Sacubitril/Valsartan in heart failure with reduced ejection fraction: clinical and echocardiographic insights from a real world population

Abstract Background Following the PARADIGM trial, some studies have identified cardiac remodeling as major background for hard end point benefits of Sacubitril/Valsartan (S/V), but few adopted a well described definition in the literature. Purpose We aimed at a comprehensive evaluation of the effects of S/V on echo-derived measures of cardiac remodeling along with clinical and laboratory data over a medium-term follow-up pointing to a real-world HFrEF population. Methods This is a prospective observational study of HFrEF patients on optimal medical therapy (OMT) initiated with S/V at Heart Failure Clinic of our institute (January 2017-January 2020). In 62 HFrEF, echocardiographic, laboratory and clinical data were collected at baseline and over 10 (Q1-Q3 8–13) months after S/V initiation. Mean age was 68±12 years, 79% men. Left ventricular reverse remodeling (LVRR) was defined as: 1) an absolute increase in LVEF ≥10 points or a LVEF ≥50% at follow-up and 2) a relative decrease in indexed left ventricular end-diastolic diameter of at least 10% or an indexed left ventricular end-diastolic diameter ≤33 mm/m2. Results Compared to baseline, S/V promoted a significant improvement of LV ejection fraction (LVEF, from 30% to 37%; p<0,0001) with an absolute median increase in LVEF of 8 points. Parallel significant reductions in left ventricular and atrial volumes, lower mitral regurgitation degree and a better diastolic dysfunction along with clinical improvement (NYHA class and NT-proBNP values) were observed at follow up. sPAP (systolic Pulmonary Arterial Pressure) was significantly decreased at follow-up evaluation (37 mmHg vs 31 mmHg p=0,005) (Table 1). Overall, LVRR as defined above was observed in 30% of patients. Younger age (64 vs 74 years, p=0,007), a shorter duration of the disease (7 vs 23 months, p=0,009), and non ischaemic etiology (79% vs 33% p=0,003), along with a smaller baseline LAESVi (Left Atrial End Systolic Volume, 41 vs 48 ml/m2 p=0,012) were more common in patients with LVRR. sPAP and Right Ventricular (RV) function estimated by tricuspid annular plane systolic excursion (TAPSE) were significantly better in LVRR patients along with TAPSE/sPAP ratio (Table 2). Conclusions Our data point to a remarkable medium-term reverse remodeling effect by S/V in HFrEF. Findings reinforce the concept that the main benefits of S/V on hard end-points are mediated by its cardiac-related effects. Both a left and right reverse remodeling occur in HFrEF patients who start S/V in the most adaptable phase of the disease supporting an early administration. Funding Acknowledgement Type of funding sources: None

Rehabilitation of Post-COVID Patients: A Virtual Reality Home-Based Intervention Including Cardio-Respiratory Fitness Training

The post-COVID syndrome is emerging as a new chronic condition, characterized by symptoms of breathlessness, fatigue, and decline of neurocognitive functions. Rehabilitation programs that include physical training seem to be beneficial to reduce such symptoms and improve patients' quality of life. Given this, and considering the limitations imposed by the pandemic on rehabilitation services, it emerged the need to integrate telerehabilitation programs into clinical practice. Some telerehabilitation solutions, also based on virtual reality (VR), are available in the market. Still, they mainly focus on rehabilitation of upper limbs, balance, and cognitive training, while exercises like cycling or walking are usually not considered. The presented work aims to fill this gap by integrating a VR application to provide cardio-respiratory fitness training to post-COVID patients in an existing telerehabilitation platform. The ARTEDIA application allows patients to perform a cycling exercise and a concurrent cognitive task. Patients can cycle in a virtual park while performing a "go/no-go" task by selecting only specific targets appearing along the way. The difficulty of the practice can be adjusted by the therapists, while the physiological response is continuously monitored through wearable sensors to ensure safety. The application has been integrated into the VRRS system by Khymeia. In the next months, a study to assess the feasibility of a complete telerehabilitation program based on physical and cognitive training will take place. Such a program will combine the existing VRRS exercises and the cardio-respiratory fitness exercise provided by the ARTEDIA application. Feasibility, acceptance, and usability will be assessed from both the patients' and the therapists' sides

Impact of loop diuretic dosage in a population of patients with acute heart failure: a retrospective analysis

BackgroundLoop diuretics are essential for managing congestion in acute heart failure (AHF) patients, but concerns exist about their dosing and administration. This study aims to explore the relationship between aggressive diuretic treatment and clinical outcomes in AHF patients.MethodsWe randomly selected 370 AHF patients from admissions at Maastricht University Medical Center between January 2011 and March 2017. Patients were divided into four quartiles based on diuretic doses administrated during index hospitalization. The primary endpoint was a composite of cardiovascular (CV) rehospitalization or death at 1 year.Results42.4% of patients experimented the primary outcome The composite endpoint rates were 35.4%, 41.6%, 38.5%, and 54.9%, respectively, from lowest to highest dose quartiles (p = 0.033). In univariate analysis, the outcome was significantly lower in the first three quartiles as compared to the fourth quartile. One-year CV mortality was 9.1%, 10.1%, 20.9% and 27.2%, respectively (p = 0.002). After adjusting for confounders, the association between loop diuretic dosage disappeared for both the primary outcome and one-year CV mortality. Most secondary outcomes and endpoints at 3 months, including worsening renal function, showed no significant differences between groups, while hypokaliemia occurrence, length of hospital stay and weight loss at index admission were higher in the fourth quartile compared to the first one.ConclusionsHigh loop diuretic doses are associated with poor outcomes in AHF patients, reflecting disease severity rather than harm from aggressive diuretic use. Furthermore, high diuretic doses do not seem to negatively affect kidney function

Activated Leukocyte Cell Adhesion Molecule Expression and Shedding in Thyroid Tumors

Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. Here we documented high levels of ALCAM expression in human thyroid tumors and cell lines. Through proteomic characterization of ALCAM expression in the human papillary thyroid carcinoma cell line TPC-1, we identified the presence of a full-length membrane-associated isoform in cell lysate and of soluble ALCAM isoforms in conditioned medium. This finding is consistent with proteolytically shed ALCAM ectodomains. Nonspecific agents, such as phorbol myristate acetate (PMA) or ionomycin, provoked increased ectodomain shedding. Epidermal growth factor receptor stimulation also enhanced ALCAM secretion through an ADAM17/TACE-dependent pathway. ADAM17/TACE was expressed in the TPC-1 cell line, and ADAM17/TACE silencing by specific small interfering RNAs reduced ALCAM shedding. In addition, the CGS27023A inhibitor of ADAM17/TACE function reduced ALCAM release in a dose-dependent manner and inhibited cell migration in a wound-healing assay. We also provide evidence for the existence of novel O-glycosylated forms and of a novel 60-kDa soluble form of ALCAM, which is particularly abundant following cell stimulation by PMA. ALCAM expression in papillary and medullary thyroid cancer specimens and in the surrounding non-tumoral component was studied by western blot and immunohistochemistry, with results demonstrating that tumor cells overexpress ALCAM. These findings strongly suggest the possibility that ALCAM may have an important role in thyroid tumor biology

Behavioral patterns in robotic collaborative assembly: comparing neurotypical and Autism Spectrum Disorder participants

Introduction: In Industry 4.0, collaborative tasks often involve operators working with collaborative robots (cobots) in shared workspaces. Many aspects of the operator's well-being within this environment still need in-depth research. Moreover, these aspects are expected to differ between neurotypical (NT) and Autism Spectrum Disorder (ASD) operators. Methods: This study examines behavioral patterns in 16 participants (eight neurotypical, eight with high-functioning ASD) during an assembly task in an industry-like lab-based robotic collaborative cell, enabling the detection of potential risks to their well-being during industrial human-robot collaboration. Each participant worked on the task for five consecutive days, 3.5 h per day. During these sessions, six video clips of 10 min each were recorded for each participant. The videos were used to extract quantitative behavioral data using the NOVA annotation tool and analyzed qualitatively using an ad-hoc observational grid. Also, during the work sessions, the researchers took unstructured notes of the observed behaviors that were analyzed qualitatively. Results: The two groups differ mainly regarding behavior (e.g., prioritizing the robot partner, gaze patterns, facial expressions, multi-tasking, and personal space), adaptation to the task over time, and the resulting overall performance. Discussion: This result confirms that NT and ASD participants in a collaborative shared workspace have different needs and that the working experience should be tailored depending on the end-user's characteristics. The findings of this study represent a starting point for further efforts to promote well-being in the workplace. To the best of our knowledge, this is the first work comparing NT and ASD participants in a collaborative industrial scenario

Evaluating the Usability of a Serious Game for Nutritional Education with Children with ADHD

Research reports a relationship between impulsive behaviors and unhealthy eating behaviors. Serious games, combining educational contents with gamification, can increase engagement in therapeutic activities and behavioral training programs. In this context, we have developed a Serious Game to promote healthy eating style in children and adolescents in which impulsivity is a predominant feature, specifically individuals with attention deficit hyperactivity disorder. An initial analysis of the usability of the Serious Game was performed on a sample of 12 participants by means of quantitative and qualitative measures. Participants' feedback, which was overall positive, was helpful for defining the required improvements. Once implemented, the serious game will be then proposed to children and their families and included in home-based educational interventions

Digital Applications in Pulmonary Rehabilitation: Preliminary Evaluation of a Hybrid Program for the Continuity of Care

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of comorbidities and death worldwide. Pulmonary Rehabilitation (PR) is a comprehensive intervention proven effective in improving COPD patients’ quality of life. However, its benefits often decrease with time because of low motivation, lack of direct surveillance, and low self-awareness. In this scenario, digital technologies can play a key role by allowing more engaging protocols and enabling home-based programs. The cooperation between clinical and technology experts is crucial to develop protocols that are effective and well-accepted by patients. This work aimed at developing and testing a hybrid PR program for patients with COPD based on digital applications that allow the personalization of the intervention, and support the delivery of healthcare services also in the context of continuity of care. Our protocol proved able to improve the patients’ condition, as traditional programs do, paving the way for the adoption of such technologies in the clinical practice

Design of serious games in engineering education: An application to the configuration and analysis of manufacturing systems

Higher education has to cope with current trends in digital technologies, in particular in the field of industrial engineering, where digital competencies are required more and more. Digital technologies, combined with serious gaming, offer new opportunities for teaching engineering in higher education, with a twofold objective: 1) offering students a rich and realistic experience exploiting advanced digital tools; 2) supporting and complementing traditional education schemes by increasing participation and involvement via serious gaming, enhanced by digital/virtual technologies. Herein, we present a framework for the design of serious games in engineering education, with a specific focus on the definition of intended learning outcomes and the development of the corresponding game activities. This framework was applied to develop a serious game application for the design and analysis of manufacturing systems. The approach was tested thanks to the cooperation of 60 bachelor engineering students and the results extensively analyzed in both quantitative and qualitative terms

Human factors and ergonomics

Technological advances, lower cost, and greater availability of extended reality (XR) have led to more widespread applications and uptake of these technologies. Simulated environments can be used to study, measure, and influence human behavior in a variety of situations, and there are many examples of application in education, training, and rehabilitation, among others. However, the quality of the user experience and effectiveness of these applications are influenced by a variety of factors including the design of, and interaction with, the technology. This chapter presents an overview of human factors/ergonomics (HF/E) issues associated with XR with reference to user experience models defined in early virtual reality research. Using case examples that show how multisensory and multimodal interaction techniques can enhance the realism and efficacy of the user experience, and how XR technology can be used to deliver engaging and effective rehabilitation programs for older users, the importance of HF/E considerations are highlighted. Recommendations for future research include: the need for deeper understanding regarding optimum design of simulation content and multimodal user interaction; cost/benefit analysis taking into account user characteristics and the context of use; a provision of guidelines to aid technology producers during the design process for development of new XR applications; and standardized protocols for the evaluation of user experiences