Chronic Thromboembolic Pulmonary Hypertension: the therapeutic assessment.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a severe and complex condition that evolves from unresolved pulmonary embolism, leading to fibrotic obstruction of pulmonary arteries, pulmonary hypertension, and potential right heart failure. The cornerstone of CTEPH management lies in a multifaceted therapeutic approach tailored to individual patient profiles, reflecting the disease's heterogeneity. This review delves into the current therapeutic strategies for CTEPH, including surgical pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and targeted pharmacological treatments such as PDE5 inhibitors, endothelin receptor antagonists, sGC stimulators, and prostanoids. Lifelong anticoagulation is also highlighted as a preventive strategy against recurrent thromboembolism. Special emphasis is placed on the interdisciplinary nature of CTEPH care, necessitating collaboration among PEA surgeons, BPA interventionists, PH specialists, and thoracic radiologists to ensure comprehensive treatment planning and execution. The review underscores the importance of selecting an appropriate treatment modality based on the patient's specific disease characteristics and the evolving landscape of CTEPH treatment, aiming to improve patient outcomes through integrated care strategies.

Investigative agents for atrial fibrillation: agonists and stimulants, progress and expectations.

INTRODUCTION: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Its prevalence has increased due to worldwide populations that are aging in combination with the growing incidence of risk factors associated. Recent advances in our understanding of AF pathophysiology and the identification of nodal players involved in AF-promoting atrial remodeling highlights potential opportunities for new therapeutic approaches. AREAS COVERED: This detailed review summarizes recent developments in the field antiarrhythmic drugs in the field AF. EXPERT OPINION: The current situation is far than optimal. Despite clear unmet needs in drug development in the field of AF treatment, the current development of new drugs is absent. The need for a molecule with absence of cardiac and non-cardiac toxicity in the short and long term is a limitation in the field. Improvement in the understanding of AF genetics, pathophysiology, molecular alterations, big data and artificial intelligence with the objective to provide a personalized AF treatment will be the cornerstone of AF treatment in the coming years.

High Rates of Organ Preservation in Rectal Cancer with Papillon Contact X-ray Radiotherapy: Results from a Swiss Cohort.

Rectal cancer typically necessitates a combination of radiotherapy (RT), chemotherapy, and surgery. The associated functional disorders and reduction in quality of life have led to an increasing interest in organ preservation strategies. Response strongly correlates with RT dose, but dose escalation with external beam remains limited even with modern external beam RT techniques because of toxicity of the surrounding tissues. This study reports on the use of Papillon, an endocavitary Radiotherapy device, in the treatment of rectal cancer. The device delivers low energy X-rays, allowing for safe dose escalation and better complete response rate. Between January 2015 and February 2024, 24 rectal cancer patients were treated with the addition of a boost delivered by Papillon to standard RT, with or without chemotherapy, in an upfront organ preservation strategy. After a median follow-up (FU) of 43 months, the organ preservation rate was 96% (23/24), and the local relapse rate was 8% (2/24). None of our patients developed grade 3 or more toxicities. Our results demonstrate that the addition of Papillon contact RT provides a high rate of local remission with sustained long-term organ preservation, offering a promising alternative to traditional surgical approaches in patients with rectal cancer.

Towards the Fifth Pillar for the Treatment of Heart Failure with Reduced Ejection Fraction: Vericiguat in Older and Complex Patients.

Heart failure with reduced ejection fraction (HFrEF) represents an emerging epidemic, particularly affecting frail, older, and multimorbid patients. Current therapy for the management of HFrEF includes four different classes of disease-modifying drugs, commonly referred to as 'four pillars', which target the neurohormonal system that is overactivated in HF and contributes to its progression. These classes of drugs include ß-blockers, inhibitors of the renin-angiotensin-aldosterone system, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. Unfortunately, these agents cannot be administered as frequently as needed to older patients because of poor tolerability and comorbidities. In addition, although these drugs have dramatically increased the survival expectations of patients with HF, their residual risk of rehospitalization and death at 5 years remains considerable. Vericiguat, a soluble guanylate cyclase (sGC) stimulator, was reported to exert beneficial effects in patients with worsening HF, including older subjects, reducing the rate of both hospitalizations and deaths, with limited adverse effects and drug interaction. In this narrative review, we present the current state of art on vericiguat, with a particular focus on elderly and frail patients.

Management of Cardiovascular Complications in Antiphospholipid Syndrome: A Narrative Review with a Focus on Older Adults.

Antiphospholipid syndrome (APS), also known as Hughes syndrome, is an acquired autoimmune and procoagulant condition that predisposes individuals to recurrent thrombotic events and obstetric complications. Central is the role of three types of antiphospholipid antibodies that target phospholipid-binding proteins: lupus anticoagulant (LAC), anti-ß2-glycoprotein I (ß2-GPI-Ab), and anti-cardiolipin (aCL). Together with clinical data, these antibodies are the diagnostic standard. However, the diagnosis of APS in older adults may be challenging and, in the diagnostic workup of thromboembolic complications, it is an underestimated etiology. The therapeutic management of APS requires distinguishing two groups with differential risks of thromboembolic complications. The standard therapy is based on low-dose aspirin in the low-risk group and vitamin K antagonists in the high-risk group. The value of direct oral anticoagulants is currently controversial. The potential role of monoclonal antibodies is investigated. For example, rituximab is currently recommended in catastrophic antiphospholipid antibody syndrome. Research is ongoing on other monoclonal antibodies, such as daratumumab and obinutuzumab. This narrative review illustrates the pathophysiological mechanisms of APS, with a particular emphasis on cardiovascular complications and their impact in older adults. This article also highlights advancements in the diagnosis, risk stratification, and management of APS.

Cardiovascular Risk Profile in Master Paralympic Athletes, a High-Risk Undertreated Population: A Cross-Sectional Longitudinal Study.

INTRODUCTION: Recently, European Society of Cardiology (ESC) validated a prediction model to estimate 10-year fatal and non-fatal cardiovascular disease risk (CVDR) in individuals (aged 40-60 years) without previous cardiovascular disease or diabetes (ESC-SCORE2) and to provide indications for treatment. At present, data describing the CVDR in Paralympic athletes (PAs) are scarce and inconsistent. Therefore, we sought to assess the prevalence of risk factors in PAs to estimate their CVDR through SCORE2. METHODS: We enrolled 99 PAs aged ≥ 40 y.o., who participated at 2012-2022 Paralympic Games, competing in 22 different sport disciplines classified according to sport type (power, skills, endurance and mixed) and disabilities: spinal cord injuries (SCI) and non-SCI. CVDR factors, anthropometric measurements and blood samples were collected. RESULTS: Among the 99 PAs (78% males, mean age 45.7 ± 4.7 y.o.), 52.5% had SCI; 54% were dyslipidemic and 23% were smokers. According to ESC-SCORE2, 29% had high and 1% very-high CVDR. Women (compared to men) and endurance (compared to other sport) exhibited better CV profile. SCI showed no differences when compared with non-SCI for CVDR, excepted for a lower HDL and lower exercise performance. None of the dyslipidemic athlete was on pharmacologically treatment, despite the altered lipid profile had already been detected at younger age. CONCLUSION: PAs are a selected population, presenting a high CV risk profile, with 30% showing either high or very-high CVDR according to ESC-SCORE2. Dyslipidemia was the most common risk factor, underestimated and undertreated, emphasizing the need for specific preventive strategies in this special setting of athletes.

Optimizing wheelchair basketball lineups: A statistical approach to coaching strategies.

This study was designed to support the tactical decisions of wheelchair basketball (WB) coaches in identifying the best players to form winning lineups. Data related to a complete regular season of a top-level WB Championship were examined. By analyzing game-related statistics from the first round, two clusters were identified that accounted for approximately 35% of the total variance. Cluster 1 was composed of low-performing athletes, while Cluster 2 was composed of high-performing athletes. Based on data related to the second round of the Championship, we conducted a two-fold evaluation of the clusters identified in the first round with the team's net performance as the outcome variable. The results showed that teams where players belonging to Cluster 2 had played more time during the second round of the championship were also those with the better team performance (R-squared = 0.48, p = 0.035), while increasing the playing time for players from Classes III and IV does not necessarily improve team performance (r2 = -0.14, p = 0.59). These results of the present study suggest that a collaborative approach between coaches and data scientists would significantly advance this Paralympic sport.

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.

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.

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.

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.

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.