Citations

Advances in cancer therapies have transformed many malignancies into chronic or manageable conditions, but have been linked to adverse, including cardiovascular, events. Vascular toxicities associated with cancer treatment range from abnormal vasoreactivity to accelerated atherosclerosis, arterial thrombotic events, vasculitis, and arterial aneurysms or dissections. 5-fluorouracil and VEGF (vascular endothelial growth factor) inhibitors are the agents most commonly linked to abnormal vasoreactivity, whereas BCR-ABL (breakpoint cluster region–Abelson murine leukemia viral oncogene homolog) inhibitors and immune checkpoint inhibitors have been associated with accelerated atherosclerosis. Arterial thrombotic events are seen with VEGF and BCR-ABL inhibitors as well as platinum drugs. Vasculitis emerged with the use of immune checkpoint inhibitors, and arterial aneurysms and dissections with VEGF inhibitors. Radiation therapy can lead to several of the outlined vascular toxicities. This review comprehensively explores the mechanisms of vascular complications associated with chemotherapy, targeted therapies, immunotherapies, and radiation therapy. Key contributors include endothelial injury and dysfunction, oxidative stress, and inflammation. An understanding of the mechanisms of vascular toxicities may facilitate optimal treatment and preventive strategies in patients with cancer.

Src homology 2-domain containing protein tyrosine phosphatase 2 (SHP2), encoded by the Ptpn11 gene (Tyrosine-protein phosphatase non-receptor type 11), is a key downstream effector of PD-1/PD-L1 signaling and is likely important, in addition to immune modulation, in tumor development and vascular homeostasis. SHP2 conveys PD-1 mediated inhibitory signaling in T cells, and is emerging as a therapeutic target. Importantly, there is an association between immune checkpoint inhibitors (ICIs), immune-related adverse events (irAEs), and cardiovascular complications, underscoring the need to understand SHP2’s role in these processes. This review aims to summarize current knowledge on SHP2/PTPN11 biology, its role in immune regulation, cancer progression, and vascular homeostasis, and to discuss emerging therapeutic strategies targeting this pathway. The concept of using SHP2 inhibitors with immune checkpoint inhibitors (ICIs) is being investigated to address ICI resistance and to improve anti-tumor efficacy substantially. SHP2 is also being studied in non-cancer cell contexts, and signaling responses can differ by large magnitudes depending on the biological context and stimuli. Under normal circumstances, SHP2 promotes vascular homeostasis in endothelial cells (ECs) and myeloid cells and inhibits inflammation, and the reduction in SHP2 activity by oxidative stress, such as in atherosclerosis or diabetes, upregulates inflammation. In contrast, in response to radiation, the fibrotic response and subsequent lung injury were increased by endothelial SHP2 induction via Notch-Jag1 signaling. Vascular smooth muscle cells SHP2 act as a pro-atherogenic effector by enhancing ERK/MAPK signaling, and the upregulation of mitochondria localized SHP2 can also induce cellular senescence-associated inflammation by upregulating mitochondrial reactive oxygen species. Taken together, the two opposite signaling effects of SHP2 suggest that both the immune and vascular system responses appear to be more modulated by the redox, cell, and compartment-specific signaling of SHP2. More studies are needed for mitigating cardiovascular toxicity to patients, particularly with ICI-based treatment regimens.

Background Safety-net hospitals (SNH) provide care to a significant proportion of low-income, uninsured, and underserved populations disproportionately affected by the COVID-19 pandemic. We evaluated the impact of safety-net burden on outcomes of COVID-19 hospitalizations. Methods We identified patients aged ≥ 18 years hospitalized with COVID-19 from the nationwide inpatient database using the International Classification of Diseases, Tenth Edition (ICD-10-CM) code U07.1. The primary study outcomes were inpatient mortality, respiratory failure requiring mechanical ventilation, and tracheostomy use. Secondary outcomes were total hospitalization costs (THC) and length of hospital stay (LOS). Multivariable logistic regression was used to compare the primary and secondary outcomes in HBH and medium safety-net burden (MBH) with lower-burden hospitals (LBH) (reference). Results An estimated 2,608,232 COVID-19 hospitalizations met the inclusion criteria, with 68.7% occurring in HBH, 22.8% in MBH, and 8.5% in LBH. On adjusted multivariable analysis, HBH was associated with increased odds of inpatient mortality (aOR 1.19, 95% CI 1.09-1.28) compared with LBH. Both HBH (aOR 1.30, 95% CI 1.21-1.40) and MBH (aOR 1.14, 95% CI 1.06-1.24) demonstrated increased odds of mechanical ventilation compared with LBH. THC was lower in HBH and MBH compared with LBH. The LOS was similar across safety net burden categories. Conclusion After adjusting for patient- and hospital-level factors, COVID-19 hospitalizations at HBH had inferior inpatient outcomes compared with LBH. Targeted policy reforms are needed to address the underlying causes of these disparities and increase our health systems’ readiness for future crises, particularly in underserved communities.

Abstract Aims Syncope remains a diagnostic challenge despite advancements in testing and treatment. Cardiac syncope is an independent predictor of mortality and can be difficult to distinguish from other causes of transient loss of consciousness (TLOC). This paper explores whether artificial intelligence (AI) can improve the evaluation and management of patients with syncope. Methods and results We conducted a literature review and incorporated the opinions of experts in the fields of syncope and AI. The cause of TLOC is often unclear, hospitalization criteria are ambiguous, diagnostic tests are frequently non-informative, and assessments are costly. Patients are left with unanswered questions and limited guidance. Artificial intelligence (AI) has the potential to optimize syncope evaluation by processing large data sets, detecting imperceptible patterns, and assisting clinicians. However, AI has limitations, including errors, lack of human empathy, and uncertain clinical utility. Liability issues further complicate its integration. We present three viewpoints: (i) AI is crucial for advancing syncope management; (ii) AI can enhance the patient experience; and (iii) AI in syncope care is inevitable. Conclusion Artificial intelligence may improve syncope diagnosis and management, particularly through machine learning–based test interpretation and wearable device data. However, it has yet to surpass human clinical judgment in complex decision-making. Current challenges include gaps in understanding syncope mechanisms, AI interpretability, generalizability, and clinical integration. Standardized diagnostic approaches, real-world validation, and curated data sets are essential for progress. Artificial intelligence may enhance efficiency and communication but raises concerns regarding confidentiality, bias, inequities, and legal implications.

ABSTRACT Background Atherothrombosis, the main event leading to acute coronary syndrome (ACS), is strongly linked to disturbed blood flow (d-flow) regions. Although the involvement of the Hippo pathway and its kinases Large Tumor Suppressor Kinase 1and 2 (LATS 1 and 2) in mechanical stress responses is known, the mechanisms by which d-flow simultaneously induces senescence, proliferation, and atherothrombosis remain unclear. Methods The role of endothelial cells (EC)-specific LATS1/2 was examined using EC specific knock-out (EKO) mice in a partial left carotid ligation (PLCL) model. Plaque spatial multi-omics analysis was performed by integrating imaging mass cytometry, sequential immunofluorescence (COMET™), and spatial metabolomics at the single-cell level in human and mouse atherosclerotic plaques. Results In tamoxifen-inducible Lats1 homo( -/- ) / Lats2 homo( -/- ) EC-specific knockout (EKO) mice, deletion of LATS1/2 induced by tamoxifen led to fatal outcomes, characterized by severe systemic edema and markedly increased vascular permeability. In contrast, Lats1 het(+ /- ) / Lats2 homo( -/- ) -EKO mice survived and developed atherothrombotic plaques exhibiting neovascularization even without further additional dietary or genetic intervention. Spatial proteomics analysis revealed that LATS1/2 depletion in ECs triggered a senescence-associated stemness (SAS) phenotype, primarily driven by CD38 upregulation. Complementary spatial metabolomics profiling demonstrated a significant increase in sulfite and taurine within LATS1/2-deficient plaques, indicating lowered sulfite oxidase (SUOX) activity. Mechanistically, CD38 upregulation was found to suppress SUOX expression, induce the reverse mode of mitochondrial complex V, and increase succinate dehydrogenase (SDH) activity along with ATP consumption. Paradoxically, despite ATP depletion, this metabolic disturbance enhanced glutamate metabolism and the tricarboxylic acid (TCA) cycle, sustaining EC proliferation under energetically stressed conditions. The combined effect of LATS1/2 deletion and CD38 activation established a unique EC phenotype defined by increased SAS, leading to proliferation, senescence, and eventual cell death. These pathological processes culminated in the formation of atherothrombotic plaques, which were attenuated by inhibition of CD38. Notably, a similar phenotype—marked by metabolically active ECs—was observed in human atherothrombotic plaques, suggesting translational relevance. Conclusion Loss of LATS1/2 in ECs induces SAS state that promotes excessive EC proliferation, senescent cell accumulation, and the development of structurally fragile, leaky neo vessels—hallmarks of atherothrombotic lesions. CD38-mediated SUOX deficiency further amplifies this pathological process by inducing mitochondrial dysfunction, depleting ATP, and triggering compensatory upregulation of glutamate and TCA cycle metabolism. These findings identify a novel LATS1/2–CD38–SUOX axis in ECs that orchestrates SAS-driven atherothrombosis. Targeting CD38 may represent a promising therapeutic strategy to mitigate vascular dysfunction and plaque instability in high-risk ACS patients. Graphical abstract Under normal physiological conditions, LATS1/2 and Lamin A work together to suppress CD38 expression. Lamin A binds directly to the CD38 promoter to repress transcription, and LATS1/2 interact with Lamin A to reinforce this suppression. This collaboration helps maintain low CD38 activity and preserves cellular NAD⁺ levels. However, under disturbed flow (d-flow), both LATS1/2 and Lamin A are downregulated. The loss of this dual repression leads to increased CD38 NADase expression. Elevated CD38 accelerates NAD⁺ consumption, causing NAD⁺ depletion—a hallmark of cellular senescence. Reduced NAD⁺ disrupts key metabolic and stress-response pathways, contributing to the onset of the senescent state. At the same time, CD38 suppresses sulfite oxidase (SUOX), leading to sulfite accumulation and mitochondrial redox imbalance. This shift activates the reverse mode of mitochondrial Complex V, which decreases ATP production and increases mitochondrial ROS, intensifying metabolic and oxidative stress in endothelial cells (ECs). In response, ECs compensate by upregulating succinate dehydrogenase (SDH), enhancing TCA cycle activity and glutamate metabolism. This metabolic adaptation provides the biosynthetic building blocks needed for cell growth and proliferation. As a result, ECs adopt a paradoxical phenotype: they show classical features of stress-induced senescence (such as NAD⁺ depletion, oxidative stress, and cell cycle arrest signals), while simultaneously undergoing metabolic activation and proliferation, also mediated by YAP. This defines a non-canonical endothelial program known as senescence-associated stemness (SAS), characterized by the formation of abnormal, proliferative, yet fragile neovessels. These dysfunctional vessels contribute to atherothrombosis, setting this process apart from the more stable lesions typical of conventional atherosclerosis.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression. Anti-inflammatory therapy, therefore, presents a unique dilemma for cancer survivors: while it may decrease cardiovascular risk, it might also promote cancer growth and metastasis by suppressing the immune response. Senescence presents a potentially targetable solution to this challenge; senescence increases the risk of both cancer therapy resistance and vascular disease. Exercise, notably, shows promise in delaying this premature senescence, potentially improving cancer outcomes and lowering vascular disease risk post-treatment. This review focuses on the long-term impact of cancer therapies on vascular health. We underscore the importance of modulating senescence to balance cancer treatment’s effectiveness and its vascular impact, and we emphasize investigating the role of exercise-mediated suppression of senescence in improving cancer survivorship.

Since the dawn of humanity, human beings have inherently sought a state of security, trying to make their existence as comfortable as possible. Accordingly, among the many factors affecting human health, comfort and well-being, the quality of the micro-environment and ecology, as well as the health care system and health-saving resources, are important. In this regard, environmental security, with its systemic nature, brings a significant contribution to the PPM model by optimizing the state of balance in the interrelationship of natural, anthropogenic, physiological and social processes. Accordingly, individualized nutrition and pharmacointervention for preventive and prophylactic purposes, being important tools for health preservation, represent an integrative approach aimed at understanding the interaction between nutrition and the environment within the formed or formed lifestyle. This review will consider the main components of human health protection, as well as their impact on the preservation of ecobiocenosis stability.

Everyone has the right to the highest attainable standard of health, and modern preventive, preventive and rehabilitative manipulations promote health and well-being. Thanks to a number of fundamental projects on the study of human health at various levels (genomic, proteomic, and metabolomic), and molecular mechanisms of the development of pathological conditions, there has been a great leap in the field of applied sectors of industrial biotechnology, including segments of the pharmaceutical and food industries, significantly replenished health-saving resources and improved the quality of life of the population. This article will review the advanced achievements of fundamental and applied research, as well as promising areas of the bioindustry.

INTRODUCTION: The performance of a high quality esophagogastroduodenoscopy (EGD) is dependent on the mucosal cleanliness. Recently, the Polprep: Effective Assessment of Cleanliness in EGD (PEACE) scale was created to assess the degree of mucosal cleanliness during EGD. The aim of this study was to validate this scoring system in a cohort of international endoscopists. METHODS: In total, 39 EGD videos, with different degrees of mucosal cleanliness were retrieved from a previously conducted prospective trial. All experts rated the cleanliness of the mucosa on each video using the PEACE scale. To evaluate agreement of all scores (0–3), intraclass correlation coefficient 2.1 was used. The agreement on adequate (scores 2 and 3) and inadequate (scores 0 and 1) cleanliness was assessed using kappa values. RESULTS: Videos evaluating esophagus, stomach, and duodenum cleanliness were reviewed by 16 endoscopists. The PEACE scores demonstrated good agreement (intraclass correlation coefficient 0.82, 95% CI 0.75–0.89), especially for esophagus (0.84; 95% CI 0.71–0.95) and stomach (0.81; 95% CI 0.69–0.91), while agreement was moderate for the duodenum (0.69; 95% CI 0.51–0.87). The agreement was similar between Eastern (0.86; 95% CI 0.79–0.92) and Western experts (0.80; 95% CI 0.72–0.88). Similarly, agreement regarding adequate cleanliness was comparable between Eastern (0.70; 95% CI 0.55–0.85) and Western (0.74; 95% CI 0.64–0.84) endoscopists being overall 0.75 (95% CI 0.65–0.85). DISCUSSION: The PEACE scoring system is a simple and reliable scale to assess the cleanliness during EGD. The score is now validated among international experts with high concordance, justifying its use in clinical practice.