Long-term Aspirin Research Articles

Association Between Low-Dose Aspirin Use and Colorectal Cancer Incidence in Taiwan

Population-based East Asian data have corroborated reports from non-Asian settings on the association between low-dose aspirin and a lower risk of colorectal cancer (CRC). To evaluate the association between duration and recency of low-dose aspirin use and CRC risk. This nested case-control study included individuals who initiated aspirin use and matched individuals who did not use aspirin. Data were collected from Taiwan National Health Insurance and Taiwan Cancer Registry from 2000 through 2015. CRC cases were age- and sex-matched in a 1:4 ratio with individuals in a control group, identified from a cohort of individuals who used and did not use aspirin through risk-set sampling. Data analysis was conducted from June 2018 to July 2019. Low-dose aspirin use was defined as receiving less than 150 mg per day, whereas 100 mg/d was most commonly used. Based on duration and recency of low-dose aspirin use between cohort entry (initiation date of low-dose aspirin for aspirin use group or randomly assigned date for those who did not use aspirin) and index date (CRC diagnosis date for individuals in the case group and the diagnosis date for the 4 corresponding matched individuals in the control group), the 3 following mutually exclusive exposure groups served as the basis for analysis: (1) long-term current low-dose aspirin use, (2) episodic low-dose aspirin use, and (3) no low-dose aspirin use (the reference group). CRC risk among the 3 exposure groups. Among 4 710 504 individuals (2 747 830 [51.7%] men; median [interquartile range] age at cohort entry in initiator group, 61 [52-71] years; median [interquartile range] age at cohort entry in nonuse group, 59 [51-68] years), 79 095 CRC cases (1.7% of study cohort) were identified. Compared with no low-dose aspirin use, the adjusted odds ratio (OR) for long-term current low-dose aspirin use and CRC risk was 0.89 (95% CI, 0.85-0.93); for episodic use, 0.88 (95% CI, 0.86-0.89). Adjusted ORs of 0.69 (95% CI, 0.63-0.76) and 0.64 (95% CI, 0.61-0.67) were observed for long-term current use and episodic low-dose aspirin use within the subcohort of individuals who initiated low-dose aspirin between age 40 and 59 years. In this study, low-dose aspirin use was associated with 11% lower CRC risk in an East Asian population, and this association was larger when low-dose aspirin use started before age 60 years.

Longitudinal analysis of healthy colon establishes aspirin as a suppressor of cancer-related epigenetic aging

BackgroundColon cancer (CC) is the third most common cancer worldwide, highlighting the importance of developing effective prevention strategies. Accumulating evidence supports that aspirin use reduces CC incidence. We reported previously that aspirin suppresses age-associated and CC-relevant DNA methylation (DNAm) in healthy colon. Here we addressed the aspirin’s effectiveness in longitudinal cohort.MethodsWe measured genome-wide DNAm in 124 healthy normal mucosa samples taken at baseline (time point 1, t1) and after 10-years follow-up (time point 2, t2) from a longitudinal female screening cohort. We investigated the time-dependent methylation drift in aspirin users and nonusers using multivariable regression and related the modulatory effect of aspirin to colonic epigenome-aging and CC.ResultsOver time, compared to nonusers, long-term (≥ 2 years) aspirin users showed less hypermethylated CpGs (proximal: 17% vs. 87%; distal: 16% vs. 70%) and more hypomethylated CpGs (proximal: 83% vs. 13%; distal: 84% vs. 30%). Overall, users showed 2% (P = 0.02) less mean methylation levels than nonusers in proximal colon and displayed repressed methylation age (mAge). Methylation loss in users occurred at several CC-specific tumor suppressors that gained methylation in nonusers. Methylation loss in users effected genes involved in immune system and inflammation, while methylation gain in nonusers effected genes involved in metabolism.ConclusionsThis is the first longitudinal study demonstrating effectiveness of aspirin-use in suppression of age-related and CC-relevant hypermethylation in the normal colon. These findings provide a rationale for future studies to evaluate loci that may serve as markers to identify individuals that will benefit most from aspirin and hence increase its efficiency in CC prevention and therapy.

Safety and Efficacy of Aspirin Desensitization Combined With Long-Term Aspirin Therapy in Aspirin-Exacerbated Respiratory Disease.

To assess the safety and efficacy of Aspirin desensitization combined with long-term Aspirin therapy in patients with Aspirinexacerbated respiratory disease (AERD). We searched the PubMed, Ovid, Cochrane Library, and Google Scholar databases from inception to October 2018 for articles in English. We only included randomized controlled trials and parallel or cross-over studies in which adults with AERD were randomly assigned to undergo Aspirin desensitization and receive long-term Aspirin therapy or placebo. A total of 869 citations were retrieved, and 6 studies met the criteria for analysis. All studies indicated that nasal symptoms, asthma symptoms, or both improved significantly after Aspirin desensitization. In addition, most studies reported a decline in corticosteroid dosage (oral and inhaled). The 4 studies that reported nasal polyps did not demonstrate a change in nasal polyps with Aspirin therapy compared with placebo. The dropout rates in all studies reviewed ranged from 5.8% to 55.7%, and the most common adverse events were gastrointestinal symptoms. Clearly, Aspirin desensitization and treatment are beneficial for AERD patients, with relief of nasal symptoms, improvement in asthma control, decrease in daily corticosteroid use, and no fatal adverse events. However, the long-term adverse effects of Aspirin desensitization and optimal dosage of Aspirin merit further investigation.

S1229 Aspirin and the Gastrointestinal Tract: A Review of Risks and Benefits

INTRODUCTION: The beneficial effects of using long-term low-dose aspirin (LDA) in different types of gastrointestinal disorders has been controversial. In this systematic review we describe the potential risks and benefits of ASA in the GI tract with the quality of supporting evidence. METHODS: A systematic search of the literature was conducted using different search engines. Studies looking at the impact of ASA on GI tract and Liver were included. GRADE methodology was used to evaluate the quality of supporting evidence. RESULTS: Low quality of evidence (QOE) suggests mild to moderate benefit in primary CRC prevention. There is weak evidence for risk reduction in esophageal (SCC & adeno), non-cardia gastric & pancreatic cancer. There is no reduction in the risk for Barrett's esophagus small intestine neuroendocrine tumors& secondary prevention of CRC. There is paucity of the data regarding other conditions as listed in the Tables 1 and 2a/b. The QOE of harmful effects of aspirin on gastroduodenal & small bowel erosions and ulcers, erosive esophagitis & diverticular complications are weak to moderate. Aspirin has weak QOE in reducing the fibrosis in chronic viral hepatitis and NAFLD. Upper GI tract and Small intestine (Table 1) Lower GI tract & Liver (Table 2a/b). CONCLUSION: Long-term LDA use has shown to have both beneficial and deleterious effects on the GI tract as well as the Liver. Also, there is paucity of date regarding the dose related risk reduction. There is moderate QOE for deleterious effects of ASA on Upper Gi tract even at a low dose. Some of these side effects can be mitigated with PPI use. Despite recent enthusiasm with potential benefits of LDA in decreasing risk of GI malignancies and hepatic fibrosis, the evidence remains weak except for CRC prevention. This review can serve as a quick reference for physicians considering LDA for their patients.Table 1.: Upper GI, small intestine and PancreasTable 2.: Colon, IBD and Diverticular diseaseTable 3.: Viral hepatitis, Alcoholic hepatitis and NAFLD

Clinical Guidelines for Drug-induced Peptic Ulcer, 2020 Revised Edition

The Korean guidelines for nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcers were previously developed under co-work with the Korean College of Helicobacter and Upper Gastrointestinal Research and Korean Society of Gastroenterology at 2009. On the other hand, the previous guidelines were based mainly on a literature review and expert opinions. Therefore, the guidelines need to be revised. In this study, a guideline development committee for drug-induced peptic ulcers was organized under the Korean College of Helicobacter and Upper Gastrointestinal Research in 2017. Nine statements were developed, including four for NSAID, three for aspirin and other antiplatelet agents, and two for anticoagulants through de novo processes based on evidence-based medicine, such as a literature search, meta-analysis, and the consensus was established using the modified Delphi method. The primary target of this guideline was adult patients taking long-term NSAIDs, aspirin, or other antiplatelet agent and anticoagulants. The revised guidelines reflect the consensus of expert opinions and are intended to assist relevant clinicians in the management and prevention of drug-induced peptic ulcers and associated conditions.

Association Between Long-Term Aspirin Use and Frailty in Men: The Physicians' Health Study.

Chronic inflammation may lead to frailty, however the potential for anti-inflammatory medications such as aspirin to prevent frailty is unknown. We sought to examine the association between long-term aspirin use and prevalent frailty. We included 12 101 men ≥60 years who participated in the Physicians' Health Study I, a completed aspirin randomized controlled trial (1982-1989). Annual questionnaires collected self-reported data on daily aspirin use, lifestyle, and clinical variables. Average aspirin use was summed into 2 categories: ≤60 days/year and >60 days/year. Frailty was assessed using a 33-item index 11 years after trial completion. A score of ≥0.21 was considered frail. Propensity score inverse probability of treatment weighting was used for statistical control of confounding. Logistic regression models estimated odds of frailty as a function of categories of average aspirin use. Mean age was 70.5 years (range 60-101). Following an average of 11 ± 0.6 years of follow-up, aspirin use was reported as ≤60 days/year for 15%; 2413 participants (20%) were frail. Frequency of aspirin use was associated with smoking, alcohol consumption, hypertension, and cardiovascular disease, but negatively associated with bleeding and Coumadin use. The odds ratio (95% confidence intervals) for frailty was 0.85 (0.76-0.96) for average aspirin use >60 days/year versus aspirin use ≤60 days/year. Results were similar using an alternate definition of frailty. Long-term regular aspirin use is inversely associated with frailty among older men, even after consideration of multimorbidity and health behaviors. Work is needed to understand the role of medications with anti-inflammatory properties on aging.

Safety and efficacy of low-dose aspirin in ischemic stroke patients with different G6PD conditions.

Aspirin is the first recommended antiplatelet agent to prevention secondary stroke, but its safety and efficacy in stroke patients with glucose-6-phosphate dehydrogenase deficiency remain unclear. We sought to evaluate its safety and efficacy in ischemic stroke patients with and without glucose-6-phosphate dehydrogenase deficiency. Patients with ischemic stroke receiving aspirin (100 mg/day) for three months were recruited for a multicenter, prospective, cohort study. Blood glucose-6-phosphate dehydrogenase activity was examined after stroke. Safety outcomes including acute hemolysis, moderate-to-severe bleeding, and death (vascular, all-cause), and efficacy outcome indicated as stroke recurrence were evaluated at three months. Risk factors associated with moderate-to-severe bleeding and all-cause death were determined using multivariate or Cox regression analysis. Among the included 1121 patients, 81 of 130 glucose-6-phosphate dehydrogenase deficient and 576 of 991 glucose-6-phosphate dehydrogenase normal patients received aspirin for three months. Acute hemolysis was observed in one of the glucose-6-phosphate dehydrogenase deficient and in none of the glucose-6-phosphate dehydrogenase normal patients (p = 0.876). The rates of moderate-to-severe bleeding were 2.5% and 0.3% (p = 0.045), and the percentages of all-cause death were 6.2% and 1.4% (p = 0.008) in the glucose-6-phosphate dehydrogenase deficient and glucose-6-phosphate dehydrogenase normal patients. Stroke recurrence rate was similar in the two groups (2.5% vs. 1.7%; p = 0.608). Glucose-6-phosphate dehydrogenase deficiency was significantly associated with increased risk of moderate-to-severe bleeding (adjust p = 0.048) and all-cause death during aspirin use (adjust p = 0.008). Long-term low-dose aspirin therapy might relate to worse safety outcomes in patients with glucose-6-phosphate dehydrogenase deficiency and large clinical trials are needed to further confirm these findings.

Evaluation and optimization of prescribed concomitant antiplatelet and anticoagulation therapy centrally managed by an anticoagulation management service.

Patients on long-term anticoagulation combined with antiplatelet therapy have an increased risk of bleeding compared to patients on anticoagulation alone. The aim of this study was to evaluate the appropriateness of antiplatelet therapy in patients who are on long-term warfarin therapy and are managed by Brigham and Women's Hospital Anticoagulation Management Service (BWH AMS). This was a single-center, prospective chart review of patients managed by BWH AMS who were on long-term warfarin therapy plus full-dose aspirin (325mg), an oral P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) and/or acetylsalicylic acid/dipyridamole. Patients' cardiovascular (CV) benefit and risk of bleeding were assessed according to clinical guidelines. The major objective of the study was to determine the proportion of patients on dual antithrombotic therapy (DAT) or triple antithrombotic therapy (TAT) whose risk of bleeding outweighed CV benefit. Of the 2677 patients evaluated for inclusion,145 were on concomitant long-term warfarin therapy plus aspirin (325mg), an oral P2Y12 inhibitor and/or acetylsalicylic acid/dipyridamole. A total of 85 patients (58.6%) had no clear indication for DAT or TAT per guideline recommendations and were categorized as bleeding risk outweighing CV benefit. The remaining 60 patients (41.4%) had an appropriate indication for DAT or TAT per guidelines and were categorized as CV benefit outweighing bleeding risk. BWH AMS pharmacists made 33 (22.9%) recommendations to providers to discontinue or de-escalate antiplatelet therapy. Interventions were accepted for 10 (30.3%) patients. Pharmacist involvement in the management of patients' antithrombotic regimens can optimize guideline-directed medical therapy and mitigate the potential risk of bleeding.

Effect of aspirin on PET parameters in primary non-small cell lung cancer and its relationship with prognosis

Background18 F-FDG is a glucose analogue whose metabolic index SUV can effectively reflect the metabolic level of tumor microenvironment. Aspirin can affect the uptake of 18F-FDG by cancer cells, reducing the SUVmax value of primary tumors, exerting antitumor effect. This study aimed to evaluate the prognostic value of long-term aspirin and the relationship between aspirin intake and PET parameters value of primary tumor in non-small cell lung cancer (NSCLC).MethodsEighty-one NSCLC patients were recruited and divided into two groups: aspirin medication group and control group, who underwent surgery and had pathological diagnosis data between January 2012 and December 2016. Clinical characteristics were retrospective analyzed to evaluate the possibility of clinical prognosis, respectively. Kaplan-Meier curves and a Cox proportional hazard model were applied to evaluate the predictors of prognosis.ResultsThe PET/CT SUVmax of the primary tumor in the aspirin group was lower than that in the control group (P < 0.05). Compared with the control group, the SUVmax, SUVmean and TLG of the primary tumor in aspirin group were lower, but the MTV value had no significant difference. Cox regression analysis showed that N stage and TNM stage were predictors of the prognosis. There was a significant difference in the use of aspirin in NSCLC patients.ConclusionAspirin can reduce SUVmax, SUVmean and TLG in primary tumor and aspirin can improve the prognosis of patients with NSCLC.

The effect of aspirin on colorectal cancer incidence in African Americans.

4085 Background: From 2011 to 2016, the incidence and mortality rate of colorectal cancer(CRC) were highest among African Americans(AA), compared to other US racial/ethnic groups. Long-term aspirin use is recommended as a strategy to reduce the risk of CRC. Yet, there is scant information on the chemopreventive effect of aspirin among AA. It is imperative to assess whether the reported chemo-preventive effect also occurs in AA. Our central hypothesis is that aspirin use in AA is associated with a lower incidence of CRC, irrespective of race/ethnicity. Methods: We conducted a secondary analysis, using data from AA participants in the Atherosclerosis Risk in Communities(ARIC) longitudinal study, who did not have CRC at enrollment, from 1987 to 1998. We extracted demographic, clinical and mortality data to compare the incidence of CRC among participants taking aspirin compared to those who were not taking aspirin, stratified by age, tobacco use, and body mass index. All-cause mortality and CRC mortality will also be assessed, and we will use Cox proportional hazard regression to determine the relationship between aspirin use and CRC incidence, and mortality. Results: At baseline in 1987, 15,026 participants enrolled in the ARIC study, 25% of whom were AA, median age 54(range 44-66), including 46.7% who reported using aspirin. We analyzed follow-up data from 10,960 participants in 1996-1998, 20% of whom were AA, and 56.9% of whom were taking aspirin. Non-AA participants were more likely to report using aspirin at baseline and follow-up, compared to AA, 53% vs 30% and 59% vs 50% respectively. After 10years, the total incidence of CRC in AA participants was 1% compared with 1.1% in non-AA(p = 0.7). There was no difference in CRC incidence by aspirin use among all participants, and when stratified by race(among all participants p = 0.81, amongAA p = 0.68, among non-AA p = 0.94). Conclusions: We found no difference in the incidence of CRC among AA compared to Caucasians, by aspirin use. Investigation of consistency and/or dose of aspirin use by race may provide further insights on the relationship between aspirin use and CRC incidence, comparing AA to Caucasians.

ENGLISH VERSION: PERSONALIZED DESENSITIZATION WITH ACETYLSALICYLIC ACID IN PATIENTS WITH HYPERSENSITIVITY TO NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

Aims: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) has various mechanisms and represents different clinical syndromes from anaphylaxis to severe bronchospasm. The prevalence of aspirin hypersensitivity among patients with asthma and nasal polyps reaches 25.6%. Respiratory reactions associated with aspirin or other NSAIDs are not immunological. The basis of these reactions is non-allergic hypersensitivity of the cross-reactive type. Desensitization followed by long-term aspirin therapy is an effective method of treating hypersensitivity to aspirin or other NSAIDs. Using aspirin 600-1200 mg/day can significantly alleviate the symptoms of asthma, allergic rhinitis. Methods: We successfully applied aspirin desensitization for method of patients with hypersensitivity to NSAIDs. According to the method, an hour before the desensitization, daily montelukast 10 mg was taken orally, then aspirin every 3 hours. Results: Three patients underwent desensitization of aspirin. The dose was selected individualy depending on the clinical manifestations of drug-induced adverse reactions (AR). ARs during desensitization were treated by iv dexamethasone administration. Subsequent doses did not cause AR. Doses of aspirin were increased to a maximum of 1250 mg daily, and were continued for the long-term use. Conclusion: It is possible to conclude that the initial dose of aspirin should be 16-40mg; it is possible to increase the dose if the initial dosage is well tolerated; symptoms of moderate intolerance are treated by 4-8 mg iv dexamethasone; prior to desensitization, we recommended to use montelukast 10 mg, it is safe to practice desensitization of aspirin according to a personalized technique by a specialist in an intensive care unit.

Aspirin and the chemoprevention of cancers: A mathematical and evolutionary dynamics perspective.

Epidemiological data indicate that long-term low dose aspirin administration has a protective effect against the occurrence of colorectal cancer, both in sporadic and in hereditary forms of the disease. The mechanisms underlying this protective effect, however, are incompletely understood. The molecular events that lead to protection have been partly defined, but remain to be fully characterized. So far, however, approaches based on evolutionary dynamics have not been discussed much, but can potentially offer important insights. The aim of this review is to highlight this line of investigation and the results that have been obtained. A core observation in this respect is that aspirin has a direct negative impact on the growth dynamics of the cells, by influencing the kinetics of tumor cell division and death. We discuss the application of mathematical models to experimental data to quantify these parameter changes. We then describe further mathematical models that have been used to explore how these aspirin-mediated changes in kinetic parameters influence the probability of successful colony growth versus extinction, and how they affect the evolution of the tumor during aspirin administration. Finally, we discuss mathematical models that have been used to investigate the selective forces that can lead to the rise of mismatch-repair deficient cells in an inflammatory environment, and how this selection can be potentially altered through aspirin-mediated interventions. This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models Analytical and Computational Methods > Analytical Methods Analytical and Computational Methods > Computational Methods.

Long-term aspirin use for primary cancer prevention: An updated systematic review and subgroup meta-analysis of 29 randomized clinical trials.

Background and objective: Long-term aspirin use for the primary prevention of cancer remains controversial, and variations in the effect of aspirin use on cancer outcomes by aspirin dose, follow-up duration, or study population have never been systematically evaluated. The objective of this study was to evaluate the effect of aspirin on primary cancer prevention and to determine whether the effect differed according to aspirin dose, follow-up duration, or study population.Materials and methods: Seven electronic databases were searched from inception to September 30, 2019. Randomized clinical trials (RCTs) that compared aspirin use versus no aspirin use in participants without pre-existing cancer and reported cancer outcomes were selected. Data were screened and extracted by different investigators. Analyses were performed using Review Manager 5.3 and Comprehensive Meta-Analysis 2.0. Total cancer incidence was defined as the primary clinical endpoint. Total cancer mortality, all-cause mortality, major bleeding, and total bleeding events were the secondary outcomes. Subgroup analyses were conducted based on aspirin dose, follow-up duration, and study populations.Results: Twenty-nine RCTs that randomized 200,679 participants were included. Compared with no aspirin, aspirin use was not associated with significant reductions in total cancer incidence (RR = 1.01, 95% CI: 0.97 to 1.04, P = 0.72), total cancer mortality (RR = 1.00, 95% CI: 0.93 to 1.07, P = 0.90), or all-cause mortality (RR = 0.98, 95% CI: 0.94 to 1.02, P =0.31); however, aspirin use was associated with a 44% increase in the risk of major bleeding (RR = 1.44, 95% CI: 1.32 to 1.57, P < 0.00001) and a 52% increase in the risk of total bleeding events (RR = 1.52, 95% CI: 1.33 to 1.74, P < 0.00001). Subgroup analyses demonstrated consistent results.Conclusions: Long-term aspirin use in individuals without pre-existing cancer was not associated with a significant reduction in total cancer incidence, cancer mortality, or all-cause mortality; however, aspirin use was associated with a significant increase in the risk of bleeding. Therefore, aspirin is not an appropriate choice for the primary cancer prevention.

Long-Term Aspirin Use and 5-Year Survival in Healthy Adults: A Population-Based Cohort Study in South Korea.

PurposeWe investigated whether long-term aspirin use is associated with 5-year all-cause mortality.Materials and MethodsParticipants were individuals aged ≥40 years who were registered in the 2010 sample cohort database of the National Health Insurance Service in South Korea. Aspirin users were divided into three groups: continuous users (2006–2010), previous users (2006–2009), and new users (2010). Individuals with a history of coronary artery disease and cerebrovascular disease were excluded. Five-year all-cause mortality was defined as mortality due to any cause from January 1, 2011 to December 31, 2015. Data were analyzed by multivariable Cox regression.ResultsIn total, 424444 individuals were included. Five-year all-cause mortality was 9% lower in continuous aspirin users than in unexposed individuals [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.86–0.97; p=0.003]. Five-year all-cause mortality rates in the new aspirin users (HR: 1.00, 95% CI: 0.90–1.11; p=0.995) and previous aspirin users (HR: 1.01, 95% CI: 0.94–1.09; p=0.776) were not significantly different from that in unexposed individuals. In the 40–60-year age group, 5-year all-cause mortality in the continuous aspirin users was 24% lower (HR: 0.76, 95% CI: 0.64–0.90; p=0.002) than that in unexposed individuals. However, in the >60-year age group, there was no significant association between aspirin use and 5-year all-cause mortality (HR: 0.96, 95% CI: 0.90–1.02; p=0.199).ConclusionLong-term aspirin use is associated with reduced 5-year all-cause mortality in healthy adults, especially those aged <60 years.

The distinct effects of aspirin on platelet aggregation induced by infectious bacteria

Bacteria induce platelet aggregation triggered by several mechanisms. The goal of this work was to characterize platelet aggregates induced by different bacterial strains and to quantify the effect of aspirin treatment using aggregation tests, as well as a novel approach based on confocal analysis. Blood samples were obtained from either healthy donors (n = 27) or patients treated with long-term aspirin (n = 15). The bacterial species included were Staphylococcus aureus, Enterococcus faecalis, and Streptococcus sanguinis. The different aggregate’s ultrastructures depending on the bacterial strain were analyzed using Scanning electron microscopy. Quantification of the size of the platelet aggregates, their mean number as well as the bacterial impregnation within the aggregates was performed using confocal laser scanning light microscopy. Light Transmission Aggregometry was also performed. Our results reported distinct characteristics of platelet aggregates depending on the bacterial strain. Using confocal analysis, we have shown that aspirin significantly reduced platelet aggregation induced by S. aureus (p = .003) and E. faecalis (p = .006) with no effect in the case of S. sanguinis (p = .529). The results of the aggregometry were concordant with those of the confocal technique in the case of S. aureus and S. sanguinis. Interestingly, aggregation induced by E. faecalis was detected only with confocal analysis. In conclusion, our confocal scanning microscopy allowed a detailed study of the platelet aggregation induced by bacteria. We showed that aspirin acts on bacterial-induced platelet aggregation depending on the species. These results are in favor of the use of aspirin considering the species and the bacterial strain involved.

Venous Stenting in Proximal Venous Outflow Obstruction – Lessons Learned from 500 Cases

Introduction - Venous stenting is emerging as an important treatment strategy in venous disease. What is the real world experience with this procedure? This study reviews our experience with venous stenting in chronic venous insufficiency, highlighting patient selection, procedural considerations, outcomes, and re-interventions. Methods - This is a retrospective study of 500 patients who underwent venous stenting for chronic proximal venous outflow obstruction (PVOO) in the iliac veins from October 2013 to August 2016 at one centre. Preoperatively, we utilized venous duplex scan and magnetic resonance venogram to assist in patient selection. Intraoperative evaluation comprised of bilateral venogram and intravascular ultrasound. Wallstents were used in all cases (Boston Scientific, MA). Patients were discharged on day of procedure with rivaroxaban 10 mg initially followed by long-term Aspirin 81 mg. Wilcoxon-Mann-Whitney, Kruskal-Wallis, and logistic regressions were used in statistical analysis of variables and outcomes. Results - Of these 500 patients, follow-up was maintained in 90% of patients with a mean follow-up 320 days. Mean age of patients was 60 years old (SD 13.4 years) and 57% were female. Preoperatively, edema was present in 90.5%, and active ulceration 10.7%. 85 patients (17%) presented with persistent symptoms after a prior endovenous thermal ablation or surgery for superficial venous disease, and 69 patients (13.8) presenting with post-thrombotic syndrome. Among patients without any known DVT history, 21.5% had findings of chronic phlebitic changes (long segment diffuse disease, occlusion of vessel, intraluminal filling defects) on venogram or IVUS. Bilateral vein stents were performed in 59%. Kruskal-Wallis tests were significant for improvement (symptoms, CEAP class, and physical exam) in patients at thirty days (p=0.027), ninety days (p=0.045), six months (p=0.037), and one year (p=0.012). Ordered logistic regressions found the presence of edema (coefficient 1.59, 95% CI [0.52, 2.65], p=0.004), active ulceration (95% CI [0.022, 3.40], p=0.047), and decreased number of stents placed (coefficient -0.56, 95% CI [-1.08, -0.036], p=0.036) to predict increased improvement at thirty days, and a history of DVT (coefficient: -0.94, 95% CI [-1.79, -0.096], p=0. 029) to predict decreased improvement at one year post-operatively. Wilcoxon-Mann-Whitney tests were significant for more improvement in patients who had unilateral versus bilateral stents placed at thirty days (p=0.013) and six months (p=0.039). Major re-interventions (61.7% for recurrent symptoms, 17.6% for persistent symptoms, 6% for DVT) were performed in 7.6% of patients. Mean time to re-intervention was 191 days, and re-interventions were more prevalent (29. 4%) among patients with a known history of DVT. Conclusion - Our experience with venous stenting in chronic PVOO on an expanded scale suggested a satisfactory outcome at one year. Those patients with a prior history of DVT have poorer outcomes after venous stenting. Unilateral stents have better outcomes than bilateral stents, but the difference may reflect complexity of disease. Approximately 8% of patients will require a secondary re-intervention. Patient selection, procedural indications, and optimal pharmacologic therapy after venous stenting need further studies and clarification.

Long-term aspirin use for cancer primary prevention

Long-term aspirin use for cancer primary prevention

Long-term aspirin use for cancer primary prevention: A protocol for updated systematic review and subgroup meta-analysis of randomized clinical trials.

Background:Long-term use of aspirin for primary prevention of cancer remains inconclusive, and variation in the effects of aspirin use on cancer outcomes by cancer site, aspirin dose, follow-up duration, or different populations has never been systematically evaluated.Methods:Seven electronic databases (PubMed, EMBASE, ClinicalTrials.gov, etc) will be searched from inception to September 30, 2019. Randomized clinical trials (RCTs) comparing aspirin versus no aspirin in participants without pre-existing cancer and reporting cancer incidence, and/or cancer mortality outcomes will be selected and assessed for inclusion. The Cochrane's Risk of Bias Tool and the Jadad scale will be used to evaluate the risk of bias and the methodologic quality of the RCTs. Data will be screened and extracted by independent investigators. Total cancer incidence will be defined as the primary clinical endpoint, and total cancer mortality, all-cause mortality, and the risk of major bleeding will be the secondary outcomes. Subgroup analyses based on cancer site, aspirin dose, follow-up duration, or different populations will be conducted. Analyses will be performed using Review Manager 5.3, Comprehensive Meta-Analysis 2.0, and Trial Sequential Analysis (TSA) software.Results:This study will systematically evaluate the effects of long-term aspirin use on total cancer incidence, cancer mortality, all-cause mortality, and the risk of major bleeding. Subgroup analyses will indicate whether the effects of aspirin on cancer outcomes are associated with cancer site, daily dose of aspirin, follow-up duration, or different subgroup of participants. The results will be submitted and published in a peer-reviewed scientific journal.Conclusions:This systematic review will systematically evaluate the efficacy and safety of long-term use of aspirin for primary prevention of cancer and determine whether there are some potential influencing factors affecting the effects of aspirin on cancer outcomes, thus strengthening the evidence base for the clinical practice and future research of this intervention.

Effect of low-dose aspirin administration on long-term survival of cirrhotic patients after splenectomy: A retrospective single-center study.

BACKGROUNDCirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral anticoagulants including aspirin. However, the long-term impact of postoperative aspirin on cirrhotic patients after splenectomy remains unknown.AIMThe main purpose of this study was to investigate the effect of postoperative long-term low-dose aspirin administration on the development of HCC and long-term survival of cirrhotic patients after splenectomy.METHODSThe clinical data of 264 adult patients with viral hepatitis-related cirrhosis who underwent splenectomy at the First Affiliated Hospital of Xi’an Jiaotong University from January 2000 to December 2014 were analyzed retrospectively. Among these patients, 59 who started taking 100 mg/d aspirin within seven days were enrolled in the aspirin group. The incidence of HCC and overall survival were analyzed.RESULTSDuring follow-up, 41 (15.53%) patients developed HCC and 37 (14.02%) died due to end-stage liver diseases or other serious complications. Postoperative long-term low-dose aspirin therapy reduced the incidence of HCC from 19.02% to 3.40% after splenectomy (log-rank test, P = 0.028). Univariate and multivariate analyses showed that not undertaking postoperative long-term low-dose aspirin therapy [odds ratio (OR) = 6.211, 95% confidence interval (CI): 1.142-27.324, P = 0.016] was the only independent risk factor for the development of HCC. Similarly, patients in the aspirin group survived longer than those in the control group (log-rank test, P = 0.041). Univariate and multivariate analyses showed that the only factor that independently associated with improved overall survival was postoperative long-term low-dose aspirin therapy [OR = 0.218, 95%CI: 0.049-0.960, P = 0.044].CONCLUSIONIn patients with viral hepatitis-related cirrhosis, long-term post-splenectomy administration of low-dose aspirin reduces the incidence of HCC and improves the long-term overall survival.

Development and Validation of the Warfarin-Aspirin Bleeding Assessment Tool (WA-BAT) in Children

Bleeding assessment tools (BATs) aim to screen and estimate bleeding risk in patients with inherited bleeding disorders. However, the use of BAT as a standardized measure for comparing bleeding in patients on long-term thromboprophylaxis has not yet been validated. We developed a self-administrable BAT to assess bleeding in patients undergoing long-term thromboprophylaxis with aspirin or warfarin. Eligible participants were invited to complete the warfarin-aspirin -BAT (WA-BAT) online. The WA-BAT was readministered a number of weeks later to determine intrarater reliability. The WA-BAT showed substantial intrarater reliability and assesses major and minor bleeding associated with long-term warfarin or aspirin use.