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     

The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury

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The cost-of-illness for invasive meningococcal disease caused by serogroup B Neisseria meningitidis (MenB) in Germany

Introduction

Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany.

Reoperation rates and risk factors for revision 4 years after dynamic stabilization of the lumbar spine

Background Context

The concept of dynamic stabilization (DS) of the lumbar spine for treatment of degenerative instability has been introduced almost two decades ago. Dynamic stabilization follows the principle of controlling movement in the coronal plane by providing load transfer of the spinal segment without fusion and, at the same time, reducing side effects such as adjacent segment disease (ASD). So far, only little is known about revision rates after DS due to ASD and screw loosening (SL).

Probleme mit dem γ-Nagel - Optimierungsmöglichkeiten

Intramedullary nailing implants have now assumed the first place in the treatment of pertrochanteric fractures.The reasons for their popularity are their high fatigue strength and the minimally invasive surgical technique required for their use.These advantages are of great benefit to the mainly geriatric and frequently multitraumatized patients concerned.The main device in this implant group is the gamma nail, which was originally developed by Grosse and Kempf. The gamma nail yielded results superior to those obtained with the dynamic hip screw, which had been the standard so far, especially when it was used in the treatment of unstable fractures.Although there was some vigorous debate over the original principles of the gamma nail, the current system is widely accepted and is available in different variants.However,owing to the high complication rate when the system was first introduced, the original gamma nail acquired the reputation of being an implant whose use made high demands.The critical analysis of implant-specific problems associated with the original gamma nail resulted in improvements to the implant and the instruments, with a noticeably reduced complication rate and better surgical technique.This article describes its current state of development.The various components are discussed individually. The results of our own investigation appear at the end of the report, reflecting this development process.