Rewiring the altered tryptophan metabolism as a novel therapeutic strategy in inflammatory bowel diseases.

OBJECTIVE: The extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp metabolism end-products are essential to intestinal homeostasis. Here, we investigated the role of metabolites from the kynurenine pathway. DESIGN: Targeted quantitative metabolomics was performed in two large human IBD cohorts (1069 patients with IBD). Dextran sodium sulphate-induced colitis experiments in mice were used to evaluate effects of identified metabolites. In vitro, ex vivo and in vivo experiments were used to decipher mechanisms involved. Effects on energy metabolism were evaluated by different methods including Single Cell mEtabolism by profiling Translation inHibition. RESULTS: In mice and humans, intestinal inflammation severity negatively correlates with the amount of xanthurenic (XANA) and kynurenic (KYNA) acids. Supplementation with XANA or KYNA decreases colitis severity through effects on intestinal epithelial cells and T cells, involving Aryl hydrocarbon Receptor (AhR) activation and the rewiring of cellular energy metabolism. Furthermore, direct modulation of the endogenous tryptophan metabolism, using the recombinant enzyme aminoadipate aminotransferase (AADAT), responsible for the generation of XANA and KYNA, was protective in rodent colitis models. CONCLUSION: Our study identified a new mechanism linking Trp metabolism to intestinal inflammation and IBD. Bringing back XANA and KYNA has protective effects involving AhR and the rewiring of the energy metabolism in intestinal epithelial cells and CD4+ T cells. This study paves the way for new therapeutic strategies aiming at pharmacologically correcting its alterations in IBD by manipulating the endogenous metabolic pathway with AADAT.

IgA vasculitis in patients with inflammatory bowel disease: new insights into the role of TNF-α blockers.

OBJECTIVE: The association of IgA vasculitis (IgAV) and IBD is rarely described, mainly during anti-TNF-α therapy. We aimed to describe the association of IgAV and IBD. METHODS: We retrospectively analysed the association of IgAV and IBD through the implication of the GETAID and FVSG networks. Characteristics of IBD and IgAV were collected using a standardized case report form. RESULTS: Forty-three cases were included. IBD [mainly Crohn's disease (CD) in 58%] preceded IgAV in 38 (88%), with median interval of 9.2 (IQR 5.4-15.4) years. In these 38 patients, at IgAV diagnosis, five (13%) had active IBD and 28 (74%) were treated with anti-TNF-α for a median duration of 31.5 (IQR 19-56) months. Main IgAV manifestations were purpura all patients (100%), joints in 20/35 (57%), renal in 15/35 (43%) and gastrointestinal in 11/35 (31%) involvement. IgAV was treated with glucocorticoids in 25 (66%), colchicine in six (16%), CYC in six (16%) and anti-TNF-α were discontinued in 15/28 (54%). No IgAV relapse occurred when TNF-α blockers were stopped, vs 23% in patients pursuing it. Conversely, five (33%) had IBD flare or complication after anti-TNF-α cessation vs one (8%) in those continuing biologics. Anti-TNF-α were resumed in six (40%), with subsequent IgAV relapse in four (67%). CONCLUSIONS: This large cohort suggests that TNF-α blockers may promote the onset of IgAV in IBD. Discontinuation of anti-TNF-α was associated with vasculitis remission but increased risk of IBD relapses, whereas continuation of anti-TNF-α was associated with IBD remission but vasculitis relapse.

Comparative real-world effectiveness of vedolizumab and ustekinumab for patients with ulcerative colitis: a GETAID multicentre cohort study.

INTRODUCTION: There are currently no comparative data on the efficacy and safety of vedolizumab and ustekinumab in ulcerative colitis (UC) after anti-TNF therapy fails. METHODS: We retrieved the full datasets of two observational, multicentre, retrospective studies of patients with UC for whom anti-TNF therapy failed and the patients were then treated with either vedolizumab or ustekinumab. The outcomes included steroid-free clinical remission, clinical remission, treatment persistence, colectomy, hospitalization, and serious and infectious adverse events. Propensity scores weighted comparison was applied. RESULTS: In total, 121 patients were included in the vedolizumab group and 97 were included in the ustekinumab group. At week 14 and week 52, in the weighted cohort, no difference was found between vedolizumab and ustekinumab for steroid-free clinical remission (OR = 0.55 [0.21-1.41], p = .21 and 0.94 [0.40-2.22], p = .89, respectively). There was no difference between vedolizumab and ustekinumab for secondary outcomes such as clinical remission, hospitalization, UC-related surgery, treatment persistence and serious and infectious adverse events. CONCLUSION: In patients with UC for whom anti-TNF therapy failed, no difference was found between vedolizumab and ustekinumab after propensity scores weighted comparison. Further studies are required to determine predictive factors of the efficacy of both biological agents.

Multidisciplinary support for ethics deliberations during the first COVID wave.

BACKGROUND: The first COVID-19 wave started in February 2020 in France. The influx of patients requiring emergency care and high-level technicity led healthcare professionals to fear saturation of available care. In that context, the multidisciplinary Ethics-Support Cell (EST) was created to help medical teams consider the decisions that could potentially be sources of ethical dilemmas. OBJECTIVES: The primary objective was to prospectively collect information on requests for EST assistance from 23 March to 9 May 2020. The secondary aim was to describe the Cell's functions during that period. RESEARCH DESIGN: This observational, real-time study of requests for Cell consultations concerned ethical dilemmas arising during a public health crisis. The EST created a grid to collect relevant information (clinical, patient's/designated representative's preferences and ethical principles strained by the situation), thereby assuring that each EST asked the same questions, in the same order. PARTICIPANTS AND RESEARCH CONTEXT: Only our university hospital's clinicians could request EST intervention. ETHICAL CONSIDERATIONS: The hospital Research Ethics Committee approved this study (no. CER-2020-107). The patient, his/her family, or designated representative was informed of this ethics consultation and most met with EST members, which enabled them to express their preferences and/or opposition. FINDINGS/RESULTS: 33 requests (patients' mean age: 80.8 years; 29 had COVID-19: 24 with dyspnea, 30 with comorbidities). 17 Emergency Department solicitations concerned ICU admission, without reference to resource constraints; others addressed therapeutic proportionality dilemmas. DISCUSSION: Intervention-request motives concerned limited resources and treatment intensity. Management revolved around three axes: the treatment option most appropriate for the patient, the feasibility of implementation, and dignified care for the patient. CONCLUSIONS: COVID-19 crisis forced hospitals to envisage prioritization of ICU access. Established decision-making criteria and protocols do not enable healthcare professionals to escape ethical dilemmas. That acknowledgement highlights ethical risks, enhances the added-value of nursing and encourages all players to be vigilant to pursue collective deliberations to achieve clear and transparent decisions.

A Scoring System to Determine Patients' Risk of Colectomy Within 1 Year After Hospital Admission for Acute Severe Ulcerative Colitis.

BACKGROUND & AIMS: There is consensus on the criteria used to define acute severe ulcerative colitis (ASUC) and on patient management, but it has been a challenge to identify patients at risk for colectomy based on data collected at hospital admission. We aimed to develop a system to determine patients' risk of colectomy within 1 y of hospital admission for ASUC based on clinical, biomarker, and endoscopy data. METHODS: We performed a retrospective analysis of consecutive patients with ASUC treated with corticosteroids, ciclosporin, or tumor necrosis factor (TNF) antagonists and admitted to 2 hospitals in France from 2002 through 2017. Patients were followed until colectomy or loss of follow up. A total of 270 patients with ASUC were included in the final analysis, with a median follow-up time of 30 months (derivation cohort). Independent risk factors identified by Cox multivariate analysis were used to develop a system to identify patients at risk for colectomy 1 y after ASUC. We developed a scoring system based on these 4 factors (1 point for each item) to identify high-risk (score 3 or 4) vs low-risk (score 0) patients. We validated this system using data from an independent cohort of 185 patients with ASUC treated from 2006 through 2017 at 2 centers in France. RESULTS: In the derivation cohort, the cumulative risk of colectomy was 12.3% (95% CI, 8.6-16.8). Based on multivariate analysis, previous treatment with TNF antagonists or thiopurines (hazard ratio [HR], 3.86; 95% CI, 1.82-8.18), Clostridioides difficile infection (HR, 3.73; 95% CI, 1.11-12.55), serum level of C-reactive protein above 30 mg/L (HR, 3.06; 95% CI, 1.11-8.43), and serum level of albumin below 30 g/L (HR, 2.67; 95% CI, 1.20-5.92) were associated with increased risk of colectomy. In the derivation cohort, the cumulative risks of colectomy within 1 y in patients with scores of 0, 1, 2, 3, or 4 were 0.0%, 9.4% (95% CI, 4.3%-16.7%), 10.6% (95% CI, 5.6%-17.4%), 51.2% (95% CI, 26.6%-71.3%), and 100%. Negative predictive values ranged from 87% (95% CI, 82%-91%) to 92% (95% CI, 88%-95.0%). Findings from the validation cohort were consistent with findings from the derivation cohort. CONCLUSIONS: We developed a scoring system to identify patients at low-risk vs high-risk for colectomy within 1 y of hospitalization for ASUC, based on previous treatment with TNF antagonists or thiopurines, C difficile infection, and serum levels of CRP and albumin. The system was validated in an external cohort.

Nancy Index Scores of Chronic Inflammatory Bowel Disease Activity Associate With Development of Colorectal Neoplasia.

BACKGROUND & AIMS: The degree of histologic and endoscopic disease activity has been associated with an increased risk of colorectal neoplasia (CRN) in patients with inflammatory bowel diseases (IBDs), but no histologic scoring systems have been validated for determining risk of CRN. We investigated the association between histologic and endoscopic disease activity and risk of first CRN in patients with IBD who had negative findings from a surveillance colonoscopy. METHODS: We performed a retrospective analysis of consecutive patients who underwent at least 2 colonoscopies at Saint Antoine Hospital in France from January 1, 1996, through March 1, 2015, and whose first procedure was a surveillance colonoscopy. Histologic IBD activity was assessed by the Nancy histologic index. Patients were followed up for a mean 5.7 ± 3.3 years. Logistic regression and generalized estimating equations were used to identify clinical, endoscopic, and histologic factors associated with detection of neoplasia in the inflamed colon mucosa. RESULTS: Among 398 patients who underwent 1277 colonoscopies, we identified 45 patients with CRN. Factors associated with CRN were primary sclerosing cholangitis (odds ratio [OR], 2.65; 95% CI, 1.06-6.61; P = .04), age (OR per 1-year increase, 1.04; 95% CI, 1.01-1.07; P = .003), and mean Nancy histologic index during follow-up evaluation (per 1-unit increase, OR, 1.69; 95% CI, 1.29-2.21; P < .001). After adjustment for established factors, chronic disease activity defined as detection of ulcerations at more than 50% of colonoscopies was not associated with an increased risk of CRN (OR, 1.24; 95% CI, 0.53-2.91; P = .62). CONCLUSIONS: In addition to established risk factors, we associated Nancy histologic index scores with development of CRN. Histologic findings based on the Nancy histologic index therefore should be included in determining the risk of colonic neoplasia in patients with IBD.

Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study.

OBJECTIVE: The efficacy of anti-tumour necrosis factors (anti-TNFs) in patients with Crohn's disease (CD) and symptomatic small bowel stricture (SSBS) is controversial. The aim of this study was to estimate the efficacy of adalimumab in these patients and to identify the factors predicting success. DESIGN: We performed a multicentre, prospective, observational cohort study in patients with CD and SSBS. The included patients underwent magnetic resonance enterography at baseline and subsequently received adalimumab. The primary endpoint was success at week 24, defined as adalimumab continuation without prohibited treatment (corticosteroids after the eight week following inclusion, other anti-TNFs), endoscopic dilation or bowel resection. The baseline factors independently associated with success were identified using a logistic regression model, leading to a simple prognostic score. Secondary endpoints were prolonged success after week 24 (still on adalimumab, without dilation nor surgery) and time to bowel resection in the whole cohort. RESULTS: From January 2010 to December 2011, 105 patients were screened and 97 were included. At week 24, 62/97 (64%) patients had achieved success. The prognostic score defined a good prognosis group with 43/49 successes, an intermediate prognosis group with 17/28 successes and a poor prognosis group with 1/16 successes. After a median follow-up time of 3.8 years, 45.7%±6.6% (proportion±SE) of patients who were in success at week 24 (ie, 29% of the whole cohort) were still in prolonged success at 4 years. Among the whole cohort, 50.7%±5.3% of patients did not undergo bowel resection 4 years after inclusion. CONCLUSIONS: A successful response to adalimumab was observed in about two-thirds of CD patients with SSBS and was prolonged in nearly half of them till the end of follow-up. More than half of the patients were free of surgery 4 years after treatment initiation. CLINICAL TRIAL REGISTRATION NUMBER: NCT01183403; Results.

Fungal microbiota dysbiosis in IBD.

OBJECTIVE: The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. DESIGN: Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. RESULTS: We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. CONCLUSIONS: Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis.

Effectiveness and Safety of Vedolizumab Induction Therapy for Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4ß7, in patients with Crohn's disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy. METHODS: From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase. RESULTS: Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma). CONCLUSIONS: In a cohort of patients with CD or UC who failed previous anti-tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients.

Subcutaneous Ustekinumab Provides Clinical Benefit for Two-Thirds of Patients With Crohn's Disease Refractory to Anti-Tumor Necrosis Factor Agents.

BACKGROUND & AIMS: Ustekinumab, a human monoclonal antibody against the p40 subunit of interleukins-12 and -23, is effective in inducing and maintaining remission in patients with luminal Crohn's disease (CD). We assessed the efficacy and safety of subcutaneous ustekinumab in patients with anti-tumor necrosis factor (anti-TNF) refractory CD. METHODS: We performed a retrospective observational study, collecting data from the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif on 122 consecutive patients with active CD refractory to anti-TNF therapy who received at least 1 subcutaneous injection of ustekinumab from March 2011 to December 2014, in 20 tertiary centers in Europe. Subjects were followed for at least 3 months. The primary outcome was clinical benefit, defined as reductions in symptoms and biochemical markers of CD and complete weaning from steroids, without surgery or immunosuppressant therapies. RESULTS: Seventy-nine patients (65%) had a clinical benefit within 3 months of receiving ustekinumab. Concomitant immunosuppressant therapy at study inclusion increased the odds for a clinical benefit from ustekinumab (odds ratio, 5.43; 95% confidence interval, 1.14-25.77; P = .03). Over a median follow-up period of 9.8 months (interquartile range, 5.3-14.5 months), the cumulative probabilities that patients maintained the clinical benefit for 6 and 12 months after introduction of ustekinumab were 93% and 68%, respectively. CONCLUSIONS: Almost two-thirds of patients with CD refractory to at least 1 anti-TNF agent receive clinical benefit from ustekinumab therapy, not requiring steroids for up to 12 months afterward. While awaiting results from ongoing trials, ustekinumab can be considered for use in these patients.

Changes in the Lémann Index Values During the First Years of Crohn's Disease.

BACKGROUND & AIMS: Stricturing or penetrating lesions develop over time in most patients with Crohn's disease. The Lémann Index indicates the degree of digestive damage at a given time in an individual. We tracked changes in Lémann Index scores in an inception cohort of patients and looked for factors associated with digestive damage. METHODS: We studied 221 patients diagnosed with Crohn's disease from 2004 through 2011 who received 2 or 3 serial morphologic evaluations over a period of 2 to 10 years. We collected cross-sectional images and had them reviewed by a gastroenterologist and a radiologist; Lémann index scores were calculated. A value of 2 was chosen as the cut-off value for substantial transparietal damage. Factors associated with a score greater than 2 at the last evaluation and progression of index scores were identified using univariate analysis and logistic regression analyses. RESULTS: The median index Lémann Index scores were 2.3 (interquartile range [IQR], 1.2-3.9) at first evaluation, 3.5 (IQR, 1.2-8.6) at 2 to 5 years after diagnosis, and 8.3 (IQR, 1.2-12.1) at 5 to 10 years after diagnosis. Index scores increased significantly at each stage compared with initial or previous values (P < .0001). After 73 months (IQR, 51-96 mo) of follow-up evaluation, 138 patients had a Lémann Index score greater than 2.0. The only early factor that predicted later damage was the first index value. Intestinal resection, time, and the percentage of time elapsed with a clinically active disease were associated with progressing damage. CONCLUSIONS: Based on an analysis of patients with Crohn's disease using the Lémann Index, nearly two thirds had substantial mucosal damage 2 to 10 years after diagnosis. High Lémann index scores at the first evaluation, time, persistent clinical activity, and intestinal resection are associated with damage.

Early administration of azathioprine vs conventional management of Crohn's Disease: a randomized controlled trial.

BACKGROUND & AIMS: Immunomodulator therapy is effective for patients with Crohn's disease (CD) but has not been shown to affect disease progression, presumably because it is given too late after diagnosis. We compared the efficacy of early treatment (within 6 months after diagnosis) with azathioprine versus conventional management of patients at high risk for disabling disease. METHODS: We performed an open-label trial of adults with a diagnosis of CD for less than 6 months who were at risk for disabling disease. From July 2005 to November 2010, patients at 24 French centers were randomly assigned to treatment with azathioprine (2.5 mg ∙ kg(-1) ∙ day(-1), n = 65) or conventional management (azathioprine only in cases of corticosteroid dependency, chronic active disease with frequent flares, poor response to corticosteroids, or development of severe perianal disease) (n = 67). The primary end point was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission during the first 3 years after inclusion. RESULTS: During the 3-year follow-up period, 16 patients in the azathioprine group were switched to mercaptopurine or methotrexate therapy because of intolerance or poor efficacy. Forty-one patients in the conventional management group required immunosuppressant therapy (61%; median time to first prescription, 11 months). In the azathioprine group, a median 67% of trimesters were spent in remission (interquartile range, 11%-85%) compared with 56% in the conventional management group (interquartile range, 29%-73%) (P = .69). Among secondary outcomes, a higher cumulative proportion of patients in the azathioprine group were free of perianal surgery than in the conventional management group (96% ± 3% and 82% ± 6% at month 36, respectively; P = .036). The cumulative proportion of patients free of intestinal surgery and anti-TNF therapy did not differ between groups. CONCLUSIONS: Based on results from a clinical trial, administration of azathioprine within 6 months of diagnosis of CD was no more effective than conventional management in increasing time of clinical remission. Clinicaltrials.gov, Number NCT00546546.

Long-term outcome of patients with Crohn's disease who respond to azathioprine.

BACKGROUND & AIMS: Little is known about the long-term outcomes of patients with Crohn's disease (CD) who have a complete response to therapy with azathioprine. We assessed the long-term effects of azathioprine in responders. METHODS: We collected data from the MICISTA registry (a database from the Rothschild and Saint-Antoine Hospitals, Paris, France) on consecutive CD patients treated with azathioprine from 1987 to 1999 who responded to therapy (steroid-free clinical remission at 1 y); they were followed up until 2011 (n = 220; 86 men; median age, 32 y; median follow-up period, 12.6 y). Data were compared with those from 440 matched patients with CD who did not receive immunosuppressants during the same inclusion period (controls). RESULTS: The cumulative rate of sustained remission 10 years after treatment with azathioprine was 38%. Among patients exposed to azathioprine during a prospective follow-up period (1995-2011, 1936 patient-years), the percentage of patient-years with active disease (flare or complication during the calendar year) was 17.6%. Compared with the control group, at baseline, responders were more often active smokers with significantly more extensive disease, perianal lesions, and extradigestive manifestations. During follow-up evaluation, responders had a significantly reduced risk of intestinal surgery (adjusted odds ratio, 0.69; 95% confidence interval, 0.52-0.91) and perianal surgery (adjusted odds ratio, 0.36; 95% confidence interval, 0.27-0.46). A significantly higher percentage of responders developed cancers, including nonmelanoma skin cancers, compared with controls (9.5% vs 4.1%; P < .01). Survival rates after 20 years were 92.8% ± 2.3% of responders vs 97.9% ± 0.8% of controls (P = .01). CONCLUSIONS: Based on a study at a single center, patients with CD who responded to azathioprine had a smaller proportion of patient-years with active disease, and were less likely to be hospitalized or undergo intestinal surgery, than patients with CD who did not receive immunosuppressants. These benefits, however, could be offset by an increased risk of malignancies.

Risk of SARS-CoV-2 infection in healthcare workers with inflammatory bowel disease: a case-control study.

Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of Novel coronavirus disease (COVID-19) due to occupational exposure is unknown. Aim: To assess the risk of COVID-19 in healthcare workers with IBD. Methods: A case control study enrolled 326 healthcare workers with IBD from 17 GETAID centres and matched non-healthcare workers with IBD controls (1:1) for gender, age, disease subtype and year of diagnosis. The study period was year 2020 during the COVID-19 outbreak. Results: In total, 59 COVID-19 were recorded among cases (n = 32) and controls (n = 27), including 2 severe COVID-19 (requiring hospitalization, mechanic ventilation) but no death. No difference was observed between healthcare workers and controls regarding the overall incidence rates of COVID-19 4.9 ± 2.2 vs. 3.8 ± 1.9 per 100 patient-semesters, P = 0.34) and the overall incidence rates of severe COVID-19 (0.6 ± 7.8 vs. 0.3 ± 5.5 per 100 patient-semesters, P = 0.42). In multivariate analysis in the entire study population, COVID-19 was associated with patients with body mass index > 30 kg/m2 (HR = 2.48, 95%CI [1.13-5.44], P = 0.02). Conclusion: Healthcare workers with IBD do not have an increased risk of COVID-19 compared with other patients with IBD.

Obesity in adult patients with inflammatory bowel disease: Clinical features and impact on disability. A cross-sectional survey from the GETAID.

BACKGROUND: In recent years, an increasing prevalence of obesity in inflammatory bowel disease (IBD) has been observed. However, only a few studies have focused on the impact of overweight and obesity on IBD-related disability. AIMS: To identify the factors associated with obese and overweight patients with IBD, including IBD-related disability. PATIENTS AND METHODS: In this cross-sectional study, we included 1704 consecutive patients with IBD in 42 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif (GETAID) using a 4-page questionnaire. Factors associated with obesity and overweight were assessed using univariate and multivariate analyses (odds ratios (ORs) are provided with 95% confidence intervals). RESULTS: The prevalence rates of overweight and obesity were 24.1% and 12.2%, respectively. Multivariable analyses were stratified by age, sex, type of IBD, clinical remission and age at diagnosis of IBD. Overweight was significantly associated with male sex (OR = 0.52, 95% CI [0.39-0.68], p < 0.001), age (OR = 1.02, 95% CI [1.01-1.03], p < 0.001) and body image subscore (OR = 1.15, 95% CI [1.10-1.20], p < 0.001) (Table 2). Obesity was significantly associated with age (OR = 1.03, 95% CI [1.02-1.04], p < 0.001), joint pain subscore (OR = 1.08, 95% CI [1.02-1.14], p < 0.001) and body image subscore (OR = 1.25, 95% CI [1.19-1.32], p < 0.001) (Table 3). CONCLUSION: The increasing prevalence of overweight and obesity in patients with IBD is associated with age and poorer body image. A holistic approach to IBD patient care should be encouraged to improve IBD-related disability and to prevent rheumatological and cardiovascular complications.

Prevalence and Determinants of Fatigue in Patients with IBD: A Cross-Sectional Survey from the GETAID.

BACKGROUND: Fatigue is commonly reported by patients with inflammatory bowel disease [IBD], but the determinants of IBD-related fatigue have yet to be determined. AIMS: To identify the factors associated with fatigue in a large population of patients with IBD. PATIENTS AND METHODS: Fatigue and nine other IBD-related disability dimensions were assessed in a cohort of 1704 consecutive patients with IBD using the IBD-disk questionnaire in a cross-sectional survey of 42 French and Belgian centres. Fatigue and severe fatigue were defined as energy subscores >5 and >7, respectively. Determinants of fatigue were assessed using univariate and multivariate analyses (odds ratios [ORs] are provided with 95% confidence intervals). RESULTS: The prevalence rates of fatigue and severe fatigue were 54.1% and 37.1%, respectively. Both fatigue and severe fatigue were significantly higher in patients with active disease than in patients with inactive disease [64.9% vs 44.7% and 47.4% vs 28.6%, respectively; p < 0.001 for both comparisons]. In the multivariate analysis stratified by age, sex, type of IBD and IBD activity, fatigue was associated with age >40 years (OR = 0.71 [0.54-0.93]), female sex (OR = 1.48 [1.13-1.93]) and IBD-related sick leave (OR = 1.61 [1.19-2.16]), and joint pain (OR = 1.60 [1.17-2.18]), abdominal pain (OR = 1.78 [1.29-2.45]), regulating defecation (OR = 1.67 [1.20-2.32]), education and work (OR = 1.96 [1.40-2.75]), body image (OR = 1.38 [1.02-1.86]), sleep (OR = 3.60 [2.66-4.88]) and emotions (OR = 3.60 [2.66-4.88]) subscores >5. CONCLUSION: Determinants of fatigue are not restricted to IBD-related factors but also include social factors, sleep and emotional disturbances, thus supporting a holistic approach to IBD patient care.

Endoscopic treatment of biliary fistulas after complex liver resection.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of endoscopic treatment for biliary fistulas after complex liver resection. BACKGROUND: The role of endoscopy in the treatment of fistulas of the common bile duct is well documented. On the contrary, results of endoscopic procedures for fistulas arising from peripheral bile ducts after liver resections are poorly studied, although more complex hepatectomies are increasingly performed. We analyzed retrospectively the results of these procedures in our experience. PATIENTS: Twenty-six patients aged 10 to 74 years were included. Fistulas arose after extended right hepatectomy, n = 14; extended left hepatectomy, n = 2; segmentectomy, n = 7; and split-liver transplantation, n = 3. All patients underwent radiologic or surgical external drainage before endoscopic retrograde cholangiopancreatography (ERCP). Mean bile outflow before endoscopy was 493.1 ± 386.1 mL/24 h (median, 400; range, 100-2000 mL). The mean time from surgery to diagnosis was 29.4 ± 45.5 days. RESULTS: The ERCP was performed after a median of 13 days after the diagnosis of biliary fistula. A sphincterotomy was required in 96.1% of patients. A 5F to 10F polyethylene stent bypassing the leaking bile duct was implanted in 21 (80.7%) of 26 patients. Fistulas were dried up completely in 25 (96.1%) of 26 patients. The mean time from initial ERCP to running dry of the leaks was 17.5 ± 12.4 days. Procedure-related morbidity was 0%. There was no mortality. CONCLUSION: Biliary fistulas arising from intrahepatic ducts after complex liver resections are more difficult to treat than distal fistulas arising from the common bile duct. However, despite a longer time for cure and the need for repeated ERCP, endoscopic therapy appears efficient and does not induce additional morbidity.

Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study.

BACKGROUND: Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real-life long-term data are currently available. AIMS: To assess the real-world effectiveness and safety of ustekinumab in patients with UC. METHODS: From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score ≤2. RESULTS: We included 103 patients with UC (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) with an insufficient response to immunosuppressants, anti-TNFs and/or vedolizumab. At week 52, 45 (44%) patients had discontinued ustekinumab mainly due to lack of effectiveness (n = 41). The cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7% and 58.4% after 3, 6, 9 and 12 months respectively. The overall steroid-free clinical remission rate at week 52 was 32% of whom 71% had subscores of null for rectal bleeding and stool frequency. Ten patients underwent colectomy within a median of 6.7 [4.3-10.6] months. Adverse effects were observed in 15 (16.9%) patients; 4 (4.5%) were severe, including one patient who died from a myocardial infarction. CONCLUSION: After 52 weeks, over one-half of patients with refractory UC were still treated by ustekinumab and one-third were in steroid-free clinical remission.