Surgical Treatment of Osteosarcoma Induced Distant Pre-Metastatic Niche in Lung to Facilitate the Colonization of Circulating Tumor Cells.

Recently, the major challenge in treating osteosarcoma patients is the metastatic disease, most commonly in the lungs. However, the underlying mechanism of recurrence and metastasis of osteosarcoma after surgical resection of primary tumor remains unclear. This study aims to investigate whether the pulmonary metastases characteristic of osteosarcoma is associated with surgical treatment and whether surgery contributes to the formation of pre-metastatic niche in the distant lung tissue. In the current study, the authors observe the presence of circulating tumor cells in patients undergoing surgical resection of osteosarcoma which is correlated to tumor recurrence. The pulmonary infiltrations of neutrophils and Gr-1+ myeloid cells are characterized to form a pre-metastatic niche upon the exposure of circulating tumor cells after surgical resection. It is found that mitochondrial damage-associated molecular patterns released from surgical resection contribute to the formation of pre-metastatic niche in lung through IL-1ß secretion. This study reveals that surgical management for osteosarcoma, irrespective of the primary tumor, might promote the formation of postoperative pre-metastatic niche in lung which is with important implications for developing rational therapies during peri-operative period.

Case Report: Pulmonary Metastases From Epithelioid Sarcoma in Extremity Favourably Responding to Immunotherapy With Camrelizumab.

Epithelioid sarcoma (ES) is a rare soft tissue sarcoma (STS), with limited therapies available for metastatic disease. Here, we describe a case of a 30-year-old male with ES of the left knee and underwent surgery and radiation therapy for the primary disease. After 2 years, he had local recurrence and underwent extensive resection surgery; however, adjuvant chemotherapies were delayed due to recurrent wound infection. Nine months after the second surgery, progressive disease was confirmed after detection of metastases to the lungs and inguinal lymph nodes. Amputation was performed for the local recurrence, followed by inguinal lymph nodes dissection. Pazopanib was transiently administered but discontinued as a result of wound dehiscence. The tumour specimens were detected with unexpected high level of PD-L1 expression and tumoural infiltrating lymphocytes. Subsequently, he received camrelizumab 2.0 mg/kg every 21 days for 18 cycles with rapid remission of the pulmonary metastases. This promising response to camrelizumab indicates that immunotherapies may be an alternative choice for patients with metastatic ES in lung based on analysing the tumour immune microenvironment.

Targeted and immuno-based therapies in sarcoma: mechanisms and advances in clinical trials.

Sarcomas represent a distinct group of rare malignant tumors with high heterogeneity. Limited options with clinical efficacy for the metastatic or local advanced sarcoma existed despite standard therapy. Recently, targeted therapy according to the molecular and genetic phenotype of individual sarcoma is a promising option. Among these drugs, anti-angiogenesis therapy achieved favorable efficacy in sarcomas. Inhibitors targeting cyclin-dependent kinase 4/6, poly-ADP-ribose polymerase, insulin-like growth factor-1 receptor, mTOR, NTRK, metabolisms, and epigenetic drugs are under clinical evaluation for sarcomas bearing the corresponding signals. Immunotherapy represents a promising and favorable method in advanced solid tumors. However, most sarcomas are immune "cold" tumors, with only alveolar soft part sarcoma and undifferentiated pleomorphic sarcoma respond to immune checkpoint inhibitors. Cellular therapies with TCR-engineered T cells, chimeric antigen receptor T cells, tumor infiltrating lymphocytes, and nature killer cells transfer show therapeutic potential. Identifying tumor-specific antigens and exploring immune modulation factors arguing the efficacy of these immunotherapies are the current challenges. This review focuses on the mechanisms, advances, and potential strategies of targeted and immune-based therapies in sarcomas.

Three-dimensional-printed custom-made patellar endoprosthesis for recurrent giant cell tumor of the patella: A case report and review of the literature.

BACKGROUND: Giant cell tumor (GCT) is a benign lesion and rarely involves the patella. This disease is characterized by a relatively high recurrence rate after primary treatment. En bloc resection has been a predominant option for recurrent GCT. However, total patellectomy can lead to disruption of the knee. Therefore, exploration of functional reconstruction of the extensor mechanism is worthwhile. CASE SUMMARY: A 54-year-old woman presented with right knee pain and swelling, and was diagnosed as having a GCT in the patella following curettage and autograft. Medical imaging revealed a lytic and expanded lesion involving the whole patella with focal cortical breaches and pathological fracture. Based on the combination of histological, radiological, and clinical features, a diagnosis of recurrent GCT in the patella was made (Campanacci grade III). After a multidisciplinary team discussion, three-dimensional (3D)-printed custom-made patellar endoprosthesis was performed following en bloc resection for reconstructing the extensor mechanism. The patient was followed for 35 mo postoperatively. No evidence of local recurrence, pulmonary metastasis, or osteoarthritis of the right knee was observed. The active flexion arc was 0°-120°, and no extension lag was detected. A favorable patellar tracking and height (Insall-Salvati ratio 0.93) were detected by radiography. CONCLUSION: We depict a case of a GCT at the right patella, which was successfully treated by patellectomy and 3D-printed custom-made endoprosthetic replacement. The patella normal reconstruction, the precise-fit articular design, and gastrocnemius flap augmentation could lead to satisfactory knee function and a low rate of complications in the short-term follow-up.

Patient-Derived Tumor Xenografts Plus Ex Vivo Models Enable Drug Validation for Tenosynovial Giant Cell Tumors.

INTRODUCTION: Tenosynovial giant cell tumor (TGCT) is a locally aggressive tumor with colony-stimulating factor 1 receptor (CSF1R) signal expression. However, there is a lack of better in vivo and ex vivo models for TGCT. This study aims to establish a favorable preclinical translational platform, which would enable the validation of efficient and personalized therapeutic candidates for TGCT. PATIENTS AND METHODS: Histological analyses were performed for the included patients. Fresh TGCT tumors were collected and sliced into 1.0-3.0 mm3 sections using a sterilized razor blade. The tumor grafts were surgically implanted into subrenal capsules of athymic mice to establish patient-derived tumor xenograft (PDTX) mouse models. Histological and response patterns to CSF1R inhibitors evaluations were analyzed. In addition, ex vivo cultures of patient-derived explants (PDEs) with endpoint analysis were used to validate TGCT graft response patterns to CSF1R inhibitors. RESULTS: The TGCT tumor grafts that were implanted into athymic mice subrenal capsules maintained their original morphological and histological features. The "take" rate of this model was 95% (19/20). Administration of CSF1R inhibitors (PLX3397, and a novel candidate, WXFL11420306) to TGCT-PDTX mice was shown to reduce tumor size while inducing intratumoral apoptosis. In addition, the CSF1R inhibitors suppressed circulating nonspecific monocyte levels and CD163-positive cells within tumors. These response patterns of engrafts to PDTX were validated by ex vivo PDE cultures. CONCLUSIONS: Subrenal capsule supports the growth of TGCT tumor grafts, maintaining their original morphology and histology. This TGCT-PDTX model plus ex vivo explant cultures is a potential preclinical translational platform for locally aggressive tumors, such as TGCT.

[Therapeutic Effect of Uncemented Allograft-prosthetic Composite for the Reconstruction of Tumorous Bone Defect].

OBJECTIVE: To investigate the surgical techniques and mid-term efficacy of reconstruction for proximal femur with allograft-prosthetic composite (APC) . METHODS: Fifteen patients who underwent uncemented APC reconstruction of proximal femur after bone tumor resection were retrospectively evaluated. Image and physical examinations were taken on the 1st,3rd,6th,9th and 12th month after surgery and every 6 months thereafter to assess union condition,greater trochanteric bone absorption and myodynamia of abductors. Musculoskeletal Tumor Society (MSTS) and Harris Hip Score (HHS) were utilized to evaluate the function of hip joint. RESULTS: Seven male and eight female patients were included with average age of 25.1 years(17-56 years) and average followup of 32.8 months(18-48 months). Four patients had giant cell tumor of the bone,3 patients had osteosarcoma,3 patients had chondrosarcoma,2 patients had malignant fibrous histiotoma,2 patients had osteoblastoma and 1 patient had Ewing sarcoma. Unions occurred in the allograft-host bone interfaces of all patients in the period of 5-9 months postoperatively. Bone absorption in the allograft-host bone interfaces,dislocation,hypersensitivity of the allograft and acetabulum abrasion were not observed,while there were no metastasis and tumor recurrence. Three patients had periprosthetic fractures intraoperatively and were well fixed with cerclage. Absorptions in the greater trochanteric happened to 6 patients. All patients had mean MSTS and HHS scores of 11.3 (7-15) and 47.3 (40.3-58.5) preoperatively and 26.1(24-29) and 80.1(66.2-92.7) postoperatively. CONCLUSION: Uncemented APC reconstruction is proper for young patients with long life expectancy and high demand of function that suffered from tumors of proximal femur.

Prognostic value of the C-reactive protein to albumin ratio: a novel inflammation-based prognostic indicator in osteosarcoma.

The prognostic role of the C-reactive protein to albumin ratio (CRP/Alb ratio) in patients with osteosarcoma has not been investigated. A total of 216 osteosarcoma patients were enrolled in the study. Univariate and multivariate survival analyses between the groups were performed and Kaplan-Meier analysis was conducted to plot the survival curves. Receiver operating characteristic curves were generated and areas under the curve (AUCs) were compared to assess the discriminatory ability of the inflammation-based indicators, including CRP/Alb ratio, Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR). The optimal cutoff value was 0.210 for CRP/Alb ratio with a Youden index of 0.319. Higher values of CRP/Alb ratio were significantly associated with poorer overall survival in univariate (HR =2.62, 95% CI =1.70-4.03; P<0.001) and multivariate (HR =2.21, 95% CI =1.40-3.49; P=0.001) analyses. In addition, the CRP/Alb ratio had significantly higher AUC values compared with GPS (P=0.003), NLR (P<0.001), and PLR (P<0.001). The study demonstrated that the CRP/Alb ratio is an effective inflammation-based prognostic indicator in osteosarcoma, which potentially has a discriminatory ability superior to that of other inflammatory indicators including GPS, NLR, and PLR.

A multi-level comparative analysis of human femoral cortical bone quality in healthy cadavers and surgical safe margin of osteosarcoma patients.

Osteosarcoma is the most common primary malignancy of bone. However, the potential variation it brings to the adjacent undamaged bone tissue is seldom investigated. In this study, we conducted a multi-level comparison of human femoral cortical bone quality in healthy cadavers (aged 42±11 years) and in resected safe margin of osteosarcoma patients (aged 49±15 years). The objective of this study was to document the changes with exposure to osteosarcoma condition in bone mechanical strength, structural morphology and elementary composition, evaluated by static and dynamic mechanical analysis (DMA), scanning electron microscopy (SEM) imaging, X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). The resected clinical samples from healthy and osteosarcoma conditioned bones were grouped into the Tumor and Healthy groups, and shaped into regular beam specimens or pulverized according to testing protocols. The results of mechanical tests confirmed osteolytic deteriorations in mineral phase of the Tumor group, in terms of significant reductions in storage modulus (-53.6%, at 1Hz), bending strength (-53.0%) and stiffness (-64.8%) as compared to the Healthy group. However, the energy dissipation/absorption ability of the collagen phase in the Tumor group did not differ from the Healthy group statistically. Although specimens showed no visible morphological difference, a decline in osteocyte lacunar density in bone specimens from the Tumor group was discovered (-54.4%, p<0.001). Higher magnification observation showed that the cell-free lacunae in the Tumor group were occluded by randomized overgrown collagen fibers. XRD and FTIR analysis further demonstrated a lower hydroxyapatite crystallinity and decreased mineral:matrix ratio in pulverized samples from the Tumor group, mainly due to the prominent Amide peaks. Taken together, these data revealed a previously unrecognized effect of osteosarcoma on the adjacent "normal" bone quality. The current study may provide insights on bone tumor pathology and an advanced understanding of surgical safe margin.

Clinicopathological and prognostic significance of chemokine receptor CXCR4 in patients with bone and soft tissue sarcoma: a meta-analysis.

The prognostic significance of CXC chemokine receptor 4 (CXCR4) in patients with bone and soft tissue sarcomas remains controversial. To investigate the impact of its expression on survival and clinicopathological features, we performed a meta-analysis. Comprehensive literature searches were conducted in PubMed, Web of Science, Embase and Cochrane Library for relevant studies. In total, 12 studies with 997 sarcoma patients were included. CXCR4 expression was found to be significantly associated with poor overall survival (HR 2.37, 95 % CI 1.86-3.01; P < 0.001). Further, when the analysis was stratified by histological subtypes (bony sarcoma including osteosarcoma and Ewing sarcoma and soft tissue sarcoma including synovial sarcoma and rhabdomyosarcoma), statistical analysis method (multivariate analysis and univariate analysis) and CXCR4 measuring method (IHC or RT-PCR), the significant correlation to poor overall survival was also observed except for that in Ewing sarcoma and RT-PCR groups. As for clinicopathological features, CXCR4 expression was significantly associated with higher rate of metastasis (OR 6.97, 95 % CI 2.28-21.31; P = 0.001) and higher tumor stage (OR 7.55, 95 % CI 1.25-45.47; P = 0.027), but not associated with gender, age and tumor site. In conclusion, CXCR4 expression may be an effective predictive factor of poor prognosis and clinicopathological features for bone and soft tissue sarcomas. Further studies are needed to validate our findings.

[Clinical Significance of Hip Rotation Center Location after Reconstruction with Modular Hemipelvic Prostheses for Pelvic Tumor].

OBJECTIVE: To investigatethe clinical significance of hip rotation center location after reconstruction with modular hemipelvic prostheses for periacetabula tumors. METHODS: Forty-two patients who received periacetabular tumor resection and reconstruction with modular hemipelvic prosthesis between January 2004 and January 2014 in our institute were included. Postoperative complications, function (measured by MSTS score), survival rate and recurrence rate were analyzed. The position of prosthetic hip rotation center was measured. By its deviation angle from the ideal rotation center, the patients were divided into inward group, normal group and outward group in the horizontal level, and upward group, normal group and downward group in the vertical direction. And the relationship between positional difference of prosthetic hip rotation center and function at 1 month, 3 months, 6 months and 12 months after surgery was analyzed. RESULTS: Of forty-two cases in total, 25 patients were male and 17 patients were female. The age of the patients ranged from 12 and 69 years (median, 38 years). The minimal followup period was 12 months (mean,36 months; range,12-86 months). The complication rate was 31.0% and hip dislocation rate was 7.1%. The overall survival rate was 69.4% at 3 years and 43.7% at 5 years. After 1 month, 3 months, 6 months, the function of the reconstructed hip gradually improved, with MSTS score showing an increasing trend. The MSTS scores at these three time points were compared, the difference was statistically significant (P < 0.05). The improvement of function after 6 months and 12 months was not obvious, with the difference not being statistically significant (P > 0.05). The deviation of hip rotation center in the longitudinal direction and the horizontal direction did not affect the function of the hip (P > 0.05). CONCLUSION: It is safe and effective for patients with pelvic tumor to receive modular hemipelvic prosthesis reconstruction once the prosthesis is fixed in the most firmly position, where soft tissue fully covered, the muscles could be rebuilt more easily and where the eccentricity of the femoral got a certain degree of recovery. The relationship between the deviation of hip rotation center and postoperative function needs to be confirmed.

[Extensively Porous-coated Distal Fixation Long Stem Prosthesis for Unstable Proximal Femur Fracture with Complex Hip Disease].

OBJECTIVES: To evaluate the clinical results of femoral proximal fracture with complex hip diseases using an uncemented extensively porous-coated long femoral stems. METHODS: 15 cases of femoral proximal fracture with complex hip diseases treated with the uncemented extensively porous-coated long femoral stem were retrospectively reviewed. All patients were followed up at 1, 3, 6, 12 months in the first year postoperatively and once a year from the second year on.Radiological evaluations were conducted using the related criteria, including anteropostierior radiograph of pelvis, anteropostierior and lateral radiograph of proximal femur, and flat tomography of lower limbs.The bone union of the femur fracture, the fixation of prosthesis, and periprosthetic bone loss were evaluated by above-mentioned radiography.The subsidence of femoral prosthesis was compared between 1 month postoperatively and the last follow-up. Complications during the follow-up period was recorded.Clinical outcomes were assessed with Harris Hip Score the last follow-up, including excellent (90-100), good (80-89), moderate (70-79) and bad (<70). RESULTS: The average follow-up period was (45.5±21.7) months. All fractures were united at mean 12.6 weeks. There were no femoral stem subsidence and evidence of loosening both radiologically and clinically. The reconstructive offset for femoral fracture was 35.8 mm, while the contralateral offset was 34.8 mm. The average Harris Hip Score was 89.5 at the last follow-up. Moreover, no loosening, dislocation or infection were observed. CONCLUSIONS: Total hip arthroplasty with extensively porous-coated long femoral stem provides a good fracture stability that promotes fracture healing and offers a successful solution for femoral proximal fracture with complex hip diseases.

Identification and functional study of osteosarcoma metastasis marker genes.

To date, osteosarcoma metastasis genes, which are key for accurate initial diagnosis of the disease, have not been well identified. In the present study, osteosarcoma samples with and without metastasis were collected from 31 patients. Specific complementary DNA subtraction techniques were used to identify the osteosarcoma metastasis transcripts, which are responsible for the metastasis of osteosarcoma. The specific differentially expressed transcripts were identified by Basic Local Alignment Search Tool analysis and the results were validated by immunoblotting. Specifically, ezrin and ß4 integrin were employed as markers to detect osteosarcoma metastasis in the initial stages. The results of the present study indicated that the two transcripts, ezrin and ß4 integrin, were highly expressed in patients with osteosarcoma metastasis, and concluded that these were osteosarcoma metastasis genes. These results indicate that ß4 integrin and/or ezrin may be used as a novel marker for the detection of osteosarcoma metastasis in the initial stages.

Cemented allograft-prosthesis composite reconstruction for the proximal femur tumor.

INTRODUCTION: Cemented allograft-prosthesis composite (APC) reconstruction is one option following resection of the proximal femur tumor. However, rare studies have focused on the indications and complications. The goal of the present study was to (1) ascertain the indications for cemented APC arthroplasty in the proximal femur; (2) identify the detailed perioperative management; and (3) illustrate our experiences to avoid the complications of cemented APC. MATERIALS AND METHODS: A total 28 patients who underwent cemented APC reconstruction of the proximal femur after tumor resection were retrospectively evaluated at a median follow-up of 56 months. Clinical records and radiographs were reviewed to evaluate patients' outcome. RESULTS: In our series, excluding three cases of death that had a short follow-up period, union occurred in 22 (88.0%) patients (range 9-18 months). Nonunion of the greater trochanter was seen in six of the 12 patients (50.0%). Eight (32.0%) hips had resorption. There were two (8.0%) hips that were observed to have asymptomatic wear of the acetabulum. The average Musculoskeletal Tumor Society (MSTS) score was 26.5 points. The average Harris Hip Score (HHS) score was 80.6 points. There were no cases of recurrence, but metastasis was found in two hips. CONCLUSIONS: Mastering indications, perioperative management, and complication prevention are all very important in the APC reconstruction after resection of the proximal femur.

[Analyzing risk factors for surgical site infection following Pilon fracture surgery].

OBJECTIVE: To study the related risk factors for surgical site infection following Pilon fracture surgery. METH ODS: The data of 561 patients with Pilon fractures treated with open reduction plate osteosynthesis at our institution's trauma centre were collected from January 2006 to December 2012. All the patients were divided into two groups: infection group and non-infection group. In the infection group, there were 23 males and 10 females, ranging in age from 21 to 69 years old, with an average of (45.50±4.40) years old. In the non-infection group, there were 296 males and 232 females, ranging in age from 16 to 76 years old, with an average of (43.50±7.19) years old. The possible risk factors such as age, gender, smoking, diabetes, alcohol abuse, open fractures, compartment syndrome and operative time were studied. The multivariate Logistic regression model was used to analyze the risk, factors. RESULTS: The infection rate of surgical site after Pilon fracture surgery was 5.88%. There were significant statistical differences between infection group and non-infection group in operative time, open fractures and compartment syndrome. However, multivariate Logistic regression analysis revealed that only operative time was significantly associated with surgical site infection (P=0.005, OR=44.92). CONCLUSION: Operation time is an independent predictor for post-operative surgical site infection of Pilon fracture treated with open reduction plate osteosynthesis. Though open fracture and compartment syndrome could increase the surgical site infection rate, they could not not be considered as independent predictors.

[Anterior decompression and fusion with n-HA/PA66 cage for the treatment of lower cervical fracture and dislocation].

OBJECTIVE: To explore the clinical effects of anterior decompression and fusion with a nano-hydroxyapatite/ polyamide 66 (n-HA/PA66) cage in treating lower cervical fracture and dislocation. METHODS: From January 2008 to December 2010, the clinical data of 42 patients with lower cervical fracture and dislocation were retrospectively analyzed. There were 29 males and 13 females aged from 20 to 65 years old. The mean age was 46.8 years. Five cases got injuried in C3, 14 cases in C4, 12 cases in C5, 7 cases in C6 and 4 cases in C7. According to Frankel grade, 4 cases were classified in grade A, 11 cases in grade B, 13 cases in grade C, 9 cases in grade D and 5 cases in grade F. Twenty-eight cases were treated with anterior corpectomy and fusion and 14 cases with anterior discectomy and fusion. Frankel grade was used to do neurologic assessment and visual analogue scale (VAS) was used to evaluate the improvement of clinical symptoms. Segmental height and sagittal lordosis were measured by radiographs and cage location. Cage appearance and fusion status were assessed by 3D-CT images. RESULTS: All patients were followed up for 3 to 5.2 years with an average of 4.1 years. Frankel grade had obviously improved than preoperative (Z = -4.845, P < 0.001). There were 2, 3, 11, 8, 11 cases classified in grade A, grade B, grade C, grade D and grade E respectively. At the third day after operation and latest follow-up,VAS was (2.6 +/- 1.8),(1.3 +/- 1.0) scores respectively. Both had improved than preoperative (P < 0.05). Up to the latest follow-up, there was only one patient (2.4%) with slight cage translocation (less than 2 mm), however, no cage prolapsed, or collapse, or breakage were found. Both segmental height and lordosis improved significantly after surgery (P < 0.001). And there was not significant difference in both parameters between each postoperative time points (P > 0.05). The mean distance of cage subsidence was 1.5 mm and the rate of cage subsidence (> 3 mm) was 4.8%. CONCLUSION: The n-HA/PA66 cage can not only restore and maintain the fusion segmental height and radian, but also promote the osseous fusion and profit the radiographic assessment after operation. Thus, it was an ideal material for prop graft.

Comparison of Early and Delayed Open Reduction and Internal Fixation for Treating Closed Tibial Pilon Fractures.

BACKGROUND: The timing of surgery for osteosynthesis of type C pilon (AO/OTA) fractures remains controversial. The aim of this study was to determine the outcome of early and delayed open reduction and internal fixation (ORIF) for treating closed type C pilon fractures. METHODS: Forty-six patients with closed type C pilon fractures matched according to age, gender, soft tissue conditions, and fracture pattern were divided into group A (early group: underwent surgery within 36 hours of the injury) or group B (delayed group: underwent surgery 10 days to 3 weeks postinjury after the soft tissue swelling subsided). In the delayed group, 9 patients were treated first by temporary external fixation. All the closed fractures were managed by ORIF with locking plates. At follow-up, the clinical and radiographic results were retrospectively analyzed. The mean follow-up time was 25.8 months (range, 14 to 48 months) in group A and 26.0 months (range, 15 to 44 months) in group B. RESULTS: There was no significant difference (P > .05) between the 2 groups regarding the rate of soft tissue complication, the rate of fracture union, and the final functional score. The patients in group A had a significantly shorter mean time to fracture union (21.5 ± 4.0 weeks vs 23.3 ± 3.7 weeks, P < .05), operating time (84.3 ± 12.1 months vs 100.6 ± 13.7 months, P < .01), and hospital stay (7.6 ± 2.6 days vs 15.2 ± 4.2 days, P < .01). CONCLUSION: If soft tissue conditions are acceptable, early ORIF for treating closed type C pilon fractures can be safe and effective, with similar rates of wound complication, fracture union, and final good functional recovery but shorter operative time, union time, and hospital stay. These results favorably compare with delayed ORIF treatment. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PDGF-regulated miRNA-138 inhibits the osteogenic differentiation of mesenchymal stem cells.

Differentiation-specific microRNAs may play a critical role in MSC differentiation, and they can be altered by PDGF signaling. We propose that PDGF modulates MSC differentiation by regulating microRNA expression. Therefore, we investigated whether PDGF treatment could alter the expression profile of miRNAs in MSCs. Furthermore, we assessed the osteoblast phenotype of MSCs after inducing osteogenic differentiation. We found that PDGF treatment significantly inhibits the osteogenic differentiation of MSCs and that miR-138 gene transcription is controlled by PDGF signaling. Our results confirm that miR-138 inhibits the osteogenic differentiation of MSCs and suppresses the phosphorylation of FAK, ERK1/2, and Runx2. Furthermore, our study clearly demonstrates that downregulation of Runx2 by miR-138 is critical for the PDGF-mediated inhibition of osteogenic differentiation of MSCs. These findings indicate that inhibition of miR-138 function in MSCs, either by treatment with anti-miR-138 or by overexpression of the miR-138 target sequence (miRNA sponge), could represent a potential therapeutic strategy for the treatment of bone homeostasis disorders caused by activation of the PDGF pathway.

Internal fixation with headless compression screws and back buttress plate for treatment of old Hoffa fracture.

OBJECTIVE: To analyze the early clinical and radiographic outcomes of Hoffa fractures treated by a standard protocol of open reduction and internal fixation using headless compression screws combined with back buttress plate in a consecutive series of 8 Chinese patients. METHODS: Open reduction and internal fixation was performed on all patients. The fractures were anatomically reduced and held temporarily by K-wire. If the ends of fractures were atrophic, autologous bone graft from the ipsilateral iliac crest was packed between the ends. Then the fracture fragments were fixed with AO 6.5 mm headless compression cannulated screws. At least two screws were used to provide rotational stability. One pre-contoured reconstruction plate was placed on the nonarticular surface posteromedially or posterolaterally as back buttress plate. RESULTS: All the patients were followed up for at least 12 months (range 12-25 months). All fractures achieved anatomical reduction and healed clinically and radiographically. At recent follow-up, the mean flexion degree was 120.6° (range 110°-135°) and the mean extension degree was 2.5° (range 0°-5°). The average visual analogue scale score was 1.6 points (range 0-3). Six patients were assessed as excellent and 2 as good according to the hospital for special surgery knee score system. There were no superficial or deep infections, or hardware breakages. No patient had giving way or locking of the knee, though some had intermittent pain and swelling after strenuous exercise. Injury mechanism had significant influence on the functional outcome (P=0.046). CONCLUSION: Headless compression screws combined with back buttress plate and/or autologous bone grafting to treat old Hoffa fracture is one of effective measures. It would be conducive to not only fracture healing but also early exercise and functional recovery.

[Locking compression plate (LCP) combined with minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of Pilon fracture].

OBJECTIVE: To summarize clinical outcomes of locking compression plate (LCP) combined with minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of Pilon fracture. METHODS: From January 2009 to December 2012, Pilon fracture patients treated by LCP with MIPPO were retrospectively analyzed. All open fractures, pathologic fractures and those who had limb vascular disease or nerve injury were excluded. Thirty-eight patients were enrolled, including 29 males and 9 females aged from 21 to 78 years old with an average of 48 years old. According to AO classification, 20 cases were type B, 18 cases were type C. Operative time, blood loss, reduction quality, time of fracture healing complications and postoperative ankle joint function were applied for evaluating clinical outcomes, AOFAS scoring were used for assessing postoperative clinical effects. RESULTS: All patients were followed up from 13 to 24 months (averaged 18 months). All patients obtained bone union without any plate failures or loss of fixation/reduction. One patient occurred superficial wound infection, and resolved with antibiotics and local wound care. Postoperative average AOFAS score was 81 (ranged 65 to 97). CONCLUSION: LCP with MIPPO for Pilon fratcure has advantages of less invasion, fewer complications and satisfactory ankle function.

[Comparison between allogeneic tendon fixation and screw fixation in ligamentous Lisfranc injury: a biomechanical analysis].

OBJECTIVE: To compare the stability provided by a allogeneic tendon with a screw for the treatment of ligamentous Lisfranc injury. METHODS: Six fresh-frozen, paired cadaveric feet were loaded in the condition of Lisfranc ligament-intact, injury and fixation models. With axial or abduction stress, the distance between medial cuneiform and second metatarsal was recorded. RESULTS: With both two types of stress, there were statistically significant differences in motion detected between the intact and post-injury conditions (all P = 0.000), and the magnitudes were greater with abduction [(4.14 +/- 1.02) mm] than axial load [(1.60 +/- 0.64) mm]. In screw fixation group, the mean position changes under axial load and abduction load were (1.53 +/- 0.62) mm and (4.06 +/- 1.05) mm in post-injury model respectively, while the changes were (0.76 +/- 0.35) mm and (1.20 +/- 0.53) mm in the fixation model (all P = 0.000) which were not statistical different to that in the intact model. In allogeneic tendon fixation group, the mean position changes were (1.66 +/- 0.65) mm and (4.21 +/- 1.00) mm in the post-injury model, while were (0.90 +/- 0.41) mm and (1.33 +/- 0.61) mm in the fixation model (all P = 0.000) which also were not statistical different to that in the intact model. CONCLUSION: Under abduction stress, a significantly greater difference was found between pre- and post-injury, which may be valuable for diagnosing and testing ligamentous Lisfranc injury. Allogeneic tendon fixation can provide similar stability as screw fixation in ligamentous Lisfranc injury.