Mitophagy modulation for the treatment of cardiovascular diseases.

BACKGROUND: Defects of mitophagy, the selective form of autophagy for mitochondria, are commonly observed in several cardiovascular diseases and represent the main cause of mitochondrial dysfunction. For this reason, mitophagy has emerged as a novel and potential therapeutic target. METHODS: In this review, we discuss current evidence about the biological significance of mitophagy in relevant preclinical models of cardiac and vascular diseases, such as heart failure, ischemia/reperfusion injury, metabolic cardiomyopathy and atherosclerosis. RESULTS: Multiple studies have shown that cardiac and vascular mitophagy is an adaptive mechanism in response to stress, contributing to cardiovascular homeostasis. Mitophagy defects lead to cell death, ultimately impairing cardiac and vascular function, whereas restoration of mitophagy by specific compounds delays disease progression. CONCLUSIONS: Despite previous efforts, the molecular mechanisms underlying mitophagy activation in response to stress are not fully characterized. A comprehensive understanding of different forms of mitophagy active in the cardiovascular system is extremely important for the development of new drugs targeting this process. Human studies evaluating mitophagy abnormalities in patients at high cardiovascular risk also represent a future challenge.

Mechanical Cardiopulmonary Resuscitation Devices: Evidence Synthesis with an Umbrella Review.

AIM: Sudden cardiac arrest is a significant cause of death worldwide. Good quality cardiopulmonary resuscitation increases patients' survival. Manual cardiopulmonary resuscitation is often ineffective as rescuers may experience physical and mental fatigue. Mechanical cardiopulmonary resuscitation devices are designed to address this issue, providing an automated approach for high-quality resuscitation. In the present comprehensive umbrella review we summarize current evidence on mechanical devices. METHODS: We searched systematic reviews on mechanical devices in MEDLINE/PubMed. Effect estimates were obtained from original reports, including 95% confidence intervals and p values, when applicable and available, focusing on return of spontaneous circulation, survival to discharge or 30 days, survival with good neurological outcome, and resuscitation-related injuries. RESULTS: From 21 potentially pertinent publications, we shortlisted 10 reviews, each including between 5 and 22 studies. AutoPulse, LUCAS, and LUCAS-2 were among the investigated devices. Most reviews concluded toward mechanical devices being similar or better than manual resuscitation for return of spontaneous circulation and 30-days survival. Regarding survival with good neurological function, some reviews lacked data, while the remaining ones reported similar results or worse outcomes in patients undergoing mechanical resuscitation. Focusing on resuscitation-related injuries, data were limited or conflicting with one review reporting higher rates of injuries with mechanical devices, and two others suggesting similar outcomes. CONCLUSIONS: Manual and mechanical cardiopulmonary resuscitation appear to be similar in terms of return of spontaneous circulation and short-term survival. Mechanical devices appear to be associated with higher resuscitation-related injuries, while there are conflicting data in terms of survival with good neurological outcomes. A comprehensive and large dedicated randomized trial is urgently needed.

Atypical Endometrial Hyperplasia and Concurrent Cancer: A Comprehensive Overview on a Challenging Clinical Condition.

The present review regarding atypical endometrial hyperplasia (AEH) focused on the main debated factors regarding this challenging clinical condition: (i) predictive variables of occult endometrial cancer (EC); (ii) the rate of EC underestimation according to different endometrial sampling methods; and (iii) the appropriateness of lymph node status assessment. When cancer is detected, approximately 90% of cases include low-risk EC, although intermediate/high-risk cases have been found in 10-13% of women with cancer. Older age, diabetes, high BMI, and increased endometrial thickness are the most recurrent factors in women with EC. However, the predictive power of these independent variables measured on internal validation sets showed disappointing results. Relative to endometrial sampling methods, hysteroscopic endometrial resection (Hys-res) provided the lowest EC underestimation, ranging between 6 and 11%. Further studies, including larger sample sizes of women undergoing Hys-res, are needed to confirm these findings. These data are urgently needed, especially for female candidates for conservative treatment. Finally, the evaluation of lymph node status measured on 660 of over 20,000 women showed a lymph node positivity of 2.3%. Although there has been an increase in the use of this procedure in AEH in recent years, the present data cannot recommend this option in AEH based on a cost/risk/benefit ratio.

Cardiovascular disease as part of Long COVID: A systematic review.

BACKGROUND: Long COVID syndrome has had a major impact on million patients' lives worldwide. The cardiovascular system is an important aspect of this multifaceted disease that may manifest in many ways. We have hereby performed a narrative review in order to identify the extent of the cardiovascular manifestations of the Long COVID syndrome. METHODS AND RESULTS: An in-depth systematic search of the literature has been conducted for this narrative review. The systematic search of PubMed and Cochrane databases yielded 3,993, of which 629 underwent full text screening. A total of 78 studies were included in the final qualitative synthesis and data evaluation. The pathophysiology of the cardiovascular sequelae of Long COVID syndrome and the cardiac manifestations and complications of Long COVID syndrome are critically evaluated. In addition, potential cardiovascular risk factors are assessed, and preventive methods and treatment options are examined in this review. CONCLUSIONS: This systematic review poignantly summarises the evidence from the available literature regarding the cardiovascular manifestations of Long COVID syndrome and reviews potential mechanistic pathways, diagnostic approaches, preventive measures and treatment options.

Investigating the Health Implications of Whey Protein Consumption: A Narrative Review of Risks, Adverse Effects, and Associated Health Issues.

This narrative review critically examines the current research on the health implications of whey protein (WP) supplementation, with a focus on potential risks and adverse effects. WP, commonly consumed for muscle building and weight loss, has been associated with various health concerns. Our comprehensive analysis involved a thorough search of multiple databases, resulting in the inclusion of 21 preclinical and human studies that collectively offer a detailed overview of WP's health impacts. The review reveals significant findings, such as WP's potential link to liver and kidney damage, alterations in gut microbiota, increased acne incidence, impacts on bone mass, and emotional and behavioural changes. These findings underscore the complexity of WP's effects on human health, indicating both beneficial and detrimental outcomes in relation to different posologies in a variety of settings. Our study suggests caution for the protein intake in situations of hepatic and renal compromised functions, as well as in acne susceptibility, while possible beneficial effects can be achieved for the intestinal microbiota, humoral and behavioural level, and finally bone and muscle mass in elderly. We emphasizes the importance of balanced WP consumption and call for more in-depth research to understand its long-term health effects. Health professionals and individuals considering WP supplementation should be aware of these potential risks and approach its use with informed caution.

Carbon-Related Quantum Emitter in Hexagonal Boron Nitride with Homogeneous Energy and 3-Fold Polarization.

Most hexagonal boron nitride (hBN) single-photon emitters (SPEs) studied to date suffer from variable emission energy and unpredictable polarization, two crucial obstacles to their application in quantum technologies. Here, we report an SPE in hBN with an energy of 2.2444 ± 0.0013 eV created via carbon implantation that exhibits a small inhomogeneity of the emission energy. Polarization-resolved measurements reveal aligned absorption and emission dipole orientations with a 3-fold distribution, which follows the crystal symmetry. Photoluminescence excitation (PLE) spectroscopy results show the predictability of polarization is associated with a reproducible PLE band, in contrast with the non-reproducible bands found in previous hBN SPE species. Photon correlation measurements are consistent with a three-level model with weak coupling to a shelving state. Our ab initio excited-state calculations shed light on the atomic origin of this SPE defect, which consists of a pair of substitutional carbon atoms located at boron and nitrogen sites separated by a hexagonal unit cell.

Blockchain technology in Cardiovascular Medicine: a glance to the future? Results from a social media survey and future perspectives.

The leverage of digital facilities in medicine for disease diagnosis, monitoring, and medical history recording has become increasingly pivotal. However, the advancement of these technologies poses a significant challenge regarding data privacy, given the highly sensitive nature of medical information. In this context, the application of Blockchain technology, a digital system where information is stored in blocks and each block is linked to the one before, has the potential to enhance existing technologies through its exceptional security and transparency. This paradigm is of particular importance in cardiovascular medicine, where the prevalence of chronic conditions leads to the need for secure remote monitoring, secure data storage and secure medical history updating. Indeed, digital support for chronic cardiovascular pathologies is getting more and more crucial. This paper lays its rationale in three primary aims: 1) to scrutinize the existing literature for tangible applications of blockchain technology in the field of cardiology; 2) to report results from a survey aimed at gauging the reception of blockchain technology within the cardiovascular community, conducted on social media; 3) to conceptualize a web application tailored specifically to cardiovascular care based on blockchain technology. We believe that Blockchain technology may contribute to a breakthrough in healthcare digitalization, especially in the field of cardiology; in this context, we hope that the present work may be inspiring for physicians and healthcare stakeholders.

Does PM 2.5 and PM 10-associated heavy metals affect short-term and long-term survival after out-of-hospital cardiac arrest? Four-year study based on regional registry.

BACKGROUND: This study aims to investigate the effect of arsenic (As), cadmium (Cd), nickel (Ni) and lead (Pb) suspended on particulate matters (PM) 2.5 and PM 10 taking into account clinical factors on 30-day and one-year survival after out-of-hospital cardiac arrest (OHCA). METHODS: A retrospective 4-year study that involved patients hospitalized after OHCA. Patients' data were obtained from Emergency Medical Services dispatch cards and the National Health Fund. The concentration of air pollutants was measured by the Environmental Protection Inspectorate in Poland. RESULTS: Among the 948 patients after OHCA, only 225 (23.7%) survived for 30 days, and 153 (16.1%) survived for 1 year. Survivors were more commonly affected by OHCA in urban areas (85 [55.6%] vs. 355 [44.7%]; P=0.013) and had slightly higher one-year mean concentration of As (0.78 vs. 0.77; P=0.01), Cd (0.34 vs. 0.34; P=0.012), and Pb (11.13 vs. 10.20; P=0.015) with no differences in daily mean concentration. Significant differences in mean concentrations of heavy metals and PM 2.5 and PM 10 were observed among different quarters. However, survival analysis revealed no differences in long-term survival between quarters. Heavy metals, PM 2.5, and PM 10 did not affect short-term and long-term survival in multivariable logistic regression. CONCLUSIONS: The group of survivors showed slightly higher mean one-year concentrations of As, Cd and Pb, but they also experienced a higher incidence of OHCA in urban areas. There were no differences in long-term survival between patients who suffer OHCA in different quarters. Heavy metals did not independently affect survival.

Changes in hospital admissions for facial fractures during and after COVID 19 pandemic: national multicentric epidemiological analysis on 2938 patients.

PURPOSE: The objective of this multicenter study was to examine the differences in maxillo-facial fractures epidemiology across the various phases of the SARS-CoV-2 pandemic. METHODS: This is a retrospective study on patients who underwent surgery for facial bone fractures in 18 maxillo-facial surgery departments in Italy, spanning from June 23, 2019, to February 23, 2022. Based on the admission date, the data were classified into four chronological periods reflecting distinct periods of restrictions in Italy: pre-pandemic, first wave, partial restrictions, and post-pandemic. Epidemiological differences across the groups were analysed. RESULTS: The study included 2938 patients. A statistically significant difference in hospitalization causes was detected between the pre-pandemic and first wave groups (p = 0.005) and between the pre-pandemic and partial restriction groups (p = 0.002). The differences between the pre- and post-pandemic groups were instead not significant (p = 0.106). Compared to the pre-pandemic period, the number of patients of African origin was significantly higher during the first wave and the post-pandemic period. No statistically significant differences were found across the periods concerning gender, age, fracture type, treatment approach, and hospital stay duration CONCLUSIONS: The COVID-19 pandemic brought about significant changes in fracture epidemiology, influenced by the restrictive measures enforced by the government in Italy. Upon the pandemic's conclusion, the fracture epidemiology returned to the patterns observed in the pre-pandemic period.

Regular Exercise Improved Fatigue and Musculoskeletal Pain in Young Adult Psoriatic Patients without Psoriatic Arthritis.

Fatigue and musculoskeletal pain are also frequent in patients with psoriasis (PsO) without arthritis (PsA). The current study aimed to assess the impact of an intervention program based on aerobic training to reduce fatigue and musculoskeletal pain in patients with PsO without PsA. A total of 118 male patients with PsO volunteered in the current interventional study and were randomly allocated to the experimental (n = 59) or control group (n = 59). The intervention consisted of a 16-week aerobic training program on a treadmill, three sessions per week, consisting of a warm-up, 35-50 min treadmill exercise (increasing 5 min/4 weeks) at a work intensity of 50-65% of peak heart-rate (increasing 5%/4 weeks), and cooling-down. The functional assessment of chronic illness therapy fatigue scale (FACIT-Fatigue), health assessment questionnaire disability index (HAQ-DI), and visual analog scale (VAS) were compared pre and post intervention. Nutritional intake, maximal aerobic power, lipid profile, serum markers of muscle damage, and body composition were also assessed. When compared to baseline, FACIT-Fatigue, HAQ-DI, and VAS scores were significantly improved without increasing markers of muscle damage. Fat mass percentage, lipid profile, and maximal oxygen consumption were also improved. In conclusion, a 16-week aerobic training program at moderate intensity was safe, well tolerated, and effective in psoriatic patients without PsA. Long-term follow-up studies are required to examine whether these promising results may improve clinical outcomes.

Efficient Mean-Field Simulation of Quantum Circuits Inspired by Density Functional Theory.

Exact simulations of quantum circuits (QCs) are currently limited to ∼50 qubits because the memory and computational cost required to store the QC wave function scale exponentially with qubit number. Therefore, developing efficient schemes for approximate QC simulations is a current research focus. Here, we show simulations of QCs with a method inspired by density functional theory (DFT), a widely used approach for studying many-electron systems. Our calculations can predict marginal single-qubit probabilities (SQPs) with over 90% accuracy in several classes of QCs with universal gate sets, using memory and computational resources linear in qubit number despite the formal exponential cost of the SQPs. This is achieved by developing a mean-field description of QCs and formulating optimal single- and two-qubit gate functionals─analogues of exchange-correlation functionals in DFT─to evolve the SQPs without computing the QC wave function. Current limitations and future extensions of this formalism are discussed.

Bivalirudin in acute coronary syndromes.

INTRODUCTION: Bivalirudin, a bivalent direct thrombin inhibitor, has been developed to reduce bleeding without any trade-off in thrombotic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). AREAS COVERED: Despite showing a superior safety profile compared with unfractionated heparin (UFH), bivalirudin is not considered the anticoagulant of choice in ACS patients undergoing PCI, mainly because of an increased rate of acute stent thrombosis (ST) shown by several randomized controlled trials (RCTs), in addition to limited availability in certain countries and increased costs. However, RCTs on bivalirudin have been characterized by several confounding factors hindering the interpretation of its safety and efficacy compared with UFH among the spectrum of ACS patients. Furthermore, a significant body of evidence has demonstrated that the risk of acute ST can be mitigated by a full-dose infusion regimen following PCI, without compromising the favorable safety profile compared to UFH. EXPERT OPINION: In light of the increased understanding of the prognostic relevance of bleeding events and the excellent safety profile of bivalirudin, recent trial evidence may allow for this anticoagulant agent to reemerge and have a more prominent role in the management of ACS patients undergoing PCI.

Role of Cardiovascular Imaging in Risk Assessment: Recent Advances, Gaps in Evidence, and Future Directions.

Optimal risk assessment for primary prevention remains highly challenging. Recent registries have highlighted major discrepancies between guidelines and daily practice. Although guidelines have improved over time and provide updated risk scores, they still fail to identify a significant proportion of at-risk individuals, who then miss out on effective prevention measures until their initial ischemic events. Cardiovascular imaging is progressively assuming an increasingly pivotal role, playing a crucial part in enhancing the meticulous categorization of individuals according to their risk profiles, thus enabling the customization of precise therapeutic strategies for patients with increased cardiovascular risks. For the most part, the current approach to patients with atherosclerotic cardiovascular disease (ASCVD) is homogeneous. However, data from registries (e.g., REACH, CORONOR) and randomized clinical trials (e.g., COMPASS, FOURIER, and ODYSSEY outcomes) highlight heterogeneity in the risks of recurrent ischemic events, which are especially higher in patients with poly-vascular disease and/or multivessel coronary disease. This indicates the need for a more individualized strategy and further research to improve definitions of individual residual risk, with a view of intensifying treatments in the subgroups with very high residual risk. In this narrative review, we discuss advances in cardiovascular imaging, its current place in the guidelines, the gaps in evidence, and perspectives for primary and secondary prevention to improve risk assessment and therapeutic strategies using cardiovascular imaging.

Management of Coronary Artery Disease in Older Adults: Recent Advances and Gaps in Evidence.

Coronary artery disease (CAD) is highly prevalent in older adults, yet its management remains challenging. Treatment choices are made complex by the frailty burden of older patients, a high prevalence of comorbidities and body composition abnormalities (e.g., sarcopenia), the complexity of coronary anatomy, and the frequent presence of multivessel disease, as well as the coexistence of major ischemic and bleeding risk factors. Recent randomized clinical trials and epidemiological studies have provided new data on optimal management of complex patients with CAD. However, frail older adults are still underrepresented in the literature. This narrative review aims to highlight the importance of assessing frailty as an aid to guide therapeutic decision-making and tailor CAD management to the specific needs of older adults, taking into account age-related pharmacokinetic and pharmacodynamic changes, polypharmacy, and potential drug interactions. We also discuss gaps in the evidence and offer perspectives on how best in the future to optimize the global strategy of CAD management in older adults.

Treatment adherence in patients without ST-elevation acute coronary syndrome.

BACKGROUND: Despite progress during the last decades, patients with coronary artery disease (CAD) remain with a high residual risk due to multiple reasons. Optimal medical treatment (OMT) provides a decrease of recurrent ischemic events after acute coronary syndrome (ACS). Therefore, treatment adherence results crucial to reduce further outcomes after the index event. No recent data are available in Argentinian population; the main objective of our study was to evaluate the adherence at 6 and 15 months in post non-ST elevation acute coronary syndrome (NST-ACS) consecutive patients. Secondary objective was to evaluate the relationship of adherence with 15-month events. METHODS: A prespecified sub-analysis in the prospective registry Buenos Aires I was performed. The adherence was evaluated using the modified Morisky-Green Scale. RESULTS: A number of 872 patients had information about adherence profile. Of them 76.4% were classified as adherents at month 6 and 83.6% at 15 (P=0.06). We did not find any difference in baseline characteristic between the adherent and non-adherent patients at 6 months. The adjusted analysis showed that non-adherent patients had a rate of ischemic events at 15th month of 20% (27/135) vs. 11.5% (52/452) in adherent patients (P=0.001). The bleeding events defined were of 3.6% in the non-adherent group vs. 5% in the adherent group without a statistical difference (P=0.238). CONCLUSIONS: Adherence to treatment is still a major issue as almost 25% of patients should be considered as non-adherent to OMT. No clinical predictor of this phenomenon was identified but our criteria were not exhaustive. Good adherence to treatment was highly associated to a reduction of ischemic events, whereas no impact on bleeding events was found. These data support a better network and collaboration with shared decision between healthcare professionals with patients and family members to improve acceptance and adherence to optimal medical strategies.

Appraising features and outlook of women and men discharged after an acute coronary syndrome: evidence from the 23,700-patient PRAISE International Registry.

BACKGROUND: Acute coronary syndromes (ACS) are a common cause of morbidity and mortality. Several studies have focused on ACS at admission, but limited evidence is available on sex-based comparison of patients discharged after ACS. We appraised the outlook of women and men discharged after ACS. METHODS: Details on women enrolled in the PRAISE registry, an international cohort study spanning 23,700 patients included between 2003 and 2019, were systematically collected. We focused on patient and procedural features, medications at discharge, and 1-year outcomes. The primary endpoint was the composite of death, myocardial infarction, or major bleeding after discharge. RESULTS: A total of 17,804 (76.5%) men and 5466 (23.5%) women were included. Several baseline differences were found, including risk factors and prior revascularization (all P<0.05). Men underwent more frequently radial access, and at discharge they received more commonly dual antiplatelet therapy and guideline-directed medical therapy (P<0.001). At 1-year follow-up, risks of death, reinfarction, major bleeding, and non-fatal major bleeding, jointly or individually, were all significantly higher in women (all P≤0.01). All such differences however did not hold true at multivariable analysis, with the exception of major bleeding, which appeared surprisingly less common in females at fully adjusted analysis (P=0.017). CONCLUSIONS: Women, albeit only apparently, had worse outcomes 1 year after discharge for ACS, but adjusted analysis suggested instead that they faced a lower risk of major bleeding after discharge. These findings support the call for more aggressive management of women after ACS.

Impact of low-dose Brain-Derived Neurotrophic Factor (BDNF) on atrial fibrillation recurrence.

BACKGROUND: Atrial fibrillation is the most common arrhythmia worldwide and is associated with significant morbidity and mortality. Despite the effectiveness of catheter-based ablation, periprocedural complication and recurrences remain a concern. In this context, we aim to appraise the potential impact of brain-derived neurotrophic factor (BDNF) on reducing episodes of paroxysmal atrial fibrillation (PAF). METHODS: 22 patients with an established diagnosis of PAF and without structural heart disease were considered. Every patient received 20 drops of GUNA-BDNF administered in the morning. During the 24 months of follow-up, the arrhythmic burden was measured by the average monthly duration of PAF episodes. RESULTS: At the end of the follow-up period (24 months), data from 22 patients, of whom 17 men and five women, were analyzed. The arrhythmic burden, measured in terms of average monthly duration of PAF episodes, was found significantly reduced after the administration of low dose BDNF (9.5 vs. 65.3 minutes per month, P<0.001). A total of 17 out of 22 patients saw their arrhythmic burden eliminated or consistently reduced, furthermore two patients underwent a drastic reduction of the average monthly duration of AF (more than 200 minutes compared to the baseline). Only four patients, despite the administration of BDNF, still experienced an arrhythmic burden of 20 minutes or more. Considering the age groups, the major reduction was observed in people aged 70 or more, who were also the most represented in the sample. These results are coherent with the poor literature currently available. CONCLUSIONS: BDNF low dose therapy has shown to have an impacting role in reducing the arrhythmic burden and recurrences of AF, with a particular effectiveness in patients over 70 and without structural heart disease. We should welcome this work, despite it limitations. Further clinical and molecular studies are needed before-considering BDNF low dose as a tool against PAF.