Osteosarcoma (OS), the most common primary cancer of bone, exhibits a high propensity for local invasion and distant metastasis. This study sought to elucidate the role of S phase kinase-associated protein (Skp2) in osteosarcoma invasion and metastasis and to explore flavokawain A (FKA), a natural chalcone from kava extract, as a potential Skp2 targeting agent for preventing osteosarcoma progression. Skp2 was found to be overexpressed in multiple osteosarcoma cell lines, including 5 standard and 8 primary patient-derived cell lines. Patients whose tumors expressed high levels of Skp2 sustained a significantly worse metastasis-free (p = 0.0095) and overall survival (p = 0.0013) than those with low Skp2. Skp2 knockdown markedly reduced in vitro cellular invasion and in vivo lung metastasis in an orthotopic mouse model of osteosarcoma. Similar to Skp2 knockdown, treatment with FKA also reduced Skp2 expression in osteosarcoma cell lines and blocked the invasion of osteosarcoma cells in vitro and lung metastasis in vivo. Together, our findings suggest that Skp2 is a promising therapeutic target in osteosarcoma, and that FKA may be an effective Skp2-targeted therapy to reduce osteosarcoma metastasis.

Background: Quality of reduction in distal radius fractures (DRF) is assessed using radiographic parameters, however few studies examine the association between radiographic measurements and functional outcomes. Our purpose was to evaluate the relationship between radiographic measurements and clinical outcome measures following surgery for DRF using detailed testing to demonstrate further associations between post-surgical radiographic measurements and function. Methods: Measurements were performed on postoperative radiographs of 38 patients following ORIF of DRF. Measurements included: radial inclination, radial height, ulnar variance, volar tilt, radiocarpal interval (d2/w2), and the intra-articular step-off. Clinical outcome measures included motion, grip strength, functional dexterity testing, Moberg pick-up test, specific activities of daily living, DASH score, pain scale, manual-assessment questionnaire. Results: Different radiographic parameters correlated with different specific tasks. The parameter correlated with most functional tasks was ulnar-variance. Radial inclination, radial-styloid scaphoid distance, and fracture classification correlated with some functions. Intraarticular step-off, and radial height were not associated with functional testing. Conclusions: Surgical radiographic results may affect post-operative function. Detailed task specific testing may enable a better evaluation of surgical outcomes. Further study and refinement of functional assessment may change our surgical goals in DRF.

As the life expectancy of the worldwide population increases, the number of hip fractures in the elderly cohort is expected to grow. It is important for surgeons to critically analyze available treatment options for these injuries, with the goal of optimizing outcomes and minimizing complications. Femoral neck fractures make up approximately half of all hip fractures. Nonoperative treatment of valgus-impacted and nondisplaced (Garden I and II) femoral neck fractures has high rates of secondary displacement, osteonecrosis, and nonunion; only patients with notable risk for perioperative complications are treated nonoperatively. Surgical intervention is the standard of care, with options including internal fixation (IF) with multiple cancellous screws or a sliding hip screw, hemiarthroplasty, or total hip arthroplasty. Patients with a posterior tilt of greater than 20°have a high rate of revision surgery when treated with IF and may benefit from primary arthroplasty. Furthermore, primary arthroplasty has demonstrated lower revision surgery rates and equivalent postoperative mortality when compared with IF. Surgeons should be aware of the functional outcomes, complications, revision surgery rates, and mortality rates associated with each treatment modality to make a patient-specific decision regarding their care.