Biomechanical Comparison of a Notched Head Locking T-Plate and a Straight Locking Compression Plate in a Juxta-Articular Fracture Model.

OBJECTIVE: This investigation compared the biomechanical properties of a 2.0 mm locking compression notched head T-plate (NHTP) and 2.0 mm straight locking compression plate (LCP), in a simple transverse juxta-articular fracture model. STUDY DESIGN: Two different screw configurations were compared for the NHTP and LCP, modelling short (configuration 1) and long working length (configuration 2). Constructs were tested in compression, perpendicular and tension non-destructive four point bending and torsion. Plate surface strain was measured at 12 regions of interest (ROI) using three-dimensional digital image correlation. Stiffness and strain were compared between screw configurations within and between each plate. RESULTS: The LCP was stiffer than the NHTP in all three planes of bending and torsion (p < 0.05). The NHTP had greater strain than the LCP during compression bending and torsion at all ROI (p < 0.0005). The short working length was stiffer in all three planes of bending and in torsion (p < 0.05) than the longer working length for both plates. The long working length showed greater strain than the short working length at most ROI. CONCLUSION: In this experimental model, a 2.0 mm LCP with two screws in the short fragment was significantly stiffer and had lower plate strain than a 2.0 mm NHTP with three screws in the short fragment. Extending the working length significantly reduced construct stiffness and increased plate strain. These findings may guide construct selection.

Auranofin improves overall survival when combined with standard of care in a pilot study involving dogs with osteosarcoma.

Osteosarcoma is the most common paediatric primary bone malignancy. The major cause of death in osteosarcoma is drug-resistant pulmonary metastasis. Previous studies have shown that thioredoxin reductase 2 is a driver of metastasis in osteosarcoma and can be inhibited by auranofin (AF). Moreover, studies have shown that AF significantly reduces pulmonary metastases in xenotransplant models. Here, we describe a phase I/II study of AF in canine osteosarcoma, a well-recognized spontaneous model of human osteosarcoma. We performed a single-arm multicentre pilot study of AF in combination with standard of care (SOC) (amputation + carboplatin). We recruited 40 dogs to the trial and used a historical SOC-only control group (n = 26). Dogs >15 kg received 9 mg AF q3d PO and dogs <15 kg received 6 mg q3d. Follow-up occurred over at least a 3-year period. Auranofin plus SOC improved overall survival (OS) (P = .036) in all dogs treated. The improved outcome was attributable entirely to improved OS in male dogs (P = .009). At the time of writing, 10 dogs (25%) survive without measurable disease in the treatment group with survival times ranging between 806 and 1525 days. Our study shows that AF improves OS in male dogs when combined with SOC. Our findings have translational relevance for the management of canine and human osteosarcoma. Our data justify a larger multicentre phase 2 trial in dogs and a phase I/II trial in human patients with refractory disease at the time of initial surgery.

Therapeutic effect of quercetin in collagen-induced arthritis.

Quercetin, a bioactive flavonoid with anti-inflammatory, immunosuppressive, and protective properties, is a potential agent for the treatment of rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is the most commonly used animal model for studying the pathogenesis of RA. This study analysed the therapeutic role of quercetin in collagen-induced arthritis in C57BL/6 mice. The animals were allocated into five groups that were subjected to the following treatments: negative (untreated) control, positive control (arthritis-induced), arthritis+methotrexate, arthritis+quercetin, and arthritis+methotrexate+quercetin. Assessments of weight, oedema, joint damage, and cytokine production were used to determine the therapeutic effect of quercetin. This study demonstrated for the first time the anti-inflammatory and protective effects of quercetin in vivo in CIA. The results also showed that the concurrent administration of quercetin and methotrexate did not offer greater protection than the administration of a single agent. The use of quercetin as a monotherapeutic agent resulted in the lowest degree of joint inflammation and the highest protection. The reduced severity of the disease in animals treated with quercetin was associated with decreased levels of TNF-α, IL-1ß, IL-17, and MCP-1. In conclusion, this study determined that quercetin, which was non-toxic, produced better results than methotrexate for the protection of joints from arthritic inflammation in mice. Quercetin may be an alternative treatment for RA because it modulates the main pathogenic pathways of RA.