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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.

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.

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.

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.

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.

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

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.

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

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.

The chapter aims to provide an overview of the role of social media for knowledge management in tourism industry. Respect than traditional tools, the social media penetration within such industry is growing thanks to opportunity for travelers and travel professionals to access critical tourism knowledge everywhere and every time. Prior research has mainly focused on how social media are changing the tourism industry, while it is lacking enough the contribution of these technologies to managing touristic knowledge. This chapter seeks to shed light on how social media support knowledge management, with particular attention to knowledge creation, sharing, and preservation processes, in tourism industry. In particular, while knowledge creation and sharing process have attracted the attention of scholars, knowledge preservation via social media seems be still in its infancy stage.

Following publication of the original article at https://doi.org/10.1186/s13054-021-03727-x the authors identified an error in the Funding section that has been corrected (https://doi.org/10.1186/s13054-021-03849-2), Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.

Purpose Building upon the practice-based framework, this paper aims to focus on working practices for understanding how knowledge is transferred among health-care professionals within hospitals. Design/methodology/approach Using an ethnographic and interpretative approach, the authors conducted preliminary research based on a quali-quantitative methodology within one of the largest hospitals in Southern Italy. Findings This study allowed to achieve several results that could be significant and relevant within the health-care sector. First, this paper identified some of the main working practices and their associated activities in health care. Moreover, this paper identified the main organizational forms and/or tools enabling hospital personnel to share and learn the various types of knowledge for each of the prior identified practices. Practical implications Hospital managers should develop strategies and policies that take into account the nature and typology of knowledge-sharing processes among health-care professionals in terms of practices. Originality/value The paper contributes to practice-based studies identifying identified some of the main working practices, as well as the main tools for sharing and learning of the various types of knowledge.

Funding Acknowledgements Type of funding sources: None. Background. Transcatheter aortic valve-in-valve (TAVI ViV) implantation is an appealing treatment option for patients with degenerated bioprostheses. However, elevated residual gradients after TAVI ViV procedure are very common. These are an unwanted effects of prosthesis-patient mismatch (PPM). Currently, the actual incidenceof PPM, its predictors and its clinical outcomes have not been completely investigated. Purpose. The aims of this study was to investigate the incidence, predictors and clinical outcome of PPM and therefore of elevated gradients after TAVI ViV. Methods. 75 patients (age 78 ± 9 years, 36 male), who underwent TAVI-ViV due to failed aortic biological valve (60 stented, 15 stentless), were enrolled. Mechanism of bioprosthetic valve failure was stenosis (34 cases, 45%), regurgitation (24 cases, 32%) or combination (17 cases, 23%). Elevated residual gradients were defined as a mean DP> 20 mmHg. PPM was identified by the indexed effective orifice area (EOAi) measured by echocardiography (moderate PPM if 0.65 < EOAi < 0.85 cm²/m²; severe PPM if EOAi < 0.6 cm²/m²). Results. ViV TAVI was feasible in all patients, 33 patients (44%) were implanted with a balloon-expandable valve and 42 (56%) with a self-expandable valve. Post-procedural post-ballooning was performed in 16 out of 42 patients (38%) receiving a self-expandable valve. Post-operative mean DP> 20 mmHg was found in 35 patients (48%). Moderate PPM was found in 24 cases (33%) and severe PPM in 15 (20%). A logistic regression analyses identified small size of surgical prosthesis (size < 23 mm) [OR: 6.061(2.127-17.267), p = 0.001] and failed stented valve [OR: 20.727(2.522-170.364), p = 0.005] as independent predictors for the occurrence PPM. Interestingly PPM did not affect early and 1 years mortality (1 years mortality 1.3 %), while mortality was higher in pts with stentless prostheses (9%) Conclusions. PPM is a frequent finding after ViV procedures. Despite elevated residual gradients, TAVI ViV resolved prosthetic dysfunction and PPM did not affect mortality. Therefore, this procedure represents a promising new option for patients with failed biological prosthetic valves.

This study aims to explore the phenomenon of KM within public organizations through the ‘organizational knowing’ perspective. It was conducted a systematic literature review by using two online databases: Scopus and WOS. A dataset of 123 publications was analysed through citation and co-citation analysis. Results have shown the existence of a network of the 42 most cited sources and 2 topic clusters. This paper contributes to the literature by presenting a comprehensive overview of KM within public sector organizations and leads to further reflections on the concept of organizational knowing as a central mechanism in the production and articulation of knowledge.

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), is an ongoing global pandemic with high morbidity and mortality.1 Patients with preexist...

Over recent years, the way public workers perform and interpret the own work has radically changed. Among these changes, what seems to have had a decisive impact is the advent of information and communication technologies. The informatization, digitalization, and computerization of procedures and jobs has made learning and the use of digital competencies necessary to face constant change and to take advantage of it. Digital competencies consist in knowing how to use the information society technologies for work, leisure, and communication with confidence and a critical spirit. So, those who manage to develop basic skills in information and communication technologies can juggle in this changing scenario. In this ongoing study, we hypothesize a relationship between digital competencies and job crafting. We hypothesize that civil servants developing this type of competencies can act proactively on their work by modifying its contents, relationships, and cognitive perception if they are creative. Implications are discussed.

Abstract: Despite the technological advancements in the last 40 years, conditions such as refractory cardiogenic shock and cardiac arrest still present a very high mortality rate in real-world clinical practice. In this light, we have reviewed the techniques, indications, contraindications, and results of the socalled Veno-Arterial Extracorporeal Circulatory Membrane Oxygenation (VA-ECMO) in the adult population to evaluate the current results of this temporary cardio-pulmonary support as salvage and/or bridge therapy in the patient suffering from refractory cardiogenic shock or cardio-circulatory arrest. The results are encouraging, especially in the setting of refractory cardiogenic shock and in-hospital cardiac arrest. Among a selected population, the prompt institution of a VA-ECMO may radically change the prognosis by sustaining vital functions while looking for the leading cause or waiting for the reversal of the temporary cardio-respiratory negative condition. The future directions aim to standardized and shared protocols, miniaturization of the machines, and possibly the institution of specialized “ECMO teams” for in and the out-of-hospital institution of the tool.

Redo multiple valve replacement is known to carry additional risk of morbidity and mortality. 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 procedural aspects of the procedure. We present the case of a 78-year-old man who presented with symptoms of heart failure due to mitro-aortic bioprosthesis degenerations who was deemed to be at extremely high risk for conventional redo surgery. A two-steps single admission transcatheter-based approach was planned with a transfemoral aortic valve-in-valve procedure followed by a trans-apical mitral valve-in-valve implantation. The outcome was good and the recovery was fast.

Iatrogenic acute aortic dissection during percutaneous coronary intervention is an extremely rare but potentially life-threatening complication occurring in less than < 0,02% of the procedures. We report the cases of 3 patients with aortic dissection during percutaneous coronary intervention successfully treated with an emergent ascending aorta replacement. The main goal is the closing of the intimal tear as fast as possible damage either with a percutaneous system (i.e. a proximal stent) or with an open heart open surgery to prevent the extension of the dissection and neurological. A conservative strategy should be pursuit only in small localized sinus dissections.

Aims Patients with coronary heart disease (CHD) are at very high risk of recurrent events. A strategy to reduce excess risk might be to deliver structured secondary prevention programmes, but their efficacy has been mostly evaluated in the short term and in experimental settings. This is a retrospective case–control study aimed at assessing, in the real world, the efficacy of a secondary prevention programme in reducing long-term coronary event recurrences after coronary artery bypass surgery (CABG). Methods and results Programme participants (henceforth ‘cases’) were men and women aged Conclusion In a real-world setting, taking part in a structured longstanding secondary prevention programme, in addition to usual cardiology care, meaningfully lowers the risk of coronary recurrences.

Aims Due to bioprosthetic valve degeneration, aortic valve-in-valve (ViV) procedures are increasingly performed. There are no data on long-term outcomes after aortic ViV. Our aim was to perform a large-scale assessment of long-term survival and reintervention after aortic ViV. Methods and results A total of 1006 aortic ViV procedures performed more than 5 years ago [mean age 77.7 ± 9.7 years; 58.8% male; median STS-PROM score 7.3% (4.2–12.0)] were included in the analysis. Patients were treated with Medtronic self-expandable valves (CoreValve/Evolut, Medtronic Inc., Minneapolis, MN, USA) (n = 523, 52.0%), Edwards balloon-expandable valves (EBEV, SAPIEN/SAPIEN XT/SAPIEN 3, Edwards Lifesciences, Irvine, CA, USA) (n = 435, 43.2%), and other devices (n = 48, 4.8%). Survival was lower at 8 years in patients with small-failed bioprostheses [internal diameter (ID) ≤ 20 mm] compared with those with large-failed bioprostheses (ID > 20 mm) (33.2% vs. 40.5%, P = 0.01). Independent correlates for mortality included smaller-failed bioprosthetic valves [hazard ratio (HR) 1.07 (95% confidence interval (CI) 1.02–1.13)], age [HR 1.21 (95% CI 1.01–1.45)], and non-transfemoral access [HR 1.43 (95% CI 1.11–1.84)]. There were 40 reinterventions after ViV. Independent correlates for all-cause reintervention included pre-existing severe prosthesis–patient mismatch [subhazard ratio (SHR) 4.34 (95% CI 1.31–14.39)], device malposition [SHR 3.75 (95% CI 1.36–10.35)], EBEV [SHR 3.34 (95% CI 1.26–8.85)], and age [SHR 0.59 (95% CI 0.44–0.78)]. Conclusions The size of the original failed valve may influence long-term mortality, and the type of the transcatheter valve may influence the need for reintervention after aortic ViV.

Background Valve thrombosis – either biological or mechanical – is proved to increase patient’s morbidity and mortality. No consensus exist on the best management in such cases. Case presentation We report the case of a 69-year-old man presenting with a late thrombosis of a transcatheter aortic valve who was medically managed until he acutely worsened, developing myocardial ischemia and cardiogenic shock. Conclusion This unlucky case raises a word of caution about the safety of a reactive management.

Resumen Introduccion Los criterios diagnosticos de fiebre de origen desconocido son: temperatura ≥ 38,3 °C medida en varias ocasiones, duracion de mas de tres semanas y en la que no se llega a un diagnostico a pesar de un estudio de una semana con el enfermo hospitalizado. Epidemiologia Mas del 50% de los pacientes con fiebre ingresados en el hospital presentan infeccion. Etiologia Puede ser de origen infeccioso (septico) o no infeccioso. Manifestaciones clinicas . Fiebre que puede acompanarse de hipotension arterial, hipoperfusion tisular, insuficiencia respiratoria, encefalopatia, oliguria. Diagnostico Las consideraciones mas importantes son la predisposicion subyacente del paciente, las posibles complicaciones de la hospitalizacion, la situacion epidemiologica y el entorno microbiologico del hospital. Tratamiento Iniciar tratamiento antibiotico empirico con la mayor precocidad posible. La sospecha del foco, el perfil de resistencias y la susceptibilidad de los patogenos del area de hospitalizacion orientaran el tratamiento.

Resumen Introduccion La sepsis y el shock septico son serios problemas de asistencia sanitaria y afectan a millones de personas globalmente cada ano (en Espana 1/270 habitantes cada ano). Su mortalidad global ronda el 25% y su incidencia va en aumento. Patogenia Ambas entidades no son estados aislados, sino que forman parte de un proceso complejo en el cual intervienen factores propios del huesped y factores propios de los microorganismos: liberacion desequilibrada de mediadores inflamatorios, marcada vasodilatacion sistemica, fenomenos de hipercoagulabilidad e hipoperfusion que conducen a una disfuncion organica que puede conllevar la muerte. Diagnostico Se basa en la sospecha clinica, aplicacion de escalas clinicas (SOFA, qSOFA) y realizacion de pruebas complementarias (analiticas, pruebas de imagen y cultivos de muestras biologicas). Tratamiento El tratamiento debe iniciarse inmediatamente siguiendo las directrices de la Surviving Sepsis Campaign. Un tratamiento adecuado en las horas iniciales tendra una sensible influencia sobre el resultado final.

The COVID-19 pandemic has spiked stress-related symptoms worldwide. This study aims to assess depressive symptoms related to the early phase of the COVID-19 outbreak among the Italian general population and to analyze anhedonia and emotion dysregulation as potential predictors of depression severity. Through an online questionnaire, we collected sociodemographic and lockdown-related information, depressive symptoms, hedonic tone, and emotion dysregulation were assessed through the Beck Depression Inventory II, the Snaith&ndash, Hamilton Pleasure Scale, and the Difficulties in Emotion Regulation Scale, respectively. In our sample (n = 500), 122 individuals (24.4%) reported depressive symptoms during the COVID-19 outbreak. Individuals with and without depression differed in gender (X2 = 4.77, df = 1, p = 0.02) and age (X2 = 15.7, df = 4, p = 0.003). Among individuals presenting with depressive symptoms, those reporting close contact with confirmed cases of COVID-19 were at higher risk for severe depression (p = 0.026). Reduced hedonic tone (p = 0.014) and emotion dysregulation (p &lt, 0.001) also predicted depression severity. To the best of our knowledge, these are among the earliest data that focus on the risk for depression among a sizeable sample of the Italian general population during the COVID-19 outbreak. Our results indicate emotion dysregulation and reduced hedonic tone as potential factors predicting COVID-19-related depression severity and provide insight into developing targeted intervention policies.

Globalization, variation in customer expectations, and the developments connected to Information & Communication Technology are usually considered as the main drivers of changes in Operations Manag...

Background Clinical outcomes of patients with paradoxical low-flow, low-gradient aortic stenosis (PLF-LG) undergoing valve replacement are controversial. PLF-LG is a combination of a small aortic valve area (AVA Purpose The aim of this study is to determine the clinical outcomes in patients with PLF-LG AS undergoing transcatheter aortic valve implantation (TAVI) compare to NF-HG patients. Methods A total of 624 patients (age 81 ± 7 years) with symptomatic severe AS and preserved LVEF who underwent TAVI, was enrolled and divided in 2 groups: group NF-HG included 554 patients (89%) and group PLF-LG including 70 patients (11%). At 1-year follow-up, death and clinical events were reported. Results TAVI was feasible in all patients. A significant reduction in mean aortic pressure gradient was observed after TAVI both in PLF-LG (baseline, 30 ± 6 mmHg; 1-year, 12 ± 4 mmHg; p Conclusions Differently from surgical series, TAVI in PLF-LG AS is a useful procedure showing similar mortality and rehospitalization rates compared to NF-HG AS patients. Abstract 624 Figure. Survival curve

Background Cardiac stromal cells are the most abundant cell type present in the heart, where they have an important homeostatic function in matrix renewal and electromechanical coupling. We have shown that YAP transcription factor (a component of the Hippo pathway) is important for the proliferation of these cells and, potentially, pathologic cardiac matrix stiffening in heart failure. Purpose Given the role of Hippo pathway in cell mechanosensation, we assessed the conditions for activation of the YAP-dependent transcriptional pathway related to geometry/strain sensing using human “cardiosphere”-derived cells. Methods Human cardiospheres (C-Sp) and C-Sp-derived cells (CDCs) were obtained from fragments of atrial appendages of patients admitted for AoC bypass. C-Sps and CDCs were cultured using published methods. To analyze cell/nuclear geometry in 2D/3D culture, we employed an adapting thresholding algorithm allowing segmentation of cell membrane/nuclei shape and the relative abundance of nuclear/cytoplasmic fluorescence intensities from z-stacked confocal immunofluorescence images. Inhibitors of signaling cascades converging onto actin cytoskeleton polymerization or of YAP/TEADs interaction were used to assess YAP target genes transcription. Results Previous results showed stiffness sensitivity of YAP nuclear translocation process. Namely, CDCs plated onto stiff (E >50kPa) culture plates exhibited high ratios of nuclear/cytoplasmic YAP, as compared to cells plated on substrates with lower stiffness (E ∼ 10kPa). Analogously, cells with a stretched cytoplasm/nuclear shape in the border regions of the 3D organoids exhibited a higher YAP nuclear localization level and expression of fibrotic markers compared with cells with a more round geometry in the center of the spheres. To uncouple the cytoskeleton tensioning-dependent YAP nuclear shuttling, we treated CDCs plated onto stiff substrates with blebbistatin and Y27632. This showed a fully reversible YAP relocation from the nucleus to the cytoplasm and a reversion of canonical target genes (CYR61, ANKRD1 and CTGF) expression. In parallel, a “softening” process of the nucleus, likely due to release from cytoskeleton traction forces, was observed by confocal imaging along the cellular z-axis. Interestingly, use of Verteporfin, a drug directly interfering with the interaction of YAP/TAZ complex with TEADs DNA binding proteins showed reversion of pro-fibrotic YAP targets independent of high cytoskeleton tensioning. Conclusions These results establish, for the first time, a deterministic relationship between pro-pathologic evolution of human adult cardiac stromal cells and activation of mechanosensing-dependent pathways. They also provide quantitative criteria for interpreting fibrotic evolution of the heart based on modifications of myocardial architecture and mechanical compliance, as well as the ability of the cells to generate tension forces affecting the nuclear structure.

Background Controversial data exist on clinical outcomes of patients with paradoxical low-flow, low-gradient aortic stenosis (PLF-LG) undergoing valve replacement. This entity is a combination of a small aortic valve area (AVA Purpose The aim of this study was to determine the clinical outcomes in patients with PLF-LG AS undergoing transcatheter aortic valve implantation (TAVI) compare to NF-HG patients. Methods A total of 609 patients (age 81±6 years) with symptomatic severe AS and preserved LVEF who underwent TAVI, was enrolled and divided in two groups: group A included patients with NF-HG (542 patients) and group B including those with PLF-LG (66 patients). At 1-year follow-up, death and clinical events were reported. Results TAVI was feasible in all patients. A significant reduction in mean aortic pressure gradient was observed after TAVI both in PLF-LG (baseline, 30±5 mmHg; 1-year, 11±4 mmHg; p Kaplan-Meier analysis Conclusions Differently from surgical series, TAVI patients with PLF-LG AS had showed similar mortality and rehospitalization rates compared to NF-HG.

Lactate levels to guide resuscitation in critically burned patients are controversial. The purpose of our study was to determine whether absolute lactate values or lower lactate clearance predict mortality, and whether these are useful tools in the resuscitation phase.We conducted a prospective, unicentric, observational study of a cohort of 214 burn patients admitted in the Burn Intensive Care Unit. We collected demographic and laboratory data, complications, absolute lactate levels and lactate clearance every 8 h since admission to 72 h. In critical patients we monitored hemodynamic parameters with transpulmonary thermodilution. We used Student's t-test or nonparametric tests, mixed models and Pearson and Spearman methods, Fisher's exact and chi-squared test.Of the 214 patients, 76.6% were male, mean age were 46 ± 15 years and 23.0 ± 19.5% of Total Basal Surface Area (TBSA) burned. Initial mean absolute levels of lactate were 2.02 ± 1.62 mmol/L in survivors vs. 4.05 ± 3.90 mmol/L in nonsurvivors. Initial elevated lactate levels increased mortality (p.001), length of ICU stay, mechanical ventilation and shock. In the subgroup of burned TBSA20%, lowering the lactate cut-off point from 2.0 to 1.8 mmol/L improved the mortality prediction (OR:9.3). We found no relationship between lactate clearance in the first 24 h and mortality. In more severe patients (20% TBSA burned and initial lactate levels2), a good correlation was found between lactate and cardiac index; but not with intrathoracic blood volume index (ITBVI). Patients with low ITBVI preload (600 mL/mInitial elevated lactate levels are a factor of poor prognosis and the cut-off point that best predicts mortality should be adjusted in the patients with TBSA burned20%. The global clearance of lactate in the first 24 h, unlike what occurs in other injuries, does not correlate with mortality. Monitoring lactate can ensure adequate peripheral perfusion during resuscitation with lower than normal fluid preload values.

Background CD 34 + stem/progenitor cells are involved in vascular homeostasis and in neovascularization of ischemic tissues. The number of circulating CD 34 + stem cells is a predictive biomarker of adverse cardiovascular outcomes in diabetic patients. Here, we provide evidence that hyperglycemia can be “memorized” by the stem cells through epigenetic changes that contribute to onset and maintenance of their dysfunction in diabetes mellitus. Methods and Results Cord‐blood–derived CD 34 + stem cells exposed to high glucose displayed increased reactive oxygen species production, overexpression of p66 shc gene, and downregulation of antioxidant genes catalase and manganese superoxide dismutase when compared with normoglycemic cells. This altered oxidative state was associated with impaired migration ability toward stromal‐cell–derived factor 1 alpha and reduced protein and mRNA expression of the C‐X‐C chemokine receptor type 4 ( CXCR 4) receptor. The methylation analysis by bisulfite Sanger sequencing of the CXCR 4 promoter revealed a significant increase in DNA methylation density in high‐glucose CD 34 + stem cells that negatively correlated with mRNA expression (Pearson r =−0.76; P =0.004). Consistently, we found, by chromatin immunoprecipitation assay, a more transcriptionally inactive chromatin conformation and reduced RNA polymerase II engagement on the CXCR 4 promoter. Notably, alteration of CXCR 4 DNA methylation, as well as transcriptional and functional defects, persisted in high‐glucose CD 34 + stem cells despite recovery in normoglycemic conditions. Importantly, such an epigenetic modification was thoroughly confirmed in bone marrow CD 34 + stem cells isolated from sternal biopsies of diabetic patients undergoing coronary bypass surgery. Conclusions CD 34 + stem cells “memorize” the hyperglycemic environment in the form of epigenetic modifications that collude to alter CXCR 4 receptor expression and migration.

Objectives: Patient selection is crucial to achieve good outcomes and to avoid futile procedures in patients undergoing transcatheter aortic valve replacement. The aim of this multicenter retrospective study was to identify independent predictors of 1-year mortality in patients surviving after transapical transcatheter aortic valve replacement. Methods: We analyzed data from the Italian registry of transapical transcatheter aortic valve replacement that includes patients undergoing operation in 21 centers from 2007 to 2012. Futility was defined as mortality within 1 year after transapical transcatheter aortic valve replacement in patients surviving at 30 days. Thirty-day survivors were divided in 2 groups: futility (group F) and nonfutility (group NF). Cox proportional hazard regression analysis was performed to identify independent predictors of futility. Results: We analyzed data from 645 patients with survival of 30 days or more after transapical transcatheter aortic valve replacement. Groups F and NF included 60 patients (10.8%) and 585 patients (89.2%), respectively. Patients in group F were more likely to have insulin-dependent diabetes (15% vs 7.2%, P = .03), creatinine 2.0 mg/dL or greater or dialysis (18.3% vs 8.2%, P = .01), logistic European System for Cardiac Operative Risk Evaluation greater than 20% (66.7% vs 50.3%, P = .02), preoperative rhythm disorders (40% vs 25.3%, P = .03), critical preoperative state (8.3% vs 1.8%, P = .002), and left ventricular ejection fraction less than 30% (15% vs 2.9%, P < .001). The multivariate analysis identified the following as independent predictors of futility: insulin-dependent diabetes (odds ratio, 3.1; P = .003), creatinine 2.0 mg/dL or greater or dialysis (odds ratio, 2.52; P - .012), preoperative rhythm disorders (odds ratio, 1.88; P - .04), and left ventricular ejection fraction less than 30% (odds ratio, 4.34; P = .001). Conclusions: According to our data, among patients undergoing transapical transcatheter aortic valve replacement, those with insulin-dependent diabetes, advanced chronic kidney disease, rhythm disorders, and low left ventricular ejection fraction have a higher risk to undergo futile procedures.

No consensus exists on the timing, safety, and efficacy of treating severe symptomatic aortic and carotid stenosis. In the older population and in the presence of multiple comorbidities that arise during the surgery, a less invasive transcatheter treatment may be the only reasonable option. We discuss this topic by analyzing a case of an 84-year-old man who underwent a combined single-stage transcatheter procedure.

Bioprosthesis are commonly used in the elderly population. Structural valve deterioration affects the long-term durability. We report an early deterioration of a Mitroflow valve caused by ring deformation and prosthetic leaflet rupture. The 69-years-old patient underwent successful redo surgery with excision of the bioprosthesis and placement of a mechanical valve.

We describe a technique using an Edwards Intuity Elite rapid deployment bioprosthesis to construct a composite graft for an aortic root replacement.

OBJECTIVES To evaluate the results of aortic valve replacement through sternotomic approach in redo scenarios (RAVR) vs transapical transcatheter aortic valve replacement (TAVR), in patients in the eighth decade of life or older already undergone previous coronary artery bypass grafting (CABG). METHODS One hundred and twenty-six patients undergoing RAVR were compared with 113 patients undergoing TaTAVR in terms of 30-day mortality and Valve Academic Research Consortium-2 outcomes. The two groups were also analysed after propensity-matching. RESULTS TaTAVR patients demonstrated a higher incidence of 30-day mortality (P = 0.03), stroke (P = 0.04), major bleeding (P = 0.03), worse 'early safety' (P = 0.04) and lower permanent pacemaker implantation (P = 0.03). TaTAVR had higher follow-up hazard in all-cause mortality [hazard ratio (HR) 3.15, 95% confidence interval (CI) 1.28-6.62; P < 0.01] and cardiovascular mortality (HR 1.66, 95% CI 1.02-4.88; P = 0.04). Propensity-matched patients showed comparable 30-day outcome in terms of survival, major morbidity and early safety, with only a lower incidence of transfusions after TaTAVR (10.7% vs RAVR: 57.1%; P < 0.01). A trend towards lower Acute Kidney Injury Network Classification 2/3 (3.6% vs RAVR 21.4%; P = 0.05) and towards a lower freedom from all-cause mortality at follow-up (TaTAVR: 44.3 ± 21.3% vs RAVR: 86.6 ± 9.3%; P =. 08) was demonstrated after TaTAVR, although cardiovascular mortality was comparable (TaTAVR: 86.5 ± 9.7% vs RAVR: 95.2 ± 4.6%; P = 0.52). Follow-up freedom from stroke, acute heart failure, reintervention on AVR and thrombo-embolisms were comparable (P = NS). EuroSCORE II (P = 0.02), perioperative stroke (P = 0.01) and length of hospitalization (P = 0.02) were the determinants of all-cause mortality at follow-up, whereas perioperative stroke (P = 0.03) and length of hospitalization (P = 0.04) impacted cardiovascular mortality at follow-up. CONCLUSIONS Reported differences in mortality and morbidity after TaTAVR and RAVR reflect differences in baseline risk profiles. Given the lower trend for renal complications, patients at higher perioperative renal risk might be better served by TaTAVR.

Innovative tools for assessing food and nutrient intakes in adolescence are essential to uncover the long-term effects of diet on chronic diseases. Here, we developed and compared a web-based self-administered food frequency questionnaire (web-FFQ) with a traditional interviewer printed FFQ (print-FFQ) among 174 Italian adolescents (aged 15&ndash, 18 years). To assess the reliability of the web-FFQ compared with the print-FFQ, we used Spearman&rsquo, s rank correlation coefficients, Wilcoxon rank test, quartile misclassification analysis, Cohen&rsquo, s weighted kappa and the Bland&ndash, Altman method. Correlation coefficients ranged from 0.14 (i.e., pizza) to 0.67 (i.e., raw vegetables) for foods, and from 0.45 (i.e., monounsaturated fatty acids, MUFA) to 0.62 (i.e., zinc) for nutrients. Results from the Wilcoxon rank test showed that food and nutrient intakes were comparable between two FFQs, except for nuts, shellfish, fruit juices and MUFA. Adolescents classified into the same or adjacent quartiles ranged from 68.2% (i.e., tea) to 89.1% (i.e., raw vegetables and dipping sauces) for foods, and from 77.2% (i.e., vitamin C) to 87.2% (i.e., folate and calcium) for nutrients. Except for pizza, the weighted kappa indicated moderate to substantial agreement for other foods and nutrients. Finally, we demonstrated that the web-FFQ significantly overestimated shellfish and fruit juice intakes, while it underestimated nuts, canned fish, olive oil, total energy intake, fatty acids and calcium. The limits of agreement analysis indicated moderate to wide individual differences for all groups. In conclusion, our self-administered web-FFQ represents an easy, suitable and cost-effective tool for assessing food and nutrient intakes in adolescents. However, the wide individual differences in level of agreement suggest that additional refinements and calibrations are necessary to investigate the effects of absolute nutrient intakes at the individual level.

Aortic stenosis is the most common primary valve disease needing surgical treatment in Europe and North America. The prevalence of this disease increases over years due to the ageing population. Age and comorbidities often represent an obstacle to surgical aortic valve replacement (AVR) for those patients considered at high and prohibitive risk. In this scenario, transcatheter aortic valve replacement (TAVR) has become an appealing therapeutic option for prohibitive-risk patients with severe symptomatic aortic stenosis who were previously only medically managed and considered unsuitable for AVR. However, the delicate balance between feasibility and appropriateness needs to be accurately defined.

Objectives This study sought to evaluate SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, California) positioning using different strategies. Background Aortic valve-in-valve (ViV) is associated with high risk of elevated gradients. Methods S3 aortic ViV procedures in stented bioprostheses were studied. Transcatheter heart valve (THV) positioning was analyzed in a centralized core lab blinded to clinical outcomes. A combined endpoint of severely elevated mean gradient (≥30 mm Hg) or pacemaker need was established. Two positioning strategies were compared: central marker method and top of S3 method. Optimal final depth was defined as S3 depth ≤20%. Results A total of 113 patients met inclusion criteria and were analyzed (76.5 ± 9.7 years of age, 65.8% male, STS score 8 ± 7.6%). THVs had incomplete shortening in comparison to fully expanded valves (92 ± 3.4%), and expansion was more complete in optimal positioning cases compared with others (93.2 ± 2.7% vs. 91.5 ± 3.5%; p = 0.027). The central marker method demonstrated greater correlation with final implantation depth than the top of S3 method (R2 of 0.48 and 0.14; p Conclusions Optimal S3 positioning in aortic ViV is associated with better outcomes. Central marker positioning is more reliable than top of S3 positioning. Central marker bottom position should be 3 mm to 6 mm above the ring.