Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Localized bullous eruptions away from infusion site due to intravenous acyclovir administration in a child

Acyclovir is an antiviral agent against herpes virus. Its local adverse effects are common and typically consist of inflammation or phlebitis at the site of intravenous infusion. Here we present a child with bullous eruptions away from infusion site due to acyclovir administration. It is exceptionally rare with only one adult case has been reported to date

Cranial Magnetic Resonance Imaging Findings in Patients with Indirect Hyperbilirubinemia

Abstract Purpose: To describe the magnetic resonance imaging (MRI) changes in the patients with indirect hyperbilirubinemia. Methods: MRI findings of eighteen neonates with indirect hyperbilirubinemia were reported by us. The differences in imaging, clinical and biochemical data between three groups were evaluated statistically. Results: Peak bilirubin levels were between 20 and 24 mg per deciliter in 5 of the newborns (group 1), 25 and 29 mg per deciliter in 6 of the newborns (group 2) and 30 mg per deciliter or more in 7 newborns (group 3). There was statistically significant difference between the neurological findings and MRI findings of the patients between three groups. Conclusion: We always demonstrated MRI changes in the patients with kernicterus. Firstly, T1 weighted changes were described in patients with hyperbilirubinemia despite normal neurological examinations. Larger studies with clinical follow up are needed for further understanding of toxic effect of bilirubin in brain. Key words: Ozet [Cukurova Med J 2012; 37(3.000): 139-145

Early extracorporeal life support experiences in 2 tertiary pediatric intensive care units in Turkey

WOS: 000343068800009PubMed ID: 25539543Background/aim: Extracorporeal membrane oxygenation (ECMO) is a unique life-support modality offered to patients unresponsive to optimal medical therapy. The aim of this study was to evaluate early experiences with ECMO support in 2 tertiary Turkish pediatric intensive care units (PICUs). Materials and methods: We retrospectively evaluated a total of 10 ECMO-supported patients between March 2012 and March 2013 in Marmara and Ege University Hospital PICUs. We reported data regarding demographics, laboratory and diagnostic information, and the clinical course of the patients. Results: The study consisted of 6 males and 4 females from 5 months to 14 years of age (mean age: 0.5 +/- 5.01 years) supported with ECMO. Out of the 10 patients, 8 were on venovenous ECMO for respiratory failure and 2 received venoarterial ECMO for cardiac failure. Mean ECMO and intensive care duration was 11.1 +/- 7.3 days and 23.5 +/- 17.8 days, respectively. Bleeding was the most common complication (60%). Forty percent of the patients were weaned from ECMO, among which 50% were discharged in good health without sequelae. Conclusion: Initial experiences build the learning curve of institutions, and our early results are encouraging. Giving time to heal to the right patient at the right time is the key to success

The prevalance of and factors associated with intra-abdominal hypertension on admission Day in critically Ill pediatric patients: A multicenter study

Purpose: To investigate admission prevalence of intraabdominal hypertension (IAH) and to determine clinical and laboratory characteristics on admission day associated with IAH in critically ill pediatric patients

Critically ill children with pandemic influenza (H1N1) in pediatric intensive care units in Turkey

WOS: 000299073000003PubMed ID: 21263368Objectives: To outline the epidemiologic features, clinical presentation, clinical courses, and outcomes in critically ill children with pandemic influenza in pediatric intensive care units. Design: Retrospective, observational, multicenter study. Setting: Thirteen tertiary pediatric intensive care units in Turkey. Patients: Eighty-three children with confirmed infection attributable to pandemic influenza detected by reverse-transcriptase polymerase chain reaction assay between November 1 and December 31, 2009 who were admitted to critical care units. Interventions: None. Measurements and Main Results: During a 2-month period, 532 children were hospitalized with pandemic influenza and 83 (15.6%) needed critical care. For the 83 patients requiring critical care, the median age was 42 (range, 2-204) months, with 24 (28.9%) and 48 (57.8%) of patients younger than 2 and 5 yrs, respectively. Twenty (24.1%) patients had no underlying illness, but 63 (75.9%) children had an underlying chronic illness. Indications for admission to the pediatric intensive care unit were respiratory failure in 66 (79.5%), neurologic deterioration in six (7.2%), and gastrointestinal symptoms in five (6.0%) patients. Acute lung injury was diagnosed in 23 (27.7%), acute respiratory distress syndrome was diagnosed in 34 (41%), and 51 (61.4%) patients were mechanically ventilated. Oseltamivir was used in 80 (96%) patients. The mortality rate for children with pandemic influenza 2009 was 30.1% compared to an overall mortality rate of 13.7% (p = .0016) among pediatric intensive care unit patients without pandemic influenza during the study period. Also, the mortality rate was 31.7% in patients with comorbidities and 25.0% in previously healthy children (p = .567). The cause of death was primary pandemic influenza infection in 16 (64%), nosocomial infection in four (16%), and primary disease progression in five (20%) patients. The odds ratio for respiratory failure was 14.7 (95% confidence interval, 1.85-111.11), and odds ratio for mechanical ventilation was 27.7 (95% confidence interval, 0.003-200). Conclusions: Severe disease and high mortality rates were seen in children with pandemic influenza. Death attributable to pandemic influenza occurred in all age groups of children with or without underlying illness. Multiple organ dysfunction syndrome is associated with increased mortality, and death is frequently secondary to severe lung infection caused by pandemic influenza. (Pediatr Crit Care Med 2012; 13:e11-e17

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research