Exposure to statin therapy decreases the incidence of venous thromboembolism after trauma.

INTRODUCTION: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in trauma patients, despite chemoprophylaxis. Statins have been shown capable of acting upon the endothelium. We hypothesized that statin therapy in the pre- or in-hospital settings leads to a decreased incidence of VTE. METHODS: We conducted a retrospective cohort study of injured patients who received statin therapy pre- or in-hospital. Adult, highest-level trauma activation patients admitted January 2018 - June 2022 were included. Patients on prehospital anticoagulants, history of inherited bleeding disorder, and who died within the first 24 hours were excluded. Statin users were matched to non-users by statin use indications including age, current heart and cardiovascular conditions and history, hyperlipidemia, injury severity, and body mass index. Time to in-hospital statin initiation and occurrence of VTE and other complications within 60 days were collected. Differences between groups were determined by univariate, multivariable logistic regression, and Cox proportional hazard analyses. RESULTS: Of 3,062 eligible patients, 79 were statin users that were matched to 79 non-users. There were no differences in admissions demographics, vital signs, injury pattern, transfusion volumes, lengths of stay, or mortality between groups. The overall VTE incidence was 10.8% (17/158). Incidence of VTE in statin users was significantly lower (3%) than non-users (19%; P = 0.003). Differences between statin users and non-users were observed for rates of DVT (0% vs 9%), PE (3% vs 15%), and sepsis (0% vs 5%). Exposure to statins was associated with an 82% decreased risk of developing VTE (hazard ratio = 0.18, 95% CI 0.04 - 0.86; P = 0.033). CONCLUSIONS: Statin exposure was associated with decline in VTE and lower individual rates of DVT, PE, and sepsis. Our findings indicate that statins should be evaluated further as a possible adjunctive therapy for VTE chemoprophylaxis after traumatic injury. LEVEL OF EVIDENCE AND STUDY TYPE: Level III, Retrospective Cohort Study.

TIME-DEPENDENT CHANGES IN PROINFLAMMATORY MEDIATORS ARE ASSOCIATED WITH TRAUMA-RELATED VENOUS THROMBOEMBOLISM.

ABSTRACT: Background: Tissue trauma and hemorrhage result in pronounced activation of the innate immune system. Given known crosstalk between inflammation and coagulation, soluble inflammatory mediators could be associated with venous thromboembolisms (VTEs) after major trauma. Objectives : This study aimed to identify plasma inflammatory mediators that are independent predictors of VTE risk in trauma patients. Methods: We performed a secondary analysis of the Pragmatic Randomized Optimal Platelets and Plasma Ratios (PROPPR) study. Plasma levels of 27 cytokines/chemokines were measured by Bio-Plex at admission and 2, 4, 6, 12, 24, 48, and 72 h later. Patients who died from exsanguination or within 24 h were excluded. Mann-Whitney tests were performed to assess no-VTE and VTE groups at each time point. Multivariable logistic regression was used to determine the adjusted effects of inflammatory mediators on VTE risk. Results: Eighty-six of the 575 patients (15%) included developed VTE. Interleukin (IL)-1ra, IL-6, IL-8, IL-10, eotaxin, granulocyte colony-stimulating factor, interferon-γ-inducible protein, monocyte chemoattractant protein 1 (MCP-1), and chemokine ligand 5 (regulated on activation, normal T cell expressed and secreted) were all significantly increased among VTE patients. Multivariable analyses demonstrated that IL-6, IL-8, interferon-γ-inducible protein, and MCP-1 were independently associated with VTE. Cox proportional hazards modeling identified IL-6, IL-8, and MCP-1 as independent predictors of accelerated VTE development. We identified significant correlations between inflammation and markers of coagulation and endothelial activation. Conclusion: Sustained systemic inflammation is a key driver of VTE risk after major trauma. Therapeutics targeting innate immune activation should be considered for development of future multimodal strategies to augment current VTE prophylaxis.

Soluble endothelial protein C receptor is an independent predictor of venous thromboembolism after severe injury: Secondary analysis of a prospective cohort study.

BACKGROUND: Venous thromboembolism is a leading cause of morbidity after trauma. Endothelial cells are essential regulators of coagulation. Although endothelial cell dysregulation is widely reported after trauma, the link between endothelial injury and venous thromboembolism has not been reported. METHODS: We conducted a secondary analysis of the Pragmatic Randomized Optimal Platelets and Plasma Ratios study. Deaths from hemorrhage or within 24 hours were excluded. Venous thromboembolism was diagnosed by duplex ultrasound or chest computed tomography. Endothelial markers soluble endothelial protein c receptor, thrombomodulin, and syndecan-1 were measured in plasma by enzyme-linked immunosorbent assay and compared over the first 72 hours from admission using the Mann-Whitney test. Multivariable logistic regression assessed the adjusted effects of endothelial markers on venous thromboembolism risk. RESULTS: Of 575 patients enrolled, 86 developed venous thromboembolism (15%). The median time to venous thromboembolism was 6 days ([Q1, Q3], [4, 13]). No differences were identified in demographics or injury severity. Soluble endothelial protein c receptor, thrombomodulin, and syndecan-1 showed significant increases over time among patients who developed venous thromboembolism compared to those who did not. Using the last available values, patients were stratified into high and low-soluble endothelial protein c receptor, thrombomodulin, and syndecan-1 groups. Multivariable analyses revealed an independent association between elevated soluble endothelial protein c receptor and venous thromboembolism risk (odds ratio 1.63; 95% confidence interval 1.01, 2.63; P = .04). Cox proportional hazards modeling demonstrated a strong yet nonsignificant trend between elevated soluble endothelial protein c receptor and time to venous thromboembolism. CONCLUSION: Plasma markers of endothelial injury, particularly soluble endothelial protein c receptor, are strongly associated with trauma-related venous thromboembolism. Therapeutics targeting endothelial function could mitigate the incidence of venous thromboembolism after trauma.

Evaluation of the Effectiveness of the 2008 Postsplenectomy Vaccination Joint Theater Trauma System Clinical Practice Guideline.

OBJECTIVES: Postsplenectomy vaccination (PSV) in an austere environment to minimize overwhelming postsplenectomy infection is challenging. We evaluated the clinical impact of a March 2008 clinical practice guideline (CPG) dictating immediate PSV at North American Treaty Organization Role 3 medical treatment facilities and subsequent complications. METHODS: Utilizing U.S. military medical databases, we characterized all U.S. patients with a splenic injury from November 2002 to January 2012 by their surgical management: laparotomy with splenectomy (LWS), laparotomy without splenectomy, or nonoperative management. Relevant data including demographics, vaccinations, and documented bacterial and fungal isolates were obtained. RESULTS: LWS comprised 63.6% of the 409 patients with a splenic injury from 2002 to 2012. The implementation of the PSV CPG improved overall vaccination compliance from 48.9% pre-PSV CPG to 86.9% post-PSV CPG (p < 0.01). It was found that 1.3% (2/159) of completely vaccinated LWS patients compared with 0% (0/101) of the incompletely vaccinated LWS patients had Streptococcus pneumoniae isolates in 391.0 and 251.4 follow-up years, respectively (p = 0.52). No Neisseria meningitidis or Haemophilus influenzae isolates were identified. CONCLUSIONS: PSV CPG implementation improved theater vaccination without increasing the incidence of encapsulated organisms.

The effects of non-invasive radiofrequency treatment and hyperthermia on malignant and nonmalignant cells.

BACKGROUND: Exposure of biological subjects to electromagnetic fields with a high frequency is associated with temperature elevation. In our recent studies, we reported that non-invasive radiofrequency (RF) treatment at 13.56 MHz with the field ranging from 1 KeV to 20 KeV/m2 inhibits tumor progression in animals with abdominal tumor xenografts and enhances the anticancer effect of chemotherapy. The RF treatment was followed by temperature elevation in tumors to approximately 46 °C during 10 min of exposure. In contrast, the temperature of normal tissues remained within a normal range at approximately 37 °C. Whether all biological effects of RF treatment are limited to its hyperthermic property remains unclear. Here, we compared how RF and hyperthermia (HT) treatments change the proliferation rate, oxygen consumption and autophagy in malignant and nonmalignant cells. METHODS: In the current study, cancer and nonmalignant cells of pancreatic origin were exposed to the RF field or to conventional HT at 46 °C, which was chosen based on our previous in vivo studies of the tumor-specific RF-induced hyperthermia. RESULTS: Only RF treatment caused declines in cancer cell viability and proliferation. RF treatment also affected mitochondrial function in cancer cells more than HT treatment did and, unlike HT treatment, was followed by the elevation of autophagosomes in the cytoplasm of cancer cells. Importantly, the effects of RF treatment were negligible in nonmalignant cells. CONCLUSION: The obtained data indicate that the effects of RF treatment are specific to cancer cells and are not limited to its hyperthermic property.