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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.

Additional file 1. The Measurement Scales and Factor loadings.

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.

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.

Calcific aortic valve disease (CAVD) is the most frequent cardiac valve pathology. Its standard treatment consists of surgical replacement either with mechanical (metal made) or biological (animal tissue made) valve prostheses, both of which have glaring deficiencies. In the search for novel materials to manufacture artificial valve tissue, we have conducted a high-throughput screening with subsequent up-scaling to identify non-degradable polymer substrates that promote valve interstitial cells (VICs) adherence/growth and, at the same time, prevent their evolution toward a pro-calcific phenotype. Here, we provide evidence that one of the two identified 'hit' polymers, poly(methoxyethylmethacrylate-co-diethylaminoethylmethacrylate), provided robust VICs adhesion and maintained the healthy VICs phenotype without inducing pro-osteogenic differentiation. This ability was also maintained when the polymer was used to coat a non-woven poly-caprolactone (PCL) scaffold using a novel solvent coating procedure, followed by bioreactor-assisted VICs seeding. Since we observed that VICs had an increased secretion of the elastin-maturing component MFAP4 in addition to other valve-specific extracellular matrix components, we conclude that valve implants constructed with this polyacrylate will drive the biological response of human valve-specific cells.

AIMS The safety and efficacy of single vs. dual antiplatelet therapy (DAPT) in patients undergoing TAVI remain to be addressed. The aim of our study was to evaluate the usefulness of a DAPT compared to a single platelet therapy in patients undergoing TAVI with a balloon-expandable prosthesis. METHODS AND RESULTS All consecutive patients enrolled in the ITER registry were included. Patients undergoing TAVI discharged with aspirin alone were compared to those taking DAPT before and after selection using propensity score with matching. Subgroup analysis was performed for those on OAT. Prosthetic heart valve dysfunction at follow-up was the primary endpoint, whereas all-cause death, cardiovascular death, bleedings, vascular complications and cerebrovascular accidents were the secondary ones. From 1,364 patients, after propensity score with matching, 605 were selected for each group (aspirin alone vs. DAPT). At 30 days, rates of VARC mortality were lower in patients with aspirin alone (1.5% vs. 4.1%, p=0.003), mainly driven by a reduction of major vascular complications (5.3% vs. 10.7%, p

The consideration that in postmodern society has assumed the sport practiced by so-called people disabled has clearly changed compared to what it was just seventy-five years ago, when for the first time the neurosurgeon Ludwig Guttman opened in 1944 in Stoke Mandeville one of the first European centers for the care and rehabilitation of subjects suffering from spinal injury. Currently we are witnessing a transition from the practice of physical activity for rehabilitation purposes to that of sports activity aimed at achieving performance even by people once viewed by law only as subjects "totally or partially unable".

In this conceptual chapter, we explore and discuss the potential of a private-collective approach to the governance of incentives to innovate in the pharmaceutical industry. We specifically consider the governance models elaborated for the development of Open Source Software (OSS). Its diffusion in the software industry led the literature to acknowledge the existence of a hybrid model of governing incentives to innovate : the private-collective model1. Lay press and medical journals report an increasing number of “Open Source Pharma” experiences but only little systematic enquiry exists on this issue. We contribute to this debate by discussing this issue from an economic and managerial perspective, focusing mainly on the incentives to innovate in different contexts and governance structures.Specifically, we discuss whether and how it is feasible to replicate the OSS model for collaboration among private, not-for-profit and public organizations in pharmaceutical research starting from the analysis of the broad incentive structures, their analogies and their differences in the pharmaceutical industry vis à vis the software industry. Even though important analogies exist, we want to suggest that drug development cannot use the exact same governance models as is used in the code writing business because each coordination or innovation process has specific antecedents. Specific details of attributes of the underlying economic and technological environment in each industry specifically shape incentives to agents and actors, both at the innovation and market stage. Our economic analysis can contribute to developing a framework to shape the legal analysis of private-collective governance in medical research and development and help to craft specific legal and contractual arrangements for the governance of incentives to innovate.

Collaborative Networked Organizations (CNOs) are increasingly common in current dynamic markets. The participants in a CNO try to achieve a common goal while acting on market opportunities. Information technology (IT) facilitates collaboration between participants within a CNO. In this paper, we show how CNOs cope with network-dynamics related to their IT-needs. Two sub-characteristics of network dynamics, respectively many-to-many relations and interaction patterns, will be investigated. In the end, we are trying to answer the question regarding what IT-needs CNOs have, to cope with CNO-dynamism. Based on a literature review we developed a framework on CNO-dynamism and executed a multi-case study within four CNOs. We conclude that all framework components are recognized within the CNOs. CNOs appeared to mainly cope with dynamics by using collaborative platforms, task management systems, and conference facilities.