Search Results (77)

Background: Venous thromboembolism (VTE) remains a clinically relevant complication following major orthopaedic procedures, particularly total hip arthroplasty (THA), total knee arthroplasty (TKA), and fracture surgery. Although low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs) are widely regarded as standard pharmacological options, aspirin (acetylsalicylic acid, ASA) has gained renewed attention because of its low cost, oral administration, and favourable bleeding profile. However, the available evidence is heterogeneous, and its interpretation is complicated by differences in patient selection, timing and duration of prophylaxis, diagnostic methodology, aspirin dosing regimens, and the increasing adoption of modern fast-track arthroplasty pathways. Methods: A structured evidence-based review was conducted in accordance with PRISMA 2020 principles. PubMed, Embase, Web of Science, and the Cochrane Library were searched through September 2025 for randomised controlled trials (RCTs), major international clinical practice guidelines, and selected high-level studies relevant to the interpretation of aspirin-based orthopaedic thromboprophylaxis. Nine RCTs, four major guideline documents, and sixteen additional Level I–II studies were included. Outcomes of interest were symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and mortality. Risk of bias was assessed using the Cochrane ROB 2 framework. Owing to marked methodological heterogeneity, no formal pooled meta-analysis was undertaken. Results: The available RCT evidence suggests that aspirin may perform adequately within structured sequential or risk-stratified prophylaxis strategies, but not in all clinical settings. In arthroplasty, EPCAT II demonstrated non-inferiority of aspirin when introduced after an initial five-day course of rivaroxaban, whereas CRISTAL showed higher early symptomatic VTE rates when aspirin was used as sole primary prophylaxis from postoperative day 0. Importantly, thromboembolic events in CRISTAL occurred earlier in the aspirin cohort, supporting the concept that anticoagulant therapy remains important during the immediate postoperative hypercoagulable phase. In trauma surgery, PREVENT CLOT established non-inferiority of aspirin compared with LMWH for 90-day mortality; however, the predominantly young study population and the inclusion of upper-extremity fractures limit extrapolation to elderly hip fracture patients. Several smaller RCTs reported no major differences between aspirin and anticoagulants, but these studies were frequently underpowered and relied on less sensitive diagnostic strategies. Historical and contemporary guidelines remain heterogeneous, and evidence from modern fast-track arthroplasty pathways suggests that current trial-based conclusions may not be directly generalisable to short-duration prophylaxis settings. Conclusions: Aspirin may have a role in orthopaedic thromboprophylaxis when used within structured, risk-adapted or sequential protocols, particularly in standard-risk arthroplasty patients and selected trauma populations. However, current evidence does not support its universal use as sole primary prophylaxis in major orthopaedic surgery, especially during the early postoperative hypercoagulable phase or in high-risk patients. Furthermore, the available literature does not permit definitive recommendations regarding the optimal aspirin dose or duration of prophylaxis. The generalisability of the existing literature is further limited by methodological heterogeneity and by the absence of RCTs directly evaluating ultra-short anticoagulant regimens versus prolonged aspirin prophylaxis in modern fast-track arthroplasty. Further high-quality, standardised trials are required. Full article

Background/Objectives: Chronic inflammation is a key factor in the development and progression of colorectal cancer (CRC). When COX-2 levels and PGE₂ production increase, nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA) and selective COX-2 inhibitors, such as celecoxib and rofecoxib, are commonly employed. This paper presents the effect of anti-inflammatory drugs, primarilyNSAIDs, on the incidence of CRC. Methods: A comprehensive literature search (119 articles) was conducted with databases such as PubMed. During our research, we used keywords such as colorectal cancer (CRC), nonsteroidal anti-inflammatory drugs (NSAIDs), ASA, COX, precision oncology, and personalized medicine. Results: The development of CRC is primarily associated with chronic inflammation and the actions of COX-2 and prostaglandin E2 (PGE₂), which promote cancer cell proliferation and angiogenesis. Anti-inflammatory drugs act by inhibiting the secretion of COX-1 and COX-2 enzymes, which leads to reduced PGE₂ production and may limit tumor growth. Aspirin has the best-documented and studied anti-cancer effect; long-term use is associated with a reduced risk of CRC development and mortality through its anti-inflammatory and antiplatelet effects, thereby limiting metastasis. Particularly beneficial effects are observed in patients with mutations in the PIK3CA gene. Factors influencing the effectiveness of CRC treatment include molecular differences and tumor location. Conclusions: The future of CRC treatment and prevention lies in personalized medicine, which accounts for each patient’s genetic profile. Decisions regarding NSAIDs use and CRC prevention should consider the potential benefits and risks of side effects. Full article

The clinical application of small-diameter vascular grafts (SDVGs; <6 mm) is limited by thrombosis and mediated by protein adsorption, platelet activation, and coagulation. To address this, we develop a dual-modified polycaprolactone (PCL) graft via covalent conjugation of bivalirudin (BV), a direct thrombin inhibitor, and aspirin (ASA), a cyclooxygenase-1 suppressor. Compared with pure PCL, the BV/ASA-modified PCL graft reduces bovine serum albumin adsorption by 35.7% and fibrinogen adsorption by 36.2%, while maintaining mechanical properties and structural integrity. Platelet adhesion, assessed by LDH viability, is reduced by 42.6%, and the blood clotting index (BCI) is increased by 67.4%, indicating enhanced anticoagulation. The modified surface enhances anticoagulation and exhibits cell viability above 80%, confirming non-toxicity. These in vitro results demonstrate that BV and ASA dual functionalization effectively improves the antithrombotic performance of PCL vascular grafts, suggesting its potential as a candidate for further preclinical evaluation in SDVG applications. Full article

Background/Objectives: Oral administration remains the most widely used route for drug delivery but is unsuitable for many central nervous system (CNS) therapeutics due to extensive hepatic first-pass metabolism and the restrictive blood–brain barrier (BBB). Acetyl salicylic acid (ASA), despite its neuroprotective and anti-inflammatory potential, exhibits poor brain bioavailability when delivered orally, limiting its therapeutic utility in ischemic stroke and chronic neurodegenerative conditions. Methods: This study reports the first use of three-dimensional (3D) bioprinting to develop brain-targeting ASA nanoparticle (NP)-loaded orally disintegrating films (ODFs) for direct systemic uptake and enhanced CNS delivery. The ODFs were fabricated using a CELLINK INKREDIBLE plus^® bioprinter and optimized for uniformity, rapid dissolution, and nanoparticle stability. Results: The films displayed consistent physicochemical properties (weight 10.86 ± 0.28 mg; thickness 0.47 ± 0.26 mm; pH 7.5–7.7) and disintegrated within 2.38 ± 0.28 min. In vitro testing on BEND3 brain endothelial cells confirmed biocompatibility, with no inflammatory response or cytotoxicity up to 62 µg/mL. In vivo biodistribution in murine models demonstrated substantial brain accumulation, achieving 14.15 ng/mg tissue following buccal administration. Conclusions: This work establishes a novel, non-invasive CNS drug delivery platform combining 3D bioprinting with ligand-functionalized ASA NPs to bypass hepatic metabolism and improve brain targeting. The rapid-dissolving ODFs demonstrated high reproducibility, safety, and effective brain deposition, highlighting their translational potential for neurological therapeutics. This approach may be extended to other small molecules with limited CNS penetration, offering a versatile pathway toward precision neuropharmacology. Full article

Background/Objectives: Acetylsalicylic acid (ASA) medication has been suggested to have a beneficial effect on cancer risk and survival. Therefore, this retrospective case–control study investigated the correlation between ASA and HNC in over 11,000,000 patients to investigate the impact of ASA intake on the risk of developing HNC, five-year survival rates, and the likelihood of secondary malignant neoplasms and malignant lymph node involvement. Methods: Retrospective clinical data was retrieved from a federated EHR network. Patients prescribed ASA were assigned to Cohort I, while those who were not prescribed ASA were assigned to Cohort II. Moreover, patients diagnosed with HNC, and prescribed ASA were assigned to Cohort III, while those with HNC but no history of ASA use were assigned to Cohort IV. Results: After matching, Cohorts I and II included 5,716,056 patients each. HNC incidence was significantly lower (OR 0.88; 95% CI 0.86–0.90) in Cohort I (+ASA) compared to Cohort II (−ASA). Furthermore, five-year survival was higher for patients taking ASA medication (survival probability 67.93%) compared to patients who did not (65.54%). These findings coincide with a lower risk of death of 22.8% (+ASA) compared to 23.6% (−ASA), which was statistically significant (p = 0.006). Patients with ASA intake also showed a lower risk of malignant neoplasms of lymph nodes (17.4% vs. 18.5%). Conclusions: Our analyses revealed a lower risk of HNC, a higher five-year survival rate, and a lower risk of malignant neoplasms of lymph nodes in patients with ASA medication. However, the retrospective design and the lack of evaluation of confounders limit the significance of our data, and, therefore, further analyses should be considered. Full article

Background/Objectives: Severe allergic asthma is usually treated with omalizumab; however, this drug may not be effective for every patient. By its action, dupilumab could be an alternative in these patients. The objective of this study was to evaluate the efficacy of dupilumab in patients with severe allergic asthma, non-responsive to omalizumab, according to the maintenance of their oral corticosteroid (OCS) dose, an exacerbation rate decrease, or poor control of the disease, despite optimized treatment. Methods: A retrospective analysis of data from severe asthma clinics was performed, observing the efficacy of the switch to dupilumab in patients who experienced a failed treatment with omalizumab. Results: Forty-two patients were included. Dupilumab proved to be effective in patients who experienced a failed omalizumab treatment, with a significant reduction in the exacerbation number and OCS use. Furthermore, remission of the disease, according to the Severe Asthma Network of Italy (SANI) criteria, was achieved in 35 patients, with complete remission in 19 (45%) and partial remission in 16 (38%). The analysis of the predictors of the success of dupilumab therapy in achieving clinical remission, through univariate analysis of the data at baseline, showed that complete remission was more easily reached in patients with concomitant aspirin (ASA) intolerance or in those with nasal polyposis. Conclusions: Dupilumab is an effective drug for the treatment of patients with severe asthma with an allergic component, with better benefits in patients with an ASA intolerance or nasal polyposis. Full article

Aspirin (ASA) is one of the most used medications worldwide and has shown various effects on cellular processes, including stem cell differentiation. However, the effect of ASA on adipogenesis of adipose tissue-derived stem cells (ASCs) remains largely unknown. Considering the potential application of ASCs in regenerative medicine and cell-based therapies, this study investigates the effects of ASA on adipogenic differentiation in human ASCs. ASCs were exposed to varying concentrations of ASA (0 µM, 400 µM, and 1000 µM) and evaluated for changes in morphology, migration, and adipogenic differentiation. While ASA exposure did not affect self-renewal potential, migration ability, or cell morphology, it significantly reduced lipid vacuole formation at 1000 µM after 21 days of adipogenic differentiation (p = 0.0025). This visible inhibition correlated with decreased expression of adipogenic markers (PPARG, ADIPOQ, and FABP4) and the proliferation marker MKi67 under ASA exposure in comparison to the control (ns). Overall, the findings demonstrate that ASA inhibits adipogenic differentiation of human ASCs in a dose-dependent manner in vitro, contrasting its known role in promoting osteogenic differentiation. This research highlights ASA’s complex effects on ASCs and emphasizes the need for further investigation into its mechanisms and potential therapeutic applications in obesity and metabolic diseases. The inhibitory effects of ASA on adipogenesis should be considered in cell-based therapies using ASCs. Full article

Background: several experimental findings and epidemiological observations indicated that aspirin/acetylsalicylic acid (ASA) may be endowed with anticancer effects against a variety of human malignancies, including thyroid carcinomas. Among these, undifferentiated/anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal human cancers, refractory to all currently available therapies. Methods: we here evaluated in a preclinical setting the effects of ASA on a panel of three ATC-derived cell lines: the CAL-62, the 8305C, and the 8505C. Results: the data obtained demonstrated the ability of ASA to inhibit, in a dose- and time-dependent manner, the proliferation of all ATC cell lines investigated, with IC₅₀ values comprised between 2.0 and 4.3 mM. Cell growth was restrained with the same efficacy when the ASA treatment was applied to three-dimensional soft-agar cultures. In addition, ASA significantly reduced migration and invasion in two of the three ATC cell lines. We finally investigated the effects of ASA on the MAPK and PI3K/Akt signaling pathways, which are often altered in ATC. The results showed that the phosphorylation status of the Akt1/2/3 kinases was significantly reduced following ASA treatment, while ERK1/2 phosphorylation was either unaffected or slightly upregulated. Conclusions: our findings support epidemiological evidence on the anticancer potential of ASA. On this basis, further investigations should be carried out to assess the usefulness of ASA as adjuvant therapy in patients affected by ATC. Full article

Background: Patients with a HeartMate 3 (HM3) left ventricular assist device (LVAD) typically receive anticoagulation and antiplatelet therapy. The HM3 has shown a marked reduction in hemocompatibility-related adverse events (HRAEs) like stroke, bleeding, and pump thrombosis. This study evaluated whether aspirin (ASA) response influences HRAE incidence and if ASA sensitivity changes over time in HM3 recipients. Methods: This single-center, cross-sectional study included 32 HM3 patients (age: 59.0 ± 10.0 years, 15.6% female). ASA sensitivity was assessed twice using the VerifyNow assay, with ASA resistance defined by ASA reactivity units (ARU) > 550. The primary endpoint was HRAE incidence in ASA responders vs. non-responders over two consecutive follow-ups; the secondary endpoint was temporal changes in ASA resistance. Results: At the first follow-up, 13 (40.6%) patients were ASA-resistant, and 8 (28.6%) were resistant at the second follow-up, without significant change (p = 0.22). ASA non-responders and responders had similar ASA doses and baseline characteristics. No significant difference in HRAE incidence was found between ASA non-responders and responders (0.0% vs. 15.8%, p = 0.14), and no additional HRAEs occurred during follow-up. Conclusions: ASA resistance varied considerably among HM3 patients without significant temporal changes, and the demonstrated excellent hemocompatibility supports recent evidence that ASA may have a limited role in the antithrombotic regimen for HM3 recipients. Full article

Background/Objectives: Comparative studies often use the p value to convey statistical significance, but fragility indices (FI) and fragility quotients (FQ) may better signify statistical strength. The use of aspirin as venous thromboembolism (VTE) chemoprophylaxis following elective arthroplasty has been debated between the orthopedic and cardiac fields. The purpose of this study was to apply both the FI and FQ to evaluate the degree of statistical fragility in the total joint arthroplasty (TJA) literature regarding aspirin (ASA) use for VTE prevention. Methods: We performed a systematic search for TJA clinical trials from 2004 to 2023 reporting comparisons between ASA and other chemoprophylaxis methods for VTE. The FI of each outcome was calculated through reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by study sample size and interquartile range (IQR) was calculated. SPSS Meta-analysis function was used to calculate the Mean Effect Size Estimate and 95% Confidence Intervals for each outcome. Results: Of 245 articles screened, 39 met search criteria, with 10 RCTs included for analysis (n = 11,481 patients). There were 38 outcome events reported, with three significant (p < 0.05) outcomes and 35 non-significant (p > 0.05) outcomes identified. The overall FI and FQ for all 38 outcomes were 6 (IQR: 5–7) and 0.059 (IQR: 0.044–0.064), respectively. Seven studies (70%) reported a loss-to-follow-up (LTF) greater than the overall FI. There was no increased risk of DVT, PE, or mortality with use of ASA (all p > 0.2). Conclusions: Despite showing non-inferiority in preventing venous thromboembolic events in TJA overall, the highest-level peer-reviewed literature concerning aspirin use following total joint arthroplasty is considered statistically fragile due to high loss-to-follow-up. In addition to the reporting of the p value, the fragility index and quotient can further provide insight into the strength and trustworthiness of outcome measures. Full article

Acetylsalicylic acid (ASA) represents a cornerstone of antiplatelet therapy for the treatment of atherosclerotic coronary artery disease (CAD). ASA is in fact indicated in case of an acute coronary syndrome or after a percutaneous coronary intervention with stent implantation. Aspirin hypersensitivity is frequently reported by patients, and this challenging situation requires a careful evaluation of the true nature of the presumed sensitivity and of its mechanisms, as well as to differentiate it from a more frequent (and more easily manageable) aspirin intolerance. Two main strategies are available to allow ASA administration for patients with CAD and suspected ASA hypersensitivity: a low-dose ASA challenge, aimed at assessing the tolerability of ASA at the antiplatelet dose of 100 mg, and desensitization, a therapeutic procedure which aims to induce tolerance to ASA. For those patients who cannot undergo ASA challenge and desensitization due to previous serious adverse reactions, or for those in whom desensitization was unsuccessful, a number of further alternative strategies are available, even if these have not been validated and approved by guidelines. The aim of this state-of-the-art review is therefore to summarize the established evidence regarding pathophysiology, clinical presentation, diagnosis, and management of aspirin hypersensitivity and to provide a practical guide for cardiologists (and clinicians) who have to face the not uncommon situation of a patient with concomitant coronary artery disease and aspirin hypersensitivity. Full article

The omega-3 polyunsaturated fatty acids (PUFAs) Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) exert multiple cardioprotective effects, influencing inflammation, platelet activation, endothelial function and lipid metabolism, besides their well-established triglyceride lowering properties. It is not uncommon for omega-3 PUFAs to be prescribed for hypertriglyceridemia, alongside antiplatelet therapy in cardiovascular disease (CVD) patients. In this regard, we studied the effect of EPA and DHA, in combination with antiplatelet drugs, in platelet aggregation and P-selectin and α_IIbβ₃ membrane expression. The antiplatelet drugs aspirin and triflusal, inhibitors of cyclooxygenase-1 (COX-1); ticagrelor, an inhibitor of the receptor P2Y₁₂; vorapaxar, an inhibitor of the PAR-1 receptor, were combined with DHA or EPA and evaluated against in vitro platelet aggregation induced by agonists arachidonic acid (AA), adenosine diphosphate (ADP) and TRAP-6. We further investigated procaspase-activating compound 1 (PAC-1) binding and P-selectin membrane expression in platelets stimulated with ADP and TRAP-6. Both DHA and EPA displayed a dose-dependent inhibitory effect on platelet aggregation induced by AA, ADP and TRAP-6. In platelet aggregation induced by AA, DHA significantly improved acetylsalicylic acid (ASA) and triflusal’s inhibitory activity, while EPA enhanced the inhibitory effect of ASA. In combination with EPA, ASA and ticagrelor expressed an increased inhibitory effect towards ADP-induced platelet activation. Both fatty acids could not improve the inhibitory effect of vorapaxar on AA- and ADP-induced platelet aggregation. In the presence of EPA, all antiplatelet drugs displayed a stronger inhibitory effect towards TRAP-6-induced platelet activation. Both omega-3 PUFAs inhibited the membrane expression of α_IIbβ₃, though they had no effect on P-selectin expression induced by ADP or TRAP-6. The antiplatelet drugs exhibited heterogeneity regarding their effect on P-selectin and α_IIbβ₃ membrane expression, while both omega-3 PUFAs inhibited the membrane expression of α_IIbβ₃, though had no effect on P-selectin expression induced by ADP or TRAP-6. The combinatory effect of DHA and EPA with the antiplatelet drugs did not result in enhanced inhibitory activity compared to the sum of the individual effects of each component. Full article

This study investigates the impact of acetylsalicylic acid (ASA), also known as aspirin, on adipose tissue-derived stem cells (ASCs), aiming to elucidate its dose-dependent effects on morphology, viability, proliferation, and osteogenic differentiation. Isolated and characterized human ASCs were exposed to 0 µM, 100 µM, 200 µM, 400 µM, 800 µM, 1000 µM, 10,000 µM, and 16,000 µM of ASA in vitro. Cell morphology, viability, and proliferation were evaluated with fluorescent live/dead staining, alamarBlue viability reagent, and CyQUANT^® cell proliferation assay, respectively. Osteogenic differentiation under stimulation with 400 µM or 1000 µM of ASA was assessed with alizarin red staining and qPCR of selected osteogenic differentiation markers (RUNX2, SPP1, ALPL, BGLAP) over a 3- and 21-day-period. ASA doses ≤ 1000 µM showed no significant impact on cell viability and proliferation. Live/dead staining revealed a visible reduction in viable cell confluency for ASA concentrations ≥ 1000 µM. Doses of 10,000 µM and 16,000 µM of ASA exhibited a strong cytotoxic and anti-proliferative effect in ASCs. Alizarin red staining revealed enhanced calcium accretion under the influence of ASA, which was macro- and microscopically visible and significant for 1000 µM of ASA (p = 0.0092) in quantification if compared to osteogenic differentiation without ASA addition over a 21-day-period. This enhancement correlated with a more pronounced upregulation of osteogenic markers under ASA exposure (ns). Our results indicate a stimulatory effect of 1000 µM of ASA on the osteogenic differentiation of ASCs. Further research is needed to elucidate the precise molecular mechanisms underlying this effect; however, this discovery suggests promising opportunities for enhancing bone tissue engineering with ASCs as cell source. Full article

Background and Objectives: Malignant melanoma (MM) remains one of the most aggressive cancers worldwide, presenting a limited number of therapeutic options at present. Aspirin (ASA), a broadly used non-steroid anti-inflammatory medicine, has recently emerged as a candidate for repurposing in cancer management, due to its therapeutic potential in the treatment of several neoplasms which include MM. Fisetin (FIS) is a flavonoid phytoestrogen instilled with multispectral pharmacological activities, including a potent anti-melanoma property. The present study aimed to assess the potential improved anti-neoplastic effect resulting from the association of ASA and FIS for MM therapy. Materials and Methods: The study was conducted using the A375 cell line as an experimental model for MM. Cell viability was assessed via the MTT test. Cell morphology and confluence were evaluated using bright-field microscopy. The aspect of cell nuclei and tubulin fibers was observed through immunofluorescence staining. The irritant potential and the anti-angiogenic effect were determined on the chorioallantoic membrane of chicken fertilized eggs. Results: The main findings related herein demonstrated that the ASA 2.5 mM + FIS (5, 10, 15, and 20 µM) combination exerted a higher cytotoxicity in A375 MM cells compared to the individual compounds, which was outlined by the concentration-dependent and massive reduction in cell viability, loss of cell confluence, cell shrinkage and rounding, apoptotic-like nuclear features, constriction and disruption of tubulin filaments, increased apoptotic index, and suppressed migratory ability. ASA 2.5 mM + FIS 20 µM treatment lacked irritant potential on the chorioallantoic membrane and inhibited blood-vessel formation in ovo. Conclusion: These results stand as one of the first contributions presenting the anti-melanoma effect of the ASA + FIS combinatorial treatment. Full article

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, ranking as the third most malignant. The incidence of CRC has been increasing with time, and it is reported that Westernized diet and lifestyle play a significant role in its higher incidence and rapid progression. The intake of high amounts of omega-6 (n − 6) PUFAs and low levels of omega-3 (n − 3) PUFAs has an important role in chronic inflammation and cancer progression, which could be associated with the increase in CRC prevalence. Oxylipins generated from PUFAs are bioactive lipid mediators and have various functions, especially in inflammation and proliferation. Carcinogenesis is often a consequence of chronic inflammation, and evidence has shown the particular involvement of n − 6 PUFA arachidonic acid-derived oxylipins in CRC, which is further described in this review. A deeper understanding of the role and metabolism of PUFAs by their modifying enzymes, their pathways, and the corresponding oxylipins may allow us to identify new approaches to employ oxylipin-associated immunomodulation to enhance immunotherapy in cancer. This paper summarizes oxylipins identified in the context of the initiation, development, and metastasis of CRC. We further explore CRC chemo-prevention strategies that involve oxylipins as potential therapeutics. Full article