Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

Objective: To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.

A Noncoding Variant Associated with Complex Microphthalmia Alters a Putative Regulatory Element.

Retinoic acid receptor beta () is a transcriptional regulator crucial for coordinating retinoic acid- (RA-) mediated morphogenic movements, cell growth, and differentiation during eye development. Loss- or gain-of-function coding variants have been associated with microphthalmia, coloboma, and anterior segment defects. We identified a variant c.

The Role of Pediatric Psychologists in Critical Care: Lessons Learned and Future Directions in Integrating Mental Health Care Into PICUs.

Pediatric psychologists are essential staff in the PICU. Their role in caring for critically ill children aligns with clinical practice guidelines for the mental health care needs of this population of patients. This article highlights the role of pediatric psychology in the PICU through illustrative case examples.

School age and adolescent heart failure following the Norwood procedure.

Background: Heart failure results in significant morbidity and mortality for young children with hypoplastic left heart syndrome (HLHS) following the Norwood procedure. The trajectory in later childhood is not well described.

Methods: We studied the outcome into adolescence of participants enrolled in the Single Ventricle Reconstruction trial who underwent the Fontan procedure or survived to 6 years without having undergone Fontan procedure.

CUX1-related neurodevelopmental disorder: deep insights into phenotype-genotype spectrum and underlying pathology.

Heterozygous, pathogenic CUX1 variants are associated with global developmental delay or intellectual disability. This study delineates the clinical presentation in an extended cohort and investigates the molecular mechanism underlying the disorder in a Cux1 mouse model. Through international collaboration, we assembled the phenotypic and molecular information for 34 individuals (23 unpublished individuals).

Mathematical analysis of hemoglobin target in univentricular parallel circulation.

Objective: The hemoglobin threshold for a decision to transfuse red blood cells in univentricular patients with parallel circulation is unclear. A pediatric expertise initiative put forth a "weak recommendation" for avoiding reflexive transfusion beyond a hemoglobin of 9 g/dL. We have created a mathematical model to assess the impact of hemoglobin thresholds in patients with parallel circulation.

CRISPR-Cas9-mediated functional dissection of the foxc1 genomic region in zebrafish identifies critical conserved cis-regulatory elements.

FOXC1 encodes a forkhead-domain transcription factor associated with several ocular disorders. Correct FOXC1 dosage is critical to normal development, yet the mechanisms controlling its expression remain unknown. Together with FOXQ1 and FOXF2, FOXC1 is part of a cluster of FOX genes conserved in vertebrates.

Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches.

Congenital PAX6-aniridia, initially characterized by the absence of the iris, has progressively been shown to be associated with other developmental ocular abnormalities and systemic features making congenital aniridia a complex syndromic disorder rather than a simple isolated disease of the iris. Moreover, foveal hypoplasia is now recognized as a more frequent feature than complete iris hypoplasia and a major visual prognosis determinant, reversing the classical clinical picture of this disease. Conversely, iris malformation is also a feature of various anterior segment dysgenesis disorders caused by PAX6-related developmental genes, adding a level of genetic complexity for accurate molecular diagnosis of aniridia.

Cumulative comorbid conditions influence mortality risk after staged palliation for hypoplastic left heart syndrome and variants.

Objective: Prematurity, low birth weight, genetic syndromes, extracardiac conditions, and secondary cardiac lesions are considered high-risk conditions associated with mortality after stage 1 palliation. We report the impact of these conditions on outcomes from a prospective multicenter improvement collaborative.

Methods: The National Pediatric Cardiology Quality Improvement Collaborative Phase II registry was queried.

A Mixed-Methods Study of Experiences During Pregnancy Among Black Women During the COVID-19 Pandemic.

Pregnant women experienced disruptions in their prenatal care during the coronavirus disease-2019 (COVID-19) pandemic. While there is emerging research about the impact of COVID-19 on experiences of pregnancy, the majority of studies that have reported on prenatal care and birth during COVID-19 have not incorporated the first-person accounts of Black women. The purpose of this mixed-methods study was to explore the perspectives of Black women on prenatal care, labor, and birth during the pandemic.

Factorial Analysis Quantifies the Effects of Pediatric Discharge Bundle on Hospital Readmission.

Background And Objectives: Factorial design of a natural experiment was used to quantify the benefit of individual and combined bundle elements from a 4-element discharge transition bundle (checklist, teach-back, handoff to outpatient providers, and postdischarge phone call) on 30-day readmission rates (RRs).

Methods: A 2 factorial design matrix of 4 bundle element combinations was developed by using patient data ( = 7725) collected from January 2014 to December 2017 from 4 hospitals. Patients were classified into 3 clinical risk groups (CRGs): no chronic disease (CRG1), single chronic condition (CRG2), and complex chronic condition (CRG3).

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

Background: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis.

Methods: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites.

Comprehensive phenotypic and functional analysis of dominant and recessive FOXE3 alleles in ocular developmental disorders.

The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles.

Voluntary wheel running complements microdystrophin gene therapy to improve muscle function in mdx mice.

We tested the hypothesis that voluntary wheel running would complement microdystrophin gene therapy to improve muscle function in young mdx mice, a model of Duchenne muscular dystrophy. mdx mice injected with a single dose of AAV9-CK8-microdystrophin or vehicle at age 7 weeks were assigned to three groups: mdxRGT (run, gene therapy), mdxGT (no run, gene therapy), or mdx (no run, no gene therapy). Wild-type (WT) mice were assigned to WTR (run) and WT (no run) groups.

Appendectomy Versus Observation for Appendicitis in Neutropenic Children With Cancer.

Background: Optimal management of neutropenic appendicitis (NA) in children undergoing cancer therapy remains undefined. Management strategies include upfront appendectomy or initial nonoperative management. We aimed to characterize the effect of management strategy on complications and length of stay (LOS) and describe implications for chemotherapy delay or alteration.

Utilizing Near-Infrared Spectroscopy (NIRS) to Identify Pediatric Trauma Patients Needing Lifesaving Interventions (LSIs): A Retrospective Study.

Objectives: The aim of this study was to investigate the role of near-infrared spectroscopy (NIRS) in identifying pediatric trauma patients who required lifesaving interventions (LSIs).

Methods: Retrospective chart review of children age 0 to 18 years who activated the trauma team response between January 1, 2015 and August 14, 2017, at a large, urban pediatric emergency department. The lowest somatic NIRS saturation and the need for LSIs (based on published consensus definition) were abstracted from the chart.

Disruption of foxc1 genes in zebrafish results in dosage-dependent phenotypes overlapping Axenfeld-Rieger syndrome.

The Forkhead Box C1 (FOXC1) gene encodes a forkhead/winged helix transcription factor involved in embryonic development. Mutations in this gene cause dysgenesis of the anterior segment of the eye, most commonly Axenfeld-Rieger syndrome (ARS), often with other systemic features. The developmental mechanisms and pathways regulated by FOXC1 remain largely unknown.

Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome.

Objective: To test whether variants in ADRB1 and CYP2C9 genes identify subgroups of individuals with differential response to treatment for Marfan syndrome through analysis of data from a large, randomized trial.

Study Design: In a subset of 250 white, non-Hispanic participants with Marfan syndrome in a prior randomized trial of atenolol vs losartan, the common variants rs1801252 and rs1801253 in ADRB1 and rs1799853 and rs1057910 in CYP2C9 were analyzed. The primary outcome was baseline-adjusted annual rate of change in the maximum aortic root diameter z-score over 3 years, assessed using mixed effects models.

Review of the impact of donor characteristics on pediatric heart transplant outcomes.

Heart transplantation (HTx) is a treatment option for end-stage heart failure in children. HTx is limited by the availability and acceptability of donor hearts. Refusal of donor hearts has been reported to be common with reasons for refusal including preexisting donor characteristics.

Evolving understanding of total artificial heart support of young infants and children.

Background: We have developed a new method of total artificial heart (TAH) support for young patients, and here share our preliminary results and evolving understanding.

Methods: This report is a retrospective chart review of all patients <10 kg who received a TAH at our institution from May 2017 to the time of this report.

Results: Our cohort includes 5 patients.