COVID-19 Gender Disparities and Mitigation Recommendations: A Narrative Review

The coronavirus disease 2019 (COVID-19) pandemic has rapidly created widespread impacts on global health and the economy. Data suggest that women are less susceptible to severe illness. However, sex-disaggregated data are incomplete, leaving room for misinterpretation, and focusing only on biologic sex underestimates the gendered impact of the pandemic on women. This narrative review summarizes what is known about gender disparities during the COVID-19 pandemic and the economic, domestic, and health burdens along with overlapping vulnerabilities related to the pandemic. In addition, this review outlines recommended strategies that advocacy groups, community leaders, and policymakers should implement to mitigate the widening gender disparities related to COVID-19.     

Fibroblast growth factor receptors in cancer: genetic alterations,diagnostics, therapeutic targets and mechanisms of resistance

Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.Subject terms: Cancer, Cancer     

Is There Material Loss at the Conical Junctions of Modular Components for Total Knee Arthroplasty?

BackgroundClinical concern exists regarding fretting corrosion and material loss from taper junctions in orthopedic devices, with previous research focusing on the modular components from total hip arthroplasty. Comparatively little has been published regarding the fretting corrosion and material loss in modular knee devices. The purpose of this study is to evaluate fretting corrosion damage and quantify material loss for conical total knee arthroplasty taper interfaces.MethodsStem tapers of 166 retrieved modular knee devices were evaluated for fretting corrosion using a semiquantitative scoring method. High precision profilometry was then used to determine volumetric material loss and maximum wear depth for a subset of 37 components (implanted for 0.25-18.76 years). Scanning electron microscopy and energy-dispersive X-ray spectroscopy were used to characterize the observed damage.ResultsMild to severe fretting corrosion was observed on the majority of tapers, with 23% receiving a maximum visually determined damage score of 4. The median rate of volumetric material loss was 0.11 mm³/y (range 0.00-0.76) for femoral components (both cone and bore taper surfaces combined) and 0.01 mm³ (range 0.00-8.10) for tibial components. Greater rates of material loss were associated with mixed metal pairings. There was a strong correlation between visual fretting corrosion score and calculated material loss (ρ = 0.68, P < .001). Scanning electron microscopy revealed varying degrees of scratching, wear, fretting corrosion, and instances of cracking with morphology not consistent with fretting corrosion, wear, or fatigue.ConclusionAlthough visual evidence of fretting corrosion damage was prevalent and correlated with taper material loss, the measured volumetric material loss was low compared with prior reports from total hip arthroplasty.     

H3K27 trimethylation loss in malignant peripheral nerve sheath tumor: a systematic review and meta-analysis with diagnostic implications

Journal of Neuro-Oncology - Multiple studies have reported the loss of trimethylation at lysine (K) 27 on histone 3 (H3K27me3) in high-grade malignant peripheral nerve sheath tumors (MPNSTs)....     

Reconstruction options and outcomes for breast sarcoma patients

Breast sarcomas constitute a rare and heterogeneous group of tumors. Given their aggressive nature and the potential for extensive resections, rates of reconstruction have been low. We retrospectively reviewed subjects derived from our institutional registry presented between 2003 and 2015. Thirty‐four patients with primary breast sarcoma were identified. The average age was 51.9 years and the average follow‐up was 58 months. The most common histological type was malignant phyllodes (61.8%). Two patients suffered cancer recurrence. Twelve patients (35.3%) underwent reconstruction. Four underwent implant‐based reconstruction, seven had autologous‐based reconstruction, and one had combined reconstruction. Major complications were one flap loss and one implant removal. Our relatively high rates of breast reconstruction suggest a newly increased willingness to offer reconstruction to this rarer patient population.