Barriers to and Outcomes of Initiating Clinical Research at Two Trauma Centers in Mexico.

INTRODUCTION: Despite efforts to advance clinical research through collaboration between Latin and North American partners, there remains persistent barriers to performing investigative work. To overcome these obstacles, a team of over 100 surgeon-leaders from 18 Latin American countries founded the Asociación de Cirujanos Traumatólogos de las Américas (ACTUAR). One of ACTUAR's first major collaborative projects, initiated in 2018, was a prospective, observational, multicenter study evaluating quality of life after open tibia fracture management. The current study identified common barriers experienced during the initiation of this study, as exemplified through two sites in Mexico. The study aims to identify obstacles to proactively overcome these in future collaborative work. METHODS: Two research assistants from University of California, San Francisco and two research coordinators from Mexico were recruited to share their experiences, identify common barriers experienced during site enrollment and on-boarding for the ACTUAR open tibia study, and discuss possible solutions. RESULTS: Barriers were organized into three categories: structural, logistical, and intrapersonal. Structural barriers included differences in patient populations and resources between private and public hospitals. Logistical barriers included ambiguous ethical review processes, internet availability, and low patient follow-up. Primary enrollment as a resident responsibility led to some intrapersonal barriers. Potential solutions were identified for each barrier and agreed upon by all collaborators. CONCLUSIONS: Multiple barriers were identified by research personnel who initiated a prospective surgical clinical research study in Mexico. Through collaborative approaches, many potential solutions may help overcome these barriers and build locally led research capacity in Latin America.

Chronic psychosocial stress compromises the immune response and endochondral ossification during bone fracture healing via ß-AR signaling.

Chronic psychosocial stress/trauma represents an increasing burden in our modern society and a risk factor for the development of mental disorders, including posttraumatic stress disorder (PTSD). PTSD, in turn, is highly comorbid with a plethora of inflammatory disorders and has been associated with increased bone fracture risk. Since a balanced inflammatory response after fracture is crucial for successful bone healing, we hypothesize that stress/trauma alters the inflammatory response after fracture and, consequently, compromises fracture healing. Here we show, employing the chronic subordinate colony housing (CSC) paradigm as a clinically relevant mouse model for PTSD, that mice subjected to CSC displayed increased numbers of neutrophils in the early fracture hematoma, whereas T lymphocytes and markers for cartilage-to-bone transition and angiogenesis were reduced. At late stages of fracture healing, CSC mice were characterized by decreased bending stiffness and bony bridging of the fracture callus. Strikingly, a single systemic administration of the ß-adrenoreceptor (AR) blocker propranolol before femur osteotomy prevented bone marrow mobilization of neutrophils and invasion of neutrophils into the fracture hematoma, both seen in the early phase after fracture, as well as a compromised fracture healing in CSC mice. We conclude that chronic psychosocial stress leads to an imbalanced immune response after fracture via ß-AR signaling, accompanied by disturbed fracture healing. These findings offer possibilities for clinical translation in patients suffering from PTSD and fracture.

Leadership development programs for healthcare professionals in low-and middle-income countries: A systematic review.

BACKGROUND: Leadership development programs are integral to the future success of public health and healthcare organisations. Despite low-and middle-income countries (LMICs) bearing a greater burden of unmet medical needs, fewer professional development opportunities exist in these settings. This study aims to provide a comprehensive understanding of available leadership development programs for healthcare professionals in LMICs. METHODS: This study conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-P systematic review and traditional meta-analyses guidelines. Articles were identified through five academic databases: Embase, PubMed, Web of Science, ERIC, and Business Source Complete. Eligibility criteria included original research published in peer-reviewed journals on non-clinical, leadership development programs offered to healthcare professionals in LMICs worldwide. RESULTS: Forty-one peer-reviewed articles met inclusion criteria, of which physicians, nurses, and public health professionals were the most common types of providers to attend leadership development programs; no programs exclusively targeted surgeons. The greatest proportion of programs were short-term interventions (ranging from 1 day to 12 weeks). Communication, organizational structure and leadership, and personal development were identified as the three most common leadership themes in the review. Regionally, leadership programs were reported most commonly in Africa, specifically in Anglophone countries. Other regions worldwide, including Latin America and the Caribbean, were underrepresented in the review. CONCLUSIONS: The findings from this review identify gaps in leadership development programs for certain groups of healthcare professionals from certain geographical regions, supporting the need for further provision of and participation in these opportunities in LMICs.

Trauma, a Matter of the Heart-Molecular Mechanism of Post-Traumatic Cardiac Dysfunction.

Trauma remains a leading global cause of mortality, particularly in the young population. In the United States, approximately 30,000 patients with blunt cardiac trauma were recorded annually. Cardiac damage is a predictor for poor outcome after multiple trauma, with a poor prognosis and prolonged in-hospitalization. Systemic elevation of cardiac troponins was correlated with survival, injury severity score, and catecholamine consumption of patients after multiple trauma. The clinical features of the so-called "commotio cordis" are dysrhythmias, including ventricular fibrillation and sudden cardiac arrest as well as wall motion disorders. In trauma patients with inappropriate hypotension and inadequate response to fluid resuscitation, cardiac injury should be considered. Therefore, a combination of echocardiography (ECG) measurements, echocardiography, and systemic appearance of cardiomyocyte damage markers such as troponin appears to be an appropriate diagnostic approach to detect cardiac dysfunction after trauma. However, the mechanisms of post-traumatic cardiac dysfunction are still actively being investigated. This review aims to discuss cardiac damage following trauma, focusing on mechanisms of post-traumatic cardiac dysfunction associated with inflammation and complement activation. Herein, a causal relationship of cardiac dysfunction to traumatic brain injury, blunt chest trauma, multiple trauma, burn injury, psychosocial stress, fracture, and hemorrhagic shock are illustrated and therapeutic options are discussed.

Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes.

Fractures heal predominantly through the process of endochondral ossification. The classic model of endochondral ossification holds that chondrocytes mature to hypertrophy, undergo apoptosis and new bone forms by invading osteoprogenitors. However, recent data demonstrate that chondrocytes transdifferentiate to osteoblasts in the growth plate and during regeneration, yet the mechanism(s) regulating this process remain unknown. Here, we show a spatially-dependent phenotypic overlap between hypertrophic chondrocytes and osteoblasts at the chondro-osseous border in the fracture callus, in a region we define as the transition zone (TZ). Hypertrophic chondrocytes in the TZ activate expression of the pluripotency factors [Sox2, Oct4 (Pou5f1), Nanog], and conditional knock-out of Sox2 during fracture healing results in reduction of the fracture callus and a delay in conversion of cartilage to bone. The signal(s) triggering expression of the pluripotency genes are unknown, but we demonstrate that endothelial cell conditioned medium upregulates these genes in ex vivo fracture cultures, supporting histological evidence that transdifferentiation occurs adjacent to the vasculature. Elucidating the cellular and molecular mechanisms underlying fracture repair is important for understanding why some fractures fail to heal and for developing novel therapeutic interventions.

Role of muscle stem cells during skeletal regeneration.

Although the importance of muscle in skeletal regeneration is well recognized clinically, the mechanisms by which muscle supports bone repair have remained elusive. Muscle flaps are often used to cover the damaged bone after traumatic injury yet their contribution to bone healing is not known. Here, we show that direct bone-muscle interactions are required for periosteum activation and callus formation, and that muscle grafts provide a source of stem cells for skeletal regeneration. We investigated the role of satellite cells, the muscle stem cells. Satellite cells loss in Pax7(-/-) mice and satellite cell ablation in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice impaired bone regeneration. Although satellite cells did not contribute as a large source of cells endogenously, they exhibited a potential to contribute to bone repair after transplantation. The fracture healing phenotype in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice was associated with decreased bone morphogenetic proteins (BMPs), insulin-like growth factor 1, and fibroblast growth factor 2 expression that are normally upregulated in response to fracture in satellite cells. Exogenous rhBMP2 improved bone healing in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice further supporting the role of satellite cells as a source of growth factors. These results provide the first functional evidence for a direct contribution of muscle to bone regeneration with important clinical implications as it may impact the use of muscle flaps, muscle stem cells, and growth factors in orthopedic applications.

Leadership development training for orthopaedic trauma surgeons: an international survey.

Purpose: This study examined the leadership development themes that global orthopaedic surgeons in differently resourced countries perceive as essential components and evaluated barriers to attending leadership development programs. Methods: This multinational, 45-question survey engaged orthopaedic surgeons (one expert per country). The questionnaire collected participants' demographics, perception of effective leadership traits, and valuation of various leadership themes based on importance and interest. Results: The survey was completed by 110 orthopaedic surgeons worldwide. Respondents most commonly reported holding a leadership position (87%) in hospital settings (62%), clinical settings (47%), and national orthopaedic societies (46%). The greatest proportion of participants reported having never attended a leadership course (42%). Participants regarded "high performing team-building," "professional ethics," and "organizational structure and ability to lead" as the most important leadership themes. No significant (P ≤ 0.05) differences were identified among perceived importance or interest in leadership themes between income levels; however, statistically significant differences were identified in the questionnaire; respondents in low- and middle-income countries (LICs/LMICs) demonstrated a stronger interest in attending a leadership course than those in high-income countries (HICs) (98% vs. 79%, P = 0.013), and fewer surgeons in LICs/LMICs had taken personality assessment tests than those in HICs (22% vs. 49%, P = 0.019). The most common barriers to attending leadership courses were lack of opportunities and invitations (57%), difficulty missing work (22%), and cost of course attendance (22%). Conclusions: These findings can better inform the development of effective curricula and provide a framework for a successful model for the future. Level of Evidence: V.

Management of open fracture and related complications: the Japanese way.

Open fractures continue to be a challenging clinical problem throughout the world, and Japan is no exception. Surgeons are faced with critical decisions throughout the care of these injuries that can have significant effects in clinical outcome, ranging from the type and timing of antibiotic administration, fixation, soft-tissue management, and interventions for postfracture complications. In October 2022, the Japanese Society for Fracture Repair (JSFR) was invited to represent Japan as the Guest Nation society at the 38th Annual Meeting of the Orthopaedic Trauma Society held in Tampa, Florida. The JSFR organized a symposium, entitled "Management of Open Fracture and related complications-the Japanese way," that featured cutting-edge approaches to open fractures in their country, including presentations on the "fix-and-flap" approach, local antibiotics perfusion delivery, and a "chipping" method for the stimulation of bone healing. This article summarizes the content of these 3 presentations from that symposium.

Establishing Consensus on Essential Resources for Musculoskeletal Trauma Care Worldwide: A Modified Delphi Study.

BACKGROUND: Despite evidence that formalized trauma systems enhance patient functional outcomes and decrease mortality rates, there remains a lack of such systems globally. Critical to trauma systems are the equipment, materials, and supplies needed to support care, which vary in availability regionally. The purpose of the present study was to identify essential resources for musculoskeletal trauma care across diverse resource settings worldwide. METHODS: The modified Delphi method was utilized, with 3 rounds of electronic surveys. Respondents consisted of 1 surgeon with expertise in musculoskeletal trauma per country. Participants were identified with use of the AO Trauma, AO Alliance, Orthopaedic Trauma Association, and European Society for Trauma and Emergency Surgery networks. Respondents rated resources on a Likert scale from 1 (most important) to 9 (least important). The "most essential" resources were classified as those rated ≤2 by ≥75% of the sampled group. RESULTS: One hundred and three of 111 invited surgeons completed the first survey and were included throughout the subsequent rounds (representing a 93% response rate). Most participants were fellowship-trained (78%) trauma and orthopaedic surgeons (90%) practicing in an academic setting (62%), and 46% had >20 years of experience. Respondents represented low-income and lower-middle-income countries (LMICs; 35%), upper-middle income countries (UMICs; 30%), and high-income countries (HICs; 35%). The initial survey identified 308 unique resources for pre-hospital, in-hospital, and post-hospital phases of care, of which 71 resources achieved consensus as the most essential. There was a significant difference (p < 0.0167) in ratings between income groups for 16 resources, all of which were related to general trauma care rather than musculoskeletal injury management. CONCLUSIONS: There was agreement on a core list of essential musculoskeletal trauma care resources by respondents from LMICs, UMICs, and HICs. All significant differences in resource ratings were related to general trauma management. This study represents a first step toward establishing international consensus and underscores the need to prioritize resources that are locally available. The information can be used to develop effective guidelines and policies, create best-practice treatment standards, and advocate for necessary resources worldwide. CLINICAL RELEVANCE: This study utilized the Delphi method representing expert opinion; however, this work did not examine patient management and therefore does not have a clinical Level of Evidence.

LEADERSHIP DEVELOPMENT TRAINING FOR BRAZILIAN ORTHOPEDIC SURGEONS.

Objective: To report on the experience and impressions of the Brazilian orthopedic trauma surgeons attending the Leadership Development Program (LDP) hosted by the Sociedade Brasileira do Trauma Ortopédico (SBTO) in Sao Paulo, Brazil on November 4, 2022. Methods: Forty-eight orthopedic trauma surgeons from five different regions throughout Brazil were provided a link to complete The Big Five Test, a validated online personality assessment. The questionnaire was available in Portuguese and was intended to provide a background on individual personality traits and their influence on interpersonal interactions. The LDP integrated content from literature reviews specific to Latin America, established leadership programs from leading business schools, and various subject matter experts. Prior to the start of the LDP, participants received a pre-course survey evaluating demographic information, a needs assessment, and the prioritization of leadership topics utilizing a 5-point Likert-scale. Attendees participated in the one-day, interactive LDP focusing on the fundamental principles of leadership development, communication, personal development, emotional intelligence and negotiation. Following the LDP, a post-course evaluation was administered to determine the participants' overall experience, and suggestions for LDP improvement. Results: Forty-one of the forty-eight course participants completed the pre-course evaluation, whereas forty-six of the forty-eight participants completed the post-course evaluations. Overwhelmingly, the lack of opportunity was most prevalently reported as the main obstacle to attending a leadership course, as cited by 56% of respondents. Conclusion: Expanding the accessibility, diversity, and customizability of leadership programs can facilitate the development of personal tools needed to move healthcare forward. Critical topics include emotional intelligence and other differentiating leadership qualities that distinguish true transformational and servant leaders. Advancing leadership skills can stimulate networking, expose learners to experiential learning styles, inspire others to create positive change, and engender creative solutions for systematic improvements and health outcomes. Level of Evidence III; Individual Case-Control Studies.

Objetivo: Relatar a experiência e as impressões de cirurgiões de trauma ortopédico brasileiros participantes do Programa de Desenvolvimento de Liderança (PDL), organizado pela Sociedade Brasileira do Trauma Ortopédico (SBTO), em São Paulo, Brasil, em 4 de novembro de 2022. Métodos: Quarenta e oito cirurgiões de trauma ortopédico de cinco regiões diferentes do Brasil receberam um link para preencher o The Big Five Test, uma avaliação de personalidade on-line validada. O questionário estava disponível em português e pretendia fornecer informações básicas sobre traços de personalidade individuais e sua influência nas interações interpessoais. O PDL integrou conteúdo de análises de literatura específicas da América Latina, e programas de liderança estabelecidos pelas principais escolas de negócios e por vários especialistas no assunto. Antes do início do PDL, os participantes receberam uma pesquisa pré-curso solicitando informações demográficas, uma avaliação de necessidades e a priorização de tópicos de liderança utilizando uma escala Likert de 5 pontos. Os participantes participaram do PDL interativo de um dia com foco nos princípios fundamentais de desenvolvimento de liderança, comunicação, desenvolvimento pessoal, inteligência emocional e negociação. Após o PDL, foi realizada uma avaliação pós-curso para determinar a experiência geral dos participantes e sugestões para melhoria do PDL. Resultados: Quarenta e um dos quarenta e oito participantes do curso concluíram a avaliação pré-curso, enquanto quarenta e seis dos quarenta e oito participantes concluíram a avaliação pós-curso. A falta de oportunidade foi relatada com maior prevalência como o principal obstáculo para frequentar um curso de liderança, conforme citado por 56% dos entrevistados. Conclusão: Expandir a acessibilidade, a diversidade e a personalização dos programas de liderança podem facilitar o desenvolvimento de ferramentas pessoais necessárias para fazer avançar os cuidados de saúde. Os tópicos críticos incluem inteligência emocional e outras qualidades de liderança diferenciadas, que distinguem verdadeiros líderes transformacionais e servidores O avanço das competências de liderança pode estimular o networking, expor os alunos a estilos de aprendizagem experiencial, inspirar outros a criar mudanças positivas e gerar soluções criativas para melhorias sistemáticas dos resultados na saúde. Nível de Evidência III; Estudos de caso-controle individuais.

Acute complications of patients with pelvic fractures after pelvic angiographic embolization.

BACKGROUND: Hemodynamically unstable patients with a pelvic fracture and arterial pelvic bleeding frequently are treated with pelvic angiographic embolization (PAE). PAE is reported to be a safe and effective method of controlling hemorrhage. However, the loss of blood supply and subsequent ischemia from embolization may lead to adverse consequences. OBJECTIVES/PURPOSES: We sought to determine (1) the frequency and types of complications observed after PAE; (2) the mortality after PAE; and (3) the clinical factors associated with complications and mortality after PAE. METHODS: We conducted a retrospective case series descriptive study at a Level I trauma center. Using our institution's trauma registry, we isolated patients with pelvic fractures treated with PAE admitted between June 1999 and December 2007. Complications attributed to PAE occurring in the initial hospital stay were recorded. We identified 98 patients with pelvic fractures treated by PAE with an average hospital stay of 25.3 days. RESULTS: The complication rate was 11% and included six patients with gluteal muscle necrosis (6%), five with surgical wound breakdown (5%), four deep infections (4%), one superficial infection, two patients with of impotence (2%), and one with bladder necrosis. The mortality rate in the PAE group reached 20%. Bilateral embolization was performed in 100% of the patients with complications. Nonselective embolization was performed in 81% of patients with complications. All of the patients with gluteal necrosis had bilateral nonselective embolization. CONCLUSIONS: Bilateral or nonselective PAE is associated with significant complications during the initial hospital stay. The value of PAE should be weighed against its possible adverse consequences. Selective unilateral arterial embolization should be considered whenever possible.

Deciphering data: How should clinical trials change your clinical practice?

INTRODUCTION: The careful consideration of how to apply findings from the scientific literature is important to every physician's clinical practice. This can pose a difficult task, particularly with the increasing speed of technological advances and complexity involved in modern clinical trials. This review introduces a new method, the WHOM criteria (Who, How, Outcomes, Minimizing bias), from which orthopedic surgeons and other physicians can efficiently evaluate novel medical literature for inclusion into their clinical practice. WHOM CRITERIA: The WHOM framework consists of four steps. The first step, Who, involves confirming whether a sample population studied is similar to one's patient under treatment, in order to ensure the results can be reasonably applied. Second, the How, comprises evaluating the intervention performed and ensuring that it could be reasonably replicated. The third step requires thoroughly evaluating the outcomes used in the study so as to ensure they are clinically meaningful to both the treating physician and the patient. Finally, there must be a careful evaluation of potential sources of bias and the ways in which errors and bias were minimized in all phases of the study. CONCLUSION: Evidence-based practice should drive clinical decision making whenever the necessary literature is available. This requires the careful evaluation of new literature on a regular basis so that physicians can render safe and effective health care in partnership with their patients. The WHOM criteria are described in order to aid clinicians in navigating published research and change practice when appropriate.

Age-related decrease in periostin expression may be associated with attenuated fracture healing in old mice.

Older adults suffer more bone fractures with higher rates of healing complications and increased risk of morbidity and mortality. An improved understanding of the cellular and molecular mechanism of fracture healing and how such processes are perturbed with increasing age may allow for better treatment options to manage fractures in older adults. Macrophages are attractive therapeutics due to their role in several phases of fracture healing. After injury, bone marrow-derived macrophages are recruited to the injury and propagate the inflammatory response, contribute to resolution of inflammation, and promote bone regeneration. A tissue resident population of macrophages named osteal macrophages are present in the periosteum and are directly associated with osteoblasts and these cells contribute to bone formation. Here, we utilized bulk RNA sequencing to analyze the transcriptional activity of osteal macrophages from old and young mice present in primary calvarial cultures. Macrophages demonstrated a diverse transcriptional profile, expressing genes involved in immune function as well as wound healing and regeneration. Periostin was significantly downregulated in macrophages from old mice compared to young. Periostin is an extracellular matrix protein with important functions that promote osteoblast activity during bone regeneration. An age-related decrease of periostin expression was verified in the fracture callus of old mice compared to young. Young periostin knockout mice demonstrated attenuated fracture healing outcomes that reflected what is observed in old mice. This study supports an important role of periostin in fracture healing, and therapeutically targeting the age-related decrease in periostin may improve healing outcomes in older populations.

Opportunities for International Orthopaedic Volunteerism: An Exploration of United States and Canada-Based Nonprofit Organizations.

BACKGROUND: In low and middle-income countries (LMICs), there are often not enough orthopaedic surgeons to treat musculoskeletal conditions. International volunteerism is 1 way that the orthopaedic community seeks to meet this need. This study explored the opportunities available for orthopaedic surgeons to volunteer overseas as offered by nonprofit organizations in the United States and Canada. METHODS: A systematic internet search was conducted using 2 distinct search strategies. A website was considered a "hit" if it was that of a U.S. or Canada-based nonprofit, volunteer, or non-governmental organization that had opportunities for international orthopaedic volunteerism. Duplicate hits were eliminated to identify distinct organizations. Data regarding the work and geographical reach of the organization, as well as changes to its volunteer programs as a result of COVID-19, were extracted from each hit. RESULTS: Of the 38 distinct organizations identified in the U.S. and Canada, the most common orthopaedic subspecialties represented were pediatrics (37%), hand (24%), and arthroplasty (18%). Foot and ankle (4 organizations; 11%), sports medicine (2 organizations; 5%), and oncology (1 organization; 3%) were the least represented subspecialities. The most common regions for volunteer trips included Latin America and the Caribbean, followed by West and East Africa. Twelve organizations (32%) were identified as having a religious affiliation. For most organizations, the trip duration was a minimum of 1 week. All volunteer organizations included operative or clinical experiences as part of their trips, and the majority of organizations (58%) reported that their trips included opportunities for training local surgeons. Many organizations (71%) reported having resumed trips after halting them during the COVID-19 pandemic. CONCLUSIONS: Many opportunities exist for orthopaedic surgeons to volunteer their time and skills abroad. Future directions for the improvement of international volunteer efforts among the orthopaedic community could include expanding the number of existing volunteer opportunities and assessing the ethics, safety, efficacy, and longevity of these programs.

Orthopaedic trauma observerships in North America for international surgeons: the visitors' perspective.

International observerships are one of many efforts aimed at addressing disparities in orthopaedic trauma care globally. However, their impact on visiting surgeons and their home countries, as well as the challenges faced by participating surgeons, are not well-documented. Methods: A survey was distributed to overseas surgeons who participated in an orthopaedic trauma observership from 2009 to 2020. Surgeons were identified through North American institutions previously recognized by the authors as having hosted international observerships. Information gathered included participant demographics, details of and perceived impact of the observership, and barriers faced before, during, and after the program. Responses from 148 international surgeons (ISs) from 49 countries were analyzed. Results: Sixty percent of observerships were at academic programs, 57% lasted 1-3 months, and 60% were self-funded. Participants identified cost and housing as primary barriers. After completing their observership, lack of funding, equipment and support staff, and excessive workload prevented participants from implementing changes at their clinical practice. Most observers believed that they gained relevant clinical (89%) and surgical knowledge (67%) and developed a professional network of North American hosts (63%). The most common suggested changes to the observership were greater hands-on experience in the operating room and structured goal setting relevant to the visiting surgeon. Conclusions: Visiting surgeons find North American orthopaedic trauma observerships helpful in improving their surgical and clinical skills. However, financial constraints and resource limitations at their clinical practice and limited operative experience during the observership present barriers to maximizing this clinical experience. To enhance the relevance of clinical observerships for ISs and impact global orthopaedic trauma care, the unique needs and challenges facing ISs must be addressed. Level of Evidence: IV-Cross-Sectional Study.

Altered early immune response after fracture and traumatic brain injury.

Introduction: Clinical and preclinical data suggest accelerated bone fracture healing in subjects with an additional traumatic brain injury (TBI). Mechanistically, altered metabolism and neuro-endocrine regulations have been shown to influence bone formation after combined fracture and TBI, thereby increasing the bone content in the fracture callus. However, the early inflammatory response towards fracture and TBI has not been investigated in detail so far. This is of great importance, since the early inflammatory phase of fracture healing is known to be essential for the initiation of downstream regenerative processes for adequate fracture repair. Methods: Therefore, we analyzed systemic and local inflammatory mediators and immune cells in mice which were exposed to fracture only or fracture + TBI 6h and 24h after injury. Results: We found a dysregulated systemic immune response and significantly fewer neutrophils and mast cells locally in the fracture hematoma. Further, local CXCL10 expression was significantly decreased in the animals with combined trauma, which correlated significantly with the reduced mast cell numbers. Discussion: Since mast cells and mast cell-derived CXCL10 have been shown to increase osteoclastogenesis, the reduced mast cell numbers might contribute to higher bone content in the fracture callus of fracture + TBI mice due to decreased callus remodeling.

Open fractures: Current treatment perspective.

Severe open fractures present challenges to orthopaedic surgeons worldwide, with increased risks of significant complications. Although different global regions have different resources and systems, there continue to be many consistent approaches to open fracture care. Management of these complex injures continues to evolve in areas ranging from timing of initial operative debridement to the management of critical-sized bone defects. This review, compiled by representative members of the International Orthopaedic Trauma Association, focuses on several critical areas of open fracture management, including antibiotic administration, timing of debridement, bone loss, soft tissue management, and areas of need for future investigation.

Current consensus and clinical approach to fragility fractures of the pelvis: an international survey of expert opinion.

Introduction: Fragility fractures of the pelvis (FFP) in elderly patients are an underappreciated injury with a significant impact on mobility, independency, and mortality of affected patients and is a growing burden for society/health care. Given the lack of clinical practice guidelines for these injuries, the authors postulate there is heterogeneity in the current use of diagnostic modalities, treatment strategies (both operative and nonoperative), and follow-up of patients with FFP. The goal of this study was to assess international variation in the management of FFP. Methods: All International Orthopaedic Trauma Association (IOTA) steering committee members were asked to select 15 to 20 experts in the field of pelvic surgery to complete a case-driven international survey. The survey addresses the definition of FFP, use of diagnostic modalities, timing of imaging, mobilization protocols, and indications for surgical management. Results: In total, 143 experts within 16 IOTA societies responded to the survey. Among the experts, 86% have >10 years of experience and 80% works in a referral center for pelvic fractures. However, only 44% of experts reported having an institutional protocol for the management of FFP. More than 89% of experts feel the need for a (inter)national evidence-based guideline. Of all experts, 73% use both radiographs and computed tomography (CT) to diagnose FFP, of which 63% routinely use CT and 35% used CT imaging selectively. Treatment strategies of anterior ring fractures were compared with combined (anterior and posterior ring) fractures. Thirty-seven percent of patients with anterior ring fractures get admitted to the hospital compared with 75% of patients with combined fractures. Experts allow pain-guided mobilization in 72% after anterior ring fracture but propose restricted weight-bearing in case of a combined fracture in 44% of patients. Surgical indications are primarily based on the inability to mobilize during hospital admission (33%) or persistent pain after 2 weeks (25%). Over 92% plan outpatient follow-up independent of the type of fracture or treatment. Conclusion: This study shows that there is a great worldwide heterogeneity in the current use of diagnostic modalities and both nonoperative and surgical management of FFP, emphasizing the need for a consensus meeting or guideline.

Encapsulation of ß-NGF in injectable microrods for localized delivery accelerates endochondral fracture repair.

Introduction: Currently, there are no non-surgical FDA-approved biological approaches to accelerate fracture repair. Injectable therapies designed to stimulate bone healing represent an exciting alternative to surgically implanted biologics, however, the translation of effective osteoinductive therapies remains challenging due to the need for safe and effective drug delivery. Hydrogel-based microparticle platforms may be a clinically relevant solution to create controlled and localized drug delivery to treat bone fractures. Here, we describe poly (ethylene glycol) dimethacrylate (PEGDMA)-based microparticles, in the shape of microrods, loaded with beta nerve growth factor (ß-NGF) for the purpose of promoting fracture repair. Methods: Herein, PEGDMA microrods were fabricated through photolithography. PEGDMA microrods were loaded with ß-NGF and in vitro release was examined. Subsequently, bioactivity assays were evaluated in vitro using the TF-1 tyrosine receptor kinase A (Trk-A) expressing cell line. Finally, in vivo studies using our well-established murine tibia fracture model were performed and a single injection of the ß-NGF loaded PEGDMA microrods, non-loaded PEGDMA microrods, or soluble ß-NGF was administered to assess the extent of fracture healing using Micro-computed tomography (µCT) and histomorphometry. Results: In vitro release studies showed there is significant retention of protein within the polymer matrix over 168 hours through physiochemical interactions. Bioactivity of protein post-loading was confirmed with the TF-1 cell line. In vivo studies using our murine tibia fracture model show that PEGDMA microrods injected at the site of fracture remained adjacent to the callus for over 7 days. Importantly, a single injection of ß-NGF loaded PEGDMA microrods resulted in improved fracture healing as indicated by a significant increase in the percent bone in the fracture callus, trabecular connective density, and bone mineral density relative to soluble ß-NGF control indicating improved drug retention within the tissue. The concomitant decrease in cartilage fraction supports our prior work showing that ß-NGF promotes endochondral conversion of cartilage to bone to accelerate healing. Discussion: We demonstrate a novel and translational method wherein ß-NGF can be encapsulated within PEGDMA microrods for local delivery and that ß-NGF bioactivity is maintained resulting in improved bone fracture repair.

Postfasciotomy Classification System for Acute Compartment Syndrome of the Leg.

OBJECTIVE: Acute compartment syndrome (ACS) is a true emergency. Even with urgent fasciotomy, there is often muscle damage and need for further surgery. Although ACS is not uncommon, no validated classification system exists to aid in efficient and clear communication. The aim of this study was to establish and validate a classification system for the consequences of ACS treated with fasciotomy. METHODS: Using a modified Delphi method, an international panel of ACS experts was assembled to establish a grading scheme for the disease and then validate the classification system. The goal was to articulate discrete grades of ACS related to fasciotomy findings and associated costs. A pilot analysis was used to determine questions that were clear to the respondents. Discussion of this analysis resulted in another round of cases used for 24 other raters. The 24 individuals implemented the classification system 2 separate times to compare outcomes for 32 clinical cases. The accuracy and reproducibility of the classification system were subsequently calculated based on the providers' responses. RESULTS: The Fleiss Kappa of all raters was at 0.711, showing a strong agreement between the 24 raters. Secondary validation was performed for paired 276 raters and correlation was tested using the Kendall coefficient. The median correlation coefficient was 0.855. All 276 pairs had statistically significant correlation. Correlation coefficient between the first and second rating sessions was strong with the median pair scoring at 0.867. All surgeons had statistically significant internal consistency. CONCLUSION: This new ACS classification system may be applied to better understand the impact of ACS on patient outcomes and economic costs for leg ACS.