Dataset Information

Association between circulating mononuclear cell mitochondrial DNA copy number and in-hospital mortality in septic patients: A prospective observational study based on the Sepsis-3 definition.

ABSTRACT:

Purpose

To explore the association between circulating mononuclear cell mitochondrial DNA copy number and the prognosis of sepsis patients based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3 definition).

Methods

A total of 200 adult patients who had recently devoloped sepsis were prospectively recruited as the study cohort. Demographic and clinical data were recorded along with a 28-day outcome. Mononuclear cell mtDNA copy number was assessed by quantitative PCR.

Results

The 28-day outcome of sepsis patients was significantly associated with circulating mononuclear cell mtDNA copy number. The median mononuclear cell relative mtDNA copy number of survivors was significantly higher than that of nonsurvivors (406.68, range 196.65-625.35 vs. 320.57, range 175.98-437.33, p = 0.001). The Cox proportional hazard survival model analysis indicated that mononuclear cell relative mtDNA copy number was significantly negative associated with the 28-day outcome. For every additional unit of mononuclear cell mtDNA relative copy number, the risk of death falls by 0.1% (HR = 0.999, 95% CI = 0.998 to 1.000, p = 0.017).

Conclusions

Our data indicate first that circulating mononuclear cellular mtDNA copy number might be helpful for outcome predictions in sepsis patients, and second that lower mtDNA copy number implied poor prognosis.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6386339 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between circulating mononuclear cell mitochondrial DNA copy number and in-hospital mortality in septic patients: A prospective observational study based on the Sepsis-3 definition.

Yang Yi Y Yang Jingjuan J Yu Biying B Li Li L Luo Lin L Wu Fengfeng F Wu Binbin B

PloS one 20190222 2

<h4>Purpose</h4>To explore the association between circulating mononuclear cell mitochondrial DNA copy number and the prognosis of sepsis patients based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3 definition).<h4>Methods</h4>A total of 200 adult patients who had recently devoloped sepsis were prospectively recruited as the study cohort. Demographic and clinical data were recorded along with a 28-day outcome. Mononuclear cell mtDNA copy number was assess ...[more]

PMID: 30794688

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Project description:OBJECTIVES:To assess the variability in short-term sepsis mortality by hospital among Centers for Medicare and Medicaid Services beneficiaries in the United States during 2013-2014. DESIGN:A retrospective cohort design. SETTING:Hospitalizations from 3,068 acute care hospitals that participated in the Centers for Medicare and Medicaid Services inpatient prospective payment system in 2013 and 2014. PATIENTS:Medicare fee-for-service beneficiaries greater than or equal to 65 years old who had an inpatient hospitalization coded with present at admission severe sepsis or septic shock. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Individual level mortality was assessed as death at or within 7 days of hospital discharge and aggregated to calculate hospital-level mortality rates. We used a logistic hierarchal linear model to calculate mortality risk-adjusted for patient characteristics. We quantified variability among hospitals using the median odds ratio and calculated risk-standardized mortality rates for each hospital. The overall crude mortality rate was 34.7%. We found significant variability in mortality by hospital (p < 0.001). The middle 50% of hospitals had similar risk-standardized mortality rates (32.7-36.9%), whereas the decile of hospitals with the highest risk-standardized mortality rates had a median mortality rate of 40.7%, compared with a median of 29.2% for hospitals in the decile with the lowest risk-standardized mortality rates. The median odds ratio (1.29) was lower than the adjusted odds ratios for several measures of patient comorbidities and severity of illness, including present at admission organ dysfunction, no identified source of infection, and age. CONCLUSIONS:In a large study of present at admission sepsis among Medicare beneficiaries, we showed that mortality was most strongly associated with underlying comorbidities and measures of illness on arrival. However, after adjusting for patient characteristics, mortality also modestly depended on where a patient with sepsis received care, suggesting that efforts to improve sepsis outcomes in lower performing hospitals could impact sepsis survival.

Project description:Patients with severe infections and especially sepsis have a high in-hospital mortality, but even hospital survivors face long-term sequelae, decreased health-related quality of life, and high risk of death, suggesting a great need for specialized aftercare. However, data regarding a potential benefit of post-discharge rehabilitation in these patients are scarce. In this retrospective matched cohort study the claim data of a large German statutory health care insurer was analyzed. 83,974 hospital survivors having suffered from septic shock, sepsis, and severe infections within the years 2009-2016 were identified using an ICD abstraction strategy closely matched to the current Sepsis-3 definition. Cases were analyzed and compared with their matched pairs to determine their 5-year mortality and the impact of post-discharge rehabilitation. Five years after hospital discharge, mortality of initial hospital survivors were still increased after septic shock (HRadj 2.03, 95%-CI 1.87 to 2.19; P<0.001), sepsis (HRadj 1.73, 95%-CI 1.71 to 1.76; P<0.001), and also in survivors of severe infections without organ dysfunction (HRadj 1.70, 95%-CI 1.65 to 1.74; P<0.001) compared to matched controls without infectious diseases. Strikingly, patients treated in rehabilitation facilities showed a significantly improved 5-year survival after suffering from sepsis or septic shock (HRadj 0.81, 95%-CI 0.77 to 0.85; P<0.001) as well as severe infections without organ dysfunction (HRadj 0.81, 95%-CI 0.73 to 0.90; P<0.001) compared to matched patients discharged to home or self-care. Long-term mortality and morbidity of hospital survivors are markedly increased after septic shock, sepsis and severe infections without organ dysfunction, but best 5-year survival was recorded in patients discharged to a rehabilitation facility in all three groups. Thus, our data suggest that specialized aftercare programs may help to improve long-term outcome in these patients and warrants more vigilance in future investigations.

Project description:RationaleImmunosuppressive medical conditions are risk factors for mortality from severe infections. It is unknown whether hospital characteristics affect this risk.ObjectivesTo determine whether the odds of death for an immunosuppressed patient with sepsis relative to a nonimmunosuppressed patient with sepsis varies according to the hospital's yearly case volume of immunosuppressed patients with sepsis.MethodsPatients with sepsis at hospitals in the Vizient database were characterized as immunosuppressed or not immunosuppressed on the basis of diagnosis codes and medication use. Hospitals were grouped into quartiles based on their average volumes of immunosuppressed patients with sepsis per year. Multilevel logistic regression with clustering of patients by hospital was used to determine whether the odds of in-hospital death from sepsis owing to a suppressed immune state varied by hospital quartile.ResultsThere were 350,183 patients with sepsis at 60 hospitals in the Vizient database from 2010 to 2012. Immunosuppressed patients with sepsis at the 15 hospitals in the lowest quartile (64 to 224 immunosuppressed patients with sepsis per year) had an increased odds of in-hospital death relative to nonimmunosuppressed patients with sepsis at these hospitals (adjusted odds ratio, 1.38; 95% confidence interval, 1.27-1.50; P < 0.001). The odds of in-hospital death for immunosuppressed patients with sepsis relative to nonimmunosuppressed patients with sepsis was similar for patients at hospitals in the second, third, and fourth quartiles (225 to 1,056 immunosuppressed patients with sepsis per year). The adjusted odds of death from sepsis owing to a suppressed immune state of 1.21 (95% confidence interval, 1.18-1.25; P < 0.001) for patients at these 45 hospitals was significantly less than for patients at the 15 hospitals in the lowest quartile (P = 0.004 for difference).ConclusionsThe risk of death from sepsis owing to a suppressed immune state was greatest at hospitals with the lowest volume of immunosuppressed patients with sepsis. Further study is needed to determine whether this finding is related to differences in patient characteristics or in care delivery at hospitals with different amounts of exposure to immunosuppressed patients.

Project description:BACKGROUND:Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. METHODS:AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. RESULTS:Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ? 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). CONCLUSIONS:AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02393781 . Registered on March 19, 2015.

Dataset Information

Association between circulating mononuclear cell mitochondrial DNA copy number and in-hospital mortality in septic patients: A prospective observational study based on the Sepsis-3 definition.

Purpose

Methods

Results

Conclusions

Publications

Association between circulating mononuclear cell mitochondrial DNA copy number and in-hospital mortality in septic patients: A prospective observational study based on the Sepsis-3 definition.

Similar Datasets

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