Protein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases.

Background: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies.

Management of Lateral Condyle Humeral Fracture Associated With Elbow Dislocation in Children. A Retrospective International Multicenter Cohort Study.

Objectives: Lateral humeral condyle fractures account for 12% to 17% of all distal humerus fractures in children, and usually occur as an isolated injury or are associated with radial neck and/or proximal ulna fractures. The presentation with a concomitant dislocation of the elbow is rare. Therefore, literature on young patients with this uncommon combination is sparse and mostly limited to case reports and small case series.

Identification of therapeutic sensitivities in a spheroid drug combination screen of Neurofibromatosis Type I associated High Grade Gliomas.

Neurofibromatosis Type 1 (NF1) patients develop an array of benign and malignant tumors, of which Malignant Peripheral Nerve Sheath Tumors (MPNST) and High Grade Gliomas (HGG) have a dismal prognosis. About 15-20% of individuals with NF1 develop brain tumors and one third of these occur outside of the optic pathway. These non-optic pathway gliomas are more likely to progress to malignancy, especially in adults.

Clinician-reported childbirth outcomes, patient-reported childbirth trauma, and risk for postpartum depression.

Childbirth trauma is common and increases risk for postpartum depression (PPD). However, we lack brief measures to reliably identify individuals who experience childbirth trauma and who may be at greater prospective risk for PPD. To address this gap, we used data from a racially diverse prospective cohort (n=1082).

Cardiac crises: Cardiac arrhythmias and cardiomyopathy during TANGO2 deficiency related metabolic crises.

Background: TANGO2 deficiency disorder (TDD) is an autosomal recessive disease associated with metabolic crisis, lethal cardiac arrhythmias, and cardiomyopathy. Data regarding treatment, management, and outcomes of cardiac manifestations of TDD are lacking.

Objective: The purpose of this study was to describe TDD-related cardiac crises.

Association of COVID-19 and Endemic Systemic Racism With Postpartum Anxiety and Depression Among Black Birthing Individuals.

Importance: The intersection of endemic structural racism and the global health crisis secondary to the COVID-19 pandemic represents a syndemic, defined as the aggregation of 2 or more endemic and epidemic conditions leading to adverse repercussions for health. Long-standing inequities have placed Black individuals at disproportionate risk for negative postpartum mental health outcomes. Studies are urgently needed to understand how the COVID-19 pandemic has added to this risk (eg, syndemic associations).

Fractures of the lateral condyle of the humerus associated with elbow dislocation in children. A systematic review of the literature.

Background: Lateral humeral condyle fractures are the second most common fracture around the elbow in children. However, the association of an elbow dislocation is a rare entity. Therefore, literature on young patients with this uncommon combination is sparse.

Radial Width of the Lateral Meniscus at the Popliteal Hiatus: Relevance to Saucerization of Discoid Lateral Menisci.

Background: A discoid lateral meniscus (DLM) is a congenital anomaly of the knee in which the lateral meniscus has an "O" shape and contains irregular, abnormal collagenous tissue. A DLM can cause mechanical symptoms and pain. Treatment of a symptomatic DLM is arthroscopic saucerization to reshape the meniscus to a more normal contour.

An update on the US adult thalassaemia population: a report from the CDC thalassaemia treatment centres.

Thalassaemia is caused by genetic globin defects leading to anaemia, transfusion-dependence and comorbidities. Reduced survival and systemic organ disease affect transfusion-dependent thalassaemia major and thalassaemia intermedia. Recent improvements in clinical management have reduced thalassaemia mortality.

Laparoscopic Surgery Requiring Abdominal Insufflation in Patients With Congenital Heart Disease.

Objective: To determine if patients with congenital heart disease are undergoing laparoscopic surgery requiring abdominal insufflation and to compare the outcomes of these procedures with those who underwent an open surgical approach.

Design, Setting, Participants: This was a retrospective study using the National Inpatient Sample from 2006 to 2014. Individuals with congenital heart disease who underwent at least one of six selected surgical procedures (laparoscopic or open) were included in the study.

Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Children With Chronic HCV: Part 2 of the DORA Study.

Background And Aims: Glecaprevir/pibrentasvir (GLE/PIB) has shown high efficacy and safety in chronic HCV-infected adults and adolescents; data in children were limited. DORA part 2 is a phase 2/3, nonrandomized, open-label study evaluating the pharmacokinetics, efficacy, and safety of a pediatric formulation of GLE and PIB in children ages 3 to < 12 years.

Approach And Results: Children with chronic HCV infection, genotype 1-6, with or without compensated cirrhosis, were divided into three cohorts by age-cohort 2 (9 to < 12 years), cohort 3 (6 to < 9 years), and cohort 4 (3 to < 6 years)-and given weight-based doses of GLE and PIB for 8, 12, or 16 weeks.

International Pediatric Otolaryngology group (IPOG) consensus on the diagnosis and management of pediatric obstructive sleep apnea (OSA).

Objective: To develop an expert-based consensus of recommendations for the diagnosis and management of pediatric obstructive sleep apnea.

Methods: A two-iterative Delphi method questionnaire was used to formulate expert recommendations by the members of the International Pediatric Otolaryngology Group (IPOG).

Results: Twenty-six members completed the survey.

Identification of a Novel Oleic Acid Analog with Protective Effects in Multiple Cellular Models of Friedreich Ataxia.

Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder for which there is no cure or approved treatment. It is characterized by the loss or impaired activity of frataxin protein, which is involved in the biogenesis of iron-sulfur clusters. Our previous studies suggested that cell death in FRDA may involve ferroptosis, an iron-dependent form of cell death requiring lipid peroxidation.

Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction.

Primary resistance to CD19-directed chimeric antigen receptor T-cell therapy (CART19) occurs in 10% to 20% of patients with acute lymphoblastic leukemia (ALL); however, the mechanisms of this resistance remain elusive. Using a genome-wide loss-of-function screen, we identified that impaired death receptor signaling in ALL led to rapidly progressive disease despite CART19 treatment. This was mediated by an inherent resistance to T-cell cytotoxicity that permitted antigen persistence and was subsequently magnified by the induction of CAR T-cell functional impairment.

A Phase II randomized controlled trial for lung and diaphragm protective ventilation (Real-time Effort Driven VENTilator management).

Lung Protective Mechanical Ventilation (MV) of critically ill adults and children is lifesaving but it may decrease diaphragm contraction and promote Ventilator Induced Diaphragm Dysfunction (VIDD). An ideal MV strategy would balance lung and diaphragm protection. Building off a Phase I pilot study, we are conducting a Phase II controlled clinical trial that seeks to understand the evolution of VIDD in critically ill children and test whether a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)) can balance lung and diaphragm protective ventilation to reduce time on MV.

Serial Magnetic Resonance Imaging (MRI) in Pyruvate Dehydrogenase Complex Deficiency.

Objectives: To report 2 additional cases of pyruvate dehydrogenase complex deficiency with reversible deep gray matter lesions following initiation of ketogenic diet and to perform a literature review of serial imaging in patients with pyruvate dehydrogenase complex.

Methods: Clinical data on 3 previously unpublished cases of patients with pyruvate dehydrogenase complex deficiency and with serial magnetic resonance imagings (MRIs) before and after institution of ketogenic diet were reported. A systematic literature review was performed to search for published cases of patients with confirmed pyruvate dehydrogenase complex deficiency who underwent serial MRIs.

Comparison of echocardiographic measurements to invasive measurements of diastolic function in infants with single ventricle physiology: a report from the Pediatric Heart Network Infant Single Ventricle Trial.

Background: While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.

Methods: Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed.

Chest ultrasound compared to chest X-ray for pediatric pulmonary tuberculosis.

Introduction: Chest ultrasound is increasingly used to radiologically diagnose childhood pneumonia, but there are limited data on its use for pulmonary tuberculosis (PTB).

Aim: Compare chest ultrasound with a chest X-ray (CXR) findings.

Methods: Children (up to 13 years) with suspected PTB were enrolled.

Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis.

FOXN1 is the master regulatory gene of thymic epithelium development. FOXN1 deficiency leads to thymic aplasia, alopecia, and nail dystrophy, accounting for the nude/severe combined immunodeficiency (nu/SCID) phenotype in humans and mice. We identified several newborns with low levels of T cell receptor excision circles (TRECs) and T cell lymphopenia at birth, who carried heterozygous loss-of-function FOXN1 variants.

Epidemiology of Serious Bacterial Infections in Infants Less Than 90 Days in a Military Health System Cohort.

Background: Management of suspected serious bacterial infections (SBIs) in infants less than 3 months old is challenging. Understanding the epidemiology of SBI is necessary to inform management decisions. Recent publications have challenged the previously accepted distribution of infections by specimen source and pathogen.

Lessons learned in the use of clinical registry data in a multi-centre prospective study: the Pediatric Heart Network Residual Lesion Score Study.

Background: Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.

Objectives: We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders' perspectives, and provide recommendations to guide future studies using this methodology.

Biomarkers of oxidative stress, inflammation, and vascular dysfunction in inherited cystathionine β-synthase deficient homocystinuria and the impact of taurine treatment in a phase 1/2 human clinical trial.

Study Objective: A phase 1/2 clinical trial was performed in individuals with cystathionine β synthase (CBS) deficient homocystinuria with aims to: (a) assess pharmacokinetics and safety of taurine therapy, (b) evaluate oxidative stress, inflammation, and vascular function in CBS deficiency, and (c) evaluate the impact of short-term taurine treatment.

Methods: Individuals with pyridoxine-nonresponsive CBS deficiency with homocysteine >50 μM, without inflammatory disorder or on antioxidant therapy were enrolled. Biomarkers of oxidative stress and inflammation, endothelial function (brachial artery flow-mediated dilation [FMD]), and disease-related metabolites obtained at baseline were compared to normal values.

Ferroptosis as a Novel Therapeutic Target for Friedreich's Ataxia.

Friedreich ataxia (FRDA) is a progressive neuro- and cardio-degenerative disorder characterized by ataxia, sensory loss, and hypertrophic cardiomyopathy. In most cases, the disorder is caused by GAA repeat expansions in the first introns of both alleles of the gene, resulting in decreased expression of the encoded protein, frataxin. Frataxin localizes to the mitochondrial matrix and is required for iron-sulfur-cluster biosynthesis.

Chest ultrasound findings in children with suspected pulmonary tuberculosis.

Introduction: Chest ultrasound is increasingly used for the diagnosis of pediatric lung disease but there are limited data for its use in pediatric pulmonary tuberculosis (PTB).

Aim: To describe chest ultrasound findings in children with suspected PTB.

Methods: Consecutive children, presenting with suspected PTB to a tertiary children's hospital in Cape Town between July 2014 and March 2016, were enrolled in this cohort study.