HMGB1 as a predictor of organ dysfunction and outcome in patients with severe sepsis
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To study the predictive value of high mobility group box-1 protein (HMGB1) and hospital mortality in adult patients with severe sepsis.
Prospective observational cohort study in 24 ICUs in Finland.
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 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 h 107% (IQR 98.8–120), which differed from healthy controls (97.5%, IQR 91.3–106.5; p = 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 ng/ml (IQR 0.51–1.0). This was lower than in patients with severe sepsis (3.6 ng/ml, IQR 1.9–6.5, p < 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 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).
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.
KeywordsHMGB1 Severe sepsis Septic shock Organ failure Mortality Outcome
The authors acknowledge all investigators and study nurses of the Finnsepsis-study in the participating hospitals and especially Seija Laitinen, chief medical laboratory technologist, for performing the HMGB1 analyses.
The study was supported by an EVO grant from Helsinki University Hospital (TYH 6235) and from Tampere University Hospital.
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