Postoperative Mortality Among Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis of Population-Based Studies.

BACKGROUND & AIMS: There have been varying reports of mortality after intestinal resection for the inflammatory bowel diseases (IBDs). We performed a systematic review and meta-analysis of population-based studies to determine postoperative mortality after intestinal resection in patients with IBD. METHODS: We searched Medline, EMBASE, and PubMed, from 1990 through 2015, to identify 18 articles and 3 abstracts reporting postoperative mortality among patients with IBD. The studies included 67,057 patients with ulcerative colitis (UC) and 75,971 patients with Crohn's disease (CD), from 15 countries. Mortality estimates stratified by emergent and elective surgeries were pooled separately for CD and UC using a random-effects model. To assess changes over time, the start year of the study was included as a continuous variable in a meta-regression model. RESULTS: In patients with UC, postoperative mortality was significantly lower among patients who underwent elective (0.7%; 95% confidence interval [CI], 0.6%-0.9%) vs emergent surgery (5.3%; 95% CI, 3.8%-7.4%). In patients with CD, postoperative mortality was significantly lower among patients who underwent elective (0.6%; 95% CI, 0.2%-1.7%) vs emergent surgery (3.6%; 95% CI, 1.8%-6.9%). Postoperative mortality did not differ for elective (P = .78) or emergent (P = .31) surgeries when patients with UC were compared with patients with CD. Postoperative mortality decreased significantly over time for patients with CD (P < .05) but not UC (P = .21). CONCLUSIONS: Based on a systematic review and meta-analysis, postoperative mortality was high after emergent, but not elective, intestinal resection in patients with UC or CD. Optimization of management strategies and more effective therapies are necessary to avoid emergent surgeries.

Hepatitis Status and its Effect upon the Progression of Chronic Kidney Disease: Presentations, Associations and Complications.

Chronic kidney disease (CKD), hepatitis B virus (HBV), and hepatitis C virus (HCV) have a high prevalence in Oman. This study aimed to examine the association between CKD and viral hepatitis through an observational cohort study conducted at the Royal Hospital of the Sultanate of Oman to evaluate the relationship of HBV and HCV with CKD. During the study, 233 patients were identified, 112 with chronic HBV (Group 1), 112 with chronic HCV (Group 2), and nine with HBV and HCV coinfection (Group 3). The population was predominantly male, especially in Groups 1 and 3. The difference in age between Groups 1 and 2 was significant, with the mean age being 48 ± 14.6 years and 55 ± 12.6 years, respectively (P <0.05). This study revealed that the prevalence of CKD in Group 1 is 51%, in Group 2 was 78%, and in Group 3 was 56%. The mean estimated glomerular filtration rate (eGFR) was 79.7 mL/min/1.73 m2 in Group 1, 73.2 mL/min/1.73 m2 in Group 2, and 57.6 mL/min/1.73 m2 in Group 3. CKD had the highest prevalence in Group 2. The lowest eGFR was found in Group 3. Group 2 showed the highest rate of declining renal function over time despite treatment. This study found a significant and independent association between viral hepatitis and the risk of CKD, especially in cases of coinfection and HCV infection. This warrants close monitoring of kidney function during screening and follow-up. Patients with CKD should be screened for viral hepatitis.

Dyssynergic Defecation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Background: Inflammatory bowel disease (IBD) patients often continue to experience nonspecific gastrointestinal symptoms despite quiescent disease. Unlike non-IBD patients, IBD patients with dyssynergic defecation (DD) may present with various symptoms such as diarrhea, fecal incontinence, constipation, and rectal discomfort. Despite its importance and treatability, DD in IBD patients is not well recognized in practice. We conducted a systematic review and meta-analysis on the prevalence, diagnosis, and management of DD in IBD patients with ongoing defecatory symptoms. Methods: We searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews (from 1966 through February 2017) to identify relevant studies on the prevalence, diagnostic methods, or management of DD in IBD patients with and without ileal pouch-anal anastomoses (IPAAs). A random effects model was used to calculate the pooled estimates with 95% confidence intervals (CIs). Heterogeneity was assessed with I2 statistics, Cochran Q statistic, and sensitivity analyses. Results: Seven studies (n = 442) were included. In patients with ongoing defecatory symptoms, the prevalence of DD without IPAA ranged from 45% to 97%, and in patients with IPAA, it ranged from 25% to 75%. The prevalence of DD in IPAA patients with and without pouchitis ranged from 17% to 67% and 29% to 50%, respectively. The pooled response rate to biofeedback therapy in patients without IPAA was 70% (95% CI, 55%-84%; I2 = 95%; P < 0.01), and it was 86% (95% CI, 67%-98%; I2 = 61%; P = 0.05) in those with IPAA. Conclusions: Despite limited data, the current literature suggests that DD is highly prevalent in active or quiescent IBD patients with ongoing defecatory symptoms and is responsive to biofeedback therapy. Although more studies are needed, DD should be considered in IBD patients with persistent defecatory symptoms.

Real-world clinical, endoscopic and radiographic efficacy of vedolizumab for the treatment of inflammatory bowel disease.

BACKGROUND: Vedolizumab is an α4ß7 integrin antagonist with proven efficacy for inducing and maintaining clinical response and remission in Crohn's disease (CD) and ulcerative colitis (UC). AIM: To evaluate clinical and objective response and remission rates with vedolizumab in a large, real world cohort. METHODS: A retrospective cohort study of adult CD and UC patients receiving vedolizumab between 2012 and 2017 was conducted. PRIMARY OUTCOME: clinical or objective response and remission at 3, 6 and 12 months after induction. Clinical remission was defined by complete, steroid-free absence of symptoms. Objective remission was defined by endoscopic mucosal healing or normalisation of radiographic appearance on contrast-enhanced ultrasound or CT/MR enterography. RESULTS: The study included 222 vedolizumab patients (122 CD, 100 UC). In CD, clinical remission at 3, 6 and 12 months was achieved in 19.8% (22/111), 22.1% (21/95) and 22.1% (15/68) of patients, respectively. Objective remission occurred in 11.5% (6/52), 21.2% (14/66), and 18.9% (7/37) of patients at 3, 6 and 12 months, respectively. In UC, clinical remission at 3, 6, and 12 months was 51.0% (51/100), 61.8% (55/89) and 61.9% (39/63), respectively. Endoscopic remission occurred in 27.5% (11/40), 41.0% (16/39) and 47.8% (22/46) of patients at 3, 6 and 12 months, respectively. In multivariable analysis, patients with UC as compared to CD, and those with milder disease activity were more likely to achieve objectively defined remission at both 6 and 12 months. CONCLUSIONS: Vedolizumab was effective for induction and maintenance of clinical and objective remission, both in Crohn's disease and ulcerative colitis.

Preoperative Ustekinumab Treatment Is Not Associated With Increased Postoperative Complications in Crohn's Disease: A Canadian Multi-Centre Observational Cohort Study.

BACKGROUND: Ustekinumab (UST), an anti-IL12/23 inhibitor is indicated for moderate-to-severe Crohn's disease (CD). However, it is unclear if patients treated with UST are at increased risk for postoperative complications. AIM: To evaluate the postoperative safety outcomes in UST-treated CD patients. METHODS: A multicentre cohort study of UST-treated CD patients at two tertiary care centres (University of Calgary, University of Alberta, Canada) undergoing abdominal surgery between 2009 and 2016 was performed. Postoperative outcomes were compared against a control cohort of anti-TNF-treated patients over the same time-period. The primary outcome was occurrence of postoperative complications up to six months postoperatively, stratified by timing (early <30 days vs. late complications ≥30 days). RESULTS: Twenty UST-treated patients and 40 anti-TNF-treated patients were included with a median preoperative treatment exposure of 6.5 months and 18 months, respectively (p=0.01). Bowel obstruction was the most common surgical indication in both cohorts. UST-treated patients were more likely to require an ostomy (70.0% vs. 12.5%, p<0.001) and be on combination therapy with either systemic corticosteroids or concurrent immunomodulators (azathioprine or methotrexate) (25.0% vs. 2.5%, p=0.01). Despite the increased concomitant use of immunosuppression in the UST-treated cohort, there were no significant differences in early or late postoperative wound infections (1/20 in UST-cohort, 2/40 in anti-TNF cohort, p=1.00), anastomotic leak (0/20 in UST-cohort, 3/40 in anti-TNF cohort, p=0.54), or postoperative ileus/obstruction (3/20 in UST-cohort, 4/40 in anti-TNF cohort, p=0.67). CONCLUSIONS: CD patients receiving preoperative UST did not experience an increase in postoperative complications, despite increased use of concurrent immunosuppression.

Clinical Predictors of the Risk of Early Colectomy in Ulcerative Colitis: A Population-based Study.

BACKGROUND: A subset of patients with ulcerative colitis (UC) will require colectomy within a few years of diagnosis. Thus, our aim was to determine the clinical predictors of early colectomy among patients with UC who are hospitalized with an acute flare. METHODS: Using population-based surveillance (1996-2009), all adults (≥18 years) hospitalized for UC within 3 years of diagnosis (n = 489) were identified. The primary outcome was a colectomy within 3 years of diagnosis. All medical charts were reviewed. A logistic regression model evaluated clinical variables that predicted colectomy within 3 years of diagnosis, and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported. RESULTS: Among patients admitted to hospital with UC within 3 years of diagnosis, 57.7% underwent colectomy, with the odds of colectomy decreasing by 12% per year. Early colectomy was more likely among patients aged 35 to 64 years versus 18 to 34 years (OR 2.18 [95% CI, 1.27-3.74]), males (OR 2.03 [95% CI, 1.24-3.34]), those with pancolitis (OR 5.38 [95% CI, 3.20-9.06]), and living in rural areas (OR 2.81 [95% CI, 1.49-5.29]). Prescription of infliximab before hospitalization increased odds of surgery (OR 5.12 [95% CI, 1.36-19.30]). CONCLUSIONS: Patients hospitalized for UC have a high risk of early colectomy. This is particularly true in middle-aged men, those living in rural areas, and those without response to infliximab.

Helminth Regulation of Immunity: A Three-pronged Approach to Treat Colitis.

By reputation, the parasite is a pariah, an unwelcome guest. Infection with helminth parasites evokes stereotypic immune responses in humans and mice that are dominated by T helper (Th)-2 responses; thus, a hypothesis arises that infection with helminths would limit immunopathology in concomitant inflammatory disease. Although infection with some species of helminths can cause devastating disease and affect the course of microbial infections, analyses of rodent models of inflammatory disease reveal that infection with helminth parasites, or treatment with helminth extracts, can limit the severity of autoinflammatory disease, including colitis. Intriguing, but fewer, studies show that adoptive transfer of myeloid immune cells treated with helminth products/extracts in vitro can suppress inflammation. Herein, 3 facets of helminth therapy are reviewed and critiqued: treatment with viable ova or larvae, treatment with crude extracts of the worm or purified molecules, and cellular immunotherapy. The beneficial effect of helminth therapy often converges on the mobilization of IL-10 and regulatory/alternatively activated macrophages, while there are reports on transforming growth factor (TGF)-ß, regulatory T cells and dendritic cells, and recent data suggest that helminth-evoked changes in the microbiota should be considered when defining anticolitic mechanisms. We speculate that if the data from animal models translate to humans, noting the heterogeneity therein, then the choice between use of viable helminth ova, helminth extracts/molecules or antigen-pulsed immune cells could be matched to disease management in defined cohorts of patients with inflammatory bowel disease.