Introduction: Patients who undergo extremity amputation have historically used socket prosthetics to ambulate and perform daily functions; however, these prosthetics can be limited by poor terminal control and wear issues. In patients who have difficulty wearing their prostheses or with upper extremity amputations, osseointegrated implants may offer better function and quality of life. The Osseointegrated Prostheses for the Rehabilitation of Amputees (OPRA) was the first such device to become commercially available. Clinical trials have demonstrated benefit in patient gait, prosthetic use, and overall well-being, and new implants may be applied for various amputation levels. Areas covered: The OPRA, the most studied osseointegrated prosthetic stem, is reviewed, presenting indications, surgical procedure, complications, and results of clinical studies. Expert commentary: Osseointegration for amputees is an expanding field that has the potential to enhance rehabilitative potential. The OPRA implant is an effective device with a long life-span and low complication profile.

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.

Background: There are little long-term health data, particularly in terms of body composition and development of metabolic syndromes, to help surgeons to guide the decision between limb salvage and amputation in patients with limb-threatening trauma. The purpose of this study was to compare long-term health outcomes after high-energy lower-extremity trauma between patients who underwent attempted flap-based limb salvage or amputation. Methods: We performed a retrospective review of servicemembers with a minimum 10-year follow-up who underwent flap-based limb salvage followed by unilateral amputation or continued limb salvage after combat-related, lower-extremity trauma between 2005 and 2011. Patient demographic characteristics, injury characteristics, and health outcomes including body mass index (BMI) and development of metabolic disease (e.g., hyperlipidemia, hypertension, heart disease, and diabetes) were compared between treatment cohorts. Adjusted BMIs were calculated for the amputation cohort to account for lost surface area. We performed multivariable and propensity score analysis to determine the likelihood of developing obesity or metabolic disease. Results: In this study, 110 patients had available long-term follow-up (mean, 12.2 years) from the time of the injury. Fifty-six patients underwent limb salvage and 54 patients underwent unilateral amputation. There was no difference in preinjury BMI (p = 0.30). After adjusting for limb loss, the amputation cohort had a trend toward higher BMIs at ≥1 years after the injury, a higher rate of obesity, and a greater increase in BMI from baseline after the injury. The development of metabolic comorbidities was common after both amputation (23 [43%] of 54) and limb salvage (27 [48%] of 56). With the numbers available, we were unable to demonstrate a difference in risk for the development of hypertension, hyperlipidemia, diabetes, heart disease, or any comorbidity other than obesity (p > 0.05). Conclusions: Amputations may be medically necessary and may decrease pain, improve mobility, and/or expedite return to activity compared with limb salvage after similar injuries. However, limb loss may negatively impact metabolic regulation and may contribute to a higher risk of obesity despite beneficial effects on mobility. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Heterotopic ossification (HO) is a devastating condition in which ectopic bone forms inappropriately in soft tissues following traumatic injuries and orthopedic surgeries as a result of aberrant mesenchymal progenitor cell differentiation. Heterotopic ossification leads to chronic pain, decreased range of motion, and an overall decrease in quality of life. While several treatments have shown promise in animal models, all must be given during early stages of formation. Methods for early determination of whether and where endochondral ossification/soft tissue mineralization (HO anlagen) develop are lacking. At-risk patients are not identified sufficiently early in the process of mesenchymal progenitor cell differentiation and soft tissue endochondral ossification for potential treatments to be effective. Hence, a critical need exists to develop technologies capable of detecting HO anlagen soon after trauma, when treatments are most effective. Here, we investigate high frequency spectral ultrasound imaging (SUSI) as a non-invasive strategy to identify HO anlagen at early time points after injury. We show that by determining quantitative parameters based on tissue organization and structure, SUSI identifies HO anlagen as early as 1-week post injury in a mouse model of burn/tenotomy and 3 days post injury in a rat model of blast/amputation. We analyze single cell RNA sequencing profiles of the mesenchymal progenitor cells responsible for HO formation and show that the early tissue changes detected by SUSI match chondrogenic and osteogenic gene expression in this population. SUSI identifies sites of soft tissue endochondral ossification at early stages of HO formation so that effective intervention can be targeted when and where it is needed following trauma-induced injury. Furthermore, we characterize the chondrogenic to osteogenic transition that occurs in the mesenchymal progenitor cells during HO formation and correlate gene expression to SUSI detection of the HO anlagen.