Clinical management guidelines for Friedreich ataxia: best practice in rare diseases.

Background: Individuals with Friedreich ataxia (FRDA) can find it difficult to access specialized clinical care. To facilitate best practice in delivering healthcare for FRDA, clinical management guidelines (CMGs) were developed in 2014. However, the lack of high-certainty evidence and the inadequacy of accepted metrics to measure health status continues to present challenges in FRDA and other rare diseases.

Accelerating improvement: The Pediatric Acute Care Cardiology Collaborative data timeliness project.

Background: The Pediatric Acute Care Cardiology Collaborative (PAC3) is a learning network focused on improving acute care cardiology patient outcomes. Data submission timeliness is a vulnerability for PAC3 and most clinical registries, directly affecting collaborative benchmarking, quality improvement (QI) and research projects.

Objective: PAC3 conducted a collaborative-wide QI project addressing data timeliness and efficiency.

Assessing Effective Practices and Barriers to Creating School and Community Partnerships for a Sudden Cardiac Death Prevention Program: A National Project ADAM® study.

Objectives: Project ADAM (Automated Defibrillators in Adam's Memory) is a national collaborative to improve outcomes for out-of-hospital sudden cardiac arrest. Given Project ADAM's expansion, we sought to identify effective methods to partner with community leaders and understand barriers to engagement. Our aim was to establish effective practices to guide affiliates and optimize site operations and partnerships.

Outcomes Following GD2-Directed Postconsolidation Therapy for Neuroblastoma After Cessation of Random Assignment on ANBL0032: A Report From the Children's Oncology Group.

Purpose: Postconsolidation immunotherapy including dinutuximab, granulocyte-macrophage colony-stimulating factor, and interleukin-2 improved outcomes for patients with high-risk neuroblastoma enrolled on the randomized portion of Children's Oncology Group study ANBL0032. After random assignment ended, all patients were assigned to immunotherapy. Survival and toxicities were assessed.

MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.

The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 have made it the first medical therapy approved for this indication in the United States, the European Union, and elsewhere.

Impaired Lymphocyte Responses in Pediatric Sepsis Vary by Pathogen Type and are Associated with Features of Immunometabolic Dysregulation.

Background: Sepsis is the leading cause of death in hospitalized children worldwide. Despite its hypothesized immune-mediated mechanism, targeted immunotherapy for sepsis is not available for clinical use.

Objective: To determine the association between longitudinal cytometric, proteomic, bioenergetic, and metabolomic markers of immunometabolic dysregulation and pathogen type in pediatric sepsis.

Efficacy of post-induction therapy for high-risk neuroblastoma patients with end-induction residual disease.

Background: High-risk neuroblastoma patients with end-induction residual disease commonly receive post-induction therapy in an effort to increase survival by improving the response before autologous stem cell transplantation (ASCT). The authors conducted a multicenter, retrospective study to investigate the efficacy of this approach.

Methods: Patients diagnosed between 2008 and 2018 without progressive disease with a partial response or worse at end-induction were stratified according to the post-induction treatment: 1) no additional therapy before ASCT (cohort 1), 2) post-induction "bridge" therapy before ASCT (cohort 2), and 3) post-induction therapy without ASCT (cohort 3).

Management of neurofibromatosis type 1-associated plexiform neurofibromas.

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management.

Near-infrared spectroscopy during cardiopulmonary resuscitation for pediatric cardiac arrest: A prospective, observational study.

Aim: Cerebral oxygenation (rSO2) is not routinely measured during pediatric cardiopulmonary resuscitation (CPR). We aimed to determine whether higher intra-arrest rSO2 was associated with return of spontaneous circulation (ROSC) and survival to hospital discharge.

Methods: Prospective, single-center observational study of cerebral oximetry using near-infrared spectroscopy (NIRS) during pediatric cardiac arrest from 2016 to 2020.

Paediatric acute care cardiology collaborative data registry validation.

Background: The Pediatric Acute Care Cardiology Collaborative (PAC) was established to improve acute care cardiology outcomes through the development of an accurate and well-validated clinical registry. We report the validation results of the initial PAC registry audits and describe a novel regional audit format developed to accommodate a rapidly expanding membership facilitate collaborative learning and allow for necessary modification due to the COVID-19 pandemic.

Materials And Methods: Six hospitals were audited using a regional audit format and three hospitals were subsequently audited virtually.

MitoScape: A big-data, machine-learning platform for obtaining mitochondrial DNA from next-generation sequencing data.

The growing number of next-generation sequencing (NGS) data presents a unique opportunity to study the combined impact of mitochondrial and nuclear-encoded genetic variation in complex disease. Mitochondrial DNA variants and in particular, heteroplasmic variants, are critical for determining human disease severity. While there are approaches for obtaining mitochondrial DNA variants from NGS data, these software do not account for the unique characteristics of mitochondrial genetics and can be inaccurate even for homoplasmic variants.

Post-cardiac arrest physiology and management in the neonatal intensive care unit.

Aim: The importance of high-quality post-cardiac arrest care is well-described in adult and paediatric populations, but data are lacking to inform post-cardiac arrest care in the neonatal intensive care unit (NICU). The objective of this study was to describe post-cardiac arrest physiology and management in a quaternary NICU.

Methods: Retrospective descriptive study of post-cardiac arrest physiology and management.

Association of atrial septal fenestration with outcomes after atrioventricular septal defect repair.

Objective: During repair of atrioventricular septal defect (AVSD), surgeons might leave an atrial level shunt when concerned about postoperative physiology, or as part of routine practice. However, the association of fenestration with outcomes is unclear. We sought to determine factors associated with mortality after biventricular repair of AVSD.

A Mesoscale 3D Culture System for Native and Engineered Biphasic Tissues: Application to the Osteochondral Unit.

Interface tissues are functionally graded tissues characterized by a complex layered structure, which therefore present a great challenge to be reproduced and cultured in vitro. Here, we describe the design and operation of a 3D printed dual-chamber bioreactor as a culturing system for biphasic native or engineered osteochondral tissues. The bioreactor is designed to potentially accommodate a variety of interface tissues and enables the precise study of tissue crosstalk by creating two separate microenvironments while maintaining the tissue compartments in direct contact.

Development of white matter microstructure and executive functions during childhood and adolescence: a review of diffusion MRI studies.

Diffusion magnetic resonance imaging (dMRI) provides indirect measures of white matter microstructure that can be used to make inferences about structural connectivity within the brain. Over the last decade, a growing literature of cross-sectional and longitudinal studies have documented relationships between dMRI indices and cognitive development. In this review, we provide a brief overview of dMRI methods and how they can be used to study white matter and connectivity and review the extant literature examining the links between dMRI indices and executive functions during development.

Compression-Only Versus Rescue-Breathing Cardiopulmonary Resuscitation After Pediatric Out-of-Hospital Cardiac Arrest.

Background: There are conflicting data regarding the benefit of compression-only bystander cardiopulmonary resuscitation (CO-CPR) compared with CPR with rescue breathing (RB-CPR) after pediatric out-of-hospital cardiac arrest (OHCA).

Objectives: This study sought to test the hypothesis that RB-CPR is associated with improved neurologically favorable survival compared with CO-CPR following pediatric OHCA, and to characterize age-stratified outcomes with CPR type compared with no bystander CPR (NO-CPR).

Methods: Analysis of the CARES registry (Cardiac Arrest Registry to Enhance Survival) for nontraumatic pediatric OHCAs (patients aged ≤18 years) from 2013-2019 was performed.