Abstract
BackgroundHigh-mobility group box 1 (HMGB1), originally described as a nuclear protein that binds to and modifies DNA, is now regarded as a central mediator of inflammation by acting as a cytokine. However, the association of HMGB1 in the peripheral blood with disease outcome and cerebrovasospasm has not been examined in patients with aneurysmal subarachnoid hemorrhage.MethodsIn this study, 303 consecutive patients were included. Upon admission, plasma HMGB1 levels were measured by ELISA. The end points were mortality after 1 year, in-hospital mortality, cerebrovasospasm and poor functional outcome (Glasgow Outcome Scale score of 1 to 3) after 1 year.ResultsUpon admission, the plasma HMGB1 level in patients was statistically significantly higher than that in healthy controls. A multivariate analysis showed that the plasma HMGB1 level was an independent predictor of poor functional outcome and mortality after 1 year, in-hospital mortality and cerebrovasospasm. A receiver operating characteristic curve showed that plasma HMGB1 level on admission statistically significantly predicted poor functional outcome and mortality after 1 year, in-hospital mortality and cerebrovasospasm of patients. The area under the curve of the HMGB1 concentration was similar to those of World Federation of Neurological Surgeons (WFNS) score and modified Fisher score for the prediction of poor functional outcome and mortality after 1 year, and in-hospital mortality, but not for the prediction of cerebrovasospasm. In a combined logistic-regression model, HMGB1 improved the area under the curve of WFNS score and modified Fisher score for the prediction of poor functional outcome after 1 year, but not for the prediction of mortality after 1 year, in-hospital mortality, or cerebrovasospasm.ConclusionsHMGB1 level is a useful, complementary tool to predict functional outcome and mortality after aneurysmal subarachnoid hemorrhage. However, HMGB1 determination does not add to the accuracy of prediction of the clinical outcomes.
Highlights
High-mobility group box 1 (HMGB1), originally described as a nuclear protein that binds to and modifies DNA, is regarded as a central mediator of inflammation by acting as a cytokine
Study population characteristics During the recruitment period 347 patients were admitted with an initial diagnosis of aneurysmal Subarachnoid hemorrhage (SAH), 312 (89.9%) patients fulfilled the inclusion criteria, and adequate data on admission and follow-up were available for 303 individuals (87.3%) who were included in the analysis (Figure 1)
This study was conducted to determine if plasma HMGB1 is increased in the circulation of humans with SAH and whether this enhancement correlates with in-hospital mortality, cerebrovasospasm and 1-year poor clinical outcomes in these patients
Summary
High-mobility group box 1 (HMGB1), originally described as a nuclear protein that binds to and modifies DNA, is regarded as a central mediator of inflammation by acting as a cytokine. The association of HMGB1 in the peripheral blood with disease outcome and cerebrovasospasm has not been examined in patients with aneurysmal subarachnoid hemorrhage. High-mobility group box 1 (HMGB1) is constitutively expressed in the nuclei of eukaryotic cells. It belongs to a family of high mobility group nuclear proteins that were described in the 1970s as gene regulators that bind to and change the configuration of DNA [5,6]. HMGB1 is a central actor in the inflammatory network because it is induced by a number of cytokines and itself induces a series of inflammatory reactions [9,10,11,12]
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