Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

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     

Dry eye in chronic stroke patients with hemiplegia: A cross-sectional study

ABSTRACT

Objective: Dry eye is reported to be associated with several neurological diseases. The aim of this study is to evaluate the patients with hemiplegia after stroke for dry eye and compare their results with a control group.

Materials and methods: Forty-five patients with hemiplegia and 45 individuals as the control group were included in the study. Tear function tests (Schirmer and tear breakup time) and a dry eye questionnaire for dry eye symptoms (ocular surface disease index) were performed and the results of the two groups were compared.

Results: Schirmer test results were significantly lower in the post-stroke hemiplegia group compared to the control group (11.3 ± 8.2 mm and 20.6 ± 11.6 mm, respectively, p < .001). Tear breakup time results were significantly lower in the post-stroke hemiplegia group compared to the control group (7.9 ± 3.1 s and 12.1 ± 4.3 s, respectively, p < .001). Ocular surface disease index scores were not significantly different between hemiplegia and control groups (21.6 ± 20.0 and 19.8 ± 13.9, respectively, p = .635). Schirmer scores lower than 10 mm (60% and 30%, p < .001) and tear breakup time results lower than 10 s (65.6% and 28.9%, p < .001) were also higher in the hemiplegia group compared to control group.

Conclusion: We found lower Schirmer test and tear breakup time results and similar OSDI scores in hemiplegia patients compared to controls. Hemiplegia patients may have dry eye without typical symptoms. This should be taken into consideration in the follow-up and rehabilitation of post-stroke hemiplegia patients.     

Predefined vs data-guided training prescription based on autonomic nervous system variation: A systematic review

Monitoring variations in the functioning of the autonomic nervous system may help personalize training of runners and provide more pronounced physiological adaptations and performance improvements. We systematically reviewed the scientific literature comparing physiological adaptations and/or improvements in performance following training based on responses of the autonomic nervous system (ie, changes in heart rate variability) and predefined training. PubMed, SPORTDiscus, and Web of Science were searched systematically in July 2019. Keywords related to endurance, running, autonomic nervous system, and training. Studies were included if they (a) involved interventions consisting predominantly of running training; (b) lasted at least 3 weeks; (c) reported pre- and post-intervention assessment of running performance and/or physiological parameters; (d) included an experimental group performing training adjusted continuously on the basis of alterations in HRV and a control group; and (e) involved healthy runners. Five studies involving six interventions and 166 participants fulfilled our inclusion criteria. Four HRV-based interventions reduced the amount of moderate- and/or high-intensity training significantly. In five interventions, improvements in performance parameters (3000 m, 5000 m, Loadmax, Tlim) were more pronounced following HRV-based training. Peak oxygen uptake () and submaximal running parameters (eg, LT1, LT2) improved following both HRV-based and predefined training, with no clear difference in the extent of improvement in . Submaximal running parameters tended to improve more following HRV-based training. Research findings to date have been limited and inconsistent. Both HRV-based and predefined training improve running performance and certain submaximal physiological adaptations, with effects of the former training tending to be greater.     

Cuboid nutcracker fracture in children: Management and results

Introduction

Compression fractures of the cuboid bone in children and adolescents are rare. Fracture morphology, associated lesions, treatment options and long-term outcomes of this very rare injury are published in a few case reports. This study with review of the literature aims to support the understanding of fracture pattern and optimize pathways of decision making.

Klinische Notfall- und Akutmedizin als hochqualitative Weiterbildung nach internationalem Vorbild: die Perspektive der Weiterzubildenden

Notfall + Rettungsmedizin -