Routine laboratory parameters to support decision on parenteral nutrition in palliative care

IntroductionParenteral nutrition (PN) is widely used in palliative care (PC), but there is limited evidence to support its use at the end of life (EOL). This aim of this was to investigate the relationship between routine laboratory parameters and survival in patients receiving PN, and to develop a decision tree model to support clinicians decide whether to start or forgo PN.MethodsThe laboratory parameters of 113 patients with advanced diseases who were admitted to a specialized palliative care unit (PCU) were analyzed at two points in time: T0 = before PN, T1 = two weeks after initiation of PN. Univariate Mann-Whitney U-tests and multivariate linear regression models, as well as a decision tree analysis were computed; all in relation to survival time.ResultsThe final regression model was significant with p = 0.001 (adjusted R2 = 0.15) and included two predictors for survival time after PN initiation: the CRP/albumin ratio and urea at T1 (ps = 0.019). Decision tree analysis revealed three important predictors for classification of survival time after PN initiation: CRP, urea, and LDH (all at T0).DiscussionThe decision tree model may help to identify patients likely to benefit from PN, thus supporting the clinical decision whether or not to start PN

Fibroblast growth factor receptor 4 promotes glioblastoma progression: a central role of integrin-mediated cell invasiveness

Glioblastoma (GBM) is characterized by a particularly invasive phenotype, supported by oncogenic signals from the fibroblast growth factor (FGF)/ FGF receptor (FGFR) network. However, a possible role of FGFR4 remained elusive so far. Several transcriptomic glioma datasets were analyzed. An extended panel of primary surgical specimen-derived and immortalized GBM (stem)cell models and original tumor tissues were screened for FGFR4 expression. GBM models engineered for wild-type and dominant-negative FGFR4 overexpression were investigated regarding aggressiveness and xenograft formation. Gene set enrichment analyses of FGFR4-modulated GBM models were compared to patient-derived datasets. Despite widely absent in adult brain, FGFR4 mRNA was distinctly expressed in embryonic neural stem cells and significantly upregulated in glioblastoma. Pronounced FGFR4 overexpression defined a distinct GBM patient subgroup with dismal prognosis. Expression levels of FGFR4 and its specific ligands FGF19/FGF23 correlated both in vitro and in vivo and were progressively upregulated in the vast majority of recurrent tumors. Based on overexpression/blockade experiments in respective GBM models, a central pro-oncogenic function of FGFR4 concerning viability, adhesion, migration, and clonogenicity was identified. Expression of dominant-negative FGFR4 resulted in diminished (subcutaneous) or blocked (orthotopic) GBM xenograft formation in the mouse and reduced invasiveness in zebrafish xenotransplantation models. In vitro and in vivo data consistently revealed distinct FGFR4 and integrin/extracellular matrix interactions. Accordingly, FGFR4 blockade profoundly sensitized FGFR4-overexpressing GBM models towards integrin/focal adhesion kinase inhibitors. Collectively, FGFR4 overexpression contributes to the malignant phenotype of a highly aggressive GBM subgroup and is associated with integrin-related therapeutic vulnerabilities