Aspirin reduces Ponatinib-induced cardiovascular toxic phenotypes and death in zebrafish.

BACKGROUND: Ponatinib (Iclusig) is an oral tyrosine kinase BCR-ABL inhibitor for treating patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML) who are resistant to the therapies with other tyrosine kinase inhibitors. However, adverse cardiovascular events caused by Ponatinib are a serious issue that affects patients' survival rates. Thus, it is necessary to search for candidate drugs to reduce the cardiovascular toxicity of Ponatinib. PURPOSE: To investigate the effects of Aspirin on Ponatinib-induced cardiovascular toxicity in zebrafish. METHODS: AB strain of wild type zebrafish (Danio rerio), Tg (cmlc2: GFP) transgenic zebrafish, and Tg (gata1: dsRed) transgenic zebrafish were used as in vivo models to assess survival, blood flow, cardiac morphology, and function. Thrombus formation was detected using O-dianisidine staining. The transcriptome of zebrafish larvae treated with Ponatinib was assessed using RNA sequencing. RESULTS: Ponatinib not only reduced survival rate but also caused cardiovascular toxic events such as pericardial edema, abnormal heart structure, low heart rate, and thrombosis. In addition, whole-body transcriptome analysis showed that Ponatinib up-regulated the expression of cyclooxygenase-1 (COX-1). Compared with other antithrombotic drugs, a COX-1 inhibitor Aspirin more effectively reduced ponatinib-induced cardiovascular toxicity events and improved the survival rate of zebrafish larvae. CONCLUSION: Our findings suggest that Aspirin exhibits the potential to reduce Ponatinib-induced cardiovascular toxicity.

Quantum Insights into Partially Molecular Imprinted Microspheres for Anticancer Therapeutics: Experimental and Theoretical Studies.

Drug solubility is a determining factor for controlled release, and solubility-dependent release kinetics can be modified by changing the drug's state in the polymer matrix through partial molecular imprinting (PMI), although research in this area remains limited. This novel PMI approach creates nanocavities within the polymer by partially retaining the imprinting molecule and trapping the drug. Such a method holds promise for developing advanced biomaterial-based drug delivery systems for anticancer therapies. In this study, we developed microspheres designed for anticancer drug delivery utilizing PMI to enhance controlled release properties. Poly(vinyl alcohol) (PVA) microspheres were partially imprinted with aspirin (ASP) to create nanocavities for gemcitabine (GEM) molecules, inducing a polymorphic shift of GEM within the polymer matrix. This novel PMI approach enhanced drug release properties by enabling control over the drug crystallinity and release rate. The PVA-ASP-GEM complex showed zero-order release kinetics, releasing 21.6% of GEM over 48 h, maintaining steady state release profile. In contrast, nonimprinted PVA-GEM microspheres exhibited first-order kinetics with a faster release of 46.85% in the same period. Quantum insights from density functional theory (DFT) calculations revealed the superior stability of the PVA-ASP-GEM complex, with a binding free energy of -56.03 kcal/mol, compared to -29.07 kcal/mol for PVA-GEM. Molecular dynamics (MD) simulations demonstrated that ASP's presence created nanocavities that restricted GEM's movement, further contributing to the controlled release. Experimental validation through differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and Raman spectroscopy confirmed the polymorphic transitions within the PVA-ASP-GEM complex. This PMI-based approach offers a promising method for modulating drug release kinetics and improving the stability of anticancer therapeutics, paving the way for innovative biomaterial-based drug delivery systems.

Biologics in Aspirin-Exacerbated Respiratory Disease and Allergic Bronchopulmonary Aspergillosis.

Biologic medications have dramatically altered the landscape for treatment of allergic conditions including aspirin-exacerbated respiratory disease (AERD) and allergic bronchopulmonary aspergillosis (ABPA). Biologics should be considered for patients who are refractory to first line therapies for ABPA. Biologics should be discussed with patients with AERD. Variable responses to different biologics indicate that there may be various endotypes of AERD and ABPA, similar to asthma. Alternative biologics may be considered in patients who fail to respond to initial treatment.

Low-dose aspirin and heparin treatment improves pregnancy outcome in recurrent pregnancy loss women with anti-ß2-glycoprotein I/HLA-DR autoantibodies: a prospective, multicenter, observational study.

Introduction: Anti-ß2-glycoprotein I (ß2GPI)/human leukocyte antigen (HLA)-DR antibodies may be a risk factor for recurrent pregnancy loss (RPL). The therapeutic modality for women with RPL and anti-ß2GPI/HLA-DR antibody positivity has not been evaluated. This prospective, multicenter, observational study aimed to assess whether low-dose aspirin (LDA) and/or heparin therapies improve pregnancy outcomes in women with RPL who tested positive for anti-ß2GPI/HLA-DR antibodies. Methods: Between August 2019 and December 2021, 462 women with RPL underwent anti-ß2GPI/HLA-DR antibody measurements and risk assessments for RPL. Each attending physician decided the treatment modality for women with RPL who tested positive for anti-ß2GPI/HLA-DR antibodies, and their pregnancy outcomes were followed up until December 2023. Finally, 47 pregnancies in 47 women with RPL and anti-ß2GPI/HLA-DR antibody positivity were included in the analysis and were divided into two groups regarding whether they were treated with LDA and/or unfractionated heparin (UFH) (LDA/UFH group, n = 39) or with neither of them (non-LDA/non-UFH group, n = 8). The rates of live birth and pregnancy complications (i.e., preeclampsia and preterm delivery before 34 gestational weeks due to placental insufficiency) were compared between the two groups. Results: The live birth rate in the LDA/UFH group was higher than that in the non-LDA/non-UFH group (87.2% vs 50.0%, p = 0.03). The pregnancy complication rate in the LDA/UFH group was significantly lower than that in the non-LDA/non-UFH group (5.9% vs 50.0%, p = 0.048). Among 21 women who tested positive for anti-ß2GPI/HLA-DR antibodies and had no other risk factors for RPL, the live birth rate in the LDA/UFH group (n = 14) was much higher than that in the non-LDA/non-UFH group (n = 7) (92.9% vs 42.9%, p = 0.03). Discussion: This study, for the first time, demonstrated that LDA and/or UFH therapies are effective in improving pregnancy outcomes in women with RPL and aß2GPI/HLA-DR antibody positivity.

MIS-C Like Features in a Patient of Atypical Kawasaki Disease: A Case Report.

ABSTRACT: Kawasaki Disease is multisystem vasculitis affecting young children and infants. While the diagnosis of a typical form of Kawasaki Disease is obvious, there are some patients who do not fulfill the classic diagnostic criteria for the disease which is termed as 'incomplete Kawasaki Disease' or 'Atypical Kawasaki Disease'. We present a case of a 6 months old child with fever who after failing to respond to IV antibiotics showed considerable improvement after administering aspirin and Intravenous Immunoglobulin thus diagnosed as Atypical Kawasaki Disease. Moreover, due to sharing of similar features by both Kawasaki Disease and Multiple Inflammatory Syndrome in Children, the case posed a diagnostic dilemma.

Higher-Than-Usual Target International Normalized Ratio (INR) Range Required With On-X Aortic Valve Secondary to Recurrent Thromboembolic Strokes: A Case Report.

Although the On-X aortic valve (AO) is considered less thrombogenic compared to its counterparts, we present a case where recurrent thromboembolic ischemic stroke occurred, first with a slightly sub-therapeutic, then even with an elevated International Normalized Ratio (INR).  A 36-year-old male, the background of On-X AO replacement but no other risk factors, developed thromboembolic stroke twice while on Warfarin, first with INR 1.4, second with INR 2.4. Despite extensive investigation, other than elevated levels of low-density lipoproteins, no other treatable cause was found with the latter episode. The INR range was increased to 2.5-3.5, and aspirin and statin were added. The occurrence of thromboembolic stroke with an On-X AO despite maintaining an INR of 2.4, presents a dilemma for future prevention. The American Heart Association (AHA) and the American College of Cardiology (ACC) guidelines for thromboembolism prevention in case of an On-X AO recommend an INR range of 1.5-2 as being effective when warfarin is used along with aspirin. The take-home message is that the recommendation of an INR range of 1.5-2 with an On-X AO should be approached with caution; aspirin should be strongly considered regardless of the presence of thromboembolic risk factors. Patients developing thromboembolism have a high risk of recurrence. Therefore, a higher INR, along with the addition of aspirin and statin should be considered. Studies are needed to establish guidelines for a reliable INR range in these scenarios.

Predictive modeling of medication adherence in post myocardial infarction patients: a bayesian approach using beta-regression.

AIMS: Predicting medication adherence in post myocardial infarction (MI) patients has the potential to improve patient outcomes. Most adherence prediction models dichotomize adherence metrics and status. This study aims to develop medication adherence prediction models that avoid dichotomizing adherence metrics and to test whether a simplified model including only 90-days adherence data would perform similarly to a full multivariable model. METHODS: Post MI adult patients were followed for 1-year post the event. Data from pharmacy records were used to calculate proportion of days covered (PDC). We used Bayesian beta-regression to model PDC as a proportion, avoiding dichotomization. For each medication group, statins, P2Y12 inhibitors and aspirin, two prediction models were developed, a full and a simplified model. RESULTS: 3692 patients were included for model development. The median (Inter quartile range) PDC at 1-year for statins, P2Y12 inhibitors and aspirin was 0.8 (0.33, 1.00), 0.79 (0.23, 0.99) and 0.79 (0.23, 0.99), respectively. All models showed good fit to the data by visual predictive checks. Bayesian R2 for statins, P2Y12 inhibitors and aspirin models were 61.4%,71.2% and 55.2%, respectively. The simplified models showed similar performance compared with full complex models as evaluated by cross validation. CONCLUSIONS: We developed Bayesian multilevel models for statins, P2Y12 inhibitors and aspirin in post MI patients that handled 1-year PDC as a proportion using the beta-distribution. In addition, simplified models, with 90-days adherence as single predictor, had similar performance compared with full complex models.

Evaluating the safety and efficacy of medical management in extracranial pseudoaneurysms: a comparative study.

OBJECTIVE: As endovascular interventions become safer and their use more prevalent for treating extracranial pseudoaneurysms, fewer pseudoaneurysms are treated with medical therapy alone. This study aimed to assess the indications for intervention and the safety of medical management. METHODS: A dual-center retrospective analysis was conducted on patients diagnosed with extracranial carotid and vertebral pseudoaneurysms between December 2006 and June 2023. RESULTS: Of 145 pseudoaneurysms, 121 (83%) received medical therapy, 22 (15%) were treated endovascularly, and 2 (1.4%) were treated with open surgery. In the medical group, there were 2 (1.9%) complications, one unrelated to the pseudoaneurysm. In the intervention group, there were 3 (16%) complications, with 1 patient requiring two retreatments and sacrifice of the vessel. Major trauma (OR 4.0, 95% CI 1.3-14; p = 0.02), use of digital subtraction angiography as the initial imaging modality (OR 9.8, 95% CI 2.5-42; p < 0.01), and a maximum lesion diameter > 6 mm (OR 5.3, 95% CI 1.4-25; p = 0.03) proved to be significant in the decision to intervene. At a median follow-up of 18.1 months, 94.7% of the lesions treated with intervention healed completely compared with 19% of aneurysms in the medical group. Among those medically managed that did not resolve, the median change in diameter was -0.4 mm (IQR -1.8 to 0.4 mm). Age ≤ 50 years and aneurysm maximum diameter ≤ 6 mm predicted healing at follow-up in the medical group with 92% specificity and 65% sensitivity (area under the curve 0.87). At follow-up, 98% of patients were functionally independent (modified Rankin Scale score ≤ 2). CONCLUSIONS: Medical management alone is safe for most extracranial pseudoaneurysms, resulting in significantly fewer complications than endovascular intervention. Maximum diameter ≤ 6 mm and age ≤ 50 years were significant predictors of pseudoaneurysm resolution with medical therapy alone. Lesions that do not heal do not cause further symptoms or require additional intervention.

National Trends in Aspirin Use and Expenditures in the United States: Analysis of The Medical Expenditure Panel Survey 2000-2021.

INTRODUCTION: Since its invention in 1897, aspirin (ASA) has been the most widely used and cost-effective antiplatelet agent to prevent and treat atherosclerotic cardiovascular disease (ASCVD). We aimed to study the trends and expenditures associated with ASA use in the USA. METHODS: We conducted a serial cross-sectional analysis using the Medical Expenditure Panel Survey data from January 2000 to December 2021, focusing on adults aged ≥ 40 years. Total and out-of-pocket expenditures associated with ASA were estimated to 2021 US dollars (USD). Trends, demographics, and predictors of ASA use among patients with and without ASCVD were also evaluated. RESULTS: A total of 53 million adults were identified during the study period. The number of ASA users increased from 2.9 million to 6.6 million with increased female (36.7%-49.7%; p trend = 0.02) and African American (13%-18.9%; p trend = 0.03) representation amongst all ASA users during the survey period. The use of low-dose ASA increased, while high-dose ASA declined significantly. Only 50% of all ASA users had known ASCVD. The most prevalent ASA users among patients with ASCVD were those aged ≥ 70 years, while patients without ASCVD, it was the 50-69 age group. The total annual expenditure on ASA averaged approximately 60 million USD, with 27.3 million USD out-of-pocket. CONCLUSION: Total and low-dose (81 mg) ASA use has increased, while high-dose (325 mg) ASA has declined. ASA use for primary prevention has risen among adults aged 50-69 years, and patients ≥ 70 years continue to use ASA without known ASCVD. Further studies are needed to understand the implications of increased ASA use, especially among those without ASCVD.

[Screening and prevention of preeclampsia using the Fetal Medicine Foundation algorithm]. / Dépistage et prévention de la prééclampsie par l'algorithme de la Fetal Medicine Foundation: une étude avant-après.

OBJECTIVE: In order to identify women at high risk of pre-eclampsia and offer them aspirin prophylactic treatment, the Fetal Medicine Foundation (FMF) recommends a first-trimester screening test. The commonly used threshold for aspirin administration is a risk >1/100, which implies treating an important number of patients. We aimed to assess the use of this strategy with a more restrictive threshold: risk >1/70 and evaluate the impact of this strategy on the prevalence of pre-eclampsia with premature delivery in nulliparous women. METHODS: A before-and-after cohort study conducted from 01/09/2014 to 01/12/2018, including nulliparous women undergoing first-trimester ultrasound at the University Hospital of Toulouse. Between 09/2014 and 09/2016 ("before cohort"), women did not undergo pre-eclampsia screening. Between 01/2017 and 12/2018 ("after cohort"), women underwent targeted pre-eclampsia screening using the FMF algorithm, and those with a risk >1/70 received 100mg aspirin. The primary outcome was pre-eclampsia with premature delivery. A univariate and then a multivariate analysis were performed to take into account potential confounding factors. RESULTS: Among the 1030 women of the before cohort, 17 women (1.7%) experienced pre-eclampsia with premature delivery, compared to 8 women (1.3%) among the 629 of the after cohort, with no significant difference between the two groups (Adjusted Odd Ratio (95%CI) = 0.73 [0.31-1.74]). In the after cohort, 18 women (2.9%) had a risk greater than 1/70 and therefore received aspirin. According to the FMF screening test, 89 women (14.1%) had a risk > 1/100, which is the usual threshold for prescribing aspirin for prophylaxis. This means that 71 women had a risk greater than 1/100 but less than 1/70 and therefore did not receive aspirin in this study, even though they would have received aspirin at the usual threshold. CONCLUSIONS: The screening and prevention strategy for pre-eclampsia using restrictive thresholds did not decrease the rate of preeclampsia with premature delivery.

How can we reduce maternal mortality due to preeclampsia? The 4P rule.

In low and middle-income countries such as Brazil, most maternal deaths are related to hypertensive complications. Preeclampsia is the leading cause of maternal mortality and morbidity. Significant proportion is associated with the following factors: lack of identification of high-risk women, lack of adequate prevention, difficulty in maintaining a high-risk prenatal follow-up, delayed diagnosis, insecurity and low use of magnesium sulphate, delayed pregnancy interruption and lack of postpartum follow-up of these high-risk cases. Four major actions are proposed to minimize this alarming clinical picture and reduce the mortality rates due to preeclampsia, called the "4 P Rule" (Adequate Prevention - Vigilant Prenatal Care - Timely Delivery (Parturition) - Safe Postpartum). From this simple "rule" we can open a range of important processes and reminders that may help in the guidance of preeclampsia management.

Aspirin in Children; are There Not Two Sides of the Same Coin?

Dose-dependent in vitro effects of aspirin on platelet inhibition and predictors of non-responsiveness have led to the recommendation of significantly higher doses of aspirin (5 mg/kg/day) in newborns and infants. The results are inconsistent with the pharmacodynamic effects of clopidogrel in newborns, where approximately 30% (0.2 mg/kg/day) of the adult dose (75 mg/day) showed equally effective antiaggregative effects. Consequently, the optimal aspirin dosage remains to be determined. The administration to newborns with congenital heart defects needs to address treatment goals, while accounting for the intricate interactions between platelets and endothelium, as well as the unique aspects of surgical and interventional procedures.

125 Years of Aspirin: Status of Analytical Methods.

Aspirin, an analgesic, antipyretic and non-steroidal anti-inflammatory drug, was a fascinating discovery that became the precursor to one of the oldest pharmaceutical success stories. It was discovered in 1899 by Felix Hoffman and patented in 1900. In 2024, Aspirin turns 125 years old and is still one of the bestselling medicines today. This review aims to celebrate 125 years of Aspirin and show the status of analytical methods available in the literature to evaluate pharmaceutical products based on Acetylsalicylic Acid (ASA). In addition, it contextualizes them with the current needs of green and clean analytical chemistry. ASA, despite being consolidated in the consumer market, embraces continuous improvement as it is a fundamental part of studies for other new purposes and studies with associations with other active ingredients. In the manuscripts available in the literature, ASA is predominantly evaluated by HPLC (41%) and UV-Vis (41%) methods, which use methanol (21.82%) and acetonitrile (18.18%), followed by buffer (16.36%). The most evaluated pharmaceutical matrix is ASA tablets (40%), followed by ASA tablets in combination with other drugs (26%). While ASA continues to innovate in the market through new forms of delivery and combinations, as well as intended purposes, the analytical methods for evaluating its pharmaceutical products do not. They continue with non-eco-efficient analytical options, which can significantly improve and meet the current demand for green and sustainable analytical chemistry.

Comparison of 75 mg versus 150 mg aspirin for the prevention of preterm preeclampsia in high-risk women at a tertiary level hospital: study protocol for a randomized double-blind clinical trial.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) pose significant risks to maternal and fetal health, with substantial mortality and morbidity rates globally, particularly in developing countries. Pre-eclampsia (PE) accounts for a notable portion of maternal morbidity and mortality, with varied prevalence across regions within countries like India. Despite advancements, disparities in healthcare access persist, influencing outcomes. PE not only affects maternal health during pregnancy but also predisposes women to long-term cardiovascular complications, emphasizing the need for early screening and preventive measures. METHODS: This prospective randomized double-blind clinical trial aims to compare the efficacy and safety of 75 mg versus 150 mg aspirin for preventing preterm pre-eclampsia in high-risk women. Screen-positive women aged 18-45 years with singleton pregnancies between 12 and 16 weeks of gestational age will be enrolled. They will be randomized in a 1:1 ratio to receive either 75 mg or 150 mg of aspirin nightly until 37 weeks of pregnancy or earlier if preterm pre-eclampsia develops. Feto-maternal outcomes, including preterm pre-eclampsia incidence and neonatal and maternal complications, will be assessed. The sample size calculation based on expected proportions of preterm pre-eclampsia in both groups indicates a total of 370 participants (185 per group) accounting for 20% attrition. DISCUSSION: This prospective randomized double-blind clinical trial aims to compare the effectiveness and safety of two doses of aspirin (75 mg vs 150 mg) in preventing preterm pre-eclampsia in high-risk women. The potential implications of this study are significant, including the optimization of aspirin prophylaxis, the development of evidence-based guidelines, and comprehensive assessment of maternal and fetal outcomes. In conclusion, the results of this study have the potential to significantly impact clinical practice by enhancing maternal and perinatal health outcomes and contributing to evidence-based obstetric care. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2023/12/060983. Trial was registered prospectively on 29 December 2023. Acknowledgement Number REF/2023/12/076358. https://acrobat.adobe.com/id/urn:aaid:sc:AP:15870322-f1f4-4460-900c-6e056ab83a44 .

Multicenter retrospective cohort study demonstrates superior safety profile of indobufen over aspirin for Post-CABG antiplatelet therapy.

Objectives: Coronary artery bypass grafting (CABG) is essential for treating coronary artery disease, with postoperative aspirin crucial to prevent graft restenosis. However, its gastrointestinal side effects may limit tolerability in some patients. Indobufen presents a potential alternative, but its safety and efficacy need further validation. This study aimed to compare the efficacy and safety of indobufen versus aspirin in patients' post-CABG. Methods: This retrospective observational study included 39 patients who underwent CABG at two centers from January to December 2023. Patients were retrospectively assigned to two groups based on the antiplatelet therapy they received: the indobufen group (n = 19) and the aspirin group (n = 20). The primary endpoint was a composite of non-fatal myocardial infarction, stroke, and revascularization due to acute coronary syndrome in the intention-to-treat population. Postoperative data on platelet count, hemoglobin, D-dimer, activated partial thromboplastin time (APTT), and hospital stay length were collected. Transfusion rate, bleeding, thrombotic events, and gastrointestinal adverse reactions were compared between the two groups. Results: Over the 8-to-18-month follow-up period, 5 patients (25%) in the aspirin group reached the primary endpoint, while none in the indobufen group did, a difference that was statistically significant (p = 0.02). Although the rates of non-fatal myocardial infarction, revascularization, stroke, and thrombotic events were higher in the aspirin group, these differences did not reach statistical significance. Importantly, the total bleeding events were markedly lower in the indobufen group (15.79% vs. 55%, p = 0.011), with major bleeding events also significantly reduced in the indobufen group (0% vs. 20%, p = 0.04). Both groups showed no significant differences were observed in postoperative hospital stay, hemoglobin, and D-dimer levels between the groups. However, the indobufen group demonstrated significantly lower platelet count and APTT. The average daily cost of indobufen was 27.8 times higher than that of aspirin. Conclusion: Indobufen demonstrates a comparable antiplatelet effect to aspirin and offers significant advantages in reducing gastrointestinal adverse reactions and bleeding risk. It can be considered a preferable alternative for patients who cannot tolerate or have contraindications to aspirin. Further large-scale clinical trials are needed to confirm its potential as the first-choice antiplatelet therapy post-CABG.

ADVERSE EVENTS in PATIENTS with CARDIOVASCULAR DISEASE TAKING PROTON PUMP INHIBITORS.

INTRODUCTION: Proton pump inhibitors (PPIs) rank among the most frequently prescribed medications to treat acid-related diseases. Mounting concerns surround the potential for serious adverse events, including cardiovascular events, associated with their prolonged use/misuse. AREAS COVERED: This comprehensive review explores cardiovascular adverse events linked to PPI use among high-risk cardiovascular patients. A structured search was conducted on PubMed. EXPERT OPINION: Many patients with cardiovascular disease who require antiplatelet treatment will require long-term PPI treatment. Interpreting the published data is not straightforward. First, because there is no plausible mechanistic explanation for PPIs to induce cardiovascular events apart from the potential interaction with the metabolism of thienopyridines. Although several observational studies have shown an increased cardiovascular risk and mortality in patients taking long-term PPIs, most available clinical trials and meta-analyses of available studies do not. However, the absence of firm evidence of this link does not necessarily imply that this association does not exist, and other hypothesis must be explored. Anemia is a common event in patients who take antiplatelet therapy and PPIs, and it is a factor associated with cardiovascular events and death. Anemia in these patients is often attributed to erosive lesions of the small intestine, where PPI may play a key role by modifying the microbiota.

Low-Dose Aspirin and Risk of Anaemia in Older Adults: Insights from a Danish Register-based Cohort Study.

AIMS: To assess the risk of anaemia among low-dose aspirin (LDA) exposure in Danish older individuals in a real-world setting. METHODS: Population based-cohort study conducted using Danish registers. The study population included older individuals (≥65 years) exposed to LDA between 2008 and 2013 for primary or secondary prevention of cardiovascular events. Over a five-year follow-up, outcomes included anaemia incidence based on haemoglobin values and hematinic deficiency incidence based on antianemic prescriptions. RESULTS: Among the 313 508 individuals included in the study population, those exposed to LDA (n = 59 869, 19.1%) had an incidence of hematinic deficiency determined by the use of antianemic treatment of 9.6%, with an incidence rate ratio of 9.11 (95% Confidence Interval, CI: 8.81-9.41) when compared to non-users of LDA (n = 253 639, 80.9%), who had an incidence of 3.7%. Anaemia determined by haemoglobin value measurements was observed in 5.9% of those exposed to LDA, with an incidence rate ratio of 7.89 (95% CI: 7.58-8.21) when compared to non-users of LDA. Approximately one in five individuals (n = 2 422, 21.5%) who experienced anaemia also experienced bleeding. Severe anaemia was observed in 1.3% of those exposed to LDA compared to 0.6% of those not exposed. Among the exposed, the reduction in haemoglobin and ferritin levels was associated with the severity of anaemia. CONCLUSION: These findings indicate that in a real-world setting, anaemia with LDA can occur in 6 to 10 older individuals out of every 100 LDA users during the first 5 years of treatment.

Platelet Proteomics and Tissue Metabolomics Investigation for the Mechanism of Aspirin Eugenol Ester on Preventive Thrombosis Mechanism in a Rat Thrombosis Model.

Platelet activation is closely related to thrombosis. Aspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterifying aspirin with eugenol using the pro-drug principle. Pharmacological and pharmacodynamic experiments showed that AEE has excellent anti-inflammatory, antioxidant, and inhibitory platelet activation effects, preventing thrombosis. However, the regulatory network and action target of AEE in inhibiting platelet activation remain unknown. This study aimed to investigate the effects of AEE on platelets of thrombosed rats to reveal its regulatory mechanism via a multi-omics approach. The platelet proteomic results showed that 348 DEPs were identified in the AEE group compared with the model group, of which 87 were up- and 261 down-regulated. The pathways in this result were different from previous results, including mTOR signaling and ADP signaling at P2Y purinoceptor 12. The metabolomics of heart and abdominal aortic tissue results showed that the differential metabolites were mainly involved in steroid biosynthesis, the citric acid cycle, phenylalanine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and glutathione metabolism. Molecular docking results showed that AEE had a better binding force to both the COX-1 and P2Y12 protein. AEE could effectively inhibit platelet activation by inhibiting COX-1 protein and P2Y12 protein activity, thereby inhibiting platelet aggregation. Therefore, AEE can have a positive effect on inhibiting platelet activation.

Hypertensive Disorders of Pregnancy in Saudi Arabia: Evaluating Maternal and Neonatal Risks, Outcomes, and Aspirin Prophylaxis: A Review Article.

Hypertensive disorders during pregnancy, including pre-eclampsia and eclampsia, pose significant risks to both maternal and neonatal health. This review article evaluates the prevalence, maternal and neonatal outcomes, and the efficacy of aspirin prophylaxis in managing these conditions in Saudi Arabia. Utilizing data from multiple retrospective studies and recent guidelines, we highlight the regional variations in the outcomes of hypertensive disorders of pregnancy. Severe complications such as Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome occurred in 6.6% of cases, while eclampsia was reported in 6.7% of cases. Cesarean sections were notably high, with rates reaching up to 79% among affected pregnancies. Maternal risk factors identified include chronic hypertension (prevalence 17%), diabetes (ranging from 10.4% to 26.3%), and advanced maternal age. Neonatal complications often involve preterm birth, reported in 26.5% to 26.7% of cases, intrauterine growth restriction (ranging from 15.7% to 25%), and increased NICU admissions, reported in 2.4% of cases. No data were found in the included studies to evaluate the prophylactic use of low-dose aspirin in reducing the incidence of pre-eclampsia or improving fetomaternal outcomes. Despite the effectiveness of aspirin, awareness and implementation of prophylaxis guidelines remain suboptimal among healthcare providers in Saudi Arabia. A national survey revealed that only a fraction of obstetrical care providers were fully knowledgeable about aspirin prophylaxis guidelines. This review underscores the necessity for enhanced educational programs and standardized guidelines to improve maternal and neonatal outcomes in hypertensive pregnancies within the region.

Highly specific screening of aspirin resistance-related single-nucleotide polymorphisms using ligase chain reaction strategy.

Aspirin (ASP) is currently the drug of choice for antiplatelet therapy. However, approximately 5%-45 % of patients are resistant to ASP and do not achieve the expected result. At present, a few studies have investigated the correlation between ASP resistance (AR) and single-nucleotide polymorphism (SNP). Traditional detection methods are time-consuming and laborious, affecting the accuracy of personalized medicine. This study aimed to establish a new assay to identify four SNPs associated with AR. A large amount of double-stranded DNA was formed after multiple cycles of specific exponential amplification by ligase chain reaction, the specific melting peak of which was visible in the detection curve, with a detection limit of 10-11mol/L. The specificity experiments of different proportions of wild-type and mutant plasmid standards showed that the novel method could detect up to 1 % allele frequency and the specificity was good. Clinical blood samples of 57 patients were tested in this study. The results were consistent with those of sequencing and more accurate and reliable than those of the high-resolution melting method. The technique used in this study was simple, sensitive and specific compared with the traditional method. Statistical analysis revealed that AR was significantly correlated with the rs12041331 site of the PEAR1 gene and the rs1695 site of the GSTP1 gene, providing an important reference value for the study of AR.