Abstract | Background: Sepsis is a life-threatening condition with poor and highly variable clinical manifestations, which has remained a major cause of morbidity and mortality. Over time, definitions of sepsis have changed. Recently, in 2016, new sepsis definitions were set. At present, rapid diagnosis of sepsis is based on new sepsis biomarkers. Presepsin is a new sepsis biomarker, first described almost 15 years ago. The aim of the present study was to evaluate the diagnostic and prognostic value of presepsin in septic patients, as well as to compare the diagnostic and prognostic ability of presepsin with other biomarkers (PCT and CRP), and scoring systems (APACHE II and SOFA score). -----
Methods: A prospective observational study was conducted in two university hospitals for infectious diseases, in Kosovo and in Croatia. One hundred consecutive septic patients were enrolled in the study. Patients were grouped according to disease outcome (survivors and non-survivors) and disease severity (sepsis, septic shock). Sepsis biomarkers (presepsin ̶ PSEP, procalcitonin ̶ PCT, and C-reactive protein ̶ CRP) were measured at four time points over the course of the disease (on admission ̶ T0, after 24 hours ̶ T1, after 72 hours ̶ T2, and on Day 7 ̶ T3), and scoring systems (SOFA score and APACHE II score) were calculated. A sandwich Human presepsin ELISA Kit was used for presepsin measurements. Generalized linear mixed effects model was used to test the changes in presepsin concentrations during the illness and to estimate the difference between two outcome groups (survivors and non-survivors), as well as between two severity groups (sepsis and septic shock). Receiver Operating Characteristic (ROC) curves and areas under the ROC curves (AUCs) were calculated to test the importance of initial presepsin concentrations on sepsis outcome and sepsis severity. Based on optimal cut-off values of presepsin, for discriminating between outcome groups and severity groups, according to ROC curve analysis, the sensitivity and specificity of the found threshold values was calculated. Multivariate analysis was used to test the association of presepsin values and SOFA and APACHE II scores. For all statistical tests, significance was set at an alpha level of 0.05. All analyses were performed using SAS software version 9.3 (SAS Institute, Cary, North Carolina, USA). -----
Results: Presepsin concentrations were significantly higher in non-survivors compared to survivors, and in septic shock patients compared to patients with sepsis without shock. PCT and CRP levels did not differ between disease outcome groups, and neither between disease severity groups. Presepsin was the only biomarker associated with disease severity and disease outcome. There was a strong correlation between presepsin and SOFA and APACHE II scores. Only initial presepsin concentrations were associated with therapy failure. -----
Conclusion: This study shows that, compared to PCT and CRP, presepsin is a better diagnostic and prognostic. Initial and subsequent presepsin concentrations were significantly associated with disease severity and disease outcome. The same was not found for PCT and CRP. |
Abstract (croatian) | Uvod: Sepsa je životno ugrožavajuće stanje sa teškim i vrlo varijabilnim kliničkim manifestacijama, te ostaje značajan uzrok morbiditeta i mortaliteta. Definicija sepse mijenjala se s vremenom. Nedavno, 2016 godine postavljena je nova definicija sepse. Brza dijagnoza sepse može se postaviti na temelju novih biomarkera sepse. Presepsin je novi biomarker sepse, prvi put opisan prije gotovo 15 godina. Cilj ove studije bio je procijeniti dijagnostičku i prognostičku vrijednost presepsina u septičkih bolesnika, kao i usporediti dijagnostičku i prognostičku sposobnost presepsina s drugim biomarkerima (PCT i CRP) I skoring sustavima (APACHE II i SOFA skor). -----
Metode: Radi se o prospektivnoj opservacijskoj studiji provedenoj u 2 kliničke bolnice za infektivne bolesti, na Kosovu te u Hrvatskoj. U studiju je uključeno 100 pacijenata sa sepsom. Pacijenti su razmješteni u skupine prema ishodu bolesti (preživjeli i umrli) te prema težini bolesti (sepsa sa i bez septičkog šoka). Biomarkeri sepse (presepsin ̶ PSEP, procalcitonin ̶ PCT i C- reaktivni protein ̶ CRP) su mjereni četiri puta tijekom bolesti (kod prijema ̶ T0, nakon 24 sata ̶ T1, nakon 72 sata ̶ T2 i sedmog dana od početka bolesti ̶ T4), te su izračunati skoring sustavi (SOFA i APACHE II skor). Za mjerenje vrijednosti presepsina korištena je “sendvič” ELISA tehnika. Generalizirani linearni mješoviti model korišten je za analiziranje promjena u koncentracijama presepsina tijekom bolesti te procjenu razlika između skupina različitog ishoda bolesti (preživjelih i umrlih), kao i skupina različite težine bolesti (sepsa sa i bez septičkog šoka). Izračunate su ROC krivulje te površine ispod ROC krivulja (AUC) kako bi se procijenio značaj početnih vrijednosti koncentracija presepsina za ishod i težinu bolesti. Temeljem optimalnih graničnih vrijednosti presepsina za razlikovanje između grupa različitog ishoda i težine bolesti, analizom ROC krivulja izračunate su osjetljivost i specifičnost navedenih graničnih vrijednosti. Za ispitivanje povezanosti vrijednosti koncentracija presepsina i vrijednosti skorova za procjenu težine bolesti (SOFA i APACHE II) korištena je multivarijatna analiza. Za sve je testove korištena razina pouzdanosti od 5 posto. Sve su analize provedene koristeći SAS software verziju 9.3 (SAS Institute, Cary, North Carolina, USA). -----
Rezultati: koncentracije presepsina bila su značajno više u skupini umrlih bolesnika u usporedbi sa preživjelima, kao i u skupini bolesnika sa sepsom i septičkim šokom u usporedbi sa bolesnicima bez šoka. Razine PCT-a i CRP-a nisu se razlikovale između skupina različitog ishoda bolesti, kao ni skupina različite težine bolesti. Presepsin je bio jedini marker čije su vrijednosti bile povezane sa težinom bolesti i njezinim ishodom. Nađena je jasna korelacija između vrijednosti presepsina i SOFA i APACHE II skorova. Jedino su početne vrijednosti presepsina bile povezane s terapijskim neuspjehom. -----
Zaključak: naša je studija pokazala kako je presepsin bolji dijagnostički i prognostički marker sepse u usporedbi s drugim ispitivanim biomarkerima (CRP-om i PCT-om). Početne i subsekventne vrijednosti presepsina bile su značajno povezane s težinom i ishodom bolesti, dok isto nije nađeno za CRP i PCT. |