Healthy First-Degree Relatives From Multiplex Families vs Simplex Families Have Higher Subclinical Intestinal Inflammation, a Distinct Fecal Microbial Signature, and Harbor a Higher Risk of Developing Crohn's Disease.

Background & Aims: Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders.

Methods: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD.

Early Serum Infliximab Levels in Pediatric Ulcerative Colitis.

Data on serum infliximab concentrations during induction in pediatric ulcerative colitis are limited. The study aim is to evaluate the relationship between serum infliximab concentrations during induction and short-term clinical remission in children with ulcerative colitis. We carried out a prospective, multi-center cohort study in pediatric patients with ulcerative colitis.

Serologic Status of Routine Childhood Vaccines, Cytomegalovirus, and Epstein-Barr Virus in Children With Inflammatory Bowel Disease.

Background: Data on the serologic status of childhood vaccines, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), are limited in inflammatory bowel disease (IBD). Therefore, we evaluated vaccine coverage and seroprotection, along with CMV and EBV seropositivity, in pediatric IBD.

Methods: In a cross-sectional study, demographic data, IBD history, vaccine records, and serum for antibodies against measles, mumps, rubella, diphtheria, tetanus, varicella, hepatitis B (HBV), CMV, and EBV were collected from children with IBD.

Long-term Outcomes of Infliximab Use for Pediatric Crohn Disease: A Canadian Multicenter Clinical Practice Experience.

Background: Data on long-term real-world outcomes of infliximab in pediatric Crohn disease are limited.

Aim: The aim of the study was to evaluate infliximab optimization and durability in children with Crohn disease.

Methods: We performed a retrospective review of children with Crohn disease who started infliximab from January 2008 to December 2012 in 4 Canadian tertiary care centers.

Immunogenicity of Influenza Vaccine for Patients with Inflammatory Bowel Disease on Maintenance Infliximab Therapy: A Randomized Trial.

Background: In patients with inflammatory bowel disease (IBD) on infliximab, data are limited on immune response to influenza vaccine and the impact of vaccine timing. The study aims were to evaluate immune responses to the influenza vaccine in IBD patients on infliximab and the impact of vaccine timing on immune responses.

Methods: In this randomized study, 137 subjects with IBD on maintenance infliximab therapy were allocated to receive the 2012/2013 inactivated influenza vaccine at the time of infliximab infusion (n = 69) or midway between infusions (n = 68).

Rising post-colectomy complications in children with ulcerative colitis despite stable colectomy rates in United States.

Background And Aims: In children with ulcerative colitis, data on temporal colectomy trends and in-hospital post-colectomy complications are limited. Thus, we evaluated time trends in colectomy rates and post-colectomy complications in children with ulcerative colitis.

Methods: We identified all children (≤18years) with a diagnosis code of ulcerative colitis (ICD-9: 556.

Nationwide temporal trends in incidence of hospitalization and surgical intestinal resection in pediatric inflammatory bowel diseases in the United States from 1997 to 2009.

Background: Data are limited on temporal trends in outcomes of hospitalization and surgery in pediatric Crohn's disease (CD) and ulcerative colitis (UC). Thus, we evaluated the U.S.

Multidimensional prognostic risk assessment identifies association between IL12B variation and surgery in Crohn's disease.

Background: The ability to identify patients with Crohn's disease (CD) at highest risk of surgery would be invaluable in guiding therapy. Genome-wide association studies have identified multiple IBD loci with unknown phenotypic consequences. The aims of this study were to: (1) identify associations between known and novel CD loci with early resective CD surgery and (2) develop the best predictive model for time to surgery using a combination of phenotypic, serologic, and genetic variables.

Immunization history of children with inflammatory bowel disease.

Background: Protection against vaccine-preventable diseases is important in children with inflammatory bowel disease (IBD) due to frequent immunosuppressive therapy use. The chronic relapsing nature and treatment regimen of IBD may necessitate modified timing of immunizations.

Objective: To evaluate the completeness of immunizations in children with IBD.

Postoperative complications following colectomy for ulcerative colitis in children.

Background And Aims: Colectomy rates for ulcerative colitis (UC) and data on postcolectomy complications in children are limited. Thus, we assessed colectomy rates, early postcolectomy complications, and clinical predictors in children with UC undergoing a colectomy.

Methods: Children (18 years old or older) with UC who underwent colectomy from 1983 to 2009 were identified (n=30).

Immunogenicity and safety of influenza vaccination in children with inflammatory bowel disease.

Background: Protection against vaccine-preventable diseases is important in inflammatory bowel disease (IBD) because of increased susceptibility and severity of infection with immunosuppressive therapy. However, immunosuppressive therapy may affect vaccine response. This study aimed to evaluate immunogenicity and safety of influenza vaccination in children with IBD.

Association of Mycobacterium avium subspecies paratuberculosis with Crohn Disease in pediatric patients.

Objectives: The aim of the present study was to determine the prevalence of Mycobacterium avium subsp paratuberculosis (MAP) DNA in intestinal biopsies from pediatric patients with granulomatous Crohn disease (CD) or ulcerative colitis (UC), and matched control subjects without inflammatory bowel disease (IBD).

Patients And Methods: DNA was extracted from formalin-fixed paraffin-embedded colonic and ileal biopsies from patients with CD (n = 22) or UC (n = 20), and from controls without IBD (n = 21). IS900 nested polymerase chain reaction was performed in triplicate to determine the presence of MAP-specific DNA.

Real-time tool to display the predicted disease course and treatment response for children with Crohn's disease.

Background: Immunomodulators and biologics are effective treatments for children with Crohn's disease (CD). The challenge of communicating the anticipated disease course with and without therapy to patients and parents is a barrier to the timely use of these agents. The aim of this project was to develop a tool to graphically display the predicted risks of CD and expected benefits of therapy.

Common variants at five new loci associated with early-onset inflammatory bowel disease.

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.

A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity.

Chronic granulomatous disease (CGD), an immunodeficiency with recurrent pyogenic infections and granulomatous inflammation, results from loss of phagocyte superoxide production by recessive mutations in any 1 of 4 genes encoding subunits of the phagocyte NADPH oxidase. These include gp91(phox) and p22(phox), which form the membrane-integrated flavocytochrome b, and cytosolic subunits p47(phox) and p67(phox). A fifth subunit, p40(phox), plays an important role in phagocytosis-induced superoxide production via a phox homology (PX) domain that binds to phosphatidylinositol 3-phosphate (PtdIns(3)P).

Age of diagnosis influences serologic responses in children with Crohn's disease: a possible clue to etiology?

Background: Crohn's disease (CD) is often associated with antibodies to microbial antigens. Differences in immune response may offer clues to the pathogenesis of the disease. The aim was to examine the influence of age at diagnosis on the serologic response in children with CD.

Increased immune reactivity predicts aggressive complicating Crohn's disease in children.

Background & Aims: The ability to identify children with CD who are at highest risk for rapid progression from uncomplicated to complicated phenotypes would be invaluable in guiding initial therapy. The aims of this study were to determine whether immune responses and/or CARD15 variants are associated with complicated disease phenotypes and predict disease progression.

Methods: Sera were collected from 796 pediatric CD cases and tested for anti-Cbir1 (flagellin), anti-outer membrane protein C, anti-Saccharomyces cerevisiae, and perinuclear antineutrophil cytoplasmic antibody by using enzyme-linked immunosorbent assay.

IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease.

Background: The IL-23 receptor (IL-23R) has been found to be associated with small bowel Crohn's disease (CD) in a whole genome association study. Specifically, the rare allele of the R381Q single nucleotide polymorphism (SNP) conferred protection against CD. It is unknown whether IL-23R is associated with IBD in children.

Serum immune responses predict rapid disease progression among children with Crohn's disease: immune responses predict disease progression.

Background And Aim: Crohn's disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course.