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Sa1293 Serum Cytokine Profiles in Patients With C. difficile Associated-Diarrhea and Non-C. difficile Antibiotic Associated Diarrhea
AGA Abstracts
factor. The serum concentrations for all the studied cytokines were compared according to these outcomes through rank sum tests. Whenever a statistically significant difference with a p<0.01 was found a logistic regression analysis of the predictor to the outcome was performed. A ROC analysis was performed to determine the area under the curve and potential cut-off values for the predictor. Results: Out of the 45 CDAD patients, 42 (93.3%) were followed-up for 60 days, 3 were lost to follow-up. The frequency of the outcome events were the following: 8 (19%) of 42 died, 15 (35.7%) of 42 had a recurrence and 11 (24.4%) of 45 were admitted to the ICU. There were no statistically significant (p<0.05) differences in the serum concentration of the 17 cytokines assayed for recurrence or ICU admission. The concentrations of the anti-inflammatory cytokine IL-10 were borderline significantly higher in patients who died compared to patient who did not (9.9±3.3 vs. 3.6±0.7, p=0.04). The serum concentrations of the regulatory cytokine IL-27 were significantly elevated in patients who died compared to those who did not (2.8±0.4 vs. 1.3±0.1, p=0.0005, see graph 1). On logistic regression, for each rise of 1.0 pg/mL of IL-27 the odds of dying increased by 10.4 (CI 95% 2.0-54.6). The area under the curve for IL-27 in predicting death was 0.90 (see graph 2). Conclusions: The serum concentration of the Th1 regulatory cytokine IL-27 is a promising biomarker to predict death in patients with CDAD. Nonetheless, the 60-day overall mortality may be more reflective of the patient's overall health condition than of the specific immune response to C. difficile. Further prospective studies on the utility of IL-27 as a predictor on death in CDAD and in non-CDAD hospital patients are warranted.
elevations of pro-inflammatory and regulatory cytokines as compared to the healthy controls. These differences notwithstanding, there are no statistically significant cytokine pattern differences between the CDAD and the AAD groups. Thus, the observed cytokine elevations appear predominantly to reflect the patient's underlying diseases and do not appear to be specific for CDAD. Studied cytokine profiles do not differentiate CDAD from AAD and do not offer information about specific pathophysiology nor do they represent promising biomarkers . These findings highlight the importance of having appropriate control groups in bedside-to-bench studies.
Sa1294 Prognostic Significance of Deprivation in Patients Undergoing Emergency Laparotomy Jolene Witherspoon, Anna Powell-Chandler, Alec Aslanyan, Chris Brown, Alex Karran, Charlotte E. Thomas, Wyn G. Lewis, Margaret Coakley Objective: Patients requiring emergency surgery are among the sickest managed by health services; frequently elderly, frail and with significant co-morbidity, the risk of death or serious complication is often unacceptably high. Deprivation is a broad concept, which includes limited access to the opportunities and resources which society might expect, such as good health, a clean and safe living environment, and protection from crime. The aim of this study was to determine the influence of the Index of Multiple Deprivation (IMD) and Health deprivation (HD) on emergency laparotomy outcome. Methods: Consecutive 285 patients [median age 69 (18-93) 141m, 144f] undergoing emergency laparotomy in a major UK teaching hospital during a single calendar year were studied prospectively and deprivation scores calculated using the IMD of Welsh Government. Primary outcome measure was post-operative 30 day in-hospital mortality. Results: Operative 30 day mortality was 18.2%, and overall in-hospital mortality 23.2%. On univariable analysis operative mortality was related to ASA grade (p<0.001), post-operative placement (Critical Care Unit vs. General Ward, p< 0.001), age (<70 yr vs. >70 yr 9.6 vs. 28.7%, p<0.001), IMD quintile [UQ (least deprived) 11.6% vs. LQ (most deprived) 21.5%, p=0.027], HD quintile (UQ 11.5% vs. LQ 23.3%, p=0.049), but not admitting speciality (p=0.052), time of day or time of night of surgery (p=0.178), or week day of surgery (p=0.961). On multivariable analysis, ASA grade (HR 2.896, 95% CI 1.599-5.246, p<0.0001), age (HR 1.043, 95% CI 1.008-1.078, p= 0.015), post-operative placement (HR 1.805, 95% CI 1.040-3.134, p=0.036), and WIMD quintile (HR 0.746, CI 0.559-0.995, p=0.046) were independently associated with operative mortality. Conclusion: Deprivation is an important and independent prognostic indicator of post emergency laparotomy mortality, with patients residing in deprived geographical areas twice as likely to suffer serious and fatal complications. At risk patients should enter targeted enhanced recovery protocols. Sa1295 Socioeconomic Differences in the Risk of Developing Clostridium difficile Diarrhea: A Case-Control Study Oforbuike Ewelukwa, Bahar Cheema, Sarita Metzger, Ronald J. Markert, Salma Akram BACKGROUND: The rising incidence of Clostridium difficile (CD) diarrhea has led to increased search for novel risk factors to assist in disease prevention and to reduce associated morbidity, mortality and cost. Several epidemiological risk factors have been identified but little is known about the effect of socioeconomic (SE) or geographic variables on the risk of developing CD. AIM: To assess the SE and geographic differences in the risk of developing CD. METHODS: Using the Veteran Affairs database, we identified 174 patients with laboratory confirmed CD between 2000 and 2011. Suitable 176 controls matched 1:1 for race, gender and year of hospital admission were identified. Using the computerized medical records, the zip codes of the patients were collected. Using the 2010 US Census data, information on the median household income (MHHI) and population size associated with the zip codes were collected. We divided the patients into SE quartiles from the poorest to the richest. Using a cutoff of $45,551, the two richest quartiles were combined while the two poorest quartiles were also combined. IBM SPSS was used to determine univariate predictors of CD and multiple logistic regression to assess whether SE was an independent risk factor for developing CD while controlling for age, albumin, hemoglobin, median household income, recent hospitalization (previous 3 months), recent antibiotic use (previous 3 months), proton pump inhibitor (PPI) use, steroid use, and chronic kidney disease (CKD). RESULTS: The highest two SE quartiles (living in regions earning > $45,551) were more likely to develop CD (odds ratio = 1.88 (95% CI = 1.02 to 3.47, p<0.044) after controlling for other variables (Table 1). Among CD cases, the highest two SE quartiles were more likely to have longer length of hospital stay (26.9±34.1 vs. 17.5±18.3). Among the CD cases, there was no significant SE quartile differences for age, PPI use, community/healthcare acquired CD, recurrences of CD, history of cancer, or other co-morbidities. CONCLUSIONS: Our study shows that patients living in regions with higher SE status (MHHI > $45,551) were more likely to have CD than those living in regions with lower SE status (MHHI < $45,551). Table 1: Multiple logistic regression of risk factors for development of CD
Sa1293 Serum Cytokine Profiles in Patients With C. difficile Associated-Diarrhea and Non-C. difficile Antibiotic Associated Diarrhea Javier A. Villafuerte-Galvez, Ishan J. Patel, Hua Xu, Xiaotong Yang, Xinhua Chen, Ciaran P. Kelly Background: Immune activation is a prominent event in C. difficile associated diarrhea (CDAD). Serum cytokine profiles may reflect, at a systemic level, the inflammatory processes that occur at the tissue level following toxin exposure. Defining cytokine profiles in patients with CDAD can inform our understanding of disease pathophysiology and identify potential disease biomarkers. Methods: Sera were collected prospectively from a cohort of CDAD and non-C. difficile antibiotic associated diarrhea (AAD) inpatients. Sera from young healthy controls (HC) were collected during routine physicals. Sera were assayed for concentrations of 17 cytokines using a Millipore® Th17 multiplex system. Concentrations were screened for differences across three groups with a Kruskal-Wallis (KW) test. The cytokines with a statistically significant KW test underwent pairwise comparisons through the rank sum test, adjusted for multiple testing by Bonferroni correction. Results: The sample consisted of 45, 15 and 35 patients in the CDAD, AAD, and HC groups respectively. There were differences across the three groups for nine out of 17 cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-15, IL-21, IL-27, TNF-α) with highly statistically significant differences observed for several of the cytokines. IL-6, IL-10, IL-15, IL-21, IL-27 and TNF-α had significantly elevated serum concentrations in CDAD versus HC. This cytokine elevation pattern involved simultaneously pro-inflammatory cytokines (IL-6, IL-15, TNF-α), as well as regulatory (IL-21, IL-27) cytokines. This raised the question of whether this pattern were specific to CDAD or a manifestation of severe underlying disease which CDAD often complicates. This led us to study an additional control group (AAD). For IL-6, IL-10, IL-21, IL-27 and TNF-α both the CDAD and AAD groups had significantly higher mean levels than the HC group. For IL-15 the CDAD group alone had significantly higher levels than the HC group. For IL-1β, IL-2 and IL-4 the AAD group alone had significantly higher levels that the HC group. There was no significant difference between the CDAD and AAD groups for any of the 17 cytokines (see table). Conclusions: In inpatients with both CDAD and AAD there are consistent, marked
AGA Abstracts
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factor. The serum concentrations for all the studied cytokines were compared according to these outcomes through rank sum tests. Whenever a statistically significant difference with a p<0.01 was found a logistic regression analysis of the predictor to the outcome was performed. A ROC analysis was performed to determine the area under the curve and potential cut-off values for the predictor. Results: Out of the 45 CDAD patients, 42 (93.3%) were followed-up for 60 days, 3 were lost to follow-up. The frequency of the outcome events were the following: 8 (19%) of 42 died, 15 (35.7%) of 42 had a recurrence and 11 (24.4%) of 45 were admitted to the ICU. There were no statistically significant (p<0.05) differences in the serum concentration of the 17 cytokines assayed for recurrence or ICU admission. The concentrations of the anti-inflammatory cytokine IL-10 were borderline significantly higher in patients who died compared to patient who did not (9.9±3.3 vs. 3.6±0.7, p=0.04). The serum concentrations of the regulatory cytokine IL-27 were significantly elevated in patients who died compared to those who did not (2.8±0.4 vs. 1.3±0.1, p=0.0005, see graph 1). On logistic regression, for each rise of 1.0 pg/mL of IL-27 the odds of dying increased by 10.4 (CI 95% 2.0-54.6). The area under the curve for IL-27 in predicting death was 0.90 (see graph 2). Conclusions: The serum concentration of the Th1 regulatory cytokine IL-27 is a promising biomarker to predict death in patients with CDAD. Nonetheless, the 60-day overall mortality may be more reflective of the patient's overall health condition than of the specific immune response to C. difficile. Further prospective studies on the utility of IL-27 as a predictor on death in CDAD and in non-CDAD hospital patients are warranted.
elevations of pro-inflammatory and regulatory cytokines as compared to the healthy controls. These differences notwithstanding, there are no statistically significant cytokine pattern differences between the CDAD and the AAD groups. Thus, the observed cytokine elevations appear predominantly to reflect the patient's underlying diseases and do not appear to be specific for CDAD. Studied cytokine profiles do not differentiate CDAD from AAD and do not offer information about specific pathophysiology nor do they represent promising biomarkers . These findings highlight the importance of having appropriate control groups in bedside-to-bench studies.
Sa1294 Prognostic Significance of Deprivation in Patients Undergoing Emergency Laparotomy Jolene Witherspoon, Anna Powell-Chandler, Alec Aslanyan, Chris Brown, Alex Karran, Charlotte E. Thomas, Wyn G. Lewis, Margaret Coakley Objective: Patients requiring emergency surgery are among the sickest managed by health services; frequently elderly, frail and with significant co-morbidity, the risk of death or serious complication is often unacceptably high. Deprivation is a broad concept, which includes limited access to the opportunities and resources which society might expect, such as good health, a clean and safe living environment, and protection from crime. The aim of this study was to determine the influence of the Index of Multiple Deprivation (IMD) and Health deprivation (HD) on emergency laparotomy outcome. Methods: Consecutive 285 patients [median age 69 (18-93) 141m, 144f] undergoing emergency laparotomy in a major UK teaching hospital during a single calendar year were studied prospectively and deprivation scores calculated using the IMD of Welsh Government. Primary outcome measure was post-operative 30 day in-hospital mortality. Results: Operative 30 day mortality was 18.2%, and overall in-hospital mortality 23.2%. On univariable analysis operative mortality was related to ASA grade (p<0.001), post-operative placement (Critical Care Unit vs. General Ward, p< 0.001), age (<70 yr vs. >70 yr 9.6 vs. 28.7%, p<0.001), IMD quintile [UQ (least deprived) 11.6% vs. LQ (most deprived) 21.5%, p=0.027], HD quintile (UQ 11.5% vs. LQ 23.3%, p=0.049), but not admitting speciality (p=0.052), time of day or time of night of surgery (p=0.178), or week day of surgery (p=0.961). On multivariable analysis, ASA grade (HR 2.896, 95% CI 1.599-5.246, p<0.0001), age (HR 1.043, 95% CI 1.008-1.078, p= 0.015), post-operative placement (HR 1.805, 95% CI 1.040-3.134, p=0.036), and WIMD quintile (HR 0.746, CI 0.559-0.995, p=0.046) were independently associated with operative mortality. Conclusion: Deprivation is an important and independent prognostic indicator of post emergency laparotomy mortality, with patients residing in deprived geographical areas twice as likely to suffer serious and fatal complications. At risk patients should enter targeted enhanced recovery protocols. Sa1295 Socioeconomic Differences in the Risk of Developing Clostridium difficile Diarrhea: A Case-Control Study Oforbuike Ewelukwa, Bahar Cheema, Sarita Metzger, Ronald J. Markert, Salma Akram BACKGROUND: The rising incidence of Clostridium difficile (CD) diarrhea has led to increased search for novel risk factors to assist in disease prevention and to reduce associated morbidity, mortality and cost. Several epidemiological risk factors have been identified but little is known about the effect of socioeconomic (SE) or geographic variables on the risk of developing CD. AIM: To assess the SE and geographic differences in the risk of developing CD. METHODS: Using the Veteran Affairs database, we identified 174 patients with laboratory confirmed CD between 2000 and 2011. Suitable 176 controls matched 1:1 for race, gender and year of hospital admission were identified. Using the computerized medical records, the zip codes of the patients were collected. Using the 2010 US Census data, information on the median household income (MHHI) and population size associated with the zip codes were collected. We divided the patients into SE quartiles from the poorest to the richest. Using a cutoff of $45,551, the two richest quartiles were combined while the two poorest quartiles were also combined. IBM SPSS was used to determine univariate predictors of CD and multiple logistic regression to assess whether SE was an independent risk factor for developing CD while controlling for age, albumin, hemoglobin, median household income, recent hospitalization (previous 3 months), recent antibiotic use (previous 3 months), proton pump inhibitor (PPI) use, steroid use, and chronic kidney disease (CKD). RESULTS: The highest two SE quartiles (living in regions earning > $45,551) were more likely to develop CD (odds ratio = 1.88 (95% CI = 1.02 to 3.47, p<0.044) after controlling for other variables (Table 1). Among CD cases, the highest two SE quartiles were more likely to have longer length of hospital stay (26.9±34.1 vs. 17.5±18.3). Among the CD cases, there was no significant SE quartile differences for age, PPI use, community/healthcare acquired CD, recurrences of CD, history of cancer, or other co-morbidities. CONCLUSIONS: Our study shows that patients living in regions with higher SE status (MHHI > $45,551) were more likely to have CD than those living in regions with lower SE status (MHHI < $45,551). Table 1: Multiple logistic regression of risk factors for development of CD
Sa1293 Serum Cytokine Profiles in Patients With C. difficile Associated-Diarrhea and Non-C. difficile Antibiotic Associated Diarrhea Javier A. Villafuerte-Galvez, Ishan J. Patel, Hua Xu, Xiaotong Yang, Xinhua Chen, Ciaran P. Kelly Background: Immune activation is a prominent event in C. difficile associated diarrhea (CDAD). Serum cytokine profiles may reflect, at a systemic level, the inflammatory processes that occur at the tissue level following toxin exposure. Defining cytokine profiles in patients with CDAD can inform our understanding of disease pathophysiology and identify potential disease biomarkers. Methods: Sera were collected prospectively from a cohort of CDAD and non-C. difficile antibiotic associated diarrhea (AAD) inpatients. Sera from young healthy controls (HC) were collected during routine physicals. Sera were assayed for concentrations of 17 cytokines using a Millipore® Th17 multiplex system. Concentrations were screened for differences across three groups with a Kruskal-Wallis (KW) test. The cytokines with a statistically significant KW test underwent pairwise comparisons through the rank sum test, adjusted for multiple testing by Bonferroni correction. Results: The sample consisted of 45, 15 and 35 patients in the CDAD, AAD, and HC groups respectively. There were differences across the three groups for nine out of 17 cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-15, IL-21, IL-27, TNF-α) with highly statistically significant differences observed for several of the cytokines. IL-6, IL-10, IL-15, IL-21, IL-27 and TNF-α had significantly elevated serum concentrations in CDAD versus HC. This cytokine elevation pattern involved simultaneously pro-inflammatory cytokines (IL-6, IL-15, TNF-α), as well as regulatory (IL-21, IL-27) cytokines. This raised the question of whether this pattern were specific to CDAD or a manifestation of severe underlying disease which CDAD often complicates. This led us to study an additional control group (AAD). For IL-6, IL-10, IL-21, IL-27 and TNF-α both the CDAD and AAD groups had significantly higher mean levels than the HC group. For IL-15 the CDAD group alone had significantly higher levels than the HC group. For IL-1β, IL-2 and IL-4 the AAD group alone had significantly higher levels that the HC group. There was no significant difference between the CDAD and AAD groups for any of the 17 cytokines (see table). Conclusions: In inpatients with both CDAD and AAD there are consistent, marked
AGA Abstracts
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