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Genetic Polymorphisms and Cytokine Profile of Different Ethnicities inSeptic Shock Patients and their Association with Mortality.

ABSTRACT: Objective:The outcomes of sepsis and septic shock patients are heterogonous, with avariable response despite standardized care. The aim of this study was toexplore the racial differences in septic shock outcomes, and theirassociation with genetic polymorphisms and cytokine levels in an Asianpopulation. Materials and methods:This was an observational cohort study with Intensive Care units of a 500bedded tertiary care hospital in Singapore. 198 patients (73 Chinese, 73Malay and 52 Indian and others) admitted to the Khoo Teck Puat HospitalIntensive Care Unit between August 2016 and June 2017, with a diagnosis ofsevere sepsis (according to) were enrolled. Plasma interlukin-6 (IL-6),interlukin-10 (IL-10) and tumour necrosis factor-a (TNFa) were measuredusing a highly sensitive quantitative sandwich enzyme-linked immunosorbentassay (ELISA) (BioVendor, Modrice, Czech Republic). The gene panel studiedincluded 16 genes. Results:The rs7038903 common variant in SVEP1 gene showed significant associationwith sepsis severity independent of other variants in ordinal logistic andlinear regression model (p = 0.001 and p = 0.002 respectively). Moreover, the association between rs7038903 and increased hazard for death remained significant after further adjusting for cytokines level. Interestingly, significant differences were seen in plasma IL6 inindividuals with or without rs7038903 C allele (28pg/ml (IQR 12-86) vs90pg/ml (IQR 49-155); P=0.022) in patients with severe sepsis in the Malayethnic group. Conclusion:Our study shows a promising polymorphism in SVEP1 gene (rs7038903) which isassociated with sepsis shock and 28 days mortality, independent of age, gender, and method of diagnosis and SOFA score. Collectively, while our findings so far have shown the additional value or measuring cytokines andgenetic markers in sepsis outcomes in the local population, further largescare studies are needed in a heterogeneous septic population with arigorous analysis to know the significance of our findings. How to cite this article:Siddiqui S, Gurung RL et al. Genetic Polymorphisms and Cytokine Profile of Different Ethnicities in Septic Shock Patients, and their Association with Mortality. Indian J Crit Care Med 2019;29(3):135-138.

SUBMITTER: Siddiqui S

PROVIDER: S-EPMC6487620 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Genetic Polymorphisms and Cytokine Profile of Different Ethnicities inSeptic Shock Patients and their Association with Mortality.

Siddiqui Shahla S Gurung Resham Lal RL Liu Sylvia S Ping Seet Edwin Chuen EC Lim Su Chi SC

Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine 20190301 3

<h4>Objective</h4>The outcomes of sepsis and septic shock patients are heterogonous, with avariable response despite standardized care. The aim of this study was toexplore the racial differences in septic shock outcomes, and theirassociation with genetic polymorphisms and cytokine levels in an Asianpopulation.<h4>Materials and methods</h4>This was an observational cohort study with Intensive Care units of a 500bedded tertiary care hospital in Singapore. 198 patients (73 Chinese, 73Malay and 52 I ...[more]

PMID: 31097890

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Project description:OBJECTIVES:Sepsis care is becoming a more common target for hospital performance measurement, but few studies have evaluated the acceptability of sepsis or septic shock mortality as a potential performance measure. In the absence of a gold standard to identify septic shock in claims data, we assessed agreement and stability of hospital mortality performance under different case definitions. DESIGN:Retrospective cohort study. SETTING:U.S. acute care hospitals. PATIENTS:Hospitalized with septic shock at admission, identified by either implicit diagnosis criteria (charges for antibiotics, cultures, and vasopressors) or by explicit International Classification of Diseases, 9th revision, codes. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We used hierarchical logistic regression models to determine hospital risk-standardized mortality rates and hospital performance outliers. We assessed agreement in hospital mortality rankings when septic shock cases were identified by either explicit International Classification of Diseases, 9th revision, codes or implicit diagnosis criteria. Kappa statistics and intraclass correlation coefficients were used to assess agreement in hospital risk-standardized mortality and hospital outlier status, respectively. Fifty-six thousand six-hundred seventy-three patients in 308 hospitals fulfilled at least one case definition for septic shock, whereas 19,136 (33.8%) met both the explicit International Classification of Diseases, 9th revision, and implicit septic shock definition. Hospitals varied widely in risk-standardized septic shock mortality (interquartile range of implicit diagnosis mortality: 25.4-33.5%; International Classification of Diseases, 9th revision, diagnosis: 30.2-38.0%). The median absolute difference in hospital ranking between septic shock cohorts defined by International Classification of Diseases, 9th revision, versus implicit criteria was 37 places (interquartile range, 16-70), with an intraclass correlation coefficient of 0.72, p value of less than 0.001; agreement between case definitions for identification of outlier hospitals was moderate (kappa, 0.44 [95% CI, 0.30-0.58]). CONCLUSIONS:Risk-standardized septic shock mortality rates varied considerably between hospitals, suggesting that septic shock is an important performance target. However, efforts to profile hospital performance were sensitive to septic shock case definitions, suggesting that septic shock mortality is not currently ready for widespread use as a hospital quality measure.

Project description:Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups.

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Genetic Polymorphisms and Cytokine Profile of Different Ethnicities inSeptic Shock Patients and their Association with Mortality.

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Genetic Polymorphisms and Cytokine Profile of Different Ethnicities inSeptic Shock Patients and their Association with Mortality.

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