Risk Of Colectomy Research Articles

Appendectomy and the Risk of Colectomy in Ulcerative Colitis: A National Cohort Study.

Ulcerative colitis (UC) is a chronic inflammatory disease usually responding well to anti-inflammatory drugs but many patients will still need colectomy. Appendectomy is associated with a lower risk of later developing UC. We aimed to assess the longitudinal relationship between appendectomy, appendicitis, and disease course in UC patients. A national cohort of UC patients with a diagnosis in 1964-2010 was identified from the Swedish National Patient Register that also provided information regarding appendicitis and/or appendectomy before or after the UC diagnosis. The risk for colectomy and UC-related hospital admissions was evaluated. Among 63,711 UC patients, 2,143 had appendectomy and 7,690 underwent colectomy. Appendectomy for appendicitis before 20 years of age and for non-appendicitis at all ages before UC diagnosis was associated with a lower risk of colectomy (hazard ratio (HR) 0.44, 0.27-0.72 and HR 0.62, 0.43-0.90, respectively), and fewer hospital admissions (incidence rate ratio (IRR) 0.68, 95% confidence interval (CI) 0.64-0.73 and IRR 0.54, 0.47-0.63, respectively). Appendectomy for appendicitis after the UC diagnosis was associated with a higher risk of colectomy (HR 1.56, 1.20-2.03), whereas no such association was found for other pathology (HR 1.40, 0.79-2.47). Appendectomy early in life and before developing UC is associated with a lower risk of colectomy as well as UC-related hospital admissions. Appendectomy for appendicitis after established UC appears associated with a worse disease course, with an increased rate of subsequent colectomy.

Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review

A comprehensive knowledge of the natural history of ulcerative colitis (UC) helps understand disease evolution, identify poor prognostic markers and impact of treatment strategies, and facilitates shared decision-making. We systematically reviewed the natural history of UC in adult population-based cohort studies with long-term follow-up. Through a systematic literature review of MEDLINE through March 31, 2016, we identified 60 studies performed in 17 population-based inception cohorts reporting the long-term course and outcomes of adult-onset UC (n= 15,316 UC patients). Left-sided colitis is the most frequent location, and disease extension is observed in 10%-30% of patients. Majority of patients have a mild-moderate course, which is most active at diagnosis and then in varying periods of remission or mild activity; about 10%-15% of patients experience an aggressive course, and the cumulative risk of relapse is 70%-80% at 10 years. Almost 50% of patients require UC-related hospitalization, and 5-year risk of re-hospitalization is ∼50%. The 5-year and 10-year cumulative risk of colectomy is 10%-15%; achieving mucosal healing is associated with lower risk of colectomy. About 50% of patients receive corticosteroids, although this proportion has decreased over time, with a corresponding increase in the use of immunomodulators (20%) and anti-tumor necrosis factor (5%-10%). Although UC is not associated with an increased risk of mortality, it is associated with high morbidity and work disability, comparable to Crohn's disease. UC is a disabling condition over time. Prospective cohorts are needed to evaluate the impact of recent strategies of early use of disease-modifying therapies and treat-to-target approach with immunomodulators and biologics. Long-term studies from low-incidence areas are also needed.

Risk factors for proximal disease extension and colectomy in left-sided ulcerative colitis.

The primary objective of this study was to assess proximal disease extension of ulcerative colitis (UC) over time, with disease behaviour pattern and risk factors for proximal disease extension and colectomy as secondary aims. All cumulative incident cases diagnosed with UC at the Academic Medical Center between January 1990 and December 2009 were studied. The cumulative risk of colectomy was calculated by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify risk factors associated with proximal disease extension and colectomy. In total, 506 UC patients were included with a median age of 33 years (IQR 23-41) at diagnosis. Ninety-five (18.8%) patients underwent colectomy during follow-up. Median follow-up was 10 years (IQR 5-15). Initial disease extent was evaluable in 416 patients, of whom 142 (34.1%) had proctitis, 155 (37.3%) left-sided colitis and 119 (28.6%) pancolitis. Proximal disease extension was observed in 120 (28.8%) patients during follow-up (51 proctitis to left-sided colitis, 39 proctitis to extensive colitis and 30 left-sided to extensive colitis). Disease behaviour was evaluable in 378 patients, of whom 244 (64.6%) had less than one relapse per year. Younger age at diagnosis (HR 0.98, 95% CI 0.96-0.99) and continuous active disease (HR 2.18, 95% CI 1.27-3.73) were independent risk factors for proximal disease extension. The cumulative risk of colectomy did not change over time between patients diagnosed before and after the year 2000 (p = 0.341). Continuous active disease (HR 7.05, 95% CI 4.23-11.77), systemic steroids (HR 3.25, 95% CI 1.37-7.71) and cyclosporine treatment (HR 2.80, 95% CI 1.66-4.72) were independent risk factors for colectomy, whereas proctitis at diagnosis (HR 0.43, 95% CI 0.22-0.86) carried a lower risk. In one-third of UC patients, left-sided disease at diagnosis will extend proximally during 10 years of follow-up. Proximal disease extension was not a risk factor for colectomy, but the risk of colectomy is rather determined by continuous disease activity, and use of systemic steroids and cyclosporine.

Changing the Game in Ulcerative Colitis: The Impact of Gut-Selective Therapy

Given the progressive nature of ulcerative colitis (UC), Prof Colombel argued that effective therapy is warranted early in the disease course, especially for patients judged at a high risk of colectomy. To slow disease progression clinicians should aim for complete recovery or absence of inflammation in the gut mucosa. This goal has recently been recommended by the US Food and Drug Administration (FDA) who advised that endoscopy should be used in conjunction with histology for the assessment of mucosal healing in UC. Considering remission in UC, Prof Feagan explained that while there is clear evidence that endoscopic remission is associated with better outcomes, challenges remain in achieving remission with current agents. Studies show utility for incorporating histopathological activity into clinical trials, but there are concerns regarding the lack of agreement among pathologists. Two newly validated indices for evaluating histologic disease activity in UC (Robarts Histopathology Index [RHI] and Nancy Histopathology Index) open the way for histopathology to be introduced in early drug development. Prof Schreiber reviewed vedolizumab, a gut-selective α4β7 integrin antagonist recommended by the European Crohn’s and Colitis Organisation (ECCO) guidelines as a first-line biologic therapy for the treatment of moderate-to-severe UC. Data from clinical trials showed that vedolizumab has the greatest efficacy in anti-tumour necrosis factor (TNF)-naïve patients and early in the disease course. Histologic healing, reported in >50% of UC patients with endoscopic remission taking vedolizumab, is likely to be a new endpoint in clinical trials. Vedolizumab has a favourable risk-benefit profile, with >77,382 patient years of post-marketing exposure worldwide.1

Proximal Disease Extension in Patients With Limited Ulcerative Colitis: A Danish Population-based Inception Cohort.

Disease extent in ulcerative colitis [UC] is dynamic and can progress over time. Little is known about risk factors for UC extension in the era of biologics. We investigated the risk of UC extension and subsequent risk of surgery in a Danish population-based cohort. All incident UC cases in a strictly defined Copenhagen area between 2003 and 2004 were followed prospectively through 2011. Disease extension was defined as patients with limited UC [E1 or E2] at diagnosis having progressed from the initial extent by colonoscopy or surgery to E2 or extensive colitis [E3]. Associations between progression or colectomy and multiple covariates were analysed by Cox regression analysis. Of 300 UC patients, 220 [73%] had E1 or E2 at diagnosis. During follow-up, 50 [23%] patients with E1/E2 progressed to E3, and 22 [10%] with E1 progressed to E2. Disease extent at diagnosis was the sole predictor of extension to E3. A total of 18 [8%] patients with E1/E2 at diagnosis had a colectomy. Progression from E1/E2 to E3, female gender and a history of smoking were risk factors for colectomy. After 7 years of follow-up, 33% of patients with limited UC experienced disease extension. Only extent at diagnosis was a clinical predictor for disease extension. The risk of colectomy was increased in former smokers and patients who progressed to extensive colitis. This highlights the need to prevent disease progression in patients with limited UC, and to identify new histological or molecular markers that might help stratify risks for disease progression.

As Infliximab Use for Ulcerative Colitis Has Increased, so Has the Rate of Surgical Resection

BackgroundInfliximab was approved for ulcerative colitis in 2005 after randomized trials showed it reduced the risk of colectomy. Its effect on population-level surgery rates is unknown. Our aim is to assess the impact of infliximab approval for ulcerative colitis on surgical intervention. MethodsRetrospective review of a private insurance claims database (2002 to 2013) was performed of patients aged 18–64 diagnosed with ulcerative colitis and with 2 years of follow-up. Outcome measures were infliximab treatment and surgical resection. Multivariable logistic regression used independent variables of time period of diagnosis, age, gender, comorbidities, and insurance type. ResultsThe cohort included 58,681 patients. Age, gender, and comorbidities were comparable across time periods. Patients diagnosed in the post-infliximab period had greater odds of undergoing infliximab treatment within the first year of diagnosis than those in the pre-infliximab era (OR = 2.88, p < 0.001). However, the odds of undergoing total colectomy or total proctocolectomy were also higher in patients diagnosed in the post-infliximab period (OR 1.5, p < 0.001). ConclusionsThe use of infliximab for ulcerative colitis has, as expected, increased since its approval, but so has the risk of surgery. Thus, the introduction of biologic therapy has not decreased the risk for surgery for this patient population.

Systematic review with meta-analysis: the impact of Clostridium difficile infection on the short- and long-term risks of colectomy in inflammatory bowel disease.

Clostridium difficile infection (CDI) is associated with increased mortality in inflammatory bowel disease (IBD), but the risk of colectomy is variable and has not been adequately studied. To perform a systematic review and meta-analysis to assess the impact ofCDI on colectomy risk in IBD. Multiple databases were searched systematically for observational studies reporting colectomy risk in IBD, stratified by the presence of CDI, and the duration of follow-up (short term 3months, and long term at least 1year). Weighted summary estimates were calculated using generalised inverse variance with random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. Twelve observational studies were identified and included 35057 IBD patients with CDI, and 929259 without CDI. CDI did not increase the short-term colectomy risk in IBD patients overall (10 studies) (OR: 1.35; 95% CI: 0.68-2.67), or in patients with ulcerative colitis (nine studies) (OR: 1.20; 95% CI: 0.39-3.76). In contrast, CDI was associated with higher long-term colectomy risk in patients with IBD overall (five studies) (OR: 2.23; 95% CI: 1.18-4.21), and in patients with ulcerative colitis (four studies) (OR: 2.96; 95% CI: 1.19-7.34). The results were stable in subgroups stratified by recruitment period, hospitalisation status and geographical location. All studies were at least of moderate quality. The results were limited in the ability to compare IBD severity and the type of anti-microbial therapy. Based on 12 observational studies with at least moderate quality, Clostridium difficile infection appears to increase colectomy risk in IBD in the long- but not short- term.

Clostridium difficile Infection and Risk of Colectomy in Patients with Inflammatory Bowel Disease: A Bias-adjusted Meta-analysis.

Clostridium difficile infection (CDI) is a common complication of inflammatory bowel diseases (IBDs) and is associated with worse outcome. Variable rates of colectomy have been reported among IBD complicated by CDI. We conducted a systematic review and meta-analysis of studies to assess the association between CDI and colectomy among patients with IBD. The literature was systematically searched using PubMed from inception through April 2016. Studies were limited to cohort, case-control, and cross-sectional studies reporting colectomy risk stratified by CDI in patients with IBD. We estimated summary ORs and 95% CIs using the quality-effects model. Study quality was assessed using an adaptation of the Newcastle-Ottawa scale. Six studies were included in the meta-analysis, comprising 8 data sets. Results from meta-analysis showed that CDI was a significant risk factor for colectomy among patients with IBD, mainly patients with ulcerative colitis, almost doubling the odds (OR 1.90; 95% CI, 1.23-2.93). There was significant heterogeneity across studies (Q = 22.02, P < 0.001; I = 68%). Funnel plots were grossly asymmetrical. Results of sensitivity analysis restricting studies to those reporting ulcerative colitis only and studies using laboratory tests to confirm CDI were consistent with the result from the main analysis. CDI is a significant risk factor for colectomy in patients with IBD. Further research is needed to investigate the attributable risks of surgery due to CDI among patients with Crohn's disease.

P724 Appendectomy is not a treatment option for ulcerative colitis

Background: Ulcerative colitis (UC) is a chronic inflammatory disease usually responding well to anti-inflammatory drugs but many patients will eventually need a colectomy, due to severe acute colitis or chronically active disease. Appendectomy has previously been shown to be associated with a lower risk of developing UC later in life. We aimed to assess the association between appendectomy and disease activity and the risk of having a colectomy in UC patients. Methods: All patients in Sweden with a UC diagnosis between 1964 and 2010 were identified from the National Patient Register. Information regarding appendectomy with or without appendicitis was gathered, including appendectomy both prior to and after the UC diagnosis. Planned and unplanned hospital admissions for UC as well as colectomy were used as markers of disease activity. Results: Appendectomy was performed in 2,143 of the 63,711 UC patients, prior to the UC diagnosis in 1,537 patients and after in 606 patients. In all, 7,690 patients underwent colectomy. The cumulative risk of colectomy for patients without appendectomy was 0.10 (95% CI 0.09 to 0.10) and 0.13 (0.12 to 0.13) after 5 and 10 years, respectively. For patients with appendectomy for appendicitis before the age of 20 and prior to UC diagnosis, the cumulative risk of colectomy was 0.05 (0.03 to 0.09) and 0.07 (0.04 to 0.11), respectively. In multivariable analysis the hazard ratio for this group was 0.44 (0.27 to 0.72) compared to UC patients without appendectomy. Appendectomy prior to UC diagnosis but at age 20 years or older did not affect the risk of colectomy after UC diagnosis (HR 0.97 (0.80 to 1.18)). Appendectomy for appendicitis after the UC diagnosis was associated with an increased risk of colectomy with HR 1.55 (1.20 to 2.02). Appendectomy after UC diagnosis for other reasons did not affect the risk of colectomy (HR 1.14 (0.57 to 2.28)). Appendectomy prior to UC diagnosis was associated with fewer planned and unplanned admissions for UC (Incidence rate ratio 0.71 (0.64 to 0.77), whereas appendectomy after UC diagnosis was associated with more admissions for UC (IRR 1.10 (1.00 to 1.21)). Conclusions: UC patients with a history of appendicitis before the age of 20 years and preceding the UC diagnosis have a lower risk for colectomy. Appendectomy for appendicitis after the UC diagnosis is associated with more admissions and increased risk of colectomy. Appendectomy for other reasons after the UC diagnosis does not seem to affect the severity of UC. Appendectomy therefore does not appear to be a treatment option in UC.

P585 Infliximab in moderate to severe ulcerative colitis: comparison between scheduled treatment strategy and bridge strategy

Background: Ulcerative colitis (UC) is a potentially severe disease that carries an increased risk of complications and colectomy. Immunosuppressant and biological therapies are relevant tools for complex patients. The ACCENT study showed that in Crohn's disease (CD) scheduled infliximab (IFX) infusions vs. episodic are associated with greater efficacy. In UC, historical difficulties of economic access had conditioned to our IBD center, to use IFX in moderate to severe UC as a bridge to thiopurines in pts 6mp/aza naïve. In UC, the mentioned strategy was insufficiently compared with a regimen of scheduled IFX treatment, that currently we use. Aims: to compare (retrospectively) in moderate to severe UC the results of induction with IFX (in thiopurine naïve pts) continuing with 6mp/aza maintenance vs. similar induction followed by scheduled IFX maintenance strategy. Methods: We included a cohort of moderate to severe UC treated with IFX in an IBD center (2006 to 2015) comparing results between IFX bridge followed by thiopurines (re-induction when available for moderate to severe relapse) vs. scheduled IFX (induction 0, 2, 6 wks and 8 wks' interval infusions maintenance). Optimization (by frequency of intervals) were allowed in both modalities. Comparisons: Kaplan Meier/Log rank test: a) Cumulative prevalence of colectomy, b) survival times relapse free, c) survival times corticosteroid free. Results: We identified 135 UC (M 60, F 75, Age (mean±SD) 35.9±13.2, UC duration 5.8±5.9 yrs, Extent: extensive 58.5%, Left-sided 41.5%, Activity: severe 78.5%, moderate 21.5%, mean Mayo sc. 10.1±1.8. Primary no responders at week 12 (n 25: 18,5%) were not considered in maintenance comparisons, performed in 110/135 pts (follow-up 37.5±24.0 months) Groups: IFX bridge (n=51) and scheduled IFX (n 59) were not different in extent, age, UC duration, Mayo sc. Cumulative prevalence of colectomy was significantly lower in the scheduled strategy (HR: 6.8805, 95% CI 1.7207 to 27.5133, p=0.0349), as well as survival times free of relapse (HR 3.1026, 95% CI 1,8368 to 5.2405, p<0.0001) and free of corticosteroids (HR 2.6057, 95% CI 1.5516 to 4.3757, p=0.0003. A proportion of UC significantly higher within the re-induced pts (IFX bridge) required a shift of biological drug compared with the scheduled strategy (p=0.016, Fisher), despite of similar rates of optimization. Infusion reactions needing definitive IFX suspension were more frequent as a tended (p=0.06) in re-induced pts. Conclusions: similarly to was described for CD pts, in the CU, the scheduled IFX treatment strategy regimen, after a moderate-severe outbreak, seem to be associated with better long-term outcome regarding colectomy requirement, relapses, and need for corticosteroids, compared with a bridge IFX strategy followed by thiopurines.

Long-term outcome of infliximab treatment in chronic active ulcerative colitis: a Swedish multicentre study of 250 patients.

Real-life long-term data on infliximab treatment in ulcerative colitis are limited. To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined. A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant. Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy. Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.

Predictors of severe outcomes in patients with Clostridium difficile infection from a Hispanic population.

Factors associated with complicated Clostridium difficile infection (CDI) may vary among populations, and predictors of severe outcomes in CDI have not been studied in Hispanic patients. The aim of this study was to identify factors associated with a higher risk of colectomy, all-cause mortality, and CDI-associated mortality in a Hispanic population. We performed a retrospective study of all hospitalized patients with a diagnosis of CDI between January 1, 2011 and September 30, 2015 in a 450-bed teaching hospital in Monterrey, northeast Mexico. Three main outcomes were defined: fulminant colitis with subsequent colectomy, all-cause mortality within 30days of diagnosis, and CDI-attributable mortality. Of 261 patients with diarrhea, 176 were diagnosed with CDI. For colectomy, Charlson comorbidity index, ICU stay and mechanical ventilation prior to CDI diagnosis, days with diarrhea prior to treatment, total days of hospital stay and days after CDI diagnosis, elevated ATLAS score, days of diarrhea post CDI treatment, and treatment failure significantly predicted the necessity of surgical treatment with colectomy. Treatment failure, persistent diarrhea, and a high ATLAS score were identified as risk factors for severe outcomes of CDI. A low albumin concentration and high creatinine were associated with higher overall mortality.

Smoking influences the need for surgery in patients with the inflammatory bowel diseases: a systematic review and meta-analysis incorporating disease duration.

BackgroundStudies examining the association between smoking and the need for surgery in patients with Crohn’s disease and ulcerative colitis have reached inconsistent conclusions. These studies often do not differentiate between patients undergoing early surgery and patients having surgery later in their disease course. Our study examined the association between smoking status and time to first bowel resection in patients with Crohn’s disease and ulcerative colitis.MethodsWe searched MEDLINE and EMBASE for studies (n = 12) reporting on the association between smoking status (current, former, and never) and surgery in IBD, and incorporated disease duration in the analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were pooled across studies using random effects models.ResultsCurrent smokers with Crohn’s disease were at increased risk of intestinal resection compared to never smokers (HR 1.27, 95% CI 1.08 to 1.49); however, there was no difference in the need for surgery when comparing former and never smokers (HR 1.11, 95% CI 0.95 to 1.30). In patients with ulcerative colitis, there was no difference in the need for colectomy when comparing current smokers to never smokers (HR 0.98, 95% CI 0.67 to 1.44). Former smokers with ulcerative colitis were at increased risk of colectomy (HR 1.38, 95% CI 1.04 to 1.83) compared to never smokers.ConclusionsCurrent smokers with Crohn’s disease are at increased risk of surgery, while former smokers with ulcerative colitis have increased risk of colectomy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0555-8) contains supplementary material, which is available to authorized users.

Tissue and peripheral eosinophilia as predictors for disease outcome in children with ulcerative colitis

BackgroundEosinophils are implicated in the pathogenesis of ulcerative colitis. AimsTo evaluate the magnitude of mucosal and blood eosinophils in newly diagnosed pediatric ulcerative colitis patients and its significance in predicting disease outcomes. MethodsWe retrospectively evaluated colorectal biopsies of 96 pediatric patients with ulcerative colitis and 50 age- and sex-matched controls. Samples were taken from diseased areas of the colon and examined by a gastrointestinal pathologist. The most inflamed site was used for assessment of mucosal eosinophils. ResultsSamples from 96 diagnostic and 70 follow-up colonoscopies were evaluated. Median age was 13.3 years (IQR 10.1–15.3). Median duration of follow-up was 12.8 years (IQR 7.2–17.1). Median number of tissue eosinophils at diagnosis was 45 (IQR 22–73) compared to 10 eosinophils (IQR 8–25) during histologic remission (p<0.0001). Peripheral absolute eosinophil counts correlated with tissue inflammation and eosinophilia (p=0.001). Mucosal eosinophilic infiltration (p=0.02) and peripheral eosinophilia (p=0.04) was associated with clinical severity at diagnosis. Multivariate analysis showed that severe eosinophilic infiltration is associated with corticosteroid therapy following diagnosis (p=0.04) but not with long-term risk for step-up therapy or colectomy. ConclusionTissue and peripheral eosinophilia correlate with ulcerative colitis severity at diagnosis and with short-term corticosteroid requirement but not with long-term outcomes.

Increased Rates of Clostridium difficile Infection and Poor Outcomes in Patients with IBD with Cytomegalovirus.

Clostridium difficile infection (CDI) and Cytomegalovirus (CMV) reactivation are associated with disease exacerbations and poor outcomes in inflammatory bowel disease (IBD). Therefore, we assessed the association between these organisms in patients with IBD and the impact on colectomy. A retrospective case-control study was conducted to assess CDI prevalence in patients with IBD with a tissue diagnosis of CMV compared with matched IBD controls without CMV from 2005 to 2011. We also assessed the impact of coinfection on colectomy risk for patients coinfected with CMV and CDI compared with IBD patients with CMV alone (CMV controls) or matched IBD patients with CDI alone (CDI controls). Colectomy-free survival was assessed using Kaplan-Meier methods, and statistical significance was determined using Log-rank analysis for unmatched comparisons and by generalized estimating equations in Cox regression for matched comparisons. CDI was more common in IBD patients with CMV (n = 12/68; 17.6%) than in matched IBD controls (n = 12/144; 8.25%) (P = 0.046). A nonsignificant increase in high-grade disease (5 or more CMV inclusions by immunohistochemistry) was detected in coinfected patients compared with CMV controls (P = 0.15). Colectomy-free survival at 1 year was 30% (95% confidence interval, 12.0-74.7) for coinfected patients and was significantly less compared with 71.5% (95% confidence interval, 58.0-88.2) of CDI controls (P < 0.001) and was numerically less than 57.1% (95% confidence interval, 44.1-74.0) of CMV controls (P = 0.095). CDI occurs more frequently in IBD patients with CMV reactivation and is associated with poor outcomes. Patients with IBD with CMV should be tested for CDI and managed aggressively.

Improving Management of Ulcerative Colitis Through Virtual Patient Simulation

Introduction: This study aimed to determine if virtual patient simulation (VPS)-based education could help gastroenterologists optimize assessment of ulcerative colitis (UC) and treatment selection based on UC severity, which are two key factors for achieving disease modifying outcomes. Methods: Education was delivered online via an interactive VPS learning platform that modelled reallife clinical encounters. Learners were presented with two patient cases of UC, with electronic health records. Following virtual interaction to learn more about patients, physicians were challenged to order lab tests, diagnoses and treatments. Possible orders were not limited by multiple choice but rather were supported by a database matching scope and depth of actual practice. Clinical decisions made by learners were analyzed using a decision engine in the VPS platform, and tailored clinical guidance (CG) was provided in response to learner decisions. Educational impact was measured by comparing participant decisions pre- and post- CG using a 2-tailed paired T-test where P< 0.005 was considered statistically significant. Results: From pre- to post- CG in the VPS, gastroenterologists (n=194) were more likely to make evidence-based choices in: Ordering suitable workup to establish UC disease activity and determine risk of colectomy, which included significant improvements in ordering an abdomen CT scan (35% pre-CG to 66% post-CG, P<.0001), flexible sigmoidoscopy (65% pre-CG to 80% post-CG, P<.0001), infliximab serum antibodies (85% pre-CG to 93% post-CG, P=0.003), serum ferritin (34% pre-CG to 63% post-CG, P< 0.0001), and stool ova and parasite exam (52% pre-CG to 74% post-CG, P< 0.0001). Diagnosing UC with a high risk of colectomy (13% pre-CG to 38% post-CG, P< 0.0001). Selecting appropriate interventions in UC to improve patient outcomes, including medication adherence counseling (42% pre-CG to 70% post-CG, P< 0.0001), ordering a registered dietician (26% pre-CG to 54% post-CG, P< 0.0001), reviewing vaccination records (27% pre-CG to 57% post-CG, P< 0.0001), and selecting therapies with better efficacy and steroid-free remission (42% pre-CG to 58% post-CG, P< 0.002). Conclusion: Gastroenterologists who participated in VPS-based education significantly improved clinical decisions related to assessment of UC severity and selection of treatments to minimize risk of colectomy. This type of intervention has the potential to improve performance in practice and patient outcomes.

Clinical Response and Complications Are Not Associated with Level of Cyclosporine in Patients with Severe Ulcerative Colitis

Introduction: Cylclosporine (CyA) salvage therapy is effective in patients with steroid refractory ulcerative colitis (UC). The optimal drug level to achieve response and minimize complications during induction therapy, however, is not known. Methods: We conducted a retrospective analysis of consecutive hospitalized patients with steroid refractory UC treated with CyA in a single tertiary care center from 5/2008 to 6/2015. Data was collected on baseline demographics, previous medication usage, and laboratory values during hospitalization. Outcomes of colectomy within 90 days and post-operative complications (infectious and non-infectious) for patients who had surgery during their initial hospitalization were compared by first, mean, and peak CyA level while in the hospital both as continuous variables and grouped by quartile. Results: A total of 81 patients with severe UC started on IV CyA were included in the analysis. Median age of cohort was 34 years. 47 patients (58%) required a colectomy within 90 days of starting CyA. Patients who responded to CyA and did not require surgery within 90 days had significantly lower C-Reactive Peptide levels (2.0 mg/L vs 3.8 mg/L, p= 0.01), higher serum albumin (3.7g/dL vs. 3.4 g/dL, p=0.03) at baseline and were more likely to have been treated with anti-TNF agents previously (33.4% vs 4.3%, p=0.0001). There were no differences between initial, mean and peak CyA levels among responders and non-responders. 37 patients (45.6 %) underwent surgery of which 10 patients (27%) had post operative complications. There was also no association with response or post-operative complications in an interquartile analysis of first ( <177, 177-263, 264-330, >331) mean ( < 237,237-277, 278-354, >355), and peak ( < 347,347-418,419-490, >490) CyA (ng/mL) levels. Conclusion: In this single center analysis, clinical response and post-operative complications were not associated with level of cyclosporine during IV induction therapy. As there were few patients in the cohort with a mean level less than 200ng/mL during IV therapy, this analysis was limited in assessing response and safety in a population with targeted dosing of low levels of cyclosporine.Table 1: Risk of Colectomy and Complications by Inter-quartile Cyclosporine Levels

MANAGEMENT OF ACUTE SEVERE ULCERATIVE COLITIS: A CLINICAL UPDATE.

ABSTRACTIntroduction: Acute severe colitis is a potentially lethal medical emergency and, even today, its treatment remains a challenge for clinicians and surgeons. Intravenous corticoid therapy, which was introduced into the therapeutic arsenal in the 1950s, continues to be the first-line treatment and, for patients who are refractory to this, the rescue therapy may consist of clinical measures or emergency colectomy. Objective: To evaluate the indications for and results from drug rescue therapy (cyclosporine, infliximab and tacrolimus), and to suggest a practical guide for clinical approaches. Methods: The literature was reviewed using the Medline/PubMed, Cochrane library and SciELO databases, and additional information from institutional websites of interest, by cross-correlating the following keywords: acute severe colitis, fulminating colitis and treatment. Results: Treatments for acute severe colitis have avoided colectomy in 60-70% of the cases, provided that they have been started early on, with multidisciplinary follow-up. Despite the adverse effects of intravenous cyclosporine, this drug has been indicated in cases of greater severity with an imminent risk of colectomy, because of its fast action, short half-life and absence of increased risk of surgical complications. Therapy using infliximab has been reserved for less severe cases and those in which immunosuppressants are being or have been used (AZA/6-MP). Indication of biological agents has recently been favored because of their ease of therapeutic use, their good short and medium-term results, the possibility of maintenance therapy and also their action as a "bridge" for immunosuppressant action (AZA/6-MP). Colectomy has been reserved for cases in which there is still no response five to seven days after rescue therapy and in cases of complications (toxic megacolon, profuse hemorrhage and perforation). Conclusion: Patients with a good response to rescue therapy who do not undergo emergency operations should be considered for maintenance therapy using azathioprine. A surgical procedure is indicated for selected cases.

Ulcerative proctitis is a frequent location of paediatric-onset UC and not a minor disease: a population-based study

ObjectiveNatural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC.Patients...

Outcome of acute severe ulcerative colitis in patients previously exposed to immunosuppressive therapy

Background and aimWe aimed to evaluate the outcome of patients with acute severe ulcerative colitis previously exposed to immunosuppressive (IMS) therapy. MethodsWe retrospectively collected data from 86 consecutive patients from 2008. Early outcome was evaluated as response to steroids, rescue therapy, and colectomy rate, whereas colectomy free-survival was determined along the follow-up. ResultsThe overall response rates to steroids and rescue therapy was 33.7% and 90.5%, respectively, while early colectomy rate was 22.1%. Patients previously treated with IMS (n=47) showed a trend towards lower response to steroids (25.5% vs 43.6%; p=0.10), and a high-risk of early colectomy (29.8% vs 12.8%; p=0.07), but a similar response to rescue therapy (87.5% vs 94.4%, p=0.62) when compared with IMS-naïve patients (n=39). The overall cumulative probability to avoid the surgery was 67.5% and 56.6% at 12 and 60 months, respectively, regardless of previous exposure to IMS (p=0.30). At multivariate analysis the risk of early colectomy was increased by previous IMS (OR 5.16, p=0.017), anaemia (OR 4.26, p=0.02), and diagnosis above 40 years (OR 5.31, p=0.011). ConclusionsPatients previously treated with IMS showed a non-significant trend towards a worse response with steroid therapy, a satisfactory response rate to rescue therapy, and a similar probability of avoiding colectomy during the follow-up vs IMS-naive patients.