Abstract BACKGROUND Pediatric brain and spinal cord tumors are the leading cause of cancer-related mortality in children. An incomplete understanding of brain tumor biology and associated limited ...access to high-quality biological samples for research are the main factors driving the lack of clinical therapeutic development for pediatric brain tumors that recur or progress. Post-mortem tissue donation provides an unprecedented resource for addressing some of these limitations. METHODS The Gift from a Child (GFAC) program by the Swifty Foundation has a unique mission to increase post-mortem pediatric brain tissue donations through advocacy as well as the education of clinicians and families. Through GFAC’s strategic collaboration with the Children’s Brain Tumor Network (CBTN), CBTN has leveraged postmortem tissue to expand the Pediatric Brain Tumor Atlas (PBTA), a cross-histology multi-omics atlas resource. As part of the effort CBTN has sequenced and released data for over 350 post-mortem pediatric brain tumor specimens including multiple brain region sampling cases with specimen and sequencing quality metrics. RESULTS Here we present an assessment of postmortem samples and available multi-omic data on postmortem samples within the PBTA dataset. Data have been harmonized and released with no publication embargo. To access data, researchers can utilize existing open source data resources and platforms including PedCbioPortal and OpenPedCan to: (1) Identify tumor spatial and temporal specific alterations (2) Establish tumor evolution trajectory leading to therapeutic resistance and tumor progression; (3) Understand tumor heterogeneity longitudinally across multiple ‘omics layers; and (4) Identify and request specimens and derived tumor models. CONCLUSIONS Together, we present the largest deeply characterized cohort of postmortem pediatric brain tumor samples as powerful expansion of the PBTA cohort of >3,000 pediatric brain tumors. CBTN’s open-science model supported by the GFAC mission highlights the value and utility of autopsy-based specimen collection on behalf of improving outcomes for children with brain tumors.
An analysis of composite adverse events, including death, myocardial infarction, stroke, cardiac arrest, new atrial fibrillation, new dialysis, major vascular events, and unplanned vascular surgery, ...revealed that GA patients were 2.2 times more likely to experience a major event than matched CS cohorts. Conclusion Conscious sedation TAVR patients are 2.2 times less likely to experience a major perioperative event compared with patients that undergo general anesthesia with respect to a composite of death, myocardial infarction, stroke, cardiac arrest, new atrial fibrillation, new dialysis, major vascular event, and unplanned vascular surgery.
Genetic variants in pharmacokinetic genes can alter the effectiveness and increase the risks of using analgesics to treat pain. The purpose of this retrospective study is to describe the clinical ...experiences that led to pharmacogenetic testing of pediatric pain management program patients for alterations in the CYP2D6, CYP2C19, and CYP2C9 genes and correlate the analgesic efficacy and adverse analgesic effects with the gene-specific findings and Metabolic Reserve (MR) index.
Nineteen patients were referred for pharmacogenetic testing between February 2010 and December 2013 due to analgesic ineffectiveness or adverse analgesic effects. CYP2D6, CYP2C19, and CYP2C9 functional status was inferred from genotyping; and MR calculated. Data from the available inpatient and outpatient medical records from January 2007 to May 2014 for these patients were reviewed and extracted to characterize patient analgesic response phenotype.
Significant CYP2D6 genetic variants were identified in 16 of the 19 (84%) patients: 4 were ultra-rapid metabolizers, 8 were deficient, 3 were poor metabolizers, and 1 was CYP2D6 null metabolizer. Of the 3 patients with functional CYP2D6 status, 2 were CYP2C19 null metabolizers. The MR scores ranged from 3.0 to 7.0, with a bimodal distribution with high frequencies corresponding to 4.0/4.5 and 7.0.
Clinical evaluation of analgesic ineffectiveness and adverse effects led to the high likelihood of identifying patients with CYP2D6, CYP2C19, and CYP2C9 alleles associated with alterations in analgesic metabolism. Further research is needed to integrate pharmacogenetic and clinical information into anticipatory guidance for pharmacogenetic testing and analgesic prescribing to children with pain.
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