, Parsippany, NJ, USA), angiopoietin-2 (Ang-2; Quantikine Ang-2 EIA, R&D Systems Inc., Minneapolis, MN, USA), soluble C5b-9 to assess the late phase of terminal complement activation (sC5b-9 EIA, Quidel Corp., San Diego, CA, USA), prothrombin selleckchem fragments (PF 1+2; Enzygnost F1+2 EIA, Dade Behring, Germany), soluble thrombomodulin (TM; Asserachrom Thrombomodulin EIA, Diagnostica Stago Inc., Parsippany, NJ, USA), and plasminogen activator inhibitor 1 (PAI-1; Oxford Biochemicals, Oxford, MI, US). protein C activity, tissue plasminogen activator (t-PA), and D-Dimers were measured with a Stago Compact (Diagnostica Stago Inc., Parsippany, NJ, USA), All measurements were performed in accordance with the manufacturers’ instructions.

Data collection, outcome measuresData were collected prospectively on patient demographics, the injury time, mechanism (blunt or penetrating) and severity, pre-hospital fluid administration, time of arrival in the trauma room and admission vital signs. The Injury Severity Score (ISS) was used as a measure of the degree of tissue injury [21]. An arterial blood gas was drawn at the same time as the research sample as part of the standard management of major trauma patients. The base deficit was used as a measure of the degree of tissue hypoperfusion. Admission base deficit is a clinically useful early marker of tissue hypoperfusion in trauma patients and an admission base deficit greater than 6 mmol/l has previously been identified as being predictive of worse outcome in trauma patients [22,23].Outcome measuresPatients were followed until hospital discharge or death.

For mortality analysis, patients surviving to hospital discharge were assumed to still be alive. Secondary outcome measures were also recorded for 28-day ventilator-free days, acute lung injury (American-European consensus conference definition) [24] and acute renal injury (Acute Dialysis Quality Initiative consensus conference definition) [25] and blood transfusions required in the first 24 hours.Statistical analysisData analysis was performed by the investigators. Normal-quantile plots were used to test for normal distribution. Relations between quartile of HMGB1 and continuous variables were tested with the Kruskall-Wallis test followed by a non-parametric test for trend. Two-group analysis was performed using the Wilcoxon rank-sum method.

Correlation was assessed by Spearman correlation coefficients. Logistic regression was used to examine the relationship between mortality and HMGB1 levels. A P �� 0.05 was chosen to represent GSK-3 statistical significance.ResultsPatient populationTable Table11 shows the characteristics of the severely injured trauma patients enrolled in the study. We enrolled 168 consecutive traumatized patients into the study over a 15-month period. Due to short transport times from the scene of injury to our trauma center in San Francisco, the mean (�� standard deviation) time from injury to blood sampling was 32 �� 6 minutes.