The study estimated a 7-fold increase in the incidence of DKA with patients on a SGLT-2 inhibitor when compared to patients on DPP-4 inhibitors with type II diabetes [13].\n\nDiabetic ketoacidosis is a serious and potentially life-threatening complication of diabetes mellitus which occurs as a result of profound insulin deficiency. It is more commonly associated with poorly controlled type I diabetes as opposed to type II diabetes, in which case an added stress is required to trigger DKA such as infection or surgery [9]. Euglycemic DKA is an uncommon form of ketoacidosis which is characterized by metabolic acidosis with a pH <7.3 and a serum bicarbonate of <18mEq/L, ketosis, and a blood glucose level of <200 mg/dL [14].\n\nThe pathogenesis of DKA is well-known and involves low insulin levels triggering lipolysis and subsequent increased levels of free fatty acids in the blood which stimulates glucagon production. Glucagon promotes the oxidation of fatty acids and results in the production of ketone bodies, which are water-soluble acidic molecules directly responsible for ketoacidosis. Interestingly, the euDKA caused by SGLT-2 inhibitors follows a different mechanism of action. SGLT-2 inhibitors deplete the circulating glucose in the serum by promoting glucosuria, removing the stimulus for beta cells to secrete insulin. This in turn causes enhanced glucagon production by alpha cells in the pancreas. Furthermore, Bonner et al. demonstrated that both SGLT-1 and SGLT-2 cotransporters are also present on the alpha cells in the pancreas by confocal imaging analysis. Additionally, they found that the inhibition of SGLT-2 cotransporters by dapagliflozin in human islets was correlated with increased glucagon secretion by alpha cells [15]. Finally, there are studies suggesting that SGLT-2 inhibitors may decrease renal excretion of ketone bodies, therefore raising the level of ketone bodies in the blood. The end result of these combined mechanisms is hyperketonemia in the setting of euglycemia [9, 16]. Additionally, euDKA associated with SGLT-inhibitors causes twice the amount of renal glucose clearance compared to DKA [17].\n\nAt this time, SGLT-2 inhibitors are not approved by regulatory authorities for the treatment of type I diabetes. However, they are currently being used off-label due to their beneficial effects of weight reduction and maintenance of lower blood glucose levels in conjunction with insulin therapy [18, 19].\n\nIt is important to note that it is not common for individuals on a SGLT-2 inhibitor to develop euDKA. In a meta-analysis published by Burke et al. in 2017, the leading risk factors that predispose an individual on a SGLT-2 inhibitor to DKA include medication noncompliance, infection, major surgeries, and underlying autoimmune diabetes in patients previously diagnosed with T2DM [20]. In our patient, acute pancreatitis secondary to hypertriglyceridemia was thought to be the main driving force that led to the development of ketoacidosis. The patient was also not eating for the initial 48 hours of admission, possibly leading to a catabolic state with subsequent ketone body formation in the setting of a SGLT-2 inhibitor. This is supported by a randomized control trial study by Yabe et al. which randomized individuals on the SGLT-2 inhibitor luseogliflozin to diets of differing carbohydrate intake and found a higher incidence of ketoacidosis among individuals in the lower carbohydrate group [21].\n\nSGLT-2 inhibitor-induced DKA is treated in a similar fashion as conventional DKA with the goal of driving the acidemia down with aggressive fluid resuscitation, insulin infusion, and close electrolyte monitoring. SGLT-2 inhibitors should be reinitiated only after consultation with an endocrinologist.\n\n4. Conclusion\nHistorically, the majority of the cases of euDKA were missed due to presence of euglycemia on presentation [22]. Similarly, in our patient the diagnosis was delayed since his anion gap acidosis was initially attributed to starvation ketosis due to his nothing by mouth status in the setting of pancreatitis. However, after careful consideration a diagnosis of dapagliflozin-induced euDKA precipitated by acute pancreatitis was made. This case elaborates the fact that SGLT-2 inhibitors should be initiated by a clinician cautiously and only after adequately weighing the risks and benefits of treatment, particularly in those with type I diabetes. Patients should be instructed to check their serum and urine ketones in case they feel unwell even if they have a normal blood glucose level. Hospitalized patients (particularly those undergoing surgery or suffering from infectious/inflammatory process) who are on SGLT-2 inhibitors at home should be evaluated and closely monitored for the development of ketonemia or ketonuria during the hospital course.\n\nAcknowledgments\nThis case report was presented as a poster presentation at the American Thoracic Society conference in San Diego, California, USA, May 2018. This case report was presented as a poster presentation at the American College of Physicians Michigan Chapter Scientific Meeting in Sterling Heights, Michigan, USA, May 2017.\n\nConflicts of Interest\nThe authors declare that they have no conflicts of interest.\n\nFigure 1 Peripancreatic inflammatory changes consistent with acute pancreatitis (arrows).\n==== Refs\n1 Girard J. Role of the kidneys in glucose homeostasis. Implication of sodium-glucose cotransporter 2 (SGLT2) in diabetes mellitus treatment Néphrologie & Thérapeutique 2017 13 1 S35 S41 28577741 \n2 Bolinder J. Ljunggren Ö. Kullberg J. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin The Journal of Clinical Endocrinology & Metabolism 2012 97 3 1020 1031 2-s2.0-84858020943 10.1210/jc.2011-2260 22238392 \n3 Fioretto P. Giaccari A. Sesti G. Efficacy and safety of dapagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in diabetes mellitus Cardiovascular Diabetology 2015 14 1 2-s2.0-84945206560 10.1186/s12933-015-0297-x 26474563 \n4 Schwartz S. S. Ahmed I. Sodium-glucose cotransporter 2 inhibitors: An evidence-based practice approach to their use in the natural history of type 2 diabetes Current Medical Research and Opinion 2016 32 5 907 919 2-s2.0-84959239256 10.1185/03007995.2016.1151774 26854518 \n5 Bays H. Sodium glucose co-transporter type 2 (SGLT2) inhibitors: Targeting the kidney to improve glycemic control in diabetes mellitus Diabetes Therapy 2013 4 2 195 220 2-s2.0-84899862290 10.1007/s13300-013-0042-y 24142577 \n6 Wright E. M. Hirayama B. A. Loo D. F. Active sugar transport in health and disease Journal of Internal Medicine 2007 261 1 32 43 10.1111/j.1365-2796.2006.01746.x 2-s2.0-33846023326 17222166 \n7 DeFronzo R. A. Davidson J. A. del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia Diabetes, Obesity and Metabolism 2012 14 1 5 14 10.1111/j.1463-1326.2011.01511.x 2-s2.0-83655193529 \n8 Abdul-Ghani M. A. Defronzo R. A. Inhibition of renal glucose reabsorption: A novel strategy for achieving glucose control in type 2 diabetes mellitus Endocrine Practice 2008 14 6 782 790 2-s2.0-64749089393 10.4158/EP.14.6.782 18996802 \n9 Ogawa W. Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: Possible mechanism and contributing factors Journal of Diabetes Investigation 2016 7 2 135 138 2-s2.0-84959366596 10.1111/jdi.12401 27042263 \n10 Candelario N. Wykretowicz J. The DKA that wasn't: A case of euglycemic diabetic ketoacidosis due to empagliflozin Oxford Medical Case Reports 2016 2016 7 144 146 2-s2.0-85007294530 10.1093/omcr/omw061 27471597 \n11 Zaccardi F. Webb D. R. Htike Z. Z. Youssef D. Khunti K. Davies M. J. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis Diabetes, Obesity and Metabolism 2016 18 8 783 794 10.1111/dom.12670 \n12 FDA FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections 2015 \n13 Blau J. E. Tella S. H. Taylor S. I. Rother K. I. Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data Diabetes/Metabolism Research and Reviews 2017 33 8 e2924 10.1002/dmrr.2924 \n14 Modi A. Agrawal A. Morgan F. Euglycemic diabetic ketoacidosis: A review Current Diabetes Reviews 2017 13 3 315 321 2-s2.0-85021148486 10.2174/1573399812666160421121307 27097605 \n15 Bonner C. Kerr-Conte J. Gmyr V. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion Nature Medicine 2015 21 5 512 517 2-s2.0-84937763347 10.1038/nm.3828 25894829 \n16 Taylor S. I. Blau J. E. Rother K. I. SGLT2 inhibitors may predispose to ketoacidosis The Journal of Clinical Endocrinology & Metabolism 2015 100 8 2849 2852 2-s2.0-84939142605 10.1210/jc.2015-1884 26086329 \n17 Benmoussa J. A. Clarke M. Penmetsa A. Euglycemic diabetic ketoacidosis: The clinical concern of SGLT2 inhibitors Journal of Clinical and Translational Endocrinology: Case Reports 2016 2 17 19 2-s2.0-84978736574 10.1016/j.jecr.2016.05.002 \n18 Ahmadieh H. Ghazal N. Azar S. T. Role of sodium glucose cotransporter-2 inhibitors in type I diabetes mellitus Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2017 10 161 167 2-s2.0-85020511602 10.2147/DMSO.S122767 \n19 Chen J. Fan F. Wang J. Y. The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis Scientific Reports 2017 7 1 44128 10.1038/srep44128 \n20 Burke K. R. Schumacher C. A. Harpe S. E. SGLT2 Inhibitors: A Systematic Review of Diabetic Ketoacidosis and Related Risk Factors in the Primary Literature Pharmacotherapy 2017 37 2 187 194 2-s2.0-85013025315 10.1002/phar.1881 27931088 \n21 Yabe D. Iwasaki M. Kuwata H. Sodium-glucose co-transporter-2 inhibitor use and dietary carbohydrate intake in Japanese individuals with type 2 diabetes: A randomized, open-label, 3-arm parallel comparative, exploratory study Diabetes, Obesity and Metabolism 2017 19 5 739 743 2-s2.0-85013497959 10.1111/dom.12848 27990776 \n22 Peters A. L. Buschur E. O. Buse J. B. Cohan P. Diner J. C. Hirsch I. B. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition Diabetes Care 2015 38 9 1687 1693 10.2337/dc15-0843 26078479\n\n",
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{
"abstract": "A 85 year old woman with a history of severe depression treated with mirtazapine and venlafaxine was admitted to the hospital twice after progressive deterioration of her general condition evolving to unconsciousness. Clinicians diagnosed a metabolic encephalopathy caused by a urinary tract infection which was treated appropriately. Although mirtazapine was stopped during the first hospitalization, the patient's general practitioner restarted mirtazapine four days before readmission. During rehospitalization, she developed extreme restlessness, hyperreflexia and an increased tone in the lower limbs. She was hypertensive and tachycardic. Excessive sweating, elevated creatine kinase levels and bilateral mydriasis were noticed. Urinary analysis showed positive levels of mirtazapine and venlafaxine and both drugs were withdrawn. Symptoms resolved within 48 h after discontinuation of her antidepressants. Conclusion To our knowledge, this is the first case of the serotonin syndrome confirmed by a positive challenge, de-challenge and re-challenge.",
"affiliations": "Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. liesbeth.decoutere@uzleuven.be",
"authors": "Decoutere|Liesbeth|L|;De Winter|Sabrina|S|;Vander Weyden|Liesbeth|L|;Spriet|Isabel|I|;Schrooten|Maarten|M|;Tournoy|Jos|J|;Fagard|Katleen|K|",
"chemical_list": "D003511:Cyclohexanols; D008803:Mianserin; D000069470:Venlafaxine Hydrochloride; D000078785:Mirtazapine",
"country": "Netherlands",
"delete": false,
"doi": "10.1007/s11096-012-9666-7",
"fulltext": null,
"fulltext_license": null,
"issn_linking": null,
"issue": "34(5)",
"journal": "International journal of clinical pharmacy",
"keywords": null,
"medline_ta": "Int J Clin Pharm",
"mesh_terms": "D000369:Aged, 80 and over; D003511:Cyclohexanols; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008803:Mianserin; D000078785:Mirtazapine; D020230:Serotonin Syndrome; D000069470:Venlafaxine Hydrochloride",
"nlm_unique_id": "101554912",
"other_id": null,
"pages": "686-8",
"pmc": null,
"pmid": "22752315",
"pubdate": "2012-10",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "15784664;19046708;14970364;12925718;9794145;12478883;21601732;10941349;9169967;10818650",
"title": "A venlafaxine and mirtazapine-induced serotonin syndrome confirmed by de- and re-challenge.",
"title_normalized": "a venlafaxine and mirtazapine induced serotonin syndrome confirmed by de and re challenge"
} | [
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{
"abstract": "Immune-related adverse events (irAEs), have been reported under immune checkpoint inhibitors. Nivolumab plus ipilimumab (N + I) demonstrated meaningful improvements in key patient-reported outcomes, in patients with pretreated microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). We report a case of severe necrotizing myositis which occurred in a patient treated with N + I combination for mCRC MSI-H. A 61-year-old woman was diagnosed with mCRC MSI-H and BRAFV600E mutated with synchronous liver, pleural, and lymph nodes metastases. After she failed to respond to standard chemotherapy (two lines with 5-fluorouracil, oxaliplatin, and irinotecan + bevacizumab), she received in a clinical trial (CheckMate 142), nivolumab 3 mg/kg, and ipilumumab 1 mg/kg every 3 weeks [4]. One week after the second infusion, she developed rapidly extending proximal muscles weakness associated with diffuse erythematous rash with grade 2/5 strength on abdominal, dorsal, and proximal limb muscles and impressive muscular edema. The creatine kinase level was at 14827 U/L (0-160 U/L), without any detectable autoantibodies. The electromyogram showed a severe myogenic syndrome, and muscular histological analysis demonstrated extensive muscular necrosis, with scarce lymphocytic infiltrates and pathological expression of class I HLA and C5b9 complement deposits with severe endomysial edema. N-I therapy was discontinued. Intravenous methylprednisolone was initiated for 3 days followed by 1 mg/kg/day orally, combined with intravenous immunoglobulins (2 g/kg/day for 2 days). At 3 years of first infusion of N + I, patient is without any new progressive disease, in partial response on the liver, pleural, and nodes metastasis, with only persistent minor psoas weakness.",
"affiliations": "Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Antoine, UPMC University Paris 06, 184, rue du Faubourg Saint-Antoine, 75012, Paris, France.;INSERM U938, Centre de Recherche Saint-Antoine (CRSA), Sorbonne Universités, UMPC University Paris 06, Paris, France.;Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Antoine, UPMC University Paris 06, 184, rue du Faubourg Saint-Antoine, 75012, Paris, France.;Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Antoine, UPMC University Paris 06, 184, rue du Faubourg Saint-Antoine, 75012, Paris, France.;INSERM U938, Centre de Recherche Saint-Antoine (CRSA), Sorbonne Universités, UMPC University Paris 06, Paris, France.;Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Antoine, UPMC University Paris 06, 184, rue du Faubourg Saint-Antoine, 75012, Paris, France. arsene.mekinian@aphp.fr.",
"authors": "Tauber|Marie|M|;Cohen|Romain|R|;Laly|Pauline|P|;Josselin|Laurence|L|;André|Thierry|T|;Mekinian|Arsène|A|",
"chemical_list": "D000074324:Ipilimumab; D000077594:Nivolumab",
"country": "Germany",
"delete": false,
"doi": "10.1007/s10067-018-4373-y",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0770-3198",
"issue": "38(2)",
"journal": "Clinical rheumatology",
"keywords": "Check point immune related adverse evens; Immunotherapy; Myositis",
"medline_ta": "Clin Rheumatol",
"mesh_terms": "D000971:Antineoplastic Combined Chemotherapy Protocols; D015179:Colorectal Neoplasms; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053842:Microsatellite Instability; D008875:Middle Aged; D009220:Myositis; D000077594:Nivolumab",
"nlm_unique_id": "8211469",
"other_id": null,
"pages": "601-602",
"pmc": null,
"pmid": "30456528",
"pubdate": "2019-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "25321335;26337719;27141885;27401894;28873125;29200081;29355075",
"title": "Severe necrotizing myositis associated with long term anti-neoplastic efficacy following nivolumab plus ipilimumab combination therapy.",
"title_normalized": "severe necrotizing myositis associated with long term anti neoplastic efficacy following nivolumab plus ipilimumab combination therapy"
} | [
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