Advanced detection of sepsis
The present invention relates to methods, monitors and systems, useful, for example, for advanced detection of sepsis in a subject.
1. A method comprising the steps of:
(a) measuring at a plurality of time points, prior to laboratory confirmation of a clinically significant infection causative of sepsis, an amount of a compound according to formula (I)
or a salt or solvate thereof, wherein R is C 10 -C 22 acyl, in fluid or tissue of a SIRS-positive subject;
(b) measuring at a plurality of time points, prior to laboratory confirmation of a clinically significant infection causative of sepsis, one or more clinical markers of the SIRS-positive subject selected from the group consisting of respiratory rate, temperature, heart rate, systolic blood pressure, diastolic blood pressure, mean artery pressure, white blood cell count, monocyte count, lymphocyte count, granulocyte count, neutrophil count, immature neutrophil to total neutrophil ratio, platelet count, serum creatinine concentration, urea concentration, lactate concentration, glucose concentration, base excess, pO 2 and HCO 3 − concentration; provided respiratory rate and temperature are measured, and
(c) measuring at a plurality of time points, prior to laboratory confirmation of a clinically significant infection causative of sepsis, an amount of one or more biomarkers in fluid or tissue of the SIRS-positive subject selected from the group consisting of ACTH, activated partial thromboplastin, albumin, antithrombin III, bacterial DNA, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), cell surface proteins CD-14 and CD-64, copeptin, C-reactive protein, cortisol, D-dimer, E-selectin, extra-hepatic arginase (ARG2), endotoxin, fibrin degrading products, high mobility group box 1 (HMGB1), HLA-DRA, interleukins IL-6, IL-8 and IL-10, LBP LPS-binding protein, plasminogen activator inhibitor-1, procalcitonin, protein C, protein S, prothrombin, soluble thrombomodulin, surface-bound tumor necrosis factor receptor I (sTNF-RI), surface-bound tumor necrosis factor receptor II (sTNF-RII), thrombin activatable fibrinolysis inhibitor, TRAF-interacting protein with a forkhead-associated domain (TIFA), triggering receptor expressed on myeloid cells 1, and tumor necrosis factor alpha (TNFα).
2. The method of claim 1 , wherein R is saturated acyl.
3. The method of claim 1 , wherein R is C 14 -C 22 acyl.
4. The method of claim 1 , wherein R is C 16 -C 20 acyl.
5. The method of claim 1 , wherein R is C 16 -C 18 acyl.
6. The method of claim 1 , wherein R is C 16 saturated acyl.
7. The method of claim 1 , wherein R is C 18 saturated acyl.
8. The method of claim 1 , wherein R is unbranched C 16 -C 18 acyl.
9. The method of claim 1 , wherein R is palmitoyl.
10. The method of claim 1 , wherein R is stearoyl.
11. The method of claim 1 , wherein the amount of a compound according to formula (I) is measured 12, 24, 36 or 48 hours prior to the onset of sepsis in said SIRS-positive patient.
12. The method of claim 1 , wherein the one or more biomarkers comprise procalcitonin.
13. The method of claim 12 , wherein the one or more clinical markers of the SIRS-positive subject comprises respiratory rate and temperature.
14. The method of claim 1 , wherein the one or more clinical markers of the SIRS-positive subject comprises respiratory rate and temperature.
15. The method of claim 1 , wherein the one or more biomarkers in fluid or tissue of the SIRS-positive subject comprises TRAF-interacting protein with a forkhead-associated domain (TIFA), extra-hepatic arginase (ARG2), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and human leukocyte antigen—antigen D-related alpha chain (HLA-DRA).
16. The method of claim 1 , wherein the one or more clinical markers of the SIRS-positive subject comprises respiratory rate or temperature, and the one or more biomarkers comprises HLA-DRA.