Integrated Efficacy and Safety Analysis of Abrocitinib in Adolescents With Moderate-to-Severe Atopic Dermatitis.

Background: Abrocitinib has demonstrated long-term efficacy (48 weeks) and safety (~4 years) in adults and adolescents with moderate-to-severe atopic dermatitis (AD). This analysis evaluated abrocitinib efficacy in adolescents through 112 weeks, and safety of up to 4.6 years of exposure.

Microbial succession at weaning is guided by microbial metabolism of host glycans.

The weaning transition from a milk-based to a solid-food diet supports critical developmental changes to the intestinal microbiome and immune system. However, the specific microbial and host features that influence microbial succession at weaning are not well understood. Here, we developed a simple approach to investigate the complex dynamics of microbial succession during weaning by co-housing gnotobiotic mice colonized with the defined pre-weaning community PedsCom and the adult-derived consortium OMM12.

Comparative molecular landscapes of immature neurons in the mammalian dentate gyrus across species reveal special features in humans.

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity, learning and memory, but their evolutionary changes across species and specialized features in humans remain poorly understood. Here we performed machine learning-augmented analysis of published single-cell RNA-sequencing datasets and identified macaque imGCs with transcriptome-wide immature neuronal characteristics. Our cross-species comparisons among humans, monkeys, pigs, and mice showed few shared (such as DPYSL5), but mostly species-specific gene expression in imGCs that converged onto common biological processes regulating neuronal development.

The radiogenomic and spatiogenomic landscapes of glioblastoma and their relationship to oncogenic drivers.

Background: Glioblastoma is a highly heterogeneous brain tumor, posing challenges for precision therapies and patient stratification in clinical trials. Understanding how genetic mutations influence tumor imaging may improve patient management and treatment outcomes. This study investigates the relationship between imaging features, spatial patterns of tumor location, and genetic alterations in IDH-wildtype glioblastoma, as well as the likely sequence of mutational events.

Long-Term Safety of Epicutaneous Immunotherapy in Peanut-Allergic Children: An Open-Label Active Treatment (REALISE Study).

Background: Due to limited treatment options for peanut allergy, patients remain at risk for allergic reactions due to accidental exposure. Epicutaneous immunotherapy (EPIT) is a novel treatment being investigated for peanut allergy.

Objective: This study assessed long-term safety of EPIT with VIASKIN® peanut patch 250 μg (VP250) via an open-label extension of the REAL Life Use and Safety of EPIT (REALISE) trial.

Hippocampal subregion volumes and preadolescent depression risk in the ABCD sample.

The hippocampus is central in the pathophysiology of depression. Subregions of the hippocampus (head, body, tail) have been implicated in adult depression, though research examining depression and hippocampal subregions in youth has been limited. This study aimed to examine associations between preadolescent hippocampal subregions and depression risk as well as their interactions with factors associated with depression risk, including biological sex and socioeconomic status (SES).

Statistical properties of functional connectivity MRI enrichment analysis in school-age autism research.

Mass univariate testing on functional connectivity MRI (fcMRI) data is limited by difficulties achieving experiment-wide significance. Recent work addressing this problem has used enrichment analysis, which aggregates univariate screening statistics for a set of variables into a single enrichment statistic. There have been promising results using this method to explore fcMRI-behavior associations.

Rapid brain tumor classification from sparse epigenomic data.

Although the intraoperative molecular diagnosis of the approximately 100 known brain tumor entities described to date has been a goal of neuropathology for the past decade, achieving this within a clinically relevant timeframe of under 1 h after biopsy collection remains elusive. Advances in third-generation sequencing have brought this goal closer, but established machine learning techniques rely on computationally intensive methods, making them impractical for live diagnostic workflows in clinical applications. Here we present MethyLYZR, a naive Bayesian framework enabling fully tractable, live classification of cancer epigenomes.

Diagnostic Accuracy Prior to Congenital Heart Defect Surgery: A Multicenter Collaboration.

Background: Echocardiography is the mainstay for diagnosing congenital heart disease (CHD). Diagnostic errors can lead to suboptimal surgical outcomes.

Objectives: This multicenter pediatric echocardiography collaborative learning initiative explores reasons for diagnostic errors, investigates associations between patient- and center-specific factors and errors, and relays the benefits of a multicenter approach to decrease these errors as a first step to improve CHD surgical outcomes.

Leukemia confers a durable imprint on healthy hematopoietic stem and progenitor cells.

Recent models of infection and experimental inflammation reveal that hematopoietic stem and progenitor cells (HSPCs) can generate a memory of the exposure. While the acute inflammatory activity rapidly resolves, cells acquire a heightened capacity to respond to subsequent stimulation. Inflammation is also a constitutive feature of cancer, including hematologic malignancies.

Fetal Callosal Anomalies: A Narrative Review and Practical Recommendations for Pediatric Neurologists.

Agenesis of the corpus callosum is a common indication for fetal neurology consultation, increasingly identified through advances in fetal sonography and fetal magnetic resonance imaging. Despite improvements in diagnostic accuracy, prognostic counseling is challenging due to highly variable neurodevelopmental outcomes. Several factors contribute to neurodevelopmental outcome variability, including associated anomalies and etiologic considerations such as genetic, acquired, and environmental factors.

Improving acute care for Primary Mitochondrial Disease: Development of a publicly available clinical care pathway.

Primary mitochondrial diseases (PMD) are an increasingly recognized cause of multi-system organ dysfunction. Children frequently require acute care in an inpatient setting, though many hospitals do not have access to metabolic specialists. We developed a publicly available, evidenced-based clinical pathway utilizing expert consensus guidelines to guide the care of PMD patients during an emergency department visit and/or hospitalization.

Bilateral giant retinal tear detachments in an infant with Donnai-Barrow syndrome: A case report and review of literature.

Purpose: To report a rare case of bilateral giant retinal tear (GRT)-related retinal detachments in a 24-month-old male with Donnai-Barrow syndrome (DBS) and to review the current literature on this disorder.

Methods: Clinical information was obtained from the medical records of a patient with Donnai-Barrow syndrome seen at the Children's Hospital of Philadelphia. A literature review was conducted to identify all published cases of genetically or clinically diagnosed Donnai-Barrow syndrome.

Non-Invasive Diagnostic Strategies for Membranous Nephropathy in the NEPTUNE Study.

Background: Clinical practice guidelines recommend that a kidney biopsy is no longer required to confirm a diagnosis of membranous nephropathy (MN) in patients with nephrotic syndrome and a positive test for anti-phospholipase A2 receptor antibodies (PLA2R-Ab). However, the optimal diagnostic strategy for using the PLA2R-Ab enzyme-linked immunosorbent assay (ELISA), PLA2R-Ab indirect immunofluorescence (IIF) test, and genetic risk score for diagnosing MN, including the tests' optimal thresholds for positivity among incident patients with proteinuria, is still unknown.

Methods: We used serum samples at or before the first clinically indicated kidney biopsy from participants in the Nephrotic Syndrome Study Network (NEPTUNE) to analyze test performance characteristics using different combinations and cut-offs of the PLA2R-Ab ELISA, IIF, and genetic risk score for diagnosing MN.

Pediatric non-congenital central nervous system infections: role of imaging in the emergency department.

Neurological emergencies in pediatric patients, including central nervous system infections like meningitis and encephalitis, account for significant morbidity and mortality. Neuroimaging plays an important role in the management of these infections, especially when children present with non-specific symptoms such as fever, seizures, or altered consciousness. While computed tomography scans are typically the initial imaging step, magnetic resonance imaging is preferred for its superior detail and lack of ionizing radiation.

Dual- Vs Single-Chamber Ventricular Pacing in Isolated Congenital Complete Atrioventricular Block in Infancy.

Background: The optimal pacemaker programming strategy for infants with isolated congenital complete atrioventricular block (CCAVB) remains unresolved. Dual-chamber pacing maintains atrioventricular synchrony and physiological heart rate variability but increases the burden of ventricular pacing on a myocardium that may be inherently prone to left ventricular (LV) dysfunction.

Objectives: This study sought to compare clinical outcomes of dual (DDD)- vs single (VVI)- chamber pacing in infants with CCAVB (DAVINCHI).

Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height.

We performed ancestry and sex specific Phenome Wide Association Studies (PheWAS) to explore disease related outcomes associated with genetically predicted height. This is the largest PheWAS on genetically predicted height involving up to 840,000 individuals of diverse ancestry. We explored European, African, East Asian ancestries and Hispanic population groups.

Sleep problems in youth with WAGR syndrome.

Objectives: Children with WAGR syndrome, an ultra-rare genetic condition associated with deletion of the brain-derived neurotrophic factor (BDNF), may be at increased risk for sleep problems, but there are limited data assessing sleep in this population. This study aimed to compare sleep disturbances and sleep-disordered breathing in youth with WAGR syndrome compared to healthy youth.

Methods: Parents of youth with WAGR syndrome and healthy controls completed an online survey including demographics, the PROMIS Pediatric Sleep Disturbance item bank, and the Pediatric Sleep Questionnaire Sleep-Related Breathing Disorders scale (PSQ-SRBD).

Development of a self-management tool for individuals with seizure clusters: Trial design and methodological report.

Background: Despite advances in anti-seizure medications (ASMs) for people with epilepsy (PWE), adverse outcomes, negative health events (NHEs), and breakthrough seizures remain common. Rescue medication (RM) can better manage repetitive seizures, but barriers to RM use persist. Self-management for PWE and a history of NHEs (SMART) is an evidence-based epilepsy self-management program aimed at reducing barriers and maximizing facilitators to self-care in high-risk PWE.

The Current State of Pediatric Cardiac Anesthesiology Staffing in the United States.

Background: The population of patients with congenital heart disease has grown, but the supply of pediatric cardiac anesthesiologists has not kept pace. The Pediatric Anesthesia Leadership Council (PALC) and the Congenital Cardiac Anesthesia Society (CCAS) formed a task force to evaluate the current state of the specialty of pediatric cardiac anesthesia, including staffing, work environment, education, compensation, and career development.

Methods: Five task force working groups developed survey questions that explored 5 different aspects of a pediatric cardiac anesthesiologist's career.