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Crosstalk of Osteoporosis and Sarcopenia in Geriatric Blunt Trauma
Vol. 223, No. 4S1, October 2016
Crosstalk of Osteoporosis and Sarcopenia in Geriatric Blunt Trauma Mahdi Malekpour, MD, Kathryn Jaap, MD, James T Dove, Kelly Bridgham, Ryan Erwin, Joseph A Blansfield, MD, FACS, Kenneth A Widom, MD, FACS, Mohsen Shabahang, MD, FACS, Denise M Torres, MD, FACS, Jeffrey L Wild, MD, FACS Geisinger Medical Center, Danville, PA INTRODUCTION: Trauma is associated with higher rates of morbidity and mortality in elderly patients due to underlying medical comorbidities including osteoporosis and sarcopenia. Abdominal CT imaging has recently been shown to be capable of identifying osteoporotic and sarcopenic patients. In this study, we aimed to evaluate the effect of osteoporosis and sarcopenia on the outcomes of geriatric blunt trauma using abdominal CT scans. METHODS: At the level of the third lumbar vertebra, left psoas area (LPA) and the Hounsfield unit (HU) of the vertebral body were measured on axial CT images. Sarcopenia was defined as any standardized and stratified LPA measurement in the lowest quartile. Osteoporosis was defined as HU < 130. We assessed the effect of osteoporosis and sarcopenia on the outcome. RESULTS: Over 3 years, 621 geriatric blunt trauma patients were admitted; 464 were osteoporotic and 157 were not osteoporotic. Osteoporotic patients were found to be more sarcopenic (27.2% vs 19.1%; p¼0.04), older, female, and had more falls (all p<0.0001). In multivariate analysis, osteoporosis was associated with longer hospitalization when it was studied as a single disease (odds ratio [OR] 1.25, 95% CI 1.02-1.55; p¼0.03). Osteoporosis was also associated with less favorable discharge destinations (OR 0.629, 95% CI 0.400-0.989; p¼0.04). This effect faded away when we studied the interaction of osteoporosis and sarcopenia in our model (OR 1.51, 95% CI 0.53-4.28; p¼0.44). CONCLUSIONS: Osteoporosis and sarcopenia were associated with each other as part of normal senility. When osteoporosis was presented as a single disease, it was linked to less favorable clinical outcomes. Thrombin Provokes PAI-1 Release from Platelets Benjamin Huebner, MD, Ernest E Moore, MD, FACS, Hunter B Moore, MD, Marguerite Kelher, Anirban Banerjee, PhD, Erik D Peltz, Christopher C Silliman, MD, PhD University of Colorado, Aurora, CO, Bonfils Blood Center, Denver Health Medical Center, Denver, CO INTRODUCTION: Injured patients exhibit early diverse coagulopathy phenotypes ranging from hyperfibrinolysis to fibrinolysis shutdown (FS) resulting in microvascular occlusion, venous thromboembolism, and an increased risk of late mortality from multi-organ failure. The primary mediator of FS is thought to be
Scientific Forum Abstracts
S159
plasminogen activator inhibitor-1 (PAI-1). Platelets contain PAI1 in a-granules and can degranulate in response to trauma, but their PAI-1 contribution in trauma patients is unknown. Thrombin, a key regulator of the coagulation system, is known to stimulate platelet degranulation, and is elevated in trauma patients. We hypothesized that thrombin provokes complete degranulation of platelet a-granules, leading to PAI-1 release, neutralization of tPA, and the FS phenotype early after injury. METHODS: Platelets were obtained from healthy donors, isolated from plasma, and the pellet was resusupended in saline at a final concentration of 3 x 108 platelets/mL. Platelets were stimulated with high-dose thrombin (5 IU/mL) for 5, 15, 30, and 120 minutes. Cells were spun down and the supernatant was removed and the final pellet was suspended again in saline and lysed. Both supernatant and cells were stored at -80 C. The supernatants and cell lyses were evaluated by total PAI-1 ELISA. RESULTS: Thrombin provoked >95% a-degranulation and release of PAI-1 at the initial 5-minute time-point (125.1 ng/mL released and 3.5 ng/mL remaining), and all time-points were similar in regard to platelet release and remaining PAI-1 (Table). Table. Variable Control (n¼4)
Thrombin (n¼4)
Time, min 5 15 30 120 5 15 30 120
PAI-1 released, ng/mL 9.9 10.5 8.3 11.4 125.1 133.3 127.4 124.3
PAI-1 remaining, ng/mL 109.9 109.9 130.0 119.7 3.5 3.3 3.6 4.8
CONCLUSIONS: Thrombin stimulates nearly complete degranulation of alpha-granules, leading to high PAI-1 release and likely mediating the FS phenotype in trauma patients. Toll-Like Receptor Signaling as a Prognostic Tool in Trauma Patients Marcus D Darrabie, Jaewoo Lee, PhD, Jennifer Cheeseman, Alexander T Limkakeng, MD, Steven N Vaslef, MD, PhD, Bruce A Sullenger, PhD, Allan D Kirk, MD, PhD, FACS Duke University Medical Center, Durham, NC INTRODUCTION: Surgical insult and trauma have been shown to cause dysregulation of the immune-inflammatory response to pathogens. Interaction of pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) with toll-like receptors (TLRs) initiate inflammatory responses and subsequent counter-inflammatory responses such as tolerance. Given that surgical patients produce high levels of circulating DAMPs, we hypothesized that TLR activity may be correlated to injury status and could be used to predict pathologic conditions involving tissue injury.
Crosstalk of Osteoporosis and Sarcopenia in Geriatric Blunt Trauma Mahdi Malekpour, MD, Kathryn Jaap, MD, James T Dove, Kelly Bridgham, Ryan Erwin, Joseph A Blansfield, MD, FACS, Kenneth A Widom, MD, FACS, Mohsen Shabahang, MD, FACS, Denise M Torres, MD, FACS, Jeffrey L Wild, MD, FACS Geisinger Medical Center, Danville, PA INTRODUCTION: Trauma is associated with higher rates of morbidity and mortality in elderly patients due to underlying medical comorbidities including osteoporosis and sarcopenia. Abdominal CT imaging has recently been shown to be capable of identifying osteoporotic and sarcopenic patients. In this study, we aimed to evaluate the effect of osteoporosis and sarcopenia on the outcomes of geriatric blunt trauma using abdominal CT scans. METHODS: At the level of the third lumbar vertebra, left psoas area (LPA) and the Hounsfield unit (HU) of the vertebral body were measured on axial CT images. Sarcopenia was defined as any standardized and stratified LPA measurement in the lowest quartile. Osteoporosis was defined as HU < 130. We assessed the effect of osteoporosis and sarcopenia on the outcome. RESULTS: Over 3 years, 621 geriatric blunt trauma patients were admitted; 464 were osteoporotic and 157 were not osteoporotic. Osteoporotic patients were found to be more sarcopenic (27.2% vs 19.1%; p¼0.04), older, female, and had more falls (all p<0.0001). In multivariate analysis, osteoporosis was associated with longer hospitalization when it was studied as a single disease (odds ratio [OR] 1.25, 95% CI 1.02-1.55; p¼0.03). Osteoporosis was also associated with less favorable discharge destinations (OR 0.629, 95% CI 0.400-0.989; p¼0.04). This effect faded away when we studied the interaction of osteoporosis and sarcopenia in our model (OR 1.51, 95% CI 0.53-4.28; p¼0.44). CONCLUSIONS: Osteoporosis and sarcopenia were associated with each other as part of normal senility. When osteoporosis was presented as a single disease, it was linked to less favorable clinical outcomes. Thrombin Provokes PAI-1 Release from Platelets Benjamin Huebner, MD, Ernest E Moore, MD, FACS, Hunter B Moore, MD, Marguerite Kelher, Anirban Banerjee, PhD, Erik D Peltz, Christopher C Silliman, MD, PhD University of Colorado, Aurora, CO, Bonfils Blood Center, Denver Health Medical Center, Denver, CO INTRODUCTION: Injured patients exhibit early diverse coagulopathy phenotypes ranging from hyperfibrinolysis to fibrinolysis shutdown (FS) resulting in microvascular occlusion, venous thromboembolism, and an increased risk of late mortality from multi-organ failure. The primary mediator of FS is thought to be
Scientific Forum Abstracts
S159
plasminogen activator inhibitor-1 (PAI-1). Platelets contain PAI1 in a-granules and can degranulate in response to trauma, but their PAI-1 contribution in trauma patients is unknown. Thrombin, a key regulator of the coagulation system, is known to stimulate platelet degranulation, and is elevated in trauma patients. We hypothesized that thrombin provokes complete degranulation of platelet a-granules, leading to PAI-1 release, neutralization of tPA, and the FS phenotype early after injury. METHODS: Platelets were obtained from healthy donors, isolated from plasma, and the pellet was resusupended in saline at a final concentration of 3 x 108 platelets/mL. Platelets were stimulated with high-dose thrombin (5 IU/mL) for 5, 15, 30, and 120 minutes. Cells were spun down and the supernatant was removed and the final pellet was suspended again in saline and lysed. Both supernatant and cells were stored at -80 C. The supernatants and cell lyses were evaluated by total PAI-1 ELISA. RESULTS: Thrombin provoked >95% a-degranulation and release of PAI-1 at the initial 5-minute time-point (125.1 ng/mL released and 3.5 ng/mL remaining), and all time-points were similar in regard to platelet release and remaining PAI-1 (Table). Table. Variable Control (n¼4)
Thrombin (n¼4)
Time, min 5 15 30 120 5 15 30 120
PAI-1 released, ng/mL 9.9 10.5 8.3 11.4 125.1 133.3 127.4 124.3
PAI-1 remaining, ng/mL 109.9 109.9 130.0 119.7 3.5 3.3 3.6 4.8
CONCLUSIONS: Thrombin stimulates nearly complete degranulation of alpha-granules, leading to high PAI-1 release and likely mediating the FS phenotype in trauma patients. Toll-Like Receptor Signaling as a Prognostic Tool in Trauma Patients Marcus D Darrabie, Jaewoo Lee, PhD, Jennifer Cheeseman, Alexander T Limkakeng, MD, Steven N Vaslef, MD, PhD, Bruce A Sullenger, PhD, Allan D Kirk, MD, PhD, FACS Duke University Medical Center, Durham, NC INTRODUCTION: Surgical insult and trauma have been shown to cause dysregulation of the immune-inflammatory response to pathogens. Interaction of pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) with toll-like receptors (TLRs) initiate inflammatory responses and subsequent counter-inflammatory responses such as tolerance. Given that surgical patients produce high levels of circulating DAMPs, we hypothesized that TLR activity may be correlated to injury status and could be used to predict pathologic conditions involving tissue injury.