Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study.

OBJECTIVES AND METHODS: With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them. RESULTS: Lower eBMD were observed in patients with PsA than in controls in both model0 (ß-coefficient=-0.014, p=0.0006) and model1 (ß-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (ß-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. CONCLUSIONS: The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

Development and proposal of a scoring system for giant cell tumour of the bone around the knee.

PURPOSE: The purpose of this study was to provide the surgeons with effective and reliable guidelines for surgical decision-making by establishing a scoring system for giant cell tumour (GCTSS) based on evidence and expert opinion. METHODS: The modified Delphi technique and analytic hierarchy process were used to establish the GCTSS. The GCTSS was defined and classified based on different surgical methods using data from 207 patients collected retrospectively between October 2003 and December 2014. Finally, prospective data of 40 patients between December 2014 and October 2015 were used to analyze concordance between score categorization and experts' consensus on surgical procedure. RESULTS: A novel GCTSS included pathological fracture, cortical bone destruction, tumour size, and articular surface involved. The total scores ranged from 1 to 12 points. The strategy for each patient was decided: a total score of 1-4 suggested intralesional curettage alone for excellent post-operative function; 5-9 points indicated intralesional curettage with internal fixation for less surgery-related complications; and 10-12 points indicated prosthesis replacement for long-term local control. The κ-statistic for the predictive validity of total score was 0.611. The κ coefficient of each group represented moderate or substantial agreement, which was acceptable. The intraclass correlation coefficient for inter- and intra-observer reliability of total score was 0.831 and 0.740, respectively. CONCLUSIONS: The novel GCTSS is a comprehensive scoring system with content validity that can aid surgeons in assessing the aggressiveness or severity of giant cell tumour and might become a prognostic tool for surgical decision-making.

[Extremely low frequency electromagnetic field induces apoptosis of osteosarcoma cells via oxidative stress].

OBJECTIVE: To investigate the effects of extremely low frequency electromagnetic field (ELF-EMF) on human osteosarcoma cells and its mechanisms. METHODS: Human osteosarcoma MG-63 cells were exposed to 50 Hz,1 mT ELF-EMF for 1, 2 and 3 h in vitro, with or without pretreatment by reactive oxygen species (ROS) inhibitor N acetylcysteine (NAC) or p38MAPK inhibitor SB203580. The proliferation of MG-63 cells was determined by MTT method; the apoptosis rate and ROS level in MG-63 cells were detected by flow cytometry. The expression of p38MAPK in MG-63 cells was determined by Western blotting. RESULTS: ELF-EMF decreased the viability of MG-63 cells, inhibited cell growth, induced cell apoptosis and increased the level of ROS significantly. The apoptosis rate declined significantly after treatment with ROS inhibitor NAC or p38MAPK inhibitor SB203580. After exposure to ELF-EMF, p38MAPK in MG-63 cells was activated, and the phosphorylation level was also inhibited after treatment with NAC. CONCLUSION: ELF-EMF can induce the apoptosis of MG-63 cells. Increased ROS and p38MAPK activation may be involved in the mechanism.

Investigating the synergy of Shikonin and Valproic acid in inducing apoptosis of osteosarcoma cells via ROS-mediated EGR1 expression.

BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumour with a poor prognosis. Shikonin (SHK) is derived from the traditional Chinese medicine Lithospermum that has been extensively studied for its notable anti-tumour effects, including for osteosarcoma. However, its application has certain limitations. Valproic acid (VPA) is a histone deacetylase inhibitor (HDACI) that has recently been employed as an adjunctive therapeutic agent that allows chromatin to assume a more relaxed state, thereby enhancing anti-tumour efficacy. PURPOSE: This study was aimed to investigate the synergistic anti-tumour efficacy of SHK in combination with VPA and elucidate its underlying mechanism. METHODS/STUDY DESIGN: CCK-8 assays were utilized to calculate the combination index. Additional assays, including colony formation, acridine orange/ethidium bromide double fluorescent staining, and flow cytometry, were employed to evaluate the effects on osteosarcoma cells. Wound healing and transwell assays were utilized to assess cell mobility. RNA sequencing, PCR, and Western blot analyses were conducted to uncover the underlying mechanism. Rescue experiments were performed to validate the mechanism of apoptotic induction. The impact of SHK and VPA combination treatment on primary osteosarcoma cells was also assessed. Finally, in vivo experiments were conducted to validate its anti-tumour effects and mechanism. RESULTS: The combination of SHK and VPA synergistically inhibited the proliferation and migration of osteosarcoma cells in vitro and induced apoptosis in these cells. Through a comprehensive analysis involving RNA sequencing, PCR, Western blot, and rescue experiments, we have substantiated our hypothesis that the combination of SHK and VPA induced apoptosis via the ROS-EGR1-Bax axis. Importantly, our in vivo experiments corroborated these findings, demonstrating the potential of the SHK and VPA combination as a promising therapeutic approach for osteosarcoma. CONCLUSION: The combination of SHK and VPA exerted an anti-tumour effect by inducing apoptosis through the ROS-EGR1-Bax pathway. Repurposing the old drug VPA demonstrated its effectiveness as an adjunctive therapeutic agent for SHK, enhancing its anti-tumour efficacy and revealing its potential value. Furthermore, our study expanded the application of natural compounds in the anti-tumour field and overcame some of their limitations through combination therapy. Finally, we enhanced the understanding of the mechanistic pathways linking reactive oxygen species (ROS) accumulation and apoptosis in osteosarcoma cells. Additionally, we elucidated the role of EGR1 in osteosarcoma cells, offering novel strategies and concepts for the treatment of osteosarcoma.

MAKO robotic assisted total hip replacement (THR) for patients with fused hips.

BACKGROUND: Previous articles about MAKO robotic-assisted total hip replacement (THR) were mainly in patients with comparatively normal anatomy. METHODS: From July 2020 to June 2021, we performed MAKO robotic-assisted THR in three hip-fused patients. We assessed the accuracy of prostheses implantation, collected clinical data, and discussed the value of this technique in this kind of patients. RESULT: All three patients achieved good leg length and prostheses position. A patient got femoral artery injury during the surgery. Moreover, she developed a thrombus. All three patients got acceptable Visual Analogue Scale scores and function recovery 6 months later. CONCLUSION: MAKO robotic-assisted THR achieved excellent prosthesis position in hip fused patients. More cases are needed to confirm this advantage. The function recovery was acceptable. Caution should be paid to protect the surrounding abnormal arteries, especially in a limited surgical field.

[Resection pseudoarthrosis for pelvic malignant tumors around acetabular].

OBJECTIVE: To discuss the resection pseudoarthrosis for pelvic malignant tumors around acetabular. METHODS: From May 1997 to June 2005, 25 patients with malignant tumors around acetabular were treated surgically with resection pseudoarthrosis. The series comprised 15 males and 10 females with an average age of 42 years old (range from 16 to 75 years old). There were 4 osteosarcomas, 12 chondrosarcomas, 1 Ewing's sarcoma, 1 neuroectodermal tumor, 1 myeloma, 1 malignant fibrohistiocytoma, 2 synovial sarcomas, and 3 metastases. Pseudoarthrosis was performed after resection of pelvic malignant tumors around acetabular. The affected side was protected postoperatively by skin traction with 2 - 3 kg weight for 6 to 8 weeks. After then, the patients walked gradually with a cane. RESULTS: Among 25 patients, 6 had complications (24%). At a follow-up ranging from 3 to 10 years, 11 patients died of lung metastases, 2 relapsed, 12 remained alive free of disease. There was an average crispation of 5 cm (range from 2.5 to 7.5 cm). The patients were functionally evaluated according to Enneking's MSTS criteria in 1993. The average MSTS functional score was 17 points (12 to 19 points). After 3 months postoperative, the patients could sit normally, walk with a cane, and even walk limpingly without cane. CONCLUSIONS: Resection pseudoarthrosis for pelvic malignant tumors around acetabular results in good clinical results at the time of mid-term and long-term follow-up. And pseudoarthrosis is advisable especially for patients with malignant highly tumors around acetabular, poor soft tissue reconstruction condition, high risk for infection, poor economy.

Lateral Fracture-Dislocation of the Calcaneus: Case Reports and a Systematic Review.

OBJECTIVE: To report a case series of calcaneal fracture-dislocations, which have not been described previously in China, and to provide a systematic review to explore the clinic manifestations, methods for diagnoses, and treatments. METHODS: Between January 2018 and December 2019, 4 patients (4 men; average age, 33.0 ± 16.67 years; range, 15-50 years) were diagnosed with fracture-dislocation of the calcaneus and treated by surgery. We also reviewed published cases and studies of calcaneal fracture-dislocations through the databases of PubMed and Web of Science between January 1977 and December 2019. RESULTS: Between January 2018 and December 2019, 4 cases were identified as calcaneal fracture-dislocations in our hospital. The main clinical manifestations include hindfoot pain, swelling, and deformity. The diagnoses were confirmed via radiographic examination. Two patients underwent open reduction and internal fixation (ORIF) and two were treated with a minimally invasive approach. Diagnosis had been missed in one patient and, consequently, presented with early signs of post-traumatic arthritis, which may require extra subtalar arthrodesis in the future. Two patients were diagnosed inaccurately but achieved satisfactory outcomes through open reduction and internal fixation. The average follow-up period was 9.75 ± 5.19 months. Except for the 1 misdiagnosed patient, the other 3 patients showed functional improvement. Only 23 fracture-dislocations of calcaneus cases were reported in the literature between January 1977 and December 2019. There were 15 Sanders type II fractures (65.22%) and 7 (30.43%) Sanders type III fractures, and there was 1 grade II open calcaneal fracture. Among them, 1 was a medial dislocation and 2 were "joint-elevation" dislocations; the rest of them (20/23, 86.96%) were lateral dislocations. A total of 11 patients (47.83%) exhibited the double-density sign, and varus tilt of the talus was revealed on plain radiographs for 9 patients (39.13%). Increased Bohler's angle was evident in lateral X-ray films for 2 patients (2/23, 8.70%). A total of 21 cases (86.96%) were treated with surgical intervention and achieved satisfactory outcomes. Only 1 patient was treated with external fixation. Another 2 patients were treated conservatively and had poor clinic outcomes. CONCLUSION: Calcaneal fracture-dislocation is a rare injury that is challenging to treat. Clinical manifestations such as fibular tendon dislocation, the double-density sign on profile radiography, and abnormal talar tilt in the distal talofibular joint are important signs that may indicate this rare injury pattern. Timely surgical intervention is essential for satisfactory clinic outcomes. Orthopaedic surgeons should be aware of this uncommon injury to avoid misdiagnosis or inappropriate treatment.

Application of Immune Infiltration Signature and Machine Learning Model in the Differential Diagnosis and Prognosis of Bone-Related Malignancies.

Bone-related malignancies, such as osteosarcoma, Ewing's sarcoma, multiple myeloma, and cancer bone metastases have similar histological context, but they are distinct in origin and biological behavior. We hypothesize that a distinct immune infiltrative microenvironment exists in these four most common malignant bone-associated tumors and can be used for tumor diagnosis and patient prognosis. After sample cleaning, data integration, and batch effect removal, we used 22 publicly available datasets to draw out the tumor immune microenvironment using the ssGSEA algorithm. The diagnostic model was developed using the random forest. Further statistical analysis of the immune microenvironment and clinical data of patients with osteosarcoma and Ewing's sarcoma was carried out. The results suggested significant differences in the microenvironment of bone-related tumors, and the diagnostic accuracy of the model was higher than 97%. Also, high infiltration of multiple immune cells in Ewing's sarcoma was suggestive of poor patient prognosis. Meanwhile, increased infiltration of macrophages and B cells suggested a better prognosis for patients with osteosarcoma, and effector memory CD8 T cells and type 2 T helper cells correlated with patients' chemotherapy responsiveness and tumor metastasis. Our study revealed that the random forest diagnostic model based on immune infiltration can accurately perform the differential diagnosis of bone-related malignancies. The immune microenvironment of osteosarcoma and Ewing's sarcoma has an important impact on patient prognosis. Suppressing the highly inflammatory environment of Ewing's sarcoma and promoting macrophage and B cell infiltration may have good potential to be a novel adjuvant treatment option for osteosarcoma and Ewing's sarcoma.

A Delta-radiomics model for preoperative evaluation of Neoadjuvant chemotherapy response in high-grade osteosarcoma.

BACKGROUND: The difficulty of assessment of neoadjuvant chemotherapeutic response preoperatively may hinder personalized-medicine strategies that depend on the results from pathological examination. METHODS: A total of 191 patients with high-grade osteosarcoma (HOS) were enrolled retrospectively from November 2013 to November 2017 and received neoadjuvant chemotherapy (NCT). A cutoff time of November 2016 was used to divide the training set and validation set. All patients underwent diagnostic CTs before and after chemotherapy. By quantifying the tumor regions on the CT images before and after NCT, 540 delta-radiomic features were calculated. The interclass correlation coefficients for segmentations of inter/intra-observers and feature pair-wise correlation coefficients (Pearson) were used for robust feature selection. A delta-radiomics signature was constructed using the lasso algorithm based on the training set. Radiomics signatures built from single-phase CT were constructed for comparison purpose. A radiomics nomogram was then developed from the multivariate logistic regression model by combining independent clinical factors and the delta-radiomics signature. The prediction performance was assessed using area under the ROC curve (AUC), calibration curves and decision curve analysis (DCA). RESULTS: The delta-radiomics signature showed higher AUC than single-CT based radiomics signatures in both training and validation cohorts. The delta-radiomics signature, consisting of 8 selected features, showed significant differences between the pathologic good response (pGR) (necrosis fraction ≥90%) group and the non-pGR (necrosis fraction < 90%) group (P < 0.0001, in both training and validation sets). The delta-radiomics nomogram, which consisted of the delta-radiomics signature and new pulmonary metastasis during chemotherapy showed good calibration and great discrimination capacity with AUC 0.871 (95% CI, 0.804 to 0.923) in the training cohort, and 0.843 (95% CI, 0.718 to 0.927) in the validation cohort. The DCA confirmed the clinical utility of the radiomics model. CONCLUSION: The delta-radiomics nomogram incorporating the radiomics signature and clinical factors in this study could be used for individualized pathologic response evaluation after chemotherapy preoperatively and help tailor appropriate chemotherapy and further treatment plans.

Enhancement effect of adenovirus-mediated antisense c-myc and caffeine on the cytotoxicity of cisplatin in osteosarcoma cell lines.

AIMS: Studies on cancer biology have shown that overexpression of oncogenes (with or without functional loss of tumor suppressor genes), which is responsible for the progression of human malignancies via a multistep process, may be reduced by antisense technology. Caffeine enhances the effect of cisplatin (CDDP) chemotherapy on osteosarcoma cells. We constructed the recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment and investigated the synergic effect of caffeine and Myc-AS on the in vitro sensitivity of osteosarcoma MG-63 cells to cisplatin. METHODS: The recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment was constructed by cloning c-myc cDNA of about 750 bp in a reverse direction into adenovirus vector, then undergoing recombination, amplification and complementation in vivo. Myc-AS and caffeine were used either alone or in combination with CDDP to treat osteosarcoma MG-63 cells in vitro. Western blot, MTT, flow cytometry (FCM) and electron microscopy were used to evaluate the expression of c-myc protein, tumor cell proliferation in vitro and apoptosis and to perform cell cycle analysis. RESULTS: Myc-AS encoding antisense c-myc fragment was obtained with a titer of 2 x 10(9) pfu/ml. Myc-AS downregulated the expression of c-myc protein after transfecting MG-63 cells for 48 h, induced tumor cell apoptosis and inhibited tumor cell proliferation in vitro. Myc-AS or caffeine can enhance the cytotoxic effects of 2.0 and 5.0 microg/ml CDDP on MG-63 cells. Moreover, the significantly enhancing effect of the Myc-AS-caffeine combination on CDDP chemotherapy of MG-63 cells was not restricted to apoptosis but also decreased tumor cell proliferation in vitro. Expression of the apoptosis-associated bcl-2 gene was downregulated and bax was upregulated, with no changes in E2F-1 expression. FCM analysis showed that CDDP treatment induced a block in S phase, and caffeine reversed this block and accelerated cell progression through the S phase. CONCLUSIONS: Myc-AS can induce obvious G2/M phase arrest in transfected cells. Myc-AS combined with caffeine can enhance apoptosis induction and chemotherapeutic effects of CDDP on osteosarcoma MG-63 cells.

[Long-term result of fibula grafting for reconstruction of the distal radius after giant cell tumor excision].

OBJECTIVE: To observe the long-term result of fibula grafting for reconstruction of the distal radius after giant cell tumor excision. METHODS: From March 1994 to November 2004, 31 cases of fibula grafting for reconstruction of the distal radius for giant cell tumors performed were analysed. There were 12 males and 19 females. The patients were from 19 to 48 years old, and the mean age was 31 years. Twenty-four patients had Campanacci grade 3 lesions, and 7 patients had Campanacci grade 2 lesions. There were 6 cases of vascularized fibular grafting and 25 cases of non-vascularized fibular grafting. All cases were evaluated by clinical and radiologic examinations; the movement of the wrist and the grip strength was measured; the MSTS score and Mayo Wrist scores were calculated. RESULTS: Clinical follow-up time after reconstruction averaged 86.3 months, range from 41 to 169 months. The mean time for bone union at the host-graft junctions was 5.1 months range from 3 to 9 months in vascularized group and 10.3 months range from 7 to 15 months in non-vascularized group. One patient who had non-vascularized fibula grafting developed non-union at the host-graft junction, and one patient had local recurrence (3.2%). Five patients developed an wrist dislocation after surgery. The average movements of the wrist were: 67.3 +/- 9.4 degrees of extension, 31.2 +/- 5.1 degrees of flexion, 14.1 +/- 4.7 degrees of radial deviation, 19.4 +/- 3.9 degrees of ulnar deviation, 33.8 +/- 6.6 degrees of pronation, 15.3 +/- 4.0 degrees of supination. Average grip strength was 33.1 kg range from 15.5 to 52.1 kg. Compared with the contralateral side, there were accounted for 73%. MSTS score averaged 25.5 from 23 to 29, Mayo wrist score averaged 56 from 40 to 65. CONCLUSIONS: En bloc resection of giant cell tumor of the distal radius followed by reconstruction with a fibula graft is proved to be an effective method and results in a good functional outcome at long term follow-up evaluation. The stability of wrist is achieved by reconstruction of the capsule.

[The surgical therapy of periacetabular malignant tumors].

OBJECTIVE: To study the limb salvage methods and treatment outcomes in malignant periacetabular bone tumors. METHODS: The data of 31 patients of periacetabular malignant tumors who had limb salvage surgery between January 1999 and December 2006 was retrospectively reviewed. There were 14 females and 17 males with a mean age of 53 years (range, 42-75 years). Twenty-four patients had chondrosarcomas, 4 patients had Ewing sarcomas, 1 patient had osteosarcoma, and the remaining 2 patients had metastatic disease. Sixteen patients had Types II pelvic resections, 5 patients had Types I and II pelvic resections, another 5 had Type I and III pelvic resections, and Type I , II and III pelvic resections in the remaining patients. Seventeen patients had reconstructions after tumor resection. RESULTS: The mean follow-up time for all patients was 52 months (range, 12-84 months). Fourteen patients were alive with no evidence of disease, 4 patients were alive with disease at the most recent follow-up, and 13 patients died of disease. The local recurrence rate and mortality rate in 24 patients with chondrosarcomas was 20.8% and 33.3% respectively. Two patients with metastatic disease died at 11 and 34 months postoperatively. One patient with osteosarcoma and 2 patients with Ewing sarcoma died of lung metastases. Enneking scoring system was used to evaluate the functional outcome in 18 alive patients. In 13 patients who had reconstructions, 6 were in excellent, 6 were in good, and 1 was in poor. While in 6 patients who had no reconstructions, 3 were in excellent, 2 were in good, and 1 was in poor. Minor complications occurred in 6 patients. CONCLUSIONS: Clear margin tumor resection with decreased local recurrence rate is critical for limb salvage surgery in periacetabular sarcomas. The ranges of tumor invasion and resection, the principle of individual treatment should be considered in functional reconstruction.

Recurrence of Giant Cell Tumor of the Spine after Resection: A Report of 10 Cases.

OBJECTIVE: To review the clinical details and further treatments for recurrent spinal giant cell tumors (SGCT), and to analyze the risk factors of recurrence and shed new light on the treatment options and prognosis of recurrent SGCT. METHODS: A retrospective analysis of recurrent SGCT between April 2003 and January 2014 was performed. A total of 10 patients comprising 3 men and 7 women with a mean age of 28.9 years (range, 21-40 years) were included in the study. All complete clinical data, radiographs, CT, MRI, scans and pathological data were reviewed. The tumor locations and the regions involved were evaluated by CT and MRI. The blood supply of the tumors was evaluated by enhanced CT and MRI. The mean follow-up was 81.3 months (range, 35.7-172.1 months). RESULTS: All patients had Enneking stage 3 tumors; 9 (90%) of them had different extents of spinal canal involvement in the primary time period. All patients underwent intralesional resection during their first surgery. Only 1 patient received local adjuvant treatments; no patient underwent selective arterial embolization or used denosumab at that time. Only 1 patient underwent adjuvant radiotherapy postoperatively, and another patient used bisphosphonates. After recurrence, 1 patient was cured using denosumab, and 2 patients' disease was controlled through use of other medical treatments or adjuvant treatments. There were 3 repeated recurrences and 7 repeated surgical procedures were performed in 5 patients. There were 6 intralesional excisions and 1 decompression surgery. The mean relapse-free time after the first surgery was 32.3 months (range, 10.5-62.6 months). The overall mean relapse-free time was 40.2 months (range, 10.5-157 months). No distant metastasis was found in our series. At the final follow-up, 4 patients were disease free, 3 patients' disease was under control, 2 has progressive disease aggravation, while 1 patient died as a result of progression of disease 133.9 months after first surgery. CONCLUSION: Intralesional excision for recurrent spinal giant cell tumors is an effective option that may have satisfactory prognosis. However, the excision and the inactivation of the lesion should be carried out carefully and thoroughly without missing any corners. Early diagnosis of recurrence may be associated with better prognosis. Adjuvant treatments perioperatively and systemic medical treatments can decrease recurrence rates and can have therapeutic effects in the recurrent SGCT.

[Endoprosthetic reconstruction after wide resection of primary bone tumor around the knee].

OBJECTIVE: To evaluate the effect and complication of the endoprosthetic reconstruction after wide resection of primary bone tumor around the knee. METHODS: The retrospective analysis was performed on 83 patients undergoing the prosthetic reconstruction after the resection of the primary tumor around the knee between December 1995 and December 2005. All the diagnoses were pathologically confirmed (58 patients with osteosarcoma, 2 with osteosarcomatosis, 1 with parosteal osteosarcoma, 4 with malignant fibrous histiocytoma, 13 with giant cell tumor of bone, 1 with leiomyosarcoma, 2 with Ewing's sarcoma, 2 with chondrosarcoma). The distal femur group was involved in 44 patients, proximal tibia group in 34 (including 33 deficit in proximal tibia, 1 deficit both in proximal tibia and distal femur), total femur replacement group in 5. After operation, the Musculoskeletal Tumor Society (MSTS) score was used to evaluate the recovery of their corresponding functions. RESULTS: The follow-up for 12 - 130 months (with a median of 41 months) revealed that the 3-year survival rate of the prosthesis was 88.2%, and the 5-year survival rate was 82.1%. As for the complications, local recurrence developed in 6 patients, peri-prosthesis infection in 2 patients, aseptic loosening in 2 patients. The mean MSTS core was 25.0 (19.0 - 29.0) in the distal femur group, 24.4 (17.0 - 28.0) in the proximal tibia group, and 19.0 (16.0 - 21.0) in the total femur replacement group. As to the statistical analysis, the function of the former two groups were greater than the latter one (F = 11.666, P < 0.001), however, there was no significant difference between the former 2 groups (F = 0.813, P = 0.370). CONCLUSIONS: Taken together, the tumor prosthesis gives a satisfactory functional outcome after the tumor around the knee is removed with a lower incidence of complication.

How to Fill the Cavity after Curettage of Giant Cell Tumors around the Knee? A Multicenter Analysis.

BACKGROUND: Intralesional excision with curettage is the standard method of giant cell tumor (GCT) treatment, but the ideal filling material after curettage remains controversial. The purpose of this study was to compare the oncological and functional outcomes which underwent cementation or bone grafting after GCT curettage around the knee. METHODS: We reported 136 cases with GCTs in distal femur or proximal tibia who accepted curettage from five clinical centers during the last 15 years. All patients were divided into two groups according to filling materials. Recurrence-free survival proportions were used to evaluate oncological outcomes while the Musculoskeletal Tumor Society (MSTS) 93 functional score was used to evaluate functional outcomes. Other parameters including surgical complication, general condition, and radiological classification had been analyzed. The valid statisitical data was analyzed using SPSS 13.0 software. RESULTS: After GCT curettage, 86 patients (63.2%) accepted bone grafting while 50 patients (36.8%) accepted cementation. There was no statistical difference in age, gender, tumor location, radiological classification, fixation, follow-up time, and MSTS 93 functional score between cementation group and bone grafting group. The recurrence-free survival proportions showed that the recurrence rate in bone grafting group was higher than it in cementation group (P = 0.034). Surgical complication was lower in cementation group than that in bone grafting group but without statistically significant difference (P = 0.141). CONCLUSIONS: Parameters including patients' age, gender, tumor location, and radiological classification did not affect surgeons' treatments in cavity filling after GCT curettage. Cementation should be recommended because of easy usage, the similar postoperative knee function with bone grafting, and the better local tumor control than bone grafting.

Zoledronic acid sensitizes rhabdomyosarcoma cells to cytolysis mediated by human γδ T cells.

Rhabdomyosarcoma (RMS) is the most common type of soft-tissue sarcoma in children. Immunotherapy has been proposed as a treatment for this deadly tumor. In the present study, the cytotoxicity of ex vivo expanded γδ T cells on RMS cell lines was evaluated and the molecular interactions involved were investigated. γδ T cells were expanded in vitro using peripheral blood mononuclear cells from 5 healthy donors and were stimulated with zoledronic acid (Zol) and interleukin 2. RMS cell lines RD and A-673 were used as target cells. The cytotoxicity of the γδ T cells against RMS was assessed in vitro and in vivo. γδ T cells were cytotoxic to RMS cells. Importantly, Zol markedly increased their cytotoxic potential. RMS cells treated with Zol-stimulated γδ T cells to produce interferon γ. γδ T cell-mediated cytotoxicity was primarily through the T cell receptor-dependent signaling pathway in blocking studies. Transfer of γδ T cells together with Zol into nude mice induced the regression of RD tumor xenotransplants. The results of the present study provide the rationale for the clinical evaluation of γδ T cells in RMS.

[Mucoadhesive buccal films of tramadol for effective pain management]. / Filmes bucais mucoadesivos de tramadol para o controle eficaz da dor.

BACKGROUND AND OBJECTIVES: Tramadol hydrochloride is a centrally-acting synthetic opioid analgesic binding to specific opioid receptors. It is used in the management of chronic pain and is recommended as first line drug in the treatment of postoperative or orthopedic injury induced acute pain. The present work is designed to prepare and evaluate mucoadhesive buccal film of tramadol hydrochloride as a novel form of prolonged analgesia for patients with orthopedic injuries. METHODS: Buccal films of tramadol hydrochloride were prepared by solvent casting method. The prepared films were evaluated for the various evaluation parameters like thickness, surface pH, weight uniformity, content uniformity, folding endurance, swelling index, in vitro drug release study, in vitro test for mucoadhesion and in vivo studies (primary mucosal irritancy test and analgesic activity). RESULTS: All the formulations exhibited good results for physicochemical characterizations. In in vitro drug release study the films exhibited controlled release more than 12hours. The formulation BFT2 (containing chitosan and PVP K-90) showed no irritant effect on buccal mucosa and elicit the significant in vivo analgesic activity with 57.14% analgesia against that of standard (61.04%). It was concluded that the mucoadhesive films of tramadol hydrochloride can be effectively used to alleviate the severe pain of orthopedic injuries with prompt onset and prolonged action.

[The choice strategy of surgical treatment for giant cell tumor close to the knee].

OBJECTIVE: To retrospectively study and analyze the methods of the surgery management for giant cell tumor close to the knee. METHODS: A retrospective analysis was performed in 121 patients who underwent surgical treatment for giant cell tumor close to the knee between 1978 and 1997. There were 71 cases had been managed with an intralesional procedure of the tumor (curettage, freezing with liquid nitrogen and autograft or allograft, Group 1), 50 cases with a semi-arthroplasty using allograft after en bloc resection (Group 2). According to the relation of the clinical signs and symptoms, tumor character, operative method and local recurrence, limp function, complication were evaluated. Based on the figure of tumor lesion on CT, a new formulation of treatment was given: (1) I diameter of tumor 3/4, en bloc resection and reconstruction. The prospectively collected records of 65 cases of patients, 45 cases with curettage, heat cauterization with electrocautery and phenol, autograft and cement (Group 1), 20 cases with arthroplasty using prosthetic (Group 2), who had a giant-cell tumor closed knee, were reviewed to determine feasibility of the new formulation of treatment. RESULTS: The first duration, the rate of the local recurrence between 2 groups showed no statistical difference. There were less complication rate and better limp function after using two different surgical treatment. The second duration, there were no statistical difference with the rate of the local recurrence, complication, and limp function. The number of patients who managed with en bloc resection and reconstruction decreased. CONCLUSIONS: The choice strategy of surgical treatment for giant cell tumor close to the knee should be based on the figure of tumor lesion on CT. It gives a new formulation of treatment to choice of an intralesional procedure and en bloc resection. An effective intralesional procedure should be the method of the first choice.

[Clinical characteristics and treatment of AO/OTA A2.3 intertrochanteric fractures with posterior coronal plane fractures].

OBJECTIVE: To explore the characteristics, the operative techniques and effect of AO/OTA A2.3 intertrochanteric fractures with posterior coronal fractures. METHODS: From January 2011 to January 2014, 33 patients suffered from AO/OTA A2.3 intertrochanteric fractures with posterior coronal fractures were treated with proximal femoral anti rotation nail, included 15 males and 18 females, with an average age of (73.1±8.2) years old ranged from 61 to 92 years old. According to AO/OTA classification, all cases were type A2.3 fracture. All cases were closed fractures and treated with limited open reduction and internal fixation. The postoperative hip function was evaluated by Harris score. RESULTS: One case was died at 19 days after operation, 32 cases were followed up from 9 to 24 months with an average of (16.3±5.1) months. Bone union time was from 6 to 9 months with an average of (7.2±1.5) months according to X rays. At the final followed up, Harris scores were 76 to 95 points with an average of (85.3±5.6) points;13 cases were classified as excellent, 16 as good, and 3 as fair. CONCLUSIONS: AO/OTA A2.3 intertrochanteric fracture with posterior coronal fractures is a special type and unstable, it's difficult to reset. It needs to be fixed with proximal femoral anti rotation nail by limited open reduction. It is necessary that postoperative rehabilitation should be chosen individually.