Metabolomics reveal distinct molecular pathways associated with future risk of Crohn's Disease.

Host - microbiome interactions are central to Crohn'sdisease (CD) pathogenesis; yet the early metabolic alterations that precededisease onset remain poorly defined. To explore preclinical metabolicsignatures of CD, we analyzed baseline serum metabolomic profiles in a nestedcase-control study within the Crohn's and Colitis Canada - Genetics, Environment, Microbiome (CCC-GEM) Project, a prospective cohort of 5,122 healthyfirst-degree relatives (FDRs) of CD patients. We included 78 individuals wholater developed CD and 311 matched FDRs who remained disease-free.

The impact of integrating pelvic MRI at diagnosis on early detection of perianal Crohn's disease in pediatrics.

Introduction: Perianal Crohn's disease (CD) can be a severe manifestation of pediatric CD. Earlier detection may alter outcomes. The aim of this study was to determine if performing pelvic magnetic resonance imaging (MR) on newly diagnosed pediatric CD patients would identify asymptomatic perianal CD and lead to earlier biologic use and less perianal surgery.

Infant Acid-Suppressant Medication, C. difficile Colonisation, and Childhood Body Mass Index in a Canadian Cohort.

Aim: To determine relationships between paediatric use of acid-suppressive medications (ASMs) (proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA)) and preschool body mass index (BMI) and mediation by C. difficile colonisation.

Methods: ASMs were parent-reported at age 3, 6 and 12 months in 1025 infants from the CHILD Cohort Study.

Investigating Airway Symptoms in Eosinophilic Esophagitis (EoE).

Objectives: Diagnostic delay of eosinophilic esophagitis (EoE) is significant, and efforts are needed to raise awareness and reduce prolonged symptoms and complications. Airway and swallowing symptoms often overlap, especially in children, complicating diagnosis and increasing delays. This study aims to report the range of airway presentations in pediatric EoE patients and identify independent predictors of an EoE diagnosis in patients with aerodigestive symptoms.

Development of a patient/proxy-reported instrument for pediatric antibiotic-associated diarrhea.

Objective: To develop and validate a patient/proxy-reported measure of the incidence and severity of pediatric antibiotic-associated diarrhea (PAAD) in inpatient and outpatient settings.

Methods: A patient advisory group, consisting of five parents and two children, was engaged as a research partner. Instrument items were developed from three sources: relevant items from two previously validated instruments; relevant constructs from a newly developed core outcome measurement set; and outcomes identified by parents and clinicians as being the most important.

Defining normal bowel wall thickness in children with inflammatory bowel disease in deep remission: A multicenter study on behalf of the pediatric committee of the International Bowel Ultrasound Group (IBUS).

Objectives: Intestinal ultrasound (IUS) is a noninvasive tool for detecting and monitoring disease activity in children with inflammatory bowel disease (IBD). Remission values for bowel wall thickness (BWT) are extrapolated from adult data. We aimed to define normal BWT in children with IBD in sustained deep remission.

Artificial intelligence-assisted approach to assessing bowel wall thickness in pediatric inflammatory bowel disease using intestinal ultrasound images.

Background And Aim: Intestinal ultrasound (IUS) potentially spares patients from repeated endoscopies under sedation and eliminates the need for alternative imaging modalities like magnetic resonance enterography and computed tomography enterography scans. However, interpreting IUS images is challenging for physicians due to the time-intensive process of identifying markers indicative of inflammatory bowel disease (IBD). This study aims for fully automating the analysis of pediatric IBD to distinguish between abnormal and normal cases.

Establishment of a National Surgical Tissue Biobank for Pediatric Crohn's Disease: An Implementation Feasibility Study.

Background: Crohn's disease (CD) is a lifelong gastrointestinal inflammatory condition that often requires surgery, particularly for patients diagnosed in childhood. CD has been linked to a combination of microbial, genetic, and environmental factors, but pathogenesis remains unknown. We outline a framework for multicenter surgical biobanking across a large geographic area, required to enable meaningful research, and evaluate feasibility using the 2016 Consolidated Standards of Reporting Trials (CONSORT) extension to randomized pilot and feasibility trials.

A Canadian multicenter pediatric eosinophilic esophagitis cohort: Evidence for a nondilation approach to esophageal narrowing.

Objectives: Improving characterization of the narrowing phenotype in pediatric eosinophilic esophagitis (EoE).

Methods: New pediatric EoE diagnoses from 2015 to 2018 were retrospectively identified in Vancouver (BC), Northern Alberta (AB), Hamilton (ON), and Nova Scotia (NS). Incidence rates were calculated using 2016 Federal census data.

Four intestinal ultrasound scores and bowel wall thickness alone correlated well with pediatric ulcerative colitis disease activity.

Objectives: Intestinal ultrasound (IUS) is a noninvasive tool in ulcerative colitis (UC), but scoring systems have mostly been developed for adults, Crohn's disease, and flaring UC. Our aim was to evaluate the performance of bowel wall thickness (BWT) and four IUS scores in pediatric patients with newly diagnosed UC.

Methods: Patients <18 years old with suspected UC were prospectively enrolled.

Pediatric inflammatory bowel disease: What's new and what has changed?

The incidence and prevalence of inflammatory bowel disease (IBD) is on the rise in North America and worldwide, with young children being the fastest growing patient population. It is therefore essential for pediatricians and pediatric sub-specialists to be able to recognize signs and symptoms suspicious for a new diagnosis of IBD, as well as potential complications associated with IBD or its treatment. This article reviews the most recent literature regarding clinical presentation, helpful diagnostic clues, newer monitoring tools being used by pediatric gastroenterologists, and emerging new biologic and small molecule treatments.

Landscape of TPMT and NUDT15 Pharmacogenetic Variation in a Cohort of Canadian Pediatric Inflammatory Bowel Disease Patients.

Background: Patients with inflammatory bowel disease (IBD) exhibit considerable interindividual variability in medication response, highlighting the need for precision medicine approaches to optimize and tailor treatment. Pharmacogenetics (PGx) offers the ability to individualize dosing by examining genetic factors underlying the metabolism of medications such as thiopurines. Pharmacogenetic testing can identify individuals who may be at risk for thiopurine dose-dependent adverse reactions including myelosuppression.

Environmental Factors Associated With Risk of Crohn's Disease Development in the Crohn's and Colitis Canada - Genetic, Environmental, Microbial Project.

Background & Aims: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers.

Methods: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project.

Pre-Diagnosis Diet Predicts Response to Exclusive Enteral Nutrition and Correlates with Microbiome in Pediatric Crohn Disease.

Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN.

Outcomes Following Acute Severe Colitis at Initial Presentation: A Multi-centre, Prospective, Paediatric Cohort Study.

Aim: To assess contemporary outcomes in children with acute severe ulcerative colitis [ASUC] at initial presentation.

Methods: Between April 2014 and January 2019, children aged <17 years, with new onset ASUC (Paediatric Ulcerative Colitis Activity Index [PUCAI ≥65) were prospectively followed in a Canadian inception cohort study. 16S rRNA amplicon sequencing captured microbial composition of baseline faecal samples.

Dual Biologic Therapy in a Patient With Niemann-Pick Type C and Crohn Disease: A Case Report and Literature Review.

Dual biologic therapy has become a new area of interest in inflammatory bowel disease (IBD). Monogenic/polygenic IBD and the role of genetics in IBD is an evolving field, with many of these patients having difficult treatment courses. We present a case of a teenage patient with Niemann-Pick disease type C and Crohn colitis, who sustained clinical remission only after escalating to dual biologic therapy (anti-tumor necrosis factor alpha [infliximab] and anti-interleukin-12/anti-interleukin-23 [ustekinumab]).

Transition Readiness in Youth with Inflammatory Bowel Disease.

Objectives: To examine readiness of adolescents and young adults (AYAs) with inflammatory bowel disease (IBD) to transition to adult care.

Study Design: A cross-sectional multicenter study evaluating transition readiness in individuals with IBD 16-19 years old prospectively recruited from 8 Canadian IBD centers using the validated ON Taking Responsibility for Adolescent to Adult Care (ON TRAC) questionnaire. Secondary aims included (1) screening for depression and anxiety using the 8-item Personal Health Questionnaire Depression Scale and The Screen for Child Anxiety Related Emotional Disorders questionnaires, respectively; (2) evaluating the association between depression and anxiety with readiness and disease activity; and (3) subjectively evaluating AYA readiness based on physician and parent assessments.

Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis.

Objective: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort.

Design: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284).

Inflammatory Bowel Disease Among Canadian Children: Comparison Between Children of Non-European Descent and Children of European Descent.

Background: Inflammatory bowel disease (IBD) phenotypes may differ between countries and ancestral groups. The study aim was to examine ancestry and subtype variations of children newly diagnosed with IBD.

Methods: Children newly diagnosed with IBD enrolled into the Canadian Children Inflammatory Bowel Disease Network inception cohort study were categorized into 8 ancestral groups.

Variation in Testing for and Incidence of Celiac Autoimmunity in Canada: A Population-Based Study.

Background & Aims: The incidence of biopsy-confirmed celiac disease has increased. However, few studies have explored the incidence of celiac autoimmunity based on positive serology results.

Methods: A population-based cohort study assessed testing of tissue transglutaminase antibodies (tTG-IgA) in Alberta from 2012 to 2020.

Unfermented β-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients.

Background & Aims: Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial, but not all fibers are alike, and some patients with IBD report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-fermenting microbes in patients with IBD, we hypothesized that fibers remain intact in select patients with reduced fiber-fermenting microbes and can then bind host cell receptors, subsequently promoting gut inflammation.