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a 47-year - old man with poorly controlled type 2 diabetes sought care at the royal darwin hospital in the tropical north of the northern territory of australia in january 2011 after several weeks of increasing lethargy and 1 week of fevers and cough . he was patient 692 in the darwin prospective melioidosis study ( 4 ) , which is approved by the human research ethics committee of the northern territory department of health and the menzies school of health research ( approval 02/38 ) . the patient s chest radiograph ( figure 1 , panel a ) showed patchy pneumonia in the right lung and a large soft - tissue mass on the left side of the chest . a computed tomography scan ( figure 1 , panel b ) confirmed the mass to be a 7-cm 6-cm loculated fluid collection in the anterior mediastinum contiguous with patchy bilateral pneumonia and associated with multiple enlarged mediastinal lymph nodes and a pericardial effusion . the patient required initial management in the intensive care unit for his pneumonia , severe sepsis , and ketoacidosis . he received 45 days of intravenous antimicrobial drugs ( meropenem for 11 days , followed by ceftazidime for 34 days ) in conjunction with oral trimethoprim / sulfamethoxazole . after discharge , he received 15 subsequent weeks of eradication therapy with trimethoprim / sulfamethoxazole . at follow up clinical studies of a patient with melioidosis , royal darwin hospital , darwin , northern territory , australia . a ) chest radiograph shows a soft - tissue mass associated with the left side of the mediastinum and obscuring the aortic arch . b ) chest computed tomography scan shows a large loculated mass in the anterior mediastinum ; the mass is contiguous with multiple enlarged mediastinal lymph nodes and with pulmonary consolidation . the unusual finding of extensive mediastinal disease raised the possibility that the patient had inhalational melioidosis . the patient described sitting most days outside his urban accommodation on an elevated and exposed mowed grassy area that overlooks ground sloping downhill to a rocky open drain , an environment that prompted the potential for targeted air sampling . the site was visited and environmental samples taken 6 weeks after the patient s hospital admission . during the sampling , squally rain showers occurred , accompanied by wind blowing up the hill and the drain flowing swiftly . each air collection entailed passing 1,000 l of air ( 50 l / min for 20 min ) through a portable microbiologic air sampler ( md8 airport ; sartorius stedim , dandenong , victoria , australia ) with a disposable gelatin filter ( 3.0 m ) for sample collection . the air sampler was placed on a tripod at 1.0 m elevation above ground level and was protected by a secured , angled overhead umbrella to prevent direct rain contact . after each air sampling , the gelatin filter was placed in 30 ml of modified ashdown selective broth and incubated at 37c , with the broth supernatant plated onto ashdown agar after 2 and 7 days ( 3 ) . sterile water ( 20 ml ) was added to 20 g soil and shaken at 220 rpm for 48 h at 37c . after the soil samples were removed from the shaker and left to stand for 12 h , 10 ml of supernatant was placed in 30 ml of modified ashdown selective broth and incubated at 37c ; the broth supernatant was plated onto ashdown agar after 2 and 7 days . suspected b. pseudomallei colonies were confirmed by using the b. pseudomallei specific tts1 real - time pcr , described previously ( 5 ) . b. pseudomallei was cultured from 1 of the 2 air samples and 1 of the 3 soil samples . multilocus - sequence typing , completed by using standard methods ( 6 ) , confirmed that 2 isolates from each of the positive air and soil samples and the isolate from the patient s blood culture were all sequence type ( st ) 562 . to further resolve the relatedness of st562 isolates , pcr - based , multilocus variable - number tandem - repeat analysis of 4 loci ( mlva-4 ) was performed as described ( 7 ) on the 4 environmental isolates , the patient s blood culture isolate , and isolates from 13 other patients in the darwin prospective study whose melioidosis was caused by st562 b. pseudomallei . mlva-4 categorized the 18 st562 isolates into 3 distinct types : 55 ( n = 7 ) , 71 ( n = 8) , and 168 ( n = 3 ) . the isolate from patient 692 , all 4 environmental isolates , and isolates from 2 of the 13 other patients were mlva-4 type 55 . to further define the relatedness of st562 isolates , whole - genome sequencing was performed on 17 of the 18 st562 isolates for which mlva-4 results were available ; to reduce duplication and cost , 1 of the 2 b. pseudomallei isolates from air samples was not sequenced because it was clonal with the other air sample . genomic dna was extracted by using the qiagen dneasy blood and tissue kit ( qiagen , chadstone , victoria , australia ) , as described ( 7 ) . ( gasan - dong , seoul , south korea ) by using hiseq 2000 ( illumina , san diego , ca , usa ) . genome analysis was performed with spandx version 2.3 ( 8) by using the st562 strain mshr4388 from the mlst database ( http://bpseudomallei.mlst.net/ ) as the reference genome . whole - genome identification of single nucleotide polymorphisms ( snps ) , followed by phylogenetic reconstruction by using maximum parsimony in paup 4.0b10 ( 9 ) , showed that all st562 isolates were closely related ; only 26 snps were observed among all 17 genomes ( figure 2 ) . the air isolate ( added to the mlst database as mshr46817 ) and the 2 soil isolates ( mshr4681 and mshr4682 ) obtained from the environment outside the residence of patient 692 were identical by whole - genome sequencing and differed from the blood culture isolate of patient 692 ( mshr4515 ) by only 3 snps . these genetic similarities support the epidemiologic link between the air and soil b. pseudomallei and the patient s infection . whole - genome core orthologous single - nucleotide polymorphism ( snp ) phylogeny of sequence type 562 burkholderia pseudomallei isolates from a patient with melioidosis and from environmental sampling at the patient s residence , darwin , northern territory , australia . mshr4515 ( mlst database identifier , http://bpseudomallei.mlst.net/ ) was a blood culture isolate from the index patient , identified as patient ( p ) 692 ( p692 , arrow ) . analysis of isolates from 13 other patients with sequence type 562 are also shown ( identifiers begin with p ) . comparison of data for nps and for multilocus variable - number tandem - repeat analysis of 4 loci ( mlva-4 ) types ( shown in parentheses ) supports the hypothesis that p692 was infected from environmental b. pseudomallei at his residence . consistency index = 1 . epidemiologic data from australia , singapore , and taiwan support the hypothesis that inhalation may replace inoculation as the predominant route of b. pseudomallei transmission during severe weather events ( e.g. , tropical monsoonal storms , cyclones , and typhoons ) ( 1012 ) . similar clinical distinctions between percutaneous and inhalational infections are observed for anthrax , plague , and tularemia ( 4 ) . animal studies have also shown the potential importance of aerosol inhalation of b. pseudomallei with high lethality ( 13,14 ) . inhalational melioidosis is supported by the increasing recognition from computed tomography scanning that enlarged mediastinal lymph nodes are not uncommon in patients with severe melioidosis pneumonia ( 4,10 ) . nevertheless , no direct evidence exists to confirm occurrence of inhalation of b. pseudomallei in melioidosis - endemic regions . a recent report from taiwan documented an air sampling technique that uses a filtration real - time quantitative pcr method to quantify ambient b. pseudomallei dna ; high positive rates were found during typhoons ( 12 ) . b. pseudomallei was recovered from air samples taken outside the residence of a patient with clinical features consistent with inhalational melioidosis . whole - genome sequencing linked the environmental b. pseudomallei to an isolate from the patient s blood culture . these data provide evidence of aerosolization of b. pseudomallei during stormy conditions in an endemic location and strong circumstantial evidence for inhalation of b. pseudomallei . the proportion of melioidosis cases resulting from inhalation rather than percutaneous inoculation or ingestion requires further study and is likely to vary substantially by location and season . | the frequency with which melioidosis results from inhalation rather than percutaneous inoculation or ingestion is unknown .
we recovered burkholderia pseudomallei from air samples at the residence of a patient with presumptive inhalational melioidosis and used whole - genome sequencing to link the environmental bacteria to b. pseudomallei recovered from the patient . |
our patient was an 8-month - old male child of indian origin and the first issue of a nonconsanguineous marriage . he presented to our center with the complaints of cough , cold , progressively increasing breathlessness , and refusal to feed over the past 3 days . past history was elicited that the child was a full - term baby weighing 2.4 kg . his important clinical course is summarized in table 1 . on presentation to us , he had tachycardia ( 160 beats per minute ) , tachypnea ( 64 breaths per minute ) , capillary refill time of 3 s , and blood pressure of 76/60 mmhg in the right arm supine position . the child had increased work of breathing , as evidenced by the subcostal and intercostal retractions . cardiac examination revealed a pansystolic murmur ( grade iii ) , in the third and fourth intercostal spaces . his weight , length , and head circumference were below the third percentile for his age ( weight 3.5 kg , length 61 cm , head circumference 37 cm ) . he had narrow and upslanting palpebral fissures , epicanthal folds , and prominent ears [ figure 1 ] . past clinical course of the patient hgt = hemoglucotest ; pcv = packed cell volume ; cbc = complete blood count ; tlc = total leucocyte counts ; dlc = differential leucocyte count ; anc = absolute neutrophil count ; alc = absolute lymphocyte count ; crp = c - reactive protein ; tof = tetralogy of fallot ; ps = pulmonary stenosis ; vsd = ventricular septal defect ; * dose of the iv calcium 2cc / kg / dose , tds for 3 days facial profile of the child . note the narrow and upslanting palpebral fissures , epicanthal folds , and prominent ears q1 : name some hereditary and nonhereditary conditions in which the facial dysmorphisms associated with the underlying heart disease can give a clue to the etiology of the condition . ans . : table 2 elaborates the conditions in which facial dysmorphisms associated with underlying heart disease can give a clue to the etiology of the condition . conditions in which facial dysmorphisms are associated with a heart disease ecd = endocardial cushion defect ; asd = atrial septal defect ; pda = patent ductus arteriosus ; ar = aortic regurgitation ; mr = mitral regurgitation ; cad = coronary artery disease ; as = aortic stenosis ; pa = pulmonary artery ; dgs = digeorge syndrome case details ( continued ) : in view of the association of conotruncal cardiac anomaly , hypocalcemia with hypoparathyroidism [ table 1 ] in the infantile period , and typical dysmorphic facies , we were prompted to suspect digeorge syndrome ( dgs ) . : dgs is a 22q11.2 microdeletion syndrome , associated with the classic triad of conotruncal cardiac anomalies , hypoplastic thymus ( resulting in immunodeficiencies ) , and hypoplasia of the parathyroid glands ( resulting in hypoparathyroidism and hypocalcemia ) . the other synonyms for dgs are 22q11.2 deletion syndrome ( preferred terminology ) , velocardiofacial syndrome , conotruncal anomaly face syndrome , sedlackova syndrome , and cayler cardiofacial syndrome . in less than 1% of all patients with dgs , there is complete athymia , resulting in severe combined immunodeficiency ( scid ) . this is called complete dgs ; the remaining 99% are partial dgs , having some thymic function preserved . in our patient , repeated blood investigations failed to show lymphopenia [ table 1 ] . detailed immunological tests could not be carried out in our patient . with a worldwide prevalence of between 1/2000 and 1/4000 live births , the actual prevalence may be higher due to high clinical expressivity , accounting for underrecognition . : dgs is caused due to the deletion of the genes in the digeorge chromosomal region ( dgcr ) on chromosome 22q11.2 , secondary to a nonallelic meiotic recombination during spermatogenesis or oogenesis . a great percentage ( 93% ) of the probands have a de novo deletion of 22q11.2 , while some ( 7% ) inherit the 22q11.2 deletion from a parent in an autosomal dominant fashion . rarely , less than 1% of the individuals with dgs have chromosomal rearrangements , such as a translocation between chromosome 22 and another autosome , involving 22q11.2 . ? ans . : the clinical features of dgs [ table 3 ] , are exceedingly variable , with over 190 features described in the literature , involving almost every organ system thus underlining the need for sensitization among physicians and surgeons from all specialties . of note , no phenotype occurs in 100% of the patients , as the penetrance of each clinical feature is diverse . thus , one should be wary of excluding differential of dgs solely on the basis of absence of a particular feature . the presence of congenital heart disease ( chd ; especially conotruncal anomalies ) , neonatal hypocalcemia ( with hypoparathyroidism ) , and palatal defects can usually be picked up in the neonatal period , and should serve as red flags for early diagnosis . authorities in this subject recommend that , given the high frequency of dgs among individuals with conotruncal anomalies , newborns with these heart anomalies should be routinely screened with fluorescence in situ hybridization ( fish ) for 22q11.2 deletion , once other causes ( down syndrome , trisomy 13 ) have been ruled out . other pointers for this condition , such as dysmorphisms , intellectual disability , and psychiatric disorders may appear only years later , often delaying the diagnosis . an emerging area of great interest is the high predilection of psychotic disorders ( including schizophrenia and bipolar disorders ) in adolescents and adults with dgs ( 25 times higher than the general population ) . other than serving as a reminder to psychiatrists , this also underlines that pediatricians and geneticists dealing with dgs / suspected dgs should diligently excavate the psychiatric history of the pedigree in detail , along with the other relevant particulars . clinical features of digeorge syndrome scid = severe combined immunodeficiency ; chd = congenital heart disease ; jra = juvenile rheumatoid arthritis case details ( continued ) : in view of suspected dgs , fish was performed using tuple1 probes on 200 interphase nuclei and 7 metaphases of the cultured blood . all the cells analyzed showed a heterozygous deletion in the 22q11.2 region [ figures 2a and b ] . presence of two green signals ( control arsa probe , locus 22q13 ) one orange signal ( tuple1 , locus 22q11.2 ) denotes hemizygous deletion in the 22q11.2 region ( b ) fish image of the patient : metaphase cell , each cell has two chromatids . presence of two pairs of green signals ( control arsa probe , locus 22q13 ) and only one pair of orange signals ( tuple1 locus 22q11.2 ) denotes hemizygous deletion in the 22q11.2 region q5 : what is the diagnostic modality for digeorge syndrome ? : the most regularly and widely used diagnostic test for detecting the 22q11.2 deletion is fish using probes for the commonly deleted region . however , around 5% of the cases may require more sophisticated and costlier methods such as multiplex ligation - dependent probe amplification ( mlpa ) and array comparative genomic hybridization ( acgh ) to detect the underlying genetic aberration . the presence of a chd in association with one or more of the following should serve as an important red flag for considering an underlying chromosomal imbalance as the possible genetic etiology : growth failure , intellectual disability , other malformations affecting a second organ , multiple anomalies , and dysmorphic features . in such cases , when the conventional karyotype fails to pick up the underlying genetic condition , an acgh can lead to increased detection of the underlying causal chromosomal imbalance . the major advantage of this acgh technique is its increased resolution , which surpasses that of conventional karyotyping by at least fivefold . in an excellent study by breckpot et al . , 150 children with an underlying chd and one or more of the red flags mentioned above were subjected to acgh , after a genetic diagnosis could not be reached despite a conventional karyotype and ruling out well - defined genetic disorders . of these 150 children , 24 ( 17.3% ) were detected as having an underlying copy number variation ( cnv ) , that is , a deletion or duplication , as responsible for their syndromic chd , as detected by acgh . some examples of the cnvs detected in this study include 1p36 deletion , 1q21.1 duplication , 8q deletion , 14q32 deletion , and 16p13.3 duplication . acgh can also diagnose , among many other cnv conditions , williams syndrome and some cases of charge syndrome . case details ( continued ) : on admission in our center , the child had leukocytosis ( total leukocyte count = 32 10/l ) and radiological evidence of bronchopneumonia . however , the child 's condition worsened on day 9 , due to congestive cardiac failure precipitated by the infection . in spite of ionotropic support and mechanical ventilation , the child timely diagnosis of this condition can alert the treating physician about the possibility of the associated comorbities known to occur with this disease . acute management in neonates and during infancy is mainly focused on the evaluation and treatment of hypocalcemia and the underlying chd as in our case . proactive prevention of the secondary complications and a watchful system - wise surveillance plan can go a long way in ensuring a healthy life for most of these individuals [ table 4 ] . however , the lack of centers performing thymic transplantation in india and the immunosuppression following the transplant make that a difficult option . prevention of secondary complications and the system - wise surveillance in patients with digeorge syndrome case details ( continued ) : the parents were offered genetic counseling , the main focus being on the future risk of recurrence , as our patient was the first issue . ans . : following the detection of 22q11.2 deletion in the proband , it is of vital importance to screen both the parents for the same ( using fish or mlpa ) in order to ascertain the origin of the deletion , sporadic or inherited . if either parent is detected with the deletion , then the risk of recurrence in the next pregnancy is 50% irrespective of the sex of the child ( autosomal dominant inheritance ) . however , if the parents of an individual with 22q11.2ds have normal studies , the risk of recurrence in the subsequent pregnancy is low , though greater than that of the general population . this is due to the possibility of germline or low - level somatic mosaicism in the parents . report retrospectively detecting 30 relatives of probands having a deletion in the 22q 11.2 region , following a diagnosis in the proband . of note , only 32% of the adults and 55% of the children in this case series ever had any major medical problems warranting care . thus , the absence of obvious clinical features should not be a reason to exclude the screening for the 22q11.2 deletion in the parents , if their child has been proven to carry the same . unfortunately , in our case the parents were unwilling to investigate themselves further . in the scenario of one child having dgs , prenatal testing by fish or mlpa can be offered in the next pregnancy , using fetal cells obtained by chorionic villus sampling ( 10 - 13 weeks of gestation ) or amniotic fluid analysis ( 15 - 18 weeks of gestation . ) in pregnancies without any family history of the disorder , the sonographic markers that should prompt one to request for prenatal diagnosis are : chd ( especially conotruncal anomalies ) and/or cleft lip and/or cleft palate , congenital diaphragmatic hernia , umbilical or inguinal hernia , tracheoesophageal fistula / esophageal atresia / laryngeal atresia , polydactyly , craniosynostosis , polymicrogyria , and renal anomalies . the prognosis for patients with dgs depends mainly on whether the dgs is partial or complete and on the severity of the underlying cardiac defect . most children with complete dgs who do not undergo a thymic transplant usually die in infancy . in contrast , the overall mortality rate in children with partial dgs is reported to be < 10% , most of them due to the underlying heart disease . however , if the child with an underlying heart disease has a successful repair , then the prognosis may be much better , the majority of the immunological problems settling with time . the endocrinological problems , too , do not tend to be devastating , most of them being treatable . learning disabilities , speech issues , and psychiatric manifestations respond well if remedial and supportive therapy is begun early . dgs is the most common microdeletion syndrome , with a notoriety of being clinically varied . timely diagnosis aids better management , more holistic counseling , and the opportunity for prenatal diagnosis in a subsequent pregnancy . the 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 can not be guaranteed . this research received no specific grant from any funding agency in the public , commercial , or not - for - profit sectors . the 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 can not be guaranteed . this research received no specific grant from any funding agency in the public , commercial , or not - for - profit sectors . | our patient presented with congenital heart disease ( chd : tetralogy of fallot ) , hypocalcemia , hypoparathyroidism , and facial dysmorphisms .
suspecting digeorge syndrome ( dgs ) , a fluorescence in situ hybridization ( fish ) analysis for 22q11.2 deletion was made .
the child had a hemizygous deletion in the 22q11.2 region , diagnostic of dgs .
unfortunately , the patient succumbed to the heart disease .
dgs is the most common microdeletion syndrome , and probably underrecognized due to the varied manifestations .
this case stresses the importance of a detailed physical examination and a high index of suspicion for diagnosing this genetic condition .
timely diagnosis can help manage and monitor these patients better and also offer prenatal diagnosis in the next pregnancy . |
the ovaries are the most common sites affected , but endometriosis can also involve the gastrointestinal tract , urinary tract , chest , and soft tissues . endometriosis of the chest is uncommon , and the diagnosis is usually established on clinical grounds . endometrial tissue may involve the pleura by migrating from the peritoneal cavity to the pleural cavity through diaphragmatic defects or via microembolization . pleuritic chest pain , pneumothorax , pleural effusions , or cyclic haemoptysis can occur with pulmonary involvement [ 35 ] . a 35-year - old female presented with episodes of a right chest pain approximately 3 - 4 days in a month and resolved spontaneously . her primary care physician had treated her with antibiotics empirically throughout the four months . during the last episode of chest pain , the patient described having a pain not resolving with analgesics combination . the patient did not have any exacerbating factors , fevers , dyspnoea , haemoptysis , weight loss , and gastrointestinal complaints . the patient 's medical history was unremarkable , and she specifically denied a history of trauma and cardiopulmonary disease . she had spent 4 months in seaside town and had also worked at a seafood restaurant . her physical examination was within normal limits , except minimal pain in the right - sided lower chest and tenderness of the left lower abdominal quadrant . routine laboratory tests and tumor markers ( afp , cea , ca 15 - 3 , ca 19 - 9 ) were within normal limits but increased serum level of ca-125 level ( 53.7 u / ml , normal value : 035 u / ml ) . her chest radiography showed a closed right - sided costophrenic angle and minimal pleural effusion without evidence of pneumonia ( figure 1(a ) ) . chest computed , tomography ( ct ) scans were performed 6 days after the onset of menstruation , and these did not demonstrate pleural effusion or any abnormality ( figure 1(b ) ) . a percutane thoracal punction ( no abnormalities were noted on histopathologic examination ) was done because she denied thoracoscopic examination . pelvic endometriosis was considered a possible diagnosis according to the results of us and mr of the abdomen . pelvic us revealed a left adnexal semisolid mass , with a thick wall and septa , measuring 71 61 cm ( figure 1(c ) ) . mr imaging evaluated a left adnexal mass in 67 57 mm diameter with , high - signalintensity areas on t1- ( figures 2(a ) and 2(b ) ) and t2-weighted ( figures 2(c ) and 2(d ) ) images . in addition , dynamic signal range was not narrowed with fat - suppressed sequence , and heterogeneous pattern was found on postcontrast series . therefore , based on imaging characteristics immature teratoma , endothermal sinus tumor , and germ cell tumor must be considered primarily . at exploratory laparotomy , a transverse incision was performed , and a 6 cm mass was found just behind the uterus , as well as adhesions between the mass and the adjacent tissues . the patient needed sharp dissection and underwent adhesiolysis with left - sided salpingo - oophorectomy . rest of endometriotic focuses on uterus , pouch of douglas , and other peritoneal surfaces were destroyed with electro - coagulation . macroscopic appearance showed multiple irregular hemorrhagic foci and chocolate cysts ( figure 3 ) . the postoperative recovery was uneventful , and the patient was discharged on the third post - operative day . leuprolide acetate ( lucrin 3.75 mg ; abbott australasia , kurnell , nsw , australia ) was used to achieve endometrial atrophy for six months after surgery . medical treatment was continued with a cyclic low - dose combined oral contraceptive ( yasmin ; bayer healthcare pharmaceuticals inc . , one year of regular followup , there was no evidence of recurrent pleural effusion , chest pain , and abdominal complaints . the endometrial cells implant on serosal surfaces into the peritoneal cavity and transport to the thorax through diaphragmatic defects and lymphatic or vascular channels . thoracal endometriosis , depending on the extent and tissue affected , can produce pleuritic chest pain , pleural effusion , hemothorax , and pneumothorax . the physical manifestations are variable , with some patients being asymptomatic and others having disabling chest or pelvic pain , adnexal masses , or unusually signs . in our patient , periodic episodes of symptoms concurrent with menstruation led to the suspicion of a relationship between these conditions . the peak incidence for pelvic endometriosis occurred between 24 and 29 years , whereas the peak incidence for thoracal involvement was between 30 and 34 years . in a series of 110 patients with thoracal endometriosis , pneumothorax , hemothorax , hemoptysis , and pulmonary nodules the right hemithorax was involved in more than 90% of all manifestations except for nodules . regardless of pathophysiology , thoracal endometriosis is generally associated with coexistent pelvic endometriosis and usually occurs 5 years after the diagnosis of pelvic endometriosis . however , most women with endometriosis have normal or nonspecific results from physical examinations , and laparoscopy is necessary for the definitive diagnosis . for the definite confirmation of presence of endometrial tissue ct - guided percutaneous transthoracic needle biopsy or thoracoscopic tissue biopsy we only able to perform thoracal ct and abdominal mr imaging in present case , because our patient denied a thoracoscopic examination . the us appearance of pelvic endometriosis exhibits diffuse low - level internal echoes , hypoechoic focal lesion , and rarely , may be anechoic , mimicking a functional ovarian cyst . patel et al . found that wall thickness is not a differentiating feature between endometriomas and other ovarian masses . using ct , endometriosis of the lung parenchyma mr imaging has been shown to have greater specificity for the diagnosis of abdominal endometriomas . . lesions with degenerated blood products , including concentrated protein , appear with high - signalintensity areas on t1- and t2-weighted images . in our case , t1-weighted mr image showed a multilocular high - signalintensity mass on the left ovary , and highness in signal intensity remained in t2-weighted image . a common feature of an endometrioma , shading , is present when a cyst that is hyperintense on a t1-weighted image becomes hypointense on a t2-weighted image . this shading reflects the chronic nature of an endometrioma and helps differentiate it from other blood - containing lesions except hemorrhagic corpus luteum cysts , which do not exhibit shading on t2-weighted images . other lesions that appear with high - signalintensity on t1-weighted images include dermoids , mucinous cystic tumors , and hemorrhagic masses . treatment for thoracal endometriosis can be medical for chest pain and effusion or surgical , depending on the severity of urgent and elective symptoms . medical treatment is one of the choices of treatment to relieve cyclic pain in endometriosis . multiple pharmacologic agents in use include combined oral contraceptives , danazol , gn - rh agonists and progestins . in our patient , medical treatment with a gn - rh agonist , which was continued with a cyclic low - dose definitive surgery includes hysterectomy and oophorectomy and is usually reserved for women with intractable pain . the conservative surgery , including left - sided oophorectomy , was performed to our patient . in our patient , , we did not establish pleural endometriosis cytologically but the monthly chest pain associated with endometrioma of the ovary supported extrapelvic lesion , clinically . | chest pain is a rare sign of thoracal endometriosis associated with endometrioma of the tubo - ovarian endometrioma .
we report the case periodic episodes of chest pain concurrent with menstruation in a 35-year - old female , in which ovarian endometrioma was diagnosed and left - sided oophorectomy was performed . after surgery ,
patient underwent medical treatment which included a gn - rh agonist and a combined oral contraceptive . in the follow - up period
, there was no evidence of chest pain . |
collapsing glomerulopathy has been recognized as a form of focal segmental glomerulosclerosis characterized by collapse of the glomerular capillary tuft and proliferation of the visceral epithelial cells . most cases have been seen in patients with hiv infection , but since 1986 an association with several non - hiv - related conditions has also been reported [ 13 ] . indeed , as early as in 1999 , one center reported that as many as two - thirds of cases of collapsing glomerulopathy ( collapsing gn ) were non - hiv - related ; labeled as collapsing idiopathic gn . it is now known that collapsing gn may occur in association with viruses ( parvovirus b19 , cytomegalovirus ( cmv ) , htlv-1 and hcv ) , bacteria ( tuberculosis ) , parasites ( leishmaniasis ) , febrile illness , drugs ( interferon alpha , pamidronate ) , autoimmune diseases , malignancy ( acute monoblastic leukemia , multiple myeloma , hemophagocytic syndrome ) , post - transplantation and certain genetic causes . a previously healthy 21-year - old african - american woman presented with a 4-day history of malaise , fever , nausea , vomiting , anorexia and left - sided abdominal pain . kg / m , had a temperature of 38.9c ( 102f ) , pulse rate of 100 bpm , respiratory rate of 22 per minute and blood pressure of 110/70 mmhg . the spleen was markedly enlarged and there was tenderness over the left upper abdominal quadrant . initial laboratory tests were significant for a normocytic normochromic anemia [ hemoglobin 5.8 g / dl ( 58 g / l ) ] , thrombocytopenia ( platelet count 103 000 cells/l ) and a lymphocyte count of 4400 cells/l ( normal 12003400 cells/l ) . ct scan of the abdomen ( without intravenous contrast ) revealed massive splenomegaly and hypodensities suggestive of infarcts . autoimmune workup including serum antinuclear antibodies , antineutrophil cytoplasmic antibodies , complements , antiphospholipid antibodies , serum and urine protein electrophoresis with immunofixation were normal . testing for lymphoproliferative diseases revealed normal flow cytometry , absent jak 2 mutation , no bcr / abl gene translocation and unremarkable bone marrow biopsy . infectious workup was negative for human immunodeficiency virus ( hiv ) 1 and 2 serology , and hiv rna by polymerase chain reaction ( pcr ) . hepatitis b and c serologies , urine histoplasma antigen , serum rapid plasma reagin and parvovirus b19 were negative . barr virus ( ebv ) dna and viremia ( as assessed by qualitative pcr methods ) was reported as positive on day 9 . subsequent testing for ebv - specific antibodies revealed positive igm vca ( viral capsid antigen ) titers ( > 1:10 ) and positive igg vca on day 10 . on admission , urinalysis showed specific gravity of 1.019 , 1 + dipstick proteinuria , 5 red blood cells , and 15 white blood cells per high power field magnification ( hpf ) , no cellular casts and sterile urine culture . no previous baseline values were available for comparison . at the time of renal consultation on day 10 of admission , serum creatinine had increased to 133 mol / l ( 1.5 mg / dl ) 24 h after administration of intravenous contrast for a repeat ct scan of the abdomen . repeat urinalysis revealed a specific gravity of 1.036 , 4 + dipstick proteinuria , 5 red blood cells and 215 white blood cells per hpf , sterile urine culture and a spot urine protein to creatinine ratio of 23 , confirmed on two separate occasions . g / l ( 3.2 g / dl ) , and total cholesterol had increased to 4.8 mmol / l ( 185 mg / dl ) from a baseline 2.2 mmol / l ( 85 mg / dl ) . renal biopsy was performed on day 15 to characterize the new - onset nephrotic syndrome as the patient had now also developed anasarca . it revealed collapse of the glomerular capillary tuft , visceral epithelial cell proliferation and vacuolization consistent with collapsing glomerulopathy ( figure 1 ) , alongside with evidence of recovering acute tubular necrosis . in situ 1.collapse of glomerular tuft ( a ) along with visceral epithelial cell proliferation and vacuolization ( b ) on pas ( periodic acid - schiff ) and jones stain . collapse of glomerular tuft ( a ) along with visceral epithelial cell proliferation and vacuolization ( b ) on pas ( periodic acid - schiff ) and jones stain . on day 18 , a therapeutic splenectomy was performed because of unremitting abdominal pain and radiologic evidence of capsular rupture . splenic tissue examination showed multifocal infarction , capsular rupture and confirmed the presence of ebv - encoded rna ( eber ) by in situ hybridization ( figure 2 ) . serum creatinine returned to a baseline of 53 mol / l ( 0.6 mg / dl ) on day 20 . follow - up ebv serology on day 21 revealed positive igg ebna ( epstein barr nuclear antigen ) titers . subsequent follow - up over the next few months showed improving proteinuria , urine sediment and serum albumin levels . at the last clinic visit ( 11 months after illness onset ) , serum creatinine was 53 g / l ( 3.9 g / dl ) , urine sediment had 1 red blood cell and 1 white blood cell per hpf , and proteinuria had lowered to < 1 g / g of creatinine in the urine . the patient continues to be conservatively managed with up - titration of raas blockade and is being closely monitored by the clinic . here we report an association between collapsing glomerulopathy and an acute ebv syndrome , manifesting itself clinically as nephrotic syndrome with massive proteinuria , hypoalbuminemia , anasarca and hypercholesterolemia . the reversible rise in creatinine was most likely due to contrast - induced acute kidney injury , also demonstrated on renal biopsy . evidence of renal involvement is reported in 316% of patients with acute infectious mononucleosis [ 6 , 7 ] . nephrotic syndrome in acute infectious mononucleosis was first published in 1963 in a case in which kidney biopsy was inconclusive . glomerular lesions have included membranous nephropathy [ 10 , 11 ] , mesangial focal proliferative disease with cellular crescents , minimal - change disease [ 13 , 14 ] and vasculitic lesions such as polyarteritis nodosa . to our knowledge , this is the first report of collapsing glomerulopathy . ebv predominantly infects b lymphocytes , the producers of immunoglobulin through specific ebv / c3d receptors on b cells . a viral glycoprotein , gp350 , bears sequence homology to the c3 complement fragment c3d . one of the main reservoirs of ebv is the nasopharyngeal mucosa , where epithelial cells endocytose circulating polymeric iga - ebv immune complexes by specific receptors and transport them to the luminal surface . ebv infection seems to represent equilibrium between viral replication in vivo and the host 's immune removal of the virus , and disease occurs when there is an imbalance in the host immunity . it could be related to an uptake of immunoglobulin ebv complexes by glomerular visceral and parietal epithelial cells similar to that in the nasopharyngeal mucosa . have shown localization of parvovirus b19 dna ( another viral cause of collapsing gn ) in glomerular parietal and visceral epithelial cells . another study suggested a causative role of ebv infection in the pathogenesis of interstitial nephritis . ebv dna has been detected in renal tissue in iga nephropathy , membranous nephropathy and focal / segmental lesions ; and is quantitatively greater in subgroups with mesangial injury , fibrinogen deposits and immunoglobulin deposits , suggesting a causative role . other studies have also reported transformation of b cells by ebv to produce more iga than igg , especially in iga nephropathy , and the same iga1 subtype that was produced by transformed b cells was found deposited in the glomerular mesangium [ 22 , 23 ] . in our patient , this may have been due to a low viral copy number or to the focal nature of the infection . differences in the detection techniques applying pcr and southern blot to the extracted dna may have also contributed to the absence of ebv detection in renal tissue . however , there was a significant association of acute ebv viremia and collapsing gn in our patient . as the acute phase of the infection cleared , proteinuria gradually improved , but persisted , suggesting the possibility of secondary autonomous phase of podocyte loss . | a 21-year - old woman presenting with acute epstein barr virus ( ebv ) infection ( infectious mononucleosis ) was noted to have renal involvement .
she had proteinuria , leukocyturia and microscopic hematuria , and 10 days after admission became nephrotic ( 23 g of protein per g of creatinine ) .
renal biopsy revealed glomerular tuft collapse , visceral epithelial cell proliferation and vacuolization consistent with collapsing glomerulopathy .
she had only transient deterioration in renal function , attributed to contrast nephropathy , but after recovery remained proteinuric .
renal disease is well described in ebv infection , but collapsing glomerulopathy has not been reported previously . |
the use of oocyte freezing for fertility preservation is becoming more widely practiced.1 although there is evidence that the success rates of oocyte cryopreservation and subsequent thaw cycles appear to approach that of a fresh in vitro fertilization ( ivf ) cycle ( coupled with reports of numerous live births ) , oocyte cryopreservation is still not considered mainstream , but has become a more accepted option for cancer patients.2 despite the controversy surrounding embryo biopsy for aneuploidy assessment ( preimplantation genetic screening [ pgs ] ) , recent advances such as trophectoderm biopsy and array comparative genomic hybridization ( a - cgh ) have provided more support for its continued and expanded use . as more patients are choosing oocyte cryopreservation for fertility preservation , and as more evidence accumulates that aneuploidy screening lowers miscarriage rates and improves implantation rates , it is likely the combination of oocyte cryopreservation and pgs will be utilized in the future.3,4 we report a successful live birth from previously vitrified oocytes from a known donor , which were thawed , fertilized , cultured to blastocyst , underwent trophectoderm biopsy , and refrozen awaiting analysis of ploidy by a - cgh . a 31-year - old with a history of two miscarriages requested pgs due to our decreased loss rates in patients with recurrent pregnancy loss utilizing pgs compared to those not using pgs.3,4 the patient was in a same - sex relationship and had failed several intrauterine inseminations and two ivf cycles using donor sperm ( donor karyotype known to be 46 , xy ) in the past . one miscarriage occurred after an insemination ( chromosomes not tested ) and one after an ivf cycle , which was found to be 45 , x. the patient was found to have uterine lining issues , including asherman s syndrome , but due to her schedule , she requested to undergo ovarian stimulation with oocyte retrieval and cryopreserve her oocytes . at the time , we felt that our oocyte thaw pregnancy rates were greater than or equal to our frozen embryo transfer pregnancy rates , and after much discussion , the patient felt most comfortable cryopreserving her oocytes over embryos with donor sperm . her plan was to address her endometrial lining issues when her schedule permitted , which would then be followed by fertilization , embryo biopsy , and an embryo transfer . ovarian stimulation for her third cycle was achieved by a combination of injectable recombinant follicle - stimulating hormone ( follistim ; organon , orange , nj , usa ) and human menopausal gonadotropin ( menopur ; ferring , suffern , ny , usa ) . an ovulation trigger of human chorionic gonadotropin ( 10,000 iu ) was administered when her two lead follicles were 18 mm , and an ultrasound - guided transvaginal oocyte retrieval was performed 3436 hours later . oocytes were frozen by both vitrification ( n = 11 ) and slow freeze ( n = 7 ) by our previously published methods , and thawed by the same methods.1,5 the oocytes were thawed 2 months later and placed in human tubal fluid media ( irvine scientific , irvine , ca , usa ) , supplemented with 6% plasmanate ( 5% usp plasma protein fraction [ human ] ; bayer , elkhart , in , usa ) , and overlaid with sage mineral oil ( cooper surgical co. , trumbull , ct , usa ) . thirteen mature oocytes survived the thaw ( 12/15 m2 frozen and one mi developed into an m2 upon thaw ) . fertilization was documented 18 hours after insemination by the presence of two pronuclei ( 2pn ) ; this patient had twelve 2pns ( seven from vitrification and five from slow freeze ) , leading to a 92% fertilization rate . on day 3 , a hole was made in the zona pellucida using a cronus laser ( research instruments , falmouth , uk ) on a nikon inverted te-2000 microscope ( nikon corporation , tokyo , japan ) using cronus software to allow hatching in all twelve embryos . resultant embryos were cultured for 5 days , but the embryos were all morulas or cleavage - stage embryos and not suitable on day 5 for biopsy ; therefore , they were cultured to day 6 . on day 6 , five ( three from vitrification and two from slow - freeze ) of her embryos underwent trophectoderm biopsy and were vitrified a second time . vitrification was performed according to the kuwayama vitrification method with cryolocks and using an irvine scientific vitrification system , which contains dimethyl sulfoxide and ethylene glycol.6 the biopsied cells were placed in eppendorf tubes , frozen in dry ice , and then transported to reprogenetics for pgs analysis once all of the biopsies were performed . this analysis was performed using the method described in gutirrez - mateo et al7 without modification . oocytes were frozen by both vitrification ( n = 11 ) and slow freeze ( n = 7 ) by our previously published methods , and thawed by the same methods.1,5 the oocytes were thawed 2 months later and placed in human tubal fluid media ( irvine scientific , irvine , ca , usa ) , supplemented with 6% plasmanate ( 5% usp plasma protein fraction [ human ] ; bayer , elkhart , in , usa ) , and overlaid with sage mineral oil ( cooper surgical co. , trumbull , ct , usa ) . thirteen mature oocytes survived the thaw ( 12/15 m2 frozen and one mi developed into an m2 upon thaw ) . fertilization was documented 18 hours after insemination by the presence of two pronuclei ( 2pn ) ; this patient had twelve 2pns ( seven from vitrification and five from slow freeze ) , leading to a 92% fertilization rate . on day 3 , a hole was made in the zona pellucida using a cronus laser ( research instruments , falmouth , uk ) on a nikon inverted te-2000 microscope ( nikon corporation , tokyo , japan ) using cronus software to allow hatching in all twelve embryos . resultant embryos were cultured for 5 days , but the embryos were all morulas or cleavage - stage embryos and not suitable on day 5 for biopsy ; therefore , they were cultured to day 6 . on day 6 , five ( three from vitrification and two from slow - freeze ) of her embryos underwent trophectoderm biopsy and were vitrified a second time . vitrification was performed according to the kuwayama vitrification method with cryolocks and using an irvine scientific vitrification system , which contains dimethyl sulfoxide and ethylene glycol.6 the biopsied cells were placed in eppendorf tubes , frozen in dry ice , and then transported to reprogenetics for pgs analysis once all of the biopsies were performed . this analysis was performed using the method described in gutirrez - mateo et al7 without modification . overall , the patient underwent three operative hysteroscopies with lysis of adhesions followed by uterine balloon catheter by three different skilled physicians without improvement in her uterine lining . ultimately , the patient decided to transfer the euploid embryos into her partner who had a normal lining . the thaw cycle utilized sequential oral estradiol supplemented by intramuscular progesterone after the endometrial stripe achieved a ring pattern and was 11 mm in the first thaw cycle and 9 mm in the second thaw cycle . an appropriately timed ultrasound guided embryo transfer was performed of euploid blastocysts . in the first embryo transfer cycle , two euploid embryos ( 35bb , 6bc ) the second attempt with a single euploid embryo ( 35bc ) resulted in a pregnancy . the couple went on to deliver a viable 8-pound , normal male infant ( confirming a - cgh results ) at 38 weeks gestation via normal spontaneous vaginal delivery . as more oocytes are frozen for fertility preservation before cancer treatment or electively , there will be increasing instances where preimplantation genetic diagnosis ( pgd ) or pgs will be indicated or requested after thawing . as more recessive genes are identified , more patients will be candidates for single gene pgd . in addition , as more cancer - causing genes are identified , cancer survivors who utilized fertility preservation will request pgd to avoid inheritance of these genes . the evolving literature on 24 chromosome screening already shows that the miscarriage rate is lower and the implantation rate is higher than ivf cycles without pgs ( and equivalent to donor oocyte unscreened embryos ) , suggesting the possibility of routine aneuploidy assessment prior to embryo transfer.4,8,9 in either case , more patients will electively request the utilization of these techniques for their previously cryopreserved oocytes . this case report demonstrates proof of a concept that it is possible to perform pgd or pgs on embryos derived from previously cryopreserved oocytes . | our objective is to describe a successful live birth from oocyte vitrification followed by thaw , fertilization , blastocyst culture , trophectoderm biopsy , vitrification , and subsequent thaw .
fifteen mature oocytes were frozen from a patient with uterine factor infertility .
thirteen oocytes survived the thaw , and five underwent trophectoderm biopsy and were refrozen .
three euploid embryos were obtained .
a single euploid embryo was transferred in the second thaw cycle to a known recipient leading to the delivery of a normal male infant .
this case report is proof of the concept that preimplantation screening and diagnosis is an option for fertility preservation patients . |
since the original description of the disease by alois alzheimer , memory difficulties are considered the initial and the most prominent and typical symptom of alzheimer 's disease . more recently , the detection of elderly subjects with mild cognitive impairment and a high risk of progression to alzheimer 's disease also relies on the presence of memory complaints , and , in proposed revised criteria for prodromal ad , like the dubois criteria , the report by patients or informants of memory decline remains part of the core diagnostic features . memory complaints thus represent an important symptom in clinical practice . on the other hand , in fact , not only elderly but also young subjects may have an unfavourable opinion about their memory capabilities . using a formal scale , the subjective memory complaints scale ( smc ; ) , as much as 75.9% of people report at least minor complaints when answering to the first general question do you have any complaints concerning your memory ? ( smc1 ) . the significance and clinical implications of the frequent report of memory difficulties in the community setting are not clear . in a meta - analysis , the presence of memory complaints was more frequent in cognitively impaired than in cognitively normal elderly subjects . a systematic review concluded that the subjective memory complaints appear to be associated with depressive symptoms and personality traits and may predict future cognitive decline . a recent study found that self perceived memory complaints are an independent predictor of dementia . in the present study , we analysed the severity and type of memory difficulties presented by patients who look for medical help in a memory clinic or hospital outpatient setting , as compared to the memory difficulties that subjects in the community report when specifically asked for . the same instrument , the subjective memory complaints scale , was applied in both samples . we tested the hypothesis that some types of memory complaints would be selectively reported by subjects in the clinical setting . the objective was to identify the memory complaints most prone to raise concern from the patients and their families and bring them to clinical care . subjects with cognitive complaints older than 50 years referred for neuropsychological evaluation at the laboratory of language studies , santa maria hospital , and a memory clinic , both in lisbon . controls were volunteers older than 50 years attending a health itinerant unit that aims to screen and promote general health , a blood donor centre , a leisure centre for retired people , and a senior citizens college and university , all in the area of lisbon . presence of dementia ( criteria of the american psychiatric association , dsm - iv - tr ) , or mmse score below the education - adjusted cutoff , neurological disorders ( stroke , tumors , significant head trauma , and epilepsy ) , psychiatric conditions ( including major depression ) , or uncontrolled medical illness ( hypertension , metabolic , endocrine , toxic , and infectious diseases ) able to interfere with cognition , psychoactive medications with possible influence on cognition , chronic alcohol or drug abuse , sensory deficits likely to interfere with assessment , and nonnative portuguese speakers .
all participants gave their informed consent . a semi - structured interview recorded clinical information , present and past medical conditions , psychiatric and neurological history , medication , social and familial status . the mini - mental state examination ( mmse ; participants with mmse below education - adjusted values for the portuguese population were excluded ( < 23 for less than 11 years of education , participants were assessed with the subjective memory complaints scale ( smc ; [ 5 , 12 ] ) . they were required to answer 10 individual items concerning difficulties in daily - life memory tasks , with total scores ranging from 0 ( absence of complaints ) to 21 ( maximal complaints score ) . the smc was always applied at the end of the clinical interview . for the assessment of depressive symptoms the geriatric depression scale ( gds ; [ 13 , 14 ] ) was used . differences in the total smc scores among the different community settings were tested with one - way anova . comparison of demographic and neuropsychological data between the participants in the community and in the clinical setting was done using student 's t test on quantitative variables and the fisher 's exact test on the nominal variable . comparison of the smc items and the smc total score between participants in the community and in the clinical setting was performed with the mann - whitney u test . eta - squared values were calculated for the individual smc items to explain the total smc score with ancova , controlling for depression score and education years . the 95% confidence intervals for eta - squared values were obtained by nonparametric bootstrap sampling ( k = 1000 ) using the boot library in the r system software ( v. 12.2.1 , r development core team ) . eight - hundred and seventy - one nondemented subjects older than 50 years were included in the study , 581 recruited in the community , and 290 in the clinical setting . participants in the clinical setting were more educated , had slightly lower mmse scores , and presented more depressive symptoms than the participants in the community ( table 1 ) . all participants in the clinical setting had complaints at least in one smc item , and 20 ( 3.4% ) participants in the community reported no memory complaints ( total smc score = 0 ) . since no differences in the total smc scores were found among the different community settings ( health itinerant unit , blood donor centre , leisure centre for retired people , and senior citizens college and university ) , the results from community participants were pooled together . participants in the clinical setting had a higher total smc score [ 10.3 4.2 ( 121 ) ] than those in the community [ 5.1 3.0 ( 015 ) ] ( figure 1 ) , and this held true for almost all types of memory complaints ( table 2 ) . the only exception was the smc7 item , did you ever lose your way in neighbourhood ? few subjects reporting this difficulty , both in the clinical setting ( 4.8% ) and in the community ( 3.1% ) . analysing the weight of the different types of complaints to the global smc score in the two groups , we found that smc3 , do you ever forget names of family members or friends ? contributed to only 11% of the total score variance in the community sample , and as much as 18% of the total score variance in the clinical sample ( as shown in figure 2 , the 95% confidence intervals for the eta - squared values of smc3 are separated ) . this was the item that contributed most to the total smc score variance in the clinical group . in contrast , smc1 , which a general question about memory complaints , smc6 , do you ever have difficulties in finding particular words ? , and smc 8 , do you think more slowly than you used to ? elderly patients who seek for medical help in a memory clinic or hospital outpatient setting reported more prominent memory difficulties as compared to the subjects in the community . nevertheless , only 20 community participants reported to be completely free from memory difficulties ( i.e. , to say , had 0 in the smc total score ) . the participants in the clinical setting scored higher in almost all smc items , reflecting more problems in different types of memory complaints . the exception was item smc7 , about being lost in the neighbourhood , to which few participants answered positively , as found in previous studies . difficulties in spatial orientation in known places may well reflect the beginning of a dementing disorder like alzheimer 's disease . in a recent study , the complaining of difficulties on finding one 's way around familiar streets was highly associated with objective cognitive impairment . the hypothesis advanced in the present work , that some types of memory complaints would be selectively reported by nondemented elderly subjects in the clinical setting , as compared to the community , was confirmed . forgetting names of family members or friends contributed more strongly to the global subjective memory complaints in the clinical setting . this memory difficulty is probably perceived as particularly worrisome , or more likely to impact on close interpersonal relationships . it is interesting that it is not just the problem with names that is involved because subjects in the clinical setting did not report more difficulties in finding particular words ( item 6 ) . the trouble with such a trivial task as remembering proper names of close people appears particularly disturbing . it is interesting that the neuronal basis for processing familiar proper nouns is different from other names and quite widespread , involving both cerebral hemispheres . the perception of this type of memory complaint as worrisome is certainly justified since 20% percent of patients with early alzheimer 's disease report forgetting the names of relatives . factors other than the memory complaints themselves may of course influence whether elderly people seek for clinical help or not . the clinical participants were more educated , possibly with more awareness of the implications of memory problems and an easier access to clinical care . they also had more depressive symptoms , which could indeed drive their concern about memory problems . an association between depressive symptoms and reporting of memory complaints has been consistently found ( see , for instance , [ 18 , 19 ] ) . a recent study , comparing patients in a memory clinic and non - help - seekers , found that beliefs about memory , as well as the presence of a close relative with dementia , were associated with the decision to seek help . it must be recognized that in the present study the evaluation of memory complaints was based on a single scale , the subjective memory complaints scale . although this scale has items considered representative of common memory complaints , the results may not necessarily be generalizable to other instruments of memory complaints evaluation . in conclusion , the clinical diagnosis of mild cognitive impairment relies on the presence of memory complaints in subjects who seek for medical help . the present study suggests that both the global severity of memory complaints and the type of memory difficulties reported , particularly forgetting names of family members or friends , are associated with the clinical setting . further research should clarify the reasons why some elderly people seek for medical help , and others do not , since important consequences for the screening of early cognitive decline in the community may ensue . | diagnosis of mild cognitive impairment relies on the presence of memory complaints . however , memory complaints are very frequent in healthy people . the objective of this study was to determine the severity and type of memory difficulties presented by elderly patients who seek for clinical help , as compared to the memory difficulties reported by subjects in the community .
assessment of subjective memory complaints was done with the subjective memory complaints scale ( smc ) .
the mini - mental state examination was used for general cognitive evaluation and the geriatric depression scale for the assessment of depressive symptoms .
eight - hundred and seventy - one nondemented subjects older than 50 years were included .
participants in the clinical setting had a higher total smc score ( 10.3 4.2 ) than those in the community ( 5.1 3.0 ) .
item 3 of the smc , do you ever forget names of family members or friends ?
contributed significantly more to the variance of the total smc score in the clinical sample ( 18% ) as compared to the community sample ( 11% ) . forgetting names of family members or friends plays an important role in subjective memory complaints in the clinical setting .
this symptom is possibly perceived as particularly worrisome and likely drives people to seek for clinical help . |
a total of 100 dentate dental students of which 50 males and 50 females aged between 20 and 25 years were randomly selected as representative of the young adult group . the selected students had no restorations in the anterior teeth and had not received orthodontic treatment . the clinical research study was conducted after explaining the student subjects in their own language along with a signed written consent approved by the institutional ethical committee . an impression of each student 's maxillary dentition was made with irreversible hydrocolloid impression material of 50 male and 50 female subjects to obtain study casts poured with dental plaster . additional duplicated sectional study casts were obtained to aid in identification and classification of the palatal form . a standardized procedure was adopted to obtain digital photograph of the maxillary central incisors , the maxillary dental arch from the study casts [ figures 1 and 2 ] and the palatal contour from the duplicated sectional casts using nikon coolpix digital camera ( s3400 ; nikon corp . the photographs were then transferred to a computer ( windows pc , microsoft ) having image editing software ( photoshop 6.0 adobe , nikon corp . japan ) to obtain individual photographic tracing printouts of the tooth form , arch form and the palatal form for evaluation by visual method . frontal photograph of the maxillary incisor teeth occlusal photograph of the maxillary dental arch the tooth form was determined on the right maxillary central incisor tooth by an outline tracing made around the buccal surface of the tooth , which corresponded to the mesial and distal contours , the incisal edge and the cervical margin . the photographic printouts of the tracing had a diagram of perpendicular lines that was placed on the tooth form outline tracing [ figure 3 ] and the tooth in each quadrant was classified visually according to william 's as follows :
square incisor tooth - mesial and distal proximal surfaces are parallel for at least half of the cervicoincisal length of the crownovoid incisor tooth - mesial and distal proximal surfaces are biconvextapering incisor tooth - mesial and distal proximal surfaces converge from incisal to cervical . square incisor tooth - mesial and distal proximal surfaces are parallel for at least half of the cervicoincisal length of the crown ovoid incisor tooth - mesial and distal proximal surfaces are biconvex tapering incisor tooth - mesial and distal proximal surfaces converge from incisal to cervical . tracing printout of the maxillary incisor tooth form one of the three basic tooth forms ( square , ovoid or tapering ) was classified to a tooth only if that form predominated in at least 75% of the outline tracing print ( three quadrants ) . if one of the basic form predominated in at least 50% of the outline tracing print ( two quadrants ) , the tooth form should be classified as a combination tooth form . the arch form was determined on the maxillary arch by an outline tracing made around the arch corresponding to the incisal edges of the incisors , canine cusp tips , buccal cusps tips of premolars and molars . the photographic printouts [ figure 4 ] of the tracing were used to classify the arch form visually as square , ovoid or tapering . tracing printout of the maxillary arch form the palatal form was determined by a contour tracing made along the surface of the maxillary cast with a deep midpoint marked along the mid palatal suture that joins the palatal cusps of two selected premolar or molar teeth . the photographic printouts [ figure 5 ] of the tracing were used to classify the palatal form visually as u - shaped , v - shaped or shallow . tracing printout of the palatal form six prosthodontists with more than 5 years of experience classified the photographic outline tracings of the tooth , arch and palatal forms visually based on the instructions obtained before evaluation . the means of prosthodontists evaluation were considered and statistically analyzed using chi - square test for distribution differences and results were tabulated . the following results were tabulated : the combination tooth form 44% predominated in males followed by square 28% , ovoid 14% and tapering 14% tooth forms when compared with the ovoid tooth form 36% predominated in females , followed by combination 32% , square 24% and tapering 8% tooth forms [ table 1 ] . the = 6.759 was found to be not significant with a p = 0.080 . descriptive statistics for comparison of predominant maxillary central incisor tooth form in males and females of saudi population the ovoid arch form 42% predominated in males followed by tapering 36% and square 22% arch forms when compared with the square arch form 44% predominated in females followed by ovoid 40% and tapering 16% arch forms [ table 2 ] . descriptive statistics for comparison of predominant maxillary arch form in males and females of saudi population the u - shaped and v - shaped palatal forms 46% respectively predominated in males followed by shallow palatal form 8% when compared with the u - shaped palatal form 74% predominated in females followed by v - shaped 14% and shallow 12% palatal forms [ table 3 ] . the = 12.20 was found to be significant with a p = 0.002 . the size and form of the maxillary anterior teeth are important to not only dental , but also facial esthetics . the most influential factors contributing to a harmonious anterior dentition are the size , shape , and arrangement of the maxillary anterior teeth , particularly the maxillary central incisors as viewed from the front . according to the glossary of prosthodontics terms ( gpt 8) the outline form as viewed in any selected plane or / and other contours of an anterior tooth . in the present study , outline form of the maxillary right central incisor tooth was considered to classify according to williams method of classification of tooth forms into square , ovoid , tapering or combination tooth forms . the dentulous arch form of an individual will remain the same even after becoming an edentulous arch and that the edentulous arch remains fairly constant in the absence of surgical intervention . boucher is of the same opinion that the original form of the dental arch is maintained even after the removal of natural teeth . the arch form is defined according to gpt 8 as the geometric shape of the dental arch when viewed in the horizontal plane ( square , tapering , ovoid , etc . ) . in 1932 , chuck classified the arch forms as tapered , ovoid and square for the first time which can also be expressed as narrow , normal and wide respectively . in the present study , the maxillary arch form was classified as square , ovoid and tapering arch forms . the form of the palatal vault or depth of the hard palate gives an idea about the original form of the dental arch before removal of the natural teeth and resorption of the residual ridge . the palatal vault is defined according to gpt 8 as the deepest and most superior part of the palate or the curvature of the palate . the palatal vault is classified as low palate , medium palate and high / deep palate , which can also be expressed as shallow / flat palate , u - shaped palate and v - shaped palate respectively . in this study , the palatal form or palatal shape was classified as u - shaped , v - shaped or shallow palatal forms . the predominant tooth form for males in the present study was combination tooth form 44% followed by square 28% , ovoid 14% and tapering 14% tooth forms . the value was lesser when compared with the previous study being combination tooth form 58% , followed by square 22% , tapering 13% and ovoid 8% tooth forms . the predominant tooth form for females in the present study was ovoid tooth form 36% followed by combination 32% , square 24% and tapering 8% tooth forms . this was in correlation with the previous study being ovoid teeth for females but the value was higher and not in correlation when compared with the previous study being predominant combination tooth form 51% , followed by square 22% , ovoid 15% and tapering 12% tooth forms . the predominant arch form for males in the present study was ovoid arch form 42% followed by tapering 36% and square 22% arch forms . the value was lesser when compared with the previous study being ovoid arch form 66.7% followed by tapering 33.3% arch forms . the value was not in correlation when compared with the previous study being predominant narrow ( tapering ) arch form 13.5% followed by flat 10.5% , wide ( square ) 10.3% , pointed 8.3% and mid ( ovoid ) 7% arch forms . the value was lesser when compared with the previous study being ovoid arch form 55.1% , followed by tapering 54.2% and square 42% arch forms . the value was higher and not in correlation when compared with the previous study being predominant square arch form 35.33% , followed by ovoid 34.67% and tapering 30% arch forms . the predominant arch form for females in the present study was square arch form 44% , followed by ovoid 40% and tapering 16% arch forms . the value was lesser when compared with the previous study being square arch form 58% , followed by tapering 45.8% and ovoid 44.9% arch forms . the value was not in correlation when compared with the previous study being predominant narrow ( tapering ) arch form 17.4% , followed by wide ( square ) 13.6% , pointed 9.3% , flat 7.8% , and mid ( ovoid ) 2.3% arch forms . the value was higher when compared with the previous study being square arch form 36.67% followed by ovoid 33.33% and tapering 30% arch forms . the predominant palatal form for males in the present study was both u and v shaped palatal forms 46% respectively , followed by shallow 8% palatal form . this was in correlation with the previous study that the palatal depth is significantly higher in males . the predominant palatal form for females in the present study was u - shaped palatal form 74% followed by v - shaped 14% and shallow 12% palatal forms . this was in correlation with the previous study that the palatal depth significantly is not higher in females . the palatal form value in the present study for both males and females combined was higher and not in correlation when compared with the previous study based on qualitative method of palatal depth assessment being predominant low palate ( shallow ) 51.4% followed by medium palate ( u - shaped ) 43.2% and high palate ( v - shaped ) 5.4% palatal forms but the value was higher and in correlation when compared with quantitative method of palatal depth assessment being predominant medium palate ( u - shaped ) 55.4% followed by high palate ( v - shaped ) 39.2% and low palate ( shallow ) 5.4% palatal forms . within the limitations of the saudi population group studied , the following inferences may be drawn :
the predominant tooth form was combination tooth in males and ovoid tooth in femalesthe predominant arch form was ovoid arch in males and square arch in femalesthe predominant palatal form was both u and v shaped ( medium and deep palates ) in males , and only u - shaped ( medium palate ) in femalesexcept for the tooth form , there was a significant difference with arch and palatal form among males and females of the population group studied . the predominant tooth form was combination tooth in males and ovoid tooth in females the predominant arch form was ovoid arch in males and square arch in females the predominant palatal form was both u and v shaped ( medium and deep palates ) in males , and only u - shaped ( medium palate ) in females except for the tooth form , there was a significant difference with arch and palatal form among males and females of the population group studied . thus during selection and arrangement of artificial teeth for edentulous saudi patients , the dentist and the laboratory technician will require basic tooth forms ( square , ovoid and tapering ) along with combination tooth forms . individual patient 's preferences during the selection and arrangement of anterior teeth should also be considered to increase the success rate of fixed and removable dental prosthetic treatment . however | aims : to determine various tooth form , arch form , and palatal form with gender identification between males and females of the saudi population.materials and methods : irreversible hydrocolloid impressions were made of the maxillary teeth of 100 dentate male and female subjects to obtain study casts .
a standardized procedure was adopted to photograph the maxillary dental arches and the maxillary central incisors on the study casts taken from each subject .
the outline form of tooth , arch , and palatal form were determined using a standardized method .
the average of six prosthodontist 's evaluation was considered who classified the outline tracings visually .
the statistical analysis was performed using chi - square and results tabulated.results:the predominant tooth is combination form in males and ovoid form in females , the predominant arch is ovoid form in males and square form in females and the predominant palatal form are both u and v shaped in males and u - shaped in females.conclusion:except for the tooth form there was a significant difference with arch and palatal form among males and females of the population group studied .
the determined tooth , arch and palatal forms are useful in selection and arrangement of artificial teeth among saudi edentulous population group . generalizing from the study is questionable as the sample size is small .
further studies should be conducted in a larger sample to confirm the study results |
bronchogenic cysts are not uncommon in either children or adults . in children , they comprise approximately 6% of all mediastinal masses . their presentation can range from an asymptomatic incidental finding to sudden respiratory distress . video - assisted thoracoscopy was utilized to remove a bronchogenic cyst that was densely adherent to the adjacent esophagus in a child . the chest tube was removed on postoperative day 1 , and the patient was discharged on postoperative day 2 . an esophagogram obtained 2 weeks after surgery was normal , and the patient 's preoperative symptoms had not returned . bronchogenic cysts should be considered in the differential diagnoses for mediastinal masses at any age . given their benign nature . they may become symptomatic due to esophageal compression as they increase in size or from development of infection . we report the case of a 9-year - old female with a symptomatic bronchogenic cyst , undiagnosed since the age of 2 years , who underwent successful thoracoscopic excision . a 9-year - old girl was first seen at the age of 2 years for cough and fever in the emergency room . a chest x - ray was obtained at that time , which was interpreted as normal . nonetheless , the patient was diagnosed with pneumonia , given a prescription for antibiotics , and released . subsequent to this , she presented several more times each year with similar complaints and with identical posteroanterior ( pa ) chest x - ray findings , resulting in several hospital admissions . her examination revealed no abnormalities , and her laboratory work was within normal limits at the time of her presentation to the pediatric surgery service . repeat chest x - rays were obtained ( figure 1 ) as well as a computed tomography ( ct ) scan of the chest ( figure 2 ) . it revealed a well - circumscribed cyst in the right chest measuring approximately 3x4 cm directly adjacent to the esophagus in the midthoracic region . it was unilocular and homogenous and did not appear to communicate with the esophagus or any neural structures . given these findings , the diagnosis of either an esophageal duplication cyst or bronchogenic cyst was entertained . a thoracoscopic approach was utilized to evaluate and remove the mass ( figure 3 ) . the medial aspect of the cyst was intimately involved with the muscular wall of the esophagus for several centimeters . a harmonic scalpel was used to separate the cyst , which was filled with a white mucoid material , from the esophagus . a small portion of the cyst wall was left in place to avoid perforation of the esophagus . the chest tube drainage was negligible , and it was removed on postoperative day one . she was seen at follow - up 2 weeks after surgery where a normal barium esophagogram ( figure 4 ) was obtained , and her preoperative symptoms were completely resolved . bronchogenic cysts are embryological remnants that are isolated from the normal development of the foregut . on rare occasions they may be found incidentally on a radiographic study or once symptoms are produced as a result of compression or infection . if communication with the airways occurs , an air - fluid level is usually present . histologically , they are lined with ciliated columnar epithelium and can contain cartilage and bronchial glands . accepted treatment is excision because of concern about continued growth and subsequent compression of surrounding structures , the risk of infection , and the unlikely but reported possibility of malignant degeneration . bronchogenic cysts comprise approximately 6% of all mediastinal masses in children , while foregut cysts as a group account for 15% . traditionally , open thoracotomy has been the method by which these cysts have been removed . even with increasingly sophisticated radiographic and percutaneous techniques , an exact diagnosis is often uncertain , and the unequivocal diagnosis must be made surgically . thoracoscopy offers both a minimally invasive diagnostic modality and also a highly successful method of definitive therapy for patients with bronchogenic cysts . although many case reports exist regarding bronchogenic cysts and their minimally invasive treatments , reports of precious few series have been published regarding their thoracoscopic excision . in 1993 , hazelrigg published a series of seven bronchogenic cysts removed thoracoscopically with favorable results . martinod et al reported a series of 20 cases of bronchogenic cysts in adults , of which they successfully removed 13 thoracoscopically . their reasons for conversion were bleeding in 2 cases and dense adhesions to surrounding vital structures in 5 . in 5 cases , thoracoscopy was performed on 22 children , 15 of which were found to have bronchogeni ccysts . of these merry et al reported in their series of 8 foregut duplications 1 recurrence with incomplete excision 1 year after surgery . two other reports of recurrence have been reported , , but so have several reporting successful obliteration of the mucosal lining with good results . reported complications in these articles include the following : bronchial / tracheal laceration ( both repaired endoscopically ) , , recurrence , esophageal injury , pneumothorax , , vascular injury . bronchogenic cysts are not uncommon and , as this case illustrates , can be easily misdiagnosed . subtle findings , as on this patient 's chest x - ray taken at 2 years of age , are overlooked if one fails to consider cystic mediastinal masses in the differential diagnosis . we assert that thoracoscopy is a safe and effective method to deal with bronchogenic cysts and involves considerably less morbidity than thoracotomy does . as experience with thoracoscopy improves , so too will its acceptance as a superior alternative to thoracotomy in most cases of bronchogenic cysts . | background : bronchogenic cysts are not uncommon in either children or adults . in children , they comprise approximately 6% of all mediastinal masses .
their presentation can range from an asymptomatic incidental finding to sudden respiratory distress.case report : video - assisted thoracoscopy was utilized to remove a bronchogenic cyst that was densely adherent to the adjacent esophagus in a child .
this was accomplished with a harmonic scalpel .
the chest tube was removed on postoperative day 1 , and the patient was discharged on postoperative day 2 . an esophagogram obtained 2 weeks after surgery was normal , and the patient 's preoperative symptoms had not returned.conclusions:bronchogenic cysts should be considered in the differential diagnoses for mediastinal masses at any age .
given their benign nature , thoracoscopy offers an excellent alternative to open thoracotomy for their removal . |
early recognition of rupture - prone atherosclerotic lesions in patients with high - graded carotid artery stenosis is an important clinical issue to prevent ischemic stroke [ 15 ] . various pathophysiological mechanisms are responsible for the plaque progression and vulnerability such as degradation of extracellular matrix components especially by matrix metalloproteinases ( mmps ) , intensified inflammatory reaction , and neovascularisation [ 3 , 57 ] . thus , mmps and inflammatory factors might also serve as possible markers for patients with unstable high - graded carotid artery stenosis [ 2 , 816 ] . however , the data that have been achieved up to date are not consistent . some studies investigated patients with symptomatic versus asymptomatic carotid stenosis or patients with or without emboli [ 12 , 1417 ] . furthermore , only very few investigations evaluated the usefulness of multiple biomarkers to predict rupture - prone atherosclerotic lesions [ 2 , 17 , 20 , 21 ] . the aim of this work was the comparison of results of multiple analyses of various relevant biomarkers in patients with stable versus unstable carotid plaques and in individuals with or without neurological symptoms to evaluate whether multiple - score evaluation is superior to the analysis of single factors . the retrospective study consisted of 110 consecutive patients with high - grade carotid artery stenosis > 70% ( determined by ultrasound ) , intended for carotid endarterectomy ( cea ) . all patients underwent a detailed neurological examination by a neurologist , and the carotid plaques were analysed by means of histology to divide the study subjects into four groups : ( 1 ) asymptomatic patients with stable plaques ( n = 25 ) ; ( 2 ) asymptomatic patients with unstable plaques ( n = 36 ) ; ( 3 ) symptomatic patients with stable plaques ( n = 13 ) ; ( 4 ) symptomatic patients with unstable plaques ( n = 36 ) . the study was performed according to the guidelines of the world medical association declaration of helsinki . the excised carotid plaques were fixed in formalin , separated into segments of 3 - 4 mm , and embedded in paraffin . from each segment sections of 2 - 3 m were prepared and routinely stained with hematoxylin / eosin ( he ) and elastin van gieson ( evg ) to assess the morphological and histological features of each plaque . stained specimens were analysed by light microscopy from two independent and experienced investigators blinded for the study groups . in accordance with our own expertise and the study of rothwell and redgrave [ 18 , 19 ] , appropriate selection into stable or unstable plaques was performed . primary antibodies against following antigens were used : cd68 ( macrophages / monocytes ; dako ) , cd45 ( inflammatory infiltrates ; novocastra , uk ) , smooth muscle cell actin ( dako , hamburg , germany ) , and factor viii ( endothelial cells ; dako ) . mmps and timps were quantified in serum samples using elisa assays from r&d system ( quantikine human mmps and timps kit ; wiesbaden - nordenstadt , germany ) according to the manufacture 's protocols . the colour development was determined by multiplate reader mithras lb940 ( berthold technologies , bad herrenalb , germany ) at 450 nm with correction at 570 nm . inflammatory markers were analysed using cytometric bead array ( bd biosciences , san jose , ca , usa ) . fibrinogen activity was determined by the clauss method ( dade behring , schwalbach , germany ) . the hscrp ( high sensitivity crp ) was determined by elisa assay ( life diagnostics ; west chester , pa , usa . additional clinical blood parameters were measured in laboratories of our clinical chemistry . one - way anova test was applied for comparison between the groups . correlations between the single factors were quantified by spearman 's rank correlation coefficient . receiver operating characteristics ( roc ) analysis was applied to evaluate the optimal positive and negative predictive value of each prognostic marker and their combinations . delong and clarke - pearson approach was used to compare roc curves to provide the best statistical evidence . all statistical comparisons were performed two sided in sense of an exploratory data analysis using p < 0.05 , p < 0.01 , and p < 0.001 as level of significance . all groups were well matched , without any significant differences with regard to patient epidemiology , associated diseases , or medication . the average age of the study population was 69 years ( range 59 to 79 ) . the majority of patients had hypertension ( > 87% ) and about one - third suffered under accompanying coronary heart disease . all patients with the exception of one individual received asa or clopidogrel , and more than half of the study subjects were on statins . significant differences between the groups were observed only for mmp-1 , -7 , -9 , and timp-1 . ( p = 0.047 , 0.005 , 0.028 , and 0.044 , resp . ) . tendency was observed also for mmp-8 ; the difference was , however , not statistically significant . in many cases , increased level of various inflammatory factors was found in the group of symptomatic patients with unstable carotid plaques . however , again the values were not statistically different . regarding causal relationships between the individual factors analysed in our study , we performed correlation analysis between mmps , timps , and all the inflammatory factors tested in blood of the patient cohort ( table 3 ) . most correlations were found between individual mmps and timps : the levels of mmp-1 correlated significantly with mmp-7 and timp-1 ( p < 0.001 and p < 0.05 , resp . ) , mmp-2 with timp-2 ( p < 0.001 ) , mm-3 with mmp-7 ( p < 0.05 ) , mmp-7 with timp-1 ( p < 0.001 ) , mmp-8 with mmp-9 and timp-1 ( p < 0.001 and p < 0.05 , resp . ) , and timp-1 with timp-2 ( p < 0.001 ) . furthermore , significant correlations were observed between some inflammatory factors and mmps : il-1 correlated with mmp-9 ( p < 0.05 ) , il-6 with mmp-7 and -8 ( p < 0.001 and p < 0.01 , resp . ) , and il-12 with mmp-2 ( p < 0.01 ) ; the amount of leukocytes was related to mmp-8 and -9 ( p < 0.01 and p < 0.001 , resp . ) and fibrinogen to mmp-7 , -8 , and -9 ( p < 0.05 and p < 0.001 , resp . ) . to evaluate whether the individual factors and their appropriate combination in blood of the study patients can be associated with carotid plaque instability or neurological symptoms , roc curve was designed accordingly . furthermore , multiple analysis was performed to assess the validity of biomarkers to further improve the predictability . in accordance with the above - described analyses between the study groups , only factors with significant differences were involved in the roc curve analysis : mmp-1 , -7 , -9 , and timp-1 . the area under curve ( auc ) and the predictive values are summarised in table 4 . the cutoffs were selected by using delong and clarke - pearson approach to provide the best statistical evidence . all patients with biomarker values higher than the ascertained cutoff points were considered as individuals with neurological symptoms or as patients with unstable plaques . furthermore , multiple roc analysis was performed for all possible combinations of the above - described biomarkers . regarding neurological symptoms , the positive predictive value ( ppv ) was quite low with around 50% for the single factors and increased over 60% by their appropriate combination . in contrast , the negative predictive value ( npv ) was significantly higher with curtly under 70% for the individual biomarkers and achieving up to 80% for the factor grouping . with regard to the maximal ppv , combination of mmp-7 and timp-1 achieved the highest value of 65.1% . on the contrary to the neurological symptoms , ppv for patients with vulnerable plaques was markedly higher with 7679% for the single factor analysis . their grouping led to an increase for up to 86.4% using combined analysis with mmp-1 , -7 , and -9 . biomarkers for prevention of stroke are promising diagnostic tool in medical praxis . due to the heterogeneity of the atherosclerotic lesions , however , single marker will never be sufficient for reliable prediction of patients at increased risk of stroke . furthermore , the values of the biomarkers and the cutoff value at risk can markedly alternate between the individual patients . so far only few studies have evaluated the usefulness of multiple biomarkers and their overall association with neurological symptoms or plaque vulnerability , especially concerning unstable carotid lesions . from the various mmps , their inhibitors , and the inflammatory factors analysed in this study , serum levels of mmp-1 , -7 , -9 , and timp-1 all these factors were already described being involved in the degradation of extracellular matrix [ 5 , 7 , 10 , 11 , 24 , 25 ] . thus , they could reliably reflect unstable carotid plaques in patients at risk of stroke . interestingly , different biomarkers can be related either to neurological symptoms or to plaque instability [ 2 , 17 ] . this is an important issue , because many researchers often equate neurological symptoms with plaque vulnerability . only 1520% of all ischemic strokes account for atherosclerotic carotid stenosis [ 5 , 26 ] . therefore , prevention of stroke on the basis of biomarker evaluation in the blood of the concerned patients should be related to plaque vulnerability . this is the reason for the discrepancy between the individual biomarker in our study related either to neurological symptoms or carotid plaque stability . from our point of view , the markers that show significant differences between patients with stable versus unstable plaques are of higher value compared to biomarkers corresponding with symptoms . this was also the reason why we have combined neurological symptoms and plaque vulnerability together . in contrast , mmp-9 seemed to be related mainly to the neurological symptoms ( table 2 ) . regarding inflammatory factors , increased levels of tnf- and il-6 were associated with plaque instability , il-10 only in the group of symptomatic patients with unstable plaques . high sensitive crp appeared to be more related to neurological symptoms than to plaque instability and fibrinogen for both . again , these data confirm the pathophysiological differences between patient symptomatic and plaque vulnerability [ 2 , 17 ] . nevertheless , our data demonstrated that whether the symptoms are caused by unstable carotid plaques or atherosclerotic changes in other vessels can also have common features that can be reflected in the blood of patients at risk of stroke . this assumption was further confirmed by the correlation analysis of the individual factors ( table 3 ) . interestingly , independent of neurological symptom or plaque instability , no statistically significant differences between patients with stable and unstable lesions were observed for mmp-2 as described in some former studies [ 1315 ] . the reason for these discrepancies is that we have characterised the plaques in accordance with redgrave and rothwell [ 18 , 19 ] , looking effectively for the true unstable plaques . in contrast , the early studies graded the plaques according to aha classification , assuming atherosclerotic lesion type v as stable , type vi as unstable . but patients with carotid lesions of type vi ( plaques with thrombotic deposits and haemorrhage ) with thick fibrous cap can still be considered as stable . and plaques of type v with thin fibrous cup under 200 m over a large necrotic core can be considered as unstable . regarding inflammatory factors , no significant differences were observed between the groups , even if some tendencies have been observed , especially for tnf- , il-6 , il-10 , crp , and fibrinogen . however , it is to consider that our patients had already an advanced stage of carotid artery stenosis > 70% and almost all of them were hypertensive . so , the level of many of the inflammatory factors in blood of our patients was already increased , compared to healthy individuals . so , inflammatory factors may correlate with advanced carotid stenosis , are , however , not specific enough to detect vulnerable plaques [ 25 , 27 ] . the main goal of the study was to evaluate whether combination of relevant biomarkers of advanced carotid lesions might be better associated with neurological symptoms or plaque vulnerability compared with single biomarkers . interestingly , high positive prediction could be associated with plaque vulnerability for up to 86% compared to only 65% regarding patient symptomatic . in contrast , negative prediction was high for the clinical symptoms with up to 80% , but the factor grouping did not significantly improve the npv for patients with unstable plaques , which was in the most cases between 50 and 60% , considering patients incorrectly as individuals at risk . so , if the level of one of them is increased , the others are increased as well ( see also table 3 ) . the combination of such biomarkers , however , does not necessarily lead to an increased predictivity over the analysis of single factors . to establish a set of relevant biomarkers for more reliable diagnosis of stroke , independent markers are necessary to improve the overall sensitivity and especially specificity . still , our data demonstrate that the use of more than one biomarker better correlates with the clinical findings and seems therefore to be superior to the analysis of single factors . these results further confirm our assumption that multivariate analyses of relevant biomarkers are necessary to reduce the risk of inaccurate diagnosis . in summary , we evaluated various predictive biomarkers and their combinations in patients with advanced carotid stenosis in order to improve the concordance with clinical findings such as neurological symptoms or / and unstable plaques . further experiments , especially large prospective clinical studies , are necessary to evaluate the relevance of such biomarkers . in addition , the proper cutoff values have to be accurately interpreted and carefully reevaluated before they can be used in clinical praxis for , for example , reliable prevention of patients at increased risk of stroke . | early recognition of vulnerable patients is an important issue for stroke prevention . in our study ,
a multiscore analysis of various biomarkers was performed to evaluate its superiority over the analysis of single factors .
study subjects ( n = 110 ) were divided into four groups : asymptomatic patients with stable ( n = 25 ) and unstable ( n = 36 ) plaques and symptomatic patients with stable ( n = 13 ) and unstable ( n = 36 ) plaques .
serum levels of mmp-1 , -2 , -3 , -7 , -8 , -9 , timp-1 , -2 , tnf- , il-1b , and il-6 , -8 , -10 , -12 were measured .
multi - score analysis was performed using multiple receiver operating characteristics ( roc ) and determination of appropriate cutoff values .
significant differences between the groups were observed for mmp-1 , -7 , -9 and timp-1 in serum of the study subjects ( p < 0.05 ) .
multiple biomarker analysis led to a significant increase in the auc ( area under curve ) . in case of plaque instability
, positive predictive value ( ppv ) for up to 86.4% could be correctly associated with vulnerable plaques .
thus , multiscore analysis might be preferable than the use of single biomarkers . |
knowledge of the anatomical variations of the axillary region has become more relevant with increasing surgeries of this region for breast cancer , reconstruction procedures and axillary by - pass . lager 's arch or the axillary arch ( aa ) is the best - known variant structure in the axilla . it is a muscular or fibromuscular slip of varying dimensions , extending from the latissimus dorsi ( ld ) muscle about the middle of the posterior axillary fold , and crosses over the neurovascular structures , to join the under surface of the tendon of the pectoralis major , the coracobrachialis , or the fascia over the bicepsbrachii [ 1 , 2 ] . a 60-year - old female presented to our breast clinic with a left breast lump sized 3 2.5 cm incidentally felt since 3 months . it was gradually increasing in size and was not associated with any other breast complaints . she was evaluated with mammography that suggested a birads 3 lesion at 12 oclock position . subsequently , her metastatic work - up included abdominal pelvic ultrasound , chest computed tomography and bone scan . intra - operatively , during the axillary lymph node dissection , we encountered an unusual muscle slip crossing the axilla from the ld muscle to the posterior surface of the pectoralis major muscle anterior to the axillary vein . all neurovascular structures and lymphoid tissue were lying posterior to this abnormal muscle ( fig . 1 ) . figure 1:aa muscle extending from ld muscle to under surface of pectoralis major tendon in the left axilla crossing over axillary neurovascular structures ( in view ) . aa , axillary arch ; pm , pectoralis major ; ld , latissimus dorsi muscle ; av , axillary vein ; tnb , thoracodorsal neurovascular bundle ; ltn , long thoracic nerve . aa muscle extending from ld muscle to under surface of pectoralis major tendon in the left axilla crossing over axillary neurovascular structures ( in view ) . aa , axillary arch ; pm , pectoralis major ; ld , latissimus dorsi muscle ; av , axillary vein ; tnb , thoracodorsal neurovascular bundle ; ltn , long thoracic nerve . the lymph nodes lateral and beneath the arch were successfully dissected , and the arch itself was left undisturbed . the procedure was uneventful , and the patient had a good post - operative recovery . on follow - up , 21 months after surgery , the patient was alive and free of known disease . however , it was karl langer in 1846 who gave a more accurate description of this variant , so thereafter , it was named after him [ 24 ] . throughout the literature , several terms have been used to describe the muscular variant running from the ld muscle towards the pectoralis major muscle : aa muscle , axillopectoral muscle and also their translations in different languages . in the following text , the anatomical description of the aa is variable among authors . according to testu 's classification ( 1884 ) , the complete aa extended between the ld and the tendon of the pectoralis major near its insertion on the humerus ; the incomplete one extended from the ld to the axillary fascia , biceps brachii muscle , coracobrachialis muscle , the distal end of the bicipital groove and the inferior edge of pectoralis minor muscle or coracoid process . the case we encountered was of unilateral complete aa . according to many anatomic texts , however , it has been recognized in only 0.25% during axillary surgical procedures [ 1 , 2 , 4 , 5 ] . the difference in surgical and anatomical incidence reflects a failure of reporting or identification during surgery . also , this discrepancy may be attributed to the specific aim of cadaveric studies to identify such anatomic anomalies . this should be kept in mind as it can be confused with axillary lymphadenopathy or soft tissue tumour [ 1 , 3 ] . aa can act as entrapment site for the neurovascular bundle during some arm movements causing circulatory deficiency , chronic pain and paraesthesia . simple division of the arch is curative in such cases [ 2 , 5 ] . jelev , through his extensive work , introduced a new definition of clinical aa as a variant muscular structure in the axilla that is a possible entrapment site for the nerves and vessels . , the existence of a superficial or deep aa could be suspected according to the vessels or nerves mostly affected . it can positively correlate its presence with neurovascular entrapment symptoms . also , it can assess its anatomic relations [ 1 , 5 ] . the surgical significance of the aa is 2-fold : ( i ) it may hide some axillary nodes , and ( ii ) it may mislead the dissection into a supra axillary plane . a group of lateral axillary nodes may be concealed under the aa while crossing over the axillary vein . missing these nodes during axillary node dissection imposes a risk for local recurrence in patients with breast cancer and melanoma . this also can lead to inaccurate staging , which in turn could negatively affect adjuvant and systemic therapy decisions for breast cancer . this may lead the surgeon to dissect in a plane above the axillary vein increasing the risk of injury to the axillary artery and brachial plexus . during sentinel node biopsy , the aa can pose difficulty as it stretches in the hyper abducted position shifting the nodes higher . in order to clearly identify , the anatomic landmarks the arch can be divided at the level of the axillary vein . furthermore , some authors suggest division of the arch in all cases to prevent possible post - operative axillary vein compression and associated lymphoedema [ 3 , 4 ] . in our case , there was no added morbidity related to dissection of nodes beneath and lateral to the arch . the presence of the aa may precipitate lymphoedema in cases where ld myocutaneous flap is used for breast reconstruction . for this reason , the aa should be divided if there is a possibility of a ld flap being required in the future . as in our case , most reported clinical cases describing the aa have been identified during axillary surgical procedures [ 2 , 4 ] . it can cause confusion during routine axillary surgery for breast cancer , which can both affect procedure safety and misguide further treatment decisions [ 3 , 4 ] . | langer 's arch is the best - known anatomic variant of definite surgical implication in the region of the axilla .
this rare anomaly is a muscular slip extending from the latissimus dorsi ( ld ) muscle to the tendons , muscles or fasciae around the superior part of the humerus . in this report
, we present a rare case of left axillary arch . during modified radical mastectomy for breast cancer , we encountered an abnormal muscle slip crossing the axilla from the ld muscle to the posterior surface of the pectoralis major muscle anterior to the neurovascular structures .
preoperative knowledge is essential to identify such unusual anomaly and avoid potential complications both intra- and postoperatively . |
a 63-year - old woman presented with sudden onset vertigo and was diagnosed with an acute infarction in the left cerebellum on october 17 , 2015 . on the brain magnetic resonance imaging ( mri ) , an acute infarction was observed in the territory of the left superior cerebellar artery ( sca ) ( fig . magnetic resonance angiography showed a mild irregularity in both proximal vas and an occlusion in the left sca ( fig . the sca was completely recanalized , and there was no definite abnormality in both vas . incidentally , we observed an unopacified streaming at the level of c5 during the selective catheter angiography of the left va originated from the left subclavian artery ( fig . the medial limb of the left va arising from the aortic arch could be found on the selective catheter angiography , which was not observed on the mra . the dominant , lateral limb of the left va was originated from the left subclavian artery ( fig . 2a , b ) and the small , medial limb was originated directly from the aortic arch between the left common carotid artery and the left subclavian artery ( fig . a right - to - left shunt was suspected on the transcranial doppler using an agitated saline solution with blood . a pulmonary arteriovenous malformation ( avm ) in the right lung was detected by transesophageal echocardiography and chest computed tomography . with an elevated level of d - dimer with 421 ng / ml , the pulmonary avm was suspected as a source of embolus causing an acute cerebellar infarction . the left va arising from the aortic arch is the third most common pattern of aortic arch branching with an incidence of 2.4 - 5.8% . however , the duplicated origin of the va is quite rare and the majority cases were found incidentally . we reported a patient with duplicated origin of the left va , and it could be suspected when an unopacified streaming was observed during the selective catheter angiography of the dominant va limb arising from left subclavian artery . it could be potentially misdiagnosed as an arterial dissection , if the possibility of duplicated origin of the va was not considered . in a previous literature , 26 cases with duplicated origin of the va were reported before 1998 and have been summarized in detail . since 1998 , we found 15 additional cases with duplicated origin of the va , including three patients with bilateral duplicated origin of vas ( table 1 ) . overall , 24 patients had a duplicated origin of the left va , including our case , and 21 patients had a duplicated origin of the right va . among them , three patients had a bilateral duplicated origin of vas . the medial limb directly from the aorta and the lateral limb from the subclavian artery was the most common pattern of the duplicated left va ( 21 of 24 , 87.5% ) . two patients had origins of both limbs in the subclavian arteries . and only one patient had origins of both limbs in the aortic arch . contrast to the left side , the duplicated limbs arising from the ipsilateral subclavian artery was the most common pattern in the right side ( 18 of 21 , 85.7% ) . and there was no available data about the origins of the duplicated va in one patient . embryologically , the va is formed by the longitudinal anastomoses between the cervical intersegmental arteries . and the connections of the intersegmental arteries to the dorsal aorta eventually regress , except the seventh intersegmental artery , which develops into the proximal subclavian artery containing an origin of the va . the left va originated from the left subclavian artery and enters the sixth transverse foramen . the variation of an aortic origin of the left va results from degeneration of the connection with the seventh intersegmental artery and a persistence of a higher intersegmental artery . in this situation , the va commonly enters the f ifth transverse foramen . likewise , persistence of the left fourth or fifth cervical intersegmental arteries and the normal origin from the seventh intersegmental artery result in a duplicated origin of the left va ( fig . the left fourth or fifth intersegmental arteries originate from the aorta between the left common carotid artery and left subclavian artery . in contrast to the left side , duplicated origins of the right va are usually arising from the right subclavian or brachiocephalic artery when the fourth or fifth cervical intersegmental artery is persistent . first , the right seventh cervical intersegmental artery is originated from the descending aorta distal to the left subclavian artery . second , the right fourth or fifth cervical intersegmental artery is originated from the ascending aorta , and the right subclavian artery is originated from the descending aorta distal to the left subclavian artery . the majority of previous cases and our case had no clinical implication from the duplicated origin of the va , although it has been suggested that the duplicated origin of the va might be a predisposing factor for certain cerebrovascular pathologies , such as aneurysm or dissection . to take hypothetical example , it could be the other route for an interventional procedure for the posterior circulation or the potential collateral channel in case of a proximal , extracranial va occlusion . for all that the duplicated origin of the va may have in the clinical implication mentioned above , there should be more evidence supporting the hypothesis that the rare variation of the va could be related to a pathologic condition or therapeutic intervention . in conclusion , the duplicated origin of the va is rare , but then it is a good example to explain the embryological development of the va . while it could be a false negative on the contrast enhanced mra , we could incidentally find the duplicated origin of the left va on selective catheter angiography by recognizing the unopacifed streaming in the original path of the va . | the duplicated origin of vertebral artery ( va ) is a very rare condition .
it could be easily misdiagnosed as an arterial dissection on selective catheter angiography , especially in a patient with acute cerebellar infarction of unknown etiology .
we report a patient with an acute cerebellar infarction and duplicated origin of the left va , which was found during the selective catheter angiography . |
the potential of comparative effectiveness research ( cer ) for dealing with practical clinical questions , enhancing the quality and effectiveness of care , and personalizing evidence - based care , is clear.1 yet cer strains the current clinical research paradigm because of its emphasis on assessing effectiveness in typical care delivery settings , its requirement for very large study populations to study effectiveness heterogeneity , and , often , its need for treatments to be allocated by randomization . in july 2012 , the patient - centered outcomes research institute ( pcori ) convened a national multi - stakeholder workshop to advance the use of electronic health data in cer.2 building on research networks that include among others , the hmo research network , the agency for healthcare research and quality ( ahrq ) american recovery and reinvestment act ( arra ) investments in data networks , the us centers for disease prevention and control ( cdc ) vaccine safety data link , the food and drug administration 's ( fda ) mini - sentinel , the national institutes of health ( nih ) health care systems research collaboratory , two components of a national research infrastructure emerged.38 these comprise clinical data research networks ( cdrns ) based on the electronic health records and other electronic sources of very large populations receiving healthcare within integrated or networked delivery systems9 and patient - powered research networks ( pprns ) built by communities of motivated patients , forming partnerships with researchers.10 cdrn and pprn brief communications included in this special focus issue provide further information about these networks . in december 2013 , pcori 's board of governors funded 11 cdrns and 18 pprns for a period of 18 months starting in march 2014 that together form pcornet ( http://www.pcornet.org ) . each cdrn is committed to building a large patient cohort with comprehensive , longitudinal electronic clinical data ; developing policies for data standardization , shared governance , efficient use of clinical information for multicenter studies , stringent attention to data security and patient privacy , and robust , scalable centralized research support tools ; and building the capacity to participate successfully in multi - network randomized trials and observational studies . each cdrn is a collaboration of health systems that include among others academic health centers , community hospitals , health plans , inpatient and outpatient hospitals and providers , federally qualified health centers , veterans administration clinics , pediatric hospitals and providers , integrated delivery systems , private electronic health record companies , and a regional health information exchange ( table 1 ) . clinical data research networks each pprn consists of patients , caregivers , or families , who are linked by the experience of a shared condition ( table 2 ) . an important commitment of these patient - based networks is to collect and curate data from at least 80% of their membership . the pprns are also expected to expand the number of patients in their network ; to collect standardized patient data ; and , when necessary , for the purposes of research , engage patients to participate in interventional research and in building , using , and governing their networks . the organizational set - up of pprns is diverse , as exemplified by the number of different partnership models that link patient foundations and associations with academic research centers . the cdrns and pprns are geographically diverse , with patients in 50 states ( figure 1 ) . patient powered research networks map of clinical data research networks ( cdrn ) and patient - powered research networks ( pprn ) across the usa . a coordinating center co - led by the harvard pilgrim health care institute and duke university ( contract awarded in september 2013 ) provides technical and logistical expertise and assistance to awardees . it has established 11 task forces ( figure 2 ) , whose members are nominated from the cdrns and pprns and whose role is to develop policies , operations , and products to support the development of pcornet . a steering committee , subject to the oversight of pcori , guides members of pcornet and advises pcori leadership ( figure 2 ) . final approval of all policies , activities , and recommendations resides with the pcori leadership . ahrq , agency for healthcare research and quality ; aspe , assistant secretary for planning and evaluation ; cdc , us centers for disease prevention and control ; cms , centers for medicare and medicaid services ; fda , food and drug administration ; nih , national institutes of health ; onc , office of the national coordinator for health information technology ; pcori , patient - centered outcomes research institute . pcornet is being developed as a distributed research network ( drn ) that facilitates multi - site , observational and interventional research across the cdrns , pprns , and other interested contributors , while minimizing the transfer of individual - level clinical data outside of the system where care is received . pcornet 's unique vision is to create a network that supports the cdrn and pprn internal network development while creating a mechanism to facilitate research across these networks . advantages of conducting research across multiple networks of pcornet comprise greater sample size and power , the ability to study effects of practice pattern and treatment variation , the inclusion of diverse populations , and the possibility of supporting analyses that assess heterogeneity of treatment effect . the distributed network will enable research studies to be conducted , while allowing each participating organization to maintain physical and operational control over their data . this structure lowers institutional barriers to participation and ensures availability of local experts who can interpret the data.11
12 the data standards , security and network infrastructure ( dssni ) task force will identify minimal data standards and technical specifications for data standardization across cdrns and pprns and develop an approach to cross - network querying that meets the security , patient privacy , institutional confidentiality , and governance needs of the network participants.13 the distributed querying approach allows simple and complex analyses to be executed behind institutional firewalls , thereby eliminating or minimizing the release of protected health information . instead , only the minimum information needed to answer a specific question is transferred to the person making a request . increasingly , even complex multi - site analyses can be accomplished without transfer of private health information by use of privacy preserving regression techniques.14
15 as part of their pcornet participation , each cdrn will develop an analyzable research dataset ( to be specified by the dssni task force ) that supports complex distributed analyses . after 18 months , this dataset should contain data on one million patients and the cdrn will be able to regularly complete queries against the dataset using the secure pcornet drn tools . an example of the type of observational studies that might be supported by the drn is a comparison of the outcomes of ischemic and hemorrhagic stroke in adults with atrial fibrillation who are new users of dabigatran or warfarin.16 the pcornet drn tools will be developed by input from the relevant task forces , including dssni , governance , and data privacy during the first 18-month phase of funding ( starting march 2014 ) . the dssni task force will develop a pcornet common data model ( cdm ) to support the development of analyzable research datasets that will permit efficient distributed analyses . the pprns aim in 18 months to have the ability to build a standardized clinical database with relevant clinical and patient - reported outcomes data from at least 80% of their membership . overall , implementation of the pcornet drn networking and querying capabilities will prioritize rapid development , testing , use , and feedback learning cycles . this process will enable experimentation in networking approaches , demonstrate approaches to secure network operations , and identify potential barriers as early as possible . over the 18-month funding phase , each cdrn and pprn will develop effective patient - engagement strategies at the level of their networks . these strategies will involve ensuring that patients have a central role in collecting data for the generation of new knowledge for patients with their condition , as well as in participating in the governance of the network , prioritizing research questions , and disseminating results.10 at the cdrn level , patient engagement strategies require developing approaches to inform patients who are members of the systems of the existence and function of the research network , to involve patients in generating research questions , and in including patients in the governance associated with the development and uses of the network.9 rapidly building a new national resource to facilitate large - scale , patient - centered cer will face a number of technical , regulatory , and organizational challenges . technical challenges , first , include successfully completing the capture of relevant longitudinal clinical data , a requirement for all cer studies . since most electronic health record systems typically do not have information on care provided outside their health system , both cdrns and pprns will need to explore approaches to dealing with this problem.17 second , in order to achieve multi - institutional querying , pcornet will have to deal with data harmonization.18 this will require understanding the context in which the data were collected , the various clinical and other terminologies in use , and changes in local systems and national standards ( such as those associated with the centers for medicare and medicaid 's meaningful use regulation ) that affect the data . this should be done without requiring a change in the way the routine medical care data are collected , and will require data harmonization.19
20 pcornet has chosen to develop a cdm , derived from the mini - sentinel cdm to enable efficient cross - networking querying.21 third , the collection , harmonization , and use of a wide range of potential patient - reported data ( eg , personal and family medical histories , use of remote monitoring devices , etc ) for research is a nascent field,22 yet promises to empower patients to provide data that more fully describe their experience of , and preferences for , the treatment and management of their condition . in the absence of a standardized ontology or lexicon for a large number of these data elements , the ability to routinely include this information in analyzable research datasets will be explored in this first phase of pcornet 's development but will probably occur fully in later phases . in addition to technical challenges , pcornet will need to examine ethical and regulatory oversight . many patients , advocates , and researchers describe the research oversight system as cumbersome , inefficient , and expensive.2325 pcornet will need to deal with problems associated with the design of appropriate clinical studies , informing prospective participants , and obtaining permissions in a manner that protects human rights while supporting the acknowledged need for more research to provide patients and clinical decision - makers with more reliable evidence.26 areas of interest that pcornet will explore through its task forces include central institutional review boards or internet - facilitated shared review systems , and , centralized support for enrolling subjects and obtaining their consent . because of the scale and complexity of the types of research envisaged , pcornet will be challenged to develop streamlined approaches to the structure and function of the network and its projects while maintaining sound ethics and regulatory compliance . pcornet will be faced with the organizational challenges associated with the rapid development of a national resource with a heterogeneous group of cdrns and pprns of varying size , populations served , health systems included and many other characteristics . although this diversity among awardees was both predictable and desirable , one area in which the diversity of networks was quickly apparent was the divergent approaches used for data management . nevertheless , each cdrn and pprn will be challenged with balancing the demands of their local networks , research cultures , and areas of particular expertise with the requirements of participating in a national research resource . this will require them to agree rapidly on a common approach to data interoperability and to the conduct of joint analyses . pcornet 's success and long - term sustainability will also depend on communicating with health system leaders and providing them with evidence of the benefits of conducting high - quality , efficient research as part of the routine delivery of care . securing the commitment of delivery systems leaders , health system administrators , and clinicians will require considerable strategy and effort by all pcornet stakeholders . finally , and importantly , pcornet is committed to supporting patient engagement across the networks and will need to deal with the challenges of successfully supporting a variety of governance structures that fully ensure that patients are involved in setting policies for pcornet and for their own networks , determining strategic direction , and prioritizing research questions.27 the pcornet drn will be open to external data and research affiliates willing to participate in research studies alongside the pcori - funded cdrns and pprns . of particular note , pcornet 's distributed networking platform is shared by the fda mini - sentinel program , the nih health care systems research collaboratory and other networks such as the hmo research network.3
6
7 any organization that is part of these networks can make itself visible to the others and choose to receive queries from any of them . pcori 's vision is for the pcornet drn to be available for use by researchers not directly affiliated with pcornet cdrns and pprns through collaborative arrangements . the proposed governance models and mechanisms for these types of collaboration will be developed during the initial 18-month funding phase , which started in march 2014 . the first phase of building pcornet will span 18 months . at the end of this time , we hope that a functional research network that can support both observational and interventional research will have emerged . we also expect a new model for efficiency and affordability in clinical research , made possible both by investments in , and use of , this evolving data infrastructure , and the involvement of host healthcare systems , clinicians , and patients together with researchers . although pcornet will need to continue to grow and improve its data resources and capabilities , a measure of success will be the willingness of external research funders , both public and private , to fund research studies using pcornet . | the patient - centered outcomes research institute ( pcori ) has launched pcornet , a major initiative to support an effective , sustainable national research infrastructure that will advance the use of electronic health data in comparative effectiveness research ( cer ) and other types of research . in december 2013 ,
pcori 's board of governors funded 11 clinical data research networks ( cdrns ) and 18 patient - powered research networks ( pprns ) for a period of 18 months .
cdrns are based on the electronic health records and other electronic sources of very large populations receiving healthcare within integrated or networked delivery systems .
pprns are built primarily by communities of motivated patients , forming partnerships with researchers .
these patients intend to participate in clinical research , by generating questions , sharing data , volunteering for interventional trials , and interpreting and disseminating results . rapidly building a new national resource to facilitate a large - scale
, patient - centered cer is associated with a number of technical , regulatory , and organizational challenges , which are described here . |
appendiceal neuroendocrine tumours ( nets ) are the commonest tumours of the appendix and may be found in 0.30.9% of all appendicectomy samples . about 6% of these share mixed histologic features of bot mucinous glandular and neuroendocrine differentiation and other names have been used in the literature for this type of tumour , such as adenocarcinoid , mucinous carcinoid , crypt cell carcinoma , and mucin - producing net . the tumour is thought to arise from pluripotent intestinal epithelial crypt - base stem cells . the term goblet cell carcinoid was first coined in 1974 by subbuswamy et al . and is still accepted by the current who classification . the median age of presentation is in the 5th decade with a second peak in the 7th decade without any sex predilection . patients with gccs are usually diagnosed incidentally following a surgical presentation ( e.g. appendicitis , bowel obstruction / perforation or abdominal pain ) [ 5 , 6 ] . there is only one published report of lung metastasis to date , but it was retrospectively considered as an adenocarcinoma rather than a gcc . it was previously considered unusual to have lung metastases ; however , the general literature on gcc is small . here , we present the first histologically proven lung metastasis from a typical gcc . a 44-year - old woman with a long - standing history of lower abdominal pain was initially referred to the gynaecology department for an ultrasonography of the abdomen / pelvis arranged by her local practitioner . levels of serum ca 125 and ca 19 - 9 were raised at that time and the patient underwent a bilateral oophorectomy and salpingectomy . histology showed both ovaries massively infiltrated by mucin - positive tumour nests admixed with scattered synaptophysin-/chromogranin - positive neuroendocrine cells . the proliferation fraction with mib1 immunostain was < 5% . these features were interpreted as metastasis from a primary appendiceal gcc . on the basis of these findings , the patient was referred to our neuroendocrine tumour unit where the possibility of further surgery ( appendicectomy and right hemicolectomy ) was discussed . at the time of referral , the patient had fully recovered from her recent surgery and was asymptomatic . in order to assess the disease status , we arranged for the patient to have a triple phase contrast ct of the chest , abdomen , and pelvis as well as functional imaging including indium-111 pentetreotide scinitigraphy ( octreoscan ) and fdg - pet . the ct scan demonstrated a malignant - looking right lung hilar lesion which measured 4.0 1.8 cm ( fig . 1 ) and also multiple intra - abdominal lymph nodes measuring up to 1 cm . fdg - pet demonstrated low - to - moderate avidity in the noted hilar lesion and there was no fdg uptake elsewhere ( fig . 2 ) . serum chromogranin a was normal , whilst the serum levels of ca 19 - 9 and ca 125 were elevated at 4,405 iu / ml ( normal : 037 iu / ml ) and 205 iu / ml ( normal : < 30 iu / ml ) , respectively . the possibility of a separate lung pathology was considered and the lung lesion was biopsied bronchoscopically . 3 ) and similar features to those of the ovarian metastases . following discussion in the multidisciplinary team meeting , a decision not to undergo further surgical intervention was taken and the patient was referred to the oncology team for systemic chemotherapy . a pretherapy contrast ct showed interlobular interstitial / septal thickening within the right lung ( fig . systemic chemotherapy was initiated with a combination of folinic acid , 5-fluorouracil , and oxaliplatin ( folfox ) . the patient received 11 cycles of palliative folfox in total , which was eventually stopped due to symptomatic deterioration . further ct imaging at that time showed an unchanged lung lesion ; however , the patient had new bony lesions , widespread peritoneal disease , pleural effusions , and ascites . a second - line chemotherapy regimen was considered but not given due to the patient 's poor performance status . she was discharged at the local hospice where she died 11 months after the initial diagnosis . appendiceal gccs usually behave more aggressively than conventional appendiceal nets . according to a suggested classification and on the basis of tumour cell differentiation and ki67 , gccs typical gcc and adenocarcinomas ex - gcc of either signet ring cell type or poorly differentiated adenocarcinoma type . as soon as the histopathological diagnosis is confirmed , according to recent guidelines , patients with gccs are usually offered further prophylactic surgery usually right hemicolectomy and/or bilateral salpingo - oophorectomy . in contrast to the common appendiceal carcinoids , gcc run an aggressive course and quite often metastasize . gcc metastases have also been reported in the liver , ribs , vertebrae , and prostate , whilst in one case gcc cells were found in the pleural fluid as well . debulking surgery with adjuvant intraperitoneal chemotherapy may improve survival in some patients with disseminated disease [ 2 , 6 , 12 , 13 ] . distant metastases occur in 1020% of all patients at presentation , and the most common sites include the ovaries , peritoneum , and liver . kanthan et al . reported a histologically proven case of a gcc metastasizing to the lung in a 60-year - old male . however , in that case , as well as in all cases of metastatic gccs in our previously reported series , the ki67 proliferation index was > 20% and the tumours , according to the new gcc classification , were poorly differentiated adenocarcinoma type. in our case , the ki67 proliferation index was surprisingly low ( < 5% ) , and therefore this is the first case in the literature with a lung metastasis from a typical gcc . the normal levels of chromogranin a and the absence of uptake in octreoscan in our patient , despite advanced disease , confirm our previous findings about the limited values of octreoscan in gcc in contrast to other metastatic appendiceal or midgut carcinoids . in gccs , according to our previous observation , fdg - pet seems to be a very good imaging modality for assessment of disease extent . in our patient , it showed uptake in the right hilar mass . the absence of uptake in the abdominal lymph nodes may have been due to their small size . fdg - pet , in general , seems to be more sensitive than octreoscan in net and high - grade tumour patients . in our case , the fact that fdg - pet showed uptake in the lung lesion , despite the absence of a high proliferation index , probably reflects the aggressiveness of gccs . in patients with advanced gcc , systemic chemotherapy is considered , although there is no well - established chemotherapy regimen for these patients . this case demonstrates the supra - diaphragmatic metastatic potential of gccs even in those patients with a low - grade histology . the overall 5-year survival for gcc ranges between 4075% and depends on the tumour stage at presentation . enets guidelines recommend lifelong screening for synchronous or metachronous malignancies . a comparable follow - up , we would recommend consideration of a contrast ct of the chest , abdomen , and pelvis for all patients with a gcc tumour regardless of histological grade because of their potential to metastasize to distant sites , including the lungs . in case of indeterminate findings , fdg - pet seems to be helpful and , if still in doubt , a guided biopsy of the suspicious lesion may be required to confirm the diagnosis . | goblet cell carcinoid tumours are often considered a subset of appendiceal neuroendocrine tumours which behave more aggressively .
they usually metastasize through transcoelomic / peritoneal invasion and common sites include the ovaries , peritoneum , and liver .
metastases may have goblet cell carcinoid , signet ring cell carcinoma or classic carcinoid histology .
we report the first case in the literature of a patient with a goblet cell carcinoid with lung metastasis , which was associated with unfavourable outcome . |
blunt trauma of the abdominal wall can lead to a traumatic abdominal wall hernia ( tawh ) . defined tawh as the herniation through disrupted musculature and fascia associated with adequate trauma , without skin penetration , and no evidence of a prior hernia defect at the site of injury . although this type of hernia is unusual , it has been described in some reviews [ 27 ] . two reviews studied tawh , especially in the lumbar position [ 8 , 9 ] . the increased abdominal pressure and shearing forces likely cause disruption of the abdominal wall muscles and fasciae . we describe the history and imaging of a patient with a traumatic abdominal wall hernia and the operative treatment . a 59-year - old male sustained a fall from a height of 9 m onto a pile of steel bars , landing on his right flank . upon arrival of helicopter emergency medical services , the patient was alert and complained of pain in the abdomen . an advanced trauma life support ( atls ) survey revealed a right - sided pneumothorax , which was treated with a chest tube . after this intervention , the patient was respiratorily and haemodynamically stable and transported to the emergency department . upon arrival , the initial assessment according to the atls protocol was performed without any new findings according to the a , b , c and d approaches . during the secondary survey , inspection revealed a large swelling at the right side of the abdomen , with abrasions of the overlying skin ( fig . 1 ) . focussed assessment with sonography for trauma identified the presence of free intraperitoneal fluid around the spleen . 1patient after blunt abdominal trauma with swelling of the right hemi - abdomen patient after blunt abdominal trauma with swelling of the right hemi - abdomen in addition , a computed tomography ( ct ) scan of the abdomen showed a traumatic hernia of the right lateral abdomen , with protrusion of bowel and laceration of the spleen ( fig . 2 ) . the patient was transported to the operating theatre , and exploration of the abdomen through a median incision revealed a transverse rupture of the total abdominal wall , including rectus muscle and external , transverse and internal abdominal muscles , with a length of 30 cm from the midline to the vertebral column on the right side ( fig . 3 ) . the small bowel , ascending colon and the right lobe of the liver were herniated due to this defect . a non - vital part of the small bowel ( 10 cm ) was resected , and haemorrhages from the mesentery and spleen were treated . this anatomical reconstruction was reinforced with an intra - abdominal polyester composite mesh ( parietex ) with at least 4 cm overlap and fixed with sutures and taggers . after closure of the linea alba , the overstretched median fascia below the umbilicus was protected by an absorbable polyglactin mesh ( vicryl ) . post - operatively , the patient developed superficial skin necrosis in the area of the abdominal wall with deglovement , which healed by secondary intention assisted by a vacuum assisted closure system . a ct scan of the abdomen 4 months after the operation showed the anatomical reconstruction of the right abdominal wall with the use of an intra - abdominal mesh fixed with taggers ( fig . 4 ) . 2preoperative abdominal computed tomography ( ct ) scan demonstrating three ruptured muscle layers on the right sidefig . 3intra - operative picture of the right inner abdominal wall with rupture of all muscle layers . . 1 parietal peritoneum , 2 rupture of abdominal muscle layers , 3 liverfig . 4post - operative abdominal ct scan demonstrating anatomical restoration of the right abdominal wall with the use of an intra - abdominal mesh fixated with taggers preoperative abdominal computed tomography ( ct ) scan demonstrating three ruptured muscle layers on the right side intra - operative picture of the right inner abdominal wall with rupture of all muscle layers . . 1 parietal peritoneum , 2 rupture of abdominal muscle layers , 3 liver post - operative abdominal ct scan demonstrating anatomical restoration of the right abdominal wall with the use of an intra - abdominal mesh fixated with taggers our patient sustained a high - energy trauma caused by a fall from a large height . this trauma gave rise to the tawh and associated devascularisation of the small bowel , necessitating bowel resection . low energy trauma can lead to smaller tawhs , which can easily be missed on physical evaluation . handlebar injury is an example of a low energy trauma that can lead to tawh [ 2 , 11 , 12 ] . the diagnosis of a tawh on physical examination can be difficult ; because of its rare occurrence , a diagnosis of tawh is not often considered . the tawh was not diagnosed by physical examination , and the very tender right hemi - abdomen was thought to be associated with intra - abdominal lesions . because life - threatening intra - abdominal injuries can occur after high - energy trauma , a ct scan should be used as a diagnostic method . the ct scan in this case led to the diagnosis of tawh after careful examination of the abdominal wall and also to multiple haematomas in the mesentery and a spleen laceration . the strong shear forces had split the three layers of the lateral abdominal wall and the peritoneum . with the routine use of ct scans after blunt trauma tawh can be operated on by an incision overlying the defect , but in this case , a midline exploratory laparotomy was necessary for the associated intra - abdominal injuries . in addition , because of the associated intra - abdominal injuries , delayed exploration of the tawh was not a treatment option in our case . we combined the primary closure in the anatomical layers with an intraperitoneal mesh because the fascia was stretched out by the trauma and the hernia was very large . we used a composite mesh because the inner side was in direct contact with the bowels . in a recent review of the open treatment of incisional hernia , also , in a recent retrospective study of 206 open sublay mesh repairs with intraperitoneal placement of a composite mesh , the infection rate was 10.2% in a 9.5-year period . in our case , resection of a small bowel section could have increased the risk of a mesh infection . the high infection rate has to be weighed against the risk of recurrence . in a series of eight acutely repaired tawhs without mesh , three developed a recurrent hernia after 8 months . in another series of seven acute repairs of tawhs , thus , the acute repair of a large tawh should not be underestimated because of the associated injuries and the risk of a recurrence . | although blunt abdominal trauma is frequent , traumatic abdominal wall hernias ( tawh ) are rare .
we describe a large tawh with associated intra - abdominal lesions that were caused by high - energy trauma .
the diagnosis was missed by clinical examination but was subsequently revealed by a computed tomography ( ct ) scan .
repair consisted of an open anatomical reconstruction of the abdominal wall layers with reinforcement by an intraperitoneal composite mesh .
the patient recovered well and the results of a post - operative ct scan are presented . |
sheehan 's syndrome ( ss ) is one of the commonest causes of hypopituitarism in underdeveloped and developing countries . it occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage.[13 ] although a small percentage of patients with ss may present as abrupt onset acute hypopituitarism immediately after delivery , most patients have a mild disease and go undiagnosed and untreated for years together.[46 ] the spectrum of clinical presentation of ss is extremely varied and ranges from non - specific complaints such as weakness , fatigue , and anemia to severe pituitary insufficiency resulting in coma and death . as in other types of hypopituitarism , other associations include anemia , pancytopenia , and cardiac abnormalities like cardiomyopathy.[810 ] ss presenting as acute kidney injury ( aki ) is rare . only few cases have been reported in the literature and most are precipitated by rhabdomyolysis.[1113 ] we report a case of aki in a middle- aged female with ss who recovered dramatically after being started on intravenous steroids and volume replacement . our case suggests that besides hypothyroid myopathy leading to rhabdomyolysis and consequently compromised renal function and aki , chronic adrenal insufficiency can also predispose to the risk of aki . a 56-year - old woman was referred to our hospital with a 45 day history of nausea , two episodes of vomiting , and few episodes of loose motions , followed by oliguria at home . she denied any history of fever , dysentery , abdominal pain , trauma , muscle pain , or change in color of urine . she also denied history of any drug intake . on enquiring , the patient gave history of longstanding ill health in the form of generalized weakness , easy fatigability , cold intolerance , constipation , hair loss , and weight gain starting after her last child birth some 22 years back . last delivery was a full - term normal delivery conducted by a local midwife at her home . she denied any history of profuse bleeding or blood transfusion during her last peripartum period . however , she had lactation failure and had menstrual cycles for a few months before complete cessation of menses after her last delivery . physical examination revealed an ill - looking , dehydrated patient with pulse of 54 beats/ minute , blood pressure of 90/60 mm hg without any postural drop , respiratory rate of 18/ minute , and oral temperature of 97.6f ( 36.4c ) . the patient had mild pallor , dry tongue , coarse and dry skin with non - pitting edema of the lower extremities . hypopigmented area was seen around right nasal orifice and there was loss of lateral eyebrows . central nervous system examination revealed slow mentation in the form of delayed response to verbal commands . examination of motor system did not reveal any focal neurodeficit , but deep tendon jerks were markedly delayed . kidney function test was deranged with initial urea of 71 mg / dl ( normal value 2040 mg / dl ) and serum creatinine of 4.5 mg / dl ( normal value 0.51.5 mg / dl ) . muscle enzymes were slightly elevated with creatine phosphokinase ( cpk ) being 168 1u / l ( normal value 1070 arterial blood gas and electrolyte analysis revealed ph of 7.31 , pco2 of 27 mm hg , bicarbonate of 13 mmol / l , serum sodium 130 mmol / l , and potassium of 3.6 mmol / l . chest x - ray was normal and 12-lead ecg revealed sinus bradycardia with low - voltage qrs complex . routine urine examination revealed pus cells 45 , rbcs 23 , absent albumin and casts . renal ultrasound revealed relatively small - sized kidneys ( right 8.5 3.2 cm , left 8.7 3.4 cm ) with increased echogenicity , with maintained corticomedullary differentiation bilaterally . the diagnosis of panhypopituitarism most likely secondary to ss associated with acute renal failure was made on the basis of her past medical history of failure to lactate post her last child birth with gradual cessation of menses , peripheral signs and symptoms of hypothyroidism , and abnormal biochemical and hormone profile . basal anterior pituitary hormones and serial kidney function tests during admission the patient was given intravenous fluids in the form of dextrose normal saline with close monitoring of urine output , replacement therapy in the form of intravenous hydrocortisone 50 mg intravenously 6 hourly , and levothyroxine given orally at a starting dose of 50 mcg/ day . on repeating renal function tests and other biochemical tests , there was dramatic improvement in serial renal function parameters . with improvement in the general condition of the patient , intravenous antibiotics were stopped in view of absence of fever and negative septic screen . she was shifted to oral prednisolone 5 mg twice daily , while levothyroxine was continued at a dose of 50 mcg / day . she was discharged on the same medication on 10th day of admission and was advised to taper prednisolone to 5 mg/ day after 2 weeks . four weeks after discharge , the patient had general sense of well - being with better appetite and renal function had normalized with creatinine 0.64 mg/ dl and serum urea 23 mg / dl . the patient was subjected to magnetic resonance imaging ( mri ) brain with sellar and parasellar focus which revealed empty sella with normal rest of the brain parenchyma [ figure 1 ] . mri pituitary sagittal view showing pituitary fossa filled with cerebrospinal fluid and stalk touching the base of pituitary floor ; features suggestive of empty sella the present report describes a 56-year - old woman with ss who presented with acute renal insufficiency owing to depletion of intravascular volume secondary to gastroenteritis . the chronic hypocortisol state has increased the predisposition to renal injury which was precipitated by mild acute gastroenteritis . ss , first described by hl sheehan in 1937 , classically refers to postpartum hypopituitarism due to pituitary necrosis occurring during severe hypotension or shock secondary to massive bleeding at or just after delivery . the frequency of ss has gradually decreased especially in developed countries , as a result of improved obstetric care including treatment of hemodynamic complications with rapid blood transfusion and/or intravenous fluid replacement . it , however , continues to be the most common cause of hypopituitarism in underdeveloped and developing countries . enlarged pituitary volume , small sellar size , prothrombotic nature of pregnancy , and autoimmunity have been suggested to play a role in the pathogenesis of ss in women who suffer from severe postpartum hemorrhage . on the other hand , the spectrum of clinical presentation of ss is quite variable and ranges from non - specific symptoms such as weakness , fatigue , and anemia to severe pituitary insufficiency resulting in coma and death . clinical manifestations of ss may change from one patient to another , as hormonal deficiency varies from loss of one trophic hormone to classical panhypopituitarism.[157 ] failure of postpartum lactation is the most consistent feature of patients with ss and failure of regaining menstrual flow postpartum is the most common symptom of ss . despite the failure to menstruate , gonadotrophin reserve may still be preserved in some patients and these patients can even conceive spontaneously . another important clinical presentation in ss is related to secondary hypothyroidism and patients may present with weight gain , cold intolerance , tiredness , aches and pains , and muscle disorders ranging from elevation of muscle enzymes to frank rhabdomyolysis and renal failure.[1113 ] our patient also had severe central hypothyroidism as was evident from history , examination , and hormone tests . adrenal insufficiency in ss can be catastrophic and can range from non - specific complaints to hypotension , sallow skin , and severe adrenal crisis , particularly under stressful conditions such as infection . only few cases have been reported in which aki was caused by rhabdomyolysis.[1113 ] aki has been defined as rapid decline in kidney function , as measured by rising serum creatinine or decline in urine output ( oligo / anuria ) . introduced by acute kidney injury network , specific criteria exist for diagnosing aki . our case presented with rapid deterioration of renal function in the form of oliguria together with rise in serum creatinine , thus meeting the criteria for aki . although , as stated earlier , aki can occur in ss , hypothyroid myopathy is the most common etiological factor.[1113 ] hypothyroid myopathy is usually manifested by delayed relaxation of tendon reflexes , muscle stiffness , proximal muscle weakness , myalgia , muscle cramps , and occasional elevated muscle enzymes , however , rhabdomyolysis is rare . rhabdomyolysis can occur spontaneously or is precipitated by hypoxemia , hypotension , sepsis , or vigorous exercise . the exact cause of rhabdomyolysis in hypothyroidism is unclear , but both impaired glycogenolysis and oxidative mitochondrial metabolism have been implicated.[1113 ] although our patient had subtle features of hypothyroid myopathy as revealed by history , examination , and lab evaluation , there was no evidence of rhabdomyolysis . the most probable cause of aki in our patient was chronic hypocortisolemia as renal function in our patient rapidly improved after initiation of intravenous hydrocortisone ; an association between adrenal insufficiency and disturbed renal function has been demonstrated repeatedly . a study was done by christine waterhouse and henry keutmenn in 1947 , in which kidney function of 13 patients with adrenal insufficiency was studied . it was concluded that there is reduction in effective vascular bed in the kidney , resulting in decreased renal plasma flow with concomitant decrease in the rate of glomerular filtration . besides , it has been found that cortisol has major effects on hemodynamics and absence of cortisol causes decrease in cardiac index with an inadequate response of systemic vascular resistance to maintain the mean arterial pressure . in summary , a middle - aged woman with ss presented with aki which reversed completely with conservative management including glucocorticoids . | sheehan 's syndrome occurs as a result of ischemic pituitary necrosis secondary to severe postpartum bleeding .
it is one of the most common causes of hypopituitarism , characterized by variable clinical presentation .
acute kidney injury occurs rarely in sheehan 's syndrome and most of the cases have been found to be precipitated by rhabdomyolysis .
we here present a case of sheehan 's syndrome with acute kidney injury where theprecipitating cause was chronic hypocortisolemia .
we believe this is the first reported case of sheehan 's syndrome in which acute kidney injury was precipitated by adrenal insufficiency . |
it has been proved previously that thp-1 cells can differentiate into macrophages following treatment with 100 nm phorbol 12-myristate 13-acetate ( pma ) for 72 h and macrophages can transform into foam cells by incubation in the presence of 50 g / ml oxidized low - density lipoprotein ( ox - ldl ) for 48 h. therefore , thp-1 macrophage - derived foam cells have been used as a model system for investigating the possible molecular mechanisms that ox - ldl influences foam cell development , which represents a promising therapeutic strategy for atherosclerosis . evidence showed that ox - ldl played a significant role in the initiation and progression of atherosclerosis . the previous study revealed that an elevated level of ox - ldl was one of the major risk factors for atherosclerosis . after differentiation , intimal macrophages intake ox - ldl via scavenger receptors , thereby transforming into foam cells . to gain a molecular understanding of the mechanism by which ox - ldl transforms the macrophages into foam cells , we generated thp-1 macrophage - derived foam cells by ox - ldl treatment . long noncoding rnas ( lncrnas ) are nonprotein coding transcribed rna molecules consisting of more than 200 nucleotides . an increasing number of studies have revealed that lncrnas have a variety of important functions , including their role in transcription , splicing , translation , nuclear factor trafficking , imprinting , genome rearrangement , and chromatin modification , . studies have shown that aberrant lncrna expression is associated with a variety of human diseases such as cardiovascular diseases and cancer , . thus , a better understanding of the roles of lncrna in atherosclerosis will advance us to find a promising strategy for regulating lipid metabolism balance . to identify the genes that are regulated by ox - ldl , we isolated total rna from 6 independent samples of thp-1 macrophages cultured in the presence or absence of 50 g / ml of ox - ldl in serum - free rpmi 1640 medium containing 0.3% bsa for 48 h using trizol ( invitrogen life technologies ) . total rna from each sample was quantified by the nanodrop nd-1000 and rna integrity was assessed by standard denaturing agarose gel electrophoresis ( fig . the sample preparation and microarray hybridization were performed based on the manufacturer 's standard protocols with minor modifications . briefly , mrna was purified from 1 g total rna after removal of rrna ( mrna - only eukaryotic mrna isolation kit , epicentre ) . then , each sample was amplified and transcribed into fluorescent crna along the entire length of the transcripts without 3 bias utilizing a random priming method . the labeled crnas were hybridized onto the human lncrna array v2.0 ( 8 60 k , arraystar ) . after having washed the slides , the arrays were scanned by the agilent scanner g2505b . agilent feature extraction software ( version 10.7.3.1 ) was used to analyze acquired array images . all microarray data were submitted to the gene expression omnibus ( accession number gse54039 ) . agilent feature extraction software ( version 10.7.3.1 ) was used to analyze acquired array images . quantile normalization and subsequent data processing were performed using the genespring gx v11.5.1 software package ( agilent technologies ) . after quantile normalization of the raw data , lncrnas and mrnas that at least 1 out of 6 samples have flags in present or marginal ( all target values ) were chosen for further data analysis . differentially expressed lncrnas and mrnas with statistical significance were identified through volcano plot filtering . pathway analysis and go analysis were applied to determine the roles of these differentially expressed mrnas played in these biological pathways or go terms . finally , hierarchical clustering was performed to show the distinguishable lncrna and mrna expression pattern among samples . to explore possible changes in rna expression during macrophage formation , we performed microarray analysis of thp-1 macrophages and thp-1 macrophage - derived foam cells using the arraystar probe dataset , which included 24,748 lncrnas and 24,420 coding transcripts . lncrna and mrna expression profiles from thp-1 macrophages ( 3 samples ) and thp-1 macrophage - derived foam cells ( 3 samples ) were produced using the arraystar human lncrna array v2.0 platform . scatter plots of normalized signal values in lncrnas and mrnas are shown in fig . 2a and b. differently expressed probe sets were identified based on student 's t - test for paired samples ' normalized expression values using the following cutoff : absolute fold change value larger than 3 and p value less than 0.01 . by using a 3 fold change as a cut - off , p - value 0.01 , 100 lncrnas and 63 mrnas were differentially expressed between thp-1 macrophage versus thp-1 macrophage - derived foam cells . it has been proved previously that thp-1 cells can differentiate into macrophages following treatment with 100 nm phorbol 12-myristate 13-acetate ( pma ) for 72 h and macrophages can transform into foam cells by incubation in the presence of 50 g / ml oxidized low - density lipoprotein ( ox - ldl ) for 48 h. therefore , thp-1 macrophage - derived foam cells have been used as a model system for investigating the possible molecular mechanisms that ox - ldl influences foam cell development , which represents a promising therapeutic strategy for atherosclerosis . evidence showed that ox - ldl played a significant role in the initiation and progression of atherosclerosis . the previous study revealed that an elevated level of ox - ldl was one of the major risk factors for atherosclerosis . after differentiation , intimal macrophages intake ox - ldl via scavenger receptors , thereby transforming into foam cells . to gain a molecular understanding of the mechanism by which ox - ldl transforms the macrophages into foam cells , we generated thp-1 macrophage - derived foam cells by ox - ldl treatment . long noncoding rnas ( lncrnas ) are nonprotein coding transcribed rna molecules consisting of more than 200 nucleotides . an increasing number of studies have revealed that lncrnas have a variety of important functions , including their role in transcription , splicing , translation , nuclear factor trafficking , imprinting , genome rearrangement , and chromatin modification , . studies have shown that aberrant lncrna expression is associated with a variety of human diseases such as cardiovascular diseases and cancer , . thus , a better understanding of the roles of lncrna in atherosclerosis will advance us to find a promising strategy for regulating lipid metabolism balance . to identify the genes that are regulated by ox - ldl , we isolated total rna from 6 independent samples of thp-1 macrophages cultured in the presence or absence of 50 g / ml of ox - ldl in serum - free rpmi 1640 medium containing 0.3% bsa for 48 h using trizol ( invitrogen life technologies ) . total rna from each sample was quantified by the nanodrop nd-1000 and rna integrity was assessed by standard denaturing agarose gel electrophoresis ( fig . the sample preparation and microarray hybridization were performed based on the manufacturer 's standard protocols with minor modifications . briefly , mrna was purified from 1 g total rna after removal of rrna ( mrna - only eukaryotic mrna isolation kit , epicentre ) . then , each sample was amplified and transcribed into fluorescent crna along the entire length of the transcripts without 3 bias utilizing a random priming method . the labeled crnas were hybridized onto the human lncrna array v2.0 ( 8 60 k , arraystar ) . after having washed the slides , the arrays were scanned by the agilent scanner g2505b . agilent feature extraction software ( version 10.7.3.1 ) was used to analyze acquired array images . all microarray data were submitted to the gene expression omnibus ( accession number gse54039 ) . agilent feature extraction software ( version 10.7.3.1 ) was used to analyze acquired array images . quantile normalization and subsequent data processing were performed using the genespring gx v11.5.1 software package ( agilent technologies ) . after quantile normalization of the raw data , lncrnas and mrnas that at least 1 out of 6 samples have flags in present or marginal ( all target values ) were chosen for further data analysis . differentially expressed lncrnas and mrnas with statistical significance were identified through volcano plot filtering . pathway analysis and go analysis were applied to determine the roles of these differentially expressed mrnas played in these biological pathways or go terms . finally , hierarchical clustering was performed to show the distinguishable lncrna and mrna expression pattern among samples . to explore possible changes in rna expression during macrophage formation , we performed microarray analysis of thp-1 macrophages and thp-1 macrophage - derived foam cells using the arraystar probe dataset , which included 24,748 lncrnas and 24,420 coding transcripts . lncrna and mrna expression profiles from thp-1 macrophages ( 3 samples ) and thp-1 macrophage - derived foam cells ( 3 samples ) were produced using the arraystar human lncrna array v2.0 platform . scatter plots of normalized signal values in lncrnas and mrnas are shown in fig . 2a and b. differently expressed probe sets were identified based on student 's t - test for paired samples ' normalized expression values using the following cutoff : absolute fold change value larger than 3 and p value less than 0.01 . by using a 3 fold change as a cut - off , p - value 0.01 , 100 lncrnas and 63 mrnas were differentially expressed between thp-1 macrophage versus thp-1 macrophage - derived foam cells . we described here a dataset composed of microarray expression profiling of ox - ldl - responsive genes . with this dataset , we were able to demonstrate a large number of ox - ldl - responsive lncrna and mrna , which advance us to further investigate their relationships and functions in foam cell formation and atherosclerosis progression . we believe that this dataset would be particularly valuable for investigating the cellular processes associated with lipid metabolism balance and the underlying molecular mechanisms . for example , we revealed that ox - ldl could significantly promote lincrna - dynlrb2 - 2 expression , which upregulated atp - binding cassette transporter a1 ( abca1 ) expression through g protein - coupled receptor 119 ( gpr119 ) . in addition , lincrna - dynlrb2 - 2 and gpr119 promoted abca1-mediated cholesterol efflux from thp-1 macrophage - derived foam cells , and inhibited inflammatory responses . moreover , we paid particular attention to rp5 - 833a20.1 as it is a key lncrna in our study of regulation of cholesterol homeostasis and inflammatory reaction . we found that lncrna rp5 - 833a20.1 was located in intron 2 of the nuclear factor i / a ( nfia ) gene and had an opposite transcription direction to that of nfia through the ucsc genome browser . in addition , we demonstrated that rp5 - 833a20.1 could inhibit nfia expression by promoting mir-382 - 5p expression . this finding sheds new light on the interplay between lncrna and atherosclerosis , and suggests that lncrna may become a promising strategy for regulating lipid metabolism balance . | atherosclerosis has a high incidence and is harmful to human health .
an elevated level of oxidized low - density lipoprotein ( ox - ldl ) is one of the major risk factors for atherosclerosis . during atherogenesis progression ,
circulating monocytes adhere to the intima and differentiate into macrophages .
after differentiation , intimal macrophages intake ox - ldl via scavenger receptors , thereby transforming into foam cells .
foam cell formation due to excessive accumulation of cholesterol by macrophages is a pathological hallmark of atherosclerosis .
to gain a molecular understanding of the effect of ox - ldl in atherosclerosis development , we conducted a genome - wide analysis of the ox - ldl - induced macrophage transformation by microarray gene expression profiling . here
we describe in details the contents and quality controls for the gene expression and related results associated with the data uploaded to gene expression omnibus ( accession number gse54039 ) . |
malignant lymphoma is a heterogeneous group of diseases with a wide spectrum of histological subtypes . traditionally , malignant lymphomas have been divided into hodgkin lymphomas and non - hodgkin lymphomas . more than 40 subgroups are defined ; both indolent and aggressive variants exist , and a wide range of treatment is used . the danish national lymphoma registry ( lyfo ) was established in 1982 , covering the western part of denmark ( jutland and funen ) , including patients with non - hodgkin lymphoma . in 1998 , the lyfo aims to register the clinical and paraclinical characteristics of patients diagnosed with malignant lymphoma in denmark . the lyfo aims to monitor the clinical course of the disease as well as to monitor and improve the quality of treatment nationwide by benchmarking departments and patient risk groups . the lyfo includes all patients diagnosed with malignant lymphoma in denmark , referred to one of the ten departments of hematology . patients with cutaneous lymphomas , some hiv+-associated lymphomas , and some lymphomas where treatment is futile are not referred to hematological departments and hence not registered in the lyfo . patients diagnosed and treated outside of denmark are not registered ; according to the database registration , it is two patients per year . patients who relapse where the initial lymphoma diagnosis was prior to start of the registry in that region are not registered . by the end of 2014 , ~23,000 patients were registered since 1982 . since it is a national quality database , all departments of hematology are obligated to register patients in the lyfo at the time of diagnosis , at the end of first - line treatment , at relapse , and at the end of follow - up or death . standardized forms are used to collect data on lymphoma patients ( table 1 ) . since 2005 , the registration is submitted electronically through a secure internet - based database system , and all information is saved electronically . for each patient , four forms are available in a consecutive manner ( figure 1 ) . at the time of diagnosis the department responsible for the treatment initiation and evaluation has the obligation to enter the form . the diagnosis is coded according to the who classification of tumours of haematopoietic and lymphoid tissues.1 since a minor subset has a discordant diagnose , this is also registered . ann arbor stage , b - symptoms , largest tumor diameter , eastern cooperative oncology group performance status , concomitant neoplastic diseases , and treatment strategy are required in the form . in addition to a number of laboratory test results ( table 1 ) , information of each nodal and extranodal involvement sites is required . the treatment form consists of detailed information on the first - line treatment : chemotherapy regimens , treatment with monoclonal antibodies , radiotherapy , radioimmunotherapy , major surgery , and date and type of eventually autologous stem - cell therapy . a response assessment is required and has been adjusted to the different versions of the international response criteria for malignant lymphoma.2 furthermore , toxicity assessment is recorded for patients experiencing toxicity grades iii and iv.3 in the case of clinical or histologically confirmed relapse or refractory disease , defined as progression within 3 months after termination of first - line treatment , a relapse form is requested . this form is also completed for all patients who were initially observed without need of treatment . the relapse form requires date of relapse , lymphoma histology at relapse , treatment information of second - line treatment , and response assessment identical to the treatment form . a follow - up form is requested at death or termination of outpatient follow - up . this form includes information on vital status , date of follow - up or death , and disease remission status . the four schemes in the database are merged to an analyzable dataset , where new data fields are derived from the entered values in the schemes . this process utilizes calculation of a number of prognostic indexes such as the international prognostic index ( ipi)4 and the follicular lymphoma international prognostic index5 and a number of nodal and extranodal sites , in addition to calculation of both result and process quality indicators . result quality indicators are mortality 30 and 180 days after diagnosis for patients receiving treatment , response to first - line treatment and kaplan - meier survival estimates 1 , 3 , and 5 years after the time of diagnosis . the process quality indicators include time from diagnosis to start of treatment , fulfillment of entered data used in the international prognostic index , and the inclusion rate in clinical trials . to ensure high registry completeness , the lyfo is cross - referenced with the danish national patient registry and the national pathology registry . since all patients with a hospital admission , both as inpatient and outpatient , are registered in the danish national patient registry with diagnosis and date of contact , all patients referred to a hematological department are identified by this cross - reference.6 departments can instantly retrieve lists of patients with missing registration in the database , both at time of diagnosis and time of an eventual relapse . all departments register in the lyfo and fulfill the demand of coverage of at least 90% . the department responsible for the treatment initiation and evaluation has the obligation to enter the form . the diagnosis is coded according to the who classification of tumours of haematopoietic and lymphoid tissues.1 since a minor subset has a discordant diagnose , this is also registered . ann arbor stage , b - symptoms , largest tumor diameter , eastern cooperative oncology group performance status , concomitant neoplastic diseases , and treatment strategy are required in the form . in addition to a number of laboratory test results ( table 1 ) , information of each nodal and extranodal involvement sites is required . the treatment form consists of detailed information on the first - line treatment : chemotherapy regimens , treatment with monoclonal antibodies , radiotherapy , radioimmunotherapy , major surgery , and date and type of eventually autologous stem - cell therapy . a response assessment is required and has been adjusted to the different versions of the international response criteria for malignant lymphoma.2 furthermore , toxicity assessment is recorded for patients experiencing toxicity grades iii and iv.3 in the case of clinical or histologically confirmed relapse or refractory disease , defined as progression within 3 months after termination of first - line treatment , a relapse form is requested . this form is also completed for all patients who were initially observed without need of treatment . the relapse form requires date of relapse , lymphoma histology at relapse , treatment information of second - line treatment , and response assessment identical to the treatment form . a follow - up form is requested at death or termination of outpatient follow - up . this form includes information on vital status , date of follow - up or death , and disease remission status . the four schemes in the database are merged to an analyzable dataset , where new data fields are derived from the entered values in the schemes . this process utilizes calculation of a number of prognostic indexes such as the international prognostic index ( ipi)4 and the follicular lymphoma international prognostic index5 and a number of nodal and extranodal sites , in addition to calculation of both result and process quality indicators . result quality indicators are mortality 30 and 180 days after diagnosis for patients receiving treatment , response to first - line treatment and kaplan - meier survival estimates 1 , 3 , and 5 years after the time of diagnosis . the process quality indicators include time from diagnosis to start of treatment , fulfillment of entered data used in the international prognostic index , and the inclusion rate in clinical trials . to ensure high registry completeness , the lyfo is cross - referenced with the danish national patient registry and the national pathology registry . since all patients with a hospital admission , both as inpatient and outpatient , are registered in the danish national patient registry with diagnosis and date of contact , all patients referred to a hematological department are identified by this cross - reference.6 departments can instantly retrieve lists of patients with missing registration in the database , both at time of diagnosis and time of an eventual relapse . all departments register in the lyfo and fulfill the demand of coverage of at least 90% . in addition to the follow - up form , which is completed at the time of termination of outpatient follow - up or death , whichever occurs first , a linkage to the danish civil registration system secures that date of death is available.7 thereby , no patient is lost to follow - up . data from the lyfo has for decades been used for both clinical epidemiological research and for monitoring the treatment of lymphoma patients in denmark.8 the danish lymphoma group , who runs the database , publishes annually a report based on data from the lyfo in collaboration with registry support center of epidemiology and biostatistics ( east).9 the quality indicators are presented for each department by year together with comments from clinicians and epidemiologists . the reports have shown improved 180 days mortality for patients with diffuse large b - cell lymphoma ( dlbcl ) , improving from 12% to 10% during the past 4 years . the annual report is publically available and is used by both clinicians and for administrative purposes . in case of one department having significant worse outcome than the others , the administrative staff will examine the numbers and differences and draw the clinicians attention to the differences in order to standardize treatment and outcome . as an example , the survival for patients with dlbcl was significantly lower in two out of ten departments in 20012007 . the survival has increased , but is now at the same level for all departments due to publication of the survival results ( figure 2 ) . a substantial number of papers originated from the lyfo have been published in the past decade in international journals , and collaboration with other national databases has resulted in unique publications.913 in 2014 , a publication of mantle cell lymphoma showed male sex to be an independent negative prognostic factor , and that both rituximab and autologous stem - cell transplant were independently associated with better outcome.11 a study on routine imaging in the follow - up setting after treatment for dlbcl compared the widespread use of routine imaging in denmark with the more restrictive use in sweden . no impact was found on survival , and the study concludes that routine imaging for dlbcl in the first complete remission is not recommended.13 data quality in the lyfo has recently been measured through a validation process , and the data quality and coverage was found to be very high with positive predictive values for individual variables ranging from 87% to 100% using individual medical records as reference and a registration completeness of 94.9% using danish national patient registry ( dnpr ) as reference.14,15 health care professionals ( eg , medical doctors , study nurses ) report to the database , and consent is not required from patients due to the danish legislation . registration in the lyfo is approved by the national board of health and the danish data protection agency ( 2006 - 54 - 2093 ) . a data entry manual is publically available , and training is performed locally . prior to submission of a form , an internal validation of the data fields is performed and the clinician has to clarify open issues ( eg , date of diagnosis , lymphoma subtype ) before submission of the form can be performed . funding from the danish regions allows the maintenance and development of the database and the database office . registry support center of epidemiology and biostatistics east is responsible for it support as well as statistical and epidemiological support . the lyfo is a nationwide registry , established in 1982 , with extensive information on all lymphoma patients treated at a department of hematology in denmark . the database is used for quality assurance , clinical epidemiological research , and administrative purposes . | aim of databasethe danish national lymphoma registry ( lyfo ) was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in denmark.study populationthe lyfo database was established in 1982 as a seminational database including all lymphoma patients referred to the departments of hematology .
the database became nationwide on january 1 , 2000.main variablesthe main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation . up to four forms are completed for each patient : a primary registration form , a treatment form , a relapse form , and a follow - up form .
variables are used to calculate six result quality indicators ( mortality 30 and 180 days after diagnosis , response to first - line treatment , and survival estimates 1 , 3 , and 5 years after the time of diagnosis ) , and three process quality indicators ( time from diagnosis until the start of treatment , the presence of relevant diagnostic markers , and inclusion rate in clinical protocols).descriptive dataapproximately 23,000 patients were registered in the period 19822014 with a median age of 65 years ( range : 16100 years ) and a male / female ratio of 1.23:1 .
patients can be registered with any of 42 different subtypes according to the world health organization classifications.conclusionlyfo is a nationwide database for all lymphoma patients in denmark and includes detailed information .
this information is used for both epidemiological research and clinical follow - up as well as for administrative purposes . |
a prospective clinical trial was conducted on a consecutive series of the patients with primary io overaction or secondary overaction due to superior oblique palsy . institutional review board approval was obtained and signed informed consent was obtained from all participants in accordance with the declaration of helsinki . exclusion criteria included presence of dvd , history of simultaneous or previous strabismus and/or ocular surgery , inadequate follow up , and concurrent conditions that might influence results such as eyelid anomalies and orbital disease . the patients who did not cooperate enough for taking measurements were also excluded such as small children and the patients with low vision who could not fixate properly . all patients received a thorough ophthalmic examination 1 day before surgery and 3 months thereafter . overaction of io was determined as overelevation in adduction and graded by a scale ranging from 0 to + 4 . output measurements were consisted of pf , margin reflex distance ( mrd ) 12 , lower lid function ( llf ) , hertel value , and lower lid crease ( llc ) . pf was measured by assessing the distance between the upper and lower eyelid margin at the point that bisected the light reflex on the cornea . mrd-1 represented the distance from the corneal light reflex to the upper eyelid margin whereas mrd-2 represented the distance to lower eyelid margin . llf was assessed by measuring eyelid excursion from extreme upgaze to extreme downgaze while holding the head still . hertel mirror exophthalmometer was used to measure the protrusion of the glob from the lateral orbital rim . all the stable measurements were taken by a handheld ruler while the patient sitting upright and fixating with that eye to a penlight held at 50 cm in front of the patient . all preoperative and postoperative measurements were always performed by the same examiner , who did not know the details of patients . to increase the reliability of the measurements , all were taken twice and the average value used , if there was any inconsistency a third measurement was considered . the hyperdeviation was measured with prism and cover test or with krimsky test if corrected visual acuity was inadequate for prism and cover test . all preoperative and postoperative examinations and measurements were made by the same observer , who was not masked to the data . all surgeries were done using a similar technique which was first described by elliot and nankin . in this original procedure , io was sutured just anterior to the insertion of the inferior rectus muscle ; however , we sutured the io posterior to the inferior rectus insertion . in brief , a lid speculum was inserted and the globe was maximally elevated and adducted . polyglactin 6 - 0 sutures were placed in the io near its insertion , with locking bites on either edge . then , the muscle was freed and the anterior arm of the suture was placed posterior to the temporal edge of the inferior rectus muscle insertion . the posterior arm was placed temporally and posteriorly within 23 mm [ fig . 1 ] . hence , the new direction of the io insertion was also different from the original procedure of elliot and nankin . in original technique , the new io insertion should be just anterior but parallel to the inferior rectus insertion . the anterior arm of disinserted inferior oblique muscle placed 12 mm posterior to lateral edge of inferior rectus insertion . the posterior arm was placed temporally and posteriorly within 23 mm to anterior arm the differences of the collected data were calculated for statistical significance using the wilcoxon test . all surgeries were done using a similar technique which was first described by elliot and nankin . in this original procedure , io was sutured just anterior to the insertion of the inferior rectus muscle ; however , we sutured the io posterior to the inferior rectus insertion . in brief , a lid speculum was inserted and the globe was maximally elevated and adducted . polyglactin 6 - 0 sutures were placed in the io near its insertion , with locking bites on either edge . then , the muscle was freed and the anterior arm of the suture was placed posterior to the temporal edge of the inferior rectus muscle insertion . the posterior arm was placed temporally and posteriorly within 23 mm [ fig . 1 ] . hence , the new direction of the io insertion was also different from the original procedure of elliot and nankin . in original technique , the new io insertion should be just anterior but parallel to the inferior rectus insertion . the anterior arm of disinserted inferior oblique muscle placed 12 mm posterior to lateral edge of inferior rectus insertion . the differences of the collected data were calculated for statistical significance using the wilcoxon test . a total of 19 eyes of 16 consecutive patients who met the criteria were included . the mean age of the patients was 8.7 7.1 years , with a range of 223 years . seven eyes ( 36.8% ) of 4 cases had primary io overaction , while 12 eyes ( 63.2% ) of 12 cases had secondary overaction due to superior oblique palsy . the surgery was performed unilaterally for one case with bilateral asymmetric primary io overaction because this case had severe amblyopia in that eye . the median preoperative grade of io overaction was 3.5 ( ranging from 3 to 4 ) , which decreased to 0 ( ranging from 0 to 2 ) ( p < 0.05 ) 3 months postoperatively . all of the eyes underwent anterior transposition of io placed 12 mm posterior to inferior rectus insertion . the mean preoperative hypertropia in the primary position was 14.1 5.9 prism diopters ( pds ) and the mean postoperative hypertropia was 2.4 4.5 pd at the 3-month follow - up visit ( p = 0.005 ) . demographic and operative data for patients who underwent anterior transposition of the inferior oblique the mean preoperative pf was 10.2 1.3 mm in which no change was observed and it was 10.2 0.9 mm postoperatively ( p = 0.79 ) . the mean preoperative mrd-1 was 4.7 0.7 mm , which decreased postoperatively to 4.2 0.6 mm ( p = 0.08 ) . the mean preoperative mrd-2 was 5.6 0.8 mm , which increased postoperatively to 5.8 0.5 mm ( p = 0.25 ) . the mean preoperative hertel value was 15.4 2.2 mm which decreased postoperatively to 15.0 2.8 mm ( p = 0.48 ) . the mean preoperative llf was 5.4 1.4 mm , which increased postoperatively to 5.6 1.2 mm ( p = 0.21 ) . the mean preoperative llc was 4.6 1.2 mm which decreased postoperatively to 4.4 1.3 mm ( p = 0.41 ) [ table 2 ] . preoperative and postoperative values of output measures abnormal head posture was observed in 12 patients and all of them had unilateral superior oblique palsy . the abnormal head posture was not noticable in 7 ( 58.3% ) of these patients and the angle of head tilt reduced in 5 patients ( 41.7% ) at the 3-month postoperative visit . within the orbit , a complex musculofibroelastic structure suspends the globe , interrelates with the eyelids , and other orbital elements . the capsulopalpebral fascia which is analogs to the levator aponeurosis in the upper lid is a major component of lower lid retractors . it originates from the belly of the inferior rectus muscle ; there are firm adhesions between capsulopalpebral fascia and inferior rectus . the capsulopalpebral fascia splits open and forms a anterior layer and a posterior layer which wrapping around the io . any procedure on io as well as anterior transposition surgery might have effect on lower lid retractors and therefore might influence lower lid configuration and functioning . anterior transposition of the inferior io , introduced by elliott and nankin , was highly effective in the treatment of dvd , primary inferior io overaction and secondary overaction due to superior oblique palsy . we also observed clinically and statistically significant decrease in the preoperative hypertropia after this procedure and 68.4% of the patients achieved a hypertropia of 5 pd or less postoperatively . anterior transposition has been shown to work in part by converting the io from an elevator to a depressor of the globe because the neurovascular bundle became a new origin for the temporal portion of the io . elliott and nankin also found that anterior transposition of io was advantageous when compared to standard recession surgery and also was devoid of difficulties and complications related to reinserting the muscle . graded anterior transposition to reduce the complication of limited elevation . in this procedure , the amount of anterior transposition was titrated to the amount of io overaction . farvardin et al . , reported combined resection and anterior transposition of io in the treatment of io overaction secondary to superior oblique palsy with successful results . fard described anterior and nasal transposition of io for the treatment of dvd associated with io overaction . limitation of elevation in abduction and/or adduction and hypotropia in primary position are known complications of anterior transposition surgery of io . functionally , less significant complications such as pf alteration , pf asymmetry , lower lid fullness , were noted in a few study . in the present study , we prospectively evaluated the alteration of the pf , lower lid contour , and function parameters with anterior transposition of the inferior io surgery . for this purpose , the pf , mrd-1 , mrd-2 , hertel value , llf , and llc were evaluated however , none of them revealed significant change postoperatively ( p > 0.05 ) . comparable to our results , no postoperative pf asymmetry has been reported by goldchmit et al . , after io anterior transposition in patients with unilateral io overaction . in their technique , the disinserted io was sutured adjacent to the lateral end of inferior rectus insertion bunched with one suture . they noted slight lower lid curvature deformity on forced upgaze in four of ten patients . farvardin and nazarpoor have observed mild fullness in 25% of the patients with superior oblique palsy following anterior transposition surgery in which the disinserted io was sutured just anterior to the lateral of inferior rectus insertion . however , they did not reported any elevation of lower lid on upgaze in their patients . however , kushner has mentioned that anterior transposition of the inferior io caused a narrowing of the pf and this could be cosmetically noticeable . he compared postoperative pf of patients who underwent io transposition surgery with control group who underwent standard recession without transposition . in this work , the outcomes of transposition surgery were evaluated in two separate groups in first group the io was placed at the level of inferior rectus insertion and in second group the io was placed 2 mm anterior to inferior rectus insertion . compared with the control both groups showed significant decrease in pf and gonzlez and cinciripini reported elevation deficiency , elevation of lower lid on upgaze and reduced inferior scleral show in the eyes following anterior transposition in which io reinserted 3 mm posterior from the limbus in the line of lateral edge of inferior rectus insertion . they speculated that the reason for lower lid elevation to be the advancement of the capsulopalpebral fascia extending to inferior rectus . some studies have reported that io transposition of 1 mm or more anterior to the inferior rectus muscle insertion as well as the lateral spreading of the posterior fibers more than 2 mm at the new insertion are risk factors for complications of this surgery such as anti - elevation syndrome and hypotropia . the lower lid elevation and fullness in lower lid on upgaze also noted more in this augmented anteriorization procedures . kushner demonstrated that if the posterior fibers of io are inserted more distant from the lateral extremity of the inferior rectus insertion , the effect on limitation of elevation would be greater , because these new fibers become more stretched . those cases can not be compared with ours because we performed anteriorization surgery in which io was placed posterior to the lateral end of the inferior rectus insertion thus , the posterior fibers had minor anteriorization . postoperatively no significant change on lower lid configuration and function parameters were observed in our patients . the small sample size and the parameters depending on patients cooperation such as pf , llf are main limitations of this study . we tried to overcome this issue by including only cooperative patients and using the average of two compatible measurements . due to close anatomic relationship of io with lower lid retractors , it is rational to expect an alteration of lower lid configuration and functioning with io surgery . in this study , we did not observe any significant effect on lower lid parameters with io anterior transposition in which we placed the io posterior to inferior rectus insertion . however , the alteration of these parameters might be more noticeable particularly in patients with greater degrees of anterior transpositions in which io placed anterior to inferior rectus insertion . placing the io posterior to the inferior rectus insertion avoiding further anterior transposition may enable successful surgical outcomes without any effect on eyelid configuration and functioning . further observations should also be done on a larger number of patients to confirm the effect of io anterior transposition on the eyelid tissues . | purpose : to evaluate the alteration of lower lid configuration and function with anterior transposition surgery of the inferior oblique ( io ) muscle.patients and methods : a prospective clinical trial was conducted on a consecutive series of patients underwent anterior transposition of the io as a sole operation .
all patients received a thorough ophthalmic examination 1 day before and 3 months after surgery .
output parameters were consisted of palpebral fissure , margin reflex distance 12 , lower lid function , hertel value , and lower lid crease .
the differences of the collected data were calculated for statistical significance by using the wilcoxon test.results:a total of 19 eyes of 16 consecutive patients were included .
the median preoperative grade of io overaction was 3.5 ( ranging from 3 to 4 ) , which decreased to 0 ( ranging from 0 to 2 ) postoperatively ( p < 0.05 ) .
no significant change was observed in all parameters 3 months postoperatively ( p > 0.05).conclusion : in this study , no significant effect on lower lid configuration and function was observed following io anterior transposition in which the disinserted muscle was placed posterior to inferior rectus insertion . |
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