Explore the vast range of titles available.

Fibroblast growth factor (FGF) 21, a hormone that increases insulin sensitivity, has shown promise as a therapeutic agent to improve metabolic dysregulation. Here we report that FGF21 directly targets cardiac myocytes by binding β-klotho and FGF receptor (FGFR) 4. In combination with high glucose, FGF21 induces cardiac myocyte growth in width mediated by extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. While short-term FGF21 elevation can be cardio-protective, we find that in type 2 diabetes (T2D) in mice, where serum FGF21 levels are elevated, FGFR4 activation induces concentric cardiac hypertrophy. As T2D patients are at risk for heart failure with preserved ejection fraction (HFpEF), we propose that induction of concentric hypertrophy by elevated FGF21-FGFR4 signaling may constitute a novel mechanism promoting T2D-associated HFpEF such that FGFR4 blockade might serve as a cardio-protective therapy in T2D. In addition, potential adverse cardiac effects of FGF21 mimetics currently in clinical trials should be investigated.

Fibroblast growth factor (FGF) 21, a hormone that increases insulin sensitivity, has shown promise as a therapeutic agent to improve metabolic dysregulation. Here we report that FGF21 directly targets cardiac myocytes by binding β-klotho and FGF receptor (FGFR) 4. In combination with high glucose, FGF21 induces cardiac myocyte growth in width mediated by extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. While short-term FGF21 elevation can be cardio-protective, we find that in type 2 diabetes (T2D) in mice, where serum FGF21 levels are elevated, FGFR4 activation induces concentric cardiac hypertrophy. As T2D patients are at risk for heart failure with preserved ejection fraction (HFpEF), we propose that induction of concentric hypertrophy by elevated FGF21-FGFR4 signaling constitutes a novel mechanism promoting T2D-associated HFpEF and that FGFR4 blockade might serve as a cardio-protective therapy in T2D. In addition, potential adverse cardiac effects of FGF21 mimetics currently in clinical trials should be investigated.

Venous tumour thrombus (VTT), where the primary tumour invades the renal vein and inferior vena cava, affects 10–15% of renal cell carcinoma (RCC) patients. Curative surgery for VTT is high-risk, but neoadjuvant therapy may improve outcomes. The NAXIVA trial demonstrated a 35% VTT response rate after 8 weeks of neoadjuvant axitinib, a VEGFR-directed therapy. However, understanding non-response is critical for better treatment. Here we show that response to axitinib in this setting is characterised by a distinct and predictable set of features. We conduct a multiparametric investigation of samples collected during NAXIVA using digital pathology, flow cytometry, plasma cytokine profiling and RNA sequencing. Responders have higher baseline microvessel density and increased induction of VEGF-A and PlGF during treatment. A multi-modal machine learning model integrating features predict response with an AUC of 0.868, improving to 0.945 when using features from week 3. Key predictive features include plasma CCL17 and IL-12. These findings may guide future treatment strategies for VTT, improving the clinical management of this challenging scenario. Venous tumour thrombus can occur within renal cell carcinoma, and can require complex additional surgery and treatment. Here, the authors analyse multiparametric data from patients treated with axitinib and develop a machine learning model to predict neoadjuvant treatment response.

The use of two quality-of-life questionnaires in a single clinical trial with an economic component can be challenging due to the associated workload in terms of data collection and an increased risk of missing data. The aim of our study was to determine whether the questionnaire chosen to measure health status, the St. George's Respiratory Questionnaire (SGRQ), could be administered on its own without adding the EuroQol five dimensions questionnaire (EQ-5D) for economic evaluation in emphysema studies. Data were prospectively collected during the REVOLENS trial assessing endobronchial coil treatment in severe emphysema. To quantify the association between the two questionnaires, correlations between the EQ-5D and the SGRQ were first tested and the concordance was then studied in order to know whether the two questionnaires were interchangeable. Finally, the Starkie et al algorithm predicting EQ-5D utility values from the SGRQ was used on REVOLENS's individual patient data. The Student's -test, correlation and concordance between EQ-5D individual value (from the REVOLENS study) and predicted value (from the Starkie et al algorithm) were studied to test this algorithm. Results showed a strong correlation but no concordance between the EQ-5D and the SGRQ, demonstrating that the two questionnaires are not interchangeable. Moreover, the algorithm predicting EQ-5D utilities from the SGRQ did not provide utility values comparable to those observed in the REVOLENS study. Indeed, our study demonstrated a strong correlation between predicted and individual EQ-5D values but no concordance. The use of both the EQ-5D and the SGRQ in a clinical study with an economic component is justified. Based on our results, the SGRQ should not be used to obtain a utility score to calculate the incremental cost-effectiveness ratio and conclude on the efficiency of an intervention in emphysema patients.