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Quantifying the transcriptomic ratios MMP8/HLA-DRA, LCN2/HLA-DRA by ddPCR is a promising approach to improve sepsis diagnosis in surgical patients.

Background: Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients.Methods: Levels of ten biomarkers indicating endothelial dysfunction, 22 indicating emergency granulopoiesis, and six denoting neutrophil degranulation were compared in three groups of patients in the first 12 h after diagnosis at three Spanish hospitals.Results: There were 100 patients with infection, 95 with sepsis and 57 with septic shock. Seven biomarkers indicating endothelial dysfunction (mid-regional proadrenomedullin (MR-ProADM), syndecan 1, thrombomodulin, angiopoietin 2, endothelial cell-specific molecule 1, vascular cell adhesion molecule 1 and E-selectin) had stronger associations with sepsis than infection alone. MR-ProADM had the highest odds ratio (OR) in multivariable analysis (OR 11⋅53, 95 per cent c.i. 4⋅15 to 32⋅08; P = 0⋅006) and the best area under the curve (AUC) for detecting sepsis (0⋅86, 95 per cent c.i. 0⋅80 to 0⋅91; P < 0⋅001). In a comparison of sepsis with septic shock, two biomarkers of neutrophil degranulation, proteinase 3 (OR 8⋅09, 1⋅34 to 48⋅91; P = 0⋅028) and lipocalin 2 (OR 6⋅62, 2⋅47 to 17⋅77; P = 0⋅002), had the strongest association with septic shock, but lipocalin 2 exhibited the highest AUC (0⋅81, 0⋅73 to 0⋅90; P < 0⋅001). Conclusion: MR-ProADM and lipocalin 2 could be alternatives to the SOFA score in the detection of sepsis and septic shock respectively in surgical patients with infection. Healthy control Infection Sepsis Septic shockBiomarkers of a,b emergency granulopoiesis and c acute-phase response. Levels of C-reactive protein (CRP) are in mg/l, those of procalcitonin (PCT) are in ng/ml, and those of the remaining biomarkers are copies of cDNA per ng mRNA. MMP, matrix metalloproteinase; LTF, lactoferrin; PRTN, proteinase; LCN, lipocalin, OLFM, olfactomedin; ELANE, elastase, neutrophil expressed; MPO, myeloperoxidase; CTSG, cathepsin G; AZU, azurocidin; BPI, bactericidal/permeability-increasing protein; DEFA, defensin α; CEACAM, carcinoembryonic antigen-related cell adhesion molecule; CD, cluster of differentiation; TCN, transcobalamin; STOM, stomatin; IL1R2, interleukin-1 receptor type 2; CHIT, chitinase. *P ≤ 0⋅050 versus healthy control;†P ≤ 0⋅050 (Kruskal-Wallis test).

Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA-DRA expression was quantified using droplet digital PCR, a next-generation PCR technology. Area under the receiver operating curve analysis (AUROC) showed that the PCT/HLA-DRA ratio outperformed PCT to detect sepsis (AUROC [CI95%], p): PCT: 0.80 [0.73–0.88], <0.001; PCT/HLA-DRA: 0.85 [0.78–0.91], <0.001. In the multivariate analysis, the ratio showed a superior ability to predict sepsis compared to that of PCT (OR [CI 95%], p): PCT/HLA-DRA: 7.66 [1.82–32.29], 0.006; PCT: 4.21 [1.15–15.43] 0.030. Multivariate analysis was confirmed using a new surgical cohort with 74 sepsis patients and 21 controls: PCT/HLA-DRA: 34.86 [1.22–995.08], 0.038; PCT: 5.52 [0.40–75.78], 0.201. In conclusion, the combination of PCT with HLA-DRA is a promising strategy for improving sepsis detection in surgical patients.

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