Variation in bacterial pneumonia diagnoses and outcomes among children hospitalized with lower respiratory tract infections.

Background: Current diagnostics do not permit reliable differentiation of bacterial from viral causes of lower respiratory tract infection (LRTI), which may lead to over-treatment with antibiotics for possible bacterial community-acquired pneumonia (CAP).

Objectives: We sought to describe variation in the diagnosis and treatment of bacterial CAP among children hospitalized with LRTIs and determine the association between CAP diagnosis and outcomes.

Design, Setting And Participants: This multicenter cross-sectional study included children hospitalized between 2017 and 2019 with LRTIs at 42 children's hospitals.

Histone Deacetylase Inhibition by Gut Microbe-Generated Short-Chain Fatty Acids Entrains Intestinal Epithelial Circadian Rhythms.

Background & Aims: The circadian clock orchestrates ∼24-hour oscillations of gastrointestinal epithelial structure and function that drive diurnal rhythms in gut microbiota. Here, we use experimental and computational approaches in intestinal organoids to reveal reciprocal effects of gut microbial metabolites on epithelial timekeeping by an epigenetic mechanism.

Methods: We cultured enteroids in media supplemented with sterile supernatants from the altered Schaedler Flora (ASF), a defined murine microbiota.

Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature.

Background And Objectives: Extremely low gestational age neonates born <28 weeks gestation are at risk for chronic disease. We sought to describe the prevalence of kidney outcomes by gestational age and determine risk factors for their development.

Design, Setting, Participants, & Measurements: The Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) study examined kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo NeuroProtection Trial (PENUT) study.

Hemostasis and tumor immunity.

Significant data have accumulated demonstrating a reciprocal relationship between cancer and the hemostatic system whereby cancer promotes life-threatening hemostatic system dysregulation (e.g., thromboembolism, consumptive coagulopathy), and hemostatic system components directly contribute to cancer pathogenesis.

Gestational Age at Delivery and Neonatal Outcomes among Infants with Gastroschisis in the Children's Hospitals Neonatal Consortium (CHNC).

Objective: The effect of gestational age (GA) on gastroschisis outcomes is unclear and delivery timing varies in practice. We aimed to correlate clinical outcomes of infants with gastroschisis and GA at delivery in the Children's Hospitals Neonatal Consortium (CHNC).

Study Design: This was a retrospective multicenter cohort study of infants with gastroschisis admitted to CHNC neonatal intensive care units (NICUs) from 2010 to 2016.

Mucosal healing with methotrexate versus azathioprine treatment in pediatric Crohn's disease as reflected by fecal calprotectin.

Background/objectives: The current treatment goal for inflammatory bowel disease (IBD) is achievement of mucosal healing (MH). While established with biologic or azathioprine (AZA) therapies, the data on MH with methotrexate (MTX( treatment is scarce. We aimed to compare MH rate as reflected by FC in children with Crohn's disease (CD) treated with either MTX or thiopurines monotherapy.

A randomized double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in children and adolescents with autism spectrum disorder.

This study was a 10-week double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in youth with autism spectrum disorder (ASD). Participants were ages 5 to 17 years with ASD and clinically significant anxiety (Pediatric Anxiety Rating Scale [PARS] score ≥10). Thirty participants were randomized to mirtazapine (7.

Meta-analysis defines predominant shared microbial responses in various diseases and a specific inflammatory bowel disease signal.

Background: Gut microbial alteration is implicated in inflammatory bowel disease but is noted in other diseases. Systematic comparison to define similarities and specificities is hampered since most studies focus on a single disease.

Results: We develop a pipeline to compare between disease cohorts starting from the raw V4 16S amplicon sequence variants.

Clinical Characteristics and Etiology of Community-acquired Pneumonia in US Children, 2015-2018.

Background: Pneumonia has a major impact on childhood health and health care costs. This study was designed to obtain contemporary information on the clinical characteristics and etiology of community-acquired pneumonia (CAP) in children from both inpatient and outpatient settings in the USA.

Methods: We conducted a prospective, multicenter, observational study of CAP among previously healthy children 2 months to 18 years of age in 6 children's hospitals in Ohio from 2015 to 2018.

Effector memory CD4 T cells induce damaging innate inflammation and autoimmune pathology by engaging CD40 and TNFR on myeloid cells.

Cytokine storm and sterile inflammation are common features of T cell-mediated autoimmune diseases and T cell-targeted cancer immunotherapies. Although blocking individual cytokines can mitigate some pathology, the upstream mechanisms governing overabundant innate inflammatory cytokine production remain unknown. Here, we have identified a critical signaling node that is engaged by effector memory T cells (T) to mobilize a broad proinflammatory program in the innate immune system.

Gut microbiome development in early childhood is affected by day care attendance.

The human gut microbiome develops during the first years of life, followed by a relatively stable adult microbiome. Day care attendance is a drastic change that exposes children to a large group of peers in a diverse environment for prolonged periods, at this critical time of microbial development, and therefore has the potential to affect microbial composition. We characterize the effect of day care on the gut microbial development throughout a single school year in 61 children from 4 different day care facilities, and in additional 24 age-matched home care children (n = 268 samples, median age of entering the study was 12 months).

Bcl-2 Is Necessary to Counteract Bim and Promote Survival of TCRαβCD8αα Intraepithelial Lymphocyte Precursors in the Thymus.

The precursors of TCRαβCD8αα intraepithelial lymphocytes (IEL) arise in the thymus through a complex process of agonist selection. We and others have shown that the proapoptotic protein, Bim, is critical to limit the number of thymic IEL precursors (IELp), as loss of Bim at the CD4CD8 double-positive stage of development drastically increases IELp. The factors determining this cell death versus survival decision remain largely unknown.

Suppression of fibrin(ogen)-driven pathologies in disease models through controlled knockdown by lipid nanoparticle delivery of siRNA.

Fibrinogen plays a pathologic role in multiple diseases. It contributes to thrombosis and modifies inflammatory and immune responses, supported by studies in mice expressing fibrinogen variants with altered function or with a germline fibrinogen deficiency. However, therapeutic strategies to safely and effectively tailor plasma fibrinogen concentration are lacking.

Stratification of risk of progression to colectomy in ulcerative colitis via measured and predicted gene expression.

An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS).

Early Change in Fecal Calprotectin Predicts One-Year Outcome in Children Newly Diagnosed With Ulcerative Colitis.

Introduction: While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS).

Innate control of adaptive immunity and adaptive instruction of innate immunity: bi-directional flow of information.

The ability of the innate and adaptive immune systems to communicate with each other is central to protective immune responses and maintenance of host health. Myeloid cells of the innate immune system are able to sense microbial ligands, perturbations in cellular homeostasis, and virulence factors, thereby allowing them to relay distinct pathogen-specific information to naïve T cells in the form of pathogen-derived peptides and a unique cytokine milieu. Once primed, effector T helper cells produce lineage-defining cytokines to help combat the original pathogen, and a subset of these cells persist as memory or effector-memory populations.

Clinical guideline highlights for the hospitalist: Evaluation and management of well-appearing febrile infants 8 to 60 days old.

Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old RELEASE DATE: August 1, 2021 PRIOR VERSION(S): n/a DEVELOPER: American Academy of Pediatrics FUNDING SOURCE: American Academy of Pediatrics TARGET POPULATION: Well-appearing, otherwise healthy infants with fever, ages 8 to 60 days, excluding those with prematurity (<37 wk gestation), focal bacterial infections except acute otitis media, high suspicion for herpes simplex virus (vesicles), clinical bronchiolitis.

Non-hematopoietic IL-4Rα expression contributes to fructose-driven obesity and metabolic sequelae.

Objective: The risks of excess sugar intake in addition to high-fat diet consumption on immunopathogenesis of obesity-associated metabolic diseases are poorly defined. Interleukin-4 (IL-4) and IL-13 signaling via IL-4Rα regulates adipose tissue lipolysis, insulin sensitivity, and liver fibrosis in obesity. However, the contribution of IL-4Rα to sugar rich diet-driven obesity and metabolic sequelae remains unknown.

Ileal Derived Organoids From Crohn's Disease Patients Show Unique Transcriptomic and Secretomic Signatures.

Background & Aims: We used patient-derived organoids (PDOs) to study the epithelial-specific transcriptional and secretome signatures of the ileum during Crohn's disease (CD) with varying phenotypes to screen for disease profiles and potential druggable targets.

Methods: RNA sequencing was performed on isolated intestinal crypts and 3-week-old PDOs derived from ileal biopsies of CD patients (n = 8 B1, inflammatory; n = 8 B2, stricturing disease) and non-inflammatory bowel disease (IBD) controls (n = 13). Differentially expressed (DE) genes were identified by comparing CD vs control, B1 vs B2, and inflamed vs non-inflamed.

Cell type-specific roles of PAR1 in Coxsackievirus B3 infection.

Protease-activated receptor 1 (PAR1) is widely expressed in humans and mice, and is activated by a variety of proteases, including thrombin. Recently, we showed that PAR1 contributes to the innate immune response to viral infection. Mice with a global deficiency of PAR1 expressed lower levels of CXCL10 and had increased Coxsackievirus B3 (CVB3)-induced myocarditis compared with control mice.