RESUMO
Inflammatory response following SARS-CoV-2 infection results in substantial increase of amounts of intravascular pro-coagulant extracellular vesicles (EVs) expressing tissue factor (CD142) on their surface. CD142-EV turned out to be useful as diagnostic biomarker in COVID-19 patients. Here we aimed at studying the prognostic capacity of CD142-EV in SARS-CoV-2 infection. Expression of CD142-EV was evaluated in 261 subjects admitted to hospital for pneumonia and with a positive molecular test for SARS-CoV-2. The study population consisted of a discovery cohort of selected patients (n = 60) and an independent validation cohort including unselected consecutive enrolled patients (n = 201). CD142-EV levels were correlated with post-hospitalization course of the disease and compared to the clinically available 4C Mortality Score as referral. CD142-EV showed a reliable performance to predict patient prognosis in the discovery cohort (AUC = 0.906) with an accuracy of 81.7%, that was confirmed in the validation cohort (AUC = 0.736). Kaplan-Meier curves highlighted a high discrimination power in unselected subjects with CD142-EV being able to stratify the majority of patients according to their prognosis. We obtained a comparable accuracy, being not inferior in terms of prediction of patients' prognosis and risk of mortality, with 4C Mortality Score. The expression of surface vesicular CD142 and its reliability as prognostic marker was technically validated using different immunocapture strategies and assays. The detection of CD142 on EV surface gains considerable interest as risk stratification tool to support clinical decision making in COVID-19.
Assuntos
COVID-19 , Vesículas Extracelulares , Biomarcadores/metabolismo , COVID-19/diagnóstico , Vesículas Extracelulares/metabolismo , Humanos , Reprodutibilidade dos Testes , Medição de Risco/métodos , SARS-CoV-2 , Tromboplastina/metabolismoRESUMO
The current standard biomarker for myocardial infarction (MI) is high-sensitive troponin. Although powerful in clinical setting, search for new markers is warranted as early diagnosis of MI is associated with improved outcomes. Extracellular vesicles (EVs) attracted considerable interest as new blood biomarkers. A training cohort used for diagnostic modelling included 30 patients with STEMI, 38 with stable angina (SA) and 30 matched-controls. Extracellular vesicle concentration was assessed by nanoparticle tracking analysis. Extracellular vesicle surface-epitopes were measured by flow cytometry. Diagnostic models were developed using machine learning algorithms and validated on an independent cohort of 80 patients. Serum EV concentration from STEMI patients was increased as compared to controls and SA. EV levels of CD62P, CD42a, CD41b, CD31 and CD40 increased in STEMI, and to a lesser extent in SA patients. An aggregate marker including EV concentration and CD62P/CD42a levels achieved non-inferiority to troponin, discriminating STEMI from controls (AUC = 0.969). A random forest model based on EV biomarkers discriminated the two groups with 100% accuracy. EV markers and RF model confirmed high diagnostic performance at validation. In conclusion, patients with acute MI or SA exhibit characteristic EV biomarker profiles. EV biomarkers hold great potential as early markers for the management of patients with MI.
Assuntos
Angina Estável/sangue , Biomarcadores/sangue , Epitopos/sangue , Vesículas Extracelulares/genética , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/metabolismo , Síndrome Coronariana Aguda/patologia , Idoso , Angina Estável/genética , Angina Estável/patologia , Antígenos CD40/sangue , Estudos de Coortes , Mapeamento de Epitopos , Epitopos/genética , Feminino , Humanos , Integrina alfa2/sangue , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Intervenção Coronária Percutânea , Molécula-1 de Adesão Celular Endotelial a Plaquetas/sangue , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Infarto do Miocárdio com Supradesnível do Segmento ST/patologiaRESUMO
Cardiovascular magnetic resonance (CMR) is the gold standard technique to comprehensively assess cardiac structure and function. A 64-year-old male, planned for surgical coronary revascularization, underwent transthoracic and transesophageal echocardiography for a mitral regurgitation, with an eccentric jet of unclear mechanism; these examinations were inconclusive because of the lack of adequate visualization of the cardiac structures. A CMR was then performed to quantify mitral regurgitation and, additionally, it documented a giant hiatus hernia with gastric sliding into the thorax. In this case, CMR helped to better define the severity of a valvular disease and provided ancillary information from the extracardiac findings.
