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Background: High-mobility group box 1 (HMGB1), a marker of inflammation, has been associated with poor outcome of critical illness.The present study was undertak en to investigate the plasma HMGB1 concentrations in patients with traumatic brain injury (TBI) and to analyze the correlation of HMGB1 with TBI outcome.Methods: We performed an observational, clinical study.Plasma HMGB1 concentration of one hundred and six healthy subjects and 106 patients with severe TBI was mea sured by enzyme-linked immunosorbent assay.Its correlation with 1-year mortality and unfavorable outcome (Glasgow Outcome Scale score of 1-3) was analyzed.Results: Thirty-one patients (29.2%) died and 48 patients (45.3%) had an unfavor able outcome at 1 year after TBI.Plasma HMGB1 level was substantially higher in patients than in healthy controls.A multivariate analysis selected plasma HMGB1 lev el as an independent predictor for 1-year mortality and unfavorable outcome of pa tients.A receiver operating characteristic curve analysis showed plasma HMGB1 level statistically significantly predicted 1-year mortality and unfavorable outcome.The prognostic value of HMGB1 was similar to that of Glasgow Coma Scale score for 1-year clinical outcomes.Conclusions: Plasma HMGB1 level emerges as a novel biomarker for predicting 1-year clinical outcomes of TBI.