to predict the clinical course of IBD patients, in regards to future need for hospitalization and/or IBD-related surgery. 24 Confocal Laser Endomicroscopy to Assess Mucosal Microcirculation: A Quantitative Analysis in a Porcine Model of Septic Shock and in Patients With Severe Sepsis Carsten Schmidt, Christian Lautenschläger, Benjamin Petzold, Gernot Marx, Andreas Stallmach Aim Microcirculatory alterations play a central role in the pathophysiology of sepsis. Even if systemic hemodynamic parameters appear to be adequate, septic patients may suffer from significant intestinal microcirculatory alterations. It has been suggested that these changes play a central role in regard to morbidity and mortality. The present study first assessed the feasibility of In Vivo detection of mucosal microcirculation in different segments of the gastrointestinal tract in an animal model of septic shock using probe-based confocal laser endomicroscopy (pCLE) (Mauna Kea Technologies, Paris, France). Subsequently, we assessed duodenal microcirculation in patients suffering from severe sepsis in the early phase of the disease. Materials and Methods First, anesthetized and mechanically ventilated pigs were observed over 8 hrs. Septic shock was triggered by inducing fecal peritonitis (0.75 g autolog- ous feces per kg body weight). Mucosal microcirculation was assessed simultaneously using pCLE in stomach, duodenum, terminal ileum and rectum at baseline, 4 hours after induction of septic shock as well as 2 hours after treatment of the condition. Second, six patients who presented with a severe sepsis on the intensive care unit were examined regarding their duodenal microcirculation after obtaining informed consent from their nearest relatives. These patients were compared to ten healthy controls. Four to six areas were examined for each site and images were analysed in a blinded fashion offline thereafter in both parts of the study. Mean capillary diameter, capillary length and functional capillary density (FCD) were measured quantitatively. Results Two hours after induction of sepsis in the animal model, FCD was markedly decreased in the duodenal (-20.8, p < 0.001), the ileal (-13.4, p < 0.001), the gastric (-11.9%, p < 0.001), and in the rectal mucosal beds (-5.5, p<0,01). After administration of 30 mg x kg-1 of gelatine (30 kDa) FCD increased in all mucosal compartments to 90.0% (duodenum), 94.4% (ileum), 95.4% (gastric) and 97% (rectum) of baseline values. Interestingly, mean vessel diameter was unchanged in all compartments investigated. In patients suffering from severe sepsis we found a significant decrease in mean vessel diameter (-5.0%, p<0.001) as well as in FCD (-9,4%, p<0.001) of the duodenal mucosa, as well. Conclusions During the early phase of septic shock, pCLE may be able to quantify microcirculatory alterations in the gastrointestinal mucosa. Fluid resuscitation improves but does not completely restore intestinal microcirculation in the septic shock model. pCLE may represent a useful tool in order to assess the efficacy of therapeutic interventions on mucosal microcirculation, possibly even in clinical practice. 25 Incidence of Spondyloarthropathy in Patients With Ulcerative Colitis: A Population-Based Study Raina Shivashankar, Eric L. Matteson, William J. Tremaine, William S. Harmsen, Alan R. Zinsmeister, Edward V. Loftus Spondyloarthropathy (SpA) is an important extraintestinal manifestation of inflammatory bowel disease (IBD). We aimed to assess the cumulative incidence and clinical spectrum of SpA for the first time in a population-based cohort of patients with ulcerative colitis (UC). Also, we aimed to compare these findings to the cumulative incidence of SpA that we previously described in our Crohn's disease (CD) cohort. The medical records of a population- based cohort of Olmsted County, MN residents diagnosed with UC from 1970 through 2004 were reviewed. Patients were followed longitudinally until moving from Olmsted County, death, or June 30, 2011. We recorded data on musculoskeletal symptoms and disease, and used the European Spondyloarthropathy Study Group and New York criteria to identify patients with SpA. The cumulative incidence of SpA subsequent to UC diagnosis was estimated using Kaplan-Meier methods. The cohort included 365 patients with UC, of which 41.9% were women. The median age at diagnosis of UC was 38.6 years (range 1- 91). Prior to UC diagnosis, the prevalence of spondyloarthropathy was 0.8% (95% confidence interval [CI], 0.2%-2.4%). The cumulative incidence of a diagnosis of spondyloarthropathy after an established diagnosis of UC was 1.9% (95% CI, 0.4%-3.6%) at 10 years, 2.8% (0.9%-4.8%) at 20 years, and 4.9% (1.4%-8.2%) at 30 years. The 10-year cumulative incidence of ankylosing spondylitis was 0.3% (0-0.9%) and both the 20-year and 30-year cumulative incidences remained the same. Sacroiliitis, oligoarthritis and polyarthritis were observed in 1.6%, 3.3% and 0.5% of patients in the post-UC diagnosis period, respectively. We have for the first time defined the actual cumulative incidence of SpA in UC using complete medical record information in a population-based cohort. The cumulative incidence of all forms of SpA increased to about one in 20 patients by 30 years from UC diagnosis. This rate is about half of the incidence rate we previously described over the same time period in our CD cohort in Olmsted County, MN (Shivashankar R et al, Am J Gastroenterol 2011; 106(Suppl 2):S445-6). SpA and its features are well appreciated to be associated with UC, but are rather infrequent, demanding heightened awareness on the part of clinicians for detecting and managing them. S-7 AGA Abstracts 26 Serologic and Genetic Profiles Suggest Distinct Immune Pathways Among Patients With Pyoderma Gangrenosum and Inflammatory Bowel Disease Adam V. Weizman, Brian L. Huang, Dror Berel, Stephan R. Targan, Marla Dubinsky, Phillip Fleshner, Andrew Ippoliti, Jerome I. Rotter, Eric A. Vasiliauskas, David Q. Shih, Dalin Li, Gil Y. Melmed, Dermot P. McGovern BACKGROUND: Pyoderma gangrenosum (PG), a dermatologic extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD) is associated with significant morbidity. There is limited data regarding the serological and genetic associations between PG and IBD. METHODS: We performed a case control study using a cohort of previously genotyped and well characterized patients with IBD at our tertiary care center, and compared characteristics between those with at least one documented episode of PG (PG+) and those without PG (PG-). Data on demographics and clinical features were obtained from chart reviews. Standard tests for association between clinical characteristics, genetic markers and serologies were used after correcting for ethnicity and gender. IBD related serology (ASCA, OmpC, I2, CBir-1, and ANCA) were obtained by ELISA. Genetic data were generated using Illumina technology. We assessed for association at both known IBD loci and utilizing a genome wide approach, adopting p-values of <0.05 and <5x10E-05 as significant, respectively. RESULTS: We identified 86 patients with PG, of whom 56 had complete genetic and serologic data (61% Crohn's disease (CD) and 38% ulcerative colitis (UC)/IBD-unclassified). 63% were female; 86% were Caucasian. Among patients with CD, those that were PG(+) were diagnosed with IBD at an older age compared to PG(-) controls(mean age 32.8 and 22.4 years, respectively, p=0.000). IBD was also diagnosed at a later age in PG(+) patients compared to PG(-) among those with UC (mean age 34.9 and 25.5 years, respectively, p=0.009). UC and CD cases were compared to 4242 PG(-) controls. Among CD patients, seropositivity for p-ANCA in all patients was significantly higher among PG(+) than PG(-) patients (p= 0.01). Seropositivity for ASCA IgA, IgG, and anti-CBir1 was higher among PG(-) than PG(+) patients (p=0.04, 0.002, 0.007, respectively). However, among those with UC, anti-CBir1 was associated with PG (p=0.015). Genetic analyses revealed an association between PG and several known IBD susceptibility genes including: IL18RAP (OR 2.0, p=0.001), PRDM1 (OR 1.6, p=0.049), STAT3 (OR 0.37, p=0.01), and TNFRSF14 (OR 0.61, p=0.03). Other genes associated with PG included CRP (OR 2.6, p=4x10E-05) genes involved in apoptosis (IFT57, OR 2.9, p=4x10E-05), cell adhesion (PGM5 [OR 2.8, p=1x10E-05], ST851A6 [OR 2.7, p=4x10E-05], NRXN3 [OR 5.4, p=6x10E-06]), and TGFβ signaling (SMAD6, OR 2.5, p=4x10E-05). CONCLUSION: There are distinct clinical, serologic, and genetic features associated with PG in CD and UC. This suggests distinct immune pathways and potential novel therapeutic targets in this subset of challenging IBD patients. 27 Clinical Course of Inflammatory Bowel Disease in Liver Transplanted PSC Patients:a Nordic Multicenter Study Kristin K. Jørgensen, Lina Lindstrom, Milada Cvancarova, Erik Schrumpf, Morten H. Vatn, Kirsten Muri Boberg Background and aims: Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease, strongly associated with inflammatory bowel disease (IBD) and a major cause of liver transplantation (Ltx) in the Nordic countries. Previous studies have shown highly variable results regarding the course of IBD after Ltx. The present study aimed at describing the natural history of IBD after liver transplantation in PSC patients and possibly identifying potential risk factors for increased disease activity and deterioration. Methods: In a multicenter study within the Nordic Liver Transplant Group we compared the clinical activity of IBD before and after Ltx by a longitudinal follow-up of the patient cohort. Results: Among the 439 PSC patients included, 353 (80%) had IBD at the time of Ltx and 11 (2.5%) patients developed de novo IBD post Ltx. The duration of IBD was median 15 (0-50) years at the time of Ltx and follow-up after Ltx was median 5 (0.3 - 20) years. Macroscopic inflammation was more frequent at the first colonoscopy after Ltx compared to the last colonoscopy before Ltx (153/218 (70%) vs.124/218 (57%), p < 0.001) (figure 1). The number of flares per person years assessed during the first three years after Ltx was higher than during the last three years before Ltx (p < 0.001) (figure 2). According to an overall evaluation of the clinical IBD-activity in each patient from: (a) diagnosis of IBD until Ltx and from (b) Ltx to last follow-up, a higher number of patients had experienced IBD-activity after compared to before Ltx (96/216 (44%) vs. 50/216 (23%) (p < 0.001). However, the cumulative risk for colectomy due to active disease after Ltx was not significantly different from the corresponding risk before Ltx (hazard ratio 0.7, 95% CI 0.3 - 1.7, p = 0.46). When comparing the inflammatory findings by endoscopy before and after Ltx in each patient, the activity of IBD was improved in 37 (17%), unchanged in 95 (44%) and deteriorated in 86 (39%) of patients (figure 1). A multivariate analysis identified age < 20 years at diagnosis of IBD as a significant risk factor for worsened IBD-activity after Ltx, whereas azathioprine showed a protective effect. Conclusion: Our results demonstrate an increase in IBD-activity after liver transplantation with regard to macroscopic inflammation, flares and an overall IBD- evaluation. However, the risk of colectomy due to high disease activity did not change significantly post transplant, which might be related to a relatively limited follow up period. The large amount of patients shown to have a worsened IBD after Ltx illustrates the importance of close follow-up after liver transplantation in order to optimise the treatment of IBD. AGA Abstracts