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The characteristics of the diet traditionally recommended for Crohn’s disease often reduce patients’ consumption of essential nutrients. Therefore, an important role belongs to nutritional support with specialized formulas, the effectiveness of which has been proven both for inducing remission and optimizing the parameters of physical development and puberty, bone mineralization. Nutritional support should be provided for patients with newly diagnosed Crohn’s disease in the form of full enteral nutrition, and subsequently in remission, exacerbation, in the pre- and postoperative periods as an addition to the standard diet. Of particular interest is the CDED ModuLife program, which is based on a combination of enteral nutrition with specially selected foods aimed at reducing the activity of intestinal inflammation in Crohn’s disease. Key words: inflammatory bowel disease, Crohn’s disease, full enteral nutrition, partial enteral nutrition, enteral nutrition formulas

The increase in incidences of pediatric Crohn’s Disease (CD) worldwide has been strongly linked with dietary shifts towards a Westernized diet, ultimately leading to altered gut microbiota and disturbance in intestinal immunity and the metabolome. Multiple clinical studies in children with CD have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission with an excellent safety profile. However, EEN is poorly tolerated, limiting its compliance and clinical application. This has spiked an interest in the development of alternative and better-tolerated nutritional therapy strategies. Several nutritional therapies have now been designed not only to treat the nutritional deficiencies seen in children with active CD but also to correct dysbiosis and reduce intestinal inflammation. In this review, we report the most recent insights regarding nutritional strategies in children with active CD: EEN, partial enteral nutrition (PEN), Crohn’s disease exclusion diet (CDED), and CD treatment-with-eating diet (CD-TREAT). We describe their setup, efficacy, safety, and (dis)advantages as well as some of their potential mechanisms of action and perspectives. A better understanding of different nutritional therapeutic options and their mechanisms will yield better and safer management strategies for children with CD and may address the barriers and limitations of current strategies in children.

Objectives The aim of the study was to assess the role of MR Enterography (MRE) in the diagnosis and follow-up of children with Crohn’s disease (CD) and to correlate disease activity indices with known MRE features of active disease.Methods This was a retrospective study including 24 patients (median age 11 years, 17 males) with clinically and histologically proven CD who underwent MRE. Two previously validated MRE scores—Magnetic Resonance Enterography Global Score (MEGS) and CD MRI index (CDMI)—were calculated. A correlative analysis was made between the Pediatric Crohn’s Disease Activity Index (PCDAI) score and MRE scores as well as individually with each MR variable. Comparison of both the MR scores was made between patients with different disease activity.Results MEGS and PCDAI scores showed strong positive correlation (r = 0.724, p = < 0.001); CDMI and PCDAI scores showed moderate positive correlation (r = 0.661, p = 0.0004). There was statistically significant difference in the MR scores between patients grouped by clinical activity. Among individual MR variables, mural thickness and enhancement best predicted the disease activity.Conclusions MRE-based scores and findings correlate with clinical activity in pediatric CD. Thereby, MRE can be considered a valuable tool in the management of CD, predicting disease activity and offering a potential alternative to endoscopy in monitoring patients during follow-up.

Infliximab (IFX) is a frequent therapeutic option for Crohn disease (CD) patients. Early detection of responders to IFX is critical for the management of CD in order to avoid long-term exposure to the drug without benefit. This retrospective study aimed at analysing which early parameters recorded during the induction period are able to predict response to IFX during the maintenance period in pediatric CD.Medical records of all CD patients ages from 2 to 18 years who received IFX at a tertiary IBD center were retrospectively analyzed. Children were classified in 3 groups according to their response at week 14 (W14) remission, clinical response or , no response. The factors recorded at W0, W2, and W6, which were associated with remission at W14 were analyzed using a logistic regression.Among the 111 patients included, 74.8% patients were responders to IFX at W14, including 38.7% in clinical remission and 36% with partial clinical response. Clinical remission at W14 was associated with normal growth (P 0.01), and normal albuminemia (P = 0.01) at baseline, It was also associated with trough levels to IFX8.3 μg/ml at week 6 (P 0.01).Trough levels to IFX8.3 μg/ml at week 6 are predictive of remission at W14 for luminal disease.

Background and ObjectiveRecurrent attentive non-invasive observation of intestinal inflammation is essential for the proper management of Crohn’s disease (CD). The goal of this study was to develop and evaluate a multimodal machine-learning (ML) model to assess ileal CD endoscopic activity by integrating information from Magnetic Resonance Enterography (MRE) and biochemical biomarkers.MethodsWe obtained MRE, biochemical and ileocolonoscopy data from the multi-center ImageKids study database. We developed an optimized multimodal fusion ML model to non-invasively assess terminal ileum (TI) endoscopic disease activity in CD from MRE data. We determined the most informative features for model development using a permutation feature importance technique. We assessed model performance in comparison to the clinically recommended linear-regression MRE model in an experimental setup that consisted of stratified 2-fold validation, repeated 50 times, with the ileocolonoscopy-based Simple Endoscopic Score for CD at the TI (TI SES-CD) as a reference. We used the predictions’ mean-squared-error (MSE) and the receiver operation characteristics (ROC) area under curve (AUC) for active disease classification (TI SEC-CD≥3) as performance metrics.Results121 subjects out of the 240 subjects in the ImageKids study cohort had all required information (Non-active CD: 62 [51%], active CD: 59 [49%]). Length of disease segment and normalized biochemical biomarkers were the most informative features. The optimized fusion model performed better than the clinically recommended model determined by both a better median test MSE distribution (7.73 vs. 8.8, Wilcoxon test, pConclusionsOptimized ML models for ileal CD endoscopic activity assessment have the potential to enable accurate and non-invasive attentive observation of intestinal inflammation in CD patients. The presented model will be made available to the community through a dedicated website upon acceptance.

Diet is associated with the onset of inflammatory bowel disease [IBD]. Up to half of IBD patients believe that diet contributes to flares. However, studies on this topic are sparse and merely focus on specific nutrients, food items or food groups. We aimed to analyse the association between dietary patterns and flare occurrence in two geographically distinct Dutch cohorts.In this longitudinal study, 724 IBD patients [Northern cohort: n = 486, Southern cohort: n = 238] were included and followed for 2 years. Habitual dietary intake was obtained via semi-quantitative food frequency questionnaires at baseline. Principal component analysis [PCA] was conducted on 22 food groups to identify dietary patterns. Flare occurrence was analysed in 427 patients in remission at baseline, using multivariable Cox proportional hazards.Compared to the Southern cohort, patients in the Northern cohort were younger at diagnosis, comprised more females, and had lower overall energy intakes [all p 0.05]. PCA revealed three dietary patterns explaining 28.8% of the total variance. The most pronounced pattern [explaining 11.6%] was characterized by intake of grain products, oils, potatoes, processed meat, red meat, condiments and sauces, and sugar, cakes and confectionery. Of the 427 patients, 106 [24.8%] developed an exacerbation during follow-up. The above dietary pattern was associated with flare occurrence (hazard ratio [HR]: 1.51, 95% confidence interval [CI]: 1.04-2.18, p = 0.029), as was female sex [HR: 1.63, 95% CI 1.04-2.55, p = 0.032].A dietary pattern, which can be seen as a 'traditional [Dutch]' or "Western' pattern was associated with flare occurrence. Confirmation in prospective studies is needed.

Mucosal healing (MH) is the main therapeutic goal of Crohn’s disease (CD). The Mucosal Inflammation Noninvasive Index (MINI) appears to be a promising tool for distinguishing MH from its inflammation. This study aims to evaluate MINI in monitoring remissions induced by exclusive enteral nutrition (EEN) in pediatric CD patients. Out of 55 newly diagnosed CD children, 31 who completed 6–8 weeks of EEN were analyzed. Clinical and biochemical data, activity of CD assessed with the Pediatric Crohn’s Disease Activity Index (PCDAI) and MINI were compared within seven days pre- and post-EEN. Response to induction therapy was defined as a decrease of PCDAI by >12.5 points. The follow-up was performed up to 12 months after EEN termination. Out of 31 children who completed 6–8 weeks of EEN, eight required corticosteroids in addition to EEN. Twenty-four patients (77%) responded to induction therapy. In responders, MINI decreased from 19 (Q1:17; Q3:22) to 12 (Q1:6; Q3:14), p < 0.001. The diagnostic accuracy of post-EEN MINI and post-EEN fecal calprotectin (FC) for treatment failure were AUC: 0.899 (95%CI: 0.737–1.000) and 0.762 (95%CI: 0.570–0.954), respectively. In the follow-up of 25 patients (80.6%), the post-EEN MINI of ≥13 points predicted CD relapse (87.5% sensitivity; 64.7% specificity), while FC had no prognostic value. MINI allows for monitoring of EEN and is superior in predicting disease relapse to FC.

Background The gut microbiome is extensively involved in induction of remission in pediatric Crohn’s disease (CD) patients by exclusive enteral nutrition (EEN). In this follow-up study of pediatric CD patients undergoing treatment with EEN, we employ machine learning models trained on baseline gut microbiome data to distinguish patients who achieved and sustained remission (SR) from those who did not achieve remission nor relapse (non-SR) by 24 weeks. Methods A total of 139 fecal samples were obtained from 22 patients (8–15 years of age) for up to 96 weeks. Gut microbiome taxonomy was assessed by 16S rRNA gene sequencing, and functional capacity was assessed by metagenomic sequencing. We used standard metrics of diversity and taxonomy to quantify differences between SR and non-SR patients and to associate gut microbial shifts with fecal calprotectin (FCP), and disease severity as defined by weighted Pediatric Crohn’s Disease Activity Index. We used microbial data sets in addition to clinical metadata in random forests (RFs) models to classify treatment response and predict FCP levels. Results Microbial diversity did not change after EEN, but species richness was lower in low-FCP samples (, Here, authors present a follow-up on a cohort of 22 pediatric CD patients undergoing EEN treatment to induce remission. They leverage machine learning techniques to show that the baseline microbiome with clinical metadata can predict sustained remission.

Pediatric inflammatory bowel disease may present differently than adult onset disease. It is important to consider a broader differential diagnosis in very early onset disease. Diagnostic and treatment decisions must consider the long term risks and benefits over a lifetime. Surgical triggers in children may include impaired growth and inability to wean from steroids in addition to standard adult indications. Effective transition of care to adult providers is a key to prevent flares and loss of follow-up.

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.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. Serum collected at diagnosis underwent both parallel reaction monitoring-targeted proteomic analysis and conventional enzyme-linked immunosorbent assay for 10 candidate biomarkers of intestinal fibrosis. Cox proportional hazard regression was used for multivariable analysis of time-dependent outcomes.In 116 subjects 58 subjects with verified B1 phenotype at diagnosis who later converted to B2 disease were compared with 58 subjects who remained B1 over 3 years of follow-up. Extracellular matrix protein 1 (ECM1) levels in the upper quartile (hazard ratio [HR] 3.43, 95% confidence limit [CL] 1.33, 8.42) were associated with future fibrostenotic disease. ASCA IgA (HR 4.99, 95% CL 1.50, 16.68) and CBir levels (HR 5.19, 95% CL 1.83, 14.74) were also associated with future intestinal fibrostenosis, although ECM1 continued to demonstrate independent association with conversion to B2 even with adjustment for serologies in multivariable analysis (HR 5.33, 95% CL 1.29, 22.13).ECM1 and other biomarkers of fibrosis may aid in determining the risk of uncomplicated inflammatory disease converting to B2 stricturing phenotypes in children with CD. Prospective validation studies to verify test performance and optimize clinical utilization are needed before clinical implementation.

BACKGROUND Asymptomatic children with Crohn’s disease (CD) require ongoing monitoring to ensure early recognition of a disease exacerbation. AIM In a cohort of pediatric CD patients, we aimed to assess the utility of serial fecal calprotectin measurements to detect intestinal inflammatory activity and predict disease relapse. METHODS In this prospective longitudinal cohort study, children with CD on infliximab therapy in clinical remission were included. Fecal calprotectin levels were assessed at baseline and at subsequent 2-5 visits. Clinical and biochemical disease activity were assessed using the Pediatric Crohn’s Disease Activity Index, C-reactive protein and erythrocyte sedimentation rate at baseline and at visits over the following 18 mo. RESULTS 53 children were included and eighteen patients (34%) had a clinical disease relapse during the study. Baseline fecal calprotectin levels were higher in patients that developed symptomatic relapse [median (interquartile range), relapse 723 μg/g (283-1758) vs 244 μg/g (61-627), P = 0.02]. Fecal calprotectin levels > 250 μg/g demonstrated good predictive accuracy of a clinical flare within 3 mo (area under the receiver operator curve was 0.86, 95% confidence limits 0.781 to 0.937). CONCLUSION Routine fecal calprotectin testing in children with CD in clinical remission is useful to predict relapse. Levels > 250 μg/g are a good predictor of relapse in the following 3 mo. This information is important to guide monitoring standards used in this population.

In recent years, there has been a significant increase in the incidence of Crohn’s disease. Despite significant medical progress, the treatment options available today do not meet the needs of all patients. Recent reports indicate that external environmental factors, including diet, are key in the pathomechanism of the disease. It was proven that the so-called Western dietary pattern is associated with an increased risk of disease. In the pediatric population, exclusive enteral nutrition is the only nutritional therapy option recommended today with proven high efficacy in inducing remission. Recent publications that indicate at least comparable efficacy and significantly better tolerability of a specialised elimination diet, the Crohn’s Disease Exclusion Diet (CDED), provide the basis for a change in recommendations. This article discusses the mechanism of action, principles of use, and scientific evidence evaluating the efficacy of CDED in the treatment of children with Crohn’s disease.

Background The objective of this study is to determine if there is an association between insurance status and access to biologics among children with Crohn’s disease (CD). Additionally, we seek to determine differences in healthcare utilization between these groups, utilizing a national sample of children with CD. Methods Children aged 8–18 with a diagnosis of CD were identified from 2012–2016 Truven Health MarketScan (IBM Watson Health). Patients were classified into Public/Medicaid or as Commercial/Privately Insured. Descriptive statistics were compared between groups and sensitivity analysis performed using inverse probability of treatment weighting. Adjusted differences in healthcare utilization were estimated by multiple linear regression models. Results We identified 6163 patients with a diagnosis of CD. There were no significant differences in each payer group’s demographic characteristics, comorbidities, or surgery rates. Over the 18-month follow-up period, 132 (20.4%) subjects in the public insurance group and 851 (15.4%) children in the private insurance group received biologics. Medicaid patients were 39% more likely to receive a biologic agent within 18 months of diagnosis compared to privately insured children (P = .0004). Postdiagnosis rates of hospitalizations and Emergency Department visits were significantly higher for the Medicaid group. Conclusions In this national sample of children with CD, publicly insured children were more likely to receive a biologic within 18 months of diagnosis compared to children with private insurance. At all points in time, publicly insured children also utilized emergency room services and required hospitalization at a significantly higher rate.

Crohn’s Disease (CD) diagnosis is a constant challenge for clinicians. Even with extensive magnetic resonance enterography (MRE) scans, identifying tissue damaged by CD can still be difficult, even for experts. Deep learning approaches for medical applications have recently gained traction as tools to complement radiologist consultation. Computer aided diagnosis can potentially save time and labor resources spent on routine manual diagnosis. For imaging of the gastrointestinal tract, these cutting-edge techniques could help distinguish subtle structures indicative of Crohn’s Disease (CD) that are not visible to the human eye. In this paper, we explore existing segmentation and neural network approaches more traditionally used for non-medical imaging and compare their diagnostic potential for identifying CD from MRE images.

Background and Aims: Intensifying therapy for Paediatric Crohn's Disease (CD) by early use of immunomodulators and biologics has been proposed for cases in which predictors of poor outcome (POPO) were present. We investigated therapy stratifying potential comparing POPO-positive and -negative CD patients from CEDATA-GPGE®, a German-Austrian Registry for Paediatric Inflammatory Bowel disease.Methods: CD patients (1–18 years) registered in CEDATA-GPGE® (2004–2018) within 3 months of diagnosis and at least two follow-up visits were included. Disease course and treatments over time were analysed regarding positivity of POPO criteria and test statistical properties.Results: 709/1084 patients included had at least one POPO criterion (65.4%): 177 patients (16.3%) had persistent disease (POPO2), 581 (53.6%) extensive disease (POPO3), 21 (1.9%) severe growth retardation POPO4, 47 (4.3%) stricturing/penetrating disease (POPO6) and 122 (11.3%) perianal disease (POPO7). Patients with persistent disease differed significantly in lack of sustained remission >1 year (Odd Ratio (OR) 1.49 [1.07–2.07], p = 0.02), patients with initial growth failure in growth failure at end of observation (OR 51.16 [19.89–131.62], p < 0.0001), patients with stricturing and penetrating disease as well as perianal disease in need for surgery (OR 17.76 [9.39–33.58], p < 0.001; OR 2.56 [1.58–4.15], p < 0.001, respectively). Positive Predictive Value for lack of sustained remission was >60% for patients with initial growth failure, persistent or stricturing/penetrating disease.Conclusion: Predictors of poor outcome with complicated courses of disease were common in CEDATA-GPGE®. An early intensified approach for paediatric CD patients with POPO-positivity (POPO2-4, 6-7) should be considered, because they have an increased risk to fare poorly.

BACKGROUND AND AIM Recent clinical findings showed proactive therapeutic drug monitoring (TDM) of adalimumab (ADL) to improve sustained remission rate in pediatric patients with Crohn's disease (CD). The present study aimed to evaluate the potential cost-effectiveness of proactive versus reactive TDM of ADL in pediatric patients with CD from the perspective of the US health-care provider. METHODS A Markov model was constructed to estimate outcomes of proactive versus reactive TDM of ADL in a hypothetical cohort of pediatric CD patients who were in remission on ADL maintenance treatment. Model inputs were derived from published literature and public data. Model outcomes included CD-related direct medical cost and quality-adjusted life-years (QALYs). Sensitivity analyses were performed to examine the robustness of base-case results. RESULTS When compared with the reactive TDM group, the proactive TDM group saved 0.1960 QALYs at lower cost by USD2021 over a 3-year time frame in base-case analysis. One-way sensitivity analysis showed the ADL drug cost to be the most influential factor. Probabilistic sensitivity analysis of 10 000 Monte-Carlo simulations found the proactive TDM group to gain 0.1958 QALYs (95% confidence interval [CI] 0.1950-0.1966; P

In pediatric Crohn’s disease (CD) patients, it is important to define the disease phenotype at diagnosis for stratifying risk. In this retrospective study, we aimed to assess the disease phenotype compared to EUROKIDS registry and analyze disease outcome of pediatric CD patients according to upper gastrointestinal (GI) tract involvement. A total of 312 patients were included. The median age at diagnosis was 13.7 years and 232 patients (74.4%) were identified to have upper GI involvement at diagnosis. In Korean pediatric CD patients, there were significant differences in male predominance (72.8% vs. 59.2, p p p p = 0.0139) and ileal involvement (OR 2.293, p = 0.0176) at diagnosis were associated with upper GI involvement. There were no significant differences in disease outcomes between patients with and without upper GI tract involvement. This study revealed that upper GI involvement is more prevalent in Korean patients with pediatric Crohn’s disease than in European patients, and the disease outcome did not appear to differ according to upper GI tract involvement.

Background Tumor necrosis factor (TNF) inhibitors are widely used in pediatric patients with inflammatory bowel disease, as well as psoriasis. However, there is growing evidence that these medications can also paradoxically induce a psoriasiform skin reaction in a subset of patients. Goals We seek to share our experience in treating severe TNF inhibitor-induced psoriasis in a pediatric patient with Crohnrs disease. Study We report a case of a 10-year-old female with Crohnrs disease, who developed psoriasis after twelve months of infliximab therapy. Her skin disease was recalcitrant to topical therapies, methotrexate, and phototherapy. Results The patient was transitioned to ustekinumab with significant improvement in her symptoms and maintenance of remission of her bowel disease. Conclusion This is the first reported case of a school-age pediatric patient with TNF inhibitor-induced psoriasis treated with ustekinumab. Controlled trials are warranted to fully assess the safety and efficacy of ustekinumab for treating TNF inhibitor-induced psoriasis in the pediatric population.J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.2106.

Endoscopic assessments of disease activity are important to diagnose and evaluate treatment responses in patients with Crohn’s disease (CD). However, the invasiveness of endoscopy limits the application of this technique in routine examination. Thus, interest has been increasing in identifying noninvasive surrogate markers to predict endoscopic CD activity. We retrospectively analyzed pediatric patients with new-onset CD from January 2013 to December 2018 at Zhejiang University Affiliated Children’s Hospital. The disease severity was scored according to the Crohn’s Disease Endoscopic Index of Severity (CDEIS). Routine blood tests were determined individually. Clinical activity was assessed based on the Pediatric Crohn’s Disease Activity Index (PCDAI). A total of 91 patients with CD had undergone one or more ileocolonoscopies (n = 146), the mean CDEIS for all the pediatric patients with CD was 7.0 (95% CI 5.7–8.2), and the mean PCDAI was 20.9 (95% CI 18.3–23.5). Pearson’s linear analysis of the CDEIS and PCDAI in pediatric patients with CD showed a moderate correlation (r = 0.508, P

The aim of this study is to evaluate the ability of magnetic resonance enterography global score (MEGS) to diagnose the activity of pediatric Crohn’s disease (CD) and its correlation with endoscopic activity score. 70 pediatric CD patients (between the ages of 6 and 17) were enrolled who underwent ileocolonoscopy and magnetic resonance enterography (MRE) within 7 days. The simplified endoscopic activity score for Crohn’s disease (SES-CD) and MEGS were acquired in the terminal ileum. Sensitivity and specificity of MEGS for detection disease activity against SES-CD was compared using the McNemar test. The correlation between MEGS and SES-CD was assessed by Spearman's rank estimation. The diagnostic accuracy of MEGS for active disease defined by SES-CD was calculated. Receiver operating characteristic curves (ROC) were constructed. Fifty-two pediatric CD patients (median age, 12 years old; 28 girls, 24 boys) were included. The incidence of upper gastrointestinal (GI) tract (23%) involvement and perianal lesions (42%) is high in pediatric Crohn’s patients, and most of them suffer from internal hemorrhoids (86.5%). MEGS showed strong correlation to SES-CD (r = 0.70, P

Patrizia Alvisi,1 Serena Arrigo,2 Salvatore Cucchiara,3 Paolo Lionetti,4 Erasmo Miele,5 Claudio Romano,6 Alberto Ravelli,7 Daniela Knafelz,8 Stefano Martelossi,9 Graziella Guariso,10 Salvatore Accomando,11 Giovanna Zuin,12 Costantino De Giacomo,13 Lucio Balzani,14 Monia Gennari,15 Marina Aloi3 On behalf of the SIGENP IBD Working Group 1Pediatric Gastroenterology Unit, Pediatric Department, Maggiore Hospital, Bologna, Italy; 2Pediatric Gastroenterology and Endoscopy Unit, G Gaslini Children’s Hospital, Genoa, Italy; 3Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy; 4Gastroenterology and Nutrition Unit, Meyer Children’s Hospital, Florence, Italy; 5Pediatric Department, Federico II University of Naples, Naples, Italy; 6Pediatric Gastroenterology, University of Messina, Messina, Italy; 7Gastroenterology and GI Endoscopy Unit, University Department of Pediatrics, Children’s Hospital, Brescia, Italy; 8Hepatology and Gastroenterology Unit, Bambino Gesù Hospital, Rome, Italy; 9Department of Pediatrics, Institute of Child Health, IRCSS Burlo Garofolo, Trieste, Italy; 10University of Padua, Padua, Italy; 11Pediatric Department, University of Palermo, G di Cristina Children’s Hospital, Palermo, Italy; 12Pediatric Unit, Buzzi Hospital, Milan, Italy; 13Pediatric Unit, Niguarda Hospital, Milan, Italy; 14Morgagni Hospital, Forlì, Italy; 15Emergency Pediatric Department, S Orsola Hospital, Bologna, Italy Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn’s disease (CD) and the published experience as rescue therapy is limited.Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months.Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively.Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P2 years was negatively correlated with final PCDAI score (P

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. Methods We analyzed FCP, LCT, and nCD64 before and after IFX induction in a pediatric Crohn’s disease (CD) cohort study. Week-14 FCP biomarker remission was defined as FCP 17.5 improvement. Predictive outcomes were calculated by receiver operating characteristics (ROCs). Results Among 56 CD patients, ROC analysis identified an infusion 4 LCT 9.4 µg/mL (AUROC, 0.799, P = 0.002) and >11.5 µg/mL (AUROC, 0.835, P = 0.003) were associated with a FCP 5 µg/mL had a median FCP improvement (dose 1 to dose 4) of 90% compared with a median of 35% with levels Conclusions This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy. Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.

Smoking is a risk factor for adult-onset Crohn&rsquo, s disease (CD). Although passive smoking from family members is a major concern, especially in pediatric CD, the number of existing epidemiological studies is limited. This multicenter case&ndash, control study aimed to assess the effects of familial smoking on pediatric CD. We examined 22 pediatric CD cases and 135 controls. The subjects&rsquo, mothers were given a self-administered questionnaire about family smoking before disease onset in the CD group or the corresponding period in the control group. Univariable logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), whereas dose&ndash, response relationship analyses were performed for more in-depth evaluations. Univariable analyses indicated that passive smoking from the mother (OR, 2.09, 95% CI, 0.61&ndash, 7.10) was not a significant, but a candidate risk factor for developing pediatric CD. In contrast, the dose&ndash, response relationship analyses revealed that passive smoking from the mother (OR, 1.17, 95% CI, 1.04&ndash, 1.31) was significantly associated with pediatric CD. Therefore, passive smoking from the mother may be predominantly associated with the development of pediatric CD. Further follow-up studies comprising environmental measurements of passive smoking exposure doses and genetic factors interaction analysis are necessary.

Background Despite the well-established efficacy of Tumor Necrosis Factor (TNF) antagonists as treatment options for Crohn’s Disease, many pediatric patients need a change in therapy due to adverse events, as well as primary and secondary loss of response, highlighting the necessity for medications with a different mechanism of action. Ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, has been approved to treat psoriatic arthritis, plaque psoriasis, and adults with Crohn’s disease. While utekinumab has been shown to be effective in inducing clinical remission in adults with Crohn’s disease refractory to anti-TNF agents, minimal data exists in the pediatric population. Aims We retrospectively describe 11 pediatric patients who received ustekinumab at the Montreal Children’s Hospital with the goal of assessing its efficacy in inducing clinical, biochemical, and endoscopic remission. Methods We abstracted baseline data, prior treatment and response, indications for starting ustekinumab, clinical response, endoscopic data, and laboratory parameters pre- and post- therapy. Clinical response was defined as decrease in abbrPCDAI (Pediatric Crohn’s Disease Activity Index) score. Results Patients ranged in age from 12–17 years old upon initiation of treatment with ustekinumab and had all previously failed either one (N=8) or both (N=3) anti-TNF therapies. Follow-up ranged from 6 to 22 months. We examined three indices of response to ustekinumab: symptomatic improvement, biomarker normalization, and endoscopic changes. Five of eleven patients demonstrated a clinical response – two maintained clinical remission across available follow-up data, while the remaining three experienced a secondary loss of response. The other six patients studied were primary non-responders. Two of these patients had normal abbrPCDAI scores upon initiation of ustekinumab and terminated therapy due to persistent stricturing disease. The other four non-responders either remained unwell or demonstrated clinical worsening, as measured by the abbrPCDAI. Of the clinical responders, 3/5 had elevated CRP values prior to initiating ustekinumab therapy, all of which normalized within one month of clinical improvement. Endoscopic data both pre- and post- ustekinumab was available in two responders and two non-responders, with endoscopic improvement seen in both of the responders and in one of the two non-responders. Conclusions These results demonstrate that ustekinumab has the potential ability to induce not only clinical and biochemical remission, but also endoscopic improvement, in the pediatric population. An area of concern is the fact that only one patient maintained remission for longer than one year. Future research should focus on maximizing and lengthening the effect of ustekinumab, as well as determining factors that influence response to therapy. Funding Agencies None

AIM To investigate the accuracy of fungal dysbiosis in mucosa and stool for predicting the diagnosis of Crohn’s disease (CD). METHODS Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer’s protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve (AUC) was calculated. RESULTS All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9 (range: 6.7-17.8) years for CD children and 13.9 (3.25-18.6) years for controls, and 10/15 (67%) of the CD and 13/20 (65%) of the control subjects were boys. CD locations at diagnosis were ileal (L1) in 4 and colonic (L3) in 11 children, while CD behavior was non-stricturing and non-penetrating (B1) in 12 and stricturing (B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools (AUC = 0.85 ± 0.057) than in mucosa (AUC = 0.71 ± 0.067) (P < 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for Saccharomyces cerevisiae and S. bayanus, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa. CONCLUSION We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD.

Background/aims Information regarding the efficacy of early infliximab treatment in pediatric patients with Crohn's disease (CD) is limited. We aimed to evaluate the impact of early combined immunosuppression on linear growth in pediatric patients with CD by performing step-up comparisons. Methods This retrospective study included pediatric patients with moderate-to-severe CD, who received a combination therapy with infliximab and azathioprine for at least 3 years and sustained corticosteroid-free remission without loss of response. The z-scores of the growth indicators obtained at the time of diagnosis and annually for 3 years thereafter were compared between the two groups. Results The early combined immunosuppression group displayed significantly increased linear growth 3 years after diagnosis (p=0.026). A significant difference was also observed in the linear growth 3 years after diagnosis between subgroups of Tanner stages 1-2 (p=0.016). Conclusions The early introduction of biologics should be considered to improve linear growth in pediatric patients with CD.

AIM To determine the distribution of anthropometric parameter (AP)-z-scores and characterize associations between medications/serum biomarkers and AP-z-scores in pediatric Crohn’s disease (CD). METHODS CD patients [< chronological age (CA) 21 years] were enrolled in a cross-sectional study. Descriptive statistics were generated for participants’ demographic characteristics and key variables of interest. Paired t-tests were used to compare AP-z-scores calculated based on CA (CA z-scores) and bone age (BA) (BA z-scores) for interpretation of AP’s. Linear regression was utilized to examine associations between medications and serum biomarkers with AP-z-scores calculated based on CA (n = 82) and BA (n = 49). We reported regression coefficients as well as their corresponding p-values and 95% confidence intervals. RESULTS Mean CA at the time of the study visit was 15.3 ± 3.5 (SD; range = 4.8-20.7) years. Mean triceps skinfold (P = 0.039), subscapular skinfold (P = 0.002) and mid-arm circumference (MAC) (P = 0.001) BA z-scores were higher than corresponding CA z-scores. Medications were positively associated with subscapular skinfold [adalimumab (P = 0.018) and methotrexate (P = 0.027)] and BMI CA z-scores [adalimumab (P = 0.029)]. Azathioprine/6-mercaptopurine were negatively associated with MAC (P = 0.045), subscapular skinfold (P = 0.014), weight (P = 0.002) and BMI (P = 0.013) CA z-scores. ESR, CRP, and WBC count were negatively associated, while albumin and IGF-1 BA z-scores were positively associated, with specific AP z-scores (P < 0.05). Mean height CA z-scores were higher in females, not males, treated with infliximab (P = 0.038). Hemoglobin (P = 0.018) was positively associated, while platelets (P = 0.005), ESR (P = 0.003) and CRP (P = 0.039) were negatively associated with height CA z-scores in males, not females. CONCLUSION Our results suggest poor efficacy of thiopurines and a possible sex difference in statural growth response to infliximab in pediatric CD. Prospective longitudinal studies are required.

BACKGROUND: In pediatric Crohn’s disease, fat mass improves over time with treatment, but lean mass deficits persist. This observational study of the associations of physical activity and dietary intake with lean mass and muscle strength in children with Crohn’s disease was ancillary to a previously reported randomized clinical trial of an intervention to improve bone health. METHODS: In this study, 138 participants were followed at baseline and at 6, 12, and 24 months with evaluation of lean and fat mass using DXA, muscle strength (peak torque), Crohn’s characteristics, dietary intake, time in moderate to vigorous physical activity (MVPA), and serum insulin-like growth factor–1 (IGF-1) and tumor necrosis factor–alpha (TNF-α). Race- and sex-specific Z-scores for leg lean mass and whole body fat mass were generated. Quasi least square regression evaluated determinants of changes in body composition and muscle strength. RESULTS: Leg lean mass and muscle strength were positively associated with time in MVPA (P < 0.05) and negatively associated with increasing clinical disease activity (P < 0.05). Both leg lean mass and strength were positively associated with IGF-1 Z-score (P ≤ 0.03) but negatively associated with serum TNF-α (P ≤ 0.04). Neither lean mass nor muscle strength was associated with caloric or protein intake. CONCLUSIONS: Persistence of lean mass deficits was related to ongoing Crohn’s disease activity but improved with greater time spent in moderate to vigorous physical activity. Future trials are needed to evaluate the efficacy of physical activity in improving lean mass in pediatric Crohn’s disease.

The incidence of Crohn's disease in the pediatric population is increasing. While pediatric patients with Crohn's disease exhibit many of the characteristics of older patients, there are important differences in the clinical presentation and course of disease that can impact the clinical decisions made during treatment. The majority of children are diagnosed in the early teen years, but subgroups of very early onset and infantile Crohn's present much earlier and have a unique clinical course. Treatment paradigms follow the traditional laddered approach, but growth and development represent special considerations that must be given to pediatric-specific complications of the treatment and disease. Surgical intervention is an important component of Crohn's management and is often employed to allow improved nutritional intake or decrease reliance on medical treatments that compromise growth.

Crohn’s disease exacerbations can often be associated with bacterial infections causing gastroenteritis. We report a child who experienced exacerbation of his Crohn’s disease associated with a positive stool culture forEdwardsiella tarda (E. tarda). Endoscopy showed features of moderate inflammation similar to exacerbation of Crohn’s disease. The patient was treated simultaneously with intravenous steroids and antibiotics, and his symptoms resolved. This case report highlights the importance of clinicians being able to promptly recognize and treat concurrent bacterial infections in Crohn’s disease exacerbations.