Search

Case-control studies have shown that patients with Crohn's disease (CD) have a microbial composition different from healthy individuals. Although the causes of CD are unknown, epidemiologic studies suggest that diet is an important contributor to CD risk, potentially via modulation of bacterial composition and gut inflammation. We hypothesized that long-term dietary clusters (DCs) are associated with gut microbiome compositions and gut inflammation. Our objectives were to identify dietary patterns and assess whether they are associated with alterations in specific gut microbial compositions and subclinical levels of gut inflammation in a cohort of healthy first-degree relatives (FDRs) of patients with CD.As part of the Genetic, Environmental, Microbial (GEM) Project, we recruited a cohort of 2289 healthy FDRs of patients with CD. Individuals provided stool samples and answered a validated food frequency questionnaire reflecting their habitual diet during the year before sample collection. Unsupervised analysis identified 3 dietary and 3 microbial composition clusters.DC3, resembling the Mediterranean diet, was strongly associated with a defined microbial composition, with an increased abundance of fiber-degrading bacteria, such as Ruminococcus, as well as taxa such as Faecalibacterium. The DC3 diet was also significantly associated with lower levels of subclinical gut inflammation, defined by fecal calprotectin, compared with other dietary patterns. No significant associations were found between individual food items and fecal calprotectin, suggesting that long-term dietary patterns rather than individual food items contribute to subclinical gut inflammation. Additionally, mediation analysis demonstrated that DC3 had a direct effect on subclinical inflammation that was partially mediated by the microbiota.Overall, these results indicated that Mediterranean-like dietary patterns are associated with microbiome and lower intestinal inflammation. This study will help guide future dietary strategies that affect microbial composition and host gut inflammation to prevent diseases.

Several studies have demonstrated higher rates of Clostridioides difficile infection (CDI) in adults with inflammatory bowel disease (IBD). We conducted a population-based study comparing the risk of hospitalization with CDI in children with and without IBD.Using health administrative data and validated algorithms, we identified all children (16 years) diagnosed with IBD in 5 Canadian provinces, then age and sex matched to 5 children without IBD. Province-specific 5-year incidence rates of hospitalization with CDI were pooled and generalized linear mixed-effects models were used to estimate the crude incidence rate ratio (IRR) comparing (1) children with and without IBD and (2) children with Crohn disease and ulcerative colitis. Hazard ratios (HR) from Cox proportional hazards models adjusting for age, sex, rural/urban household, and income were pooled using fixed-effects models.The incidence rate of CDI identified during hospitalization was 49.06 [95% confidence interval (CI), 39.40-61.08] per 10,000 person-years (PY) in 3593 children with IBD compared to 0.39 (95% CI, 0.13-1.21) per 10,000 PY in 16,284 children without IBD (crude IRR, 133.4, 95% CI, 42.1-422.7; adjusted HR, 68.2, 95% CI, 24.4-190.4). CDI was identified less often in children with Crohn disease than ulcerative colitis (crude IRR, 0.51, 95% CI, 0.32-0.82; adjusted HR, 0.69, 95% CI, 0.46-1.05).Children with IBD have a markedly higher incidence of CDI identified during a hospitalization relative to children without IBD. Consequently, symptomatic children with IBD who are hospitalized should be screened for CDI.

Neuere Evidenz deutet darauf hin, dass Morbus Crohn aus einer Dysbiose des Mikrobioms und anderen Umweltfaktoren herrühren könnte. Einer der stärksten Risikofaktoren im Zusammenhang mit der Immunaktivierung scheint in der Ernährung zu liegen. Es hat sich gezeigt, dass Diäten bei 70 bis 80% der therapienaiven Kinder zu Krankheitsbeginn Entzündungen lindern und eine Remission induzieren, und bei Patienten, die auf die derzeit empfohlene medizinische Therapie nicht mehr ansprechen oder ein Rezidiv entwickelt haben, eine Remission induzieren. Jüngste Studien brachten auch die diätetische Modulation des Mikrobioms mit der klinischen Remission in Verbindung, während die Wiederaufnahme der vorher gewohnten Diät zu einer Reaktivierung der Entzündungsreaktion und zu einer Reversion der Dysbiose führte. Während die Ernährungstherapie in der Regel im Rahmen einer Erstlinientherapie als Brücke zu Immunmodulatoren Anwendung fand, deuten neuere Erkenntnisse darauf hin, dass neue Behandlungsparadigmen, die eine Ernährungstherapie beinhalten, unterschiedliche Behandlungsstrategien ermöglichen könnten. In dieser fallbasierten Analyse der Fachliteratur wird die Morbus-Crohn-Ausschlussdiät (Crohn’s disease exclusion diet, CDED) als Monotherapie, Kombinationstherapie mit Medikamenten, als Rescue-Behandlung bei Patienten mit refraktärer Erkrankung und als Behandlung mit dem Ziel der Reduzierung der medikamentösen Therapie diskutiert.

Background Inflammatory bowel disease (IBD) phenotypes may differ between countries and ancestral groups. The study aim was to examine ancestry and subtype variations of children newly diagnosed with IBD. Methods Children newly diagnosed with IBD enrolled into the Canadian Children Inflammatory Bowel Disease Network inception cohort study were categorized into 8 ancestral groups. Prospectively collected data at diagnosis and follow-up were compared between ancestral groups. Results Among 1447 children (63.2% Crohn’s disease, 30.7% ulcerative colitis), 67.8% were European, 9.4% were South Asian, 3.8% were West Central Asian and Middle Eastern, 2.3% were African, 2.2% were East/South East Asian, 2.0% were Caribbean/Latin/Central/South American, 9.9% were mixed, and 2.6% were other. Children of African descent with ulcerative colitis had an older age of diagnosis compared with children of European descent (median 15.6 years vs 13.3 years; P = .02). Children of European descent had a higher proportion of positive family history with IBD (19.3% vs 12.1%; P = .001) compared with children of non-European descent. Children of European descent also had a lower proportion of immigrants and children of immigrants compared with children of non-European descent (9.8% vs 35.9%; P < .0001; and 3.6% vs 27.2%; P < .0001, respectively) . Conclusions Important differences exist between different ancestral groups in pediatric patients with IBD with regard to age of diagnosis, family history, and immigrant status. Our study adds to the knowledge of the impact of ancestry on IBD pathogenesis.

Background and Aims Although venous thromboembolism [VTE] is a well-known complication of inflammatory bowel disease [IBD] in adults, limited data exist on the risk in children. We report the incidence of VTE among children with and without IBD. Methods We conducted a matched cohort study within a distributed network of population-based Canadian provincial health administrative databases. Children Results The 5-year incidence of VTE among 3593 children with IBD was 31.2 [95% CI 23.7–41.0] per 10 000 person-years [PY] compared to 0.8 [95% CI 0.4–1.7] per 10 000 PY among 16 289 children without IBD [unadjusted IRR 38.84, 95% CI 16.59–90.83; adjusted HR 22.91, 95% CI 11.50–45.63]. VTE was less common in Crohn’s disease than ulcerative colitis [unadjusted IRR 0.47, 95% CI 0.27–0.83; adjusted HR 0.52, 95% CI 0.29–0.94]. The findings were similar for deep vein thrombosis and pulmonary embolism when comparing children with and without IBD. Conclusions The risk of VTE is much higher in children with IBD than controls without IBD. While the absolute risk is low, we found a higher incidence rate than previously described in the pediatric literature. Conference Presentation: An abstract based on the data included in this paper was presented at Canadian Digestive Diseases Week [Montréal, Canada] in March 2020.

Data on pediatric inflammatory bowel disease (IBD)-associated indirect and out-of-pocket (OOP) costs are limited. We aimed to estimate indirect (lost work hours and productivity) and OOP pediatric IBD-associated costs in Canada.In a nation-wide cross-sectional analysis, caregivers of children with IBD were invited to complete a questionnaire on lost work hours and OOP costs related to IBD in the 4 weeks prior to the survey. Participants were reinvited to periodically answer the same questionnaire every 3-9 months for 2 years. Lost productivity was calculated using the Human Capital method. Costs were reported in 2018 inflation-adjusted Canadian dollars. Predictors of high cost users (top 25%) were examined using binary logistic regression.Consecutive 243 (82 incident cases) of 262 (92.7%) approached participants completed the first survey with a total of 450 surveys longitudinally completed over 2 years. The median annual indirect cost per patient was $5966 (IQR $1809-$12,676), with $5721 (IQR $1366-$11,545) for Crohn's disease (CD) and $7007 (IQR $2428-$14,057) for ulcerative colitis (UC) ( P = 0.11). The annual median per patient OOP costs were $4550 with $4550 for CD and $5038 for UC ( P = 0.53). Longer travel distance to clinic was associated with higher OOP costs (odds ratio = 4.55; Plt; 0.0001; 95% confidence interval: 1.99-10.40).Indirect and OOP IBD-associated costs are substantial and more likely to affect families living in remote communities.

Objectives With the increased prevalence of childhood-onset inflammatory bowel disease (IBD), there is a greater need for a planned transition process for adolescents and young adults (AYA). The Canadian IBD Transition Network and Crohn’s and Colitis Canada joined in collaborative efforts to describe a set of care consensus statements to provide a framework for transitioning AYA from pediatric to adult care. Methods Consensus statements were drafted after focus group meetings and literature reviews. An expert panel consisting of 20 IBD physicians, nurses, surgeon, adolescent medicine physician, as well as patient and caregiver representatives met, discussed and systematically voted. The consensus was reached when greater than 75% of members voted in agreement. When greater than 75% of members rated strong support, the statement was rendered a strong recommendation, suggesting that a clinician should implement the statement for all or most of their clinical practice. Results The Canadian expert panel generated 15 consensus statements (9 strong and 6 weak recommendations). Areas of focus of the statements included: transition program implementation, key stakeholders, areas of potential need and gaps in the research. Conclusions These consensus statements provide a framework for the transition process. The quality of evidence for these statements was generally low, highlighting the need for further controlled studies to investigate and better define effective strategies for transition in pediatric to adult IBD care.

Background & Aims Altered gut microbiota composition and function have been associated with inflammatory bowel diseases, including ulcerative colitis (UC), but the causality and mechanisms remain unknown. Methods We applied 16S ribosomal RNA gene sequencing, shotgun metagenomic sequencing, in vitro functional assays, and gnotobiotic colonizations to define the microbial composition and function in fecal samples obtained from a cohort of healthy individuals at risk for inflammatory bowel diseases (pre-UC) who later developed UC (post-UC) and matched healthy control individuals (HCs). Results Microbiota composition of post-UC samples was different from HC and pre-UC samples; however, functional analysis showed increased fecal proteolytic and elastase activity before UC onset. Metagenomics identified more than 22,000 gene families that were significantly different between HC, pre-UC, and post-UC samples. Of these, 237 related to proteases and peptidases, suggesting a bacterial component to the pre-UC proteolytic signature. Elastase activity inversely correlated with the relative abundance of Adlercreutzia and other potentially beneficial taxa and directly correlated with known proteolytic taxa, such as Bacteroides vulgatus. High elastase activity was confirmed in Bacteroides isolates from fecal samples. The bacterial contribution and functional significance of the proteolytic signature were investigated in germ-free adult mice and in dams colonized with HC, pre-UC, or post-UC microbiota. Mice colonized with or born from pre-UC–colonized dams developed higher fecal proteolytic activity and an inflammatory immune tone compared with HC-colonized mice. Conclusions We have identified increased fecal proteolytic activity that precedes the clinical diagnosis of UC and associates with gut microbiota changes. This proteolytic signature may constitute a noninvasive biomarker of inflammation to monitor at-risk populations that can be targeted therapeutically with antiproteases.

Objective To assess the prevalence of upper gastrointestinal adenomatous polyps in a cohort of pediatric familial adenomatous polyposis (FAP) patients to determine if early screening is warranted. Study Design All 11 pediatric FAP patients diagnosed in Manitoba between January 2012 and December 2019 were recruited. Patient records were examined and data on age of diagnosis, gene mutation, age of first screening endoscopy, number of endoscopies, number of gastric and colonic polyps, associated pathology, medications, symptoms and FAP-related surgeries were extracted and descriptive statistics reported. Results A total of 11 children were diagnosed with FAP over the study period with a mean age at diagnosis of 6.3 ± 3.2 years with 72.3% males and median follow-up of 4.8 years. The mean age at first gastroscopy was 10.9 ± 2.9 years and 10.8 ± 3.0 years at colonoscopy. Eight patients (72%) had upper gastrointestinal polyps, with adenomatous changes seen in seven of them on pathology. No patients had invasive carcinoma or high-grade dysplasia. All patients developed tubular adenomas on colorectal polyp pathology. Four (36%) patients underwent surgical colectomy. Conclusions Early-onset upper gastrointestinal adenomatous polyps in a pediatric FAP are common. Our study provides further data to support consideration of further, large-scale research into the benefit of early endoscopic screening for upper gastrointestinal malignancy in FAP patients.

The gluten-free diet (GFD) has gained popularity beyond its main medical indication as the treatment for gluten-induced immune-mediated disorders such as celiac disease (CD), dermatitis herpetiformis, gluten ataxia, wheat allergy, and non-celiac gluten sensitivity. However, the diet carries some disadvantages such as elevated costs, nutritional deficiencies, and social and psychological barriers. The present work aims to review indications, proven benefits, and adverse events of a gluten-free diet. Close follow-up with patients following the diet is recommended. More data is needed to assess the effectiveness of the diet in managing mental and cognitive disorders and to establish a connection between the brain and gluten.

Background Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD. Methods Patients aged Results Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2–14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p Conclusions The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.

Background Anti-tumor necrosis factor (anti-TNF) antagonists such as infliximab (IFX) are widely used for the treatment of inflammatory bowel disease (IBD). Early studies suggested that combination therapy with IFX and an immunomodulator drug (IM) such as azathioprine (AZA) or methotrexate (MTX) may help in optimising biologic pharmacokinetics, minimising immunogenicity, and improving outcomes. On the other hand, IM especially AZA, may increase infection and cancer risks with no clear evidence on long-term benefits of combination therapy. As such, stopping IM and continuation of an anti-TNF agent as a monotherapy in patients in remission seem to be a sensible strategy. However, there is no evidence to prove the efficacy of this strategy. The aim of this work was to examine frequency and factors associated with the first relapse after IM withdrawal in a cohort of children with IBD on combination therapy. Methods In a retrospective multicenter pediatric study, we determined the percentage of patients and investigated potential factors associated with the first relapse in a cohort of children and young adults with IBD on combination therapy of anti-TNF and IM after stopping IM. Cox regression analysis was used to assess factors associated with IBD relapse following IM withdrawal. Results A total of 79 patients (42, males, 62 Crohn’s disease) with 74 (93.7%) on IFX were included. In addition to the anti-TNF agent, 33 (41.8%) were on AZA and the rest were on MTX. The median duration of combination therapy was 2.0 (IQR 1.2–2.8) years. All participants were in clinical remission at the time of IM withdrawal. The median duration of follow-up after IM withdrawal was 11.0 (IQR 5.0–16.2) months. Only 8 (10.1%) patients relapsed over that period of follow-up. Age, sex, disease phenotype at diagnosis, family history of IBD, type of IM, and biochemical markers and clinical disease activity indices prior to IM stoppage did not predict a future relapse. Among those with CD on IFX who maintained remission, the median last IFX trough level before IM withdrawal was 6.25 Ug/ml (IQR: 4.04–8.70) vs. 3.8 Ug/ml (IQR: 2.40–11.6) in those who relapsed (p = 0.4). Conclusion Over short-term follow-up, the majority of children on combination therapy of IM and an anti-TNF agent remain in clinical remission after IM withdrawal.

Background The study’s objective was to investigate the incidence and risk factors associated with Clostridioides difficile (previously known as Clostridium) infection (CDI) in children with inflammatory bowel disease (IBD) in the province of Manitoba. Methods Our longitudinal population-based cohort was comprised of all children and young adults aged Results Among 261 children with IBD, 20 (7.7%) developed CDI with an incidence rate of 5.04 cases per 1000 person-years, and the median age at diagnosis (interquartile range) was 12.96 (9.33–15.81) years. The incidence rates of CDI among UC and CD patients were 4.16 cases per 1000 person-years and 5.88 cases per 1000 person-years, respectively (P = 0.46). Compared with children without CDI, those who had CDI were at increased risk of future exposure to systemic corticosteroids (adjusted hazard ratio [aHR], 4.38; 95% confidence interval [CI], 1.46–13.10) and anti–tumor necrosis factor (anti-TNF) biologics (aHR, 3.31; 95% CI, 1.11–9.90). The recurrence rate of CDI in our pediatric IBD population was 25%. Conclusions Our findings confirm that children with IBD are at high risk of developing CDI, which may predict future escalation of IBD therapy.

Background & AimsWe aim to provide guidance for medical treatment of luminal Crohn’s disease in children.MethodsWe performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn’s disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them.ResultsThe consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation.ConclusionsEvidence-based medical treatment of Crohn’s disease in children is recommended, with thorough ongoing assessments to define treatment success.

Objective Although anti-Saccharomyces cerevisiae antibodies (ASCAs) could be a useful biomarker in differentiating Crohn disease (CD) from ulcerative colitis (UC), their role as prognostic markers in children with CD has been underinvestigated. This longitudinal prospective observational study aimed to assess the prognostic value of ASCA status among children with CD managed using biologics. Methods The study population comprised children with inflammatory bowel disease diagnosed with CD from 2012 to 2018. Cox regression model with adjustment for a priori covariates was used to examine the response to anti-tumor necrosis factor (TNF) biological therapy among ASCA-positive patients in comparison to ASCA-negative patients. Results There were 273 measurements available from the study cohort comprising children with CD, who were followed up for a median duration of 14 months (interquartile range 5-42). ASCA-positive patients had a higher risk for moderate to severe clinical disease (odds ratio 2.88; 95% confidence interval [CI] 1.2-7.55) and extensive endoscopic distribution (odds ratio 3.30; CI 1.12-9.74) at baseline in comparison to ASCA-negative patients, respectively. In comparison to ASCA immunoglobulin G (IgG)-negative patients, ASCA IgG-positive patients who were treated with biologics had a significantly lower relapse rate (adjusted hazard ratio 0.12; CI 0.02-0.93). Ten (14%) patients had an unstable ASCA value with either ASCA immunoglobulin A or ASCA IgG status changing from positive to negative or vice versa. Conclusions ASCA-positive children with CD present with more extensive (endoscopic) and clinically severe disease. ASCA IgG is a useful prognostic marker among children with CD who receive biologics.

In addition to its morbidities, inflammatory bowel disease (IBD) has a major financial burden on patients and healthcare systems. However, there is a paucity of evidence on IBD-attributable costs in children.To determine the trends of IBD-attributable direct costs over time using a population-based analysis.Data were extracted from Manitoba Health Provider Claims and other population registry datasets from 1995 to 2017. Children with IBD were matched by age, sex and location with children without IBD. IBD-attributable direct costs were calculated using utilization counts from the administrative data and cost estimates from different sources. Inpatient hospitalisation and outpatient procedure costs were estimated using the resource intensity weight (RIW) that is attached to each record in the data. Costs were expressed in Canadian dollars.We included 733 (428 with Crohn's disease) prevalent cases who were diagnosed with IBD before the age of 18 years and were followed for 2450 person-years. A matched control group of 6763 persons who were followed for 21 558 person-years was included. The median annual costs of physician services billed per patient increased from $381 (IQR 215-1064) in 1995 to $936 (IQR 579-1932) in 2017 (P 0.001). The annual medication costs per patient increased from a median of $270 in 1995 to $7944 in 2017 (P 0.0001). The median annual direct cost per patient was $1810 in 2004 as compared to $14 791 (P 0.0001) in 2017.Over two decades, there was a significant increase in the paediatric IBD-attributable direct costs mainly driven by medication costs.

Background and aims Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. Approach and results We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. Conclusions We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.

Background Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay. Methods We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression. Results Overall (64% Crohn’s disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0–9.2) months. For the overall cohort, diagnostic delay was >9.2 months; in CD, >10.8 months and in UC/IBD-U, >6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41–4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005–0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay. Conclusions Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

Background and Aims: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. Approach and Results: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of

We determined the frequency and factors associated with the first clinical relapse after immunomodulator (IM) withdrawal in a cohort of children with inflammatory bowel disease on combination therapy. A total of 105 patients (89 with Crohn disease [CD]) in clinical remission were included (91 [86.7%] were on infliximab, 53 [50.5%] with methotrexate, and 52 on azathioprine). The median duration of combination therapy was 2.1 years (interquartile range [IQR] 1.3-2.8). Only 11 (10.5%) patients experienced a clinical relapse over a median duration of follow-up of 12.0 months (IQR 5.0-19.0) after IM discontinuation. The median baseline pediatric CD activity index in those with CD who relapsed after IM discontinuation was 47.5 (IQR: 35.0-55.0) versus those who did not relapse (median 35.0, IQR: 20.0-52.5; P = 0.04). In the patients who did not relapse, the median IFX trough level at IM discontinuation was 6.2 and 3.8 μg/mL in those who relapsed.

Background & Aims Increased intestinal permeability has been associated with Crohn’s disease (CD), but it is not clear whether it is a cause or result of the disease. We performed a prospective study to determine whether increased intestinal permeability is associated with future development of CD. Methods We assessed the intestinal permeability, measured by the urinary fractional excretion of lactulose-to-mannitol ratio (LMR) at recruitment in 1420 asymptomatic first-degree relatives (6–35 years old) of patients with CD (collected from 2008 through 2015). Participants were then followed up for a diagnosis of CD from 2008 to 2017, with a median follow-up time of 7.8 years. We analyzed data from 50 participants who developed CD after a median of 2.7 years during the study period, along with 1370 individuals who remained asymptomatic until October 2017. We used the Cox proportional hazards model to evaluate time-related risk of CD based on the baseline LMR. Results An abnormal LMR (>0.03) was associated with a diagnosis of CD during the follow-up period (hazard ratio, 3.03; 95% CI, 1.64–5.63; P = 3.97 × 10–4). This association remained significant even when the test was performed more than 3 years before the diagnosis of CD (hazard ratio, 1.62; 95% CI, 1.051–2.50; P = .029). Conclusions Increased intestinal permeability is associated with later development of CD; these findings support a model in which altered intestinal barrier function contributes to pathogenesis. Abnormal gut barrier function might serve as a biomarker for risk of CD onset.

Recent evidence has demonstrated that Crohn’s disease may have its roots in dysbiosis of the microbiome and other environmental factors. One of the strongest risk factors linked to immune activation appears to be diet. Exclusion diets have been shown to ameliorate inflammation and induce remission in 70−80% of treatment-naïve children at disease onset, and to induce remission in patients that lose response or are refractory to currently recommended medical therapy. Recent studies have also linked dietary modulation of the microbiome with clinical remission, while reintroduction of the previous habitual diet led to reactivation of inflammation and reversion of the dysbiotic state. While dietary therapy has usually been used as a first line therapy as a bridge to immunomodulators, newer insights suggest that new treatment paradigms involving dietary therapy may allow different treatment strategies. This case-based narrative review will discuss the Crohn’s disease exclusion diet (CDED) as monotherapy, combination therapy with drugs, as a rescue therapy in refractory patients and for de-escalation from medical therapy.