Search

The paper analyzes the evolution of sporting activity for disabled people, focusing in particular on the problems concerning the performance of risky sporting activities by people with mental disabilities; these problems per- tain to the relationship between the protection of health understood as the interest of the community and the protection of health understood as the right to the pursuit of happiness, which also involve the question of the limits to the acts of disposing of one's body, and which are resolved through a continuous dialogue between the sports system and the state system.

A fronte dell’attuale interesse da parte dei giuristi per beni, soggetti e istituti sino ad oggi sconosciuti alla codicistica ed alla dottrina tradizionale (l’ambiente, la biodiversità, l’ecosistema, i beni comuni, le generazioni future, la proprietà intergenerazionale), che anzi negavano la loro stessa esistenza nel mondo del commercio giuridico, il libro ripercorre le vicende storiche e gli interventi legislativi in tema di usi civici e di proprietà collettive, antichi istituti che spesso a tali nuovi concetti giuridici vengono associati, sia per il loro stretto legame con il territorio sia per un gioco di assonanze tra il termine collettivo ed il termine comune. L’autore, nel ricostruire la storia di tali “altri modi di possedere” a noi pervenuti dal medioevo, e nel definirli “fossili giuridici viventi” per la loro capacità di sopravvivere nel tempo e di adattarsi alla mutevole realtà sociale senza apparenti modificazioni, evidenzia la loro irriconducibilità alla dogmatica romanistica-codicistica; egli giunge così alla conclusione che, contrariamente a quanto sino ad oggi ritenuto dalla quasi costante giurisprudenza e da una parte della dottrina, le proprietà collettive e gli usi civici siano istituti di diritto privato, arbitrariamente ricondotti ad un vago diritto pubblico nel quale peraltro non esiste alcuna pubblica amministrazione né alcun rapporto di soggezione speciale con essa (al pari di altri istituti, come l’immemoriale). Peraltro, sottolinea l’autore, a dimostrazione della difficoltà di ricondurre i cc. dd. domini collettivi all’interno di un unico istituto e della loro natura privatistica, il legislatore, con la recente l. 20 novembre 2017, n. 168, non soltanto ne ha assegnato la gestione ad associazioni di diritto privato ma li ha riconosciuti come ordinamenti giuridici primari.

Summary Background & aims COVID-19 patients present a high hospitalization rate with a high mortality risk for those requiring intensive care. When these patients have other comorbid conditions and older age, the risk for severe disease and poor outcomes after ICU admission are increased. The present work aims to describe the preliminary results of the ongoing NUTRICOVID study about the nutritional and functional status and the quality of life of adult COVID-19 survivors after ICU discharge, emphasizing the in-hospital and discharge situation of this population. Methods A multicenter, ambispective, observational cohort study was conducted in 16 public hospitals of the Community of Madrid with COVID-19 survivors who were admitted to the ICU during the first outbreak. Preliminary results of this study include data retrospectively collected. Malnutrition and sarcopenia were screened at discharge using MUST and SARC-F; the use of healthcare resources was measured as the length of hospital stay and requirement of respiratory support and tracheostomy during hospitalization; other study variables were the need for medical nutritional treatment; and patients’ functional status (Barthel index) and health-related quality of life (EQ-5D-5L). Results A total of 176 patients were included in this preliminary analysis. Most patients were male and older than 60 years, who suffered an average (SD) weight loss of 16.6% (8.3%) during the hospital stay, with a median length of stay of 53 (27–89.5) days and a median ICU stay of 24.5 (11–43.5) days. At discharge, 83.5% and 86.9% of the patients were at risk of malnutrition and sarcopenia, respectively, but only 38% were prescribed medical nutrition therapy. In addition, more than 70% of patients had significant impairment of their mobility and to conduct their usual activities at hospital discharge. Conclusions This preliminary analysis evidences the high nutritional and functional impairment of COVID-19 survivors at hospital discharge and highlights the need for guidelines and systematic protocols, together with appropriate rehabilitation programs, to optimize the nutritional management of these patients after discharge.

The work analyzes the evolution of sports bets in light of values of the legal system. It traces the events that have seen permissive or repressive attitudes prevail on the part of the legislator. It also analyze the problems of relations between the sports and the states systems in the regulation of sports betting.

The paper focus on fraudulent or unethical behaviors in which there is no awareness, reasoning, or intention, but an incorrect action that results from lack of knowledge in terms of action errors. Using error management framework, we focus on the potential positive effects of errors, to link the errors with the more general goal of learning. Literature has shown that errors are often related to communication failures and of sharing of information. To enrich our understanding about fraudulent or unethical behaviors, this article contributes to the extant literature by investigating how knowledge sharing behaviors impact on the process of learning from error within the firm, to preventing future fraudulent or unethical behavior. The study reports a case study for examining the characteristics of the knowledge sharing behaviors, and how these behaviors characteristics impact the process of learning from error within the organization, to preventing future fraudulent or unethical behavior

The research aims to explore how PhD students interacted with professors and peers and transferred knowledge during pandemic time. We firstly aim to provide an overview of communication media used by students, as well as to classify them for different kinds, social presence, and media richness. Furthermore, our research also aims to explore how doctoral students took their courses by interacting with professors and with peers, in terms of learning (KT) and social exchange relations (LMX, TMX, POS), through online learning platforms and communication media. We conducted exploratory research on 25 PhD students from 5 Italian PhD Programs in ‘economic and statistical sciences’ area. Data was collected through (a) the focus group interview with PhD students for collecting their opinions and experiences on the usage of media for communicating with professors and peers and (b) an online questionnaire aimed to measure their experiences or perceptions on technology usage and social relations. Results shown that PhD students used e-learning platform for communicating with peers and professors, so developing good social relations -even at a distance- which have encouraged knowledge transfer among them.

The essay analyzes the recent regulatory and jurisprudential developments in gaming and betting, focusing peculiarly on the public administration’s re- sponsibility pro le for the act committed by its concessionaires towards the consumer. The script criticized, in particular, the orientation of the Court of Cassation according to which the supervisory and control powers weighting on the p.a. towards the gaming and betting concessionaire give rise to indirect liability pursuant to art. 2049 of the Italian Civil Code.

The research was funded by “Operative National Plan - European Capital for Regional Development” (PON-FERS 2007-2013, Industry 2015). Authors considered the Sicilian Little and Middle Enterprise (LME) producing wastes from operational processes as like woody chips, wood shavings, shells of hazelnut or almond and so on. A previous survey carried out on a consistent sample of Sicilian LME showed that electrical power required by operational processes ranges substantially around three main values (250 / 500 / 635 kWe) and research was addressed to obtain previous values of electrical power by process of conversion of biomass. People takes in consideration the exploitation of biomass through pyrolysis process since it produces syngas usable as fuel in gas-turbine of CHP plant, bio-oil and bio-char too, both of them able to supply thermal energy to many section of expected plant. The whole paper describes the general plane of research (three sections of loop of plants) and particularly guidelines for: calculus of sizes of biomass stockpile storage (storage and drying - first section); design of equipments of pyrolysis process and exhausts treatment (pyrolysis process – second section); design of cogeneration system (CHP techniques – third section). The final result of research will specify too the economical decreasing of operational costs of LME and the remarkable environmental benefits arose by exploitation of biomass. For room reasons, the part one of paper describes the generalized characteristics of research and results of calculations to design drying and storage section.

In the clinical practice a noteworthy proportion of severe symptomatic aortic stenosis patients presents with low-flow low-gradients features, these having reported a less favorable prognosis even when surgically or transcatheter treated.We retrospectively analyzed the prospectively collected data on 1051 consecutive patients undergone balloon-expandable transcatheter aortic valve replacement at our Institution from January 2008 to January 2020. We divided the population according with a mean aortic gradient (MAG) or ≥40 mmHg and we performed a propensity-matched analysis based on the Society of Thoracic Surgery Score and age, obtaining two homogeneous groups of 314 patients each (Groups A and B, respectively). We then analyzed the outcomes of the two groups by implementing adjusted Cox models adjusted for significant clinical differences between the two groups, such as sex, ejection fraction, comorbidities and other variables not included in the propensity-matched analysis. The only variable associated with both cardiovascular and all-cause events was an ejection fraction ≤35%. Finally, a sensitivity analysis found that an ejection fraction ≤35% was associated with an increase cardiovascular and all-cause mortality only in patients with an indexed end-diastolic volume97 ml/mIn our series a MAG40 mmHg was not found to be per se an independent risk factor for cardiac and all-cause mortality after transcatheter aortic valve replacement. The ejection fraction was found to be an independent risk factor only in the context of enlarged left ventricular dimensions.

The increasing incidence of calcific aortic valve disease necessitates the elaboration of new strategies to retard the progression of the pathology with an innovative solution. While the increasing diffusion of the transcatheter aortic valve replacements (TAVRs) allows a mini-invasive approach to aortic valve substitution as an alternative to conventional surgical replacement (SAVR) in an always larger patient population, TAVR implantation still has contraindications for young patients. In addition, it is liable to undergo calcification with the consequent necessity of re-intervention with conventional valve surgery or repeated implantation in the so-called TAVR-in-TAVR procedure. Inspired by applications for non-cardiac pathologies or for vascular decalcification before stenting (i.e., coronary lithotripsy), in the present study, we show the feasibility of human valve treatment with a mini-invasive device tailored to deliver shockwaves to the calcific leaflets. We provide evidence of efficient calcium deposit ruptures in human calcified leaflets treated ex vivo and the safety of the treatment in pigs. The use of this device could be helpful to perform shockwaves valvuloplasty as an option to retard TAVR/SAVR, or as a pretreatment to facilitate prosthesis implantation and minimize the occurrence of paravalvular leak.

Introduction Valve-in-Valve transcatheter aortic valve implantation (ViV-TAVI) is an appealing treatment option for patients with degenerated aortic bioprosthetic valves. However, high post-procedural transprosthetic gradients are very common after ViV-TAVI than after TAVI for native-valve aortic stenosis. Aim We sought to evaluate transprosthetic gradients (ΔP) and hemodynamic outcome in patients undergoing ViV-TAVI according to valve type and balloon post-dilation (balloon-expandable vs self-expandable with and without post-dilation). Material and methods We retrospectively analyzed 111 patients undergoing ViV-TAVI. A balloon-expandable valve was used in 35 patients (32%, Group 1), a self-expandable valve in 76 cases of which 39 (35%, Group 2) without balloon post-dilation and 37 (33%, Group 3) with balloon post-dilation. A comprehensive transthoracic echocardiography (TTE) was performed in all patients at baseline, at discharge and at 6-months follow-up. Results Successful ViV-TAVI was performed in 110 patients (99%). Baseline peak and mean ΔP, left ventricular volumes, ejection fraction, and pulmonary artery systolic pressure were similar among groups. A significant improvement in all echocardiographic parameters was observed in all groups over time (Table 1). In particular, a significant reduction in postprocedural gradients was observed at discharge and at 6-months follow-up compared to baseline in all groups. Immediately after ViV-TAVI procedure, the lowest value of mean ΔP was observed in Group 3 (12±7 mmHg) compared to both Group 1 (20±9 mmHg) and Group 2 (17±8 mmHg, p=0.001). This result was confirmed at 6-months follow-up (p=0.012). Rate of small valve size (≤23 mm) implanted was similar among groups (Group 1: 78%, Group 2: 60%, Group 3: 62%, p=0.123). Similar 1-year all-cause mortality was observed among groups (9%, 13%, 0%, respectively, p=0.135). Conclusions In patients with failed surgical aortic prosthesis, ViV-TAVI is an effective option and is associated with sustained improved hemodynamics in all patients. Anyway, the choice of prosthetic valve type and implantation technique are relevant on residual transprosthetic gradients and should be taken into account for a better long-term outcome. Funding Acknowledgement Type of funding sources: None.

Background Low-flow low-gradient (LF-LG) aortic stenosis (AS) may occur with preserved or depressed left ventricular ejection fraction (EF), and both situations represent the most challenging subset of patients with AS to manage and generally have a poor prognosis with conservative therapy but a high operative mortality if treated surgically. Few and controversial data exist on the outcomes of these patients compared to normal-flow high-gradient (NF-HG) AS following transcatheter aortic valve replacement (TAVR). Purpose This study aims to better characterize patients with different transvalvular flow-gradient patterns undergoing TAVR and to examine the prognostic value of these flow state. Methods Overall, 1208 patients with severe symptomatic AS undergoing TAVR were categorized according to flow-gradient patterns as follow: 976 patients NF-HG (DPmean >40 mmHg), 107 paradoxical LF-LG (pLF-LG: DP mean 50%, and SVi Results TAVR was feasible in all AS subtypes. When compared with NF-HG and pLF-LG, LF-LG had a worse symptomatic status (NYHA III–IV 86% vs 62% and 67%, respectively, p Conclusions TAVR is an effective procedure in all patients with severe AS regardless of transvalvular flow-gradient patterns. However, special care should be given to characterized hemodynamic of AS, as patients with pLF-LG had similar survival rate than patients with NF-HG, whereas survival in LF-LG patients was 2-fold higher. Therefore, being able to identify patients less likely to improve after TAVR may help to guide treatment decision. Funding Acknowledgement Type of funding sources: None.

Iatrogenic acute aortic dissections during percutaneous coronary interventions are an extremely rare but potentially life-threatening complication, occurring in less than 0.02% of transcatheter procedures. We report three patients with different characteristics suffering from iatrogenic aortic dissection during percutaneous coronary intervention successfully treated with an emergency open-heart surgery. A conservative strategy should be pursuit only in small, localized lesions.

Background: Conversion of cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all of which are predisposing factors to cardiac fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response of these cells to mechanical cues through activation of the Hippo transcriptional pathway. The objective of the present study was to assess the role of cellular/nuclear straining forces acting in myofibroblast differentiation of cardiac stromal cells under the control of YAP (yes-associated protein) transcription factor and to validate this finding using a pharmacological agent that interferes with the interactions of the YAP/TAZ (transcriptional coactivator with PDZ-binding motif) complex with their cognate transcription factors TEADs (TEA domain transcription factors), under high-strain and profibrotic stimulation. Methods: We employed high content imaging, 2-dimensional/3-dimensional culture, atomic force microscopy mapping, and molecular methods to prove the role of cell/nuclear straining in YAP-dependent fibrotic programming in a mouse model of ischemia-dependent cardiac fibrosis and in human-derived primitive cardiac stromal cells. We also tested treatment of cells with Verteporfin, a drug known to prevent the association of the YAP/TAZ complex with their cognate transcription factors TEADs. Results: Our experiments suggested that pharmacologically targeting the YAP-dependent pathway overrides the profibrotic activation of cardiac stromal cells by mechanical cues in vitro, and that this occurs even in the presence of profibrotic signaling mediated by TGF-β1 (transforming growth factor beta-1). In vivo administration of Verteporfin in mice with permanent cardiac ischemia reduced significantly fibrosis and morphometric remodeling but did not improve cardiac performance. Conclusions: Our study indicates that preventing molecular translation of mechanical cues in cardiac stromal cells reduces the impact of cardiac maladaptive remodeling with a positive effect on fibrosis.

Background Permanent pacemaker implantation (PPI) remains one of the main drawbacks of transcatheter aortic valve replacement (TAVR), but scarce data exist on PPI after valve-in-valve (ViV) TAVR, particularly with the use of newer-generation transcatheter heart valves (THVs). Objectives The goal of this study was to determine the incidence, factors associated with, and clinical impact of PPI in a large series of ViV-TAVR procedures. Methods Data were obtained from the multicenter VIVID Registry and included the main baseline and procedural characteristics, in-hospital and late (median follow-up: 13 months [interquartile range: 3 to 41 months]) outcomes analyzed according to the need of periprocedural PPI. All THVs except CoreValve, Cribier-Edwards, Sapien, and Sapien XT were considered to be new-generation THVs. Results A total of 1,987 patients without prior PPI undergoing ViV-TAVR from 2007 to 2020 were included. Of these, 128 patients (6.4%) had PPI after TAVR, with a significant decrease in the incidence of PPI with the use of new-generation THVs (4.7% vs. 7.4%; p = 0.017), mainly related to a reduced PPI rate with the Evolut R/Pro versus CoreValve (3.7% vs. 9.0%; p = 0.002). There were no significant differences in PPI rates between newer-generation balloon- and self-expanding THVs (6.1% vs. 3.9%; p = 0.18). In the multivariable analysis, older age (odds ratio [OR]: 1.05 for each increase of 1 year; 95% confidence interval [CI]: 1.02 to 1.07; p = 0.001), larger THV size (OR: 1.10; 95% CI: 1.01 to 1.20; p = 0.02), and previous right bundle branch block (OR: 2.04; 95% CI: 1.00 to 4.17; p = 0.05) were associated with an increased risk of PPI. There were no differences in 30-day mortality between the PPI (4.7%) and no-PPI (2.7%) groups (p = 0.19), but PPI patients exhibited a trend toward higher mortality risk at follow-up (hazard ratio: 1.39; 95% CI: 1.02 to 1.91; p = 0.04; p = 0.08 after adjusting for age differences between groups). Conclusions In a contemporary large series of ViV-TAVR patients, the rate of periprocedural PPI was relatively low, and its incidence decreased with the use of new-generation THV systems. PPI following ViV-TAVR was associated with a trend toward increased mortality at follow-up.

The Italian legislative decree of 28 February 2021, 36, has deeply amended the regulations on sports employment contractsThe essay focuses particularly on a few aspects of the reform which have not been addressed properly, since the reform appears to be, in several parts, not taking into account the actual situation of the amateur sport. More specifically, by equalizing situations that differ from each other, the reform appears to have failed to take into proper consideration the peculiarities and the actual development of the relationships that arise in the varied sports world�

The essay analyzes the recent regulatory and jurisprudential developments in gaming and betting, focusing peculiarly on the public administration’s responsibility pro le for the act committed by its concessionaires towards the consumer. The script criticized, in particular, the orientation of the Court of Cassation according to which the supervisory and control powers weighting on the p.a. towards the gaming and betting concessionaire give rise to indirect liability pursuant to art. 2049 of the Italian Civil Code.

Fully percutaneous transfemoral transcatheter aortic valve replacement (TF-TAVR) is currently the standard of the catheter-based treatment of severe aortic stenosis patients. Even though experience, lower delivery catheters profile and improved vascular closure devices performances have resulted in an overall reduction of both vascular and bleeding complications after TAVR, femoral pseudoaneurysm due to incomplete local hemostasis may occur, prolonging the in-hospital length of stay, causing discomfort to the patient and potentially evolving in serious consequences affecting the outcome. We report two successful percutaneous ultrasound-guided closure of both the main and secondary femoral access pseudoaneurysm.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ricerca Corrente Introduction We previously demonstrated that mechanical stress deriving from coronary flow/pressure patterns in the human saphenous vein (SV) conduits induce release of Thrombospondin-1 (TSP-1) by smooth muscle cells, and this activates adventitial progenitors (SVPs) pathologic activation. Purpose In this study, we show a cooperation of the TGF-β/TSP-1 signaling with the mechanically-activated Hippo transcriptional pathway in fibrotic SVPs commitment. Methods Human derived-SVPs were isolated using a MACS based protocol with a positive selection for CD34 and a negative depletion of CD31+ cells. We performed an RNA-seq analysis of SVPs subjected to 10% uniaxial deformation (n=5), followed by differential gene expression and pathway analyses. We validated results in vitro and in two animal models of vein arterialization. Results A response of SVPs to mechanical stimulation was assessed from variations in cell alignment, circularity and area. The susceptibility of SVPs to uniaxial strain was revealed by a trend of the cells to orientate in orthogonal direction to the strain field and changes in cell shape. Mechanically stimulated cells for 72 hrs showed a significant increase in their motility as verified by migration assays in the presence of medium supplemented with 10% serum. RNA-seq analysis of the total transcriptome expressed in these cells with/without mechanical stimulation was performed. The differentially expressed genes (DEGs) analysis highlighted a maximum variation of the transcriptome at 72hrs of mechanical stimulation vs. static controls with n=819 DEGs. A gene enrichment analysis revealed an involvement of the HIPPO/YAP/TEAD and of the TGF-β/SMAD transcriptional circuitries in mechanically-stimulated cells. In keeping, immunofluorescence and RT-qPCR showed an increase in YAP nuclear translocation and activity. We treated cells with a cytoskeleton inhibitor (Forskolin, FRSK) and a drug (Verteporfin, VTP) that prevents the interaction of the YAP/TAZ complex with TEADs. Both drugs inhibited expression of YAP-transcriptional targets and cellular motility in response to serum. We then treated cells with TGF-β1, TSP-1 alone or in combination. Under these conditions we observed an increased expression of YAP targets and CollA1, a higher amount of Collagen secretion in the supernatant and a higher association of YAP with pSMAD3. All these effects were blunted by VTP. YAP nuclear localization was finally validated in two models of vein arterialization in mice and pigs. Conclusions Our data suggest a convergent activation of Hippo/TGF-β pathways in the failure of the aorto-coronary bypass and highlight a future novel strategy to limit its progression in patients.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ricerca corrente Introduction Valve interstitial cells (VICs) are heterogeneous fibroblast-like cells populating the aortic valve (AoV), involved in the extracellular matrix homeostasis. Under pathological conditions, VICs acquire the phenotype of calcific cells causing calcific aortic valve disease (CAVD) [1]. Purpose In order to find distinctive traits of the phenotype in calcific VICs, we employed single cell RNA-sequencing (scRNASeq) to compare the gene expression signatures of VICs from stenotic AoVs (sVICs) vs. valves with insufficiency (iVICs), a pathology characterized by a lower level of calcification. Methods Before being used for scRNAseq profiling, VICs from the two pathological settings were amplified for three passages, after which they were loaded into the Drop-seq platform that encapsulated them in oil droplets with lysis buffer and barcoded primer beads. Beads were then subjected to reverse transcription, followed by library preparation. Libraries were sequenced with a coverage ranging from 50,000 to 100,000 reads per cell. Results A total of 5844 iVICs and 5610 sVICs were successfully separated and barcoded. Four independent VICs donors/pathology were processed and UMAP representation/clustering of cells coming from the eight samples identified the existence of 8 distinct cellular phenotypes, including embryonic progenitor mesenchymal (EMBVICs), ‘activated’ (ACVICs), ‘osteoblastic’ (OBVICs) and ‘quiescent’ (QVICs). The analysis of the cellular composition did not reveal substantial differences in the abundance of the different phenotypes in the two pathologies. On the other hand, differential gene expression followed by functional pathways enrichment showed a significant upregulation in sVICs vs. iVICs of genes/pathways related to Interferon-I (INF-I) in all the identified cellular phenotypes with the exception of QVICs. These included e.g for ACVICs, IFITM1 (log2FC = 1.76 P=3e-101), IFI6 (log2FC = 2.38; P = 1e-69), IFITM3 (log2FC 0.9 P = 5e-58), ISG15 (log2FC = 1.7 P= 4e-53) and IFI27 (log2FC = 1.54 P = 6e-41) genes. Conclusions This study reveals the involvement of the interferon-I pathway signaling in CAVD, supporting an autophagic/inflammatory/senescent phenotype switching in relevant VICs types resident in the human AoV.

Background Familial hypercholesterolemia (FH) is a disorder characterized by elevated LDL–C and premature vascular calcifications. Aortic stenosis (AS) is the most frequent complication of bicuspid aortic valve (BAV), often requiring aortic valve replacement. Cardiac surgery in patients with severely calcified ascending aorta is challenging. Case Presentation A 28 year old male from Albania presented to the ED for dyspnea and low–threshold angina. The patient had family history for CAD and a sister with known FH treated with PCSK9–i. He had BAV, known hypercholesterolemia (max cholesterol 660 mg/dL), treated since 2015 with rosuvastatin plus ezetimibe, with reported irregular intake. He was treated with PCI and bioresorbable vascular scaffold on LAD coronary artery. He underwent surgical removal of limb xanthomas. At admission, the patient was asymptomatic at rest. Cardiac auscultatory findings included an ejection murmur in the aortic area. He presented upper and inferior eyelid xanthelasmas, bilateral calcaneal tendon thickening, elbows and knee xanthoma removal scars. Blood tests were unremarkable, except for lipid profile (LDL–C 443 mg/dL, HDL 36 mg/dL, TG 73 mg/dL). The echocardiography showed BAV, severe AS (Vmax 4,2 m/s, MPG 41 mmHg, AVA 0.46 cm2/m2), EF 60%. A coronary angiography excluded significant stenosis in the epicardial coronary vessels. An aortic CT scan showed sinotubular junction with preserved diameters and severe multiple parietal calcifications, ascending aorta with diffuse atheromatous disease. The patient underwent mechanical aortic valve replacement, ascending aorta thromboendarterectomy, non–coronary sinus enlargement patch, double CABG (SVG–OM, SVG–LAD) due to diffuse hypokinesia of the left ventricle after the interruption of extracorporeal circulation. At a 3–month outpatient re–evaluation, due to the unsatisfactory response to the regular intake of rosuvastatin plus ezetimibe (TC 309 mg/dL, TG 52 mg/dL, HDL 34 mg/dL, LDL–C 264 mg/dL), a PCSK9–i was prescribed. Genetic studies for FH are ongoing. Discussion This case underlines the importance of aortic evaluation before aortic valve replacement, even in young FH patients, in which severe aortic calcification can influence surgical approach. Conclusion We described the multidisciplinary management of a severe symptomatic AS in a young male with FH and sinotubular junction parietal calcifications, which represented a challenging substrate for valve replacement.

The article analyzes the traditional concept of necessary violence sport and proposes the replacement of this definition with that of regulated aggression sport. The aim of the work is to outline the difference between violent actions and sporting activities. The use of violence, in fact, is incompatible with the practice of sport.

Rationale: Despite the preferred application of arterial conduits, the greater saphenous vein (SV) remains indispensable for coronary bypass grafting (CABG), especially in multi-vessel coronary artery disease (CAD). The objective of the present work was to address the role of mechanical forces in the activation of maladaptive vein bypass remodeling, a process determining progressive occlusion and recurrence of ischemic heart disease.Methods: We employed a custom bioreactor to mimic the coronary shear and wall mechanics in human SV vascular conduits and reproduce experimentally the biomechanical conditions of coronary grafting and analyzed vein remodeling process by histology, histochemistry and immunofluorescence. We also subjected vein-derived cells to cyclic uniaxial mechanical stimulation in culture, followed by phenotypic and molecular characterization using RNA and proteomic methods. We finally validated our results in vitro and using a model of SV carotid interposition in pigs.Results: Exposure to pulsatile flow determined a remodeling process of the vascular wall involving reduction in media thickness. Smooth muscle cells (SMCs) underwent conversion from contractile to synthetic phenotype. A time-dependent increase in proliferating cells expressing mesenchymal (CD44) and early SMC (SM22α) markers, apparently recruited from the SV adventitia, was observed especially in CABG-stimulated vessels. Mechanically stimulated SMCs underwent transition from contractile to synthetic phenotype. MALDI-TOF-based secretome analysis revealed a consistent release of Thrombospondin-1 (TSP-1), a matricellular protein involved in TGF-β-dependent signaling. TSP-1 had a direct chemotactic effect on SV adventitia resident progenitors (SVPs); this effects was inhibited by blocking TSP-1 receptor CD47. The involvement of TSP-1 in adventitial progenitor cells differentiation and graft intima hyperplasia was finally contextualized in the TGF-β-dependent pathway, and validated in a saphenous vein into carotid interposition pig model.Conclusions: Our results provide the evidence of a matricellular mechanism involved in the human vein arterialization process controlled by alterations in tissue mechanics, and open the way to novel potential strategies to block VGD progression based on targeting cell mechanosensing-related effectors.

Background: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28). Methods: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma. Results: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures

Multiple valve replacements are known to carry additional risk of morbidity and mortality in redo context. Currently, a transcatheter-based valve-in-valve approach could be useful in reducing potential serious consequences. On the other hand, this approach poses several technical challenges regarding the device and the procedural aspects. We present the case of a 78-year-old man who presented with symptoms of heart failure due to mitral and aortic bioprosthesis degenerations who was deemed to be at extremely high risk for a conventional redo surgery. A two-step transcatheter-based approach was planned and a transfemoral aortic valve-in-valve procedure was followed by a transapical mitral valve-in-valve implantation with a favorable early and long-term outcome.

Muscle wasting represents a constant pathological feature of common chronic gastrointestinal diseases, including liver cirrhosis (LC), inflammatory bowel diseases (IBD), chronic pancreatitis (CP) and pancreatic cancer (PC), and is associated with increased morbidity and mortality. Recent clinical and experimental studies point to the existence of a gut‐skeletal muscle axis that is constituted by specific gut‐derived mediators which activate pro‐ and anti‐sarcopenic signalling pathways in skeletal muscle cells. A pathophysiological link between both organs is also provided by low‐grade systemic inflammation. Animal models of LC, IBD, CP and PC represent an important resource for mechanistic and preclinical studies on disease‐associated muscle wasting. They are also required to test and validate specific anti‐sarcopenic therapies prior to clinical application. In this article, we review frequently used rodent models of muscle wasting in the context of chronic gastrointestinal diseases, survey their specific advantages and limitations and discuss possibilities for further research activities in the field. We conclude that animal models of LC‐, IBD‐ and PC‐associated sarcopenia are an essential supplement to clinical studies because they may provide additional mechanistic insights and help to identify molecular targets for therapeutic interventions in humans.

Situs viscerum inversus always poses clinical and diagnostic challenge. We report the case of an unexpected and late discover of dextrocardia requiring aortic valve replacement.

Background Current research demonstrates that health information technology can improve the efficiency and quality of health services. However, many implementation projects have failed due to behavioural problems associated with technology usages, such as underuse, resistance, sabotage, and even rejection by potential users. Therefore, user acceptance was one of the main factors contributing to the success of health information technology implementation. However, research suggests that behavioural models do not universally hold across cultures. The present article considers national cultural values (power distance, uncertainty avoidance, individualism/collectivism, masculinity/femininity, and time orientation) as individual difference variables that affect user behaviour and incorporates them into the Technology Acceptance Model (TAM) as moderators of technology acceptance relationships. Therefore, this research analyses which national cultural values affect technology acceptance behaviour in hospitals. Methods The authors develop and test seven hypotheses regarding this relationship using the partial least squares (PLS) technique, a structural equation modelling method. The authors collected data from 160 questionnaires completed by clinicians and non-clinicians working in one hospital. Results The findings show that uncertainty avoidance, masculinity/femininity, and time orientation are the national cultural values that affect technology acceptance in hospitals. In particular, individuals with masculine cultural values, higher uncertainty avoidance, and a long-term orientation influence behavioural intention to use technology. Conclusion The bureaucratic model still decisively characterises the Italian health sector and consequently affects the choices of firms and workers, including the choice of technology adoption. Cultural values of masculinity, risk aversion, and long-term orientation affect intention to use through social norms rather than through perceived utility.

Additional file 1. The Measurement Scales and Factor loadings.

Transfemoral transcatheter aortic valve replacement (TAVR) is currently the standard catheter-based treatment of severe aortic stenosis patients. Being the transfemoral route not feasible, other access sites could be chosen. Transaortic TAVR via either a J mini-sternotomy or a right anterolateral mini-thoracotomy is a good option for patients having tricky thoracoabdominal aorta. Some tips and tricks may help in getting a fast and safe transaortic procedure.

In an attempt to deepen how the way of working is changing due to the digital transformation, this research aims at understanding the process by which individuals adopt blockchain technology in accountancy. We conducted a meta-synthesis of the qualitative literature on the topic of blockchain technology adoption in the context of accountancy. Drawing from 10 systematically selected qualitative studies, we analyzed the process of blockchain technology adoption in accountancy, with particular reference to the impacts on accounting professionals, in terms of individual attitudes and behaviors, as well as organizations. Our findings contribute to the existing literature in at least two ways. First, our research explores the topic of blockchain adoption in the accountancy domain and stresses the relevance of the use of that emerging technology by accounting professionals and organizations, as well as the main problems that could limit its adoption and use. Second, we provide an overview of the process of blockchain technology adoption with specific reference to the questions of “why” and “how” blockchain is (or is not) adopted by accounting professionals and organizations, in an effort to shed light on a critical issue that has yet to be explored in accountancy.

Aims Haemodynamic classifications of severe aortic stenosis (AS) have important prognostic implications, with low flow state (defined on the basis of a stroke volume index, SVi Methods In this single centre study, 1078 patients (mean age 81±7 years) with severe symptomatic AS (AVA40 mmHg), 94 (9%) with paradoxical low flow LG (pLF-LG: DP mean 50%, and SVi Results TAVR was feasible in all AS subtypes with similar rate of unsuccessful procedure (1.3% NF-HG, 1.1% pLF-LG, 0% LF-LG P=470). Valvular function after TAVR was excellent over time with respect to aortic pressure gradient (mean and peak) and aortic valve area regardless of flow state group (Figure A). Overall, intraoperative (P=957) and 30-day mortality (P=817) did not differ significantly among the 3 groups. Longer follow-up showed that, compared to NF-HG patients, pLF-LG had similar all-cause mortality rate [HR 1.35(0.95–1.90), P=0.094] up to 5 years and LF-LG had a significant higher mortality rate [HR 1.89(1.43–2.49), P Conclusions We provided evidence that TAVR is an effective procedure in all patients with severe AS regardless of transvalvular flow-gradient patterns. A careful haemodynamic classifications of severe AS is of utmost importance for identifying patients who benefits the most from TAVR procedure.

The aim of this study is to investigate the entrepreneurial process of new venture creation through a psychoanalytic approach. Building upon existing psychoanalytic literature, the manuscript proposes a framework for explaining the entrepreneurial process that results in individuals forming ideas for new venture creation. The framework is composed of a set of interrelated processes explaining entrepreneurial behaviour through the identification of three stages: dream, business idea, and new venture creation. Though it acknowledges previous managerial and organizational literature, this paper focuses more on “the dark side” of the entrepreneurial process by stressing the unconscious mechanisms that encourage new business ventures. The proposed framework provides a more detailed understanding of entrepreneurs’ actions and offers new insights into the evolution of the entrepreneurial process.

D. lgs. February 28, 2021, n. 36 has profoundly changed the discipline regarding sports employment contracts. The essay focuses in particular on some critical issues of the reform, which appears in many ways detached from the “living” reality of the world of amateur sports. Having equalized different situations the reform seems not to have taken into account the specificities and concrete attitudes of relationships existing in the multifaceted world of sport.

Mitral regurgitation (MR) is frequently associated with severe aortic stenosis, but its influence on outcomes after transcatheter aortic valve implantation (TAVI) remains controversial. This study sought to assess the baseline etiology and degree of MR in TAVI population, identify the predictors of MR changes and investigate the clinical and prognostic impact of baseline MR at mid and long-term follow-up.We enrolled 572 consecutive patients who underwent TAVI. MR degree and etiology were evaluated by echocardiography at baseline and 1-year follow-up. Clinical outcomes were obtained up to 3-year follow-up.At baseline, 168 patients (29%) had moderate-to-severe MR (MR ≥ 2). Organic MR was more frequently associated with MR ≥ 2 (MR 2: 20%, MR ≥ 2: 43%, p 0.001). Relevant MR had improved more in functional MR (79%) compared to organic MR (50%, p = 0.001). At the multivariate analysis, the coexistence of coronary artery disease (p = 0.026), absence of atrial fibrillation (p = 0.038) and functional etiology (p = 0.025) were predictors of MR improvement after TAVI. Patients with baseline MR ≥ 2 had a higher mortality rate than those with MR 2 at 1-year and 3-year follow-up. Moreover, a landmark analysis starting from 1-year to 3-year follow-up, demonstrated that organic MR was associated with an increased risk of mortality throughout 3-year follow-up compared with functional MR, irrespective of MR severity.Baseline MR ≥ 2 in TAVI patients was associated with early and late mortality rate. At 1-year, significant improvement in MR severity was observed mainly in patients with functional MR ≥ 2. Organic MR ≥ 2 had a negative impact on 3-year, but not 1-year, mortality rate.

Background Tracheostomy is one of the most frequent techniques in intensive care units (ICU). Fiberoptic bronchoscopy (FB) is a safety measure when performing a percutaneous dilatational tracheostomy (PDT), but the controversy surrounding the routine use of FB as part of the procedure remains open. National surveys in some European countries showed that the use of FB is non-standardized. Retrospective studies have not shown a significant difference in complications between procedures performed with or without a bronchoscope. International guidelines have not been able to establish recommendations regarding the use of FB in PDT due to lack of evidence. Design This is a multicenter (three centers at the time of publishing this paper) randomized controlled clinical trial to examine the safety of percutaneous tracheostomy using FB. We will include all consecutive adult patients admitted to the ICU in whom percutaneous tracheostomy for prolonged mechanical ventilation is indicated and with no exclusion criteria for using FB. Eligible patients will be randomly assigned to receive blind PDT or PDT under endoscopic guidance. All procedures will be performed by experienced intensivists in PDT and FB. A Data Safety and Monitoring Board (DSMB) will monitor the trial. The primary outcome is the incidence of perioperative complications. Discussion FB is a safe technique when performing PDT although its use is not universally accepted in all ICUs as a routine practice. Should PDT be monitored routinely with endoscopic guidance? This study will assess the role of FB monitoring during PDT. Trial registration ClinicalTrials.gov NCT04265625. Registered on February 11, 2020

This record contains raw data related to the article "Human cardiosphere-derived stromal cells exposed to SARS-CoV-2 evolve into hyper-inflammatory/pro-fibrotic phenotype and produce infective viral particles depending on the levels of ACE2 receptor expression" Abstract Aims: Patients with severe respiratory syndrome caused by SARS-CoV-2 undergo cardiac complications due to hyper-inflammatory conditions. Although the presence of the virus has been detected in the myocardium of infected patients, and infection of induced pluripotent cell-derived cardiomyocytes has been demonstrated, the reported expression of Angiotensin-Converting Enzyme-2 (ACE2) in cardiac stromal cells suggests that SARS-CoV-2 may determine cardiac injury by sustaining productive infection and increasing inflammation. Methods and results: We analysed expression of ACE2 receptor in primary human cardiac stromal cells derived from cardiospheres, using proteomics and transcriptomics before exposing them to SARS-CoV-2 in vitro. Using conventional and high sensitivity PCR methods, we measured virus release in the cellular supernatants and monitored the intracellular viral bioprocessing. We performed high-resolution imaging to show the sites of intracellular viral production and demonstrated the presence of viral particles in the cells with electron microscopy. We finally used RT-qPCR assays to detect genes linked to innate immunity and fibrotic pathways coherently regulated in cells after exposure to the virus. Conclusions: Our findings indicate that cardiac stromal cells are susceptible to SARS-CoV-2 infection and produce variable viral yields depending on the extent of cellular ACE2 receptor expression. Interestingly, these cells also evolved towards hyper-inflammatory/pro-fibrotic phenotypes independently of ACE2 levels. Thus, SARS-CoV-2 infection of myocardial stromal cells could be involved in cardiac injury and explain the high number of complications observed in severe cases of COVID-19., This work has been financed by a Grant from Regione Lombardia (POR FESR 2014-2020-LINEA 2A COVID-grant no. 1850333) granted to M.Pe. and A.A. M.Pe. and A.A. are supported by Institutional grants (Ricerca Corrente, 5 per 1000) issued by the Italian Ministry of Health. A.A. was supported also by COVID-2020-12371817 and COVID-2020-12371675 programme grants from the Italian Ministry of Health.

Background. Transcatheter aortic valve replacement (TAVR) is an established technique to treat severe symptomatic aortic stenosis patients with a wide range of surgical risk. Currently, the common femoral artery is the first choice as the main access route for the procedure. The objective of this observational study is to report our experience on percutaneous and surgical cut-down transfemoral TAVRs comparing the two approaches. Methods. From January 2014 to January 2019, five hundred eleven consecutive patients underwent TAVR for severe symptomatic aortic stenosis. We analyzed only elective transfemoral procedures. After propensity score-matching based on age, sex, EuroSCORE II, mean aortic gradient, and left ventricular ejection fraction, we obtained two homogeneous populations: surgical cut-down (n = 119) and percutaneous (n = 225), which were labeled Group 1 and Group 2, respectively. Results. The main findings were that there were no significant procedural outcome differences between the two groups, but Group 2 patients had a shorter length of hospital stay and were more frequently discharged home. At follow-up, Group 1 patients had lower survival rates. Conclusions. An accurate preoperative assessment of the femoral access is mandatory to achieve satisfactory outcomes with transfemoral TAVRs. Nevertheless, the percutaneous approach allows shorter in-hospital stay and the need for rehabilitation, thus potentially decreasing the costs of the procedure.

Objectives: One of the most severe and devastating complications following coronary artery bypass grafting (CABG) are cerebro-vascular accidents. Atherosclerotic disease of the ascending aorta and epi-aortic trunks has been considered the most probable cause of cerebral embolization during CABG due to aortic manipulation and clamping. The aim of this study is to investigate if single or double aortic clamping may impact the incidence of neurological events.Methods: This is a retrospective study which includes a consecutive series of patients who underwent CABG from a single CABG-experienced surgeon at our Institution from March 2006 to December 2012. Patients were divided into two homogenous groups based on the surgical technique adopted: single-aortic clamping (SAC) (118 patients) and double aortic clamp (DAC) (133 pt).Results: Median surgical time was statistically longer for the DAC group than for the SAC group (p= 0.015), but no significant differences were found for the primary outcomes of stroke and transient ischemic attack. The two groups presented a similar 30-day survival. The follow-up was completed at 82% (median 11 years). The Kaplan-Meier estimates a survival at 11 years of 81% and 88% for the DAC and SAC group, respectively. Conclusions: Incidence of stroke seems to be independent from cross-clamping technique and, more generally, we could infer that the global rate of stroke after CABG in low to moderate risk patients is probably more influenced by other factors that further studies need to address. Moreover, the appearance of the aorta at the time of surgery is crucial to analyse to better personalize the strategy.