Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine

BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.Peer reviewe

Abdominal abscess in Crohn's disease: multidisciplinary management

Crohn's disease (CD) is characterized by full-thickness inflammation of the bowel. For this reason, perforating complications such as intra-abdominal abscesses or fistulas are common. A concomitant intra-abdominal abscess with active CD of the small bowel is a challenging dilemma for gastroenterologists and surgeons. Since there is active and severe disease, this should be treated with immunosuppressive drugs. However, in the presence of an intra-abdominal abscess, immunosuppression can be dangerous. There are several treatment options for intra-abdominal abscesses in CD. Nowadays, the first-line treatment is antibiotic therapy with or without percutaneous drainage. Historically, patients were treated with surgical drainage. With the development of percutaneous drainage, treatment shifted to a more nonsurgical approach. Success rates for percutaneous drainage in the literature vary from 74 to 100%, and it is considered to be a relatively safe procedure. It has been reported that surgery can be avoided after successful percutaneous drainage in a variable number of patients (14-85%). If sepsis is controlled, CD medication should be started to prevent recurrence. It is important to monitor the effect upon CD lesions to avoid further perforating complications. Finally, an undrainable or small abscess can be treated with antibiotics alone, although high recurrence rates have been described with this approach. Patients with a concomitant stenosis, an enterocutaneous fistula or refractory active disease are likely to require surgery. Percutaneous drainage in combination with delayed surgery is useful to improve the patient's condition prior to surgery and is associated with less morbidity, a lower stoma rate and more limited resection. In conclusion, when feasible, percutaneous drainage and antibiotics should be the treatment of choice in patients with an intra-abdominal abscess in CD. If surgery is inevitable, this must be delayed to reduce postoperative septic complications and high stoma rate

Challenges to the Design, Execution, and Analysis of Randomized Controlled Trials for Inflammatory Bowel Disease

Treatment of inflammatory bowel disease has greatly improved with the development of targeted, monoclonal antibody-based therapies. Tumor necrosis factor antagonists are frequently used to treat patients with Crohn's disease or ulcerative colitis, but they have side effects and their efficacy often decreases with use. New, more effective drugs are therefore needed and in development. However, many agents that appeared to be promising in preclinical studies have failed to show efficacy in clinical trials. We discuss possible reasons for the failures of these reagents in trials, which include the high rate of response to placebo, an inadequate range of doses, inappropriate timing of end point measurements, the changing therapeutic environment, and the competitive trial system. We also review regulatory guidelines for end points and trial design and recommend ways to improve trial

Chronic cigarette smoke exposure induces microbial and inflammatory shifts and mucin changes in the murine gut

Inflammatory Bowel Diseases (IBD) are complex multifactorial diseases characterized by an inappropriate host response to an altered commensal microbiome and dysfunctional mucus barrier. Cigarette smoking is the best known environmental risk factor in IBD. Here, we studied the influence of chronic smoke exposure on the gut microbiome and mucus layer composition in conventional mice. We compared smoke-exposed to air-exposed mice (n = 12) after a smoke exposure of 24 weeks. Both Illumina sequencing (n = 6) and denaturing gradient gel electrophoresis (DGGE) (n = 12) showed that bacterial activity and community structure were significantly altered in the colon due to smoke exposure. Interestingly, an increase of Lachnospiraceae sp. activity in the colon was observed. Also, changes in the mRNA expression Muc2 and Muc3 increased in the ileum, whereas Muc4 increased in the distal colon of smoke-exposed mice (n = 6). Furthermore, we observed increased Cxcl2 and decreased Ifn-γ in the ileum, and increased Il-6 and decreased Tgf-β in the proximal colon. Tight junction gene expression remained unchanged. We infer that the modulating role of chronic smoke exposure as a latently present risk factor in the gut may be driven by the altered epithelial mucus profiles and changes in microbiome composition and immune factors

Interstitial and Granulomatous lung disease in inflammatory bowel disease patients.

BACKGROUND: Interstitial lung [ILD] disease and granulomatous lung disease [GLD] are rare respiratory disorders that have been associated with inflammatory bowel disease [IBD]. Clinical presentation is polymorphic and aetiology is unclear. METHODS: This was an ECCO-CONFER project. Cases of concomitant ILD or GLD and IBD, or drug-induced ILD/GLD, were collected. The criteria for diagnosing ILD and GLD were based on definitions from the American Thoracic Society and the European Respiratory Society and on the discretion of reporting clinician. RESULTS: We identified 31 patients with ILD. The majority had ulcerative colitis [UC] [n = 22]. Drug-related ILD was found in 64% of these patients, 25 patients [80.6%] required hospitalisation, and one required non-invasive ventilation. The causative drug was stopped in all drug-related ILD, and 87% of patients received systemic steroids. At follow-up, 16% of patients had no respiratory symptoms, 16% had partial improvement, 55% had ongoing symptoms, and there were no data in 13%. One patient was referred for lung transplantation, and one death from lung fibrosis was reported. We also identified 22 GLD patients: most had Crohn's disease [CD] [n = 17]. Drug-related GLD was found in 36% of patients and 10 patients [45.4%] required hospitalisation. The causative drug was stopped in all drug-related GLD, and 81% of patients received systemic steroids. Remission of both conditions was achieved in almost all patients. CONCLUSIONS: ILD and GLD, although rare, can cause significant morbidity. In our series, over half of cases were drug-related and therefore focused pharmacovigilance is needed to identify and manage these cases