Effect Of Aspirin Research Articles

IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer.

Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer. Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry. In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p=.008) and tumor-infiltrating lymphocyte infiltration was higher (p=.02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p=.001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p=.027 and p=.034, respectively). These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.

Inflammation and platelet reactivity during adjunctive colchicine versus aspirin in patients with acute coronary syndrome treated with potent P2Y12 inhibitor.

In patients undergoing percutaneous coronary intervention (PCI), the use of anti-inflammatory therapy with colchicine is associated with a reduction of recurrent ischemic events. The mechanisms of such findings are not fully elucidated. To investigate the effects of colchicine versus aspirin on inflammation and platelet reactivity in patients with acute coronary syndrome (ACS) undergoing PCI. This observational study compared laboratory measurements in ACS patients receiving single antiplatelet therapy with ticagrelor or prasugrel plus colchicine (MACT) (n = 185) versus conventional dual-antiplatelet therapy (DAPT) with aspirin plus ticagrelor or prasugrel (n = 497). The primary outcome was the frequency of high residual inflammation, defined as high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L at 1 month post-PCI. Multiple sensitivity analyses were performed for the primary outcome, including multivariable adjustment, propensity-score matching, and inverse-probability weighted methods. One month after PCI, patients treated with MACT had significantly lower levels of hs-CRP compared to those treated with DAPT (0.6 [0.4-1.2] vs. 0.9 [0.6-2.3] mg/L, p < 0.001). The frequency of high residual inflammation was also lower in the MACT group (10.8% vs. 27.2%, p < 0.001) (odds ratio [95% confidence interval] = 0.33 [0.20-0.54], p < 0.001). This effect was consistent across sensitivity analyses. There was no difference in platelet reactivity between MACT and DAPT (49.6 ± 49.0 vs. 51.5 ± 66.4 P2Y12 reaction unit [PRU] measured by VerifyNow, p = 0.776). In ACS patients undergoing PCI, MACT was associated with a lower rate of high residual inflammation without increasing platelet reactivity compared to conventional DAPT. NCT04949516 for MACT pilot trial and NCT04650529 for Gyeongsang National University Hospital registry.

Dose-Dependent Effect of Aspirin Use in Reducing Diabetes-Associated Dementia Risk Among Elderly Patients With Type 2 Diabetes Mellitus

ObjectiveThis study investigated the association between aspirin use and diabetes-associated dementia in older patients with type 2 diabetes mellitus (T2DM), assessing aspirin's potential protective effects, intensity of use, and dose-dependency against dementia. DesignA cohort study evaluating the dose-dependent protective impact of aspirin against dementia in a population-based sample. Setting and ParticipantsOlder patients with T2DM (≥60 years), comparing aspirin users with nonusers. MethodsUsed a time-varying Cox hazards model to assess dementia incidence. ResultsOlder aspirin users exhibited a significant reduction in dementia risk (adjusted hazard ratio [aHR], 0.44; 95% CI, 0.41–0.46). The lowest aHRs for dementia were observed at a daily intensity of 0.91 defined daily doses (DDDs), and higher daily dosages (>0.91 DDD) showed gradually increasing aHRs (although still <1). Analysis of cumulative DDD revealed a dose-response relationship, with progressively lower aHRs across quartiles (0.16, 0.42, 0.57, and 0.63 for quartiles 4, 3, 2, and 1, respectively) compared with never aspirin users (P for trend < .0001). Conclusions and ImplicationsAspirin use in older patients with T2DM significantly reduces dementia risk. The optimal daily intensity of aspirin use (0.91 DDD) is associated with the lowest aHR for dementia. These findings suggest a dose-dependent relationship, supporting the potential benefits of higher cumulative dosages of aspirin in reducing dementia risk in this population.

Low-dose aspirin for the prevention of preterm birth in nulliparous women: systematic review and meta-analysis

ObjectiveThe objective was to assess the efficacy and safety of low-dose aspirin for the prevention of preterm birth in nulliparous women.Data sourcesWe searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to June 2022.Study eligibility criteriaRandomized controlled trials that compared aspirin to placebo in nulliparous women were eligible.MethodsThis study was reported in accordance with the PRISMA 2020 checklist. The primary outcomes of this study were the rates of preterm birth at less than 37 weeks and less than 34 weeks of gestation. The secondary outcomes included postpartum hemorrhage, placental abruption, cesarean section, any hypertensive disorder of pregnancy and small for gestational age. Relative risks with their 95% confidence intervals were calculated for analysis. Heterogeneity was assessed by Cochran’s Q test and Higgins’s I2. A random-effects model was used when I2 was > 50% to generate the RR and 95% CI; otherwise, a fixed-effects model was used. The risk of publication bias was assessed by funnel plots. We performed sensitivity analysis by sequentially omitting each included study to confirm the robustness of the analysis.ResultsSeven studies with a total of 29,029 participants were included in this review. Six studies were assessed as having a low risk of bias or an unclear risk of bias, and one study was judged as having a high risk of bias. In nulliparous women, low-dose aspirin was associated with a significant reduction in the rate of preterm birth at less than 34 weeks of gestational age (RR 0.84,95% CI: 0.71–0.99; I2 = 0%; P = 0.04), but we did not observe a significant difference in the rate of preterm birth at less than 37 weeks of gestation (RR 0.96,95% CI: 0.90–1.02; I2 = 31%; P = 0.18). Low-dose aspirin was associated with a significant increase in the rates of postpartum hemorrhage (RR 1.32,95% CI: 1.14–1.54; I2 = 0%; P = 0.0003), placental abruption (RR 2.18,95% CI: 1.10–4.32; I2 = 16%; P = 0.02) and cesarean section (RR 1.053, 95% CI: 1.001–1.108; I2 = 0%; P = 0.05) in nulliparous women. We also did not observe a significant effect of low-dose aspirin on the rates of any hypertensive disorder of pregnancy (RR 1.05, 95% CI: 0.96–1.14; I2 = 9%; P = 0.28) or small for gestational age (RR 0.96, 95% CI: 0.91–1.02; I2 = 0%; P = 0.16) in nulliparous women. Funnel plots indicated that no significant publication bias existed in this meta-analysis. Except for preterm birth at less than 34 weeks of gestation, placental abruption and cesarean section, the sensitivity analysis showed similar results, which confirmed the robustness of this meta-analysis.ConclusionsLow-dose aspirin might reduce the risk of preterm birth at less than 34 weeks of gestation in nulliparous women. The use of low-dose aspirin in nulliparous women increased the risk of postpartum hemorrhage and might increase the risk of placental abruption and cesarean section.

Chitosan-Aspirin Combination Inhibits Quorum-Sensing Synthases (lasI and rhlI) in Pseudomonas aeruginosa.

Quorum sensing (QS) controls the virulence of P. aeruginosa. This study aims to determine the anti-QS activity of aspirin alone and in combination with chitosan to reach maximum inhibition. We tested ten virulent Pseudomonas aeruginosa (P. aeruginosa) isolates and screened for N-acyl homoserine lactone (AHL) production using Agrobacterium tumefaciens as a biosensor. P. aeruginosa isolates were treated with sub-minimum inhibitory concentrations (MICs) of aspirin and chitosan-aspirin. We used broth microdilution and checkerboard titration methods to determine the MICs and the synergistic effect of these two compounds, respectively. Real-time polymerase chain reaction (PCR) was used to estimate the anti-QS activity of the aspirin-chitosan combination on the expression of lasI and rhlI genes. Aspirin decreased the motility and production of AHLs, pyocyanin, and biofilm. Chitosan potentiated the inhibitory effect of aspirin. The chitosan-aspirin combination inhibited lasI and rhlI gene expression in PAO1 (ATCC 15692) by 7.12- and 0.92-fold, respectively. In clinical isolates, the expression of lasI and rhlI was decreased by 1.76 × 102- and 1.63 × 104-fold, respectively. Molecular docking analysis revealed that aspirin could fit into the active sites of the QS synthases lasI and rhlI with a high binding affinity, causing conformational changes that resulted in their inhibition. The chitosan-aspirin combination provides new insights into treating virulent and resistant P. aeruginosa.

Aspirin for preeclampsia prevention in low- and middle-income countries: mind the gaps

Preeclampsia is a syndrome that continues to be a major contributor to maternal and neonatal mortality, especially in low-income countries. Low-dose aspirin reduces the risk of preeclampsia, but the mechanism is still unknown. Risk factors to identify women at risk of preeclampsia are based on clinical characteristics. Women identified as high-risk would benefit from aspirin treatment initiated preferably at the end of the first trimester. Current efforts have largely focused on developing screening algorithms that incorporate clinical risk factors, maternal biomarkers, and uterine artery Doppler evaluated in the first trimester. However, most studies on preeclampsia are conducted in high-income settings, raising uncertainties about whether the information gained can be totally applied in low-resource settings. In low- and middle-income countries, lack of adequate antenatal care and late commencement of antenatal care visits pose significant challenges for both screening for preeclampsia and initiating aspirin treatment. Further, the preventive effect of first-trimester screening based on algorithms and subsequent aspirin treatment is primarily seen for preterm preeclampsia, and reviews indicate minimal or no impact on reducing the risk of term preeclampsia. The lack of evidence regarding the effectiveness of aspirin in preventing term preeclampsia is a crucial concern, as 75% of women will develop this subtype of the syndrome. Regarding adverse outcomes, low-dose aspirin has been linked to a possible higher risk of postpartum hemorrhage, a condition as deadly as preeclampsia in many low- and middle-income countries. The increased risk of postpartum hemorrhage among women in low-income settings should be taken into consideration when discussing which pregnant women would benefit from the use of aspirin and the ideal aspirin dosage for preventing preeclampsia. Additionally, women's adherence to aspirin during pregnancy is crucial for determining its effectiveness and complications, an aspect often overlooked in trials. In this review, we analyze the knowledge gaps that must be addressed to safely increase low-dose aspirin use in low- and middle-income countries and we propose directions for future research.

Performance of the first-trimester Fetal Medicine Foundation competing risks model for preeclampsia prediction: an external validation study in Brazil

Background: The current version of the Fetal Medicine Foundation competing risks model for preeclampsia prediction has not been previously validated in Brazil.Objectives: (1) To validate the Fetal Medicine Foundation combined algorithm for the prediction of preterm preeclampsia in the Brazilian population and (2) to describe the accuracy and calibration of the Fetal Medicine Foundation algorithm when considering the prophylactic use of aspirin, by clinical criteria.Study design: Cohort study, including consecutive singleton pregnancies undergoing preeclampsia screening at 11-14 weeks, examining maternal characteristics, medical history, and biophysical markers between October 2010 and December 2018 in a university hospital in Brazil. Risks were calculated using the 2018 version of the algorithm available on the Fetal Medicine Foundation website, and cases were classified as low- or high-risk using cut-off of 1/100 to evaluate predictive performance. Expected and observed cases with PE according to the FMF estimated risk range (≥1 in 10; 1 in 11 to 1 in 50; 1 in 51 to 1 in 100; 1 in 101 to 1 in 150; and <1 in 150) were compared. After identifying high-risk pregnant women who used aspirin, the treatment effect of 62% reduction in preterm preeclampsia identified in the ASPRE trial was used to evaluate the predictive performance adjusted for the effect of aspirin. The number of potentially unpreventable cases in the group without aspirin use was estimated.Results: Among 2,749 pregnancies, preterm preeclampsia occurred in 84 (3.1%). With a risk cut-off of 1/100, the screen-positive rate was 25.8%. The detection rate was 71.4%, with a false positive rate of 24.4%. The area under the curve was 0.818 (95% confidence interval 0.773 to 0.863). In the risk range ≥1/10, there is an agreement between the number of expected and observed cases, and in the other ranges, the predicted risk was lower than the observed rates. Accounting for the effect of aspirin resulted in an increase in detection rate and positive predictive values and a slight decrease in the false positive rate. With 27 cases of preterm preeclampsia in the high-risk group without aspirin use, we estimate that 16 of these cases of preterm preeclampsia would have been avoided if this group had received prophylaxis.Conclusions: In a high prevalence setting, the Fetal Medicine Foundation algorithm can identify women who are more likely to develop preterm preeclampsia. Not accounting for the effect of aspirin underestimates the screening performance.

Mobile phone text messaging for medication adherence in secondary prevention of cardiovascular disease.

Mobile phone text messaging for medication adherence in secondary prevention of cardiovascular disease.

Analysis of the Effectiveness of Clopidogrel Combined with Aspirin in the Treatment of Coronary Heart Disease in Community-Dwelling Elderly

Objective: To analyze the combined therapeutic effect of clopidogrel (CLO) and aspirin (ASP) on coronary heart disease (CHD) in community-dwelling elderly. Methods: Thirty elderly patients with CHD who were admitted to the Xinxin Community Health Service Station, Pangzhuang Street, Quanshan District, Xuzhou City, from November 2020 to November 2022 were selected and randomly grouped into an observation group and a control group, with 15 cases in each group. The observation group was given the combination of CLO and ASP and the reference group was given only ASP. The total effective rate and other treatment indicators between the two groups were compared. Results: The total effective rate of the observation group (93.33%) was higher than that of the reference group (60.00%) (P &lt; 0.05). The adverse drug reaction rate (13.33%) and long-term cardiovascular adverse event rate (6.67%) of the observation group were lower than those of the reference group at 46.67% and 40.00% respectively, (P &lt; 0.05). Before treatment, the two groups had no difference in the quality-of-life scores (P &gt; 0.05). After treatment, the quality-of-life scores of the observation group were higher than those of the reference group (P &lt; 0.05). Conclusion: CLO combined with ASP improved the therapeutic effect of community-dwelling elderly patients with CHD, reduced adverse reactions during medication, prevented adverse cardiovascular events, and comprehensively improved the patient’s quality of life.

Effect of Centhaquine on the Coagulation Cascade in Normal State and Uncontrolled Hemorrhage: A Multiphase Study Combining Ex Vivo and In Vivo Experiments in Different Species.

Centhaquine is a novel vasopressor acting on α2A- and α2B-adrenoreceptors, increasing venous return and improving tissue perfusion. We investigated the effects of centhaquine on blood coagulation in normal state and uncontrolled hemorrhage using ex vivo and in vivo experiments in different species. Thromboelastography (TEG) parameters included clotting time (R), clot kinetics [K and angle (α)], clot strength (MA), and percent lysis 30 min post-MA (LY30). In normal rat blood, centhaquine did not alter R, K, α, MA, or LY30 values of the normal vehicle group or the antithrombotic effects of aspirin and heparin. Subsequently, New Zealand white rabbits with uncontrolled hemorrhage were assigned to three resuscitation groups: Sal-MAP 45 group (normal saline to maintain a mean arterial pressure, MAP, of 45 mmHg), Centh-MAP 45 group (0.05 mg kg-1 centhaquine plus normal saline to maintain a MAP of 45 mmHg), and Sal-MAP 60 group (normal saline to maintain a MAP of 60 mmHg). The Sal-MAP 45 group was characterized by no change in R, reduced K and MA, and increased α. In the Centh-MAP 45 group, TEG showed no change in R, K, and α compared to saline; however, MA increased significantly (p = 0.018). In the Sal-MAP 60 group, TEG showed no change in R, an increase in α (p < 0.001), a decrease in K (p < 0.01), and a decrease in MA (p = 0.029) compared to the Centh-MAP 45 group. In conclusion, centhaquine does not impair coagulation and facilitates hemostatic resuscitation.

Aspirin for Metabolic Dysfunction–Associated Steatotic Liver Disease Without Cirrhosis

ImportanceAspirin may reduce severity of metabolic dysfunction–associated steatotic liver disease (MASLD) and lower the incidence of end-stage liver disease and hepatocellular carcinoma, in patients with MASLD. However, the effect of aspirin on MASLD is unknown.ObjectiveTo test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD.Design, Setting, and ParticipantsThis 6-month, phase 2, randomized, double-blind, placebo-controlled clinical trial was conducted at a single hospital in Boston, Massachusetts. Participants were aged 18 to 70 years with established MASLD without cirrhosis. Enrollment occurred between August 20, 2019, and July 19, 2022, with final follow-up on February 23, 2023.InterventionsParticipants were randomized (1:1) to receive either once-daily aspirin, 81 mg (n = 40) or identical placebo pills (n = 40) for 6 months.Main Outcomes and MeasuresThe primary end point was mean absolute change in hepatic fat content, measured by proton magnetic resonance spectroscopy (MRS) at 6-month follow-up. The 4 key secondary outcomes included mean percentage change in hepatic fat content by MRS, the proportion achieving at least 30% reduction in hepatic fat, and the mean absolute and relative reductions in hepatic fat content, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Analyses adjusted for the baseline value of the corresponding outcome. Minimal clinically important differences for study outcomes were not prespecified.ResultsAmong 80 randomized participants (mean age, 48 years; 44 [55%] women; mean hepatic fat content, 35% [indicating moderate steatosis]), 71 (89%) completed 6-month follow-up. The mean absolute change in hepatic fat content by MRS was −6.6% with aspirin vs 3.6% with placebo (difference, −10.2% [95% CI, −27.7% to −2.6%]; P = .009). Compared with placebo, aspirin treatment significantly reduced relative hepatic fat content (−8.8 vs 30.0 percentage points; mean difference, −38.8 percentage points [95% CI, −66.7 to −10.8]; P = .007), increased the proportion of patients with 30% or greater relative reduction in hepatic fat (42.5% vs 12.5%; mean difference, 30.0% [95% CI, 11.6% to 48.4%]; P = .006), reduced absolute hepatic fat content by MRI-PDFF (−2.7% vs 0.9%; mean difference, −3.7% [95% CI, −6.1% to −1.2%]; P = .004]), and reduced relative hepatic fat content by MRI-PDFF (−11.7 vs 15.7 percentage points; mean difference, −27.3 percentage points [95% CI, −45.2 to −9.4]; P = .003). Thirteen participants (32.5%) in each group experienced an adverse event, most commonly upper respiratory tract infections (10.0% in each group) or arthralgias (5.0% for aspirin vs 7.5% for placebo). One participant randomized to aspirin (2.5%) experienced drug-related heartburn.Conclusions and RelevanceIn this preliminary randomized clinical trial of patients with MASLD, 6 months of daily low-dose aspirin significantly reduced hepatic fat quantity compared with placebo. Further study in a larger sample size is necessary to confirm these findings.Trial RegistrationClinicalTrials.gov Identifier: NCT04031729

Is Low Dose Aspirin Reduced the Risk of Preeklampsia?

Background: The maternal mortality rate is the number of maternal deaths resulting from pregnancy, childbirth and postpartum processes, which is an indicator of women's health status. Efforts that can be made to accelerate the reduction in maternal mortality are by ensuring that every mother is able to access quality health services. Low-dose aspirin has been proven to be a safe and effective primary prevention of preeclampsia. This study aims to determine the effect of low dose aspirin on the incidence of preeclampsia.&#x0D; Subjects and Method: Cross sectional research was conducted at the Community Health Center, Blora, Central Java, Indonesia. A sample of 200 pregnant women was selected using random sampling. The dependent variable is preeclampsia. The independent variables are age, income, aspirin consumption, primigravida, multigravida and hypertension. Data were collected by questionnaire and analyzed by multiple logistic regression.&#x0D; Results: The results of logistic regression analysis in this study concluded that the risk of preeclampsia increased at age &lt;20 years or ≥35 years (OR= 4.62; 95% CI= 1.89 to 11.28; p= 0.001), gravida 2-3 (OR= 3.03; CI 95 %= 1.01 to 9.05; p= 0.047), gravida ≥3 (OR= 4.41; 95% CI= 1.07 to 18.18; p= 0.040) and history of hypertension (OR= 2.41; 95% CI= 1.02 to 5.69; p= 0.005 ). The risk of preeclampsia decreased with income &gt; IDR 2,000,000 (OR= 0.44; 95% CI= 0.22 to 0.87; p= 0.019) and administration of low-dose aspirin (OR= 0.13; 95% CI= 0.05 to 0.35; p &lt;0.001).&#x0D; Conclusion: The risk of preeclampsia increases with age, gravida 2-3, gravida ≥3 and history of hypertension. The risk of preeclampsia decreases with high income and administration of low-dose aspirin.&#x0D; Keywords: preeclampsia, maternal age, hypertension.&#x0D; Correspondence: Era Kurniati. Masters Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta, Central Java 57126, Indonesia. Email: erakurnia3@gmail.com. Mobile: 081325639317.

Effectiveness of Aspirin on Major COPD Outcomes: A Prevalent New-User Design Observational Study

Observational studies that have reported an association between aspirin use in chronic obstructive pulmonary disease (COPD) with reductions in mortality and COPD exacerbations were shown to be affected by time-related biases. We assessed this association using a prevalent new-user study design that avoids these biases. We used the United Kingdom’s Clinical Practice Research Datalink (CPRD) to form a cohort of patients with COPD. Aspirin initiators were matched on time and propensity score with nonusers during 2002–2018. The outcomes were all-cause mortality and COPD exacerbation within a one-year follow-up. Hazard ratios (HR) and 95% confidence interval (CI) of each outcome associated with aspirin use compared to nonuse were estimated using an as-treated approach. The study cohort included 10,287 initiators of aspirin and 10,287 matched nonusers. The cumulative incidence of all-cause mortality at one year was 11.5% for aspirin users and 9.2% for nonusers. The HR of all-cause mortality associated with aspirin initiation was 1.22 (95% CI: 1.08–1.37), while for severe exacerbation it was 1.21 (95% CI 1.08–1.37), compared with nonuse. The HR of a first moderate or severe exacerbation with aspirin use was 0.90 (95% CI 0.85–0.95). These estimates did not vary by platelet count. This large population-based study, designed to emulate a trial, found aspirin use in patients with COPD associated with a higher risk of all-cause mortality and severe exacerbation, but a lower risk of moderate or severe exacerbation. Further research is warranted to assess this reduction in moderate or severe exacerbations, particularly in patients with cardiovascular risk factors.

Effect of aspirin on cardiovascular events in patients undergoing hemodialysis with hyperphosphatemia: A post hoc analysis of the LANDMARK trial.

The clinical benefits of aspirin in patients undergoing hemodialysis remain unclear. The secondary analysis of the LANDMARK trial investigated whether aspirin use was associated with cardiovascular events (CVEs) and all-cause mortality was performed. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity score matching. The risk of CVEs was comparable between participants with aspirin use at baseline and those without at baseline, between participants with aspirin use during the study period and those without during the study period, and between participants with new aspirin prescription and those without aspirin use during the study period. Aspirin use was not significantly associated with a lower risk of CVEs in participants undergoing hemodialysis patients at risk of vascular calcification.

The IRELAnD study—investigating the role of early low-dose aspirin in diabetes mellitus: a double-blinded, placebo-controlled, randomized trial

Although aspirin therapy is being increasingly advocated with the intention of risk modification for a wide range of pregnancy complications, women with prepregnancy diabetes mellitus are commonly excluded from clinical trials. The primary aim of this study was to examine the effect of aspirin therapy on a composite measure of adverse perinatal outcome in pregnancies complicated by pregestational diabetes mellitus. A double-blinded, placebo-controlled randomized trial was conducted at 6 university-affiliated perinatology centers. Women with type 1 diabetes mellitus or type 2 diabetes mellitus of at least 6 months' duration were randomly allocated to 150-mg daily aspirin or placebo from 11 to 14 weeks' gestation until 36 weeks. Established vascular complications of diabetes mellitus, including chronic hypertension or nephropathy, led to exclusion from the trial. The primary outcome was a composite measure of placental dysfunction (preeclampsia, fetal growth restriction, preterm birth <34 weeks' gestation, or perinatal mortality). The planned sample size was 566 participants to achieve a 35% reduction in the primary outcome, assuming 80% statistical power. Secondary end points included maternal and neonatal outcomes and determination of insulin requirements across gestation. Data were centrally managed using ClinInfo and analyzed using SAS 9.4. The 2 treatment groups were compared using t tests or chi-square tests, as required, and longitudinal data were compared using a repeated-measures analysis. From February 2020 to September 2022, 191 patients were deemed eligible, 134 of whom were enrolled (67 randomized to aspirin and 67 to placebo) with a retrospective power of 64%. A total of 101 (80%) women had type 1 diabetes mellitus and 25 (20%) had type 2 diabetes mellitus. Reaching the target sample size was limited by the impact of the COVID-19 pandemic. Baseline characteristics were similar between the aspirin and placebo groups. Treatment compliance was very high and similar between groups (97% for aspirin, 94% for placebo). The risk of the composite measure of placental dysfunction did not differ between groups (25% aspirin vs 21% placebo; P=.796). Women in the aspirin group had significantly lower insulin requirements throughout pregnancy compared with the placebo group. Insulin requirements in the aspirin group increased on average from 0.7 units/kg at baseline to 1.1 units/kg by 36 weeks' gestation (an average 83% within-patient increase), and increased from 0.7 units/kg to 1.3 units/kg (a 181% within-patient increase) in the placebo group, over the same gestational period (P=.002). Serial hemoglobin A1c levels were lower in the aspirin group than in the placebo group, although this trend did not reach statistical significance. In this multicenter, double-blinded, placebo-controlled randomized trial, aspirin did not reduce the risk of adverse perinatal outcome in pregnancies complicated by prepregnancy diabetes mellitus. Compared with the placebo group, aspirin-treated patients required significantly less insulin throughout pregnancy, indicating a beneficial effect of aspirin on glycemic control. Aspirin may exert a plausible placenta-mediated effect on pregestational diabetes mellitus that is not limited to its antithrombotic properties.

Protective Effects of Aspirin Supplemented With Quercetin in L-NAME-Induced Preeclampsia-Like Rats.

Aspirin supplemented with quercetin was reported to enhance the therapeutic effects of aspirin in a rat model of preeclampsia. In this study, the underlying mechanisms were further explored. Preeclampsia was induced by L-NAME (50 mg/kg/day) via oral gavage from gestation day (GD)14 to GD19. Aspirin (1.5 mg/kg/day) administration was performed using aspirin mixed with rodent dough from GD0 to GD19. The administration of quercetin (2 mg/kg/day) was performed by intraperitoneal infusion from GD0 to GD19. Protein levels were evaluated using ELISA or Western blot, and microRNA (miRNA) level was evaluated by RT-PCR. Aspirin supplemented with quercetin ameliorated the increase of systolic blood pressure (SBP), proteinuria, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels, and improved the pregnancy outcomes in preeclampsia rats. Aspirin supplemented with quercetin inhibited miR-155 expression in preeclampsia rats. The decreased miR-155 level in placenta further increased the protein level of SOCS1 and inhibited the phosphorylation of p65. In this study, we demonstrated that aspirin supplemented with quercetin enhanced the effects of aspirin for the treatment of preeclampsia.

Clinical features of recurrent preeclampsia: a retrospective study of 109 recurrent preeclampsia patients.

Our study aimed to investigate the clinical features of recurrent preeclampsia (rPE) and evaluate the preventive effect of low-dose aspirin (LDA) in rPE. We retrospectively analyzed the data of 109 patients who experienced preeclampsia in two consecutive pregnancies and delivered at Peking University First Hospital from January 2016 to December 2022. We analyzed the pregnancy outcomes of patients with rPE and assessed whether the use of LDA during pregnancy could improve these outcomes. Our results revealed that patients with rPE had a higher body mass index (BMI) and a higher incidence of diabetes during pregnancy compared to their first onset of preeclampsia (29.01 ± 4.70 kg/m2 vs. 27.13 ± 4.25 kg/m2, P < 0.05; 11.01% vs. 1.83%, P < 0.05). Furthermore, the incidence of severe preeclampsia was higher at recurrence in patients with rPE compared to their first onset (83.49% vs. 70.64%, P < 0.05), as well as the incidence of severe preeclampsia with chronic hypertension (34.86% vs. 8.26%, P < 0.05). Additionally, the incidence of gestational diabetes and postpartum hemorrhage was higher in patients with rPE compared to their first preeclampsia onset (25.69% vs. 5.50%, P < 0.05; 20.18% vs. 5.83%, P < 0.05). Compared to the first onset of preeclampsia, patients with rPE had an earlier gestational age at delivery (35.42 ± 3.06 weeks vs. 36.60 ± 2.74 weeks, P < 0.05), lower birth weight of neonates (2478.39 ± 828.44 g vs. 2883.71 ± 712.94 g, P < 0.05), and a higher risk of premature birth (67.00% vs. 47.19%, P < 0.05). However, in patients with rPE, the use of LDA delayed the gestational age at delivery, increased the birth weight of the neonate, reduced the premature birth rate, and increased the perinatal survival rate. In conclusion, patients with rPE are at an increased risk of adverse maternal and fetal outcomes. However, the use of LDA during pregnancy effectively improves these outcomes.

Abstract A089: Influence of pre-diagnosis aspirin use on epithelial ovarian cancer tumor immune microenvironment markers: results from the Nurses’ Health Study (NHS) and NHSII

Abstract Background: Daily aspirin use versus never use is associated with a 10-20% lower risk of developing epithelial ovarian cancer (EOC). Among women with EOC, aspirin use after diagnosis compared with never use is associated with a 30% improvement in ovarian cancer-specific survival. Inhibition of enzymes in prostaglandin synthesis is a key mechanism responsible for the anti-inflammatory and anti-neoplastic effects of aspirin. Prostaglandins influence immune inflammatory cells in the tumor microenvironment therefore our objective was to evaluate how aspirin use may influence the EOC tumor immune microenvironment. Methods: Tissue microarrays (TMAs) representing EOC tumor tissues from participants in the Nurses’ Health Study (NHS) and NHSII were assessed for total T cells, T cell activation and T cell exhaustion markers within the tumor (epithelium) area using multiplex immunofluorescence. Data on aspirin use and information on EOC risk factors and lifestyle variables were collected by questionnaire every two years. Beta-binomial models were used to estimate odds ratios (ORs) and 95% CIs; these models estimate the odds that a cell was positive for the marker(s) of interest comparing recent regular aspirin use (2+ times per week in the questionnaire cycle prior to diagnosis) versus never use, accounting for the total tumor cells in each core. Former users of aspirin were excluded. Multivariable models were adjusted for cohort, histotype (type 1 versus type 2), age and year of cancer diagnosis, number of CD3+ T cells (in tertiles), hysterectomy, tubal ligation, duration of oral contraceptive use, family history of breast or ovarian cancer, parity and body mass index (as fixed effects) and the participant (random effect) to account for multiple tissue cores per case. Results: We compared tumor tissues from 209 participants with recent pre-diagnosis use of aspirin with 88 participants who never used aspirin. Compared with cases who never used aspirin, recent aspirin users had higher odds of having tumors with recently activated cytotoxic T cells (CD3+CD8+CD69+, OR=1.69, 95% CI: 1.10, 2.59) and T cells expressing exhaustion markers (CD3+Lag-3+, OR=1.63, 95% CI: 1.09, 2.43; CD3+Tim-3+, OR= 1.62, 95% CI: 0.96, 2.72). In contrast, there was no association between recent aspirin use versus never use and odds of a tumor being positive for total T cells (CD3+, OR=1.20, 95% CI: 0.80, 1.79). Conclusions: Our data suggest that recent aspirin use before diagnosis was associated with higher odds of having EOC tumors expressing both recently activated cytotoxic T cells and T cell exhaustion markers. By improving our biological understanding of how aspirin use influences the ovarian tumor immune microenvironment, these results will assist to inform the optimal use of aspirin to improve EOC patient outcomes. Future work will focus on additional immune markers, assess non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use and evaluate associations between aspirin/NSAID use with EOC survival considering the context of tumor immune microenvironment biomarkers. Citation Format: Nicola S. Meagher, Cassandra Hathaway, Mary K. Townsend, Mollie E. Barnard, Jose R. Conejo-Garcia, Brooke L. Fridley, Daryoush Saeed-Vafa, Britton Trabert, Shelley S. Tworoger, Melissa A. Merritt. Influence of pre-diagnosis aspirin use on epithelial ovarian cancer tumor immune microenvironment markers: results from the Nurses’ Health Study (NHS) and NHSII [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A089.

Synergistic effects of omega-3 polyunsaturated fatty acids and aspirin in the clinical practice – a narrative review

Abstract The review aimed to illustrate the structure, role and effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) in combination with acetylsalicylic acid (aspirin, ASA) in various clinical cases. This verification of earlier single studies may be a guide in the further treatment of civilization diseases. The results of the presented narrative review suggest that aspirin supplementation with omega-3 fatty acids reduces pro-inflammatory biomarkers in sepsis and acute respiratory distress syndrome. Including adequate amounts of omega 3-PUFAs in therapy, rather than increasing the dose of acetylsalicylic acid, may contribute to beneficial effects in treating thrombosis and preventing myocardial infarction or other cardiovascular diseases, which is particularly important in aspirin-resistant patients. As suggested in the literature, a low daily dose of omega-3 fatty acids was effective in slowing the progression of kidney disease with IgA nephropathy. Aspirin supplementation with omega-3 fatty acids has improved clinical and immunological outcomes in the treatment of periodontitis or the therapy of colorectal cancer tumor lesions. The synergistic effect of both compounds is proposed as a new therapeutic option in the treatment of Parkinson’s disease. Further research into the synergistic effects of omega-3 fatty acids in combination with acetylsalicylic acid may provide a breakthrough in drug dose reduction, ultimately enabling more effective and safer pharmacotherapy for the patient. Therefore, studies on polyunsaturated fatty acids in combination with nonsteroidal anti-inflammatory drugs in vivo are needed.

The Effect of Aspirin and Ibuprofen on the Phagocytic Ability of Macrophages

The Effect of Aspirin and Ibuprofen on the Phagocytic Ability of Macrophages