Exploring the impact of acetylsalicylic acid and conditioned medium obtained from mesenchymal cells, individually and in combination, on cognitive function, histological changes, and oxidant-antioxidant balance in male rats with hippocampal injury.

BACKGROUND: The hippocampus is susceptible to damage, leading to negative impacts on cognition. Conditioned medium (CM) obtained from adipose tissue-derived mesenchymal stem cells (MSCs) and acetylsalicylic acid (ASA) have shown neuroprotective effects independently. This study explored the synergistic potential of ASA and CM from adipose-derived MSCs against hippocampal injury. METHODS: Adult male Wistar rats received bilateral hippocampal ethidium bromide (EB) injections to induce hippocampal damage. Rats were treated with ASA and/or CM derived from adipose tissue MSCs every 48 h for 16 days. Behavioral tests (open field test, Morris water maze, novel object recognition, and passive avoidance), oxidative stress, Western blot analysis of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) expression, and hippocampal histological investigation were conducted. RESULTS: Administration of EB caused impairments in spatial, recognition, and passive avoidance memory, as well as heightened oxidative stress, reduced BDNF/CDNF expression, and pyramidal cell loss in the hippocampal CA1 region. Administration of ASA, CM, or a combination of both mitigated these hippocampal damages and cognitive deficits, elevated BDNF and CDNF levels, and alleviated the CA1 necrosis caused by EB. Moreover, co-administering ASA and CM resulted in greater improvements in spatial memory compared to administering ASA alone, suggesting possible synergistic interactions. CONCLUSIONS: The ability of ASA, CM obtained from adipose tissue-derived MSCs, and their combination therapy to alleviate hippocampal injuries highlights their promising therapeutic potential as a neuroprotection strategy against brain damage. Our findings provide preliminary evidence of the potential synergistic effects of ASA and CM, which warrants further investigations.

Current goals of NSAID-ERD management: patient-centered approaches involving NSAID desensitization with and without biologics.

Classic approach of non-steroidal anti-inflammatory drugs (NSAIDs) - exacerbated respiratory disease (NSAID-ERD) includes pharmaceutical and surgical treatments, as well as avoidance of COX-1-inhibitor NSAIDs. The introduction of biologics in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) represents an alternative therapeutic approach to the classical aspirin therapy after desensitization (ATAD) in some regions, and with convincing results. However, their use is limited due to approval and/or high-cost restrictions. NSAID-ERD is a mainly type 2 (T2) and highly eosinophilic disease, and monoclonal antibodies targeting IgE or interleukins (IL)-5, IL-4, and IL-13 have been shown to be effective for both severe asthma and severe CRSwNP. So far, dupilumab demonstrated greater efficacy in NSAID-ERD than in aspirin-tolerant patients with regards to several clinical outcomes. Patients with NSAID-ERD respond very rapidly to omalizumab also, with reduction in the release of prostaglandin D2 and cysteinyl leukotrienes. Patients favored biologic treatment over ATAD in multiple retrospective analyses, which must be acknowledged when choosing one or the other option. While this review will summarize ATAD in general, it will more prominently focus on when ATAD should be considered, even when T2 biologics are available. Additionally, there are conflicting studies as to whether patients on a T2 biologic become desensitized to NSAIDs, as omalizumab proved to restore tolerance to aspirin in only two thirds of patients. This goal of NSAIDs tolerance should be considered as part of disease control future approaches, representing one of many aspects in a patient-centered care approach.

Obstetric care provider's knowledge about the use of low dose aspirin for preeclampsia prevention in low and middle income countries: a systematic review and meta-analysis.

INTRODUCTION: Preeclampsia can elevate the likelihood of unfavorable consequences for a mother, such as severe morbidity and mortality. World Health Organization recommends low dose acetylsalicylic acid (aspirin, 75 mg per day) for the prevention of preeclampsia in women at moderate or high risk of developing the condition. The use of low dose aspirin is dependent on the knowledge of health care providers working in the antenatal care units. We found inconsistent figures regarding the knowledge level of health care providers on low dose aspirin for preeclampsia prevention around different low and middle income countries in the world. Thus, determining the pooled knowledge level of health care providers is very important. METHODS: This systematic review and meta-analysis (SRMA) was conducted on the knowledge level of among obstetric care providers towards preeclampsia prevention in low and middle income countries. We identified relevant literature in the English language only. A comprehensive search was conducted on databases such as PubMed, Google Scholar, HINARI, and Scopus. Subsequently, all datasets were exported to Mendeley reference manager and transferred to a Microsoft Excel spreadsheet to eliminate duplicate data during the review process. The extracted Microsoft Excel spreadsheet format data was imported to STATA software version 17 (STATA corporation, Texas, USA) for analysis. Then random effect model was used to estimate the pooled level of knowledge of health care providers on low dose aspirin for preeclampsia prevention in low income countries. Cochrane Q-test and I2 statistics were computed to assess heterogeneity among all the studies included in this SRMA. RESULT: A total of 1231 articles were identified through our search strategies, including Google Scholar, PubMed, Hinari and Scopus. Ultimately, six articles met the eligibility criteria for inclusion in the final SRMA. The pooled knowledge level of healthcare providers regarding the use of low-dose aspirin for preeclampsia prevention in low-income countries was found to be 16.38% (95% CI: 4.36-28.40). The Cochrane heterogeneity index, with a substantial I2 value of 98.89% and a significant P-value of 0.01, indicated significant heterogeneity among the primary studies included. CONCLUSION: the knowledge level of obstetric care providers in low and middle income countries is found very low and all the governmental and non-governmental organizations should strive to enhance the knowledge of obstetric care providers on the use of low dose aspirin for preeclampsia prevention in low and middle income countries.

Effectiveness of long-term low-dose aspirin in the prevention of gastric cancer after Helicobacter pylori eradication: study design and rationale of Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT).

BACKGROUND: In addition to Helicobacter pylori (H. pylori) infection eradication, some medications, including aspirin, metformin, and statins, have been suggested to have protective effects against gastric cancer (GC) development in observational studies. We launched the Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT) to evaluate the effectiveness of long-term low-dose aspirin use for the prevention of development and mortality of GC after H. pylori eradication. METHODS/DESIGN: AGCPT is a prospective population-based double-blind, randomized clinical trial. The study sample was targeted at 21,000 participants aged from 35 to 70 years old, both sexes, in Ardabil, a province in northwest Iran with relatively high rates of GC incidence and mortality. All eligible participants were initially tested for H. pylori infection using a H. pylori stool antigen test. Participants with positive tests undergo H. pylori eradication by standard treatment regimens. All participants with a negative test and those with a positive test with a subsequent confirmed H. pylori eradication test were entered into the intervention phase. In the intervention phase, participants were allocated randomly into either the treatment (daily oral consumption of 81 mg enteric-coated aspirin tablets) arm or the control (placebo) arm using permuted balanced blocks. Subjects will be followed for an average period of 10 years to evaluate the incidence and mortality rates of GC. DISCUSSION: In addition to preventing other diseases like cardiovascular events, aspirin may prevent GC incidence and mortality. AGCPT will investigate the difference between the two study arms in the proportion of the cumulative incidence and mortality rates of GC. The study's results may help policymakers and researchers update the strategies for GC prevention. TRIAL REGISTRATION: This trial with the registry name of "The effect of Low-dose Aspirin in the Prevention of Gastric Cancer" was registered in the Iranian Registry of Clinical Trials, IRCT.ir, under the identifier IRCT201105082032N3. Registered on April 21, 2017.

Predictive Model of Internal Bleeding in Elderly Aspirin Users Using XGBoost Machine Learning.

Objective: This study aimed to develop a predictive model for assessing internal bleeding risk in elderly aspirin users using machine learning. Methods: A total of 26,030 elderly aspirin users (aged over 65) were retrospective included in the study. Data on patient demographics, clinical features, underlying diseases, medical history, and laboratory examinations were collected from Affiliated Dongyang Hospital of Wenzhou Medical University. Patients were randomly divided into two groups, with a 7:3 ratio, for model development and internal validation, respectively. Least absolute shrinkage and selection operator (LASSO) regression, extreme gradient boosting (XGBoost), and multivariate logistic regression were employed to develop prediction models. Model performance was evaluated using area under the curve (AUC), calibration curves, decision curve analysis (DCA), clinical impact curve (CIC), and net reduction curve (NRC). Results: The XGBoost model exhibited the highest AUC among all models. It consisted of six clinical variables: HGB, PLT, previous bleeding, gastric ulcer, cerebral infarction, and tumor. A visual nomogram was developed based on these six variables. In the training dataset, the model achieved an AUC of 0.842 (95% CI: 0.829-0.855), while in the test dataset, it achieved an AUC of 0.820 (95% CI: 0.800-0.840), demonstrating good discriminatory performance. The calibration curve analysis revealed that the nomogram model closely approximated the ideal curve. Additionally, the DCA curve, CIC, and NRC demonstrated favorable clinical net benefit for the nomogram model. Conclusion: This study successfully developed a predictive model to estimate the risk of bleeding in elderly aspirin users. This model can serve as a potential useful tool for clinicians to estimate the risk of bleeding in elderly aspirin users and make informed decisions regarding their treatment and management.

Association of Aspirin Use With Risk of Intracerebral Hemorrhage in Patients Without History of Stroke or Transient Ischemic Attack in the UK Biobank.

BACKGROUND: The association between aspirin use and the risk of intracerebral hemorrhage (ICH) among individuals without previous stroke events is inconclusive. AIM: We investigated the association between regular aspirin use and ICH risk in middle-aged and older adults without previous stroke or transient ischemic attack (TIA). METHODS: This prospective population-based study included participants older than 40 years with no history of stroke or TIA from the UK Biobank. The main exposure was regular aspirin use. Cox regression analyses and propensity score matching analyses estimated the hazard ratios (HRs) for aspirin use for incident fatal and non-fatal ICH. We conducted prespecified subgroup analyses for selecting individuals at high risk of ICH when using aspirin. Multiple sensitivity analyses were performed to test the robustness of our results. RESULTS: A total of 449,325 participants were included into final analyses (median [IQR] age 58 [50 - 63] years, 54.6% females), of whom 58,045 reported aspirin use. During a median follow-up of 12.75 (IQR 12.03 - 13.47) years, 1,557 (0.3%) incident ICH cases were identified, of which 399 (25·6%) were fatal. Aspirin was not associated with increased risk of overall (HR 1.11, 95% CI 0.95 - 1.27, P = 0.188), fatal (HR 1.03, 95% CI 0.78 - 1.36, P = 0.846) and non-fatal (HR 1.12, 95% CI 0.95 - 1.33, P = 0.186) ICH. Propensity score matching analysis showed similar results. Subgroup analysis indicated that aspirin use in individuals older than 65 years or with concurrent anticoagulant use was correlated with increased risk of ICH. CONCLUSIONS: In this large cohort study of middle-aged and older adults without stroke or TIA events, there was no significant association between aspirin use and ICH risk in the real-world setting. However, it is possible that aspirin use in those aged over 65 years and concurrent anticoagulant treatment may increase the risk of ICH.

Aspirin is associated with improved outcomes in patients with sepsis-induced myocardial injury: An analysis of the MIMIC-IV database.

BACKGROUND: The effectiveness of aspirin treatment in septic patients remains a subject of debates. OBJECTIVE: To explore the association between aspirin usage and the prognosis of patients with sepsis-induced myocardial injury (SIMI), as well as the timing of aspirin administration. METHODS: Patients with SIMI were screened in the MIMIC-IV database and categorized into aspirin and non-aspirin groups based on their medications during intensive care unit (ICU) stay, and propensity matching analysis (PSM) was subsequently performed to reduce bias at baseline between the groups. The primary outcome was 28-day all-cause mortality. Cox multivariate regression analysis was conducted to evaluate the impact of aspirin on the prognosis of patients with SIMI. RESULTS: The pre-PSM and post-PSM cohorts included 1170 and 1055 patients, respectively. In the pre-PSM cohort, the aspirin group is older, has a higher proportion of chronic comorbidities, and lower SOFA and SAPS II scores when compared to the non-aspirin group. In the PSM analysis, most of the baseline characterization biases were corrected, and aspirin use was also associated with lower 28-day mortality (hazard ratio [HR] = 0.51, 95 % confidence interval [CI]: 0.42-0.63, P < 0.001), 90-day mortality (HR = 0.58, 95 % CI: 0.49-0.69, P < 0.001) and 1-year mortality (HR = 0.65, 95 % CI: 0.56-0.76, P < 0.001), irrespective of aspirin administration timing. A sensitivity analysis based on the original cohort confirmed the robustness of the findings. Additionally, subsequent subgroup analysis revealed that the use of vasopressin have a significant interaction with aspirin's efficacy. CONCLUSION: Aspirin was associated with decreased mortality in SIMI patients, and this beneficial effect persisted regardless of pre-ICU treatment.

Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage.

The recent study by Kaiwen Wang et al., titled "Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage," explores the association between postoperative intracranial bleeding (PIB) and various risk factors, including smoking, pre-hemorrhagic antiplatelet therapy, and dyslipidemia. While the study highlights that smoker, particularly women, are at increased risk for subarachnoid hemorrhage and acknowledges the risks of pre-hemorrhagic antiplatelet use, it overlooks the potential risk of PIB associated with early postoperative aspirin administration. This critique underscores the need to approach the study's findings with caution, given the broader context of aspirin's risk profile. Specifically, aspirin has been associated with a 37% higher relative risk of any intracranial hemorrhage, as indicated by other randomized trials. Additionally, the study's implications regarding the benefits of aspirin in stroke prevention must be critically evaluated, as the increased risk of intracranial bleeding may outweigh the potential benefits. This abstract emphasizes the importance of careful consideration of aspirin's adverse effects in the context of postoperative care.

Interindividual variability in platelet reactivity among individuals with or without antiplatelet therapy: results from a large tertiary care hospital.

Antiplatelet therapy is crucial for reducing thrombotic events in patients with atherosclerotic disease, but the response vary widely among individuals. The identification of patients at high (HPR), optimal (OPR) or low platelet reactivity (LPR) is dependent on high interlaboratory variability. We report results of a large dataset of patients to assess the gold standard light transmission aggregometry (LTA). A total of 11,913 patients who sequentially underwent LTA assessment using several stimuli (ADP-2µM, collagen-2 µg/ml, arachidonic acid 0.5 mM, epinephrine 10µM) with a standardized methodology between 2004 and 2022 were screened. After application of inclusion-exclusion criteria, 5,901 patients were included and divided into five groups: healthy-volunteers (HV; N = 534); controls (CTR; N = 1073); aspirin-treated patients (ASA; 75-150 mg/die; N = 3280); clopidogrel-treated patients (CLOP; 75 mg/die; N = 495) and patients treated with dual antiplatelet therapy, ASA plus CLOP (DAPT; N = 519). The mean PA% in response to ADP 2 µm was 72.4 ± 33.3 in the CTR population, 40.6 ± 29.9 in the ASA group, 25.1 ± 35.1 in the CLOP group and 10.2 ± 18.5 in the DAPT group. The mean PA% in response to collagen 2 ug/ml was 90.7 ± 10.5 in the CTR population, 40.8 ± 26.3 in the ASA group, 79.4 ± 21.8 in the CLOP group and 17.9 ± 19.9 in the DAPT group. The percentage of patients at OPR following ADP stimuli was 66%, 25%, and 26%, in the ASA, CLOP, and DAPT group, respectively. The percentage of patients at OPR following collagen stimuli was 56%, 22%, and 41%, in the ASA, CLOP, and DAPT group, respectively. LTA was significantly increased in response to ADP (72.4 ± 33.3vs62.7 ± 37.1; p < 0.001) and AA (90.7 ± 15.6vs87.6 ± 20.5; p < 0.001) in CTR compared to HV. Our findings support the concept that a significant proportion of individuals present a hyper- or hypo-reactive platelet phenotype potentially affecting the safety and efficacy of antiplatelet therapy. The variability in response to antiplatelet therapy was particularly evident in patients undergoing single as opposed to dual antiplatelet therapy regimens. These data support ongoing strategies of guided selection of antiplatelet therapy in patients with cardiovascular disease.

Should We Use Aspirin or P2Y12 Inhibitor Monotherapy in Stable Ischemic Heart Disease?

PURPOSE OF REVIEW: To summarize the recent evidence and guideline recommendations on aspirin or P2Y12 inhibitor monotherapy in patients with stable ischemic heart disease and provide insights into future directions on this topic, which involves transition to a personalized assessment of bleeding and thrombotic risks. RECENT FINDINGS: It has been questioned whether the evidence for aspirin as the foundational component of secondary prevention in patients with coronary artery disease aligns with contemporary pharmaco-invasive strategies. The recent HOST-EXAM study randomized patients who had received dual antiplatelet therapy for 6 to 18 months without ischemic or major bleeding events to either clopidogrel or aspirin for a further 24 months, and demonstrated that the patients in the clopidogrel arm had significantly lower rates of both thrombotic and bleeding complications compared to those in the aspirin arm. The patient-level PANTHER meta-analysis showed that in patients with established coronary artery disease, P2Y12 inhibitor monotherapy was associated with lower rates of myocardial infarction, stent thrombosis as well as gastrointestinal bleeding and hemorrhagic stroke compared to aspirin monotherapy, albeit with similar rates of all-cause mortality, cardiovascular mortality and major bleeding. Long-term low-dose aspirin is recommended for secondary prevention in patients with stable ischemic heart disease, with clopidogrel monotherapy being acknowledged as a feasible alternative. Dual antiplatelet therapy for six months after percutaneous coronary intervention remains the standard recommendation for patients with stable ischemic heart disease. However, the duration of dual antiplatelet therapy may be shortened and followed by P2Y12 inhibitor monotherapy or prolonged based on individualized evaluation of the patient's risk profile.

Aspirin Monotherapy vs No Antiplatelet Therapy in Stable Patients With Coronary Stents Undergoing Low-to-Intermediate Risk Noncardiac Surgery.

BACKGROUND: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited. OBJECTIVES: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation. METHODS: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery. RESULTS: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027). CONCLUSIONS: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548).

Effect of Low-Dose Aspirin Use After Thermal Ablation in Patients with Hepatocellular Carcinoma: A Retrospective Study.

Purpose: To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation. Methods: A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed. Results: A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1-14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5-11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1-95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7-64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups. Conclusion: Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.

Time to treatment and disability attributed to index stroke in the POINT trial.

BACKGROUND: In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, dual antiplatelet therapy (DAPT) was associated with reduced disability attributable to the index stroke compared to antiplatelet monotherapy. However, it is unknown whether earlier treatment with DAPT versus aspirin is associated with greater benefit. METHODS: We analyzed patients enrolled in POINT with minor ischemic stroke who had available data recording the treatment initiation time and modified Rankin Scale (mRS) at 90 days. Patients were randomized to DAPT (aspirin plus clopidogrel) vs. aspirin alone within 12 h of symptom onset. We estimated the effect of DAPT on disability (defined as mRS>1) ascribed to the index event and major hemorrhage at 90 days, stratified by tertiles of time from symptom onset-to-treatment-initiation. RESULTS: A total of 2559 patients were included; median onset-to-treatment-initiation time was 8.3 h (IQR:5.8-11.0). Comparing DAPT to aspirin, the rate of disability attributed to the index event at 90-day follow-up was 5.1 % vs. 8.6 % (OR 0.57; 95 % CI:0.33-0.99) in patients treated <6.7 h, 7.5 % vs. 9.9 % (OR 0.74; 95 % CI:0.45-1.19) in those treated 6.7-10.0 h, and 8.6 % vs. 10.6 % (OR 0.80; 95 % CI:0.50-1.26) in those treated >10.0 h after symptom onset (p for interaction=0.65). There was no difference in major hemorrhage across time strata. CONCLUSIONS: While not statistically significant, these results suggest the possibility of greater efficacy at reducing disability ascribed to minor stroke with earlier treatment with DAPT compared to aspirin. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Identifier: NCT00991029.

Sensitive objective markers for measuring aspirin responsiveness in pregnancy: An explorative scoping review.

BACKGROUND: Aspirin is frequently used in pregnancy to decrease the risk of developing pre-eclampsia. Studies have highlighted this potential benefit which in theory happens by inhibition of platelet function. However, questions remain on the appropriate dosing and the reliability of serum markers in determining aspirin responsiveness in pregnancy (ARP). OBJECTIVE: review the literature on ARP and identify the gaps, followed by investigating the objective biomarkers used to assess ARP. This includes the factors associated such as aspirin formulations, doses, and patient comorbidities. METHODS: A comprehensive search was conducted using keywords such as 'aspirin', 'pregnancy', and 'responsiveness' in relevant databases such as PubMed, SCOPUS, Cochrane from inception to March 2024. Our inclusion criteria enrolled pregnant women aged 18 years old and above, irrespective of their trimester status, who were prescribed aspirin for any medical indication. RESULTS: The research findings encompass three key areas. Firstly, examination of the impact of different aspirin formulations on responsiveness revealed no significant differences between different formulations. Secondly, nine papers were identified with varied dosages of administered aspirin, highlighting a need for standardized approach to dosing, and investigating higher dosing and its impact. Thirdly, there is a lack of consensus on biomarkers used to assess ARP. Finally, this synthesis sheds light on prognostic factors of developing aspirin non-responsiveness, such as medical comorbidities. CONCLUSION: This scoping review identifies several residual uncertainties on ARP. The main gaps are validation of serum markers, understanding the influence of underlying morbidity on ARP, and determining appropriate aspirin dosing in pregnancy.

Lignin Nanoparticles as pH-responsive Nanocarriers for Gastric-Irritant Oral Drug Aspirin.

INTRODUCTION: Although lignin is one of the most naturally abundant biopolymers, the overall status of its utilization has long been subpar. The ability of Lignin to readily self-assemble into nanoparticles, along with its good biocompatibility and minimal toxicity, makes it a perfect agent for nanocarriers and drug delivery. METHOD: Hence, in this study, we have attempted to examine lignin nanoparticles (LNPs) as an efficient pH-responsive nanocarrier for gastric-irritant oral NSAID, aspirin. Alkali lignin (AL) was extracted from rice straw via alkaline treatment, and the lignin nanoparticles were synthesized from lignin using the acid precipitation method. The average particle size was 201.37 ± 1.20 nm, and the synthesized LNPs exhibited a spherical shape and smooth outer surface along with high polydispersity (PDI= 0.284 ± 0.012). The LNPs showed moderate hemocompatibility during in vitro hemolysis studies. The nanoparticles presented nearly similar chemical structures to the AL from which they were developed, and the FT-IR absorption spectra confirmed the similarity of this chemical structure to the LNPs and AL. Aspirin was successfully loaded into the LNPs with a satisfactory drug loading value of 39.12 ± 1.50 and an excellent encapsulation efficiency value of 91.44 ± 0.59. RESULTS: Finally, the LNPs were capable of protecting the loaded drug at the acidic pH of the stomach (1.2) with just 29.20% release of the loaded aspirin after 10 h of observation in vitro. Contrarily, the LNPs were capable of rapidly releasing the aspirin at the basic pH of the intestine (7.4) with nearly 90% release of the loaded drug after 10 h observation in vitro. The basic pH of the intestine might lead to gradual dissociation of the LNPs followed by swift release of the loaded cargo. CONCLUSION: These findings substantiate that the LNPs carry the potential to be an apt and safe nanocarrier for oral drugs like aspirin as well as parenteral drugs, and LNPs can be utilized as an efficient alternative to enteric coating.

Aspirin-clopidogrel combination therapy for ischemic stroke patients: Clinical efficacy and cost-effectiveness analyses in low-resource setting.

Understanding the cost-effectiveness of aspirin-clopidogrel combination therapy is crucial in determining its influence on coagulation parameters, specifically prothrombin time (PT) and activated partial thromboplastin time (APTT). The aim of this study was to assess the cost-effectiveness and clinical impact of using the aspirin-clopidogrel combination compared to aspirin alone in managing ischemic stroke. Employing an observational research design, inpatient ischemic stroke cases receiving the aspirin-clopidogrel combination were compared to those treated with aspirin alone. Focusing on the hospital's perspective on costs, the research specifically analyzed medical expenses without discounting costs or effects. The analysis involved comparing the direct medical costs and coagulation parameters between the two treatment groups. Our data revealed that the aspirin-clopidogrel combination demonstrated superior cost-effectiveness over aspirin alone, indicated by the incremental cost-effectiveness ratio (ICER) values for PT (IDR -246,930/second) and APTT (IDR -119,270/second). This indicated that the combination therapy was associated with lower costs while yielding better clinical parameter values. The ICER analysis placed the aspirin-clopidogrel combination in the southeast quadrant, marking its dominance over aspirin monotherapy by demonstrating higher effectiveness at lower costs. These results suggest that combination therapy might be a favorable alternative for managing ischemic stroke, presenting a viable option for consideration in clinical practice. The findings underscore the potential economic and clinical advantages of employing the aspirin-clopidogrel combination in routine stroke management protocols.

Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study.

BACKGROUND: Liver transplantation (LT) is a potentially curative therapy for patients with hepatocellular carcinoma (HCC). HCC-recurrence following LT is associated with reduced survival. There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT. AIM: To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC, and patient outcomes following LT. METHODS: This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022, from a single Australian centre. Drug use was defined as statin, aspirin or metformin therapy for ≥ 29 days, within 24 months post-LT. A cox proportional-hazards model with time-dependent covariates was used for survival analysis. Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality, HCC-recurrence and HCC-related mortality. Sensitivity analysis was performed to account for immortality time bias and statin dosing. RESULTS: Three hundred and five patients were included in this study, with 253 (82.95%) males with a median age of 58.90 years. Aetiologies of liver disease were 150 (49.18%) hepatitis C, 73 (23.93%) hepatitis B (HBV) and 33 (10.82%) non-alcoholic fatty liver disease (NAFLD). 56 (18.36%) took statins, 51 (16.72%) aspirin and 50 (16.39%) metformin. During a median follow-up time of 59.90 months, 34 (11.15%) developed HCC-recurrence, 48 (15.74%) died, 17 (5.57%) from HCC-related mortality. Statin, aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality [hazard ratio (HR): 1.16, 95%CI: 0.58-2.30; HR: 1.21, 95%CI: 0.28-5.27; HR: 0.61, 95%CI: 0.27-1.36], HCC-recurrence (HR: 0.52, 95%CI: 0.20-1.35; HR: 0.51, 95%CI: 0.14-1.93; HR 1.00, 95%CI: 0.37-2.72), or HCC-related mortality (HR: 0.32, 95%CI: 0.033-3.09; HR: 0.71, 95%CI: 0.14-3.73; HR: 1.57, 95%CI: 0.61-4.04) respectively. Statin dosing was not associated with statistically significant differences in HCC-related outcomes. CONCLUSION: Statin, metformin or aspirin use was not associated with improved HCC-related outcomes post-LT, in a largely historical cohort of Australian patients with a low proportion of NAFLD. Further prospective, multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

Sonoelectrochemical degradation of aspirin in aquatic medium using ozone and peroxymonosulfate activated with FeS2 nanoparticles.

The catalytic performance of nano-FeS2 in the sonoelectrochemical activation of peroxymonosulfate (PMS) and ozone to remove aspirin (ASP) was studied for the first time. The crystal structure and Fe bonds in the catalyst were confirmed through XRD and FTIR analysis. Within 30 min, ASP (TOC) was removed by 99.2 % (81.6 %) and 98.6 % (77.4 %) in nano-FeS2/PMS and nano-FeS2/O3 sonoelectrochemical systems, respectively. Water anions, especially (almost 50 %), had an inhibitory effect on ASP removal. The probes confirmed that SO4•-and HO• were the key to ASP degradation in nano-FeS2/PMS and nano-FeS2/O3 systems, respectively. The effective activation of oxidants due to the ideal distribution of Fe2+ by catalyst was the main mechanism of ASP removal, in which electric current (EC) and ultrasound (US) played a crucial role through the recycling of Fe ions, dissolution and cleaning of the catalyst. LC-MS analysis identified thirteen byproducts in the ASP degradation pathways. The energy consumption of the proposed sonoelectrochemical systems was lower than previous similar systems. This study presented economic and sustainable hybrid systems for pharmaceutical wastewater remediation.

Recurrent cardiovascular and limb events in 294,428 patients with coronary or peripheral artery disease or ischemic stroke on antiplatelet monotherapy: The RESRISK cohort study.

BACKGROUND AND AIMS: Utilising real-world data, we quantified the burden of cardiovascular risk factors and long-term residual risk of atherothrombotic events among routine care cohorts with coronary (CAD) or peripheral (PAD) artery disease or ischemic stroke (IS) on guideline-recommended antiplatelet monotherapy (APMT). METHODS: Retrospective cohort study using data (2010-2020) from the United Kingdom Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics, including adults with CAD, PAD or IS who were first prescribed APMT (CAD/IS: aspirin; PAD: clopidogrel). Primary outcomes (recurrent events): major adverse cardiovascular events (MACE) for CAD/PAD/IS cohorts, major adverse limb events (MALE) for PAD. RESULTS: 266,478 CAD, 13,162 PAD, and 14,788 IS patients were included (mean age: 71 years; women 37.7%-47.5 %). Risk factor burden was high and attainment of recommended goals was low. There were 73,691, 3,121 and 7,137 MACE among CAD, PAD and IS patients, respectively (median follow-up: 89.9, 42.4 and 75.9 months, respectively), and 4,767 MALE among PAD patients. MACE incidence rate per 1000 person-years was higher in IS (268.7; 95%CI 265.3-272.0) than CAD (92.9; 95%CI 92.5-93.4) or PAD cohorts (97.2; 95%CI 94.6-99.8). MALE incidence rate was 195.9 (95%CI 192.2-199.6) per 1000 person-years. IS patients presented a lower rate of hospitalisations and longer time-to-first hospitalisation, but once hospitalised, they had a longer length-of-stay. PAD patients had the highest hospitalisation rate. CONCLUSIONS: Among a contemporary cohort with cardiovascular disease on APMT, long-term residual atherothrombotic risk remains high despite being on APMT. Greater attention to risk factor control and use of appropriate evidence-based therapy is required to reduce residual risk among this very high-risk population.