Increasing Diversity in Orthopaedics: The Problem, Strategies, and Solutions.

It is important to educate and equip the orthopaedic community with tools to address health care disparities and improve orthopaedic specialty recruitment for racial minorities. How patients and providers are affected by systemic racism in healthcare and what that means in orthopaedic surgery, methods to identify bias and improve access to orthopaedic care for racial minorities, and how to structure a program and department environment to encourage and promote diversity are important topics of discussion.

Racial Diversity Among American Cardiologists: Implications for the Past, Present, and Future.

In the United States, race-based disparities in cardiovascular disease care have proven to be pervasive, deadly, and expensive. African American/Black, Hispanic/Latinx, and Native/Indigenous American individuals are at an increased risk of cardiovascular disease and are less likely to receive high-quality, evidence-based medical care as compared with their White American counterparts. Although the United States population is diverse, the cardiovascular workforce that provides its much-needed care lacks diversity. The available data show that care provided by physicians from racially diverse backgrounds is associated with better quality, both for minoritized patients and for majority patients. Not only is cardiovascular workforce diversity associated with improvements in health care quality, but racial diversity among academic teams and research scientists is linked with research quality. We outline documented barriers to achieving workforce diversity and suggest evidence-based strategies to overcome these barriers. Key strategies to enhance racial diversity in cardiology include improving recruitment and retention of racially diverse members of the cardiology workforce and focusing on cardiovascular health equity for patients. This review draws attention to academic institutions, but the implications should be considered relevant for nonacademic and community settings as well.

Characterization of the structure, vascularity, and stem/progenitor cell populations in porcine Achilles tendon (PAT).

This study aimed to characterize porcine Achilles tendon (PAT) in terms of its structural components, vascularity, and resident tendon cells. We found that PAT is composed of a paratenon sheath, a core of fascicles, and an endotenon/interfascicular matrix (IFM) that encases the fascicle bundles. We analyzed each of these three tendon components structurally using tissue sections and by isolating cells from each component and analyzing in vitro. Many blood vessel-like tissues were present in the paratenon and IFM but not in fascicles, and the vessels in the paratenon and IFM appeared to be inter-connected. Cells isolated from the paratenon and IFM displayed characteristics of vascular stem/progenitor cells expressing the markers CD105, CD31, with α-smooth muscle actin (α-SMA) localized surrounding blood vessels. The isolated cells from paratenon and IFM also harbored abundant stem/progenitor cells as evidenced by their ability to form colonies and express stem cell markers including CD73 and CD146. Furthermore, we demonstrate that both paratenon and IFM-isolated cells were capable of undergoing multi-differentiation. In addition, both paratenon and IFM cells expressed elastin, osteocalcin, tubulin polymerization promoting protein (TPPP), and collagen IV, whereas fascicle cells expressed none of these markers, except collagen I. The neurotransmitter substance P (SP) was also found in the paratenon and IFM-localized surrounding blood vessels. The findings of this study will help us to better understand the vascular and cellular mechanisms of tendon homeostasis, injury, healing, and regeneration.

Medical comorbidities increase the rate of surgical site infection in primary Achilles tendon repair.

PURPOSE: To assess the effects of medical comorbidities on the incidence of surgical site infection following primary Achilles tendon repair. A secondary aim was to assess the effects of specific medical comorbidities on the cost and extent of healthcare utilization related to surgical site infection following primary Achilles tendon repair. METHODS: 24,269 patients undergoing primary Achilles tendon repair between 2005 and 2012 were examined. Current Procedural Terminology codes for primary Achilles tendon repair, and incision and drainage were used to search for and compile patient data from the United Healthcare Orthopedic and Medicare databases. Primary outcome measures regarding surgical site infection following primary Achilles tendon repair included the rate of occurrence, cost, and duration of treatment. RESULTS: Patients with one or more preexisting medical comorbidities at the time of surgery had an increased rate of surgical site infection compared to those without. Diabetes and vascular complications were associated with the highest surgical site infection rates. The rate of surgical incision and drainage was higher in patients with cardiac arrhythmias and uncomplicated hypertension. The presence of a medical comorbidity significantly increased the cost and duration of surgical site infection treatment. CONCLUSIONS: Medical comorbidities can complicate the postoperative course for patients undergoing Achilles tendon repair, which increases the cost of care and duration of treatment. A better understanding of the relationship between each medical comorbidity and surgical site infections following Achilles tendon repair may be ascertained with additional prospective studies, thus, allowing for a more accurate evaluation and stratification of surgical candidates to improve patient outcomes. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Altered bone-regulating myokine expression in skeletal muscle Of Duchenne muscular dystrophy mouse models.

INTRODUCTION: Duchenne muscular dystrophy (DMD) has been well characterized as a disease that affects both skeletal muscle and bone. The pathophysiology responsible for the deficits in bone tissue is still unclear. METHODS: Quantitative reverse-transcription polymerase chain reaction and Western blot analyses of known myokines from skeletal muscle were performed on dystrophic mouse models and wild-type (WT) controls to identify differentially expressed bone-regulating myokines. RESULTS: Twenty-four of 43 myokine genes demonstrated significantly different mRNA expression in the skeletal muscles of dystrophic mice when compared with muscles of WT mice. Several differently expressed bone-regulating myokine genes were identified, and their protein levels were also verified by Western blot. CONCLUSIONS: Dystrophic skeletal muscle demonstrated a significantly altered myokine gene expression profile. mRNA and protein levels of several bone-regulating myokines were significantly altered in dystrophic skeletal muscle, which suggests pathological role of bone-regulating myokines on bone homeostasis in DMD. Muscle Nerve 58: 573-582, 2018.

How Do Hindfoot Fusions Affect Ankle Biomechanics: A Cadaver Model.

BACKGROUND: While successful subtalar joint arthrodesis provides pain relief, resultant alterations in ankle biomechanics need to be considered, as this procedure may predispose the remaining hindfoot and tibiotalar joint to accelerated degenerative changes. However, the biomechanical consequences of isolated subtalar joint arthrodesis and additive fusions of the Chopart's joints on tibiotalar joint biomechanics remain poorly understood. QUESTIONS/PURPOSES: We asked: What is the effect of isolated subtalar fusion and sequential Chopart's joint fusions of the talonavicular and calcaneocuboid joints on tibiotalar joint (1) mechanics and (2) kinematics during loading for neutral, inverted, and everted orientations of the foot? METHODS: We evaluated the total force, contact area, and the magnitude and distribution of the contact stress on the articular surface of the talar dome, while simultaneously tracking the position of the talus relative to the tibia during loading in seven fresh-frozen cadaver feet. Each foot was loaded in the unfused, intact control condition followed by three randomized simulated hindfoot arthrodesis modalities: subtalar, double (subtalar and talonavicular), and triple (subtalar, talonavicular, and calcaneocuboid) arthrodesis. The intact and arthrodesis conditions were tested in three alignments using a metallic wedge insert: neutral (flat), 10° inverted, and 10° everted. RESULTS: Tibiotalar mechanics (total force and contact area) and kinematics (external rotation) differed owing to hindfoot arthrodeses. After subtalar arthrodesis, there were decreases in total force (445 ± 142 N, 95% CI, 340-550 N, versus 588 ± 118 N, 95% CI, 500-676 N; p < 0.001) and contact area (282 mm(2), 95% CI, 222-342 mm(2), versus 336 ± 96 mm(2), 95% CI, 265-407 mm(2); p < 0.026) detected during loading in the neutral position; these changes also were seen in the everted foot position. Hindfoot arthrodesis also was associated with increased external rotation of the tibiotalar joint during loading: subtalar arthrodesis in the neutral loading position (3.3° ± 1.6°; 95% CI, 2°-4.6°; p = 0.004) and everted loading position (4.8° ± 2.6°; 95% CI, 2.7°-6.8°; p = 0.043); double arthrodesis in neutral (4.4° ± 2°; 95% CI, 2.8°-6°; p = 0.003) and inverted positions (5.8° ± 2.6°; 95% CI, 3.7°-7.9°; p = 0.002), and triple arthrodesis in all loaded orientations including neutral (4.5° ± 1.8°; 95% CI, 3.1°-5.9°; p = 0.002), inverted (6.4° ± 3.5°; 95% CI, 3.6°-9.2°; p = 0.009), and everted (3.6° ± 2°; 95% CI, 2°-5.2°; p = 0.053) positions. Finally, after subtalar arthrodesis, additive fusions at Chopart's joints did not appear to result in additional observed differences in tibiotalar contact mechanics or kinematics with the number of specimens available. CONCLUSIONS: Using a cadaveric biomechanical model, we identified some predictable trends in ankle biomechanics during loading after hindfoot fusion. In our tested specimens, fusion of the subtalar joint appeared to exert a dominant influence over ankle loading. CLINICAL RELEVANCE: A loss or deficit in function of the subtalar joint may be sufficient to alter ankle loading. These findings warrant consideration in the treatment of the arthritic hindfoot and also toward defining biomechanical goals for ankle arthroplasty in the setting of concomitant hindfoot degeneration or arthrodesis.

Arthroscopic Bone Marrow Stimulation and Concentrated Bone Marrow Aspirate for Osteochondral Lesions of the Talus: A Case-Control Study of Functional and Magnetic Resonance Observation of Cartilage Repair Tissue Outcomes.

PURPOSE: This study compares retrospective functional and magnetic resonance imaging (MRI) outcomes after arthroscopic bone marrow stimulation (BMS) with and without concentrated bone marrow aspirate (cBMA) as a biological adjunct to the surgical treatment of osteochondral lesions (OCLs) of the talus. METHODS: Twenty-two patients who underwent arthroscopic BMS with cBMA (cBMA/BMS group) for an osteochondral lesion (OCL) of the talus and 12 patients who underwent arthroscopic BMS (BMS alone) for an OCL of the talus were retrospectively reviewed. The Foot and Ankle Outcome Score (FAOS) pain subscale and Short Form 12 general health questionnaire physical component summary score (SF-12 PCS) provided patient-reported outcome scores pre- and postoperatively. MRI scans were assessed postoperatively using the magnetic resonance observation of cartilage repair tissue (MOCART) score. All patients had postoperative MRI performed at the 2-year postoperative visit, and quantitative T2 mapping relaxation time values were assessed in a subset of the cBMA/BMS group. RESULTS: The mean FAOS and SF-12 PCS scores improved significantly pre- to post-operatively (P < .01) at a mean follow-up of 48.3 months (range, 34 to 82 months) for the cBMA/BMS group and 77.3 months (range, 46 to 100 months) for the BMS-alone group. The MOCART score in the cBMA/BMS group was significantly higher than that in the BMS-alone group (P = .023). Superficial and deep T2 relaxation values in cBMA/BMS patients were higher in repair tissue compared with measurements in adjacent native articular cartilage (P = .030 and P < .001, respectively). CONCLUSIONS: BMS is an effective treatment strategy for treatment of OCLs of the talus and results in good medium-term functional outcomes. Arthroscopic BMS with cBMA also results in similar functional outcomes and improved border repair tissue integration, with less evidence of fissuring and fibrillation on MRI.

Tissue engineering of ligaments for reconstructive surgery.

PURPOSE: The use of musculoskeletal bioengineering and regenerative medicine applications in orthopaedic surgery has continued to evolve. The aim of this systematic review was to address tissue-engineering strategies for knee ligament reconstruction. METHODS: A systematic review of PubMed/Medline using the terms "knee AND ligament" AND "tissue engineering" OR "regenerative medicine" was performed. Two authors performed the search, independently assessed the studies for inclusion, and extracted the data for inclusion in the review. Both preclinical and clinical studies were reviewed, and the articles deemed most relevant were included in this article to provide relevant basic science and recent clinical translational knowledge concerning "tissue-engineering" strategies currently used in knee ligament reconstruction. RESULTS: A total of 224 articles were reviewed in our initial PubMed search. Non-English-language studies were excluded. Clinical and preclinical studies were identified, and those with a focus on knee ligament tissue-engineering strategies including stem cell-based therapies, growth factor administration, hybrid biomaterial, and scaffold development, as well as mechanical stimulation modalities, were reviewed. CONCLUSIONS: The body of knowledge surrounding tissue-engineering strategies for ligament reconstruction continues to expand. Presently, various tissue-engineering techniques have some potential advantages, including faster recovery, better ligamentization, and possibly, a reduction of recurrence. Preclinical research of these novel therapies continues to provide promising results. There remains a need for well-designed, high-powered comparative clinical studies to serve as a foundation for successful translation into the clinical setting going forward. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

The role of stem cells and tissue engineering in orthopaedic sports medicine: current evidence and future directions.

The use of stem cell therapies for the treatment of orthopaedic injuries continues to advance. The purpose of this review was to provide an update of the current role and future directions of stem cell strategies in sports medicine. The application of cell-based treatments in the sports medicine arena has expanded in recent years. Promising preclinical results have led to translation of these novel therapies into the clinical setting. Early well-designed comparative clinical studies have also shown positive outcomes. Despite significant advances in this arena, there remains a need for additional high-powered and well-designed clinical trials to confirm the safety and efficacy of treatment.

Sensory response following knee joint damage in rabbits.

BACKGROUND: Altered sensory information arising from damaged knee joint structures has been hypothesized as a contributing factor to persistent muscle dysfunction following injury. METHODS: Composite femoral nerve sensory signal was measured in 24 rabbits randomly allocated (8 per group) to receive surgical anterior cruciate ligament (ACL) transection with or without autograft reconstruction or nothing (control). Two-weeks after the intervention composite afferent signals were recorded from the femoral nerve. Side-to-side ratios (surgical side vs contralateral healthy side) for peak femoral nerve afferent composite signal were used for comparison. RESULTS: Femoral nerve afferent signal ratios were significantly higher in the ACL-R (2.21 ± 0.74) group when compared to the ACL-T (1.28 ± 0.61, P=0.02) group and Control group (1.31 ± 0.78, P=0.03). CONCLUSION: The magnitude of sensory information recorded on the femoral nerve is increased following ACL injury and reconstruction surgery, but not after an isolated ACL injury in rabbits.

How Research Improves Clinical Care: The Case for Orthopaedic Surgeon Research Leadership and Collaboration: AOA Critical Issues Symposium.

ABSTRACT: Improving the performance and impact of orthopaedic research is a critical leadership challenge. Musculoskeletal (MSK) conditions are a leading cause of disability worldwide, for which research investment and performance lags far behind the burden of disease. In the United States, MSK disorders account for the highest health care costs, have increased in incidence at the fastest rate, and exceed the combined costs of cardiovascular diseases and neoplasms. Despite the cost to society, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), with primary responsibility for MSK research, receives <1.4% of the funds allocated to the National Institutes of Health (NIH). Although orthopaedic surgeons are leading providers of MSK clinical care, the dearth of orthopaedic clinician-scientists also greatly reduces representation of MSK scientific and clinical expertise among academic and scientific leaders. The goals of this symposium were to highlight the critical need for greater prioritization and investment in orthopaedic research and to engage orthopaedic leaders in addressing these needs. Compelling stories of research success from 3 orthopaedic chairs were featured to highlight how orthopaedic surgeon leadership in bench-to-bedside research substantially advances MSK clinical care. Seminar participants also emphasized the need to improve evidence-based clinical practice for which multicenter prospective cohort and registry studies represent opportunities for broader involvement. Prioritization of orthopaedic clinician-scientist development and formation of multidisciplinary partnerships with basic and translational scientists were emphasized as critical needs to advance MSK health. It is critical for orthopaedic chairs to "be invested in" and to "invest in" the success of orthopaedic research. This investment includes developing a professional climate that values research achievement and collaboration as well as implementing strategies to support and sustain research success. Finally, orthopaedic leaders need to advocate for federal research funding to be proportional to the economic burden of disease for which MSK conditions carry the highest current and projected costs. With health-care costs accounting for nearly one-fifth of the U.S. economy, increasing the investment in orthopaedic research to reduce the prevalence, disability, and morbidity from MSK disease needs to be a top orthopaedic and national leadership priority.

Ankle and hindfoot motion of healthy adults during running revealed by dynamic biplane radiography: Side-to-side symmetry, sex-specific differences, and comparison with walking.

This study aimed to characterize ankle and hindfoot kinematics of healthy men and women during overground running using biplane radiography, and to compare these data to those previously obtained in the same cohort during overground walking. Participants ran across an elevated platform at a self-selected pace while synchronized biplane radiographs of their ankle and hindfoot were acquired. Motion of the tibia, talus, and calcaneus was tracked using a validated volumetric model-based tracking process. Tibiotalar and subtalar 6DOF kinematics were obtained. Absolute side-to-side differences in ROM and kinematics waveforms were calculated. Side-to-side and sex-specific differences were evaluated at 10 % increments of stance phase with mixed model analysis. Pearson correlation coefficients were used to assess the relationship between stance-phase running and walking kinematics. 20 participants comprised the study cohort (10 men, mean age 30.8 ± 6.3 years, mean BMI 24.1 ± 3.1). Average absolute side-to-side differences in running kinematics waveforms were 5.6°/2.0 mm or less at the tibiotalar joint and 5.2°/3.2 mm or less at the subtalar joint. No differences in running kinematics waveforms between sides or between men and women were detected. Correlations were stronger at the tibiotalar joint (42/66 [64 %] of correlations were p < 0.05), than at the tibiotalar joint (38/66 [58 %] of correlations were p < 0.05). These results provide a normative reference for evaluating native ankle and hindfoot kinematics which may be informative in surgical or rehabilitation contexts. Sex-specific differences in ankle kinematics during overground running are likely not clinically or etiologically significant. Associations seen between walking and running kinematics suggest one could be used to predict the other.

Influence of Talar and Calcaneal Morphology on Subtalar Kinematics During Walking.

BACKGROUND: Cadaver biomechanical testing suggests that the morphology of articulating bones contributes to the stability of the joints and determines their kinematics; however, there are no studies examining the correlation between bone morphology and kinematics of the subtalar joint. The purpose of this study was to investigate the influence of talar and calcaneal morphology on subtalar kinematics during walking in healthy individuals. METHODS: Forty ankles (20 healthy subjects, 10 women/10 men) were included. Participants walked at a self-selected pace while synchronized biplane radiographs of the hindfoot were acquired at 100 images per second during stance. Motion of the talus and calcaneus was tracked using a validated volumetric model-based tracking process, and subtalar kinematics were calculated. Talar and calcaneal morphology were evaluated using statistical shape modeling. Pearson correlation coefficients were used to assess the relationship between subtalar kinematics and the morphology features of the talus and calcaneus. RESULTS: This study found that a shallower posterior facet of the talus was correlated with the subtalar joint being in more dorsiflexion, more inversion, and more internal rotation, and higher curvature in the posterior facet was correlated with more inversion and eversion range of motion during stance. In the calcaneus, a gentler slope of the middle facet was correlated with greater subtalar inversion. CONCLUSION: The morphology of the posterior facet of the talus was found to a primary factor driving multiplanar subtalar joint kinematics during the stance phase of gait. CLINICAL RELEVANCE: This new knowledge relating form and function in the hindfoot may assist in identifying individuals susceptible to subtalar instability and in improving implant design to achieve desired kinematics after surgery.

Addressing the Impact of Race and Ethnicity on Musculoskeletal Spine Care in the United States.

➤ Despite being a social construct, race has an impact on outcomes in musculoskeletal spine care.➤ Race is associated with other social determinants of health that may predispose patients to worse outcomes.➤ The musculoskeletal spine literature is limited in its understanding of the causes of race-related outcome trends.➤ Efforts to mitigate race-related disparities in spine care require individual, institutional, and national initiatives.

Optimal assessment for anterior talofibular ligament injury utilizing stress ultrasound entails internal rotation during plantarflexion.

OBJECTIVES: An optimal load and ankle position for stress ultrasound of the injured anterior talofibular ligament (ATFL) are unknown. The objectives of this study were to compare stress ultrasound and ankle kinematics from a 6 degree-of-freedom (6-DOF) robotic testing system as a reference standard for the evaluation of injured ATFL and suggest cut-off values for ultrasound diagnosis. METHODS: Ten fresh-frozen human cadaveric ankles were used. Loads and ankle positions examined by the 6-DOF robotic testing system were: 40 N anterior load, 1.7 Nm inversion, and 1.7 Nm internal rotation torques at 30° plantarflexion, 15° plantarflexion, and 0° plantarflexion. Bony translations were measured by ultrasound and a robotic testing system under the above conditions. After measuring the intact ankle, ATFL was transected at its fibular attachment under arthroscopy. Correlations between ultrasound and robotic testing systems were calculated with Pearson correlation coefficients. Paired t-tests were performed for comparison of ultrasound measurements of translation between intact and transected ATFL and unloaded and loaded conditions in transected ATFL. RESULTS: Good agreement between ultrasound measurement and that of the robotic testing system was found only in internal rotation at 30° plantarflexion (ICC â€‹= â€‹0.77; 95% confidence interval 0.27-0.94). At 30° plantarflexion, significant differences in ultrasound measurements of translation between intact and transected ATFL (p â€‹< â€‹0.01) were found in response to 1.7 Nm internal rotation torque and nonstress and stress with internal rotation (p â€‹< â€‹0.01) with mean differences of 2.4 â€‹mm and 1.9 â€‹mm, respectively. CONCLUSION: Based on the data of this study, moderate internal rotation and plantarflexion are optimal to evaluate the effects of ATFL injury when clinicians utilize stress ultrasound in patients. LEVEL OF EVIDENCE: III.

Feasibility and Usability of Augmented Reality Technology in the Orthopaedic Operating Room.

PURPOSE OF REVIEW: Augmented reality (AR) has gained popularity in various sectors, including gaming, entertainment, and healthcare. The desire for improved surgical navigation within orthopaedic surgery has led to the evaluation of the feasibility and usability of AR in the operating room (OR). However, the safe and effective use of AR technology in the OR necessitates a proper understanding of its capabilities and limitations. This review aims to describe the fundamental elements of AR, highlight limitations for use within the field of orthopaedic surgery, and discuss potential areas for development. RECENT FINDINGS: To date, studies have demonstrated evidence that AR technology can be used to enhance navigation and performance in orthopaedic procedures. General hardware and software limitations of the technology include the registration process, ergonomics, and battery life. Other limitations are related to the human response factors such as inattentional blindness, which may lead to the inability to see complications within the surgical field. Furthermore, the prolonged use of AR can cause eye strain and headache due to phenomena such as the vergence-convergence conflict. AR technology may prove to be a better alternative to current orthopaedic surgery navigation systems. However, the current limitations should be mitigated to further improve the feasibility and usability of AR in the OR setting. It is important for both non-clinicians and clinicians to work in conjunction to guide the development of future iterations of AR technology and its implementation into the OR workflow.

A plantar closing wedge osteotomy of the medial cuneiform for residual forefoot supination in flatfoot reconstruction.

BACKGROUND: Residual forefoot supination is commonly encountered during a flatfoot reconstruction, and a new technique for its treatment is described. Contrary to the standard Cotton osteotomy, a plantar closing wedge osteotomy of the medial cuneiform (PCWOMC) was performed, which has a number of advantages. METHODS: We followed 10 feet in 9 patients who had a PCWOMC performed as the last step of a standard flatfoot reconstruction for the correction of residual forefoot supination. These patients were evaluated pre- and postoperatively by standardized radiographic parameters, Short Form-12 (SF-12), and Foot and Ankle Outcome Score (FAOS). RESULTS: Patients were followed for an average of 25.8 months with final radiographic analysis performed at an average of 9.9 months. A significant difference (P < .001) between pre- and postoperative parameters was demonstrated for both lateral talus-first metatarsal angle and medial-cuneiform-to-ground distance. Likewise, there was a statistically significant improvement in the SF-12 score and 4 out of 5 components of the FAOS. One patient developed internal hardware-related symptoms, which were relieved following implant removal. All osteotomies healed uneventfully. CONCLUSION: A PCWOMC can be considered an alternative to the Cotton osteotomy for the treatment of forefoot supination deformity in adult flatfoot reconstruction. The main advantage of this technique over the Cotton osteotomy was simplicity, as an additional dorsal incision and bone graft were not required. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Mitigating Scar Tissue Formation in Tendon Injuries: Targeting HMGB1, AMPK Activation, and Myofibroblast Migration All at Once.

Tendon injuries, while prevalent, present significant challenges regarding their structural and functional restoration. Utilizing alpha-smooth muscle actin (α-SMA)-Ai9-scleraxis (Scx)-green fluorescent protein (GFP) transgenic mice, which exhibit both Scx (a tendon cell marker) and α-SMA (a myofibroblast marker), we explored the effects of metformin (Met) on tendon healing, repair, and its mechanisms of action. Our findings revealed that intraperitoneal (IP) injections of Met, administered before or after injury, as well as both, effectively prevented the release of HMGB1 into the tendon matrix and reduced circulating levels of HMGB1. Additionally, Met treatment increased and activated AMPK and suppressed TGF-ß1 levels within the healing tendon. Tendon healing was also improved by blocking the migration of α-SMA+ myofibroblasts, reducing the prevalence of disorganized collagen fibers and collagen type III. It also enhanced the presence of collagen type I. These outcomes highlight Met's anti-fibrotic properties in acutely injured tendons and suggest its potential for repurposing as a therapeutic agent to minimize scar tissue formation in tendon injuries, which could have profound implications in clinical practice.

Metformin improves tendon degeneration by blocking translocation of HMGB1 and suppressing tendon inflammation and senescence in aging mice.

This study aimed to characterize aging-induced tendinopathy in mouse Achilles tendon and also to assess the treatment effects of metformin (Met) on aging tendon. We showed that compared to young tendon, aging tendon was in an inflammatory and senescent state as shown by increased expression of inflammatory disulfide HMGB1 (dsHMGB1), inflammatory macrophage marker CD68, and senescent cell markers SA-ß-gal, p53, and p16. Moreover, aging tendon was degenerated marked by accumulation of proteoglycans and lipids in its interior. However, treatment of aging tendon by intraperitoneal (IP) injection of Met, a specific inhibitor of HMGB1, reduced dsHMGB1 levels, decreased the expression of CD68, SA-ß-gal, CCN1, and p16 in vitro and in vivo. Furthermore, Met treatment also increased the number of NS, SSEA-1, and CD73 positive stem cells in culture and improved the tendon structure in aging mouse. These findings of this study indicate that Met exerts anti-inflammatory and anti-senescent effects on aging tendon.

Patient-Reported Outcome Measures After Surgical Management of Unstable Lisfranc Injuries in Athletes.

Background: Athletes sustaining Lisfranc joint instability after a low-energy injury often undergo surgical fixation. Limited studies report validated patient-reported outcome measures (PROMs) for this specific patient population. Our purpose was to report PROMs of athletes experiencing instability after a low-energy Lisfranc injury and undergoing surgical fixation. Methods: Twenty-nine athletes (23 competitive, 6 recreational) sustained an unstable Lisfranc injury (14 acute, 15 chronic) and met our inclusion criteria. Injuries were classified as acute if surgically managed within 6 weeks. All athletes completed validated PROMs pre- and postoperatively. The cohort underwent various open reduction internal fixation methods. We evaluated outcomes with the Foot and Ankle Ability Measure (FAAM) activities of daily living (ADL) and sports subscales. Results: Fourteen of 29 (48%) athletes reported PROMs at ≥2 years with a median follow-up time of 44.5 months. Substantial improvement for both FAAM ADL (50% vs 93%; P < .001) and sports (14.1% vs 80%; P = .002) subscales were found, when comparing preoperative to postoperative scores at ≥2 years. Conclusion: This study provides outcomes information for the young athletic population that were treated operatively for low-energy Lisfranc injury with apparent joint instability. Based on the FAAM sports subscale, these patients on average improved between their 6-month evaluation and their final ≥2 years but still scored 80% of the possible 100%, which indicates continued but "slight" difficulty with lower extremity function. Level of Evidence: Level IV, case series.