CD22 CAR T-cell associated hematologic toxicities, endothelial activation and relationship to neurotoxicity.

Background: Hematologic toxicities, including coagulopathy, endothelial activation, and cytopenias, with CD19-targeted chimeric antigen receptor (CAR) T-cell therapies correlate with cytokine release syndrome (CRS) and neurotoxicity severity, but little is known about the extended toxicity profiles of CAR T-cells targeting alternative antigens. This report characterizes hematologic toxicities seen following CD22 CAR T-cells and their relationship to CRS and neurotoxicity.

Methods: We retrospectively characterized hematologic toxicities associated with CRS seen on a phase 1 study of anti-CD22 CAR T-cells for children and young adults with relapsed/refractory CD22+ hematologic malignancies.

Gene-environment interactions increase the risk of paediatric-onset multiple sclerosis associated with household chemical exposures.

Background: We previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis.

Methods: Using a case-control paediatric multiple sclerosis study, gene-environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated.Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of and the absence of and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including (rs2069852), (rs2187163) and (rs7665090).

Mendelian etiologies identified with whole exome sequencing in cerebral palsy.

Objectives: Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single-gene disorders is under-characterized. To explore the genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort of patients with CP.

Methods: We performed comprehensive phenotyping and WES on a prospective cohort of individuals with cryptogenic CP (who meet criteria for CP; have no risk factors), non-cryptogenic CP (who meet criteria for CP; have at least one risk factor), and CP masqueraders (who could be diagnosed with CP, but have regression/progressive symptoms).

Precision and accuracy of hyperglycemic clamps in a multicenter study.

Application of glucose clamp methodologies in multicenter studies brings challenges for standardization. The Restoring Insulin Secretion (RISE) Consortium implemented a hyperglycemic clamp protocol across seven centers using a combination of technical and management approaches to achieve standardization. Two-stage hyperglycemic clamps with glucose targets of 200 mg/dL and >450 mg/dL were performed utilizing a centralized spreadsheet-based algorithm that guided dextrose infusion rates using bedside plasma glucose measurements.

A Phase I and Surgical Study of Ribociclib and Everolimus in Children with Recurrent or Refractory Malignant Brain Tumors: A Pediatric Brain Tumor Consortium Study.

Purpose: Genomic aberrations in cell cycle and PI3K pathways are commonly observed in pediatric brain tumors. This study determined the MTD/recommended phase II dose (RP2D) of ribociclib and everolimus and characterized single-agent ribociclib concentrations in plasma and tumor in children undergoing resection.

Patients And Methods: Patients were enrolled in the phase I study according to a rolling 6 design and received ribociclib and everolimus daily for 21 and 28 days, respectively.

Spinal Epidural Abscess Post Spinal Anesthesia: An Uncommon Complication of a Common Procedure.

Spinal epidural abscess (SEA) is a severe pyogenic infection of the epidural space. Bacteria gain access to the epidural space either by hematogenous spread, contiguous spread from a neighboring infected structure, or through iatrogenic inoculation. The diagnosis of SEA is a challenge, largely because of its rarity.

Association between time of day and CPR quality as measured by CPR hemodynamics during pediatric in-hospital CPR.

Introduction: Patients who suffer in-hospital cardiac arrest (IHCA) are less likely to survive if the arrest occurs during nighttime versus daytime. Diastolic blood pressure (DBP) as a measure of chest compression quality was associated with survival from pediatric IHCA. We hypothesized that DBP during CPR for IHCA is lower during nighttime versus daytime.

Survival and Cardiopulmonary Resuscitation Hemodynamics Following Cardiac Arrest in Children With Surgical Compared to Medical Heart Disease.

Objectives: To assess the association of diastolic blood pressure cutoffs (≥ 25 mm Hg in infants and ≥ 30 mm Hg in children) during cardiopulmonary resuscitation with return of spontaneous circulation and survival in surgical cardiac versus medical cardiac patients. Secondarily, we assessed whether these diastolic blood pressure targets were feasible to achieve and associated with outcome in physiology unique to congenital heart disease (single ventricle infants, open chest), and influenced outcomes when extracorporeal cardiopulmonary resuscitation was deployed.

Design: Multicenter, prospective, observational cohort analysis.

Functional outcomes among survivors of pediatric in-hospital cardiac arrest are associated with baseline neurologic and functional status, but not with diastolic blood pressure during CPR.

Aim: Diastolic blood pressure (DBP) during cardiopulmonary resuscitation (CPR) is associated with survival following pediatric in-hospital cardiac arrest. The relationship between intra-arrest haemodynamics and neurological status among survivors of pediatric cardiac arrest is unknown.

Methods: This study represents analysis of data from the prospective multicenter Pediatric Intensive Care Quality of cardiopulmonary resuscitation (PICqCPR) Study.

Ventilation Rates and Pediatric In-Hospital Cardiac Arrest Survival Outcomes.

Objectives: The objective of this study was to associate ventilation rates during in-hospital cardiopulmonary resuscitation with 1) arterial blood pressure during cardiopulmonary resuscitation and 2) survival outcomes.

Design: Prospective, multicenter observational study.

Setting: Pediatric and pediatric cardiac ICUs of the Collaborative Pediatric Critical Care Research Network.

Association of Blood Pressure Level With Left Ventricular Mass in Adolescents.

Hypertension is associated with left ventricular hypertrophy (LVH), a risk factor for cardiovascular events. Since cardiovascular events in youth are rare, hypertension has historically been defined by the 95th percentile of the normal blood pressure (BP) distribution in healthy children. The optimal BP percentile associated with LVH in youth is unknown.

The association of immediate post cardiac arrest diastolic hypertension and survival following pediatric cardiac arrest.

Aim: In-hospital cardiac arrest occurs in >5000 children each year in the US and almost half will not survive to discharge. Animal data demonstrate that an immediate post-resuscitation burst of hypertension is associated with improved survival. We aimed to determine if systolic and diastolic invasive arterial blood pressures immediately (0-20 min) after return of spontaneous circulation (ROSC) are associated with survival and neurologic outcomes at hospital discharge.

Urban air quality and associations with pediatric multiple sclerosis.

Background: We previously identified air quality as a risk factor of interest for pediatric multiple sclerosis. The purpose of this study is to more closely examine the association between the six criteria air pollutants and pediatric MS as well as identify specific areas of toxic release using data from the Toxic Release Inventory.

Methods: Pediatric MS cases ( = 290) and healthy controls ( = 442) were included as part of an ongoing case-control study.

Chest compression rates and pediatric in-hospital cardiac arrest survival outcomes.

Aim: The primary aim of this study was to evaluate the association between chest compression rates and 1) arterial blood pressure and 2) survival outcomes during pediatric in-hospital cardiopulmonary resuscitation (CPR).

Methods: Prospective observational study of children ≥37 weeks gestation and <19 years old who received CPR in an intensive care unit (ICU) as part of the Pediatric Intensive Care Unit Quality of CPR Study (PICqCPR) of the Collaborative Pediatric Critical Care Research Network (CPCCRN). Arterial blood pressure and compression rate were determined from manually extracted arterial line waveform data during the first 10 min of CPR.

SHIP-AHOY (Study of High Blood Pressure in Pediatrics: Adult Hypertension Onset in Youth).

Although hypertension is identifiable in children and adolescents, there are many knowledge gaps on how to best define and manage high blood pressure in the young. SHIP-AHOY (Study of High Blood Pressure in Pediatrics: Adult Hypertension Onset in Youth) is being conducted to address these knowledge gaps. Five hundred adolescents will be recruited and will undergo ambulatory blood pressure monitoring, echocardiographic, vascular, and cognitive assessments, as well as epigenetic studies to identify mechanisms that underlie the development of hypertensive target organ damage.

Improving outcomes after pediatric cardiac arrest - the ICU-Resuscitation Project: study protocol for a randomized controlled trial.

Background: Quality of cardiopulmonary resuscitation (CPR) is associated with survival, but recommended guidelines are often not met, and less than half the children with an in-hospital arrest will survive to discharge. A single-center before-and-after study demonstrated that outcomes may be improved with a novel training program in which all pediatric intensive care unit staff are encouraged to participate in frequent CPR refresher training and regular, structured resuscitation debriefings focused on patient-centric physiology.

Methods/design: This ongoing trial will assess whether a program of structured debriefings and point-of-care bedside practice that emphasizes physiologic resuscitation targets improves the rate of survival to hospital discharge with favorable neurologic outcome in children receiving CPR in the intensive care unit.

Association Between Diastolic Blood Pressure During Pediatric In-Hospital Cardiopulmonary Resuscitation and Survival.

Background: On the basis of laboratory cardiopulmonary resuscitation (CPR) investigations and limited adult data demonstrating that survival depends on attaining adequate arterial diastolic blood pressure (DBP) during CPR, the American Heart Association recommends using blood pressure to guide pediatric CPR. However, evidence-based blood pressure targets during pediatric CPR remain an important knowledge gap for CPR guidelines.

Methods: All children ≥37 weeks' gestation and <19 years old in Collaborative Pediatric Critical Care Research Network intensive care units with chest compressions for ≥1 minute and invasive arterial blood pressure monitoring before and during CPR between July 1, 2013, and June 31, 2016, were included.

Examining the contributions of environmental quality to pediatric multiple sclerosis.

Background: Multiple sclerosis (MS) is a presumed autoimmune disease caused by genetic and environmental factors. It is hypothesized that environmental exposures (such as air and water quality) trigger the innate immune response thereby activating a pro-inflammatory cascade.

Objective: To examine potential environmental factors in pediatric MS using geographic information systems (GIS).

Review of methods for measuring β-cell function: Design considerations from the Restoring Insulin Secretion (RISE) Consortium.

The Restoring Insulin Secretion (RISE) study was initiated to evaluate interventions to slow or reverse the progression of β-cell failure in type 2 diabetes (T2D). To design the RISE study, we undertook an evaluation of methods for measurement of β-cell function and changes in β-cell function in response to interventions. In the present paper, we review approaches for measurement of β-cell function, focusing on methodologic and feasibility considerations.

NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that occurs in the setting of insulin resistance and increased adiposity. It has rapidly evolved into the most common liver disease seen in the pediatric population and is a management challenge for general pediatric practitioners, subspecialists, and for health systems. In this guideline, the expert committee on NAFLD reviewed and summarized the available literature, formulating recommendations to guide screening and clinical care of children with NAFLD.

Characterizing Early Psychosocial Functioning of Parents of Children with Moderate to Severe Genital Ambiguity due to Disorders of Sex Development.

Purpose: We examined the psychosocial characteristics of parents of children with disorders of sex development at early presentation to a disorders of sex development clinic. Parental anxiety, depression, quality of life, illness uncertainty and posttraumatic stress symptoms were assessed. Additionally we evaluated the relationship of assigned child gender to parental outcomes.

Cardiovascular Risk Factors in Severely Obese Adolescents: The Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) Study.

Importance: Severe obesity is increasingly common in the adolescent population but, as of yet, very little information exists regarding cardiovascular disease (CVD) risks in this group.

Objective: To assess the baseline prevalence and predictors of CVD risks among severely obese adolescents undergoing weight-loss surgery.

Design, Setting, And Participants: A prospective cohort study was conducted from February 28, 2007, to December 30, 2011, at the following 5 adolescent weight-loss surgery centers in the United States: Nationwide Children's Hospital in Columbus, Ohio; Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio; Texas Children's Hospital in Houston; University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania; and Children's Hospital of Alabama in Birmingham.

Neurologic injury in neonates with congenital heart disease during extracorporeal membrane oxygenation: an analysis of extracorporeal life support organization registry data.

The aim of this article is to describe the epidemiology and factors associated with acute neurologic injury in neonates with congenital heart disease (CHD) undergoing extracorporeal membrane oxygenation (ECMO). It is a retrospective cohort study. Multi-institutional data for purposes of this study were obtained from the extracorporeal life support organization registry Neonates with CHD supported with ECMO during 2005-2010.

Survey of the professors of child neurology: neurology versus pediatrics home for child neurology.

Background: The optimal academic home for child neurology programs between adult neurology versus pediatric departments remains an open question. The Professors of Child Neurology, the national organization of child neurology department chairs, division chiefs, and training program directors, was surveyed to evaluate the placement of child neurology programs.

Methods: Professors of Child Neurology members were surveyed regarding the placement of child neurology programs within adult neurology versus pediatric departments.