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Liquid nitrogen (LN) has been used as an adjuvant cryotherapy for bone tumors including giant-cell tumor of the bone (GCTB) to remove residual tumor cells after curettage. This study evaluated variables related to the efficacy of LN-based cryoablation in the context of adjuvant treatment of GCTB using porcine femur bone model.A porcine femur bone model was adopted to simulate intralesional cryotherapy. A LN-holding cavity (point 1, nadir) in the medial epicondyle, 4 holes (points 2-5) in the shaft situated 5, 10, 15, and 20 mm away from the proximal edge of the cavity, and 2 more holes (points 6 and 7) in the condyle cartilage (10 and 20 mm away from the distal edge of the cavity) were made. The cooling rate was compared between the 5 points. The cellular morphological changes and DNA damage in the GCTB tissue attributable to LN-based cryotherapy were determined by HE stain and TUNEL assay. Cartilage tissue at points 6 and 7 was examined for the extent of tissue injury after cryotherapy.The temperature kinetics at points 1, 2 reached the reference target and were found to be significantly better than the reference (both p0.05). The target temperature kinetics were not achieved at points 4 and 5, which showed a significantly lower cooling rate than the reference (both p0.001) without reaching the -60°C target. Compared with untreated samples, significantly higher proportion of shrunken or apoptotic cells were found at points 1-3; very small proportion were observed at points 4, 5. Significantly increased chondrocyte degeneration was observed at point 6, and was absent at point 7.The cryotherapy effective range was within 5 mm from nadir. Complications were restricted to within this distance. The cooling rate was unchanged after three repeated cycles of cryotherapy.

Angiogenesis plays an important role in the development of bone and bone regeneration to provide the required molecules. Mesenchymal stem cells (MSCs) are pluripotent, self-renewing, and spindle-shaped cells, which can differentiate into multiple lineages such as chondrocytes, osteocytes, and adipocytes. MSCs derived from bone marrow (BMMSCs), adipose tissue (ADMSCs), and Wharton’s jelly (UCMSCs) are popular in the field of tissue regeneration. MSCs have been proposed that can promote bone regeneration by enhancing vascularization. In this study, the angiogenic potential of secretomes of undifferentiated and osteo-differentiated BMMSCs, ADMSCs, and UCMSCs seeded on human decellularized allogeneic bone were compared. Human umbilical vein endothelial cells (HUVECs) were treated with MSC secretomes. Cell growth, cell migration, and angiogenesis of HUVECs were analyzed by MTT, wound healing, and tube formation assays. Angiogenic gene expression levels of MSCs were evaluated using real-time quantitative PCR. Antibody neutralization was performed to validate the candidate target. Our study demonstrates that the angiogenic gene expression profile is tissue-dependent and the angiogenic ability of secretomes is independent of the state of differentiation. We also explore that IL-1b is important for MSC angiogenic potential. Taken together, this study proves that IL-1b in the secretomes plays a vital role in angiogenesis.

The use of cryoablation/cryosurgery in treating solid tumors has been proven as a unique technique that uses lethal temperatures to destroy the tumors and impart better functions for the affected organs. This novel technique recently demonstrated the best clinical results in chondrosarcoma (CSA) with faster recovery, less recurrence, and metastasis. Due to the resistant nature of CSA to chemo and radiation therapy, cryoablation comes to light as the best alternative approach. Therefore, for the first time, we aimed to compare CSA-untreated with cryoablation treated samples to discover some potential markers that may provide various clues in terms of diagnosis and pathophysiology and may facilitate the development of novel methods to treat sarcoma efficiently. To find the altered proteins among both groups, a mass-based label-free approach was employed and identified a total of 160 significantly altered proteins. Among these, 138 proteins were dysregulated with1- to -0.1-fold, 18 proteins were up-regulated with3 folds, and four proteins were similarly expressed in the untreated group compared to the treated. Interestingly, the differential expressions of proteins from the untreated group showed contrast expressions in the treated group. Furthermore, the functional enrichment analysis revealed that most of the identified proteins from this study were associated with various significant pathways such as glycolysis, MAPK activation, PI3K-Akt signaling, extracellular matrix degradation, etc. In addition, two protein expressions, such as fibronectin and annexin-1, were validated by immunoblot analysis. Therefore, this study signifies the most comprehensive discovery of altered protein expressions to date and the first large-scale detection of protein profiles from CSA-cryoablation treated compared to untreated. This work may serve as the basis for future research to open novel treatment options for chondrosarcoma.

Background: Liposarcoma (LPS) is one of the most common soft tissue sarcoma (STS) subtypes. Both well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) have 12q13-15 amplification. Mouse double minute 2 homolog (MDM2) is one of the most important oncogenes within this region. Ferroptosis is a unique type of necrotic cell death featured accumulation of lipid-based reactive oxygen species (ROS) derived from the oxidative modification of phospholipid membranes. Cysteine metabolism is the critical part of ferroptosis regulation. Cystine-glutamate antiporter (system xc-; xCT), encoded by two subcomponents, the solute carrier family 7 member 11 (SLC7A11) and SLC3A2, is responsible for cystine supply from extra-cellular environment. Imported cystine is then reduced to cysteine, a key component of tripeptide glutathione (GSH). Glutathione peroxidase 4 (GPX4) requires GSH to repair lipid peroxidation and prevent ferroptosis. Inactivation of GPX4, either through cystine deprivation due to xCT inhibitor erastin, or by GPX4 inhibitor Ras-selective lethal small molecule 3 (RSL3), will lead to accumulation of lipid-based ROS, and eventually ferroptosis cell death. The tumor suppressor p53 (TP53) could suppress the expression of SLC7A11 and induce ferroptosis. TP53 could also indirectly suppress 3-hydroxy-3-methyl-glutaryl (HMG)-coenzyme A (CoA) reductase (HMGCR) activity, a key pathway for generation of biomolecules with anti-ferroptosis property. MDM2, the key oncogene in DDLPS, and homolog MDM4 could facilitate ferroptotic death in TP53-dependent or -independent mechanisms. Methods: We explored public domain database to identify possible aberrations of ferroptosis-related genes in DDLPS. We then examined the sensitivity of DDLPS cell lines to possible ferroptosis-inducing agents. Furthermore, we used nutlin-3, a MDM2 inhibitor, to modulate the MDM2 expression in DDLPS cell line, and explored the potential synergistic effect of nutlin-3 with ferroptosis-inducing agents. Finally, we used immunoblotting study to reveal the potential mechanism responsible to possible synergistic effect. Results: Expression level of GPX4 is significantly lower in DDLPS than adipose tissue and WDLPS, and DPP4 was general higher in LPS than adipose tissue. HMGCR, SLC7A11 and SLC3A2 were mostly up-regulated in LPS in comparison with benign counterpart. Both DDLPS cell lines showed sensitivity to erastin and RSL3. In addition, nutlin-3 could exert synergistic ferroptosis-inducing effect and cytotoxicity with erastin and RSL3 in sequential manner. Furthermore, nultin-3 treatment could upregulate SLC3A2 with altered cystine/glutamate exchange in DDLPS cell lines, indicating possible mechanism responsible for nultin-3 resistance and the synergistic effect of nultin-3 with erastin or RSL3. Conclusion: Our study showed that modulation of ferroptosis is a potential treatment strategy in DDLPS. Citation Format: Chueh-Chuan Yen, San-Chi Chen, Chih-Hsueh Chen, Jir-You Wang, Chao-Ming Chen, Po-Kuei Wu, Muh-Hwa Yang. Exploring ferroptosis pathway for the development of therapeutic strategy in liposarcoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4777.

We designed a patella cryo-free method to protect patella from cryoinjury during recycled frozen bone-prosthesis-composite reconstruction for proximal tibial malignancy. This study aimed to use animal model to ensure safety and efficacy of this method and reported our clinical outcomes.Six swine proximal tibias along with patella and patellar tendon were harvested and dived into group A (n = 3, traditional patella freezing) and group B (n = 3, patella cryo-free). Temperature curve measurement, histological analysis, and TUNEL assay were performed in both groups. Clinically, we retrospectively reviewed 23 patients with proximal tibia malignant bone tumor (13: traditional patella freezing method; 10: patella cryo-free method). The clinical and functional outcomes were reported and compared in both groups.Temperature curve of the group B showed that ideal therapeutic temperature (-60°C) required to kill tumor cells can be achieved in the proximal tibia while the innocent patella can be kept in room temperature at all time. Histological analysis showed better preservation of the cartilage tissue in patella of group B. TUNEL assay showed significantly more apoptotic cells in the frozen tibia of both groups and frozen patella of group A. When reviewing our clinical results, less complication of the patella as well as better functional preservation were found in patients subjecting to patella cryo-free method. No local recurrence was observed in either group.Patellar cryo-free technique could protect patella from cryoinjury during freezing and therefore preserve more extensor functions for patients with proximal tibial malignant bone tumors.

The comparison of output powers between self-Raman Nd:YVO4 lasers and Nd:YVO4/KGW Raman lasers operating at lime and orange wavelengths is presented. We exploit the LBO crystal with cutting angle θ = 90° and φ = 8° for the lime wavelengths, and then we change the angle to θ = 90° and φ = 3.9° for the orange wavelengths. In self-Raman Nd:YVO4 lasers, experimental results reveal that thermal loading can impact on the output performances, especially at the high pump power. However, by using a KGW crystal as Raman medium can remarkably share the thermal loading from gain medium. Besides, the designed coating for high reflectively at the Stokes field on the surface of KGW also improved the beam quality and reduced the lasing threshold. For self-Raman Nd:YVO4 lasers, we have achieved the output powers of 6.54 W and 5.12 W at 559 nm and 588 nm, respectively. For Nd:YVO4/KGW Raman lasers, the output powers at 559 nm and 589 nm have been increased to 9.1 W and 7.54 W, respectively. All lasers operate at a quasi-CW regime with the repetition rate 50 Hz and the duty cycle 50%.

Osteosarcoma is a highly malignant musculoskeletal tumor that is commonly noticed in adolescent children, young children, and elderly adults. Due to advances in surgery, chemotherapy and imaging technology, survival rates have improved to 70–80%, but chemical treatments do not enhance patient survival, in addition, the survival rate after chemical treatments is still low. The most obvious clinical feature of osteosarcoma is new bone formation, which is called “sun burst”. Estrogen receptor alpha (ERα) is an essential feature of osteogenesis and regulates cell growth in various tumors, including osteosarcoma. In this study, we sought to investigate the role of ERα in osteosarcoma and to determine if ERα can be used as a target to facilitate the chemosensitivity of osteosarcoma to current treatments. The growth rate of each cell clone was assayed by MTT and trypan blue cell counting, and cell cycle analysis was conducted by flow cytometry. Osteogenic differentiation was induced by osteogenic induction medium and quantified by ARS staining. The effects of ERα on the chemoresponse of OS cells treated with doxorubicin were evaluated by colony formation assay. Mechanistic studies were conducted by examining the levels of proteins by Western blot. The role of ERα on OS prognosis was investigated by an immunohistochemical analysis of OS tissue array. The results showed an impaired growth rate and a decreased osteogenesis ability in the ERα-silenced P53(+) OS cell line U2OS, but not in P53(−) SAOS2 cells, compared with the parental cell line. Cotreatment with tamoxifen, an estrogen receptor inhibitor, increased the sensitivity to doxorubicin, which decreased the colony formation of P53(+) U2OS cells. Cell cycle arrest in the S phase was observed in P53(+) U2OS cells cotreated with low doses of doxorubicin and tamoxifen, while increased levels of apoptosis factors indicated cell death. Moreover, patients with ER−/P53(+) U2OS showed better chemoresponse rates (necrosis rate &gt, 90%) and impaired tumor sizes, which were compatible with the findings of basic research. Taken together, ERα may be a potential target of the current treatments for osteosarcoma that can control tumor growth and improve chemosensitivity. In addition, the expression of ERα in osteosarcoma can be a prognostic factor to predict the response to chemotherapy.

Background The administration of an intra-articular injection (IAI) of tranexamic acid (TXA) has been demonstrated to be effective in reducing both blood loss and transfusion rate during total knee arthroplasty (TKA); however, few studies have reported the efficiency of a peri-articular injection (PAI) of TXA. We studied the efficiency of a PAI of TXA in reducing blood loss during TKA. Methods Fifty patients undergoing primary simultaneous bilateral TKA were enrolled in this retrospective study. The right knee received a PAI of 1 g of TXA (Group I), and the left knee received an IAI of 1 g of TXA (Group II). The clinical outcome measures were a change in blood loss from Hemovac drains and surgical time. Results The decrease in blood loss from the Hemovac was significantly lower in Group I (460.1 ± 36.79 vs. 576.0 ± 34.01, P Conclusions A PAI of TXA may reduce blood loss more efficiently than an IAI of TXA during TKA without increased complications such as surgical site infection, poor wound healing, skin necrosis, pulmonary embolism, and deep vein thrombosis.

Recycled autografts have been commonly used in biological reconstruction in conjunction with wide bone resection. Extracorporeal irradiation (ECIR) and freezing are the two major options for pretreating tumor-bearing autografts before transplant. This study, for the first time, compared the effects of these two techniques on bone morphogenetic protein (BMP)-2 activity. Bone tissue extracted from human femoral heads were treated through either ECIR at different doses (5000, 15,000, and 30,000 rad) or liquid nitrogen (LN) freezing for different durations (5, 10, and 15 min). The amount of BMP was analyzed through enzyme-linked immunosorbent assay (ELISA assay). Furthermore, we also used tandem mass spectrometry to analyze change of BMP-2 and BMP-7 expression after high dosage of irradiation (30,000 rad) and long-time of freezing (15 min). To directly evaluate the effect of ECIR or LN freezing treatment on the activity of BMP, commercial recombinant human BMP-2 (rhBMP-2) was added to the culture of human mesenchymal stem cells (hMSCs). The post-treatment activity of rhBMP-2 was quantitated by measuring the osteogenic differentiation of hMSCs with Alizarin Red S staining. Through Western blotting, the activation of the BMP signaling pathway by phospho-Smad antibodies was analyzed. Our results showed that post-treatment levels of BMP did not differ among the ECIR and LN freezing treatments in ELISA assay, but tandem mass spectrometry showed significantly lower expression of BMP-2 after 30,000 rad of irradiation. Both ECIR and freezing lowered the expression of regulatory factors involved in the BMP-activated signaling cascades and similar results were also observed in osteogenic differentiation of hMSCs. However, LN freezing preserved better bioactivity of rhBMP-2 whereas dosage-dependent declination was observed in ECIR groups. In conclusion, considering BMP-2 activity, LN freezing-treated autografts may result in a better osteoinduction outcomes than those treated using ECIR. Further investigation of the factors involved in bone formation is required.

BACKGROUND To evaluate a single surgeon's experience with minimally invasive total knee arthroplasty (MIS-TKA) and report the 9-year learning curve and trends in clinical outcomes based on assessment of surgical skills, radiographic alignments, and patient's function scores. METHODS This retrospective study included a total of 4107 knees from 3403 patients undergoing bilateral or unilateral MIS-TKA between March 2004 and February 2013. MIS-TKA was performed through a modified mini-midvastus approach. Postsurgical care regime was standardized for all patients. Data of consecutive 3-month intervals were collected and compared for changes of trends in outcomes over time, including tourniquet time, intraoperative complications, radiographic alignment, the Knee Society Score (KSS), and functional scores. RESULTS Significant increase in the number of cases undergoing MIS-TKA per 3-month interval over the study period was observed. As surgeon's experience increased over time, tourniquet time was decreased from an average of 70 minutes to approximately 35 minutes. A total of 65 (1.68%) intraoperative complications were recorded and the frequencies were in a significant decreasing trend. The rate of malalignment was in a decreasing trend and steady desired alignment (6°) was achieved at the 15th three-month interval. KSS and function scores increased from 87.4 to 91.5 and 92.6 to 96.8, respectively. CONCLUSION Although a surgeon may become competent with MIS-TKA and achieved the preliminary learning curve within one year, experience accumulation continuously improved technical proficiency in MIS-TKA. This study confirmed significant improvements in surgical skills, postoperative alignment, and patients' function over time.

Purpose:The aim of this study was to evaluate outcomes of internal fixation for displaced femoral neck fracture (FNF) between 50 and 60 years old. The patient and surgical factors for the failure were identified.Methods:We retrospectively reviewed the records of 102 displaced FNF patients between 50 and 60 years old (mean age 54.9 years) who had undergone internal fixation between 2005 and 2016. The minimum follow-up was 12 months. Primary end points included loss of reduction, non-union, and osteonecrosis of the femoral head (ONFH). Preoperative Pauwel’s angle, fixation timing and methods, reduction quality, removal of implant and medical comorbidities were analysed.Results:The overall failure rate was 44.1%. In multivariate logistic regression analysis, poor reduction quality (adjusted odds ratio [aOR] 4.38; 95% confidence interval [CI], 1.54–12.46) and internal fixation delayed more than 6 hours (aOR 3.24; 95% CI, 1.08–9.69) were risk factors for all causes of failure. In a stratified analysis, poor reduction quality (aOR 3.81; 95% CI, 1.11–13.04) and a history of alcohol dependency (aOR 4.91; 95% CI, 1.09–22.13) were risk factors for loss of reduction. Internal fixation delayed >6 hours (aOR 3.67; 95% CI, 1.05–12.77) and removal of implant (aOR 3.32; 95% CI, 1.02–10.77) were risk factors for ONFH.Conclusions:The outcome of internal fixation of displaced FNF in patients between 50 and 60 years old is suboptimal. The patient selection is important. Non-alcohol dependency lowered early failure. Implant retention reduced ONFH. Surgery within 6 hours and good quality of reduction yield better results.

In this work, the effect of surface self-nanocrystallization on low-temperature gas carburizing for AISI316L austenitic stainless steel has been studied. The surface ultrasonic rolling processing (SURP) was used to prepare nanostructured surface layers, and then the un-SURP and SURP samples were treated by LTGC at 470 °C for 10 h, 20 h and 30 h. In order to analyze the effect of surface self-nanocrystallization on low-temperature gas carburizing, optical microscopy (OM), atomic force microscope (AFM), scanning electron probe micro-analyzer (EPMA) and nano-indentation analyzer were used. The results show depth of SURP-induced plastic deformation layer was about 330 μm. Meanwhile, the surface hardness and elastic modulus were increased but the surface roughness decreased obviously after SURP. After low-temperature gas carburizing, according to the results of the thickness, carbon concentration, nano-hardness and elastic modulus of the carburized layer, the conclusion is that surface self-nanocrystallization carried by SURP has a negative effect on the low-temperature gas carburizing for AISI316L austenitic stainless steel and with the increase of carburizing time, the greater the adverse effect on carburizing.

Background Evidence about the risk of bleeding and thromboembolism because of aspirin mono-therapy in total knee arthroplasty (TKA) is scant. We wanted to validate the risks of bleeding and thromboembolism with continued aspirin mono-therapy in unilateral and simultaneous bilateral TKA. Methods We enrolled a series of 1655 patients who underwent unilateral or simultaneous bilateral TKA between December 2010 and December 2012. Drainage amount, postoperative hemoglobin level, change in hemoglobin, calculated blood loss, incidence and the amount of blood transfused, and the proportion of thromboembolic events were compared between patients who were and patients who were not on continued aspirin mono-therapy. Results Calculated blood loss (969.1 ± 324.9 vs. 904.0 ± 315.5 ml), transfusion amounts (1.3 ± 1.5 vs. 1.0 ± 1.3 IU), and percentage of transfused patients (53.0% vs. 40.2%) were higher in unilateral TKA patients on continued aspirin mono-therapy. Outcome parameters and the proportion of DVT between groups were not significantly different. One patient (0.3%) not on aspirin mono-therapy developed a pulmonary embolism, and two others (0.6%) had cerebrovascular events. Conclusion Despite the slightly higher risks of bleeding, continuing aspirin mono-therapy during TKA might be safe with low risks of perioperative cerebrovascular, cardiovascular, and venous thromboembolic events.

In the last few decades, biological reconstruction techniques have improved greatly for treating high-grade osteosarcoma patients. To conserve the limb, and its function the affected tumor-bearing bones have been treated using liquid nitrogen and irradiation processes that enable the removal of entire tumors from the bone, and these treated autografts can be reconstructed for the patients. Here, we focus on the expressions of the growth factor family proteins from the untreated and treated autografts that play a crucial role in bone union, remodeling, and regeneration. In this proteomic study, we identify several important cytoskeletal, transcriptional, and growth factor family proteins that showed substantially low levels in untreated autografts. Interestingly, these protein expressions were elevated after treating the tumor-bearing bones using liquid nitrogen and irradiation. Therefore, from our preliminary findings, we chose to determine the expressions of BMP2, TGF-Beta, and FGFR proteins by the target proteomics approach. Using a newly recruited validation set, we successfully validate the expressions of the selected proteins. Furthermore, the increased growth factor protein expression after treatment with liquid nitrogen may contribute to bone regeneration healing, assist in faster recovery, and reduce local recurrence and metastatic spread in high-grade sarcoma patients.

This retrospective, single-centre study compares the clinical and radiographic outcomes of limb reconstruction using recycled autografts to that using allografts. Patients with histopathologically verified high-grade osteosarcoma treated with wide bone resection and limb reconstruction using allografts or recycled autografts from January 1998 through December 2012 were retrospectively screened for enrolment eligibility. The final study cohort included 255 patients (allograft, 91; recycled autograft, 164). Data regarding post-operative complications, salvage treatment, and graft survival were collected. A modified International Society of Limb Salvage classification system was used to evaluate the radiographic findings. The time to graft–host union did not differ significantly between the two graft types. Patients receiving recycled autografts had fewer complications compared than did those receiving allografts (recycled autografts vs. allograft: structural failure, 4.3 vs. 13.2%; late infection, 2.4 vs. 7.7%; all p

The recycled autograft in biological reconstruction for osteosarcoma has satisfactory outcome. There are few studies about its efficacy in pathological fracture. The aim of the study is to compare the clinical results of recycled autograft to those of allograft in patients with high-grade osteosarcoma with pathological fracture. Between October 2010 and March 2018, 30 patients with osteosarcoma combining pathological fracture underwent biological reconstruction. Eleven patients received recycled autograft via extracorporeal irradiation or freezing nitrogen and nineteen patients restored bone defect via allograft to accomplish biological reconstruction. The mean follow-up was 58.1 months (range 12–120). The mean time to graft-host union of limbs reconstructed using recycled autografts and allografts was 17.45 ± 13.54 and 12.63 ± 12.62 months, respectively, with no significant difference observed between groups (p = 0.176). The five year probability of graft failure therefore did not significantly differ between groups (p = 0.245). The patient five year survival rate was similar (p = 0.229). Post-operative complication rates were similar for the recycled autograft group (54.5%) and the allograft group (57.9%). The recycled autograft showed comparable clinical results, graft-host union time, complication rate, and graft survival to allograft in biological reconstruction for osteosarcoma with pathological fracture.

Background Coronavirus disease 2019 (COVID-19) posed a major threat to the clinical practice of orthopedic surgeons, especially in the emergency department. We aim to present: (1) the criteria established by the Surgery Management Committee of Taipei Veterans General Hospital in response to COVID-19 and (2) the impact of COVID-19 screening on orthopedic trauma patients in the emergency department. Methods From April 1 to April 30, 2020, all orthopedic trauma patients in the emergency department were screened for COVID-19 if they fulfilled any of the following: (1) travel from abroad within 14 days, (2) high-risk occupation, (3) contact or cluster history with a COVID-19-positive patient, and (4) any associated symptom, including fever up to 38°C, cough, sore throat, rhinorrhea, loss of taste or smell, muscle soreness, malaise, or shortness of breath. We recorded details on the injury, fever, management, and associated outcomes. Results Of the 163 orthopedic trauma patients presenting to the emergency department, 24 were screened for COVID-19; of these, 22 received surgery. Sixty-two patients received surgery without screening for COVID-19. Fever was the most common reason to screen for COVID-19 (N = 20; 83.3%). No patients were COVID-19 positive. Screened patients had a significantly longer mean interval from presentation to the emergency department to surgery (2.7 ± 2.5 vs. 1.5 ± 0.8 days, p = 0.037). Of the 20 patients screened because of fever, the focus was not identified in 12 (60.0%) patients. The other eight had urinary tract infection (N = 6; 27.2%), septic hip (N = 1; 4.6%), and concomitant pneumonia and urinary tract infection (N = 1; 4.6%). The mean duration of fever and hospital stay was 4.3 ± 4.6 and 8.7 ± 4.9 days, respectively. There were no thromboembolic events, surgical complications, or in-hospital mortality. Conclusion We developed safe and reliable screening criteria for this COVID-19 pandemic. The delay in surgery was reasonable and did not adversely affect in-patient outcomes.

Giant cell tumors of bone (GCT) are benign tumors that show a locally aggressive nature and affect bones&rsquo, architecture. Recently, cryoablation and irradiation treatments have shown promising results in GCT patients with faster recovery and less recurrence and metastasis. Therefore, it became a gold standard surgical treatment for patients. Hence, we have compared GCT-untreated, cryoablation, and irradiation-treated samples to identify protein alterations using high-frequency liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Our label-free quantification analysis revealed a total of 107 proteins (p &lt, 0.01) with 26 up-regulated (&lt, 2-folds to 5-fold), and 81 down-regulated (&gt, 0.1 to 0.5 folds) proteins were identified from GCT-untreated and treated groups. Based on pathway analysis, most of the identified up-regulated proteins involved in critical metabolic functions associated with tumor proliferation, angiogenesis, and metastasis. On the other hand, the down-regulated proteins involved in glycolysis, tumor microenvironment, and apoptosis. The observed higher expressions of matrix metalloproteinase 9 (MMP9) and TGF-beta in the GCT-untreated group associated with bones&rsquo, osteolytic process. Interestingly, both the proteins showed reduced expressions after cryoablation treatment, and contrast expressions identified in the irradiation treated group. Therefore, these expressions were confirmed by immunoblot analysis. In addition to these, several glycolytic enzymes, immune markers, extracellular matrix (ECM), and heat shock proteins showed adverse expressions in the GCT-untreated group were identified with favorable regulations after treatment. Therefore, the identified expression profiles will provide a better picture of treatment efficacy and effect on the molecular environment of GCT.

Background Administration of an intra-muscular injection (IMI) of tranexamic acid (TXA) had been demonstrated to be effective in reducing both blood loss and the transfusion rate during total knee arthroplasty (TKA). However, few studies have reported on the efficiency of IMI of TXA. We studied the efficiency of IMI of TXA to reduce blood loss during TKA. Methods In this prospective study, 50 patients undergoing primary simultaneous bilateral TKA were enrolled. The right knee received a IMI of 1 g of TXA (Group I), and the left knee received an intra-articular injection (IAI) of 1 g of TXA (Group II). The clinical outcome measures were a change in hemoglobin levels, blood loss from Hemovac, and number of allogeneic blood units. Results Compared with Group II, the decrease in blood loss from Hemovac was significantly less for Group I (460.1 ± 36.79 vs. 576.0 ± 34.01, P

Background Cementation of a highly cross-linked polyethylene liner into a well-fixed acetabular shell provided a good durability for liner wear. However, its efficacy in treating recurrent instability due to malposition cup is less reported. The aim of this study is to evaluate the outcome of this surgical technique to treat hip instability. Methods From 2009 to 2019, we have identified 38 patients who had been surgically treated for recurrent instability, including cementation liner (N=20) and revision cup (N=18) procedures. Patients were followed for a mean of 45.66 months. We have recorded and analyzed all causes of implant failure including recurrent instability. Clinical outcomes were assessed including complication and Harris Hip Score (HHS) preoperatively and at the latest follow-up. Results Revision-free survivorship for any cause was 95.0% at 1 year, and 84.4 % at 5 years in cementation liner group and 88.9% at 1 year and 5 years in revision cup group. Mean Harris hip score improved from 48.3 points preoperatively to 79.5 points at the last follow-up in cementation liner group and mean HHS improved from 43.3 points preoperatively to 77.2 points in revision cup group. There were two implant failures in each group, including One is due to persistent hip instability and the other is due to periprosthetic joint infection in the cementation liner group and two implant failure are due to persistent hip instability in the revision cup group. Functional scores and implant survival were similar in both groups. Conclusion We demonstrated that orientation correction via the cementation of the polyethylene liner into well-fixed acetabular shell is a promising option to treat and prevent instability.

Background Bone tumors are often treated with intralesional curettage. High-speed burring, an adjuvant therapy, was performed to maximize the tumor cell killing; however, tumor recurrence might still occur, which may be caused by residual tumor or local tumor spread during surgery. Methods A porcine cadaver (femur) was utilized to determine whether the use of a high-speed burr causes bone cement spray. To mimic residual tumor after curettage, luminescent cement was smeared on two locations of the bone cavity, the wall and the bottom. The cavity in the femoral bone was then placed in the middle of a sheet of drawing paper featuring 10 cm, 20 cm, and 30 cm concentric circles. The luminescent cement was then burred totally with a high-speed burr. Results The intensity of the area in the wall in circle I was 72.6% ± 5.8%; within circle II, it was 22.1% ± 4.2%; and within circle III, it was 5.4% ± 1.5%. The intensity of the area within the bottom of the femoral bone within circle I was 66.5% ± 6.1%, within circle II was 28.1 ± 4.8%, and within circle III, it was 5.4% ± 1.4%. The amount of luminescent cement seeding decreased with distance, but there was no difference while burring at different locations of the bone cavity. Under the handpiece cover, a greater amount of cement spray was retained in circle I during burring of the cement in the bottom of the cavity and less was sprayed out in circle III. Conclusions High-speed burring may cause explosive bone cement spray, which could extend to 20 cm. The intensities of spray did not decrease, even when the handpiece cover was used. The wide range of bone cement spray caused by high-speed burr was inspected in this pilot study, which may lead to tumor seeding. Level of evidence Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Background Chondrosarcoma is the second most common primary sarcoma of the bone. Surgery remains the gold standard for treatment due to chemotherapy and radiotherapy resistance in chondrosarcoma. The main aim of our study was to analyze patients with primary chondrosarcoma of the bone who were treated in a single tumor center. Our study team identified the prognostic factors for overall survival, metastasis-free survival, and recurrence-free survival. Methods From 1998 to 2012, 55 consecutive patients were treated surgically. All patients were followed for local recurrence or distant metastasis. Uni- and multivariate analyses were performed for overall, metastasis-free, and recurrence-free survival. Results Local recurrence developed in 29 of the 55 patients (52.7%). Recurrence-free survival in the multivariate analysis showed a significant association with the surgical margin, and high-grade lesions were an independent factor for local recurrence. In total, 11 patients died of the disease in the study, and the 5- and 10-year survival rates were 84.4% and 78.1%, respectively. The tumor grade and local recurrence were significant factors in the univariate analysis but were insignificant in the Cox regression with time-dependent covariates (p = 0.327 and p = 0.82, respectively). The development of distant metastasis was a significant poor prognostic factor in both the uni- and multivariate analyses. Conclusion Chondrosarcoma of the bone is a disease with surgery-dependent outcomes; but, however, patients often develop subsequent recurrence of the disease. The surgical margins were statistically associated with the risk of subsequent local recurrence but did not predict survival. The development of distant metastases was an independent prognostic factor for poor survival.

Biological reconstruction of allografts and recycled autografts have been widely implemented in high-grade osteogenic sarcoma. For treating tumor-bearing autografts, extracorporeal irradiation (ECIR) and liquid nitrogen (LN) freezing techniques are being used worldwide as a gold standard treatment procedure. Both the methods aim to eradicate the tumor cells from the local recurrence and restore the limb function. Therefore, it is essential and crucial to find, and compare the alterations at molecular and physiological levels of the treated and untreated OGS recycled autografts to obtain valuable clinical information for better clinical practice. Thus, we aimed to investigate the significantly expressed altered proteins from ECIR-and cryotherapy/freezing- treated OGS (n = 12) were compared to untreated OGS (n = 12) samples using LC-ESI-MS/MS analysis, and the selected proteins from this protein panel were verified using immunoblot analysis. From our comparative proteomic analysis identified a total of 131 differentially expressed proteins (DEPs) from OGS. Among these, 91 proteins were up-regulated (2.5 to 3.5-folds), and 40 proteins were down-regulated (0.2 to 0.5 folds) (p

Freezing nitrogen ethanol composite (FNEC) showed effective cryoablative ability for bone tumor ex vivo and in vivo comparable to liquid nitrogen (LN). We therefore wished to compare the radiant cooling damage of the surrounding tissue between FNEC and LN. The evaluation of the radiant cooling damage was demonstrated human bone xenograft transplantation (HXT) in a mouse model. Characterizations and quantifications of the damaging effects on morphologic features and apoptosis of the cryoablative surrounding bone tissue, muscle and epidermal layer of skin were compared. The radiant cooled damaging effects including epidermal rupture, hair follicle atrophy, dermis and subcutaneous crystal vacuolation of skin were significantly greater in LN than FNEC. Muscular apoptosis, structural shrinkage and bone cellular apoptosis were supposedly 15%-33% destroying degrees of LN more than FNEC. We concluded that FNEC is an innovative cryogenic material, and it could cause less cryoablative damage to surrounding normal tissue than LN. The findings might support the safety of FNEC being applied in clinical cryoablation therapy.

Background: Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor that typically affects young patients. Similar to other soft tissue sarcomas, it has high pulmonary metastasis ability, whereas compared with other soft tissue sarcomas, it has high brain metastasis ability. Because of the rarity of the disease, most studies on ASPS have been case reports and small series studies. Method: We performed a retrospective study to evaluate the clinical and pathological features and oncological results in a consecutive series of patients with localized or metastatic ASPS treated at our institute between 1994 and 2014. Demographics, location, severity of disease, treatment provided, progression-free survival, and overall survival were evaluated. Results: A total of 13 patients were investigated. The most common locations of primary tumor were the thigh (n = 6, 47%), followed by the flank (n = 3, 23%), forearm (n = 2, 15%), and calf (n = 2, 15%). Three patients were initially diagnosed as having hemangiomas elsewhere. These patients received unplanned intralesional excision. All the patients received wide tumor resection at our institute. Over the average follow-up period of 80.5 months (range: 36–133 months), the 5-year overall survival rate was 67.5%. Four patients were continuously disease free (31%), six were living with disease (46%), and three died of disease (23%). Of nine patients who presented with distant pulmonary metastasis, two had bony and brain metastases. The 5-year survival rate was 66.7% in patients who received chemotherapy and those who did not (p = 0.941). Conclusion: The treatment strategy for ASPS is wide resection, and postoperative chemotherapy may be crucial for long-term survival. In addition, this type of tumor has a high distant metastasis rate at the time of diagnosis, particularly in the lungs and brain. Keywords: Alveolar soft part sarcoma, Chemotherapy, Metastasis, Surgery

Background: Subsidence remains a common complication after revision hip arthroplasty which may lead to prolonged weight-bearing restrictions, leg-length discrepancies or considerable loss of function. We evaluated the effectiveness of cement augmentation in the proximal femoral metaphysis during a revision of femoral components to prevent post-operative stem subsidence. Methods: Forty patients were enrolled. Follow-up averaged 67.7 months (range: 24–149). Twenty-seven patients had a Paprosky type II defect and 13 had a type IIIa defect. All revision hip arthroplasty used a cementless, cylindrical, non-modular cobalt–chromium stem. The defect in the metaphysis was filled with antibiotic-loaded bone cement. Thirteen patients who had undergone stem revision only was allowed to walk immediately without weight-bearing restrictions. Twenty-seven patients who had undergone revision total hip arthroplasty was allowed partial weight-bearing within 6 weeks after surgery in the consideration of acetabular reconstruction. Results: Three patients (7.5%) had post-surgery stem subsidences of three mm, five mm, and 10 mm, respectively, at three, one, and 14 months. There were no acute surgical site infections. There were three femoral stem failures: two delayed infections and one periprosthetic Vancouver B2 fracture. Both five- and 10-year survivorships of the femoral implant were 90.1%. Conclusion: An adequate length of the scratch-fit segment and diaphyseal ingrowth remain of paramount importance when revising femoral components. To fill metaphyseal bone defects with antibiotic-loaded bone cement may be an alternative method in dealing with proximal femoral bone loss during a femoral revision. Keywords: Bone defect, Cement augmentation, Femur, Revision hip arthroplasty, Subsidence

Allogeneic bone grafts are a promising material for bone implantation due to reduced operative trauma, reduced blood loss, and no donor-site morbidity. Although human decellularized allogeneic bone (hDCB) can be used to fill bone defects, the research of revitalizing hDCB blocks with human mesenchymal stem cells (hMSCs) for osteochondral regeneration is missing. The hMSCs derived from bone marrow, adipose tissue, and Wharton’s jelly (BMMSCs, ADMSCs, and UMSCs, respectively) are potential candidates for bone regeneration. This study characterized the potential of hDCB as a scaffold for osteogenesis and chondrogenesis of BMMSCs, ADMSCs, and UMSCs. The pore sizes and mechanical strength of hDCB were characterized. Cell survival and adhesion of hMSCs were investigated using MTT assay and F-actin staining. Alizarin Red S and Safranin O staining were conducted to demonstrate calcium deposition and proteoglycan production of hMSCs after osteogenic and chondrogenic differentiation, respectively. A RT-qPCR was performed to analyze the expression levels of osteogenic and chondrogenic markers in hMSCs. Results indicated that BMMSCs and ADMSCs exhibited higher osteogenic potential than UMSCs. Furthermore, ADMSCs and UMSCs had higher chondrogenic potential than BMMSCs. This study demonstrated that chondrogenic ADMSCs- or UMSCs-seeded hDCB might be potential osteochondral constructs for osteochondral regeneration.

After wide excision of proximal humeral bony malignancy, prognosis-based reconstruction was performed at Taipei Veterans General Hospital. Bone prosthesis composite (BPC) was carried out among patients with a favored prognosis, while cement-spacer prosthesis composite (CSPC) was preserved for patients with poor prognosis. The aim of our study is to compare the clinical outcomes between the BPC and CSPC reconstruction procedures. From January 2000 to December 2014, we retrospectively reviewed the clinical outcomes of 34 patients who underwent shoulder hemiarthroplasty following wide excision of a malignant lesion of the proximal humerus, 15 of whom were treated with a BPC reconstruction and 19 cases were treated with a CSPC reconstruction. The mean postoperative follow-up was 51.9 months for the BPC group and 29.0 months for the CSPC group. At the end of the study, four patients (two in the BPC group and two in the CSPC group) developed local recurrence. Thirteen patients (1 in the BPC group and 12 in the CSPC group) had died of disease progression. The postoperative visual analogue scale score of BPC and CSPC groups was similar (P = 0.262). Functional outcome, measured using the Musculoskeletal Tumor Society score and shoulder range of motion, favored the BPC procedure (P

Backgroud/Purpose Most patients who undergo two-stage exchange arthroplasty surgery for total knee arthroplasty prosthetic joint infection (TKA-PJI) receive a six-week course of systemic antibiotic treatment after the first stage procedure. However, the optimal duration of therapy has not been conclusively determined. Methods We included 64 patients with periprosthetic knee infection who had undergone two-stage exchange arthroplasty. Between March 2003 and December 2009, 21 patients were given a short-course (less than 1 week) antibiotic treatment, and 43 were given a standard-course (4–6 weeks) treatment during the interim period. We compared length of hospital stay, duration of intravenous and overall systemic antibiotic treatments, and rate of recurrent periprosthetic knee infection between groups. Results Short-course antibiotic treatment was associated with a shorter hospital stay and a shorter duration of intravenous and systemic antibiotic treatment. Implant survival regarding re-resection arthroplasty and chronic oral antibiotic suppression as primary endpoints was not significant different statistically between two groups (p = 0.317). The 1-year implant survival rates were 91.7% in the short-course group and 89.8% in the standard-course group. The 5-year implant survival rates were 85.2% and 74.0%, respectively. Conclusion After the first stage of resection arthroplasty for a two-stage exchange arthroplasty, a short course of antibiotic treatment had similar implant survival rates in comparison to the standard 6-week course. With radical debridement combined with an antibiotic-loaded cement spacer along with serial monitoring of the patient, a short course antibiotic treatment may be adequate in patients with TKA-PJI.

Three-dimensional (3D) printing technology can generate objects in almost any shape and geometry. This technique also has clinical applications, such as the fabrication of specific devices based on a patient's anatomy. A demonstration study is presented of a 54-year-old man who needed a thermoplastic splint to limit arm movement while a dehisced left shoulder wound healed. The patient's upper extremity was scanned using the appropriate noncontact scanner and 3D technology software, and the polylactic acid splint was printed over the course of 66 hours. This patient-specific splint was worn during the day, and after 2 weeks the wound was healed sufficiently to permit hospital discharge. Creation of an individualized splint is one of many potential medical uses of 3D technology. Although the lengthy printing time imposes limitations, the implications for practice are positive.

BACKGROUND: Immediately recycling the resected bone segment in a biologic limb salvage reconstruction is an option after wide resection of bone. Intraoperative extracorporeal irradiation and freezing are the two major tumor-killing techniques applied on the fresh tumor-bearing autografts. However, graft-derived tumor recurrence and complications are concerns affecting graft survival. QUESTIONS/PURPOSES: We therefore asked: (1) Is there a difference in the proportion of patients achieving union by 18 months after surgery between the groups with extracorporeal-irradiated autografts and frozen-treated autografts? (2) Is there any difference in the frequency of graft-related complications for patients receiving either an extracorporeal-irradiated or a frozen-treated autograft? (3) Is there a difference between the techniques in terms of graft-derived recurrence? (4) Are there differences in failure-free grafts, and limb and overall survivorship between autografts treated by extracorporeal irradiation or by freezing? METHODS: During the study period we treated a total of 333 patients with high-grade osteosarcoma. One hundred sixty-nine patients were excluded. Overall, 79 of the enrolled 164 patients received recycled autografts treated with extracorporeal irradiation whereas the other 85 received frozen-treated autografts. The mean followup was 82 ± 54 months for the extracorporeal irradiation group and 70 ± 25 months for the frozen autograft group, and one patient was lost to followup. Complications and graft failure (revision required for primary graft removal) were characterized by adapting the International Society of Limb Society (ISOLS) system modified for inclusion of biologic and expandable reconstruction. The primary study endpoints were the proportion of patients in each group who achieved radiographic union, and had an ISOLS grade of fair or good host graft fusion at 6, 9, 12, and 18 months after surgery. Five-year survival data for graft failure and limb amputation were analyzed by a cumulative incidence function regression model whereas the Kaplan-Meier function was used to test the 5-year overall survival rate between the two techniques. RESULTS: With the numbers available, no differences were found in the accumulated proportion of patients achieving union between the groups at 6, 9, 12, and 18 months. Radiographic evaluation did not show differences in the average scores of compared criteria. However in the subchondral bone subcriterion, more patients receiving frozen-treated autografts had higher scores (p = 0.03). Complications leading to a second surgery were not different between extracorporeal irradiation and frozen autografts in aspects of soft tissue failure (Type 1B), nonunion (Type 2B), structural failure (Type 3A and Type 3B), or infection (Type 4A and Type 4B). No graft-originating tumor recurrence was found and there was no difference in Type 5A tumor progression originating from soft tissue in the groups (odds ratio, 0.8; 95% CI, 0.3-2.1; p = 0.7). Neither group showed a difference in the cumulative incidence for graft failure and limb amputation. Five-year overall survival rates were 83% and 84% (p = 0.69) for extracorporeal-irradiated and frozen autografts respectively. A decrease in survivorship was seen at 50 to 100 months after surgery for the extracorporeal irradiation group. CONCLUSION: We segregated the ISOLS criteria evaluating the graft-mediated tumor progression into host- or graft-derived complications (Types 5B and 5C) in this study. With the available data, there was no difference in the incidence of tumor recurrence derived from irradiation- or frozen-treated autografts. Ongoing evaluations comparing 10-year survivorship for both groups will be helpful to elucidate the possible difference found after 100 months. LEVEL OF EVIDENCE LEVEL: III, therapeutic study

Intraoperative assessment of valgus–varus stability is crucial for choosing articular surfaces with different levels of constraint. Legacy constrained condylar knee (CCK) prostheses are readily available to assemble and use with a CCK articular surface or a posterior stabilized (PS) articular surface in revision knee arthroplasty surgeries. We wanted to validate outcomes of revision total knee arthroplasty (TKA) using legacy CCK prostheses combined with a PS articular surface. Thirty-seven patients were enrolled and followed up for more than 2 years. Range of motion (ROM), the Knee Society score (KSS), the Knee Society functional score (KSS-F), and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to evaluate outcomes. Follow-up was a mean of 86.5 months (range: 28–152 months). The mean age of the participants was 69.8 years (range: 31–86 years). The mean ROM was 110.5 degrees, the KSS was 86.2 points, the KSS-F was 68.3 points, and the WOMAC score was 22.6 points. Seven participants had implant failures: five because of delayed infections and two because of posterior dislocations. In conclusion, revision TKA using a CCK prosthesis combined with a PS articular surface might provide satisfactory mid-term outcomes. Delayed infection was the most common cause of implant failure. Dislocation might occur in middle-old or older patients despite careful intraoperative examination of valgus–varus stability, extension–flexion gap balancing, and signs of recurvatum.