Low-density lipoprotein cholesterol (LDL-C) plays a central role in lipid metabolism and is a well-established therapeutic target for the prevention of atherosclerotic cardiovascular diseases (CVDs). In recent years, increasingly aggressive lipid-lowering strategies have been adopted to achieve ultra-low LDL-C concentrations (<55 mg/dL or even <30 mg/dL) in high-risk patients. While the benefits of LDL-C reduction in lowering the incidence of myocardial infarction and ischemic stroke are well documented, emerging clinical evidence has raised concerns about a potential association between very low LDL-C levels and an increased risk of bleeding, particularly hemorrhagic stroke and gastrointestinal hemorrhage. This review critically examines the molecular mechanisms by which reduced LDL-C levels may influence the hemostatic system and vascular integrity. It explores the complex interplay between cholesterol availability and platelet function, endothelial barrier stability, and coagulation pathways. In addition, we assess experimental and clinical studies supporting this association and discuss how these findings may inform risk stratification and personalized lipid-lowering strategies. A deeper understanding of the biological basis of this paradoxical risk is essential for achieving a safe, balanced, and effective approach to cardiovascular prevention.
Background: Artificial intelligence (AI) is poised to fundamentally reshape healthcare delivery, offering unprecedented advancements in diagnostics, treatment personalization, and operational efficiency. However, a growing body of international research reveals a critical “optimism–knowledge gap”: healthcare professionals are enthusiastic about AI’s potential but possess limited technical knowledge and practical experience. This gap compromises the safe and effective implementation of AI tools. The Italian healthcare context presents a unique and amplifying challenge, as it is defined by the stringent “human-in-the-loop” oversight mandated by the Garante per la protezione dei dati personali (Italy’s Data Protection Authority). This legal framework makes clinician competence not just a goal, but a prerequisite for regulatory compliance. Objective: This study aimed to provide an exploratory quantitative assessment of AI awareness, practical application, and understanding of its limitations among a sample of clinicians in Italy. It specifically sought to compare the preparedness of hospital-based clinicians and general practitioners (GPs) and to identify the workforce’s perceived educational needs within this unique legal environment. Methods: A descriptive, cross-sectional survey was conducted from February to August 2025. Using a non-probability convenience sampling method via professional networks, the survey yielded 362 total responses. Data were analyzed descriptively and inferentially using Chi-square () tests to compare cohort responses on familiarity, practical exposure, knowledge of limitations, and interest in further training. Results: A universal and high demand for education was found, with 89.9% of all respondents being “Moderately” or “Very” interested in learning more about AI. This optimism coexists with dangerously low practical exposure. The gap was most profound among GPs, 44.1% of whom have “Never” used an AI tool—a rate significantly higher than hospital clinicians (34.9%; , p = 0.045). Furthermore, 32.6% of GPs admitted that they “understand some benefits but not the limitations.” Conclusions: Italian clinicians mirror the global optimism–knowledge gap. These findings underscore the urgent need for structured, continuous education in AI literacy to address ethical and regulatory imperatives within the Italian healthcare system.
The association between sepsis and thrombotic complications is still not well known. Different mechanisms have been shown to be involved in the sepsis-induced prothrombotic state, but clinical scenarios may differ. In this review, we have summarized the role that bacterial products such as porins and toxins can have in the induction of the prothrombotic state during sepsis and the interaction that they can have with each other. Furthermore, the above-mentioned mechanisms might be involved in the pattern of the clinical presentation of thrombotic events during bacterial sepsis, which would secondarily explain the association between sepsis and venous thromboembolism, the association between sepsis and disseminated intravascular coagulation, and the association between sepsis and microangiopathic venous thromboembolism.
Background: Medication adherence is one of the critical factors in optimizing treatment outcomes for chronic diseases such as atopic dermatitis (AD). Existing studies use aggregate data, but there is a need for assessment of medication adherence phases, such as the initiation and discontinuation of therapy. The aim of this study was to assess medication adherence across patients with moderate to severe AD, investigating the impact of drug treatment characteristics, particularly the route of administration, on adherence levels during treatment. Methods: A retrospective observational study on an Italian sample included 821 newly diagnosed AD patients from January 2021 to June 2022. Medication adherence was evaluated by EMERGE guidelines, focusing on initiation and discontinuation. Discontinuation was assessed at 6 and 12 months, comprising sensitivity analysis. Statistical analysis included chi-square tests and descriptive statistics on treatment duration. Results: Treatment initiation is significantly lower for tacrolimus ointment (38% non-initiation) than for dupilumab injection (12% non-initiation), due to initial healthcare support for dupilumab patients. After six months, 75.6% of dupilumab injection patients remained on therapy, while 24.4% of patients continued tacrolimus ointment treatment. After one year, therapy persistence was 68.7% among users of dupilumab, while only 22.5% of patients remained on tacrolimus therapy. Dupilumab demonstrated a significantly longer median treatment duration compared to tacrolimus (4.4 vs. 2.6 months; p < 0.01). Conclusions: The observed differences in adherence patterns between topical tacrolimus and subcutaneous dupilumab suggest that distinct contextual and behavioral factors influence patient adherence during therapy.
The introduction of direct oral anticoagulants (DOACs), particularly factor Xa (FXa) inhibitors, has transformed the prevention and treatment of thromboembolic events. These agents have largely replaced vitamin K antagonists across most indications due to their predictable pharmacokinetics, reduced rates of intracranial bleeding, and overall ease of use. Nevertheless, a substantial residual bleeding risk remains, particularly gastrointestinal bleeding and clinically relevant non-major bleeding in elderly, frail, or polymedicated patients. Furthermore, the management of patients with severe renal dysfunction, active cancer, especially gastrointestinal or genitourinary malignancies and those requiring complex pharmacological regimens, continues to pose significant challenges. These limitations have intensified interest in targeting earlier steps of the coagulation cascade, specifically factor XI (FXI) and its activated form (FXIa). FXI occupies a unique mechanistic position: it contributes substantially to pathological thrombosis while playing only a limited role in physiological hemostasis. Genetic, observational, and mechanistic evidence consistently demonstrates that FXI deficiency confers protection against venous thromboembolism and cardiovascular events while causing minimal spontaneous bleeding. This biological paradigm has catalyzed the development of novel FXI/FXIa inhibitors, including small-molecule agents (asundexian, milvexian) and biological therapies (abelacimab). Clinical trials such as AXIOMATIC-TKR, PACIFIC-AF, and OCEANIC-AF, and ongoing programmes including ASTER and MAGNOLIA suggest that FXI inhibition may preserve antithrombotic efficacy while substantially reducing bleeding risk. This review summarizes the current landscape of oral FXa inhibitors, outlines the biological rationale for FXI/FXIa inhibition, and discusses the evolving clinical evidence supporting what may represent the next major advance in anticoagulant therapy.
Background/Objectives: The present study aimed to analyze systemic antibiotic prescription patterns in the Salerno Local Health Authority (ASL Salerno) during 2024. The objective was to describe territorial antibiotic consumption and monitor prescribing appropriateness from epidemiological, pharmacological, and antimicrobial stewardship perspectives, using the World Health Organization (WHO) AWaRe classification system as a reference. Methods: A retrospective analysis of antibiotic prescriptions was conducted across ASL Salerno in 2024. Total prescription and associated expenditures were assessed, along with distribution across districts and pharmacological classes. Antibiotics were categorized according to the Anatomical Therapeutic Chemical (ATC) system and further classified using the WHO AWaRe framework (Access, Watch, Reserve) to evaluate prescribing appropriateness and potential patterns of antimicrobial resistance. Results: More than 1 million antibiotic prescriptions were recorded, totaling approximately €15 million in expenditure. Prescribing patterns showed a predominance of penicillins and cephalosporins, followed by macrolides, fluoroquinolones, and J01X class. A substantial proportion of prescriptions belonged to the Watch category, particularly third-generation cephalosporins, fluoroquinolones, and fosfomycin. Some districts demonstrated a higher reliance on Watch antibiotics, while others showed increased use of Access agents such as amoxicillin, doxycycline, and amikacin. Conclusions: The surveillance analysis highlights significant variability in antibiotic prescribing practices within ASL Salerno and a substantial use of Watch-group antibiotics. These findings suggest the need for strengthened antimicrobial stewardship interventions, such as targeted education, auditing, and decision-support tools. Continuous monitoring of prescribing trends is essential to encourage appropriate antibiotic use and contribute to the containment of antimicrobial resistance.