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Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study.

ABSTRACT: INTRODUCTION: Cell-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. RESULTS: Plasma 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. CONCLUSIONS: mt-DNA and H-FBAP might be promising markers for predicting 15-day mortality in massive PE, with mt-DNA having better prognostic accuracy.

SUBMITTER: Arnalich F

PROVIDER: S-EPMC3707013 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study.

Arnalich Francisco F Maldifassi Maria Constanza MC Ciria Enrique E Codoceo Rosa R Renart Jaime J Fernández-Capitán Carmen C Herruzo Rafael R Garcia-Rio Francisco F López-Collazo Eduardo E Montiel Carmen C

Critical care (London, England) 20130524 3

<h4>Introduction</h4>Cell-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 stu ...[more]

PMID: 23705965

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Project description:IntroductionMany emergency department (ED) patients with acute pulmonary embolism (PE) who meet low-risk criteria may be eligible for a short length of stay (LOS) (<24 hours), with expedited discharge home either directly from the ED or after a brief observation or hospitalization. We describe the association between expedited discharge and site of discharge on care satisfaction and quality of life (QOL) among patients with low-risk PE (PE Severity Index [PESI] Classes I-III).MethodsThis phone survey was conducted from September 2014 through April 2015 as part of a retrospective cohort study across 21 community EDs in Northern California. We surveyed low-risk patients with acute PE, treated predominantly with enoxaparin bridging and warfarin. All eligible patients were called 2-8 weeks after their index ED visit. PE-specific, patient-satisfaction questions addressed overall care, discharge instruction clarity, and LOS. We scored physical and mental QOL using a modified version of the validated Short Form Health Survey. Satisfaction and QOL were compared by LOS. For those with expedited discharge, we compared responses by site of discharge: ED vs. hospital, which included ED-based observation units. We used chi-square and Wilcoxon rank-sum tests as indicated.ResultsSurvey response rate was 82.3% (424 of 515 eligible patients). Median age of respondents was 64 years; 47.4% were male. Of the 145 patients (34.2%) with a LOS<24 hours, 65 (44.8%) were discharged home from the ED. Of all patients, 89.6% were satisfied with their overall care and 94.1% found instructions clear. Sixty-six percent were satisfied with their LOS, whereas 17.5% would have preferred a shorter LOS and 16.5% a longer LOS. There were no significant differences in satisfaction between patients with LOS<24 hours vs. ≥24 hours (p>0.13 for all). Physical QOL scores were significantly higher for expedited-discharge patients (p=0.01). Patients with expedited discharge home from the ED vs. the hospital had no significant difference in satisfaction (p>0.20 for all) or QOL (p>0.19 for all).ConclusionED patients with low-risk PE reported high satisfaction with their care in follow-up surveys. Expedited discharge (<24 hours) and site of discharge were not associated with differences in patient satisfaction.

Project description:INTRODUCTION:Syncope is common among emergency department (ED) patients with acute pulmonary embolism (PE) and indicates a higher acuity and worse prognosis than in patients without syncope. Whether presyncope carries the same prognostic implications has not been established. We compared incidence of intensive care unit (ICU) admission in three groups of ED PE patients: those with presyncope; syncope; and neither. METHODS:This retrospective cohort study included all adults with acute, objectively confirmed PE in 21 community EDs from January 2013-April 2015. We combined electronic health record extraction with manual chart abstraction. We used chi-square test for univariate comparisons and performed multivariate analysis to evaluate associations between presyncope or syncope and ICU admission from the ED, reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS:Among 2996 PE patients, 82 (2.7%) had presyncope and 109 (3.6%) had syncope. ICU admission was similar between groups (presyncope 18.3% vs syncope 25.7%) and different than their non-syncope counterparts (either 22.5% vs neither 4.7%; p<0.0001). On multivariate analysis, both presyncope and syncope were independently associated with ICU admission, controlling for demographics, higher-risk PE Severity Index (PESI) class, ventilatory support, proximal clot location, and submassive and massive PE classification: presyncope, aOR 2.79 (95% CI, 1.40, 5.56); syncope, aOR 4.44 (95% CI 2.52, 7.80). These associations were only minimally affected when excluding massive PE from the model. There was no significant interaction between either syncope or presyncope and PESI, submassive or massive classification in predicting ICU admission. CONCLUSION:Presyncope appears to carry similar strength of association with ICU admission as syncope in ED patients with acute PE. If this is confirmed, clinicians evaluating patients with acute PE may benefit from including presyncope in their calculus of risk assessment and site-of-care decision-making.

Dataset Information

Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study.

Publications

Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study.

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