Search Results (781)

In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), antiplatelet therapy is the cornerstone of treatment for secondary prevention. Although dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y₁₂ inhibitor is the current standard of care, being, respectively, recommended for 6 and 12 months in patients with chronic and acute coronary syndrome without a need for oral anticoagulation, the continuous improvement in PCI technology and pharmacology have significantly reduced the need for long-term DAPT. Mounting evidence supports the administration of P2Y₁₂ inhibitor monotherapy, particularly ticagrelor, after a short period of DAPT following PCI as a strategy to reduce bleeding without a trade-off in ischemic events compared to standard DAPT. In addition, there is a growing literature supporting P2Y₁₂ inhibitor monotherapy also for long-term secondary prevention of ischemic events. However, the data to this extent are not as robust as compared to the first-year post-PCI period, with aspirin monotherapy still remaining the mainstay of treatment for most patients. This review aims to summarize the rationale for long-term antiplatelet therapy, the pharmacology of current antiplatelet drugs tested for long-term administration as monotherapy, and current evidence on the available comparisons between different long-term antiplatelet monotherapies in patients with CAD. Full article

Gaultherin [methyl salicylate 2-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside] is a natural salicylate found in some plant species belonging primarily to the Ericaceae and Rosaceae families. Biological studies conducted since the beginning of the 21st century have suggested the potential use of gaultherin in treating various diseases related to inflammation and oxidative stress, including rheumatoid arthritis, sciatica, neuralgia, and muscular pain. The accumulated results indicated a targeted range of biological effects, particularly anti-inflammatory, antipyretic, and anti-rheumatic properties associated with reduced adverse outcomes. The molecular mechanisms involve the influence on several signalling pathways, including NF-κB, MAPK, and potentially AMPK, as well as the inhibition of critical pro-inflammatory enzymes, such as COX-2. This inhibition is achieved without affecting the COX-1 isoform, thereby preventing side effects such as bleeding ulcers or intracranial haemorrhage. This overview summarises the current knowledge about pharmacokinetics, molecular mechanisms, pharmacology, and biocompatibility of gaultherin. Additionally, four methods for isolating gaultherin from plant material and its distribution within the plant kingdom were the focal points of review and discussion. The paper also describes significant differences between synthetic aspirin and natural gaultherin in their biological potential and side effects, resulting from their different mechanisms of action. As a prodrug of salicylic acid, gaultherin releases salicylic acid gradually through enzymatic hydrolysis in the gastrointestinal tract. This controlled release minimises direct gastric irritation and accounts for its superior gastrointestinal safety profile compared to aspirin. Unlike aspirin, which irreversibly inhibits COX-1 and can lead to serious side effects with chronic use, gaultherin selectively inhibits COX-2 while sparing COX-1. These properties position gaultherin as a compelling natural alternative for patients requiring long-term anti-inflammatory therapy with reduced risk of gastrointestinal or bleeding complications. Full article

The objective of this study was to evaluate the serum biomarkers implicated in the interaction of platelets and endothelium, as well as the efficacy of antiplatelet therapy in patients with aortic stenosis (AS) and coronary artery disease (CAD). A total of 78 adult patients with CAD on aspirin therapy participated in this study, including 49 consecutive patients with AS and 29 control subjects. The analysis included the following serum biomarkers: thrombomodulin (TM), platelet factor 4 (PF4), P-selectin, and CD40L. The efficacy of antiplatelet treatment was evaluated using the VerifyNow Aspirin test (ASPI test) and P2Y12 assay test (ADP test). Patients with AS exhibited increased serum levels of TM (7.64 ± 3.5 ng/mL vs. 6.28 ± 2.1 ng/mL, p = 0.011) and PF4 (25.16; Q1: 8.3; Q3: 29.6 μg/mL vs. 12.85; Q1: 5.7; Q3: 14.5 μg/mL, p = 0.021) compared to the control group. P-selectin and CD40L levels did not differ between groups. There were no significant differences in platelet aggregation in the ASPI (474.04 ± 66.7 ARU vs. 471.31 ± 56.2 ARU; p = 0.822) or ADP (224.88 ± 46.4 PRU vs. 216.62 ± 29.6 PRU; p = 0.394) tests. Bleeding incidence did not differ significantly between groups. The coexistence of AS in patients with CAD is associated with elevated levels of the aforementioned biomarkers, which are indicative of endothelial damage and platelet activation. However, the efficacy of antiplatelet treatment was independent of the presence of AS. Full article

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition worldwide and represents a major global health challenge. Pharmacological and pharmacodynamic results indicate that aspirin eugenol ester (AEE) performs various pharmacological activities. However, it is unclear whether AEE can ameliorate the NAFLD. This study investigated the ameliorative effects of AEE on glucose and lipid metabolism disorders by in vitro and in vivo experiments. In the cellular model, TC increased to 0.104 μmol/mg and TG increased to 0.152 μmol/mg in the model group, while TC decreased to 0.043 μmol/mg and TG decreased to 0.058 μmol/mg in the AEE group. In the model group, the area occupied by lipid droplets within the visual field was significantly elevated to 17.338%. However, the administration of AEE resulted in a substantial reduction in this area to 10.064%. AEE significantly reduced the lipid droplet area and TC and TG levels (p < 0.05), increased bile acids in the cells and in the medium supernatant (p < 0.05), and significantly up-regulated the expression of LRH-1, PPARα, CYP7A1, and BSEP mRNA levels (p < 0.05) compared to the model group. In the animal model, different doses of AEE administration significantly down-regulated the levels of TC, TG, LDL, GSP, and FBG (p < 0.05) compared to the high-fat-diet (HFD) group, and 216 mg/kg of AEE significantly improved hepatocellular steatosis, attenuated liver injury, and reduced the area of glycogen staining (p < 0.05). In the HFD group, the glycogen area within the visual field exhibited a significant increase to 18.250%. However, the administration of AEE resulted in a notable reduction in the glycogen area to 13.314%. Liver and serum metabolomics results show that AEE can reverse the metabolite changes caused by a HFD. The major metabolites were involved in seven pathways, including riboflavin metabolism, glycerophospholipid metabolism, tryptophan metabolism, primary bile acid biosynthesis, biosynthesis of unsaturated fatty acids, nicotinate and nicotinamide metabolism, and tryptophan metabolism. In conclusion, AEE had a positive regulatory effect on NAFLD. Full article

Embolic stroke of undetermined source (ESUS) was proposed in 2014 as a clinical category to subgroup non-lacunar cryptogenic ischemic strokes that appear embolic but lack an identifiable cause despite thorough investigation. The initial hypothesis was that anticoagulation might offer superior secondary prevention compared to antiplatelet therapy, prompting several large clinical trials. This review synthesizes current knowledge on ESUS. ESUS represents about 17% of ischemic strokes and often affects younger patients with fewer traditional risk factors. Although these patients lack major cardioembolic sources (e.g., atrial fibrillation) or significant arterial stenosis, many have covert embolic substrates. Major trials—NAVIGATE ESUS, RE-SPECT ESUS, and the atrial cardiopathy-focused ARCADIA—found no benefit of anticoagulants over aspirin, challenging the original ESUS framework. These results highlight the heterogeneity within ESUS and underscore the need for individualized diagnostic and therapeutic strategies. Full article

The objective was to conduct a review and meta-analysis of questionnaire-based surveys of dengue knowledge, attitudes, perceptions, and practices (KAP)s among the general public in Sri Lanka as no prior island-wide survey existed. The electronic database PubMed and other bibliography were searched for literature on dengue questionnaire-based KAP surveys in Sri Lanka from 2000–2023. Data pertaining to the three domains were extracted from sixteen eligible articles, pooled, and analyzed separately using random effect models. Meta-analyses of the three domains were performed using R version 3.6.3. The population surveyed (8955) was <0.045% of the total Sri Lankan population. The publication frequency increased over time and surveys were distributed in Colombo and suburbs 43.7% (7/16), Kandy 25% (4/16,) Gampaha 12.5% (2/16), and 6.3% (1/16) one each in Kurunegala, Matara, Batticaloa, and Jaffna. Knowledge on dengue transmission, vector breeding, and fever as a symptom was >80%, while on vector species, preferred feeding times, recurrence of dengue it was > 55% and on warning signs of severity it was 25%. Attitudes towards community participation in dengue prevention activities and knowledge of dengue risk factors (avoidance of aspirin and dark colored drinks) were poor, while practice of control measures (removal of water collecting receptacles, roof-gutter management) lacked regularity. Full article

Background: The optimal antithrombotic therapy after transcatheter aortic valve replacement (TAVR) remains uncertain. Limited data exist comparing novel oral anticoagulants (NOACs) with standard antiplatelet therapy in this population. Methods: We conducted a retrospective analysis of 171 patients who underwent TAVR between January 2018 and August 2024. Patients were categorized according to the discharge antithrombotic regimen as follows: NOACs (n = 27, 16%), vitamin K antagonists (VKAs; n = 8, 5%), and antiplatelet therapy only (APT-only; aspirin and/or clopidogrel without oral anticoagulation; n = 136, 79%). Due to the small VKA sample size, the primary analysis compared NOACs with APT-only. VKA outcomes were reported descriptively without statistical comparisons. Results: Compared with APT-only, NOAC users had significantly higher 30-day mortality (33% vs. 12%, p = 0.017) and 1-year mortality (41% vs. 20%, p = 0.048). NOACs were associated with higher rates of major adverse cardiovascular events (MACCE) at 30 days (22% vs. 8%, p = 0.051) and 1 year (34% vs. 17%, p < 0.001). After inverse probability treatment weighting, NOACs showed increased odds of 30-day MACCE (OR 5.59, 95% CI 2.56–12.18, p < 0.001) and increased hazard of 1-year mortality (HR 2.22, 95% CI 1.22–4.03, p = 0.009). Conclusions: NOAC use was associated with inferior outcomes compared to antiplatelet therapy in post-TAVR patients, although residual confounding cannot be excluded. Given the limited sample size and retrospective design, these hypothesis-generating findings require validation in larger prospective studies before they can influence clinical practice. Full article

Background: Cancer stem cells (CSCs) are a subpopulation of cancer cells known for their self-renewal capacity, tumorigenicity, and resistance to treatment. Toll-like receptor 3 (TLR3) plays a complex role in cancer, exhibiting both pro-apoptotic and pro-tumorigenic effects. This study investigates the pro-tumorigenic role of TLR3, specifically its impact on CSCs in head and neck cancer. Methods: We have investigated Detroit 562, FaDu and SQ20B cell lines, the latter being stably transfected with a plasmid containing inducible shRNA for TLR3, by cultivating them to form tumor spheres in order to study CSCs. Results: Our findings demonstrate that TLR3 activation promotes stemness in head and neck cancer cell lines. This is evidenced by increased tumor sphere formation, promotion of epithelial-to-mesenchymal transition (EMT), upregulated stemness gene expression, and elevated aldehyde dehydrogenase (ALDH) activity. Conditional TLR3 knockdown abolished tumor sphere formation, confirming its important role. Furthermore, TLR3 activation triggers the secretion of damage-associated molecular patterns (DAMPs) into the tumor microenvironment, leading to increased cancer cell migration. This was inhibited by DAMP inhibitors. In patient tissue samples, we observed co-localization of TLR3 with stemness markers CD133 and ALDH1, as well as with heat shock protein 70 (HSP70) and receptor for advanced glycation end products (RAGE). We then explored potential CSC-targeted therapies, initially combining the apoptosis inducer poly (I:C) with DAMP inhibitors and γ-irradiation. While this combination proved effective in adherent cells, it failed to eliminate tumor spheres. Nevertheless, we discovered that proton radiotherapy, particularly when combined with aspirin (HMGB1 inhibitor) and poly (I:C), effectively eliminates CSCs. Conclusions: This novel combination holds promise for the development of new therapeutic strategies for head and neck cancers, particularly given the promising results of proton therapy in treating this disease. Full article

Background: Hypertensive disorders of pregnancy (HDPs) are a major cause of maternal morbidity and mortality worldwide. Very little progress has been made in reducing HDP-related maternal deaths in low- and middle-income countries (LMICs), including South Africa, over the past decade. Aim: The aim of this study was to describe maternal deaths arising from HDPs at tertiary/quaternary hospital in Johannesburg, South Africa, with specific focus on maternal characteristics, management, timing of death, causes, and avoidable factors and to use the information to inform clinical practice. Methods: We conducted a retrospective review of patient clinical records covering the period 1 January 2015 to 31 December 2018. Data on maternal demographic and pregnancy characteristics, management, causes, and timing of death were extracted from the clinical records and transferred into a Microsoft Excel^® Spreadsheet and analysed using descriptive statistics. Results: During the study period, 70 maternal deaths were recorded, of which 23 (32.8%) were due to HDP-related complications. The majority of the maternal deaths, 20 (86.9%), occurred during the postpartum period, predominantly affecting Black African women, 23 (100%), with a median age of 27 years. Notably, 18 (78.2%) of the deceased had booked early and attended antenatal care (ANC). Eclampsia emerged as the most common final cause of death. Key avoidable factors included non-adherence to established protocols, particularly failure to initiate aspirin prophylaxis in at-risk women, as well as incorrect or inadequate administration of antihypertensive therapy and magnesium sulphate (MgSO₄) prophylaxis. Conclusions: HDP-related maternal deaths are largely preventable. They primarily result from poor quality of care due to a lack of adherence to evidence-based protocol. Full article

Background/Objectives: Acetylsalicylic acid (ASA) medication has been suggested to have a beneficial effect on cancer risk and survival. Therefore, this retrospective case–control study investigated the correlation between ASA and HNC in over 11,000,000 patients to investigate the impact of ASA intake on the risk of developing HNC, five-year survival rates, and the likelihood of secondary malignant neoplasms and malignant lymph node involvement. Methods: Retrospective clinical data was retrieved from a federated EHR network. Patients prescribed ASA were assigned to Cohort I, while those who were not prescribed ASA were assigned to Cohort II. Moreover, patients diagnosed with HNC, and prescribed ASA were assigned to Cohort III, while those with HNC but no history of ASA use were assigned to Cohort IV. Results: After matching, Cohorts I and II included 5,716,056 patients each. HNC incidence was significantly lower (OR 0.88; 95% CI 0.86–0.90) in Cohort I (+ASA) compared to Cohort II (−ASA). Furthermore, five-year survival was higher for patients taking ASA medication (survival probability 67.93%) compared to patients who did not (65.54%). These findings coincide with a lower risk of death of 22.8% (+ASA) compared to 23.6% (−ASA), which was statistically significant (p = 0.006). Patients with ASA intake also showed a lower risk of malignant neoplasms of lymph nodes (17.4% vs. 18.5%). Conclusions: Our analyses revealed a lower risk of HNC, a higher five-year survival rate, and a lower risk of malignant neoplasms of lymph nodes in patients with ASA medication. However, the retrospective design and the lack of evaluation of confounders limit the significance of our data, and, therefore, further analyses should be considered. Full article

Background/Objectives: Despite progress in secondary prevention, people with chronic coronary syndrome (CCS) still face a residual risk of ischemic events. Antithrombotic therapy reduces this risk and helps stabilize chronic cardiovascular disease. Studies have shown that combining low-dose rivaroxaban with aspirin—an approach called dual-pathway inhibition (DPI)—can lower this risk and reduce major adverse cardiovascular events (MACEs). However, researchers have not yet gathered enough real-world data to confirm the efficacy and safety of this strategy. The DUTCH CCS registry aims to collect real-world data on how effective and safe low-dose rivaroxaban combined with aspirin is for patients with CCS in The Netherlands. The study aims to provide insights into the outcomes, benefits, and risks of DPI in a real-world setting, beyond the scope of controlled clinical trials. Methods: The DUTCH CCS registry operates as a national, multicenter, prospective observational study. It enrolls 1000 patients with CCS who receive rivaroxaban (2.5 mg twice daily) and aspirin (80 mg or 100 mg once daily). The study targets individuals at high ischemic risk due to coronary artery disease (CAD) and follows a single-arm design. Researchers will measure the primary efficacy endpoint by tracking MACEs, clinically driven coronary, peripheral, or carotid revascularization, and stent thrombosis over one year. They will assess the primary safety endpoint by recording major bleeding events at one year. The team will collect data at both 3-month and 1-year follow-ups. Conclusions: As an observational study, this registry is not designed to establish causality. However, it seeks to improve our understanding of how DPI performs in real-world secondary prevention for CCS patients. The results may help update treatment guidelines and inform clinical decisions in everyday practice. Full article

Background: Brain metastases are a common and devastating complication of non-small cell lung cancer (NSCLC), severely affecting prognosis and quality of life. Despite increasing interest in the role of platelets in tumor progression and dissemination, the potential impact of antiplatelet therapy on brain metastasis in NSCLC remains underexplored. Methods: In this retrospective observational study, we analyzed data from 650 patients diagnosed with NSCLC over a four-year period to evaluate whether prior or subsequent exposure to antiplatelet agents correlates with a reduced incidence of brain metastases. Results: Patients exposed to antiplatelet therapy, predominantly aspirin, presented with more comorbidities and were generally older. Despite these differences, they showed a significantly lower risk of developing brain metastases during the disease course (6.9% vs. 20.0%, p < 0.001), particularly among those with advanced-stage disease at diagnosis. A longer time to metastasis development was also observed in antiplatelet users (77.5 vs. 62.6 months, p < 0.001), along with improved progression-free survival. Additionally, patients on antiplatelets before diagnosis had a lower probability of presenting brain metastases at the time of diagnosis (3.9% vs. 12.1%, p = 0.014), and no cases of brain metastases occurred in patients who started antiplatelet therapy shortly after diagnosis. These findings highlight the potential of antiplatelet agents to interfere with key mechanisms of metastatic spread, including immune evasion and premetastatic niche formation. Conclusions: Importantly, this study provides one of the first real-world analyses suggesting a consistent and stage-dependent association between antiplatelet use and reduced brain metastatic burden in NSCLC. By bridging the gap between preclinical insights and clinical outcomes, our work offers a novel and clinically relevant perspective that supports further research into the integration of antiplatelet therapy in NSCLC management. Full article

Introduction: The treatment efficacy of prostate cancer (PCa) radiotherapy (RT) can be inadvertently affected by the concurrent usage of non-oncologic medications. Many studies have associated the intake of several non-oncologic drugs with cancer specific outcomes. In this study, we report the impact of daily non-oncologic medications including aspirin, metformin, and statins on time to progression for patients with high-risk PCa. Methods: Patients with high- and very high risk PCa (NCCN definition of Gleason score ≥ 8, prostate-specific antigen (PSA) ≥ 20, or ≥cT3a) who received definitive RT at two institutions were included in this analysis. Progression was defined as either biochemical (PSA > nadir + 2 ng/mL), locoregional (prostate or lymph nodes, biopsy-proven), or development of distant metastases. Progression-free survival (PFS) was defined as the time elapsed from the start of RT to progression or last follow-up. Cox proportional hazards models evaluated the associations between non-oncologic medications and PFS. Results: There were 237 patients eligible for this analysis, of which 47 (19.8%) and 178 (75.1%) had at least clinical T3 disease or at least Gleason 8 disease, respectively. During RT, 82 (34.6%), 88 (37.1%), and 29 (12.2%) patients were taking aspirin, statin, or metformin, respectively. Overall, 54 patients (22.8%) experienced disease progression. Neither aspirin nor statin usage had a significant association with PFS. Patients prescribed metformin displayed worse PFS compared to patients not taking metformin (aHR: 2.46, 95% CI: 1.06–5.72). Conclusions: Aspirin and statin usage was not associated with likelihood of progression in this large cohort of patients with high-/very high risk PCa. Metformin use was associated with poorer PFS, albeit with a small event rate due to fewer patients taking metformin. Further studies are needed to clarify the impact of common non-oncologic medication use on outcomes for patients with high-risk PCa. Full article

Background/Objectives: Primary prevention, germline, familial, or other pre- or post-diagnostic and standard treatment-elevated progression or recurrence risk and mitigating adverse events from systemic treatment are all clinical opportunities to reduce the risk of lethal prostate cancer. This review attempted to provide a practical and realistic consensus via an international committee of experts who, in general, harbor career-long experience in this discipline. Methods: A PubMed review primarily utilizing the latest meta-analyses, systematic reviews, and methodologically robust epidemiologic recent data adjusting for multiple confounding variables was conducted. The goal of this committee was to highlight tangible options for clinicians and patients. Results: Behavioral patterns and metrics known to reduce cardiovascular morbidity, mortality, and all-cause mortality (premature death) appear to prevent numerous lethal common cancers, including prostate cancer. This practical approach allows for the greatest probability of patient success since cardiovascular disease (CVD) is the primary cause of death in men with and without prostate cancer, and a notable source of morbidity and mortality in men with advanced disease due to systemic conventional treatment as well as the inflammatory contribution of cancer itself. Heart-healthy dietary patterns, exercise, healthy weight/waist circumference, eliminating tobacco, minimizing alcohol exposure, and other behaviors to reduce the risk of CVD should be prioritized. CVD-preventive medications, including aspirin, GLP-1 agonists, metformin, statins, etc., should receive attention to improve compliance for those that already qualify for these agents and to increase the probability of enhancing the quality and quantity of life. Dietary supplements do not have favorable data currently to espouse their utilization to prevent lethal prostate cancer but may have an ancillary role in mitigating some adverse effects of treatment. Conclusions: Remarkably, heart-healthy lifestyle changes, metrics, and promising repurposed medications known to reduce cardiovascular events, promote longevity, and improve mental health could simultaneously prevent lethal prostate cancer. This serendipitous association provides clinicians and their patients a higher probability of success, regardless of their prostate cancer pathway or circumstance. Full article

Cardiovascular disease is the primary cause of mortality and morbidity in patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD) undergoing hemodialysis. This paper examines the challenges of managing acute coronary syndrome (ACS) in ESRD patients, focusing on the delicate balance between thrombotic and bleeding risks. The review explores the mechanisms underlying the increased thrombotic risk in ESRD, including elevated platelet aggregation, endothelial dysfunction, and alterations in coagulation factors. Paradoxically, ESRD patients also exhibit higher bleeding tendencies due to platelet dysfunction and other uremia-related factors. The efficacy and safety of various antiplatelet therapies, including aspirin and P2Y12 inhibitors, are evaluated in this population. While potent P2Y12 inhibitors such as ticagrelor and prasugrel have demonstrated potential in reducing ischemic events, they are associated with an increased bleeding risk. The optimal duration of anti-platelet therapy (DAPT) in ESRD patients remains controversial, with studies suggesting potential benefits of prolonged DAPT but also increased bleeding risk. This review underscores the necessity for further research and patient inclusion in clinical trials to establish evidence-based guidelines for tailoring antithrombotic therapy in this high-risk population. Full article