Search Results (11,045)

Background/Objectives: Low-dose atropine eye drops are widely used to slow myopia progression in children, but by reducing accommodation they may affect near ocular alignment and binocular visual function. Evidence on ocular alignment and strabismus-related findings remains insufficiently synthesized. This review examined low-dose atropine for pediatric myopia control in relation to ocular alignment and strabismus-related findings. Methods: PubMed/MEDLINE and Web of Science Core Collection were searched from inception to 16 April 2026. English-language studies addressing low-dose atropine, myopia control, ocular alignment, strabismus, binocular vision, accommodation, and vergence were screened. Of 247 records, 166 underwent screening after duplicate removal. Twenty-three database-derived and four manually identified full-text articles were reviewed. Eleven studies were included. Results: Of eleven included studies, six were clinical or interventional studies and five were case reports or case series. Case-based reports described near-predominant esodeviation, convergence excess-type deviation, elevated accommodative convergence/accommodation (AC/A) ratios, diplopia, reduced fusion, and acquired esotropia during fixed low-dose or escalating atropine use; most fixed low-dose cases improved after discontinuation or treatment modification. Clinical and interventional studies did not show consistent worsening of ocular alignment, near point of convergence (NPC), fusional vergence, or binocular vision. More consistent changes included pupil dilation, receded near point of accommodation (NPA), reduced accommodative amplitude and facility, selected fusional vergence changes, and short-term binocular or accommodative fluctuations. Conclusions: Low-dose atropine appears to be useful for pediatric myopia control and is generally well tolerated. However, selected cases may be temporally associated with ocular alignment abnormalities or strabismus-related findings. Careful monitoring may be warranted in children with unstable binocular systems and during dose escalation. Full article

Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like quercetin), stilbenes (like resveratrol), phenolic acids and curcuminoids (like curcumin) are major classes that have shown strong anticancer action against a variety of cancers, including prostate, colorectal and breast cancers. Through targets including PI3K/Akt, MAPK, NF-κB, and p53 signaling networks, these substances influence important molecular pathways involved in tumor initiation and development, including oxidative stress, inflammation, apoptosis, cell cycle control, angiogenesis and metastasis. The clinical translation of polyphenols is still constrained by poor bioavailability, fast metabolism, low aqueous solubility and inefficient pharmacokinetic characteristics, which lead to insufficient systemic exposure and therapeutic efficacy despite strong preclinical data. Their therapeutic applicability is further complicated by variations in absorption and possible dose-related restrictions. To overcome these limitations, the anticancer efficacy of polyphenols has been enhanced via delivery technologies like polymeric nanoparticles, lipid-based carriers, nanoemulsions and phytosome complexes, which have shown improved stability, increased bioavailability and targeted delivery to tumor tissues. This review provides a comprehensive and integrative analysis of plant-derived polyphenols by linking molecular mechanisms, pharmacokinetic limitations and emerging delivery strategies within a translational framework. By bridging these interconnected domains, this review highlights the potential of polyphenols as viable candidates in next-generation cancer therapeutics and underscores the need for well-designed clinical studies to facilitate their successful integration into oncology practice. Full article

The prevalent endocrine disruptor bisphenol A (BPA) is associated with aging-related conditions, including metabolic disorders. It has been shown that BPA promotes bone fragility through oxidative stress-induced apoptosis and impaired osteoblast differentiation. The identification of sustainable bioactive substances that alleviate BPA-induced bone toxicity is thus of biomedical and environmental significance. Wolffia globosa (WG), the world’s smallest flowering aquatic plant, has recently gained attention as a high-protein, antioxidant-rich nutraceutical, yet its impact on BPA-induced osteoblast dysfunction has not been systematically investigated. This study presents a comprehensive assessment of WG ethanolic extract (WGE) in MC3T3-E1 pre-osteoblasts, incorporating thorough phytochemical characterization, acute high-dose and chronic low-dose BPA exposure models, and multi-faceted mechanistic analysis. LC-MS/MS profiling identified luteolin (116.17 ± 0.69 µg/g), rosmarinic acid (54.80 ± 2.12 µg/g), and apigenin (48.77 ± 0.61 µg/g) as the predominant bioactive compounds. WGE exhibited potent antioxidant capacity across DPPH and ABTS radical scavenging assays, complemented by high ORAC and FRAP values, reflecting broad-spectrum antioxidant mechanisms. Treatment with WGE (25 and 50 µg/mL) resulted in significant alleviation of BPA-induced cytotoxicity, decreased intracellular ROS levels, and inhibited apoptosis. WGE (12.5 µg/mL) also modulated autophagy-related markers (LC3-II, Beclin-1, and p62), suggesting potential autophagic participation, although flux verification was not conducted. Treatment with WGE (12.5 µg/mL) also restored BPA-suppressed osteogenesis under chronic exposure, as evidenced by enhanced alkaline phosphatase activity, and increased both mineralization and upregulation of osteogenic genes including runt-related transcription factor2 (Runx2), collagen type I alpha 1 (Colla1), alkaline phosphatase (ALP), and osteocalcin (OCN). These effects were accompanied by partial reactivation of Wnt/β-catenin signaling. This study is the first to demonstrate that WGE protects osteoblasts from BPA toxicity by concurrently strengthening antioxidant defenses, limiting apoptosis, modulating autophagy-related markers, and supporting β-catenin-mediated osteogenesis, highlighting WG as a promising sustainable nutraceutical candidate for the prevention of environmental toxin-related bone fragility. Full article

Metformin (MET) plays crucial regulatory roles in mammalian oocyte meiosis, yet the concentration-dependent biphasic impacts of MET on porcine oocyte in vitro maturation (IVM) and the related molecular mechanisms remain poorly clarified. This study aimed to explore the distinct effects and underlying pathways of low- and high-dose MET in porcine oocytes. Different concentrations of MET (0, 7.5, 15, 30, 150, and 300 μM) were supplemented during oocyte IVM, with phenotypic detection, untargeted metabolomic analysis, and Nrf2 inhibitor (ML385) intervention performed for mechanism exploration. Results showed that 15 μM low-dose MET facilitated oocyte maturation, mitochondrial function and redox balance, while 300 μM high-dose MET caused obvious developmental damage. Mechanistically, low-dose MET triggered noncanonical AMPK activation independent of the AMP/ATP ratio and enhanced AMPK–Nrf2 antioxidant signaling, whereas high-dose MET induced energy stress and oxidative injury via inhibiting mitochondrial complex I. Blockade of Nrf2 further abolished the protective effects of low-dose MET. Collectively, this finding illustrates the biphasic actions of MET on porcine oocytes and provides a theoretical reference for optimizing porcine in vitro embryo production. Full article

The pharmacokinetics (PK) and pharmacokinetic–pharmacodynamic (PK/PD) relationships of cefquinome in small ruminants remain incompletely characterized, particularly for long-acting (LA) formulations. This study evaluated cefquinome disposition after intravenous (IV), subcutaneous (SC) and LA subcutaneous (SC-LA) administration in lactating sheep and goats using nonlinear mixed-effects models (NLMEs) and Monte Carlo (MC) simulations. Cefquinome exhibited low volumes of distribution (0.21–0.31 L/kg), with goats showing higher clearance and shorter terminal half-lives than sheep. The SC-LA formulation reduced the absorption rate constant and increased both the mean absorption time and terminal half-life by 4–6-fold, resulting in sustained systemic exposure over 48 h. PK/PD analysis showed higher PK/PD cut-off values for the LA formulation, with values of 0.125 μg/mL for the fT > MIC index and 0.25 μg/mL for the fAUC/MIC index, respectively, whereas IV and SC regimens achieved lower thresholds. MC simulations indicated that only the LA formulation achieved ≥ 90% probability of target attainment (PTA) values at MICs equivalent to tentative epidemiological cut-off values (TECOFF) for respiratory pathogens. Notably, fAUC/MIC provided a more informative descriptor of efficacy for the LA formulation. These findings highlight the advantage of LA formulations and demonstrate improved performance compared with conventional dosing regimens in sheep and goats. Full article

Sarcoidosis is a multisystem granulomatous disorder of uncertain origin which still presents major therapeutic dilemmas. Longstanding dependence on corticosteroids, while effective for acute inflammation, carries considerable adverse effects over time. Advances in deciphering sarcoidosis pathobiology—including aberrant Janus kinase (JAK)- signal transducer and activator of transcription (STAT) signaling, mechanistic target of rapamycin (mTOR)-driven metabolic shifts, Th1/Th17.1 immune skewing, effector T-cell exhaustion, and granuloma-centered cytokine circuits—have revealed several targets for intervention. The treatment options are rapidly changing: the SARCORT trial showed that low-dose prednisolone is non-inferior to higher prednisolone doses; the pivotal PREDMETH trial validated methotrexate as a feasible first-line steroid-sparing option; efzofitimod, a novel immunomodulator targeting neuropilin-2, produced steroid-reducing effects in Phase IIbut not in Phase III trials; and JAK inhibitors are accumulating evidence across cutaneous and systemic presentations. The 2025 World Association for Sarcoidosis and Other Granulomatoses (WASOG) statement supports a move toward earlier steroid-sparing approaches. This review methodically connects sarcoidosis molecular and pathophysiological mechanisms to new targeted treatments, examines clinical trial evidence, and proposes future directions toward biomarker-driven individualized care. Full article

Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae) is a major cruciferous crop pest worldwide with resistance to multiple insecticide classes, highlighting the need for sustainable alternatives. Entomopathogenic fungi (EPF) are promising biocontrol agents, but their efficacy is limited by slow pathogenicity, environmental sensitivity, and low persistence on insect cuticles. This study evaluated integrated formulation strategies to enhance the virulence of Beauveria namnaoensis PM-02 against P. xylostella under laboratory and greenhouse conditions. Putative copper and zinc nanoparticle preparations were generated using fungal biomass extracts, with nanoparticle formation inferred from visual changes in the reaction mixtures. Oil-emulsified fungal formulations and combinations with emamectin benzoate were also evaluated. Larval mortality increased significantly with concentration, indicating a clear dose-dependent response. The combined treatment of oil-emulsified fungus and emamectin benzoate, along with emamectin benzoate alone, resulted in the highest larval mortality (100%), whereas fungus alone caused the lowest mortality (43.3%). Lethal concentration (LC₅₀₎ analysis indicated high toxicity of the combined treatment, while lethal time (LT₅₀) values demonstrated more rapid mortality for emamectin benzoate (0.176 days) and the combined treatment (0.830 days) compared with fungus alone (6.25 days). Under greenhouse conditions, the combined treatment showed the highest efficacy, reducing larval survival to 30% and demonstrating enhanced insecticidal activity. Overall, integrated formulation strategies significantly improved fungal efficacy against P. xylostella. Full article

Background/Objectives: Metabolic syndrome (MetS) is a pressing global health challenge comprising obesity, hyperglycemia, hypertension, and hyperlipidemia. Conventional polypharmacy often presents long-term compliance issues and side effects. Eucommia ulmoides Oliv., a traditional medicinal and edible plant rich in iridoids, lignans, flavonoids, and polysaccharides, has emerged as a promising natural intervention. This review aims to systematically summarize the bioavailability and multifaceted pharmacological mechanisms of E. ulmoides and its bioactive components in alleviating MetS. Methods: We comprehensively reviewed the recent in vitro and in vivo literature to map the functional evidence, specific signaling pathways, and gut microbiota–host interactions associated with E. ulmoides extracts and its key phytochemicals (e.g., asperuloside) against various metabolic dysfunctions. Results: Current evidence indicates that E. ulmoides operates through a “multi-component, multi-target, and multi-pathway” paradigm. For hyperlipidemia and obesity, it activates hepatic lipid metabolism (PPARα/CPT1A, FXR/CYP7A1) and mitigates oxidative stress (Nrf2/ARE). Furthermore, it dose-dependently reshapes the gut microbiota by enriching beneficial bacteria like Akkermansia and increasing butyrate production, exerting profound gut–liver axis regulation. It also ameliorates hypertension by activating the ACE2-Ang-(1–7)-Mas axis, improves insulin resistance via the AMPK/PI3K/Akt cascade, and manages hyperuricemia by modulating XOD and renal transporters. Notably, the low oral bioavailability of its glycosides highlights the crucial role of gut microbial hydrolysis in its efficacy. Conclusions: E. ulmoides holds substantial therapeutic potential as a multi-target natural supplement for MetS. However, future translational applications necessitate large-scale randomized clinical trials, multi-omics studies to further clarify host–microbiome interactions, and the development of standardized formulations to ensure clinical efficacy. Full article

Cement clinker production is a thermal- and emissions-intensive process requiring high-temperature heat for drying, calcination, and sintering. This review provides a process-based assessment of refuse-derived fuel (RDF), solid recovered fuel (SRF), tire-derived fuel (TDF), and biomass as partial substitutes for coal and petcoke in modern dry-process cement kilns. The study synthesized the evidence from plant-scale trials, pilot and laboratory experiments, process modeling, computational fluid dynamics, emissions studies, life-cycle assessment (LCA), techno-economic analysis (TEA), and regional case studies to evaluate alternative fuels across fuel properties, kiln-zone suitability, process stability, clinker quality, emissions performance, and environmental outcomes. The review shows that stable co-processing generally requires fuels with net calorific values above 14 MJ kg⁻¹ and moisture contents below 15%, although TDF can provide 26–33 MJ kg⁻¹ and sustain high-energy kiln duty when sulfur, zinc, and steel residues are controlled. RDF, SRF, and biomass require pre-processing, homogenization, calibrated dosing, and continuous fuel-quality monitoring to limit incomplete burnout, deposit formation, volatile circulation, and clinker-quality variation. LCA studies show that 20% RDF thermal substitution can reduce global warming potential by about 3.3–4.2%, increasing to approximately 6.7% when avoided landfill methane credits are included. Modern abatement systems can maintain particulate matter at about 10–30 mg Nm⁻³ and PCDD/F below 0.1 ng TEQ Nm⁻³ under stable operation. The review concludes that alternative fuels are quality-dependent co-processing options whose mitigation role is complementary to clinker-factor reduction, energy-efficiency improvement, low-clinker binders, electrified heating, oxy-fuel calcination, and carbon capture. Full article

This study adapted and applied a spatially distributed analytical model to estimate the annual representative leached fraction and the annual potential leached mass of atrazine in the Cauquenes catchment in Chile under contrasting Mediterranean hydroclimatic conditions. The model was based on van der Zee and Boesten and Rakonjac et al. and was modified to account for the strong seasonality of precipitation and evapotranspiration by using representative daily hydrological conditions derived from monthly averages. Spatially distributed soil, climate, land-cover, and atrazine application data were integrated at the pixel scale, including locally corrected soil organic carbon, hydraulic properties, precipitation, evapotranspiration, leaf area index, and annual atrazine dose. The model was applied to two contrasting years, 2018 and 2023, and outputs were aggregated at the pixel, land-cover, hotspot, and catchment scales. The results showed a marked hydroclimatic control on potential atrazine leaching. In the drier year, 2018, both the annual representative leached fraction and the annual potential leached mass were generally very low across the catchment, whereas in the wetter year, 2023, moderate-to-high leaching values became much more spatially extensive, and hotspot areas expanded substantially. At the catchment scale, potential leached mass increased from 0.088 kg in 2018 to 179.784 kg in 2023, while the percentage of applied mass potentially leached increased from 5.50 × 10⁻⁵% to 0.112%. Land-cover classes influenced the results both through the spatial allocation of atrazine application and through LAI-dependent partitioning of evapotranspiration. Global sensitivity analysis using the Morris method identified K_OC and DT50 as the dominant controls on annual potential leached mass, and spatial uncertainty propagation was performed. Overall, the proposed framework provides a potential annual screening estimate and may serve as a preliminary screening tool to prioritize areas for targeted monitoring and future model benchmarking in Chile. Full article

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication of bisphosphonate therapy, whose risk is currently assessed through qualitative staging systems that do not integrate pharmacological determinants of cumulative drug exposure. The aim of this study is to present the Bisphosphonate Accumulation Index (BAI), a pharmacologically derived, dimensionless scalar quantifying cumulative exposure to bone-targeted antiresorptive agents by integrating relative potency, administered dose, dosing frequency, route-specific bioavailability, and treatment duration, for use as a pre-procedural assessment tool in patients receiving bisphosphonates. Methods: The BAI combines five pharmacologically grounded parameters from peer-reviewed literature: (1) relative antiresorptive potency referenced to etidronate; (2) dose per administration (mg); (3) monthly dosing frequency; (4) bioavailability route; and (5) years of treatment within the preceding 10-year window. The model includes nine bisphosphonates registered in Italy. Results: The BAI spans approximately five orders of magnitude (from <1000 for short-term oral therapy to >120,000 for monthly intravenous zoledronic acid). Four analyses support the model: sensitivity analysis identifies relative potency as the main source of variance; ecological calibration against nine MRONJ incidence data points yielded r = 0.911 (p = 0.0006, R² = 0.829), indicating that the BAI accounts for approximately 83% of the population-level variance in published incidence rates across heterogeneous regimens (ecological correlation; this does not establish individual-level predictive validity); Monte Carlo simulation on 10,000 patients generated a plausible exposure-strata distribution (6.1% low, 66.6% moderate, 27.3% high); and concordance analysis with a DDD-based metric showed discordance in 7/8 regimens. Conclusions: The BAI is a transparent, reproducible, pharmacologically grounded metric of cumulative antiresorptive exposure addressing the quantitative gap identified in the AAOMS 2022 Position Paper. The BAI measures pharmacological exposure, which is a necessary but insufficient component of MRONJ risk; clinical modifiers such as corticosteroid co-administration, diabetes, renal function, and procedure type are not integrated and must be evaluated independently. The provisional exposure strata reported here (<1000, 1000–10,000, >10,000) are hypothesis-generating and intended solely to guide the design of validation studies; they should not be used as clinical decision rules until prospective patient-level validation has been completed. Full article

Background: Many patients with heart failure with reduced ejection fraction (HFrEF) remain undertreated in routine practice. Delayed treatment intensification, poor adherence, and fragmented follow-up are common barriers. Low-cost digital support may help reduce this implementation gap. Objective: This study evaluated whether a simple digital support pathway was associated with better 6-month treatment adherence and guideline-directed medical therapy (GDMT) optimization in ambulatory patients with stable HFrEF. Methods: This single-center matched cohort study compared a prospective digital-support cohort with a historical usual-care cohort. The intervention combined smartphone-based telemanagement, home blood pressure and heart-rate reporting, daily weight surveillance, and scheduled video consultations. The co-primary endpoints were treatment adherence at 6 months and GDMT optimization, assessed by change in foundational HFrEF drug classes and by a prespecified exploratory GDMT optimization score. Results: After 1:1 propensity-score matching, 200 patients were included, with 100 patients in each cohort. Treatment adherence at 6 months was higher in the digital-support cohort than in usual care (82.0% vs. 64.0%, p = 0.004). The intervention cohort also had more frequent class addition, more dose escalation, a greater increase in foundational drug classes, and a larger improvement in GDMT optimization score (all p < 0.001). Heart failure hospitalization and the composite of heart failure hospitalization or all-cause death were less frequent in the digital-support cohort, but these clinical outcomes were exploratory. Conclusions: A pragmatic low-cost digital support pathway was associated with better adherence and more complete GDMT optimization in ambulatory patients with HFrEF. The findings support further prospective multicenter evaluation. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide, have demonstrated efficacy for weight loss in obesity; however, up to 40% of weight lost may derive from lean body mass. The ketogenic diet independently improves insulin sensitivity and promotes fat oxidation while preserving lean tissue. This study aimed to describe changes in body composition, insulin sensitivity, and cardiometabolic markers in patients who followed a personalized ketogenic dietary protocol while receiving low-dose semaglutide over a 6-month insulin resistance reversal program. Methods: Seven analyzed adults (six female, one male) with overweight or obesity (baseline BMI 25.6–47.2 kg/m²) participated in a clinician-supervised 6-month program combining a whole-food ketogenic diet with semaglutide (≤1.0 mg/week). Body composition and fasting metabolic markers were assessed at 1, 3, and 6 months. Results: Mean total weight loss was 21.9 kg, of which a mean of 92% was attributable to BIA-estimated fat mass. Skeletal muscle mass was largely preserved as measured by BIA (mean loss 1.2 kg), and one patient gained lean tissue. Fasting insulin declined by a mean of 15.6 µIU/mL. Visceral fat decreased by a mean of 37.0%. Six of seven patients showed reductions in high-sensitivity C-reactive protein. Triglycerides decreased in six of seven patients, and HDL cholesterol increased in all seven. LDL cholesterol responses were heterogeneous. Conclusions: In this small, uncontrolled case series, combining a ketogenic diet with low-dose semaglutide was associated with substantial fat loss, apparent preservation of lean mass as measured by BIA, and improvements in insulin sensitivity and cardiometabolic markers. Because the semaglutide dose and dietary protocol were individualized to each patient’s response, the program illustrates a personalized approach to insulin resistance. These preliminary findings are hypothesis-generating and warrant confirmation in controlled prospective studies. Full article

The development of age-appropriate pediatric dosage forms remains an important challenge, particularly for acid-labile drugs requiring gastro-resistant protection. Pantoprazole, a proton pump inhibitor, must be protected from gastric acid until intestinal absorption; however, conventional enteric-coated tablets may be difficult to use in younger children, while manipulation of dosage forms or mixing with food can compromise dose accuracy and drug release performance. Multiparticulate systems, such as minitablets, pellets, or granules, offer flexible dosing but may still require a suitable vehicle to improve acceptability, handling, and ease of swallowing. In this study, enteric-coated pantoprazole minitablets were developed and evaluated after dispersion in selected hydrogel vehicles intended to serve as standardized alternatives to food-based carriers. Hydrogels based on hypromellose (HPMC), carbomer (CAR), and sodium alginate (SA) were characterized in terms of pH, rheological properties, firmness, acid penetration, and their effect on pantoprazole release. Dissolution performance was assessed using both conventional pharmacopoeial testing and dynamic non-pharmacopoeial conditions. Low-concentration gels prepared from high-viscosity HPMC grades showed the most favorable performance, combining suitable spoonable consistency with limited impact on drug release. Among them, 5% HPMC 65SH4000 was particularly promising, as it did not markedly delay pantoprazole release in either pharmacopoeial or dynamic dissolution testing. CAR gels provided advantageous rheological properties, including high viscosity at rest and shear-thinning behavior, and allowed efficient pantoprazole release after transition to buffer conditions; however, their interaction with enteric-coated minitablets should be further optimized with respect to gel amount, concentration, and neutralization strategy. SA gel showed strong structural persistence and delayed release under pharmacopoeial conditions, although this effect was less pronounced in the dynamic model. Overall, the findings indicate that appropriately selected hydrogels may improve the practical use of pediatric multiparticulate formulations, but their composition, pH, rheology, and interaction with enteric coatings must be carefully evaluated. Full article

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