Impact of Adjunct Corticosteroid Therapy on Quality of Life for Children With Suspected Pneumonia.

Objective: To determine the association between adjunct corticosteroid therapy and quality of life (QoL) outcomes in children with signs and symptoms of lower respiratory tract infection and clinical suspicion for community-acquired pneumonia (CAP) in the emergency department (ED).

Methods: Secondary analysis from a prospective cohort study of children aged 3 months to 18 years with signs and symptoms of LRTI and a chest radiograph for suspected CAP in the ED, excluding children with recent (within 14 days) systemic corticosteroid use. The primary exposure was receipt of corticosteroids during the ED visit.

Strategies to Counteract Impact of Harmful Bias in Selection of Medical Residents.

Human biases impact medical care in ways that perpetuate health disparities. Research has demonstrated that biases negatively affect patient outcomes and stifle diversity across the physician workforce, further compounding health disparities by worsening patient-physician concordance. Taken as one, the application, interview, recruitment, and selection processes employed by residency programs has been one of the critical junctures where bias has exacerbated inequities among future physicians.

FOXA2 Cooperates with Mutant KRAS to Drive Invasive Mucinous Adenocarcinoma of the Lung.

Unlabelled: The endoderm-lineage transcription factor FOXA2 has been shown to inhibit lung tumorigenesis in in vitro and xenograft studies using lung cancer cell lines. However, FOXA2 expression in primary lung tumors does not correlate with an improved patient survival rate, and the functional role of FOXA2 in primary lung tumors remains elusive. To understand the role of FOXA2 in primary lung tumors in vivo, here, we conditionally induced the expression of FOXA2 along with either of the two major lung cancer oncogenes, EGFRL858R or KRASG12D, in the lung epithelium of transgenic mice.

Incorporation of biomarkers into a prediction model for paediatric radiographic pneumonia.

Objective: The aim of this study was to evaluate biomarkers to predict radiographic pneumonia among children with suspected lower respiratory tract infections (LRTI).

Methods: We performed a single-centre prospective cohort study of children 3 months to 18 years evaluated in the emergency department with signs and symptoms of LRTI. We evaluated the incorporation of four biomarkers (white blood cell count, absolute neutrophil count, C-reactive protein (CRP) and procalcitonin), in isolation and in combination, with a previously developed clinical model (which included focal decreased breath sounds, age and fever duration) for an outcome of radiographic pneumonia using multivariable logistic regression.

Thermoneutral housing shapes hepatic inflammation and damage in mouse models of non-alcoholic fatty liver disease.

Introduction: Inflammation is a common unifying factor in experimental models of non-alcoholic fatty liver disease (NAFLD) progression. Recent evidence suggests that housing temperature-driven alterations in hepatic inflammation correlate with exacerbated hepatic steatosis, development of hepatic fibrosis, and hepatocellular damage in a model of high fat diet-driven NAFLD. However, the congruency of these findings across other, frequently employed, experimental mouse models of NAFLD has not been studied.

Trajectories of Executive Functions After Early Childhood Traumatic Brain Injury: Teacher Ratings in the Initial 81 Months Postinjury.

Objective: To explore teacher-rated trajectories of executive functioning (EF) after early childhood traumatic brain injury (TBI) and to identify injury-related, academic, and family factors associated with growth trajectories using latent class growth analysis.

Participants: A total of 121 children who sustained a TBI or orthopedic injury (OI) between the ages of 3 and 7 years were recruited from 3 tertiary care children's hospitals and a general hospital in Ohio, including 57 with moderate or severe TBI and 64 with OI.

Design: Assessments were completed at baseline (0-3 months postinjury) and an average of 6, 12, 18, and 81 months postinjury.

Intestinal epithelial HDAC3 and MHC class II coordinate microbiota-specific immunity.

Aberrant immune responses to resident microbes promote inflammatory bowel disease and other chronic inflammatory conditions. However, how microbiota-specific immunity is controlled in mucosal tissues remains poorly understood. Here, we found that mice lacking epithelial expression of microbiota-sensitive histone deacetylase 3 (HDAC3) exhibited increased accumulation of commensal-specific CD4+ T cells in the intestine, provoking the hypothesis that epithelial HDAC3 may instruct local microbiota-specific immunity.

Iron status and burden of anemia in children with recessive dystrophic epidermolysis bullosa.

Background And Objectives: To describe the prevalence, severity, and management of anemia in a cohort of children with recessive dystrophic epidermolysis bullosa (RDEB) and to highlight the use of soluble transferrin receptor (sTfR) to diagnose iron deficiency in this chronic inflammatory state.

Methods: We studied a cohort of 114 patients with RDEB followed at a pediatric hospital-based Epidermolysis Bullosa Center from 2010 to 2020; data were prospectively tracked in a comprehensive clinical database that captured all visits, laboratory tests, iron infusions, and transfusions. The primary outcome was occurrence of anemia, which was assessed by age and sex, with and without transfusion support.

Mucosal Microbiota Associated With Eosinophilic Esophagitis and Eosinophilic Gastritis.

Objective: The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls.

Methods: We conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies, and stool collected.

Good intentions gone wrong: The B cell block to epithelial repair.

Cellular dynamics that influence mucosal healing are not well understood. In this issue of Immunity, Frede, Czarnewski, Monasterio et al. find that B cells accumulate in the colon following intestinal injury.

Customized Postoperative Therapy Improves Bile Drainage in Biliary Atresia: A Single Center Preliminary Report.

Background: Controversies in management of biliary atresia (BA) after hepatoportoenterostomy (HPE) lead to variable treatment protocols. We implemented standardized medical management after HPE, customizing the use of antibiotics and corticosteroids based on patient-specific factors.

Methods: In this retrospective analysis, 20 consecutive infants underwent HPE for BA and were compared to a historical cohort.

Thrombin-mediated activation of PAR1 enhances doxorubicin-induced cardiac injury in mice.

The chemotherapeutic drug doxorubicin is cardiotoxic and can cause irreversible heart failure. In addition to being cardiotoxic, doxorubicin also induces the activation of coagulation. We determined the effect of thrombin-mediated activation of protease-activated receptor 1 (PAR1) on doxorubicin-induced cardiac injury.

A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX).

Background: Fragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy.

Design: CONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral symptoms in children and adolescents with FXS.

Methods: Patients were randomized to 12 weeks of ZYN002 (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care.

Antibiotic use and outcomes among children hospitalized with suspected pneumonia.

Background: Although viral etiologies predominate, antibiotics are frequently prescribed for community-acquired pneumonia (CAP).

Objective: We evaluated the association between antibiotic use and outcomes among children hospitalized with suspected CAP.

Designs, Settings And Participants: We performed a secondary analysis of a prospective cohort of children hospitalized with suspected CAP.

Naturally-aged microglia exhibit phagocytic dysfunction accompanied by gene expression changes reflective of underlying neurologic disease.

Age-associated microglial dysfunction contributes to the accumulation of amyloid-β (Aβ) plaques in Alzheimer's disease. Although several studies have shown age-related declines in the phagocytic capacity of myeloid cells, relatively few have examined phagocytosis of normally aged microglia. Furthermore, much of the existing data on aging microglial function have been generated in accelerated genetic models of Alzheimer's disease.

Dietary phytate primes epithelial antibacterial immunity in the intestine.

Although diet has long been associated with susceptibility to infection, the dietary components that regulate host defense remain poorly understood. Here, we demonstrate that consuming rice bran decreases susceptibility to intestinal infection with , a murine pathogen that is similar to enteropathogenic infection in humans. Rice bran naturally contains high levels of the substance phytate.

Targeting the contact system in a rabbit model of extracorporeal membrane oxygenation.

Previous studies suggested that contact pathway factors drive thrombosis in mechanical circulation. We used a rabbit model of veno-arterial extracorporeal circulation (VA-ECMO) to evaluate the role of factors XI and XII in ECMO-associated thrombosis and organ damage. Factors XI and XII (FXI, FXII) were depleted using established antisense oligonucleotides before placement on a blood-primed VA-ECMO circuit.

A Murine Model of Veno-Arterial Extracorporeal Membrane Oxygenation.

The mechanisms driving the pathologic state created by extracorporeal membrane oxygenation (ECMO) remain poorly defined. We developed the first complete blood-primed murine model of veno-arterial ECMO capable of maintaining oxygenation and perfusion, allowing molecular studies that are unavailable in larger animal models. Fifteen C57BL/6 mice underwent ECMO by cannulating the left common carotid artery and the right external jugular vein.

Crosstalk between hemostasis and immunity in cancer pathogenesis.

Studies spanning the last 3 decades have fundamentally altered our understanding of the interplay between the hemostatic and immune systems. A plethora of studies have revealed that there is bidirectional crosstalk between these two systems at multiple levels that likely evolved as a means to coordinate the host response to numerous challenges, including trauma, infection, and thermal or chemical injury. Such challenges require reestablishment of vascular integrity, the clearance of pathogens, and removal of cellular and external debris.

The Australian and New Zealand Fontan Registry Quality of Life Study: Protocol for a population-based assessment of quality of life among people with a Fontan circulation, their parents, and siblings.

Introduction: Advances in the care of patients with single-ventricle congenital heart disease have led to a new generation of individuals living with a Fontan circulation. For people with Fontan physiology, physical, psychological and neurodevelopmental challenges are common. The objective of this study is to describe and develop a deeper understanding of the factors that contribute to quality of life (QOL) among children, adolescents and adults living with a Fontan circulation across Australia and New Zealand, their parents and siblings.

Human intestinal myofibroblasts deposited collagen VI enhances adhesiveness for T cells - A novel mechanism for maintenance of intestinal inflammation.

Objective: Inflammatory bowel diseases (IBD) cause chronic intestinal damage and extracellular matrix (ECM) remodeling. The ECM may play an active role in inflammation by modulating immune cell functions, including cell adhesion, but this hypothesis has not been tested in IBD.

Design: Primary human intestinal myofibroblast (HIMF)-derived ECM from IBD and controls, 3D decellularized colon or ECM molecule-coated scaffolds were tested for their adhesiveness for T cells.

The education passport: connecting programmatic assessment across learning and practice.

Competency-based medical education (CBME) shifts us from static assessment learning to developmental assessment learning. However, implementation challenges associated with CBME remain a major hurdle, especially after training and into practice. The full benefit of developmental assessment learning over time requires collaboration, cooperation, and trust among learners, regulators, and the public that transcends each individual phase.

Epithelial cell-expressed type II IL-4 receptor mediates eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic, food-driven allergic disease, characterized by eosinophil-rich inflammation in the esophagus. The histopathological and clinical features of EoE have been attributed to overproduction of the type 2 cytokines IL-4 and IL-13, which mediate profound alterations in the esophageal epithelium and neutralizing of their shared receptor component (IL-4Rα) with a human antibody drug (dupilumab) demonstrates clinical efficacy. Yet, the relative contribution of IL-4 and IL-13 and whether the type II IL-4 receptor (comprised of the IL-4Rα chain in association with IL-13Rα1) mediates this effect has not been determined.

Eosinophil-lymphocyte interactions in the tumor microenvironment and cancer immunotherapy.

Eosinophils are important effector cells and therapeutic targets in allergic diseases. Emerging data indicate that eosinophils infiltrate a variety of solid tumor types and have pleiotropic activities by at least two non-mutually exclusive mechanisms: direct interactions with tumor cells, and intricate cross-talk with lymphocytes. In light of the immune checkpoint inhibition revolution in cancer therapy, we review eosinophil-lymphocyte interactions in the tumor microenvironment.