bluuebunny/crossref_metadata_2025 huggingface dataset:
Cheek and Periorbital Peculiar Discoid Lupus Erythematosus: Rare Clinical Presentation Mimicking Tinea Faciei, Cutaneous Granulomatous Disease or Blepharitis
Authors: Nakamura Satoshi , Yamada Tomoko , Umemoto Naoka , Nakamura Toshinobu , Wakatabi Koji , Iida Eri , Masaki Masumi , Kakurai Maki , Demitsu Toshio
Published: June 2015

We present clinically peculiar facial discoid lupus erythematosus (DLE) that mimicked tinea faciei. Although DLE is a chronic autoimmune dermatosis, it has a variety of rare clinical presentations, including periorbital DLE, comedonic DLE and hypertrophic DLE recently. In this case, a scaly, erythematous lesion on the eyelid and the central healed, mildly elevated, annularly distributed facial DLE mimicked tinea faciei, complicating our diagnosis.
Urine Osmolarity and Risk of Dialysis Initiation in a CKD Cohort
Authors: Bankir Lise , Plischke Max , Bouby Nadine , Haas Martin
Published: June 2015

Background: Several experimental studies in rats and a few association studies in humans suggest that the antidiuretic action of vasopressin may accelerate the progression of chronic kidney disease. We undertook a retrospective analysis in a monocentric cohort of 273 patients with chronic kidney disease stages 1-4, focusing on a strong variable of interest, urinary osmolarity, and a strong endpoint, dialysis initiation. Data was analyzed in a multivariate proportional sub-distribution hazards model for competing risk data with appropriate co-variates. Main Results: Over a median follow-up period of 92 months, dialysis was initiated in 105 patients. After adjustments for baseline creatinine clearance, and other confounding factors, a higher risk for initiation of dialysis was found in patients with higher urinary osmolarity. After 72 months, the estimated adjusted cumulative incidence probability for dialysis initiation was 15, 24, and 34% in patients with baseline urinary osmolarity of 315, 510, and 775 mosm/l, respectively (p = 0.033). Key Messages: In this retrospective, longitudinal study, a higher baseline urinary osmolarity was strongly associated with a higher risk of end-stage renal disease (after appropriate adjustments). Further, prospective studies are required to evaluate the possible benefit of interventions aiming at reducing urinary osmolarity as a potential treatment for slowing chronic kidney disease progression.
Impact of the Provision of Safe Drinking Water on School Absence Rates in Cambodia: A Quasi-Experimental Study
Authors: Hunter Paul R. , Risebro Helen , Yen Marie , Lefebvre Héléne , Lo Chay , Hartemann Philippe , Longuet Christophe , Jaquenoud François
Published: June 2015

Background: Education is one of the most important drivers for helping people in developing countries lift themselves out of poverty. However, even when schooling is available absenteeism rates can be high. Recently, focus is being given on whether or not WASH interventions can help reduce absenteeism in developing countries. However, none has focused exclusively on the role of drinking water provision. We report a study on the association between absenteeism and provision of treated water in containers maintained in schools. Methods and Findings: We undertook a quasi-experimental longitudinal study of absenteeism rates in 8 schools, 4 of which received one 20 l container of treated drinking water per day. The water had been treated by filtration and ultraviolet disinfection. Weekly absenteeism rates were compared across all schools using the negative binomial model in generalized estimating equations. There was a strong association between the provision of free water and reduced absenteeism (Incidence rate ratio = 0.39 (95% confidence intervals 0.27-0.56)). However, there was also a strong association with season (wet versus dry) and a significant interaction between receiving free water and season. In one of the intervention schools, it was discovered that the water supplier was not fulfilling his contract and was not delivering sufficient water each week. In this school, we showed a significant association between the number of water containers delivered each week and absenteeism (IRR = 0.98 95% CI 0.96-1.00). Conclusion: There appears to be a strong association between providing free and safe drinking water and reduced absenteeism, although only in the dry season. The mechanism for this association is not clear but may be in part due to improved hydration leading to improved school experience for the children.
The Impact of Green Tea Consumption on the Prevention of Hemorrhagic Stroke
Authors: Lee Seung-Mi , Choi Nam-Kyong , Yoon Byung-Woo , Park Jong-Moo , Han Moon-Ku , Park Byung-Joo
Published: June 2015

Background: Different types of tea may have varying effects on the risk of hemorrhagic stroke, but previous studies have generated inconsistent results. We performed a nationwide, multi-center, case-control study to evaluate the association between the consumption of tea and the risk of hemorrhagic stroke. Methods: This study included 940 patients aged 30 to 84 with non-traumatic acute hemorrhagic stroke who did not have a history of stroke or hemorrhage-prone brain lesions, as well as 940 community controls and 940 hospital controls matched to each patient by age and gender. Pre-trained interviewers obtained information on potential confounders. Consumption of tea was assessed by using a food frequency questionnaire. Participants were asked to indicate the number of cups of tea (green, black, and oolong tea) they consumed per day or per week during the preceding year. Results: The adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated by conditional logistic regression. The adjusted ORs of hemorrhagic stroke were 0.71 (95% CI: 0.59-0.87), 0.86 (95% CI: 0.55-1.37), and 1.34 (95% CI: 0.91-1.98) for consumption of green, oolong, and black tea, respectively, compared with no consumption. There was no significant linear trend for green tea consumption. Conclusions: Consumption of green tea may protect against hemorrhagic stroke, whereas consumption of black tea may have no meaningful effect on risk.
Genes Encoding Vascular Endothelial Growth Factor A (VEGF-A) and VEGF Receptor 2 (VEGFR-2) and Risk for Bronchopulmonary Dysplasia
Authors: Mahlman Mari , Huusko Johanna M. , Karjalainen Minna K. , Kaukola Tuula , Marttila Riitta , Ojaniemi Marja , Haataja Ritva , Lavoie Pascal M. , Rämet Mika , Hallman Mikko ,   on behalf of the Gen-BPD Study Group
Published: June 2015

Background: Bronchopulmonary dysplasia (BPD) is one of the main consequences of prematurity, with notably high heritability. Vascular endothelial growth factor A (VEGF-A) and its main receptor, vascular endothelial growth factor receptor 2 (VEGFR-2), have been implicated in the pathogenesis of BPD. Objective: To study whether common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are associated with BPD. Methods: In this association study, six tagging single nucleotide polymorphism (tSNPs) for VEGFA and 25 tSNPs for VEGFR2 were genotyped in a prospectively collected, genetically homogeneous discovery population of 160 infants (44 infants with grade 2-3 BPD) born before 30 completed gestational weeks. The replication population of 328 infants included 120 cases of BPD. Results:VEGFR2 SNP rs4576072 was associated with BPD grade 2-3 with a minor allele frequency in 23.9% of the cases compared to 9.1% in controls (p = 0.0005, odds ratio 3.15, 95% CI: 1.62-6.12) in the discovery population. This association was not observed in the more heterogeneous replication population. Conclusions: In line with the results of recent large-scale genetic studies, our findings indicate that common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are not consistently associated with BPD. This finding does not rule out the involvement of VEGFA and VEGFR2 in BPD pathogenesis since, in addition to common variations within the gene region, other mechanisms also play important roles in the regulation of gene function.
Bortezomib-Containing Regimens Are Effective in Multiple Myeloma - Results of a Non-Interventional Phase IV Study
Authors: Knauf Wolfgang , Tapprich Christoph , Schlag Rudolf , Schütz Stefan , Alkemper Burkhard , Gaede Bernd , Reschke Daniel , Schmits Rudolf , Schwarzer Andreas
Published: June 2015

Background/Aims: The incorporation of bortezomib into the chemotherapeutic regimens for non-transplant patients with multiple myeloma resulted in improved outcomes in controlled studies. This prospective, non-interventional study assessed the effectiveness and safety of bortezomib-containing regimens in daily practice. Methods: Patients with untreated or relapsed multiple myeloma not eligible for high-dose chemotherapy followed by autologous stem cell transplantation and who were scheduled for bortezomib mono- or combination therapy or melphalan-prednisone (MP) alone were included in this study. Dosage and treatment decisions were at the discretion of the physicians. Results: 353 patients received bortezomib-containing therapies and 37 patients MP alone. Overall response rates at treatment end were 65.9% for bortezomib-containing therapies and 50.0% for MP. Partial or complete remissions considered best responses were achieved in 82.6% (first line) and 63.8% (second or later line) of the bortezomib-treated patients. The median duration of response to bortezomib-containing therapies was 18.2 months in 109 first-line and 11.3 months in 110 second- or later-line patients. Adverse drug reactions of any grade were reported during the treatment phase in 79.6% (bortezomib) and 70.3% (MP) of treated patients. Conclusion: Bortezomib-containing therapies were effective in patients with multiple myeloma in a real-life setting. The increasingly individualized treatment regimens of multiple myeloma require standardized assessments of response in daily practice.
Alcohol Abuse and Alcoholic Liver Cirrhosis Leading to Spontaneous Muscle Hematoma: An Event Fraught with Danger
Authors: Mangla Ankit , Hamad Hussein , Yadav Udit , Telfer Margaret
Published: June 2015

Alcohol abuse is associated with both potentiating and antagonizing hemostatic states. Liver cirrhosis is an independent causal factor for many bleeding complications. The long-term effects of alcohol abuse coupled with advanced liver cirrhosis are additive in favor of bleeding. We report the case of a patient with a history of alcohol abuse who presented with liver cirrhosis and nontraumatic muscle hematoma diagnosed as a spontaneous hematoma of the gastrocnemius muscle. He was managed conservatively with infusions of fresh frozen plasma and platelets, which resulted in resolution of the hematoma. The pathogenesis of ‘spontaneous' muscle hematoma remains anecdotal, but since it is reported in patients on anticoagulant therapy or with hemostatic disorders, it is hypothetically related to severely deranged coagulation. Here we review the relevant literature pertaining to the pathogenesis, presentation and treatment options available for treating this often fatal complication of bleeding diatheses.
Inflammatory Polyp in the Common Bile Duct with Pancreaticobiliary Maljunction
Authors: Uchida Yuichiro , Ome Yusuke , Shimata Keita , Nagahisa Yoshio , Okabe Michio , Kawamoto Kazuyuki , Park Tae Bum , Itoh Tadashi , Ogasahara Keizo
Published: June 2015

A 63-year-old woman was admitted because of epigastric pain and obstructive jaundice. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography revealed a 25-mm papillary nodule in the middle to inferior portion of the common bile duct (CBD). Pancreaticobiliary maljunction (PBM) was also identified. Contrast-enhanced computed tomography also showed an enhanced nodule in the CBD, and we suspected intraductal papillary neoplasm of the bile duct. We performed pylorus-preserving pancreatoduodenectomy. Postoperative pathological examination revealed an inflammatory polyp in the middle CBD. Inflammatory polyp in the bile duct is rare and there are no previous reports accompanied by PBM. PBM is a major risk factor for biliary tract cancer. Preoperative diagnosis of a benign disorder was difficult in this case.
Effect of Preexisting Cognitive Impairment on In-Patient Treatment and Discharge Management among Elderly Patients with Hip Fractures
Authors: Bliemel Christopher , Lechler Philipp , Oberkircher Ludwig , Colcuc Christian , Balzer-Geldsetzer Monika , Dodel Richard , Ruchholtz Steffen , Buecking Benjamin
Published: June 2015

Objective: To examine the influence of cognitive impairment on the functional outcomes and complication rates of patients with hip fracture during in-patient treatment. Methods: A total of 402 patients who were surgically treated for hip fractures were consecutively enrolled at a single trauma center. The patients were grouped according to their results on the Mini-Mental State Examination (MMSE), i.e., ≥20 points (group I) and ≤19 points (group II). Complication and in-hospital mortality rates as well as postoperative functional outcomes according to the Barthel Index (BI) were compared between the groups. A multivariate regression analysis was performed to control for additional factors. Results: 33% of the patients had MMSE scores ≤19 points. The complication rates were similar between the groups (p > 0.05). Likewise, the overall in-hospital mortality rates were similar between the patients in group I (4.5%) and those in group II (9.8%; β = 0.218, p < 0.740). Functional outcomes, as assessed by the BI, were lower in group II (β = -0.266, p < 0.001). The patients in group II were transferred to a rehabilitation clinic less frequently (52.3 vs. 76.0%, p < 0.001). Conclusions: Patients with lower MMSE scores are at a higher risk for poorer functional outcomes. Perioperative care should focus on the preservation of functional abilities to protect these patients from an additional loss of independence and disadvantageous clinical course.
A Possible Clue for the Production of Anti-Glomerular Basement Membrane Antibody Associated with Ureteral Obstruction and Hydronephrosis
Authors: Takeuchi Yasuo , Takeuchi Emiko , Kamata Kouju
Published: June 2015

Background: Anti-glomerular basement membrane (anti-GBM) antibody-mediated glomerulonephritis (anti-GBM GN) is an autoimmune disease with rapidly progressive glomerulonephritis. Based on a case report of anti-GBM GN following hydronephrosis, we hypothesized that hydronephrosis may act as a trigger for the development of anti-GBM antibodies. Patients and Methods: We evaluated 11 patients who were diagnosed with hydronephrosis. It was measured with serum anti-GBM antibody. These patients' medical histories as well as risk factors for the development of anti-GBM antibodies and causes of hydronephrosis were reviewed. Renal function and hematuria were also considered. The serum anti-GBM antibody was measured with enzyme-linked immunosorbent assays (ELISA) or chemiluminescent enzyme immunoassays (CLEIA). Histopathological findings of renal biopsy specimens were also evaluated. Results: No patient had a medical history of renal disease. Five patients had a history of smoking. Ten of the 11 patients had renal dysfunction as evidenced by serum creatinine levels of 0.85-13.8 mg/dl, while 8 patients had RBCs in their urinary sediment at the time of diagnosis for hydronephrosis. Two of the patients assessed by ELISA and CLEIA were positive for anti-GBM antibodies. In 1 of these 3 patients, anti-GBM antibodies and renal dysfunction improved upon treatment for hydronephrosis. Another of the 3 patients developed anti-GBM GN, but anti-GBM antibodies and renal dysfunction improved dramatically upon treatment. In the 3rd patient without improved hydronephrosis, anti-GBM antibodies and renal dysfunction remained unchanged. Conclusion: Our results provide insights into the development of anti-GBM antibodies in patients with ureteral obstruction and hydronephrosis.
Diagnostic Dilemma in Primary Blastomyces dermatitidis Meningitis: Role of Neurosurgical Biopsy
Authors: Brown Desmond A. , Whealy Mark A. , Van Gompel Jamie J. , Williams Lindsy N. , Klaas James P.
Published: June 2015

A 52-year-old male on chronic prednisone for polymyalgia rheumatica presented with a subacute history of headaches, nausea, phonophobia, intermittent diplopia and gait instability. He was hospitalized 2 weeks prior to presentation with extensive evaluations only notable for leptomeningeal inflammation on MRI. His symptoms progressively worsened and he developed aphasia. He was transferred to our facility where extensive spinal fluid examinations were repeated and were again nondiagnostic. Ultimately, a diagnostic skull-based biopsy was performed which demonstrated Blastomyces dermatitidis fungal meningitis. Despite extensive sampling and cultures, only 1 of the intraoperative samples yielded diagnostic results. This underscores the low sensitivity of current methods to diagnose CNS blastomycosis. This case suggests that a neurosurgical biopsy may be necessary and should be considered early in the diagnostic process, especially if a definitive diagnosis is elusive. If a biopsy is performed, sampling should be ample and from multiple areas. Following the diagnosis, our patient was treated with liposomal amphotericin B and then voriconazole with a good clinical response.
Free Recall Episodic Memory Performance Predicts Dementia Ten Years prior to Clinical Diagnosis: Findings from the Betula Longitudinal Study
Authors: Boraxbekk Carl-Johan , Lundquist Anders , Nordin Annelie , Nyberg Lars , Nilsson Lars-Göran , Adolfsson Rolf
Published: June 2015

Background/Aims: Early dementia diagnosis is a considerable challenge. The present study examined the predictive value of cognitive performance for a future clinical diagnosis of late-onset Alzheimer's disease or vascular dementia in a random population sample. Methods: Cognitive performance was retrospectively compared between three groups of participants from the Betula longitudinal cohort. Group 1 developed dementia 11-22 years after baseline testing (n = 111) and group 2 after 1-10 years (n = 280); group 3 showed no deterioration towards dementia during the study period (n = 2,855). Multinomial logistic regression analysis was used to investigate the predictive value of tests reflecting episodic memory performance, semantic memory performance, visuospatial ability, and prospective memory performance. Results: Age- and education-corrected performance on two free recall episodic memory tests significantly predicted dementia 10 years prior to clinical diagnosis. Free recall performance also predicted dementia 11-22 years prior to diagnosis when controlling for education, but not when age was added to the model. Conclusion: The present results support the suggestion that two free recall-based tests of episodic memory function may be useful for detecting individuals at risk of developing dementia 10 years prior to clinical diagnosis.
Lichen Planopilaris in the Androgenetic Alopecia Area: A Pitfall for Hair Transplantation
Authors: Baquerizo Nole Katherine L. , Nusbaum Bernard , Pinto Giselle M. , Miteva Mariya
Published: June 2015

Background: Classic lichen planopilaris (LPP) is a patchy form of primary lymphocytic cicatricial alopecia localized on the vertex of the scalp. It is important, however, to be aware of other, less recognized presentations that may be missed without dermatoscopy and pathology. Methods and Results: We report 26 patients with LPP presenting with subtle erythema and scaling colocalized in the area of patterned thinning (androgenetic alopecia, AGA). All patients had been treated for seborrheic dermatitis in the past. Dermatoscopy showed the presence of 2-4 hairs emerging as a tuft from the same ostium surrounded by erythema, peripilar casts and interfollicular scaling associated with hair miniaturization. Histopathology obtained from those areas corresponded to LPP with concomitant follicular miniaturization. Conclusion: Subtle or focal cases of LPP may be missed for seborrheic dermatitis when overlapping with AGA. Dermatoscopy-guided biopsy from the affected scalp is the best approach to make a timely diagnosis. This is particularly important in patients with AGA evaluated to undergo hair transplantation, as active LPP is a contraindication for these patients.
NADIR: A Non-Interventional Study on the Prophylaxis of Chemotherapy-Induced Neutropenia Using Lipegfilgrastim - First Interim Analysis
Authors: Kurbacher Christian M. , Fietz Thomas , Diel Ingo J. , Egert Matthias , Hurtz Hans-Jürgen , Lück Andreas , Weide Rudolf , Salat Christoph , Wolff Thomas , Zaiss Matthias , Klare Peter , Losem Christoph , Illmer Thomas , Weißenborn Georg , Steffens Claus-Christoph , Schulze Matthias , Tesch Hans , Oskay-Oezcelik Gülten , Teichmann Beate , Harde Johanna , Scheuerlein Robert Willy
Published: June 2015

Background: The non-interventional study (NIS) NADIR was designed to assess the effectiveness and safety of lipegfilgrastim, a novel glycopegylated granulocyte-colony stimulating factor, in reducing the risk of both febrile and severe neutropenia. Methods: Here, the interim analysis of NIS Nadir performed under real-world conditions at 80 oncology practices across Germany is reported. For a patient to be included, lipegfilgrastim at a subcutaneous single dose of 6 mg had to be administered during at least 1 cycle of the chemotherapy under consideration. Results: The interim analysis included 224 patients. Median patient age was 61.1 years (interquartile range 51.2-70.2 years). Main tumor type was breast cancer followed by lung cancer, and non-Hodgkin's lymphoma (46.0, 13.4, and 10.7%, respectively). When lipegfilgrastim was given as primary prophylaxis, no patient developed febrile neutropenia (FN). 1.3% of patients developed FN when primary prophylaxis was withheld. Only 68.6% of patients undergoing chemotherapy and at high risk (> 20%) of developing FN were treated with lipegfilgrastim during the first cycle, exposing disparity between real-world practices and current treatment guidelines. Lipegfilgrastim was well tolerated. The only grade 3/4 treatment-related adverse event was anemia in 1 patient. Conclusion: Lipegfilgrastim was effective and safe when administered for the prevention of chemotherapy-induced neutropenia under real-world conditions.
Romiplostim Treatment in Adults with Immune Thrombocytopenia of Varying Duration and Severity
Authors: Janssens Ann , Tarantino Michael , Bird Robert J. , Mazzucconi Maria Gabriella , Boccia Ralph V. , López Fernández Maria Fernanda , Kozak Tomas , Steurer Michael , te Boekhorst Peter , Dillingham Kerry , Kreuzbauer Georg , Woodard Paul
Published: June 2015

Romiplostim is recommended for the second- and third-line treatment of primary immune thrombocytopenia (ITP). We conducted a large, single-arm study (clinicaltrials.gov; NCT00508820) with broad entry criteria to evaluate the safety of romiplostim in adult ITP. Patients (n = 407) with ITP lasting 0.03-57.14 years and low platelet counts (median 14.0 × 109/l) or uncontrolled bleeding received romiplostim for up to 4 years. The rates of treatment-related, serious adverse events, serious hemorrhage events, thromboembolic events and fatal events were similar to those reported in previous romiplostim trials (0.2, 0.4, 0.2 and 0.1/100 patient-weeks, respectively). Bone marrow reticulin was observed in 4 patients, but biopsies were not routinely performed so the true incidence of this event cannot be determined. Type I collagen (nonserious, unrelated) was reported in 1 patient who likely had myelodysplastic syndrome. No new class of adverse events was reported. Platelet responses were achieved by >90% of the patients, typically within 1-2 weeks of the initiation of romiplostim treatment. From week 8, median platelet counts were >100 × 109/l; 47% of the patients received rescue medications (the use decreased over time). This study confirms and extends the tolerability/efficacy findings of previous romiplostim clinical studies. It was performed on a large ITP population, which is likely more representative of clinical practice.
Balance and Mobility as Predictors of Post-Stroke Cognitive Impairment
Authors: Ursin Marie Helene , Bergland Astrid , Fure Brynjar , Tørstad Audhild , Tveit Arnljot , Ihle-Hansen Hege
Published: June 2015

Background: The number of patients with cognitive impairment following stroke is increasing due to the rise in the number of stroke survivors. Health authorities highlight the need for prediction and early diagnostics. The aims of this study were to investigate if balance and mobility may predict cognitive impairment 1 year after stroke. Methods: The participants were patients with first-ever stroke or transient ischaemic attack (TIA). The exclusion criteria were pre-stroke cognitive impairment and dementia. Measurements of balance comprised the Berg Balance Scale (BBS) and the Figure of Eight test (Fig8). Mobility was measured by maximum walking speed and the Timed Up and Go test. Dementia and mild cognitive impairment were merged into a main outcome: cognitive impairment. Unadjusted and adjusted multivariate logistic regression models were performed. Results: One hundred and eighty subjects performed balance and mobility measures at baseline, and 158 participated in the follow-up; 13 died and 9 did not complete the follow-up. Two variables made a significant contribution in the adjusted analyses (Fig8, BBS). The strongest predictor of cognitive impairment was Fig8 with an odds ratio of 1.06. Conclusion: The results of Fig8 and BBS measured in the acute phase of stroke were predictors of cognitive impairment 1 year later in this cohort of first-ever stroke or TIA.
Is Drinking with Parents Associated with High-Risk Drinking among Adolescents?
Authors: Pape Hilde , Rossow Ingeborg , Storvoll Elisabet E.
Published: June 2015

Background/Aims: What are the implications of drinking with parents (DWP) on adolescents' drinking behavior? We expanded the meagre body of research on this controversial issue by assessing the association between the frequency of DWP and adolescent high-risk drinking, taking a number of parental factors into account. Method: Data stemmed from a subsample of 14-17-year-old current drinkers (n = 7,616) who participated in a cross-sectional Norwegian school survey (response rate: 84%). Results: One in four reported DWP during the past year. The higher the frequency of DWP, the higher was the prevalence of high-risk drinking. Parental drunkenness, permissive alcohol-related parenting, and indicators of suboptimal parenting more generally also correlated with DWP. After controlling for these confounders, only frequent DWP remained significantly associated with high-risk drinking. Conclusions: DWP was related to adolescent high-risk drinking, yet the association was in part attributable to parents' drinking and parenting style. The risk of involvement in high-risk drinking was about the same for adolescents reporting no DWP and infrequent DWP, while it was significantly elevated among those reporting frequent DWP. This study thus demonstrated that the frequency of DWP matters and that parents who drink with their adolescent children differ from other parents in important ways.
A Cell Culture Model of Latent and Lytic Herpes Simplex Virus Type 1 Infection in Spiral Ganglion
Authors: Liu Yuehong , Li Shufeng
Published: June 2015

Purpose of the Study: Reactivation of latent herpes simplex virus type 1 (HSV-1) in spiral ganglion neurons (SGNs) is supposed to be one of the causes of idiopathic sudden sensorineural hearing loss. This study aims to establish a cell culture model of latent and lytic HSV-1 infection in spiral ganglia. Procedures: In the presence of acyclovir, primary cultures of SGNs were latently infected with HSV-1 expressing green fluorescent protein. Four days later, these cells were treated with trichostatin A (TSA), a known chemical reactivator of HSV-1. TCID50 was used to measure the titers of virus in cultures on Vero cells. RNA from cultures was detected for the presence of transcripts of ICP27 and latency-associated transcript (LAT) using reverse transcription polymerase chain reaction. Results: There is no detectable infectious HSV-1 in latently infected cultures, whereas they could be observed in both lytically infected and latently infected/TSA-treated cultures. LAT was the only detectable transcript during latent infection, whereas lytic ICP27 transcript was detected in lytically infected and latently infected/TSA-treated cultures. Conclusion: Cultured SGNs can be both latently and lytically infected with HSV-1. Furthermore, latently infected SGNs can be reactivated using TSA, yielding infectious virus.
Management of Conjunctival Melanoma: Critical Assessment of Sentinel Lymph Node Biopsy
Authors: Aziz Hassan A. , Gastman Brian R. , Singh Arun D.
Published: June 2015

Conjunctival melanoma (CoM) is a rare and aggressive form of melanoma. There is a lack of consensus on a unified management plan for this disease. Recently, a few centers have adopted the regional sentinel lymph node biopsy into the staging process of CoM. This study presents a critical assessment of the role of sentinel lymph node biopsy in CoM and presents a simplified management algorithm based on high-risk clinical and pathological features.
Conjunctival Attachment of a Live Paralysis Tick, Ixodes holocyclus, in a Child: A Case Report
Authors: Teong Joanne M.Y. , Adler Paul A. , Doggett Stephen L. , Daneshvar Dariush , Shields Melissa K.
Published: June 2015

We describe a rare clinical finding of conjunctival tick attachment in a child. A 10-year-old boy presented to the clinic with right-eye itch. He was found to have a live tick firmly attached to his right temporal conjunctiva. The tick was identified as the larval stage of the paralysis tick, Ixodes holocyclus. The tick was removed completely by conjunctival excision. Although various methods of removing a tick have been described in the literature, the goal of treatment is the safe and complete removal of the tick to prevent further transmission of pathogens, allergens, and toxins to the patient.
Determination of Caudatin in Rat Plasma by UPLC-MS/MS: Application to a Preclinical Pharmacokinetic Study
Authors: Zhu Qiqi , Hu Yuanyuan , Shan Yuanyuan , Wang Yiyan , Wu Xiaolong , Mao Baiping , Ge Ren-Shan
Published: June 2015

In this study, a simple, sensitive, and robust analytical method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for the determination of caudatin in rat plasma using carbamazepine as internal standard (IS). This method was linear over the concentration range 2.5-300 ng/ml with a lower limit of quantification (LLOQ) of 2.5 ng/ml. Inter- and intra-day precision (RSD%) were all within 10% and the accuracy (RE%) was equal or lower than 5%. Recoveries of caudatin and IS were more than 80% and matrix effects were not significant. Stability studies showed that caudatin was stable under a variety of storage conditions. The method was successfully applied to a pharmacokinetic study involving oral administration of caudatin to rats.
Comparison of Outcomes after Reperfusion Therapy between In-Hospital and Out-of-Hospital Stroke Patients
Authors: Yoo Joonsang , Song Dongbeom , Lee Kijeong , Kim Young Dae , Nam Hyo Suk , Heo Ji Hoe
Published: June 2015

Background: Patients may experience stroke while being admitted to the hospital (in-hospital stroke (IHS)) and they may be important candidates for reperfusion therapy. IHS patients may have various comorbidities and show worse outcomes compared with patients with an out-of-hospital stroke (OHS). On the other hand, the time from onset to treatment may be shorter in IHS patients than OHS patients. Most outcome studies of reperfusion therapy have been based on findings in OHS patients, and little information is currently available regarding outcomes of IHS, whether the outcomes differ between patients with IHS and those with OHS who receive reperfusion therapy. Methods: This is a retrospective observational study using prospectively registered data. Consecutive patients who underwent the reperfusion therapy (intravenous (IV), intra-arterial (IA), or combined IV and IA) between July 2002 and June 2014 in a university hospital were included for this study. We compared the demographics, time interval from symptom onset to treatment, and outcomes between IHS and OHS patients and analyzed the factors associated with in-hospital mortality. Results: A total of 686 patients received the reperfusion therapy during the study period. Of them, 256 (37.3%) patients received the IV tissue plasminogen activator (t-PA) therapy only, 243 (35.4%) patients received the IA therapy only, and 187 (27.3%) patients received the combined IV and IA therapy. Among these, 104 (15.2%) were IHS patients. The time intervals from symptom onset to IV t-PA administration (87.5 ± 48.4 vs. 113.4 ± 38.3 min, p < 0.001) and IA puncture (221.8 ± 195.0 vs. 343.6 ± 155.4 min, p < 0.001) were shorter for IHS than OHS. The rates of successful recanalization and symptomatic intracerebral hemorrhage, and the favorable functional outcome at 3 months were similar between the groups. In-hospital all-cause mortality was higher in IHS than OHS (16.3 vs. 8.4%, p = 0.019), but after adjustment, IHS was not an independent factor. The stroke mortality did not differ between the groups (9.6 vs. 6.9%, p = 0.432). Conclusions: Although IHS patients more frequently had comorbid diseases and higher overall in-hospital mortality, the standard outcomes of the reperfusion therapy were similar between IHS and OHS patients, which might be, in part, ascribed to the shorter interval from symptom onset to treatment in IHS. Considering a substantial portion of IHS patients, we should pay more attention to these patients.
Preoperative Endoscopy and Its Impact on Perioperative Management in Bariatric Surgery
Authors: Wiltberger Georg , Bucher Julian Nikolaus , Schmelzle Moritz , Hoffmeister Albrecht , Dietrich Arne
Published: June 2015

Background: The role of preoperative upper-gastrointestinal endoscopy for bariatric surgery is still understood only with controversy. The aim of this study was to evaluate the prevalence of endoscopic findings and its impact on perioperative management. Methods: Patients who underwent bariatric surgery at our center between 2010 and 2013 were systematically analyzed from a prospective database. Results: Two hundred and twelve patients with a median body mass index of 50 kg/m2 (range 29-87) underwent 216 bariatric procedures at our center between 2010 and 2013. All patients received preoperative upper endoscopy. In 159 cases (75%), the endoscopy was performed at our center. These cases were included in this study. In 37 cases (23%), no abnormal findings were detected. In 122 cases (76%), upper endoscopy revealed pathologies. No further treatment was necessary in 24 cases (15%). Medical treatment was changed in 81 cases (51%). The operation was delayed due to medical treatment and re-endoscopy in 13 cases (8%). The surgical approach was changed in 4 cases (3%). Conclusion: Routinely performed preoperative endoscopy before bariatric surgery revealed a high prevalence of gastrointestinal diseases with a significant impact on perioperative management in two thirds of the cases. Therefore, we recommend routine gastroscopy about 2-4 weeks prior to surgery.
Seronegative Neuromyelitis Optica Spectrum Disorder following Exposure to Hepatitis B Vaccination
Authors: Heekin Richard , Gandhy Chetan , Robertson Derrick
Published: June 2015

Controversy exists regarding a potential link between exposure to recombinant hepatitis B vaccine (HBV) and central nervous system demyelinating diseases. Here, we present a case of seronegative neuromyelitis optica spectrum disorder (NMOSD) following exposure to HBV. A 28-year-old man developed painful eye movements 11 days after exposure to HBV. Within 24 h, he experienced vision loss, ascending numbness, and ataxia. T-spine MRI showed a cord lesion spanning T6-T9. Brain MRI showed bilateral optic nerve contrast enhancement and a right-sided internal capsule lesion. Cerebrospinal fluid analysis was normal, including negative oligoclonal bands and normal IgG index. AQP4-IgG serology was negative. The patient's visual symptoms improved after treatment with steroids and plasma exchange. He received plasma exchange weekly for 4 weeks with decreased numbness and tingling as well as improved coordination. Treatment with mycophenolate mofetil was started, and the patient remains clinically stable with near resolution of his prior symptoms. Neuromyelitis optica is characterized by optic neuritis and/or longitudinally extensive transverse myelitis. While our patient tested seronegative for AQP4-IgG (which remains negative in 10-50% of NMOSD cases, despite testing with the most sensitive assays available), he did meet NMOSD diagnostic criteria. In a literature review, we found 7 cases of NMOSD onset or relapse associated with exposure to various vaccines, but to our knowledge this represents the first published report of NMOSD onset following exposure to HBV. While causality between vaccination and CNS demyelinating disease remains elusive, it is important to report these cases to help develop safer vaccinations and provoke further inquiry into the pathogenesis of NMOSD.
Familial Hemiplegic Migraine Type 1 Associated with Parkinsonism: A Case Report
Authors: Bruun Marie , Hjermind Lena Elisabeth , Thomsen Carsten , Danielsen Else , Thomsen Lise Lykke , Pinborg Lars Hageman , Khabbazbavani Nastaran , Nielsen Joergen Erik
Published: June 2015

Familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) are allelic disorders caused by mutations in the CACNA1A gene on chromosome 19p13. It is well described that FHM1 can present with cerebellar signs, but parkinsonism has not previously been reported in FHM1 or EA2 even though parkinsonism has been described in SCA6. We report a 63-year-old woman with FHM1 caused by an R583Q mutation in the CACNA1A gene, clinically presenting with migraine and permanent cerebellar ataxia. Since the age of 60 years, the patient also developed parkinsonism with rigidity, bradykinesia and a resting tremor. An MRI showed a normal substantia nigra, but a bilateral loss of substance in the basal ganglia, which is in contrast to the typically normal MRI in idiopathic Parkinson's disease. Dopamine transporter (DAT) imaging with single-photon emission computed tomography demonstrated a decreased DAT-binding potential in the putamen. We wish to draw attention to FHM1 associated with parkinsonism; however, whether the reported case is a consequence of FHM1 being allelic to SCA6, unknown modifiers to the specific R583Q CACNA1A mutation or idiopathic Parkinson's disease remains unanswered.
Cerebrospinal Fluid Biomarkers in Familial Forms of Alzheimer's Disease and Frontotemporal Dementia
Authors: Rostgaard Nina , Waldemar Gunhild , Nielsen Jørgen Erik , Simonsen Anja Hviid
Published: June 2015

As dementia is a fast-growing health care problem, it is becoming an increasingly urgent need to provide an early diagnosis in order to offer patients the best medical treatment and care. Validated biomarkers which reflect the pathology and disease progression are essential for diagnosis and are important when developing new therapies. Today, the core protein biomarkers amyloid-β42, total tau and phosphorylated tau in the cerebrospinal fluid (CSF) are used to diagnose Alzheimer's disease (AD), because these biomarkers have shown to reflect the underlying amyloid and tau pathology. However, the biomarkers have proved insufficient predictors of dementias with a different pathology, e.g. frontotemporal dementia (FTD); furthermore, the biomarkers are not useful for early AD diagnosis. Familial dementias with a known disease-causing mutation can be extremely valuable to study; yet the biomarker profiles in patients with familial dementias are not clear. This review summarizes CSF biomarker findings from studies on symptomatic and presymptomatic individuals carrying a mutation in one of the genes known to cause early-onset familial AD or FTD. In conclusion, the biomarker profile of inherited AD is quite similar between carriers of different mutations as well as similar to the profile found in sporadic AD, whereas familial FTD does not seem to have a clear biomarker profile. Hence, new biomarkers are needed for FTD.
Various Neurological Symptoms by Neurolymphomatosis as the Initial Presentation of Primary Testicular Lymphoma
Authors: Sunami Yoshitaka , Gotoh Akihiko , Hamano Yasuharu , Yahata Yuriko , Sakurai Hiroko , Shirane Shuichi , Edahiro Yoko , Komatsu Norio
Published: June 2015

Neurological symptoms induced by the infiltration of malignant lymphoma into the nervous systems are subsumed under the term neurolymphomatosis (NL). Here, we report the case of a 30-year-old Japanese man with primary testicular lymphoma complicated, as seen in various neurological findings, by secondary NL prior to testicular swelling. Painless right scrotal enlargement was noticed more than 1 month after the appearance of neurological complications such as right upper extremity numbness, dysarthria, facial palsy, and diplopia. Proactive investigation and biopsies of extranodal sites at high risk of central nervous system infiltration of malignant lymphoma, such as the testes, should be considered when secondary NL is suspected based on imaging findings.
Lambl's Excrescences: Association with Cerebrovascular Disease and Pathogenesis
Authors: Roldan Carlos A. , Schevchuck Oleksandr , Tolstrup Kirsten , Roldan Paola C. , Macias Leonardo , Qualls Clifford R. , Greene Ernest R. , Hayek Reyaad , Charlton Gerald A. , Sibbitt, Jr. Wilmer L.
Published: June 2015

Background: Lambl's excrescences (LEx) are detected by transesophageal echocardiography (TEE) and are characterized as thin, elongated, and hypermobile structures located at the leaflets' coaptation point of the heart valves. The association of LEx with cerebrovascular disease (CVD) is still undefined and yet patients with LEx and suspected CVD receive unproven effective antiplatelet or anticoagulant therapy or even undergo valve surgery. Also, the association of LEx with aging and atherogenic, inflammatory, or thrombogenic parameters has not been reported. Methods: Seventy-seven patients with systemic lupus erythematosus (SLE) (71 women, age 37 ± 12 years) and 26 age- and sex-matched healthy controls (22 women, age 34 ± 11 years) prospectively underwent routine history and physical exam, transcranial Doppler, brain MRI, TEE, carotid duplex, and clinical and laboratory evaluations of atherogenesis, inflammation, platelet activity, coagulation, and fibrinolysis. Subjects without stroke/TIA on enrollment (with and without LEx) had a median follow-up of 57 months. Results: On enrollment, 33 (43%) of 77 patients had CVD manifested as acute stroke/TIA (23 patients), cerebromicroembolism by transcranial Doppler (17 patients), or cerebral infarcts by MRI (14 patients). Mitral or aortic valve LEx were equally frequent in healthy controls (46%) as in patients with and without any CVD (39 and 43%), stroke/TIA (35 and 43%), cerebromicroembolism (41 and 42%), or cerebral infarcts (36 and 43%) (all p ≥ 0.72). Also, other mechanisms for CVD other than LEx such as Libman-Sacks vegetations, patent foramen ovale or interatrial septal aneurysm, aortic or carotid atherosclerosis, or thrombogenesis were found in ≥94% of patients with CVD. In addition, 36 subjects with and 44 without LEx had similar low incidence of stroke/TIA (1 (1.3%) and 2 (2.5%), respectively, p = 1.0) during follow-up. Finally, LEx were not associated with aging, atherogenic risk factors, atherosclerosis, inflammation, or thrombogenesis. Conclusions: In this study, LEx are similarly prevalent in healthy controls and SLE patients, are not associated with CVD, and are not associated with pathogenic risk factors. Therefore, the study findings suggest that LEx may not be cardioembolic substrates, may not represent pathologic valve structures, and may not require therapy.
Parameters Used to Discontinue Dialysis in Acute Kidney Injury Recovery: A Survey of United States Nephrologists
Authors: Mallappallil Mary C. , Mehta Ravindra , Yoshiuchi Ellen , Briefel Gary , Lerma Edgar , Salifu Moro
Published: June 2015

Background: Despite advances in the approach to cure acute kidney injury (AKI), including definition, classification and treatment methods, there are no standard criteria to withdraw dialysis in the setting of improving AKI. We conducted this survey to elucidate parameters that United States (US) nephrologists used to determine when to stop dialysis with improving renal function in AKI. We hypothesized that there would be a difference in approach to weaning a patient off dialysis based on years in practice or the number of cases of AKI treated per year. Methods: This was an anonymous electronic survey of practicing nephrologists who treated AKI. Data was de-identified and analyzed using descriptive statistics. Results: The commonest criteria used to stop dialysis when renal function improved was, in decreasing order of importance, resolution in oliguria (51%), resolution of volume overload (29%), improvement in serum creatinine (26.7%) and resolution of hyperkalemia (21%). The most common reasons for re-starting dialysis within 28 days did not show a specific trend but respondents (20%) reported re-starting if estimated glomerular filtration rates (eGFR) declined. There was no significant pattern in approach to withdrawing dialysis or resuming dialysis based on the number of years in nephrology practice. However, responses of nephrologists who saw more than 20 AKI patients/year were significantly different in stopping dialysis with clinical stabilization of blood pressure (p < 0.001), improvement in respiratory parameters (p = 0.005), improvement in pre-dialysis blood urea nitrogen (BUN) levels despite the same dose of dialysis (p = 0.05) and resolution of oliguria (p = 0.025) compared to those who saw fewer cases. Conclusion: Resolution of oliguria was the commonest factor used to help deciding to stop dialysis in improving AKI. However, considerable variation was noted among US nephrologists who participated in this survey, regarding what criteria they used to withdraw dialysis in the setting of improving AKI. These results call for more studies in withdrawing dialysis in the setting of AKI that could lead to guideline formulation.
Maternal Folate Concentration in Early Pregnancy and Newborn Telomere Length
Authors: Entringer Sonja , Epel Elissa S. , Lin Jue , Blackburn Elizabeth H. , Buss Claudia , Shahbaba Babak , Gillen Daniel L. , Venkataramanan Raman , Simhan Hyagriv N. , Wadhwa Pathik D.
Published: June 2015

Background/Aims: Telomere biology plays a fundamental role in genomic integrity and cell physiology. The newborn setting of telomere length (TL) likely has important implications for telomere dynamics over the lifespan; however, its determinants are poorly understood. Folate is essential for DNA integrity. The maternal compartment is the only source of folate for the developing fetus. We, therefore, tested the hypothesis that variation in maternal folate during pregnancy is associated with newborn TL. Methods: A prospective, longitudinal study was conducted in 119 mother-newborn dyads. Eligible mothers were enrolled at 9.5 (SD ±2.1) weeks gestation and followed through birth. Concentrations of maternal serum folate were measured in the first trimester of pregnancy. Newborn telomere length was measured in cord blood mononuclear cells (CBMC). Results: After accounting for the effects of other established determinants of newborn TL, each 10 ng/ml increase in maternal total folate was associated with a 5.8% increase in median TL (p = 0.03). The median TL in newborns of mother in the lowest quartile of total folate levels was approximately 10% shorter than that of newborns of mothers in the highest folate quartile. Conclusions: Our findings suggest that fetal TL exhibits developmental plasticity, and provide evidence that maternal nutrition may exert a ‘programming' effect on this system.