Hemolytic Uremic Syndrome Caused by Enteroviral Infection

A 4-year-old boy presented with enteroviral infection complicated with atypical hemolytic uremic syndrome (aHUS). Enterovirus RNA was detected by reverse transcription polymerase chain reaction (RT-PCR) of both blood and kidney biopsy specimens. A survey of the complement system did not reveal a specific complement defect. Supportive therapy with blood components transfusion, plasma therapy, and immunosuppressants was administered, however, renal function did not recover. The results of this report demonstrate that the enterovirus is the cause of aHUS

Can Machine Learning Models Predict Asparaginase-associated Pancreatitis in Childhood Acute Lymphoblastic Leukemia

Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved.Asparaginase-associated pancreatitis (AAP) frequently affects children treated for acute lymphoblastic leukemia (ALL) causing severe acute and persisting complications. Known risk factors such as asparaginase dosing, older age and single nucleotide polymorphisms (SNPs) have insufficient odds ratios to allow personalized asparaginase therapy. In this study, we explored machine learning strategies for prediction of individual AAP risk. We integrated information on age, sex, and SNPs based on Illumina Omni2.5exome-8 arrays of patients with childhood ALL (N=1564, 244 with AAP aged 1.0 to 17.9 y) from 10 international ALL consortia into machine learning models including regression, random forest, AdaBoost and artificial neural networks. A model with only age and sex had area under the receiver operating characteristic curve (ROC-AUC) of 0.62. Inclusion of 6 pancreatitis candidate gene SNPs or 4 validated pancreatitis SNPs boosted ROC-AUC somewhat (0.67) while 30 SNPs, identified through our AAP genome-wide association study cohort, boosted performance (0.80). Most predictive features included rs10273639 (PRSS1-PRSS2), rs10436957 (CTRC), rs13228878 (PRSS1/PRSS2), rs1505495 (GALNTL6), rs4655107 (EPHB2) and age (1 to 7 y). Second AAP following asparaginase re-exposure was predicted with ROC-AUC: 0.65. The machine learning models assist individual-level risk assessment of AAP for future prevention trials, and may legitimize asparaginase re-exposure when AAP risk is predicted to be low.Peer reviewe

Clinical characteristics and risk behavior as a function of HIV status among heroin users enrolled in methadone treatment in northern Taiwan

<p>Abstract</p> <p>Background</p> <p>Methadone treatment was introduced in Taiwan in 2006 as a harm-reduction program in response to the human immunodeficiency virus (HIV), which is endemic among Taiwanese heroin users. The present study was aimed at examining the clinical and behavioral characteristics of methadone patients in northern Taiwan according to their HIV status.</p> <p>Methods</p> <p>The study was conducted at four methadone clinics. Participants were patients who had undergone methadone treatment at the clinics and who voluntarily signed a consent form. Between August and November 2008, each participant completed a face-to-face interview that included questions on demographics, risk behavior, quality of life, and psychiatric symptoms. Data on HIV and hepatitis C virus (HCV) infections, methadone dosage, and morphine in the urine were retrieved from patient files on the clinical premises, with permission of the participants.</p> <p>Results</p> <p>Of 576 participants, 71 were HIV positive, and 514 had hepatitis C. There were significant differences between the HIV-positive and HIV-negative groups on source of treatment payment, HCV infection, urine test results, methadone dosage, and treatment duration. The results indicate that HIV-negative heroin users were more likely to have sexual intercourse and not use condoms during the 6 months prior to the study. A substantial percent of the sample reported anxiety (21.0%), depression (27.2%), memory loss (32.7%), attempted suicide (32.7%), and administration of psychiatric medications (16.1%). There were no significant differences between the HIV-positive and HIV-negative patients on psychiatric symptoms or quality of life.</p> <p>Conclusions</p> <p>HIV-positive IDUs were comorbid with HCV, indicating the need to refer both HIV- and HCV-infected individuals for treatment in methadone clinics. Currently, there is a gap between psychiatric/psychosocial services and patient symptoms, and more integrated medical services should be provided to heroin-using populations.</p

Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts

<p>Abstract</p> <p>Background</p> <p>To investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.</p> <p>Methods</p> <p>A total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.</p> <p>Results</p> <p>We newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/μl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/μl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/μl, p = 0.004).</p> <p>Conclusions</p> <p>TLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.</p

SEPTIN12 Genetic Variants Confer Susceptibility to Teratozoospermia

It is estimated that 10–15% of couples are infertile and male factors account for about half of these cases. With the advent of intracytoplasmic sperm injection (ICSI), many infertile men have been able to father offspring. However, teratozoospermia still remains a big challenge to tackle. Septins belong to a family of cytoskeletal proteins with GTPase activity and are involved in various biological processes e.g. morphogenesis, compartmentalization, apoptosis and cytokinesis. SEPTIN12, identified by c-DNA microarray analysis of infertile men, is exclusively expressed in the post meiotic male germ cells. Septin12+/+/Septin12+/− chimeric mice have multiple reproductive defects including the presence of immature sperm in the semen, and sperm with bent neck (defect of the annulus) and nuclear DNA damage. These facts make SEPTIN12 a potential sterile gene in humans. In this study, we sequenced the entire coding region of SEPTIN12 in infertile men (n = 160) and fertile controls (n = 200) and identified ten variants. Among them is the c.474 G>A variant within exon 5 that encodes part of the GTP binding domain. The variant creates a novel splice donor site that causes skipping of a portion of exon 5, resulting in a truncated protein lacking the C-terminal half of SEPTIN12. Most individuals homozygous for the c.474 A allele had teratozoospermia (abnormal sperm <14%) and their sperm showed bent tail and de-condensed nucleus with significant DNA damage. Ex vivo experiment showed truncated SEPT12 inhibits filament formation in a dose-dependent manner. This study provides the first causal link between SEPTIN12 genetic variant and male infertility with distinctive sperm pathology. Our finding also suggests vital roles of SEPT12 in sperm nuclear integrity and tail development

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)