Interpretable clinical visualization model for prediction of prognosis in osteosarcoma: a large cohort data study.

Background: Currently, the clinical prediction model for patients with osteosarcoma was almost developed from single-center data, lacking external validation. Due to their low reliability and low predictive power, there were few clinical applications. Our study aimed to set up a clinical prediction model with stronger predictive ability, credibility, and clinical application value for osteosarcoma. Methods: Clinical information related to osteosarcoma patients from 2010 to 2016 was collected in the SEER database and four different Chinese medical centers. Factors were screened using three models (full subset regression, univariate Cox, and LASSO) via minimum AIC and maximum AUC values in the SEER database. The model was selected by the strongest predictive power and visualized by three statistical methods: nomogram, web calculator, and decision tree. The model was further externally validated and evaluated for its clinical utility in data from four medical centers. Results: Eight predicting factors, namely, age, grade, laterality, stage M, surgery, bone metastases, lung metastases, and tumor size, were selected from the model based on the minimum AIC and maximum AUC value. The internal and external validation results showed that the model possessed good consistency. ROC curves revealed good predictive ability (AUC > 0.8 in both internal and external validation). The DCA results demonstrated that the model had an excellent clinical predicted utility in 3 years and 5 years for North American and Chinese patients. Conclusions: The clinical prediction model was built and visualized in this study, including a nomogram and a web calculator (https://dr-lee.shinyapps.io/osteosarcoma/), which indicated very good consistency, predictive power, and clinical application value.

Sox11 Modified Tendon-Derived Stem Cells Promote the Repair of Osteonecrosis of Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a leading cause of mobility impairment which may lead to a total hip replacement. Recent studies have found tendon derived stem cells (TDSCs) might be an ideal cell source for musculoskeletal tissue regeneration. And our previous study has shown Sox11 could promote osteogenesis of bone marrow-derived MSCs. However, the effect of TDSCs or Sox11 over-expressing TDSCs (TDSCs-Sox11) on bone regeneration in ONFH has not been investigated. In the present study, TDSCs were infected with AAV carrying Sox11 or empty vector. We showed that Sox11 could promote the proliferation and osteogenic differentiation of TDSCs, as well as angiogenesis in vitro. The western blot analysis showed that Sox11 could activate the PI3K/Akt signaling pathway to promote osteogenesis of TDSCs. Finally, using a rabbit model of hormone-induced ONFH, our result demonstrated that local administration of TDSCs or TDSCs overexpressing Sox11 could accelerate bone regeneration in necrotic femoral heads, and TDSCs overexpressing Sox11 showed better effects. TDSCs over-expressing Sox11 might be a promising cell source for stem cell therapy to promote bone regeneration, such as ONFH, fracture, bone defect, and so on.

Comparison of 10-Year Survival Outcomes for Early Single Hepatocellular Carcinoma following Different Treatments.

INTRODUCTION: To compare the actual 10-year survival outcomes of early single hepatocellular carcinoma (HCC) patients between 3 first-line treatments: radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT). METHODS: A total of 1255 early single HCC patients retrieved from the Surveillance Epidemiology and End Results (SEER) database were included. Patients survived ≥10 years, and patients died <10 years were compared. Significant predictors associated with 10-year survival were identified by multivariate logistic regression analysis. The 10-year survival outcomes of 3 treatments were compared using multivariate model risk adjustment and inverse probability of treatment weighted (IPTW) adjustment. RESULTS: Of the 1255 patients, 472 patients underwent SR, 259 patients underwent LT, and 524 patients underwent RFA. 149 patients achieved 10-year survival. Multivariate logistic regression analysis showed that age, race, treatment, and fibrosis score were significant predictors for 10-year survival, and LT had the best advantage of 10-year survival, followed by SR. Comparable 10-year survival outcomes were found between SR and RFA after IPTW. Then, a subgroup analysis was performed based on the tumor size, and the results showed that for ≤50 mm tumor, SR showed no significant advantages over RFA for 10-year survival. CONCLUSIONS: Estimates of the observational association of different treatments with 10-year survival are sensitive to the analytic method. LT showed the best outcomes for patients. No significant differences for 10-year survival were found between SR and RFA in the IPTW cohort. Subgroup analysis showed that for >50 mm tumor, SR showed significant advantages over RFA after IPTW.

Snail promotes the generation of vascular endothelium by breast cancer cells.

A further understanding of tumor angiogenesis is urgently needed due to the limited therapeutic efficacy of anti-angiogenesis agents. However, the origin of endothelial cells (EC) in tumors remains widely elusive and controversial. Snail has been thoroughly elucidated as a master regulator of the epithelial-mesenchymal transition (EMT), but its role in endothelium generation is not yet established. In this study, we reported a new and unexpected function of Snail in endothelium generation by breast cancer cells. We showed that high Snail-expressing breast cancer cells isolated from patients showed more endothelium generated from these cells. Expression of Snail was positively correlated with endothelial markers in breast cancer patients. The ectopic expression of Snail induced endothelial marker expression, tube formation and DiI-AcLDL uptake of breast cancer cells in vitro, and enhanced tumor growth and microvessel density in vivo. Snail-mediated endothelium generation depended on VEGF and Sox2. Mechanistically, Snail promoted the expression of VEGF and Sox2 through recruiting the p300 activator complex to these promoters. We showed the dual function of Snail in tumor initiation and angiogenesis in vivo and in vitro through activation of Sox2 and VEGF, suggesting Snail may be an ideal target for cancer therapy.

Mechanical loading mediates human nucleus pulposus cell viability and extracellular matrix metabolism by activating of NF-κB.

Lower back pain is one of the most frequent complaints in US orthopedic outpatient departments. Intervertebral disc degeneration (IDD) is an important cause of lower back pain. Previous studies have found that mechanical loading was associated with IDD, but the underlying mechanism remains unclear. In the present study, a human nucleus pulposus cell line was used to establish an in vitro mechanical loading model. Mechanical loading, western blot analysis, quantitative PCR, ELISA, cell viability assay and IHC staining were used in the current study. It was found that a short loading time of 4 h followed by a long period of rest (20 h) exerted protective effects against matrix degradation in nucleus pulposus cells, whilst a longer loading time of 20 h followed by a shorter period of rest (4 h) resulted in cell apoptosis and extracellular matrix (ECM) degradation. Excessive mechanical loading may induce ECM degradation by activation of the NF-κB signaling pathway. Taken together, these findings demonstrated that whilst moderate mechanical loading exerted beneficial effects on nucleus pulposus cells, excessive mechanical loading inhibited human nucleus pulposus cell viability and promoted ECM degradation by activating NF-κB.

Risk factors and clinical characteristics of deep knee infection in patients with intra-articular injections: A matched retrospective cohort analysis.

BACKGROUND: Deep knee infection (DKI), consisting of sepsis arthritis (SA) and chronic low-grade infection (CLGI), is a rare but catastrophic adverse event that can result from intra-articular (IA) injections. The purpose of this study was to assess the risk factors for DKI and describe the clinical characteristics of DKI in patients who received IA injections. METHODS: Fifty patients with IA injection-induced DKI who underwent surgical treatment between January 2010 and May 2016 served as cases and were matched with non-infected controls who received IA injections in a proportion of 1:5 based on age, gender, and date of admission. All IA injections (both cases and controls) were performed within 6 months of admission at our institution or at a referring institution. Risk factors for injection-induced DKI were analyzed, and the clinical characteristics between SA and CLGI were compared. RESULTS: The final multivariate logistic regression analysis demonstrated that body mass index ≥25kg/m2 [odds ratio (OR) = 2.3; 95% confidence interval (CI): 1.1-4.7], corticosteroid injections (OR = 3.21; 95% CI: 1.63-6.31), rheumatoid arthritis (OR = 2.61; 95% CI: 1.20-5.68) and injections performed by general practitioners (OR = 5.23; 95% CI: 2.00-13.67) increased the risk of DKI following IA injections. Of 50 cases, there were 21 SA cases and 29 CLGI cases. SA cases had significantly higher metrics in the categories of fever, local warmth, swelling, rest pain, night pain, limited motion, serum WBC, and CRP levels than CLGI cases. CONCLUSIONS: We identified risk factors and clinical characteristics of injection-induced DKI, which may offer improved guidance on IA injections and knowledge of DKI in patients with IA injections, especially in CLGI patients.

Inadvertent Introduction of Tissue Coring Into Joints During Arthrocentesis: An Experimental Study.

BACKGROUND The aim of this study was to investigate whether needles introduce skin plugs into joints during arthrocentesis. MATERIAL AND METHODS In the first part of this study, the arthrocentesis site was scrubbed with a fluorescein sodium swab, and 90 needles were inserted through the joint tissue and collected for examination under a fluorescence microscope. In the second part of this study, the joints were injected using 720 needles of different gauges. Two different randomly assigned needle insertion techniques were used: needle insertion straight through the joint capsule (subgroup 1) or insertion of the needle into the subcutaneous tissue followed by flushing of the needle with 0.5 mL of 0.9% normal saline prior to advancing the needle through the joint capsule (subgroup 2). RESULTS Of the 90 needle tips examined in the first part of this study, 21 had high-grade fluorescein contamination. In the second part of this study, the incidence of tissue, epidermis, and dermis contamination in subgroup 1 was 57.2%, 43.1%, and 25.0%, respectively. There was no significant difference in the incidence among different gauge needles, except for a difference in epidermis contamination between the 21-gauge and 23-gauge needles. Compared to subgroup 1, subgroup 2 had a significantly lower OR for tissue contamination. CONCLUSIONS It is common to introduce tissue coring with epidermis and dermis into the joint during arthrocentesis, which poses a potential risk for septic arthritis. However, tissue contamination of the joint may be reduced by flushing saline through the needle into the subcutaneous tissues prior to entering the joint capsule.