A general viscosity model of Campi Flegrei (Italy) melts

Viscosities of shoshonitic and latitic melts, relevant to the Campi Flegrei caldera magmas, have been experimentally determined at atmospheric pressure and 0.5 GPa, temperatures between 840 K and 1870 K, and H2O contents from 0.02 to 3.30 wt%. The concentric cylinder technique was employed at atmospheric pressure to determine viscosity of nominally anhydrous melts in the viscosity range of 101.5 - 103 Pa·s. The micropenetration technique was used to determine the viscosity of hydrous and anhydrous melts at atmospheric pressure in the high viscosity range (1010 Pa·s). Falling sphere experiments were performed at 0.5 GPa in the low viscosity range (from 100.35 to 102.79 Pa·s) in order to obtain viscosity data of anhydrous and hydrous melts. The combination of data obtained from the three different techniques adopted permits a general description of viscosity as a function of temperature and water content using the following modified VFT equation: where η is the viscosity in Pa·s, T the temperature in K, w the H2O content in wt%, and a, b, c, d, e, g are the VFT parameters. This model reproduces the experimental data (95 measurements) with a 1σ standard deviation of 0.19 and 0.22 log units for shoshonite and latite, respectively. The proposed model has been applied also to a more evolved composition (trachyte) from the same area in order to create a general model applicable to the whole compositional range of Campi Flegrei products. Moreover, speed data have been used to constrain the ascent velocity of latitic, shoshonitic, and trachytic melts within dikes. Using petrological data and volcanological information (geometrical parameters of the eruptive fissure and depth of magma storage), we estimate a time scale for the ascent of melt from 9 km to 4 km depth (where deep and shallow reservoirs, respectively, are located) in the order of few minutes. Such a rapid ascent should be taken into account for the hazard assessment in the Campi Flegrei area

Understanding the heart-brain axis response in COVID-19 patients: A suggestive perspective for therapeutic development

In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role of the deregulation of the heart-brain axis (HBA), a bidirectional flow of information, in leading to severe multiorgan disease syndrome (MODS) in patients with confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Noteworthy, HBA dysfunction may worsen the outcome of the COVID-19 patients. In this review, we discuss the critical role HBA plays in both promoting and limiting MODS in COVID-19. We also highlight the role of HBA as new target for novel therapeutic strategies in COVID-19 in order to open new translational frontiers of care. This is a translational perspective from the Italian Society of Cardiovascular Researches

Paraoxonase-1 Is Not a Major Determinant of Stent Thrombosis in a Taiwanese Population

BACKGROUND: Clopidogrel is a prodrug that undergoes in vivo bioactivation to show its antiplatelet effects. Recent studies have shown that cytochrome P450 (CYP), ATP-binding cassette transporters (ABCB1), and paraoxonase-1 (PON1) play crucial roles in clopidogrel bioactivation. Here, we aim to determine the effects of genetic polymorphisms of CYP (CYP 2C19*2, CYP 2C19*3, and CYP 2C19*17), ABCB1 (ABCB1 3435C>T, ABCB1 129T>C, and ABCB1 2677G>T/A), and PON1 (PON1 Q192R, PON1 L55M, and PON1 108C>T) on the development of stent thrombosis (ST) in patients receiving clopidogrel after percutaneous coronary intervention (PCI). METHODS AND RESULTS: We evaluated the incidence of ST (0.64%) in 4964 patients who were recruited in the CAPTAIN registry (Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions). The presence of genetic polymorphisms was assessed in 20 subjects who developed ST after aspirin and clopidogrel therapy and in 40 age- and sex-matched control subjects who did not develop ST, which was documented after 9 months of angiographic follow-up. ST was acute in 5 subjects, subacute in 7, late in 7, and very late in 1. The presence of CYP 2C19*2 allele was significantly associated with ST (adjusted odds ratio [ORadj]: 4.20, 95% confidence interval [CI], 1.263-9.544; P = 0.031). However, genetic variations in PON1 and ABCB1 showed no significant association with ST. CONCLUSION: We conclude that in a Taiwanese population, PON1 Q192R genotype is not associated with ST development after PCI. However, the presence of CYP 2C19*2 allele is a risk factor for ST development after PCI

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Impact of Chronic Kidney Disease and Platelet Reactivity on Clinical Outcomes Following Percutaneous Coronary Intervention

We investigated the interaction between chronic kidney disease (CKD) and high platelet reactivity (HPR) in determining long-term clinical outcomes following elective PCI for stable coronary artery disease (CAD). A total of 500 patients treated with aspirin and clopidogrel were divided based on the presence of CKD (defined as glomerular filtration rate of < 60 ml/min/1.73 m2) and HPR (defined as a P2Y12 reaction unit value ≥ 240 at VerifyNow assay). Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5 years. Patients with both CKD and HPR showed the highest estimates of MACE (25.6%, p = 0.005), all-cause death (17.9%, p = 0.004), and cardiac death (7.7%, p = 0.004). The combination of CKD and HPR was an independent predictor of MACE (HR 3.12, 95% CI 1.46–6.68, p = 0.003). In conclusion, the combination of CKD and HPR identifies a cohort of patients with the highest risk of MACE at 5 years

Evidence of thermal-driven processes triggering the 2005–2014 unrest at Campi Flegrei caldera

An accelerating process of ground deformation that began 10 years ago is currently affecting the Campi Flegrei caldera. The deformation pattern is here explained with the overlapping of two processes: short time pulses that are caused by injection of magmatic fluids into the hydrothermal system; and a long time process of heating of the rock. The short pulses are highlighted by comparison of the residuals of ground deformation (fitted with an accelerating polynomial function) with the fumarolic CO2/CH4 and He/CH4 ratios (which are good geochemical indicators of the arrival of magmatic gases). The two independent datasets show the same sequence of five peaks, with a delay of ∼200 days of the geochemical signal with respect to the geodetic signal. The heating of the hydrothermal system, which parallels the long-period accelerating curve, is inferred by temperature–pressure gas geoindicators. Referring to a recent interpretation that relates variations in the fumarolic inert gas species to open system magma degassing, we infer that the heating is caused by enrichment in water of the magmatic fluids and by an increment in their flux. Heating of the rock caused by magmatic fluids can be a central factor in triggering unrest at calderas

Viscosity of high-K basalt from the 5th April 2003 Stromboli paroxysmal explosion

The 5th April 2003 paroxysmal event was the strongest explosion that has occurred at Stromboli in the last 50 years. This event lasted only few minutes and was characterised by two violent explosions, followed by gas and pyroclast emission. In order to constrain models of the dynamics of the paroxystic event the viscosity of anhydrous and hydrous Stromboli high potassium (HK)-basaltic melts have been measured. Viscosity has been investigated in the low viscosity range with the falling sphere method at superliquidus temperatures (1423 to 1673 K) and 0.5 GPa and in the high viscosity range with micropenetration near the glass transition temperature (723 to 1035 K) at atmospheric pressure. Falling sphere experiments were performed in a piston cylinder apparatus with melts whose water content varies from nominally anhydrous (0.02 wt.% H2O) to 4.16 wt.% H2O. The combination of high- and low-viscosity data permits a general description of the viscosity as a function of temperature and water contentusing a modified Tamman–Vogel–Fulcher equation. Using these new viscosity data, an estimation of the flow regime and magma velocity is performed. Our data suggest that the ascent of magma from the 7–8 km deep reservoir to a shallower reservoir located at about 3 km of depth, may occur within minutes. Moreover, we infer a turbulent flow regime. Finally, our estimates of the ascent velocity agree qualitatively with results from petrological studies (e.g. [Bertagnini, A., Métrich, N., Landi, P., Rosi, M., 2003. Stromboli volcano (Aeolian Archipelago, Italy): an open window on the deep-feeding system of a steady state basaltic volcano. Journal of Geophysical Research 108, 2336–2350.]), which indicate a turbulent flow regime and rapid ascent velocities such to inhibit volatile-loss-induced crystallization. We conclude that hazard evaluation at Stromboli Island should incorporate the likelihood of very rapid ascent of less-evolved melts from depth