Transcutaneous auricular vagus nerve stimulation attenuates inflammatory bowel disease in children: a proof-of-concept clinical trial.

Background: Vagus nerve stimulation is an investigational anti-inflammatory therapy targeting the nervous system to modulate immune activity. This study evaluated the efficacy and safety of transcutaneous auricular VNS (ta-VNS) in patients with pediatric-onset Crohn's disease (CD) or ulcerative colitis (UC).

Methods: Participants were 10-21 years of age with mild/moderate CD or UC and fecal calprotectin (FC) > 200 ug/g within 4 weeks of study entry.

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.

Early Change in Fecal Calprotectin Predicts One-Year Outcome in Children Newly Diagnosed With Ulcerative Colitis.

Introduction: While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS).

Blood-Derived DNA Methylation Signatures of Crohn's Disease and Severity of Intestinal Inflammation.

Background & Aims: Crohn's disease is a relapsing and remitting inflammatory disorder with a variable clinical course. Although most patients present with an inflammatory phenotype (B1), approximately 20% of patients rapidly progress to complicated disease, which includes stricturing (B2), within 5 years. We analyzed DNA methylation patterns in blood samples of pediatric patients with Crohn's disease at diagnosis and later time points to identify changes that associate with and might contribute to disease development and progression.

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).

Microbiota-sensitive epigenetic signature predicts inflammation in Crohn's disease.

Altered response to the intestinal microbiota strongly associates with inflammatory bowel disease (IBD); however, how commensal microbial cues are integrated by the host during the pathogenesis of IBD is not understood. Epigenetics represents a potential mechanism that could enable intestinal microbes to modulate transcriptional output during the development of IBD. Here, we reveal a histone methylation signature of intestinal epithelial cells isolated from the terminal ilea of newly diagnosed pediatric IBD patients.

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.

Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.

Gene expression profiling can be used to uncover the mechanisms by which loci identified through genome-wide association studies (GWAS) contribute to pathology. Given that most GWAS hits are in putative regulatory regions and transcript abundance is physiologically closer to the phenotype of interest, we hypothesized that summation of risk-allele-associated gene expression, namely a transcriptional risk score (TRS), should provide accurate estimates of disease risk. We integrate summary-level GWAS and expression quantitative trait locus (eQTL) data with RNA-seq data from the RISK study, an inception cohort of pediatric Crohn's disease.

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.

Update in the treatment of paediatric ulcerative colitis.

Ulcerative colitis is an important disease in the paediatric population. Ulcerative colitis is one of the chronic inflammatory bowel diseases, and is medically incurable. However, the arsenal of medications has grown as knowledge of the pathogenesis of this disease advances.

Can we alter the natural history of Crohn disease in children?

The natural history of Crohn disease is characterized by recurrent bouts of active disease, the consequences of which can severely impair sufferers' physical and social functioning. Not only does the illness cause day-to-day morbidity for children but the consequence of the chronic inflammatory process also commonly results in the need for major intestinal surgery. The present challenge facing physicians treating children with Crohn disease is to alleviate symptoms and prolong periods of remission via the use of specifically targeted therapies while minimizing toxicity and promoting normal growth and development.

Therapeutic efficacy and safety of 6-mercaptopurine and azathioprine in patients with Crohn's disease.

The purine analogues 6-mercaptopurine (6-MP) and azathioprine have been found to be safe and efficacious in both inducing remission of Crohn's disease in adults and maintaining remission in adults and children. In addition, steroid-sparing effects are demonstrable in trials of both adults and children with Crohn's disease. Anecdotal reports of adults and very limited data from children also suggest that azathioprine and 6-MP might help prevent postoperative recurrence of Crohn's disease.