A Finite Element Model of Locked Plating in Femoral Shaft Fractures

Introduction: The Locking Compression Plate (LCP) system is a versatile technology that can be used either through conventional compression plating techniques or as an internal fixator with locking head screws. There have been only a few biomechanical studies examining the role of locked screw configuration on construct stability with most recommendations based upon empirical evidence or data from compression plating. This study will attempt to determine how different locked screw configurations, fracture gaps (distance between bone fragments), and interface gaps (distance between plate and bone) will affect the peak stress(von Mises stress) experienced by the plate-screw construct and, thereby, look at ways to minimize the risk of hardware failure. Materials Methods: A finite element model (FEM) was developed of a transverse mid shaft femoral fracture bridged by an eight-hole titanium LCP. Seven different screw configurations were investigated. Three different fracture gaps and three different interface gaps were studied as well. Results: The 1368 configuration was found to experience the least peak stress of 2.10 GPa while the 2367, 2457, and all filled configurations were found to have the highest peak stress (25.29 GPa, 22.78 GPa, and 23.54 GPa, respectively). Peak stress increased when the interface gap increased. Peak stress also increased as the fracture gap increased, with the largest jump between the 1 mm and 2 mm gaps. Conclusions: Every fracture is unique, and has a vast amount of parameters that must be considered when the surgeon is developing a treatment plan. For transverse femoral shaft fractures, the results of this study suggest that a working length of 2 screw holes on either side of the fracture may also lead to lower peak stress. In addition, our results demonstrate that minimizing the fracture gap and interface gap will lead to decreased stress in the plate-screw construct.

IRAK4 inhibition: a promising strategy for treating RA joint inflammation and bone erosion

Flares of joint inflammation and resistance to currently available biologic therapeutics in rheumatoid arthritis(RA)patients could reflect activation of innate immune mechanisms.Herein,we show that a TLR7 GU-rich endogenous ligand,miR-Let7b,potentiates synovitis by amplifying RA monocyte and fibroblast(FLS)trafficking.miR-Let7b ligation to TLR7 in macrophages(MΦs)and FLSs expanded the synovial inflammatory response.Moreover,secretion of M1 monokines triggered by miR-Let7b enhanced Th1/Th17 cell differentiation.We showed that IRAK4 inhibitor(i)therapy attenuated RA disease activity by blocking TLR7-induced M1 MΦor FLS activation,as well as monokine-modulated Th1/Th17 cell polarization.IRAK4i therapy also disrupted RA osteoclastogenesis,which was amplified by miR-Let7b ligation to joint myeloid TLR7.Hence,the effectiveness of IRAK4i was compared with that of a TNF inhibitor(i)or anti-IL-6R treatment in collagen-induced arthritis(CIA)and miR-Let7b-mediated arthritis.We found that TNF or IL-6R blocking therapies mitigated CIA by reducing the infiltration of joint F480+iNOS+MΦs,the expression of certain monokines,and Th1 cell differentiation.Unexpectedly,these biologic therapies were unable to alleviate miR-Let7b-induced arthritis.The superior efficacy of IRAK4i over anti-TNF or anti-IL-6R therapy in miR-Let7b-induced arthritis or CIA was due to the ability of IRAK4i therapy to restrain the migration of joint F480+iNOS+MΦs,vimentin+fibroblasts,and CD3+T cells,in addition to negating the expression of a wide range of monokines,including IL-12,MIP2,and IRF5 and Th1/Th17 lymphokines.In conclusion,IRAK4i therapy may provide a promising strategy for RA therapy by disconnecting critical links between inflammatory joint cells.