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soperated for colon cancer without UC served as controls. On H&E stainings the Geboeshistological inflammatory activity score (0-22 points) was determined by an experiencedIBD pathologist. Sirius Red stainings and collagen I and III immunohistochemistry stainingswere performed for collagen, and α-smooth muscle (αSMA) for detection of myofibroblastsand smooth muscle cells. Staining intensity signals were investigated by image analysissoftware (Image J, NIH). Results We examined 13 colectomy specimens from patients withacute UC, 16 from patients with longstanding UC, and 7 colorectal cancer controls. Patientswith short disease duration had a higher Geboes score of 19 (13-20) points, versus 8.5 (2-16) points in specimens with longer disease duration (p=0.001). Acute and longstandingUC had a thicker muscularis mucosa (MM) than controls (0.10 vs 0.10 vs 0.05 mm, p=0.019). Both UC groups had less submucosal αSMA expression (number of αSMA positivevs total number of cells; 29% vs 33% vs 54%, p=0.009). Between acute and late UC therewas no difference in collagen deposition, however between UC together and controls therewas more collagen I expression in the mucosa, MM and muscularis externa (50% vs 10%,p=0.02; 28% vs 10%, p=0.048; 71% vs 20%, p=0.003). In both early and long UC duration,we did not find a correlation between inflammation or collagen deposition or MM thickness.There was a negative correlation between inflammation and αSMA positivity in the submucosa(R=-0.51, p=0.003) and MM (R=-0.37, p=0.04). Conclusion In our series of colectomyspecimens, there is more collagen deposition in UC than in controls. No association betweendisease duration and increased collagen deposition could be found. Expression of αSMAhowever is lower in UC and correlates with inflammation. Fibrosis in UC does not appearto increase significantly over time.

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Failure of Infliximab Treatment in Crohn's Disease Is Associated With thePresence of FibrosisJessica R. de Bruyn, Sybren L. Meijer, Manon E. Wildenberg, Gijs R. van den Brink,Geert R. D'Haens

Introduction Intestinal fibrosis in Crohn's disease (CD) is a process stimulated by chronicinflammation leading to an increased presence of myofibroblasts and collagen deposition inall layers of the intestinal wall. However, once the fibrotic process has been initiated itmay progress independently of inflammation. Infliximab (IFX) is a highly effective anti-inflammatory treatment in CD. Despite initial good response, considerable proportionsof patients lose response during maintenance treatment. We aimed to investigate if thisphenomenon could be explained by the presence of pre-existing fibrosis. Methods Wecollected ileocecal resection specimens from patients operated between 2005 and 2012 whohad failed IFX treatment (at least 3 gifts IFX), and from patients operated without previousIFX treatment. Demographics and pre-operative C-reactive protein (CRP) were recorded.Inflammation was scored on H&E stains by an experienced IBD pathologist (scoring range0-13 points). Sirius Red and collagen I immunohistochemistry stainings were performed forcollagen deposition, and α-smooth muscle (αSMA) for detection of myofibroblasts andsmooth muscle cells. Staining intensity was measured using image analysis software (ImageJ, NIH). Results We examined 12 specimens from patients operated after IFX failure, and20 specimens from IFX-naive patients. Median duration of IFX treatment was 77 (IQR 21-189) weeks. CRP levels did not differ between treated and non-treated patients (respectively17 (3-51) mg/L vs 6 (3-24) mg/L). Both IFX-failure and IFX-Naive groups had significantinflammation but this did not differ significantly (11 (IQR 6-12) vs 10 (IQR 7-12) points).More collagen I deposition in the IFX-failure group was found in the submucosa (numberof collagen I positive cells versus total number of cells; respectively 71% vs 57%, p=0.03),with a trend to more collagen I deposition in the mucosa and muscularis externa (respectively50% vs 30%, p=0.069 and 46% vs 23%, p=0.067). IFX-Naive patients had more αSMAexpression in the muscularis externa (39% vs 34%, p=0.01). There was a strong negativecorrelation between inflammation and submucosal αSMA positivity in patients who hadfailed IFX (R=-0.84, p=0.001). No correlation between IFX duration and inflammation orcollagen deposition was found. Conclusion In our series of ileocoecal resection specimens,there is more collagen I deposition in the submucosa with a trend in the mucosa andmuscularis externa. Moreover there is a strong negative correlation between inflammationand submucosal αSMA positivity in these patients. Fibrotic deposition could be a cause forIFX failure in CD patients.

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Patterns of Antibiotic Exposure and Clinical Disease Activity in InflammatoryBowel Disease: A 4 Year Prospective StudyJana G. Hashash, Claudia M. Ramos Rivers, Miguel Regueiro, Arthur Barrie, MarcSchwartz, Leonard Baidoo, Jason M. Swoger, Michael A. Dunn, David G. Binion

Background and Aim: The normal intestinal microbiota plays beneficial roles in protectionagainst pathogen invasion, development of the immune system and in nutrition but is also feltto play a central role in the pathogenesis of inflammatory bowel disease (IBD). Antimicrobialtreatment is known to cause both short- and long-term changes in the composition of thenormal human microbiota. The relationship between patterns of antibiotic use and overallclinical behavior in IBD has not been explored. We sought to prospectively characterizepatterns of antibiotic use (for IBD and non-IBD issues) and clinical IBD activity in a cohortof pts followed over 4 years. Methods: Prospective observational study from a longitudinalIBD natural history registry between 2009 and 2012. Demographic information, diseasetype, quality of life (QOL) as measured by SIBDQ, and healthcare utilization data wascollected. Patterns of IBD related hospitalizations, clinic visits, telephone calls, and emergencydepartment (ED) visits were analyzed. Antibiotic prescriptions were identified using electronicmedical record data and were categorized by drug class (antihelminths, macrolides, quino-lones, penicillin, cephalosporin, etc). Laboratory data was analyzed. Cumulative rates overthe 4 year study period were compared. Results: A total of 718 pts followed over 4 yearswere included (47.6% male, mean age 46.7±15.2y SD). Most pts (59.9%) had CD while38.6% had UC, and 1.5% were indeterminate. Four-hundred seventy-six (66.3%) pts wereexposed to antibiotics during the 4-year study period while 33.7% did not receive antibiotics.There was no difference in the gender or age of pts who received antibiotics compared tothose who did not. The antibiotic exposed group was more likely to include CD pts (63%

S-442AGA Abstracts

vs. 53.7%; p 0.05), require narcotics (43.7% vs. 14.9%; p<0.0001), receive anti-depressanttherapy (43.1% vs. 18.6%; p<0.001) and require prednisone (52.7% vs. 31%; p<0.0001).There was no difference in the rates of immunomodulator use between groups, but antibioticexposed pts were more likely to be on biologic therapy (52% vs. 36.5%; p<0.0001). Antibioticexposed IBD pts had higher healthcare utilization as shown in Table 1. Antibiotic exposedIBD pts compared with non-antibiotic exposed IBD had a lower QOL (mean SIBDQ 50.2±11.5vs 56.4±9.5; p<0.0001) and higher rates of CRP elevation (49.2% vs 31.8%; p<0.0001).There were 3,559 total antibiotic prescriptions; most common were metronidazole (23.7%),quinolones (22.9%), macrolides (10.4%), penicillins (9.8%) and cephalosporins (8.4%).Conclusion: A majority of IBD pts receive antibiotic treatment and these exposed individualsdemonstrate a more severe clinical course, but the causative nature of this association isunclear. Further examination of antibiotic treatment on gut microbiome and IBD naturalhistory is warranted.Differences in healthcare utilization

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Impact of Metabolic Syndrome on Hospitalization Rate of Crohn's DiseasePatients Seen At a Tertiary Care CenterPaul S. Fitzmorris, Ioana B. Smith, Jeffrey Juneau, Euriko G. Torrazza Perez, BrandiBlackburn, Donny D. Kakati, Talha A. Malik

Background: Recent studies have suggested that markers of mesenteric inflammation, suchas increased adipose tissue, may be associated with poor outcomes in Crohn's disease (CD).As an extrapolation of this observation, this study sought to test the hypothesis that CDpatients with Metabolic Syndrome (MetS) have worse outcomes compared to CD patientswithout MetS. Methods: To test this hypothesis we designed a retrospective cohort studythat compared the outcomes of CD with MetS (primary exposed cohort) and CD patientwithout MetS (primary unexposed cohort). We also compared secondary exposed andunexposed cohorts based on presence and absence of component conditions of MetS.According to the International Diabetes Federation, MetS is defined by the presence of ≥3of 5 components: enlarged abdominal girth (which was assumed if BMI >30), type 2 diabetesmellitus (DM), hypertension (HTN), low serum high density lipoprotein levels (HDL) andhigh triglycerides (TG). Generalized Poisson Regression Model for Rate Data was performedto estimate the age-, sex- and duration of disease (DOD)-adjusted incidence rate ratio (IRR)of hospitalization, while accounting for individual periods of observation among CD patientswith and without MetS. Results: Of the 1139 patients with CD seen at our institutionbetween 2000 and 2013, 945 met the following criteria: They had data that allowed fordiagnosis of MetS at initial observation, and they were followed for at least one year. Themean DOD and mean duration of observation (DOO) were 13 years (SD=10.71) and 4 years(SD=3.52), respectively. 38 of the 945 CD patients had MetS. The rate of hospitalizationfor a CD exacerbation was 0.05/person-year among CD patients with MetS vs. 0.0002/person-year among CD patients without MetS. The results revealed that CD patients withMetS were almost twice as likely to have a CD-related hospitalization during the observationperiod compared with CD patients without MetS (IRR=1.95 95%CI=1.18-3.24 P=0.01).Regarding individual components of MetS, high TG (IRR=2.20 95%CI=1.50-3.24 p< 0.0001)and low HDL (IRR=2.18 95%CI=1.52-3.14 p< 0.0001) had the strongest association withincreased likelihood of hospitalization. DM (IRR=1.41 95%CI=0.77-2.46 p=0.267) and HTN(IRR=1.25 95%CI 0.9-1.74 p=0.18) were also associated with increased rate of CD-relatedhospitalization, although this association was not statistically significant. Initial BMI of > 30kg/m2 was not associated with increased rate of CD-related hospitalization (IRR=0.99 95%CI=0.76-1.29 p=0.947). Conclusions: CD Patients with MetS have a higher rate of CD-relatedhospitalization compared with CD Patients without MetS. This association appears to bedriven predominantly by high TG and low HDL. Future studies need to shed further lighton the role of low HDL and high TG on CD outcomes.

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The Impact of Vaccinations on Infectious Disease Incidence Among IBDPatientsMichael V. Chiorean, Danielle La Selva

Background: IBD patients on immunosuppressive therapy are at increased risk of infectionsincluding those that are preventable by vaccines. The preventive effect of standard immuniza-tions among IBD patients is unknown. Aims: to determine the rate of immunizations forcommon infections (flu, pneumonia) and the prevalence of infectious events among patientswith inflammatory bowel disease related to their immunosuppressive (IS) use and vaccinationstatus. Methods: Patients enrolled in a single institution IBD database were considered eligiblefor the study. Demographic information, IS drugs use (steroids, immunomodulators andbiologics), immunization status and the incidence of related infections (flu, pneumonia)were collected from the EMR. The rate of vaccinations was determined per calendar yearand time tertiles and time trends were estimated. All categorical variables were analyzedusing the chi-square test. Results: There were 3225 patients in the IBD database followedbetween 2007 and 2013; 47% with Crohn's disease, 45% male and 46.6% exposed to ISdrugs. The rate of any vaccination for flu and pneumonia was respectively, 47.6% and16.8% among IS users vs. 39.1% and 9.6% among non-users. There was a significant timetrend in both flu and pneumonia vaccinations (p<0.01 between first and third tertile forboth flu and pneumonia). There was a '09 spike in flu vaccination rate likely related to theemergence of H1N1. Patients older than 50 (69% vs. 39%, p<0.0001) and IS users (p<0.0001)were more likely to receive vaccines but there was no difference based on sex. The incidence