PROGNOSTIC ACCURACY OF MACHINE LEARNING MODELS FOR IN-HOSPITAL MORTALITY AMONG CHILDREN WITH PHOENIX SEPSIS ADMITTED TO THE PEDIATRIC INTENSIVE CARE UNIT.

Objective: The Phoenix sepsis criteria define sepsis in children with suspected or confirmed infection who have ≥2 in the Phoenix Sepsis Score. The adoption of the Phoenix sepsis criteria eliminated the Systemic Inflammatory Response Syndrome criteria from the definition of pediatric sepsis. The objective of this study is to derive and validate machine learning models predicting in-hospital mortality for children with suspected or confirmed infection or who met the Phoenix sepsis criteria for sepsis and septic shock.

RNA Sequencing Analysis of Monocytes Exposed to Airway Fluid From Children With Pediatric Acute Respiratory Distress Syndrome.

Objectives: Monocytes are plastic cells that assume different polarization states that can either promote inflammation or tissue repair and inflammation resolution. Polarized monocytes are partially defined by their transcriptional profiles that are influenced by environmental stimuli. The airway monocyte response in pediatric acute respiratory distress syndrome (PARDS) is undefined.

Assessing Social Determinants of Health During Critical Illness: Implications and Methodologies.

A growing body of literature has identified social determinants of health (SDoH) as potential contributors to health disparities in pediatric critical illness. Pediatric critical care providers should use validated screening tools to identify unmet social needs and ensure appropriate referral through multisector partnerships. Pediatric critical care researchers should consider factors outside of race and insurance status and explore the association between neighborhood-level factors and disparate health outcomes during critical illness.

Clinical and inflammatory features of traffic-related diesel exposure in children with asthma.

Background: Epidemiologic studies have revealed associations between traffic-related pollutants such as diesel particulate matter (PM) and asthma outcomes in children, but the inflammatory features associated with diesel PM exposure in children with asthma are not understood.

Objective: To evaluate symptoms, exacerbations, and lung function measures in children with uncontrolled asthma and their associations with residential proximity to major roadways and to determine associations between diesel PM exposure and systemic inflammatory cytokines, circulating markers of T-cell activation and exhaustion, and metabolomic features using biomarker studies.

Methods: Children 5 to 17 years of age with physician-diagnosed, uncontrolled asthma despite treatment with an asthma controller medication completed a research visit involving questionnaires, lung function testing, and venipuncture for biomarker studies.

Plasma metabolomics identifies differing endotypes of recurrent wheezing in preschool children differentiated by symptoms and social disadvantage.

Preschool children with recurrent wheezing are a heterogeneous population with many underlying biological pathways that contribute to clinical presentations. Although the morbidity of recurrent wheezing in preschool children is significant, biological studies in this population remain quite limited. To address this gap, this study performed untargeted plasma metabolomic analyses in 68 preschool children with recurrent wheezing to identify metabolomic endotypes of wheezing.

HIGH THROUGHPUT QUANTITATION OF HUMAN NEUTROPHIL RECRUITMENT AND FUNCTIONAL RESPONSES IN AN AIR-BLOOD BARRIER ARRAY.

Dysregulated neutrophil recruitment drives many pulmonary diseases, but most preclinical screening methods are unsuited to evaluate pulmonary neutrophilia, limiting progress towards therapeutics. Namely, high throughput therapeutic screening systems typically exclude critical neutrophilic pathophysiology, including blood-to-lung recruitment, dysfunctional activation, and resulting impacts on the air-blood barrier. To meet the conflicting demands of physiological complexity and high throughput, we developed an assay of 96-well Leukocyte recruitment in an Air-Blood Barrier Array (L-ABBA-96) that enables -like neutrophil recruitment compatible with downstream phenotyping by automated flow cytometry.

Association between comorbidities at ICU admission and post-Sepsis physical impairment: A retrospective cohort study.

Purpose: Few studies have measured the association between pre-existing comorbidities and post-sepsis physical impairment. The study aimed to estimate the risk of physical impairment at hospital discharge among sepsis patients, adjusting for pre-existing physical impairment prior to ICU admission and in-hospital mortality.

Materials And Methods: We analyzed all consecutive adult patients admitted to an ICU in a tertiary community hospital, Kameda Medical Center, with sepsis diagnosis from September 2014 to October 2020.

Dysfunctional neutrophil type 1 interferon responses in preschool children with recurrent wheezing and IL-4-mediated aeroallergen sensitization.

Background: The innate mechanisms associated with viral exacerbations in preschool children with recurrent wheezing are not understood.

Objective: We sought to assess differential gene expression in blood neutrophils from preschool children with recurrent wheezing, stratified by aeroallergen sensitization, at baseline and after exposure to polyinosinic:polycytidylic acid (poly(I:C)) and also to examine whether poly(I:C)-stimulated blood neutrophils influenced airway epithelial gene expression.

Methods: Blood neutrophils were purified and cultured overnight with poly(I:C) and underwent next-generation sequencing with Reactome pathway analysis.

Environmental Injustice Is Associated With Poorer Asthma Outcomes in School-Age Children With Asthma in Metropolitan Atlanta, Georgia.

Background: Environmental justice mandates that no person suffers disproportionately from environmental exposures. The Environmental Justice Index (EJI) provides an estimate of the environmental burden for each census tract but has not yet been used in asthma populations.

Objective: We hypothesized that children from census tracts with high environmental injustice determined by the EJI would have a greater burden of asthma exacerbations, poorer asthma control, and poorer lung function over 12 months.

Altered Symptom Perception in Children With Asthma Is Associated With Poor Childhood Opportunity and Adverse Outcomes.

Background: Effective asthma self-management requires that children recognize their asthma symptoms when they occur. However, some children have altered symptom perception, which impairs their ability to respond to their asthma symptoms in a timely manner.

Objective: To characterize the prevalence and features of altered symptom perception in children aged 5 to 18 years.

Development and Validation of a Model for Endotracheal Intubation and Mechanical Ventilation Prediction in PICU Patients.

Objectives: To develop and externally validate an intubation prediction model for children admitted to a PICU using objective and routinely available data from the electronic medical records (EMRs).

Design: Retrospective observational cohort study.

Setting: Two PICUs within the same healthcare system: an academic, quaternary care center (36 beds) and a community, tertiary care center (56 beds).

Metabolomics identifies disturbances in arginine, phenylalanine, and glycine metabolism as differentiating features of exacerbating atopic asthma in children.

Background: Asthma exacerbations are highly prevalent in children, but only a few studies have examined the biologic mechanisms underlying exacerbations in this population.

Objective: High-resolution metabolomics analyses were performed to understand the differences in metabolites in children with exacerbating asthma who were hospitalized in a pediatric intensive care unit for status asthmaticus. We hypothesized that compared with a similar population of stable outpatients with asthma, children with exacerbating asthma would have differing metabolite abundance patterns with distinct clustering profiles.

Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing.

Background: Preschool children with recurrent wheezing are heterogeneous, with differing responses to respiratory viral infections. Although neutrophils are crucial for host defense, their function has not been studied in this population.

Objective: We performed functional immunophenotyping on isolated blood neutrophils from 52 preschool children with recurrent wheezing (aeroallergen sensitization, n = 16; no sensitization, n = 36).

Frequency of HLA-DRCD38 T cells identifies and quantifies T-cell activation in hemophagocytic lymphohistiocytosis, hyperinflammation, and immune regulatory disorders.

Background: Quantifying T-cell activation is essential for the diagnosis and evaluation of treatment response in various hyperinflammatory and immune regulatory disorders, including hemophagocytic lymphohistiocytosis. Plasma soluble IL-2 receptor (sIL-2R) is a well-established biomarker for evaluating systemic T-cell activation. However, the limited availability of sIL-2R testing could result in delayed diagnosis.

Prognostic and predictive value of endothelial dysfunction biomarkers in sepsis-associated acute kidney injury: risk-stratified analysis from a prospective observational cohort of pediatric septic shock.

Background: Sepsis-associated acute kidney injury (SA-AKI) is associated with high morbidity, with no current therapies available beyond continuous renal replacement therapy (CRRT). Systemic inflammation and endothelial dysfunction are key drivers of SA-AKI. We sought to measure differences between endothelial dysfunction markers among children with and without SA-AKI, test whether this association varied across inflammatory biomarker-based risk strata, and develop prediction models to identify those at highest risk of SA-AKI.

RNA Sequencing Analysis of CD4 T Cells Exposed to Airway Fluid From Children With Pediatric Acute Respiratory Distress Syndrome.

Unlabelled: CD4 T cells contribute to lung inflammation in acute respiratory distress syndrome. The CD4 T-cell response in pediatric acute respiratory distress syndrome (PARDS) is unknown.

Objectives: To identify differentially expressed genes and networks using a novel transcriptomic reporter assay with donor CD4 T cells exposed to the airway fluid of intubated children with mild versus severe PARDS.

Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1.

Background: Sepsis is associated with significant mortality. Yet, there are no efficacious therapies beyond antibiotics. PCSK9 loss-of-function (LOF) and inhibition, through enhanced low-density lipoprotein receptor (LDLR) mediated endotoxin clearance, holds promise as a potential therapeutic approach among adults.

Social determinants of health influence preschool and caregiver experiences during symptoms and exacerbations of wheezing.

Background: Social determinants of health have been inadequately studied in preschool children with wheezing and their caregivers but may influence the care received.

Objective: To evaluate the symptom and exacerbation experiences of wheezing preschool children and their caregivers, stratified by risk of social vulnerability, over 1 year of longitudinal follow-up.

Methods: A total of 79 caregivers and their preschool children with recurrent wheezing and at least 1 exacerbation in the previous year were stratified by a composite measure of social vulnerability into "low" (N = 19), "intermediate" (N = 27), and "high" (N = 33) risk groups.

Identification of a pediatric acute hypoxemic respiratory failure signature in peripheral blood leukocytes at 24 hours post-ICU admission with machine learning.

Background: There is no generalizable transcriptomics signature of pediatric acute respiratory distress syndrome. Our goal was to identify a whole blood differential gene expression signature for pediatric acute hypoxemic respiratory failure (AHRF) using transcriptomic microarrays within twenty-four hours of diagnosis. We used publicly available human whole-blood gene expression arrays of a Berlin-defined pediatric acute respiratory distress syndrome (GSE147902) cohort and a sepsis-triggered AHRF (GSE66099) cohort within twenty-four hours of diagnosis and compared those children with a PO/FO < 200 to those with a PO/FO ≥ 200.

Outcomes of children with life-threatening status asthmaticus requiring isoflurane therapy and extracorporeal life support.

Background: Severe, refractory asthma is a life-threatening emergency that may be treated with isoflurane and extracorporeal life support. The objective of this study was to describe the clinical response to isoflurane and outcomes after discharge of children who received isoflurane and/or extracorporeal life-support for near-fatal asthma.

Methods: This was a retrospective descriptive study using electronic medical record data from two pediatric intensive care units within a single healthcare system in Atlanta, GA.

Poorer Caregiver Mental and Social Health Is Associated With Worse Respiratory Outcomes in Preschool Children With Recurrent Wheezing.

Background: Mental and social health in caregivers of preschool children has been inadequately studied, but it may influence respiratory symptom recognition and management.

Objective: To identify preschool caregivers at highest risk for poor mental and social health outcomes on the basis of patient-reported outcome measures.

Methods: Female caregivers 18 to 50 years old (N = 129) with a preschool child aged 12 to 59 months with recurrent wheezing and at least 1 exacerbation in the previous year completed 8 validated patient-reported outcome measures of mental and social health.

Cluster analysis of plasma cytokines identifies two unique endotypes of children with asthma in the pediatric intensive care unit.

Children with life-threatening asthma exacerbations who are admitted to a pediatric intensive care unit (PICU) are a heterogeneous group with poorly studied inflammatory features. We hypothesized that distinct clusters of children with asthma in a PICU would be identified based on differences in plasma cytokine levels and that these clusters would have differing underlying inflammation and asthma outcomes within 1 year. Plasma cytokines and differential gene expression were measured in neutrophils isolated from children admitted to a PICU for asthma.