Background/Objectives: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with ischemic stroke, systemic thromboembolism, heart failure, and mortality. Although oral anticoagulation (OAC) remains the cornerstone of stroke prevention, long-term therapy may be limited by bleeding risk, contraindications, intolerance, nonadherence, or thromboembolic events despite treatment. Left atrial appendage closure (LAAC) has therefore emerged as a non-pharmacological alternative for selected patients with nonvalvular AF. This review aimed to synthesize current evidence on LAAC, focusing on comparative efficacy versus OAC, device evolution, imaging-guided strategies, antithrombotic management, procedural optimization, unresolved challenges, and emerging technologies. Methods: This state-of-the-art narrative review was informed by targeted, non-systematic searches of PubMed and Scopus for publications from January 2009 to June 2026. Evidence was selected purposively to represent clinically relevant guidelines, randomized trials, registries, comparative observational studies, systematic reviews, meta-analyses, imaging studies, device-comparison studies, and reports of emerging technologies. The selected evidence was synthesized narratively; no exhaustive screening process, PRISMA flow diagram, formal risk-of-bias assessment, or quantitative synthesis was performed. Results: Randomized evidence was context dependent. OPTION supported LAAC as an alternative to oral anticoagulation in selected anticoagulation-eligible patients undergoing atrial fibrillation ablation. CHAMPION-AF established noninferiority of Watchman FLX to non–vitamin K antagonist oral anticoagulants for its composite efficacy endpoint in a predominantly moderate-risk, anticoagulation-eligible population and demonstrated less non-procedural bleeding, although ischemic stroke occurred numerically more often after LAAC. In contrast, CLOSURE-AF did not establish noninferiority of LAAC to physician-directed medical therapy in an older population at high risks of both stroke and bleeding. These findings indicate that the comparative value of LAAC depends strongly on patient selection, comparator therapy, endpoint composition, procedural risk, and trial design. Observational, registry, and emerging evidence was considered supportive or hypothesis-generating rather than equivalent to randomized evidence. OPTION enrolled only patients undergoing or recently undergoing AF ablation who were suitable for anticoagulation. CHAMPION-AF included 3000 anticoagulation-eligible patients but had relatively low baseline bleeding risk, while CLOSURE-AF studied 912 substantially older, higher-risk patients and did not meet its noninferiority criterion. Conclusions: LAAC has evolved into a precision-guided intervention integrating patient risk, left atrial appendage anatomy, device choice, imaging, antithrombotic therapy, and structured surveillance. Further studies are needed to optimize patient selection, standardize post-procedural therapy, and clarify its long-term role compared with contemporary direct oral anticoagulant therapy.

Perioperative management of antirheumatic medications in adults with rheumatoid arthritis (RA) undergoing orthopedic surgery requires balancing postoperative infection and impaired wound healing against disease flare, pain, and delayed rehabilitation. This systematic review aimed to evaluate how perioperative continuation, withholding, interruption timing, restart timing, dose modification, or exposure to antirheumatic medications relates to postoperative outcomes in adults with RA undergoing arthroplasty and non-arthroplasty orthopedic procedures. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched from database inception to 18 April 2026 for English-language full-text clinical studies. The primary outcomes were surgical site infection/periprosthetic joint infection, delayed wound healing, and postoperative RA flare. Secondary outcomes included reoperation, revision, readmission, mortality, venous thromboembolism, dislocation, and other procedure-specific complications. Original studies were classified as direct perioperative strategy evidence, medication-exposure evidence, or supportive clinical-context evidence. Forty-three original clinical studies were included, together with six non-original contextual sources. The evidence was predominantly observational, clinically heterogeneous, and of very low certainty. Methotrexate continuation was not associated with an evident increase in early postoperative complications, whereas direct evidence for other conventional synthetic agents was limited. Longer interruption of biologic or targeted synthetic therapy did not consistently reduce infection or wound-healing complications, while several studies associated treatment interruption with postoperative flare. Chronic baseline glucocorticoid exposure was associated with adverse outcomes but was clinically distinct from short-term perioperative administration; stress-dose supplementation was not directly evaluated. Medication decisions should therefore be individualized according to drug class, disease control, glucocorticoid burden, surgical procedure, and patient risk profile.

Background: Bone and soft-tissue sarcomas are rare, heterogeneous malignancies whose surveillance remains dominated by imaging despite substantial molecular diversity and variable patterns of relapse. Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) offer minimally invasive approaches for monitoring tumor biology, but their performance in sarcoma depends strongly on subtype, disease burden, assay design, and biological shedding. Methods: This narrative review synthesizes evidence published from 2015 to 2026 on ctDNA and CTCs for baseline risk assessment, treatment-response monitoring, minimal residual disease (MRD) detection, molecular relapse, and integration with imaging-based surveillance in bone and soft-tissue sarcomas. Results: Current evidence supports a genomics-guided framework in which liquid-biopsy strategy is selected according to sarcoma subtype, molecular architecture, and clinical purpose. ctDNA is the most mature analyte, with best-supported evidence in osteosarcoma, where tumor-informed assays predict postoperative relapse, and in translocation-associated sarcomas, where breakpoint-guided assays enable highly specific longitudinal monitoring. Copy-number-based approaches are relevant for complex-karyotype tumors, while mutation-, methylation-, fragmentomic-, and RNA-based strategies may be useful in selected contexts. However, detection rates vary, false-negative results occur in low-shedding or low-volume disease, and clinical utility for changing treatment remains incompletely established. CTCs provide complementary cellular and prognostic information, particularly in osteosarcoma, but remain limited by platform heterogeneity and incomplete standardization. Conclusion: Liquid biopsy may refine risk stratification, support treatment-response assessment, clarify indeterminate imaging findings, and identify molecular relapse in selected sarcoma patients. At present, it should be interpreted as an adjunct to imaging and specialist multidisciplinary care rather than as a replacement for standard radiologic surveillance.

Microplastics (MPs) are recently discovered environmental pollutants that have been increasingly gaining importance due to their harmful effects on human health, especially via inhalation and deposition in the respiratory tract. We review the potential respiratory system exposures and pathways of inhaled microplastics as well as the evidence regarding the impact on pulmonary inflammation, fibrosis, cell damage, and carcinogenic pathways. PubMed, Scopus, and Google Scholar were used for the literature review of studies published within the last 10 years. The research studies that met inclusion criteria were reviewed, and abstracts and titles of the studies were retrieved. Many research studies have demonstrated that inhaled microplastics can bypass mucociliary clearance and end up in the distal airways and alveoli. Once localized, the microplastic can come with chronic inflammation, oxidative stress, genetic damage, and interaction with other air pollutants. In experimental studies, particles of polystyrene and polyethylene were found to be cytotoxic and genotoxic, but it is hard to apply the results to human exposure due to the fact that the concentrations used in the lab are often higher than those in the environment. Human data is indeed scarce; it is established that the lungs of human beings contain microplastics, and the associations with fibrotic and inflammatory lung disorders support the biological relevance of microplastics. A summary of the evidence available indicates that there are several ways in which the presence of microplastics could impact respiratory health. However, the interrelationship between oxidative stress, inflammation and fibrosis is less defined, as most of the evidence has been generated in experimental rather than real environments, and is not well established in the public domain. The evidence, both experimental and human, is present for potential research into microplastics' relation to lung cancer in humans, as well as reduction of exposure and regulation.

Background: Pediatric solid tumors respond poorly to T-cell-directed immunotherapy despite expressing developmentally restricted, cancer-testis, fusion-derived, and lineage-associated antigens, suggesting that therapeutic failure may reflect defective conversion of intracellular antigen expression into surface peptide–major histocompatibility complex class I (pMHC-I) display. This review examines the antigen-presentation bottleneck as a framework for tumor immune invisibility and therapeutic resistance. Methods: We conducted a narrative mechanistic synthesis of pediatric and translational evidence on antigen repertoires, MHC-I and antigen-processing machinery dysfunction, mechanisms of presentation loss, therapeutic restoration, pMHC-directed immunotherapy, and MHC-independent bypass strategies. Results: Antigen expression does not reliably predict natural presentation. Presentation failure may result from HLA loss, coordinated transcriptional repression, developmental and epigenetic states, altered trafficking, SUMOylation, and autophagy-mediated MHC-I degradation. Potentially reversible defects can be targeted through cytokine signaling, NF-κB/IRF1/NLRC5 reactivation, epigenetic or lineage reprogramming, and inhibition of post-translational MHC-I loss; irreversible defects favor MHC-independent surface targeting. Conclusions: Pediatric solid tumors may be antigen-invisible rather than antigen-poor. Therapeutic matching should assess antigen abundance, HLA integrity, antigen-processing competence, natural peptide presentation, quantitative pMHC density, and spatial and longitudinal heterogeneity, then restore presentation or deliberately bypass it. The framework distinguishes the presentation phenotype (quantitative pMHC insufficiency versus qualitative loss or functional absence of a required HLA/APM element) from the underlying mechanism (soft/potentially reversible versus hard/structural) because these dimensions have different biomarker and therapeutic implications.