Aims/hypothesis The strict rules applied in Italy during the recent COVID-19 pandemic, with the prohibition to attend any regular outdoor activity, are likely to influence the degree of metabolic control in patients with type 2 diabetes. We explored such putative effect immediately after the resolution of lockdown rules, in the absence of any variation of pharmacologic treatment. Methods One-hundred and fourteen patients with adequate metabolic control took part in this single-centre, prospective, observational study. The metabolic profile tested 1 week after the end of the lockdown was compared with the last value and the mean of the last three determinations performed before the pandemic emergency (from 6 months to 2 years before). Results After 8 weeks of lockdown, an increase of HbA1c > 0.3% (mean +0.7%) was observed in 26% of the participants; these were also characterized by a persistent elevation in serum triglycerides able to predict the worsening of glucose control. Conclusions Lockdown determined a relevant short-term metabolic worsening in approximately one-fourth of previously well-controlled type 2 diabetic individuals; pre-lockdown triglycerides were the only parameter able to predict such derangement of glucose control.

Context Mechanisms mediating the cardiovascular and renal protection exerted by SGLT2 inhibitors are still partially unknown. We investigated whether dapagliflozin modulates systemic and renal vascular function and structure, and induces epigenetic modifications. Subjects and Methods Forty hypertensive patients with type 2 diabetes were randomly assigned to 4-week treatment with dapagliflozin 10 mg or hydrochlorothiazide (HCT) 12.5 mg. Routine analyses; plasma renin activity; aldosterone, catecholamine, and 24-hour urinary electrolyte levels; flow-mediated dilation (FMD) of the brachial artery; carotid-femoral pulse-wave velocity (PWV); augmentation index; and resistive index and dynamic renal resistive index (DRIN) were measured at baseline and after treatment. Circulating miRNAs (miRs) related to heart failure (miR30e-5p, miR199a-3p), endothelial dysfunction (miR27b and miR200b), and renal function (miR130b-3p, miR21-5p) were assessed and related to the effects of treatments. Results Dapagliflozin and HCT marginally lowered blood pressure. Fasting glucose was lowered, whereas 24-hour diuresis, glycosuria, and osmolar clearance were increased by dapagliflozin (P < 0.001 for all), without affecting sodium excretion and glomerular filtration rate. Magnesium levels significantly increased after dapagliflozin treatment (P = 0.02). Neither dapagliflozin nor HCT modified FMD or PWV. DRIN did not vary in the dapagliflozin group, whereas it increased in the HCT group (P = 0.047 for time by treatment interaction). Both treatments induced variations in the expression of some miRs; dapagliflozin, but not HCT, significantly up-regulated miR30e-5p and downregulated miR199a-3p. Conclusion A putative epigenetic regulation of the protecting cardiovascular effect exerted by SGLT2 inhibitors was found. Dapagliflozin might exert nephroprotection by preserving renal vasodilating capacity.

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Background Remdesivir, an antiviral agent able to reduce inflammatory cascade accompanying severe, life-threatening pneumonia, became the first drug approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus 2 related severe acute respiratory syndrome (SARS CoV2). As from its previously known clinical indications, the use of remdesivir in the presence of severe renal impairment is contraindicated; however, the impact of remdesivir on renal function in aging patients has not been elucidated. Subjects and Methods This retrospective observational study involved 109 individuals consecutively admitted in internal medicine section, Azienda Ospedaliero Universitaria Pisana hospital, in November–December 2020 due to a confirmed diagnosis of SARS CoV2 and receiving remdesivir according to international inclusion criteria. Biochemical variables at admission were evaluated, together with slopes of estimated glomerular filtration rate (eGFR) built during remdesivir treatment. Participants were followed until discharge or exitus. Results Patients were stratified according to age (80 formed the study cohort and 29 served as controls); CKD stage III was present in 46% of them. No patients showed any sign of deteriorated renal function during remdesivir. Fourteen patients in the elderly cohort deceased; their eGFR at baseline was significantly lower. Recovered patients were characterized by a relevant eGFR gaining during remdesivir treatment. Conclusion We show here for the first time as remdesivir does not influence eGFR in a cohort of elderly people hospitalized for SARS CoV2, and that eGFR gain during such treatment is coupled with a better prognosis.

Objective: Bariatric surgery may ameliorate renal function through vascular mechanisms. This study tested surgery's ability to improve measured glomerular filtration rate (mGFR) and identified clinical, renal, and systemic vascular predictors of such improvement. Methods: Twenty-five nondiabetic subjects with severe obesity were studied before and 1 year after Rouxen-Y gastric bypass, evaluating mGFR and renal plasma flow, basal renal resistive index (RI) and dynamic renal RI, renal visceral fat, and systemic vascular parameters, including flow-mediated dilation, aortic pulse wave velocity, and carotid intima media thickness and stiffness. Results: After Roux-en-Y gastric bypass, BMI decreased by 31%. At follow-up, body surface area (BSA)adjusted mGFR increased (from 86.9 ± 15.2 to 109.0 ± 18.2 mL/min/1.73 m 2 , P < 0.001), whereas the absolute mGFR did not change. Renal plasma flow did not vary. RI decreased; flow-mediated dilation, pulse wave velocity, carotid intima media thickness, and carotid stiffness improved. mGFR changes after surgery (ΔmGFR/BSA) were associated with younger age and lower fasting glucose. Among vascular variables, an improved ΔmGFR/BSA was associated with smaller brachial artery diameter, lower intima media thickness, and lower RI; this latter association remained after adjusting for covariates. No measure of adiposity was associated with ΔmGFR. Conclusions: In subjects with obesity and normal renal function, bariatric surgery improves mGFR/BSA (although absolute mGFR is unchanged) and renal and systemic vascular function. Lower renal intravascular resistance can predict these improvements, maximizing them in relatively young individuals.

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Background and purpose: Neuroinflammation and probably systemic inflammation, with abnormal α-synuclein deposition, participate in the development of Parkinson's disease (PD). The P2X7 receptor/NLRP3 inflammasome complex is upregulated in the brain of PD patients. By a prospective approach, the degree of systemic activation of such complex, and its regulatory mechanisms, were explored in treatment-naïve PD individuals. Methods:The expression and functional activity of the inflammasome were measured in peripheral blood mononuclear cells of 25 newly diagnosed PD patients and 25 controls at baseline and after 12 months of pharmacological treatment, exploring the intracellular signalling involved and its epigenetic regulation.Results: De novo PD patients were characterized by a systemic hyper-expression of the P2X7R/NLRP3 inflammasome platform, probably able to modulate lymphomonocyte αsynuclein, whose brain deposits represent the main pathogenetic factor of PD. A reduced c-Jun N-terminal kinase (JNK) phosphorylation might be the intracellular signalling mediating this effect. miR-7 and miR-30, implied in the pathogenesis of PD and in the post-transcriptional control of α-synuclein and NLRP3 expression, were also increased in PD. After 1 year of usual anti-Parkinson treatments, such inflammatory platform was significantly reduced.Conclusions: Mononuclear cells of newly diagnosed PD subjects display a hyperexpression of the P2X7R/NLRP3 inflammasome platform that seems to modulate cellular α-synuclein content and is reduced after PD treatment; an impaired JNK phosphorylation might be the intracellular signalling mediating this effect, undergoing an epigenetic regulation by miR-7 and miR-30.