Impact of Patients’ Gender on Efficacy of Immunotherapy in Patients With Metastatic Kidney Cancer: A Systematic Review and Meta-analysis

Recent meta-analyses on checkpoint inhibitors in cancer report conflicting data regarding the association of patient gender with inhibitor efficacy. In advanced kidney cancer, checkpoint inhibitors have shown improved outcomes in first- and second-line settings compared with standard of care, but the role of patient gender on treatment outcome is unclear. We aimed to assess the efficacy of immunotherapy according to patient gender in advanced kidney cancer.We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed using PubMed, Scopus, Web of Science, and The Cochrane Library to identify eligible studies published through February 16, 2019. Studies were included if they reported on the differential outcomes of male and female patients with metastatic kidney cancer receiving immunotherapy. Our outcomes of interest were overall survival (OS) or progression-free survival (PFS).Four randomized controlled trials comprising a total of 3664 patients (2715 males and 949 females) met our inclusion criteria. Both men and women with metastatic kidney cancer had an OS and PFS advantage with immunotherapy compared with standard-of-care, but no statistically significant difference between the genders was observed (OS hazard ratio [HR] for men, 0.69; 95% confidence interval [CI], 0.59-0.8; P = .40; HR for women, 0.62; 95% CI, 0.48-0.81; P = .13; PFS HR for men, 0.7; 95% CI, 0.59-0.82; P = .24; HR for women, 0.68; 95% CI, 0.52-0.90; P = .105).In patients with advanced kidney cancer receiving checkpoint inhibitors, there seems to be no association of patient gender with treatment outcome.     

A finite element study of a fractured tibia treated with a unilateral external fixator: The effects of the number of pins and cortical thickness

IntroductionIn the early stage of fracture fixation, the aim of a unilateral external fixator (UEF) to stimulate healing and maintain stability may be suppressed by using inadequate number of pins. Cortical thinning due to age or osteoporosis endangers a successful fracture fixation.Materials and methodsThis study evaluates the initial strength and stability of the fracture fixation and tissue differentiation under the influences of variable cortical thickness (5 mm to 1 mm) and variable number of pins (1 to 4 in each bone fragment). A finite element program was utilised to develop 20 three-dimensional models of simplified diaphyseal tibia with fracture callus fixed with UEF. A mechano-regulation code based on the deviatoric strain theory was written and applied to simulate tissue differentiation. The values of von Mises stress, interfragmentary strain (IFS), and fibrocartilage index (FCI) were evaluated.ResultsCortical thinning from 5 mm to 1 mm increased IFS and FCI by an average of 30.3% and 18.7%, respectively, and resulted in higher stresses in the UEF and bone. Using 1 pin in each bone fragment produced excessive IFS in the models with 1 mm, 2 mm and 3 mm cortical thickness. Inserting the second pin into the bone fragment could considerably reduce the IFS and fibrocartilaginous tissue formation in the fracture site and improve load transmission to the fixator. Whereas inserting the fourth pin could minimally affect the mechano-biological environment of healing.ConclusionsThis study suggests that initial instability due to cortical thinning can be efficiently alleviated by adding the number of pins up to 3 in a UEF; additionally, it may improve the knowledge about applying UEFs adequately stable, whilst promoting inclination toward endochondral ossification, simultaneously.