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Background and Objectives: Primary objectives: to compare the rates of sustained clinical remission at 12 months in patients treated with antitumour necrosis factor (anti-TNF) and immunomodulators who withdraw anti-TNF treatment versus those who maintain it., Secondary Objectives: to evaluate the effect of anti-TNF withdrawal on relapse-free time, endoscopic and radiological activity, safety, quality of life and work productivity; and to identify predictive factors for relapse., Design: Prospective, quadruple-blind, multicentre, randomised, controlled trial. Patients with ulcerative colitis or Crohn's disease in clinical remission for >6 months and absence of severe endoscopic (and radiological in Crohn's disease) lesions were randomised to maintain anti-TNF treatment (maintenance arm (MA)) or to withdraw it (withdrawal arm (WA)). All patients maintained immunomodulators. Patients were followed-up until month 12 or up to clinical relapse., Results: One-hundred forty patients were randomised: 70 were allocated to the MA and 70 to the WA. The proportion of patients with sustained clinical remission at 12 months was similar in the MA and WA: 59/70 (84%), 95% CI=74% to 92% versus 53/70 (76%), 95% CI=64% to 85%. The proportion of patients with significant endoscopic lesions at the end of follow-up was 8.5% in the MA and 19% in the WA (p=0.1); a higher proportion of patients had faecal calprotectin >250 µg/g at the end of follow-up in the WA (p=0.01). The same percentage of patients in both groups had at least one adverse event (69%). The proportion of patients with serious adverse events was also similar in both groups (4% in MA vs 7% in WA)., Conclusion: Anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic and radiological remission has no impact on sustained clinical remission at 1 year although objective markers of activity were higher in patients who withdrew treatment., Trial Registration Number: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-001410-10 https://clinicaltrials.gov/study/NCT02994836., Competing Interests: Competing interests: MBdA has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, GALAPAGOS, Pfizer, Sandoz, Biogen, Fresenius, Lilly, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma. MCh has served as speaker, consultant or research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Biogen, Gilead and Lilly. ED has served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Galapagos, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, Tillots. JPG has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma.Marisa Iborra reports grants and personal fees from MSD, Janssen, Abbvie, Takeda, Kern and Chiesi, during the conduct of the study.Eduardo Leo has received grants or honoraria for scientific activities, presentations or as a scientific advisor for MSD, Pfizer, Abbvie, Takeda, Janssen, Tillotts Pharma, Shire Pharmaceuticals, Ferring, Dr. Falk Pharma, Adacyte and Otsuka Pharmaceutical. PNM reports grants and personal fees from MSD, grants from Otsuka, AbbVie; personal fees from Takeda, Kern, Biogen, Ferring. JP received financial support for research from AbbVie and Pfizer; consultancy fees/honorarium from AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celsius, Celltrion, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Morphic, Pandion, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Robarts, Sanofi, Takeda, Theravance and Wasserman; reports payment for lectures including service on speaker bureau from Abbott, Ferring, Janssen, Pfizer and Takeda; and reports payment for development of educational presentations from Abbott, Janssen, Pfizer Roche and Takeda. MR has served as a speaker or advisory member from TaKeda, Janssen, Galapagos, Ferring and Pfizer. MV has received educational funding from Janssen, Kern Pharma and Takeda. Rest of authors have nothing to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Background and Aims: The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life., Methods: Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16., Results: A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection., Conclusions: Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab., (© The Author(s) 2021. 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.)

Background: Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others., Aims: Our aim was to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date., Methods: Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018., Results: The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2-19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9-13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7-5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9-2.2) for ocular manifestations, and 0.7% (95% CI 0.6-0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn's disease, p < 0.001), gender (female, p < 0.001), the need for an immunomodulator (p < 0.001) or biologic drugs (p < 0.001), a previous family history of IBD (p < 0.001), and an extensive location of IBD (p < 0.001) were risk factors for the presence of EIMs., Conclusions: One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn's disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear.

Aim: To evaluate the rate of adverse events (AEs) during consecutive gastric and duodenal polypectomies in several Spanish centers., Methods: Polypectomies of protruded gastric or duodenal polyps ≥ 5 mm using hot snare were prospectively included. Prophylactic measures of hemorrhage were allowed in predefined cases. AEs were defined and graded according to the lexicon recommended by the American Society for Gastrointestinal Endoscopy. Patients were followed for 48 h, one week and 1 mo after the procedure., Results: 308 patients were included and a single polypectomy was performed in 205. Only 36 (11.7%) were on prior anticoagulant therapy. Mean polyp size was 15 ± 8.9 mm (5-60) and in 294 cases (95.4%) were located in the stomach. Hemorrhage prophylaxis was performed in 219 (71.1%) patients. Nine patients presented AEs (2.9%), and 6 of them were bleeding ( n = 6, 1.9%) (in 5 out of 6 AE, different types of endoscopic treatment were performed). Other 24 hemorrhagic episodes could be managed without any change in the outcome of the endoscopy and, consequently, were considered incidents. We did not find any independent risk factor of bleeding., Conclusion: Gastroduodenal polypectomy using prophylactic measures has a rate of AEs small enough to consider this procedure a safe and effective method for polyp resection independently of the polyp size and location., Competing Interests: Conflict-of-interest statement: None of the authors of this manuscript, Henry Córdova, Lidia Argüello, Carme Loras, Antonio Naranjo Rodríguez, Faust Riu Pons, Joan B Gornals, David Nicolás-Pérez, Xavier Andújar Murcia, Luis Hernández, Santos Santolaria, Carles Leal, Carles Pons, Enrique Pérez-Cuadrado-Robles, Orlando García-Bosch, Michel Papo Berger, José Luis Ulla Rocha, Cristina Sánchez-Montes, Gloria Fernández-Esparrach have any conflicts of interest or financial ties to disclose.

Aim: To evaluate the early and long-term efficacy of infliximab in ulcerative colitis and to determine predictors of response and colectomy., Methods: This is an ambidirectional cohort study in a tertiary referral center including patients who started infliximab within 2005 and 2008 and monitored until 2014. Efficacy was evaluated by partial Mayo scores at weeks 2, 4, 8, 30, and 54. Long-term treatment maintenance with infliximab and colectomy requirements were recorded., Results: Fifty-three patients were included with a median follow-up of 69.5 months. Clinical remission at the time point assessments was 40.8, 47.2, 54.7, 54.7, and 49.1 %. At the time of maximal follow-up, the proportion of patients under infliximab maintenance was 24.5 %. A higher level of albumin (OR 1.4, CI 95 % 1.06-1.8; p = 0.017) was predictive of a higher remission rate at week 8. Concomitant immunomodulators beyond 6 months were predictive of infliximab's long-term maintenance (OR 15.8, CI 95 % 1.8-135.4; p = 0.012). Colectomy was required in 41.5 %. Factors associated with a higher rate of colectomy at week 54 were previous treatment with cyclosporine (OR 3.4, CI 95 % 1.2-9.7; p = 0.012), absence of response at week 8 (OR 10.3, CI 95 % 3.3-31.7; p < 0.001), and not receiving concomitant immunomodulators (OR 4.1, CI 95 % 1.8-9; p = 0.002). Colectomy rates within the first 54 weeks were closely dependent on the number of variables present: none (0 %), 1 (26.3 %), 2 (71.4 %), or 3 (100 %) of them (log rank <0.0001)., Conclusions: Low albumin, previous treatment with cyclosporine, absence of a concomitant immunomodulator, and lack of response at week 8 negatively affected the efficacy of infliximab in ulcerative colitis.

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.

Objective: The aim of this study was to determine the diagnostic accuracy of magnetic resonance colonography (MRC) for the evaluation of disease activity and severity in patients with ulcerative colitis (UC) using endoscopy as the reference standard., Methods: Fifty patients with UC underwent colonoscopy and MRC for the evaluation of disease activity. All patients were prospectively and consecutively included. Endoscopic activity was evaluated globally and on a segment basis using the modified Baron score (MBS), and also classified as absent, mild to moderate (inflammation without ulcers) or severe (presence of ulceration). MRC parameters evaluated in each segment were: wall thickness, pre- and post-contrast wall signal intensity, relative contrast enhancement (RCE), mural oedema, ulcers, enlarged lymph nodes and the comb sign., Results: Independent predictors for endoscopic activity on a segment basis were RCE (p=0.006), presence of oedema (p=0.003), enlarged lymph nodes (p<0.001) and the comb sign (p<0.001). A segmental simplified MRC index (MRC-S) ≥ 1 detected endoscopic inflammation with high diagnostic accuracy (sensitivity 87%, specificity 88%, area under the curve (AUC) 0.95; p<0.001). MRC-S index ≥ 2 detected severe lesions with high sensitivity (83%) and specificity (82%) with an AUC of 0.91 (p<0.001). The MRC-S index strongly correlated with the MBS (r=0.81, p<0.001) and with the subjective assessment of the radiologists for the evaluation of disease severity (r=0.77, p<0.001)., Conclusions: MRC has a high accuracy for the diagnosis of disease activity and severity in UC.

Background: Information on efficacy and predictors of response to adalimumab in ulcerative colitis (UC) clinical practice is limited., Aim: Assessment of response to adalimumab and its predictors in an observational cohort study., Methods: Retrospective cohort study based on data obtained from ENEIDA registry. All patients diagnosed with UC treated with adalimumab were included. Response to adalimumab was evaluated at weeks 12, 28, and 54 according to the partial Mayo score, and requirement of colectomy until end of follow-up., Results: 48 patients with UC treated with adalimumab were included; 39 (81.3%) had previously received infliximab. Response rates at weeks 12, 28 and 54 were 70.8%, 43.2% and 35% respectively. Response to prior treatment with infliximab was the only predictive factor of response to adalimumab at week 12, which was obtained in 90% of infliximab remitters, 53.8% of responders and 33.3% of primary non-responders (p=0.01). Colectomy was required in 11 patients (22.9%), after a mean time of 205 days. The only clinical independent predictor of colectomy was non-response to adalimumab at week 12: colectomy rates were 5/34 (14.7%) in responders and 6/14 (42.9%) in non-responders (p=0.035), time free of colectomy was significantly reduced in non-responders (p=0.01). Adalimumab withdrawal due to adverse events occurred in 4.2% of patients., Conclusion: This study shows that adalimumab is an effective treatment in patients with UC. If used as a second anti-TNF, previous achievement of remission with the first anti-TNF predicts response, and failure to achieve response at week 12 predicts colectomy., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Aim: In refractory pouchitis, infliximab (IFX) has been used as rescue therapy; however, there is no clinical evidence for the use of adalimumab (ADA). The aim of this study was to report the efficacy of ADA in patients with refractory pouchitis previously treated with IFX., Methods: A retrospective, open-label, case series was designed. Patients with chronic refractory pouchitis treated with ADA were included. All patients were previously treated with IFX. The short-term and mid-term efficacy of ADA was evaluated., Results: Eight patients with chronic refractory pouchitis treated with ADA were included. After 8 weeks, 13% of the patients achieved remission and 62% showed a clinical response. At week 26, 13% achieved remission and 38% showed a clinical response. At week 52, 50% of the patients avoided a permanent ileostomy but only 25 achieved remission., Conclusion: ADA treatment was found to be an alternative for patients with chronic refractory pouchitis previously treated with IFX.

Background: Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch-anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients., Methods: A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short-term IFX efficacy was evaluated at week 8 and mid-term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available., Results: Thirty-three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21-67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX., Conclusions: IFX was effective in the short- and mid-term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Ahead of Print article withdrawn by publisher. Present therapy of inflammatory bowel diseases (IBD) is aimed at relieving inflammation and treating signs and symptoms. Despite an optimized use of immunosuppressors and the new biologic agents, the need for intestinal resection in Crohn's disease (CD)has remained stable.1[1] Primary and secondary failure to respond to approved therapies, and in some cases inability to provide a surgical solution to a particular patient due to extension and/or location of lesions, represent unmet needs in the treatment of IBD. Two streams of research, experimental and clinical, are the origin of the increasing utilization of cell therapies for severe immune-mediated diseases including IBD, these include stem cell therapies, and selected/conditioned immune cell therapy, such as dendritic and regulatory T cells (Tregs). Over the last decade, significant responses have been documented to hematopoietic stem cells transplantation (HSCT) in many therapy-resistant immune-mediated disorders. Durable remission after immune reconstitution and tissue remodeling suggests an effect beyond profound immunosuppression. Although promising, HSCT for CD is still experimental and its toxicity leaves this option for a considerably reduced number of refractory patients in whom the disease is not amenable to surgical resection. In CD, where loss of tolerance towards commensal bacteria has been invoked in disease development, it would be justified to test the efficacy of tolerance-promoting cell therapies. Various approaches are being explored and have shown promising results in experimental models of autoimmunity. These include administration of mesenchimal stem cells, Tregs or tolerogenic dendritic cells.

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.)

Background: Drugs available for the treatment of inflammatory bowel disease fail to induce and maintain remission in a significant number of patients., Aim: To assess the value of stem cell therapies for treatment of inflammatory bowel disease based on published studies., Methods: Publications were identified through a MEDLINE search using the Medical Subject Heading terms: inflammatory bowel diseases, or Crohn's disease, or ulcerative colitis, and stem cell, or stromal cell or transplant., Results: Haematopoietic stem cell therapy as a primary treatment for inflammatory bowel disease was originally supported by animal experiments, and by remissions in patients undergoing transplant for haematological disorders. Later, transplantation specifically performed for patients with refractory Crohn's disease showed long-lasting clinical remission and healing of inflammatory intestinal lesions. Use of autologous nonmyeloablative regimens and concentration of the procedures in centres with large experience are key in reducing treatment-related mortality. Initial trials of mesenchymal stem cell therapy with local injection in Crohn's perianal fistulas had positive results., Conclusions: Autologous haematopoietic stem cell transplant changes the natural course of Crohn's disease, and may be a therapeutic option in patients with refractory disease if surgery is not feasible due to disease location or extension., (© 2010 Blackwell Publishing Ltd.)

Background: The main objective was to identify risk factors for extent progression in distal ulcerative colitis. The secondary objective was to determine clinical characteristics of disease at the time of progression., Methods: Data were obtained from a prospective database. Distal colitis was defined as disease limited to rectum and sigmoid colon (n = 178), extensive colitis as involvement of at least the descending colon (n = 179), and colitis with progression when there was a change of category from distal to extensive (n = 63). To study clinical characteristics at the time of progression, a nested case-control study was performed., Results: Compared to distal colitis, colitis with progression was associated to significantly higher prevalence of extraintestinal manifestations (42.9% versus 15.5%) steroid-refractory course (28.0% versus 2.2%), requirement of thiopurines (44.3% versus 17.3%), cyclosporine (25.4% versus 1.9%), infliximab (9.5% versus 1.2%), surgery (20.6% versus 0.6%), and incidence of neoplasia (6.3% versus 0%). However, these differences appeared after disease progression. Regression analysis demonstrated that preexisting independent predictive factors for progression were younger age at diagnosis (hazard ratio [HR] 0.979 95% confidence interval [CI] 0.959-0.999) and presence of sclerosing cholangitis (HR 12.83, 95% CI 1.36-121.10). The nested case-control study showed that at the time of progression the flare was more severe in cases than in matched controls, with significant differences in markers of disease severity, therapeutic requirements, hospitalizations, and surgery., Conclusions: Patients with distal ulcerative colitis diagnosed at a younger age or with associated sclerosing cholangitis are at higher risk for progression. Disease flare associated with progression follows a severe course with high therapeutic requirements.

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.

Conventional colonoscopy combined with histologic analysis represents the standard of reference for the evaluation of colorectal disease and is usually the initial examination in patients with a suspected or established diagnosis of inflammatory bowel disease (IBD). However, it is increasingly being recognized that colonoscopy is limited to providing information regarding mucosal alterations. Colonoscopy cannot help estimate the depth of involvement of colonic lesions and does not provide information regarding the presence of extraluminal complications such as abscesses or fistulas. Recent technologic advances in magnetic resonance (MR) imaging, with its high spatial and tissue resolution, have raised expectations as to the potential role of this modality in the evaluation of colonic lesions in patients with IBD, as either a complement or an alternative to colonoscopy. MR colonography allows the characterization of colonic changes in acute and chronic IBD and can depict a wide spectrum of related lesions, including ulcers, edema, wall thickening, hyperemia, and fistulas, as well as potential extraluminal complications. The bulk of available evidence indicates that MR colonography can be useful as a problem-solving tool in the evaluation of IBD, as an alternative to colonoscopy whenever tissue sampling is not required, and for the assessment of the entire colon in cases of incomplete colonoscopy.

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.