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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.

Opting for a preemptive kidney transplant (PKT) can help avoid costs and morbidity associated with dialysis. However, while multiple studies have shown clinical benefits of PKT, other studies have not demonstrated this, leading to controversy in the literature regarding the exact benefits of PKT. Therefore, this study aimed to determine the clinical outcomes of PKT versus non-preemptive kidney transplantation (nPKT) in adult patients. Multiple databases were searched up to May 4, 2022. Independent reviewers selected studies for inclusion and extracted relevant data. Risk of bias was assessed using the Downs and Black checklist. Eighty-seven studies including 859,715 adult kidney transplant patients were included the review. The risk of patient death (relative risk [95% confidence interval] 0.74 [0.60–0.91]) was significantly lower in PKT versus nPKT patients for living donor (LD) transplants, whereas the risk of overall graft loss was significantly lower in PKT compared to nPKT patients for both LD (0.72 [0.62–0.83]) as well as deceased donor (DD) transplants (0.80 [0.69–0.92]). The evidence suggests that LD PKT patients have a lower risk of patient death and graft loss compared to nPKT patients, and DD PKT patients have a lower risk of graft loss than nPKT patients. • Living donor PKT patients have a lower risk of patient death and graft loss compared to nPKT patients. • Deceased donor PKT patients have a lower risk of overall graft loss than nPKT patients. [ABSTRACT FROM AUTHOR]

Occupational therapists and certified driving rehabilitation specialists are uniquely skilled to assess functional abilities underlying driving performance. However, little information exists on the utility of clinical assessments to determine driving performance in people with epilepsy. This case study demonstrates how an occupational therapy evaluation battery was used to examine differences in visual and cognitive abilities and simulated driving performance before and after epilepsy surgery. Specifically, a 43-yr-old White man with right anterior lobe epilepsy underwent temporal lobectomy and had his driving-related abilities and simulated driving performance assessed pre- and postsurgery. The occupational therapy evaluation indicated improvements in executive skills, attention, and information processing speed postsurgery. Visuospatial abilities worsened after surgery, likely contributing to the modest increase in vehicle position errors on the driving simulator. Nevertheless, simulated driving performance improved after temporal lobectomy. Reductions in the number of visual scanning, lane maintenance, and speed regulation errors were recorded. [ABSTRACT FROM AUTHOR]