Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room.
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ABSTRACT:
SUBMITTER: Kung CT
PROVIDER: S-EPMC3441240 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room.
Kung Chia-Te CT Hsiao Sheng-Yuan SY Tsai Tsung-Cheng TC Su Chih-Min CM Chang Wen-Neng WN Huang Chi-Ren CR Wang Hung-Chen HC Lin Wei-Che WC Chang Hsueh-Wen HW Lin Yu-Jun YJ Cheng Ben-Chung BC Su Ben Yu-Jih BY Tsai Nai-Wen NW Lu Cheng-Hsien CH
Journal of translational medicine 20120621
<h4>Background and aim</h4>The sensitivity and specificity of biomarkers and scoring systems used for predicting fatality of severe sepsis patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating plasma DNA levels in severe septic patients presenting at the Emergency Department (ED).<h4>Methods</h4>Sixty-seven consecutive patients with severe sepsis and 33 controls were evaluated. Plasma DNA levels were estimated by real-time quantitative polymerase chain ...[more]
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Project description:BackgroundGiven the acknowledged problems in sepsis diagnosis, we use a novel way with the application of the latent class analysis (LCA) to determine the operative characteristics of C-reactive protein (CRP), D-dimer (DD) and Procalcitonin (PCT) as diagnostic tests for sepsis in patients admitted to hospital care with a presumptive infection.MethodsCross-sectional study to determine the diagnostic accuracy of three biological markers against the gold standard of clinical definition of sepsis provided by an expert committee, and also against the likelihood of sepsis according to LCA. Patients were recruited in the emergency room within 24 hours of hospitalization and were follow-up daily until discharge.ResultsAmong 765 patients, the expert committee classified 505 patients (66%) with sepsis, 112 (15%) with infection but without sepsis and 148 (19%) without infection. The best cut-offs points for CRP, DD, and PCT were 7.8 mg/dl, 1616 ng/ml and 0.3 ng/ml, respectively; but, neither sensitivity nor specificity reach 70% for any biomarker. The LCA analysis with the same three tests identified a "cluster" of 187 patients with several characteristics suggesting a more severe condition as well as better microbiological confirmation. Assuming this subset of patients as the new prevalence of sepsis, the ROC curve analysis identified new cut-off points for the tests and suggesting a better discriminatory ability for PCT with a value of 2 ng/ml.ConclusionsUnder a "classical" definition of sepsis three typical biomarkers (CRP, PCT and DD) are not capable enough to differentiate septic from non-septic patients in the ER. However, a higher level of PCT discriminates a selected group of patients with severe sepsis.
| S-EPMC3850719 | biostudies-literature
Project description:RationaleSevere sepsis is common and highly morbid, yet the epidemiology of severe sepsis at the frontier of the health care system-pre-hospital emergency care-is unknown.ObjectivesWe examined the epidemiology of pre-hospital severe sepsis among emergency medical services (EMS) encounters, relative to acute myocardial infarction and stroke.MethodsRetrospective study using a community-based cohort of all nonarrest, nontrauma King County EMS encounters from 2000 to 2009 who were transported to a hospital.Measurements and main resultsOverall incidence rate of hospitalization with severe sepsis among EMS encounters, as well as pre-hospital characteristics, admission diagnosis, and outcomes. Among 407,176 EMS encounters, we identified 13,249 hospitalizations for severe sepsis, of whom 2,596 died in the hospital (19.6%). The crude incidence rate of severe sepsis was 3.3 per 100 EMS encounters, greater than for acute myocardial infarction or stroke (2.3 per 100 and 2.2 per 100 EMS encounters, respectively). More than 40% of all severe sepsis hospitalizations arrived at the emergency department after EMS transport, and 80% of cases were diagnosed on admission. Pre-hospital care intervals, on average, exceeded 45 minutes for those hospitalized with severe sepsis. One-half or fewer of patients with severe sepsis were transported by paramedics (n = 7,114; 54%) or received pre-hospital intravenous access (n = 4,842; 37%).ConclusionsEMS personnel care for a substantial and increasing number of patients with severe sepsis, and spend considerable time on scene and during transport. Given the emphasis on rapid diagnosis and intervention for sepsis, the pre-hospital interval may represent an important opportunity for recognition and care of sepsis.
| S-EPMC3622444 | biostudies-literature
Project description:IntroductionEndothelium-derived molecules may be predictive to organ injury. Heat shock protein (HSP) A12B is mainly located in endothelial cells, which can be detected in the plasma of septic patients. Whether it is correlated with prognosis of sepsis remains unclear.MethodsExtracellular HSPA12B (eHSPA12B) was determined in plasma of septic mice at 6 h, 12 h, 24 h and 48 h after cecal ligation and puncture (CLP). It was also detected in plasma of patients with severe sepsis, sepsis, systemic inflammatory response syndrome and healthy volunteers. The predictive value for prognosis of severe sepsis was assessed by receiver operating curve (ROC) and Cox regression analyses.ResultseHSPA12B was elevated in plasma of CLP mice at 6 h and peaked at 24 h after surgery. A total of 118 subjects were included in the clinical section, including 66 patients with severe sepsis, 21 patients with sepsis, 16 patients with SIRS and 15 volunteers. Plasma eHSPA12B was significantly higher in patients with severe sepsis than in patients with sepsis, SIRS and volunteers. The level of eHSPA12B was also higher in non-survivals than survivals with severe sepsis. The area under the curve (AUC) of eHSPA12B in predicting death among patients with severe sepsis was 0.782 (0.654-0.909) in ROC analysis, much higher than that of IL-6 and IL-10. Cox regression analysis showed that cardiovascular diseases, IL-6 and eHSPA12B were risk factors for mortality in patients with severe sepsis. Survival curve demonstrated a strikingly significant difference between 28-day survival rates of patients with an eHSPA12B lower or not lower than 1.466 ng/ml.ConclusionsPlasma eHSPA12B is elevated in both septic mice and patients. It may be a good predictor for poor outcome in patients with severe sepsis.
| S-EPMC4076283 | biostudies-literature
Project description:Background: Emergency rooms (ERs) overcrowded by older adults have been the focus of public health policies during the recent COVID-19 outbreak too. This phenomenon needed a change in the nursing care of older frail people. Health policies have tried to mitigate the frequent use of ER by implementing community care to meet the care demands of older adults. The present study aimed to investigate the predictors of emergency room access (ERA) and not-urgent emergency room access (NUERA) of community-dwelling frail older adults in order to provide an indication for out-of-hospital care services. Method: Secondary analysis of an observational longitudinal cohort study was carried out. The cohort consisted of 1,246 community-dwelling frail older adults (over 65 years) in the Latium region in Italy. The ER admission rate was assessed over 3 years from the administration of the functional geriatric evaluation (FGE) questionnaire. The ordinal regression model was used to identify the predictors of ERA and NUERA. Moreover, the ERA and NUERA rate per 100 observations/year was analyzed. Results: The mean age was 73.6 (SD ± 7.1) years, and 53.4% were women. NUERAs were the 39.2% of the ERAs; robust and pre-frail individuals (79.3% of the sample) generated more than two-third of ERAs (68.17%), even if frails and very frails showed the higher ER rates per observation/year. The ordinal logistic regression model highlighted a predictive role on ERAs of comorbidity (OR = 1.13, p < 0.001) and frailty level (OR = 1.29; p < 0.001). Concerning NUERAs, social network (OR 0.54, P = 0.015) and a medium score of pulmo-cardio-vascular function (OR 1.50, P = 0.006) were the predictors. Conclusion: Comorbidity, lack of social support, and functional limitations increase both ERA and NUERA rates generated by the older adult population. Overall, bio-psycho-social frailty represents an indicator of the frequency of ERAs. However, to reduce the number of ERAs, intervention should focus mainly on the robust and pre-frail needs for prevention and care.
| S-EPMC8446358 | biostudies-literature
Project description:Homelessness, HIV, and substance use are interwoven problems. Furthermore, homeless individuals are frequent users of emergency services. The main purpose of this study was to identify risk factors for frequent emergency room (ER) visits and to examine the effects of housing status and HIV serostatus on ER utilization. The second purpose was to identify risk factors for frequent ER visits in patients with a history of illicit drug use.A retrospective analysis was performed on 412 patients enrolled in a Boston-based health care for the homeless program (HCH). This study population was selected as a 2:1 HIV seronegative versus HIV seropositive match based on age, sex, and housing status. A subgroup analysis was performed on 287 patients with history of illicit drug use. Chart data were analyzed to compare demographics, health characteristics, and health service utilization. Results were stratified by housing status. Logistic models using generalized estimating equations were used to predict frequent ER visits.In homeless patients, hepatitis C was the only predictor of frequent ER visits (OR 4.49, p<0.01). HIV seropositivity was not predictive of frequent ER visits. In patients with history of illicit drug use, mental health (OR 2.53, 95% CI 1.07-5.95) and hepatitis C (OR 2.85, 95% CI 1.37-5.93) were predictors of frequent ER use. HIV seropositivity did not predict ER use (OR 0.45, 95% CI 0.21 - 0.97).In a HCH population, hepatitis C predicted frequent ER visits in homeless patients. HIV seropositivity did not predict frequent ER visits, likely because HIV seropositive HCH patients are engaged in care. In patients with history of illicit drug use, hepatitis C and mental health disorders predicted frequent ER visits. Supportive housing for patients with mental health disorders and hepatitis C may help prevent unnecessary ER visits in this population.
| S-EPMC4407893 | biostudies-other
Project description:IntroductionCell-free plasma mitochondrial DNA (mt-DNA) and nuclear DNA (n-DNA) are biomarkers with prognostic utility in conditions associated with a high rate of cell death. This exploratory study aimed to determine the plasma levels of both nucleic acids in patients with massive and submassive pulmonary embolism (PE) and to compare them with other biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and troponin I (Tn-I) METHODS: This was a prospective observational study of 37 consecutive patients with massive PE, 37 patients with submassive PE, and 37 healthy subjects. Quantifications of plasma mt-DNA and n-DNA with real-time quantitative polymerase chain reaction (PCR), and plasma H-FABP and Tn-I by commercial assays, were done on blood samples drawn within 4 hours after presentation at the emergency department.ResultsPlasma mt-DNA and n-DNA concentrations were much higher in patients with massive PE (median, 2,970 GE/ml; interquartile range (IQR), 1,050 to 5,485; and 3,325 GE/ml, IQR: 1,080 to 5,790, respectively) than in patients with submassive PE (870 GE/ml and 1,245 GE/ml, respectively; P < 0.01) or controls (185 GE/ml and 520 GE/ml, respectively). Eighteen patients with massive PE died of a PE-related cause by day 15 of observation. Plasma mt-DNA and n-DNA values were 2.3-fold and 1.9-fold higher in the subgroup of nonsurviving patients than in survivors. H-FABP and Tn-I values were also higher in patients with massive PE who died (7.3 ng/ml and 0.023 ng/ml, respectively) than in those who survived (6.4 ng/ml, and 0.016 ng/ml, respectively). By receiver operating curve (ROC) analysis, the best cutoff values for predicting 15-day mortality were 3,380 GE/ml for mt-DNA, 6.8 ng/ml for H-FABP, 3,625 GE/ml for n-DNA, and 0.020 ng/ml for Tn-I, based on the calculated areas under the curve (AUCs) of 0.89 (95% confidence interval (CI), 0.78 to 0.99), 0.76 (95% CI, 0.69 to 093), 0.73 (95% CI, 0.58 to 0.91), and 0.59 (95% CI, 0.41 to 0.79), respectively. By stepwise logistic regression, a plasma mt-DNA concentration greater than 3,380 GE/ml (adjusted odds ratio (OR), 8.22; 95% CI, 1.72 to 39.18; P < 0.001) and a plasma value of H-FBAP >6.8 ng/ml (OR, 5.36; 95% CI, 1.06 to 27.08; P < 0.01) were the only independent predictors of mortality.Conclusionsmt-DNA and H-FBAP might be promising markers for predicting 15-day mortality in massive PE, with mt-DNA having better prognostic accuracy.
| S-EPMC3707013 | biostudies-literature
Project description:BackgroundCritically ill patients who develop ARDS have substantial associated morbidity and mortality. Circulating mitochondrial DNA (mtDNA) released during critical illness causes endothelial dysfunction and lung injury in experimental models. This study hypothesized that elevated plasma mtDNA is associated with ARDS in critically ill patients with trauma and sepsis.MethodsPlasma mtDNA concentrations were measured at ED presentation and approximately 48 h later in separate prospective cohorts of critically ill patients with trauma and sepsis. ARDS was classified according to the Berlin definition. The association of mtDNA with ARDS was tested by using multivariable logistic regression, adjusted for covariates previously shown to contribute to ARDS risk in each population.ResultsARDS developed in 41 of 224 (18%) trauma patients and in 45 of 120 (38%) patients with sepsis. Forty-eight-hour mtDNA levels were significantly associated with ARDS (trauma: OR, 1.58/log copies/?L; 95% CI, 1.14-2.19 [P = .006]; sepsis: OR, 1.52/log copies/?L; 95% CI, 1.12-2.06 [P = .007]). Plasma mtDNA on presentation was not significantly associated with ARDS in either cohort. In patients with sepsis, 48-h mtDNA was more strongly associated with ARDS among those with a nonpulmonary infectious source (OR, 2.20/log copies/?L; 95% CI, 1.36-3.55 [P = .001], n = 69) than those with a pulmonary source (OR, 1.04/log copies/?L; 95% CI, 0.68-1.59 [P = .84], n = 51; P = .014 for interaction).ConclusionsPlasma mtDNA levels were associated with incident ARDS in two critical illness populations. Given supportive preclinical data, our findings suggest a potential link between circulating mtDNA and lung injury and merit further investigation as a potentially targetable mediator of ARDS.
| S-EPMC6965693 | biostudies-literature
Project description:BackgroundCritically ill children are those in need of immediate attention on arrival to an emergency room. The importance of glycemic level measurement as well as maintaining the patency of the airway, effective breathing and circulation cannot be overemphasied. It has been highlighted that the peak hyperglycemia and hypoglycemia predict poor prognosis, longer lengths of hospital stay and higher mortality. The study aims to assess the relationship between glycemic level and treatment outcomes as well as length of hospital stay.MethodsAnalytical cross sectional method was used to study critically ill children aged ?1 month to ?10 years admitted into the Children Emergency Room of Enugu State University Teaching Hospital, Enugu. Their admission blood glucose was done. Interviewer administered questionnaire was used to collect information including sociodemographics, duration of hospitalization and outcome of treatment. Data was analysed using SPSS version 20. Chi square, logistic regressions and Kruskal Wallis tests were done as appropriate.ResultsA total of 300 patients were recruited. One hundred and seventeen (39%) had hyperglycemia, 62 (20.7%) patients had hypoglycaemia and 121 (40.3%) had euglycemia. Two hundred and fifty two (84%) were discharged while 48 (16%) died. There was significant association between glycemic levels and treatment outcome (p = < 0.001). Among the 48 who died, 12 (25.0%) had euglycemia, 21 (43.75%) had hypoglycaemia while 15 (31.25%) had hyperglycemia. On multivariate analysis, there was statistically significant association between hypoglycaemia and mortality (p = < 0.001). Unadjusted, those children with hypoglycaemia at presentation were about 4.7 times (UOR = 0.21, 95% Cl: 0.08-0.38) and adjusted, about 5 times (AOR = 0.20, 95% CI: 0.09-0.47) less likely to survive compared with those with euglycemia. Although not statistically significant, those with hyperglycemia were about 1.3 times less likely to survive compared with euglycemic children, adjusted and unadjusted (UOR = 0.75, 95% Cl: 0.33-1.68).ConclusionWhile both hypo- and hyperglycemia are associated with mortality, hypoglycaemia had a greater effect than hyperglycemia. Glycemic levels significantly affects treatment outcome.
| S-EPMC5434620 | biostudies-literature
Project description:Fibrinogen plays a key role in hemostasis and is the first coagulation factor to reach critical levels in massively bleeding trauma patients. Consequently, rapid estimation of plasma fibrinogen (FIB) is essential upon emergency room (ER) admission, but is not part of routine coagulation monitoring in many centers. We investigated the predictive ability of the laboratory parameters hemoglobin (Hb) and base excess (BE) upon admission, as well as the Injury Severity Score (ISS), to estimate FIB in major trauma patients.In this retrospective study, major trauma patients (ISS ?16) with documented FIB analysis upon ER admission were eligible for inclusion. FIB was correlated with Hb, BE and ISS, alone and in combination, using regression analysis.A total of 675 patients were enrolled (median ISS 27). FIB upon admission correlated strongly with Hb, BE and ISS. Multiple regression analysis showed that Hb and BE together predicted FIB (adjusted R2 = 0.46; loge(FIB) = 3.567 + 0.223.Hb - 0.007.Hb2 + 0.044.BE), and predictive strength increased when ISS was included (adjusted R2 = 0.51; loge(FIB) = 4.188 + 0.243.Hb - 0.008.Hb2 + 0.036.BE - 0.031.ISS + 0.0003.ISS2). Of all major trauma patients admitted with Hb <12 g/dL, 74% had low (<200 mg/dL) FIB and 54% had critical (<150 mg/dL) FIB. Of patients admitted with Hb <10 g/dL, 89% had low FIB and 73% had critical FIB. These values increased to 93% and 89%, respectively, among patients with an admission Hb <8 g/dL. Sixty-six percent of patients with only a weakly negative BE (<-2 mmol/L) showed low FIB. Of patients with BE <-6 mmol/L upon admission, 81% had low FIB and 63% had critical FIB. The corresponding values for BE <-10 mmol/L were 89% and 78%, respectively.Upon ER admission, FIB of major trauma patients shows strong correlation with rapidly obtainable, routine laboratory parameters such as Hb and BE. These two parameters might provide an insightful and rapid tool to identify major trauma patients at risk of acquired hypofibrinogenemia. Early calculation of ISS could further increase the ability to predict FIB in these patients. We propose that FIB can be estimated during the initial phase of trauma care based on bedside tests.
| S-EPMC4056007 | biostudies-other
Project description:A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69-0.99) and a specificity 0.84 (95% CI 0.58-0.94) with an AUC of 0.93 (95% CI 0.89-1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85-1.00) and specificity of 0.95 (95% CI 0.74-0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.
| S-EPMC4723089 | biostudies-literature