Revision surgeries for tumor endoprostheses around the knee joint: a mid-long-term follow-up of 20 cases.

BACKGROUND: Tumor endoprostheses of the knee joint after limb salvage surgery is associated with high rates of complications, which has introduced great challenges to a delayed revision surgery. The aim of the study was to summarize the failures, functional outcomes and prosthetic survival in revision tumor endoprostheses of the knee joint. METHODS: The clinical data of 20 patients with malignant tumors who received prosthetic revisions after limb salvage surgery from January, 2000 until January, 2018 were retrospectively reviewed. The cohort was constituted of 11 male and 9 female patients with a mean age of 34.1 years (range, 16 to 66 years). Infection cases received two-stage revisions after removing prostheses initially, while all other cases received one-stage revisions. Revision reasons and complications were well documented and analyzed. RESULTS: All patients received complete follow-up with a mean time of 64.7 months (range, 27 to 155 months). A total of 6 (6/20, 30.0%) patients experienced a second complication after revision surgery, of whom, one patient with deep infection experienced repeated infections after prosthetic revision and received amputation surgery; one patient revised of prosthetic fracture experienced an infection and received a second-stage infection revision; one case revised of prosthetic loosening had deep infection receiving anti-infective therapy with prostheses still in position; one case having wound complication healed after receiving two times of debridement surgery; one MBGCT patient experienced a second aseptic loosening 6 years after the initial loosening thus undergoing a second revision; a recurrent osteosarcoma patient died of pulmonary metastasis 3 years after revision surgery. Kaplan-Meier survival curve indicated a 5-year survival rate of initial prostheses was 75%. The Musculoskeletal Tumor Society (MSTS-93) score [20.9 (range, 15 to 27 scores)] at 1 year after revision surgeries was significantly improved (p < 0.001) when compared with the score [17.2 (range, 13 to 21 scores)] before revisions. CONCLUSION: Prosthetic mechanical problems, aseptic loosening and infections were primary reasons for revisions after tumor endoprostheses of the knee joint. Although revision surgeries were complicated while still associated with high risk of failure, which remains the remedy strategy for limb salvage and functional recovery in those patients.

Inhibition of the epigenetic suppressor EZH2 primes osteogenic differentiation mediated by BMP2.

Bone-stimulatory therapeutics include bone morphogenetic proteins (e.g. BMP2), parathyroid hormone, and antibody-based suppression of WNT antagonists. Inhibition of the epigenetic enzyme enhancer of zeste homolog 2 (EZH2) is both bone anabolic and osteoprotective. EZH2 inhibition stimulates key components of bone-stimulatory signaling pathways, including the BMP2 signaling cascade. Because of high costs and adverse effects associated with BMP2 use, here we investigated whether BMP2 dosing can be reduced by co-treatment with EZH2 inhibitors. Co-administration of BMP2 with the EZH2 inhibitor GSK126 enhanced differentiation of murine (MC3T3) osteoblasts, reflected by increased alkaline phosphatase activity, Alizarin Red staining, and expression of bone-related marker genes (e.g. Bglap and Phospho1). Strikingly, co-treatment with BMP2 (10 ng/ml) and GSK126 (5 µm) was synergistic and was as effective as 50 ng/ml BMP2 at inducing MC3T3 osteoblastogenesis. Similarly, the BMP2-GSK126 co-treatment stimulated osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells, reflected by induction of key osteogenic markers (e.g. Osterix/SP7 and IBSP). A combination of BMP2 (300 ng local) and GSK126 (5 µg local and 5 days of 50 mg/kg systemic) yielded more consistent bone healing than single treatments with either compound in a mouse calvarial critical-sized defect model according to results from µCT, histomorphometry, and surgical grading of qualitative X-rays. We conclude that EZH2 inhibition facilitates BMP2-mediated induction of osteogenic differentiation of progenitor cells and maturation of committed osteoblasts. We propose that epigenetic priming, coupled with bone anabolic agents, enhances osteogenesis and could be leveraged in therapeutic strategies to improve bone mass.

Surgical resection and reconstructive techniques using autologous femoral head bone-grafting in treating partial acetabular defects arising from primary pelvic malignant tumors.

BACKGROUND: The aim of this study is to present and evaluate surgical resection and reconstructive techniques using autologous femoral head bone-grafting in treating partial acetabular defects arising from primary pelvic malignant tumors. METHODS: From January 2009 until January 2015, a total of 20 primary pelvic malignancy cases involving the acetabulum were retrospectively investigated. Surgical resections and reconstructions were conducted based on the type of the tumor with custom osteotomy guides and autologous femoral head bone-grafting. In all cases, prosthesis survival period, complication occurrence, and clinical outcomes data were collected and analyzed. RESULTS: Thirteen male and 7 female patients with an average age of 48 years old (range 23-69 years old) were followed for a median of 69 months (range 48-112 months). Of these cases, 17 included chondrosarcomas and 3 additional patients with a malignant giant cell tumor of bone (MBGCT) as proven by pathology. During follow-up, 3 cases of chondrosarcoma recurred (15%), of which two cases received hemi-pelvic amputation, 1 case of MBGCT relapsed and developed pulmonary metastases. Two cases of acetabular prosthesis with an impending dislocation received closed reduction followed by 6 weeks of hip abduction brace fixation. One case of prosthesis loosening was revised. In another case a deep infection occurred with debridement and prosthesis removal. Musculoskeletal Tumor Society 1993 (MSTS-93) score was utilized to conduct functional evaluation: 13 cases were good, 6 were average and one was poor. CONCLUSION: The precision of the osteotomies performed is likely crucial for this type of reconstructive strategy to be successful. The use of custom guides for acetabular osteotomies and femoral head reconstruction can improve functional outcomes with relatively low complications at the intermediate length of follow-up.

Cyclin D1 Gene Silencing Promotes IL-1ß-Induced Apoptosis in Rat Chondrocytes.

This study investigated the effects of cyclin D1 gene silencing on cell proliferation and apoptosis of interleukin-1ß (IL-1ß)-induced osteoarthritis (OA) chondrocytes. Chondrocytes from healthy sprague-dawley rats were divided into blank, OA model (chondrocytes underwent IL-1ß inducement), OA trial (chondrocytes underwent IL-1ß inducement with cyclin D1-shRNA treatment), and negative control (NC; chondrocytes underwent IL-1ß inducement and control-shRNA treatment) groups. Cell proliferation was assessed by CCK-8 assay, and cell cycle and apoptosis by flow cytometry. qRT-PCR and Western blotting were performed to detect cyclin D1 and apoptosis-related factors expression levels. Chondrocyte proliferation increased after 72-96 h after incubation. The OA trial group exhibited reduced cell proliferation at 48, 72, and 96 h after treatment. The OA model, OA trial, and NC groups all contained more cells arrested in G1 phase and had higher apoptosis rates than the blank group. Additionally, the OA trial group contained more cells arrested in G1 phase, with increased apoptosis rates compared to the OA model and NC groups. The OA model group had lowest expression of cyclin D1 whereas the blank group contained the highest among the four groups. qRT-PCR also showed that the OA model, OA trial, and NC groups all had increased expression levels of Bax and reduced expression levels of Bcl-2 and P53 compared to the blank group, whereby by the OA group had the most significant change. The combined evidence in our study shows that cyclin D1 gene silencing suppresses proliferation and induces apoptosis of rat chondrocytes in IL-1ß-induced OA. J. Cell. Biochem. 119: 290-299, 2018. © 2017 Wiley Periodicals, Inc.

MicroRNA-661 Enhances TRAIL or STS Induced Osteosarcoma Cell Apoptosis by Modulating the Expression of Cytochrome c1.

AIM: Osteosarcoma (OS) is an aggressive bone malignancy that affects rapidly growing bones and is associated with a poor prognosis. Our previous study showed that cytochrome c1 (CYC1), a subunit of the cytochrome bc1 complex (complex III) of the mitochondrial electron chain, is overexpressed in human OS tissues and cell lines and its silencing induces apoptosis in vitro and inhibits tumor growth in vivo. Here, we investigated the mechanism underlying the modulation of CYC1 expression in OS and its role in the resistance of OS to apoptosis. METHODS: qRT-PCR, luciferase reporter assay, western blotting, fow cytometry, and animal experiments were performed in this study. RESULTS: MicroRNA (miR)-661 was identified as a downregulated miRNA in OS tissues and cells and shown to directly target CYC1. Ectopically expressed miR-661 inhibited OS cell growth, promoted apoptosis, and reduced the activity of mitochondrial complex III. miR-661 overexpression enhanced TRAIL or STS induced apoptosis and promoted the release of cytochrome c into the cytosol, which induced caspase-9 activation, and these effects were abolished by a caspase-3 inhibitor. Overexpression of CYC1 rescued the effects of miR-661 on sensitizing OS cells to TRAIL or STS induced apoptosis, indicating that the antitumor effect of miR-661 is mediated by the downregulation of CYC1. In vivo, miR-661 overexpression sensitized tumors to TRAIL or STS induced apoptosis in a xenograft mouse model, and these effects were attenuated by co-expression of CYC1. CONCLUSION: Taken together, our results indicate that miR-661 plays a tumor suppressor role in OS mediated by the downregulation of CYC1, suggesting a potential mechanism underlying cell death resistance in OS.

Reduction Osteotomy versus Extensive Release on Clinical Outcome Measures in Simultaneous Bilateral Total Knee Arthroplasty.

BACKGROUND During total knee arthroplasty (TKA) in varus knee deformities, reduction osteotomy (RO) and medial soft tissue release are alternative techniques to aid in achieving deformity correction. In this study, we investigated the effect of RO compared to extensive medial soft tissue release (ER) on clinical outcome measures in simultaneous bilateral TKA. MATERIAL AND METHODS We prospectively enrolled 24 patients (48 knees) with bilateral varus knee deformity from July 2014 to December 20l5. For each patient, one knee was assigned to the RO group and the contralateral knee was assigned to ER group. One year postoperative, follow-up outcomes were collected and analyzed. RESULTS Time to 90° flexion of the knee was significantly different in the RO group (1.6±0.3 days) compared to the ER group (2.0±0.4 days) (p<0.001). Using a 10-item patient reported outcome questionnaire, total scores were significantly different between the RO group (86.3±3.2) and the ER group (82.4±2.7) (p<0.001). Analysis of variance showed a significant difference on the visual analogue scale (VAS) score (p<0.001) but no significant difference in the range of motion (ROM) of the knee (p>0.05) during the follow-up year. CONCLUSIONS Knees treated with RO were associated with greater improvements in pain and function than knees treated with conventional ER technique. Additionally, RO technique did not confer an increased risk for adverse clinical outcomes. RO may therefore by a safe method to decrease postoperative pain, achieve earlier functional recovery, and increase patients' subjective satisfaction after TKA.

Efficacy of a Four-Hour Drainage Clamping Technique in the Reduction of Blood Loss Following Total Hip Arthroplasty: A Prospective Cohort Study.

BACKGROUND During total hip arthroplasty (THA) drainage is used by most surgeons. However, the optimal drainage strategy remains controversial. The aim of this prospective cohort study was to determine the safety and efficacy of a four-hour drainage clamping technique in patients undergoing THA. MATERIAL AND METHODS There were 64 patients who underwent THA from March 2012 to December 2015 who were enrolled in the study; 32 patients were randomly assigned to four hours of a drainage clamping technique (clamping group); 32 patients were treated with a non-clamping drainage technique (non-clamping group). All perioperative clinical details were recorded for comparative analysis. RESULTS The postoperative drainage volume and calculated blood loss were significantly greater in the drainage non-clamping group, p<0.001 and p=0.028, respectively. Significantly more patients in the drainage non-clamping group required a blood transfusion, seven cases versus one case (p=0.023). Significantly more units of blood were transfused in the drainage non-clamping group (p=0.001). No significant differences were found for all other clinical outcome factors. CONCLUSIONS The four-hour drainage clamping technique following THA, compared with drainage non-clamping technique reduced blood loss and requirement for blood transfusion. There was no increase in adverse clinical events using the four-hour drainage clamping method. Therefore, four-hour drainage clamping has the potential for routine use in THA.

Comparison of Local Infiltration Analgesia With Femoral Nerve Block for Total Knee Arthroplasty: A Prospective, Randomized Clinical Trial.

BACKGROUND: Total knee arthroplasty (TKA) is usually associated with severe postoperative pain, which can prevent rehabilitation of patients' knee function and influence the satisfaction of surgery. Local infiltration analgesia (LIA) as a new method to managing postoperative pain has been applied in clinical practice recently. However, the safety and efficacy of LIA compared with femoral nerve block (FNB) in postoperative pain management of TKA still remains controversial. Thus, we conducted an original clinical trial to compare LIA and FNB. METHOD: One hundred fifty-seven patients undergoing TKA were enrolled in a randomized, double-blind, single-center study. The patients received either FNB (group A) or periarticular infiltration of local anesthetic (group B). The morphine consumption used in patient-controlled analgesia after surgery, postoperative Visual Analogue Scale (VAS), Knee Society Score, and range of motion before and after surgery in both groups were analyzed, as well as the adverse effects. RESULTS: Group A consisted 78 patients, and group B contained 79 patients. The patients' characteristics including age and body mass index had no significant difference (P > .05). Morphine consumption, VAS at rest, range of motion, and Knee Society Score were similar between the 2 groups. Our study showed group B, the local anesthetic group had less VAS with movement on postoperative day 1 (P = .01) than that of group A, which means a better pain control. Because of the study design, the surgery time showed no significant difference. Eighteen patients in group A and 21 patients in group B experienced mild-to-medium nausea or vomiting. One patient in group B had dizziness and one patient in group A suffered a neuropraxic injury to the femoral nerve. No urinary retention case was seen during inpatient days. There were no significant differences between the 2 groups about side effects. CONCLUSIONS: Our research showed that no significant differences were observed between the 2 treatment groups. LIA could provide a similar analgesic effect to FNBs with a low incidence of complications.

The Effect of Patella Eversion on Clinical Outcome Measures in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

BACKGROUND: During total knee arthroplasty (TKA), surgical exposure requires mobilization technique of the patella. With this trial, we intended to investigate the effect of patella eversion on clinical outcome measures in simultaneous bilateral TKA. METHODS: We prospectively enrolled 44 patients (88 knees) from April 2008 to June 20l4.One knee was operated with patella eversion (group A) and the other with patella lateral retraction (group B) randomly. Follow-up results, including the operation time, complications, and the time of achieving straight leg raise (SLR) and 90° knee flexion, were recorded. The data of range of motion (ROM) and Visual Analogue Scale score were collected separately at 7 days, 3 months, 6 months, and 1 year postoperatively. RESULTS: The time of achieving SLR was 2.7 ± 0.8 days in group A and 2.1 ± 0.7 DAYS in group B, which were significantly different (P = .032). Significant difference was found on active and passive ROM during the follow-up times between groups A and B, except the passive ROM at 6 months postoperatively. No significant difference was found on operation time, complications, patella baja or tilt, time of achieving 90°knee flexion, and Visual Analogue Scale score during the follow-up times. CONCLUSIONS: Patellar eversion was adverse to the early knee function recovery after TKA; it would delay the time of achieving SLR and decrease the passive and active ROM. In addition, more carefully and scientifically designed randomized controlled trials are still required to further prove the claim.

No difference in clinical outcome between patella eversion and lateral retraction in total knee arthroplasty: a systemic review and meta-analysis.

PURPOSE: Surgical exposure during total knee arthroplasty (TKA) requires mobilization technique of the patella. Proponents of minimally invasive TKA claim that lateral retraction, rather than eversion, of the patella may be beneficial. Many randomized controlled studies attempt to identify this issue; however, no final conclusion arrives. With this systemic review and meta-analysis, we intended to test whether patella eversion during TKA had deleterious effects. METHODS: A comprehensive literature search was performed in PubMed, MEDLINE, EMBASE and other internet database. We retrieved all the relevant studies designed to interpret this issue. The searching time frame was from the establishing of these databases until July 2014. RESULTS: Six randomized controlled trials assessing a total of 414 patients and 451 knees were included. The duration of surgery was much shorter (p = 0.003), and the length of skin incision was much longer (p < 0.00001). No significant difference was found on other measurements, including length of hospital stay, quadriceps strength, complications, straight leg raise, Visual Analogue Scale score and functional scores. CONCLUSIONS: Patella eversion could decrease the duration of the surgery; nevertheless, the length of skin incision was longer; no significant difference was found on other measurements, especially the quadriceps strength and complications which were concerned. Patella eversion and patella lateral retraction could achieve similar clinical outcomes. LEVEL OF EVIDENCE: Systematic review and meta-analysis, Level I.

Releasing of tourniquet before wound closure or not in total knee arthroplasty: a meta-analysis of randomized controlled trials.

The purpose of this study is to examine our hypothesis that releasing tourniquet intraoperatively before wound closure is better than releasing postoperatively after wound closure and bandaging. We carried out a systematic review using meta-analysis of selected randomized controlled trials comparing tourniquet releasing before and after wound closure in TKA. The results showed that tourniquet releasing before wound closure significantly increased the total blood loss (P<0.00001), calculated blood loss (P<0.0001) as well as postoperative blood loss (P=0.007). However, it decreased the risk of both minor (P=0.0007) and major complications (P=0.05). The available evidence indicated that releasing tourniquet before wound closure for hemostasis increased perioperative blood loss, nevertheless, the risk of complications decreased significantly.

The Comparison of Local Infiltration Analgesia with Peripheral Nerve Block following Total Knee Arthroplasty (TKA): A Systematic Review with Meta-Analysis.

Total knee arthroplasty (TKA) is usually associated with severe post-operative pain, which can prevent rehabilitation of patients' knee function and influence the satisfaction of surgery. Local infiltration analgesia (LIA) is a method that has been applied in clinical practice recently. However, the clinical use of this method is still under discussion. In this paper, we systematically reviewed randomized clinical trails (RCTs) comparing LIA with peripheral nerve block (PNB) to verify the efficacy and safety of LIA. During the analysis, we strictly filtered papers and chose ones that had fewer disturbance variables. We also analyzed the heterogeneity. We conclude that when compared with PNB, pain control with LIA is at least comparable.

Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS-STING Pathway.

The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here, a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes is presented, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study proposes a new method for treating OS using mild PTT and immune mudulation, showing promise in overcoming current treatment limitations.

Custom-made semi-joint prosthesis replacement combined ligament advanced reinforcement system (LARS) ligament reconstruction for the limb salvage surgery of malignant tumors in the distal femur in skeletal immature children.

Purpose: To explore the application of Custom-made Semi-joint prosthesis replacement combined with Ligament Advanced Reinforcement System (LARS) ligament reconstruction for the limb salvage surgery (LSS) of malignant tumors in the distal femur and provide selections for the LSS of malignant tumors in skeletal immature children. Methods: A total of 8 children with malignant tumors in the distal femur who underwent Custom-made Semi-joint prosthesis replacement combined LARS ligament reconstruction for LSS from January, 2018 until December, 2019 in our bone and soft tissue tumor center were retrospectively recruited. The prosthesis related complications, oncological prognosis and knee function were observed, and the surgical efficacy was comprehensively evaluated. Results: The average follow-up time was 36.6 months (30-50 months). The average osteotomy length was 13.2 cm (8-20 cm) according to the preoperative imaging results and the length of the customized prosthesis. Two years after operation, the average MSTS-93 score was 24.4 (16-29) which indicated good limb functions. The range of motion of the knee was 0°-120°, with an maximum average of 100°. At last follow-up, the average height of the children increased by 8.4 cm (6-13 cm), and the average limb shortening was 2.7 cm (1.8-4.6 cm). One patient had wound complications in the early postoperative period, wound scab fell off to form superficial ulcer, in whom debridement and suturing were performed. One patient developed hematogenous disseminated prosthesis infection 2 years after surgery, and the prosthesis is now in situ with anti-infection treatment. One patient developed pulmonary metastasis during follow-up, and received chemotherapy and targeted therapy with lesion well controlled. At the last follow-up, there was no local tumor recurrence or prosthesis loosening. Conclusion: Under the premise of appropriate case selection, customized semi-joint prosthesis replacement combined with LARS ligament reconstruction provides a new option for LSS in children with distal femur malignant tumors. LARS ligament reconstruction ensures the stability and range of motion of the knee joint, which maximally preserves the epiphysis of the tibia side and the growth function of the tibia side, reduces the complications of limb length inequality in the long term and creates conditions for limb lengthening or total joint replacement in adults.

Feasibility and preliminary efficacy of tantalum components in the management of acetabular reconstruction following periacetabular oncologic resection in primary malignancies.

BACKGROUND: The aim of the study was to investigate the feasibility and preliminary efficacy of tantalum components utility in the reconstruction of acetabular defects following periacetabular oncologic resection of primary malignancies. METHODS: We prospectively collected a consecutive of 15 cases that were treated with tantalum components for acetabular reconstruction after periacetabular oncologic resection from January 2018 to December 2018. The cohort included 8 male and 7 female patients, with a mean age of 47.6 years (range, 33 to 67 years). Pathology types: chondrosarcoma (n = 9), malignant bone giant cell tumor (n = 3) and osteosarcoma (n = 3). Clinical outcomes, functional and radiographic results were recorded in detail for analysis. RESULTS: Patients received planned oncologic resection and tantalum components reconstruction without casualty; they were followed up with a mean of 39.7 months (35-45 months). The mean operation time was 4.0 h (3.0-6.0 h), and the mean blood loss was 1260 ml (800-2200 ml). Functional outcomes were assessed by MSTS-93 scale, with an average of 21.8 (12.0-26.0 scores), among which 3 cases were excellent, 11 were good and 1 was fair. The mean Harris Hip Score was 79.1scores (46.0-92.0 scores) at 1-year follow-up postoperatively. 3(3/15, 20.0%) cases experienced postoperative complications: 2 cases with hip dislocation received closed reduction under general anesthesia and were fixed with hip joint abduction braces for 6 weeks; one case had a superficial infection and received debridement with a delayed wound healing. Oncologic prognosis: one case relapsed at 8-month follow-up and received hemi-pelvic amputation; and another osteosarcoma patient experienced relapse with pulmonary metastasis and received further chemotherapy. No prosthetic loosening, displacement or fracture occurred during the follow-up period. CONCLUSION: Preliminary results suggested that the use of tantalum components in the management of acetabular reconstruction following periacetabular oncologic resection provided reasonable improvement on functional outcomes and early stability of the prostheses. Porous tantalum components are conducive to bony ingrowth, which is a potential alternative to various existing reconstruction techniques to achieve better functional outcomes.

Influence of Patella Position on Soft Tissue Balance and Clinical Outcomes in Patients Undergoing Minimally Invasive Total Knee Arthroplasty, a Randomized Clinical Trial.

BACKGROUND: We hypothesized that subluxating patellar during minimally invasive total knee arthroplasty (MIS-TKA) would affect intraoperative soft tissue balance and postoperative clinical outcome. METHODS: From December 2018 to May 2020, 189 patients receiving primary MIS-TKA were enrolled. The gap-balance technique was used, with patients randomly assigned to undergo osteotomy and balance of soft tissue with patella reduced (group A; n = 93) or subluxated (group B; n = 96). The gap and varus?valgus angle were compared between groups in both extension and flexion position. The gap and varus?valgus angle were also compared before and after reducing patellar in group B. Femoral prosthesis rotation, mechanical femoral axis-to-tibial axis angle, Knee Society Score (KSS), visual analog scale (VAS), and range of motion (ROM) were compared postoperatively between two groups. Follow-up was 12 months. RESULTS: The flexion gap and the varus angle were significantly greater (0.4 mm and 0.7 degree) after patella reduction than before reduction, but the extension joint gap and varus angle were comparable before and after patella reduction. The femoral prosthesis tended to be internally rotated (0.65 degree) in group B. ROM and VAS was better in the group A than in group B at 1 month after surgery, but the differences were not significant at 3, 6 and 12 months. KSS was comparable between the groups after surgery. CONCLUSIONS: During MIS-TKA, as far as possible, soft tissue balance should be achieved with the patella reduced; otherwise, the femoral prosthesis may be installed more internally and, after patella reduction, the flexion gap and varus angle would increase. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ChiCTR2000034106, https://www.chictr.org.cn/hvshowproject.aspx?id=39987.

Inhibition of sphingolipid metabolism in osteosarcoma protects against CD151-mediated tumorigenicity.

Osteosarcoma is the most common primary bone tumor, with a poor prognosis owing to the lack of efficient molecular-based targeted therapies. Previous studies have suggested an association between CD151 and distinct consequences in osteosarcoma tumorigenicity. However, the potential of CD151 as a therapeutic target has not yet been sufficiently explored. Here, we performed integrated transcriptomic and metabolomic analyses of osteosarcoma and identified sphingolipid metabolism as the top CD151-regulated pathway. CD151 regulates sphingolipid metabolism primarily through SPTCL1, the first rate-limiting enzyme in sphingolipid biosynthesis. Mechanistically, depletion of CD151 enhanced c-myc polyubiquitination and subsequent degradation. c-myc is vital for the transcriptional activation of SPTLC1. Functionally, sphingolipid synthesis and the SPTLC1 inhibitor, myriocin, significantly suppressed the clonogenic growth of CD151-overexpression cells. Importantly, myriocin selectively restrained CD151-high expression tumor growth in preclinical patient-derived xenograft models. Collectively, these data establish that CD151 is a key mediator of sphingolipid metabolism and provide a new approach to developing novel CD151-based targeted therapies for osteosarcoma.