Ninety-Day Survival Rate of Patients with Sepsis Relates to Programmed Cell Death 1 Genetic Polymorphism rs11568821

Mansur, Ashham; Hinz, José; Hillebrecht, Bronja; Bergmann, Ingo; Popov, Aron Frederik; Ghadimi, Michael; Bauer, Martin; Beißbarth, Tim; Mihm, Sabine

doi:10.2310/jim.0000000000000059

Cited by 24 publications

(26 citation statements)

References 42 publications

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“…The lack of a significant association between the CD14 rs2569190 TT genotype and 90-day mortality suggest little or no biological impact of the TT genotype on long-term mortality. As shown by our group, the 90-day mortality risk among patients with sepsis is related to the functional programmed cell death 1 genetic polymorphism rs11568821 GG genotype [ 30 ], which has been shown to influence transcriptional activity [ 31 ] and increase PD-1 expression [ 32 ]; PD-1 is thought to play an important role in the so-called sepsis-induced immunosuppression [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

The CD14 rs2569190 TT Genotype Is Associated with an Improved 30-Day Survival in Patients with Sepsis: A Prospective Observational Cohort Study

et al. 2015

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According to previous investigations, CD14 is suggested to play a pivotal role in initiating and perpetuating the pro-inflammatory response during sepsis. A functional polymorphism within the CD14 gene, rs2569190, has been shown to impact the pro-inflammatory response upon stimulation with lipopolysaccharide, a central mediator of inflammation in sepsis. In this study, we hypothesized that the strong pro-inflammatory response induced by the TT genotype of CD14 rs2569190 may have a beneficial effect on survival (30-day) in patients with sepsis. A total of 417 adult patients with sepsis (and of western European descent) were enrolled into this observational study. Blood samples were collected for rs2569190 genotyping. Patients were followed over the course of their stay in the ICU, and the 30-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure as a secondary variable. Moreover, organ support-free days were evaluated as a secondary outcome parameter. TT-homozygous patients were compared to C-allele carriers. Kaplan-Meier survival analysis revealed a higher 30-day mortality risk among C-allele carriers compared with T homozygotes (p = 0.0261). To exclude the effect of potential confounders (age, gender, BMI and type of infection) and covariates that varied at baseline with a p-value < 0.2 (e.g., comorbidities), we performed multivariate Cox regression analysis to examine the survival time. The CD14 rs2569190 C allele remained a significant covariate for the 30-day mortality risk in the multivariate analysis (hazard ratio, 2.11; 95% CI, 1.08-4.12; p = 0.0282). The 30-day mortality rate among C allele carriers was 23%, whereas the T homozygotes had a mortality rate of 13%. Additionally, an analysis of organ-specific SOFA scores revealed a significantly higher SOFA-Central nervous system score among patients carrying the C allele compared with T-homozygous patients (1.9±1.1 and 1.6±1.0, respectively; p = 0.0311). In conclusion, CD14 rs2569190 may act as a prognostic variable for the short-term outcome (30-day survival) in patients with sepsis.

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Section: Discussionmentioning

confidence: 99%

The CD14 rs2569190 TT Genotype Is Associated with an Improved 30-Day Survival in Patients with Sepsis: A Prospective Observational Cohort Study

et al. 2015

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“…As described previously, 28 29 the patient exclusion criteria were the following: (1) age less than 18 years; (2) being pregnant or nursing an infant; (3) immunosuppressive therapy (eg, cyclosporine or azathioprine) or cancer-related chemotherapy; (4) documented or suspected acute myocardial infarction within the previous 6 weeks; (5) a history of New York Heart Association functional class IV chronic heart failure; (6) HIV infection; (7) a do not resuscitate or do not treat order or the patient and/or his or her legal representative not being committed to aggressive management; (8) not being expected to survive the 28-day observation period or not being likely to be placed on life support because of an uncorrectable medical condition, including a poorly controlled neoplasm or end-stage lung disease; (9) a chronic vegetative state or a similar long-term neurological condition; (10) current participation in any interventional study (of a drug or device); (11) inability to be fully evaluated during the study period and (12) being a study-site employee or a family member of a study-site employee involved in conducting this study.…”

Section: Methodsmentioning

confidence: 99%

Primary bacteraemia is associated with a higher mortality risk compared with pulmonary and intra-abdominal infections in patients with sepsis: a prospective observational cohort study

et al. 2015

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ObjectiveTo investigate whether common infection foci (pulmonary, intra-abdominal and primary bacteraemia) are associated with variations in mortality risk in patients with sepsis.DesignProspective, observational cohort study.SettingThree surgical intensive care units (ICUs) at a university medical centre.ParticipantsA total of 327 adult Caucasian patients with sepsis originating from pulmonary, intra-abdominal and primary bacteraemia participated in this study.Primary and secondary outcome measuresThe patients were followed for 90 days and mortality risk was recorded as the primary outcome variable. To monitor organ failure, sepsis-related organ failure assessment (Sequential Organ Failure Assessment, SOFA) scores were evaluated at the onset of sepsis and throughout the observational period as secondary outcome variables.ResultsA total of 327 critically ill patients with sepsis were enrolled in this study. Kaplan-Meier survival analysis showed that the 90-day mortality risk was significantly higher among patients with primary bacteraemia than among those with pulmonary and intra-abdominal foci (58%, 35% and 32%, respectively; p=0.0208). To exclude the effects of several baseline variables, we performed multivariate Cox regression analysis. Primary bacteraemia remained a significant covariate for mortality in the multivariate analysis (HR 2.10; 95% CI 1.14 to 3.86; p=0.0166). During their stay in the ICU, the patients with primary bacteraemia presented significantly higher SOFA scores than those of the patients with pulmonary and intra-abdominal infection foci (8.5±4.7, 7.3±3.4 and 5.8±3.5, respectively). Patients with primary bacteraemia presented higher SOFA-renal score compared with the patients with other infection foci (1.6±1.4, 0.8±1.1 and 0.7±1.0, respectively); the patients with primary bacteraemia required significantly more renal replacement therapy than the patients in the other groups (29%, 11% and 12%, respectively).ConclusionsThese results indicate that patients with sepsis with primary bacteraemia present a higher mortality risk compared with patients with sepsis of pulmonary or intra-abdominal origins. These results should be assessed in patients with sepsis in larger, independent cohorts.

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“…This limits their generalizability to populations that are disproportionately affected by these conditions [23,29,30]. Currently no study has correlated genomic data with long-term outcomes beyond 90-day mortality [24,25,27,28,31].…”

Section: Genetic Susceptibilitymentioning

confidence: 99%

Factors Underlying Racial Disparities in Sepsis Management

DiMeglio

Dubensky

Schadt

et al. 2018

Preprint

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Sepsis, a syndrome characterized by systemic inflammation during infection, continues to be one of the most common causes of patient mortality in hospitals across the United States. While standardized treatment protocols have been implemented, wide variability in clinical outcomes persist across racial groups. Specifically, Black and Hispanic populations are frequently associated with higher rates of morbidity and mortality in sepsis compared to the Caucasian population. While this is often attributed to systemic bias against minority groups, a growing body of literature has found patient, community, and hospital-based factors to be driving racial differences. In this article, we provide a focused review on some of the factors driving racial disparities in sepsis. We also suggest potential interventions aimed at reducing health disparities in the prevention, early identification, and clinical management of sepsis.

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Ninety-Day Survival Rate of Patients with Sepsis Relates to Programmed Cell Death 1 Genetic Polymorphism rs11568821

Abstract: Data provide first associative evidence for PD-1 rs11568821 as a prognostic indicator in patients with sepsis.

Cited by 24 publications

References 42 publications

The CD14 rs2569190 TT Genotype Is Associated with an Improved 30-Day Survival in Patients with Sepsis: A Prospective Observational Cohort Study

The CD14 rs2569190 TT Genotype Is Associated with an Improved 30-Day Survival in Patients with Sepsis: A Prospective Observational Cohort Study

Primary bacteraemia is associated with a higher mortality risk compared with pulmonary and intra-abdominal infections in patients with sepsis: a prospective observational cohort study

Factors Underlying Racial Disparities in Sepsis Management

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