Oxidative Stress and Antioxidant Status in Adult Patients with Transfusion-Dependent Thalassemia: Correlation with Demographic, Laboratory, and Clinical Biomarkers.

Iron overload in beta transfusion-dependent thalassemia (ß-TDT) may provoke oxidative stress and reduction of the antioxidant defenses, with serious consequences for the disease course and complications. The present study evaluated the oxidant/antioxidant status of ß-TDT patients and its correlation with demographic, clinical, laboratory, and instrumental biomarkers. The OXY-adsorbent assay and the d-ROMs (Diacron, Grosseto, Italy) were evaluated in 58 ß-TDT patients (mean age: 37.55 ± 7.83 years, 28 females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload was quantified with R2* magnetic resonance imaging. Mean OXY was 323.75 ± 113.19 µmol HClO/mL and 39 (67.2%) patients showed a decreased OXY-Adsorbent level (<350 µmol HClO/mL), of whom 22 (37.9%) showed severely reduced levels. Mean d-ROMs was 305.12 ± 62.19 UA; 12 (20.7%) patients showed oxidative stress, and 4 (6.9%) elevated oxidative stress. OXY showed a significant negative correlation with global and segmental cardiac iron levels. D-ROMs levels significantly correlated with markers of cardiovascular risk (aging, glycemia, and N-terminal pro-B-type natriuretic peptide). Antioxidant depletion is frequent in ß-TDT patients, where OXY might serve as additive biomarker to assess heart iron status, whereas the d-ROMs might be helpful to assess the cardiovascular risk burden.

Vitamin D and Ceramide Metabolomic Profile in Acute Myocardial Infarction.

Sphingolipids (SLs) influence several cellular pathways, while vitamin D exerts many extraskeletal effects in addition to its traditional biological functions, including the modulation of calcium homeostasis and bone health. Moreover, Vitamin D and SLs affect the regulation of each others' metabolism; hence, this study aims to evaluate the relationship between the levels of 25(OH)D and ceramides in acute myocardial infarction (AMI). In particular, the blood abundance of eight ceramides and 25(OH)D was evaluated in 134 AMI patients (aged 68.4 ± 12.0 years, 72% males). A significant inverse correlation between 25(OH)D and both Cer(d18:1/16:0) and Cer(d18:1/18:0) was found; indeed, patients with severe hypovitaminosis D (<10 ng/mL) showed the highest levels of the two investigated ceramides. Moreover, diabetic/dyslipidemic patients with suboptimal levels of 25(OH)D (<30 ng/mL) had higher levels of both the ceramides when compared with the rest of the population. On the other hand, 25(OH)D remained an independent determinant for Cer(d18:1/16:0) (STD Coeff -0.18, t-Value -2, p ≤ 0.05) and Cer(d18:1/18:0) (-0.2, -2.2, p < 0.05). In light of these findings, the crosstalk between sphingolipids and vitamin D may unravel additional mechanisms by which these molecules can influence CV risk in AMI.

Systemic Immune-Inflammation Index and Systemic Inflammatory Response Index as Predictors of Mortality in ST-Elevation Myocardial Infarction.

(1) Background: The systemic inflammatory response index (SIRI; neutrophil count × monocyte/lymphocyte count), and the systemic immune-inflammation index (SII; platelet count × neutrophil count/lymphocyte count) are recently proposed biomarkers to assess the immune and inflammatory status. However, data on SIRI and SII are still relatively lacking and do not definitively and exhaustively define their role as predictors of an adverse prognosis in acute myocardial infarction (AMI). The aim of the present study was to evaluate SII and SIRI determinants as well as to assess SIRI and SII prognostic power in ST-elevation myocardial infarction (STEMI). (2) Methods: A total of 105 STEMI patients (74 males, 70 ± 11 years) were studied (median follow-up 54 ± 25 months, 24 deaths). (3) Results: The main determinants of SIRI and SII were creatinine and brain natriuretic peptide (BNP) (multivariate regression). Patients with higher SIRI (>75th percentile, 4.9) and SII (>75th percentile, 1257.5) had lower survival rates than those in the low SIRI/SII group (Kaplan-Meier analysis). Univariate Cox regression revealed that high SIRI and SII were associated with mortality (HR: 2.6, 95% CI: 1.1-5.8, p < 0.05; 2.2, 1-4.9, p ≤ 0.05, respectively); however, these associations lost their significance after multivariate adjustment. (4) Conclusions: SIRI and SII association with mortality was significantly affected by confounding factors in our population, especially creatinine and BNP, which are associated with both the inflammatory indices and the outcome.

Environmental Temperature, Other Climatic Variables, and Cardiometabolic Profile in Acute Myocardial Infarction.

Objectives: To evaluate CV profiles, periprocedural complications, and in-hospital mortality in acute myocardial infarction (AMI) according to climate. Methods: Data from 2478 AMI patients (1779 men; mean age 67 ∓ 13 years; Pasquinucci Hospital ICU, Massa, Italy; 2007-2018) were retrospectively analyzed according to climate (LAMMA Consortium; Firenze, Italy) by using three approaches as follows: (1) annual warm (May-October) and cold (November-April) periods; (2) warm and cold extremes of the two periods; and (3) warm and cold extremes for each month of the two periods. Results: All approaches highlighted a higher percentage of AMI hospitalization for patients with adverse CV profiles in relation to low temperatures, or higher periprocedural complications and in-hospital deaths. In warmer times of the cold periods, there were fewer admissions of dyslipidemic patients. During warm periods, progressive heat anomalies were characterized by more smoker (approaches 2 and 3) and young AMI patient (approach 3) admissions, whereas cooler times (approach 3) evidenced a reduced hospitalization of diabetic and dyslipidemic patients. No significant effects were observed for the heat index and light circulation. Conclusions: Although largely overlapping, different approaches identify patient subgroups with different CV risk factors at higher AMI admission risk and adverse short-term outcomes. These data retain potential implications regarding pathophysiological mechanisms of AMI and its prevention.

Machine learning to identify a composite indicator to predict cardiac death in ischemic heart disease.

BACKGROUND: Machine learning (ML) employs algorithms that learn from data, building models with the potential to predict events by aggregating a large number of variables and assessing their complex interactions. The aim of this study is to assess ML potential in identifying patients with ischemic heart disease (IHD) at high risk of cardiac death (CD). METHODS: 3987 (mean age 68 ± 11) hospitalized IHD patients were enrolled. We implemented and compared various ML models and their combination into ensembles. Model output constitutes a new ML indicator to be employed for stratification. Primary variable importance was assessed with ablation tests. RESULTS: An ensemble classifier combining three ML models achieved the best performance to predict CD (AUROC of 0.830, F1-macro of 0.726). ML indicator use through Cox survival analysis outperformed the 18 variables individually, producing a better stratification compared to standard multivariate analysis (improvement of ∼20%). Patients in the low risk group defined through ML indicator had a significantly higher survival (88.8% versus 29.1%). The main variables identified were Dyslipidemia, LVEF, Previous CABG, Diabetes, Previous Myocardial Infarction, Smoke, Documented resting or exertional ischemia, with an AUROC of 0.791 and an F1-score of 0.674, lower than that of 18 variables. Both code and clinical data are freely available with this article. CONCLUSION: ML may allow a faster, low-cost and reliable evaluation of IHD patient prognosis by inclusion of more predictors and identification of those more significant, improving outcome prediction towards the development of precision medicine in this clinical field.

Interplay between Vitamin D and Sphingolipids in Cardiometabolic Diseases.

Sphingolipids (SLs) are structural, bioactive molecules with several key cellular roles, whereas 1,25-dihydroxyvitamin D (1,25(OH)D), the active form of vitamin D, is considered the major regulator of calcium homeostasis, although it also exerts other extraskeletal effects. Many studies reported the physiological connection between vitamin D and SLs, highlighting not only the effects of vitamin D on SL metabolism and signaling but also the influence of SLs on vitamin D levels and function, thus strongly suggesting a crosstalk between these molecules. After a brief description of 1,25(OH)D and SL metabolism, this review aims to discuss the preclinical and clinical evidence on the crosstalk between SLs and 1,25(OH)D, with a special focus on cardiometabolic diseases.

Lipids Metabolism and Cardiometabolic Diseases.

Cardiometabolic diseases (CMD) remains the major cause of morbidity and mortality in Western countries, with a marked increased in the last years [...].

A Close Association between Body Weight, Health-Related Quality of Life, and Risk Behaviors in a Sample of Italian High School Students.

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.

Low Vitamin D Levels Are Associated with Increased Cardiac Iron Uptake in Beta-Thalassemia Major.

We evaluated the association of vitamin D and parathormone (PTH) levels with cardiac iron and function in beta-thalassemia major (ß-TM) patients. Two-hundred and seventy-eight TM patients (39.04 ± 8.58 years, 56.8% females) underwent magnetic resonance imaging for the assessment of iron overload (T2* technique), biventricular function parameters (cine images), and replacement myocardial fibrosis (late gadolinium enhancement technique). Vitamin D levels were deficient (<20 ng/dL) in 107 (38.5%) patients, insufficient (20-30 ng/dL) in 96 (34.5%) patients, and sufficient (≥30 ng/dL) in 75 (27.0%) patients. Deficient vitamin D patients had a significantly higher frequency of myocardial iron overload (MIO; global heart T2* < 20 ms) than patients with sufficient and insufficient vitamin D levels and a significantly higher left ventricular end-diastolic volume index and mass index than patients with sufficient vitamin D levels. PTH was not associated with cardiac iron, function, or fibrosis. In the multivariate regression analysis, vitamin D, serum ferritin, and pancreatic iron levels were the strongest predictors of global heart T2* values. In receiver operating characteristic curve analysis, a vitamin D level ≤ 17.3 ng/dL predicted MIO with a sensitivity of 81.5% and a specificity of 75.3% (p < 0.0001). In TM, the periodic and regular assessment of vitamin D levels can be beneficial for the prevention of cardiac iron accumulation and subsequent overt dysfunction.

An Entangled Relationship between Bullying Perception and Psychosocial Dimensions in a Sample of Young Adolescents.

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.

The Sphingolipid-Signaling Pathway as a Modulator of Infection by SARS-CoV-2.

Ceramides and other related sphingolipids, important cellular components linked to metabolic homeostasis and cardiometabolic diseases, have been found to be involved in different steps of the SARS-CoV-2 life cycle. Hence, changes in their physiological levels are identified as predictors of COVID-19 severity and prognosis, as well as potential therapeutic targets. In this review, an overview of the SARS-CoV-2 life cycle is given, followed by a description of the sphingolipid metabolism and its role in viral infection, with a particular focus on those steps required to finalize the viral life cycle. Furthermore, the use and development of pharmaceutical strategies to target sphingolipids to prevent and treat severe and long-term symptoms of infectious diseases, particularly COVID-19, are reviewed herein. Finally, research perspectives and current challenges in this research field are highlighted. Although many aspects of sphingolipid metabolism are not fully known, this review aims to highlight how the discovery and use of molecules targeting sphingolipids with reliable and selective properties may offer new therapeutic alternatives to infectious and other diseases, including COVID-19.

Acute Myocardial Infarction in the Era of COVID-19: A Challenge in a Challenge.

From the very beginning, the coronavirus pandemic (COVID-19) has tested the healthcare systems, having unpredictable and extreme adverse impacts on acute care clinical settings [...].

The Positive Impact of Early Frailty Levels on Mortality in Elderly Patients with Severe Aortic Stenosis Undergoing Transcatheter/Surgical Aortic Valve Replacement.

Background: Frailty is highly common in older patients (pts) undergoing transcatheter aortic valve replacement (TAVR), and it is associated with poor outcomes. The selection of patients who can benefit from this procedure is necessary and challenging. The aim of the present study is to evaluate outcomes in older severe aortic valve stenosis (AS) pts, selected by a multidisciplinary approach for surgical, clinical, and geriatric risk and referred to treatment, according to frailty levels. Methods: A total of 109 pts (83 ± 5 years; females, 68%) with AS were classified by Fried's score in pre-frail, early frail, and frail and underwent surgical aortic valve replacement SAVR/TAVR, balloon aortic valvuloplasty, or medical therapy. We evaluated geriatric, clinical, and surgical features and detected periprocedural complications. The outcome was all-cause mortality. Results: Increasing frailty was associated with the worst clinical, surgical, geriatric conditions. By using Kaplan-Meier analysis, the survival rate was higher in pre-frail and TAVR groups (p < 0.001) (median follow-up = 20 months). By using the Cox regression model, frailty (p = 0.004), heart failure (p = 0.007), EF% (p = 0.043), albumin (p = 0.018) were associated with all-cause mortality. Conclusions: According to tailored frailty management, elderly AS pts with early frailty levels seem to be the most suitable candidates for TAVR/SAVR for positive outcomes because advanced frailty would make each treatment futile or palliative.

Sphingolipid Levels and Signaling via Resveratrol and Antioxidant Actions in Cardiometabolic Risk and Disease.

Resveratrol (RSV) is a phenolic compound with strong antioxidant activity, which is generally associated with the beneficial effects of wine on human health. All resveratrol-mediated benefits exerted on different systems and pathophysiological conditions are possible through resveratrol's interactions with different biological targets, along with its involvement in several key cellular pathways affecting cardiometabolic (CM) health. With regard to its role in oxidative stress, RSV exerts its antioxidant activity not only as a free radical scavenger but also by increasing the activity of antioxidant enzymes and regulating redox genes, nitric oxide bioavailability and mitochondrial function. Moreover, several studies have demonstrated that some RSV effects are mediated by changes in sphingolipids, a class of biolipids involved in a number of cellular functions (e.g., apoptosis, cell proliferation, oxidative stress and inflammation) that have attracted interest as emerging critical determinants of CM risk and disease. Accordingly, this review aimed to discuss the available data regarding the effects of RSV on sphingolipid metabolism and signaling in CM risk and disease, focusing on oxidative stress/inflammatory-related aspects, and the clinical implications of this relationship.

The impact of HCV chronic positivity and clearance on extrahepatic morbidity in thalassemia major patients: an observational study from MIOT Network.

BACKGROUND: No study has evaluated the effect of hepatitis C virus (HCV) infection on the wide spectrum of complications affecting patients with thalassemia. OBJECTIVES: This multicenter study prospectively assessed the relationship of HCV infection with diabetes mellitus and cardiovascular complications in patients with thalassemia major (TM). METHODS: We considered 1057 TM patients (539 females; 29.79±10.08 years) enrolled in the MIOT Network and categorized into 4 groups: negative patients (group 1a, N=460), patients who spontaneously cleared the virus within 6months (group 1b, N=242), patients who eradicated the virus after the treatment with antiviral therapy (group 2, N=102), and patients with chronic HCV infection (group 3, N=254). RESULTS: Group 1a and 1b were considered as a unique group (group 1). For both groups 1 and 3, a match 1:1 for age and sex with group 2 was performed. The effective study cohort consisted of 306 patients (three groups of 102 patients). During a mean follow-up of 67.93±39.20months, the group 3 experienced a significantly higher % increase/month in aspartate transaminase levels and left ventricular mass index than both groups 1 and 2. The changes in iron overload indexes were comparable among the three groups. Compared to group 1, the chronic HCV group showed a significantly higher risk of diabetes (hazard ratio-HR=5.33; p=0.043) and of cardiovascular diseases (HR=3.80; p=0.034). CONCLUSION: Chronic HCV infection is associated with a significant higher risk of diabetes mellitus and cardiovascular complications in TM patients and should be approached as a systemic disease in which extrahepatic complications increase the weight of its pathological burden.

Vitamin D Determinants, Status, and Antioxidant/Anti-inflammatory-Related Effects in Cardiovascular Risk and Disease: Not the Last Word in the Controversy.

Beyond its key role in calcium homeostasis, vitamin D has been found to significantly affect the cardiovascular (CV) system. In fact, low vitamin D levels have been associated with increased CV risk, as well as increased CV morbidity and mortality. The majority of effects of this molecule are related directly or indirectly to its antioxidative and anti-inflammatory properties. Generally, vitamin D insufficiency is considered for 25-hydroxyvitamin D (25(OH)D) levels between 21-29 ng/mL (corresponding to 52.5-72.5 nmol/L), deficiency as 25(OH)D levels less than 20 ng/mL (<50 nmol/L), and extreme deficiency as 25(OH)D less than 10 ng/mL (<25 nmol/L). However, the definition of an optimal vitamin D status, as defined by 25(OH)D, remains controversial for many extra-bone conditions, including CV disease. In this review, confounding factors affecting the 25(OH)D measurement and status will be discussed. In particular, available evidence on the mechanism and role of vitamin D in relation to CV risk and disease through its antioxidant effect will be reported, also facing the aspect regarding the debate on the minimum blood 25(OH)D level required to ensure optimal CV health.

Relationship between eating disorders perception and psychosocial profile in school-dropout adolescents.

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 < 0.05) and are associated with lower HRQoL (p < 0.001) and lower well-being perception (p < 0.001). EDs are associated with an impairment of physical (p < 0.05) and psychological well-being perception (p < 0.001), emotional responses (p < 0.001), self-perception (p < 0.001), and a reduction of general well-being (p < 0.05). CONCLUSIONS: Although it is complicated to distinguish between causes and consequences, these findings suggest a complex and multifaceted, association between ED and HRQoL domains. Thus, multiple factors need taking into account in the policy of EDs prevention, identifying all the components of well-being to focus and personalize healthy programs in adolescences.

Adolescence is a transitional period from childhood to adulthood during which important biological, cognitive and social changes are experienced. In this phase, characterized by increased psychological vulnerability, classic risk behavior can develop, including altered eating behavior leading to eating disorders (EDs). EDs represent a varied group of pathological conditions influenced by various individual factors, including emotional state, cognitive functioning, and social context, probably associated to physical, emotional, and social changes that in young people can lead to great instability. Our results shown that is complicated to distinguish between causes and consequences that cause EDs, suggesting a complex and multifaceted association between ED and psychological domains. This is important in order to develop preventive and early intervention programs in the schools and in other educational institutions, focusing on what are considered potential predictor of EDs.

Lipoprotein(a), Cardiovascular Events and Sex Differences: A Single Cardiological Unit Experience.

Lipoprotein(a)-Lp(a), which retains proatherogenic and prothrombotic properties, may be modified by hormonal and metabolic factors. However, few studies have focused on differences related to sex and cardiometabolic risk factors in the relationship between Lp(a) and cardiovascular disease, especially in terms of prognosis. This study aimed at evaluating the predictive value of Lp(a) (cut-off 30 mg/dL) for hard events (HEs: mortality and non-fatal myocardial infarction) according to sex and cardiometabolic risk factors in 2110 patients (1501 males, mean age: 68 ± 9 years) undergoing coronary angiography for known or suspected coronary artery disease. There were 211 events over a median follow-up period of 33 months. Lp(a) > 30 mg/dL did not confer a worse prognosis on the overall population. However, Kaplan-Meier subgroup analysis evidenced a worse prognosis in type 2 diabetes (T2D) females with elevated Lp(a) (log-rank test: p = 0.03) vs. T2D males and no-T2D patients, but not in other high-risk cardiovascular states (e.g., smoking, hypertension, reduced left ventricular ejection fraction or obesity). After Cox multivariate adjustment, Lp(a) remained an independent determinant for HEs in the T2D female subgroup, conferring an HR of 2.9 (95% CI 1.1-7.7, p < 0.05). Lp(a) is therefore a strong independent predictor of HR in T2D women, but not in T2D men, or in noT2D patients.