INTRODUCTION:Cystic fibrosis (CF) patients often contend with chronic rhinosinusitis with nasal polyposis (CRSwNP), with higher relapse rates after surgery compared to non-CF individuals. CRSwNP has a significant impact on their quality of life and increases pulmonary infections risk. Traditional medical and surgical interventions are frequently inadequate. Dupixent is endorsed for persistent CRSwNP following conventional treatment in non-CF subjects; its effectiveness in CF patients remains unexplored considering that those patients are frequently affected by mixed endotypes of CRS with some type-2 features. This study delves into the assessment of Dupixent in CF-related CRSwNP and compares it with a matched control group. METHODS:This is a non-randomised single-centre trial enrolling CF patients and non-CF controls. SNOT-22 and NPS scores before, 1 and 6 months after therapy were documented. RESULTS:Dupixent exhibited a significant reduction in SNOT-22 scores after 6 months in both CF and control groups (V = 21, p value = 0.031, both). While NPS scores showed non-significant improvement in CF, the control group experienced a notable reduction after 6 months (V = 10, both; p value = 0.10; p value = 0.034, respectively). No statistical differences were observed between CF and control groups in SNOT-22 and NPS scores after 6 months. CONCLUSIONS:This pilot study observed Dupixent's potential in managing CRSwNP in CF patients since SNOT-22 improvement was statistically significant and comparable to the non-CF patients. Although NPS scores improved without statistical significance, no differences emerged between CF and control groups. Therefore, Dupixent achieved comparable results between CF and non-CF patients suffering from CRSwNP.

Alzheimer’s disease (AD) is a progressive, multifactorial neurodegenerative disorder ranking first as cause of dementia in the elderly. It is characterized by the progressive deterioration of the central nervous system, leading to impaired cognitive function and reduced ability to perform daily activities. Pathological hallmarks of AD include the accumulation of β-amyloid plaques and neurofibrillary tangles which ultimately cause neuronal death and synaptic loss. The vast majority of AD cases are sporadic, with aging representing the primary non-modifiable risk factor contributing to disease susceptibility and progression. However, several factors encompassing genetic predisposition, systemic inflammation, chronic diseases, infections, traumatic brain injury, lifestyle factors, and environmental exposures may affect AD onset. This work aims to describe and discuss the main molecular pathways involved in AD pathophysiology and to examine how these mechanisms cross-interact in promoting neurodegeneration and disease progression.

Dual antiplatelet therapy (DAPT) remains a key element of secondary prevention after percutaneous coronary intervention. However, its optimal duration and intensity continue to pose challenges due to the trade-off between ischaemic protection and bleeding risk. Over the past decade, evidence has progressively emerged for strategies of DAPT modulation, with particular emphasis on de-escalation approaches. Randomized trials have consistently shown that reducing antiplatelet intensity, whether by lowering the dose, discontinuing one drug, or switching to a less potent agent, can mitigate bleeding events without jeopardizing ischaemic outcomes in selected patients. In contrast, escalation strategies have received less widespread adoption, reflecting more limited evidence, weaker guideline support, and the fact that most contemporary patients are at greater risk of bleeding than thrombosis. This review aims to summarize the evidence supporting DAPT modulation strategies, to critically appraise available trials, and to highlight ongoing studies in the field.

BACKGROUND AND AIMS:After percutaneous coronary intervention (PCI), growing evidence supports P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) as a safer and equally effective antiplatelet strategy compared with continued DAPT. However, the optimal timing of aspirin discontinuation remains uncertain. METHODS:A systematic review and meta-analysis of randomized controlled trials investigating different timings of aspirin discontinuation after a short course of DAPT in PCI patients, compared with continued DAPT, was conducted. Pairwise random-effects and network meta-analyses were performed. The primary endpoint was major adverse cardiovascular events (MACE). Secondary endpoints included major bleeding, major or minor bleeding, net adverse cardiovascular events (NACE), all-cause death and myocardial infarction. The study was registered in PROSPERO (CRD420251140207). RESULTS:Eleven randomized trials including 37,443 patients were identified. In pairwise analyses, compared with 12-month DAPT, there were no significant differences in the risk of MACE with aspirin discontinuation at either ≤1 month (risk ratio [RR] 1.01; 95% confidence interval [CI] 0.85-1.20) or 3 months (RR 0.95; 95% CI 0.67-1.36), with no significant differences between discontinuation timings. Both major and major or minor bleeding were significantly reduced with ≤1-month (RR 0.46; 95% CI 0.23-0.94; P = 0.038 and RR 0.43; 95% CI 0.36-0.51; P < 0.001, respectively) and 3-month (RR 0.59; 95% CI 0.39-0.89; P = 0.027 and RR 0.57; 95% CI 0.53-0.60; P = 0.005, respectively) discontinuation, with a more pronounced reduction in major or minor bleeding with ≤1-month discontinuation (P = 0.044 for interaction). NACE was significantly reduced with ≤1-month discontinuation, and no significant differences between discontinuation timings emerged. Network meta-analyses yielded consistent results, and for major or minor bleeding, the indirect comparison showed superiority of ≤1-month over 3-month aspirin discontinuation (RR, 0.75; 95% CI, 0.57-0.99; P = 0.044). In a sensitivity analysis restricted to acute coronary syndromes, early aspirin discontinuation was associated with a higher risk of stent thrombosis (RR 1.81; 95% CI 1.15-2.84; P = 0.019), with the excess risk observed mainly with very early aspirin discontinuation (<1 month). CONCLUSIONS:Aspirin discontinuation at either ≤1 or 3 months with continued P2Y12 inhibitor monotherapy is associated with similar MACE, lower bleeding, and lower NACE compared with continued DAPT. Discontinuation within the first month may confer additional bleeding benefit, but at the cost of excess stent thrombosis, particularly in patients at higher ischaemic risk.

INTRODUCTION:Despite technical advances in percutaneous coronary intervention (PCI) and new iterations of drug-eluting stents (DES), complications still occur, including stent thrombosis and in-stent restenosis (ISR). Drug-coated balloons (DCBs) provide a promising option for the treatment of coronary lesions - particularly when DES are undesirable or contraindicated - allowing for PCI without the implantation of metallic devices, thus adhering to the 'leave nothing behind' principle. AREAS COVERED:A comprehensive literature search has been performed on PubMed, Web of Science and Cochrane, up to November 2024, with no significant restrictions. This article provides an overview of available DCB and summarizes the evidence supporting their use in different settings, including ISR, small-vessel disease, de novo large-vessel disease, and bifurcations. EXPERT OPINION:Trials of DCB are heterogeneous with respect to population, sample size, follow-up, anatomical pattern, and device used. Furthermore, they usually have limited statistical power for clinical endpoints. Based on current knowledge, DES may be preferrable for DES-ISR, de novo lesions in large vessels and for the treatment of the main branch in true bifurcations, with DCB approved for small-vessel disease and selected ISR lesions. Ongoing trials are expected to provide definitive insights into the efficacy and safety of DCB in different scenarios.

BACKGROUND:Eustachian tube represents the anterior part of the middle ear. Its role is to maintain the pressure balance between the external and middle ear, especially in some jobs such as divers. OBJECTIVES:This clinical study aimed to evaluate Eustachian tube (ET) dysfunction in a cohort of professional divers. The primary objectives were: 1) to compare the prevalence of ET dysfunction in experienced divers versus non-divers, and 2) to assess the potential impact of diving-related immersion factors on ET function. MATERIALS AND METHODS:This case-control study enrolled 34 professional divers from the Italian Navy (Group A) and 35 individuals with no diving experience (Group B). Both groups underwent clinical and physical examinations, assessment of ET function via tympanometry, and completed the Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7). RESULTS:Tympanometry revealed that 2.9% of participants in both groups had a pathological tympanogram, with no significant differences between groups. ETDQ-7 scores were similarly distributed. However, significant differences were found in tympanometric results after the Valsalva maneuver (p = 0.004 for right ear pressure peaks and p = 0.001 for left ear pressure peaks, comparing Groups A and B). Professional divers showed a low risk of developing ET dysfunction, comparable to non-divers, and this risk was not associated with the duration or frequency of diving activity. CONCLUSIONS:Navy divers show a lower incidence of ET dysfunction. SIGNIFICANCE:This article could explain to the readers the functioning of the ET function between navy divers and normal divers.

INTRODUCTION:Left atrial appendage occlusion (LAAO) represents a strategy to minimize thromboembolic risk in atrial fibrillation (AF) patients. However, LAAO carries some risks of periprocedural bleeding, device embolization, peri-device leaks or device-related thrombosis; the latter is due to direct blood contact with the device, justifying and represents the rationale behind antithrombotic therapy following LAAO. AREAS COVERED:A comprehensive literature search (PubMed, Web of Science, Cochrane) has been performed up to November 2024. Antithrombotic drugs after LAAO include vitamin K antagonists (VKA), direct oral anticoagulants (DOAC), antiplatelet drugs, and their combinations. Initially, high-intensity regimens were implemented, while current strategies prioritize simplified approaches to promote device healing without increasing the bleeding risk. The aims of our review were to define the rationale and implications for post-LAAO antithrombotic therapy and provide an overview of current evidence on various antithrombotic regimens. EXPERT OPINION:The optimal post-LAAO antithrombotic regimen remains controversial, highlighting the need for randomized trials on this topic. Current data suggest that DOACs have the lowest probability of thromboembolic events and major bleeding, while DAPT may be preferred in patients who do not tolerate OAC; finally, single antiplatelet therapy or no antithrombotic therapy are alternative options for patients at high bleeding risk.

Efforts to enhance risk stratification in patients with coronary artery disease have driven the pursuit of early detection of rupture-prone plaques-before destabilization and the onset of life-threatening thrombosis-giving rise to the concept of the vulnerable plaque (VP). Invasive diagnostic modalities closely mirror histology and provide instrumental information on VP hallmarks and their prognostic significance. However, limited positive predictive value and invasive nature restrict their use for systematic screening. Noninvasive techniques offer broader application potential, but their specificity and resolution remain inferior to those of invasive techniques. A deeper understanding of the complex interplay between traditional ischemic risk factors, anatomic settings, rheological effects and systemic influences contributing to plaque evolution and rupture has refined our approach to identifying and managing VPs. Systemic therapies have been shown to counteract plaque progression and stabilize VPs by thickening the fibrous cap, decreasing atheroma and necrotic core volumes, and reducing inflammation. In parallel, the hypothesis of sealing and passivating VPs by intravascular imaging-guided preventive stenting is gaining support after the promising results of clinical trials and substantial advances in contemporary device performance and biocompatibility. Upcoming evidence will be instrumental in defining the net benefit of novel diagnostic tools and therapeutic strategies for VPs.

Management of patients with head and neck cancer (HNC) is a complex process that involves extensive knowledge on (at least) the discipline of surgery, radiation oncology, medical oncology and molecular biology. It includes prevention, cancer treatment, follow up schedule and potential risk from treatment (radiation exposure). A major point is that perhaps now more than ever process management needs to be at the center of the HNC care. Process management transcends all specialties: it should be recognized as a component of the team to embrace rather than fear change. Process management can guarantee the quality of the decisional process and the technical quality of the equipment, such as access to care for all, implementation of technology to control data entry, standardization of procedures and safety. Each step of the process needs adequate controls to avoid errors, ensure optimal treatment strategy and increase patient satisfaction. The application of process management method can lead to reduce treatment start times, fall risk and therefore, improve quality of HNC patient care and safety.

Intravascular imaging (IVI), particularly intravascular ultrasound (IVUS) and optical coherence tomography (OCT), addresses the intrinsic limitations of two-dimensional coronary angiography by offering high-resolution information regarding vessel and plaque morphology before percutaneous coronary intervention (PCI) as well as enabling accurate assessment of stent expansion and apposition after implantation. These anatomical insights can translate into improved procedural success and late clinical outcomes. The magnitude of benefit appears closely related to lesion morphology and procedural complexity. While angiographic guidance may be sufficient in straightforward anatomies, IVI assumes a pivotal role in complex disease subsets. IVUS, with its deeper tissue penetration, real-time imaging capability, and lack of need for contrast flushing, is particularly advantageous for large-vessel interventions, chronic total occlusions, and contrast-sparing strategies. In contrast, OCT, offering superior axial resolution, excels in characterizing plaque composition and in detecting stent-related complications. Hybrid IVUS-OCT catheters have the potential to integrate the complementary strengths of both IVI modalities, thereby streamlining procedural workflows and broadening clinical applicability. Although current guidelines endorse IVI use in anatomically complex coronary artery disease, real-world adoption remains low, largely influenced by operator proficiency, regional differences, and reimbursement arrangements. Further research is warranted to identify lesion subsets in which one modality confers clear clinical benefit and to delineate the threshold of procedural complexity at which IVI becomes cost-effective.

Upper aerodigestive tract (UADT) carcinomas have a high and rapidly increasing incidence, particularly in industrialized countries. The identification of diagnostic and prognostic biomarkers remains a key objective in oncological research. However, conflicting data have been reported regarding Lipocalin-2 (LCN-2 or NGAL), Matrix Metalloproteinase-9 (MMP-9), and the MMP-9/NGAL complex in UADT carcinomas. For this reason, the primary aim of this study was to investigate the involvement and modulation of the LCN-2 system in UADT cancer by selecting patients at first diagnosis and excluding any pharmacological or interventional treatments that could act as confounding factors. In this clinical retrospective pilot study, we investigated LCN-2 and MMP-9 tissue gene expression, as well as circulating levels of LCN-2, MMP-9, and the MMP-9/NGAL complex. Our findings revealed a downregulation of LCN-2 and an upregulation of MMP-9 gene expression in tumor tissues compared to healthy counterparts. A similar trend was observed in circulating levels, with decreased LCN-2 and increased MMP-9 in cancer patients compared to healthy controls. Additionally, serum levels of the MMP-9/NGAL complex were significantly elevated in UADT cancer patients relative to controls. Our study suggests a potentially distinct role for the free form of LCN-2 and its conjugated form (MMP-9/NGAL complex) in UADT tumors. These findings not only provide new insights into the molecular mechanisms underlying tumor progression but also highlight the potential clinical relevance of these biomarkers. The differential expression patterns observed suggest that the LCN-2 and MMP-9/NGAL complex could serve as valuable tools for improving early diagnosis, monitoring disease progression, and potentially guiding therapeutic strategies. Further research is needed to validate their utility in clinical settings and to explore their prognostic and predictive value in personalized treatment approaches.

In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), antiplatelet therapy is the cornerstone of treatment for secondary prevention. Although dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitor is the current standard of care, being, respectively, recommended for 6 and 12 months in patients with chronic and acute coronary syndrome without a need for oral anticoagulation, the continuous improvement in PCI technology and pharmacology have significantly reduced the need for long-term DAPT. Mounting evidence supports the administration of P2Y12 inhibitor monotherapy, particularly ticagrelor, after a short period of DAPT following PCI as a strategy to reduce bleeding without a trade-off in ischemic events compared to standard DAPT. In addition, there is a growing literature supporting P2Y12 inhibitor monotherapy also for long-term secondary prevention of ischemic events. However, the data to this extent are not as robust as compared to the first-year post-PCI period, with aspirin monotherapy still remaining the mainstay of treatment for most patients. This review aims to summarize the rationale for long-term antiplatelet therapy, the pharmacology of current antiplatelet drugs tested for long-term administration as monotherapy, and current evidence on the available comparisons between different long-term antiplatelet monotherapies in patients with CAD.

BACKGROUND:Trials assessing the prognostic influence of the completeness, timing, and guidance of percutaneous coronary intervention (PCI) for haemodynamically stable acute myocardial infarction (MI) and multivessel coronary artery disease (MV-CAD) have provided heterogeneous results. AIMS:We aimed to comprehensively and simultaneously assess the available evidence on the completeness, timing, and guidance of PCI for acute MI and MV-CAD. METHODS:Major electronic databases were screened to identify randomised trials comparing at least two PCI strategies for acute MI and MV-CAD. Recurrent MI and cardiac death were the primary and co-primary outcomes. Frequentist and Bayesian 5- and 3-node network meta-analyses were conducted along with complementary analyses to explore potential sources of heterogeneity. RESULTS:Fourteen trials, including 14,433 patients, were pooled. In the frequentist 5-node analysis, angiography-guided immediate complete revascularisation (CR) reduced MI compared with infarct-related artery (IRA)-only revascularisation (hazard ratio [HR] 0.42, 95% confidence interval [CI]: 0.27-0.66), angiography-guided staged CR (HR 0.56, 95% CI: 0.36-0.87), and functionally guided staged CR (HR 0.37, 95% CI: 0.20-0.69). Functionally guided immediate CR was associated with reduced MI compared with IRA-only revascularisation (HR 0.53, 95% CI 0.34-0.82). The Bayesian analysis confirmed only an advantage of angiography-guided immediate CR over IRA-only revascularisation. In frequentist 3-node analysis, immediate CR reduced MI (HR 0.51, 95% CI: 0.37-0.70) and cardiac death (HR 0.68, 95% CI: 0.50-0.93) compared with IRA-only revascularisation and MI compared with staged CR (HR 0.55, 95% CI: 0.38-0.79). The Bayesian analysis did not confirm the reduction in cardiac death. CR, regardless of the type of guidance and especially when immediate, reduced the rate of any revascularisation compared with IRA-only revascularisation. CONCLUSIONS:In haemodynamically stable patients with acute MI and non-complex MV-CAD undergoing PCI, immediate CR following successful culprit lesion treatment reduces recurrent MI compared with IRA-only revascularisation and staged CR. Whether CR is associated with reduced cardiovascular death remains uncertain.

INTRODUCTION:Atherosclerosis, the primary cause of coronary artery disease (CAD), progresses through subclinical, chronic, and acute phases, culminating in acute myocardial infarction (AMI). Historically viewed as a lipid-driven disorder, it is now recognized as an inflammatory disease. Despite achieving optimal low-density lipoprotein cholesterol reduction, many patients experience residual cardiovascular risk, largely attributed to persistent inflammation. AREAS COVERED:A comprehensive literature search has been performed on PubMed, Web of Science and Cochrane, up to July 2025, with no significant restrictions. The review explores the role of inflammation in plaque progression and destabilization, discusses emerging biomarkers for risk stratification, and summarizes current and investigational anti-inflammatory therapies. Special attention is given to the evolving understanding of acute versus chronic post-AMI inflammation and how this distinction may guide therapeutic strategies. EXPERT OPINION:Anti-inflammatory therapy has reshaped the landscape of cardiovascular prevention, yet challenges remain in patient selection, timing, and target identification. Novel imaging techniques and artificial intelligence-driven risk models offer promising avenues for personalized therapy. Future efforts should focus on precision-based approaches that target detrimental immune activation while preserving reparative processes, ensuring maximal clinical benefit.