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Association between heat shock protein 70 gene polymorphisms and clinical outcomes in intensive care unit patients with sepsis.

ABSTRACT: OBJECTIVE:The objective of the following study is to evaluate the associations between single nucleotide polymorphisms (SNPs) in the Heat Shock Protein 70 (HSP70) gene, gene expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-?) and medical intensive care unit (MICU) stay and organ failure in sepsis. MATERIALS AND METHODS:MICU patients with sepsis were genotyped for rs1061581, rs2227956, rs1008438 and rs1043618 polymorphisms in HSP70 gene using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis or allele-specific PCR. Messenger ribonucleic acid (mRNA) expression of IL-6 and TNF-? were quantitated in peripheral blood lymphocytes. Outcomes were recorded. RESULTS:108 patients (48 male) aged 40.7 ± 16.0 (mean ± standard deviation) years included H1N1 infection (36), scrub typhus (29) and urosepsis (12). Seventy-one (65.7%) had dysfunction of three or more organ systems, 66 patients (61.1%) were treated by mechanical ventilation, 21 (19.4%) needed dialysis. ICU stay was 9.3 ± 7.3 days. Mortality was 38.9%. One or more SNPs were noted in 101/108 (93.5%) and organ failure was noted in only 1/7 patients without a single SNP. The A allelotypes of rs1061581 and rs1008438 were associated with hematological dysfunction (P = 0.03 and 0.07) and longer ICU stay (P = 0.05 and 0.04), whereas IL-6 and TNF-? mRNA levels were associated with central nervous system dysfunction. CONCLUSIONS:HSP70 genotypes may determine some adverse outcomes in patients with sepsis.

SUBMITTER: Ramakrishna K

PROVIDER: S-EPMC4033853 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Association between heat shock protein 70 gene polymorphisms and clinical outcomes in intensive care unit patients with sepsis.

Ramakrishna Kartik K Pugazhendhi Srinivasan S Kabeerdoss Jayakanthan J Peter John Victor JV

Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine 20140401 4

<h4>Objective</h4>The objective of the following study is to evaluate the associations between single nucleotide polymorphisms (SNPs) in the Heat Shock Protein 70 (HSP70) gene, gene expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and medical intensive care unit (MICU) stay and organ failure in sepsis.<h4>Materials and methods</h4>MICU patients with sepsis were genotyped for rs1061581, rs2227956, rs1008438 and rs1043618 polymorphisms in HSP70 gene using polymerase chain ...[more]

PMID: 24872649

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Project description:Rationale: A small but growing number of hospitals are experimenting with emergency department-embedded critical care units (CCUs) in an effort to improve the quality of care for critically ill patients with sepsis and acute respiratory failure (ARF).Objectives: To evaluate the potential impact of an emergency department-embedded CCU at the Hospital of the University of Pennsylvania among patients with sepsis and ARF admitted from the emergency department to a medical ward or intensive care unit (ICU) from January 2016 to December 2017.Methods: The exposure was eligibility for admission to the emergency department-embedded CCU, which was defined as meeting a clinical definition for sepsis or ARF and admission to the emergency department during the intervention period on a weekday. The primary outcome was hospital length of stay (LOS); secondary outcomes included total emergency department plus ICU LOS, hospital survival, direct admission to the ICU, and unplanned ICU admission. Primary interrupted time series analyses were performed using ordinary least squares regression comparing monthly means. Secondary retrospective cohort and before-after analyses used multivariable Cox proportional hazard and logistic regression.Results: In the baseline and intervention periods, 3,897 patients met the inclusion criteria for sepsis and 1,865 patients met the criteria for ARF. Among patients admitted with sepsis, opening of the emergency department-embedded CCU was not associated with hospital LOS (β = -1.82 d; 95% confidence interval [CI], -4.50 to 0.87; P = 0.17 for the first month after emergency department-embedded CCU opening compared with baseline; β = -0.26 d; 95% CI, -0.58 to 0.06; P = 0.10 for subsequent months). Among patients admitted with ARF, the emergency department-embedded CCU was not associated with a significant change in hospital LOS for the first month after emergency department-embedded CCU opening (β = -3.25 d; 95% CI, -7.86 to 1.36; P = 0.15) but was associated with a 0.64 d/mo shorter hospital LOS for subsequent months (β = -0.64 d; 95% CI, -1.12 to -0.17; P = 0.01). This result persisted among higher acuity patients requiring ventilatory support but was not supported by alternative analytic approaches. Among patients admitted with sepsis who did not require mechanical ventilation or vasopressors in the emergency department, the emergency department-embedded CCU was associated with an initial 9.9% reduction in direct ICU admissions in the first month (β = -0.099; 95% CI, -0.153 to -0.044; P = 0.002), followed by a 1.1% per month increase back toward baseline in subsequent months (β = 0.011; 95% CI, 0.003-0.019; P = 0.009). This relationship was supported by alternative analytic approaches and was not seen in ARF. No associations with emergency department plus ICU LOS, hospital survival, or unplanned ICU admission were observed among patients with sepsis or ARF.Conclusions: The emergency department-embedded CCU was not associated with clinical outcomes among patients admitted with sepsis or ARF. Among less sick patients with sepsis, the emergency department-embedded CCU was initially associated with reduced rates of direct ICU admission from the emergency department. Additional research is necessary to further evaluate the impact and utility of the emergency department-embedded CCU model.

Project description:BACKGROUND:Recent studies have evaluated the associations between polymorphisms of the heat-shock protein 70 (HSP70) encoding genes and noise-induced hearing loss (NIHL). However, the conclusions of these studies are conflicting. The objective of this meta-analysis was to clarify the association between all known polymorphisms of HSP70 genetic loci and susceptibility to NIHL, based on existing reports. METHODS:We conducted a meta-analysis of the association between Hsp70 polymorphisms (rs1043618, rs1061581, rs2075800, rs2227956, and rs2763979) and NIHL risk in both Chinese and Caucasian males. All statistical analysis was done with was conducted using the "meta" package (version 4.6-0) of R version 3.3.2 and RStudio version 1.0.44. Online databases were searched for eligible case-control studies on February 13, 2017. The odds ratio (OR), 95% confidence interval (CI), and P value were calculated using Mantel-Haenszel statistics under a random- or fixed-effect model. RESULTS:A total of five studies, reported via four articles from online databases, were included in our meta-analysis. For rs1061581 (from three studies), a significant association was detected in the allele model, homozygote model, and dominant model (G versus A: OR (95% CI) = 1.32(1.05-1.67), GG versus AA: OR (95% CI) = 1.93(1.1-3.36), GG + AG versus AA: OR (95% CI) = 1.45(1.05-2.02)), but not in the heterozygote model or the recessive model. For rs1043618 (from five studies), rs2075800 (from two studies), rs2227956 (from four studies), rs2763979 (from two studies), no significant association was found for any genetic model. After subgroup analyses by ethnicity, significant associations were observed for the allele model, heterozygote model, and dominant model for rs1061581 and any genetic model for rs2227956 in Caucasians. CONCLUSIONS:The rs1043618, rs2075800, and rs2763979 polymorphisms were not found to be associated with susceptibility to NIHL; however, the rs1061581 and rs2227956 polymorphisms were significantly associated with NIHL in Caucasian males.

Project description:BACKGROUND:Advancing age is a strong risk factor for adverse outcomes across multiple disease processes. However, septic surgical and trauma patients are unique in that they incur two or more inflammatory insults. The effects of advanced age on sepsis pathophysiology and outcomes remain unclear. METHODS:We performed a single-center, prospective observational cohort study of surgical intensive care unit patients with severe sepsis/septic shock. Peripheral blood was collected for genomic, cytokine, and biomarker analysis at 0.5 day, 1 day, 4 days, 7 days, 14 days, 21 days, and 28 days after sepsis onset. Based on sensitivity analysis, cohorts were defined as "young" (<55 years) and "aged" (?55 years). We compared age-defined cohorts to determine differences in patient characteristics, biomarker profiles, and clinical outcomes. RESULTS:The cohort included 173 patients with severe sepsis (n = 93; 53.8%) or septic shock (n = 80; 46.2%), with a mean age of 60.9 (±14.5) years. Intra-abdominal sepsis was the leading source (n = 81; 46.8%), followed by necrotizing soft tissue infection (n = 33, 19.1%) and pneumonia (n = 30; 17.3%). Aged patients had a higher comorbidity burden, but were otherwise similar to the young cohort. The aged cohort had a higher severity of early physiologic derangement (median APACHE II, 23 vs. 18; p = 0.002), greater incidence of multiple organ failure (64.3% vs. 40.4%, p = 0.006), and hospital mortality (15.9% vs. 2.1%; p = 0.016). Six-month mortality was significantly higher in the aged cohort as compared with young cohort (31% vs. 9%; p = 0.003). Aged septic patients biomarker trajectories suggestive of persistent immunosuppression (absolute lymphocyte count, soluble programed death ligand-1) and catabolism (Urine 3MH-Cr ratio, insulin growth factor, IGF1BP3, albumin) out to 28 days after sepsis. CONCLUSION:Aged, critically ill surgical patients have greater organ dysfunction and incidence of adverse clinical outcomes after sepsis. Biomarker profiles suggest an immunophenotype of persistent immunosuppression and catabolism. Advanced age may necessitate novel therapeutic strategies to promote multisystem organ recovery and improve survival after sepsis. LEVEL OF EVIDENCE:Prognostic, level II.

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Association between heat shock protein 70 gene polymorphisms and clinical outcomes in intensive care unit patients with sepsis.

Publications

Association between heat shock protein 70 gene polymorphisms and clinical outcomes in intensive care unit patients with sepsis.

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