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Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

The triad formed by thyroid dysfunction, metabolic syndrome (MetS), and cardiovascular (CV) risk forms a network with many connections that aggravates health outcomes. Thyroid hormones (THs) play an important role in glucose and lipid metabolism and hemodynamic regulation at the molecular level. It is noteworthy that a bidirectional association between THs and MetS and their components likely exists as MetS leads to thyroid dysfunction, whereas thyroid alterations may cause a higher incidence of MetS. Thyroid dysfunction increases insulin resistance, the circulating levels of lipids, in particular LDL-C, VLDL-C, and triglycerides, and induces endothelial dysfunction. Furthermore, THs are important regulators of both white and brown adipose tissue. Moreover, the pathophysiological relationship between MetS and TH dysfunction is made even tighter considering that these conditions are usually associated with inflammatory activation and increased oxidative stress. Therefore, the role of THs takes place starting from the molecular level, then manifesting itself at the clinical level, through an increased risk of CV events in the general population as well as in patients with heart failure or acute myocardial infarction. Thus, MetS is frequently associated with thyroid dysfunction, which supports the need to assess thyroid function in this group, and when clinically indicated, to correct it to maintain euthyroidism. However, there are still several critical points to be further investigated both at the molecular and clinical level, in particular considering the need to treat subclinical dysthyroidism in MetS patients.

The thyroid–heart relationship has a long and articulated history of its own, a history that encompasses physiological and pathophysiological knowledge. In recent years, molecular biology studies, in an experimental context, have highlighted the extraordinary dialogue that exists among the two systems in the field of cardioprotection, which is an extremely important area for the treatment of cardiac diseases in both acute and chronic phases. In addition, in the last few years, several studies have been carried out on the prognostic impact of alterations in thyroid function, including subclinical ones, in heart disease, in particular in heart failure and acute myocardial infarction, with evidence of a negative prognostic impact of these and, therefore, with the suggestion to treat these alterations in order to prevent cardiac events, such as death. This review provides a comprehensive summary of the heart–thyroid relationship.

Abstract Background Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis. Methods The dynamics of lung uptake of 18F-labeled FAPI ([18F]FAPI-74) was assessed in the bleomycin mouse model at various time points and using different concentrations of bleomycin by PET/CT. FAPα was measured in BALFs from these bleomycin-treated and control mice. FAPα levels were also assessed in BALFs from controls and patients with idiopathic pulmonary fibrosis (IPF). Results Bleomycin-treated mice presented a significantly higher uptake of [18F]FAPI-74 during lung fibrinogenesis (days 10 and 16 after instillation) compared to control mice. No significant difference was observed at initial inflammatory phase (3 days) and when fibrosis was already established (28 days). [18F]FAPI-74 tracer was unable to show a dose-response to bleomycin treatment. On the other hand, BALF FAPα levels were steeply higher in bleomycin-treated mice at day 10 and a significant dose-response effect was observed. Moreover, FAPα levels were strongly correlated with lung fibrosis as measured by the modified Aschroft histological analysis, hydroxyproline and the percentage of weight loss. Importantly, higher levels of FAPα were observed in IPF patients where the disease was progressing as compared to stable patients and controls. Moreover, patients with FAPα BALF levels higher than 192.5 pg/mL presented a higher risk of progression, transplantation or death compared to patients with lower levels. Conclusions Our preclinical data highlight a specific increase of [18F]FAPI-74 lung uptake during the fibrotic phase of the bleomycin murine model. The measurement of FAPα in BALF appears to be a promising marker of the fibrotic activity in preclinical models of lung fibrosis and in IPF patients. Further studies are required to confirm the role of FAPα in BALF as biomarker of IPF activity and assess the relationship between FAPα levels in BALF and [18F]FAPI-74 uptake on PET/CT in patients with fibrotic lung disease.

Transitioning from childhood into adolescence is an extraordinary time of life, associated with major physical, emotional, cognitive, and social changes and characterized by dynamic development in which interaction with the environment modulates the individual resources responsible for well-being and health. This sensitive period is the time when, in addition to hormonal, metabolic, and neural changes, certain behavioral strategies begin to take shape that will shortly go on to define the emotional, social, and cultural identity of the individual. This narrative review aimed to uncover the crucial processes underlying the transition by identifying processes that are responsible for cognitive, psychosocial, and emotional development, in the absence of disease. For this aim, we highlight (1) the physical, psychological, and social determinants during the transition from childhood to adolescence; (2) the role of health-related variables in resilience or vulnerability mechanisms; and (3) recent school-based strategies to promote health and well-being. Recognizing that health and well-being are the result of the interaction of many biological, psychological, social, cultural, and physical factors will lead to comprehensive health promotion involving all actors joining the growth process, from health professionals and the educational community to parents and community. Furthermore, it is important that psychosocial dimensions are strengthened already during childhood to prevent the onset of frailty and illness in adolescence.

Incidental findings in research with human participants may have implications for a person's present health or future health outcomes. Current guidelines focus on methods for handling and reporting incidental findings from biological test data but incidental findings might also arise from non-biological tests. This article presents three examples in which the results from non-biological test data can be predictive of future disease and should be disclosed to research participants. It is intended to increase awareness and facilitate further discussion about the reporting of incidental findings from non-biological data.

Abstract Background In body-mind relationship field, eating disorders (ED) are considered disabling disorders that can alter physical health status, inducing profound alterations in psychosocial, cognitive and emotional dimensions. These disorders, characterized by a strong comorbidity with other diseases, usually begin during childhood or adolescence, and include anorexia nervosa, bulimia nervosa and binge eating. Aim of this study was to investigate the associations between eating disorders perception and dimensions of health-related quality of life (HRQoL) and well-being perception (WBP) in school-dropout adolescents. Methods Data were collected in 450 adolescents (19 ± 2 years, male 308), and HRQoL, WBP, and ED were assessed by means a battery of standardized questionnaire. Results EDs are more pronounced in females than in males (p

Transient left ventricular dysfunction (TLVD), a temporary condition marked by reversible impairment of ventricular function, remains an underdiagnosed yet significant contributor to morbidity and mortality in clinical practice. Unlike the well-explored atherosclerotic disease of the epicardial coronary arteries, the diverse etiologies of TLVD require greater attention for proper diagnosis and management. The spectrum of disorders associated with TLVD includes stress-induced cardiomyopathy, central nervous system injuries, histaminergic syndromes, various inflammatory diseases, pregnancy-related conditions, and genetically determined syndromes. Furthermore, myocardial infarction with non-obstructive coronary arteries (MINOCA) origins such as coronary artery spasm, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD) may also manifest as TLVD, eventually showing recovery. This review highlights the range of ischemic and non-ischemic clinical situations that lead to TLVD, gathering conditions like Tako-Tsubo Syndrome (TTS), Kounis syndrome (KS), Myocarditis, Peripartum Cardiomyopathy (PPCM), and Tachycardia-induced cardiomyopathy (TIC). Differentiation amongst these causes is crucial, as they involve distinct clinical, instrumental, and genetic predictors that bode different outcomes and recovery potential for left ventricular function. The purpose of this review is to improve everyday clinical approaches to treating these diseases by providing an extensive survey of conditions linked with TLVD and the elements impacting prognosis and outcomes.

Magnetic resonance (MR) with sodium (23Na) is a noninvasive tool providing quantitative biochemical information regarding physiology, cellular metabolism, and viability, with the potential to extend MR beyond anatomical proton imaging. However, when using clinical scanners, the low detectable 23Na signal and the low 23Na gyromagnetic ratio require the design of dedicated radiofrequency (RF) coils tuned to the 23Na Larmor frequency and sequences, as well as the development of dedicated phantoms for testing the image quality, and an MR scanner with multinuclear spectroscopy (MNS) capabilities. In this work, we propose a hardware and software setup for evaluating the potential of 23Na magnetic resonance imaging (MRI) with a clinical scanner. In particular, the reliability of the proposed setup and the reproducibility of the measurements were verified by multiple acquisitions from a 3T MR scanner using a homebuilt RF volume coil and a dedicated sequence for the imaging of a phantom specifically designed for evaluating the accuracy of the technique. The final goal of this study is to propose a setup for standardizing clinical and research 23Na MRI protocols.

The prenatal diagnosis of congenital heart disease (CHD) represents, for both parents, a particularly stressful and traumatic life event from a psychological point of view. The present review sought to summarize the findings of the most relevant literature on the psychological impact of prenatal diagnosis of CHD on parents, describing the most common mechanisms employed in order to face this unexpected finding. We also highlight the importance of counseling and the current gaps in the effects of psychological support on this population.

Introduction: Adolescents experience rapid physical, cognitive, and psychosocial growth with different factors contributing to health and well-being. In this view, an important role is played by body weight and related perceptions. The purpose was to determine, in a sample of Italian high school students, whether health-related quality of life (HRQoL) is associated with the different weight status categories (underweight, normal weight, overweight, obese), even considering sex differences. Material and methods: Data were collected from 1826 adolescents (n = 735 males). HRQOL was analyzed using the Italian version of KIDSCREEN-52. Results: Overweight adolescents showed reductions in psychological well-being (p < 0.05) and self-perception (p < 0.05) compared with individuals in other BMI categories. Subjects with obesity reported increased bullying victimization (p < 0.05) and reductions in self-perception and eating disorders (p < 0.001), while underweight individuals were characterized by altered adherence to the Mediterranean diet (p < 0.001), eating disorders (p < 0.001), and problematic use of social media (p < 0.05). No sex differences were found, except for socio-economic status perceptions, where underweight girls reported higher economic well-being than boys (p < 0.05). Conclusions: Our findings may suggest that there is an association between weight status categories and HRQoL that is more pronounced in underweight and overweight adolescents. The association between BMI categories and psychosocial dimensions opens the need to define specific domains on which such preventive interventions should focus, always through a personalized perspective.

The American Heart Association (AHA) has recently released a statement on cardiovascular management of pregnant women from an anesthesiological point of view. Although managing such situation is extremely frequent in clinical practice, poor attention is paid to the topic and many cardiologists and anesthesiologists in small centers have to cope with cardiovascular complications during pregnancy, being at the forefront as consultants. Consequently, we deem appropriate to dwell on this statement. The aim of the present commentary is to summarize the main practical indications provided by the AHA from a strictly cardiological point of view.

Abstract BNT162b2 vaccine, developed by BioNTech and Pfizer ha recently approved for use in children aged 5 to 11 years. Recent data show evidence of safety on the administration and serious adverse events have been rarely reported. However, allergic systemic reactions could occur. In some cases, a correct allergic evaluation allows identifying patients at risk of developing an anaphylactic reaction. Risk assessment of allergic reactions to COVID-19 vaccines is useful to limit contraindications to vaccination and help to safely vaccinate people supposed to be at risk of allergic reactions.

Background: Bullying is a hostile behavior repeated over a time period, affecting children and adolescents in different social settings, mainly small and stable ones like school, with negative effects on mental and physical health. In this study, we aimed to provide the degree of impairment of different variables related to health and well-being in bullying conditions, with attention to sex differences. Methods: Data were obtained from 5390 adolescents (mean age 13.08 ± 1.89; male 2729), and health-related quality of life (HRQoL) was assessed using the KIDSCREEN-52 questionnaire. Results: In all students, mood and emotion, self-perception, and parental relationships are the dimensions more compromised in bullying conditions, while lifestyle habit is the variable less involved. Bullied girls show a significant impairment of all HRQoL variables both with respect to the socially accepted counterpart and to the male population. Conclusions: Our study highlights the strict association between bullying and emotional and social dimensions, suggesting that enhancing them preventively could facilitate earlier detection of problems, thereby reducing health risks.

Abstract Background Cardiovascular magnetic resonance permits assessment of irreversible myocardial fibrosis and contractile function in patients with previous myocardial infarction. We aimed to assess the prognostic value of myocardial fibrotic tissue with preserved/restored contractile activity. Methods In 730 consecutive myocardial infarction patients (64 ± 11 years), we quantified left ventricular (LV) end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (EF), regional wall motion (WM) (1 normal, 2 hypokinetic, 3 akinetic, 4 dyskinetic), and WM score index (WMSI), and measured the transmural (1–50 and 51–100) and global extent of the infarct scar by late gadolinium enhancement (LGE). Contractile fibrotic (CT-F) segments were identified as those showing WM-1 and WM-2 with LGE ≤ or ≥ 50%. Results During follow-up (median 2.5, range 1–4.7 years), cardiac events (cardiac death or appropriate implantable defibrillator shocks) occurred in 123 patients (17%). At univariate analysis, age, LVEDV, LVESV, LVEF, WMSI, extent of LGE, segments with transmural extent > 50%, and CT-F segments were associated with cardiac events. At multivariate analysis, age > 65 years, LVEF 1.7, and dilated LVEDV independently predicted cardiac events, while CT-F tissue was the only independent predictor of better outcome. After adjustment for LVEF

In this study we evaluated heart rate variability (HRV) changes in a pianist, playing in a laboratory, to investigate whether HRV changes are guided by music temporal features or by technical difficulty and/or subjective factors (e.g., experienced effort). The pianist was equipped with a wearable telemetry device for ECG recording during the execution of 4 classical and 5 jazz pieces. From ECG we derived the RR intervals series (tachogram), and, for each piece, analyzed HRV in the time (RR, RMSSD, Stress Index) and frequency domains (Total spectral power) and performed non-linear analysis (Multiscale Entropy). We also studied the correlation (Pearson) between the time course of music volume envelope and tachogram. Results showed a general reduction of parasympathetic and an increase of sympathetic activity, with the greatest changes during the classical pieces execution, the pianist appraised as more demanding than the jazz ones. The most marked changes occurred during the most technically/emotionally demanding piece, and correlation analysis revealed a negative association between music volume envelope time course and tachogram only for this piece, suggesting a modulation of the limbic system on the synchronization between heart rhythm and music temporal features. Classical music was also associated with the increase of entropy (1st scale) with respect to rest, indicating its effectiveness in driving flexible, healthy, heart dynamics. In conclusion, HRV seems modulated not only by the music temporal features, but also by the pianist’s emotional involvement, which is greatly influenced, in a non-trivial manner, by the technical demands and musician expertise.

Background and Objectives: Roughly 10% of cancer patients experience an episode of bleeding. The bleeding severity can range from occasional trivial bleeds to major bleeding. The treatment for the bleeding may vary, depending on the clinical condition and anatomical site, and may include various strategies, among which TAE is a cornerstone of major bleeding management. However, the existing literature on tumor hemorrhages is inconsistent. The objective of this multicenter retrospective cohort study was to evaluate the effectiveness and safety of arterial embolization in the treatment of tumor hemorrhages in patients with solid cancers. Materials and Methods: The data for patients with solid cancers undergoing TAE for the management of tumor hemorrhages from January 2020 to May 2023 were gathered. Results: A total of 92 patients with cancer-related bleeding were treated between January 2020 and May 2023. No bleeding was detected by X-ray angiography (XA) in 12 (13%) cases; therefore, a blind embolization was performed. The most common bleeding site was the liver (21.7%). A total of 66 tumor hemorrhages were spontaneous. The most commonly used embolic agent was polyvinyl alcohol (PVA) particles (30.4%). Technical success was achieved in 82 (89.1%) cases, with an 84.8% clinical success rate related to 14 cases of rebleeding. Proximal embolization was performed for 19 (20.7%) patients. Complications were recorded for 10 (10.9%) patients. The 30-day bleeding-related mortality was 15.2%. The technical success, clinical success, proximal embolization rate, and 30-day rebleeding were worse in the subset of patients undergoing TAE with coils. Conclusions: Transcatheter arterial embolization (TAE) represents a viable and potentially life-saving therapeutic approach in the management of tumor hemorrhages, demonstrating a notable effectiveness and safety. The TAE of bleeding tumors using coils resulted in a higher rate of non-superselective proximal embolization, with a trend toward lower clinical success rates and higher rebleeding episodes.

The incidence of heart valve disease (HVD) has been rising over the last few decades, mainly due to the increasing average age of the general population, and mitral valve (MV) disease is the second most prevalent HVD after calcific aortic stenosis, but MV disease is a heterogeneous group of different pathophysiological diseases. It is widely proven that regular physical activity reduces all-cause mortality rates, and exercise prescription is part of the medical recommendations for patients affected by cardiovascular diseases. However, changes in hemodynamic balance during physical exercise (including the increase in heart rate, preload, or afterload) could favor the progression of the MV disease and potentially trigger major cardiac events. In young patients with HVD, it is therefore important to define criteria for allowing competitive sport or exercise prescription, balancing the positive effects as well as the potential risks. This review focuses on mitral valve disease pathophysiology, diagnosis, risk stratification, exercise prescription, and competitive sport participation selection, and offers an overview of the principal mitral valve diseases with the aim of encouraging physicians to embody exercise in their daily practice when appropriate.

BackgroundStrenuous exercise has been associated with functional and structural cardiac changes due to local and systemic inflammatory responses, reflecting oxidative, metabolic, hormonal, and thermal stress, even in healthy individuals. We aimed to assess changes in myocardial structure and function using cardiovascular magnetic resonance (CMR) imaging in master triathletes early after a full-distance Ironman Triathlon race.Materials and methodsTen master triathletes (age 45 ± 8 years) underwent CMR within 3 h after a full-distance Ironman Triathlon race (3.8 km swimming, 180 km cycling, and 42.2 km running) completed with a mean time of 12 ± 1 h. All the triathletes had a 30-day follow-up CMR. Cine balanced steady-state free precession, T2-short tau inversion recovery (STIR), tagging, and late gadolinium enhancement (LGE) imaging sequences were performed on a 1.5-T MR scanner. Myocardial edema was defined as a region with increased T2 signal intensity (SI) of at least two SDs above the mean of the normal myocardium. The extent of myocardial edema was expressed as the percentage of left ventricular (LV) mass. Analysis of LV strain and torsion by tissue tagging included the assessment of radial, longitudinal, and circumferential peak systolic strain, rotation, and twist.ResultsCompared with postrace, biventricular volumes, ejection fraction, and LV mass index remained unchanged at 30-day follow-up. Global T2 SI was significantly higher in the postrace CMR (postrace 10.5 ± 6% vs. follow-up 3.9 ± 3.8%, P = 0.004) and presented with a relative apical sparing distribution (P < 0.001) matched by reduction of radial peak systolic strain of basal segments (P = 0.003). Apical rotation and twist were significantly higher immediately after the competition compared with follow-up (P < 0.05).ConclusionStrenuous exercise in master triathletes is associated with a reversible regional increase in myocardial edema and reduction of radial peak systolic strain, both presenting with a relative apical sparing pattern.

Incidental findings in research with human participants may have implications for a person’s present health or future health outcomes. Current guidelines focus on methods for handling and reporting incidental findings from biological test data but incidental findings might also arise from non-biological tests. This article presents three examples in which the results from non-biological test data can be predictive of future disease and should be disclosed to research participants. It is intended to increase awareness and facilitate further discussion about the reporting of incidental findings from non-biological data.

Background and Objectives: Transcatheter arterial embolization (TAE) is part of the daily practice of most interventional radiologists worldwide. The ideal liquid embolic agent is far from being identified. Non-adhesive liquid embolic agents (NALEA) harden from the outside to the inside, resulting in deep penetration, known as “magma-like” progression, which permits a more distal embolization with good control of the embolic material. This multicenter retrospective cohort study aims to assess the efficacy, feasibility and safety of transcatheter arterial embolization (TAE) with ethylene-vinyl alcohol (EVOH)-based NALEAs (Onyx and Squid) in acute bleeding outside of the neurovascular area. Materials and Methods: This study is a multicenter analysis of retrospectively collected data of consecutive patients who had undergone, from January 2015 to December 2022, transcatheter arterial embolization with non-adhesive EVOH-based agents in the setting of acute non-neurovascular bleeding. Results: Fifty-three patients underwent transcatheter arterial embolization for acute non-neurovascular bleeding. Eight (15.1%) procedures were performed in patients with coagulopathy. The most used concentration of EVOH-based NALEAs was 34 (i.e., 8%), with a mean dose of 0.5 (±0.3) mL. The mean CT-to-groin time, the mean procedure time, the mean CT-to-embolization time and the mean fluoroscopy time were 22.9 (±12.4) min, 27.5 (±7) min, 50.3 (±13.1) min and 7.5 (±2.8) min, respectively. Technical success was achieved in all cases with a 96.2% clinical success rate. Complications were recorded in six (11.3%) patients. No statistically significant differences were observed between the group of patients with coagulopathy and the group of patients without coagulopathy in terms of efficacy and safety endpoints. Conclusions: Transcatheter arterial embolization (TAE) performed with non-adhesive EVOH-based embolic agents is an effective, feasible and safe strategy for the management of acute non-neurovascular bleeding, even in the subgroup of patients with coagulopathy.

Obesity is a serious public health issue and associated with an increased risk of cardiovascular disease events and mortality. The risk of cardiovascular complications is directly related to excess body fat mass and ectopic fat deposition, but also other obesity-related complications such as pre-type 2 diabetes, obstructive sleep apnoea, and non-alcoholic fatty liver diseases. Body mass index and waist circumference are used to classify a patient as overweight or obese and to stratify cardiovascular risk. Physical activity and diet, despite being key points in preventing adverse events and reducing cardiovascular risk, are not always successful strategies. Pharmacological treatments for weight reduction are promising strategies, but are restricted by possible safety issues and cost. Nonetheless, these treatments are associated with improvements in cardiovascular risk factors, and studies are ongoing to better evaluate cardiovascular outcomes. Bariatric surgery is effective in reducing the incidence of death and cardiovascular events such as myocardial infarction and stroke. Cardiac rehabilitation programs in obese patients improve cardiovascular disease risk factors, quality of life, and exercise capacity. The aim of this review was to critically analyze the current role and future aspects of lifestyle changes, medical and surgical treatments, and cardiac rehabilitation in obese patients, to reduce cardiovascular disease risk and mortality, and to highlight the need for a multidisciplinary approach to improving cardiovascular outcomes.

Abstract Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with a high risk of sudden cardiac death. Three different prediction models for the indication of implanted cardioverter defibrillator (ICD) are now available: the 5 year ARVC risk score, the International Task Force Consensus (ITFC) criteria, and the Heart Rhythm Society (HRS) criteria. We compared these three prediction models in a validation cohort of patients with definite ARVC. Methods and results In a cohort of 140 patients with definite ARVC, the 5 year ARVC risk score and the ITFC and HRS criteria were compared for the prediction of a major combined endpoint of sudden cardiac death, appropriate ICD intervention, resuscitated cardiac arrest, and sustained ventricular tachycardia. During the follow‐up, 65 major events occurred. The 5 year ARVC risk score with a threshold >10%, derived from the maximally selected rank statistic, predicted 62 (95%) events [odds ratio (OR) 9.1, 95% confidence interval (CI) 2.6–32, P = 0.0006], the ITFC criteria 53 (81%, OR 4.8, 95% CI 2.2–10.3, P = 0.0001), and the HRS criteria 29 (45%, OR 4.2, 95% CI 1.9–9.3, P = 0.0003). At the analysis of decision curve for ICD implantation, a 5 year ARVC risk score >10% showed a greater net benefit than the ITFC and HRS criteria over a wide range of threshold probability of events. Finally, at multivariate analysis, the 5 year ARVC risk score >10% was the only independent predictor of major events. Conclusions The 5 year score with a threshold of >10% was more effective for predicting events than the ITFC and HRS criteria.

Abstract Background Limited number of studies examined the relationship between factors (lifestyle, social, emotional, cognitive) affecting adolescents’ health and well-being. The aims of this study were to identify the more important variables of the different components affecting adolescents’ health [lifestyle habits (LH); emotional status (ES); social context (SC); and cognitive abilities (CA)], and explore the relationship between the aforementioned components. Methods Data were collected between 2017 and 2018 from 756 eligible students, recruited from 5 Italian junior high school, by using KIDSCREEN-52 and cognitive processing using the Stroop Test. School engagement was estimated through questions concerning the scholastic achievement. Results Of 756 adolescents, 395 were boys with a mean (SD) age of 12.19 (0.81) years. Compared to International T-value of reference group for KIDSCREEN-52, autonomy, bullying, psychological well-being and mood were lower than the reference groups, while self-perception score was higher. For LH, the most important predictor was autonomy (p

Summary: Background: Gam-COVID-Vac (SPUTNIK V) has been granted emergency use authorization in 70 nations and has been administered to millions worldwide. However, there are very few peer-reviewed studies describing its effects. Independent reports regarding safety and effectiveness could accelerate the final approval by the WHO. We aimed to study the long-term humoral immune response in naïve and previously infected volunteers who received SPUTNIK V. Methods: Humoral immune responses, assayed by anti-SARS-CoV-2-spike-RBD IgG ELISA and neutralization assays, were measured in 602 healthcare workers at 0, 14, 28, 60 and 180 days after receiving SPUTNIK V between December 2020 and July 2021 in Tucumán, Argentina. Findings: Seroconversion was detected in 97% of individuals after 28 days post-vaccination (dpv) (N = 405). Anti-RBD titers began to decrease after 60 dpv (N = 328), but remained detectable in 94% at 90 dpv (N = 224). At 180 dpv, anti-RDB titers persisted in 31% (N = 146). Previous infection triggered an increased immune response to the first dose and increased neutralization activity against variants of concern (VOC). Second doses in previously infected individuals further increased titers, even 90 dpv (N = 75). Basal antibody titers had more influence on post-vaccination anti-RBD responses than the time elapsed between diagnosis and vaccination (N = 274). Interpretation: Data presented herein provides essential knowledge regarding the kinetics of antibodies induced by SPUTNIK V up to six months after immunization, and suggests that when considering one-dose vaccination policies for individuals with previous SARS-CoV-2 infection, serological studies to determine basal titers may be important, independent of when diagnosis occurred. Funding: Tucumán Public Health System (SIPROSA), Argentinean National Research Council (CONICET), National University of Tucumán (UNT).

IntroductionVery limited data exist on normal age-related ECG variations in adolescents and no data have been published regarding the ECG anomalies induced by intensive training, which are relevant in pre-participation screening for sudden cardiac death prevention in the adolescent athletic population. The purpose of this study was to establish normal age-related electrocardiographic measurements (P wave duration, PR interval, QRS duration, QT, and QTc interval) grouped according to 2-year age intervals.MethodsA total of 2,151 consecutive healthy adolescent Soccer athletes (trained for a mean of 7.2 ± 1.1 h per week, 100% male Caucasians, mean age 12.4 ± 1.4 years, range 7–18) underwent pre-participation screening, which included ECG and transthoracic echocardiography in a single referral center.ResultsTheir heart rate progressively slowed as age increased (p < 0.001, ranging from 80.8 ± 13.2 to 59.5 ± 10.2 bpm), as expected. The P wave, PR interval, and QRS duration significantly increased in older age classes (p = 0.019, p = 0.001, and p < 0.001, respectively), and after Bonferroni's correction, the difference remained significant in all age classes for QRS duration. The QTc interval diminished progressively with increasing age (p = 0.003) while the QT interval increased progressively (p < 0.001).ConclusionsSignificant variations in the normal ECG characteristics of young athletes exist between different age groups related to increasing age and training burden, thus, age-specific reference values could be adopted, as already done for echocardiographic measurements, and may help to further discriminate potentially pathologic conditions.

Background: Oxidative stress and impaired autophagy are directly and indirectly implicated in exercise-mediated muscle injury. Trehalose, spermidine, nicotinamide, and polyphenols possess pro-autophagic and antioxidant properties, and could therefore reduce exercise-induced damage to skeletal muscle. The aim of this study was to investigate whether a mixture of these compounds was able to improve muscle injury biomarkers in endurance athletes through the modulation of oxidative stress and autophagic machinery. Methods and Results: sNOX2-dp; H2O2 production; H2O2 breakdown activity (HBA); ATG5 and p62 levels, both markers of autophagic process; and muscle injury biomarkers were evaluated in five endurance athletes who were allocated in a crossover design study to daily administration of 10.5 g of an experimental mixture or no treatment, with evaluations conducted at baseline and after 30 days of mixture consumption. Compared to baseline, the mixture intake led to a remarkable reduction of oxidative stress and positively modulated autophagy. Finally, after the 30-day supplementation period, a significant decrease in muscle injury biomarkers was found. Conclusion: Supplementation with this mixture positively affected redox state and autophagy and improved muscle injury biomarkers in athletes, allowing for better muscle recovery. Moreover, it is speculated that this mixture could also benefit patients suffering from muscle injuries, such as cancer or cardiovascular patients, or elderly subjects.

BackgroundHealth and well-being promotions are key points of educational programs for adolescents within schools. There are several health education programs mainly based on lifestyle habit changes; however, social and emotional dimensions should be considered within these educational strategies. ObjectiveThis study aimed to (1) develop a new web-based school support system to assess and analyze individual, classroom, and scholastic institute data on lifestyle habits, social context, emotional status, and scholastic performance; (2) create a web tool for managing the well-being of adolescents through a dynamic and personalized interface that provides immediate feedback that allows the school to monitor progress; and (3) evaluate, in a pilot study, the feasibility of this web-based school support system in order to build health programs that are specific to the needs of the studied population. MethodsThe AVATAR (a new purpose for the promotion and evaluation of health and well-being among healthy teenagers) method consists of integrating the information coming from different questionnaires. In particular, to allow planning didactic and educational actions based on the results obtained, the AVATAR approach allows subdivision of the results of the different observed variables and the 4 components into the following 3 percentile categories: modify, improve, and maintain. The AVATAR web platform was designed to collect data on lifestyle, emotional status, and social context from junior high schools in terms of the fundamental aspects of adolescent daily life, with free use by the scholastic community (scholars, teachers, and parents). In this pilot/feasibility study, data from 331 students were acquired between 2018 and 2019 at the beginning of the scholastic year (pre) and at the end following the school-based program (post). ResultsPreliminary results showed that after school planning and specific program implementation, defined after AVATAR feedback, students reported better well-being perception characterized by higher perception in psychological well-being (P=.001), mood (P=.001), self-perception (P=.006), and autonomy (P=.001), and an increase in the perception of financial resources (P=.001), which helped in developing healthy lifestyle habits (P=.007). In the social context assessment, students reported stronger relationships with family (P=.02) and peers (P=.001), and a lower perception of bullying (P=.001). ConclusionsThe AVATAR web-based platform is a feasible and flexible tool for the health and well-being management of adolescents from epidemiological, preventive, and educational points of view. In particular, it can be used to (1) promote information campaigns aimed at modifying risk behaviors in the student population, (2) sensitize students and put them at the center of their growth path, (3) inform institutions about the health and well-being of the school population, (4) ensure health programs are acceptable and feasible to users before launching on a large scale, and (5) improve the relationship of users (school) and educational agencies with research groups.

Nonalcoholic fatty liver disease (NAFLD)-associated liver fibrosis is likely related to coronary artery disease (CAD) by the mediation of systemic inflammation. This study aimed at evaluating the predictive value of neutrophil-to-lymphocyte-ratio (NLR) and fibrosis-4 index (FIB-4), indices of inflammation and fibrosis, respectively, on CAD mortality. Data from 1460 CAD patients (1151 males, age: 68 ± 10 years, mean ± SD) were retrospectively analyzed. Over a median follow-up of 26 months (interquartile range (IQR) 12–45), 94 deaths were recorded. Kaplan–Meier survival analysis revealed worse outcomes in patients with elevation of one or both biomarkers (FIB-4 > 3.25 or/and NLR > 2.04, log-rank p-value < 0.001). In multivariate Cox regression analysis, the elevation of one biomarker (NLR or FIB-4) still confers a significant independent risk for mortality (hazard ratio (HR) = 1.7, 95% confidence interval (95% CI): 1.1–2.7, p = 0.023), whereas an increase in both biomarkers confers a risk corresponding to HR = 3.5 (95% CI: 1.6–7.8, p = 0.002). Categorization of patients with elevated FIB-4/NLR could provide valuable information for risk stratification and reduction of residual risk in CAD patients.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic with dramatic health and socioeconomic consequences. The Coronavirus Disease 2019 (COVID-19) challenges health systems to quickly respond by developing new diagnostic strategies that contribute to identify infected individuals, monitor infections, perform contact-tracing, and limit the spread of the virus. In this brief report, we developed a highly sensitive, specific, and precise “In-House” ELISA to correctly discriminate previously SARS-CoV-2-infected and non-infected individuals and study population seroprevalence. Among 758 individuals evaluated for anti-SARS-CoV-2 serology in the province of Tucumán, Argentina, we found a weak correlation between antibodies elicited against the RBD, the receptor-binding domain of the Spike protein, and the nucleocapsid (N) antigens of this virus. Additionally, we detected mild levels of anti-RBD IgG antibodies in 33.6% of individuals diagnosed with COVID-19, while only 19% showed sufficient antibody titers to be considered as plasma donors. No differences in IgG anti-RBD titers were found between women and men, neither in between different age groups ranging from 18 to 60. Surprisingly, individuals from a high altitude village displayed elevated and longer lasting anti-RBD titers compared to those from a lower altitude city. To our knowledge, this is the first report correlating altitude with increased humoral immune response against SARS-CoV-2 infection.

The role of thyroid hormones (THs) in the cardiovascular (CV) system, through several direct and indirect effects is recognized. Even very small modification in TH levels (as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome) may adversely affect the CV system, whereas thyroid hormones benefit the CV system and improve the prognosis. There is also evidence of vitamin D effects on cardiometabolic disease (e.g., through modulation of endothelial and smooth muscle cell activity, renin-angiotensin-aldosterone system, nitric oxide, oxidative stress, and inflammatory response), as well as an association between vitamin D [25(OH)D] deficiency and autoimmune thyroid diseases or cancer, and a relationship between vitamin D concentration and titers of antibodies and thyroid autoimmunity replacement. Interestingly, experimental data indicate a direct effect of vitamin D on Type 2 deiodinase expression causing subsequential peripheral conversion of T4 into T3. However, the functional links among THs, vitamin D and the cardiovascular system, and clinical effects of coexisting abnormalities in this new troublesome triad, have not yet been reviewed. The main aim of this review is to discuss pathophysiology of this relationship, proposing new mechanistic insights involving vitamin D in the modulation of cardiometabolic disease and thyroid profile.

Oxidative stress and inflammation are key factors in cardiometabolic diseases. We set out to evaluate the relationship between serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) with cardiometabolic risk factors in coronary artery disease (CAD) patients, and their additive and multiplicative interactive effects on outcomes (cardiac death/CD and hard events (HE)—death plus reinfarction). A total of 2712 patients (67 ± 11 years, 1960 males) who underwent coronary angiography was retrospectively analyzed and categorized into no-CAD patients (n = 806), stable-CAD patients (n = 1545), and patients with acute myocardial infarction (AMI) (n = 361). UA and NLR were reciprocally correlated and associated with cardiometabolic risk factors. During a mean follow-up period of 27 ± 20 months, 99 ± 3.6% deaths, and 213 ± 7.8% HE were registered. The Kaplan–Meier survival estimates showed significantly worse outcomes in patients with elevated UA or NLR levels. Multivariate Cox regression analysis demonstrated that NLR independently predicted CD and HE. There was no multiplicative interaction between UA and NLR; however, the use of measures of additive interaction evidenced a positive additive interaction between UA and NLR for CD and HE. Although it is clear that correlation does not imply causation, the coexistence of NRL and UA appears to have a synergistic effect, providing further information for the risk stratification of CAD patients.

Sodium–glucose co-transporter-2 inhibitors or gliflozins, the newest anti-hyperglycemic class, induce cardioprotective benefits in patients with type 2 diabetes (T2D). As platelet activation and oxidative stress play a key role in atherothrombotic-related complications, we hypothesized that gliflozins might modulate oxidative stress, platelet activation and thrombus formation. We performed an interventional open-label single-arm before-after study in 32 T2D patients on top of their ongoing metformin therapy. The population was divided into two groups: treatment with GLP-1 receptor agonists (GLP-1RA, Group A) and gliflozins (Group B). Oxidative stress, platelet activation and thrombus growth were assessed before and after 15 days of treatment. Compared to the baseline, gliflozins treatment significantly decreased sNOX2-dp (−45.2%, p < 0.001), H2O2 production (−53.4%, p < 0.001), TxB2 (−33.1%, p < 0.001), sP-selectin (−49.3%, p < 0.001) and sCD40L levels (−62.3%, p < 0.001) as well as thrombus formation (−32%, p < 0.001), whereas it potentiated anti-oxidant power (HBA, +30.8%, p < 0.001). Moreover, a significant difference in oxidative stress, platelet activation and thrombus formation across groups A and B was found. In addition, an in vitro study on stimulated platelets treated with gliflozins (10–30 μM) showed a reduction in oxidative stress, platelet activation and thrombus growth. Our results showed that gliflozins have antiplatelet and antithrombic activity related to an NOX2 down-regulation, suggesting a new mechanism responsible for cardiovascular protection.

Trehalose, spermidine, nicotinamide, and polyphenols have been shown to display pro-autophagic and antioxidant properties, eventually reducing cardiovascular and ischemic complications. This study aimed to investigate whether a mixture of these components improves maximal walking distance (MWD) in peripheral artery disease (PAD) patients. Nitrite/nitrate (NOx), endothelin-1, sNOX2-dp, H2O2 production, H2O2 break-down activity (HBA), ATG5 and P62 levels, flow-mediated dilation (FMD), and MWD were evaluated in 20 PAD patients randomly allocated to 10.5 g of mixture or no-treatment in a single-blind study. The above variables were assessed at baseline and 60 days after mixture ingestion. Compared with baseline, mixture intake significantly increased MWD (+91%; p < 0.01) and serum NOx (+96%; p < 0.001), whereas it significantly reduced endothelin-1 levels (−30%, p < 0.01). Moreover, mixture intake led to a remarkable reduction in sNOX2dp (−31%, p < 0.05) and H2O2 (−40%, p < 0.001) and potentiated antioxidant power (+110%, p < 0.001). Finally, mixture ingestion restored autophagy by increasing ATG5 (+43%, p < 0.01) and decreasing P62 (−29%, p < 0.05). No changes in the above-mentioned variables were observed in the no-treatment group. The treatment with a mixture of trehalose, spermidine, nicotinamide, and polyphenols improves MWD in PAD patients, with a mechanism possibly related to NOX2-mediated oxidative stress downregulation and autophagic flux upregulation. Clinical Trial Registration unique identifier: NCT04061070.

Retinoids are micronutrients that are stored as retinyl esters in the retina and hepatic stellate cells (HSCs). HSCs are key players in fibrogenesis in chronic liver diseases. The enzyme responsible for hydrolysis and release of retinyl esters from HSCs is unknown and the relationship between retinoid metabolism and liver disease remains unclear. We hypothesize that the patatin-like phospholipase domain-containing 3 (PNPLA3) protein is involved in retinol metabolism in HSCs. We tested our hypothesis both in primary human HSCs and in a human cohort of subjects with non-alcoholic fatty liver disease (N = 146). Here we show that PNPLA3 is highly expressed in human HSCs. Its expression is regulated by retinol availability and insulin, and increased PNPLA3 expression results in reduced lipid droplet content. PNPLA3 promotes extracellular release of retinol from HSCs in response to insulin. We also show that purified wild-type PNPLA3 hydrolyzes retinyl palmitate into retinol and palmitic acid. Conversely, this enzymatic activity is markedly reduced with purified PNPLA3 148M, a common mutation robustly associated with liver fibrosis and hepatocellular carcinoma development. We also find the PNPLA3 I148M genotype to be an independent (P = 0.009 in a multivariate analysis) determinant of circulating retinol-binding protein 4, a reliable proxy for retinol levels in humans. This study identifies PNPLA3 as a lipase responsible for retinyl-palmitate hydrolysis in HSCs in humans. Importantly, this indicates a potential novel link between HSCs, retinoid metabolism and PNPLA3 in determining the susceptibility to chronic liver disease.