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Su1357 Non-Surgical Porto-Mesenteric Vein Thrombosis Is Associated With Worse Outcomes in Inflammatory Bowel Diseases
AGA Abstracts
was identified in an additional 43.3% of patients at year 0 and 31.5% at year 5. Major polypharmacy at year 0 was associated with increasing age (44.3 versus 37.3, p <0.001), disability (14.3% versus 5.1%, p = 0.016), functional GI disorders (15. 0% versus 6.0 %, p = 0.021) and psychiatric disease (44.4% versus 12.1%, p<0.001). Major polypharmacy was associated with significantly higher use rates of certain drug classes, including vitamins and minerals (74.2% versus 47.0%, p < 0.001), GI symptomatic drugs (63.6% versus 35.9%, p < 0.001), neuropsychiatric medications (44.7% versus 13.7%, p < 0.001), cardiovascular medications (38.6% versus 8.5%, p < 0.001), and narcotic analgesics (22.1% versus 6.8%, p < 0.001). Over 5 years of follow up, major polypharmacy was not associated with significant differences in the risk of disease flares (61.7 versus 58.9%, p=0.78), therapy escalation (27.8 versus 34.0%, p=0.22), IBD-related hospitalization (39.7 versus 41.4%, p = 0.79), or IBDrelated surgery (25.0% versus 28.2%, p = 0.57). CONCLUSIONS: In this cohort, polypharmacy was present in a substantial proportion of patients with Crohn's disease. Major polypharmacy was associated with increasing age, disability, functional GI disorders, and concomitant psychiatric disease. Over 5 years of follow up, patients with major polypharmacy did not have significant differences in the risk of disease flares, therapy escalation, IBD-related hospitalization, or IBD-related surgery.
studies have adequately assessed whether IBD is an independent risk factor for infectious complications in elderly patients Our aim is to critically analyze the effect of IBD on infectious complications in elderly patients. Methods: A retrospective cohort study was conducted of pts aged 65 yrs and older at a tertiary care center, between 1/1/2007- 11/1/2012, comparing infectious risk in pts with IBD and without IBD. The control group, who were consecutive patients seen in outpatient clinic, were pts aged 65 yrs and older, that were immunocompetent. Pts with diabetes mellitus, rheumatologic diseases, or malignancy were excluded. The use of steroids, TNF inhibitors and immunomodulators were assessed in all pts. All infectious complications were assessed in pts with IBD. Major infections were defined as systemic infections, infections requiring hospitalization, or infections that directly led to the death of the pt. The electronic medical records were reviewed to collect data on demographic information, diagnosis of IBD, and presence of infection. Populations were compared using chi-square and logistic regression analyses. Results: 292 records of pts aged 65 yrs and older were reviewed, of which 146 had IBD and 146 did not have IBD (controls). Of the total pts, 134 (45.9%) had an infection. 66 (45.2%) pts with IBD and 68 (46.6%) pts without IBD had an infection. 39 (29.1%) of the total pts had a major infection, 28 of which were in the IBD cohort. After adjusting for age, the OR for infections in IBD pts was 1.38 (CI 0.82, 2.33). After adjusting for age, the OR for major infections in IBD pts was 7.00 (CI 2.60, 18.85). Conclusion: Although IBD is not a significant independent risk factor for overall infectious complications in elderly pts, it is an independent risk factor for major infections in this population. Major infectious complications, in general, have the potential to cause profound impacts on pts. These findings reinforce the importance of diagnosing and managing infectious complications in elderly IBD pts, given their increased propensity to develop severe infectious complications.
Su1357 Non-Surgical Porto-Mesenteric Vein Thrombosis Is Associated With Worse Outcomes in Inflammatory Bowel Diseases Zubin Arora, Xianrui Wu, Udayakumar Navaneethan, Bo Shen Introduction: Porto-mesenteric vein thrombosis (PVT) is a well recognized complication in inflammatory bowel disease (IBD) patients after intra-abdominal/pelvic surgery, which was not shown to be associated with a worse clinical outcome. However, the impact of nonsurgery-related PVT on the outcome of IBD has not been systematically studied. Aim: To evaluate risk factors for non-surgery-related PVT in IBD patients and the impact of PVT on the outcome of IBD. Methods: In this case-control study, we searched and identified IBD patients with one or more abdominal imaging indicative of PVT and no history of intraabdominal surgery in the preceding 3 months (n=20) from January 2004 to October 2013. The patients were matched for age, sex, and phenotype with IBD controls who had no PVT on abdominal imaging and no prior history of PVT (n=60). Patients with cirrhosis, primary sclerosing cholangitis, and malignancy were excluded. Subsequent IBD-related ER visit, hospital admission or surgery within 12 months after diagnosis of PVT was the primary outcome. Univariate and multivariate analyses were performed. Results: Of the 20 patients in the study group, 6 (30%) had ulcerative colitis and 14 (70%) had Crohn's disease and 11 (55%) were male. There were no significant differences in IBD duration, body mass index, smoking, oral contraceptive use, NSAID use, extra-intestinal manifestations, disease activity or symptomatology between the study and control groups. The risk factors associated with the development of PVT are listed in Table 1. Hypercoagulability workup was available in 11 patients in the study group out of which 5 (45.4%) tested positive. 13 (65%) patients were treated with anticoagulation therapy. Warfarin was used for anticoagulation in 10 (76.9%) and subcutaneous low molecular weight heparin was used in 3 (23.1%) patients. When treated, the duration of anticoagulation was 6 months in 10 (76.9%) patients, 12 months in 2 (15.4%) patients, and lifelong therapy was initiated in 1 (7.7%) patient. At 1year follow-up, PVT patients were more likely to require corticosteroids (47.4% vs. 23.3%, p=0.04), have an IBD-related emergency room visit (26.3% vs. 1.7%, p=0.003), require hospitalization for medical management (60.0% vs. 20.0%, p=0.001) or undergo IBD related surgery (65.0% vs. 26.7%, p=0.003), than the non-PVT controls. There was no statistical difference in rate of poor outcomes between patients who received anticoagulation and those who did not (92.3% vs. 71.4%, p=0.27). The risk factors associated with poor disease outcome (requirement of corticosteroids, ER visit, hospitalization, and surgery) are listed in Table 2. Conclusions: Corticosteroid use in the last 6 months and hospital admission are associated with the development of PVT. The presence of PVT, in addition to other traditional factors, is associated with poor clinical outcome in IBD. Table 1. Multivariate analysis: Risk factors associated with PVT development.
Su1359 Aberrant DNA Methylation of Colonic Serrated Lesions and Subsequent Colorectal Neoplasia in Ulcerative Colitis and Crohn's Colitis David H. Johnson, Mohammed M. Aboelsoud, Tracy C. Yab, Xiaoming Cao, Thomas C. Smyrk, Edward V. Loftus, Douglas W. Mahoney, David A. Ahlquist, John B. Kisiel Background: Serrated epithelial changes (SEC) and sessile serrated adenoma (SSA) in chronic ulcerative colitis (CUC) and Crohn's colitis (CD) are potentially pre-malignant. The molecular phenotype of these lesions is unknown and may influence neoplastic risk. Aim: Measure 1) aberrant DNA methylation and mutation in SEC and SSA in inflammatory bowel disease (IBD) patients (pts) and 2) rate of subsequent adenomatous colorectal neoplasia (CRN) Methods: A cohort of CUC and CD pts with SEC and SSA were identified in tissue archives. DNA was extracted from paraffin-embedded SEC and SSA (serrated-IBD) tissues and age matched frozen colorectal cancers (IBD-CRC) and IBD controls. Quantitative allele-specific real time target and signal amplification (QuARTS) assays measured β-actin, methylated NDRG4 (mNDRG4) and BMP3 (mBMP3). Where sufficient DNA was available, mutant KRAS (7 alleles) was assayed by QuARTS; BRAF and p53 mutations by Sanger sequencing. Serrated IBD pts were followed for development of subsequent CRN, measured by KaplanMeier method (with 95% confidence intervals [CI]). Pts with CRN events or colectomy <3 mos from SEC/SSA diagnosis, or no subsequent colonoscopy, were excluded from time to event analysis. Results: A total of 74 samples were assayed for mBMP3 and mNDRG4 (44 serrated-IBD [34 SEC + 10 SSA], 17 IBD-CRC and 13 IBD-controls). Median age was 55 years (yrs) (interquartile range [IQR] 46-62) and not significantly different among groups. Disease duration was similar for serrated-IBD and for CRC with 18 yrs (12-32) and 20 yrs (9-27), respectively (p=0.8), but was significantly less (2 yrs [0.5-12]) in IBD-controls (p= 0.008, Wilcoxon). KRAS was assayed from 28 serrated lesions (18/34 SEC + 10 SSA) and all IBD-CRC and IBD-controls. Of serrated-IBD samples assayed, BRAF (1/35) and p53 (1/ 20) mutations were too rare for further study. Median β-actin corrected copy number of mBMP3 was 14 (0.3-58) for IBD-CRC, 1.3 (0.02-12) for serrated-IBD, and 0 (0-0) for IBDcontrols (p=0.0003); copies of mNDRG4 were 35 (7-55) for IBD-CRC, 9 (4-18) for serratedIBD and 0 (0-0) for IBD-controls (p<0.0001); mutant KRAS copies were 0.07 (0-12) for IBD-CRC, 0.35 (0.02-8) for serrated IBD and 0 (0-0) for IBD-controls (p<0.001). Sensitivity at >90% specificity among IBD controls was calculated for each marker (table). Of 21 serrated-IBD pts with at least 1 subsequent colonoscopy, all were positive for mNDRG4; the cumulative incidence of subsequent CRN was 19% (95% CI 6-43%) at 1 yr and 38% (95% CI 19-61%) at 2 yrs. Institutional IBD CRN rate was previously estimated at 6%/yr. Conclusions: Serrated IBD lesions are aberrantly methylated and contain frequent KRAS mutations. Although caution is warranted from small sample size, the high rate of subsequent adenomatous dysplasia observed in these pts may be of potential relevance for use in surveillance algorithms. Tissue detection rate of IBD-associated neoplasms at >90% specificity
Table 2. Multivariate analysis: Risk factors associated with 1-yr poor outcomes (IBD-related ER visit, hospitalization or surgery)
IBD, inflammatory bowel disease; CRC, colorectal cancer *Sufficient DNA was not available for KRAS assay on 16 samples ** β-actin did not amplify on a single KRAS assay
Su1358 IBD Is an Independent Risk Factor for Major Infectious Complications in Elderly Patients Christina Tofani, Teresa Valentin, Ann Tierney, Gary R. Lichtenstein
Su1360 Effect of a Low-Complex Carbohydrate Diet on Inflammatory Bowel Disease Robynne K. Chutkan, Eugenia R. Hamshaw, Farah Ashraf
Background: Infections cause increased morbidity and mortality in elderly patients. Infectious diseases also lead to more hospitalizations in the elderly. Patients with IBD are at an increased risk for infectious complications. Current literature suggests that the increased risk of infection observed in IBD patients, is in part due to their use of immunosuppressive agents. No recent
AGA Abstracts
BACKGROUND & AIMS: The relationship between diet and the activity and symptomatology of inflammatory bowel disease (IBD) is unclear. The aim of this study was to assess the effectiveness of the Specific Carbohydrate Diet (SCD), a low-complex carbohydrate diet that
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was identified in an additional 43.3% of patients at year 0 and 31.5% at year 5. Major polypharmacy at year 0 was associated with increasing age (44.3 versus 37.3, p <0.001), disability (14.3% versus 5.1%, p = 0.016), functional GI disorders (15. 0% versus 6.0 %, p = 0.021) and psychiatric disease (44.4% versus 12.1%, p<0.001). Major polypharmacy was associated with significantly higher use rates of certain drug classes, including vitamins and minerals (74.2% versus 47.0%, p < 0.001), GI symptomatic drugs (63.6% versus 35.9%, p < 0.001), neuropsychiatric medications (44.7% versus 13.7%, p < 0.001), cardiovascular medications (38.6% versus 8.5%, p < 0.001), and narcotic analgesics (22.1% versus 6.8%, p < 0.001). Over 5 years of follow up, major polypharmacy was not associated with significant differences in the risk of disease flares (61.7 versus 58.9%, p=0.78), therapy escalation (27.8 versus 34.0%, p=0.22), IBD-related hospitalization (39.7 versus 41.4%, p = 0.79), or IBDrelated surgery (25.0% versus 28.2%, p = 0.57). CONCLUSIONS: In this cohort, polypharmacy was present in a substantial proportion of patients with Crohn's disease. Major polypharmacy was associated with increasing age, disability, functional GI disorders, and concomitant psychiatric disease. Over 5 years of follow up, patients with major polypharmacy did not have significant differences in the risk of disease flares, therapy escalation, IBD-related hospitalization, or IBD-related surgery.
studies have adequately assessed whether IBD is an independent risk factor for infectious complications in elderly patients Our aim is to critically analyze the effect of IBD on infectious complications in elderly patients. Methods: A retrospective cohort study was conducted of pts aged 65 yrs and older at a tertiary care center, between 1/1/2007- 11/1/2012, comparing infectious risk in pts with IBD and without IBD. The control group, who were consecutive patients seen in outpatient clinic, were pts aged 65 yrs and older, that were immunocompetent. Pts with diabetes mellitus, rheumatologic diseases, or malignancy were excluded. The use of steroids, TNF inhibitors and immunomodulators were assessed in all pts. All infectious complications were assessed in pts with IBD. Major infections were defined as systemic infections, infections requiring hospitalization, or infections that directly led to the death of the pt. The electronic medical records were reviewed to collect data on demographic information, diagnosis of IBD, and presence of infection. Populations were compared using chi-square and logistic regression analyses. Results: 292 records of pts aged 65 yrs and older were reviewed, of which 146 had IBD and 146 did not have IBD (controls). Of the total pts, 134 (45.9%) had an infection. 66 (45.2%) pts with IBD and 68 (46.6%) pts without IBD had an infection. 39 (29.1%) of the total pts had a major infection, 28 of which were in the IBD cohort. After adjusting for age, the OR for infections in IBD pts was 1.38 (CI 0.82, 2.33). After adjusting for age, the OR for major infections in IBD pts was 7.00 (CI 2.60, 18.85). Conclusion: Although IBD is not a significant independent risk factor for overall infectious complications in elderly pts, it is an independent risk factor for major infections in this population. Major infectious complications, in general, have the potential to cause profound impacts on pts. These findings reinforce the importance of diagnosing and managing infectious complications in elderly IBD pts, given their increased propensity to develop severe infectious complications.
Su1357 Non-Surgical Porto-Mesenteric Vein Thrombosis Is Associated With Worse Outcomes in Inflammatory Bowel Diseases Zubin Arora, Xianrui Wu, Udayakumar Navaneethan, Bo Shen Introduction: Porto-mesenteric vein thrombosis (PVT) is a well recognized complication in inflammatory bowel disease (IBD) patients after intra-abdominal/pelvic surgery, which was not shown to be associated with a worse clinical outcome. However, the impact of nonsurgery-related PVT on the outcome of IBD has not been systematically studied. Aim: To evaluate risk factors for non-surgery-related PVT in IBD patients and the impact of PVT on the outcome of IBD. Methods: In this case-control study, we searched and identified IBD patients with one or more abdominal imaging indicative of PVT and no history of intraabdominal surgery in the preceding 3 months (n=20) from January 2004 to October 2013. The patients were matched for age, sex, and phenotype with IBD controls who had no PVT on abdominal imaging and no prior history of PVT (n=60). Patients with cirrhosis, primary sclerosing cholangitis, and malignancy were excluded. Subsequent IBD-related ER visit, hospital admission or surgery within 12 months after diagnosis of PVT was the primary outcome. Univariate and multivariate analyses were performed. Results: Of the 20 patients in the study group, 6 (30%) had ulcerative colitis and 14 (70%) had Crohn's disease and 11 (55%) were male. There were no significant differences in IBD duration, body mass index, smoking, oral contraceptive use, NSAID use, extra-intestinal manifestations, disease activity or symptomatology between the study and control groups. The risk factors associated with the development of PVT are listed in Table 1. Hypercoagulability workup was available in 11 patients in the study group out of which 5 (45.4%) tested positive. 13 (65%) patients were treated with anticoagulation therapy. Warfarin was used for anticoagulation in 10 (76.9%) and subcutaneous low molecular weight heparin was used in 3 (23.1%) patients. When treated, the duration of anticoagulation was 6 months in 10 (76.9%) patients, 12 months in 2 (15.4%) patients, and lifelong therapy was initiated in 1 (7.7%) patient. At 1year follow-up, PVT patients were more likely to require corticosteroids (47.4% vs. 23.3%, p=0.04), have an IBD-related emergency room visit (26.3% vs. 1.7%, p=0.003), require hospitalization for medical management (60.0% vs. 20.0%, p=0.001) or undergo IBD related surgery (65.0% vs. 26.7%, p=0.003), than the non-PVT controls. There was no statistical difference in rate of poor outcomes between patients who received anticoagulation and those who did not (92.3% vs. 71.4%, p=0.27). The risk factors associated with poor disease outcome (requirement of corticosteroids, ER visit, hospitalization, and surgery) are listed in Table 2. Conclusions: Corticosteroid use in the last 6 months and hospital admission are associated with the development of PVT. The presence of PVT, in addition to other traditional factors, is associated with poor clinical outcome in IBD. Table 1. Multivariate analysis: Risk factors associated with PVT development.
Su1359 Aberrant DNA Methylation of Colonic Serrated Lesions and Subsequent Colorectal Neoplasia in Ulcerative Colitis and Crohn's Colitis David H. Johnson, Mohammed M. Aboelsoud, Tracy C. Yab, Xiaoming Cao, Thomas C. Smyrk, Edward V. Loftus, Douglas W. Mahoney, David A. Ahlquist, John B. Kisiel Background: Serrated epithelial changes (SEC) and sessile serrated adenoma (SSA) in chronic ulcerative colitis (CUC) and Crohn's colitis (CD) are potentially pre-malignant. The molecular phenotype of these lesions is unknown and may influence neoplastic risk. Aim: Measure 1) aberrant DNA methylation and mutation in SEC and SSA in inflammatory bowel disease (IBD) patients (pts) and 2) rate of subsequent adenomatous colorectal neoplasia (CRN) Methods: A cohort of CUC and CD pts with SEC and SSA were identified in tissue archives. DNA was extracted from paraffin-embedded SEC and SSA (serrated-IBD) tissues and age matched frozen colorectal cancers (IBD-CRC) and IBD controls. Quantitative allele-specific real time target and signal amplification (QuARTS) assays measured β-actin, methylated NDRG4 (mNDRG4) and BMP3 (mBMP3). Where sufficient DNA was available, mutant KRAS (7 alleles) was assayed by QuARTS; BRAF and p53 mutations by Sanger sequencing. Serrated IBD pts were followed for development of subsequent CRN, measured by KaplanMeier method (with 95% confidence intervals [CI]). Pts with CRN events or colectomy <3 mos from SEC/SSA diagnosis, or no subsequent colonoscopy, were excluded from time to event analysis. Results: A total of 74 samples were assayed for mBMP3 and mNDRG4 (44 serrated-IBD [34 SEC + 10 SSA], 17 IBD-CRC and 13 IBD-controls). Median age was 55 years (yrs) (interquartile range [IQR] 46-62) and not significantly different among groups. Disease duration was similar for serrated-IBD and for CRC with 18 yrs (12-32) and 20 yrs (9-27), respectively (p=0.8), but was significantly less (2 yrs [0.5-12]) in IBD-controls (p= 0.008, Wilcoxon). KRAS was assayed from 28 serrated lesions (18/34 SEC + 10 SSA) and all IBD-CRC and IBD-controls. Of serrated-IBD samples assayed, BRAF (1/35) and p53 (1/ 20) mutations were too rare for further study. Median β-actin corrected copy number of mBMP3 was 14 (0.3-58) for IBD-CRC, 1.3 (0.02-12) for serrated-IBD, and 0 (0-0) for IBDcontrols (p=0.0003); copies of mNDRG4 were 35 (7-55) for IBD-CRC, 9 (4-18) for serratedIBD and 0 (0-0) for IBD-controls (p<0.0001); mutant KRAS copies were 0.07 (0-12) for IBD-CRC, 0.35 (0.02-8) for serrated IBD and 0 (0-0) for IBD-controls (p<0.001). Sensitivity at >90% specificity among IBD controls was calculated for each marker (table). Of 21 serrated-IBD pts with at least 1 subsequent colonoscopy, all were positive for mNDRG4; the cumulative incidence of subsequent CRN was 19% (95% CI 6-43%) at 1 yr and 38% (95% CI 19-61%) at 2 yrs. Institutional IBD CRN rate was previously estimated at 6%/yr. Conclusions: Serrated IBD lesions are aberrantly methylated and contain frequent KRAS mutations. Although caution is warranted from small sample size, the high rate of subsequent adenomatous dysplasia observed in these pts may be of potential relevance for use in surveillance algorithms. Tissue detection rate of IBD-associated neoplasms at >90% specificity
Table 2. Multivariate analysis: Risk factors associated with 1-yr poor outcomes (IBD-related ER visit, hospitalization or surgery)
IBD, inflammatory bowel disease; CRC, colorectal cancer *Sufficient DNA was not available for KRAS assay on 16 samples ** β-actin did not amplify on a single KRAS assay
Su1358 IBD Is an Independent Risk Factor for Major Infectious Complications in Elderly Patients Christina Tofani, Teresa Valentin, Ann Tierney, Gary R. Lichtenstein
Su1360 Effect of a Low-Complex Carbohydrate Diet on Inflammatory Bowel Disease Robynne K. Chutkan, Eugenia R. Hamshaw, Farah Ashraf
Background: Infections cause increased morbidity and mortality in elderly patients. Infectious diseases also lead to more hospitalizations in the elderly. Patients with IBD are at an increased risk for infectious complications. Current literature suggests that the increased risk of infection observed in IBD patients, is in part due to their use of immunosuppressive agents. No recent
AGA Abstracts
BACKGROUND & AIMS: The relationship between diet and the activity and symptomatology of inflammatory bowel disease (IBD) is unclear. The aim of this study was to assess the effectiveness of the Specific Carbohydrate Diet (SCD), a low-complex carbohydrate diet that
S-446