Long-Term Health Outcomes of Limb Salvage Compared with Amputation for Combat-Related Trauma.

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.

A Barbed Proximal Femoral Nailing System for Isolated Intertrochanteric Femur Fractures: Operative Outcomes.

Intertrochanteric femur fractures are associated with high morbidity/mortality, necessitating strategies to limit time under anesthesia, blood loss, and additional trauma while achieving maximal fixation in osteopenic bone. The Orthopedic Designs North America, Inc. Talon DistalFix Femoral Nail System uses deployable barbs to maximize axial and rotational control without distal interlock screws. The purpose of this study was to evaluate perioperative features and postoperative outcomes in patients treated with the DistalFix Femoral Nailing System for isolated intertrochanteric femur fractures. Seventy-one consecutive patients underwent intramedullary fixation for isolated intertrochanteric fractures with the DistalFix system between January 2019-July 2020. Median operative time was 35 (33 - 40) minutes. Median estimated blood loss was 125 (75 - 150) cc. Median fluoroscopy time was 2.4 (2.2 - 2.9) minutes and dosage was 27.1 (18.0 - 35.2) mGy. Union occurred in 98% of patients; none experienced implant cutout, and 81.1% returned to previous mobility. The DistalFix system achieves a high rate of union and return to function while limiting operative risk factors. (Journal of Surgical Orthopaedic Advances 32(1):036-040, 2023).

Tourniquet-induced ischemia creates increased risk of organ dysfunction and mortality following delayed limb amputation.

Tourniquets are critical for the control of traumatic extremity hemorrhage. In this study, we sought to determine, in a rodent blast-related extremity amputation model, the impact of prolonged tourniquet application and delayed limb amputation on survival, systemic inflammation, and remote end organ injury. Adult male Sprague Dawley rats were subjected to blast overpressure (120±7 kPa) and orthopedic extremity injury consisting femur fracture, one-minute soft tissue crush injury (20 psi), ± 180 min of tourniquet-induced hindlimb ischemia followed by delayed (60 min of reperfusion) hindlimb amputation (dHLA). All animals in the non-tourniquet group survived whereas 7/21 (33%) of the animals in the tourniquet group died within the first 72 h with no deaths observed between 72 and 168 h post-injury. Tourniquet induced ischemia-reperfusion injury (tIRI) likewise resulted in a more robust systemic inflammation (cytokines and chemokines) and concomitant remote pulmonary, renal, and hepatic dysfunction (BUN, CR, ALT. AST, IRI/inflammation-mediated genes). These results indicate prolonged tourniquet application and dHLA increases risk of complications from tIRI, leading to greater risk of local and systemic complications including organ dysfunction or death. We thus need enhanced strategies to mitigate the systemic effects of tIRI, particularly in the military prolonged field care (PFC) setting. Furthermore, future work is needed to extend the window within which tourniquet deflation to assess limb viability remains feasible, as well as new, limb-specific or systemic point of care tests to better assess the risks of tourniquet deflation with limb preservation in order to optimize patient care and save both limb and life.

Key early proinflammatory signaling molecules encapsulated within circulating exosomes following traumatic injury.

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-1ß, 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-1ß, 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.

Alarming Cargo: The Role of Exosomes in Trauma-Induced Inflammation.

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.

High Frequency Spectral Ultrasound Imaging Detects Early Heterotopic Ossification in Rodents.

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 (MPC) differentiation. HO 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 MPC 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. In this study, we investigate high frequency spectral ultrasound imaging (SUSI) as a noninvasive 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 postinjury in a mouse model of burn/tenotomy and 3 days postinjury in a rat model of blast/amputation. We analyze single cell RNA sequencing profiles of the MPCs 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 MPCs during HO formation and correlate gene expression to SUSI detection of the HO anlagen.

Surgical Elbow Dislocation Approach to the Distal Humerus for Apparent Capitellar and Lateral Condyle Fractures in Adults.

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.

Osseointegrated prostheses for the rehabilitation of amputees (OPRA): results and clinical perspective.

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.

Comparative effectiveness of guided weight loss and physical activity monitoring for weight loss and metabolic risks: A pilot study.

Many consumer-based physical activity monitors (PAMs) are available but it is not clear how to use them to most effectively promote weight loss. The purpose of this pilot study was to compare the effectiveness of a personal PAM, a guided weight loss program (GWL), and the combination of these approaches on weight loss and metabolic risk. Participants completed the study in two cohorts: Fall 2010 and Spring 2011. A sample of 72 obese individuals in the Ames, IA area were randomized to one of 3 conditions: 1) (GWL, N = 31), 2) PAM, N = 29, or 3) a combination group (PAM + GWL, N = 29). Weight and metabolic syndrome score (MetS), computed from waist circumference (WC), BMI, blood pressure (BP), and lipids were assessed at baseline and following an 8-week intervention. Weight was also assessed four months later. Two-way (Group × Time) ANOVAs examined intervention effects and maintenance. Effect sizes were used to compare magnitude of improvements among groups. During the intervention, all groups demonstrated significant improvements in weight and MetS (mean weight loss = 4.16 kg, p < 0.001). Mean weight continued to decline modestly during follow-up, with average weight loss of 4.82 kg from baseline (p < 0.01). There were no group differences for weight loss but the PAM + GWL group had significantly larger changes in MetS score (d = 0.06-0.77). The use of PAM resulted in significant improvements in weight and MetS that were maintained across a four-month follow-up. Evidence suggests that the addition of GWL contributed to enhanced metabolic outcomes.

[Nle3,d-Phe6 ]-γ2 -melanocyte-stimulating hormone possesses the renal excretory but not the cardiovascular actions of the native γ2 -melanocyte-stimulating hormone in anaesthetized rats.

The present study compared the cardiovascular and renal actions of γ(2) -melanocyte-stimulating hormone (γ(2) MSH) with those of the synthetic analogue [Nle(3) ,d-Phe(6) ]-γ(2) MSH (NDP-γ(2) MSH) and explored the effects of high dietary salt intake on the renal actions of NDP-γ(2) MSH. Both peptides were infused systemically (3-1000 nmol/kg) and intrarenally (500 fmol/min) into innervated and renally denervated rats fed either a normal (0.4% NaCl) or high-salt (4% NaCl; HS) diet. Mean arterial pressure (MAP), glomerular filtration rate (GFR), urinary sodium excretion (U(N) (a) V), urinary output (UV) and fractional sodium excretion were determined, as was expression of the melanocortin MC(3) receptor in inner medullary collecting duct (IMCD) epithelial cells. Both renal and systemic infusion of γ(2) MSH increased MAP by 23 ± 2% and 54 ± 4%, respectively, but equivalent doses of NDP-γ(2) MSH had no significant pressor effects. Both peptides had similar natriuretic and diuretic effects in rats fed a normal salt diet. However, NDP-γ(2) MSH increased U(N) (a) V and UV by two- to threefold in rats fed the normal salt diet and by six- to sevenfold in rats fed the HS diet. Furthermore, NDP-γ(2) MSH induced a 3.5-fold increase in GFR only in rats fed the HS diet. These renal effects of NDP-γ(2) MSH were not abolished by prior renal denervation. Rats fed the HS diet also exhibited a 4.5-fold increase in MC(3) receptor expression in IMCD epithelial cells. Intrarenal infusion of NDP-γ(2) MSH induced the natriuretic but not the cardiovascular effects exhibited by γ(2) MSH. The renal activities may be attributed to a direct binding of NDP-γ(2) MSH to MC(3) receptors expressed in IMCD cells, leading to a potent natriuretic effect that is independent of renal innervation.

Knowledge of local anesthetic use among dermatologists.

BACKGROUND: Local anesthesia is widely used in general dermatology practices. The onus is on the practitioner to have a sound knowledge of the pharmacology and dosing of any drug used, including local anesthesia. The dermatologist should also be aware of the signs, symptoms, and management of toxicity of local anesthetic use. The level of knowledge of dermatologists on this topic has not been previously assessed. OBJECTIVE: To assess levels of knowledge of local anesthetic pharmacology, local anesthetic systemic toxicity (LAST), and the management of the latter of dermatologists. METHODS: A survey designed to test knowledge of absolute dosing limits; calculation of patient-specific dosing using clinical vignettes; and awareness of the signs, symptoms, and management of LAST was distributed electronically to the membership of three professional dermatological organizations in the United Kingdom and Ireland, including one specialist dermatologic surgery group. RESULTS: Knowledge of local anesthetic use of dermatologists was comprehensive enough to practice safely, without necessarily being entirely accurate. Awareness of the signs and symptoms of local anesthetic toxicity was good, but awareness of the specific agent now recommended for the management of LAST in official guidelines was poor. CONCLUSIONS: Knowledge of local anesthetic dosing and toxicity is reasonable among dermatologists. Awareness of the guidelines for management of LAST, released by the American and Great Britain and Ireland associations of anesthetists, and in particular the use of lipid emulsion in this setting, could be improved.