Factor XI Inhibition With Heparin Reduces Clot Formation in Simulated Pediatric Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) supplies circulatory support and gas exchange to critically ill patients. Despite the use of systemic anticoagulation, blood exposure to ECMO surfaces causes thromboembolism complications. Inhibition of biomaterial surface-mediated activation of coagulation factor XI (FXI) may prevent device-associated thrombosis. Blood was collected from healthy volunteers (n = 13) following the U.S. Army Institute of Surgical Research standard operating procedure for testing in an ex vivo ECMO circuit. A roller-pump circuit circulated either 0.5 U/ml of unfractionated heparin alone or in combination with the anti-FXI immunoglobulin G (IgG) (AB023) for 6 hours or until clot formation caused device failure. Coagulation factor activity, platelet counts, time to thrombin generation, peak thrombin, and endogenous thrombin potential were quantified. AB023 in addition to heparin sustained circuit patency in all tested circuits (5/5) after 6 hours, while 60% of circuits treated with heparin alone occluded (3/8), log-rank p < 0.03. AB023 significantly prolonged the time to clot formation as compared to heparin alone (15.5 vs . 3.3 minutes; p < 0.01) at the 3-hour time point. AB023 plus heparin significantly reduced peak thrombin compared to heparin alone (123 vs . 217 nM; p < 0.01). Inhibition of contact pathway activation of FXI may be an effective adjunct to anticoagulation in extracorporeal life support.

Circulatory HMGB1 is an early predictive and prognostic biomarker of ARDS and mortality in a swine model of polytrauma.

Acute respiratory distress syndrome (ARDS) is a leading cause of morbidity and mortality in polytrauma patients. Pharmacological treatments of ARDS are lacking, and ARDS patients rely on supportive care. Accurate diagnosis of ARDS is vital for early intervention and improved outcomes but is presently delayed up to days. The use of biomarkers for early identification of ARDS development is a potential solution. Inflammatory mediators high-mobility group box 1 (HMGB1), syndecan-1 (SDC-1), and C3a have been previously proposed as potential biomarkers. For this study, we analyzed these biomarkers in animals undergoing smoke inhalation and 40% total body surface area burns, followed by intensive care for 72 h post-injury (PI) to determine their association with ARDS and mortality. We found that the levels of inflammatory mediators in serum were affected, as well as the degree of HMGB1 and Toll-like receptor 4 (TLR4) signal activation in the lung. The results showed significantly increased HMGB1 expression levels in animals that developed ARDS compared with those that did not. Receiver operating characteristic (ROC) analysis showed that HMGB1 levels at 6 h PI were significantly associated with ARDS development (AUROC=0.77) and mortality (AUROC=0.82). Logistic regression analysis revealed that levels of HMGB1 ≥24.10 ng/ml are associated with a 13-fold higher incidence of ARDS [OR:13.57 (2.76-104.3)], whereas the levels of HMGB1 ≥31.39 ng/ml are associated with a 12-fold increase in mortality [OR: 12.00 (2.36-93.47)]. In addition, we found that mesenchymal stem cell (MSC) therapeutic treatment led to a significant decrease in systemic HMGB1 elevation but failed to block SDC-1 and C3a increases. Immunohistochemistry analyses showed that smoke inhalation and burn injury induced the expression of HMGB1 and TLR4 and stimulated co-localization of HMGB1 and TLR4 in the lung. Interestingly, MSC treatment reduced the presence of HMGB1, TLR4, and the HMGB1-TLR4 co-localization. These results show that serum HMGB1 is a prognostic biomarker for predicting the incidence of ARDS and mortality in swine with smoke inhalation and burn injury. Therapeutically blocking HMGB1 signal activation might be an effective approach for attenuating ARDS development in combat casualties or civilian patients.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): update and insights into current practices and future directions for research and implementation.

BACKGROUND: In this review, we assess the state of Resuscitative Endovascular Occlusion of the Aorta (REBOA) today with respect to out-of-hospital (OOH) vs. inhospital (H) use in blunt and penetrating trauma, as well as discuss areas of promising research that may be key in further advancement of REBOA applications. METHODS: To analyze the trends in REBOA use, we conducted a review of the literature and identified articles with human or animal data that fit the respective inclusion and exclusion criteria. In separate tables, we compiled data extracted from selected articles in categories including injury type, zone and duration of REBOA, setting in which REBOA was performed, sample size, age, sex and outcome. Based on these tables as well as more detailed review of some key cases of REBOA usage, we assessed the current state of REBOA as well as coagulation and histological disturbances associated with its usage. All statistical tests were 2-sided using an alpha=0.05 for significance. Analysis was done using SAS 9.5 (Cary, NC). Tests for significance was done with a t-test for continuous data and a Chi Square Test for categorical data. RESULTS: In a total of 44 cases performed outside of a hospital in both military and civilian settings, the overall survival was found to be 88.6%, significantly higher than the 50.4% survival calculated from 1,807 cases of REBOA performed within a hospital (p<.0001). We observe from human data a propensity to use Zone I in penetrating trauma and Zone III in blunt injuries. We observe lower final metabolic markers in animal studies with shorter REBOA time and longer follow-up times. CONCLUSIONS: Further research related to human use of REBOA must be focused on earlier initiation of REBOA after injury which may depend on development of rapid vascular access devices and techniques more so than on any new improvements in REBOA. Future animal studies should provide detailed multisystem organ assessment to accurately define organ injury and metabolic burden associated with REBOA application. Overall, animal studies must involve realistic models of injury with severe clinical scenarios approximating human trauma and exsanguination, especially with long-term follow-up after injury.

Exploring the Burn Model System National Database: Burn injuries, substance misuse, and the CAGE questionnaire.

Burn survivors who misuse alcohol and/other substances have been associated with poorer long-term outcomes and clinical complications following injury. The self-reported CAGE questionnaire (Cut down, Annoyed, Guilty, and Eye-opener) is an outcomes assessment tool used to screen for potential substance misuse. Understanding the persistence and emergence of potential substance misuse through examination of CAGE scores may provide important information about this population. Using data collected from the Burn Model System National Database, demographic and clinical characteristics of individuals who reported positive CAGE scores (total score of ≥2) and those who reported negative CAGE scores (total score of 0 or 1) for either alcohol or other drugs were compared.

Translation and Cross-cultural Validation of the English Young Adult Burn Outcome Questionnaire (YABOQ) in Spanish.

The Young Adult Burn Outcome Questionnaire (YABOQ) is a validated, English-language patient-reported outcome assessment of young adults' recovery from burn injury across 15 scale domains. We evaluated the cross-cultural validity of a newly developed Spanish version of the YABOQ. Secondary data from English- and Spanish-speaking burn survivors (17 to 30 years of age) were obtained from the Multicenter Benchmarking Study. We conducted classic psychometric analyses and evaluated the measurement equivalence of the English and Spanish YABOQs in logistic and ordinal logistic regression differential item functioning analyses. All multi-item scales in the Spanish YABOQ demonstrated adequate reliability except the Pain and Itch scales. One item in the Perceived Appearance scale showed differential item functioning across English- and Spanish-speaking burn survivors, but the observed differential item functioning had no clinically significant impact on scale-level Perceived Appearance scores. Our findings support the cross-cultural validity of the YABOQ Physical Function, Perceived Appearance, Sexual Function, Emotion, Family Function, Family Concern, Satisfaction with Symptom Relief, Satisfaction with Role, Work Reintegration and Religion scales among English- and Spanish-speaking young adult burn survivors. This work supports the use of these English and Spanish YABOQ scales to assess the effect of therapeutic interventions on young adults' burn outcomes in pooled analyses and to assess disparities in young adults' burn outcomes across language groups.

Investigation into Possible Association of Oxandrolone and Heterotopic Ossification Following Burn Injury.

Oxandrolone, a testosterone analog, is used to counteract the catabolic effects of burn injury. Recent animal studies suggest a possible hormonal association with heterotopic ossification (HO) development postburn. This work examines oxandrolone administration and HO development by exploring historical clinical data bridging the introduction of oxandrolone into clinical practice. Additionally, we examine associations between oxandrolone administration and HO in a standardized mouse model of burn/trauma-related HO. Acutely burned adults admitted between 2000 and 2014, survived through discharge, and had a HO risk factor of 7 or higher were selected for analysis from a single burn center. Oxandrolone administration, clinical and demographic data, and elbow HO were recorded and were analyzed with logistic regression. Associations of oxandrolone with HO were examined in a mouse model. Mice were administered oxandrolone or vehicle control following burn/tenotomy to examine any potential effect of oxandrolone on HO and were analyzed by Student's t test. Subjects who received oxandrolone had a higher incidence of elbow HO than those that did not receive oxandrolone. However, when controlling for oxandrolone administration, oxandrolone duration, postburn day oxandrolone initiation, HO risk score category, age, sex, race, burn size, and year of injury, there was no significant difference between rates of elbow HO between the two populations. In agreement with the review, in the mouse model, while there was a trend toward the oxandrolone group developing a greater volume of HO, this did not reach statistical significance.

Challenges to the Standardization of Burn Data Collection: A Call for Common Data Elements for Burn Care.

The use of common data elements (CDEs) is growing in medical research; CDEs have demonstrated benefit in maximizing the impact of existing research infrastructure and funding. However, the field of burn care does not have a standard set of CDEs. The objective of this study is to examine the extent of common data collected in current burn databases.This study examines the data dictionaries of six U.S. burn databases to ascertain the extent of common data. This was assessed from a quantitative and qualitative perspective. Thirty-two demographic and clinical data elements were examined. The number of databases that collect each data element was calculated. The data values for each data element were compared across the six databases for common terminology. Finally, the data prompts of the data elements were examined for common language and structure.Five (16%) of the 32 data elements are collected by all six burn databases; additionally, five data elements (16%) are present in only one database. Furthermore, there are considerable variations in data values and prompts used among the burn databases. Only one of the 32 data elements (age) contains the same data values across all databases.The burn databases examined show minimal evidence of common data. There is a need to develop CDEs and standardized coding to enhance interoperability of burn databases.