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Background Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. Methods We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. Results Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn’s disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. Conclusion The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.

Inflammatory bowel disease (IBD; Crohn’s disease, CD and Ulcerative colitis, UC) and irritable bowel syndrome (IBS) have overlapping symptoms. Few prevalence studies of IBS in quiescent IBD have used colonoscopy with histology to confirm inactive disease. The aims were (1) to determine the percentage of IBD patients in deep remission whose persistent IBS-like symptoms (IBD/IBS+) would cause them to be classified as having active disease, based on the calculation of Harvey Bradshaw Index (HBI) or UC disease activity index (UCDAI); (2) to identify demographic and disease characteristics that are associated with IBD/IBS+. This was a prospective study at a single tertiary care IBD center. 96/112 patients with colonoscopy and histology confirmed quiescent disease consented and completed Rome III criteria for IBS Survey, and the hospital anxiety and depression scale (HADS). Other demographic and disease specific data were collected. 36% (28/77) and 37% (7/19) of CD and UC patients, respectively, met diagnostic criteria for IBS. Significantly higher HBI/UCDAI scores (p = 0.005) and low short inflammatory bowel disease questionnaire (SIBDQ) scores (p ≤ 0.0001) were seen in IBD/IBS+ patients. 29% of patients in deep remission were mis-categorized by HBI/UCDAI as having active disease when they fulfilled Rome III criteria for IBS. Psychiatric diagnosis (OR 3.53 95% CI 1.2–10.2) and earlier onset of IBD (OR 1.056 95% CI 1.015–1.096) were associated with IBD/IBS+. Patients fulfilling IBS criteria had higher hospital anxiety and depression scale (HADS). IBD/IBS+ affect scoring of IBD disease activity scales and become less useful in guiding treatment plans.

Health-related quality of life (HRQoL) is significantly impacted in patients with inflammatory bowel disease (IBD). Many studies have assessed HRQoL in patients of all ages, and few focus on the elderly.To determine the influence of advanced age ( 65 years) and age at diagnosis on patients with IBD.This is a retrospective study of prospectively collected data from a single IBD tertiary referral center. Patients had disease activity indices [Harvey-Bradshaw index (HBI), Ulcerative Colitis Disease Activity Index (UCDAI), and Short Inflammatory Bowel Disease Questionnaire (SIBDQ)] recorded during every clinic visit. Three groups of patients: 65 years, 41-64 years, and 40 years with 5 SIBDQ entries were included. Influence of disease type, disease duration, extent of involvement, and comorbidities such as cardiovascular (CV) disease, pulmonary disease, diabetes mellitus (DM), and psychological disorders were noted as confounders. Statistical analysis was performed using ANOVA, Pearson correlation, and logistic regression model.Disease severity indices significantly affected SIBDQ score in both Crohn's disease (CD) and ulcerative colitis (UC) (p 0.001 for HBI in CD, p 0.001 UCDAI in UC). Disease extent (p = 0.011) and psychological disorders (p 0.001) significantly affected SIBDQ score in CD. Chronological age, age at diagnosis, disease duration, number of clinic visits, CV disease, pulmonary disease, and DM were not significant predictors of SIBDQ score (p 0.05).HRQoL was negatively influenced by disease extent and psychological disorders in CD but not in UC patients. Advanced age was not a predictor of poor HRQoL in both CD and UC.

Background Disease location, behavior, and average activity over time vary significantly amongst patients with inflammatory bowel disease (IBD). Despite this heterogeneity patients are often subjected to a “one size fits all” treatment plan. Clinical and multi-omic profiles which predict responsiveness to treatment are needed given the expanding range of therapeutic options for IBD. Methods The Study of Prospective Adult Research Cohort of IBD (SPARC IBD) is a prospective, longitudinal cohort study of patients with IBD ages 18 and older managed according to local standards at 17 academic medical centers in the US. Demographic data, disease-related data, and patient-reported outcomes are collected at baseline, during routine GI office visits, and quarterly by data abstraction from the electronic health record, patient surveys, and highly structured electronic case report forms (eCRF) created with Epic Systems (IBD SmartForm). Biosamples are collected at baseline (blood and stool), at the time colonoscopy (stool and tissue), and after key medication changes (blood and stool). Clinical data is transferred from sites on a periodic basis and stored in the Crohn’s & Colitis Foundation’s exchange platform called IBD Plexus. A portion of the biosamples are analyzed and the rest are banked for future use. Results Between November 2016 and October 2019, 2582 patients have enrolled in SPARC IBD (66% Crohn’s disease [CD], 33% ulcerative colitis (UC), and 1% IBD-U). Females comprise 52.5% of the cohort. Median age at enrollment is 37 years (range18-85). The majority of patients are white (80.5%) and non-Hispanic or Latino (84.5%). Median disease duration is 12 years (range 0–53). Distribution of disease location in the CD sub-group is 44% with small bowel and colonic disease, 28% with isolated small bowel disease, and 15% with isolated colonic disease. In the UC sub-group, 50.5% of patients have extensive colitis, followed by 23.5% with left-sided colitis, and 8.8% with proctitis. Among CD patients, 17.6% have stricturing disease, 12.5% have penetrating disease, 5.8% have both stricturing and penetrating disease and 16.2% have perianal involvement. At time of study enrollment 60% of CD patients, 41% of UC patients and 37% of IBD-U patients were on a biologic. The majority of patients with CD (88%) and UC (89%) were in remission. Conclusions SPARC IBD is a prospective cohort study of adult IBD patients which combines high-resolution phenotyping with biosample collection at multiple points in time. The unique aspects of this study including the multiple modalities for clinical data collection, the geographic diversity of patients enrolled, as well as the biosample procurement at multiple time points position SPARC IBD to aid in the discovery of novel biomarkers which can predict therapeutic responsiveness.

Inflammatory bowel disease (IBD) has a bimodal distribution with approximately 15 % of patients manifesting after age 65. Previous reports suggest an increased risk of surgical complications in the elderly.To compare surgical outcomes in elderly IBD patients (≥ 65 years at the time of surgery) to matched younger IBD cohorts.This was a retrospective cohort study at a single academic center of patients who underwent surgery for IBD. Forty-two elderly patients (≥ 65 years) were matched at least 1:1 (median 1:5) to patients in each of three control groups [18-35 years (n = 71); 36-49 years (n = 62); 50-64 years (n = 58)] according to gender, disease type/location, and type of surgery. Postoperative complications were compared. Patient characteristics were used in multivariate risk models. Analysis was performed using ordinary logistic regression.Twenty ileal or ileocolonic resections, 12 partial or total colectomies, four stricturoplasties, and six laparoscopic partial or total colectomies were performed in the elderly group. The post-operative complication rate was not statistically different between the elderly and younger cohorts (38 % vs. 39 % vs. 40 % vs. 48 % in the 18-35, 36-49, 50-64, and ≥ 65 years groups, respectively, p = 0.26). The only significant risk factors for complication were Charlson comorbidity index (p = 0.0002), preoperative hemoglobin (p = 0.0065), total parenteral nutrition use (p = 0.024), and failed medical therapy (as the indication for surgery) (p =0.0001).The surgical complication rate among elderly and younger IBD patients was similar. Advanced age by itself should not be considered a risk factor for adverse operative outcome.

Patients with chronic medically complex disorders like inflammatory bowel diseases (BD) often have mental health and psychosocial comorbid conditions. There is growing recognition that factors other than disease pathophysiology impact patients' health and wellbeing. Provision of care that encompasses medical care plus psychosocial, environmental and behavioral interventions to improve health has been termed "whole person care" and may result in achieving highest health value. There now are multiple methods to survey patients and stratify their psychosocial, mental health and environmental risk. Such survey methods are applicable to all types of IBD programs including those at academic medical centers, independent health systems and those based within independent community practice. Once a practice determines that a patient has psychosocial needs, a variety of resources are available for referral or co-management as outlined in this paper. Included in this white paper are examples of psychosocial care that is integrated into IBD practices plus innovative methods that provide remote patient management.

Objective To examine the impact of pregnancy on health-related quality of life (HRQoL) of women with inflammatory bowel disease (IBD). Methods This was a retrospective study in a tertiary referral center and included women with ≥2 short inflammatory bowel disease questionnaire (SIBDQ) scores obtained during their pregnancy. Regression models were used to identify independent factors influencing SIBDQ scores and changes of SIBDQ scores at different time points. Results A total of 32 women (23 CD, 9 UC) with a mean age at pregnancy of 29.4 years and a mean disease duration of 7.8 years were included in the study. The mean pre-pregnancy SIBDQ score in our cohort was 49, which was significantly lower than the values during (55, P

Transient lower esophageal sphincter relaxation (TLESR) is frequently associated with reflux events and terminates with a primary or secondary peristaltic wave. However, it is unclear whether the presence and properties of the refluxate affect TLESR-termination events. The aims of this study were to determine the pattern of terminating esophageal motor activity after TLESR in healthy subjects and factors affecting the type of terminating motor event. Fifteen healthy subjects (7 men, age 18–56) were studied. High-resolution manometry and impedance/pH monitoring were performed simultaneously in supine position for 2 h after subjects took a 1,000-kcal meal (Awake Study). This procedure was repeated during the night under polysomnographic recording for 6–8 h after consuming a 1,000-kcal meal (Sleep Study). We categorized three types of TLESR-terminating motor events, primary peristalsis (PP), full secondary contraction (FSC), which propagated the entire esophagus, and partial secondary contractions (PSC), which started distal to the upper esophageal sphincter. Overall, 289 TLESR events were found. The percentages of TLESR events terminated by PP, FSC, and PSC were 22%, 14%, and 64%, respectively. TLESR events terminated by PP were less likely to be accompanied by reflux events. TLESR events terminated by FSC were significantly more likely to have evidence for proximal esophageal reflux and esophago-pharyngeal reflux. Findings were similar in awake and sleep states. We concluded that, in healthy recumbent subjects, the most common TLESR-termination event is a secondary contraction, rather than PP. Presence and distribution of the refluxate is a major influence on the type of terminating contraction.

The mechanism against entry of gastric content into the pharynx during high-intensity vocalization such as seen among professional singers is not known. We hypothesized that phonation-induced upper esophageal sphincter (UES) contraction enhances the pressure barrier against entry of gastroesophageal contents into pharynx. To determine and compare the effect of phonation on luminal pressures of the esophagus and its sphincters, we studied 17 healthy volunteers (7 male, 10 female) by concurrent high-resolution manometry and voice analysis. We tested high- and low-pitch vowel sounds. Findings were verified in six subjects by UES manometry using a water-perfused sleeve device. Eight of the volunteers (2 male, 6 female) had concurrent video fluoroscopy with high-resolution manometry and voice recording. Fluoroscopic images were analyzed for laryngeal movement. To define the sex-based effect, subgroup analysis was performed. All tested phonation frequencies and intensities induced a significant increase in UES pressure (UESP) compared with prephonation pressure. The magnitude of the UESP increase was significantly higher than that of the distal esophagus, the lower esophageal sphincter (LES), and the stomach. Concurrent videofluoroscopy did not show posterior laryngeal movement during phonation, eliminating a purely mechanical cause for phonation-induced UESP increase. Subgroup analysis demonstrated phonation-induced UESP increases in males that were significantly greater than those of females. Phonation induces a significant increase in UESP, suggesting the existence of a phonation-induced UES contractile reflex. UESP increase due to this reflex is significantly higher than that of the distal esophagus, LES, and stomach. The phonation-induced UESP increase is influenced by sex.

Introduction of biologic agents in inflammatory bowel disease (IBD) has increased the likelihood of disease remission. Despite resolution of active inflammation, a subset of IBD patients report persistent defecatory symptoms. To evaluate a group of patients with inflammatory bowel disease with suspected functional defecatory disorders, by use of anorectal manometric testing and subsequent biofeedback therapy. A group of IBD patients with persistent defecatory problems despite clinical improvement were included in this study. These patients had no evidence of left-sided disease. Endoscopic and radiographic study findings and timing in relation to the manometry study were recorded. Anorectal manometry was performed by the standard protocol and included rectal sensory assessment, ability to expel a balloon, and pressure dynamics with simulated defecation. Thirty IBD patients (Crohn’s 23 patients; ulcerative colitis six patients) presented with defecatory disorders including constipation (67 %) increased stooling (10 %), and rectal urgency and/or incontinence and rectal pain (6 %). All but one patient had anorectal manometric criteria of dyssynergia (presence of anismus motor pattern and inability to expel the balloon). Of the patients who completed biofeedback therapy, 30 % had a clinically significant (≥7-point) improvement in SIBDQ score, with a reduction in health-care utilization after a six-month period (p = 0.02). Despite remission, some inflammatory bowel disease patients have persistent defecatory symptoms. Defecatory symptoms may not be predictive of an underlying inflammatory disorder. Lack of inflammatory activity and absence of left-sided disease should prompt investigation of functional disorders. Anorectal manometric testing and biofeedback therapy for patients with a diagnosis of dyssynergia may be a useful therapy.

To examine the impact of pregnancy on health-related quality of life (HRQoL) of women with inflammatory bowel disease (IBD).This was a retrospective study in a tertiary referral center and included women with ≥2 short inflammatory bowel disease questionnaire (SIBDQ) scores obtained during their pregnancy. Regression models were used to identify independent factors influencing SIBDQ scores and changes of SIBDQ scores at different time points.A total of 32 women (23 CD, 9 UC) with a mean age at pregnancy of 29.4 years and a mean disease duration of 7.8 years were included in the study. The mean pre-pregnancy SIBDQ score in our cohort was 49, which was significantly lower than the values during (55, P0.001) and post-pregnancy (53, P = 0.01). The score during pregnancy directly correlated with the pre-pregnancy SIBDQ score (correlation co-efficient 0.50, P = 0.003). Half of the patients had a ≥7-point increase in SIBDQ scores during pregnancy. Change in SIBDQ scores during pregnancy was inversely related to the pre-pregnancy score (-0.47, 95% CI -0.75 to -0.20) and changes in disease activity during pregnancy (-1.80, 95% CI -0.75 to -0.20).Half of the pregnant women with IBD in our cohort experienced improvement in their HRQoL. Pre-pregnancy HRQoL is predictive of HRQoL during pregnancy, supporting the need for optimizing disease activity prior to conception.

Background: Reactivation of latent Mycobacterium tuberculosis (TB) is a rare, yet devastating infectious complication associated with anti-tumor necrosis factor alpha (TNF-α) therapy. We evaluated the performance of the QuantiFERON TB Gold test (QFT-G) for TB screening in a cohort of inflammatory bowel disease (IBD) patients in the United States. Methods: We performed a retrospective, observational study of patients initiated and/or maintained on an anti-TNF-α agent in a single IBD referral center and recorded the frequency and the test results of QFT-G testing and the rate of TB reactivation. Results: 512 QFT-G tests were done in 340 patients. Five patients (1.5%) had a positive, nine (2.7%) indeterminate, and 326 patients (95.8%) had a negative QFT-G. After a mean follow-up of 17 months there was one case of TB reactivation (0.3%). The use of immunosuppressive therapy or anti-TNF therapy at the time of testing did not affect the results of the QFT-G testing. Test–retest had substantial concordance (κ = 0.72). 25% of patients (n = 85) had TST testing. Concordance between the TST and QFT-G was found to be moderate (κ = 0.4152, P = 0.0041). Conclusions: Most patients with negative QFT-G tolerated anti-TNF therapy with no evidence of TB reactivation. Concomitant use of immunosuppressive therapy or anti-TNF did not seem to affect QFT-G results. One patient had an indeterminate QFT-G while on infliximab and later developed miliary TB. Concordance with TST is moderate. (Inflamm Bowel Dis 2011;)

Gastroesophageal reflux (GER) is thought to be induced by decreasing intraesophageal pressure during obstructive sleep apnea (OSA). However, pressure changes in the upper esophageal sphincter (UES) and gastroesophageal junction (GEJ) pressure during OSA events have not been measured. The aim of this study was to determine UES and GEJ pressure change during OSA and characterize the GER and esophagopharyngeal reflux (EPR) events during sleep.We studied 15 controls, nine patients with GER disease (GERD) and without OSA, six patients with OSA and without GERD, and 11 patients with both OSA and GERD for 6 to 8 h postprandially during sleep. We concurrently recorded the following: (1) UES, GEJ, esophageal body (ESO), and gastric pressures by high-resolution manometry; (2) pharyngeal and esophageal reflux events by impedance and pH recordings; and (3) sleep stages and respiratory events using polysomnography. End-inspiration UES, GEJ, ESO, and gastric pressures over intervals of OSA were averaged in patients with OSA and compared with average values for randomly selected 10-s intervals during sleep in controls and patients with GERD.ESO pressures decreased during OSA events. However, end-inspiratory UES and GEJ pressures progressively increased during OSA, and at the end of OSA events were significantly higher than at the beginning (P.01). The prevalence of GER and EPR events during sleep in patients with OSA and GERD did not differ from those in controls, patients with GERD and without OSA, and patients with OSA and without GERD.Despite a decrease in ESO pressure during OSA events, compensatory changes in UES and GEJ pressures prevent reflux.

Background: Impairment of health-related quality of life (HRQoL) is an important concern in inflammatory bowel disease (IBD; ulcerative colitis [UC], Crohn's disease [CD]). Between 2%–10% of patients with IBD have primary sclerosing cholangitis (PSC). There has been limited examination of the disease-specific HRQoL in this population compared to non-PSC IBD controls. Methods: This was a retrospective, case–control study performed at a tertiary referral center. Cases comprised 26 patients with a known diagnosis of PSC and IBD (17 UC, 9 CD). Three random controls were selected for each case after matching for IBD type, gender, age, and duration of disease. Disease-specific HRQoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Disease activity for CD was measured using the Harvey–Bradshaw index (HB) and using the UC activity index for UC. Independent predictors of HRQoL were identified. Results: There was no significant difference in the age, gender distribution, or disease duration between PSC-IBD and controls. There was no difference in use of immunomodulators or biologics between the 2 groups. Mean SIBDQ score was comparable between PSC-IBD patients (54.5) and controls (54.1), both for UC and CD. Likewise, the disease activity scores were also similar (2.8 versus 3.1, P = 0.35). On multivariate analysis, higher disease activity score (−1.33, 95% confidence interval [CI] 95% CI −1.85 to −0.82) and shorter disease duration were predictive of lower HRQoL. Coexisting PSC did not influence IBD-related HRQoL. There was a higher proportion of permanent work disability in PSC-IBD (7.7%) compared to controls (0%). Conclusions: PSC does not seem to influence disease-specific HRQoL in our patients with IBD but is associated with a higher rate of work disability. (Inflamm Bowel Dis 2010)

It is well recognized that the nature of the immune response is different in the intestinal tract than in peripheral lymphoid organs. The immunologic tone of the gut-associated lymphoid tissue is one of suppression rather than active immunity, distinguishing pathogens from normal flora. Failure to control mucosal immune responses may lead to inflammatory diseases such as Crohn's disease (CD) and ulcerative colitis (UC) and celiac disease. It has been suggested that this normally immunosuppressed state may relate to unique antigen-presenting cells and unique T-cell populations. The intestinal epithelial cell (IEC) has been proposed to act as a nonprofessional antigen-presenting cell (APC). Previous studies have suggested that antigens presented by IECs result in the activation a CD8+ regulatory T-cell subset in a nonclassical MHC I molecule restricted manner. We therefore analyzed the expression of nonclassical MHC I molecules by normal IECs and compared this to those expressed by inflammatory bowel disease (IBD) IECs. Normal surface IEC from the colon and, to a much lesser extent, the small bowel express nonclassical MHC I molecules on their surface. In contrast, mRNA is expressed in all intestinal epithelial cells. Surface IEC express CD1d, MICA/B, and HLA-E protein. In contrast, crypt IECs express less or no nonclassical MHC I molecules but do express mRNA for these molecules. Furthermore, the regulation of expression of distinct nonclassical class I molecules is different depending on the molecule analyzed. Interestingly, IECs derived from patients with UC fail to express any nonclassical MHC I molecules (protein and HLA-E mRNA). IECs from CD patients express HLA-E and MICA/B comparable to that seen in normal controls but fail to express CD1d. Thus, in UC there may be a failure to activate any nonclassical MHC I molecule restricted regulatory T cells that may result in unopposed active inflammatory responses. In CD only the CD1d-regulated T cells would be affected. (Inflamm Bowel Dis 2007)

Background: Approximately 35% of patients with ulcerative colitis (UC) will require surgery some time during the course of their disease. However, this past decade has seen major changes in the medical management of UC with FDA-approval of anti tumor necrosis factor alpha (Anti-TNF), for moderate to severe UC. Anti-TNF has demonstrated beneficial impact on the short-term colectomy rates in patients with UC. However, limited data are available regarding the long-term efficacy. The aim of this study was to determine the trends in the rate of colectomy in pre and post biologics era in hospitalized patients with UC. Methods: Nationwide Inpatient Sample (NIS), maintained by the Healthcare Cost and Utilization Project of the Agency for Healthcare Quality and Research, is the largest all-payer inpatient hospitalization database in the US. Hospitalizations from prior to the approval of biologics for ulcerative colitis (the pre-biologic era (1998-2005) and for post-biologic period from 2006-2011 were used. Our study included all patients hospitalized for primary diagnosis of Ulcerative Colitis (ICD-9-CM 556.x) and secondary diagnosis of UC related comorbidities and procedures. Surgeries were classified as elective if the admission was coded as being elective, the source of admission was not the emergency room and surgery occurred on day 0 or 1 of hospitalization. It was defined as emergent if the patient was admitted from the emergency room, the admission was characterized as emergent, and the procedure was performed within 0, 1 day of admission. A previously published risk score was used to adjust for severity of ulcerative colitis hospitalization. Results: A total of 399,579 admissions with primary diagnosis of UC and 38,505 (10%) colectomies were recorded during this period. 212,951 (53%) were females and average age was 46 years. Descriptive data of the group are shown in table 1. There was no difference in colectomy rate in pre and post biologic periods (figures 1). Females, whites and teaching hospital had significantly high rates of colectomies (table 1). Rate of colectomy is significantly increased up to age 70 with lowest rate among the age-group 10-20 yrs (p

Molecular analyses of tumors are increasingly useful for prognosis and for guiding therapy. Colonoscopic biopsy provides the first source of tissue for most cases of colorectal carcinoma and therefore might become an important source for molecular analyses. We have addressed the question whether molecular analyses of colonoscopic biopsy yield results similar to the findings from the surgical specimen. Further, we analyzed 2 separate areas of the colectomy specimen to assess tumor heterogeneity. We evaluated 3 samples from each of 67 patients for point mutations in the KRAS gene, loss of heterozygosity (LOH) at the Adenomatous Polyposis Coli (APC) and Deleted in Colon Cancer (DCC) genes and for microsatellite instability (MSI) using polymerase chain reaction based techniques. The average time interval between biopsy and surgery was 2.2+/-0.15 weeks. Lesions were from all colon segments and all surgical stages. The degree of agreement between the biopsy and surgical sites was high for APC LOH, MSI, and KRAS mutations (kappa=0.85, 1.00, and 0.93, respectively) but less so for DCC LOH (kappa=0.62). Colonoscopic biopsies are an acceptable source of neoplastic DNA for studies of KRAS, APC LOH, and MSI, but less so for DCC LOH, primarily resulting from technical considerations.

genome-wide association study (GWAS) using Illumina OmniExpress, comparing patients with and without perianal disease (n=780). Serum was analyzed by ELISA for anti-Saccharomyces cerevisiae (ASCA), anti-outer membrane porin C (anti-OmpC), anti-Cbir1, and antiPseudomonas fluorescens (anti-I2). Data analysis was undertaken using univariate logistic regression for clinical and serologic data (statistical significance at p ,0.001). Multivariate regression was used for GWAS data, with principal components/disease location as covariates. We report single nucleotide polymorphisms (SNPs) that reached p=10E-6. Results: Perianal disease was documented in 35% (n=297). Perianal disease was associated with colonic and ileocolonic disease locations (p,0.0001), as well as with upper GI (p=0.0006) and rectal disease (p,0.0001). Anti-OmpC was significantly more prevalent among individuals with perianal disease (p, 0.0001). Two statistically significant SNPs were identified. One was a SNP at chromosome 8q24 (rs6470545, p=9x10E-6), which is 200 kilobases upstream from the proto-oncogene MYC, and near a colon cancer locus (rs6983267) known to control MYC expression. Three nearby SNPs (rs10091329, rs6470537, rs6470552) in close linkage disequilibrium (r2 .0.8) had p-values of 10E-5. Another SNP on chromosome 8 in a gene desert was also associated with perianal disease (rs10092418, p=8x10E-6). Conclusions: We report novel genetic and serologic associations with perianal disease in a large cohort of Crohn's disease patients. The association between perianal disease and a locus near MYC, which encodes a transcription factor with broad activity in cell proliferation, apoptosis, and differentiation, suggests novelmechanisms in the development of perianal disease. Replication will be important to confirm findings and direct further investigation into this unique Crohn's disease phenotype. *Dr. Weizman and Dr. Murdoch contributed equally to this study.

BACKGROUND: Adalimumab (ADA) and certolizumab pegol (CZP) are injectable biologics currently approved for moderate to severe Crohn's disease (CD) failing to respond adequately to conventional therapy. Unlike infliximab, ADA and CZP do not use weight-based dosing. Recent data involving patients with psoriasis suggest that the efficacy of adalimumab may be reduced in obese patients, although this association has not been found in CD. The aim of this study was to determine whether obesity influences treatment efficacy and need for dose escalation of ADA or CZP in patients with CD. METHODS: A retrospective chart review was performed to identify patients with CD treated with ADA or CZP at our institution from January 2006 to October 2011. The primary outcomes of interest were the proportion of patients with a clinical response to induction with ADA and CZP, and the proportion of patients that underwent dose escalation (for ADA) or reinduction (for CZP) in obese v nonobese patients. Patients were defined as nonobese (body mass index (BMI) 30). Patients were excluded if less than 3 months of follow up data were available. Statistical analysis was done by chi-square analysis and student's t-test. RESULTS: 135 Crohn's patients (107 ADA, 28 CZP) were included. 35/135 patients had a BMI >30. Median age was 38 (range 19-73), 63% were female, and median disease duration was 11 years (range 0-37). There were no significant differences in clinical response to ADA induction (obese 23/29 79.3%, nonobese 58/78 74.4%; p =.80). A higher proportion of obese patients underwent dose escalation with ADA although this was not statistically significant (obese 12/29 41.4%, nonobese 21/78 26.9%; p =.16). There were no differences in response to dose escalation (obese 58%, nonobese 62%) or proportion of patients that remain on therapy (obese 55%, nonobese 55%). Patients receiving CZP had no significant differences in clinical response to induction (obese 2/6 33%, nonobese 12/22 54%; p=.64) or rates of reinduction (obese 20%, nonobese 36%; p=.64) and proportion of patients remaining on therapy (obese 17%, nonobese 14%). However these numbers are limited by small sample size. The mean duration of therapy was 12 months (range 4-56) for ADA and 7 months (range 3-26) for CZP. CONCLUSIONS: In this cohort of Crohn's patients, obesity was associated with similar rates of clinical response to ADA and CZP compared with nonobese patients. Obese patients had higher rates of dose escalation of ADA, although this difference was not statistically significant. Obesity did not impact the proportion of patients that remain on therapy.

of chronic immunosuppression to avoid colectomy. METHODS: Adult UC patients completed a mailed discrete-choice experiment survey with 9 treatment-choice questions that offered a choice of a hypothetical medication or surgical therapy with varying features. Medication features included improvement in disease activity, 10-year risk of dying from lymphoma and a serious infection, and risk of dying from colorectal cancer. Surgical features included having a J-pouch with/without incontinence or an ostomy, and 10-year risk of dying from a serious infection. Random parameters logit was used to estimate rates at which patients were willing to trade among treatment features in selecting surgery versus medication. RESULTS: 141 patients completed the survey. Avoiding surgery and surgery type (ostomy versus j-pouch) influenced patients' choices more than the risk of dying from lymphoma or infection, or severity of disease activity (mild vs. remission) over the ensuing 10 years. To avoid having an ostomy, patients were willing to accept >5% 10-year risk of dying from infection or lymphoma from medical therapy regardless of medication efficacy. However, patients were significantly less tolerant of medication risk if the surgical option was a Jpouch; and patients were equally satisfied with J-pouch surgery as with an incompletely effective medical therapy. Risk acceptability also varied significantly in certain subgroups: females were more tolerant of medication-related infection; patients ≥ 60 years old were less tolerant of surgery-related infection; patients with longer disease history were more willing to accept ostomy; and patients with a disease flare within the last year were less tolerant of lymphoma (all p-values

Background: Tuberculosis (TB) is a recognized risk in patients with Inflammatory Bowel Disease (IBD), especially given the therapeutic use of anti-TNF agents in the last decade. This large database study sought to determine if the risk of TB has increased since the introduction of biologic therapies for the treatment of IBD. Patients/Methods: Linked records of statistical abstracts for all hospital admissions in the Oxford region from 1963 to 1998 (ORLS1 database), Oxford region from 1998-2008 (ORLS2) and subsequently all of England from 1998-2008 (HES database), were used to identify hospital admissions for those patients who had a diagnosis of TB following an admission for IBD. Rates and rate-ratios (RR) of TB infection were determined in Crohn's disease and ulcerative colitis, compared to a nonIBD reference cohort (minimum matching ratio 30:1). TB rates were stratified by age, sex, district and index year of IBD hospitalization for the combined cohort. This was used to determine stratum-standardized rates for each group. Results: 18/4884 Crohn's disease (CD) and 13/6768 ulcerative colitis (UC) patients had TB in ORLS 1. 10/5438 CD and 7/7842 UC patients had TB in ORLS2. 172/103285 CD and 124/143253 UC patients had TB in the HES database, giving a 10-year average annual incidence rate for hospitalized CD and UC patients of 38.7 and 15.6 per 100000 pt.yr, respectively (England, 1998-2008). RR for Tuberculosis in hospitalized CD patients, compared with the reference cohort, was significantly elevated in all three databases, though slightly higher in ORLS1 compared with ORLS2 and HES (5.35 vs 3.06 vs 3.85). RR for TB in UC patients was only significantly elevated in the HES database, with little variation in RR across the three database populations. Conclusions: We report the highest incidence rates of TB, compared with existing literature, potentially reflecting the higher disease burden of hospitalized IBD patients. Compared to relatively healthy hospitalized controls, Crohn's disease is associated with a 3 to 5-fold higher risk of TB, while UC exhibits a 2-fold higher risk. Comparing the periods before and after the introduction of anti-TNF agents for IBD, TB rates appear to have dropped. Strict attention must be paid to the risk of TB infection in hospitalized IBD patients.

Introduction:There has been an increased rate of Clostridium difficile infection (CDI) with disproportionately higher impact on the inflammatory bowel disease (IBD) populationCrohn's disease (CD) and Ulcerative Colitis (UC). Treatment protocol has traditionally consisted of vancomycin or metronidazole. The outcome of probiotic treatment in this unique population is not defined. We sought to evaluate the impact of probiotics on rates of subsequent CDI and disease course. Methods:This was a retrospective observational study of all IBD pts followed at a single IBD center with CDI confirmed by suggestive gastrointestinal symptoms and either positive toxin A/B ELISA stool test or nucleic acid amplification stool test (NAAT). Pt demographics and disease characteristics were collected. We evaluated the performance of probiotics used by assessing rate of subsequent CDI over the following year. Probiotic used was Florajen (reported to have 20 billion live, freeze dried, human source strains of lactobacillus acidophilus). IBD clinical course the year following CDI was evaluated using inflammatory markers, corticosteroid usage, and disease related complications including hospitalizations and surgeries. Results:There were 101 IBD (62 CD, 39 UC) pts who had CDI confirmed (35 inpts and 66 outpts). 31 IBD pts (20 CD, 11 UC) with CDI were in the probiotic group (P) and 70 IBD pts (42 CD and 28 UC) were in the control group (C). There was no difference in disease duration, IBD maintenance therapy, disease type/ behavior between these groups. Initial antibiotic therapy used for treatment of CDI was metronidazole (M) in 48 pts, vancomycin (V) in 38 pts and combination of metronidazole + vancomycin (M+V) in 15 pts. The rate of subsequent CDI (>1) over the following year was 39% (12/31pts) in P group and 16% (11/70pts) in the C group (p=0.01). Probiotic treatment rates were 15% (7/48) in the M group, 42% (16/38) in the V group, and 53% (8/15) in the M+V group. There was a higher rate of probiotic treatment in the V group compared with the M group (42% vs 15%; p=0.04) and in the M+V group compared with the M group (15% vs 53%; p=0.002). There was no difference in probiotic use between V andM+V groups (42% vs 53%; p=0.46). Recurrence rate was not affected by IBDmaintenance therapy (biologic/immunomodulator or both). Antibiotic used in initial CDI had no impact on rate of hospitalizations, IBD related surgeries or mean ESR and CRP values over the following year. Conclusions:In our cohort, use of lactobacillus acidophilus single strain probiotic during initial CDI was associated with higher rates of subsequent CDI. Probiotic usage was higher in the CDI treatment groups with vancomycin alone and in combination with metronidazole. Further studies are necessary to define appropriate roles for probiotic strains in combination with antibiotics for preventing CDI recurrence.

for more than three months, 272 (53%) patients had peripheral joint pain and/or swelling and 105 (21%) had both back pain and peripheral joint pain and/or swelling. Ninety-four IBD patients were thus far examined (table 1). Axial involvement occurred in 8 (9%) patients, peripheral involvement in 45 (48%) patients and 41 (44%) patients had axial, as well as, peripheral involvement. No differences in manifestations were observed between CD and UC. AS was found in 2 (2%) IBD patients with IBP. HLA-B27 was positive in 5 (5%) of patients and was more frequently seen in IBD patients with IBP than in IBD patients without IBP (26 vs. 1%). Three (3%) patients could be classified as axial SpA and 4 (4%) as peripheral SpA. Conclusion: Joint complaints are reported by themajority of IBD patients, more frequent in CD patients and in female patients. Arthralgia is the most often seen joint manifestation in IBD patients and mainly affects the knees and small joints of the hands. Joint manifestations did not differ between CD and UC. A positive HLA-B27 was more frequently observed in IBD patients with IBP. Table 1: Characteristics of 94 IBD patients with joint manifestations

BACKGROUND: Screening and treatment for latent tuberculosis (TB) before the use of antiTNF therapy has decreased the risk of active TB. In Spain, which has a high prevalence of TB, the recommended TB screening according to national guidelines includes 2-step tuberculin skin test (TST) and chest X-ray. No data are available on the risk of developing a positive response in serial TST in inflammatory bowel disease (IBD) patients receiving long-term infliximab therapy whose initial 2-step TST was negative. The aim of this study was to determine the likelihood of detecting latent TB by the positive conversion of serial TST in a cohort of IBD patients treated with infliximab. The outcome of patients with positive conversion in the TST was also investigated. METHODS: This prospective single-center study included all consecutive IBD patients with negative 2-step TST before starting infliximab treatment. TST was positive if induration was ≥5 mm in first test or the induration was ≥5 mm in the second test (if the first TST was