The Chinese Glioma Cooperative Group (CGCG) Guideline Panel for adult diffuse gliomas provided recommendations for diagnostic and therapeutic procedures. The Panel covered all fields of expertise in neuro-oncology, i.e. neurosurgeons, neurologists, neuropathologists, neuroradiologists, radiation and medical oncologists and clinical trial experts. The task made clearer and more transparent choices about outcomes considered most relevant through searching the references considered most relevant and evaluating their value. The scientific evidence of papers collected from the literature was evaluated and graded based on the Oxford Centre for Evidence-based Medicine Levels of Evidence and recommendations were given accordingly. The recommendations will provide a framework and assurance for the strategy of diagnostic and therapeutic measures to reduce complications from unnecessary treatment and cost. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China.
Graphical AbstractHighlights d Characterization of the mutational landscape of secondary glioblastoma d Clonal and subclonal METex14 promote glioma progression and mark worse prognosis d PLB-1001 is a highly selective, efficient, and BBB-permeable MET kinase inhibitor d PLB-1001 provides a safe and efficacious therapeutic approach for glioma treatment SUMMARY Low-grade gliomas almost invariably progress into secondary glioblastoma (sGBM) with limited therapeutic option and poorly understood mechanism. By studying the mutational landscape of 188 sGBMs, we find significant enrichment of TP53 mutations, somatic hypermutation, MET-exon-14-skipping (METex14), PTPRZ1-MET (ZM) fusions, and MET amplification. Strikingly, METex14 frequently co-occurs with ZM fusion and is present in $14% of cases with significantly worse prognosis. Subsequent studies show that METex14 promotes glioma progression by prolonging MET activity. Furthermore, we describe a MET kinase inhibitor, PLB-1001, that demonstrates remarkable potency in selectively inhibiting MET-altered tumor cells in preclinical models. Importantly, this compound also shows blood-brain barrier permeability and is subsequently applied in a phase I clinical trial that enrolls MET-altered chemo-resistant glioma patients. Encouragingly, PLB-1001 achieves partial response in at least two advanced sGBM patients with rarely significant side effects, underscoring the clinical potential for precisely treating gliomas using this therapy.
Background: To investigate the risk factors related to aggravation and clinical outcomes in coronavirus disease 2019 (COVID-19) patients. Methods:We performed a retrospective study on the risk factors for disease progression of cases with COVID-19. Based on the clinical types, the patients were divided into a progression group and an improvement group. Multivariable logistic regression and ROC curve analysis were performed to explore the risk factors for disease progression.Results: A total of 101 patients were included in this study; diseases progression occurred in 17 patients, 84 patients improved, 6 were transferred to intensive care unit (ICU), and 5 died. The mean time to obtain negative nucleic acid results was 12.5 ± 5.0 days. Multivariate logistic analysis indicated that age (OR, 0.104; p ¼ .002), C-reactive protein (CRP) (OR, 0.093; p < .001) and lymphocyte count (OR, 3.397; p ¼ .022) were risk factors for disease progression. ROC curve analysis revealed that the AUC of age, CRP and lymphocyte count for disease progression were 0.873, 0.911 and 0.817, respectively. Conclusions:Older age increased CRP and decreased lymphocyte count resulted in potential risk factors for COVID-19 progression. This may be helpful in identifying patients whose condition worsens at an early stage. KEYWORDS COVID-19 risk factors outcomeARTICLE HISTORY
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