Aspirin AND COX

BACKGROUND: Studies have suggested that medication with statins improves survival in patients with gastric cancer, but methodological issues have limited the interpretability and prohibited conclusive results. We aimed to provide valid evidence as to whether statin use improves survival of gastric adenocarcinoma. METHODS: This nationwide and population-based cohort study included virtually all patients who underwent curatively intended surgery (gastrectomy) for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2019 for disease-specific mortality and 2020 for all-cause mortality...

BACKGROUND: Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodelling. We examined the associations between levels of phosphate, calcium, and alkaline phosphatase, and fracture risk in initially-healthy older individuals. METHODS: A post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16,703 Australian participants aged ≥70 years and 2,411 US participants aged ≥65 years...

BACKGROUND: Systemic thromboxane A2 generation, assessed by quantifying the concentration of stable thromboxane B2 metabolites (TXB2-M) in the urine adjusted for urinary creatinine, is strongly associated with mortality risk. We sought to define optimal TXB2-M cutpoints for aspirin users and nonusers and determine if adjusting TXB2-M for estimated glomerular filtration rate (eGFR) in addition to urinary creatinine improved mortality risk assessment. METHODS: Urinary TXB2-M were measured by competitive ELISA in 1363 aspirin users and 1681 nonusers participating in the Framingham Heart Study...

Patients with heart failure with reduced ejection fraction (HFrEF) and diabetes mellitus (DM) have an increased risk of adverse events, including thromboembolism. In this analysis, we aimed to explore the association between DM and HFrEF using data from the "Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction" (WARCEF) trial. We analyzed factors associated with DM using multiple logistic regression models and evaluated the effect of DM on long-term prognosis, through adjusted Cox regressions. The primary outcome was the composite of all-cause death, ischemic stroke, or intracerebral hemorrhage; we explored individual components as the secondary outcomes and the interaction between treatment (warfarin or aspirin) and DM on the risk of the primary outcome, stratified by relevant characteristics...

BACKGROUND AND AIMS: Thromboxane (TX) A2, released by activated platelets, plays an important role in atherothrombosis. Urinary 11-dehydro-TXB2 (U-TXM), a stable metabolite reflecting the whole-body TXA2 biosynthesis, is reduced by ∼70% by daily low-dose aspirin. The U-TXM represents a non-invasive biomarker of in vivo platelet activation and is enhanced in patients with diabetes. This study assessed whether U-TXM is associated with the risk of future serious vascular events or revascularizations (SVE-R), major bleeding, or cancer in patients with diabetes...

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled...

OBJECTIVES: To examine the association between low-dose aspirin use and risk of colorectal cancer (CRC). METHODS: In this nationwide cohort study, we identified individuals aged ≥50 years residing for 6 months or more in Norway in 2004-2018, and obtained data from national registers on drug prescriptions, cancer occurrence, and sociodemographic factors. Multivariable Cox regression models were used to estimate the association between low-dose aspirin use and CRC risk...

Present research was designed to synthesize and characterize the flurbiprofen derivatives and to evaluate their analgesic, anti-inflammatory and gastro-protective activities in post-operative and chronic inflammatory pain models. Flurbiprofen derivatives were produced by using three-step processes involving esterification, hydrazide production, and schiff base, each of which modified a different carboxyl group. All the newly synthesized flurbiprofen derivatives ( NS5-NS8 ) were characterized by 1 H NMR,13 C NMR,19 F NMR and HR-ESI-MS, and the post-operative, inflammatory pain and ulcerogenic activities were determined in well-established in-vivo animal models...

BACKGROUND: Effective therapies for reducing cardiovascular disease (CVD) risk in people with elevated lipoprotein(a) are lacking, especially for primary prevention. Because of the potential association of lipoprotein(a) with thrombosis, we evaluated the relationship between aspirin use and CVD events in people with elevated lipoprotein(a). METHODS AND RESULTS: We used data from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of baseline cardiovascular disease...

Post-randomization events, also known as intercurrent events, such as treatment noncompliance and censoring due to a terminal event, are common in clinical trials. Principal stratification is a framework for causal inference in the presence of intercurrent events. The existing literature on principal stratification lacks generally applicable and accessible methods for time-to-event outcomes. In this paper, we focus on the noncompliance setting. We specify 2 causal estimands for time-to-event outcomes in principal stratification and provide a nonparametric identification formula...

BACKGROUND: With the emergence of many side effects from synthetic drugs, there is an urgent need to find a natural alternative to these products. Therefore, our primary aim was to evaluate the anti-inflammatory activity of Tamarix aphylla (TA) and investigate the potential mechanism underlying this action. METHODS: Initially, to ensure the safety of the extract and for dose selection, we performed an acute oral toxicity Assay through the oral administration of graded doses up to 4 g\kg in Wistar rats...

PURPOSE: It is unclear whether exposure to commonly prescribed medications influences survival and treatment response in patients with de novo high-risk metastatic prostate cancer (mPCa) treated with androgen receptor pathway inhibitors (ARPIs). METHODS: We performed a secondary analysis of the LATITUDE trial to determine whether receipt of concomitant medications influenced the effect of abiraterone acetate and prednisone, in addition to androgen deprivation therapy (ADT), on overall survival (OS) and prostate cancer-specific mortality (PCSM) in patients with de novo mPCa...

PURPOSE: Many atrial fibrillation (AF) patients use cardiovascular medications for indications other than AF. These medications can affect morbidity and mortality. We aim to investigate the characteristics of AF patients who use different medication classes and their clinical course. METHODS: We collected data from the prospective, multicenter registry, JoFib study. We identified classes of non-AF medications (medications not used for rate control, rhythm control, or anticoagulation), described demographic and clinical characteristics, and investigated AF-related outcomes according to these medication classes...

The paper reflects the results of molecular docking and mathematical DFT simulation for antiplatelet drugs and the target platelet receptor/ferment interaction in the limited area. The results of Raman spectra simulation are implemented and obtained from the interaction of the clopidogrel metabolite of the P2Y12 receptor. The interaction of aspirin with the COX-1 enzyme was also investigated. As a result, theoretical Raman spectra of the drug-receptor area were obtained. The theoretical data were compared with the experimental SERS results...

PURPOSE OF REVIEW: Aspirin-exacerbated respiratory disease (AERD) is a syndrome of high type 2 inflammation and is known to critically involve mast cell activation. The mast cell is an important cell in the baseline inflammatory processes in the upper and lower airway by maintaining and amplifying type 2 inflammation. But it also is prominent in the hypersensitivity reaction to COX-1 inhibition which defines this condition. RECENT FINDINGS: Recent work highlights the mast cell as a focal point in AERD pathogenesis...

Triple-negative breast cancer (TNBC) is a leading cause of cancer mortality and lacks modern therapy options. Modulated electro-hyperthermia (mEHT) is an adjuvant therapy with demonstrated clinical efficacy for the treatment of various cancer types. In this study, we report that mEHT monotherapy stimulated interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) expression, and consequently cyclooxygenase 2 (COX-2), which may favor a cancer-promoting tumor microenvironment. Thus, we combined mEHT with nonsteroid anti-inflammatory drugs (NSAIDs): a nonselective aspirin, or the selective COX-2 inhibitor SC236, in vivo...

Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, diclofenac, ibuprofen, or celecoxib have a well-established and unquestionable role in the human therapeutic arsenal, but still new perspectives are being discovered. This review presents new anti-inflammatory mechanisms of NSAIDs action, other than the classical one, i.e., the inhibition of cyclooxygenase (COX) isoforms leading to the prostanoids synthesis blockage. Literature data show that this group of drugs can activate anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARγ), inhibit pro-inflammatory nuclear factor-κB (NF-κB) activation or modulate the components of the unfolded protein response (UPR) pathway...

IMPORTANCE: There is limited information on modifiable risk factors for young-onset dementia (YOD). OBJECTIVE: To examine factors that are associated with the incidence of YOD. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until March 31, 2021, for England and Scotland, and February 28, 2018, for Wales. Participants younger than 65 years and without a dementia diagnosis at baseline assessment were included in this study...

BACKGROUND: Inflammation has been implicated in the pathogenesis of diabetes. This study investigated the randomised treatment effect of low-dose aspirin on incident type 2 diabetes and fasting plasma glucose (FPG) concentrations among older adults. METHODS: ASPREE was a double-blind, placebo-controlled trial of daily oral low-dose aspirin. The study population included community-dwelling individuals aged 70 years or older (≥65 years for US minority ethnic groups) in the USA and Australia who were free of cardiovascular disease, independence-limiting physical disability, or dementia...

JAK2 V617F (JAK2VF) clonal hematopoiesis (CH) has been associated with atherothrombotic cardiovascular disease (CVD). We assessed the impact of Jak2VF CH on arterial thrombosis and explored the underlying mechanisms. A meta-analysis of 3 large cohort studies confirmed the association of JAK2VF with CVD and with platelet counts and adjusted mean platelet volume (MPV). In mice, 20% or 1.5% Jak2VF CH accelerated arterial thrombosis and increased platelet activation. Megakaryocytes in Jak2VF CH showed elevated proplatelet formation and release, increasing prothrombogenic reticulated platelet counts...