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Objectives: Parkinson’s disease is the most common neurodegenerative disease. Combining levodopa with other drugs, including decarboxylase inhibitors (DCI) is its most effective treatment. Urinary tract infection (UTI) is the most common cause of hospitalization in Parkinson’s patients, making it crucial to find an appropriate treatment to reduce the incidence of this complication. This study aimed to investigate UTIs in Parkinson’s patients using levodopa with DCI supplements. Methods: In this systematic review and meta-analysis, databases such as PubMed, Scopus, Embase, Cochrane, and Web of Science were searched up to March 2024. Only randomized controlled trials involving Parkinson’s patients were included in the present study. Parkinson’s patients who used levodopa along with carbidopa or benserazide were considered the intervention group, while those who used levodopa with another drug were considered the control group. Results: Nine interventional studies were ultimately analyzed. The relative risk (RR) of UTI in patients taking DCI was 26% lower than those who did not (RR Treatment/Control = 0.74, 95% CI: 0.58-0.95, p = 0.019). Furthermore, observations at different times of follow-up showed that at 13-24 weeks and at > 24 weeks of treatment with DCI, there was a reduction in the incidence of UTI (RR = 0.68, 95% CI: 0.46-1.01 and RR = 0.77, 95% CI: 0.58-1.0, respectively). On the contrary, there was an increase of the risk of UTI in the first 12 weeks of treatment with DCI (RR = 1.11, 95% CI: 0.37-3.33). Conclusions: The results of this study indicated that using DCI drugs is associated with a reduced relative risk of developing UTIs. The beneficial effect of the drug showed after 12 weeks of treatment after an initial negative effect on the risk of UTI.

Seaweeds possess considerable potential for developing and enhancing pharmaceutical drugs because of their wide variety as abundant sources of numerous bioactive secondary metabolites, making them well-suited for developing and enhancing pharmaceutical drugs. This study evaluated the antioxidant, secondary metabolites, total phenolic content, and total flavonoid content of various crude extracts (methanol, ethanol) and their fractions (50 % and 70 %) of Sargassum polycystum. Fourier transform infrared (FT‐IR) analysis was also performed to identify the active chemical composition of the crude extracts. The results showed that various extracts contained varying concentrations of terpenoid, saponin, phlobatannin, cardiac glycosides, phenolic, and flavonoid. FT-IR analysis confirmed the presence of phenols, carboxylic acid, ketones, ethers, aromatics, amides, and sulfonates. 100 % methanolic extract contained the maximum concentrations of total phenols (80.13 mg of GAE/g) and total flavonoids (38.33 mg of quercetin/g). 100 % methanol extracts exhibited higher antioxidant activity in the DPPH assay (78.32 %, IC50 = 1.59 mg/ml) and ABTS assay (69.82 %, IC50 = 2.39 mg/ml). The bio-functional activity of crude extracts depended on their extract and concentration. The present study demonstrates that the macroalgae S. polycystum contains noteworthy secondary metabolites and natural antioxidants, indicating their potential utilization in various pharmacological and functional food applications.

Crossed-fused renal ectopia (CFRE) is a rare congenital anomaly where both kidneys are fused on the same side. We report a case of a 52-year-old male patient who presented with central abdominal pain associated with hematuria and dysuria, with a history of left open ureterolithotomy. Abdominal computed tomography (CT) showed an 18-mm left distal ureteric stone and a CFRE with a bilateral duplex-collecting system. Left ureteroscopy and laser lithotripsy with magnetic double-J stent insertion were carried out successfully, and the patient was discharged on the same day in fair general condition.

Emphysematous prostatic abscess (EPA) is a rare condition characterized by gas and abscess accumulation in the prostate. In this case report we report a successfully treated EPA with liver abscess due to Klebsiella pneumoniae in a 49-year-old man. He was admitted with abdominal pain and fever. Physical examination revealed tender, palpable resonance urinary bladder, and prostatic tenderness on rectal digital examination. High inflammatory markers were found. Abdominal computer tomography (CT) confirmed EPA. The patient was treated with broad-spectrum antibiotics, strict blood glucose control, suprapubic catheterization, and transurethral deroofing of the prostatic abscess. After three weeks patient discharged in good condition.

Background: The "neutral" thyrotropin receptor autoantibodies (N-TSHR-Ab) directed at the TSHR ectodomain's hinge region have been shown to induce thyroid cell damage in vitro . During these earlier studies, we developed a mouse monoclonal antibody (MC1) specific for a peptide (amino acid 322-340) in the region (MC1-Mab) which was able to induce thyroid cell stress and apoptosis when administered in vivo . Methods: In order to examine the effect of in vivo generated N-TSHR-Abs, rather than an acutely administered monoclonal antibody, we immunized Balb/c mice with the hinge region peptide over 18 weeks. Serum TSHR antibodies, specific TSHR hinge region antibodies, serum thyroglobulin (TG) and anti-TG as well as thyroxine and thyrotropin (TSH) levels were examined to evaluate the response to the immunization. Histological examination of the thyroid glands and flow cytometry of spleen T cells, B cells and macrophages were also performed to explore the underlying mechanisms. Results: We found that TSHR-peptide immunized mice developed N-TSHR-Abs against the peptide which resulted in thyroid damage shown by thyroid follicular destruction with follicular cell apoptosis, M1 macrophage infiltration, thyroglobulin release, and induction of thyroglobulin antibodies. This resulted in hypothyroidism with increased TSH levels. Conclusion: This study demonstrated that endogenous neutral antibodies to the TSHR could induce thyroid cell damage from apoptosis and M1 macrophage infiltration and resulted in hypothyroidism.

This research has evaluated the MPs distribution, characteristics, and potential threats of MPs in surface water and sediments from Hatiya Island. The results showed that the abundance of MPs was 139 ± 44 items/m 3 in surface water and 493 ± 80 items/kg dw in sediments, indicating higher levels of MPs contamination in sediment samples. Fibers were the predominant kind of microplastics, and microscopic sizes (0.3-1.5 mm) MPs were generally more frequent and largely present in both the surface water and sediments. Fourier-transform infrared spectroscopy (FTIR) confirmed that polyethylene terephthalate was the major polymer component of microplastics in surface water, whereas polyethylene was the most abundant polymer in sediments. MPs contamination risk was examined based on multiple risk assessment models. Nemerow pollution index (NPI) and pollutant load index (PLI) show minimal pollution levels of MPs. But potential hazard index (PHI), potential ecological risk factor (Er), and potential ecological risk index (RI), indicate severe MPs contamination due to the presence of polyurethane, polycarbonate, polyvinyl chloride, epoxy that were hazardous MPs and exhibited a critical concern for MPs risk. These statistics will help to understand the environmental difficulties generated by MPs and which hazard is waiting for mankind in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The thyroid eye disease (TED) of Graves disease is associated with high titers of stimulating TSH receptor antibodies, retro-orbital inflammation, fibroblast release of cytokines and chemokines, and adipogenesis, which in turn leads to proptosis, muscle fibrosis, and dysfunction. Part of this scenario is the induction of fibroblast proliferation and autophagy secondary to synergism between the TSH receptor (TSHR) and the insulin-like growth factor-1 receptor (IGF-1R). While TED is well associated with thyroid-stimulating antibodies to the TSHR, which is also well expressed on fibroblasts, in fact the TSHR reactome has a variety of TSHR antibodies with varying biological activity. Therefore, we have now evaluated the possible role of neutral TSHR antibodies (N-TSHR-mAbs), directed at the hinge region of the TSHR, which do not induce cell proliferation but are known to have effects on multiple proteins in thyroid cells including stress-related signaling molecules. We examined the consequences of an N-TSHR-mAb acting on TSHR-expressing fibroblasts and found marked cell stress, which initiated signaling pathways involving inflammasome activation. This response ended in widespread cell death by pyroptosis through activation of caspase 8 and gasdermin D. Hence, not only can stimulating TSHR autoantibodies influence TED inflammation but the N-TSHR antibodies, representing more of the reactome, may also exaggerate the retro-orbital inflammatory response seen in TED., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

Background Context: There are a number of risk factors- from biological, psychological, and social domains- for non-specific chronic low back pain (cLBP). Many cLBP treatments target risk factors on the assumption that the targeted factor is not just associated with cLBP but is also a cause (i.e, a causal risk factor). In most cases this is a strong assumption, primarily due to the possibility of confounding variables. False assumptions about the causal relationships between risk factors and cLBP likely contribute to the generally marginal results from cLBP treatments., Purpose: The objectives of this study were to a) using rigorous confounding control compare associations between modifiable causal risk factors identified by Mendelian randomization (MR) studies with associations in a cLBP population and b) estimate the association of these risk factors with cLBP outcomes., Study Design/setting: Cross sectional analysis of a longitudinal, online, observational study., Patient Sample: 1,376 participants in BACKHOME, a longitudinal observational e-Cohort of U.S. adults with cLBP that is part of the NIH Back Pain Consortium (BACPAC) Research Program., Outcome Measures: Pain, Enjoyment of Life, and General Activity (PEG) Scale., Methods: Five risk factors were selected based on evidence from MR randomization studies: sleep disturbance, depression, BMI, alcohol use, and smoking status. Confounders were identified using the ESC-DAG approach, a rigorous method for building directed acyclic graphs based on causal criteria. Strong evidence for confounding was found for age, female sex, education, relationship status, financial strain, anxiety, fear avoidance and catastrophizing. These variables were used to determine the adjustment sets for the primary analysis. Potential confounders with weaker evidence were used for a sensitivity analysis., Results: Participants had the following characteristics: age 54.9 ± 14.4 years, 67.4% female, 60% never smokers, 29.9% overweight, 39.5% obese, PROMIS sleep disturbance T-score 54.8 ± 8.0, PROMIS depression T-score 52.6 ± 10.1, Fear-avoidance Beliefs Questionnaire 11.6 ± 5.9, Patient Catastrophizing Scale 4.5 ± 2.6, PEG 4.4 ± 2.2. In the adjusted models alcohol use, sleep disturbance, depression, and obesity were associated with PEG, after adjusting for confounding variables identified via a DAG constructed using a rigorous protocol. The adjusted effect estimates- the expected change in the PEG outcome for every standard deviation increase or decrease in the exposure (or category shift for categorical exposures) were the largest for sleep disturbance and obesity. Each SD increase in the PROMIS sleep disturbance T-score resulted in a mean 0.77 (95% CI: 0.66, 0.88) point increase in baseline PEG score. Compared to participants with normal BMI, adjusted mean PEG score was slightly higher by 0.37 points (95% CI: 0.09, 0.65) for overweight participants, about 0.8 to 0.9 points higher for those in obesity classes I and II, and 1.39 (95% CI: 0.98, 1.80) points higher for the most obese participants. Each SD increase in the PROMIS depression T-score was associated with a mean 0.28 (95% CI: 0.17, 0.40) point increase in baseline PEG score, while each SD decrease in number of alcoholic drinks per week resulted in a mean 0.12 (95%CI: 0.01, 0.23) increase in baseline PEG score in the adjusted model., Conclusions: Several modifiable causal risk factors for cLBP - alcohol use, sleep disturbance, depression, and obesity- are associated with PEG, after adjusting for confounding variables identified via a DAG constructed using a rigorous protocol. Convergence of our findings for sleep disturbance, depression, and obesity with the results from MR studies, which have different designs and biases, strengthens the evidence for causal relationships between these risk factors and cLBP (1). The estimated effect of change in a risk factors on change in PEG were the largest for sleep disturbance and obesity. Future analyses will evaluate these relationships with longitudinal data.

Forty-two percent of women who experienced intimate partner violence (IPV) reported that their experience of IPV resulted in an injury. This review aims to review the existing literature from low- and middle-income countries (LMICs) on IPV-related injuries as well as identify IPV-related injury patterns and locations. A systematic electronic database search was conducted between August and September 2021 (Prospero ID: CRD42021281519). Five databases yielded 408 articles; 328 remained for title and abstract screening after duplicates were removed. Of the 59 eligible for full-text review, 19 articles were eligible for extraction. After quality assessment, 18 articles were included in the study. Most (56%) studies were observational studies. Studies represented 15 different countries. The majority of the studies (89%) had authors whose institutional affiliation was located in the country where the study took place. Soft tissue injuries were the most commonly reported injury type followed by fractures and burns. The most common injury locations were the head, neck, and face followed by both upper and lower limbs. The most commonly cited injury mechanism was bodily force. The findings of this study echo what has been written in the literature regarding IPV-related injury patterns from high-income countries (HICs). One limitation of this study is that the search only included literature published in English. The injury patterns identified in this article confirm the need for awareness and action on the part of both medical and surgical providers in order to best address IPV in LMICs., (© 2024 Springer Publishing Company, LLC.)

Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest form is provided with the online version of the article (http://links.lww.com/JBJS/I28).

Objectives: Open tibia fractures are associated with substantial morbidity and impact on quality of life. Despite increasing incidence in low-resource settings, most open tibia fracture research comes from high-resource settings. This study aimed to assess the impact of socioeconomic status on treatment modality and evaluate predictors of health-related quality of life following open tibia fractures in Ghana., Design: A single-center prospective observational study was conducted in Kumasi, Ghana, from May 2020 to April 2022. Adults with open tibial shaft fractures presenting within 2 weeks of injury were eligible. Demographics, comorbidities, socioeconomic factors, and hospital course were collected at enrollment. Follow-up was scheduled at 8, 12, 26, and 52 weeks. A telephone survey assessing reasons for loss to follow-up was initiated on enrollment completion., Results: A total of 180 patients were enrolled. Most patients were employed before injury (79.9%), had government insurance (67.2%), and were from rural areas (59.4%). Fracture classification was primarily Gustilo-Anderson type 3A (49.1%). No relationship between socioeconomic predictors and treatment modality was identified. The largest barriers to follow-up were preference for bonesetter treatment (63.1%), treatment cost (48.8%), and travel cost (29.8%). Of the lost to follow-up patients contacted, 67 (79.8%) reported receiving traditional bonesetter care. Reasons for seeking traditional bonesetter care included ease of access (83.6%), lower cost (77.6%), and familial influence (50.7%)., Conclusion: No association was identified between socioeconomic predictors and choice of treatment. Bonesetter treatment plays a substantial role in the care of open tibia fractures in Ghana, largely because of ease of access and lower cost., Competing Interests: The authors have no conflict of interest to report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Fracture-related infection is a major complication related to musculoskeletal injuries that not only has important clinical consequences, but also a substantial socioeconomic impact. Although fracture-related infection is one of the oldest disease entities known to mankind, it has only recently been defined and, therefore, its global burden is still largely unknown. In this Personal View, we describe the origin of the term fracture-related infection, present the available data on its global impact, and discuss important aspects regarding its prevention and management that could lead to improved outcomes in both high-resource and low-resource settings. We also highlight the need for health-care systems to be adequately compensated for the high cost of human resources (trained staff) and well-equipped facilities required to adequately care for these complex patients. Our aim is to increase awareness among clinicians and policy makers that fracture-related infection is a disease entity that deserves prioritisation in terms of research, with the goal to standardise treatment and improve patient outcomes on a global scale., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abstract: Traumatic and nontraumatic orthopaedic conditions are major contributors to global morbidity and account for the majority of life-years lived with disability worldwide. Additionally, the burden of musculoskeletal injuries has increased substantially over the past 3 decades. Unfortunately, in low and middle-income countries (LMICs), access to orthopaedic care is limited, leading to a disproportionate burden of disease. The Lancet Commission on Global Surgery has emphasized the urgent need for unified international commitment and research collaboration to achieve universal access to safe and affordable surgical care. However, conducting high-quality orthopaedic research in LMICs remains challenging as a result of disparities in training, access to resources, infrastructure, and equipment availability. Partnerships between high-income countries (HICs) and LMICs have emerged in recent decades as an effective approach to combatting some of these challenges. These partnerships aim to bridge the gaps by facilitating collaborative research and knowledge exchange. The establishment of successful partnerships requires a collaborative and reciprocal approach that starts with a clear understanding of mutual research aims and the availability of resources. Despite the potential benefits, various factors can make establishing such partnerships difficult. However, these partnerships can have a substantial impact in delivering quality orthopaedic education and research training, thus improving access to care in resource-limited environments. This paper represents the collaborative effort of multiple international academic orthopaedic surgeons with extensive experience in HIC-LMIC partnerships. Our aims were to outline the best practices for conducting orthopaedic research within these relationships and to provide guidance for future successful collaborations., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H723 )., (Copyright © 2023 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Advanced chemical recycling techniques provide new avenues for handling and recycling mixed plastic waste; pyrolysis is a prominent approach involving heating plastic waste in an oxygen-free environment to create pyrolysis oils. Pyrolysis oils must be thoroughly characterized before being refined into fuels and chemical feedstocks. Here, a method based on supercritical fluid chromatography with ultraviolet detection was developed to analyze plastic waste pyrolysis oils. Multiple stationary phases were examined, and 2-ethyl pyridine was chosen as the best stationary phase for resolving pyrolysis oil components. Different standards and different plastic waste pyrolysis oils were compared across the different stationary phases. Up to three columns were serially coupled to increase efficiency and column capacity. It was found that a general method using ethanol as a modifier and two 2-ethyl pyridine columns could effectively resolve plastic waste pyrolysis oils. The potential for differentiating polyethylene and polypropylene feedstocks was demonstrated using principal component analysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jean-Francois Borny reports financial support was provided by The Lummus Technology, LLC. Jean-Francois Borny reports a relationship with Lummus Technology LLC that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: There is high burden of long bone fractures in low- and middle-income countries (LMICs). Given a limited availability of fluoroscopy in LMICs, the Surgical Implant Generation Network (SIGN) developed two types of intramedullary nails: the SIGN standard nail and the SIGN Fin Nail. A limited number of studies have analyzed healing outcomes with the SIGN Fin Nail and the current study is the largest one to date. The purpose of this study is to compare outcomes between the SIGN standard nail and SIGN Fin Nails in adult femoral shaft fractures treated with a retrograde approach., Method: A retrospective cohort study of adults with femoral shaft fractures was performed using the Sign Online Surgical Database (SOSD). The primary outcome was achieving full painless weight bearing and the secondary outcomes assessed were radiographic healing and infection. A propensity-score adjustment was performed for potential confounders and effect modification due to fracture location was tested using a Mantel-Haenszel test for heterogeneity., Results: Of 19,928 adults with femoral shaft fractures, 2,912 (14.7%) had the required 6-month follow-up to be included. The overall propensity score weighted relative risk between the Fin and Standard Nail for achieving painless weight-bearing was 0.99, 95% CI [0.96-1.03] and for radiographical healing was 0.99, 95%CI [0.97-1.02]. The propensity score weighted relative risk for infection was 1.30, 95% [0.85-1.97]. Use of the Fin nail was also significantly associated with shorter surgery times (p < 0.005, effect size = 24 min). Sub-group analysis based on fracture location and injury cause demonstrated no change in relative risk., Conclusion: The Fin nail showed no change in relative risk in terms of achieving full painless weightbearing or radiographic healing compared to the standard nail for retrograde nailing of femoral shaft fractures in adults. The heterogeneous nature of the cohort and large sample size allow for generalizability and add to a growing base of literature supporting use of the Fin Nail for retrograde femoral nailing. However, there are limitations as we could not correct for comminution at the fracture site or measure radiographic alignment or shortening., Competing Interests: No conflicts of interest to disclose. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Orthopaedic trauma remains a leading cause of patient morbidity, mortality, and global health care burden. Although significant advances have been made in the diagnosis, treatment, and rehabilitation of these injuries, complications such as malunion, nonunion, infection, disuse muscle atrophy and osteopenia, and incomplete return to baseline function still occur. The significant inherent clinical variability in fracture care such as differing patient demographics, injury patterns, and treatment protocols make standardized and replicable study, especially of cellular and molecular based mechanisms, nearly impossible. Hence, the scientists dedicated to improving therapy and treatments for patients with orthopaedic trauma rely on preclinical models. Preclinical models have proven to be invaluable in understanding the timing between implant insertion and bacterial inoculation on the bioburden of infection. Posttraumatic arthritis (PTOA) can take years to develop clinically, but with a porcine pilon fracture model, posttraumatic arthritis can be reliably induced, so different surgical and therapeutic strategies can be tested in prevention. Conversely, the racehorse presents a well-accepted model of naturally occurring PTOA. With preclinical polytrauma models focusing on chest injury, abdominal injury, multiple fractures, and/or head injury, one can study how various injury patterns affect fracture healing can be systemically studied. Finally, these preclinical models serve as a translational bridge to for clinical application in human patients. With selection of the right preclinical model, studies can build a platform to decrease the risk of emerging technologies and provide foundational support for therapeutic clinical trials. In summary, orthopaedic trauma preclinical models allow scientists to simplify a complex clinical challenge, to understand the basic pathways starting with lower vertebrate models. Then, R&D efforts progress to higher vertebrate models to build in more complexity for translation of findings to the clinical practice., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Introduction: Fracture-related infections (FRIs) are a major cause of trauma-associated morbidity worldwide. In 2018, an expert group supported by the AO Foundation, European Bone and Joint Infection Society developed a consensus definition of FRI. Still, there is limited knowledge on the applicability of this definition in low- and middle-income countries (LMICs). Given the unique barriers that cause low follow-up rates for orthopaedic trauma patients in LMICs, this study aims to evaluate the diagnostic performance of a telephone questionnaire in identifying patients with FRIs after open tibia fracture fixation in Tanzania., Materials and Methods: Patients from a randomized controlled trial investigating the infection prevention benefit of locally applied gentamycin for open tibial fractures were included. Patients completed FRI based telephone questionnaires 7-10 days prior to scheduled follow-ups at 6 weeks, 3 months, 6 months, 9 months, and 1 year. The questionnaire included two "confirmatory" criteria questions for FRI (i.e., open wound and purulent drainage) and three "suggestive" criteria questions (i.e., wound drainage, fever, and warmth). Contingency tests were performed to identify the sensitivity and specificity between answers and adjudicated FRI diagnoses at the corresponding in-person follow-up. Data was analysed using STATA version 15.0 and MedCalc's online diagnostic test calculator., Results: There were a total of 234 complete questionnaires and 85 unique patients included. The sensitivity and specificity of having any positive answer in the questionnaire was highest at 6 months (100 % and 92.5 %, respectively). For all time-points pooled, sensitivity was 71.4 % and specificity was 93.0 %. Drainage had the highest sensitivity (71.4 %) while fever had the highest specificity (99.6 %). For confirmatory criteria, sensitivity was 14.3 % and specificity was 96.0 %. Contrastingly, the sensitivity for suggestive criteria was higher (71.4 %), with a similar specificity (93.8 %)., Conclusion: Our study indicates that telephone questionnaires have adequate diagnostic performance when assessing FRIs. The presence of drainage identified the majority of patients with FRI, and specificities were high across confirmatory and suggestive criteria. Our study is one of the first to evaluate telephone questionnaires as a diagnostic tool for FRIs in patients with open tibia fractures in a LMIC hospital and validates the FRI consensus definition criteria., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To estimate the indirect economic impact of tibial fractures and their associated adverse events (AEs) in Tanzania., Design: A secondary analysis of the pilot Gentamicin Open (pGO)-Tibia randomized control trial estimating the indirect economic impact of suffering an AE, defined as a fracture-related infection (FRI) and/or nonunion, after an open tibial fracture in Tanzania., Setting: The pGO-Tibia trial was conducted from November 2019 to August 2021 at the Muhimbili Orthopaedic Institute in Dar es Salaam, Tanzania., Patients/participants: One hundred adults with open tibial shaft fractures participated in this study., Intervention: Work hours were compared between AE groups. Cost data were analyzed using a weighted-average hourly wage and converted into purchasing power parity-adjusted USD., Main Outcome Measurements: Indirect economic impact was analyzed from the perspective of return to work (RTW), lost productivity, and other indirect economic and household costs. RTW was analyzed using a survival analysis., Results: Half of patients returned to work at 1-year follow-up, with those experiencing an AE having a significantly lower rate of RTW. Lost productivity was nearly double for those experiencing an AE. There was a significant difference in the mean outside health care costs between groups. The total mean indirect cost was $2385 with an AE, representing 92% of mean annual income and an increase of $1195 compared with no AE. There were significantly more patients with an AE who endorsed difficulty affording household expenses postinjury and who borrowed money to pay for their medical expenses., Conclusions: This study identified serious economic burden after tibial fractures, with significant differences in total indirect cost between those with and without an AE., Level of Evidence: II., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Background: Infection remains a costly, devastating complication following the treatment of open fractures. The appropriate timing of debridement is controversial, and available evidence has been conflicting., Methods: This study is a retrospective analysis of the SIGN (Surgical Implant Generation Network) Surgical Database (SSDB), a prospective registry of fracture cases in predominantly low-resource settings. Skeletally mature patients (≥16 years of age) who returned for follow-up at any time point after intramedullary nailing of an open femoral or tibial fracture were included. Patients were excluded if they had delays in debridement exceeding 7 days after the injury. Utilizing a model adjusting for potential confounders, including patient demographic characteristics, injury characteristics, country income level, and hospital type and resources, local logistic regression analysis was performed to evaluate the probability of infection with increasing time to debridement in 6-hour increments., Results: In this study, 27.3% of patients met the eligibility criteria and returned for follow-up, with a total of 10,651 fractures from 61 countries included. Overall, the probability of infection increased by 0.17% for every 6-hour delay in debridement. On subgroup analysis, the probability of infection increased by 0.23% every 6 hours for Gustilo-Anderson type-III injuries compared with 0.13% for Gustilo-Anderson type-I or II injuries. The infection risk increased every 6 hours by 0.18% for tibial fractures compared with 0.13% for femoral fractures., Conclusions: There was a linear and cumulative increased risk of infection with delays in debridement for open femoral and tibial fractures. Such injuries should be debrided promptly and expeditiously. The size and international nature of this cohort make these findings uniquely generalizable to nearly all environments where such injuries are treated., Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H654 )., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

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., Competing Interests: Declaration of Competing Interest This work was not supported by any funding. The authors do not have any relevant disclosures to the scope of this work., (Copyright © 2023. Published by Elsevier Ltd.)

Effective nonunion and bone defect management requires consideration of multiple potential contributing factors including biomechanics, biology, metabolic, and patient factors. This article reviews these factors as well as several potential nonunion or bone defect treatments including bone grafts, bone graft substitutes, the induced membrane technique, and distraction osteogenesis. A summary of these concepts and guidelines for an overall approach to management are also provided., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Background: The rate of open tibia fractures is rapidly increasing across the globe due to a recent rise in road traffic accidents, predominantly in low- and low-middle-income countries. These injuries are orthopedic emergencies associated with infection rates as high as 40% despite the use of systemic antibiotics and surgical debridement. The use of local antibiotics has shown some promise in reducing the burden of infection in these injuries due to increasing local tissue availability; however, no trial has yet been appropriately powered to evaluate for definitive evidence and the majority of current studies have taken place in a high-resource countries where resources and the bio-burden may be different., Methods: This is a prospective randomized, masked, placebo-controlled superiority trial designed to evaluate the efficacy of locally administered gentamicin versus placebo in the prevention of fracture-related infection in adults (age > 18 years) with primarily closeable Gustillo-Anderson class I, II, and IIIA open tibia fractures. Eight hundred ninety patients will be randomized to receive an injection of either gentamicin (treatment group) or saline (control group) at the site of their primarily closed open fracture. The primary outcome will be the occurrence of a fracture-related infection occurring during the course of the 12-month follow-up., Discussion: This study will definitively assess the effectiveness of local gentamicin for the prevention of fracture-related infections in adults with open tibia fractures in Tanzania. The results of this study have the potential to demonstrate a low-cost, widely available intervention for the reduction of infection in open tibia fractures., Trial Registration: Clinicaltrials.gov NCT05157126. Registered on December 14, 2021., (© 2023. The Author(s).)

Randomized controlled trials are the gold standard to establishing causal relationships in clinical research. However, these studies are expensive and time consuming to conduct. This article aims to provide orthopaedic surgeons and clinical researchers with methodology to optimize inference and minimize bias in observational studies that are often much more feasible to undertake. To mitigate the risk of bias arising from their nonexperimental design, researchers must first understand the ways in which measured covariates can influence treatment, outcomes, and missingness of follow-up data. With knowledge of these relationships, researchers can then build causal diagrams to best understand how to control sources of bias. Some common techniques for controlling for bias include matching, regression, stratification, and propensity score analysis. Selection bias may result from loss to follow-up and missing data. Strategies such as multiple imputation and time-to-event analysis can be useful for handling missingness. For longitudinal data, repeated measures allow observational studies to best summarize the impact of the intervention over time. Clinical researchers familiar with fundamental concepts of causal inference and techniques reviewed in this article will have the power to improve the quality of inferences made from clinical research in orthopaedic trauma surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Background: Graves' disease is associated with TSH receptor (TSHR) antibodies of variable bioactivity including "neutral" antibodies (N-TSHR-Ab) that bind to the hinge region of the TSHR ectodomain. We have previously found that such antibodies induced thyroid cell apoptosis via excessive mitochondrial and ER stress with elevated reactive oxygen species (ROS). However, the detailed mechanisms by which excess ROS was induced remained unclear., Objectives: To determine how ROS is induced by N-TSHR-monoclonal antibodies (mAb, MC1) mediated signaling and to measure stress in polyorganelles., Methods: Total ROS and mitochondrial ROS was measured by fluorometry of live rat thyrocytes. Live-cell imaging of labelled organelles was carried out using red or green fluorescent dyes. Proteins were detected by Li-Cor Western immunoblots and immunocytochemistry., Results: Endocytosis of N-TSHR-mAb induced ROS, disturbed vesicular trafficking, damaged organelles and failed to induce lysosomal degradation and autophagy. We found that the endocytosis triggered signaling cascades involving Gα13 and PKC-δ leading to intrinsic thyroid cell apoptosis., Conclusions: These studies define the mechanism of ROS induction in thyroid cells following the endocytosis of N-TSHR-Ab/TSHR complexes. We suggest that a viscous cycle of stress initiated by cellular ROS and induced by N-TSHR-mAbs may orchestrate overt intra-thyroidal, retro-orbital, and intra-dermal inflammatory autoimmune reactions in patients with Graves' disease., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: The main 2 forms of treatment for extraarticular proximal tibial fractures are intramedullary nailing (IMN) and locked lateral plating (LLP). The goal of this multicenter, randomized controlled trial was to determine whether there are significant differences in outcomes between these forms of treatment., Design: Multicenter, randomized controlled trial., Setting: 16 academic trauma centers., Patients/participants: 108 patients were enrolled. 99 patients were followed for 12 months. 52 patients were randomized to IMN, and 47 patients were randomized to LLP., Intervention: IMN or lateral locked plating., Main Outcome Measurements: Functional scoring including Short Musculoskeletal Functional Assessment, Bother Index, EQ-5Dindex and EQ-5DVAS. Secondary measures included alignment, operative time, range of motion, union rate, pain, walking ability, ability to manage stairs, need for ambulatory aid and number, and complications., Results: Functional testing demonstrated no difference between the groups, but both groups were still significantly affected 12 months postinjury. Similarly, there was no difference in time of surgery, alignment, nonunion, pain, walking ability, ability to manage stairs, need for ambulatory support, or complications., Conclusions: Both IMN and LLP provide for similar outcomes after these fractures. Patients continue to improve over the course of the year after injury but remain impaired even 1 year later., Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Open tibial fractures have a high risk of infection that can lead to severe morbidity. Antibiotics administered locally at the site of the open wound are a potentially effective preventive measure, but there are limited data evaluating aminoglycoside antibiotics. The objective of this study was to assess the feasibility of a clinical trial to test the efficacy of local gentamicin in reducing the risk of fracture-related infection after open tibial fracture., Methods: This study is a single-center, pilot, masked, randomized controlled trial conducted at the Muhimbili Orthopaedic Institute. Participants were randomized intraoperatively after wound closure to receive gentamicin solution or normal saline solution injected at the fracture site. Follow-ups were completed at 2 weeks, 6 weeks, 3 months, 6 months, 9 months, and 1 year postoperatively. The primary feasibility outcomes were the rate of enrollment and retention. The primary clinical outcome was the occurrence of fracture-related infection., Results: Of 199 patients screened, 100 eligible patients were successfully enrolled and randomized over 9 months (11.1 patients/month). Complete data were recorded at baseline and follow-up for >95% of cases. The rate of follow-up at 6 weeks, 3 months, 6 months, 9 months, and 1 year were 70%, 68%, 69%, 61%, and 80%, respectively. There was no difference in adverse events or any of the measured primary and secondary outcomes., Conclusion: This pilot study is among the first to evaluate locally administered gentamicin in open tibial fractures. Results indicate a rigorous clinical trial with acceptable rates of enrollment and follow-up to address this topic is possible in this setting., Competing Interests: The authors have no conflicts of interest to disclose, (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Background: The burden of disability because of traumatic limb amputation, particularly transfemoral amputation (TFA) is disproportionately carried by low- and middle-income countries. The need for improved access to prosthesis services in these settings is well-documented, but perspectives on the burden imposed by TFA and the challenges associated with subsequent prosthesis provision vary among patients, caregivers and healthcare providers., Objectives: To examine the burden of TFA and barriers to prosthesis provision as perceived by patient, caregiver and healthcare professional, at a single tertiary referral hospital in Tanzania., Method: Data were collected from five patients with TFA and four caregivers recruited via convenience sampling, in addition to 11 purposively sampled healthcare providers. All participants participated in in-depth interviews regarding their perceptions of amputation, prostheses and underlying barriers to improving care for persons with TFA in Tanzania. A coding schema and thematic framework were established from interviews using inductive thematic analysis., Results: All participants noted financial and psychosocial burdens of amputation, and perceived prostheses as an opportunity for return to normality and independence. Patients worried about prosthesis longevity. Healthcare providers noted significant obstacles to prosthesis provision, including infrastructural and environmental barriers, limited access to prosthetic services, mismatched patient expectations and inadequate coordination of care., Conclusion: This qualitative analysis identifies factors influencing prosthesis-related care for patients with TFA in Tanzania which are lacking in the literature. Persons with TFA and their caregivers experience numerous hardships exacerbated by limited financial, social and institutional support., Contribution: This qualitative analysis informs future directions for research into improving prosthesis-related care for patients with TFA in Tanzania., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2023. The Authors.)

Introduction: An increasing number of fellowship-trained orthopaedic trauma surgeons are working in non-Level I centers. This study aimed to examine trends of management of complex orthopaedic trauma in Level I centers versus non-Level I centers and its potential effect on patient outcomes., Methods: Data from the National Trauma Data Bank from 2008 to 2017 were analyzed. Non-Level I to Level I center ratios for complex fractures and complication rates, median hours to procedure for time-sensitive fractures, and uninsured/underinsured rates of Level I and non-Level I centers were recorded., Results: Three hundred one thousand patients were included. A statistically significant downward trend was identified in the percent of all complex orthopaedic trauma at Level I centers and per-hospital likelihood of seeing a complex orthopaedic fracture in a Level I versus non-Level I hospital. Per-hospital complication rates were consistently lower in non-Level I hospitals after controlling for injury severity and payer mix. Time-sensitive fractures were treated earlier in non-Level I centers., Discussion: This study demonstrates a reduction of complex trauma treatment in Level I centers that did not translate to adverse effects on patient outcomes. Policymakers should notice this trend to ensure the continued quality of orthopaedic trauma training and maintenance of expertise in complex fracture management., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

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., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Chronic low back pain (cLBP) afflicts 8. 2% of adults in the United States, and is the leading global cause of disability. Neuropsychiatric co-morbidities including anxiety, depression, and substance abuse- are common in cLBP patients. In particular, cLBP is a risk factor for opioid addiction, as more than 50% of opioid prescriptions in the United States are for cLBP. Misuse of these prescriptions is a common precursor to addiction. While associations between cLBP and neuropsychiatric disorders are well established, causal relationships for the most part are unknown. Developing effective treatments for cLBP, and associated co-morbidities, requires identifying and understanding causal relationships. Rigorous methods for causal inference, a process for quantifying causal effects from observational data, have been developed over the past 30 years. In this review we first discuss the conceptual model of cLBP that current treatments are based on, and how gaps in causal knowledge contribute to poor clinical outcomes. We then present cLBP as a "Big Data" problem and identify how advanced analytic techniques may close knowledge gaps and improve clinical outcomes. We will focus on causal discovery, which is a data-driven method that uses artificial intelligence (AI) and high dimensional datasets to identify causal structures, discussing both constraint-based (PC and Fast Causal Inference) and score-based (Fast Greedy Equivalent Search) algorithms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huie, Vashisht, Galivanche, Hadjadj, Morshed, Butte, Ferguson and O'Neill.)

Prevention of fracture-related infection (FRI) remains a substantial challenge in orthopaedic trauma care. There is evolving evidence to support the use of local antibiotics for both the prevention and treatment of musculoskeletal infection. Local antibiotics can achieve higher local tissue concentrations with a lower risk of systemic complications compared to intravenously administered antibiotics. These antibiotics may be administered in powder or liquid form without carrier, or if sustained release is desired, using a carrier. Polymethylmethacrylate (PMMA), ceramics, and hydrogels are examples of antibiotic carriers. Unlike PMMA, ceramics and hydrogels have the advantage of not requiring a second surgery for removal. The VANCO trial supported the use of powdered vancomycin in high-risk fracture cases for the reduction of Gram-positive infections; although, data is limited. Future studies will evaluate the use of aminoglycoside antibiotics to address Gram-negative infection prevention. While theoretical concerns exist with the use of local antibiotics, available studies suggest local antibiotics are safe with a low-risk of adverse effects.

Background: While surgeons in low and middle-income countries have increasing experience with intramedullary nailing (IMN), external fixation (EF) continues to be commonly used for the management of open tibial fractures. We examined outcomes with extended follow-up of the participants enrolled in a clinical trial comparing these treatments., Methods: Adults who were ≥18 years old with acute AO/OTA type-42 open tibial shaft fractures were randomly assigned to statically locked, hand-reamed IMN or uniplanar EF. These participants were reevaluated 3 to 5 years after treatment. The primary outcome was death or reoperation for the treatment of deep infection, nonunion, or malalignment. Unresolved complications such as persistent fracture-related infection, nonunion, or malalignment were collected and analyzed. Secondary outcomes included the EuroQol-5 Dimension-3 Level (EQ-5D-3L) questionnaire, the Function IndeX for Trauma (FIX-IT) score, radiographic alignment, and the modified Radiographic Union Scale for Tibial fractures (mRUST)., Results: Of the originally enrolled 240 participants,126 (67 managed with IMN and 59 managed with EF) died or returned for follow-up at a mean of 4.0 years (range, 2.9 to 5.2 years). Thirty-two composite primary events occurred, with rates of 23.9% and 27.1% in the IMN and EF groups, respectively. Six of these events (3 in the IMN group and 3 in the EF group) were newly detected after the original 1-year follow-up. Unresolved complications in the form of chronic fracture-related infection or nonunion were present at long-term follow-up in 25% of the participants who sustained a primary event. The EQ-5D-3L index scores were similar between the 2 groups and only returned to preinjury levels after 1 year among patients without complications or those whose complications resolved., Conclusions: This observational study extended follow-up for a clinical trial assessing IMN versus EF for the treatment of open tibial fractures in sub-Saharan Africa. At a mean of 4 years after injury, fracture-related infection and nonunion became chronic conditions in nearly a quarter of the participants who experienced these complications, regardless of reintervention., Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H177 )., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Tibial plateau fractures with an ipsilateral compartment syndrome are a clinical challenge with limited guidance regarding the best time to perform open reduction and internal fixation (ORIF) relative to fasciotomy wound closure. This study aimed to determine if the risk of fracture-related infection (FRI) differs based on the timing of tibial plateau ORIF relative to closure of ipsilateral fasciotomy wounds., Methods: A retrospective cohort study identified patients with tibial plateau fractures and an ipsilateral compartment syndrome treated with 4-compartment fasciotomy at 22 US trauma centers from 2009 to 2019. The primary outcome measure was FRI requiring operative debridement after ORIF. The ORIF timing relative to fasciotomy closure was categorized as ORIF before, at the same time as, or after fasciotomy closure. Bayesian hierarchical regression models with a neutral prior were used to determine the association between timing of ORIF and infection. The posterior probability of treatment benefit for ORIF was also determined for the three timings of ORIF relative to fasciotomy closure., Results: Of the 729 patients who underwent ORIF of their tibial plateau fracture, 143 (19.6%) subsequently developed a FRI requiring operative treatment. Patients sustaining infections were: 21.0% of those with ORIF before (43 of 205), 15.9% at the same time as (37 of 232), and 21.6% after fasciotomy wound closure (63 of 292). ORIF at the same time as fasciotomy closure demonstrated a 91% probability of being superior to before closure (RR, 0.75; 95% CrI, 0.38 to 1.10). ORIF after fasciotomy closure had a lower likelihood (45%) of a superior outcome than before closure (RR, 1.02; 95% CrI; 0.64 to 1.39)., Conclusion: Data from this multicenter cohort confirms previous reports of a high FRI risk in patients with a tibial plateau fracture and ipsilateral compartment syndrome. Our results suggest that ORIF at the time of fasciotomy closure has the highest probability of treatment benefit, but that infection was common with all three timings of ORIF in this difficult clinical situation., Competing Interests: Declaration of Competing Interests None., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Limb loss leads to significant disability. Prostheses may mitigate this disability but are not readily accessible in low- and middle-income countries (LMICs). Cost-effectiveness data related to prosthesis provision in resource-constrained environments such as Tanzania is greatly limited., Objectives: This study aimed to compare the cost-effectiveness of a prosthesis intervention compared with that of no prosthesis for persons with transfemoral amputations in an LMIC., Study Design: This is a prospective cohort study., Methods: Thirty-eight patients were prospectively followed up. Clinical improvement with prosthesis provision was measured using EuroQuol-5D, represented as quality-adjusted life years gained. Direct and indirect costs were measured. The primary outcome was incremental cost per quality-adjusted life year, measured at 1 year and projected over a lifetime using a Markov model. Reference case was set as a single prosthesis provided without replacement from a payer perspective. Additional scenarios included the societal perspective and replacement of the prosthesis. Uncertainty was measured with one-way probabilistic sensitivity analysis., Results: From the payer perspective, the incremental cost-effectiveness ratio (ICER) was $242 for those without prosthetic replacement over a lifetime, and the ICER was $390 for those with prosthetic replacement over a lifeime. From the societal perspective, prosthesis provision was both less expensive and more effective. One-way sensitivity analysis demonstrated the ICER remained below the willingness to pay threshold up to prosthesis costs of $763., Conclusions: These findings suggest prosthesis provision in an LMIC may be cost-effective, but further studies with long-term follow up are needed to validate the results., (Copyright © 2022 International Society for Prosthetics and Orthotics.)

Background: International orthopaedic resident rotations in low and middle-income countries (LMICs) are gaining popularity among high-income country (HIC) residency programs. While evidence demonstrates a benefit for the visiting residents, few studies have evaluated the impact of such rotations on the orthopaedic surgeons and trainees in LMICs. The purpose of this study was to further explore themes identified in a previous survey study regarding the local impact of visiting HIC resident rotations., Methods: Using a semistructured interview guide, LMIC surgeons and trainees who had hosted HIC orthopaedic residents within the previous 10 years were interviewed until thematic saturation was reached., Results: Twenty attending and resident orthopaedic surgeons from 8 LMICs were interviewed. Positive and negative effects of the visiting residents on clinical care, education, interpersonal relationships, and resource availability were identified. Seven recommendations for visiting resident rotations were highlighted, including a 1 to 2-month rotation length; visiting residents at the senior training level; site-specific prerotation orientation with an emphasis on resident attitudes, including the need for humility; creation of bidirectional opportunities; partnering with institutions with local training programs; and fostering mutually beneficial sustained relationships., Conclusions: This study explores the perspectives of those who host visiting residents, a viewpoint that is underrepresented in the literature. Future research regarding HIC orthopaedic resident rotations in LMICs should include the perspectives of local surgeons and trainees to strive for mutually beneficial experiences to further strengthen and sustain such academic partnerships., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H127 )., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Purpose: Heterotopic ossification (HO) is a process by which bone forms abnormally in soft tissues. Known risk factors for developing HO include male sex, spinal cord injury, trauma, and surgery. We investigated additional risk factors in the development of HO after hip arthroplasty., Methods: We performed a retrospective review of electronic medical records of 4070 individuals who underwent hip arthroplasty from September 2010 to October 2019 at the University of California, San Francisco Hospital. Demographics, anthropometrics, medications, and comorbid conditions were used in logistic regression analysis to identify factors associated with the development of HO., Results: A total of 2541 patients underwent primary hip arthroplasty in the analyzed timeframe (46.04% men, mean age at procedure: 62.13 ± 13.29 years). The incidence of postsurgical HO was 3% (n = 80). A larger proportion of individuals who developed HO had underlying osteoporosis (P < 0.001), vitamin D deficiency (P < 0.001), spine disease (P < 0.001), type 1 or 2 diabetes (P < 0.001), amenorrhea (P = 0.037), postmenopausal status (P < 0.001), parathyroid disorders (P = 0.011), and history of pathologic fracture (P = 0.005). Significant predictors for HO development were Black/African American race [odds ratio (OR) 2.97, P = 0.005], preexisting osteoporosis (OR 2.72, P = 0.001), spine disease (OR 2.04, P = 0.036), and low estrogen states (OR 1.99, P = 0.025). In the overall group, 75.64% received perioperative nonsteroidal anti-inflammatory drugs (NSAIDs), which negatively correlated with HO formation (OR 0.39, P = 0.001)., Conclusions: We identified new factors potentially associated with an increased risk of developing HO after primary hip arthroplasty, including African American race, osteoporosis, and low estrogen states. These patients may benefit from HO prophylaxis, such as perioperative NSAIDs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Objectives: To quantify the total hospital costs associated with the treatment of lower extremity long-bone fracture aseptic and septic unhealed fracture, to determine if insurance adequately covers these costs, and to examine whether insurance type correlates with barriers to accessing care., Design: Retrospective cohort study., Setting: Academic Level II trauma center., Patients: All patients undergoing operative treatment of OTA/AO classification 31, 32, 33, 41, 42, and 43 fractures between 2012 and 2020 at a single Level II trauma center with minimum of 1-year follow-up., Main Outcome Measures: The primary outcome was the total cost of treatment for all hospital-based episodes of care. Distance traveled from primary residence was measured as a surrogate for barriers to care., Results: One hundred seventeen patients with uncomplicated fracture healing, 82 with aseptic unhealed fracture, and 44 with septic unhealed fracture were included in the final cohort. The median cost of treatment for treatment of septic unhealed fracture was $148,318 [interquartile range(IQR) 87,241-256,928], $45,230 (IQR 31,510-68,030) for treatment of aseptic unhealed fracture, and $33,991 (IQR 25,609-54,590) for uncomplicated fracture healing. The hospital made a profit on all patients with commercial insurance, but lost money on all patients with public insurance. Among patients with unhealed fracture, those with public insurance traveled 4 times further for their care compared with patients with commercial insurance (P = 0.004)., Conclusions: Septic unhealed fracture of lower extremity long-bone fractures is an outsized burden on the health care system. Public insurance for both septic and aseptic unhealed fracture does not cover hospital costs. The increased distances traveled by our Medi-Cal and Medicare population may reflect the economic disincentive for local hospitals to care for publicly insured patients with unhealed fractures., Level of Evidence: Economic Level V. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, and patent/licensing arrangements) that might pose a conflict of interest in connection with the submitted article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Spinal cord injuries (SCIs) frequently occur in combination with other major organ injuries, such as traumatic brain injury (TBI) and injuries to the chest, abdomen, and musculoskeletal system (e.g., extremity, pelvic, and spine fractures). However, the effects of appendicular fractures on SCI recovery are poorly understood. We investigated whether the presence of SCI-concurrent appendicular fractures is predictive of a less robust SCI recovery. Patients enrolled in the Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) prospective cohort study were identified and included in this secondary analysis study. Inclusion criteria resulted in 147 patients, consisting of 120 with isolated SCIs and 27 with concomitant appendicular fracture. The primary outcome was American Spinal Injury Association (ASIA) Impairment Scale (AIS) neurological grades at hospital discharge. Secondary outcomes included hospital length of stay, intensive care unit (ICU) length of stay, and AIS grade improvement during hospitalization. Multivariable binomial logistical regression analyses assessed whether SCI-concomitant appendicular fractures associate with SCI function and secondary outcomes. These analyses were adjusted for age, gender, injury severity, and non-fracture polytrauma. Appendicular fractures were associated with more severe AIS grades at hospital discharge, though covariate adjustments diminished statistical significance of this effect. Notably, non-fracture injuries to the chest and abdomen were influential covariates. Secondary analyses suggested that appendicular fractures also increased hospital length of stay. Our study indicated that SCI-associated polytrauma is important for predicting SCI functional outcomes. Further statistical evaluation is required to disentangle the effects of appendicular fractures, non-fracture solid organ injury, and SCI physiology to improve health outcomes among SCI patients.

Objectives: To compare outcomes in patients with open tibia shaft fractures based on defect size., Design: Retrospective review., Setting: Eighteen trauma centers., Population: The study included 132 patients with diaphyseal tibia bone defects >1 cm and ≥50% cortical loss treated with intramedullary nail., Outcomes: The primary outcome was number of secondary surgeries to promote healing (bone graft, revision fixation, or bone transport). Additional outcomes included occurrence of secondary surgeries (bone graft, infection, amputation, and flap failure) and proportion healed at one year. Results are compared by "radiographic apparent bone gap" of <2.5 or ≥2.5 cm., Results: The estimated conditional probability of bone grafting within one year given graft-free at 90 days was 44% and 47% in the <2.5 cm and ≥2.5 cm groups, respectively. An estimated infection risk of 14% was observed in both groups [adjusted hazard ratio (HR) 0.98, 95% confidence interval (CI): 0.33-2.92], estimated amputation risk was 9% (<2.5 cm) and 4% (≥2.5 cm) (unadjusted HR 0.66, 95% CI: 0.13-3.29), and estimated flap failure risk (among those with flaps) was 10% and 13%, respectively (unadjusted HR 1.71, 95% CI: 0.24-12.25). There was no appreciable difference in the proportion healed at one year between defect sizes [adjusted HR: 1.07 (95% CI, 0.63-1.82)]., Conclusions: Larger size bone defects were not associated with higher number of secondary procedures to promote healing or a lower overall one-year healing rate., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: P. Tornetta III, MD, has reported intellectual property with Smith + Nephew. J. R. Hsu, MD, has reported consulting relationships with Smith + Nephew, Stryker, and Globus Medical. The remaining authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Disparities exist in treatment modalities, including arthroscopic surgery, for orthopaedic injuries between high-income countries (HICs) and low- and middle-income countries (LMICs). Arthroscopy training is a self-identified goal of LMIC surgeons to meet the burden of musculoskeletal injury. The aim of this study was to determine the necessary "key ingredients" for establishing arthroscopy centers in LMICs in order to build capacity and expand training in arthroscopy in lower-resource settings., Methods: This study utilized semi-structured interviews with orthopaedic surgeons from both HICs and LMICs who had prior experience establishing arthroscopy efforts in LMICs. Participants were recruited via referral sampling. Interviews were qualitatively analyzed in duplicate via a coding schema based on repeated themes from preliminary interview review. Subgroup analysis was conducted between HIC and LMIC respondents., Results: We identified perspectives shared between HIC and LMIC stakeholders and perspectives unique to 1 group. Both groups were motivated by opportunities to improve patients' lives; the LMIC respondents were also motivated by access to skills and equipment, and the HIC respondents were motivated by teaching opportunities. Key ingredients identified by both groups included an emphasis on teaching and the need for high-cost equipment, such as arthroscopy towers. The LMIC respondents reported single-use materials as a key ingredient, while the HIC respondents reported local champions as crucial. The LMIC respondents cited the scarcity of implants and shaver blades as a barrier to the continuity of arthroscopy efforts., Conclusions: Incorporation of the identified key ingredients, along with leveraging the motivations of the host and the visiting participant, will allow future international arthroscopy partnerships to better match proposed interventions with the host-identified needs., Clinical Relevance: Arthroscopy is an important tool for treatment of musculoskeletal injury. Increasing access to arthroscopy is an important goal to achieve greater equity in musculoskeletal care globally. Developing successful partnerships between HICs and LMICs to support arthroscopic surgery requires sustained relationships that address local needs., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A400)., (Copyright © 2022 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Case: A 15-year-old adolescent boy sustained both talar and navicular extrusions after a dirt-bike accident. The talus and navicular were discarded during initial debridement because of contamination. Given extensive soft-tissue injury and bone loss, the patient's family opted for transtibial amputation, as described by Ertl, over limb salvage. Simultaneous osteomyoplastic reconstruction and acute targeted muscle reinnervation were performed., Conclusion: Transtibial amputation is a viable treatment option for total talar and navicular extrusions, particularly if an optimal functional outcome is unachievable with limb salvage. Simultaneous osteomyoplastic reconstruction and acute targeted muscle reinnervation can potentially decrease neuroma formation and phantom limb pain., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B875)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Abstract: Globally, the burden of musculoskeletal conditions continues to rise, disproportionately affecting low and middle-income countries (LMICs). The ability to meet these orthopaedic surgical care demands remains a challenge. To help address these issues, many orthopaedic surgeons seek opportunities to provide humanitarian assistance to the populations in need. While many global orthopaedic initiatives are well-intentioned and can offer short-term benefits to the local communities, it is essential to emphasize training and the integration of local surgeon-leaders. The commitment to developing educational and investigative capacity, as well as fostering sustainable, mutually beneficial partnerships in low-resource settings, is critical. To this end, global health organizations, such as the Consortium of Orthopaedic Academic Traumatologists (COACT), work to promote and ensure the lasting sustainability of musculoskeletal trauma care worldwide. This article describes global orthopaedic efforts that can effectively address musculoskeletal care through an examination of 5 domains: clinical care, clinical research, surgical education, disaster response, and advocacy., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G840)., (Copyright © 2021 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Introduction: The modified Radiographic Union Score for Tibia (RUST) fractures was developed to better describe fracture healing, but its utility in resource-limited settings is poorly understood. This study aimed to determine the validity of mRUST scores in evaluating fracture healing in diaphyseal femur fractures treated operatively at a single tertiary referral hospital in Tanzania., Methods: Radiographs of 297 fractures were evaluated using the mRUST score and compared with outcomes including revision surgery and EuroQol five dimensions questionnaire (EQ-5D) and visual analog scale (VAS) quality-of-life measures. Convergent validity was assessed by correlating mRUST scores with EQ-5D and VAS scores. Divergent validity was assessed by comparing mRUST scores in patients based on revision surgery status., Results: The mRUST score had moderate correlation (Spearman correlation coefficient 0.40) with EQ-5D scores and weak correlation (Spearman correlation coefficient 0.320) with VAS scores. Compared with patients who required revision surgery, patients who did not require revision surgery had higher RUST scores at all time points, with statistically significant differences at 3 months (2.02, P < 0.05)., Discussion: These results demonstrate that the mRUST score is a valid method of evaluating the healing of femoral shaft fractures in resource-limited settings, with high interrater reliability, correlation with widely used quality of life measures (EQ-5D and VAS), and expected divergence in the setting of complications requiring revision surgery., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Open fractures, especially of the tibia, require prompt intervention to achieve optimal patient outcomes. While open tibial shaft fractures are common injuries in low- and middle-income countries (LMICs), there is a dearth of literature examining delays to surgery for these injuries in low-resource settings. This study investigated risk factors for delayed management of open tibial fractures in Tanzania., Methods: We conducted an ad hoc analysis of adult patients enrolled in a prospective observational study at a tertiary referral center in Tanzania from 2015 to 2017. Multivariable models were utilized to analyze risk factors for delayed hospital presentation of ≥2 hours, median time from injury to the treatment hospital, and delayed surgical treatment of ≥12 hours after admission among patients with diaphyseal open tibial fractures., Results: Two hundred and forty-nine patients met the inclusion criteria. Only 12% of patients used an ambulance, 41% were delayed ≥2 hours in presentation to the first hospital, 75% received an interfacility referral, and 10% experienced a delay to surgery of ≥12 hours after admission. After adjusting for injury severity, having insurance (adjusted odds ratio [aOR] = 0.48; 95% confidence interval [CI] = 0.24 to 0.96) and wounds with approximated skin edges (aOR = 0.37; 95% CI = 0.20 to 0.66) were associated with a decreased risk of delayed hospital presentation. Interfacility referrals (2.3 hours greater than no referral; p = 0.015) and rural injury location (10.9 hours greater than urban location; p < 0.001) were associated with greater median times to treatment hospital admission. Older age (aOR = 0.54 per 10 years; 95% CI = 0.31 to 0.95), single-person households (aOR = 0.12 compared with ≥8 people; 95% CI = 0.02 to 0.96), and an education level greater than pre-primary (aOR = 0.16; 95% CI = 0.04 to 0.62) were associated with fewer delays to surgery of ≥12 hours after admission., Conclusions: Prehospital network and socioeconomic characteristics are associated with delays to open tibial fracture care in Tanzania. Reducing interfacility referrals and implementing surgical cost-reduction strategies may help to reduce delays to open fracture care in LMICs., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G914)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Severe lower extremity trauma among working-age adults is highly consequential for returning to work; however, the economic impact attributed to injury has not been fully quantified. The purpose of this study was to examine work and productivity loss during the year following lower extremity trauma and to calculate the economic losses associated with lost employment, lost work time (absenteeism), and productivity loss while at work (presenteeism)., Methods: This is an analysis of data collected prospectively across 3 multicenter studies of lower extremity trauma outcomes in the United States. Data were used to construct a Markov model that accumulated hours lost over time due to lost employment, absenteeism, and presenteeism among patients from 18 to 64 years old who were working prior to their injury. Average U.S. wages were used to calculate economic loss overall and by sociodemographic and injury subgroups., Results: Of 857 patients working prior to injury, 47.2% had returned to work at 1 year. The average number of productive hours of work lost was 1,758.8/person, representing 84.6% of expected annual productive hours. Of the hours lost, 1,542.3 (87.7%) were due to working no hours or lost employment, 71.1 (4.0%) were due to missed hours after having returned, and 145.4 (8.3%) were due to decreased productivity while working. The 1-year economic loss due to injury totaled $64,427/patient (95% confidence interval [CI], $63,183 to $65,680). Of the 1,758.8 lost hours, approximately 88% were due to not being employed (working zero hours), 4% were due to absenteeism, and 8% were due to presenteeism. Total productivity loss was higher among older adults (≥40 years), men, those with a physically demanding job, and the most severe injuries (i.e., those leading to amputation as well as Gustilo type-IIIB tibial fractures and type-III pilon/ankle fractures)., Conclusions: Patients with severe lower extremity trauma carry a substantial economic burden. The costs of lost productivity should be considered when evaluating outcomes., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/G910 )., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Introduction: Fit and alignment are observable objectives of the prosthesis rendering process for individuals with lower limb amputation. Nevertheless, there is a dearth of validated measures to directly assess the quality of this clinical procedure., Objectives: The objectives of this scoping review are to evaluate existing measurement parameters and clinical outcomes used in investigations of transtibial socket fit or prosthetic alignment and to identify gaps in the literature regarding tools for evaluation of prosthetic fitting., Study Design: Scoping literature review., Methods: A comprehensive search was conducted in the following databases: MEDLINE (through PubMed), Embase (through Elsevier), Scopus (through Elsevier), and Engineering Village (through Elsevier), resulting in 6107 studies to be screened., Results: Sixty-three studies were included in the review. When measuring fit, studies most frequently reported on patient-reported comfort (n = 22) and socket size compared with the residual limb volume (n = 9). Alignment was most frequently measured by the prosthetists' judgment and/or use of an alignment jig (n = 34). The measurement parameters used to determine alignment or fit varied greatly among the included studies., Conclusion: This review demonstrated that most measures of socket fit rely on a patient's self-report and may vary with biopsychosocial factors unrelated to the socket fitting process. Meanwhile, alignment is determined mostly by the prosthetist's judgment, paired with objective measurements, such as alignment jigs and gait analysis. Efforts to standardize and validate measures of these parameters of prosthetic fitting are vital to improving clinical practice and reporting outcomes., (Copyright © 2021 International Society for Prosthetics and Orthotics.)