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HMGB1 as a predictor of organ dysfunction and outcome in patients with severe sepsis.

by: Sari Karlsson, Ville Pettilä, Jyrki Tenhunen, Raili Laru-Sompa, Marja Hynninen, Esko Ruokonen
Intensive Care Med (23 February 2008)


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OBJECTIVE: To study the predictive value of high mobility group box-1 protein (HMGB1) and hospital mortality in adult patients with severe sepsis. STUDY DESIGN: Prospective observational cohort study in 24 ICUs in Finland. PATIENTS: Two hundred and forty-seven adult patients with severe sepsis. MEASUREMENTS AND MAIN RESULTS: Blood samples for HMGB1 analyses were drawn from 247 patients at baseline and from 210 patients 72[Symbol: see text]h later. The mean APACHE II and SAPS II scores were 24 (SD 9) and 44 (SD 17), respectively. The hospital mortality was 26%. The serum HMGB1 concentrations were measured first by semi-quantitative Western immunoblotting (WB) analysis. The median HMGB1 concentration on day 0 was 108% (IQR 98.5-119) and after 72[Symbol: see text]h 107% (IQR 98.8-120), which differed from healthy controls (97.5%, IQR 91.3-106.5; p[Symbol: see text]=[Symbol: see text]0.028 and 0.019, respectively). The samples were re-analysed by ELISA (in a subgroup of 170 patients) to confirm the results by WB. The median concentration in healthy controls was 0.65[Symbol: see text]ng/ml (IQR 0.51-1.0). This was lower than in patients with severe sepsis (3.6[Symbol: see text]ng/ml, IQR 1.9-6.5, p[Symbol: see text]<[Symbol: see text]0.001). HMGB1 concentrations (WB and ELISA) did not differ between hospital survivors and non-survivors. In ROC analyses for HMGB1 levels (WB) on day 0 and 72[Symbol: see text]h with respect to hospital mortality, the areas under the curve were 0.51 and 0.56 (95% CI 0.40-0.61 and 0.47-0.65). CONCLUSIONS: Serum HMGB1 concentrations were elevated in patients with severe sepsis, but did not differ between survivors and non-survivors and did not predict hospital mortality.


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