Expanding horizons in pulmonary hypertension management: A systematic review and meta-analysis of non-pharmacological interventions.

BACKGROUND: Pulmonary hypertension (PH) is a progressive and life-threatening disorder characterized by elevated pulmonary arterial pressure, leading to right heart failure and reduced exercise capacity. Traditional pharmacological and surgical treatments offer limited efficacy and significant side effects, necessitating the exploration of alternative therapeutic options. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of non-pharmacological interventions, including exercise, dietary modifications, and psychosocial therapies, in the management of pulmonary hypertension. METHODS: Comprehensive searches were conducted in PubMed, Cochrane Library, and Scopus up to 2024, identifying randomized controlled trials and observational studies examining non-pharmacological interventions for PH. Primary outcomes assessed included pulmonary arterial pressure, right heart function, exercise capacity, and quality of life, with secondary analysis on safety and adverse effects. Data synthesis was performed using random-effects meta-analysis. RESULTS: The review included 30 studies, totaling 2000 participants with various forms of PH. Meta-analysis demonstrated significant improvements in exercise capacity as measured by the 6 min walk distance (mean increase of 45 meters, 95 % CI: 30-60, p<0.001), enhanced quality of life scores, and reduction in pulmonary arterial pressure (mean reduction of 5 mmHg, 95 % CI: 3-7, p<0.01). Non-pharmacological therapies also showed a favorable safety profile, with minor adverse effects reported. CONCLUSION: Non-pharmacological interventions provide a viable and effective complement to traditional treatments for pulmonary hypertension, significantly improving functional capacity and hemodynamic parameters without severe adverse effects. These findings support the integration of tailored non-pharmacological strategies into the therapeutic regimen for PH patients, emphasizing the need for broader implementation and further research to optimize intervention protocols.

Evaluating the efficacy and safety of temporary mechanical circulatory support devices in acute cardiogenic shock: A subgroup-specific systematic review.

OBJECTIVE: This systematic review aims to assess the comparative effectiveness and safety of temporary mechanical circulatory support (MCS) devices in various subgroups of patients with acute cardiogenic shock, providing insights for personalized clinical decision-making. METHODS: We conducted a comprehensive search across major databases to identify studies that reported on the use of temporary MCS devices like TandemHeart, Impella, and VA-ECMO in acute cardiogenic shock. Special attention was given to subgroup analyses based on etiologies of shock, patient demographics, and comorbid conditions. RESULTS: Our analysis revealed that while devices like TandemHeart and Impella offer significant hemodynamic support, their effectiveness and safety profiles vary across different patient subgroups. VA-ECMO demonstrated the highest flow rates and potential for mortality benefits but requires careful management due to associated risks. The lack of randomized controlled trials in specific patient subgroups highlights a gap in the current literature, underscoring the need for targeted research. CONCLUSION: The review underscores the necessity of a personalized approach in selecting temporary MCS devices for patients with acute cardiogenic shock, guided by specific patient characteristics and clinical scenarios. Future research should focus on addressing the identified evidence gaps through well-designed studies that provide robust subgroup-specific data, enabling clinicians to optimize treatment strategies and improve patient outcomes in this critical care context.

Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models.

The ongoing SARS-CoV-2 pandemic is controlled but not halted by public health measures and mass vaccination strategies which have exclusively relied on intramuscular vaccines. Intranasal vaccines can prime or recruit to the respiratory epithelium mucosal immune cells capable of preventing infection. Here we report a comprehensive series of studies on this concept using various mouse models, including HLA class II-humanized transgenic strains. We found that a single intranasal (i.n.) dose of serotype-5 adenoviral vectors expressing either the receptor binding domain (Ad5-RBD) or the complete ectodomain (Ad5-S) of the SARS-CoV-2 spike protein was effective in inducing i) serum and bronchoalveolar lavage (BAL) anti-spike IgA and IgG, ii) robust SARS-CoV-2-neutralizing activity in the serum and BAL, iii) rigorous spike-directed T helper 1 cell/cytotoxic T cell immunity, and iv) protection of mice from a challenge with the SARS-CoV-2 beta variant. Intramuscular (i.m.) Ad5-RBD or Ad5-S administration did not induce serum or BAL IgA, and resulted in lower neutralizing titers in the serum. Moreover, prior immunity induced by an intramuscular mRNA vaccine could be potently enhanced and modulated towards a mucosal IgA response by an i.n. Ad5-S booster. Notably, Ad5 DNA was found in the liver or spleen after i.m. but not i.n. administration, indicating a lack of systemic spread of the vaccine vector, which has been associated with a risk of thrombotic thrombocytopenia. Unlike in otherwise genetically identical HLA-DQ6 mice, in HLA-DQ8 mice Ad5-RBD vaccine was inferior to Ad5-S, suggesting that the RBD fragment does not contain a sufficient collection of helper-T cell epitopes to constitute an optimal vaccine antigen. Our data add to previous promising preclinical results on intranasal SARS-CoV-2 vaccination and support the potential of this approach to elicit mucosal immunity for preventing transmission of SARS-CoV-2.