In the Search for Biomarkers of Pulmonary Arterial Hypertension, Are Cytokines IL-2, IL-4, IL-6, IL-10, and IFN-Gamma the Right Indicators to Use?

Pulmonary arterial hypertension (PAH) is a complex disorder characterized by increased pressure in the pulmonary arteries, leading to right heart failure. While the exact mechanisms underlying PAH are not fully understood, cytokines have been implicated in the pathogenesis of the disease. Cytokines play a crucial role in regulating immune responses and inflammation. These small proteins also play a key role in shaping the immunophenotype, which refers to the specific characteristics and functional properties of immune cells, which can have a significant impact on the development of PAH. The aim of this study was to determine the immunophenotype and the concentration of selected cytokines, IL-2, IL-4, IL-6, IL-10, and IFN-gamma, in patients diagnosed with PAH (with particular emphasis on subtypes) in relation to healthy volunteers. Based on the obtained results, we can conclude that in patients with PAH, the functioning of the immune system is deregulated as a result of a decrease in the percentage of selected subpopulations of immune cells in peripheral blood and changes in the concentration of tested cytokines in relation to healthy volunteers. In addition, a detailed analysis showed that there are statistically significant differences between the PAH subtypes and the tested immunological parameters. This may indicate a significant role of the immune system in the pathogenesis of PAH.

Atypical Cardiac Location of Melanoma of Unknown Origin.

The subject was a 66-year-old woman, suffering from the chest pain evoked by physical activity. Transthoracic echocardiography (TTE) revealed an abnormal structure, 41 × 29 mm. In MSCT, a hypodensic mobile tissue lesion that was infiltrating the whole thickness of left ventricle was confirmed. PET excluded the existence of other remote lesions. After surgical tumor removal, histopathological differential diagnosis revealed melanoma, myoepithelial cancer, and MPNST "high-grade" sarcoma. A control TTE detected a tumor that was 14 × 10 mm. After immunohistochemical results, immunotherapy with pembrolizumab was used, which resulted in complete tumor resolution. Presently, surgical resection and neoadjuvant targeted immunochemotherapy remain the treatment of choice for clinical stage III/IV melanoma.

Tricuspid Regurgitation Velocity/Tricuspid Annular Plane Systolic Excursion (TRV/TAPSE) Ratio as a Novel Indicator of Disease Severity and Prognosis in Patients with Precapillary Pulmonary Hypertension.

BACKGROUND: Tricuspid annular plane systolic excursion (TAPSE) and tricuspid regurgitation velocity (TRV) are two echocardiographic parameters with prognostic value in patients with pulmonary hypertension (PH). When analyzed concurrently as the TRV/TAPSE ratio, they allow the ventricular-pulmonary artery coupling (RVPAC) to be assessed. This could better predict disease severity in patients with PH. OBJECTIVE: Our study aimed to evaluate the prognostic value of the TRV/TAPSE ratio echocardiographic parameter in adults with precapillary PH. METHODS: This study included 39 patients (74% women; average age, 63 years) with precapillary PH (pulmonary arterial hypertension and chronic thromboembolic PH) The mean follow-up period was 16.6 ± 13.3 months. Twelve patients (31%) died during the observation time. We measured TAPSE as a surrogate of RV contractility and TRV reflecting RV afterload, while ventricular-arterial coupling was evaluated by the ratio between these two parameters (TRV/TAPSE). To assess disease progression and the patient's functional capacity, the World Health Organization functional class (WHO FC) was determined. Patient physical capacity was also evaluated using the 6 min walk test (6MWT). The analysis included values of N-terminal prohormone brain natriuretic peptide (NT-proBNP), which were taken routinely during the follow-up visit. RESULTS: The mean calculated TRV/TAPSE ratio was 0.26 ± 0.08 m/s/mm. Upon comparison of the TRV/TAPSE ratio to the disease prognostic indicators, we observed a statistically significant correlation between TRV/TAPSE and the results of the WHO FC, 6MWT, and NT-proBNP. The TRV/TAPSE ratio is thus a good predictor of mortality in PH patients (AUC, 0.781). Patients with a TRV/TAPSE ratio > 0.30 m/s/mm had a shorter survival time, with log-rank test p < 0.0001. Additionally, ROC analysis revealed higher AUC for TRV/TAPSE than for TAPSE and TRV alone. CONCLUSIONS: TRV/TAPSE is a promising practicable echocardiographic parameter reflecting RVPAC. Moreover, TRV/TAPSE could be viable risk stratification parameter and could have prognostic value in patients with PH.

How Do Minerals, Vitamins, and Intestinal Microbiota Affect the Development and Progression of Heart Disease in Adult and Pediatric Patients?

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, far ahead of cancer. Epidemiological data emphasize the participation of many risk factors that increase the incidence of CVDs, including genetic factors, age, and sex, but also lifestyle, mainly nutritional irregularities and, connected with them, overweight and obesity, as well as metabolic diseases. Despite the importance of cardiovascular problems in the whole society, the principles of prevention of CVDs are not widely disseminated, especially among the youngest. As a result, nutritional neglect, growing from childhood and adolescence, translates into the occurrence of numerous disease entities, including CVDs, in adult life. This review aimed to draw attention to the role of selected minerals and vitamins in health and the development and progression of CVDs in adults and children. Particular attention was paid to the effects of deficiency and toxicity of the analyzed compounds in the context of the cardiovascular system and to the role of intestinal microorganisms, which by interacting with nutrients, may contribute to the development of cardiovascular disorders. We hope this article will draw the attention of society and the medical community to emphasize promoting healthy eating and proper eating habits in children and adults, translating into increased awareness and a reduced risk of CVD.

Gut-Lung Axis in Focus: Deciphering the Impact of Gut Microbiota on Pulmonary Arterial Hypertension.

Recent advancements in the understanding of pulmonary arterial hypertension (PAH) have highlighted the significant role of the gut microbiota (GM) in its pathogenesis. This comprehensive review delves into the intricate relationship between the GM and PAH, emphasizing the influence of gut microbial composition and the critical metabolites produced. We particularly focus on the dynamic interaction between the gut and lung, examining how microbial dysbiosis contributes to PAH development through inflammation, altered immune responses, and changes in the gut-lung axis. Noteworthy findings include variations in the ratios of key bacterial groups such as Firmicutes and Bacteroidetes in PAH and the pivotal roles of metabolites like trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and serotonin in the disease's progression. Additionally, the review elucidates potential diagnostic biomarkers and novel therapeutic approaches, including the use of probiotics and fecal microbiota transplantation, which leverage the gut microbiota for managing PAH. This review encapsulates the current state of research in this field, offering insights into the potential of gut microbiota modulation as a promising strategy in PAH diagnosing and treatment.

Noise induced unanimity and disorder in opinion formation.

We propose an opinion dynamics model based on Latané's social impact theory. Actors in this model are heterogeneous and, in addition to opinions, are characterised by their varying levels of persuasion and support. The model is tested for two and three initial opinions randomly distributed among actors. We examine how the noise (randomness of behaviour) and the flow of information among actors affect the formation and spread of opinions. Our main research involves the process of opinion formation and finding phases of the system in terms of parameters describing noise and flow of the information for two and three opinions available in the system. The results show that opinion formation and spread are influenced by both (i) flow of information among actors (effective range of interactions among actors) and (ii) noise (randomness in adopting opinions). The noise not only leads to opinions disorder but also it promotes consensus under certain conditions. In disordered phase and when the exchange of information is spatially effectively limited, various faces of disorder are observed, including system states, where the signatures of self-organised criticality manifest themselves as scale-free probability distribution function of cluster sizes. Then increase of noise level leads system to disordered random state. The critical noise level above which histograms of opinion clusters' sizes loose their scale-free character increases with increase of the easy of information flow.