Bi-allelic ATG4D variants are associated with a neurodevelopmental disorder characterized by speech and motor impairment.

Autophagy regulates the degradation of damaged organelles and protein aggregates, and is critical for neuronal development, homeostasis, and maintenance, yet few neurodevelopmental disorders have been associated with pathogenic variants in genes encoding autophagy-related proteins. We report three individuals from two unrelated families with a neurodevelopmental disorder characterized by speech and motor impairment, and similar facial characteristics. Rare, conserved, bi-allelic variants were identified in ATG4D, encoding one of four ATG4 cysteine proteases important for autophagosome biogenesis, a hallmark of autophagy.

Racial and ethnic disparities in childhood and young adult acute lymphocytic leukaemia: secondary analyses of eight Children's Oncology Group cohort trials.

Background: Previous studies have identified racial and ethnic disparities in childhood acute lymphocytic leukaemia survival. We aimed to establish whether disparities persist in contemporaneous cohorts and, if present, are attributable to differences in leukaemia biology or insurance status.

Methods: Patients with newly diagnosed acute lymphocytic leukaemia in inpatient and outpatient centres in the USA, Canada, Australia, and New Zealand, aged 0-30 years, who had race or ethnicity data available, enrolled on eight completed Children's Oncology Group trials (NCT00103285, NCT00075725, NCT00408005, NCT01190930, NCT02883049, NCT02112916, NCT02828358, and NCT00557193) were included in this secondary analysis.

Psychogenic non-epileptic seizures in youth: Individual and family psychiatric characteristics.

Introduction: Youth with psychogenic non-epileptic seizures (PNES) are an understudied group associated with significant medical and psychiatric morbidity. Several studies have examined characteristics associated with youth's development of this disorder, though the exploration of family factors including psychiatric illness, has been lacking. This study sought to establish the need for a more comprehensive future study.

Opinions from the experts: Experiences of adolescents with severe obesity participating in meal replacement therapy.

Background: Meal replacement therapy (MRT) is a structured treatment that is effective for short-term weight reduction in adolescents with severe obesity. However, like other interventions, MRT response is variable.

Objective: The goal of the current study was to characterize the experience of adolescents with severe obesity participating in MRT.

Associations Between Life-Course Lipid Trajectories and Subclinical Atherosclerosis in Midlife.

Importance: Childhood lipid levels have been associated with adult subclinical atherosclerosis; however, life-course lipid trajectories and their associations with cardiovascular disease risk are poorly characterized.

Objectives: To examine the associations of lipid levels at different ages and discrete lipid trajectory patterns from childhood to adulthood with subclinical atherosclerosis in midlife.

Design, Setting, And Participants: This cohort study used data from the Bogalusa Heart Study, a prospective, population-based cohort study conducted in a semirural, biracial community in Bogalusa, Louisiana, with follow-up from 1973 to 2016 (median follow-up, 36.

In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions.

Conventional therapy for hereditary tyrosinemia type-1 (HT1) with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) delays and in some cases fails to prevent disease progression to liver fibrosis, liver failure, and activation of tumorigenic pathways. Here we demonstrate cure of HT1 by direct, in vivo administration of a therapeutic lentiviral vector targeting the expression of a human fumarylacetoacetate hydrolase (FAH) transgene in the porcine model of HT1. This therapy is well tolerated and provides stable long-term expression of FAH in pigs with HT1.

The impact of COVID-19 on disease epidemiology, family dynamics, and social justice in Minnesota: All that you cannot see.

Objective: The COVID-19 pandemic presented a challenge to established seed grant funding mechanisms aimed at fostering collaboration in child health research between investigators at the University of Minnesota (UMN) and Children's Hospitals and Clinics of Minnesota (Children's MN). We created a "rapid response," small grant program to catalyze collaborations in child health COVID-19 research. In this paper, we describe the projects funded by this mechanism and metrics of their success.

Empiric antibiotics for children with suspected Lyme disease.

In our prospective cohort of children undergoing evaluation for non-cutaneous Lyme disease, 02 (13.9% of those with Lyme disease) were not initially treated with an appropriate antibiotics and 356 (13.3% without Lyme disease) received potentially unnecessary antibiotics.

Physical Symptoms, Distress, and Functional Disability in Youth With Chronic Orthostatic Intolerance.

Objective: Youth with chronic orthostatic intolerance (OI) can experience significant physical, social, and academic functional debilitation. Previous studies have indicated associations among symptom severity, psychosocial factors, and functional disability. However, empirically tested models explaining how different medical and psychosocial factors may contribute to functional disability are lacking.

Cardiovascular computed tomography in pediatric congenital heart disease: A state of the art review.

Cardiac computed tomography (CCT) has increasingly been used in the assessment of both children and adults with congenital heart disease (CHD), in part due to advances in CCT technology and an increased prevalence of adults with palliated CHD. It serves as a complimentary modality to echocardiography, cardiac magnetic resonance imaging and cardiac catheterization. CCT can provide unique diagnostic information, is less invasive and less likely to require sedation compared to other modalities.

A pilot study of genomic-guided induction therapy followed by immunotherapy with difluoromethylornithine maintenance for high-risk neuroblastoma.

Background: Survival for patients with high-risk neuroblastoma (HRNB) remains poor despite aggressive multimodal therapies.

Aims: To study the feasibility and safety of incorporating a genomic-based targeted agent to induction therapy for HRNB as well as the feasibility and safety of adding difluoromethylornithine (DFMO) to anti-GD2 immunotherapy.

Methods: Twenty newly diagnosed HRNB patients were treated on this multicenter pilot trial.

Examination of serum metabolome altered by cigarette smoking identifies novel metabolites mediating smoking-BMI association.

Objective: The authors hypothesize that an untargeted metabolomics study will identify novel mechanisms underlying smoking-associated weight loss.

Methods: This study performed cross-sectional analyses among 1,252 participants in the Bogalusa Heart Study and assessed 1,202 plasma metabolites for mediation effects on smoking-BMI associations. Significant metabolites were tested for associations with smoking genetic risk scores among a subset of participants (n = 654) with available genomic data, followed by direction dependence analysis to investigate causal relationships between the metabolites and smoking and BMI.

Pediatric Lyme Disease Presenting as a Ruptured Popliteal Cyst: A Report of 3 Cases.

Cases: This case report describes 3 pediatric patients presenting with acute calf or knee pain, calf swelling, and a ruptured popliteal cyst diagnosed by magnetic resonance imaging. Lyme disease was serologically confirmed in each case. In all instances, treatment was delayed because of atypical presentation.

Sex-based disparities in outcome in pediatric acute lymphoblastic leukemia: a Children's Oncology Group report.

Background: Boys with acute lymphoblastic leukemia (ALL) have historically experienced inferior survival compared to girls. This study determined whether sex-based disparities persist with contemporary therapy and whether patterns of treatment failure vary by sex.

Methods: Patients 1 to 30.

Malnutrition and Pressure Injury Risk in Vulnerable Populations: Application of the 2019 International Clinical Practice Guideline.

Nutrition plays a vital role in promoting skin integrity and supporting tissue repair in the presence of chronic wounds such as pressure injuries (PIs). Individuals who are malnourished are at greater risk of polymorbid conditions, adverse clinical outcomes, longer hospital lengths of stay, PI development, and mortality, and incur increased healthcare costs compared with patients who are adequately nourished. In addition, some patient populations tend to be more vulnerable to PI formation, such as neonates, patients with obesity, older adults, and individuals who are critically ill.

Native Aortic Root Thrombosis in Single-Ventricle Patients with Native-to-Neoaortic Anastomoses.

In single-ventricle patients with native-to-neoaortic anastomoses, the native aortic root serves as a conduit to the coronary arteries. Thrombosis of the native aortic root has been described only in small, limited reports. We described our center's experience with this rare adverse event.

The incidence of recurrent laryngeal nerve injury resulting in vocal cord paralysis following interventional congenital catheterisation procedures.

Background: Recurrent laryngeal nerve injury leading to vocal cord paralysis is a known complication of cardiothoracic surgery. Its occurrence during interventional catheterisation procedures has been documented in case reports, but there have been no studies to determine an incidence.

Objective: To establish the incidence of left recurrent laryngeal nerve injury leading to vocal cord paralysis after left pulmonary artery stenting, patent ductus arteriosus device closure and the combination of the procedures either consecutively or simultaneously.

A Standardized Peer Review Program Improves Assessment and Documentation of Child Sexual Abuse.

Introduction: The objective was to assess the impact of interventions associated with ongoing expert peer review on the quality of child abuse medical providers' written and photograph documentation in child sexual abuse cases.

Methods: Pediatricians participated in a HIPAA compliant blind peer review process on a web platform developed to provide the American Board of Pediatrics maintenance of certification. Participants submit sequential photograph and written documentation of child sexual abuse examinations over 1 year.

Oral Aversion in Infants With Congenital Heart Disease: A Single-Center Retrospective Cohort Study.

Objectives: Neonates undergoing cardiac surgery are at risk for oral aversion (OA). OA is not well described outside of the index hospitalization and impacts patients and families. We evaluated the prevalence of OA at 1 year old after neonatal cardiopulmonary bypass (CPB) surgery.

Intubation practice and outcomes among pediatric emergency departments: A report from National Emergency Airway Registry for Children (NEAR4KIDS).

Background: Tracheal intubation (TI) practice across pediatric emergency departments (EDs) has not been comprehensively reported. We aim to describe TI practice and outcomes in pediatric EDs in contrast to those in intensive are units (ICUs) and use the data to identify quality improvement targets.

Methods: Consecutive TI encounters from pediatric EDs and ICUs in the National Emergency Airway Registry for Children (NEAR4KIDS) database from 2015 to 2018 were analyzed for patient, provider, and practice characteristics and outcomes: adverse TI-associated events (TIAEs), oxygen desaturation (SpO < 80%), and procedural success.