Abstract Background Mucosal healing (MH) has become a treatment goal for inflammatory bowel disease (IBD), especially for ulcerative colitis. However, MH is less feasible to assess frequently in patients with Crohn’s disease (CD). In this study, we investigated Protein Fingerprint Assays (PFA) of collagen degradation and formation, and neutrophil and macrophage activity markers in the ImageKids study as non-invasive markers of MH. Methods This is a proteomics planned sub-study of the multi-center prospective ImageKids study which included serum samples from children with CD (n=178) undergoing MRE and ileocolonoscopy concurrently (ImageKids study: NCT01881490). Serum from healthy age and gender-matched controls were obtained from BioIVT (n=83). PFA panel for mucosal damage (C1M, C3M, C4M, C6M, ELP-3), Immune cell activity panel (CPa9-HNE, VICM, C4G), and tissue fibrosis panel (PRO-C1, PRO-C3, PRO-C4, PRO-C5, PRO-C6, PRO-C11, PRO-C22) were determined. MH was classified as having an SES-CD score of 0 and global radiologist assessment of inflammation in the MRE of 0, using a visual analogue scale (VAS) 0-100mm, and mucosal damage (MD) was defined as having SES-CD or MRE VAS>0. Spearman rho correlations, one-way ANOVA with Tukey correction, and receiver operator characteristics (ROC) curves were applied for statistical analysis. Results Some of the previous biomarkers demonstrated to correlate with the SES-CD score and ulcer size (C1M, C3M, C6M, PRO-C4, VICM, PRO-C1, PRO-C3). CPa9-HNE, ELP-3, and PRO-C22 also correlate with the SES-CD score (table 1). The combined SES-CD and MRE VAS score of MH correlated positively with CPa9-HNE (r=0.30, p<0.0001), VICM (r=0.39, p<0.0001), C1M (r=0.29, p=0.0001), C3M (r=0.22, p=0.0022), C6M (r=0.35 p<0.0001), PRO-C4 (r=0.2, p<0.0001), PRO-C22 (r=0.32, p<0.0001), (figure 1 and 2) and showed significantly lower serum levels in pCD patients with MH compared to patients with mild, moderate, or severe mucosal damage (p<0.001) (figure 2). PRO-C3 correlated negatively with the combined SES-CD and MRE VAS score (r=-0.17, p=0.0211). These PFA biomarkers were combined in a multivariate regression model, demonstrating increased accuracy to identify patients in MH healing compared to the individual biomarkers (p<0.001, MH vs. MD: AUC=0.82 [CI:0.69-0.95), MH+Mild MD vs. moderate+severe MD: AUC=0.77 [0.70-0.84], (figure 3). Conclusion PFA biomarkers of Neutrophil activity (CPa9-HNE), Macrophage activity (VICM), mucosal damage (C1M, C3M, C4M, C6M, ELP-3), and tissue fibrosis (PRO-C3, PRO-C22) are potential surrogate biomarkers for identifying pCD patients with mucosal healing and for monitoring of mucosal damage and stenosis.

count. Meckel’s scan, endoscopy, and colonoscopy were performed and grossly normal. Biopsies again revealed long-term ileitis. Her rash was evaluated by dermatology and was not biopsied due to its consistency with her baseline atopic dermatitis.

Abstract Background Most patients with inflammatory bowel disease (IBD) eventually develop intestinal fibrosis due to increased extracellular matrix (ECM) remodelling. There is a huge medical need for non-invasive serological biomarkers for intestinal fibrosis and inflammation, as magnetic resonance enterography (MRE) and endoscopy are less desirable for repeated monitoring. Therefore, we aimed to investigate Protein FingerPrint assays (PFA) of collagen remodelling and citrullinated vimentin as surrogate markers of intestinal stenosis and tissue inflammation in paediatric Crohn’s disease (pCD) patients. Methods This is a proteomics planned sub-study of the multi-center prospective ImageKids study that enrolled children with CD undergoing MRE and colonoscopy concurrently (ImageKids study: NCT01881490). We included those in Tanner stage 5 with available serum sample for these initial analyses, as age and stage of physical development affects ECM remodelling. Serum from healthy age and gender matched controls were obtained from Central BioHub. PFA biomarkers of collagen degradation (C1M, C3M, C4M, C6M), collagen formation (PRO-C1, PRO-C3, PRO-C4, PRO-C5, PRO-C6) and citrullinated vimentin (VICM) were measured. Intestinal stenosis was determined by MRE and mucosal inflammation by the SES-CD. Student’s t-test, Pearson r correlation and one-way-ANOVA with Tukey correction was applied for statistical analysis. Results 50 pCD adolescents were included (mean age ± 14.53 years, 30 (60%) females, 11 (22%) in clinical remission and 18 (36%) with moderate-severe disease), along with 83 serum samples from healthy controls. SES-CD correlated with C1M (r=0.58, p=0.0001), C3M (r=0.46, p=0.0033), C6M (r=0.48, p=0.0021), PRO-C4 (r=0.58, p=0.0001), VICM (r=0.48, p=0.0018), PRO-C1 (r=-0.39, p=0.015) and PRO-C3 (r=-0.33, p=0.043). C1M (p<0.0001), C3M (p<0.05), and C6M p<0.001) were elevated in patients with severe ulcers compared to patients without ulcers, and vice versa for VICM (figure 1). PRO-C6 (p<0.05) was significantly elevated between patients with vs. without intestinal stenosis, and PRO-C5 (p<0.01), C4M (p<0.05), and PRO-C4 (p<0.05) were significantly lower (figure 2). Conclusion PFA biomarkers of collagen degradation and formation are associated with inflammation and/or intestinal fibrosis pCD. Furthermore, the biomarkers C1M, C3M, C4M, C6M, reflecting mucosal damage and tissue inflammation, were elevated in pCD patients with severe ulcers. PRO-C6, PRO-C5 and C4M were the best PFA biomarkers to reflect MRE-confirmed stenosis. PFA biomarker of collagen remodelling could potentially be applied as surrogate biomarkers for monitoring of mucosal damage/tissue inflammation and fibrostenotic stricture development.

ABSTRACTObjectives:We aimed to explore the ability of magnetic resonance enterography (MRE) to impute the simple endoscopic score of Crohn disease (SES‐CD) in children with CD, in whom failure of ileal intubation is common and may impair SES‐CD calculation in clinical studies.Methods:This is a substudy of the prospective ImageKids study in which children with CD underwent ileocolonoscopy (scored by SES‐CD) and MRE (scored on a 100 mm visual analogue scale [VAS] and by MaRIA). Mucosal healing (MH) was defined as SES‐CD <3, MRE‐VAS <20 mm, and/or MaRIA <7.Results:A total of 237 children (22 centers, age 11.5 ± 3.3 years), were enrolled. Ileal intubation has failed in 40 of 237 (17%). The agreement between SES‐CD and MRE was 75% (k = 0.508, P < 0.001) in the ileum, and 68% to 85% in the colonic segments (k = 0.21–0.50, P < 0.001). The sensitivity and specificity of ileal MRE‐VAS for MH were 91.7% (95% confidence interval 0.84–0.96) and 53.1% (95% confidence interval 0.43–0.63), respectively. The ileal MaRIA score (calculated in 33/40) was higher in the children without ileal intubation than in the others (20.5 ± 7.1 vs 15.1 ± 10.8, respectively, P = 0.0018). In 7% (16/237) of children, isolated active ileal disease would have been missed when considering SES‐CD only. A multivariable model predicted the ileal SES‐CD subscore from the MaRIA: SES‐CDileum = 1.145 + 0.169 × MaRIAileum rounded to the nearest whole number (R2 = 0.17). Applying this model to the children without ileal intubation revealed that 29 of 33 (88%) had ileal disease; 8 of 29 patients (28%) with normal colonic SES‐CD had imputed ileal SES‐CD ≥3.Conclusions:MRE is useful for imputing the ileal disease in pediatric clinical studies, overcoming the problem of ileal nonintubation.

Background and Objective: Radiation exposure increases cancer risk in children with Crohn disease (CD). Magnetic resonance enterography (MRE) can image the gastrointestinal tract without exposure to radiation. The aim of the present study was to determine whether our MRE protocol could diagnose terminal ileitis and the degree of inflammatory activity in children with CD.Methods: Retrospective review of patients 18 years of age or younger who underwent MRE for known or suspected CD from June 15, 2007 to April 1, 2010. MRE was performed with Volumen and water as oral contrast and gadolinium-based intravenous contrast. No antiperistaltic agent was used. Each MRE was compared with ileal biopsies obtained within 90 days. Severity of inflammation on MRE was scored and compared with the Pediatric Crohn Disease Activity Index (PCDAI).Results: Seventy-two patients underwent 80 MREs during the study period. Forty-two of the 72 patients (58.3%) underwent colonoscopy within 90 days of MRE, and the terminal ileum was intubated in 33. Compared with histology, MRE had a sensitivity of 71.4% and a specificity of 100% for terminal ileitis. The positive and negative predictive values were 100% and 70%, respectively. PCDAI was calculated in 39 of the 72 patients (54.2%) and had a statistically significant positive correlation with MRE score of 0.37 (P = 0.020426).Conclusions: In children with known or suspected CD, our MRE protocol has a high specificity and positive predictive value for terminal ileitis. Severity of inflammation on MRE had a statistically significant positive correlation with PCDAI.

Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. Intra-abdominal abscess is one of the serious complications of penetrating disease. While medical management of aggressive disease is critical to reduce the inflammatory response, use of immunosuppressive or biologic agents may be problematic in the setting of an abscess. Conventional medical management of CD-related abscesses has included a combination of bowel rest, parenteral nutrition, and antibiotics. Percutaneous drainage may augment medical management by avoiding or delaying the need for surgical intervention. There is little available data to guide the management decisions of intra-abdominal abscesses in the pediatric population. Objective: To evaluate the management and outcomes for Crohn's related intra-abdominal abscesses in the pediatric population. We conducted a retrospective review of medical records of all pediatric patients (6-21 years) diagnosed with Crohn's disease related intra-abdominal abscess at Hasbro Children's Hospital in Providence, Rhode Island over a 10-year period (2002-2012). Patients with perianal and peri-rectal abscesses in the absence of an intra-abdominal abscess were excluded from our study. 17 out of 271 patients were identified. The patient characteristics are summarized in Table 1. Imaging modalities to diagnose abscess included CT, MR enterography and ultrasound (Table 2) The number of CT scans per patient from IBD diagnosis ranged from 0-7 (average 2.7). Initial management and outcome measures are summarized in Table 3. 94% of patients were initially managed medically with IV antibiotics and bowel rest, 5 of which underwent percutaneous drainage. About half of the patients required TPN for an average duration of 3 weeks. At medical stabilization, 3 patients were escalated to an anti-TNF agent. After initiation of anti-TNF therapy, there were no abscess recurrences, infections or adverse effects reported in the follow-up period (average clinical follow-up of 10 months). This pilot study at our institution shows considerable variability in the diagnosis and treatment of intra-abdominal abscesses in pediatric patients with CD. These patients were seen over a 10-year period. During this period, the impact of increasing use of immunomodulators and biologic agents is unknown. It is still unclear if medical management (with or without percutaneous drainage) followed by escalation of medical therapy to an anti-TNF is safe or equivalent to surgical management. Future prospective studies will be needed to clarify the true incidence and optimal management of this severe complication of CD.

Crohn’s disease is a chronic inflammatory disorder of the GI tract that often presents during childhood and adolescence. Children with Crohn’s disease are often subjected to repeated radiologic examinations throughout the course of their illness, thereby raising great concern over the potential harm of cumulative radiation exposure. Magnetic resonance enterography is a new modality that provides detailed images of the GI tract without exposure to ionizing radiation. This article reviews past methods of bowel imaging, the scope of the problem with regard to radiation exposure, as well as the technical aspects, indications, and current evidence for magnetic resonance enterography in children with Crohn’s disease. Various examples of inflammatory, stricturing and penetrating disease activity are provided.