Prevalence of and Factors Associated With Extraintestinal Manifestations and Their Remission in Inflammatory Bowel Disease: The EXTRA-Intestinal Manifestation Prospective Study From the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

INTRODUCTION: Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are challenging clinical situation. No prospective study assessed remission risk factors of EIMs. The aim of this study was to prospectively investigate the epidemiology, risk factors of EIM occurrence, and EIM remission in a large IBD cohort. METHODS: We conducted a cross-sectional study in 30 French referral centers. Between May 2021 and June 2021, all consecutive patients attending to hospital appointment were systematically invited to fill out a questionnaire. RESULTS: A total of 1,971 consecutive patients with IBD were analyzed. There were 1,056 women (53.8%), and the median age of patients was 41 years (31-54). The median disease duration was 11 years (1-18). Overall, 544 (27.6%) had at least 1 EIM. In 20.2% of cases, patients had multiple EIMs. The most frequent EIMs were rheumatological (19%) and dermatological (10%) manifestations. Immunosuppressant treatment (odds ratio [OR] = 2.56; P < 0.001) was a risk factor of EIM, while the Montreal A3 classification (OR = 0.61, P = 0.023) and male gender (OR = 0.61, P < 0.001) were associated with a lower risk of EIM occurrence. IBD current clinical remission (OR = 2.42; P < 0.001) and smoking cessation (OR = 2.98; P < 0.001) were associated factors of EIM remission. Conversely, age at IBD diagnosis (OR = 0.98; P < 0.018) was associated with a lower risk of EIM remission. DISCUSSION: One quarter of patients had at least 1 EIM. Beyond factors associated with the presence of EIMs, patients with IBD current clinical remission and smoking cessation are more likely to achieve EIM remission, while increasing age at IBD diagnosis is associated with decreased chance of remission.

Prevalence of Self-Reported Venous Thromboembolism and Cardiovascular Risk Factors in Patients with Ulcerative Colitis: The GETAID FOCUS Study.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease have an increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD). The study aims to determine the prevalence of CVD and VTE risk factors in a large population of patients with ulcerative colitis (UC). METHODS: We conducted a cross-sectional study in 33 French and Belgium referral centers. A questionnaire was developed to explore self-reported risk factors for VTE and CVD, based on the latest international guidelines, in consecutive patients with UC. RESULTS: A total of 1071 patients with UC were included. There were 539 women (50.3%), and the median age of patients was 44 years [32; 57]. The median disease duration was 10 years [6; 17]. In the cohort, 36.5% of patients reported no cardiovascular risk factor (CVRF) and 72% had ≤ 1 CVRF. Regarding cardiovascular risk markers (CVRM) 36.9% of patients reported no CVRM and 78% had ≤ 1 CVRM. Of the 1071 patients, 91.3% of patients reported no VTE strong risk factor and 96% had ≤ 1 VTE moderate risk factor. CONCLUSION: This is the first cohort specifically designed to assess both VTE and CVD risks in patients with UC. More than one third of patients with UC had no CVRF and around three quarters had ≤ 1 CVRF. In addition, more than nine out of ten patients had no VTE strong risk factor and ≤ 1 moderate risk factor. Physicians should be aware of these factors in their patients.

Endoscopic submucosal dissection in tumors extending to the dentate line compared to proximal rectal tumors: a systematic review with meta-analysis.

Endoscopic submucosal dissection (ESD) is a validated treatment for early rectal tumors, but whether this therapy is efficient or not for rectal tumors extending to the dentate line (RTDL) remains unclear. We performed a systematic review and meta-analysis to assess the effectiveness and safety of ESD in RTDL compared to non-RTDL. A search in PubMed, Scopus and the Cochrane library up to April 2020 was conducted to identify studies that compared ESD in both localizations (RTDL and non-RTDL), reporting at least one main outcome (en bloc, complete resection, recurrence). Secondary outcomes were adverse event occurrence. Five observational studies including 739 patients with a total of 201 RTDL and 538 non-RTDL were considered. The proportion of female sex (66% vs. 36.9%, P < 0.001) and tumor size [mean difference = 7.75, 95% confidence interval (CI): 3.01-12.49, P = 0.001] were higher in the RTDL group. There were no differences in en bloc resection rates between RTDL and non-RTDL groups [odds ratio (OR): 0.95, 95% CI: 0.50-1.79, P = 0.087]. The complete resection rate was significantly higher in the non-RTDL group (OR: 1.72, 95% CI: 1.18-2.53, P = 0.005, I2 = 0%). However, recurrence rates were comparable (RD: -0.04, 95% CI: -0.07 to 0.00, P = 0.06, I2 = 0%). Concerning adverse events, there were no differences in terms of perforation (OR: 0.9, 95% CI: 0.26-3.08, P = 0.86, I2 = 0%) or delayed bleeding (OR: 0.64, 95% CI: 0.17-2.42, P = 0.51, I2 = 35%). Anal pain rate was 28% (95% CI: 21.4-35.8%). ESD is an effective and safe therapeutic approach for RTDL with comparable recurrence rate to non-RTDL. The lower complete resection rate in RTDL needs to be clarified in studies.

Probe-based Confocal Laser Endomicroscopy for In Vivo Assessment of Histological Healing in Ulcerative Colitis: Development and Validation of the ENHANCE Index.

BACKGROUND AND AIMS: Histological healing may represent the ultimate therapeutic goal in ulcerative colitis [UC], but it requires biopsies. Our aim was to develop a non-invasive index able to assess histological disease activity in ulcerative colitis, using probe-based confocal laser endomicroscopy [pCLE]. METHODS: One hundred patients with quiescent UC were prospectively included in five French centres. After fluorescein intravenous injection, during colonoscopy, the colorectal mucosa was analysed by white light imaging and pCLE, and then biopsied in different locations. Five endoscopists performed central reading of pCLE images blinded to clinical, endoscopic, and histological data. One expert pathologist performed a central histological reading [Nancy index: gold standard]. Univariate and multivariate analyses were performed to identify the endomicroscopic items associated with the presence of histologically active disease. RESULTS: Over 1000 pCLE videos sequences performed in 100 UC patients in endoscopic remission [Mayo 0 and 1] were evaluated. We observed that vessel diameter >20 µm, dilated crypt lumen, fluorescein leakage, and irregular crypt architecture were statistically associated with histologically proven inflammation according to the Nancy index. Hence, we built a pCLE index of mucosal inflammation with overall accuracy of 79.6% and overall sensitivity and specificity of, respectively, 57.8% and 82.8%. Negative predictive value, especially when a pCLE index ≤1 was observed, was high [93.1%]. CONCLUSIONS: Using a robust methodology, large vessel diameter, dilated crypt lumen, fluorescein leakage,and irregular crypt architecture are reliable endomicroscopic items defining the ENHANCE index for real-time assessment of histological disease activity in UC.

Systematic review with meta-analysis: comparative risk of lymphoma with anti-tumour necrosis factor agents and/or thiopurines in patients with inflammatory bowel disease.

BACKGROUND: The risk of lymphoma in patients with inflammatory bowel disease (IBD) treated with anti-TNF agents remains unclear. AIM: To assess the comparative risk of lymphoma with anti-TNF agents and/or thiopurines in IBD METHODS: We searched PubMed, EMBASE and Cochrane Library to identify studies that evaluated lymphoproliferative disorders associated with anti-TNF agents with or without thiopurines. The risk of lymphoma was assessed through four comparator groups: combination therapy (anti-TNF plus thiopurine), anti-TNF monotherapy, thiopurine monotherapy and control group. Pooled incidence rate ratios (IRR) were estimated through Poisson-normal models. RESULTS: Four observational studies comprising 261 689 patients were included. As compared with patients unexposed to anti-TNF and thiopurines, those exposed to anti-TNF monotherapy, thiopurine monotherapy or combination therapy had pooled IRR (per 1000 patient-years) of lymphoma of 1.52 (95% CI: 1.06-2.19; P = 0.023), 2.23 (95% CI: 1.79-2.79; P < 0.001) and 3.71 (95% CI: 2.30-6.00; P ≤ 0.01), respectively. The risk of lymphoma associated with combination therapy was higher than with thiopurines or anti-TNF alone with pooled IRR of 1.70 (95% CI: 1.03-2.81; P = 0.039) and 2.49 (95% CI: 1.39-4.47; P = 0.002), respectively. The risk did not differ between anti-TNF monotherapy and thiopurine monotherapy with pooled IRR of 0.72 (95% CI: 0.48-1.07; P = 0.107). All observational studies were of high quality according to the Newcastle-Ottawa scale. CONCLUSIONS: There is an increased risk of lymphoma in IBD patients treated with anti-TNF agents, either alone or when combined with thiopurines.