The critical area setting, especially ED, is particularly suited to reveal the potential greater utility of P-SEP over PCT in the early diagnosis of sepsis. Several studies have shown that P-SEP has diagnostic and prognostic power substantially similar to PCT, but, unlike PCT, P-SEP increases earlier in bacterial infection and can be measured effectively and accurately within 17 min directly in the emergency department 
. A 2013 prospective study, conducted on 859 consecutive ED patients with at least two SIRS criteria (as defined prior to SEPIS-3), showed that P-SEP plasma levels is useful both for the diagnosis and for prognosis of sepsis, since P-SEP has been shown to be effective in stratifying the severity of sepsis, septic shock and in predicting mortality at 28 days. This study showed that the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy vary according to the cutoff used for P-SEP plasma levels. Using a cutoff of 449 ng/L P-SEP grades the severity of sepsis with sensitivity of 82.4%, specificity of 72.4%, PPV of 71.3% and NPV of 83.2% with a predictive accuracy of 77.0%; using a cutoff of 550 ng/L P-SEP predicts septic shock with sensitivity, specificity, PVV and NPV of 85.7%, 63.6%, 28.5% and 96.3%, respectively, and a predictive accuracy of 66.8%; using a cutoff of 556 ng/mL P-SEP predicts mortality at 28 days with sensitivity of 62.2%, specificity of 66.8%, PPV of 48.3%, NPV of 78.0% and predictive accuracy of 65.3% 
. In 2015, Carpio et al. performed another single-center prospective observational study, including 120 patients with SIRS or sepsis criteria (prior to SEPSIS-3) and 123 healthy controls, confirmed that P-SEP at a cutoff of 581 ng/L is effective in diagnosing sepsis, graduating severity of disease and differentiating between SIRS and sepsis in ED, with sensitivity of 61% and specificity of 100% 
. Also in this study, as in the previous one, the performance of P-SEP varies according to the cutoff considered: using a cutoff of 273 ng/L, a sensitivity of 95.5% and specificity of 21.7% were found, while using a cutoff of 686 ng/L these values were 46.5% and 91.3%, respectively. A study performed by de Guadiana Romualdo et al. in 2014, including 226 patients admitted to the ED with SIRS criteria, of which 37 had positive blood culture (bacteremic SIRS group) and 189 had negative blood culture (non-bacteremic SIRS group), reported sensitivity, specificity, PPV and NVP values of 81.1%, 63%, 30% and 94.4%, respectively, for the diagnosis of SIRS using a cutoff of 729 ng/L 
. In 2017 the same author examined a cohort of 223 admitted in ED for suspected sepsis using two different P-SEP cutoffs, 312 and 849 ng/L, and found sensitivity values of 97.1% and of 67.1% and specificity values of 16.9% and 80.8%, respectively 
. It has been reported that, using a 101.6 ng/L cutoff, P-SEP, measured at the time of diagnosis in the ED 24 h before admission to the ICU, has values of sensitivity, specificity, PPV and NPV of 81.9%, 96.5%, 82.4% and 96.3%, respectively, thus allowing for better management in both severe sepsis and septic shock 
. The different cutoff values reported in the different studies are likely due to heterogeneity regarding the clinical setting (ED, ICU), the sepsis criteria adopted (before or after SEPSIS-3) and the type of sample (plasma, serum or whole blood) for the measurement of the P-SEP.