Circulating amino acid levels in infants undergoing congenital heart disease surgery: near global decrease following cardiopulmonary bypass and impact of perioperative feeding patterns.

Introduction: Amino acids (AAs) serve diverse roles, and insufficient delivery is associated with worse outcomes in ill patients. In the case of congenital heart disease (CHD) surgery with cardiopulmonary bypass (CPB), AA levels are often dysregulated. Changes at the individual AA level, impact of clinical factors, and association with outcomes are less understood.

Alteration in Indole Metabolites After Cardiopulmonary Bypass Surgery in Neonates and Infants.

Importance: Cardiopulmonary bypass (CPB) surgery is associated with changes in the intestinal microbiome. Metabolism of tryptophan into the indole pathway is entirely facilitated by the intestinal microbiome, and indole metabolites play a critical role in intestinal epithelial integrity, intestinal and systemic vascular tone, and intestinal and systemic immune response.

Objectives: To evaluate the impact of CPB on microbial-derived indole metabolites and their association with clinical outcomes.

Increased Endothelin-1 Is Associated With Morbidity in Single Ventricle Heart Disease in Children Undergoing Fontan Palliation.

Background: Endothelin-1 (ET1) is a potent vasoconstrictor and stimulator of pulmonary artery smooth muscle cell proliferation. We previously demonstrated that failure to suppress ET1 is associated with morbidity in infants with single ventricle heart disease (SVHD) undergoing stage 2 palliation.

Objectives: The aim of this study is to evaluate whether persistent failure to suppress ET1 is associated with impaired recovery among children with SVHD undergoing the stage 3 (Fontan) operation.

Cardiopulmonary bypass with deep hypothermic circulatory arrest results in organ-specific transcriptomic responses in pediatric swine.

The organ-level molecular response to cardiac surgery with cardiopulmonary bypass (CPB) remains inadequately understood and may be heterogeneous. Here, we measured organ-specific gene expression in a piglet model of CPB with deep hypothermic circulatory arrest (DHCA). Infant piglets underwent peripheral CPB with 75 min of DHCA and 6 h of critical care after separation from CPB.

Perturbations of tryptophan catabolism via the kynurenine pathway are associated with stage 2 postoperative outcomes in single ventricle heart disease.

Preliminary evidence suggests perturbations of the kynurenine pathway (KP) of tryptophan metabolism in infants with single ventricle heart disease (SVHD). In 72 infants with SVHD undergoing stage 2 palliation (S2P) and 41 controls, we quantified serum KP metabolite concentrations via tandem mass spectroscopy pre-S2P and post-S2P at 2, 24, and 48 h and assessed metabolite relationships with post-S2P outcomes (length of stay, hypoxemia burden, and intubation duration). Pre-S2P, SVHD infants had lower tryptophan and serotonin levels and higher kynurenic acid, 3-hydroxykynurenine, and picolinic acid levels than controls.

Prenatal black carbon exposure and DNA methylation in umbilical cord blood.

Background/objectives: Prenatal exposure to ambient air pollution is associated with adverse cardiometabolic outcomes in childhood. We previously observed that prenatal black carbon (BC) was inversely associated with adiponectin, a hormone secreted by adipocytes, in early childhood. Changes to DNA methylation have been proposed as a potential mediator linking in utero exposures to lasting health impacts.

Disruption of the Circulating Proteome in Neonates Receiving Extracorporeal Membrane Oxygenation Following Congenital Heart Disease Surgery: A Nested Case-Control Study.

This nested case-control study identified broad dysregulation of the circulating proteome in neonates receiving postoperative extracorporeal membrane oxygenation support after congenital heart disease surgery, including differential responses in those not surviving to hospital discharge. Tissue hypoxia and mitochondrial-associated proteins may represent novel candidate biomarkers for poor extracorporeal membrane oxygenation outcomes.

Differentially methylated regions interrogated for metastable epialleles associate with offspring adiposity.

Assess if cord blood differentially methylated regions (DMRs) representing human metastable epialleles (MEs) associate with offspring adiposity in 588 maternal-infant dyads from the Colorado Health Start Study. DNA methylation was assessed via the Illumina 450K array (~439,500 CpG sites). Offspring adiposity was obtained via air displacement plethysmography.

Arginine-NO metabolites are associated with morbidity in single ventricle infants undergoing stage 2 palliation.

Background: Infants with single ventricle heart disease (SVHD) suffer morbidity from insufficient pulmonary blood flow, which may be related to impaired arginine metabolism. No prior study has reported quantitative mapping of arginine metabolites to evaluate the relationship between circulating metabolite levels and outcomes.

Methods: Prospective cohort study of 75 SVHD cases peri-Stage 2 and 50 healthy controls.

The proteomic fingerprint in infants with single ventricle heart disease in the interstage period: evidence of chronic inflammation and widespread activation of biological networks.

Introduction: Children with single ventricle heart disease (SVHD) experience significant morbidity across systems and time, with 70% of patients experiencing acute kidney injury, 33% neurodevelopmental impairment, 14% growth failure, and 5.5% of patients suffering necrotizing enterocolitis. Proteomics is a method to identify new biomarkers and mechanisms of injury in complex physiologic states.

Cord blood DNA methylation of immune and lipid metabolism genes is associated with maternal triglycerides and child adiposity.

Objective: Fetal exposures may impact offspring epigenetic signatures and adiposity. The authors hypothesized that maternal metabolic traits associate with cord blood DNA methylation, which, in turn, associates with child adiposity.

Methods: Fasting serum was obtained in 588 pregnant women (27-34 weeks' gestation), and insulin, glucose, high-density lipoprotein cholesterol, triglycerides, and free fatty acids were measured.

Prenatal exposures to per- and polyfluoroalkyl substances and epigenetic aging in umbilical cord blood: The Healthy Start study.

Background: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, environmentally persistent chemicals, and prenatal exposures have been associated with adverse child health outcomes. Prenatal PFAS exposure may lead to epigenetic age acceleration (EAA), defined as the discrepancy between an individual's chronologic and epigenetic or biological age.

Objectives: We estimated associations of maternal serum PFAS concentrations with EAA in umbilical cord blood DNA methylation using linear regression, and a multivariable exposure-response function of the PFAS mixture using Bayesian kernel machine regression.

Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia.

Background: The time-limited combination of venetoclax and obinutuzumab (VenG) was established by the German CLL Study Group in the CLL14 trial for the upfront management of newly diagnosed chronic lymphocytic leukemia (CLL), showing a superior progression free survival benefit. The incidence of grade 3-4 neutropenia was reported in the range of 52.8%-57.

Psychotropic medications in oncology.

Context: Psychological distress is common in patients with cancer, and oncology providers are often tasked with utilizing psychotropic medications to treat such symptoms.

Objective: This study aims to characterize how oncology providers prescribe psychotropic medications and to assess their comfort level with prescribing these medications.

Methods: A cross-sectional survey was sent to oncology medical doctors, nurse practitioners, and physician assistants who prescribe psychotropic medications to patients with cancer at a large academic medical center in the Mountain West.