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Peer reviewe

Refractory ulcerative proctitis: How to treat it?

International audienceUlcerative proctitis is defined as a mucosal inflammation limited to the rectum. Ulcerative proctitis is responsible for distressing symptoms and alteration of patient quality of life. Effective treatment is important to prevent or delay proximal extension of the disease and to improve quality of life. Refractory ulcerative proctitis is defined as the failure of topical and oral 5-aminosalicylic acid and corticosteroids. Medical management of refractory ulcerative proctitis may be challenging as there is little evidence regarding drug efficacy in this clinical situation. Data are currently available for azathioprine, topical tacrolimus and anti-TNF monoclonal antibodies as rescue treatment for refractory ulcerative proctitis. Other biologics may be of benefit despite a lack of dedicated clinical trials. Ultimately, experimental therapies such as epidermal growth factor enemas, appendectomy or fecal transplantation may be tried before restorative proctocolectomy with J pouch anastomosis, which has demonstrated good results with regards to clinical remission and quality of life

Diagnosis, Natural History and Treatment of Eosinophilic Enteritis: a Review

International audiencePURPOSE OF REVIEW:To review recent findings regarding eosinophilic enteritis, including epidemiology, pathogenesis, natural history, and treatment.RECENT FINDINGS:A 2017 population-based study using a US healthcare system database identified 1820 patients with a diagnosis of eosinophilic enteritis among 35,826,830 individuals. The majority of patients with eosinophilic enteritis in this study were women (57.7%), Caucasian (77.5%), and adults (> 18 years of age) (83.5%). The overall prevalence of eosinophilic enteritis was estimated at 5.1/100,000 persons. Eosinophilic enteritis, also known as eosinophilic gastroenteritis, is a rare primary eosinophilic gastrointestinal disorder (EGID) of unknown etiology characterized by the presence of an intense eosinophilic infiltrate on histopathological examination of the intestinal mucosa. The etiology of eosinophilic enteritis remains unknown. However, there is evidence to support the role of allergens in the pathogenesis of this disorder, as children and adults with EGIDs often have positive skin testing to food allergens and a family history of allergic diseases. Recent studies unraveling the role of IgE-mediated but also delayed Th2-type responses have provided insight into the pathogenesis of this disease. Eosinophilic enteritis causes a wide array of gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, bloating, or ascites, and its diagnosis requires a high degree of clinical likelihood, given the nonspecific clinical presentation and physical examination findings. Oral corticosteroids are considered to be the mainstay of treatment and are generally used for a short period with good response rates. Antihistamine drugs and sodium cromoglycate have also been used to treat patients with eosinophilic enteritis. Preliminary studies have demonstrated the potential benefit of biological therapies targeting the eosinophilic pathway such as mepolizumab, an anti-IL5 antibody, or omalizumab, an anti-IgE monoclonal antibody. Eosinophilic enteritis is generally considered to be a benign disease without relapse, but up to 50% of patients may present a more complex natural history characterized by unpredictable relapses and a chronic course

Dose de-escalation to adalimumab 40 mg every three weeks in patients with inflammatory bowel disease—A multicenter, retrospective, observational study

International audienceBACKGROUND:Data about the outcomes after adalimumab dose de-escalation in inflammatory bowel disease (IBD) are scarce.OBJECTIVES:To assess the outcomes after adalimumab dose de-escalation, and to identify potential factors associated with failure.METHODS:Retrospective, observational study including all IBD patients who had undergone adalimumab dose de-escalation to 40 mg every three weeks across seven GETAID centers, between June 2011 and September 2017. Failure of adalimumab dose de-escalation was defined as the need for treatment re-escalation, discontinuation of adalimumab, or clinical, biochemical and/or morphologic disease relapse.RESULTS:Fifty-six patients were identified (n = 46 Crohn's disease, n = 10 ulcerative colitis). Median (IQR) duration of follow-up after adalimumab dose de-escalation was 15.9 (7.9-30.6) months. Adalimumab dose de-escalation was a failure in 21/56 (37.5%) patients and successful in 35/56 (62.5%) patients. Median (IQR) time until failure was 8.9 (4.6-15.6) months. At multivariate analysis, inactive disease at magnetic resonance imaging and/or endoscopy in the year before adalimumab dose de-escalation decreased the risk of failure with a factor five (P = 0.02).CONCLUSIONS:Adalimumab dose de-escalation to 40 mg every three weeks is possible in almost two thirds of IBD patients. Objective morphologic signs of active disease should be ruled out before considering a de-escalation strategy with adalimumab

Stricturing Crohn's disease-like colitis in a patient treated with belatacept

International audienceCytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) modifying agents have been involved in the development of intestinal inflammation, especially therapeutic monoclonal antibodies directed against CTLA-4. Here we report the appearance of a severe stricturing Crohn's disease-like colitis in a patient with a kidney allograft who was treated with belatacept, a recombinant CTLA-4-Ig fusion protein

Rapid bacterial identification, resistance, virulence and type profiling using selected reaction monitoring mass spectrometry

International audienceMass spectrometry (MS) in Selected Reaction Monitoring (SRM) mode is proposed for in-depth characterisation of microorganisms in a multiplexed analysis. Within 60-80 minutes, the SRM method performs microbial identification (I), antibiotic-resistance detection (R), virulence assessment (V) and it provides epidemiological typing information (T). This SRM application is illustrated by the analysis of the human pathogen Staphylococcus aureus, demonstrating its promise for rapid characterisation of bacteria from positive blood cultures of sepsis patients

BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets

During neurogenesis, neural stem/progenitor cells (NPCs) undergo an irreversible fate transition to become neurons. The Notch pathway is important for this process, and repression of Notch-dependent Hes genes is essential for triggering differentiation. However, Notch signaling often remains active throughout neuronal differentiation, implying a change in the transcriptional responsiveness to Notch during the neurogenic transition. We identified Bcl6, an oncogene, as encoding a proneurogenic factor that is required for proper neurogenesis of the mouse cerebral cortex. BCL6 promoted the neurogenic conversion by switching the composition of Notch-dependent transcriptional complexes at the Hes5 promoter. BCL6 triggered exclusion of the co-activator Mastermind-like 1 and recruitment of the NAD+-dependent deacetylase Sirt1, which was required for BCL6-dependent neurogenesis. The resulting epigenetic silencing of Hes5 led to neuronal differentiation despite active Notch signaling. Our findings suggest a role for BCL6 in neurogenesis and uncover Notch-BCL6-Sirt1 interactions that may affect other aspects of physiology and disease.SCOPUS: ar.jinfo:eu-repo/semantics/publishe