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Introduction: Crohn's disease (CD) varies by location, potentially affecting therapy efficacy and surgery risk, although research on this topic is conflicting. This study aims to investigate the independent association between CD location and therapeutic patterns., Methods: We analyzed patients with CD diagnosed from January 2005 to May 2023 registered in the nationwide ENEIDA registry. A univariate Cox regression analysis assessed the association of disease location with biologic use and persistence (with treatment discontinuation as a failure event), as well as the use of intestinal resections. A multivariate model was constructed to evaluate the independent association of disease location with therapeutic patterns, controlling for potential confounders such as sex, age at inclusion and diagnosis, disease duration and behavior, previous surgery or biological therapy, extraintestinal manifestations, and perianal disease., Results: The study included 17,292 patients with a median follow-up period of 6 years (interquartile range 2-10 years). Ileocolonic location was associated with a higher biologic use than colonic location (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.22-1.38) and ileal disease (HR 1.21, 95% CI 1.16-1.27), independently predicting biologic use (P < 0.001). Ileal location was associated with a lower biologic persistence than ileocolonic location (HR 1.14, 95% CI 1.07-1.21) and colonic disease (HR 1.10, 95% CI 1.01-1.20), independently predicting biologic persistence (P = 0.019). Ileal disease was associated with a higher likelihood of intestinal resections than colonic (HR 2.82, 95% CI 2.45-3.25) and ileocolonic location (HR 1.13, 95% CI 1.05-1.22), independently predicting the use of surgery (P < 0.001)., Discussion: CD location with ileal predominance is associated with a distinct therapeutic pattern, including higher biologic use, lower treatment persistence, and increased rates of intestinal resections., (Copyright © 2024 by The American College of Gastroenterology.)

Aims: The objective of the current study was to compare two patient assessment strategies using colonoscopy and MRI alternatively as first- and second-line examinations., Methods: Clinical data, endoscopy and magnetic resonance imaging (MRI) examinations of 100 patients diagnosed with ileocolonic Crohn's disease (CD) performed within 1 week were blindly reviewed by 4 clinical investigators. Two investigators evaluated MRI followed by colonoscopy for 50 cases and the same examinations in reverse order for another 50 cases; the other 2 investigators evaluated the same cases switching the order of examinations. The assessments included the likelihood of the presence of inflammation, stenosis, fistula and abscess, and therapeutic recommendations., Results: Information from the first examination was considered sufficient for management in 80% of cases for MRI and only 34% of cases for colonoscopy (p < 0.001). Adding MRI to the information from colonoscopy changed the clinicians' confidence grade in a higher proportion of patients than adding colonoscopy to information from MRI for the diagnosis of disease activity (10 vs 4%, p = 0.03), stenosis (25 vs 9%, p < 0.001), fistula (31 vs 0%, p < 0.001) and internal abscess (27 vs 0%, p < 0.001). Indications for anti-tumour necrosis factor (TNF) therapy (51 vs 37%, F = 0.006), and surgery (12 vs 5%, F = 0.019) were more frequent after MRI than after colonoscopy as first examination. As a second examination, MRI led to change in therapy in a higher proportion of patients than colonoscopy (28 vs 8%, p < 0.001)., Conclusions: In CD, information provided by MRI has a higher impact on patient management than colonoscopy and may be considered as a first-line examination for CD assessment., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNFα and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investigate the expression and effects of IL-19 on cells from active Crohn's disease (CD) patient. Twenty-three active CD patients and 20 healthy controls (HC) were included. mRNA and protein IL-19 levels were analyzed in monocytes. IL-19 effects were determined in vitro on the T cell phenotype and in the production of cytokines by immune cells. We observed that unstimulated and TLR-activated monocytes expressed significantly lower IL-19 mRNA in active CD patients than in HC (logFC = -1.97 unstimulated; -1.88 with Pam3CSK4; and -1.91 with FSL-1; p<0.001). These results were confirmed at protein level. Exogenous IL-19 had an anti-inflammatory effect on HC but not on CD patients. IL-19 decreased TNFα production in PBMC (850.7 ± 75.29 pg/ml vs 2626.0 ± 350 pg/ml; p<0.01) and increased CTLA4 expression (22.04 ± 1.55% vs 13.98 ± 2.05%; p<0.05) and IL-4 production (32.5 ± 8.9 pg/ml vs 13.5 ± 2.9 pg/ml; p<0.05) in T cells from HC. IL-10 regulated IL-19 production in both active CD patients and HC. We observed that three of the miRNAs that can modulate IL-19 mRNA expression, were up-regulated in monocytes from active CD patients. These results suggested that IL-19 had an anti-inflammatory role in this study. Defects in IL-19 expression and the lack of response to this cytokine could contribute to inflammatory mechanisms in active CD patients.

Background: The use of magnetic resonance imaging (MRI) for assessment of Crohn's disease (CD) is expanding. The aim of this study is to define and provide an external validation of the MRI predictors of active CD, severe CD, and a quantitative Magnetic Resonance Index of Activity (MaRIA)., Methods: In all, 48 patients with clinically active (n = 29) or inactive (n = 19) CD underwent ileocolonoscopy (reference standard) and MRI. T2-weighted and pre- and postcontrast-enhanced T1-weighted sequences were acquired. Endoscopic activity was evaluated by the Crohn's Disease Endoscopic Index of Severity (CDEIS), and also classified as absent, mild (inflammation without ulcers), or severe (presence of ulceration)., Results: In complete agreement with a previous derivation study, independent predictors of disease severity using CDEIS as a reference were wall thickness, relative contrast enhancement (RCE), presence of edema, and ulcers on MRI. Estimation of activity in each segment using this regression model, or another with simplified coefficients (MaRIA(S) = 1.5*wall thickness + 0.02*RCE + 5*edema + 10*ulceration) correlated with CDEIS (r = 0.798, P< 0.001; r = 0.80 P < 0.001, respectively). In the validation cohort both indexes had a high and equal accuracy for diagnosis of active disease: receiver operator characteristic (ROC) area 0.93, sensitivity 0.87, specificity 0.87 using a cutoff point ≥ 7, and for diagnosis of severe disease: ROC area 0.96, sensitivity 0.92, specificity 0.92 using a cutoff point ≥ 11. The total of segment values (MaRIA(T)) correlated with global CDEIS (r = 0.83, P< 0.001)., Conclusions: The MRI variables that should be evaluated in clinical practice to diagnose active CD and severe CD are validated, as well as the quantitative index of activity for use in research studies., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)

Objective: Assessment of disease extension and activity is crucial to guide treatment in Crohn's disease. The objective of the current cross-sectional study was to determine the accuracy of MR for this assessment., Design: 50 patients with clinically active (n = 35) or inactive (n = 15) Crohn's disease underwent ileocolonoscopy (reference standard) and MR. T2-weighted and precontrast and postcontrast-enhanced T1-weighted sequences were acquired. Endoscopic activity was evaluated by CDEIS (Crohn's Disease Endoscopic Index of Severity); in addition endoscopic lesions were classified as absent, mild (inflammation without ulcers) or severe (presence of ulceration)., Results: The comparison of intestinal segments with absent, mild and severe inflammation demonstrated a progressive and significant (p<0.001) increase in the following MR parameters: wall thickness, postcontrast wall signal intensity, relative contrast enhancement, presence of oedema, ulcers, pseudopolyps and lymph node enlargement. Independent predictors for CDEIS in a segment were wall thickness (p = 0.007), relative contrast enhancement (p = 0.01), presence of oedema (p = 0.02) and presence of ulcers at MR (p = 0.003). There was a significant correlation (r = 0.82, p<0.001) between the CDEIS of the segment and the MR index calculated according to the logistic regression analysis coefficients. The MR index had a high accuracy for the detection of disease activity (area under the receiver operating characteristic (ROC) curve 0.891, sensitivity 0.81, specificity 0.89) and for the detection of ulcerative lesions (area under the ROC curve 0.978, sensitivity 0.95, specificity 0.91) in the colon and terminal ileum., Conclusion: The accuracy of MR for detecting disease activity and assessing severity brings about the possibility of using MR as an alternative to endoscopy in the evaluation of ileocolonic Crohn's disease.

Corticosteroids and immunomodulators have been the mainstay therapies for Crohn's disease. Corticosteroids are highly effective to control symptoms in the short-term, but they are not effective in maintaining remission, they heal the mucosa in a reduced proportion of cases, and long-time exposure is associated with an increased risk of infections and mortality. Immunomodulators, azathioprine and methotrexate, heal the mucosa in a higher proportion of patients that corticosteroids but their onset of action is slow and they benefit less than half of patients with Crohn's disease. In the last decade, medical therapy for Crohn's disease has experienced a remarkable change due to the introduction of biologic therapy, and particularly the use of anti-tumour necrosis factor-alpha agents. Infliximab, adalimumab, and certolizumab pegol have demonstrated efficacy for induction and maintenance of remission in active Crohn's disease. These agents have raised the bar for what is a suitable symptomatic response in Crohn's disease and modification of the natural history of the disease has become a major goal in the treatment of Crohn's disease. There are several data in the literature that suggest that early use of biologic therapy and achievement of mucosal healing contribute to disease course modification. However, many questions on early biological therapy for Crohn's disease remain still unanswered.