Background: Approximately 25% of patients with ulcerative colitis (UC) experience a severe flare requiring steroid therapy to avoid colectomy. We performed a systematic review and meta-analysis to assess the efficacy of tacrolimus as a rescue therapy for active UC. Methods: Electronic databases were searched for relevant studies assessing the efficacy of tacrolimus for active UC. Outcomes included short and long term clinical response, colectomy free rates, and rate of adverse events in randomized controlled trials (RCTs) and observational studies. Results: Two RCTs comparing high trough concentration (10-15ng/ml) versus placebo (n = 103) and 23 observational studies (n = 831) were identified. Clinical response at 2 weeks was significantly higher with tacrolimus compared to placebo (risk ratio (RR) = 4.61, 95% confidence interval (CI) = 2.09-10.17, p = 0.15x10^-3) among RCTs. Rates of clinical response at 1 and 3 months were 0.73 (95% CI = 0.64-0.81) and 0.76 (95% CI = 0.59-0.87), and colectomy free rates remained high at 1, 3, 6, and 12 months (0.86, 0.84, 0.78, 0.69, respectively) among observational studies. Among RCTs, adverse events were more frequent compared to placebo (RR = 2.01, 95% CI = 1.20-3.37, p = 0.83x10^-2), but there was no difference in severe adverse events (RR = 3.15, 95% CI = 0.14-72.9, p = 0.47). Severe adverse events were rare among observational studies (0.11, 95% CI = 0.06-0.20). Conclusions: In the present meta-analysis, tacrolimus was associated with high clinical response and colectomy free rates without increased risk of severe adverse events for active UC.

Vedolizumab is increasingly used to treat patients with ulcerative colitis (UC) and Crohn’s disease (CD), however, its safety during the perioperative period remains unclear. We compared the 30-day postoperative complications among patients treated preoperatively with vedolizumab, anti-tumor necrosis factor (TNF)-α agents or non-biological therapy. The retrospective study cohort was comprised of patients receiving vedolizumab, anti-TNF-α agents or non-biological therapy within 4 weeks of surgery. The rates of 30-day postoperative complications were compared between groups using univariate and multivariate analysis. Propensity score-matched analysis was performed to compare the outcome between groups. Among 443 patients (64 vedolizumab, 129 anti-TNF-α agents, and 250 non-biological therapy), a total of 144 patients experienced postoperative complications (32%). In multivariate analysis, age >65 (odds ratio (OR) 3.56, 95% confidence interval (CI) 1.30–9.76) and low-albumin (OR 2.26, 95% CI 1.28–4.00) were associated with increased risk of 30-day postoperative complications. For infectious complications, steroid use (OR 3.67, 95% CI 1.57–8.57, P=0.003) and low hemoglobin (OR 3.03, 95% CI 1.32–6.96, P=0.009) were associated with increased risk in multivariate analysis. Propensity score matched analysis demonstrated that the risks of postoperative complications were not different among patients preoperatively receiving vedolizumab, anti-TNF-α agents or non-biological therapy (UC, P=0.40; CD, P=0.35). In the present study, preoperative vedolizumab exposure did not affect the risk of 30-day postoperative complications in UC and CD. Further, larger studies are required to confirm our findings.

INTRODUCTION: The bleeding source of hematochezia is unknown without performing colonoscopy. We sought to identify whether colonoscopy is a risk-stratifying tool to identify etiology and predict outcomes and whether presenting symptoms can differentiate the etiologies in patients with hematochezia. METHODS: This multicenter retrospective cohort study conducted at 49 hospitals across Japan analyzed 10,342 patients admitted for outpatient-onset acute hematochezia. RESULTS: Patients were mostly elderly population, and 29.5% had hemodynamic instability. Computed tomography was performed in 69.1% and colonoscopy in 87.7%. Diagnostic yield of colonoscopy reached 94.9%, most frequently diverticular bleeding. Thirty-day rebleeding rates were significantly higher with diverticulosis and small bowel bleeding than with other etiologies. In-hospital mortality was significantly higher with angioectasia, malignancy, rectal ulcer, and upper gastrointestinal bleeding. Colonoscopic treatment rates were significantly higher with diverticulosis, radiation colitis, angioectasia, rectal ulcer, and postendoscopy bleeding. More interventional radiology procedures were needed for diverticulosis and small bowel bleeding. Etiologies with favorable outcomes and low procedure rates were ischemic colitis and infectious colitis. Higher rates of painless hematochezia at presentation were significantly associated with multiple diseases, such as rectal ulcer, hemorrhoids, angioectasia, radiation colitis, and diverticulosis. The same was true in cases of hematochezia with diarrhea, fever, and hemodynamic instability. DISCUSSION: This nationwide data set of acute hematochezia highlights the importance of colonoscopy in accurately detecting bleeding etiologies that stratify patients at high or low risk of adverse outcomes and those who will likely require more procedures. Predicting different bleeding etiologies based on initial presentation would be challenging.