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Background: Polyurethane (PU)-coated breast implants are known for their strong integration into breast tissue and the formation of capsules around them. However, capsular contracture can pose both aesthetic and clinical challenges., Objectives: The objectives of this study were to analyze the biological and morphological characteristics of the capsular tissue surrounding PU-coated implants, irrespective of their contracture status, and to assess their potential suitability as a flap in revisional breast surgery for capsular contracture., Methods: A total of 23 tissue samples were harvested from the capsules surrounding PU-coated breast implants in 12 female patients during replacement or revisional surgery. We evaluated collagen abundance, cellular and vascular density, inflammation, collagen band types and alignment, synovial metaplasia, capsule thickness, and the expression of inflammatory biomarkers and myofibroblasts with immunohistochemical techniques. Scanning electron microscopy was employed to assess implant surface characteristics over time., Results: We found a significant association of capsule contraction with longer implantation durations and greater implant surface roughness (P = .018 and P = .033, respectively). Synovial metaplasia was significantly more frequent in noncontracted capsules (P = .0049). Both capsule types consisted of paucicellular, type I collagen-rich compact fibrous tissue with low vascularization. There was a marked reduction in inflammatory cells within the foreign body granuloma. The expression of inflammatory biomarkers in the capsular tissue was negligible., Conclusions: Given the reduced levels of inflammatory and vascular components within the dense, fibrous capsular tissue, we consider them to be viable alternatives for capsular flaps in revisional surgery. This strategy has the potential to mimic the reconstruction achieved with acellular dermal matrix., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society.)

Objective  To reproduce in an animal model the surgical technique of Masquelet used in the treatment of critical bone defects and to analyze the characteristics of the membrane formed around the bone cement. Methods  A 10mm critical defect was created in the femoral shaft of 21 Sprague-Dawley rats. After resection of the central portion of the diaphysis, the defect was stabilized with a Kirschner wire introduced through the medullary canal and with the interposition of a bone cement spacer. After 2, 4, and 6 weeks of the surgical procedure, the animals were euthanized and evaluated on radiographs of the posterior limb regarding the size of the defect, alignment and stability of the osteosynthesis. The membranes formed around the spacer were subjected to histological analysis to assess thickness, connective tissue maturation and vascular density. Results  Over time, the membranes initially made up of loose connective tissue were replaced by membranes represented by dense connective tissue, rich in thick collagen fibers. At six weeks, membrane thickness was greater (565 ± 208μm) than at four (186.9 ± 70.21μm, p = 0.0002) and two weeks (252.2 ± 55.1μm, p = 0.001). All membranes from the initial time showed foci of osteogenic differentiation that progressively reduced over time. Conclusion  In addition to the structural and protective function of the membrane, its intrinsic biological characteristics can actively contribute to bone regeneration. The biological activity attributed by the presence of foci of osteogenesis confers to the membrane the potential of osteoinduction that favors the local conditions for the integration of the bone graft., Competing Interests: Conflito de Interesses Os autores não têm conflito de interesses a declarar., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Autocrine stimulation of tumor cells is an important mechanism for the growth of skeletal tumors. In tumors that are sensitive, growth factor inhibitors can dramatically reduce tumor growth. In this study, our aim was to investigate the effects of Secreted phosphoprotein 24 kD (Spp24) on the growth of osteosarcoma (OS) cells in the presence and absence of exogenous BMP-2 both in vitro and in vivo. Our study demonstrated that Spp24 inhibited proliferation and promoted apoptosis of OS cells as confirmed by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay and immunohistochemical staining. We found that BMP-2 increased the mobility and invasiveness of tumor cells in vitro whereas Spp24 inhibited both of these processes alone and in the presence of exogenous BMP-2. Phosphorylation of Smad1/5/8 and Smad8 gene expression was enhanced by treatment with BMP-2 but inhibited by treatment with Spp24. Subcutaneous and intratibial tumor models in nude mice demonstrated that BMP-2 promoted OS growth in vivo, while Spp24 significantly inhibited tumor growth. We conclude that the BMP-2/Smad signaling pathway is involved in the pathogenesis of OS growth and that Spp24 inhibits the growth of human OS induced by BMP-2 both in vitro and in vivo. Interruption of Smad signaling and increased apoptosis appear to be the primary mechanisms involved. These results confirm the potential of Spp24 as a therapeutic agent for the treatment of OS and other skeletal tumors., (© 2023 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Although the relationship between hip arthroplasty and the development of sarcoma was first described in the literature about forty years ago, this association is extremely rare. In the present case report, we describe the association between orthopedic implants and soft tissue sarcoma in a 79-year-old man who underwent primary total hip arthroplasty (THA) for coxarthrosis 24 years ago. In the present case report, we describe the clinical evolution and the radiographic and histopathological findings of the lesion. In the intraoperative period of the second revision surgery, loosening of the acetabular and femoral components in association with extensive areas of necrosis and metallosis was evidenced. We performed debridement of the hip and right thigh region and removed the implants. Due to the extent of the lesion and to necrosis, it was not possible to perform a new joint reconstruction. The histopathological diagnosis of high-grade undifferentiated pleomorphic sarcoma associated with extensive areas of metallosis was confirmed in tissue adjacent to the implant. The patient developed pulmonary metastases and died 6 months after the diagnosis. Despite the rarity of this association, sarcomas should be considered in the differential diagnosis of aseptic loosening, especially in the presence of metallosis in the peri-implant tissue. To our knowledge, the 24-year latency period between primary THA and the establishment of a sarcoma diagnosis is one of the longest reported to date., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Objectives  The present paper aims to (1) verify the incidence and volume of blood transfusion among patients undergoing unilateral cemented total knee arthroplasty (TKA) in a single Brazilian reference center; (2) identify pre and perioperative variables to determine subjects with higher risk (i.e., predictive factors) for blood transfusion within 48 hours following surgery; (3) estimate the risk of blood transfusion during the first 48 hours after the procedure. Methods  The initial sample consisted of all patients undergoing TKA from August 2010 to August 2013. After applying the exclusion criteria, 234 patients aged 30 to 83 years old and diagnosed with primary or secondary osteoarthritis due to rheumatoid arthritis remained in the study. Results  Preoperative hemoglobin levels ≤ 12.3 g/dL and ischemia time ≥ 87 minutes were independent predictors for post-TKA blood transfusion, with a relative risk of 2.48 and 1.78, respectively. Approximately half of the TKA patients (51.3%) presenting these two variables required a blood transfusion. Conclusion  The incidence of post-TKA blood transfusion was 33.7%. On average, each transfused patient received 480 mL of packed red blood cells. Preoperative hemoglobin levels ≤ 12.3 g/dL ( p  < 0.001) and ischemia time ≥ 87 minutes ( p  < 0.047) were independent predictors for blood transfusion in TKA using a pneumatic cuff, with a relative risk of 2.48 and 1.78, respectively. Age, gender, diagnosis, or body mass index were not considered independent predictors for the need for blood transfusion up to 48 hours after the procedure., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objective  To describe the epidemiological and clinical profile of patients with Dupuytren disease treated by selective fasciectomy and the factors associated with the severity of the disease. Methods  Retrospective descriptive observational study involving 247 patients with Dupuytren disease, from 2013 to 2019. Multivariate logistic regression was performed for data analysis. Results  Most patients were male (83.8%), self-declared white (65.2%), alcoholics (59.6%) and 49% were smokers, with a mean age of 66 ± 9 years old, with 77.2% presenting symptoms of the disease after the age of 51 years old. Approximately 51.9, 29.6 and 17.3%, respectively, had arterial hypertension, diabetes mellitus and dyslipidemia comorbidities. Bilateral involvement of the hands was observed in 73.3% of the patients. The rate of intra- and post-selective fasciectomy complications was of 0.6 and 24.3%, respectively, with 5.2% of the patients needing reintervention after 1 year of follow-up. After multivariate analysis, males were associated with bilateral involvement of the hands (odds ratio [OR] = 2.10; 95% confidence interval [CI]: 1.03-4.31) and with a greater number of affected rays (OR = 3.41; 95% CI: 1.66-7.03). Dyslipidemia was associated with reintervention (OR = 5.7; 95% CI = 1.03-31.4) and bilaterality with a higher number of complications (35.7 versus 19.7%). Conclusion  A low rate of reintervention and operative complications was observed in patients with Dupuytren disease treated by selective fasciectomy. Male gender was associated with severe disease (bilaterality and more than two affected rays), and dyslipidemia with reintervention., Competing Interests: Conflito de interesses: Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The treatment of large segmental defects of long bones resulting from trauma, infection, or bone tumor resections is a major challenge for orthopedic surgeons. The reconstruction of bone defects with acellular allografts can be used as an osteoconductive approach. However, devitalized allografts are associated with high rates of clinical failure as a result of poor intrinsic osteoinduction properties and a lack of further remodeling. Nevertheless, evidence suggests that due to its anabolic properties, teriparatide (PTH 1-34 ) could be effective as an adjuvant therapy for massive allograft healing. Therefore, our goal was to investigate in a murine critical-sized defect model whether the intermittent administration of PTH 1-34 improves the incorporation and revitalization of acellular structural bone allografts. Thus, a 2.5-mm critical-sized defect was established in the right femur of C57BL/6 mice, followed by the reconstruction with a devitalized cortical structural allograft. A titanium micro locking plate was applied to the anterior femoral surface and secured in place with self-tapping locking screws. Subsequently, daily doses of PTH 1-34 (30, and 40 µg/kg) or saline were administered to the mice for 14 days after surgery. The mice were maintained without PTH 1-34 therapy for an additional 7 days before being euthanized at 3 weeks post-surgery. Bone graft consolidation was assessed on radiographic images and by histomorphometric analysis. Additionally, to determine the frequency of osteoprogenitor cells in the bone marrow and their in vitro osteogenic capacity, stromal cells were isolated from the bone marrow of animals treated with 30 or 40 µg/kg/day of PTH 1-34 following the same protocol used for the experimental animals. Our results suggest that intermittent PTH 1-34 treatment at 30 µg/kg/day after femoral allograft reconstruction surgery accelerated the healing process as evidenced by new bone formation induced on endosteal and periosteal surfaces, enhanced revitalization of allogeneic graft, and increased frequency and osteogenic capacity of bone marrow stromal cells (BMSC). These findings should encourage further studies aimed at investigating the potential therapeutic use of intermittent PTH 1-34 , specifically with regards to the optimal dosing regimen in clinically challenging orthopedic scenarios., 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 © 2021. Published by Elsevier Ltd.)

COVID-19 pandemics required substantial reorganization and adaptation of healthcare services all over the world. This study aims to analyze the effect of operational strategies implemented in Brazil to manage the extra strain placed on healthcare services by the COVID-19 pandemic of 2020. In particular, this investigation examines the strategy to convert an institute specialized in elective orthopedic procedures of high complexity into a trauma unit for all musculoskeletal trauma patients of an entire federative unit. A retrospective study was conducted comparing hospital variables at the peak period of the pandemic (from March 16, 2020 to June 30, 2020) with the same period in 2019 as a comparative baseline. The variables analyzed included number of professionals away from work, surgeries performed, outpatient care, transfers, length of stay, number of patients diagnosed with COVID-19 and patient mortality. During the COVID-19 peak period, there was a 48.5% reduction in surgical productivity and 72.4% reduction in outpatient care compared with the same period in 2019. The number of transfers increased substantially (124.5%), while 94 confirmed cases and 77 suspected cases of COVID-19 were reported. The mortality rate increased by 245%. The present study highlighted the effect of COVID-19 on a tertiary orthopedic hospital. Despite the dramatic changes in hospital operations, due to the implementation of protocols to manage the pandemic, the results demonstrated the feasibility and efficiency of such protocols in prioritizing quality and safety for patients and the healthcare workforce., Competing Interests: Conflitos de Interesse Os autores não têm conflitos de interesse a declarar., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Intracapsular proximal femoral fracture is a frequent injury in elderly patients, often associated with low-energy trauma and reduced bone mass. In young patient, it is uncommon, usually caused by high-energy trauma and accompanied by damage to the adjacent soft tissues. However, reports of open intracapsular proximal femoral fracture due to indirect trauma are rare in the orthopedic literature. In the present article, we describe a case of this injury in a 35-year-old man involved in a car accident. The proximal femur was exposed at the gluteal region due to a mechanism similar to dislocation of the posterior hip. We describe the initial treatment and subsequent management until achieving a definitive solution using total hip arthroplasty and muscle transfer to reconstruct the abductor mechanism of the hip. At 10 months of follow-up, the patient presented good functional outcome, with gradual recovery of the abductive strength and a Harris Hip Score of 91 points. In addition, a radiographic study showed that the cemented total prosthesis was well-positioned. This therapeutic strategy (total hip arthroplasty with muscle transfer to reconstruct the abductor musculature) was successful to treat an intracapsular proximal femoral fracture with bone exposure., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Although osteosarcoma is a rare disease, with a global incidence rate estimated at 5.0/million/year, it is the most frequent primary bone sarcoma in children and adolescents. In translational research, the patient-derived xenograft (PDX) model is considered an authentic in vivo model for several types of cancer, as tumorgrafts faithfully retain the biological characteristics of the primary tumors. Our goal was to investigate the association between PDX formation and clinical findings of osteosarcoma patients and the ability of the model to preserve in immunocompromized mice the characteristics of the parental tumor. A fresh sample of the patient tumor obtained from a representative biopsy or from surgical resection was implanted into nude mice. When tumor outgrowths reached ~1,500mm³, fresh PDX fragments were re-transplanted into new hosts. Engraftment in mice was obtained after a latency period of 19-225 days (median 92 days) in 40.54% of the implanted samples. We confirmed the histopathological fidelity between the patient tumor and their respective established PDXs, including the expression of biomarkers. PDX take rate was higher in surgical resection samples, in post-chemotherapy surgical samples and in samples from patients with metastatic disease at presentation. In conclusion, we have shown that the osteosarcoma PDX model reliably recapitulates the morphological aspects of the human disease after serial passage in mice. The observation that more aggressive forms of osteosarcoma, including those with metastatic disease at presentation, have a higher efficiency to generate PDXs provides a promising scenario to address several unanswered issues in clinical oncology.

Objective  To evaluate radiographic parameters of sagittal and spinopelvic alignment in patients with hip osteoarthritis (OA) undergoing primary total hip arthroplasty (THA) to define the primary surgical approach in individuals with concomitant spinal and hip joint disease. Methods  Longitudinal, prospective, comparative study with 27 patients undergoing THA and 43 subjects without OA. Results  An association between hip and spine degenerative disease in patients with OA was noted. After THA, radiographic parameters of pelvic tilt angle, sagittal vertical axis (EVS) and seventh cervical vertebra/sacrofemoral distance (C7/DSF) ratio were similar to values from volunteers without joint disease. Global coronal alignment (ACG), sagittal alignment, spinopelvic T1 and T9 tilts (IT1EP and IT9EP), sacral tilt (IS), pelvic version (VP), pelvic type and lumbopelvic complex (CLP) did not change after THA. Conclusion  Among the sagittal and spinopelvic alignment parameters evaluated, the pelvic tilt angle, the EVS, and the C7/DSF ratio were corrected after THA and can guide the surgeon in the decision-making process for patients with concomitant spinal and hip joint disease. Spinal deformity may compensate for hip changes., Competing Interests: Conflito de interesses Os autores declaram não haver conflito de interesses., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

In vitro-expanded bone marrow stromal cells (BMSCs) have long been proposed for the treatment of complex bone-related injuries because of their inherent potential to differentiate into multiple skeletal cell types, modulate inflammatory responses, and support angiogenesis. Although a wide variety of methods have been used to expand BMSCs on a large scale by using good manufacturing practice (GMP), little attention has been paid to whether the expansion procedures indeed allow the maintenance of critical cell characteristics and potency, which are crucial for therapeutic effectiveness. Here, we described standard procedures adopted in our facility for the manufacture of clinical-grade BMSC products with a preserved capacity to generate bone in vivo in compliance with the Brazilian regulatory guidelines for cells intended for use in humans. Bone marrow samples were obtained from trabecular bone. After cell isolation in standard monolayer flasks, BMSC expansion was subsequently performed in two cycles, in 2- and 10-layer cell factories, respectively. The average cell yield per cell factory at passage 1 was of 21.93 ± 12.81 × 10 6 cells, while at passage 2, it was of 83.05 ± 114.72 × 10 6 cells. All final cellular products were free from contamination with aerobic/anaerobic pathogens, mycoplasma, and bacterial endotoxins. The expanded BMSCs expressed CD73, CD90, CD105, and CD146 and were able to differentiate into osteogenic, chondrogenic, and adipogenic lineages in vitro. Most importantly, nine out of 10 of the cell products formed bone when transplanted in vivo. These validated procedures will serve as the basis for in-house BMSC manufacturing for use in clinical applications in our center., Competing Interests: The authors indicated no potential conflicts of interest., (Copyright © 2019 Rhayra B. Dias et al.)

Introduction: The role of vitamin D on bone microarchitecture and fragility is not clear., Objective: To investigate whether vitamin D deficiency (25(OH)D <20 ng/mL) increases cortical bone loss and the severity of fractures., Design: Cross-sectional study of 287 elderly women with at least one prevalent low-impact fracture., Methods: Biochemistry, X-rays to identify vertebral fractures (VFs) and to confirm non-vertebral fractures (NonVFs), and high-resolution peripheral quantitative computed tomography (HR-pQCT) to evaluate bone microstructure., Results: Serum 25(OH)D levels were associated with body mass index (BMI: r = -0.161, P = 0.006), PTH (r = -0.165; P = 0.005), CTX (r = -0.119; P = 0.043) and vBMD at cortical bone (Dcomp: r = 0.132; P = 0.033) and entire bone (D100: r = 0.162 P = 0.009) at the distal radius, but not at the tibia. Age and PTH levels were potential confounding variables, but in the multiple linear regressions only BMI (95% CI: 0.11-4.16; P < 0.01), 25(OH)D (95% CI: -0.007 to 1.70; P = 0.05) and CTX (95% CI: -149.04 to 21.80; P < 0.01) predicted Dcomp, while BMI (95% CI: 1.13-4.18; P < 0.01) and 25(OH)D (95% CI: 0.24-1.52; P < 0.01) predicted D100. NonVFs predominated in patients with 25(OH)D <20 ng/mL (P = 0.013). Logistic regression analysis showed a decrease in the likelihood of presenting grade 2-3 VFs/NonVFs for every increase in 25(OH)D (OR = 0.962, 95% CI: 0.940-0.984; P = 0.001), BMI (OR = 0.932, 95% CI: 0.885-0.981; P = 0.007) and D100 at radius (OR = 0.994, 95% CI: 0.990-0.998; P = 0.005)., Conclusion: In elderly patients with prevalent fractures, vitamin D deficiency was associated with cortical bone loss and severity of fractures.

Objectives  To evaluate the factors that influence the outcome of osteosynthesis after closed reduction of the fracture of the femoral neck in young adult patients. Methods  A retrospective study was conducted, reviewing the data of patients operated in a large orthopedic hospital from 2003 to 2011; a total of 81 patients met the inclusion criteria. The time interval between the fracture and the surgery, the initial fracture deviation, the quality of the reduction, and the placement of the implant were evaluated. Results  The present study observed a strong relationship between the quality of the reduction and therapeutic success. The degree of the initial deviation and the time elapsed between the initial trauma and the osteosynthesis did not influence the surgical outcome regarding bone consolidation. The correct positioning of the implants was associated with a satisfactory evolution in the postoperative period. Conclusion  The quality of the reduction and the positioning of the implants are factors that influence the results of osteosynthesis in fractures of the femoral neck in young adult patients.

The correlation between BMP-2 and osteosarcoma growth has gained increased interest in the recent years, however, there is still no consensus. In this study, we tested the effects of BMP-2 on osteosarcoma cells through both in vitro and in vivo experiments. The effect of BMP-2 on the proliferation, migration and invasion of osteosarcoma cells was tested in vitro. Subcutaneous and intratibial tumor models were used for the in vivo experiments in nude mice. The effects of BMP-2 on EMT of osteosarcoma cells and the Wnt/β-catenin signaling pathway were also tested using a variety of biochemical methods. In vitro tests did not show a significant effect of BMP-2 on tumor cell proliferation. However, BMP-2 increased the mobility of tumor cells and the invasion assay demonstrated that BMP-2 promoted invasion of osteosarcoma cells in vitro. In vivo animal study showed that BMP-2 dramatically enhanced tumor growth. We also found that BMP-2 induced EMT of osteosarcoma cells. The expression levels of Axin2 and Dkk-1 were both down regulated by BMP-2 treatment, while β-catenin, c-myc and Cyclin-D1 were all upregulated. The expression of Wnt3α and p-GSK-3β were also significantly upregulated indicating that the Wnt/β-catenin signaling pathway was activated during the EMT of osteosarcoma driven by BMP-2. From this study, we can conclude that BMP-2 significantly promotes growth of osteosarcoma cells (143B, MG63), and enhances mobility and invasiveness of tumor cells as demonstrated in vitro. The underlying mechanism might be that BMP-2 promotes EMT of osteosarcoma through the Wnt/β-catenin signaling pathway. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1638-1648, 2019., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objective: Percutaneous fixation of the acetabulum is a treatment option for select acetabular fractures. Intra-operative fluoroscopy is required, and despite various described imaging strategies, it is debatable as to which combination of fluoroscopic views provides the most accurate and reliable assessment of screw position., Materials and Methods: Using five synthetic pelvic models, an experimental setup was created in which the anterior acetabular columns were instrumented with screws in five distinct trajectories. Five fluoroscopic images were obtained of each model (Pelvic Inlet, Obturator Oblique, Iliac Oblique, Obturator Oblique/Outlet, and Iliac Oblique/Outlet). The images were presented to 32 pelvic and acetabular orthopaedic surgeons, who were asked to draw two conclusions regarding screw position: (1) whether the screw was intra-articular and (2) whether the screw was intraosseous in its distal course through the bony corridor., Results: In the assessment of screw position relative to the hip joint, accuracy of surgeon's response ranged from 52% (iliac oblique/outlet) to 88% (obturator oblique), with surgeon confidence in the interpretation ranging from 60% (pelvic inlet) to 93% (obturator oblique) (P < 0.0001). In the assessment of intraosseous position of the screw, accuracy of surgeon's response ranged from 40% (obturator oblique/outlet) to 79% (iliac oblique/outlet), with surgeon confidence in the interpretation ranging from 66% (iliac oblique) to 88% (pelvic inlet) (P < 0.0001)., Conclusions: The obturator oblique and obturator oblique/outlet views afforded the most accurate and reliable assessment of penetration into the hip joint, and intraosseous position of the screw was most accurately assessed with pelvic inlet and iliac oblique/outlet views., Evidence: Clinical Question.

Introduction: Nonunion is a challenging condition in orthopaedics as its etiology is not fully understood. Clinical interventions currently aim to stimulate both the biological and mechanical aspects of the bone healing process by using bone autografts and surgical fixation. However, recent observations showed that atrophic nonunion tissues contain putative osteoprogenitors, raising the hypothesis that its reactivation could be explored to achieve bone repair., Methods: Here we characterized atrophic nonunion stromal cells (NUSC) in vitro, using bone marrow stromal cells (BMSC) and osteoblasts as controls cells of the osteoblastic lineage, and evaluated its ability to form bone in vivo., Results: NUSC had proliferative and senescence rates comparable to BMSC and osteoblasts, and homogeneously expressed the osteolineage markers CD90 and CD73. Regarding CD105 and CD146 expression, NUSC were closely related to osteoblasts, both with an inferior percentage of CD105 + /CD146 + cells as compared to BMSC. Despite this, NUSC differentiated along the osteogenic and adipogenic lineages in vitro; and when transplanted subcutaneously into immunocompromised mice, new bone formation and hematopoietic marrow were established., Conclusions: This study demonstrates that NUSC are osteogenically competent, supporting the hypothesis that their endogenous reactivation could be a strategy to stimulate the bone formation while reducing the amount of bone autograft requirements., Competing Interests: All authors state no conflicts of interest., (Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Background: Tendinopathy pathogenesis is associated with inflammation. Regulatory T (Treg) cells contribute to early tissue repair through an anti-inflammatory action, with the forkhead box P3 (FOXP3) transcription factor being essential for Treg function, and the FC-receptor-like 3 (FCRL3) possibly negatively regulating Treg function. FCRL3 -169T>C and FOXP3 -2383C>T polymorphisms are located near elements that regulate respective genes expression, thus it was deemed relevant to evaluate these polymorphisms as risk factors for tendinopathy development in athletes., Methods: This case-control study included 271 volleyball athletes (146 tendinopathy cases and 125 controls) recruited from the Brazilian Volleyball Federation. Genotyping analyses were performed using TaqMan assays, and the association of the polymorphisms with tendinopathy evaluated by multivariate logistic regression., Results: Tendinopathy frequency was 63% patellar, 22% rotator cuff and 15% Achilles tendons respectively. Tendinopathy was more common in men (OR = 2.87; 95% CI = 1.67-4.93). Higher age (OR = 8.75; 95% CI = 4.33-17.69) and more years of volleyball practice (OR = 8.38; 95% CI = 3.56-19.73) were risk factors for tendinopathy. The FCRL3 -169T>C frequency was significantly different between cases and controls. After adjustment for potential confounding factors, the FCRL3 -169C polymorphism was associated with increased tendinopathy risk (OR = 1.44; 95% CI = 1.02-2.04), either considering athletes playing with tendon pain (OR = 1.98; 95% CI = 1.30-3.01) or unable to train due to pain (OR = 1.89; 95% CI = 1.01-3.53). The combined variant genotypes, FCRL3 -169TC or -169CC and FOXP3 -2383CT or -2383TT, were associated with an increased risk of tendinopathy among athletes with tendon pain (OR = 2.24; 95% CI: 1.14-4.40 and OR = 2.60; 95% CI: 1.11-6.10). The combined analysis of FCRL3 -169T>C and FOXP3 -2383C>T suggests a gene-gene interaction in the susceptibility to tendinopathy., Conclusions: FCRL3 -169C allele may increase the risk of developing tendinopathy, and together with knowledge of potential risk factors (age, gender and years playing) could be used to personalize elite athletes' training or treatment in combination with other approaches, with the aim of minimizing pathology development risk.

Background: Neurofibromatosis 1 (NF1) presents a wide range of clinical manifestations, including bone alterations. Studies that seek to understand cellular and molecular mechanisms underlying NF1 orthopedic problems are of great importance to better understand the pathogenesis and the development of new therapies. Dental pulp stem cells (DPSCs) are being used as an in vitro model for several diseases and appear as a suitable model for NF1. The aim of this study was to evaluate in vitro chondrogenic differentiation of DPSCs from individuals with NF1 using two-dimensional (2D) and three-dimensional (3D) cultures., Results: To fulfill the criteria of the International Society for Cellular Therapy, DPSCs were characterized by surface antigen expression and by their multipotentiality, being induced to differentiate towards adipogenic, osteogenic, and chondrogenic lineages in 2D cultures. Both DPSCs from individuals with NF1 (NF1 DPSCs) and control cultures were positive for CD90, CD105, CD146 and negative for CD13, CD14, CD45 and CD271, and successfully differentiated after the protocols. Chondrogenic differentiation was evaluated in 2D and in 3D (pellet) cultures, which were further evaluated by optical microscopy and transmission electron microscopy (TEM). 2D cultures showed greater extracellular matrix deposition in NF1 DPSCs comparing with controls during chondrogenic differentiation. In semithin sections, control pellets hadhomogenous-sized intra and extracelullar matrix vesicles, whereas NF1 cultures had matrix vesicles of different sizes. TEM analysis showed higher amount of collagen fibers in NF1 cultures compared with control cultures., Conclusion: NF1 DPSCs presented increased extracellular matrix deposition during chondrogenic differentiation, which could be related to skeletal changes in individuals with NF1.

Objective: The purpose of this study was to reproduce a mouse model of bone sarcomas for use in cancer research., Methods: A fresh sample of the tumor tissue was implanted subcutaneously into nude mice. When the patient-derived xenograft (PDX) reached a volume of 1500 mm 3 , it was harvested for re-implantation into additional mice. Histology was used to compare the morphological characteristics of different generations of sarcoma xenografts with the primary tumor., Results: Sixteen sarcoma tissue samples were engrafted into nude mice. Nine patients were diagnosed with osteosarcoma, two with chondrosarcoma, two with malignant peripheral nerve sheath tumor, one with synovial sarcoma, one with pleomorphic sarcoma, and one with Ewing's sarcoma. PDX tumors were generated in 11 of the 16 implanted specimens (69% success rate in P1). Six P1 tumors grew sufficiently for transfer into additional mice, producing the P2 generation, and three P2 tumors established the P3 generation., Conclusion: PDX tumors generated from bone sarcomas were successfully established in immunodeficient mice and reproduced the characteristics of the primary tumor with a high degree of fidelity. The preclinical PDX model described herein may represent an important tool for translational oncology research and for evaluating therapeutic strategies for bone sarcomas. Level of Evidence I; Experimental study., Competing Interests: All authors declare no potential conflict of interest related to this article.

Introduction: Ectopic forms of schistosomiasis are those in which the parasitic element is localized outside the portal system, the natural habitat of the helminth. Although the prevalence rates of schistosomiasis are high in Brazil, clinical and epidemiological data on ectopic forms of the disease are still scarce., Methods: Cross-sectional, retrospective and descriptive epidemiological study in which cases with a confirmed histopathological diagnosis of an ectopic form of schistosomiasis were analyzed. The cases were selected from a database of the anatomic pathology files of a referral center., Results: Of the 21 cases identified, seven affected the female genital tract and five the male genital tract; four cases were identified in the peritoneum; two cases involved lymph nodes and two involved adipose tissue; and renal involvement was detected in one case., Conclusions: The lack of knowledge of the clinical presentation of ectopic forms of schistosomiasis makes the early identification and treatment of this form difficult, with direct implications in the reduction of morbidity and mortality in endemic areas.

Vertical femoral neck fractures (Pauwels type III classification) in young adults generally occur as a consequence of high-energy trauma and are frequently seen in association with multiple injuries. Considering the controversies regarding the optimal fixation for this fracture, our aim was to evaluate the clinical outcome of a closed fixation strategy for vertical femoral neck fractures in young adults using two parallel and one transverse cancellous lag screws. This was a single-surgeon, prospective study including 20 young adults with average age of 38.75 years (range 18-59 years) with a high-energy Pauwels III femoral neck fracture. Closed reduction and internal fixation with three cancellous lag screws were performed. The first screw was inserted crosswise to avoid further shear forces. Second and third parallel screws were placed above the lesser trochanter and centrally on the greater trochanter, respectively. Clinical outcomes were assessed by comparing postoperative and final follow-up radiographs 24 months post-injury. Eleven patients had an isolated vertical femoral neck fracture. Of these, five had further femoral neck comminution. Nine patients had an associated ipsilateral femoral shaft fracture. All fractures were displaced at the time of the first radiological evaluation. Closed reduction quality was considered excellent or good in 15 patients. After 24 months, bone union was achieved in 16 cases. Osteonecrosis of the femoral head developed in association with two fractures, and a nonunion developed in association with two fractures. We conclude that vertical high-energy femoral neck fractures can be treated successfully with internal fixation with two parallel cancellous lag screws positioned above the lesser trochanter and a third screw inserted centrally on the greater trochanter at an angle perpendicular to the fracture line., (© 2017 Elsevier Ltd. All rights reserved.)

Introduction: Femoral shaft fractures generally occur in young adults following a high-energy trauma and are prone to delayed union/non-union. Novel therapies to stimulate bone regeneration will have to mimic some of the aspects of the biology of fracture healing; however, which are these aspects is unclear. Locked intramedullary nailing is the current treatment of choice for the stabilisation of femur shaft fractures, and it is associated with accelerated healing and increased union rates. These benefits were partially attributed to the reaming procedure, which, regardless of significantly destroying the haematoma, stimulates the healing response. To better understand how reaming influences healing, we evaluated the viability of the nucleated cell fraction and the frequency of CD146 + skeletal progenitors, which contain multipotent cells, in the post-reaming haematoma. We also screened the concentrations of inflammatory mediators and growth factors in the fracture site after reaming compared with those in the original haematoma., Methods: Pre- and post-reaming haematomas were percutaneously aspirated from the fracture site of 15 patients with closed femoral shaft fractures. Cellular viability and the percentage of CD146+ progenitors were analysed by flow cytometry. The concentrations of cytokines and growth factors were determined by ELISA., Results: AnnexinV/Pi analysis showed that the viability of the total nucleated cell fraction was decreased in the post-reaming haematoma. However, the procedure increased the percentage of CD146+ skeletal progenitors in the fracture site. Analysis of cytokines and growth factors in supernatants showed a decreased concentration of the inflammatory mediators IL-6, CCL-4, and MCP-1, along with an increase of anti-inflammatory IL-10, and the growth factors bFGF and PDGF-AB., Conclusion: These findings support the view that the positive effects of reaming on fracture healing might result from mechanically grafting the fracture site with a population of skeletal progenitors that contain multipotent cells; transitioning the signalling environment to a less inflammatory state, and enhancing the availability of specific osteogenic and angiogenic factors. A better understanding of the requisite stimuli for optimal bone repair, considering the disturbances made by orthopaedic treatments, will be determinant for the development of innovative treatments for bone repair., (© 2017 Elsevier Ltd. All rights reserved.)

Osteoarthritis (OA) is the main cause of disability worldwide, due to progressive articular cartilage loss and degeneration. According to recent research, OA is more than just a degenerative disease due to some metabolic components associated to its pathogenesis. However, no biomarker has been identified to detect this disease at early stages or to track its development. Metabolomics is an emerging field and has the potential to detect many metabolites in a single spectrum using high resolution nuclear magnetic resonance (NMR) techniques or mass spectrometry (MS). NMR is a reproducible and reliable non-destructive analytical method. On the other hand, MS has a lower detection limit and is more destructive, but it is more sensitive. NMR and MS are useful for biological fluids, such as urine, blood plasma, serum, or synovial fluid, and have been used for metabolic profiling in dogs, mice, sheep, and humans. Thus, many metabolites have been listed as possibly associated to OA pathogenesis. The goal of this review is to provide an overview of the studies in animal models and humans, regarding the use of metabolomics as a tool for early osteoarthritis diagnosis. The concept of osteoarthritis as a metabolic disease and the importance of detecting a biomarker for its early diagnosis are highlighted. Then, some studies in plasma and synovial tissues are shown, and finally the application of metabolomics in the evaluation of synovial fluid is described.