Peripheral vascular disease:

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Platelets are among the most abundant cells in the body and play important roles in coagulation and immunity. Platelets are formed when hematopoietic stem cells proliferate and differentiate into megakaryocytes via the regulation of various cytokines. After the megakaryocytes mature in the bone marrow cavity, proplatelets are released into the blood circulation where they eventually remodel into mature platelets. Given that the production and functions of platelets involve the regulation of many factors-such as hematopoietic stem cells, the hematopoietic microenvironment, and cytokines-the causes and mechanisms of platelet-related diseases are diverse, often involving platelet production, clearance, and distribution. In this review, we examined the regulation of platelet production and summarized common disorders affecting platelet quantity, namely, thrombocytopenia and thrombocytosis. In addition, we reviewed previous clinical studies and summarized the medication strategies commonly used for the treatment of different platelet disorders in different clinical scenarios.

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CONCLUSIONS: These results show that ALDH1A1 is downregulated in calcified valves, hence promoting VIC transition into an osteoblastic phenotype. Retinoic acid receptor alpha agonists, including all-trans retinoic acid through a drug repositioning strategy, represent a promising and innovative pharmacological approach to prevent calcification of native aortic valves and BPV.

Populations most affected by cardiovascular health disparities, including underrepresented populations with lower socioeconomic status, people with disabilities, and those living in underserved rural communities, are disproportionately exposed to adverse social determinants of health. Specifically, economic instability and suboptimal living conditions within the neighborhood and built environment directly determine access to resources and opportunities for healthful behaviors. In this scientific statement, we examined the technology-enabled interventions that address cardiovascular health behaviors from adolescence to adulthood in populations most affected by health disparities. We used a broad definition of technology, including wearables, applications, and telehealth, for behavior tracking. Aligning with Life's Essential 8, we focused on interventions targeting behavior change related to physical activity, sedentary time, dietary intake, tobacco cessation, and sleep health to improve cardiovascular health. The digital determinants of health are important adjuncts to the social determinants and operate at the individual, interpersonal, community, and societal levels. The digital determinants of health include the impact of digital technologies (eg, wearables, telemedicine) across health outcomes. Evidence of effective interventions using technology to improve cardiovascular health through positive behavior change is critical for preventing cardiovascular disease events. Stronger evidence is needed to inform and implement effective approaches that are scalable and cost-effective across communities and health care institutions to advance digital equity in cardiovascular health. Dissemination of digital solutions to improve cardiovascular health in communities or across health care systems must ensure effective, feasible, available, and affordable solutions for populations most in need.

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Patients with interrupted inferior vena cava (I-IVC) and azygos continuation who undergo Fontan completion via hepatoazygos shunting (HAS) exhibit unique hemodynamic challenges. This study evaluates age-related shifts in systemic venous return dominance, hepatic flow distribution (HFD), power loss (PL), and flow disturbances using patient-specific computational fluid dynamics (CFD). Data analysis from 95 I-IVC patients showed a non-linear shift in upper-to-lower body systemic flow dominance with ratios of 2, 1, and 0.5 (correlating to ages ~3, ~10, and ~20 respectively). CFD simulations for 17 selected patients revealed a trend of increasing HFD toward the right pulmonary artery (RPA), with median splits of 45%-49%, 48%-52%, and 40%-60% for the respective flow ratios. Power loss increased significantly with lower-body flow dominance. Median values for absolute PL were 4.75 mW (ratio 2), 16.5 mW (ratio 1), and 33.7 mW (ratio 0.5). Indexed PL showed a similar trend, rising from 0.04 mW/m² to 0.11 mW/m² across the flow ratios. Vorticity (VOR) and viscous dissipation rates (VDR), key metrics of flow disturbances, also increased with lower-body flow dominance, showing strong correlations with PL (R = 0.58-0.76). Kruskal-Wallis based statistical analysis identified significant statistical differences in absolute PL (p = 0.0045) and flow disturbances (p < 0.001), emphasizing the impact of age-related flow dynamics on Fontan efficiency. Our findings emphasize the need for targeted interventions in patients with I-IVC with azygos continuation to mitigate evolving hemodynamic inefficiencies and optimize Fontan outcomes during critical growth periods.

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Abstract: Catheter-related thrombosis (CRT) poses serious risks for cancer patients. Identifying risk factors and implementing targeted interventions can prevent CRT. To explore thromboelastogram parameters and clinical risk factors for CRT in elderly lung cancer patients. A total of 663 elderly lung cancer patients were selected from three hospitals in Hunan, Hainan, and Qinghai provinces in China from January 1, 2022, to June 30, 2024. The patients were divided into two groups: a CRT group (221 patients) and a non-CRT group (442 patients), with a ratio of 1:2. A between-group comparison and binary logistic regression were used to analyze risk factors for CRT in elderly lung cancer patients. Binary logistic regression analysis showed that decreased (odds ratio [OR]: 0.849, 95% confidence interval [CI]: 0.763-0.945,  = 0.003), decreased (0.571, 95% CI: 0.404-0.807,  = 0.001), advanced age (OR: 1.073, 95% CI: 1.033-1.113,  < 0.001), elevated platelet count (OR: 1.006, 95% CI: 1.004-1.009,  < 0.001), increased hemoglobin level (OR: 1.020, 95% CI: 1.009-1.031,  < 0.001), shortened PT (OR: 0.904, 95% CI: 0.830-0.985,  = 0.022), surgery ≤ 1 month (OR: 2.258, 95% CI: 1.420-3.590,  = 0.001), male sex (OR: 4.534, 95% CI: 2.815-7.304,  < 0.001), diabetes (OR: 2.478, 95% CI: 1.373-4.472,  = 0.003), hypertension (OR: 2.386, 95% CI: 1.505-3.784,  < 0.001), physical activity disorders (OR: 9.038, 95% CI: 4.462-18.309,  < 0.001) were independent risk factors for CRT in elderly lung cancer patients. Independent risk factors for CRT in elderly lung cancer patients include decreased -values and decreased -values, shortened PT, advanced age, elevated platelet count, increased hemoglobin level, surgery ≤ 1 month, male sex, diabetes, hypertension, and physical activity disorders.

Abstract: Peripheral artery disease (PAD) is the narrowing of the arteries that carry blood to the lower extremities. PAD has been traditionally associated with atherosclerosis. However, recent studies have found that thrombotic events triggered by medial arterial calcification (MAC) is the primary cause of chronic limb ischemia below the knee. MAC is localized around the elastic fibers surrounding smooth muscle cells (SMCs) in arteries. Matrix GLA protein (MGP) binds circulating calcium and prevents hydroxyapatite mineral deposition, while also modulating pro-osteogenic signaling by attenuating BMP-2-mediated activation of gene expression. mice develop severe MAC and die around 8 weeks after birth due to aortic rupture or heart failure. We previously discovered a rare genetic disease Arterial Calcification due to Deficiency of CD73 (ACDC), in which patients present with extensive MAC in their lower extremity arteries. Using a patient-specific induced pluripotent stem cell model, we found that rapamycin inhibited calcification. Here we investigated whether rapamycin could reduce MAC in vivo using the murine model. and mice received 5mg/kg rapamycin or vehicle. Calcification content was assessed via microCT, and vascular morphology and extracellular matrix content were assessed histologically. Immunostaining and western blot analysis were used to examine SMC phenotype and extracellular matrix content. Rapamycin prolonged mice lifespan, decreased mineral density in the arteries, maintained SMC contractile phenotype, and improved vessel structure, however, calcification volume was unchanged. mice with SMC-specific deletion of Raptor or Rictor did not recapitulate treatment with rapamycin. These findings suggest rapamycin promotes beneficial vascular remodeling in vessels with MAC.

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CONCLUSIONS: Moderate expression of cardiac β3AR, at levels observed in human cardiac myocardium, exerts metabolic and antioxidant effects through activation of the pentose-phosphate pathway and NRF2 pathway through S-nitrosation of Keap1, thereby preserving myocardial oxidative metabolism, function, and integrity under pathophysiological stress.

Mitral regurgitation and tricuspid regurgitation are the most common valvular heart diseases in patients with heart failure and have independent prognostic value. Transcatheter interventions are now available for the treatment of valvular heart disease, and their efficacy and safety have been tested in randomized controlled trials. However, evidence is still limited and sometimes inconclusive because several aspects of these trials limit their interpretation or consistency. These include heterogeneity in the pathogenesis and clinical characteristics of patients, the dynamic nature of secondary atrioventricular valve disease severity, the role of heart failure medications and devices, dependency on procedural results and operators' skills, smaller number of patients enrolled and the power to detect differences in trials, and limitations to use patients' reported outcomes with unblinded study protocols. These specific aspects of trials in patients with atrioventricular valve disease are reviewed in this article with a focus on possible solutions to generate further evidence for the efficacy and safety for transcatheter treatments of atrioventricular valve disease in patients with heart failure.

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CONCLUSIONS: Our study revealed that maternal genetic factors and plasma aspirin hydrolysis are not among the decisive factors in determining the effectiveness of low-dose aspirin in preventing preeclampsia among high-risk women. Instead, placental GLYAT appears to play a key role by limiting the effect of salicylic acid in the placenta.