Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of death by cancer in the world. What makes this pathological condition particularly lethal is a combination of clinical and molecular heterogeneity, lack of early diagnostic indexes, and underwhelming results from current therapeutic protocols. A major cause of PDAC chemoresistance seems to lie in the ability of cancer cells to spread out and fill the pancreatic parenchyma, exchanging nutrients, substrates, and even genetic material with cells from the surrounding tumor microenvironment (TME). Several components can be found in the TME ultrastructure, including collagen fibers, cancer-associated fibroblasts, macrophages, neutrophils, mast cells, and lymphocytes. Cross-talk between PDAC and TME cells results in the latter being converted into cancer-favoring phenotypes; this behavior could be compared to an influencer guiding followers into supporting his activity. Moreover, TME could be a potential target for some of the newest therapeutic strategies; these include the use of pegvorhyaluronidase-α and CAR-T lymphocytes against HER2, FAP, CEA, MLSN, PSCA, and CD133. Other experimental therapy options are being currently studied, aiming to interfere with the KRAS pathway, DNA-repairing proteins, and apoptosis resistance in PDAC cells. Hopefully these new approaches will grant better clinical outcomes in future patients.

Cardiovascular (CV) disease remains the leading cause of morbidity and mortality worldwide, highlighting the necessity of understanding its underlying molecular and pathophysiological pathways. Conversely, physical activity (PA) and exercise are key strategies in reducing CV event risks. Detecting latent CV conditions in apparently healthy individuals, such as athletes, presents a unique challenge. The early identification and treatment of CV disorders are vital for long-term health and patient survival. Cardiac troponin is currently the most commonly used biomarker for assessing CV changes in both athletes and the general population. However, there remains considerable debate surrounding the mechanisms underlying exercise-induced troponin elevations and its release in non-ischemic contexts. Thus, there is a pressing need to identify and implement more sensitive and specific biomarkers for CV disorders in clinical practice. Indeed, research continues to explore reliable biomarkers for evaluating the health of athletes and the effectiveness of physical exercise. It is essential to analyze current evidence on troponin release in non-ischemic conditions, post-strenuous exercise, and the complex biological pathways that influence its detection. Furthermore, this study summarizes current research on cytokines and exosomes, including their physiological roles and their relevance in various CV conditions, especially in athletes. In addition, this paper gives special attention to underlying mechanisms, potential biomarkers, and future perspectives.

Atherosclerosis is the leading cause of death worldwide, especially in patients with type 2 diabetes mellitus (T2D). GLP-1 receptor agonists and DPP-4 inhibitors were demonstrated to play a markedly protective role for the cardiovascular system beyond their glycemic control. Several cardiovascular outcome trials (CVOT) reported the association between using these agents and a significant reduction in cardiovascular events in patients with T2D and a high cardiovascular risk profile. Moreover, recent evidence highlights a favorable benefit/risk profile in myocardial infarction and percutaneous coronary revascularization settings. These clinical effects result from their actions on multiple molecular mechanisms involving the immune system, platelets, and endothelial and vascular smooth muscle cells. This comprehensive review specifically concentrates on these cellular and molecular processes mediating the cardiovascular effects of incretins-like molecules, aiming to improve clinicians’ knowledge and stimulate a more extensive use of these drugs in clinical practice as helpful cardiovascular preventive strategies.

Although it is known that exercise improves cardiovascular health and extends life expectancy, a significant number of people may also experience an elevation in cardiac troponin levels as a result of exercise. For many years, researchers have argued whether exercise-induced cardiac troponin rises are a consequence of a physiological or pathological reaction and whether they are clinically significant. Differences in cardiac troponin elevation and cardiac remodeling can be seen between athletes participating in different types of sports. When forecasting the exercise-induced cardiac troponin rise, there are many additional parameters to consider, as there is a large amount of interindividual heterogeneity in the degree of cardiac troponin elevation. Although it was previously believed that cardiac troponin increases in athletes represented a benign phenomenon, numerous recent studies disproved this notion by demonstrating that, in specific individuals, cardiac troponin increases may have clinical and prognostic repercussions. This review aims to examine the role of cardiac troponin in athletes and its role in various sporting contexts. This review also discusses potential prognostic and clinical implications, as well as future research methods, and provides a straightforward step-by-step algorithm to help clinicians interpret cardiac troponin rise in athletes in both ischemic and non-ischemic circumstances.

Carcinoid heart disease (CHD) affects right-sided valves and causes significant mortality and morbidity. Even though the pathophysiology of the disease is not entirely understood, it is known that chronic exposure to high levels of circulating serotonin is the main factor responsible for developing valvular heart disease. Cardiac imaging plays a critical role in the management of CHD, so the final diagnosis can be performed through multimodal imaging techniques and the measurement of biomarkers. Moreover, in observational studies, surgical treatment of carcinoid-induced valve disease has been found to improve outcomes. Despite advancements in pre-operative preparation in recent years, mortality rates remain high in elderly patients and those with multiple comorbidities due to the risk of intra-operative carcinoid crisis and high post-operative bleeding. In this comprehensive review, we will analyze the causes of carcinoid syndrome and how it can result in severe right heart failure. The role of different imaging modalities in detecting heart valve disease will be discussed together with the therapeutic options at our disposal, such as medical treatment, surgery, and the novel role of transcatheter intervention.

Primary tricuspid regurgitation (TR) is an underrecognized valve disease characterized by structural abnormalities of the tricuspid valve (TV) apparatus, including leaflet prolapse, flail, rheumatic degeneration, carcinoid involvement and congenital malformations such as Ebstein’s anomaly. Historically neglected and often misclassified as functional, primary TR has recently gained attention due to advances in multimodality imaging and increased awareness of its pathophysiological complexity and adverse outcomes. A major challenge that remains is the accurate diagnosis of primary TR, as well as the optimal timing for intervention, particularly in asymptomatic patients. While surgical repair or replacement has been the traditional approach, recent developments in transcatheter therapies, such as tricuspid edge-to-edge repair, have broadened the therapeutic landscape for patients considered at high surgical risk. In this context, personalized medicine has emerged as a central paradigm in the management of this valvular disease. Tailored therapeutic decisions should include anatomical, functional, and clinical parameters, as well as patient-specific risk factors such as age and comorbidities. Advanced imaging modalities, including 3D echocardiography and cardiac magnetic resonance, are essential for guiding this individualized approach. This review summarizes the current understanding of the etiology, pathophysiology, diagnostic tools, and treatment strategies for primary TR, highlighting the critical role of personalized treatment pathways in optimizing clinical outcomes.