Antibiotic exposure is associated with minimal gut microbiome perturbations in healthy term infants.

Background: The evolving infant gut microbiome influences host immune development and later health outcomes. Early antibiotic exposure could impact microbiome development and contribute to poor outcomes. Here, we use a prospective longitudinal birth cohort of n = 323 healthy term African American children to determine the association between antibiotic exposure and the gut microbiome through shotgun metagenomics sequencing as well as bile acid profiles through liquid chromatography-mass spectrometry.

A randomized, placebo-controlled, cross-over trial of ketamine in Rett syndrome.

Background: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

Design: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

Methods: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite treatment.

Systematic dissection of pleiotropic loci and critical regulons in excitatory neurons and microglia relevant to neuropsychiatric and ocular diseases.

Advancements in single-cell multimodal techniques have greatly enhanced our understanding of disease-relevant loci identified through genome-wide association studies (GWASs). To investigate the biological connections between the eye and brain, we integrated bulk and single-cell multiomic profiles with GWAS summary statistics for eight neuropsychiatric and five ocular diseases. Our analysis uncovered five latent factors explaining 61.

One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

States Do Not Delineate the "Accepted Medical Standards" for Brain Death/Death by Neurologic Criteria Determination.

Background: The Uniform Determination of Death Act requires brain death/death by neurologic criteria (BD/DNC) determination to be in accordance with "accepted medical standards." The medical organizations responsible for delineating these guidelines are only specified statutorily in two states. State health organizations (SHOs) are composed of policy experts and medical professionals who are responsible for addressing medical, ethical, and legislative problems related to health.

Practice patterns for acquiring neuroimaging after pediatric in-hospital cardiac arrest.

Aims: To determine which patient and cardiac arrest factors were associated with obtaining neuroimaging after in-hospital cardiac arrest, and among those patients who had neuroimaging, factors associated with which neuroimaging modality was obtained.

Methods: Retrospective cohort study of patients who survived in-hospital cardiac arrest (IHCA) and were enrolled in the ICU-RESUS trial (NCT02837497).

Results: We tabulated ultrasound (US), CT, and MRI frequency within 7 days following IHCA and identified patient and cardiac arrest factors associated with neuroimaging modalities utilized.

Association between procedure duration and adverse events in congenital cardiac catheterization.

Background: Procedure duration is an important predictor of patient outcomes in surgery. However, the relationship between procedure duration and adverse events in congenital cardiac catheterization is largely unexplored.

Methods: All cases entered into the Congenital Cardiac Catheterization Project on Outcomes from 2014 to 2017 were included.

Transitioning from the safety of the womb to the outside world for neonates with life-threatening cardiovascular conditions: The IMmediate Postpartum Access to Cardiac Therapy (IMPACT) Procedure.

The IMmediate Postpartum Access to Cardiac Therapy (IMPACT) procedure is a multidisciplinary, collaborative, highly coordinated clinical service in which a planned delivery and intensive neonatal care are offered for conditions where there is a high likelihood of postnatal instability. This process includes prenatal consultation with the parent(s), involving each service engaged with the delivery, postnatal resuscitation, and procedural care. A Cesarean section delivery is planned in an operating room with immediate access to a multifunctional procedural suite where the neonate can undergo rapid cardiac evaluation and initiation of interventional treatments which can have a positive, life-saving impact.

The ACTION VAD registry: A collective five-year experience.

Background: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) began in 2018 as a collaborative learning health system committed to improving outcomes in pediatric heart failure, including children and adults with congenital heart disease, supported with ventricular assist devices (VADs). This report describes patient and device characteristics, and outcomes through 1-year post-implant.

Methods: The ACTION VAD registry report was created from data submitted to the ACTION learning network from April 2018 to June 2023.

Primary Antibody Deficiencies: Curation Of Gene-Disease Relationships Using A ClinGen Validation Framework.

Background: The Clinical Genome Resource (ClinGen) is an international collaborative effort between scientists and clinicians, diagnostic and research laboratories as well as the patient community. Using a standardized framework, ClinGen has established guidelines to classify gene-disease relationships as Definitive, Strong, Moderate, and Limited based on available scientific and clinical evidence. When the genetic and functional evidence for a gene-disease relationship has conflicting interpretations or contradictory evidence, they can be Disputed or Refuted.

Maralixibat Reduces Serum Bile Acids and Improves Cholestatic Pruritus in Adolescents With Alagille Syndrome.

Background: Alagille syndrome (ALGS) is a multisystem cholestatic disorder. Maralixibat is approved for the treatment of cholestatic pruritus in ALGS with limited data in adults.

Methods: Participants were included if they received ≥ 2 doses of maralixibat at age ≥ 16 years in one of the three previously published maralixibat ALGS clinical trials.

Frequency and reasons that parents decline genetic testing for critically ill neonates.

Purpose: Current literature reports strong support among parents for genetic testing for ill neonates; yet, some parents decline this testing for unknown reasons. We aimed to document the proportion of parents who decline, describe their clinical and demographic characteristics, and categorize their rationales.

Methods: We reviewed medical records to collect and compare clinical and demographic information for patients whose parents consented to and declined recommended genetic testing.

Biomarker Panels for Discriminating Risk of CKD Progression in Children.

Background: We have previously studied biomarkers of tubular health (EGF), injury (KIM-1), dysfunction (alpha-1 microglobulin), and inflammation (TNFR-1, TNFR-2, MCP-1, YKL-40, suPAR), and demonstrated that plasma KIM-1, TNFR-1, TNFR-2 and urine KIM-1, EGF, MCP-1, urine alpha-1 microglobulin are each independently associated with CKD progression in children. In this study, we used bootstrapped survival trees to identify a combination of biomarkers to predict CKD progression in children.

Methods: The CKiD Cohort Study prospectively enrolled children 6 months to 16 years old with an eGFR of 30-90 ml/min/1.

Explanatory capacity of measures of community context for paediatric injury hospitalisations in the USA.

Objective: Community context influences children's risk for injury. We aimed to measure the explanatory capacity of two ZIP code-level measures-the Child Opportunity Index V.3.

Interpreting positive celiac serology in children with new-onset type 1 diabetes.

Objectives: The association of celiac disease (CD) in type 1 diabetes mellitus (T1DM) is well-established, yet variation exists in screening practices. This study measures the accuracy of early screening with tissue transglutaminase Immunoglobulin A (TTG-IgA) and endomysial antibody (EMA) in newly diagnosed T1DM.

Methods: This is a retrospective study of children with T1DM between 2013 and 2019 with early CD screening and follow-up.

Validation of Diagnosis Codes for Low Birth Weight and Small-for-Gestational Age in the Medicaid Analytic Extract Database.

Background: The accuracy of low birth weight (LBW) and small for gestational age (SGA) in administrative healthcare records is crucial for perinatal studies but has few validity studies.

Methods: Using 1999-2010 MAX linked to birth certificates (BC), we identified mother-infant dyads (≥30 days enrollment after delivery, with valid gestational age (GA) and birth weight (BW)). LBW and SGA were identified based on ICD-9-CM codes.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.

Impact of Frailty on Surgical Outcomes of Patients With Cushing Disease Using the Multicenter Registry of Adenomas of the Pituitary and Related Disorders Registry.

Background And Objectives: Despite growing interest in how patient frailty affects outcomes (eg, in neuro-oncology), its role after transsphenoidal surgery for Cushing disease (CD) remains unclear. We evaluated the effect of frailty on CD outcomes using the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) data set from a collaboration of US academic pituitary centers.

Methods: Data on consecutive surgically treated patients with CD (2011-2023) were compiled using the 11-factor modified frailty index.

Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.

Background: The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.

Aims: To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.

Methods: We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior.

Trochleoplasty in Pediatric Patients - A Systematic Review.

Background: Trochleoplasty is a surgical consideration for the treatment of high-grade trochlear dysplasia. The safety profile of this procedure remains particularly unclear in the skeletally immature population where concerns exist regarding physeal arrest and the development of premature patellofemoral arthritis. The purpose of this study was to systematically review the literature to evaluate trochleoplasty use, outcomes and complications observed among pediatric patients.

Acquired factor V inhibitor in a case of pediatric venous thrombosis.

Background: The development of acquired factor (F)V with inhibitor (AFVwI) is rare, resulting mainly in bleeding complications, although sporadic cases of thrombosis in adults have been reported.

Key Clinical Question: How do you diagnose and manage a pediatric case of acute deep venous thrombosis associated with the concurrent finding of AFVwI?

Clinical Approach: A 13-year-old female with Crohn's Disease and May-Thurner anatomy developed extensive deep venous thrombosis of the left lower extremity, complicated by the finding of AFVwI, discovered during the evaluation of a prolonged prothrombin time and a low FV activity. Anticoagulation was initiated with low-molecular-weight heparin followed by a direct oral anticoagulant, rivaroxaban, without any complications.

Friedreich ataxia: what can we learn from non-GAA repeat mutations?

Friedreich ataxia (FRDA) is a slowly progressive neurological disease resulting from decreased levels of the protein frataxin, a small mitochondrial protein that facilitates the synthesis of iron-sulfur clusters in the mitochondrion. It is caused by GAA (guanine-adenine-adenine) repeat expansions in the gene in 96% of patients, with 4% of patients carrying other mutations (missense, nonsense, deletion) in the gene. Compound heterozygote patients with one expanded GAA allele and a non-GAA repeat mutation can have subtle differences in phenotype from typical FRDA, including, in patients with selected missense mutations, both more severe features and less severe features in the same patient.

Cord blood for autologous transfusion in infants with congenital anomalies: Volumes, sterility, and stability during storage.

Background: Neonates with congenital anomalies frequently require perioperative allogeneic red blood cell (RBC) transfusion. Whole cord blood for autologous transfusion to neonates may provide an alternative RBC source, but whether sufficient volumes can be collected after delayed cord clamping to reduce allogeneic RBC requirements is unknown.

Study Design And Methods: Inclusion criteria were mothers delivering a viable infant >34 weeks' gestation.

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.