Effect of methadone on QTc in infants.

Objective: Methadone has been associated with prolongation of the QTc interval (QTc) on electrocardiogram (ECG). In infants, the effects of methadone on the QTc are not well described. Our study's objective is to evaluate the QTc in infants being treated with methadone.

Considerations for treatment duration in responders to immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have improved overall survival for cancer patients, however, optimal duration of ICI therapy has yet to be defined. Given ICIs were first used to treat patients with metastatic melanoma, a condition that at the time was incurable, little attention was initially paid to how much therapy would be needed for a durable response. As the early immunotherapy trials have matured past 10 years, a significant per cent of patients have demonstrated durable responses; it is now time to determine whether patients have been overtreated, and if durable remissions can still be achieved with less therapy, limiting the physical and financial toxicity associated with years of treatment.

Nrf2 through Aryl Hydrocarbon Receptor Regulates IL-22 Response in CD4 T Cells.

IL-17A and IL-22 derived from Th17 cells play a significant role in mucosal immunity and inflammation. TGF-β and IL-6 promote Th17 differentiation; however, these cytokines have multiple targets. The identification and screening of additional molecules that regulate IL-17A and IL-22 responses in certain inflammatory conditions is of great clinical significance.

Design and development of the Pediatric Urology Recovery After Surgery Endeavor (PURSUE) multicentre pilot and exploratory study.

Introduction: Lower urinary tract reconstruction in paediatric urology represents a physiologically stressful event that is associated with high complication rates, including readmissions and emergency room visits. Enhanced recovery after surgery (ERAS) protocol is a set of multidisciplinary, perioperative strategies designed to expedite surgical recovery without adversely impacting readmission or reoperation rates. Early paediatric urology data demonstrated ERAS reduced complications in this population.

Biliary-Atresia-Associated Mannosidase-1-Alpha-2 Gene Regulates Biliary and Ciliary Morphogenesis and Laterality.

Background/aims: Infectious and genetic factors are invoked, respectively in isolated biliary atresia (BA), or syndromic BA, with major extrahepatic anomalies. However, isolated BA is also associated with minor extrahepatic gut and cardiovascular anomalies and multiple susceptibility genes, suggesting common origins.

Methods: We investigated novel susceptibility genes with genome-wide association, targeted sequencing and tissue staining in BA requiring liver transplantation, independent of BA subtype.

Assessing the epidemiology and seasonality of influenza among children under two hospitalized in Amman, Jordan, 2010-2013.

Background: The disease burden of influenza-associated hospitalizations among children in Jordan is not well established. We aimed to characterize hospitalizations attributed to influenza in a pediatric population.

Methods: We conducted a cross-sectional study from our viral surveillance cohort in children under 2 years hospitalized with acute respiratory symptoms and/or fever from March 2010 to March 2013.

Personalising Outcomes after Child Cardiac Arrest (POCCA): design and recruitment challenges of a multicentre, observational study.

Introduction: Blood and imaging biomarkers show promise in prognosticating outcomes after paediatric cardiac arrest in pilot studies. We describe the methods and early recruitment challenges and solutions for an ongoing multicentre (n=14) observational trial, Personalising Outcomes following Child Cardiac Arrest to validate clinical, blood and imaging biomarkers individually and together in a clinically relevant panel.

Methods And Analysis: Children (n=164) between 48 hours and 17 years of age who receive chest compressions irrespective of provider, duration, or event location and are admitted to an intensive care unit are eligible.

Germline-driven replication repair-deficient high-grade gliomas exhibit unique hypomethylation patterns.

Replication repair deficiency (RRD) leading to hypermutation is an important driving mechanism of high-grade glioma (HGG) occurring predominantly in the context of germline mutations in RRD-associated genes. Although HGG presents specific patterns of DNA methylation corresponding to oncogenic mutations, this has not been well studied in replication repair-deficient tumors. We analyzed 51 HGG arising in the background of gene mutations in RRD utilizing either 450 k or 850 k methylation arrays.

Systems Analysis of Biliary Atresia Through Integration of High-Throughput Biological Data.

Biliary atresia (BA), blockage of the proper bile flow due to loss of extrahepatic bile ducts, is a rare, complex disease of the liver and the bile ducts with unknown etiology. Despite ongoing investigations to understand its complex pathogenesis, BA remains the most common cause of liver failure requiring liver transplantation in children. To elucidate underlying mechanisms, we analyzed the different types of high-throughput genomic and transcriptomic data collected from the blood and liver tissue samples of children suffering from BA.

The Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source.

Background & Aims: Calcineurin is a ubiquitously expressed central Ca-responsive signaling molecule that mediates acute pancreatitis, but little is known about its effects. We compared the effects of calcineurin expression by hematopoietic cells vs pancreas in mouse models of pancreatitis and pancreatitis-associated lung inflammation.

Methods: We performed studies with mice with hematopoietic-specific or pancreas-specific deletion of protein phosphatase 3, regulatory subunit B, alpha isoform (PPP3R1, also called CNB1), in mice with deletion of CNB1 (Cnb1) and in the corresponding controls for each deletion of CNB1.

The Pediatric Sinus Staging System: A Computed Tomography-Based Approach to Grading Pediatric Sinus Disease.

Objectives/hypothesis: Pediatric chronic rhinosinusitis (CRS) is a prevalent disease with few objective measurements available to predict which patients will require surgical intervention. The Lund-Mackay (LM) score for computed tomography (CT) scans is one objective data point available for the adult population; however, a dedicated scoring system in the pediatric population has not been popularized. We present a Pediatric Sinus Staging System (PSSS) that considers both opacification and the varying developmental stages of each sinus.

Evaluating the diagnostic accuracy of the WHO Severe Acute Respiratory Infection (SARI) criteria in Middle Eastern children under two years over three respiratory seasons.

Objective: The World Health Organization created the Severe Acute Respiratory Infection (SARI) criteria in 2011 to monitor influenza (flu)-related hospitalization. Many studies have since used the SARI case definition as inclusion criteria for surveillance studies. We sought to determine the sensitivity, specificity, positive predictive value, and negative predictive value of the SARI criteria for detecting ten different respiratory viruses in a Middle Eastern pediatric cohort.

Four Biomarkers Linked to Activation of Cluster of Differentiation 8-Positive Lymphocytes Predict Clinical Outcomes in Pediatric Acute Liver Failure.

Background And Aims: Immune dysregulation contributes to the pathogenesis of pediatric acute liver failure (PALF). Our aim was to identify immune activation markers (IAMs) in PALF that are associated with a distinct clinical phenotype and outcome.

Approach And Results: Among 47 PALF study participants, 12 IAMs collected ≤6 days after enrollment were measured by flow cytometry and IMMULITE assay on blood natural killer and cluster of differentiation 8-positive (CD8 ) lymphocytes and subjected to unsupervised hierarchical analyses.

Advanced practice providers and children's hospital-based pediatric otolarynology practices.

Introduction: Advanced practice providers (APPs), including nurse practitioners and physician assistants, have been deployed in children's hospital-based academic pediatric otolaryngology practices for many years. However, this relationship in terms of prevalence, roles, financial consequences and satisfaction has not been examined. The objective of this study is to explore how APPs impact healthcare delivery in this setting.

Emergent high fatality lung disease in systemic juvenile arthritis.

Objective: To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).

Methods: In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.

Results: LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab.

Health-Related Quality of Life and Cognitive Functioning in Pediatric Liver Transplant Recipients.

The goal of this work was to examine the change in health-related quality of life (HRQOL) and cognitive functioning from early childhood to adolescence in pediatric liver transplantation (LT) recipients. Patients were recruited from 8 North American centers through the Studies of Pediatric Liver Transplantation consortium. A total of 79 participants, ages 11-18 years, previously tested at age 5-6 years in the Functional Outcomes Group study were identified as surviving most recent LT by 2 years and in stable medical follow-up.

Integration of physical abuse clinical decision support at 2 general emergency departments.

Objective: The study sought to develop and evaluate an electronic health record-based child abuse clinical decision support system in 2 general emergency departments.

Materials And Methods: A combination of a child abuse screen, natural language processing, physician orders, and discharge diagnoses were used to identify children <2 years of age with injuries suspicious for physical abuse. Providers received an alert and were referred to a physical abuse order set whenever a child triggered the system.

Pediatric Cranioplasty.

Historically, the approach to pediatric cranioplasty has been largely extrapolated from the treatment of adults. More recently, however, the intricacies of pediatric cranial reconstruction have become better understood, and the surgical management has been refined contemporaneously. Each patient's cranial defect bears a unique set of challenges and, as such, the choice of cranioplasty technique must be tailored accordingly.

Quantifying radiation therapy response using apparent diffusion coefficient (ADC) parametric mapping of pediatric diffuse intrinsic pontine glioma: a report from the pediatric brain tumor consortium.

Background And Purpose: Baseline diffusion or apparent diffusion coefficient (ADC) characteristics have been shown to predict outcome related to DIPG, but the predictive value of post-radiation ADC is less well understood. ADC parametric mapping (FDM) was used to measure radiation-related changes in ADC and compared these metrics to baseline ADC in predicting progression-free survival and overall survival using a large multi-center cohort of DIPG patients (Pediatric Brain Tumor Consortium-PBTC).

Materials And Methods: MR studies at baseline and post-RT in 95 DIPG patients were obtained and serial quantitative ADC parametric maps were generated from diffusion-weighted imaging based on T2/FLAIR and enhancement regions of interest (ROIs).

Functional Repair Assay for the Diagnosis of Constitutional Mismatch Repair Deficiency From Non-Neoplastic Tissue.

Purpose: Constitutional mismatch repair deficiency (CMMRD) is a highly penetrant cancer predisposition syndrome caused by biallelic mutations in mismatch repair (MMR) genes. As several cancer syndromes are clinically similar, accurate diagnosis is critical to cancer screening and treatment. As genetic diagnosis is confounded by 15 or more pseudogenes and variants of uncertain significance, a robust diagnostic assay is urgently needed.