Toll-like receptor activation as a biomarker in traumatically injured patients

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Darrabie, Marcus D

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Cheeseman, Jennifer

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Limkakeng, Alexander T

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Borawski, Joseph

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Sullenger, Bruce A

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Elster, Eric A

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Kirk, Allan D

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Lee, Jaewoo

dc.date.accessioned

2018-08-01T23:14:12Z

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2018-08-01T23:14:12Z

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2018-11-01

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2018-08-01T23:14:11Z

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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.

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0022-4804

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1095-8673

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https://hdl.handle.net/10161/17305

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Elsevier BV

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Journal of Surgical Research

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10.1016/j.jss.2018.05.059

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Toll-like receptor activation as a biomarker in traumatically injured patients

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Journal article

duke.contributor.orcid

Limkakeng, Alexander T|0000-0002-9822-5595

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Kirk, Allan D|0000-0003-2004-5962

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Lee, Jaewoo|0000-0003-3760-1806

pubs.begin-page

270

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277

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School of Medicine

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Duke

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Surgery, Emergency Medicine

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Surgery

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Clinical Science Departments

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Duke Cancer Institute

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Institutes and Centers

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Molecular Genetics and Microbiology

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Basic Science Departments

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Pharmacology & Cancer Biology

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Surgery, Surgical Sciences

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Immunology

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Pediatrics

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Surgery, Abdominal Transplant Surgery

pubs.publication-status

Accepted

pubs.volume

231

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