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.

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.

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.

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.

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.

Psychometric validation of the French Multidimensional Chronic Asthenia Scale (MCAS) in a sample of 621 patients with chronic fatigue.

BACKGROUND: Psychometric validation of the Multidimensional Chronic Asthenia Scale (MCAS) was conducted in order to provide an effective tool for assessing the health-related quality of life of French-speaking patients with chronic asthenia (CA). METHODS: Items resulting from the initial formulation of the self-reported MCAS (along with other materials) were completed by French-speaking volunteers with inactive or active inflammatory bowel disease (IBD-I vs. IBD-A) or chronic fatigue syndrome (CFS). Responses from 621 participants (180 patients with IBD-A, 172 with IBD-I, 269 with CFS) collected in a single online survey were divided into three subsamples to test the construct validity of the MCAS (Step 1, N = 240), to confirm its factorial structure (Step 2, N = 204) and to explore its convergent-discriminant validity with the Fatigue Symptoms Inventory (FSI) and revised Piper Fatigue Scale (r-PFS, Step 3, N = 177). RESULTS: Steps 1 and 2 showed that, as expected, MCAS has four dimensions: feeling of constraint (FoC), physical (PC), life (LC) and interpersonal consequences (IC), which are also related to the duration of CA (i.e., the longer it lasts, the more the dimensions are impacted). The results further showed that the MCAS is sensitive enough to capture between-group differences, with the CFS group being the most impaired, followed by IBD-A and IBD-I. While convergent-discriminant validity between the 4 factors of MCAS and FSI and r-PFS, respectively, was satisfactory overall, Step 3 also pointed to some limitations that call for future research (e.g., shared variances between the PC and IC dimensions of MCAS and behavioral dimension of r-PFS). CONCLUSION: Despite these limitations, the MCAS clearly constitutes a promising tool for measuring quantitative differences (i.e., severity/intensity) in CA associated with various diseases, but also, and importantly, the clinically important differences in domains of its expression (i.e., qualitative differences).

Evaluation by a Machine Learning System of Two Preparations for Small Bowel Capsule Endoscopy: The BUBS (Burst Unpleasant Bubbles with Simethicone) Study.

Background: Bubbles often mask the mucosa during capsule endoscopy (CE). Clinical scores assessing the cleanliness and the amount of bubbles in the small bowel (SB) are poorly reproducible unlike machine learning (ML) solutions. We aimed to measure the amount of bubbles with ML algorithms in SB CE recordings, and compare two polyethylene glycol (PEG)-based preparations, with and without simethicone, in patients with obscure gastro-intestinal bleeding (OGIB). Patients & Methods: All consecutive outpatients with OGIB from a tertiary care center received a PEG-based preparation, without or with simethicone, in two different periods. The primary outcome was a difference in the proportions (%) of frames with abundant bubbles (>10%) along the full-length video sequences between the two periods. SB CE recordings were analyzed by a validated computed algorithm based on a grey-level of co-occurrence matrix (GLCM), to assess the abundance of bubbles in each frame. Results: In total, 105 third generation SB CE recordings were analyzed (48 without simethicone and 57 with simethicone-added preparations). A significant association was shown between the use of a simethicone-added preparation and a lower abundance of bubbles along the SB (p = 0.04). A significantly lower proportion of "abundant in bubbles" frames was observed in the fourth quartile (30.5% vs. 20.6%, p = 0.02). There was no significant impact of the use of simethicone in terms of diagnostic yield, SB transit time and completion rate. Conclusion: An accurate and reproducible computed algorithm demonstrated significant decrease in the abundance of bubbles along SB CE recordings, with a marked effect in the last quartile, in patients for whom simethicone had been added in PEG-based preparations, compared to those without simethicone.

Usefulness of co-treatment with immunomodulators in patients with inflammatory bowel disease treated with scheduled infliximab maintenance therapy.

BACKGROUND AND AIMS: Concomitant use of immunosuppressants (IS) with scheduled infliximab (IFX) maintenance therapy for Crohn's disease (CD) or ulcerative colitis (UC) is debated. The aim of this study was to assess whether IS co-treatment is useful in patients with inflammatory bowel disease (IBD) on scheduled IFX infusions. METHODS: 121 consecutive patients with IBD (23 UC, 98 CD) treated by IFX and who received at least 6 months of IS co-treatment (azathioprine (AZA) or methotrexate (MTX)) were studied. In each patient, the IFX treatment duration was divided into semesters which were independently analysed regarding IBD activity. RESULTS: Semesters with IS (n=265) and without IS (n=319) were analysed. IBD flares, perianal complications and switch to adalimumab were less frequently observed in semesters with IS than in those without IS (respectively: 19.3% vs 32.0%, p=0.003; 4.1% vs 11.8%, p=0.03; 1.1% vs 5.3%, p=0.006). Maximal C-reactive protein (CRP) level and IFX dose/kg observed during the semesters were lower in semesters with IS. Within semesters with IS, IBD flares and perianal complications were less frequently observed in semesters with AZA than in those with MTX. In multivariate analysis, IS co-treatment was associated with a decreased risk of IBD flare (OR 0.52; 95% CI 0.35 to 0.79) CONCLUSION: In patients with IBD receiving IFX maintenance therapy, IS co-treatment is associated with reduced IBD activity, IFX dose and switch to adalimumab. In this setting, co-treatment with AZA seems to be more effective than co-treatment with MTX. Benefit of such a combination treatment has to be balanced with potential risks, notably infections and cancers.

Risk factors for neoplasia in inflammatory bowel disease patients with pancolitis.

OBJECTIVES: Colorectal cancer (CRC), developing from dysplastic lesions, is the main long-term complication of pancolitis. The aims of the present study were to assess the risks for neoplasia and advanced neoplasia (AN), respectively, in ulcerative colitis (UC) and Crohn's disease (CD) patients with pancolitis, and to search for protective and risk factors for colorectal neoplasia. METHODS: A total of 855 inflammatory bowel disease (IBD) patients with longstanding pancolitis (276 UC, 56 IBD unclassified (IBDu), and 523 CD) had pathological examination of a proctocolectomy specimen (n=255) or multiple biopsy samples from a surveillance colonoscopy (n=600) after median disease duration of 115 months. Risk factors for low-grade dysplasia (LGD) and AN, respectively, were searched for in the whole group of patients and in a case-control comparison after matching for IBD phenotype. RESULTS: A total of 75 patients eventually developed colorectal neoplasia: 14 adenomas, 28 nonadenomatous LGD, and 33 ANs. The 25-year cumulative risks for neoplasia and AN, respectively, were 32.8±5.7% and 25.9±5.7% in UC and IBDu vs. 12.1±2.7% and 3.9±2.0% in CD (P<0.0001). In CD, patients with UC-like endoscopic appearance (n=126) had an increased risk for AN compared with those with discrete lesions (at 25 years, 10.6±7.2 vs. 1.5±0.9%). In the case-control comparison, factors associated with an increased risk of AN were primary sclerosing cholangitis (hazard ratio (HR) 4.72 (1.54-14.52)) and family history of CRC (HR 3.37 (1.02-11.14)), whereas previous segmental colectomy was protective (HR 0.25 (0.07-0.88)). CONCLUSIONS: The risk of AN in longstanding pancolitis is higher in UC or IBDu than in CD. In CD, this risk is significantly increased in patients with UC-like endoscopic lesions. The surveillance program should focus on these latter patients.

Increased incidence of systemic serious viral infections in patients with inflammatory bowel disease associates with active disease and use of thiopurines.

Background: The magnitude and drivers of the risk of serious viral infections in Inflammatory Bowel diseases (IBD) are unclear. Objective: The objective of this study was to assess the incidence and risk factors for systemic serious viral infections in IBD patients. Methods: Using MICISTA, a database detailing prospective characteristics and complications of IBD, we identified patients that were followed for IBD in 2005-2014 outside the context of organ transplantation, HIV infection or chronic viral hepatitis. We estimated incidences of systemic serious viral infections, defined by the need for hospitalization or permanent organ damage. Standardized incidence ratios (SIRs) were calculated using the French hospital database. We performed a case-control study nested in MICISTA for assessing the role of exposure to IBD drugs and IBD clinical activity in the risk of developing infection. Results: We identified 31 patients with serious viral infections among 2645 patients followed for 15,383 person-years. We observed 13 cases of cytomegalovirus, 10 Epstein-Barr virus, 5 varicella zoster virus and 3 herpes simplex virus infections. No deaths occurred. The incidence rate of infections in patients with IBD was 2.02/1000 person-years, and the SIR was 3.09 (95% confidence interval (CI), 1.98-4.20; p = 0.0002) in the study population. By multivariate analysis, increased risk of infection was associated with exposure to thiopurines (odds ratio (OR), 3.48; 95% CI, 1.36-8.90; p = 0.009), and clinically active IBD at onset of infection (OR, 3.35; 95% CI, 1.23-9.23; p = 0.02). Conclusions: The incidence of systemic serious viral infections in patients with IBD is tripled compared to general population. Clinically active IBD and exposure to thiopurines are the main drivers of the risk.

Impact of Aphthous Colitis at Diagnosis on Crohn's Disease Outcomes.

BACKGROUND: The natural history of intestinal lesions in Crohn's disease [CD] is not fully understood. Although the extent of lesions at diagnosis usually defines the extent of the disease, some lesions seen at diagnosis, particularly aphthous ulcers [AUs], may resolve before follow-up. The aim of this study was to evaluate the outcomes of CD patients with colonic AUs seen at diagnosis. METHODS: CD patients with aphthous colitis at diagnosis who had been followed since 2001 were included in a case control study matched with two groups of controls: one without colonic involvement at diagnosis and a second group with colonic lesions more severe than AUs at diagnosis. RESULTS: Seventy-five patients were included, with a median follow-up of 7.3 years [interquartile range 2.7-9.8]. Seventy-one per cent of those having a second colonoscopy at least 6 months after diagnosis were stable or healed. Medical treatments were similar between the three groups. The AU group's rate of ileal surgery was similar to those without colitis. In multivariate analysis, the independent factors associated with ileal resection were ileal involvement (odds ratio [OR]: 8.8; 95% confidence interval [CI] [7.68-33.75]; p = 0.002) and the presence of severe colitis (OR = 0.5; 95% CI [0.32-0.79], p = 0.003). The risk of ileal surgery was not influenced by the presence of aphthous colitis (OR: 0.63; 95% CI [0.37-1.1]; p = 0.1). CONCLUSION: Aphthous colitis at diagnosis seems to resolve in most patients. This suggests that these lesions are of little clinical significance and may not need to be considered prior to ileal resection in CD or when making other important therapeutic decisions.

Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study.

BACKGROUND: The role of the gut microbiota in Crohn's disease (CD) is established and fecal microbiota transplantation (FMT) is an attractive therapeutic strategy. No randomized controlled clinical trial results are available. We performed a randomized, single-blind, sham-controlled pilot trial of FMT in adults with colonic or ileo-colonic CD. METHOD: Patients enrolled while in flare received oral corticosteroid. Once in clinical remission, patients were randomized to receive either FMT or sham transplantation during a colonoscopy. Corticosteroids were tapered and a second colonoscopy was performed at week 6. The primary endpoint was the implantation of the donor microbiota at week 6 (Sorensen index > 0.6). RESULTS: Eight patients received FMT and nine sham transplantation. None of the patients reached the primary endpoint. The steroid-free clinical remission rate at 10 and 24 weeks was 44.4% (4/9) and 33.3% (3/9) in the sham transplantation group and 87.5% (7/8) and 50.0% (4/8; one patient loss of follow-up while in remission at week 12 and considered in flare at week 24) in the FMT group. Crohn's Disease Endoscopic Index of Severity decreased 6 weeks after FMT (p = 0.03) but not after sham transplantation (p = 0.8). Conversely, the CRP level increased 6 weeks after sham transplantation (p = 0.008) but not after FMT (p = 0.5). Absence of donor microbiota engraftment was associated with flare. No safety signal was identified. CONCLUSION: The primary endpoint was not reached for any patient. In this pilot study, higher colonization by donor microbiota was associated with maintenance of remission. These results must be confirmed in larger studies (NCT02097797). Video abstract.

CAD-CAP: a 25,000-image database serving the development of artificial intelligence for capsule endoscopy.

Background and study aims Capsule endoscopy (CE) is the preferred method for small bowel (SB) exploration. With a mean number of 50,000 SB frames per video, SBCE reading is time-consuming and tedious (30 to 60 minutes per video). We describe a large, multicenter database named CAD-CAP (Computer-Assisted Diagnosis for CAPsule Endoscopy, CAD-CAP). This database aims to serve the development of CAD tools for CE reading. Materials and methods Twelve French endoscopy centers were involved. All available third-generation SB-CE videos (Pillcam, Medtronic) were retrospectively selected from these centers and deidentified. Any pathological frame was extracted and included in the database. Manual segmentation of findings within these frames was performed by two pre-med students trained and supervised by an expert reader. All frames were then classified by type and clinical relevance by a panel of three expert readers. An automated extraction process was also developed to create a dataset of normal, proofread, control images from normal, complete, SB-CE videos. Results Four-thousand-one-hundred-and-seventy-four SB-CE were included. Of them, 1,480 videos (35 %) containing at least one pathological finding were selected. Findings from 5,184 frames (with their short video sequences) were extracted and delimited: 718 frames with fresh blood, 3,097 frames with vascular lesions, and 1,369 frames with inflammatory and ulcerative lesions. Twenty-thousand normal frames were extracted from 206 SB-CE normal videos. CAD-CAP has already been used for development of automated tools for angiectasia detection and also for two international challenges on medical computerized analysis.

Sexual health and fertility for individuals with inflammatory bowel disease.

The impact of a chronic disease such as inflammatory bowel disease (IBD) on sexual functioning and body image can significantly impair the quality of life of patients. This review considers the sexual and fertility aspects of IBD patients and their daily management. Modern IBD healthcare management should include appropriate communication on sexuality and consider psychological, physiological, and biological issues. Patients with IBD have less children than the general population, and voluntary childlessness is frequent. The most influential factors reported by IBD patients who experience fertility alteration are psychological and surgery-related problems. Pregnancy is a major concern for patients, and any pregnancy for IBD patients should be closely followed-up to keep the chronic disease in a quiescent state. Preconceptional consultation is of great help.

Multi-criterion, automated, high-performance, rapid tool for assessing mucosal visualization quality of still images in small bowel capsule endoscopy.

Background and study aims Capsule endoscopy (CE) is the preferred method for small bowel (SB) exploration. Its diagnostic yield can be reduced by poor mucosal visualization. We aimed to evaluate three electronic parameters - colorimetry, abundance of bubbles, and brightness - to assess the adequacy of mucosal visualization of SB-CE images. Patients and methods Six-hundred still images were randomly extracted from 30 complete and normal SB-CEs. Three experts independently evaluated these images according to a 10-point assessment grid. Any frame with a mean score above seven was considered adequately cleansed. Each image was analyzed electronically according to the three preset parameters, individually and then combined, with the experts' score as reference. A random forests methodology was used for machine learning and testing. Results The combination of the three electronic parameters achieved better discrimination of adequately from inadequately cleansed frames as compared to each individual parameter taken separately (sensitivity 90.0 % [95 %C. I. 84.1 - 95.9], specificity 87.7 % [95 %C. I. 81.3 - 94.2]). Conclusion This multi-criterion score constitutes a comprehensive, reproducible, reliable, automated and rapid cleansing score for SB-CE frames. A patent is pending at the European patent office.

Incidence of autoimmune diseases in celiac disease: protective effect of the gluten-free diet.

BACKGROUND & AIMS: Celiac disease may be associated with autoimmune diseases. The aims of the present study were to determine in celiac patients which factors modulate the risk of autoimmune disease and to evaluate the effect of the gluten-free diet. METHODS: The occurrence of autoimmune disease and compliance to gluten-free diet were specified retrospectively in 924 celiac patients recruited from 27 French pediatric and adult gastroenterology centers. RESULTS: One or several autoimmune diseases had developed in 178 patients. The cumulative risk of autoimmune disease was 8.1% +/- 1% at age 15, and 15.7% +/- 1.5% at age 30. Factors associated with an increased risk were family history of autoimmunity (hazard ratio, 2.36; 95% confidence interval, 1.71-3.31) and diagnosis of celiac disease before 36 years of age (hazard ratio, 2.65; 95% confidence interval, 1.79-3.85). After diagnosis of celiac disease, 55 of 788 patients developed an autoimmune disease. The cumulative risk of subsequent autoimmune disease was lower in patients compliant to a gluten-free diet versus noncompliant patients (at 10 years, 6% +/- 2% vs 15.6% +/- 5.9%, respectively; P = .02). The incidence of autoimmune diseases was 5.4 per 1000 patient-years during adherence to a gluten-free diet versus 11.3 per 1000 patient-years during nonadherence to the diet (P = .002). Results were similar in both the pediatric and the adult populations. CONCLUSIONS: Celiac patients most at risk for autoimmune disease are those diagnosed early in life and having a family history of autoimmunity. The gluten-free diet has a protective effect.

Development of a computed cleansing score to assess quality of bowel preparation in colon capsule endoscopy.

BACKGROUND AND STUDY AIMS: Colon capsule endoscopy (CCE) does not possess an objective and reliable scoring system to assess the quality of visualization of the colon mucosa. The aim of this study was to establish a colonic computed assessment of cleansing (CAC) score able to discriminate "adequately cleansed" from "inadequately cleansed" CCE still frames. PATIENTS AND METHODS: Twelve normal and complete CCEs, using the Pillcam Colon 2 system (Medtronic, Minnesota, United States), were prospectively selected amongst a database. A CAC score, defined as the ratio of color intensities red over green (R/G ratio), and red over brown (R/(R + G) ratio) was calculated for each extracted colonic frame. After sorting and random selection, two sets of still frames representative of the range of these ratios were obtained. These images were analyzed twice in random order by two experienced CCE readers who were blinded to the CAC scores. A receiver operating characteristic (ROC) curve was forged for both types of ratios and a threshold established, yielding the highest diagnostic performance in terms of adequate cleansing assessment. RESULTS: Four-hundred-and-eight frames were extracted. Regarding the R/G ratio, a threshold value of 1.55 was calculated, with a sensitivity of 86.5 % and a specificity of 77.7 %. Regarding the R/(R + G) ratio, a threshold value of 0.58 was calculated with a sensitivity of 95.5 % and a specificity of 62.9 %. CONCLUSION: The two proposed CAC scores based on the ratio of color intensities come with high sensitivities for discriminating between "adequately cleansed" and "inadequately cleansed" CCE still frames, but they lack specificity. Further refinement, with implementation of additional image parameters, is warranted.

Clinical activity is an independent risk factor of ischemic heart and cerebrovascular arterial disease in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: In inflammatory bowel disease (IBD), the impact of established cardiovascular risk factors and disease-related factors on the risk of acute arterial events is still unclear. We aimed to identify risk factors of acute arterial events in patients with IBD. METHODS: All consecutive patients followed at Saint-Antoine Hospital between 1996 and 2015 with subsequent occurrence of acute arterial events (acute coronary syndrome or ischemic stroke) were identified. Traditional cardiovascular risk factors, treatment exposure, systemic inflammation (mean serum CRP level greater than or equal to 5 mg/L) and IBD clinical activity were assessed. A nested case-control study was performed including cases and controls without arterial ischemic event, matched on age, gender, and disease extent. RESULTS: A total of 30 patients (median age at acute vascular event occurrence: 42 years (interquartile range: 25-59)) developed acute coronary syndrome (n = 22) or ischemic stroke (n = 8). In univariate analysis, clinical disease activity and the persistence of systemic inflammation, diabetes, dyslipidemia and hypertension were significantly associated with an increased risk of acute arterial events. Neither protective nor aggravating effects associated with treatment exposure were identified. In multivariate analysis, the presence of diabetes (Odds ratio (OR): 14.5, 95% confidence interval (CI): 1.1-184.7) and clinical disease activity (OR: 10.4, 95% CI: 2.1-49.9) remained significantly associated with the risk of acute arterial event. CONCLUSION: Disease activity may have an independent impact on the risk of acute arterial events in patients with IBD. These findings may highlight new potential benefits of optimizing anti-inflammatory treatment in patients with persisting clinical activity.