Two Authors, Independently, Performed the Selection of the Studies to Include in the Review

APPENDIX

Search methods

An Internet-based search of the MEDLINE was performed using the terms “biomarkers”, “sepsis”, “systemic inflammatory response syndrome” and “diagnosis” in various combinations.

All articles published between 1st January 2012 and 1st January 2014 evaluating the performance of biomarkers for sepsis diagnosis in patients suffering systemic inflammatory response syndrome were eligible for inclusion.

Two authors, independently, performed the selection of the studies to include in the review.

Inclusion criteria

Prospective studies enrolling 100 adults (> 18 years old) and meta analysis of clinical studies.

Exclusion criteria:

Animal studies, case reports, narrative reviews, editorials, and letters.

Studies in languages other than English.

Human studies that used only healthy volunteers as control of sepsis.

Studies in which receiver operating curve (ROC), sensitivity and specificity were not clearly documented.

Data extraction and analysis

The following data were extracted from each study: design, sample size, setting,population type, exclusion criteria, typology of the biomarkers, number of biomarkers, timing of sampling of the biomarkers, sensitivity, specificity, AUC for an discrimination of sepsis, statistical analysis for the combination of biomarkers (see Table 3 and Table 4).

Results

11 studies published in 2013and 12 studies published in 2012 met the inclusion criteria and entered the analysis.

A biomarker entry the chart in Figure 2 only if it was associated with an AUC ≥ 0.85% (the same AUC found for PCT in Wacker et al meta analysis36) in at least one study according to previous selection criteria.

Table3. Studies published in 2012 according to selection criteria.

ICU: intensive care unit; ED: emergency departments; MW: medical ward; AUC: area under the curve; Sn: sensibility; Sp: specificity; BM: biomarkers; CRP: C-reactive protein; PLA II G II: phospholipase A2 group IIa; PCT: procalcitonin; IL-6: interleukin-6; sCD163: soluble haemoglobin scavenger receptor; nCD64: CD64 expression on neutrophils; sTREM: soluble triggering receptor expressed on myeloid cells-1; suPAR: soluble urokinase plasminogen activator receptor; miRNA: microRNA; LBP: lipopolysaccharide binding protein.

Table 4. Studies published in 2013 according to selection criteria.

ED: emergency departments; MW: medical ward; ICU: intensive care unit; SW: surgical ward; BM: biomarkers; AUC: area under the curve; Sn: sensibility; Sp: specificity; CRP: c reactive protein; PCT: procalcitonin; pro-ADM: proadrenomedullin; IL-6: interleukin 6; IL-8: interleukin-8; IL-27: interleukin-27; IL-1 beta: interleukin-1beta;CD64: CD64 expression on neutrophils; sCD14-ST: soluble CD14 subtype (presepsin);sCD163: soluble haemoglobin scavenger receptor; sTREM: Soluble triggering receptor expressed on myeloid cells-1; sCD25: Soluble IL2 receptor alpha;LBP: lipopolysaccharide binding protein.