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.

Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children.

Background: B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes.

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.

Molecular Genetics of Pheochromocytoma/Paraganglioma.

Pheochromocytomas and paragangliomas (PPGL) are neuroendocrine tumors which secrete catecholamines, causing cardiovascular compromise. While isolated tumors and locoregional disease can be treated surgically, treatment options for metastatic disease are limited, and no targeted therapies exist. Approximately 25% of PPGL are causatively associated with germline pathogenic variants, which are known risk factors for multifocal and metastatic PPGL.

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.

The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2023 Update on Outcomes and Research.

The Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database (CHSD) continues to be the most comprehensive database of congenital and pediatric cardiothoracic surgical procedures in the world and contains information on 664,210 operations as of June 30, 2023. The 35th harvest of the STS CHSD data was undertaken in Spring 2023, spanning the 4-year period January 1, 2019, through December 31, 2022, and included 144,919 operations performed at 114 participating sites in North America. The harvest analysis was successfully executed by the STS Research and Analytic Center.

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.

Is It Time to Incorporate Liquid Biopsy into High-Risk Cancer Surveillance Protocols in Li-Fraumeni Syndrome?

In the first prospective study evaluating circulating tumor DNA (ctDNA) for early cancer detection, Wong, Luo, and colleauges demonstrate the feasibility of liquid biopsy as an augmentation to current surveillance protocols for patients with Li-Fraumeni syndrome, an inherited cancer predisposition associated with high cancer risk in both pediatric and adult populations. Though additional clinical validation in larger cohorts is needed, this research highlights that a multimodal approach is likely necessary to improve the sensitivity of liquid biopsy assays for early cancer detection. See related article by Wong, Lou et al.

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.

Evaluation of novel candidate filtration markers from a global metabolomic discovery for glomerular filtration rate estimation.

Creatinine and cystatin-C are recommended for estimating glomerular filtration rate (eGFR) but accuracy is suboptimal. Here, using untargeted metabolomics data, we sought to identify candidate filtration markers for a new targeted assay using a novel approach based on their maximal joint association with measured GFR (mGFR) and with flexibility to consider their biological properties. We analyzed metabolites measured in seven diverse studies encompasing 2,851 participants on the Metabolon H4 platform that had Pearson correlations with log mGFR and used a stepwise approach to develop models to < -0.