Blood glutathione S-transferase-π as a time indicator of stroke onset.

BACKGROUND: Ability to accurately determine time of stroke onset remains challenging. We hypothesized that an early biomarker characterized by a rapid increase in blood after stroke onset may help defining better the time window during which an acute stroke patient may be candidate for intravenous thrombolysis or other intravascular procedures. METHODS: The blood level of 29 proteins was measured by immunoassays on a prospective cohort of stroke patients (N = 103) and controls (N = 132). Mann-Whitney U tests, ROC curves and diagnostic odds ratios were applied to evaluate their clinical performances. RESULTS: Among the 29 molecules tested, GST-π concentration was the most significantly elevated marker in the blood of stroke patients (p<0.001). More importantly, GST-π displayed the best area under the curve (AUC, 0.79) and the best diagnostic odds ratios (10.0) for discriminating early (N = 22, <3 h of stroke onset) vs. late stroke patients (N = 81, >3 h after onset). According to goal-oriented distinct cut-offs (sensitivity(Se)-oriented: 17.7 or specificity(Sp)-oriented: 65.2 ug/L), the GST-π test obtained 91%Se/50%Sp and 50%Se/91%Sp, respectively. Moreover, GST-π showed also the highest AUC (0.83) and performances for detecting patients treated with tPA (N = 12) compared to ineligible patients (N = 103). CONCLUSIONS: This study demonstrates that GST-π can accurately predict the time of stroke onset in over 50% of early stroke patients. The GST-π test could therefore complement current guidelines for tPA administration and potentially increase the number of patients accessing thrombolysis.

A multiparameter panel method for outcome prediction following aneurysmal subarachnoid hemorrhage.

PURPOSE: Accurate early anticipation of long-term irreversible brain damage during the acute phase of patients with aneurysmal subarachnoid hemorrhage (aSAH) remains difficult. Using a combination of clinical scores together with brain injury-related biomarkers (H-FABP, NDKA, UFD1 and S100beta), this study aimed at developing a multiparameter prognostic panel to facilitate early outcome prediction following aSAH. METHODS: Blood samples of 141 aSAH patients from two separated cohorts (sets of 28 and 113 patients) were prospectively enrolled and analyzed with 14 months of delay. Patients were admitted within 48 h following aSAH onset. A venous blood sample was withdrawn within 12 h after admission. H-FABP, NDKA, UFD1, S100beta and troponin I levels were determined using classical immunoassays. The World Federation of Neurological Surgeons (WFNS) at admission and the Glasgow Outcome Score (GOS) at 6 months were evaluated. RESULTS: In the two cohorts, blood concentration of H-FABP, S100beta and troponin I at admission significantly predicted unfavorable outcome (GOS 1-2-3). A multivariate analysis identified a six-parameter panel, including WFNS, H-FABP, S100beta, troponin I, NDKA and UFD-1; when at least three of these parameters were simultaneously above cutoff values, prediction of unfavorable outcome reached around 70% sensitivity in both cohorts for 100% specificity. CONCLUSION: The use of this panel, including four brain injury-related proteins, one cardiac marker and a clinical score, could be a valuable tool to identify aSAH patients at risk of poor outcome.

A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients.

BACKGROUND: Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite. METHODS: Cerebrospinal fluid (CSF) originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC) count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and 5 WBC/microL) patients. The concentration of H-FABP, GSTP-1 and S100beta in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1beta, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-gamma, TNF-alpha, CCL2, CCL4, CXCL8 and CXCL10) were determined by bead suspension arrays. RESULTS: CXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL) analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity. CONCLUSION: This study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis.