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Ileal strictures are the major indication for resective surgery in Crohn's disease (CD). We aimed to define ileal gene programs present at diagnosis linked with future stricturing behavior during five year follow-up, and to identify potential small molecules to reverse these gene signatures. Antimicrobial serologies and pre-treatment ileal gene expression were assessed in a representative subset of 249 CD patients within the RISK multicenter pediatric CD inception cohort study, including 113 that are unique to this report. These data were used to define genes associated with stricturing behavior and for model testing to predict stricturing behavior. A bioinformatics approach to define small molecules which may reverse the stricturing gene signature was applied. 19 of the 249 patients developed isolated B2 stricturing behavior during follow-up, while 218 remained B1 inflammatory. Using deeper RNA sequencing than in our prior report, we have now defined an inflammatory gene signature including an oncostatin M co-expression signature, tightly associated with extra-cellular matrix (ECM) gene expression in those who developed stricturing complications. We further computationally prioritize small molecules targeting macrophage and fibroblast activation and angiogenesis which may reverse the stricturing gene signature. A model containing ASCA and CBir1 serologies and a refined eight ECM gene set was significantly associated with stricturing development by year five after diagnosis (AUC (95th CI) = 0.82 (0.7-0.94)). An ileal gene program for macrophage and fibroblast activation is linked to stricturing complications in treatment naïve pediatric CD, and may inform novel small molecule therapeutic approaches.

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

Abstract Background Pediatric patients with Crohn disease (CD) are frequently malnourished, yet how this affects surgical outcomes has not been evaluated. This study aims to determine the effects of malnourishment in children with CD on 30-day outcomes after surgery. Study design The ACS NSQIP-Pediatric database from 2012 to 2015 was used to select children aged 5–18 with CD who underwent bowel surgery. BMI-for-age Z-scores were calculated based on CDC growth charts and 2015 guidelines of pediatric malnutrition were applied to categorize severity of malnutrition into none, mild, moderate, or severe. Malnutrition's effects on 30-day complications. Propensity weighted multivariable regression was used to determine the effect of malnutrition on complications were evaluated. Results 516 patients were included: 349 (67.6%) without malnutrition, 97 (18.8%) with mild, 49 (9.5%) with moderate, and 21 (4.1%) with severe malnutrition. There were no differences in demographics, ASA class, or elective/urgent case type. Overall complication rate was 13.6% with malnutrition correlating to higher rates: none 9.7%, mild 18.6%, moderate 20.4%, and severe 28.6% (p < 0.01). In propensity-matched, multivariable analysis, malnutrition corresponded with increased odds of complications in mild and severely malnourished patients (mild OR = 2.1 [p = 0.04], severe OR 3.26 [p = 0.03]). Conclusion Worsening degrees of malnutrition directly correlate with increasing risk of 30-day complications in children with CD undergoing major bowel surgery. These findings support BMI for-age z scores as an important screening tool for preoperatively identifying pediatric CD patients at increased risk for postoperative complications. Moreover, these scores can guide nutritional optimization efforts prior to elective surgery. Level of Evidence IV. [ABSTRACT FROM AUTHOR]

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Background and Aims: Ileal strictures are the major indication for resective surgery in Crohn's disease (CD). We aimed to define ileal gene programs present at diagnosis linked with future stricturing behavior during five year follow-up, and to identify potential small molecules to reverse these gene signatures., Methods: Antimicrobial serologies and pre-treatment ileal gene expression were assessed in a representative subset of 249 CD patients within the RISK multicenter pediatric CD inception cohort study, including 113 that are unique to this report. These data were used to define genes associated with stricturing behavior and for model testing to predict stricturing behavior. A bioinformatics approach to define small molecules which may reverse the stricturing gene signature was applied., Results: 19 of the 249 patients developed isolated B2 stricturing behavior during follow-up, while 218 remained B1 inflammatory. Using deeper RNA sequencing than in our prior report, we have now defined an inflammatory gene signature including an oncostatin M co-expression signature, tightly associated with extra-cellular matrix (ECM) gene expression in those who developed stricturing complications. We further computationally prioritize small molecules targeting macrophage and fibroblast activation and angiogenesis which may reverse the stricturing gene signature. A model containing ASCA and CBir1 serologies and a refined eight ECM gene set was significantly associated with stricturing development by year five after diagnosis (AUC (95th CI) = 0.82 (0.7-0.94))., Conclusion: An ileal gene program for macrophage and fibroblast activation is linked to stricturing complications in treatment naïve pediatric CD, and may inform novel small molecule therapeutic approaches., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The purpose of this article is to prospectively determine the accuracy of MR enterography in detecting Crohn disease lesions from the jejunum to the anorectal region in pediatric patients, in comparison with main reference investigations., Subjects and Methods: Fifty consecutive children with known Crohn disease underwent MR enterography with oral contrast agent and gadolinium-chelate intravenous injection. Two radiologists detected and localized lesions by dividing the bowel into nine segments (450 analyzed segments in 50 patients). Ileocolonoscopy, barium studies, intestinal ultrasound, and capsule endoscopy were considered as first- and second-level reference examinations and were performed within 15 days of MR enterography., Results: MR enterography detected lesions in 164 of 450 segments, with 155 true-positive and nine false-positive findings; overall sensitivity, specificity, and positive and negative predictive values for small- and large-bowel lesions were 94.5%, 97%, 94.5%, and 97%, respectively (ĸ = 0.93; 95% CI, 0.89-0.97). Sensitivity and specificity values were 88% and 97%, respectively, for the jejunum, 100% and 97% for the proximal-to-mid ileum, 100% and 100% for the distal ileum, 93% and 100% for the cecum, 70% and 97% for the ascending colon, 80% and 100% for the transverse colon, 100% and 92% for the descending colon, 96% and 90% for the sigmoid colon, and 96% and 88% for the rectum. From jejunum to rectum, the AUC value ranged between 0.916 (jejunum) and 1.00 (distal ileum). Perianal fistulas were diagnosed in 15 patients, and other complications were found in 13 patients., Conclusion: MR enterography showed an accuracy comparable to that of reference investigations, for both small- and large-bowel lesions. Because MR enterography is safer and more comprehensive than the reference examinations, it should be considered the primary examination for detecting Crohn disease lesions in children.