Toll-like receptor activation as a biomarker in traumatically injured patients
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© 2018 Elsevier Inc. Background: Surgical insult and trauma have been shown to cause dysregulation of the immune and inflammatory responses. Interaction of damage-associated molecular patterns (DAMPs) with toll-like receptors (TLRs) initiates innate immune response and systemic inflammatory responses. Given that surgical patients produce high levels of circulating damage-associated molecular patterns, we hypothesized that plasma-activated TLR activity would be correlated to injury status and could be used to predict pathological conditions involving tissue injury. Methods: An observational study was performed using samples from a single-institution prospective tissue and data repository from a Level-1 trauma center. In vitro TLR 2, 3, 4, and 9 activation was determined in a TLR reporter assay after isolation of plasma from peripheral blood. We determined correlations between plasma-activated TLR activity and clinical course measures of severity. Results: Eighteen patients were enrolled (median Injury Severity Score 15 [interquartile range 10, 23.5]). Trauma resulted in significant elevation in circulation high mobility group box 1 as well as increase of plasma-activated TLR activation (2.8-5.4-fold) compared to healthy controls. There was no correlation between circulating high mobility group box 1 and trauma morbidity; however, the plasma-activated TLR activity was correlated with acute physiology and chronic health evaluation II scores (R square = 0.24-0.38, P < 0.05). Patients who received blood products demonstrated significant increases in the levels of plasma-activated TLRs 2, 3, 4, and 9 and had a trend toward developing systemic inflammatory response syndrome. Conclusions: Further studies examining TLR modulation and signaling in surgical patients may assist in predictive risk modeling and reduction in morbidity and mortality.
Published Version (Please cite this version)10.1016/j.jss.2018.05.059
Publication InfoDarrabie, Marcus D; Cheeseman, Jennifer; Limkakeng, Alexander T; Borawski, Joseph; Sullenger, Bruce A; Elster, Eric A; ... Lee, Jaewoo (2018). Toll-like receptor activation as a biomarker in traumatically injured patients. Journal of Surgical Research, 231. pp. 270-277. 10.1016/j.jss.2018.05.059. Retrieved from https://hdl.handle.net/10161/17305.
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Assistant Professor of Surgery
David C. Sabiston, Jr. Distinguished Professor of Surgery
I am a surgeon with interest in immune management of transplant recipients. I am particularly interested in therapies that influence T cell costimulation pathways and adjuvant therapies that facilitate costimulation blockade to prevent the rejection of transplanted organs without undue suppression of protective immunity. I am also interested in understanding how injury, such as that occurring during trauma or in elective surgery, influences immune responses and subsequent healing following injur
Assistant Professor of Surgery
Professor of Surgery
My personal research interest is finding new ways to diagnose acute coronary syndrome. In particular, I am interested in novel biomarkers and precision medicine approaches to this problem. I also have an interest in sepsis and empirical bioethics. As Vice Chief of Research for the Duke Division of Emergency Medicine, I also work with researchers from many fields spanning global health, innovation, clinical trials, basic discovery, and translational research. The
Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery, in the School of Medicine
The main focus of my translational research laboratory is to develop RNA based therapeutic agents for the potential treatment of a range of diseases. To this end, we have and will continue to take advantage of the fact that RNA is not just a passive carrier of genetic instructions inside of cells during the conversion of information from DNA to RNA to protein. Rather, RNA is an extremely versatile biological macromolecule. Certian RNAs can bind to specific protiens with high affinities,
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