AUTHOR=Davoudian Sadaf , Piovani Daniele , Desai Antonio , Mapelli Sarah N. , Leone Roberto , Sironi Marina , Valentino Sonia , Silva-Gomes Rita , Stravalaci Matteo , Asgari Fatemeh , Madera Alessandra , Piccinini Daniele , Fedeli Carlo , Comina Denise , Bonovas Stefanos , Voza Antonio , Mantovani Alberto , Bottazzi Barbara TITLE=A cytokine/PTX3 prognostic index as a predictor of mortality in sepsis JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.979232 DOI=10.3389/fimmu.2022.979232 ISSN=1664-3224 ABSTRACT=Background

Early prognostic stratification of patients with sepsis is a difficult clinical challenge. Aim of this study was to evaluate novel molecules in association with clinical parameters as predictors of 90-days mortality in patients admitted with sepsis at Humanitas Research Hospital.

Methods

Plasma samples were collected from 178 patients, diagnosed based on Sepsis-3 criteria, at admission to the Emergency Department and after 5 days of hospitalization. Levels of pentraxin 3 (PTX3), soluble IL-1 type 2 receptor (sIL-1R2), and of a panel of pro- and anti-inflammatory cytokines were measured by ELISA. Cox proportional-hazard models were used to evaluate predictors of 90-days mortality.

Results

Circulating levels of PTX3, sIL-1R2, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-1ra, TNF-α increased significantly in sepsis patients on admission, with the highest levels measured in shock patients, and correlated with SOFA score (PTX3: r=0.44, p<0.0001; sIL-1R2: r=0.35, p<0.0001), as well as with 90-days mortality. After 5 days of hospitalization, PTX3 and cytokines, but not sIL-1R2 levels, decreased significantly, in parallel with a general improvement of clinical parameters. The combination of age, blood urea nitrogen, PTX3, IL-6 and IL-18, defined a prognostic index predicting 90-days mortality in Sepsis-3 patients and showing better apparent discrimination capacity than the SOFA score (AUC=0.863, 95% CI: 0.780−0.945 vs. AUC=0.727, 95% CI: 0.613-0.840; p=0.021 respectively).

Conclusion

These data suggest that a prognostic index based on selected cytokines, PTX3 and clinical parameters, and hence easily adoptable in clinical practice, performs in predicting 90-days mortality better than SOFA. An independent validation is required.