RESUMO
Sodium-glucose co-transporter type 2 (SGLT2) inhibitor therapy to treat type 2 diabetes unexpectedly reduced all-cause mortality and hospitalization due to heart failure in several large-scale clinical trials, and has since been shown to produce similar cardiovascular disease-protective effects in patients without diabetes. How SGLT2 inhibitor therapy improves cardiovascular disease outcomes remains incompletely understood. Metabolic flexibility refers to the ability of a cell or organ to adjust its use of metabolic substrates, such as glucose or fatty acids, in response to physiological or pathophysiological conditions, and is a feature of a healthy heart that may be lost during diabetic cardiomyopathy and in the failing heart. We therefore undertook studies to determine the effects of SGLT2 inhibitor therapy on cardiac metabolic flexibility in vivo in obese, insulin resistant mice using a [U13C]-glucose infusion during fasting and hyperinsulinemic euglycemic clamp. Relative rates of cardiac glucose versus fatty acid use during fasting were unaffected by EMPA, whereas insulin-stimulated rates of glucose use were significantly increased by EMPA, alongside significant improvements in cardiac insulin signaling. These metabolic effects of EMPA were associated with reduced cardiac hypertrophy and protection from ischemia. These observations suggest that the cardiovascular disease-protective effects of SGLT2 inhibitors may in part be explained by beneficial effects on cardiac metabolic substrate selection.
RESUMO
OBJECTIVES: To report a tertiary referral centre's experience of microwave ablation (MWA) for suspected renal cell carcinoma (RCC), describing complications and oncological outcomes. PATIENTS AND METHODS: Consecutive MWA procedures (n = 113) for renal masses (October 2016 to September 2019) were maintained on a prospective database. Data describing patient, disease, procedure, complications, and oncological outcomes were analysed. RESULTS: The median (range) age was 68 (33-85) years, 73% were male, and the median Charlson Comorbidity Index was 0. The median (interquartile range [IQR]) tumour diameter was 25 (20-32) mm. In all, 95% had renal mass biopsy, with histologically confirmed cancer in 75%. The median (IQR) R.E.N.A.L. (Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location) nephrometry score was 7 (6-8). The median ablation time was 6 min and length of stay was 1 day for 95% of the patients. Clavien-Dindo complication Grades I, II, IIIb and IV occurred in 18%, 1.8%, 0.9% and 0.9%, respectively. The median follow-up was 12 months and the median (IQR) renal function change was -4 (-18 to 0)%. One patient (0.9%) had local recurrence, treated with re-ablation; two developed metastatic progression; and two (1.8%) had indeterminate findings on follow-up (one lung nodule and one possible local recurrence), managed with ongoing protocolised computed tomography surveillance. Post-procedure complications were associated with total ablation time (odds ratio [OR] 1.152/min, 95% confidence interval [CI] 1.040-1.277) and total ablation energy (OR 1.017/kJ, 95% CI 1.001-1.033). CONCLUSIONS: We describe the largest UK series of MWA treatment for T1a/small T1b renal masses to date. MWA was well tolerated, with 95% discharged the following day and low complication/re-admission rates. Current follow-up demonstrates favourable disease control. MWA appears to be safe and effective and should be considered in future prospective comparisons of treatments for T1a/small T1b renal masses.
