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.

Proactive measurement of infliximab drug levels in children with Crohn's disease.

Background: Proactively monitoring infliximab levels is an emerging area of interest in pediatric Crohn's disease. There are only limited data on therapeutic drug monitoring for children with Crohn's disease. The goal of our study was to determine the utility of therapeutic drug monitoring in achieving clinical remission in a cohort of pediatric Crohn's disease patients receiving infliximab.

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).

Inadequate Bowel Preparation in Pediatric Colonoscopy-Prospective Study of Potential Causes.

Objectives: Inadequate bowel preparation (IBP) for colonoscopy leads to missed diagnosis, longer anesthesia time, higher chance of complications and increased costs. Adult studies have demonstrated that patient characteristics such as male gender and obesity are associated with IBP. Little is known about factors affecting bowel preparation in children.

Clinical and Host Biological Factors Predict Colectomy Risk in Children Newly Diagnosed With Ulcerative Colitis.

Background: Develop a clinical and biological predictive model for colectomy risk in children newly diagnosed with ulcerative colitis (UC).

Methods: This was a multicenter inception cohort study of children (ages 4-17 years) newly diagnosed with UC treated with standardized initial regimens of mesalamine or corticosteroids (CS) depending upon initial disease severity. Therapy escalation to immunomodulators or infliximab was based on predetermined criteria.

Association of Baseline Luminal Narrowing With Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn Disease.

Background: Transmural healing (TH) is associated with better long-term outcomes in Crohn disease (CD), whereas pretreatment ileal gene signatures encoding myeloid inflammatory responses and extracellular matrix production are associated with stricturing. We aimed to develop a predictive model for ileal TH and to identify ileal genes and microbes associated with baseline luminal narrowing (LN), a precursor to strictures.

Materials And Methods: Baseline small bowel imaging obtained in the RISK pediatric CD cohort study was graded for LN.

Natural History of Very Early Onset Inflammatory Bowel Disease in North America: A Retrospective Cohort Study.

Background: The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described.

Methods: We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review.

Clinical and biological predictors of response to standardised paediatric colitis therapy (PROTECT): a multicentre inception cohort study.

Background: Lack of evidence-based outcomes data leads to uncertainty in developing treatment regimens in children who are newly diagnosed with ulcerative colitis. We hypothesised that pretreatment clinical, transcriptomic, and microbial factors predict disease course.

Methods: In this inception cohort study, we recruited paediatric patients aged 4-17 years with newly diagnosed ulcerative colitis from 29 centres in the USA and Canada.

Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response.

Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants.

Variation in Care in the Management of Children With Crohn's Disease: Data From a Multicenter Inception Cohort Study.

Background: Variation in care is common in medical practice. Reducing variation in care is shown to improve quality and increase favorable outcomes in chronic diseases. We sought to identify factors associated with variation in care in children with newly diagnosed Crohn's disease (CD).

Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course.

Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies.

The Effect of Early-Life Environmental Exposures on Disease Phenotype and Clinical Course of Crohn's Disease in Children.

Objectives: Environmental factors play an important role in the pathogenesis of Crohn's Disease (CD). In particular, by virtue of the instability of the microbiome and development of immunologic tolerance, early life factors may exert the strongest influence on disease risk and phenotype.

Methods: We used data from 1119 CD subjects recruited from RISK inception cohort to examine the impact of early life environment on disease progression.

Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children.

Background: In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens.

Aim: The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy).

Methods: Patients were recruited from 29 participating centers.

Enhanced Contribution of HLA in Pediatric Onset Ulcerative Colitis.

Background: The genetic contributions to pediatric onset ulcerative colitis (UC), characterized by severe disease and extensive colonic involvement, are largely unknown. In adult onset UC, Genome Wide Association Study (GWAS) has identified numerous loci, most of which have a modest susceptibility risk (OR 0.84-1.

Biologics Delay Progression of Crohn's Disease, but Not Early Surgery, in Children.

Background & Aims: Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from diagnosis. We investigated the recent risk of bowel surgery in an inception cohort of pediatric patients with CD and whether early use of biologics (tumor necrosis factor antagonists) alters later disease course.

Methods: We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group registry on 1442 children (age, ≤16 y) diagnosed with CD from January 2002 through December 2014.

Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study.

Background: Previous retrospective studies of paediatric ulcerative colitis have had limited ability to describe disease progression and identify predictors of treatment response. In this study, we aimed to identify characteristics associated with outcomes following standardised therapy after initial diagnosis.

Methods: The PROTECT multicentre inception cohort study was based at 29 centres in the USA and Canada and included paediatric patients aged 4-17 years who were newly diagnosed with ulcerative colitis.

Histologic Correlates of Clinical and Endoscopic Severity in Children Newly Diagnosed With Ulcerative Colitis.

To characterize rectal histology in an inception cohort of children newly diagnosed with ulcerative colitis (UC) and to explore its relationship with clinical indices of disease severity. The PROTECT (Predicting Response to Standardized Pediatric Colitis Therapy) Study enrolled children 17 years of age and younger newly diagnosed with UC. Baseline rectal biopsies were evaluated for acute and chronic inflammation, eosinophilic inflammation (peak eosinophil count > 32 eosinophils/high powered field, eosinophilic cryptitis or abscesses), and architectural/nonarchitectural chronic changes.

Safety and Pharmacokinetic Study of Fidaxomicin in Children With Clostridium difficile-Associated Diarrhea: A Phase 2a Multicenter Clinical Trial.

Background: Fidaxomicin is an approved therapy for Clostridium difficile-associated diarrhea (CDAD) in adults. The safety of fidaxomicin in children has not been reported.

Methods: In this study (ClinicalTrials.

Incidence of Low Seroimmunity to Hepatitis B Virus in Children With Inflammatory Bowel Disease.

Objectives: Patients with inflammatory bowel disease (IBD) often receive immunosuppressive therapy, which may make them vulnerable to infections such as hepatitis B. We hypothesized that hepatitis B virus titers are low in the vaccinated pediatric population with IBD. The aims of our study were to identify the incidence of lower titers of hepatitis B surface antibody (HBsAb) and determine which patient factors may be associated with lower HBsAb titers.

Gallbladder Ejection Fraction Is Unrelated to Gallbladder Pathology in Children and Adolescents.

Objectives: Biliary dyskinesia is a common diagnosis that frequently results in cholecystectomy. In adults, most clinicians use a cut off value for the gallbladder ejection fraction (GBEF) of <35% to define the disease. This disorder is not well characterized in children.

Dissecting Allele Architecture of Early Onset IBD Using High-Density Genotyping.

Background: The inflammatory bowel diseases (IBD) are common, complex disorders in which genetic and environmental factors are believed to interact leading to chronic inflammatory responses against the gut microbiota. Earlier genetic studies performed in mostly adult population of European descent identified 163 loci affecting IBD risk, but most have relatively modest effect sizes, and altogether explain only ~20% of the genetic susceptibility. Pediatric onset represents about 25% of overall incident cases in IBD, characterized by distinct disease physiology, course and risks.

Clinical Presentation and Five-Year Therapeutic Management of Very Early-Onset Inflammatory Bowel Disease in a Large North American Cohort.

Objective: To evaluate the presentation, therapeutic management, and long-term outcome of children with very early-onset (VEO) (≤ 5 years of age) inflammatory bowel disease (IBD).

Study Design: Data were obtained from an inception cohort of 1928 children with IBD enrolled in a prospective observational registry at multiple centers in North America.

Results: One hundred twelve children were ≤ 5 years of age with no child enrolled at <1 year of age.

Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease.

Background & Aims: It is important to determine the effects of immunomodulators on the ability of children to remain on infliximab therapy for Crohn's disease (durability of therapy), given the potential benefits and risks of concomitant therapy-especially with thiopurines in male patients. We investigated how immunomodulatory treatment affects the durability of infliximab therapy.

Methods: We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, from January 2002 through August 2014, on 502 children with Crohn's disease who participated in a prospective multicenter study.