Oncogene-induced matrix reorganization controls CD8+ T cell function in the soft-tissue sarcoma microenvironment.

CD8+ T cell dysfunction impedes anti-tumor immunity in solid cancers but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined. Therefore, we investigated how ECM composition modulates CD8+ T cell function in undifferentiated pleomorphic sarcoma (UPS), an immunologically active desmoplastic tumor. Using an autochthonous murine model of UPS and data from multiple human patient cohorts, we discovered a multifaceted mechanism wherein the transcriptional co-activator YAP1 promotes collagen VI (COLVI) deposition in the UPS TME. In turn, COLVI induces CD8+ T cell dysfunction and immune evasion by remodeling fibrillar collagen and inhibiting T cell autophagic flux. Unexpectedly, collagen I (COLI) opposed COLVI in this setting, promoting CD8+ T cell function and acting as a tumor suppressor. Thus, CD8+ T cell responses in sarcoma depend upon oncogene-mediated ECM composition and remodeling.

Sarcoma Cells Secrete Hypoxia-Modified Collagen VI to Weaken the Lung Endothelial Barrier and Promote Metastasis.

Intratumoral hypoxia correlates with metastasis and poor survival in patients with sarcoma. Using an impedance sensing assay and a zebrafish intravital microinjection model, we demonstrated here that the hypoxia-inducible collagen-modifying enzyme lysyl hydroxylase PLOD2 and its substrate collagen type VI (COLVI) weaken the lung endothelial barrier and promote transendothelial migration. Mechanistically, hypoxia-induced PLOD2 in sarcoma cells modified COLVI, which was then secreted into the vasculature. Upon reaching the apical surface of lung endothelial cells, modified COLVI from tumor cells activated integrin ß1 (ITGß1). Furthermore, activated ITGß1 colocalized with Kindlin2, initiating their interaction with F-actin and prompting its polymerization. Polymerized F-actin disrupted endothelial adherens junctions and induced barrier dysfunction. Consistently, modified and secreted COLVI was required for the late stages of lung metastasis in vivo. Analysis of patient gene expression and survival data from The Cancer Genome Atlas (TCGA) revealed an association between the expression of both PLOD2 and COLVI and patient survival. Furthermore, high levels of COLVI were detected in surgically resected sarcoma metastases from patient lungs and in the blood of tumor-bearing mice. Together, these data identify a mechanism of sarcoma lung metastasis, revealing opportunities for therapeutic intervention. SIGNIFICANCE: Collagen type VI modified by hypoxia-induced PLOD2 is secreted by sarcoma cells and binds to integrin ß1 on endothelial cells to induce barrier dysfunction, which promotes sarcoma vascular dissemination and metastasis.

Overcoming the Barriers to Diversity in Orthopaedic Surgery: A Global Perspective.

BACKGROUND: Diversity in orthopaedics continues to lag behind that in other surgical specialties. This pattern exists globally and is not unique to gender or race. This review offers a global perspective on overcoming the barriers to diversity in orthopaedics. METHODS: A literature search of MEDLINE and Embase was conducted and a narrative review was undertaken. Publications that discussed any aspect of diversity or solutions to diversity within orthopaedics or academic orthopaedics were identified. RESULTS: A total of 62 studies were included. Studies showed that diversity in orthopaedic training is limited by structural barriers such as long hours, requirements to relocate during training, training inflexibility, and a lack of exposure to orthopaedics. Implicit bias during the selection process for training, discrimination, and a lack of role models are additional barriers that are experienced by both minority and female surgeons. The global lack of diversity suggests that there are also inherent "cultural barriers" that are unique to orthopaedics; however, these barriers are not uniformly experienced. Perceptions of orthopaedics as promoting an unhealthy work-life balance and the existence of a "boys' club" must be addressed. Strong, committed leaders can embed cultural norms, support trainees, and act as visible role models. Targeted efforts to increase diverse recruitment and to reduce bias in selection processes for medical school and specialty training will increase diversity in the "training pipeline." CONCLUSIONS: Diversity in orthopaedics continues to lag behind that in other specialties. Increasing diversity is important for providing a more inclusive training environment, improving patient care, and reducing health disparities. Structural and cultural barriers need to be addressed to improve diversity in orthopaedics. Promoting a culture supportive of all surgeons is essential to reframing perceptions that may prevent individuals from even considering a career as an orthopaedic surgeon. Changing attitudes require focused efforts from committed leadership in a "top-down" approach that prioritizes diversity. The efforts from national bodies seeking to tackle the lack of diversity, as well as the establishment of organizations committed to diversity, such as the International Orthopaedic Diversity Alliance, provide reasons to be optimistic for the future.

Outcomes following Free Fibula Physeal Transfer for Pediatric Proximal Humerus Reconstruction: An International Multi-Institutional Study.

BACKGROUND: Vascularized fibula epiphyseal flap was first described in 1998 for proximal humeral reconstruction in children/infants. The authors aim to review their international, multi-institutional, long-term outcomes. METHODS: An international, multi-institutional review (2004 to 2020) was conducted of patients younger than 18 years undergoing free vascularized fibula epiphyseal transfer for proximal humeral reconstruction. Donor- and recipient-site complications, pain, and final ambulatory status were reviewed. Growth of the transferred bone was assessed under the guidance of a pediatric musculoskeletal radiologist. RESULTS: Twenty-seven patients were included with a median age of 7 years (range, 2 to 13 years). Average follow-up was 120 ± 87.4 months. There were two flap failures (7.4%). Recipient-site complications included fracture [ n = 11 (40.7%)], avascular necrosis of the fibula head [ n = 1 (3.7%)], fibular head avulsion [ n = 1 (3.7%)], infection [ n = 1 (3.7%)], and hardware failure [ n = 1 (3.7%)]. Operative fixation was necessary in one patient with a fracture. The case of infection necessitated fibula explantation 2 years postoperatively, and ultimately, prosthetic reconstruction. Sixteen patients developed peroneal nerve palsy (59.3%): 13 of these cases resolved within 1 year (81% recovery), and three were permanent (11.1%). One patient (3.7%) complained of upper extremity pain. Longitudinal growth was confirmed in all but three cases [ n = 24 (88.9%)] at an average rate of 0.83 ± 0.25 cm/year. CONCLUSIONS: The vascularized fibula epiphysis for proximal humerus reconstruction in children preserves the potential for future growth and an articular surface for motion. Peroneal nerve palsy is common following harvest, although this is often transient. Future efforts should be geared toward reducing postoperative morbidity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

AOA Critical Issues Symposium: Mind the Gap: Addressing Confidence, Imposter Syndrome, and Perfectionism in Surgical Training.

ABSTRACT: Orthopaedic surgeons in training and in their careers can experience a lack of confidence and imposter syndrome. Confidence is built early through continuous improvement, accomplishments, support, and reinforcement. Although it is normal to lack confidence at times, the goal is to recognize this issue, work on visualizing success, and know when to seek help. Mentors can help mentees to build confidence and to normalize thoughts of insecurity and imposter syndrome. It is critical to develop and to maintain resilience, grit, emotional intelligence, courage, and vulnerability during training and throughout one's entire orthopaedic career. Leaders in the field must be aware of these phenomena, be able to talk about such issues, have methods to combat the harmful effects of imposter syndrome, and create a safe, supportive environment conducive to learning and working. Leading well builds not only confidence in oneself but also self-confidence in others. Leaders who are able to build the confidence of individuals will enhance team dynamics, wellness, and overall productivity as well as individual and organizational success.

Leading an Organization in the 21st Century: The Importance of Environmental Sustainability, Social Responsibility, and Good Governance.

The concept of environmental sustainability, social responsibility, and good governance (ESG) is now well established in the corporate world and in for-profit organizations. However, it is not a concept that has reached medical and surgical association boardrooms in a meaningful way. It is important to define the concept of physician and corporate author expertise and objectives of ESG, provide a rationale for using ESG within orthopaedic organizations, and identify specific areas (primarily the "S" and the "G") where the American Academy of Orthopaedic Surgeons and other groups can align with this strategy.

A Glass Ceiling in Orthopedic Surgery: Publication Trends by Gender.

Women are underrepresented across the field of orthopedic surgery and may face barriers to academic advancement. Research presentation at national meetings and publication record are important drivers of advancement in academic orthopedic surgery. However, little is known regarding potential gender differences in publication after orthopedic conference research presentation. This investigation analyzed research presentations at the Annual Meeting of the American Academy of Orthopaedic Surgeons in 2016 and 2017. Author gender was determined through a search of institutional and professional networking websites for gender-specific pronouns. Resulting publications were identified using a systematic search of PubMed and Google Scholar databases. A total of 1696 of 1803 (94.1%) abstracts from 2016 to 2017 had identifiable gender for both the first and last authors, with 1213 (71.5%) abstracts ultimately being published. There were no differences in average sample size or level of evidence between genders. Abstracts authored by women were significantly less likely to lead to publication compared with those by men (67.1% vs 72.1%, P=.023), with articles authored by women having a longer median time to publication (median, 20 months [interquartile range, 19] vs 17 months [interquartile range, 15]; P=.003). This discrepancy was most apparent in adult reconstruction, with women having a 15.5% lower rate of publication (55.1% [27/49] vs 70.6% [307/435]; P=.026) and lower publication journal impact factor (2.7±1.4 vs 3.4±3.4, P=.040) than men. Potential reasons for these discrepancies, including disproportionate domestic obligations, inadequate mentorship, and bias against female researchers, should be addressed. [Orthopedics. 2023;46(2):e118-e124.].

Comparative oncology reveals DNMT3B as a molecular vulnerability in undifferentiated pleomorphic sarcoma.

PURPOSE: Undifferentiated pleomorphic sarcoma (UPS), an aggressive subtype of soft-tissue sarcoma (STS), is exceedingly rare in humans and lacks effective, well-tolerated therapies. In contrast, STS are relatively common in canine companion animals. Thus, incorporation of veterinary patients into studies of UPS offers an exciting opportunity to develop novel therapeutic strategies for this rare human disease. Genome-wide studies have demonstrated that UPS is characterized by aberrant patterns of DNA methylation. However, the mechanisms and impact of this epigenetic modification on UPS biology and clinical behavior are poorly understood. METHODS: DNA methylation in mammalian cells is catalyzed by the canonical DNA methyltransferases DNMT1, DNMT3A and DNMT3B. Therefore, we leveraged cell lines and tissue specimens from human and canine patients, together with an orthotopic murine model, to probe the functional and clinical significance of DNMTs in UPS. RESULTS: We found that the DNA methyltransferase DNMT3B is overexpressed in UPS relative to normal mesenchymal tissues and is associated with a poor prognosis. Consistent with these findings, genetic DNMT3B depletion strongly inhibited UPS cell proliferation and tumor progression. However, existing hypomethylating agents, including the clinically approved drug 5-aza-2'-deoxycytidine (DAC) and the DNMT3B-inhibiting tool compound nanaomycin A, were ineffective in UPS due to cellular uptake and toxicity issues. CONCLUSIONS: DNMT3B represents a promising molecular susceptibility in UPS, but further development of DNMT3B-targeting strategies for these patients is required.

Coaching, Separate from Mentoring, May Provide Skill Acquisition, Improved Well-Being, and Career Advancement in Orthopaedic Surgery: AOA Critical Issues.

ABSTRACT: Coaching is separate from mentoring, and can include life coaching, skills coaching, and behavior coaching. Life coaching can focus on purpose, work-life balance, well-being, and career path. Skills coaching encourages mastery and promotes autonomy. Behavior coaching may be mandated for a disruptive surgeon. Coaching has been shown to reduce burnout and promote well-being and can potentially advance a surgeon's career trajectory and leadership skills.

Percutaneous doxycycline sclerotherapy in a horse with a mandibular aneurysmal bone cyst.

OBJECTIVE: To describe the use and outcome of sclerotherapy with intralesional doxycycline foam in a horse with a mandibular aneurysmal bone cyst. STUDY DESIGN: Case report. ANIMALS: Client-owned 1 year old Standardbred filly. METHODS: The horse presented for progressive mandibular swelling. A 10 mg/mL doxycycline foam was prepared for intralesional injection. Three doses were injected into the lesion under computed tomographic guidance at 6 and 15 weeks after initial treatment. Volume reduction was monitored after each treatment with 3D volumetric rendering and region of interest segmentation using commercially available software. RESULTS: The volume of the lesion decreased from 458.7455 cm3 before treatment, to 363.3101 cm3 at 6 weeks, 273.5855 cm3 at 15 weeks, and 247.2316 cm3 6 months later, resulting in a total reduction of 54% of the initial volume. Bone formation was noted in the lesion. No adverse effects related to doxycycline foam injections were noted. The mandibular swelling was resolved after treatment. CONCLUSION: Intralesional doxycycline sclerotherapy was shown to be efficacious in reducing the volume of the aneurysmal bone cyst in the horse presented in this report. There was complete resolution of mandibular swelling with no side effects related to the intralesional injections.

Oncofusion-driven de novo enhancer assembly promotes malignancy in Ewing sarcoma via aberrant expression of the stereociliary protein LOXHD1.

Ewing sarcoma (EwS) is a highly aggressive tumor of bone and soft tissues that mostly affects children and adolescents. The pathognomonic oncofusion EWSR1::FLI1 transcription factor drives EwS by orchestrating an oncogenic transcription program through de novo enhancers. By integrative analysis of thousands of transcriptomes representing pan-cancer cell lines, primary cancers, metastasis, and normal tissues, we identify a 32-gene signature (ESS32 [Ewing Sarcoma Specific 32]) that stratifies EwS from pan-cancer. Among the ESS32, LOXHD1, encoding a stereociliary protein, is the most highly expressed gene through an alternative transcription start site. Deletion or silencing of EWSR1::FLI1 bound upstream de novo enhancer results in loss of the LOXHD1 short isoform, altering EWSR1::FLI1 and HIF1α pathway genes and resulting in decreased proliferation/invasion of EwS cells. These observations implicate LOXHD1 as a biomarker and a determinant of EwS metastasis and suggest new avenues for developing LOXHD1-targeted drugs or cellular therapies for this deadly disease.

Rising within the leadership of an orthopaedic society: learning from the presidents.

Orthopaedic societies, with their diverse membership from across the world, serve a mission to endorse the progress and innovation in the field of orthopaedics and traumatology with a focus on improving patient care, as well as to encourage and develop education, teaching and research. Such organizations, whether small or large, have been successful in meeting the professional, educational and training needs of its members. The past and future presidents of these societies share insights addressing their professional experiences, lessons learnt and their vision for future leaders of the field. The objective of this article is to summarize the thoughts of presidents of orthopaedic societies from around the globe and to inspire younger and aspiring members of the global orthopaedic fraternity.

Multicenter, retrospective comparison of implant survival, complications and cost between plate and screw and intramedullary nail fixation for metastatic lesions of the diaphyseal humerus.

Background: The humerus is a common site of metastatic disease that can be fixated with either plate and screw or intramedullary nail (IMN) constructs. A multicenter retrospective comparison study was undertaken to compare implant survival, complication rate and cost between the two constructs. No prior studies have included a cost comparison. Methods: Databases of two academic practices were queried retrospectively to identify patients with metastases of the humerus. Inclusion criteria were a lesion in the proximal metaphysis to distal diaphysis and amenable to both implant options with available cost data. Follow-up was at least 6 months barring death or discharge to hospice sooner. Demographic, clinical and outcome data was recorded. Costs were estimated based on contract pricing. Operating room (OR) costs were estimated using per minute OR costs proposed by other investigators. Results: One hundred and one humeri in 96 patients were included (72 plates and 29 nails). The most common malignancies were renal cell, myeloma and lung. Half presented with a displaced fracture. Demographics were similar in both groups. Lesions were larger in the plate group. Surgical times were longer in the plate group, 146 vs. 75 min, P<0.001. Estimated blood loss (EBL) was higher in the plate group, 510 vs. 221 mL, P<0.001. A trend toward increased failure was seen in the plate group, 12.5% vs. 0% (P=0.056). The most common complications in the plate group were pain, stiffness and swelling compared to pain, refracture and PE in the nail group. Local disease progression was equivalent. Implant costs were higher in the IMN group ($2,753 vs. $1,553, P<0.001), while OR costs were lower ($2,349 vs. $4,395, P<0.001). Overall cost of implantation was lower in the IMN group ($5,102 vs. $5,949, P=0.005). Conclusions: IMN of metastases of the humerus offers a faster, potentially more durable construct with lower blood loss, faster OR times and decreased cost of implantation.

Focal reactive periostitis ossificans in a long bone: radiologic and pathologic findings.

Florid reactive periostitis ossificans (FRPO) is a benign juxta-cortical lesion of unknown etiology which most commonly occurs in the hands and feet. We report the radiographic, CT, and MR features of a pathologically confirmed FRPO in the distal femur, a location in which only a handful of cases has been reported. A 26-year-old male who presented with distal thigh pain initially underwent radiograph and CT, which illustrated a well-circumscribed, ossified lesion associated with the cortex of the femur without contiguity with the medullary canal. A subsequent MRI demonstrated heterogeneous signal intensity corresponding to the ossified portion of the lesion with a T2 hyperintense cartilaginous cap and surrounding edema. The lesion was surgically excised and pathologic diagnosis of FRPO, a mixture of osteoid, mature bone, cartilage and fibrous tissue, with associated inflammatory cells, was confirmed. Follow up four months after surgery revealed significant improvement in the patient's pain.

Life or limb: an international qualitative study on decision making in sarcoma surgery during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic is unprecedented as a global crisis over the last century. How do specialist surgeons make decisions about patient care in these unprecedent times? DESIGN: Between April and May 2020, we conducted an international qualitative study. Sarcoma surgeons from diverse global settings participated in 60 min interviews exploring surgical decision making during COVID-19. Interview data were analysed using an inductive thematic analysis approach. SETTING: Participants represented public and private hospitals in 14 countries, in different phases of the first wave of the pandemic: Australia, Argentina, Canada, India, Italy, Japan, Nigeria, Singapore, Spain, South Africa, Switzerland, Turkey, UK and USA. PARTICIPANTS: From 22 invited sarcoma surgeons, 18 surgeons participated. Participants had an average of 19 years experience as a sarcoma surgeon. RESULTS: 17/18 participants described a decision they had made about patient care since the start of the pandemic that was unique to them, that is, without precedence. Common to 'unique' decisions about patient care was uncertainty about what was going on and what would happen in the future (theme 1: the context of uncertainty), the impact of the pandemic on resources or threat of the pandemic to overwhelm resources (theme 2: limited resources), perceived increased risk to self (theme 3: duty of care) and least-worst decision making, in which none of the options were perceived as ideal and participants settled on the least-worst option at that point in time (theme 4: least-worst decision making). CONCLUSIONS: In the context of rapidly changing standards of justice and beneficence in patient care, traditional decision-making frameworks may no longer apply. Based on the experiences of surgeons in this study, we describe a framework of least-worst decision making. This framework gives rise to actionable strategies that can support decision making in sarcoma and other specialised fields of surgery, both during the current crisis and beyond.

Adult Pleomorphic Rhabdomyosarcomas: Assessing Outcomes Associated with Radiotherapy and Chemotherapy Use in the National Cancer Database.

PURPOSE: Practice patterns for treatment of localized adult pleomorphic rhabdomyosarcoma (PRMS) remain quite variable given its rarity. Current national guidelines recommend management similar to that of other high-grade soft tissue sarcomas (STS), which include surgery with perioperative radiation (RT) with or without chemotherapy. Using the National Cancer Database (NCDB), we assessed practice patterns and overall outcomes of patients with localized PRMS. Patients and Methods. Patients with stage II/III PRMS treated with surgical resection from 2004 to 2015 were identified from the NCDB. Predictors of RT and chemotherapy use were assessed using multivariable logistic regression analysis. The association of radiation and chemotherapy status on overall survival was assessed using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Of 243 total patients, RT and chemotherapy were not uniformly utilized, with 44% receiving chemotherapy and in those who did not undergo amputation 62% receiving RT. In those who did not undergo amputation, RT was associated with improved survival on both univariate (HR: 0.49, 95% CI 0.32-0.73, P < 0.001) and multivariate analysis (HR: 0.40, 95% CI 0.26-0.62, P < 0.001), corresponding to greater 5-year overall survival (59% vs. 38%, P < 0.001). Chemotherapy was associated with a higher rate of 5-year overall survival (63% vs. 39%, P < 0.001). However, the survival benefit of chemotherapy did not reach statistical significance on multivariate analysis (HR: 0.65, 95% CI 0.41-1.03, P=0.064). Notable predictors of omission of RT included female gender (OR: 0.40, 95% CI 0.22-0.74, P < 0.01) and age ≥ 70 (OR: 0.55, 95% CI 0.30-1.00, P=0.05). Correspondingly, factors associated with omission of chemotherapy included age ≥70 (OR: 0.17, 95% CI 0.08-0.39, P < 0.001). CONCLUSIONS: A significant proportion of patients with localized adult PRMS are not receiving RT. Likewise, use of chemotherapy was heterogeneous. Our findings note potential benefits and underutilization of RT, for which further investigation is warranted.

A Rare Incident of Intraarticular Fibromatosis of the Knee: A Case Report.

CASE: Our patient is a 34-year-old male aHthlete who presented for consultation after left knee discomfort and pressure for greater than 2 years. Advanced imaging revealed a nonspecific intraarticular suprapatellar lesion with subsequent ultrasound-guided core biopsy demonstrating a spindle cell proliferation consistent with superficial fibromatosis. Thus, the patient underwent an open en bloc surgical resection by a fellowship-trained orthopaedic oncologist. CONCLUSION: As the first reported case of intraarticular fibromatosis of the knee, this case highlights the importance of a thoughtful approach to the management of nonspecific intraarticular lesions through a comprehensive and collaborative strategy to decrease patient morbidity and optimize outcomes.

Definitive Local Therapy Is Associated with Improved Survival in Metastatic Soft Tissue Sarcomas.

Background: Definitive local therapy is often utilized in patients with metastatic soft tissue sarcomas (STS) to reduce morbidity associated with local tumor progression. We hypothesize that it is associated with improved overall survival (OS). Methods: Patients with newly diagnosed metastatic STS treated with chemotherapy were identified from the National Cancer Database and dichotomized into cohorts: 1. definitive local therapy (defined as either definitive dose radiotherapy, definitive surgery, or surgery with perioperative radiotherapy) or 2. conservative therapy (defined as systemic therapy with or without palliative therapy). The association between definitive local therapy and OS, and factors associated with the receipt of definitive local therapy were assessed. Results: Total of 4180 patients were identified. Compared with the conservative therapy, receipt of any definitive local therapy was associated with improved OS (median 17.9 vs. 10.1 months). The survival benefit remained on multivariate analyses and propensity-score matched analyses, with a stepwise improvement with surgery and combined modality local therapy, specifically radiotherapy (HR: 0.77; p < 0.001), surgery (HR: 0.67; p < 0.001), and combined surgery and radiotherapy (HR: 0.42; p < 0.001). Conclusions: Analysis of a large national cancer registry of patients with metastatic STS suggests that chemotherapy plus definitive local therapy is associated with a significant survival benefit compared to the standard chemotherapy alone.

How Does Representation of Women on Editorial Boards Compare Among Orthopaedic, General Surgery, and Internal Medicine Journals?

BACKGROUND: Women have historically been underrepresented as editors of peer-reviewed medical journals. Studies have demonstrated that there are differences in editorial board reviewer behavior based on gender, suggesting that greater representation by women on editorial boards may improve the quality and diversity of the review process. Therefore, the current representation of women on the editorial boards of orthopaedic journals, particularly compared with peer-reviewed surgical and medical journals, is of interest. QUESTIONS/PURPOSES: (1) What is the representation of women as members of editorial boards of prominent orthopaedic surgery journals? (2) How does it compare with representation on the editorial boards of journals in general surgery and internal medicine? METHODS: The top 15 journals with a strong clinical emphasis based on Impact Factor (Clarivate Analytics) calculated by the 2018 Journal Citation Reports were identified for orthopaedic surgery, general surgery (and all general surgical subspecialties), and internal medicine (with representative internal medicine subspecialties). Clinical publications with their primary editorial office located in the United States led predominantly by physicians or basic scientists were eligible for inclusion. The members of an editorial board were identified from the journals' websites. The gender of editors with gender-neutral names (and editors whose gender we considered uncertain) was identified by an internet search for gender-specific pronouns and/or pictures from an institutional profile. Fisher exact tests and t-tests were used to analyze categorical and continuous variables, respectively. Significance was set at p < 0.05. RESULTS: Of the editors analyzed, women made up 9% (121 of 1383) of editorial boards in the orthopaedic journals with the highest Impact Factors, compared with 21% (342 of 1665) of general surgery journals (p < 0.001) and 35% (204 of 587) of internal medicine journals (p < 0.001). The overall mean composition of editorial boards of orthopaedic journals was 10% ± 8% women, compared with that of general surgery, which was 19% ± 6% women (p < 0.001), and that of internal medicine, which was 40% ± 19% women (p < 0.001). CONCLUSION: Women make up a smaller proportion of editorial boards at orthopaedic surgery journals than they do at general surgery and internal medicine journals. However, their representation appears to be comparable to the proportion of women in orthopaedics overall (approximately 6%) and the proportion of women in academic orthopaedics (approximately 19%). Ways to improve the proportion of women on editorial boards might include structured mentorship programs at institutions and personal responsibility for championing mentorship and diversity on an individual level. CLINICAL RELEVANCE: Increasing representation of women on editorial boards may improve the diversity of perspectives and quality of future published research, generate visible role models for young women considering orthopaedics as a career, and improve patient care through enriching the diversity of our specialty.