Comparing magnetic resonance enterography and endoscopy findings to the motility of magnetic resonance imaging in pediatric Crohn's disease.

Background: Quantitative magnetic resonance imaging (MRI) can evaluate bowel motility in children with Crohn's disease. As inflammation increases, motility decreases.

Objective: Our aim was to show that quantitative MRI correlates with magnetic resonance enterography (MRE).

Do children with dysphagia and normal esophageal motility according to Chicago Classification always have "normal" esophageal motility?

Background: Internationally adopted Chicago Classification (CC) criteria based on adult normative data have been used to diagnose children with esophageal motility disorders undergoing high-resolution esophageal manometry (HREM). The aim of this study was to compare HREM parameters of children without dysphagia and children with dysphagia and normal findings according to CC.

Methods: HREM metrics of 41 children (13.

Comparison of predictive accuracy of knee height equations in children.

Knee height can be a proxy for height when standing height cannot be reliably measured. We compared two commonly used equations (Chumlea and Rumapea) that estimate standing height from knee height. We prospectively enrolled 210 children without scoliosis or kyphosis aged 7-12 years (mean age: 10.

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.

Exome Sequencing Implicates DGKZ , ESRRA , and GXYLT1 for Modulating Granuloma Formation in Crohn Disease.

Non-caseating granulomas may indicate a more aggressive phenotype of Crohn disease (CD). Genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis. Whole-exome sequencing was performed on peripheral blood-derived DNA from 17 pediatric patients with GCD and 19 with non-GCD (NGCD), and from an independent validation cohort of 44 GCD and 19 NGCD cases.

Real world population pharmacokinetic study in children and young adults with inflammatory bowel disease discovers novel blood and stool microbial predictors of vedolizumab clearance.

Background: Vedolizumab for inflammatory bowel disease (IBD) is often intensified based on distinct pharmacokinetics in children. Prior adult-specific population pharmacokinetic models have identified limited covariates of drug clearance.

Aims: To establish a population pharmacokinetic model for children and young adults to identify novel covariates of drug clearance to better account for paediatric-specific inter-patient variability in vedolizumab pharmacokinetics; a key secondary exploratory aim was to identify microbial signatures of pharmacokinetic outcomes in a subset of patients.

Antibodies-to-infliximab accelerate clearance while dose intensification reverses immunogenicity and recaptures clinical response in paediatric Crohn's disease.

Background: Antibodies to infliximab (ATI) are associated with secondary loss of response and increased risk for drug reactions. Limited studies have associated ATI with increased infliximab clearance.

Aims: We assessed the impact of ATI on infliximab clearance and loss of response in an inception paediatric Crohn's disease cohort with 1-year follow-up.

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).

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.

Real-World Infliximab Pharmacokinetic Study Informs an Electronic Health Record-Embedded Dashboard to Guide Precision Dosing in Children with Crohn's Disease.

Standard-of-care infliximab dosing regimens were developed prior to the routine use of therapeutic drug monitoring and identification of target concentrations. Not surprisingly, subtherapeutic infliximab concentrations in pediatric Crohn's disease (CD) are common. The primary aim was to conduct a real-world pharmacokinetic (PK) evaluation to discover blood biomarkers of rapid clearance, identify exposure targets, and a secondary aim to translate PK modeling to the clinic.

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn's Disease.

Background: The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations.

Endoscopic Removal of a Single, Painless, Juvenile Polyp in the Small Intestine Causing Anemia.

Juvenile polyps are the most common gastrointestinal polyps in childhood. Typically, they are located in the colon and present with intermittent and painless hematochezia. A few case reports have described juvenile polyps in the small intestine, all presenting as intussusception requiring surgery.

Analysis of Using the Total White Blood Cell Count to Define Severe New-onset Ulcerative Colitis in Children.

Objectives: The aim of this study was to assess common laboratory tests in identifying severe ulcerative colitis in children at diagnosis.

Methods: A cohort of 427 children 4 to 17 years of age newly diagnosed with ulcerative colitis (UC) was prospectively enrolled. Boosted classification trees were used to characterize predictive ability of disease attributes based on clinical disease severity using Pediatric Ulcerative Colitis Activity Index (PUCAI), severe (65+) versus not severe (<65) and total Mayo score, severe (10-12) versus not severe (<10); mucosal disease by Mayo endoscopic subscore, severe (3) versus not severe (<3); and extensive disease versus not extensive (left-sided and proctosigmoiditis).

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.

Serum Protein Biomarkers of Fibrosis Aid in Risk Stratification of Future Stricturing Complications in Pediatric Crohn's Disease.

Objectives: Avoiding fibrostenotic complications is of paramount concern in the management of Crohn's disease (CD). We sought to investigate the association of candidate biomarkers of fibrosis collected at diagnosis with the future development of fibrostenotic CD.

Methods: Using the Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort, a multicenter prospective observational pediatric inception cohort, subjects with an inflammatory phenotype (B1) at diagnosis who later converted to a stricturing phenotype (B2) within 3 years were compared with those who remained B1.

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.

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.

Prioritizing Crohn's disease genes by integrating association signals with gene expression implicates monocyte subsets.

Genome-wide association studies have identified ~170 loci associated with Crohn's disease (CD) and defining which genes drive these association signals is a major challenge. The primary aim of this study was to define which CD locus genes are most likely to be disease related. We developed a gene prioritization regression model (GPRM) by integrating complementary mRNA expression datasets, including bulk RNA-Seq from the terminal ileum of 302 newly diagnosed, untreated CD patients and controls, and in stimulated monocytes.

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).

Age-of-diagnosis dependent ileal immune intensification and reduced alpha-defensin in older versus younger pediatric Crohn Disease patients despite already established dysbiosis.

Age-of-diagnosis associated variation in disease location and antimicrobial sero-reactivity has suggested fundamental differences in pediatric Crohn Disease (CD) pathogenesis. This variation may be related to pubertal peak incidence of ileal involvement and Peyer's patches maturation, represented by IFNγ-expressing Th1 cells. However, direct mucosal evidence is lacking.

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.