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Association of CD14 rs2569190 polymorphism with mortality in shock septic patients who underwent major cardiac or abdominal surgery: A retrospective study.

ABSTRACT: The aim of this study was to investigate the relationship between the CD14 rs2569190 polymorphism and death related to septic shock in white European patients who underwent major cardiac or abdominal surgery. We carried out a retrospective study in 205 septic shock patients. The septic shock diagnosis was established by international consensus definitions. The outcome variable was the death within 28, 60 and 90 days after septic shock diagnosis. The CD14 rs2569190 polymorphism was analyzed by Agena Bioscience's MassARRAY platform. For the genetic association analysis with survival was selected a recessive inheritance model (GG vs. AA/AG). One hundred thirteen out of 205 patients (55.1%) died with a survival median of 39 days (95%CI?=?30.6; 47.4). Patients with rs2569190 GG genotype had shorter survival probability than rs2569190 AA/AG genotype at 60 days (62.3% vs 50%; p?=?0.035), and 90 days (62.3% vs 52.6%; p?=?0.046). The rs2569190 GG genotype was associated with increased risk of septic shock-related death in the first 60 days (adjusted hazard ratio (aHR)?=?1.67; p?=?0.016) and 90 days (aHR?=?1.64; p?=?0.020) compared to rs2569190 AA/AG genotype. In conclusion, the presence of CD14 rs2569190 GG genotype was associated with death in shock septic patients who underwent major surgery. Further studies with bigger sample size are required to verify this relationship.

SUBMITTER: Jimenez-Sousa MA

PROVIDER: S-EPMC5807421 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Association of CD14 rs2569190 polymorphism with mortality in shock septic patients who underwent major cardiac or abdominal surgery: A retrospective study.

Jiménez-Sousa María Ángeles MÁ Liu Pilar P Medrano Luz María LM Fernández-Rodríguez Amanda A Almansa Raquel R Gómez-Sánchez Esther E Rico Lucía L Lorenzo Mario M Fadrique Alejandra A Tamayo Eduardo E Resino Salvador S

Scientific reports 20180209 1

The aim of this study was to investigate the relationship between the CD14 rs2569190 polymorphism and death related to septic shock in white European patients who underwent major cardiac or abdominal surgery. We carried out a retrospective study in 205 septic shock patients. The septic shock diagnosis was established by international consensus definitions. The outcome variable was the death within 28, 60 and 90 days after septic shock diagnosis. The CD14 rs2569190 polymorphism was analyzed by Ag ...[more]

PMID: 29426837

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Project description:BackgroundSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, being the primary cause of death from infection, especially if not recognized and treated promptly. The aim of this study was to analyze whether IL-6 rs1800795 polymorphism is associated with septic shock-related death in European white patients who underwent major surgery.MethodsWe performed a retrospective study on 202 septic shock patients who underwent major cardiac or abdominal surgery. The septic shock was established according to the international septic shock definition. The primary outcome variable was the death within 90 days after diagnosis of septic shock. The IL-6 rs1800795 polymorphism was genotyped by Sequenom's MassARRAY platform.ResultsThe median age of the patients was 73 years, 63.4% were male, and more than 40% of patients had heart disease and hypertension. Overall, the survival analysis showed that 111 (55%) patients died with a survival median of 39 days (95% CI 30.7; 47.2). The genetic analysis association with survival was performed under a recessive genetic model (CC vs. GG/CG). Patients with IL-6 rs1800795 CC genotype had higher mortality rate than the IL-6 rs1800795 GG/CG genotype at days 7 [31.6% (6/19) vs. 10.4% (19/183); log-rank test (p = 0.005)] and 28 [57.9% (11/19) vs. 33.3% (61/183); log-rank test (p = 0.009)], and 90 [68.4% (13/19) vs. 53.5% (98/183); log-rank test (p = 0.006)]. The IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death during the first 7 days [adjusted hazard ratio (aHR 4.65; p = 0.002), 28 days (aHR 2.50; p = 0.006), and 90 days (aHR 2.28; p = 0.006)] with septic shock. When patients were stratified by type of surgery, those with IL-6 rs1800795 CC genotype who underwent cardiac surgery had higher risk of death during the first 7 days (aHR 18.39; p = 0.001) and 28 days (aHR 6.1; p = 0.025) than IL-6 rs1800795 GG/GC carrier, whereas patients with IL-6 rs1800795 CC genotype who underwent abdominal surgery had higher risk of death during all follow-up (aHR 1.98; p = 0.050) than IL-6 rs1800795 GG/GC carrier.ConclusionsThe presence of IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death in patients who underwent major cardiac or abdominal surgery. These findings need robust validation in bigger independent cohorts.

Project description:Importance:Body mass index (BMI) has been the most common obesity measure to assess perioperative risk; however, cardiometabolic risk is associated with the burden of visceral fat. Definitive evidence on the association of visceral fat measures, such as waist circumference and waist-to-hip ratio (WHR), with postoperative complications is lacking. Objective:To compare the value of waist circumference with the value WHR and BMI in predicting adverse outcomes, including major septic complications and persistent disability, following major abdominal surgery. Design, Setting, and Participants:This planned secondary analysis of the Restrictive vs Liberal Fluid Therapy for Major Abdominal Surgery (RELIEF) randomized clinical trial took place at 47 centers in 7 countries between October 2013 and September 2016, with 90-day follow-up. A total of 2954 adult RELIEF participants were coenrolled in this secondary analysis. Data analysis took place from December 2018 to September 2019. Exposures:Waist circumference, WHR, and BMI measurements. Main Outcomes and Measures:The primary outcomes were 30-day major septic complications and 90-day persistent disability or death. Results:Of 2954 eligible participants, 2755 were included (mean [SD] age, 65.9 [12.9] years; 1426 [51.8%] men) in the final analysis. A total of 564 participants (20.6%) experienced at least 1 major septic complication within 30 days after surgery (sepsis, 265 [9.7%]; surgical site infection, 409 [14.9%]; anastomotic leak, 78 [2.8%]; pneumonia, 104 [3.8%]). Waist circumference had a statistically significantly larger odds ratio (OR) and discrimination indices as well as a smaller prediction error than WHR or BMI for 30-day major septic complications or death (waist circumference: OR, 1.44; 95% CI, 1.28-1.62; P?<?.001; area under the receiver operating characteristic curve, 0.641; net reclassification index, 0.266; integrated discrimination improvement [score?×?104], 152.98; Brier score, 0.162; WHR: OR, 1.15; 95% CI, 1.03-1.28; P?=?.01; area under the receiver operating characteristic curve, 0.621; net classification index, 0.199; integrated discrimination improvement [score?×?104], 28.47; Brier score, 0.164; BMI: OR, 1.33; 95% CI, 1.17-1.50; P?<?.001; area under the receiver operating characteristic curve, 0.629; net reclassification index, 0.205; integrated discrimination improvement [score?×?104], 85.61; Brier score, 0.163) but not for any other outcomes. Conclusions and Relevance:In this secondary analysis of the RELIEF randomized clinical trial, waist circumference was observed to be superior to other adiposity indices in predicting 30-day major septic complications alone or in conjunction with death following elective major abdominal surgery. Findings suggest that waist circumference is a useful adiposity measure that should be incorporated in preoperative risk assessment for such complications. Trial Registration:ClinicalTrials.gov identifier: NCT01424150.

Project description:BackgroundPatients with septic shock have the highest risk of death from sepsis, however, racial disparities in mortality outcomes in this cohort have not been rigorously investigated. Our objective was to describe the association between race/ethnicity and mortality in patients with septic shock.MethodsOur study is a retrospective cohort study of adult patients in the OneFlorida Data Trust (Florida, United States of America) admitted with septic shock between January 2012 and July 2018. We identified patients as having septic shock if they received vasopressors during their hospital encounter and had either an explicit International Classification of Disease (ICD) code for sepsis, or had an infection ICD code and received intravenous antibiotics. Our primary outcome was 90-day mortality. Our secondary outcome was in-hospital mortality. Multiple logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) for variable selection was used to assess associations.FindingsThere were 13,932 patients with septic shock in our cohort. The mean age was 61 years (SD 16), 68% of the cohort identified as White (n = 9419), 28% identified as Black (n = 3936), 2% (n = 294) identified as Hispanic ethnicity, and 2% as other races not specified in the previous groups (n = 283). In our logistic regression model for 90-day mortality, patients identified as Black had 1.57 times the odds of mortality (95% CI 1.07-2.29, p = 0.02) compared to White patients. Other significant predictors included mechanical ventilation (OR 3.66, 95% CI 3.35-4.00, p < 0.01), liver disease (OR 1.75, 95% CI 1.59-1.93, p < 0.01), laboratory components of the Sequential Organ Failure Assessment score (OR 1.18, 95% CI 1.16-1.21, p < 0.01), lactate (OR 1.10, 95% CI 1.08-1.12, p < 0.01), congestive heart failure (OR 1.19, 95% CI 1.10-1.30, p < 0.01), human immunodeficiency virus (OR 1.35, 95% CI 1.04-1.75, p = 0.03), age (OR 1.04, 95% CI 1.04-1.04, p < 0.01), and the interaction between age and race (OR 0.99, 95% CI 0.99-1.00, p < 0.01). Among younger patients (<45 years), patients identified as Black accounted for a higher proportion of the deaths. Results were similar in the in-hospital mortality model.InterpretationIn this retrospective study of septic shock patients, we found that patients identified as Black had higher odds of mortality compared to patients identified as non-Hispanic White. Our findings suggest that the greatest disparities in mortality are among younger Black patients with septic shock.FundingNational Institutes of Health National Center for Advancing Translational Sciences (1KL2TR001429); National Institute of Health National Institute of General Medical Sciences (1K23GM144802).

Dataset Information

Association of CD14 rs2569190 polymorphism with mortality in shock septic patients who underwent major cardiac or abdominal surgery: A retrospective study.

Publications

Association of CD14 rs2569190 polymorphism with mortality in shock septic patients who underwent major cardiac or abdominal surgery: A retrospective study.

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