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Background: The modified pouchitis disease activity index (mPDAI) based on clinical symptoms and endoscopic findings is used to diagnose pouchitis, but validated instruments to monitor pouchitis are still lacking. We recently established an endoscopic classification that described 7 endoscopic phenotypes with different outcomes. We assessed symptoms and compared mPDAIs among phenotypes in inflammatory bowel disease (IBD)., Methods: We retrospectively reviewed pouchoscopies and classified them into 7 main phenotypes: normal ( n  = 25), afferent limb (AL) involvement ( n  = 4), inlet involvement ( n  = 14), diffuse ( n  = 7), focal inflammation of the pouch body ( n  = 25), cuffitis ( n  = 18), and pouch-related fistulas ( n  = 10) with a single phenotype were included. Complete-case analysis was conducted., Results: One hundred and three IBD patients were included. The median mPDAI was 0 (IQR 0-1.0) in patients with a normal pouch. Among inflammatory phenotypes, the highest median mPDAI was 4.0 (IQR 2.25-4.75) in cuffitis, followed by 3.0 (IQR 2.5-4.0) in diffuse inflammation, 2.5 (IQR 1.25-4.0) in inlet involvement, 2.5 (IQR 2.0-3.5) in AL involvement, 2.0 (IQR 1.0-3.0) in focal inflammation, and 1.0 (IQR 0.25-2.0) in the fistula phenotype. Perianal symptoms were frequently observed in pouch-related fistulas (8/10, 80%) and cuffitis (13/15, 87%). Among patients with cuffitis, all had incomplete emptying (6/6, 100%)., Conclusions: We correlated the mPDAI with the endoscopic phenotypes and described the limited utility of symptoms in distinguishing between inflammatory phenotypes. Further studies are warranted to understand which symptoms should be monitored for each phenotype and whether mPDAI can be minimized after pouch normalization., Competing Interests: S.A., J.E.O., N.A.C., V.R., L.R.G., Y.Y., C.T., J.R., K.B.S., R.D.H., K.U., B.D.S., N.H.H., and A.S. have no relevant disclosures. R.D.C. is on the speaker’s bureau from AbbVie and Takeda. He is a consultant/advisor for AbbVie Laboratories, BM/celgene, Eli Lilly, Gilead Sciences, Janssen, Pfizer, Takeda, UCB Pharma. He has received clinical trial support/grants from Abbvie, BMS/Celgene, Boehringer Ingelheim, Crohn’s and Colitis Foundation of America, Genentech, Gilead Sciences, Hollister, Medimmune, Mesoblast Ltd., Osiris Therpeutics, Pfizer, Receptos, RedHill Biopharma, Sanofi-Aventis, Schwarz Pharma, Seres Therapeutics, Takeda Pharma, UCB Pharma. His wife is on the board of directors of Aerpio Therapeutics, Novus Therapeutics, Vital Therapeutics, Inc, and NantKwest. M.A.R. has served as a consultant for Pfizer. S.R.D. has served as a consultant for Pfizer and is on the speaker’s bureau for AbbVie. J.P. has received grant support from AbbVie and Takeda. He has served as a consultant for Veraste,. CVS Caremark and is on the advisory board for Takeda, Janssen and Pfizer. E.B.C. is the founder and chief medical officer of AVnovum Therapeutics. D.T.R. has received grant support from Takeda; and has served as a consultant for Abbvie, Altrubio, Amgen, AvaloTherapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Patients with inflammatory bowel disease (IBD) who undergo proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. We previously proposed a novel endoscopic classification of pouchitis describing 7 phenotypes with differing outcomes. This study assessed phenotype transitions over time., Methods: We classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb (AL) involvement, (3) inlet (IL) involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch-related fistulas noted more than 6 months after ileostomy takedown. Among 2 endoscopic phenotypes, the phenotype that was first identified was defined as the primary phenotype, and the phenotype observed later was defined as the subsequent phenotype., Results: We retrospectively reviewed 1359 pouchoscopies from 426 patients (90% preoperative diagnosis of ulcerative colitis). The frequency of primary phenotype was 31% for AL involvement, 42% for IL involvement, 28% for diffuse inflammation, 72% for focal inflammation, 45% for cuffitis, 18% for pouch-related fistulas, and 28% for normal pouch. The most common subsequent phenotype was focal inflammation (64.8%), followed by IL involvement (38.6%), cuffitis (37.8%), AL involvement (25.6%), diffuse inflammation (23.8%), normal pouch (22.8%), and pouch-related fistulas (11.9%). Subsequent diffuse inflammation, pouch-related fistulas, and AL or IL stenoses significantly increased the pouch excision risk. Patients who achieved subsequent normal pouch were less likely to have pouch excision than those who did not (8.1% vs 15.7%; P = .15)., Conclusions: Pouch phenotype and the risk of pouch loss can change over time. In patients with pouch inflammation, subsequent pouch normalization is feasible and associated with favorable outcome., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Despite significant differences in surgical outcomes between pediatric and adult patients with ulcerative colitis (UC) undergoing colectomy, counseling on pediatric outcomes has largely been guided by data from adults. We compared differences in pouch survival between pediatric and adult patients who underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA)., Methods: This was a retrospective single-center study of patients with UC treated with IPAA who subsequently underwent pouchoscopy between 1980 and 2019. Data were collected via electronic medical records. We stratified the study population based on age at IPAA. Differences between groups were assessed using t tests and chi-square tests. Kaplan-Meier curves were used to compare survival probabilities. Differences between groups were assessed using a log-rank test., Results: We identified 53 patients with UC who underwent IPAA before 19 years of age and 329 patients with UC who underwent IPAA at or after 19 years of age. Subjects who underwent IPAA as children were more likely to require anti-tumor nerosis factor (TNF) postcolectomy compared with adults (41.5% vs 25.8%; P < .05). Kaplan-Meier estimates revealed that pediatric patients who underwent IPAA in the last 10 years had a 5-year pouch survival probability that was 28% lower than that of those who underwent surgery in the 1990s or 2000s (72% vs 100%; P < .001). Further, children who underwent IPAA and received anti-TNF therapies precolectomy had the most rapid progression to pouch failure when compared with anti-TNF-naive children and with adults who were either exposed or naive precolectomy (P < .05)., Conclusions: There are lower rates of pouch survival for children with UC who underwent IPAA following the uptake of anti-TNF therapy compared with both historical pediatric control subjects and contemporary adults., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Models to predict colectomy in ulcerative colitis (UC) are valuable for identification, clinical management, and follow-up of high-risk patients. Our aim was to develop a clinical predictive model based on admission data for one-year colectomy in adults hospitalized for severe UC., Methods: We performed a retrospective analysis of patients hospitalized at a tertiary academic center for management of severe UC from 1/2013 to 4/2018. Multivariate regression was performed to identify individual predictors of one-year colectomy. Outcome probabilities of colectomy based on the prognostic score were estimated using a bootstrapping technique., Results: Two hundred twenty-nine individuals were included in the final analytic cohort. Four independent variables were associated with one-year colectomy which were incorporated into a point scoring system: (+) 1 for single class biologic exposure prior to admission; (+) 2 for multiple classes of biologic exposure; (+) 1 for inpatient salvage therapy with cyclosporine or a TNF-alpha inhibitor; (+) 1 for age <40. The risk probabilities of colectomy within one year in patients assigned scores 1, 2, 3, and 4 were 9.4% (95% CI, 1.7-17.2), 33.7% (95% CI, 23.9-43.5), 58.5% (95% CI, 42.9-74.1), 75.0% (95% CI, 50.5-99.5). An assigned score of zero was a perfect predictor of no colectomy., Conclusion: Risk factors most associated with one-year colectomy for severe UC included: prior biologic exposure, need for inpatient salvage therapy, and younger age. We developed a simple scoring system using these variables to identify and stratify patients during their index hospitalization., (© The Author(s) 2021. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Inpatient management of severe ulcerative colitis is complicated by the use of prior immunosuppressant therapies. Our aim was to determine the rate of 1-year colectomy among individuals receiving inpatient calcineurin inhibitor (CNI)-based therapy stratified by prior biologic therapy., Methods: A retrospective cohort study was performed between January 1, 2013 and April 1, 2018. Only individuals requiring inpatient administration of intravenous cyclosporine or oral tacrolimus were included in the analysis. Individuals were stratified according to prior biologic therapy exposure. The primary outcome of interest was 1-year risk of colectomy. Kaplan-Meier curves were generated for time-to-event data, and regression models were performed to examine the effects of covariates on the clinical endpoint., Results: Sixty-nine (62.3% male) patients were treated with an inpatient CNI-based therapy and were included in the analysis. Fifteen (21.7%) patients were biologic-naïve, 42 (60.9%) patients had prior exposure to 1 class of biologic therapy, and 12 (17.4%) patients had prior exposure to 2 classes of biologic therapy (third-line CNI therapy). Third-line CNI therapy showed a greater risk of 1-year colectomy risk when compared with the risk for patients who were biologic-naïve (hazard ratio, 3.63; 95% confidence interval, 1.17-13.45; P = 0.025). In a multivariate proportional hazards model, third-line CNI therapy remained significantly associated with 1-year colectomy risk (hazard ratio, 7.94; 95% confidence interval, 1.97-39.76; P = 0.003)., Conclusions: The use of CNI-based therapy in individuals exposed to multiple classes of prior biologic therapies leads to a significantly increased risk of 1-year colectomy. Future studies will be required to compare inpatient management strategies with the expanding novel therapies in UC., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: As the reliability of fecal calprotectin (Fcal) remains debatable to detect endoscopic ulcerations in patients with pure ileal Crohn's disease (CD), we aimed to compare its performances with those observed in patients with colonic or ileocolonic location., Methods: Using a prospectively maintained database, we analyzed 123 CD patients with Fcal measurement and ileocolonoscopy performed within 1 month with no therapeutic intervention during this interval. Receiver operating characterstic curves (ROC) were used to determine the best Fcal threshold to detect endoscopic ulcerations, taking into account the clinical relevance and usual recommended indices. Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were presented with 95% confidence intervals., Results: The mean Fcal level was significantly higher in patients with endoscopic ulcerations in the L1 group (P = 0.025) and the L2-L3 group (P < 0.001). Using ROC curves, Fcal >200 µg/g and Fcal >250 µg/g were the best thresholds to detect endoscopic ulcerations in the L1 group (sensitivity = 75.0, 95% CI, 47.6-92.7; specificity = 87.5, 95% CI, 67.6-97.3; PPV = 80.0, 95% CI, 51.9-95.7; and NPV = 84.0; 95% CI, 63.9-95.5) and in the L2-L3 group (sensitivity = 84.1 95% CI, 69.9-93.4; specificity = 74.4, 95% CI, 57.9-87.0; PPV = 78.7, 95% CI, 64.3-89.3, and NPV = 80.6, 95% CI, 64.0-91.8), respectively. We compared the AUC between L1 and L2-L3 groups, and no difference was shown (0.89 vs 0.84, respectively, P = 0.46). We also compared 2-by-2 sensitivity, specificity, PPV, NPV, and accuracy and we did not observe any significant difference., Conclusion: Fecal calprotectin is highly effective to detect endoscopic ulcerations regardless of CD location but requires a lower cutoff value in patients with pure ileal involvement., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although several studies have associated the use of nonsteroidal anti-inflammatory drugs with disease flares in patients with inflammatory bowel disease (IBD), little is known about the impact of daily aspirin use on clinical outcomes in patients with IBD., Methods: We conducted a retrospective analysis of a prospectively collected registry of patients with IBD from May 2008 to June 2015. Patients with any disease activity with daily aspirin use were matched 1:4 to controls by age, sex, disease, disease location, and presence of cardiac comorbidity. Patients with at least 18 months of follow-up were included in the final analysis. The primary outcomes of interest were having an IBD-related hospitalization, IBD-related surgery, and requiring corticosteroids during the follow-up period., Results: A total of 764 patients with IBD were included in the analysis, of which 174 patients were taking aspirin. There was no statistical difference in age, gender, diagnosis (Crohn's disease vs ulcerative colitis), disease duration, Charlson Comorbidity Index, smoking status, medication usage, or baseline C-reactive protein between groups. After controlling for covariables and length of follow-up in the entire population, aspirin use was not associated with a risk of being hospitalized for an IBD-related complication (odds ratio [OR], 1.46; P = 0.10), corticosteroid use (OR, 0.99; P = 0.70), or having an IBD-related surgery (OR, 0.99; P = 0.96)., Conclusion: In this single-center analysis, aspirin use did not impact major clinical outcomes in patients with IBD. Although the effect of aspirin use on mucosal inflammation was not directly assessed in this study, these findings support the safety of daily aspirin use in this population., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This study aims to evaluate sarcopenia defined by skeletal muscle index (SMI) with cutoffs adjusted for sex and body mass index as a predictive marker for postoperative outcomes among individuals with inflammatory bowel disease., Methods: The SMI was measured using the cross-sectional computed tomography images at the lumbar spine. Multivariate logistic regression was performed to identify independent risk factors of postoperative complications., Results: Ninety-one patients were included in the study. In multivariate analysis, sarcopenia (odds ratio = 5.37; confidence interval: 1.04-27.6) was predictive of infectious postoperative complications., Conclusions: Sarcopenia as defined by the SMI is a predictor for 30-day postoperative infection complications in inflammatory bowel disease surgeries., (© The Author(s) 2020. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background and Aims: Vedolizumab is a gut-selective antibody to α 4  β 7 integrin, approved to treat moderate-to-severe ulcerative colitis and Crohn's disease in adults. Clinical trial data on patients meeting protocol-specified criteria may not reflect real-world clinical practice. This is a descriptive analysis of 4 years of post-marketing safety data on vedolizumab., Methods: The Vedolizumab Global Safety Database contains all adverse event reports collated by Takeda Pharmaceutical Company Ltd since vedolizumab approval [May 20, 2014]. Adverse event reports received between approval and May 19, 2018 were identified using Medical Dictionary for Regulatory Activities version 21.0 Preferred Terms. Adverse event frequencies were calculated and categorised., Results: In approximately 208 050 patient-years of vedolizumab exposure, 32 752 patients reported 80 218 events. In patients with Crohn's disease or ulcerative colitis, 37 662 and 34 259 events occurred in 14 191 and 14 042 patients, respectively, and 8297 events occurred in 4519 individuals with other [off-label] or unreported indications. Overall, 5230 [14%; Crohn's disease] and 3580 [10%; ulcerative colitis] events were serious. Most frequently reported were gastrointestinal events (Crohn's disease, 6156 [16%]; ulcerative colitis, 5701 [17%]). Patients with Crohn's disease or ulcerative colitis reported 251 malignancies [<1%], 402 hepatobiliary events [<1%], and 5876 infections (1137 serious [19%], 301 opportunistic [5%]). Patients aged ≥70 years [2326 patients] reported <10% of events., Conclusions: Adverse event patterns were consistent with clinical trials, with no new safety concerns. Most reported events were non-serious and event frequency was low, considering patient-years of exposure. Although limitations of post-marketing safety reports require acknowledgement, these real-world data support a favourable safety profile of vedolizumab., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Options for medical management of patients with acute severe colitis [ASC] failing intravenous (i.v.) steroids are limited and include rescue therapy with either infliximab or ciclosporin. In patients failing infliximab, second-line rescue therapy with ciclosporin is an alternative. The aim of this study was to investigate the efficacy and safety of ciclosporin in patients with steroid-refractory ASC failing first-line rescue therapy with infliximab., Methods: This is a retrospective, tertiary centre study undertaken from 2010 to 2017. Included were patients hospitalized for ASC and treated with i.v. ciclosporin after failing i.v. steroids and infliximab within the previous 2 months. Time to colectomy, clinical response, and occurrence of adverse events were analysed., Results: Forty patients with steroid-resistant ASC were included. Patients were followed for a median of 13 months (interquartile range [IQR] 5-32 months). Colectomy-free survival was 65%, 59.4%, and 41.8% at 1 month, 3 months and 1 year, respectively. Sixty percent of patients [24/40] achieved clinical remission at a median of 2 weeks [IQR 1-3 weeks]. Infliximab levels before ciclosporin infusion were available for 26 patients [median level 17.5 mg/mL, IQR 8-34 mg/mL] and were not associated with adverse events. Sixteen patients [40%] experienced adverse events after ciclosporin treatment, but none resulted in drug discontinuation., Conclusions: In patients with i.v. steroid-refractory ASC who failed infliximab therapy, second-line rescue therapy with ciclosporin was shown to be effective and safe. This is the largest patient cohort to receive ciclosporin as second-line rescue therapy for ASC. We believe that ciclosporin may be offered to selected patients prior to referral for colectomy., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Recurrence of Crohn's disease after surgical resection and primary anastomosis is an important clinical challenge. Previous studies have demonstrated the benefit of imidazole antibiotics, but have been limited by adverse events and medication intolerance. We evaluated whether administration of low-dose metronidazole [250 mg three times per day] for 3 months reduces endoscopic postoperative recurrence rates., Methods: We performed a retrospective cohort study of patients with Crohn's disease who underwent ileal resection with a primary anastomosis and subsequently received care at our center. We compared the cases who received low-dose metronidazole for 3 months with control patients who did not receive this therapy. Data collected included demographics, risk factors for recurrence, and medications before and after surgery. The primary end point was the number of patients with ≥i2 [Rutgeerts] endoscopic recurrence by 12 months. Variables found to be predictive in univariate analysis at p < 0.10 were introduced in the Cox model for multivariate analysis., Results: In all, 70 patients with Crohn's disease [35 cases and 35 controls] met inclusion criteria. Risk factors for Crohn's recurrence were similar between groups. The number of patients with ≥i2 endoscopic recurrence within 12 months following ileal resection was significantly lower in the metronidazole group [7 of 35 patients; 20%] compared with the number in the control group [19 of 35 patients; 54.3%] [p = 0.0058]. Eight participants [22.9%] in the metronidazole group experienced adverse events, and 3 of these patients [8.6%] discontinued the therapy., Conclusion: Low-dose metronidazole reduces endoscopic recurrence of Crohn's disease postoperatively and is well tolerated. This intervention should be considered as a therapy option following ileocolonic resection., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: To assess faecal calprotectin [Fcal] levels before and after therapeutic de-escalation, to predict clinical relapse in patients with inflammatory bowel disease [IBD]., Methods: From a prospectively maintained database, we enrolled 160 IBD patients [112 Crohn's disease/48 ulcerative colitis] in clinical remission, with Fcal measured within 8 weeks before therapeutic de-escalation. Clinical relapse was defined using the Harvey-Bradshaw index or Simple Clinical Colitis Activity Index., Results: Using a receiver operating characteristic [ROC] curve, Fcal >100 µg/g was the best threshold to predict clinical relapse after therapeutic de-escalation (area under the curve [AUC] = 0.84). In multivariate analysis, clinical remission >6 months before therapeutic de-escalation (hazard ratio [HR] = 0.57 [0.33-0.99]; p = 0.044) was associated with decreased risk of relapse, whereas current steroid medication ( = 1.67[1.00-2.79]; p <0.0001) was a risk factor. Fcal >100 µg/g was predictive of clinical relapse (HR = 3.96 [2.47-6.35]; p < 0.0001) in the whole cohort but also in patients receiving anti-tumour necrosis factor [TNF] agents [n = 85 patients; p <0.0001], anti-integrins [n = 32; p = 0.003], or no biologics [n = 43; p = 0.049], or attempting to discontinue steroids [n = 37; p = 0.001]. One patient [1/98] and seven patients [7/88, 8.0%] with baseline Fcal <100 µg/g relapsed within 3 months and 6 months after therapeutic de-escalation, respectively. A total of 74 Fcal measurements were performed in 52 patients after therapeutic de-escalation. Monitoring Fcal >200 µg/g [ROC curve with AUC = 0.96] was highly predictive of clinical relapse in multivariate analysis ([HR = 31.8 [3.5-289.4], p = 0.002). Only two relapses [2/45, 4.4%] occurred within 6 months while Fcal <200 µg/g., Conclusions: Fcal level is highly accurate to predict and monitor the risk of relapse after therapeutic de-escalation in IBD patients and could be used in daily practice., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: IV ciclosporin therapy is effective in steroid-refractory ulcerative colitis. The optimal drug level to achieve response and minimize complications during induction therapy is not known., Aim: The primary aim was to evaluate if serum ciclosporin drug levels are associated with increased risk of colectomy within 90 days of hospitalization. Secondary aims were to determine if ciclosporin levels are associated with avoidance of colectomy at 7 and 30 days, if ciclosporin levels are associated with drug-related and postoperative complications, and if patient-specific factors are associated with response to ciclosporin., Methods: We conducted a retrospective analysis of 81 hospitalized patients with steroid-refractory ulcerative colitis treated with ciclosporin. Risk factors for colectomy within 7, 30, and 90 days, medication-specific and postoperative complications were compared by first, mean, and peak ciclosporin level during IV induction therapy., Results: There were 47 patients (58%) who underwent surgery. There were no differences between initial, mean, and peak ciclosporin levels among responders and nonresponders and treatment-related or postoperative complications. Responders within 90 days had lower C-reactive-protein levels (20mg/L vs. 38mg/L, P = 0.01), lower serum albumin concentrations (3.4g/dL vs. 3.7g/dL, P = 0.03), and higher rates of kidney injury (50% vs 17%, P = 0.002)., Conclusion: Initial, mean, and peak serum levels of ciclosporin did not correlate with response or toxicity. However, C-reactive-protein levels levels and kidney injury may be helpful in predicting clinical response to ciclosporin.

Background: Vedolizumab is approved for moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). We present prospective, 1-year data of the real-world effectiveness and safety of vedolizumab in inflammatory bowel disease., Methods: Consecutive patients receiving vedolizumab for treatment of UC or CD with at least 14 weeks of follow-up, regardless of outcome, were included. Patients had clinical activity scores (Harvey-Bradshaw Index [HBI] or Simple Clinical Colitis Activity Index [SCCAI]) and inflammatory markers prospectively measured at baseline and weeks 14, 30, and 52. Clinical response was defined as a reduction ≥3 in HBI or SCCAI, clinical remission as HBI ≤4 or SCCAI ≤2, steroid-free remission as clinical remission without the need for corticosteroids, and mucosal healing (assessed at 6 months) as a Mayo endoscopic subscore of 0 or 1 or CD-SES <3., Results: A total of 132 patients were included: 61 (45%) male, 94 (71%) with CD, 42 (29%) with UC; 22% and 34% of CD and UC patients, respectively, achieved steroid-free remission by week 14. This increased to 31% in CD patients and plateaued at 35% in UC patients at 12 months. Increasing remission rates to 6 months were seen in patients with CD, but minimal improvements after 3 months of therapy occurred in those with UC. Mucosal healing was achieved in 52% of UC and 30% of CD patients. Most adverse events were minor; 74% remained on vedolizumab at 12 months., Conclusions: In this real-world study, vedolizumab demonstrated similar efficacy and safety seen in pivotal trials, with sustained clinical response in the majority of patients. Similar rates of response were seen in UC and CD patients. 10.1093/ibd/izx067&#95;video1izx067&#95;Video5754037470001.

Background: The purpose of this study was to compare the long-term safety of infliximab and nonbiologic agents as Crohn's disease (CD) therapy., Methods: Patients with CD were prospectively evaluated in this large, observational registry., Results: Patients (n = 6273) participated in this observational registry from July 1999 through March 2012; 3440 (54.8%) received infliximab (20,971 patient-years), and 2833 (45.2%) received other treatments only (14,806 patient-years). Overall, 59,875 infliximab infusions were administered (80%, 5 mg/kg); 3006 (89.9%) patients received ≥2 infusions. Adverse events (AEs), most commonly those related to CD (eg, abdominal pain, diarrhea), and serious AEs occurred at a higher rate among infliximab-treated patients. Mortality (0.57/100 patient-years, 0.67/100 patient-years) and malignancy rates (0.69/100 patient-years, 0.71/100 patient-years) for infliximab-treated and other-treatments-only patients, respectively, were generally similar. Serious infection rates were higher for infliximab-treated (2.15/100 patient-years) than other-treatments-only patients (0.86/100 patient-years). Infliximab dose was not associated with mortality or serious infection. An increased risk of serious infection was observed with age (>52 years vs ≤30 years) when examined in infliximab-treated patients. Nonserious cerebrovascular accidents (13 events, 0.06/100 patient-years; 5 events, 0.03/100 patient-years) and pulmonary embolisms (11 events, 0.05/100 patient-years; 4 events 0.03/100 patient-years) also occurred at higher rates among infliximab-treated patients than other-treatments-only patients., Conclusions: Through more than 13 years of registry experience and an overall median duration of patient follow-up >6 years, mortality was similar between the infliximab-treated and other-treatments-only groups. These final cumulative results are representative of real-world experience among infliximab-treated patients with CD and are consistent with the known risks of disease activity and tumor necrosis factor antagonist therapy.

Background: Clinical and endoscopic recurrence are common after surgery in Crohn's disease (CD). Vedolizumab has been increasingly used to treat CD, however, its effectiveness in preventing postoperative recurrence remains unknown. We aimed to investigate the use of vedolizumab in the postoperative setting and compare the risk of recurrence between patients receiving vedolizumab and anti-tumor necrosis factor (TNF)-α agents., Methods: Medical records of CD patients who underwent surgery between April 2014 and June 2016 were reviewed. We first analyzed how frequently vedolizumab is used to prevent postoperative recurrence and compared the patient characteristics with those being treated with other therapies. Furthermore, the rates of endoscopic remission, defined as a simple endoscopic score for CD of 0, at 6-12 months after surgery were compared between patients receiving vedolizumab and anti-TNF-α agents. Clinical, biological, and histologic outcomes such as Harvey-Bradshaw index, C-reactive protein, and histologic inflammation also were compared between the 2 groups. Risks of recurrence were assessed by univariate, multivariate, and propensity score-matched analyses., Results: Among 203 patients that underwent a CD related surgery, 22 patients received vedolizumab as postoperative treatment. There were 58, 38, and 16 patients who received anti-TNF-α agents, immunomodulators, and metronidazole, respectively, whereas 69 patients were monitored without any medication. Patients receiving vedolizumab were young and frequently had perianal disease. Patients postoperatively treated with vedolizumab or anti-TNF-α agents were mostly treated with the same agent pre- and postoperatively. Rate of endoscopic remission at 6-12 months in the vedolizumab group was 25%, which was significantly lower as compared to anti-TNF-α agent group (66%, P = 0.01). Vedolizumab use was the only factor that was associated with an increased risk of endoscopic recurrence on both univariate (odds ratio (OR) 5.58, 95% confidence interval (CI) 1.51-24.3, P = 0.005) and multivariate analysis (OR 5.77, 95%CI 1.71-19.4, P = 0.005). The results were supported by a propensity score-matched analysis demonstrating lower rates of endoscopic remission (25 vs 69%, P = 0.03) in patients treated with vedolizumab as compared to anti-TNF-α agents., Conclusion: In the present retrospective cohort study of real-world experience, vedolizumab was shown to be commonly used as postoperative treatment for CD especially in high risk patients. Multivariate and propensity score-matched analyses showed that postoperative endoscopic recurrence in CD was higher with vedolizumab than with anti-TNF-α agents, but further investigation including controlled trials is required before determining the utility of vedolizumab in preventing postoperative recurrence of CD.

Background and Aims: Safety and efficacy of budesonide multimatrix, an oral extended-release second-generation corticosteroid designed for targeted delivery throughout the colon, were examined for induction of remission in patients with mild to moderate ulcerative colitis refractory to baseline mesalamine therapy., Methods: A randomised, double-blind, placebo-controlled, multicentre trial evaluated efficacy and safety of budesonide multimatrix for induction of remission [ulcerative colitis disease activity index score ≥ 4 and ≤ 10] in 510 adults randomised to once-daily oral budesonide multimatrix 9 mg or placebo for 8 weeks. Patients continued baseline treatment with oral mesalamine ≥ 2.4 g/day., Results: Combined clinical and endoscopic remission at Week 8 was achieved by 13.0% and 7.5% of patients receiving budesonide multimatrix [n = 230] or placebo [n = 228], respectively, in the modified intention-to-treat population [p = 0.049]. Clinical remission [ulcerative colitis disease activity index rectal bleeding and stool frequency subscale scores of 0] was similar in both groups [p = 0.70]. More patients receiving budesonide multimatrix vs placebo achieved endoscopic remission [ulcerative colitis disease activity index mucosal appearance subscale score of 0; 20.0% vs 12.3%; p = 0.02] and histological healing [27.0% vs 17.5%; p = 0.02]. Adverse event rates were similar [budesonide multimatrix, 31.8%; placebo, 27.1%]. Mean morning cortisol concentrations decreased at Weeks 2, 4, and 8 with budesonide multimatrix but remained within the normal range., Conclusion: Budesonide multimatrix was safe and efficacious for inducing clinical and endoscopic remission for mild to moderate ulcerative colitis refractory to oral mesalamine therapy., (Copyright © 2017 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background: Although Crohn's disease (CD) is usually diagnosed at a younger age, a growing population of patients with inflammatory bowel disease is diagnosed above age 60 (elderly). The aim of this study was to compare disease phenotype, behavior, and therapy in elderly patients with CD to young patients diagnosed between 18 to 25 years., Methods: This retrospective case-control study identified patients diagnosed with CD at age 60 or above (elderly) and matched them by gender and disease duration with 2 "young" controls diagnosed between 18 and 25 years. Demographic data, disease information, and medical and surgical history were collected from the University of Chicago Medicine inflammatory bowel disease database., Results: Thirty-two patients were identified in the "elderly" group and matched to 64 "young" patients. Crohn's colitis was more common in older patients (37.5% versus 15.6%, P = 0.02) who were also less likely to have ileocolonic, perianal, or penetrating disease with less extraintestinal manifestations. After 1998, there was no difference in the use of steroids, 5-aminosalicylates, immunomodulators, biologics, or immunomodulators + biologics. No difference was found in the rates of bowel surgery between the 2 groups. Elderly patients developed fewer therapy-related noninfectious complications and Crohn's-related abscesses. Three serious infections (staphylococcal septicemia, pneumonia, and cryptococcal meningitis) were identified in 3 elderly patients on combination immunomodulators + biologics., Conclusions: Elderly CD is more likely to present with Crohn's colitis and less likely to present with ileocolonic, perianal, or penetrating disease with less extraintestinal manifestations. Elderly are more likely to develop serious therapy-related infectious complications. Larger prospective trials are needed to evaluate the risks of CD immunosuppressive therapy in elderly patients.

Background: Historically, limits to the ability to detect dysplasia in chronic inflammatory bowel disease (IBD)-associated colitis resulted in the recommendation that neoplasia of any grade be treated by proctocolectomy. We hypothesized that with improved optical technologies, most neoplasia in colitis is now detectable and reassessed the prevalence of colitis-associated neoplasia., Methods: We retrospectively reviewed all our patients with IBD who had pathologist-confirmed neoplasia on surveillance colonoscopy and underwent a subsequent colectomy. We included patients whose index lesions were found between 2005 and 2014 (the dates of our high definition equipment) and recorded the location and grade of these lesions. These findings were compared to the surgical specimens, and in patients with partial colectomies, included follow-up., Results: Thirty-six patients with IBD (19 [53%] ulcerative colitis and 17 [47%] Crohn's disease) were found to have neoplastic lesions on surveillance colonoscopy and underwent a subsequent partial colectomy or total proctocolectomy. Forty-four index lesions were identified by colonoscopy (29 white light and 7 methylene blue chromoscopy): 30 low-grade dysplasia, 6 high-grade dysplasia, and 8 adenocarcinoma. None of the low-grade dysplasia or adenocarcinoma index lesions were associated with synchronous carcinoma at colectomy. One of the patients with high-grade dysplasia had adenocarcinoma of the appendix., Conclusions: In this experience with high definition colonoscopes in chronic colitis, no synchronous adenocarcinomas were found when colectomy was performed for low-grade dysplasia or index adenocarcinoma, and only 1 adenocarcinoma in the appendix was found in the setting of high-grade dysplasia. These findings suggest that active surveillance or subtotal colectomy may be safe options for patients with IBD and some grades of neoplasia., Competing Interests: The authors have no relevant conflicts of interest.

Background and Objective: Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (n=20 242)., Design and Methods: The study populations included the Northern Finland Birth Cohort 1966 (n=4996), Netherlands Study of Depression and Anxiety (n=1883) and LifeLines Cohort Study (n=13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test., Results: In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype (Pinteraction=0.03 and 0.007, respectively; adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations)., Conclusion: In conclusion, our findings in 20 242 individuals suggest that UCP2 gene polymorphisms may cause liver dysfunction through the interaction with body fat rather than alcohol intake., (© 2015 The authors.)

Background: Many therapeutic options are available for patients with distal forms of ulcerative colitis (UC). Rectal therapies (e.g., suppositories, foams, gels, and enemas) may be recommended either alone or in combination with oral treatment. Compared with oral therapies, rectal therapies are underused in patients with distal forms of UC, although rectal therapies have favorable efficacy and safety profiles., Methods: This systematic review identified 48 articles for inclusion after a comprehensive PubMed search and the identification of additional relevant articles through other sources. Inclusion criteria were clinical studies examining efficacy and safety of 5-aminosalicylic acid, corticosteroid, and non-5-aminosalicylic acid rectal therapies (suppositories, foams, gels, and enemas) that induce or maintain remission in patients with ulcerative proctitis, ulcerative proctosigmoiditis, or left-sided colitis (i.e., distal forms of UC). The quality of the evidence presented was evaluated using the GRADE system., Results: Overall, a greater percentage of patients with distal forms of UC receiving 5-aminosalicylic acids or corticosteroid rectal formulations derived greater therapeutic benefit after treatment compared with patients receiving placebo. Furthermore, most uncontrolled studies of rectal therapies reported that patients with distal forms of UC had marked improvement from baseline after treatment. The overall safety profile of rectal therapies was favorable. Treatment with second-generation corticosteroids, such as budesonide and beclomethasone dipropionate, did not increase the incidence of steroid-related adverse effects., Conclusions: The current literature supports the use of rectal therapies for both induction and maintenance of remission in patients with distal forms of UC.

Background: Certolizumab pegol (CERT) is indicated for reducing the signs and symptoms of Crohn's disease (CD) and maintaining clinical response. Patients losing response received an extra "capture" re-induction dose in the PRECiSE 4 study. We examined the use of certolizumab in a retrospective cohort of patients with CD at a single inflammatory bowel disease center., Methods: We conducted a retrospective chart review of all adult patients with CD treated with CERT at the University of Chicago from April 22, 2008 to May 1, 2011. Demographics, disease characteristics, inflammatory bowel disease therapies, surgeries, CERT dosing, and clinical outcomes were recorded. Predictors of clinical response, re-induction dosing, and maintenance dose escalation were evaluated. Univariate, multivariate, and Kaplan-Meier analyses were performed for predictive variables of clinical response, re-induction dosing, and maintenance dose increases., Results: One hundred ten patients were identified; 23 were excluded. The remaining 87 patients had a sustained clinical response of 31.0%, remission of 14.9%, minimal or no response of 31.0%; 37.9% initially responded but lost response. In total, 35.6% of patients received a single re-induction dose of 400 mg after a mean of 29 weeks, predicted by prior anti-tumor necrosis factor (P = 0.007) and absence of perianal disease (P = 0.006); only 5 patients (16.1%) maintained a durable response or remission; 11.5% increased maintenance dosage after a mean of 50 weeks; all but 1 subsequently stopped CERT., Conclusions: Some patients with CD (31%) achieved a sustained response. The majority of patients receiving re-induction dosing did not achieve a sustained clinical response. Previous treatment with anti-tumor necrosis factor therapy was associated with reduced responses, suggesting that CERT may be more effective as an initial anti-tumor necrosis factor therapy.

Background: The incidence of lupus-like reactions (LLRs) in patients with inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor (ATNF) has not been well defined. We aimed to characterize the features and predictors associated with LLR., Methods: We studied a cohort of adult patients with IBD treated with ATNF by a single specialist during 2009. Patients with LLR were characterized and compared with those without LLR for possible predictors., Results: Twenty of 289 patients (6.9%) had LLR (19.9 cases per 1000 patient-years). Female gender and IBD-unclassified were more prevalent in the LLR group (85% versus 54%, P = 0.009; and 15% versus 2.2%, P = 0.018, respectively), with a hazard ratio of 3.89 (95% confidence interval = 1.12-13.55; P = 0.033) and 7.38 (95% confidence interval = 1.93-28.23; P = 0.003), respectively. ATNF duration was shorter in the LLR group (median, 1 year [interquartile range, 0-3] versus 3 years [interquartile range, 1-6.5], P = 0.005). Arthropathy was universal, followed by fatigue and dermatitis (30% each). Antinuclear antibodies were universally positive, and 16 of 20 had anti-double-stranded DNA. ATNF was discontinued in all; 8 patients required corticosteroids and 1 required hydroxychloroquine followed by complete clinical resolution (mean 7.9 ± 5.9 months). Antinuclear antibodies reverted or normalized in 7 of 16 patients (44%). Fourteen patients (70%) were switched to a second ATNF, 2 with concomitant immunomodulators, and 12 as monotherapy. One patient on ATNF monotherapy developed a second LLR and was successfully switched to a third ATNF., Conclusion: LLRs secondary to ATNFs are more frequent than previously reported, more common in women and IBD-unclassified. It is reversible with cessation of the culprit agent and steroids. Switching to an alternative ATNF rarely results in recurrence.

Background: Natalizumab is an efficacious agent for induction and maintenance of remission in patients with Crohn's disease (CD) who have failed anti-tumor necrosis factor agents. We aimed to assess the impact of endoscopic severity and mucosal healing on the long-term outcome of natalizumab treatment in CD., Methods: We retrospectively assessed endoscopic severity according to the Simple Endoscopic Score for Crohn's Disease in patients with CD who received natalizumab therapy. The degree of endoscopic severity before natalizumab treatment and mucosal healing after treatment and their correlation with long-term outcome were studied., Results: Thirty-two patients with CD (15 male, median age 32.5 years) receiving natalizumab underwent at least 1 colonoscopy before or during natalizumab treatment. All patients had previously failed immunomodulator(s), and 31 failed anti-tumor necrosis factor agent(s). Mean duration of natalizumab treatment was 14.1 months. Baseline Simple Endoscopic Score for CD was categorized into quartiles, and those with a greater score were less likely to respond to treatment as assessed by Kaplan-Meier survival analysis (n = 32, log-rank test, P = 0.0055). Mucosal healing (decrease of Simple Endoscopic Score for CD of >70%) was achieved in 11 of 26 patients (42.3%), and this was correlated with an improved long-term outcome (log-rank test, P = 0.0063)., Conclusions: The degree of endoscopic inflammation correlates to response to natalizumab and maintenance of remission. These findings provide prognostic information for patient management decisions.

Background: Natalizumab is an efficacious agent for the induction and maintenance of remission in patients with Crohn's disease (CD) who have failed anti-tumor necrosis factor (TNF) agents. We aimed to assess the efficacy and safety of natalizumab outside of clinical trial at a US tertiary center., Methods: Retrospective case review of patients with CD receiving natalizumab., Results: Forty-nine patients with CD (28 women; median age, 33 years) receiving natalizumab from April 2008 to November 2011 were identified. Median duration of disease was 180 months (range, 36-576 months); 40 patients had ileocolonic disease, 1 had ileal disease, and 8 had colonic disease. Twenty-one patients had penetrating disease, and 28 had a history of CD-related surgical treatment. Forty-seven patients previously failed treatment with at least 1 anti-TNF agent. Median duration of natalizumab treatment was 7 months (interquartile range, 3-21.5 months). Twenty-four patients (49%) were continuing natalizumab at the time of this review, and 25 discontinued treatment because of the lack of response, side effects, or positive JC virus antibody. Seventeen patients (35%) successfully continued treatment with natalizumab for longer than 12 months, and nonpenetrating disease phenotype was identified as a predictor of longer response (compared with penetrating phenotype; P = 0.013). Nine patients (18.4%) experienced adverse effects, 5 of which were serious, but no case of progressive multifocal leukoencephalopathy occurred., Conclusions: This is the largest series of natalizumab-treated patients with CD. Our results show that natalizumab is an efficacious and safe treatment agent for patients refractory to anti-TNF agents and that nonpenetrating disease phenotype has more durable response over time.

Background: Pivotal trials for adalimumab (ADA) demonstrated effectiveness versus placebo for induction and maintenance of remission in moderate to severely active Crohn's disease (CD). Although the approved maintenance regimen in the U.S. is 40 mg subcutaneously every 14 days, some patients require dose-escalation ([DE] either an increase in the delivered dose or decrease in the interval of treatment). Our objective was to determine which patient-, disease-, and therapy-related factors were associated with DE in CD patients treated with ADA., Methods: This retrospective medical record review of patients included all patients treated with ADA for CD at the University of Chicago Inflammatory Bowel Disease Center between 2003 and 2008. Patient-related factors, disease-related factors, and therapy-related factors were analyzed. Survival and logistic regression analyses were performed., Results: In all, 75 patients treated with ADA between December 2003 and June 2008 were identified. Thirty-one subjects (41%) required DE (32% male, median age 37.6, median disease duration 22.7 years) after a median 20 weeks of therapy (range 2-75). Patient-, clinical-, and therapy-related factors were similar between DE and non-DE. Need for DE was predicted by a family history of inflammatory bowel disease (IBD) (P = 0.0187). Time to DE was predicted by male gender, isolated colonic disease, and smoking history (all P < 0.05); however, only male gender was an independent predictor of time to DE., Conclusions: In all, 41% of CD patients required ADA DE, with shorter time to DE in smokers, men, and patients with isolated colonic disease. Patients, caregivers, and insurers should anticipate DE when utilizing ADA in CD., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Background: The aim of this study was to assess the clinical benefit and tolerability of adalimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF), in patients with ulcerative colitis (UC)., Methods: Patients with active UC, including those who had lost response or developed intolerance to the chimeric anti-TNF antibody infliximab, were enrolled in a 24-week uncontrolled trial. Patients were treated with subcutaneous adalimumab 160 mg at week 0, 80 mg at week 2, and 40 mg every other week starting at week 4. After week 8 the dose could be escalated to 40 mg weekly for incomplete response. Outcome measures included clinical response and remission and mucosal healing., Results: Twenty patients were enrolled, of whom 13 had previously received infliximab. Seven patients had dose escalation of adalimumab between weeks 8 and 16, from 40 mg every other week to 40 mg weekly, due to incomplete response. The rates of clinical response were 25% at week 8 and 50% at week 24. The rates of clinical remission were 5% at week 8 and 20% at week 24. The rate of mucosal healing was 30% at week 8. The rates of clinical response and remission and mucosal healing were similar in infliximab-naïve and previously exposed patients. None of the patients experienced hypersensitivity reactions during treatment with adalimumab., Conclusions: Adalimumab is well tolerated and appears to be a clinically beneficial option for patients with UC, including those who have previously lost their response to or cannot tolerate infliximab.

Background: Fistulas are a common complication of Crohn's disease (CD) and are difficult to treat effectively. This study aimed to assess the effects of fistula on annual costs of healthcare and resource utilization for patients with CD., Methods: A retrospective analysis, using the PharMetrics database, of patients with a diagnosis of CD from January 1, 2000 through June 30, 2005 was conducted. Using paid claim amounts, healthcare costs and resource utilization were compared for patients with and without fistula in the year following diagnosis. Further analysis compared costs for adult, pediatric, and older adult patients with and without fistula., Results: This analysis included 13,454 patients with CD, of whom 12,683 (94.3%) had no diagnosis of fistula. The total median (range) cost per patient was higher for the fistula cohort ($10,863 [$0-$1,307,019]) than the nonfistula cohort ($6268 [$0-$1,181,485]), driven mainly by higher hospital and surgery costs. Median healthcare costs and resource utilization rates were generally higher for patients with fistula compared with those without fistula in all 3 age groups, with some of the largest differences observed in the pediatric cohort., Conclusions: Fistulas are often a difficult and costly complication of CD. This study determined that patients with fistulizing CD have higher healthcare costs and resource consumption than patients without fistula. Use of therapies that heal fistulas may help deter some of the high costs and intensive resource utilization found in this study. Economic analyses need to account for these issues when assessing the cost-effectiveness of therapies targeting fistulizing disease.

The Child Health and Development Studies is a > or =40-year follow-up of 20,754 pregnancies occurring between 1959 and 1967 in California. There were 84 cases of undescended testes at birth persisting to at least age 2 years among 7,574 liveborn sons whose mothers were interviewed in early pregnancy. Cases were matched to three controls on birth year and race. Compared with mothers of controls, mothers of cryptorchid boys consumed more caffeine during pregnancy (odds ratio = 1.4, 95% confidence interval: 1.1, 1.9 for an interquartile range equivalent to three cups of coffee per day) but were not more likely to smoke or drink alcohol when all behaviors were considered together. Other maternal and perinatal risk factors were not significantly associated with persistent cryptorchidism and did not confound the association with caffeine.

Background: The goal of this work was to critically evaluate the published studies on the treatment of ulcerative proctitis (UP) and left-sided ulcerative colitis (L-UC). The results of this review provided the content for the accompanying treatment guidelines, Clinical Guidelines for the Medical Management of Left-sided Ulcerative Colitis and Ulcerative Proctitis: Summary Statement., Methods: All English language articles published between 1995 and September 2005 were identified through a comprehensive literature search using OVID and PubMed. The quality of the data supporting or rejecting the use of specific therapies was categorized by a data quality grading scale. An "A+" grade was assigned to treatment supported by multiple high-quality randomized controlled trials with consistent results, whereas a "D" grade was given to therapy supported only by expert opinion. The therapeutic efficacy of a treatment was defined by its success in treating UP and L-UC compared with placebo. A medication was ranked as "excellent" if it was specifically studied for UP and L-UC and had consistently positive results compared with placebo or another agent. Quality and efficacy scores were agreed on by author consensus., Results: For the acute treatment of UP or L-UC, the rectally administered corticosteroids and mesalazine (5-ASA), either alone or in combination with oral 5-ASAs, are the most effective therapy: evidence quality, A+; efficacy, excellent. Only rectally administered 5-ASA received an A+/excellent rating for maintenance of remission. Infliximab received an A+ grade for induction and maintenance of remission but only a "good" rating because the studies were performed in all UC, not specifically UP or L-UC., Conclusions: This critical evaluation of treatment provides a "report card" on medications available for the management of patients with UP and L-UC. The guidelines should provide a useful reference and supplement for physicians treating UC patients.

There are few published guidelines for the treatment of inflammatory bowel disease. Physicians choose therapy based on evidence-based data, peer and expert opinion, and personal experience. This article provides treatment guidelines for the induction and maintenance of ulcerative proctitis and left-sided colitis and the management of disease refractory to 5-aminosalicylic acid (5-ASA) compounds and corticosteroids The guidelines are derived from evidence-based data and, when lacking, expert opinion or the authors' experience. The comprehensive review of the literature is presented in the accompanying article, "The Medical Management of Left-Sided Ulcerative Colitis and Ulcerative Proctitis: Critical Evaluation of Therapeutic Trials". Rectally administered 5-ASA and corticosteroid suppositories are effective treatment for most ulcerative proctitis patients. Corticosteroid and 5-ASA enemas, which reach the splenic flexure of the colon, are recommended for patients with left-sided ulcerative colitis. The combination of rectally administered 5-ASA enemas and oral 5-ASA agents may afford better treatment of left-sided colitis and possibly prevent proximal extension of disease. Patients refractory to 5-ASAs and corticosteroids may require an immunomodulator or biological response modifier therapy. Those who have ongoing signs and symptoms of ulcerative proctitis and left-sided ulcerative colitis despite maximal medical therapy require a proctocolectomy.

Purpose: This research evaluates the utility of two different definitions of successful aging in predicting well-being., Design and Methods: We assessed the definitions of (a) self-rating and (b) Rowe and Kahn's criteria of absence of disease, disability, and risk factors; maintaining physical and mental functioning; and active engagement with life. We made associations with well-being for each definition using data from 867 Alameda County Study participants aged 65-99 years., Results: The percentage of those rating themselves as aging successfully was 50.3% compared with 18.8% classified according to Rowe and Kahn's criteria. Although absence of chronic conditions and maintaining functioning were positively associated with successful aging for both definitions, many participants with chronic conditions and with functional difficulties still rated themselves as aging successfully; none were so classified according to Rowe and Kahn's criteria. On 14 of 15 measures, self-rated successful aging resulted in sharper contrasts for well-being., Implications: Understanding criteria used by older persons to assess their own successful aging should enhance the conceptualization and measurement of this elusive concept.

Several recent prospective analyses involving community-based populations have demonstrated a protective effect on survival for frequent attendance at religious services. How such involvement increases survival are unclear. To test the hypothesis that religious attendance might serve to improve and maintain good health behaviors, mental health, and social relationships, changes and consistencies in these variables were studied between 1965 and 1994 for 2,676 Alameda County Study participants, from 17 to 65 years of age in 1965, who survived to 1994. Measures included smoking, physical activity, alcohol consumption, medical checkups, depression, social interactions, and marital status. Those reporting weekly religious attendance in 1965 were more likely to both improve poor health behaviors and maintain good ones by 1994 than were those whose attendance was less or none. Weekly attendance was also associated with improving and maintaining good mental health, increased social relationships, and marital stability. Results were stronger for women in improving poor health behaviors and mental health, consistent with known gender differences in associations between religious attendance and survival. Further understanding the mechanisms involved could aid health promotion and intervention efforts.

Data from clinical trials suggest the efficacy of the chimeric tumor necrosis factor alpha monoclonal antibody infliximab in improving clinical, endoscopic, and histologic outcomes in patients with moderately to severely active Crohn's disease (CD) and fistulizing CD. To determine whether the efficacy and safety record of infliximab reported in clinical trials would be reflected in clinical use, clinical experience with infliximab was assessed in patients with CD at the University of Chicago, Chicago, Illinois. All patients with CD at this institution receiving infliximab in the first year of its release were prospectively followed up for 1 year. Disease activity was scored at the time of the initial infusion and at 1, 3, 7, and 12 weeks after infusion. Results were analyzed separately for patients with luminal or fistulous CD. Clinical response, remission, corticosteroid tapering, and adverse event data were collected. A total of 129 patients with luminal (n = 81) or fistulous (n = 48) disease received a mean of 2.38 and 3.23 infusions of infliximab per patient, respectively. After the initial infusion course, clinical response and remission rates at 3 weeks were 65% and 31% for patients with luminal disease and 78% and 24% for patients with fistulous disease, respectively. Clinical response and remission after the first infusion occurred at a median of 8 days and 9 days, respectively. In those patients who subsequently relapsed, relapses occurred after a mean of 8.5 weeks and 12.2 weeks in patients with luminal and fistulizing disease, respectively. Corticosteroid tapering was possible in > 90% of patients (luminal disease) after the initial infusion and complete withdrawal in 54% after the second infusion, with a sustained median steroid dose of 0 mg from the 4-month time-point onward. Infusion reactions or adverse events occurred in 5-13% of patients during or immediately after the initial infusion of infliximab; most were mild and easily managed and did not increase in incidence with subsequent infusions. Clinical experience with infliximab closely mirrors the findings of controlled clinical trials. Repeated administration of infliximab was efficacious and relatively well tolerated in patients with CD and demonstrated corticosteroid-sparing benefits.

Cyclosporin (CSA) has emerged as a medical alternative to colectomy in severe, steroid-refractory ulcerative colitis (UC) patients. This is the first formal quality-of-life study comparing such patients treated with intravenously administered cyclosporin with those treated surgically with colectomy. Quality-of-life analyses were conducted in all patients who underwent colectomy or received intravenous CSA for severe UC from 1991 to 1995 using the Inflammatory Bowel Disease Questionnaire, a visual-analog scale (VAS), and the Oresland scale, with additional questions regarding health care utilization and medication use. The 18 CSA-treated patients reported a better ability to sleep (p = 0.002; VAS), better stool consistency (p < 0.001; VAS), less abdominal or rectal pain (p = 0.009, VAS), and fewer daytime (p < 0.001; Oresland), nighttime (p = 0.006; Oresland), and daily trips to the toilet (p < 0.001; VAS) than the 46 surgical patients. The mean number and rate of hospitalizations within the first year was also lower in the CSA patients (p < 0.001 for both). The surgical patients reported fewer initial visits to their specialist (p < 0.001) and less medication use (p < 0.001; Oresland). Patients with severe steroid-refractory UC treated with intravenously administered CSA scored as well as or better than their surgical counterparts. The use of CSA in selected patients is substantiated both by clinical results and quality-of-life analysis.

Much remains to be understood about how low socioeconomic status (SES) increases cardiovascular disease and mortality risk. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (1984-1993) were used to estimate the associations between acute myocardial infarction and income, all-cause mortality, and cardiovascular mortality in a population-based sample of 2,272 Finnish men, with adjustment for 23 biologic, behavioral, psychologic, and social risk factors. Compared with the highest income quintile, those in the bottom quintile had age-adjusted relative hazards of 3.14 (95% confidence interval (CI) 1.77-5.56), 2.66 (95% CI 1.25-5.66), and 4.34 (95% CI 1.95-9.66) for all-cause mortality, cardiovascular mortality, and AMI, respectively. After adjustment for risk factors, the relative hazards for the same comparisons were 1.32 (95% CI 0.70-2.49), 0.70 (95% CI 0.29-1.69), and 2.83 (95% CI 1.14-7.00). In the lowest income quintile, adjustment for risk factors reduced the excess relative risk of all-cause mortality by 85%, that of cardiovascular mortality by 118%, and that of acute myocardial infarction by 45%. These data show how the association between SES and cardiovascular mortality and all-cause mortality is mediated by known risk factor pathways, but full "explanations" for these associations will need to encompass why these biologic, behavioral, psychologic, and social risk factors are differentially distributed by SES.

The association between leisure-time physical activity and 28-year (1965-1993) risk of death from all causes and cardiovascular disease was studied in 6,131 adults who participated in the Alameda County Study in Northern California. Because study participants were interviewed on a number of occasions, it was possible to include in the analyses information on changes over time in levels of leisure-time physical activity as well as changes in a wide variety of other risk factors. There were 47,616 person-years of observation for males (639 deaths from all causes and 321 from cardiovascular disease) and 57,666 person-years of observation for females (587 deaths from all causes and 388 from cardiovascular disease). In analyses in which only the baseline values of all covariates were included, a four-point increase on the leisure-time physical activity scale, the interquartile range, was associated with reduced risk of death from all causes (relative risk (RR) = 0.90, 95% confidence interval (CI) 0.83-0.99) and cardiovascular disease (RR = 0.85, 95% CI 0.75-0.97). When time-varying information on leisure-time physical activity and all other covariates was included, there was still a protective effect for all-cause and cardiovascular disease mortality (RR = 0.84, 95% CI 0.77-0.92 and RR = 0.81, 95% CI 0.71-0.93, respectively). The association between leisure-time physical activity and risk of death was not altered when information on variations over time in leisure-time physical activity and many determinants and consequences of physical activity were explicitly included in survival models.

Six-year predictors of successful aging were analyzed for 356 Alameda County Study men and women aged 65-95 years measured prospectively in 1984 and followed to 1990. Successful aging was defined as needing no assistance nor having difficulty on any of 13 activity/mobility measures plus little or no difficulty on five physical performance measures. After adjusting for baseline successful aging, sex, and age, the authors found that 1984 predictors of 1990 successful aging included income above the lowest quintile (odds ratio (OR) = 2.01, 95% confidence interval (CI) 0.99-4.11), > or = 12 years of education (OR = 1.67, 95% CI 0.98-2.84), white ethnicity (OR = 2.12, 95% CI 0.93-4.86), diabetes (OR = 0.10, 95% CI 0.01-0.79), chronic obstructive pulmonary disease (OR = 0.41, 95% CI 0.17-0.97), arthritis (OR = 0.43, 95% CI 0.26-0.71), and hearing problems (OR = 0.48, 95% CI 0.25-0.89). Adjusting for all variables, the authors found that behavioral and psychosocial predictors included the absence of depression (OR = 1.94, 95% CI 1.10-3.42), having close personal contacts (OR = 1.82, 95% CI 1.05-3.18), and often walks for exercise (OR = 1.77, 95% CI 1.00-3.12). Cross-sectional comparisons at follow-up revealed significantly higher community involvement, physical activity, and mental health for those aging successfully.

Background: Previous studies have reported an increased risk of death in those who report their health is poor, however, the role of underlying and subclinical disease in this association has not been carefully studied., Methods: The associations between perceived health status and mortality from all causes and cardiovascular disease, incidence of myocardial infarction, carotid atherosclerosis, forced expiratory volume, and maximal exercise capacity were studied in the Kuopio Ischaemic Heart Disease Risk Factor Study, a population-based study of 2682 men, aged 42-60, in eastern Finland., Results: There were strong, statistically significant, age-adjusted associations between level of perceived health and mortality from all causes (RH(bad versus good) = 3.67), cardiovascular causes (RH(bad versus good) = 6.64), and incidence of myocardial infarction (RH(bad versus good) = 3.87). Perceived health levels were strongly associated with risk factors and disease indicators. The associations with mortality and myocardial infarction outcomes were considerably weakened with progressive adjustment for eight risk factors and prevalent disease. Higher levels of perceived health were associated with less carotid atherosclerosis, and greater forced expiratory volume and maximal exercise capacity. Associations between level of perceived health and these indicators were considerably stronger in those with prevalent diseases than in those who were healthy., Conclusions: The overall pattern of results suggests that perceived health levels mainly reflect underlying disease burden.

We investigated the relationship between baseline internal health locus of control (IHLC) and 6-year change in physical functioning in 356 older adults. IHLC was strongly related to change in physical functioning for women at all levels of baseline functioning, but only affected men with lower baseline functioning. Cross-sectional analyses indicated no relationship between IHLC and health seeking activities except changing eating patterns when sick. Other findings were that IHLC was related to depression and not having childhood illness for men and to number of negative life events for women. For both genders IHLC was related to the importance placed on good health.

We compared 356 older men and women and found that income, education, and marital status had significantly stronger associations with 6-year change in functioning for men; internal health locus of control was stronger for women. Large but not significant differences occurred for age, perceived health, and days going out per week (stronger for women) plus exercise and smoking (stronger for men). We found no difference for ethnicity, chronic conditions, and social contacts. Gender specific models incorporating factors amenable to change predicted significantly higher follow-up functioning for those with positive health behaviors, supporting the value of preventive interventions.

The association between five socioeconomic indices (lifetime occupation, education, income, ownership of material possessions, and childhood socioeconomic status) and plasma fibrinogen levels was investigated in middle-aged Finnish men who were part of the Kuopio Ischemic Heart Disease Risk Factor Study. The Kuopio Ischemic Heart Disease Risk Factor Study is based on a representative age-stratified sample of 2,682 men aged 42, 48, 54, and 60 years. The data were collected between 1984 and 1989. The present analysis is restricted to the 2,011 men for whom information on fibrinogen and all covariates was available. The covariates were alcohol consumption, body mass index, physical fitness, smoking, coffee consumption, high density lipoprotein cholesterol, low density lipoprotein cholesterol, blood leukocyte count, and prevalent disease (at least one sign of ischemic heart disease, hypertension, diabetes, or previous stroke). An age-adjusted inverse association was found between levels of plasma fibrinogen and four of the five socioeconomic indices: current income, education, lifetime occupation status, and current material possessions. After adjustment for the covariates, the association persisted for education, current income, and lifetime occupation. Analysis of the joint effect of childhood and adult socioeconomic status indicated that those who were economically disadvantaged at both times had the highest fibrinogen levels, but the fibrinogen levels of those who were not poor as adults had no variation by childhood socioeconomic status.

The association between presumed protective factors and social risk factors for hospitalization and mortality was studied during a 14-year follow-up period in a cohort of 8,168 Swedish men aged 18-20 years at baseline. Using Cox regression analysis, the authors found that five protective factors (high social class, home well-being, school well-being, good emotional control, and self-perceived good health) were associated with lower risks of hospitalization and death. Four social risk factors (contact with police or child welfare authorities, running away from home, having divorced parents, and ever using narcotics) were significantly associated with increased risk of hospitalization and mortality. The relative hazard decreased with the number of protective factors and increased with the number of social risk factors, almost linearly. The relative hazard was 0.24 for hospitalization among those with six protective factors and 0.24 for mortality for those with five or six protective factors. The relative hazard for hospitalization was 3.09 among those with five social risk factors compared with those with none, while for mortality the relative hazard among those with four or five social risk factors was 5.74 compared with those with none. While these results indicate strong cumulative effects for both the social risk factors and the protective factors, the associations of individual factors with the two outcome measures were generally reduced in models which simultaneously adjusted for all factors, which presumably indicates collinearity among the factors. There was only limited support for a buffering, or interacting, effect between the risk factors and the protective factors.