Acute pancreatitis gut dysbiosis persists at 1-year follow-up and is associated with clinical outcomes.

Objectives: Pediatric acute pancreatitis (AP) is associated with gut dysbiosis. We aimed to determine if dysbiosis persisted during follow-up and whether it is associated with clinical outcomes.

Methods: Prospective enrollment of participants <21 years with first AP.

Vancomycin dosing in neonates: enhancing outcomes using population pharmacokinetics and simulation.

Introduction: Optimizing vancomycin dosing in neonates is a critical yet complex goal. Traditional trough concentration-based dosing strategies correlate poorly with therapeutic efficacy and often fail to account for the significant renal function variability and drug clearance in neonates. The 24-hour area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) ≥ 400 mg h/L has emerged as a superior pharmacodynamic target.

Skin Staphylococcus aureus detection and relationship to atopic dermatitis outcomes using culture and metagenomic sequencing.

Staphylococcus aureus (SA) skin colonization in pediatric atopic dermatitis (AD) increases risk for severe AD and development of other allergic diseases. Despite this, there is no consensus regarding the optimal method to detect SA. Studies comparing metagenomic shotgun sequencing (MSS) and culture-based methods in SA detection and relationships to AD outcomes are lacking.

Microbial metabolite drives ageing-related clonal haematopoiesis via ALPK1.

Clonal haematopoiesis of indeterminate potential (CHIP) involves the gradual expansion of mutant pre-leukaemic haematopoietic cells, which increases with age and confers a risk for multiple diseases, including leukaemia and immune-related conditions. Although the absolute risk of leukaemic transformation in individuals with CHIP is very low, the strongest predictor of progression is the accumulation of mutant haematopoietic cells. Despite the known associations between CHIP and increased all-cause mortality, our understanding of environmental and regulatory factors that underlie this process during ageing remains rudimentary.

Early-life wheeze trajectories are associated with distinct asthma transcriptomes later in life.

Background: Early childhood wheeze is characterized by heterogeneous trajectories having differential associations with later-life asthma development.

Objective: We sought to determine how early-life wheeze trajectories impact later life asthma gene expression.

Methods: The Children's Respiratory Environmental Workgroup is a collective of 12 birth cohorts, 7 of which conducted an additional visit with a nasal lavage collected and subjected to bulk RNA-sequencing.

SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals.

The immune response to viral infection is shaped by past exposures to related virus strains, a phenomenon known as imprinting. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), much of the population has been imprinted by a viral spike from an early strain, either through vaccination or infection during the early stages of the COVID-19 pandemic. As a consequence of this imprinting, infection with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited by the imprinting strain.

Recommendations for Pneumonia in Hospitalized Children With Neurologic Impairment.

Objectives: Children with neurologic impairment (CNI) are commonly hospitalized with pneumonia but are often excluded from practice guidelines. We sought to develop evidence-based, expert-panel endorsed recommendations for the care of CNI hospitalized with pneumonia.

Methods: We conducted an extensive literature search that formed the basis of drafted candidate recommendations for diagnostic testing, antimicrobial treatment, airway clearance, and discharge criteria.

SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals.

The immune response to viral infection is shaped by past exposures to related virus strains, a phenomenon known as imprinting. For SARS-CoV-2, much of the population has been imprinted by a viral spike from an early strain, either through vaccination or infection during the early stages of the COVID-19 pandemic. As a consequence of this imprinting, infection with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited by the imprinting strain.

Characterization of initial CLABSI culture results to support antimicrobial de-escalation in pediatric GI inpatients.

Objectives: Central Line-associated Bloodstream Infections (CLABSIs) pose a serious mortality and morbidity risk. An institutional protocol was developed for the evaluation and empirical antibiotic treatment of possible CLABSIs. The potential impact of de-escalating antimicrobial therapy based on initial Gram stain and molecular identification was assessed.

Farm animal exposure, respiratory illnesses, and nasal cell gene expression.

Background: Farm exposures in early life reduce the risks for childhood allergic diseases and asthma. There is less information about how farm exposures relate to respiratory illnesses and mucosal immune development.

Objective: We hypothesized that children raised in farm environments have a lower incidence of respiratory illnesses over the first 2 years of life than nonfarm children.

Acute pancreatitis is associated with gut dysbiosis in children.

Background: Pediatric acute pancreatitis (AP) is associated with significant morbidity. Therefore, improved understanding of children who will develop severe AP is critical. Adult studies have reported AP associated gut dysbiosis, but pediatric studies are lacking.

Kruppel-like factor 2+ CD4 T cells avert microbiota-induced intestinal inflammation.

Intestinal colonization by antigenically foreign microbes necessitates expanded peripheral immune tolerance. Here we show commensal microbiota prime expansion of CD4 T cells unified by the Kruppel-like factor 2 (KLF2) transcriptional regulator and an essential role for KLF2+ CD4 cells in averting microbiota-driven intestinal inflammation. CD4 cells with commensal specificity in secondary lymphoid organs and intestinal tissues are enriched for KLF2 expression, and distinct from FOXP3+ regulatory T cells or other differentiation lineages.

MGS2AMR: a gene-centric mining of metagenomic sequencing data for pathogens and their antimicrobial resistance profile.

Background: Identification of pathogenic bacteria from clinical specimens and evaluating their antimicrobial resistance (AMR) are laborious tasks that involve in vitro cultivation, isolation, and susceptibility testing. Recently, a number of methods have been developed that use machine learning algorithms applied to the whole-genome sequencing data of isolates to approach this problem. However, making AMR assessments from more easily available metagenomic sequencing data remains a big challenge.

Obesity Alters cytokine signaling and gut microbiome in septic mice.

Sepsis is a leading cause of mortality. Plasma cytokine levels may identify those at increased risk of mortality from sepsis. Our aim was to understand how obesity alters cytokine levels during early sepsis and its correlation with survival.

Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth.

The dynamics of immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants and young children by analyzing blood samples and weekly nasal swabs collected before, during, and after infection with Omicron and non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, showed no sign of decay for up to 300 days.

The microbiome in adolescents with irritable bowel syndrome and changes with percutaneous electrical nerve field stimulation.

Background: Irritable bowel syndrome (IBS), a disorder of the gut-brain axis, is affected by the microbiome. Microbial studies in pediatric IBS, especially for centrally mediated treatments, are lacking. We compared the microbiome between pediatric IBS patients and healthy controls (HC), in relation to symptom severity, and with percutaneous electrical nerve field stimulation (PENFS), a non-invasive treatment targeting central pain pathways.

Intestinal permeability in patients undergoing stem cell transplantation correlates with systemic acute phase responses and dysbiosis.

Intestinal permeability may correlate with adverse outcomes during hematopoietic stem cell transplantation (HSCT), but longitudinal quantification with traditional oral mannitol and lactulose is not feasible in HSCT recipients because of mucositis and diarrhea. A modified lactulose:rhamnose (LR) assay is validated in children with environmental enteritis. Our study objective was to quantify peri-HSCT intestinal permeability changes using the modified LR assay.

IEC-intrinsic IL-1R signaling holds dual roles in regulating intestinal homeostasis and inflammation.

Intestinal epithelial cells (IECs) constitute a critical first line of defense against microbes. While IECs are known to respond to various microbial signals, the precise upstream cues regulating diverse IEC responses are not clear. Here, we discover a dual role for IEC-intrinsic interleukin-1 receptor (IL-1R) signaling in regulating intestinal homeostasis and inflammation.

Analysis of the fecal metagenome in long-term survivors of pancreas cancer.

Background: The 5-year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long-term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota.