Cardiovascular Disease Among Women and Birthing Individuals After Delivering a Child With Congenital Heart Disease.

Background: Individuals have a higher risk of cardiovascular disease later in life if they give birth to a child with congenital heart disease (CHD). The mechanism of this association has not been well documented.

Objectives: The authors aimed to describe the prevalence of cardiovascular disease and risk factors in women and birthing individuals 18 to 23 years after delivery of a child with CHD compared to normative data.

Genome Instability and Senescence Are Markers of Cornelia de Lange Syndrome Cells.

Cornelia de Lange syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder. Pathogenic variants in genes encoding the structural subunits and regulatory proteins of the cohesin complex (, , , , and ) are the primary contributors to the pathogenesis of CdLS. Pathogenic variations in these genes disrupt normal cohesin function, leading to the syndrome's diverse and complex clinical presentation.

Lessons learned from 20 years of preclinical testing in pediatric cancers.

Programs for preclinical testing of targeted cancer agents in murine models of childhood cancers have been supported by the National Cancer Institute (NCI) since 2004. These programs were established to work collaboratively with industry partners to address the paucity of targeted agents for pediatric cancers compared with the large number of agents developed and approved for malignancies primarily affecting adults. The distinctive biology of pediatric cancers and the relatively small numbers of pediatric cancer patients are major challenges for pediatric oncology drug development.

Pediatric subspecialty workforce: what is needed to secure its vitality and survival?

The pediatric subspecialty workforce is challenged by shortages and geographic maldistribution of subspecialists. We invited leaders in pediatrics to discuss how the field's vitality and survival can be secured. These leaders presented their own opinions and not the opinion of the society or organization that they are presenting.

Assessing Methotrexate Adherence in Juvenile Idiopathic Arthritis Using Electronic Health Record-Linked Pharmacy Dispensing Data.

Objective: We linked pharmacy dispensing data to clinical data in the electronic health record (EHR) to (1) identify characteristics associated with adherence to methotrexate (MTX) and (2) determine the association between adherence and disease activity in patients with juvenile idiopathic arthritis (JIA).

Methods: We conducted a single-center retrospective cohort study of incident MTX recipients with JIA treated between January 2016 and September 2023 for ≥12 months. Using pharmacy dispensing data, complemented by EHR data, we estimated adherence using medication possession ratios (MPRs) over the first 365 days of treatment.

Greater urinary calcium excretion is associated with diminished bone accrual in youth with type 1 diabetes.

Context: The adverse skeletal effects of type 1 diabetes (T1D) include deficient bone accrual and lifelong increased fracture risk. The contributors to impaired bone accrual in people with T1D are incompletely understood.

Objective: To determine if urinary calcium excretion is associated with impaired bone accrual in youth with T1D and to characterize the contribution of glycemic control and markers of bone mineral metabolism to urinary calcium excretion.

Patterns of recurrence after radiotherapy for high-risk neuroblastoma: Implications for radiation dose and field.

Background: Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields.

Methods: Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis.

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial.

Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years.

Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD.

Design, Setting, And Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital.

Clinical practice guideline-inconsistent management of fever and neutropenia in pediatric oncology: A Children's Oncology Group study.

Background: The primary objective was to measure the proportion of episodes where care delivery was inconsistent with selected recommendations of a clinical practice guideline (CPG) on fever and neutropenia (FN) management. The influence of site size on CPG-inconsistent care delivery, and association between patient outcomes and CPG-inconsistent care were described.

Methods: This retrospective, multicenter study included patients less than 21 years old with cancer who were at high risk of poor FN outcomes and were previously enrolled to a Children's Oncology Group (COG) study at participating National Cancer Institute Community Oncology Research Program (NCORP) institutions from January 2014 through December 2015.

Conjugated hyperbilirubinemia is associated with increased morbidity and mortality after neonatal heart surgery.

Background: Cholestasis characterised by conjugated hyperbilirubinemia is a marker of hepatobiliary dysfunction following neonatal cardiac surgery. We aimed to characterise the incidence of conjugated hyperbilirubinemia following neonatal heart surgery and examine the effect of conjugated hyperbilirubinemia on post-operative morbidity and mortality.

Methods: This was a retrospective study of all neonates who underwent surgery for congenital heart disease (CHD) at our institution between 1/1/2010 and 12/31/2020.

Predicting pediatric emergence delirium using data-driven machine learning applied to electronic health record dataset at a quaternary care pediatric hospital.

Objectives: Pediatric emergence delirium is an undesirable outcome that is understudied. Development of a predictive model is an initial step toward reducing its occurrence. This study aimed to apply machine learning (ML) methods to a large clinical dataset to develop a predictive model for pediatric emergence delirium.

Patent ductus arteriosus and coarctation of the aorta in association with PRDM6 variants.

Patent ductus arteriosus (PDA) and coarctation of the aorta (CoA) are relatively common congenital heart defects. Pathogenic variants in PRDM6, which encodes a smooth-muscle-cell-specific transcription factor, have now been etiologically associated with non-syndromic PDA. We present three patients with PDA and CoA found to harbor PRDM6 variants, including a novel, likely-pathogenic variant.

Assessment of proxy-reported responses as predictors of motor and sensory peripheral neuropathy in children with B-lymphoblastic leukemia.

Chemotherapy-induced peripheral neuropathy (CIPN), a common condition in children with acute lymphoblastic leukemia, can be challenging to diagnose. Using data from Children's Oncology Group AALL0932 physical function study, we sought to determine if parent/guardian proxy-reported responses from the Pediatric Outcomes Data Collection Instrument could identify children with motor or sensory CIPN diagnosed by physical/occupational therapists (PT/OT). Four variables moderately discriminated between children with and without motor CIPN (c-index 0.

Minimal residual disease predicts outcomes in KMT2A-rearranged but not KMT2A-germline infant acute lymphoblastic leukemia: Report from Children's Oncology Group study AALL0631.

We measured minimal residual disease (MRD) by multiparameter flow cytometry at three time points (TP) in 117 infants with KMT2A (lysine [K]-specific methyltransferase 2A)-rearranged and 58 with KMT2A-germline acute lymphoblastic leukemia (ALL) on Children's Oncology Group AALL0631 study. For KMT2A-rearranged patients, 3-year event-free survival (EFS) by MRD-positive (≥0.01%) versus MRD-negative (<0.

Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse.

Purpose: Blinatumomab, a bispecific T-cell engager immunotherapy, is efficacious in relapsed/refractory B-cell ALL (B-ALL) and has a favorable toxicity profile. One aim of the Children's Oncology Group AALL1331 study was to compare survival of patients with low-risk (LR) first relapse of B-ALL treated with chemotherapy alone or chemotherapy plus blinatumomab.

Patients And Methods: After block 1 reinduction, patients age 1-30 years with LR first relapse of B-ALL were randomly assigned to block 2/block 3/two continuation chemotherapy cycles/maintenance (arm C) or block 2/two cycles of continuation chemotherapy intercalated with three blinatumomab blocks/maintenance (arm D).

Extracorporeal Membrane Oxygenation for Neonates With Congenital Diaphragmatic Hernia: Prevalence of Seizures and Outcomes.

Objectives: We aimed to determine the prevalence of electrographic seizures and associated odds of adverse outcomes of electrographic seizures in neonates with congenital diaphragmatic hernia (CDH) receiving extracorporeal membrane oxygenation (ECMO).

Design: Retrospective, descriptive case series.

Setting: Neonatal ICU (NICU) in a quaternary care institution.

Into the Unknown: Characterizing Fellow Uncertainty During the Transition to Unsupervised Practice.

Background: Helping fellows confront and manage uncertainty in the course of diagnosis and treatment of patients has been a growing focus of medical education. How these same fellows confront uncertainty as they make a transition in their professional development is less commonly a focus of training programs. Better understanding of how fellows experience these transitions will allow fellows, training programs, and hiring institutions to navigate transitions more easily.

Clinical practice guideline recommendation summaries for pediatric oncology health care professionals: A qualitative study.

Objective: To develop a summary format of clinical practice guideline (CPG) recommendations to improve understandability among health care professionals.

Methods: We developed a summary format based on current research and used the "Think Aloud" technique in one-on-one cognitive interviews to iteratively improve it. Interviews of health care professionals from Children's Oncology Group-member, National Cancer Institute Community Oncology Research Program sites were conducted.

Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association.

ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency, and an abnormal type II transferrin glycosylation pattern. Here, we present 11 new patients and clinical updates with biochemical characterization on one previously reported patient. We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma, and lysosomal abnormalities on hepatic histology.

Congenital Hyperinsulinism: An Historical Perspective.

Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in neonates, infants, and children. Since the first case descriptions in the 1950s, the field has advanced significantly. It was the development of the insulin radioimmunoassay by Yalow and Berson a decade later that made it possible to demonstrate that this form of persistent hypoglycemia was caused by insulin, and a few years later, Drash described the successful treatment of children with hyperinsulinism with the antihypertensive diazoxide, which until today remains the only approved treatment for hyperinsulinism.