Serological Markers as Predictors of Anti-TNF Response in Children with Crohn's Disease.

Background: To advance personalized medicine in pediatric Crohn's disease (CD), we aimed to explore the utility of serological biomarkers in predicting response to anti-tumor necrosis factor (TNF).

Methods: Children with CD were enrolled at initiation of anti-TNF and followed prospectively at 4 and 12 months thereafter, as well as at last follow-up. At baseline, 10 serological markers of the "PROMETHEUS® IBD sgi Diagnostic test" were measured, including pANCA, ASCA IgG and IgA, anti-CBir1, anti-OmpC, anti-A4-Fla2, anti-Fla-X, SAA, ICAM-1 and VCAM-1.

Pediatric Gastrointestinal Outcomes During the Post-Acute Phase of COVID-19: Findings from RECOVER Initiative from 29 Hospitals in the US.

Importance: The profile of gastrointestinal (GI) outcomes that may affect children in post-acute and chronic phases of COVID-19 remains unclear.

Objective: To investigate the risks of GI symptoms and disorders during the post-acute phase (28 days to 179 days after SARS-CoV-2 infection) and the chronic phase (180 days to 729 days after SARS-CoV-2 infection) in the pediatric population.

Design: We used a retrospective cohort design from March 2020 to Sept 2023.

The intestinal microbiome of inflammatory bowel disease across the pediatric age range.

Dysbiosis is associated with pediatric and adult-onset inflammatory bowel disease (IBD), but the role of dysbiosis and the microbiome in very early onset IBD (VEO-IBD) has not yet been described. Here, we aimed to demonstrate the impact of age and inflammation on microbial community structure using shotgun metagenomic sequencing in children with VEO-IBD, pediatric-onset IBD, and age-matched pediatric healthy controls (HC) observed longitudinally over the course of 8 weeks. We found disease-related differences in alpha and beta diversity between HC and children with IBD or VEO-IBD.

Trajectory of body mass index and obesity in children with Crohn's disease compared to healthy children.

Background: There is increasing recognition that children with Crohn's Disease (CD) can develop obesity.

Methods: Using the RISK Study, an inception cohort of pediatric CD participants, and Bone Mineral Density in Childhood Study (BMDCS), a longitudinal cohort of healthy children, multivariable linear mixed effects, generalized linear mixed effects, and logistic regression models were used to evaluate factors associated with change in body mass index z-score (BMIZ), obesity, and excessive weight gain, respectively.

Results: 1029 CD participants (625 exposed to antitumor necrosis factor (anti-TNF) therapy) and 1880 healthy children were included.

One-shot distributed algorithms for addressing heterogeneity in competing risks data across clinical sites.

Objective: To characterize the interplay between multiple medical conditions across sites and account for the heterogeneity in patient population characteristics across sites within a distributed research network, we develop a one-shot algorithm that can efficiently utilize summary-level data from various institutions. By applying our proposed algorithm to a large pediatric cohort across four national Children's hospitals, we replicated a recently published prospective cohort, the RISK study, and quantified the impact of the risk factors associated with the penetrating or stricturing behaviors of pediatric Crohn's disease (PCD).

Methods: In this study, we introduce the ODACoRH algorithm, a one-shot distributed algorithm designed for the competing risks model with heterogeneity.

Progression of Pediatric Crohn's Disease Is Associated With Anti-Tumor Necrosis Factor Timing and Body Mass Index Z-Score Normalization.

Background & Aims: The evolution of complicated pediatric Crohn's disease (CD) in the era of anti-tumor necrosis factor (aTNF) therapy continues to be described. Because CD progresses from inflammatory to stricturing (B2) and penetrating (B3) disease behaviors in a subset of patients, we aimed to understand the risk of developing complicated disease behavior or undergoing surgery in relation to aTNF timing and body mass index z-score (BMIz) normalization.

Methods: Multicenter, 5-year longitudinal data from 1075 newly diagnosed CD patients were analyzed.

Enterobacteriaceae Growth Promotion by Intestinal Acylcarnitines, a Biomarker of Dysbiosis in Inflammatory Bowel Disease.

Background & Aims: Altered plasma acylcarnitine levels are well-known biomarkers for a variety of mitochondrial fatty acid oxidation disorders and can be used as an alternative energy source for the intestinal epithelium when short-chain fatty acids are low. These membrane-permeable fatty acid intermediates are excreted into the gut lumen via bile and are increased in the feces of patients with inflammatory bowel disease (IBD).

Methods: Herein, based on studies in human subjects, animal models, and bacterial cultures, we show a strong positive correlation between fecal carnitine and acylcarnitines and the abundance of Enterobacteriaceae in IBD where they can be consumed by bacteria both in vitro and in vivo.

Exome Sequencing Implicates DGKZ , ESRRA , and GXYLT1 for Modulating Granuloma Formation in Crohn Disease.

Non-caseating granulomas may indicate a more aggressive phenotype of Crohn disease (CD). Genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis. Whole-exome sequencing was performed on peripheral blood-derived DNA from 17 pediatric patients with GCD and 19 with non-GCD (NGCD), and from an independent validation cohort of 44 GCD and 19 NGCD cases.

Missing data matter: an empirical evaluation of the impacts of missing EHR data in comparative effectiveness research.

Objectives: The impacts of missing data in comparative effectiveness research (CER) using electronic health records (EHRs) may vary depending on the type and pattern of missing data. In this study, we aimed to quantify these impacts and compare the performance of different imputation methods.

Materials And Methods: We conducted an empirical (simulation) study to quantify the bias and power loss in estimating treatment effects in CER using EHR data.

Clinical and lifestyle patterns in Asian children with inflammatory bowel disease in the U.S.

Background: While there are many epidemiologic studies of Asian immigrants to the West and risk of inflammatory bowel disease (IBD), the phenotype and lifestyle of Asian patients, particularly children, with IBD are not well described. In this study, we describe lifestyle practices, such as dietary pattern, as well as disease phenotype in Asian American children with IBD.

Methods: We reviewed the records of children with IBD, ages 0 to 21 years old, and race identified as Asian, Indian, or Pacific Islander.

Using multiple imputation of real-world data to estimate clinical remission in pediatric inflammatory bowel disease.

To evaluate the performance of the multiple imputation (MI) method for estimating clinical effectiveness in pediatric Crohn's disease in the ImproveCareNow registry; to address the analytical challenge of missing data. Simulation studies were performed by creating missing datasets based on fully observed data from patients with moderate-to-severe Crohn's disease treated with non-ustekinumab biologics. MI was used to impute sPCDAI remission statuses in each simulated dataset.

Prospective Validation of the Lémann Index in Children: A Report From the Multicentre Image Kids Study.

Background: The Lémann Index [LI] and the recently updated LI are tools for measuring structural bowel damage in adults with Crohn's disease [CD] but have not been evaluated in children. We aimed to validate the updated LI in the prospective multicentre ImageKids study of paediatric CD.

Methods: We included children with CD undergoing magnetic resonance enterography [MRE], pelvic magnetic resonance imaging [MRI] and ileocolonoscopy.

Development and Validation of the TUMMY-UC: A Patient-Reported Outcome for Pediatric Ulcerative Colitis.

Background & Aims: The TUMMY-UC is a patient-reported outcome measure for pediatric ulcerative colitis (UC) with an observer-reported outcome version for children aged <8 years. It includes eight items selected by concept elicitation interviews. We aimed to finalize the TUMMY-UC by cognitive interviews (stage 2) and to evaluate the index for its psychometric properties (stage 3).

Enterococci enhance Clostridioides difficile pathogenesis.

Enteric pathogens are exposed to a dynamic polymicrobial environment in the gastrointestinal tract. This microbial community has been shown to be important during infection, but there are few examples illustrating how microbial interactions can influence the virulence of invading pathogens. Here we show that expansion of a group of antibiotic-resistant, opportunistic pathogens in the gut-the enterococci-enhances the fitness and pathogenesis of Clostridioides difficile.

Tofacitinib Salvage Therapy for Children Hospitalized for Corticosteroid- and Biologic-Refractory Ulcerative Colitis.

Objectives: Colectomy rates following acute severe ulcerative colitis have plateaued around 20% despite intravenous corticosteroid and intensified anti-tumor necrosis factor (TNF) biologic dosing. Recent studies have shown tofacitinib to provide additional benefit in further decreasing colectomy rates among hospitalized adult patients with corticosteroid- and anti-TNF-nonresponsive ulcerative colitis. Pediatric data describing the effectiveness of tofacitinib for this indication does not yet exist.

Outcomes and Predictors of Sustained Remission After Drug Withdrawal in Pediatric Crohn Disease.

Objectives: The primary aim of this study was to determine the proportion of pediatric Crohn disease (CD) subjects in sustained drug-free remission 52 weeks after stopping pharmacological therapy. We also aimed to explore the effects of the Crohn Disease Exclusion Diet (CDED) and microbiome composition on remission.

Methods: We performed a prospective study following 18 CD patients ages 13-21 years in deep clinical remission withdrawing from immunomodulator (n = 7) or anti-TNFα (n = 11) monotherapy at two tertiary care centers.

Targeted Assessment of Mucosal Immune Gene Expression Predicts Clinical Outcomes in Children with Ulcerative Colitis.

Background And Aims: We aimed to determine whether a targeted gene expression panel could predict clinical outcomes in paediatric ulcerative colitis [UC] and investigated putative pathogenic roles of predictive genes.

Methods: In total, 313 rectal RNA samples from a cohort of newly diagnosed paediatric UC patients (PROTECT) were analysed by a real-time PCR microfluidic array for expression of type 1, 2 and 17 inflammation genes. Associations between expression and clinical outcomes were assessed by logistic regression.

Increased Lifetime Risk of Intestinal Complications and Extraintestinal Manifestations in Crohn's Disease and Ulcerative Colitis.

Patients with Crohn's disease (CD) or ulcerative colitis (UC) have high morbidity rates owing to debilitating intestinal complications and extraintestinal manifestations (EIMs). We retrospectively identified patients in the Truven MarketScan databases with an incident CD or UC diagnosis from January 2008 to September 2015 to quantify the incremental lifetime risk of experiencing an intestinal complication or EIM after CD or UC diagnosis. Seven intestinal complications and 13 categories of EIMs by site were identified, and lifetime risk of experiencing an intestinal complication or EIM from age at CD or UC diagnosis to end of life was estimated using parametric models.

A Microbial Signature for Paediatric Perianal Crohn's Disease.

Background And Aims: Perianal fistulising disease can affect up to 25% of patients with Crohn's disease [CD] and lead to significant morbidity. Although the role of the gut microbiota in inflammatory bowel disease [IBD] has been increasingly recognised, its role in fistula development has scarcely been studied. Here, we aimed to define the microbial signature associated with perianal fistulising CD in children.

Learning Longitudinal Patterns and Subtypes of Pediatric Crohn Disease Treated With Infliximab via Trajectory Cluster Analysis.

Background: The objective of this study is to identify subgroups of pediatric Crohn disease (CD) who had differential responses to the infliximab treatment through trajectory cluster analysis of disease activity using data from electronic health records.

Methods: We conducted a retrospective study of 295 pediatric patients with CD who had been treated with infliximab for a minimum of one year at the Center for Inflammatory Bowel Disease at The Children's Hospital of Philadelphia between January 2010 and December 2017. The evolution of disease was described, and subgroups of patients were identified using trajectory analysis of longitudinal data of C-reactive protein (CRP).

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).

Remodeling of the maternal gut microbiome during pregnancy is shaped by parity.

Background: The maternal microbiome has emerged as an important factor in gestational health and outcome and is associated with risk of preterm birth and offspring morbidity. Epidemiological evidence also points to successive pregnancies-referred to as maternal parity-as a risk factor for preterm birth, infant mortality, and impaired neonatal growth. Despite the fact that both the maternal microbiome and parity are linked to maternal-infant health, the impact of parity on the microbiome remains largely unexplored, in part due to the challenges of studying parity in humans.

Tofacitinib Therapy in Children and Young Adults With Pediatric-onset Medically Refractory Inflammatory Bowel Disease.

Objectives: Tofacitinib, a selective Janus kinase inhibitor, effectively induces and maintains remission in adults with inflammatory bowel disease (IBD), but data are limited in children. This study aimed to evaluate the efficacy and safety of tofacitinib for medically refractory pediatric-onset IBD.

Methods: This single-center retrospective study included subjects ages 21 years and younger who started tofacitinib for medically refractory IBD.