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

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

Traditional plaster casts and dental digital models : intra-examiner reliability of measurements

The aim of this study was to compare the intra-examiner reliability of measurements made on plaster cast and dental digital models. MATERIAL AND METHODS: Five young patients with different occlusal patterns were selected and their dental casts and corresponding digital models were obtained. Twenty expert orthodontists were asked to measure two times both the traditional and digital models. The measurements taken included: lower inter-canine distance, lower inter-molar distance, lower right first molar mesio-distal length, lower right lateral incisor mesiodistal length and overbite. The absolute differences between the two sets of repeated measurements were computed for each of the five couples of parameters and compared with Student's paired T tests. RESULTS: Four parameters showed no statistical difference when the error of measurement of the traditional models was compared to the error of measurement of the digital models. They where the lower inter-canine distance (p = 0.11), the lower inter-molar distance (p = 0.24), the lower right first molar mesio-distal length (p = 0.4), the lower right lateral incisor mesio-distal length (p = 0.39). On the contrary, the error of measurement for the overbite was lower (P < 0.001) for digital models (Mean = 0.24, SD = 0.21) compared to traditional models (Mean = 0.69, SD = 0.53). CONCLUSIONS: Digital and traditional casts offer the same intra-examiner reliability in most cases, but for some measurements, when digital cross sections could help, digital models seem to produce a smaller error

Models for silicate melts viscosity

D. Giordano (1,2), J.K. Russell (2), R. Moretti (3), A. Mangiacapra (3,4), M. Potuzàk (4), C. Romano (1) & D.B. Dingwell (4

Texture and composition of pumices and scoriae from the Campi Flegrei caldera (Italy): implications on the dynamics of explosive eruptions

The Campi Flegrei (CF) caldera is one of the most dangerous quiescent volcanic systems in the world. Its activity mostly resulted in low magnitude explosive eruptions, such as that of the Monte Nuovo tuff cone that represents the last eruptive event within the caldera (AD 1538). However, there have been more energetic Plinian events, i.e., the Agnano Monte Spina eruption (4.1 ky), and very highly-explosive, caldera-forming eruptions, i.e., the Campanian Ignimbrite eruption (39 ky). Here, we integrate new and literature data on the groundmass texture and composition of pyroclastic products from the three above eruptions with the aim of unraveling how volatiles content, degassing mechanisms and crystallization processes influence magma explosivity and eruption dynamics at CF. Previous studies indicate that the investigated rocks share similar major element bulk and phenocryst chemistry; also similar is the water content of their trapped melt inclusions. These observations suggest that the magmas feeding these eruptions had comparable physico-chemical properties during storage in the shallow crust. However, our investigations indicate that the studied rocks differ in texture and composition of the groundmass and viscosity of the related magmas. We ascribe such differences to the variable style of volatile exsolution and outgassing from the melt, primarily in response to changes of the rate of magma ascent to the surface. We conclude that the magma ascent rate was the key-parameter in driving explosive eruptions at CF and we suggest that this parameter may be influenced by magma/water interaction and/or magma chamber geometry and replenishment

Defining a 3D physical model for the hydrothermal circulation at Campi Flegrei caldera (Italy)

Our study is aimed to develop a 3D physical model of the Campi Flegrei geothermal system, in order to achieve a more accurate and comprehensive representation of the hydrothermal processes occurring in the caldera. The new model, developed by using the TOUGH2 code simulator, accounts for the caldera rocks' physical properties, bathymetry and water table topography. In particular, the computational domain is constrained by density values obtained by tomographic inversion of gravity data collected during several surveys at CF both onshore and offshore the caldera. Empirical relations between density and porosity and between porosity and permeability, derived by published data on samples cored in deep wells or collected in outcrops, allowed us to characterize the main rocks physical parameters controlling the dynamic of the CF geothermal system. We have performed and compared several simulations investigating the effects of the injection at depth, underneath Solfatara crater, of a hot gaseous mixture rich in CO2. We show that, with respect to the available literature on 2D axisymmetric models, the effects of the water table topography together with the bathymetry and the heterogeneous distribution of the rocks' physical properties, lead to important differences in the hydrothermal circulation of fluids at CF. These constraints allow the activation of convective cells with different behaviors, which produce variable patterns of temperature inside the hydrothermal system. As a consequence, the predominant effect is again represented by a central plume below the Solfatara crater, but with a non-axisymmetric structure and a wider extension. Additionally, high temperature zones are present near the coastline and in the middle part of the submerged area of the caldera with a SE–NW alignment. Moreover, our results indicate that, the submerged part of the CF caldera would deserve a more accurate study and survey, being affected by phenomenon of heating and degassing. This information could be very useful in terms of hazard assessment and volcanic risk mitigation in such an active and densely inhabited volcanic and geothermal area.Published172-1821.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive2.4. TTC - Laboratori di geochimica dei fluidi4.5. Studi sul degassamento naturale e sui gas petroliferiJCR Journalrestricte