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We read with interest the paper by Ekkelenkamp et al ,1 who found that the early use of validated simulators during endoscopy training expedites the learning of procedural skills. Indeed, traditional teaching concepts do not take full advantage of advanced technology. We therefore prospectively investigated the impact of our self-developed custom wireless-enabled tablet PC-based multimedia training and test system on gastrointestinal endoscopy self-assessment program (GESAP®) exam performance. Control and the tablet groups were tested at the beginning and the end of their rotation by administration of all 200 random generator selected, equally distributed questions from all 11 categories (biliary, colorectal, oesophagus, intestines, nutrition, pancreas, patient preparation, paediatrics, surgery) parsed from the current GESAP® pool. Medical students and residents doing an inpatient service rotation were alternatingly assigned to either the active test (tablet PC) or traditional education (control) group, respectively. The multimedia training package included access to the institutional collaborative online course management systems (Moodle and Blackboard), eBooks, eJournals, educational slide kits, podcasts, videos, animations, images from major biomedical and scientific publishers or professional societies, as well as twitter …

Objective Vedolizumab is a gut-selective antibody to α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). We report an integrated summary of the safety of vedolizumab. Design Safety data (May 2009–June 2013) from six trials of vedolizumab were integrated. Adverse events were evaluated in patients who received ≥1 dose of vedolizumab or placebo and were reported as exposure-adjusted incidence rates as the number of patients experiencing the event per 100 person-years (PYs) of exposure. Predictors of serious infection were assessed using a Cox proportional hazards model. Results In total, 2830 patients had 4811 PYs of vedolizumab exposure (median exposure range, 1–1977 days). No increased risk of any infection or serious infection was associated with vedolizumab exposure. Serious clostridial infections, sepsis and tuberculosis were reported infrequently (≤0.6% of patients). No cases of progressive multifocal leucoencephalopathy were observed. Independent risk factors for serious infection in UC were prior failure of a tumour necrosis factor α antagonist (HR, 1.99; 95% CIs 1.16 to 3.42; p=0.0122) and narcotic analgesic use (HR, 2.68; 95% CI 1.57 to 4.58; p=0.0003), and in CD were younger age (HR, 0.97; 95% CI 0.95 to 0.98; p

Objective Etrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC. Design In the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD). Results In the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively. Conclusion Etrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted.

Background and aims: As the first point of contact with enteric antigens, intestinal epithelial cells (IEC) may be key in regulating mucosal immune responses. We determined therefore if murine colonic epithelial cells (CEC) have tolerogenic or activating effects on CD4 T cells. Methods: Using a novel CEC, macrophages, and CD4 T cell coculture system, mitogen and antigen specific responses of naive and antigen primed CD4 T cells were assessed. Results: Although a proportion of CEC express the costimulatory molecules B7.1, B7.2, CD40, and CD54, they were unable to promote mitogen or antigen driven activation of CD4 T cells, even in the presence of exogenous costimulatory signals. CD4 T cells cocultured with CEC were CD25 lo and CD45RB lo and remained in the G1 phase of the cell cycle. CEC were also able to prevent CD4 T cell activation by professional antigen presenting cells. CEC mediated suppression of T cell activation was cell contact dependent and transforming growth factor β independent. Conclusions: These observations suggest that CEC contribute to the maintenance of T cell tolerance in the gut by preventing inappropriate activation of CD4 T cells.

Tacrolimus is currently approved only in patients receiving allogeneic liver or kidney transplants.1 We and others have demonstrated its successful use in refractory colitis.2,3 Here we report the first patient who was successfully maintained in remission during pregnancy and delivered a healthy baby. Our patient was diagnosed with ulcerative colitis at the age of 25 years. Her first baby was delivered by Caesarean section prematurely at 29 weeks’ gestation. Frequent flare ups of her pancolitis required repeated steroid rescue and she was soon started on azathioprine. Unfortunately, she was unable to tolerate purine analogues due to heterozygous thiopurine methyltransferase deficiency causing severe pancytopenia and life threatening sepsis. Discussing the remaining therapeutic options, the patient refused proctocolectomy and ileoanal pouch anastomosis and chose a trial …