Prehospital Validation of the Assessment of Blood Consumption (ABC) Score.

INTRODUCTION: The Assessment of Blood Consumption (ABC) score is a previously validated scoring system designed to predict which severely injured trauma patients will require massive transfusion. When the ABC score is used in the prehospital setting to activate massive transfusion at the receiving hospital, a 23% decrease in mortality has been demonstrated. However, the ABC score was developed and validated using hospital data from the emergency department (ED). The sensitivity and specificity of the ABC score when calculated using data from the prehospital setting are unknown. We hypothesized that the sensitivity and specificity of the prehospital ABC score will be similar to the sensitivity and specificity of the ED ABC score. METHODS: A 5-year retrospective analysis (2015-2019) of highest-activation adult trauma patients arriving to a quaternary Level I trauma center by hospital-based helicopter air medical service (HEMS) was performed. Demographic, prehospital, ED triage, and blood product utilization data were collected. Prehospital ABC score was calculated using the highest heart rate, lowest systolic blood pressure, and focused assessment with sonography for trauma (FAST) exam results obtained prior to arrival at the trauma center. ED ABC score was calculated using ED triage vital signs and ED FAST results. Sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristics (AUROC) curve were calculated for each ABC score. RESULTS: 2,067 patients met inclusion criteria. Mean age 39 (±17) years, 76% male, 22% penetrating mechanism. Of these, 128 patients (6%) received massive transfusion using the definition from the original study. Prehospital ABC score at a cutoff of 2 was 51% sensitive and 85% specific for predicting massive transfusion, with 83% correctly classified and an AUROC = 0.73. ED ABC score at the same cutoff was 60% sensitive and 84% specific, with 83% correctly classified and an AUROC = 0.81. By logistic regression, the odds of massive transfusion increased by 2.76 for every 1-point increase in prehospital ABC score (95%CI 2.25-3.37, p < 0.001). CONCLUSIONS: The ABC score is a useful prehospital tool for identifying who will require massive transfusion. Future studies to evaluate the effect of the prehospital ABC score on clinical care and mortality are necessary.

Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes.

The process of integrating the reverse-transcribed HIV-1 DNA into the host chromosomal DNA is catalyzed by the virally encoded enzyme integrase (IN). Integration requires two metal-dependent reactions, 3' end processing and strand transfer. Compounds that contain a diketo acid moiety have been shown to selectively inhibit the strand transfer reaction of IN in vitro and in infected cells and are effective as inhibitors of HIV-1 replication. To characterize the molecular basis of inhibition, we used functional assays and binding assays to evaluate a series of structurally related analogs. These studies focused on investigating the role of the conserved carboxylate and metal binding. We demonstrate that an acidic moiety such as a carboxylate or isosteric heterocycle is not required for binding to the enzyme complex but is essential for inhibition and confers distinct metal-dependent properties on the inhibitor. Binding requires divalent metal and resistance is metal dependent with active site mutants displaying resistance only when the enzymes are evaluated in the context of Mg(2+). The mechanism of action of these inhibitors is therefore likely a consequence of the interaction between the acid moiety and metal ion(s) in the IN active site, resulting in a functional sequestration of the critical metal cofactor(s). These studies thus have implications for modeling active site inhibitors of IN, designing and evaluating analogs with improved efficacy, and identifying inhibitors of other metal-dependent phosphotransferases.