Dysfonction mitochondriale au cours de l’inflammation et stimulation du métabolisme énergétique en phase cicatricielle dans un modèle murin de colite chimio-induite

International audienc

Anal Fistulas in Severe Perineal Crohn's Disease Mri Assessment in the Determination of Long-Term Healing Rates

International audienceBackground & aims - The European Crohn's and Colitis Organization recommends magnetic resonance imaging (MRI) of anal fistulas to decide on the drug/surgery strategy. No evidence is available on the long-term impact of MRI features on fistula healing. The aim of this study was to evaluate the benefit of combined drug/surgery strategies for the treatment of perianal Crohn's fistulas based on MRI factors at referral.Methods - The clinical event (anal abscess, new fistula tract, cellulitis), therapeutic intervention (introduction/optimization of immunosuppressant/biologics, anal surgery, intestinal resection, stoma), and MRI data were prospectively recorded for patients with Crohn's disease (CD) and anal fistulas. Healing was defined by fulfilment of all the following conditions: no discharge or pain, closure of the external opening of the fistula, no visible internal opening, no abscess, and no subsequent draining seton or drainage procedure performed during at least 1 year of follow-up.Results - Seventy CD patients with anal fistulas and MRI evaluations were followed for 70 months. The cumulative rates of fistula healing were 25%, 40%, 50%, and 70% at 12, 24, 36, and 72 months, respectively. Severe, complex, branched, and high fistulas were associated with a less favorable outcome. Surgical closure of the tract improved the healing rates better than treatment with biologics or thiopurines. Male sex, A1 luminal phenotype, and anal ulceration at referral were independently associated with a higher healing rate.Conclusions - Therapeutic strategies for perianal fistulizing CD require robust anatomical and healing evaluations. Combined strategies using biologics to improve both drainage and secondary closure of the fistula tracts merit further study.<br

Cumulative Exposure to Infliximab, But Not Trough Concentrations, Correlate With Rate of Infection

International audienceBackground & aims: Infliximab increases the risk of infection in patients with inflammatory bowel diseases (IBD), but there is controversy over the relationship between drug concentration and infections. We aimed to assess factors associated with infection in infliximab-treated patients, including pharmacokinetic features.Methods: We collected data from 209 patients with IBD (102 men; mean age, 39 y; 159 with Crohn's disease; 54 received combination therapy) who received a infliximab maintenance regimen from November 2016 through April 2017 in France. Data were collected from each infusion visit (total of 640 infusions). Infliximab exposure was estimated based on the area under the curve (AUC) of drug concentration in pharmacokinetic models; individual exposures over the 6-month period were estimated based on the sum of the AUC (ΣAUC).Results: The mean infliximab trough level was 5.46 mg/L, and the mean ΣAUC was 3938±1427 mg d/L. A total of 215 infections were collected from the 640 infusion visits; 123 patients (59%) had at least 1 infection. Factors independently associated with infection after multivariate analysis were smoking (odds ratio [OR], 2.05; P=.046), IBD flare (OR, 2.71; P=.006), and a high ΣAUC of infliximab (above 3234 mg x d/L) (OR, 2.02; P=.02). The ΣAUC was higher in patients with an occurrence of infection (P=.04) and correlated with the number of infections (P=.04). Trough concentration of infliximab alone was not associated with infection.Conclusions: Almost two-thirds of patients treated with infliximab developed an infection; risk was individually correlated with cumulative increase in drug exposure, but not infliximab trough level

Allogenic stem cells for Crohnandapos;s anal fistulas: Treating early improves the deep remission rate

International audienceAim: The aim of this study was to evaluate the real-life clinical and radiological efficacy of darvadstrocel injection into complex perianal fistulas in Crohn&#039;s disease. Secondary endpoints were to assess symptomatic efficacy, adverse effects and factors associated with complete combined clinical-radiological response (deep remission).Methods: After marketing the product in France, all first patients treated consecutively were included. A complete clinical response was defined by a complete closure of all external openings with no discharge on pressure. A complete radiological response (MRI), evaluated at least after six months of follow-up, was defined by a completely fibrotic sequela without abscess. A deep remission was defined as the association of a complete clinical response with a complete radiological response.Results: A total of 43 patients were included (M/F: 22/21, median age 37 [26-45] years). The fistulas were already drained with seton(s) and were on biologic treatment. After a median follow-up of 383 (359-505) days, 28 (65%) patients showed a clinical response (22 complete and 6 partial) and 16 (37%) achieved a deep remission. The Perineal Disease Activity Index decreased significantly after treatment: 39 (91%) patients reported symptomatic improvement in terms of discharge, pain, and induration, and 28 (65%) no longer had any perineal symptoms. No severe adverse events were reported. A short history of Crohn&#039;s disease &lt;3 years was significantly associated with deep remission (OD 4.5 [1.0-19.1], p = 0.04).Conclusion: Darvadstrocel injection resulted in a clinical response for two thirds of patients and deep remission for one third. A shorter duration of Crohn&#039;s disease was associated with deep remission

A simple clinical and biological score to promote and enhance Ferroportine disease screening.

International audienc

A simple clinical score to promote and enhance ferroportin disease screening

International audienceBackground & aims - Ferroportin disease is a rare genetic iron overload disorder which may be underdiagnosed, with recent data suggesting it occurs at a higher prevalence than suspected. Costs and the lack of defined criteria to prompt genetic testing preclude large-scale molecular screening. Hence, we aimed to develop a readily available scoring system to promote and enhance ferroportin disease screening. Methods - Our derivation cohort included probands tested for ferroportin disease from 2008 to 2016 in our rare disease network. Data were prospectively recorded. Univariate and multivariate logistic regression were used to determine significant criteria, and odds ratios were used to build a weighted score. A cut-off value was defined using a ROC curve with a predefined aim of 90% sensitivity. An independent cohort was used for cross validation. Results - Our derivation cohort included 1,306 patients. Mean age was 55±14 years, ferritin 1,351±1,357 μg/L, and liver iron concentration (LIC) 166±77 μmol/g. Pathogenic variants (n = 32) were identified in 71 patients. In multivariate analysis: female sex, younger age, higher ferritin, higher LIC and the absence of hypertension or diabetes were significantly associated with the diagnosis of ferroportin disease (AUROC in whole derivation cohort 0.83 [0.78-0.88]). The weighted score was based on sex, age, the presence of hypertension or diabetes, ferritin level and LIC. An AUROC of 0.83 (0.77-0.88) was obtained in the derivation cohort without missing values. Using 9.5 as a cut-off, sensitivity was 93.6 (91.7-98.3) %, specificity 49.5 (45.5-53.6) %, positive likelihood ratio 1.8 (1.6-2.0) and negative likelihood ratio 0.17 (0.04-0.37). Conclusion - We describe a readily available score with simple criteria and good diagnostic performance that could be used to screen patients for ferroportin disease in routine clinical practice. Lay summary - Increased iron burden associated with metabolic syndrome is a very common condition. Ferroportin disease is a dominant genetic iron overload disorder whose prevalence is higher than initially thought. They can be difficult to distinguish from each other, but the limited availability of genetic testing and the lack of definitive guidelines prevent adequate screening. We herein describe a simple and definitive clinical score to help clinicians decide whether to perform genetic testing