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.

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.

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.

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.

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.

Retrospective cohort study of methotrexate use in the treatment of pediatric Crohn's disease.

Background: Methotrexate (MTX) use as an alternative to thiopurines in the treatment of Crohn's disease (CD) in children is increasing. This study was undertaken to assess safety and efficacy of MTX in children with CD.

Methods: Patients treated with MTX with a minimum of 1-year follow-up were identified in the Pediatric IBD Collaborative Research Group Registry, a prospective inception cohort study started in 2002.

Liver enzyme elevations within 3 months of diagnosis of inflammatory bowel disease and likelihood of liver disease.

Background: Inflammatory bowel disease-associated liver diseases (IBD-LDs) include autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and an overlap syndrome. Prospective unbiased multicenter data regarding the frequency of IBD-LD in patients with pediatric inflammatory bowel disease (IBD) are lacking. We examined early alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) elevations in children diagnosed as having IBD and assessed the likelihood of IBD-LD.

Effects of recombinant human growth hormone on protein turnover in the fasting and fed state in adolescents with Crohn disease.

The primary purpose of this study was to test whether recombinant human growth hormone (rhGH) supplementation would enhance protein synthesis and accretion of lean body mass. Eight adolescents (six males and two females; 17.2 +/- 2.

Exploring potential noninvasive biomarkers in eosinophilic esophagitis in children.

Background And Aims: Eosinophilic esophagitis (EE) continues to present clinical challenges, including a need for noninvasive tools to manage the disease. To identify a marker able to assess disease status in lieu of repeated endoscopies, we examined 3 noninvasive biomarkers, serum interleukin (IL)-5, serum eosinophil-derived neurotoxin (EDN), and stool EDN, and examined possible correlations of these with disease phenotype and activity (symptoms and histology) in a longitudinal study of children with EE.

Subjects And Methods: Children with EE were studied for up to 24 weeks (12 weeks on 1 of 2 corticosteroid therapies and 12 weeks off therapy).

Significance of esophageal Crohn disease in children.

Background And Aim: Esophageal Crohn disease (ECD) is more common than it was originally thought to be. Only limited information, however, is available regarding its significance and effect on clinical course in the pediatric population. The aim of the study was to determine the prevalence of ECD in our patient population and compare clinical features and severity of disease among patients with ECD and nonesophageal Crohn disease (NECD).

Factors that determine risk for surgery in pediatric patients with Crohn's disease.

Background & Aims: We examined the incidence of Crohn's disease (CD)-related surgery in a multi-center, inception cohort of pediatric patients with CD. We also examined the effect of starting immunomodulator therapy within 30 days of diagnosis.

Methods: Data from 854 children with CD from the Pediatric Inflammatory Bowel Disease Collaborative Research Group who were diagnosed with CD between 2002 and 2008 were analyzed.

Utility of fecal lactoferrin in identifying Crohn disease activity in children.

Objectives: Fecal lactoferrin (FL) is a noninvasive biomarker that is elevated in Crohn disease (CD) compared to irritable bowel syndrome. The purpose of this study was to evaluate FL in identifying children with active versus inactive CD.

Patients And Methods: Fresh stool samples were collected from children with CD scheduled for endoscopy or a clinic visit, and from new outpatients who were scheduled for colonoscopy.

Extraintestinal manifestations of pediatric inflammatory bowel disease and their relation to disease type and severity.

Objectives: Although it is known that extraintestinal manifestations (EIMs) commonly occur in pediatric inflammatory bowel disease (IBD), little research has examined rates of EIMs and their relation to other disease-related factors in this population. The purpose of this study was to determine the rates of EIMs in pediatric IBD and examine correlations with age, sex, diagnosis, disease severity, and distribution.

Patients And Methods: Data were prospectively collected as part of the Pediatric IBD Collaborative Research Group Registry, an observational database enrolling newly diagnosed IBD patients <16 years old since 2002.

Retrospective Evaluation of the Safety and Effect of Adalimumab Therapy (RESEAT) in pediatric Crohn's disease.

Objectives: Adalimumab, an anti-tumor necrosis factor immunoglobulin-1 antibody, is increasingly being reported as a potential treatment option for children with moderate-to-severe Crohn's disease (CD). The aim of this study was to characterize common indications, safety, tolerability, and clinical response to adalimumab in pediatric CD in a large, multicenter, patient cohort.

Methods: Data were obtained using a retrospective, uncontrolled chart review at 12 sites of the Pediatric Inflammatory Bowel Disease Collaborative Research Group.

Variation in care in pediatric Crohn disease.

Objectives: Variation in medical care can be a barrier to improving clinical outcomes. We aim to describe the variation in care of Crohn disease as provided by a broad sample of pediatric gastroenterologists.

Methods: Two hundred forty-six Crohn disease patients of 93 pediatric gastroenterologists from 48 practice sites starting treatment with either thiopurine or infliximab were studied.

Factors predictive of Crohn disease following colectomy in medically refractory pediatric colitis.

Objectives: Crohn disease (CD) has been diagnosed following colectomy for ulcerative colitis (UC). This study aims to determine the frequency of this occurrence, and to identify predictive factors leading to a CD diagnosis.

Materials And Methods: A retrospective chart review was performed in patients who have undergone colectomy.

Effects of infliximab and parenteral nutrition on albumin and fibrinogen synthesis rates in pediatric Crohn disease.

Objectives: Tumor necrosis factor-alpha (TNF-alpha) may play a significant role in growth disturbance in pediatric Crohn disease. The aim of this study was to determine the effects of anti-TNF-alpha therapy on albumin and fibrinogen synthesis during both fasting and parenteral nutrition infusion in pediatric patients with active Crohn disease.

Patients And Methods: Children with active Crohn disease scheduled for their initial dose of infliximab underwent assessment immediately before and 2 weeks following infliximab infusion.

Carbohydrate and lipid metabolism following infliximab therapy in pediatric Crohn's disease.

Improvements in insulin resistance after anti-TNF-alpha therapy have been reported in inflammatory conditions, although no changes were noted in adult patients with Crohn's disease. There is no information concerning insulin resistance and substrate metabolism in children with Crohn's disease after anti-TNF-alpha therapy. Our aim was to describe changes in carbohydrate and lipid metabolism in children with active Crohn's disease after their initial dose of infliximab.