Evaluating the discriminating capacity of cell death (apoptotic) biomarkers in sepsis
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Le résumé fourni par la source
BACKGROUND: Sepsis biomarker panels that provide diagnostic and prognostic discrimination in sepsis patients would be transformative to patient care. We assessed the mortality prediction and diagnostic discriminatory accuracy of two biomarkers reflective of cell death (apoptosis), circulating cell-free DNA (cfDNA), and nucleosomes. METHODS: The cfDNA and nucleosome levels were assayed in plasma samples acquired in patients admitted from four emergency departments with suspected sepsis. Subjects with non-infectious systemic inflammatory response syndrome (SIRS) served as controls. Samples were acquired at enrollment (T0) and 24 h later (T24). We assessed diagnostic (differentiating SIRS from sepsis) and prognostic (28-day mortality) predictive power. Models incorporating procalcitonin (diagnostic prediction) and APACHE II scores (mortality prediction) were generated. RESULTS: Two hundred three subjects were included (107 provided procalcitonin measurements). Four subjects exhibited uncomplicated sepsis, 127 severe sepsis, 35 septic shock, and 24 had non-infectious SIRS. There were 190-survivors and 13 non-survivors. Mortality prediction models using cfDNA, nucleosomes, or APACHEII yielded AUC values of 0.61, 0.75, and 0.81, respectively. A model combining nucleosomes with the APACHE II score improved the AUC to 0.84. Diagnostic models distinguishing sepsis from SIRS using procalcitonin, cfDNA(T0), or nucleosomes(T0) yielded AUC values of 0.64, 0.65, and 0.63, respectively. The three parameter model yielded an AUC of 0.74. CONCLUSIONS: To our knowledge, this is the first head-to-head comparison of cfDNA and nucleosomes in diagnosing sepsis and predicting sepsis-related mortality. Both cfDNA and nucleosome concentrations demonstrated a modest ability to distinguish sepsis survivors and non-survivors and provided additive diagnostic predictive accuracy in differentiating sepsis from non-infectious SIRS when integrated into a diagnostic prediction model including PCT and APACHE II. A sepsis biomarker strategy incorporating measures of the apoptotic pathway may serve as an important component of a sepsis diagnostic and mortality prediction tool.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Evaluating the discriminating capacity of cell death (apoptotic) biomarkers in sepsis
- Date Crossref
- 13/11/2018
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Naval Medical Research Command pays non établi dans la noticeStructure de recherche
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University of South Alabama Department of Pharmacology and Center for Lung Biology pays non établi dans la noticeUniversité ou école supérieure
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Children’s Institute pays non établi dans la noticeOrganisation à but non lucratif
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Duke University Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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Precision for Medicine (United States) pays non établi dans la noticeEntreprise
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Durham VA Medical Center pays non établi dans la noticeÉtablissement de santé
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Duke University Health System pays non établi dans la noticeUniversité ou école supérieure
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Wayne State University Henry Ford Hospital pays non établi dans la noticeUniversité ou école supérieure
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Henry Ford Hospital pays non établi dans la noticeÉtablissement de santé
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University of North Carolina at Chapel Hill pays non établi dans la noticeUniversité ou école supérieure
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University of North Carolina Health Care Department of Emergency Medicine pays non établi dans la noticeÉtablissement de santé
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Naval Medical Research Center Biological Defense Research Directorate pays non établi dans la noticeStructure de recherche
Naval Medical Research Command, Department of Pharmacology and Center for Lung Biology — University of South Alabama et Children’s Institute, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.