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Severe polytraumatic injury initiates a robust immune response. Broad immune dysfunction in patients with such injuries has been well-documented; however, early biomarkers of immune dysfunction post-injury, which are critical for comprehensive intervention and can predict the clinical course of patients, have not been reported. Current circulating markers such as IL-6 and IL-10 are broad, non-specific, and lag behind the clinical course of patients. General blockade of the inflammatory response is detrimental to patients, as a certain degree of regulated inflammation is critical and necessary following trauma. Exosomes, small membrane-bound extracellular vesicles, found in a variety of biofluids, carry within them a complex functional cargo, comprised of coding and non-coding RNAs, proteins, and metabolites. Composition of circulating exosomal cargo is modulated by changes in the intra- and extracellular microenvironment, thereby serving as a homeostasis sensor. With its extensively documented involvement in immune regulation in multiple pathologies, study of exosomal cargo in polytrauma patients can provide critical insights on trauma-specific, temporal immune dysregulation, with tremendous potential to serve as unique biomarkers and therapeutic targets for timely and precise intervention.

Background Assessment of immune status in critically ill patients is often based on serial tracking of systemic cytokine levels and clinical laboratory values. Exosomes are extracellular vesicles that can be secreted and internalized by cells to transport important cellular cargo in the regulation of numerous physiological and pathological processes. Here, we characterize the early compartmentalization profile of key proinflammatory mediators in serum exosomes in the steady state and following trauma. Adult male Sprague-Dawley rats (91 including naïve) were divided into one of four traumatic injury model groups incorporating whole-body blast, fracture, soft-tissue crush injury, tourniquet-induced ischemia, and limb amputation. Serum was collected at 1, 3, 6, and 24 h, and 3- and 7-day post-injury. Electrochemiluminescence-based immunoassays for 9 key proinflammatory mediators in whole serum, isolated serum exosomes, and exosome depleted serum were analyzed and compared between naïve and injured rats. Serum clinical chemistry analysis was performed to determine pathological changes. Results In naïve animals, substantial amounts of IL-1β, IL-10, and TNF-α were encapsulated, IL-6 was completely encapsulated, and CXCL1 freely circulating. One hour after blast injury alone, levels of exosome encapsulated IFN-γ, IL-10, IL-6, IL-13, IL-4, and TNF-α increased, whereas freely circulating and membrane-associated levels remained undetectable or low. Rats with the most severe polytraumatic injuries with end organ complications had the earliest rise and most pronounced concentration of IL-1β, IL-10, TNF-α, and IL-6 across all serum compartments. Moreover, CXCL1 levels increased in relation to injury severity, but remained almost entirely freely circulating at all timepoints. Conclusion These findings highlight that conventional ELISA-based assessments, which detect only free circulating and exosome membrane-bound mediators, underestimate the full immunoinflammatory response to trauma. Inclusion of exosome encapsulated mediators may be a better, more accurate and clinically useful early strategy to identify, diagnose, and monitor patients at highest risk for post-traumatic inflammation-associated complications.

Objectives: Access to fractures of the distal humeral capitellum, trochlea, and lateral condyle is difficult through traditional approaches due to limited anterior articular exposure for direct reduction and fixation. The purpose of this study is to evaluate the relative articular exposure of a surgical dislocation (SD) approach to the distal humerus compared with olecranon osteotomy (OO). Methods: Eight paired elbows from 4 cadavers underwent either SD or OO approach. Methylene blue staining demarcated visualized articular surface before disarticulation of the elbows. The main outcome measures were average visualized total distal humeral articular surface and anterior and posterior surface, and capitellar surface relative to the total surfaces was compared for each surgical approach using unpaired parametric t-tests. Results: Intraclass correlation between raters was 0.995. The median exposed articular surface for SD and OO approaches was 90.0% and 62.8%, respectively. The overall exposure was significantly greater for the dislocation technique (P = 0.0003). With respect to specific regions of the distal humeral articular surface, SD allowed significantly greater visualization of the anterior surface (95.9% vs. 48.9%, P < 0.0001) and capitellum (100% vs. 40.4%, P < 0.0001). Conclusion: The surgical elbow dislocation approach to the distal humerus permits near total exposure of the anterior articular surface and the entire capitellum. Our data support this approach for anterior articular fractures of the distal humerus, to include those fractures that extend to the medial surface of the trochlea.

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