Search Results (127)

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality in Central and Eastern Europe (CEE), where late-stage diagnosis, structural healthcare limitations, and regional epidemiological confounders complicate early detection. This review aimed to synthesize the evidence from Romania, Poland, Hungary, and Bulgaria and to outline a context-adapted multimodal screening strategy for CEE settings. Methods: A structured review of PubMed-, Scopus-, and Web of Science-indexed literature published from 2010 through 27 December 2025 was performed, focusing on lung cancer epidemiology, screening, implementation barriers, risk stratification, and adjunctive diagnostic approaches in the four selected CEE countries. A total of 297 articles were included. Results: The evidence confirms a persistently high burden of late-stage lung cancer across CEE, driven by tobacco exposure, air pollution, radon, comorbidities, diagnostic delays, fragmented registries, workforce shortages, and marked socioeconomic and geographic inequalities. In addition, tuberculosis-related granulomatous lesions and chronic inflammatory lung disease complicate nodule interpretation and reduce screening specificity in parts of the region. Screening experience from Poland and Hungary supports the feasibility of low-dose computed tomography (LDCT) when paired with volumetric assessment and structured follow-up. Risk-prediction models may improve participant selection, while biological triage may help reduce unnecessary invasive procedures, although prospective validation remains limited. Conclusions: In CEE, lung cancer screening should be implemented as a multimodal, context-adapted program combining risk-based enrollment, volumetric LDCT, selective biological triage, smoking-cessation support, and centralized multidisciplinary delivery. Full article

Background/Objectives: Primary spinal sarcomas, encompassing both bone and soft tissue histotypes, demand individualized reconstruction due to heterogeneous tumor biology, anatomic complexity, and host environments compromised by radiation, systemic therapy, or prior surgery. This narrative review reframes post-resection spinal reconstruction through a precision-medicine lens. Methods: A structured literature review was performed using PubMed and Scopus, targeting articles published between 2000 and 2026. Searches encompassed spinal sarcoma reconstruction, radiation and fusion, biologic reconstruction, and emerging technologies. Results: Tumor grade, radiation exposure, and systemic therapy timing emerge as multiplicative determinants of reconstructive environment quality, with drug-class-specific perioperative effects warranting stratified management. Vascularized bone grafts achieve reliable fusion in compromised hosts where avascular constructs fail. A precision-oriented reconstructive ladder is proposed as a conceptual, hypothesis-generating framework to guide strategy selection. Hybrid PSI-VBG constructs may further expand reconstructive possibilities. The evidence base remains largely composed of small, retrospective series. Conclusions: Individualized strategies anchored in tumor biology and host environment are the cornerstone of durable spinal sarcoma reconstructions. The proposed framework requires prospective, multi-institutional validation. Standardized outcome definitions, prospective registries, and histotype-stratified analyses are needed to advance the field. Full article

Background: Conventional therapeutic and diagnostic approaches, despite improving clinical outcomes, remain limited by poor bioavailability, inadequate targeting, suboptimal pharmacokinetics, and systemic toxicity, particularly in complex diseases. To overcome this, nanomedicine has emerged as a transformative strategy, employing engineered nanoparticles to enhance drug stability, controlled release, targeted delivery, and diagnostic performance, thereby enabling theranostic applications. This review evaluates major nanoparticle platforms in therapy and diagnosis, comparing their mechanisms, applications, and challenges while highlighting their potential to advance precision medicine and theranostic strategies. Method: For providing the context and evidence, relevant literatures were sourced from Google Scholar, PubMed, and ScienceDirect using targeted keywords including “drug delivery,” “diagnostics,” “nanoparticles,” “nanomedicine,” “nano drug delivery,” “nanotheranostics,” “targeted therapy,” “controlled drug release,” “solid lipid nanoparticles (SLNs),” “lipid nano carriers (LNCs),” and “inorganic nanoparticles.” Although no strict time limit was applied during the literature search, clinical trial data were collected and analyzed up to January 2026. Given that clinical trial registries are continuously updated, the included trials represent the status at the time of data retrieval. However, it is pertinent to note that the earliest relevant studies appeared in 1973. Conclusions: This review highlights nanoparticle fundamentals, major material classes, mechanisms of action, and applications in targeted therapy, imaging, and theranostics. It also addresses translational barriers related to safety, scalability, biological complexity, and regulatory compliance. Overcoming these challenges through standardized characterization and interdisciplinary collaboration is crucial for clinical adoption. Future efforts should focus on AI-driven design, computational tools, smart nanomedicines, and advanced biosensing technologies to integrate nanoparticle-enabled precision diagnostics and therapy into routine clinical practice. Full article

Background: Lupus nephritis (LN), a major complication of systemic lupus erythematosus, remains a key determinant of morbidity and mortality despite therapeutic progress. Objective: An expert report aims to present multidisciplinary insights from leading Italian centers on current LN management and future perspectives. Methods: Seven specialists—including nephrologists and rheumatologists with expertise in lupus nephritis—addressed key aspects of LN management, including treatment goals, available therapeutic options, treatment selection across disease stages, and emerging strategies. Results: The authors highlight evolving treatment paradigms—shifting from traditional induction–maintenance strategies to early combination regimens integrating biologics such as belimumab and calcineurin inhibitors like voclosporin—aligned with updated EULAR and KDIGO guidelines. Regional experiences underscore individualized therapy tailored by histology, disease activity, and patient profile. Multidisciplinary collaboration between nephrologists and rheumatologists, equitable access to innovative therapies, and integration of registries and digital records are identified as priorities. Conclusions: Emerging agents, including obinutuzumab, anifrolumab, and CAR-T cell therapies, represent promising advances toward steroid-sparing and potentially curative strategies. Continued research, biomarker development, and application of artificial intelligence are pivotal to optimizing outcomes and achieving personalized LN management. Full article

Background. Despite technological innovations and improvements in stents and devices, sex-related discrepancies are still reported in the outcomes after ST-segment elevation myocardial infarction (STEMI), depending on biological and sex-specific pathophysiological differences, which have not been completely understood. The aim of the present study was to provide real-world data on the prognostic role of sex among patients with STEMI, enclosed into a recent up-to-date international registry. Methods. The ISACS-STEMI COVID-19 is a large-scale retrospective registry, including STEMI patients treated with mechanical reperfusion between 1 March and 30 June, 2019 and 2020. Patients, treated in 109 centers across Europe, Latin America, Southeast Asia, and North Africa, were grouped according to sex. Primary endpoint: In-hospital mortality; secondary endpoints: Time delay, 30-day mortality, and postprocedural Thrombolysis In Myocardial Infarction (TIMI) 3 flow. Results. We included 16,083 patients, 24.3% females (54.3% hospitalized in 2019, 45.7% in 2020). Women with STEMI were older, more often diabetic and hypertensive (p < 0.001), with a higher prevalence of hypercholesterolemia (p = 0.02), longer ischemia time (p = 0.01), ambulance referral (p = 0.03) and cardiogenic shock at presentation (p = 0.05), but less frequently smokers, with a previous cardiovascular event (p < 0.001) or anterior STEMI (p = 0.03) as compared to males. Preprocedural TIMI 0 flow, multivessel disease, need for thrombectomy (p < 0.001 and p = 0.001, respectively), use of Glycoprotein IIbIIIa inhibitors or cangrelor, radial access and implantation of drug-eluting stents (p < 0.001, p < 0.001 and p = 0.001, respectively) were also more common in men. Impaired postprocedural epicardial reperfusion (TIMI flow 0–2) was observed more frequently in females as compared to males (10% vs. 7.2%; adjusted OR [95% CI] = 1.30 [1.13–1.49], p = 0.01). In-hospital mortality was 5.8%, significantly higher among women (8.3% vs. 5%, p < 0.001, adjusted HR [95% CI] = 1.26 [1.06–1.5], p = 0.01). Similar data were observed for 30-day mortality (10.3% vs. 6.2%, p < 0.001, adjusted HR [95% CI] = 1.22 [1.06–1.38], p = 0.007). Conclusions. Among STEMI patients being treated with the most updated standard of care for primary percutaneous coronary intervention, female sex is still associated with higher complexity and impaired prognosis, displaying suboptimal epicardial reperfusion and increased in-hospital and 30-day mortality. Full article

The coronavirus (COVID-19) pandemic necessitated unprecedented regulatory responses that enabled rapid therapeutic deployment. The integrated medico-legal framework—comprising the FD&C Act Section 564 (Emergency Use Authorization/EUA), PREP Act (liability immunity), and CICP (injury compensation)—facilitated emergency response while protecting all stakeholders. This normative legal and policy analysis examines nirmatrelvir/ritonavir (Paxlovid) as a case study, integrating emerging pharmacokinetic evidence demonstrating its passage across the blood–brain and blood–placenta barriers. The EUA-PREP-CICP framework achieved notable results: nirmatrelvir/ritonavir’s authorization enabled deployment approximately 1 year after trials began, demonstrating an 89% reduction in the risk of hospitalization or death and potentially preventing thousands of hospitalizations. The PREP Act enabled focused pharmaceutical development and protected frontline healthcare workers during the crisis, though access barriers and transparency concerns remain areas warranting ongoing attention. The CICP provided administrative compensation for qualifying injuries, with acknowledged limitations in filing timelines and causation standards. Pharmacokinetic studies published after authorization revealed biological barrier crossing, representing normal scientific progress through continued investigation. The EUA-PREP-CICP nexus functioned as an integrated system: EUA enabled rapid evidence-based access, PREP immunity facilitated development and deployment, and CICP provided injury remedy. Based on this experience, this study proposes targeted enhancements to further strengthen this framework: systematic post-authorization surveillance timelines, enhanced special population monitoring through registries, modest procedural refinements to CICP, and improved surveillance infrastructure. These evidence-based improvements would build on the framework’s demonstrated strengths, optimizing performance for future emergencies while preserving the essential functions that helped address the COVID-19 pandemic. Full article

Rheumatoid arthritis (RA) is a systemic autoimmune disease that can involve the ocular surface and deeper ocular tissues, leading to a spectrum of ophthalmic manifestations ranging from dry eye disease to vision-threatening inflammation, such as scleritis and peripheral ulcerative keratitis (PUK). This paper presents the results of a narrative review conducted using PubMed and Google Scholar from database inception to March 2026. Eligible publications describing clinical features and management of RA-associated ocular disease were synthesized, and no unpublished data were included. According to the literature, dry eye disease (DED) is the most frequent ocular manifestation of RA, and it is primarily managed with lubrication and topical anti-inflammatory therapies, including cyclosporine and lifitegrast. Additional options for refractory disease include neurostimulation and evaporation-targeted therapy. Scleritis and PUK are less common but represent severe inflammatory complications that generally require systemic immunosuppression. Conventional management includes systemic corticosteroids and steroid-sparing agents such as methotrexate (MTX), azathioprine (AZA), cyclophosphamide (CYC), and mycophenolate mofetil (MMF) in aggressive cases. Escalation to biologic disease-modifying antirheumatic drugs (bDMARDs), specifically tumor necrosis factor-alpha (TNF-α) inhibitors and rituximab (RTX), is supported for refractory scleritis and corneal melt, although evidence is largely observational. Among anti-TNF agents, monoclonal antibodies, such as infliximab and adalimumab, appear more effective than etanercept for ocular inflammation. Rituximab is preferred for vasculitis-associated or refractory disease, and Janus Kinase (JAK) inhibitors represent an emerging option requiring careful safety monitoring. Evidence for DED therapies includes randomized controlled trials (RCTs), whereas data for RA-associated scleritis and PUK are largely derived from registries, case series, and case reports. Prospective studies with standardized ocular outcomes are needed to refine treatment algorithms and compare the effectiveness of biologic versus targeted synthetic agents. Full article

Positive mental health (PMH) has recently become a key topic in biomedical research. Previous studies have explored the correlation between biological and psychological measures, but only a few have focused on the relationship between PMH and aging. This study aimed: (i) to explore the association between PMH and biological aging; (ii) to determine if and to what extent the observed association could be explained by shared genetic and environmental effects. A total of 401 twins (age 19–81 years, 32% male) from the Italian Twin Registry were recruited, and the twin study design was applied. A self-report psychological test battery was used to evaluate several PMH components. Blood samples were collected from participants to determine telomere length (TL) and mitochondrial DNA copy number (mtDNAcn). TL was negatively associated with attachment anxiety (r = −0.11, p = 0.037). A bivariate twin model provided heritability estimates of 0.14 (95% CI 0.001–0.43) for TL and 0.32 (0.16–0.45) for attachment anxiety, and a substantial negative genetic correlation [r_g = −0.55 (−1.00–0.00)] between them. Under the limitations of a cross-sectional study with a self-report wellbeing assessment, these results suggest that anxiety in the relationship with a partner may contribute to accelerated TL shortening, and shared genetic factors may underlie this link. Full article

Inflammatory bowel diseases (IBD) frequently affect women of reproductive age. Disease activity may arise during pregnancy, at times in severe forms, thereby generating complex clinical scenarios. Adequate control of disease activity throughout pregnancy and the achievement of a safe delivery with a healthy newborn, therefore, represent vital objectives in therapeutic management. In recent years, the therapeutic armamentarium for moderate to severe IBD has expanded exponentially, with the introduction of biological agents and small molecules. However, although these therapies have largely superseded conventional treatment in complex settings, they do not share the same safety profile in pregnancy. Concerns persist regarding potential transplacental transfer and possible teratogenic effects, which justify mandatory caution in their use during pregnancy. Nonetheless, clinicians may readily encounter scenarios of active IBD during pregnancy in patients who have previously experienced failure of the biological agents most extensively studied in this context, thus necessitating an evaluation of the safety of more novel therapeutic options. This review examines the available evidence on Janus kinase inhibitors. Current data, which are highly heterogeneous and of low quality, preclude any recommendation for the use of these small molecules during pregnancy. Prospective registries and large-scale observational studies are mandatory, pending the feasibility of dedicated trials, to better characterise these inhibitors, which could prove valuable, should the evidence ultimately support their use, in women with biologic multi-failure active IBD during pregnancy. Full article

Background: The Biologically Oriented Preparation Technique (BOPT) protocol has demonstrated excellent clinical and biological outcomes in restorations with vertical preparation designs. However, its provisional phase remains highly dependent on the operator’s skill. The EasyBOPT (eBOPT) protocol introduces a standardized digital workflow aimed at simplifying this process and enhancing its reproducibility. The primary objective of this study is to describe the eBOPT protocol and to compare its clinical outcomes with the conventional BOPT approach in a prospective case series. Materials and Methods: A case series was conducted including ten patients requiring full-coverage restorations in the maxillary anterior region. The study protocol was registered on 15 July 2024 at ClinicalTrials.gov, with the following registry name: Periodontal outcomes and digital volumetric variation following BOPT restorations, and with the following registration number: NCT06485999. Five patients were treated using the conventional BOPT protocol and five with the eBOPT protocol. Both groups followed identical diagnostic, preparation, and definitive restoration phases, differing only in the provisionalization technique. In the eBOPT group, a digital workflow based on dual scanning (physiologic and retracted gingiva), “best-fit” alignment, and CAD-CAM fabrication of a standardized 45° emergence provisional restoration was employed. Operative time per tooth, gingival healing time, and the need for additional adjustments were recorded. Results: The mean clinical time per tooth was significantly lower with the eBOPT protocol (12.30 ± 1.50 min) compared to the conventional protocol (31.20 ± 2.10 min; p < 0.001). The mean gingival healing time was also reduced with eBOPT (4.4 ± 0.9 weeks) relative to the traditional approach (9.6 ± 1.5 weeks; p = 0.0014). Only the conventional group required additional provisional adjustments (80% of cases; p = 0.048). Conclusions: The EasyBOPT protocol enables faster, more predictable, and less operator-dependent provisionalization while maintaining the biological stability and gingival health achieved with conventional BOPT. This digital workflow simplifies the clinical application of the BOPT concept and enhances its reproducibility. Full article

Outlier detection is a fundamental component of data preprocessing and quality monitoring across diverse scientific domains, including engineering, biomedical sciences, and finance. While many variables in controlled environments approximate a normal distribution, real-world data, particularly biological, environmental, and epidemiological measures, are frequently characterized by pronounced right-skewness. To address the shortcomings of conventional methods, this study introduces the Dynamic Threshold for Outlier Detection (DTOD), which reframes outlier detection as a concrete operational workflow. The DTOD framework dynamically adjusts detection thresholds based on a functional relationship between skewness and tail morphology. Validation through large-scale simulation experiments across light-, middle-, and high-skewness levels confirms the method’s versatility. The DTOD proves particularly effective at two ends of the spectrum: enhancing sensitivity for detecting subtle anomalies in light-skewed data while serving as a conservative, high-confidence screening tool that controls false positives in high-skewness environments. In real-world application to North American Association of Central Cancer Registries (NAACCR) data, the method successfully identified outliers with abnormally high unknown tumor size rates in colorectal cancer and maintained a low misclassification rate in highly skewed lung cancer data. Ultimately, the DTOD provides a promising, interpretable solution for improving data quality in skewed scenarios. Full article

Background: Frailty strongly influences outcomes after transcatheter aortic valve implantation (TAVI), but conventional risk models insufficiently capture functional and cognitive vulnerability. We compared conventional surgical risk scores with multidimensional frailty assessment and a biological score. Methods: This observational registry included 528 consecutive patients with severe symptomatic aortic stenosis undergoing TAVI between January 2019 and November 2024. Frailty was assessed using the Essential Frailty Toolset (EFT), Katz Index, and cognitive screening, alongside French Aortic National CoreValve and Edwards 2 (FRANCE-2) and Age, Creatinine, and Ejection Fraction (ACEF) scores. HALP was calculated as (haemoglobin × albumin × lymphocytes) ÷ platelets. Primary endpoints were 30-day, 6-month, and 1-year all-cause mortality. Secondary outcomes included non-fatal major adverse cardiovascular events (MACE), complications, and quality-of-life improvement. Results: One-year mortality was 12.7%. EFT and Katz Index showed the strongest discrimination for 1-year mortality (AUC 0.72 and 0.75), outperforming EuroSCORE II and STS-PROM (AUC 0.66 and 0.68). After adjustment, EFT (HR 1.91, 95% CI 1.47–2.48), Katz Index (HR 0.57, 95% CI 0.47–0.70, and cognitive impairment (HR 2.24, 95% CI 1.34–3.75) independently predicted 1-year mortality. HALP was not associated with outcomes. FRANCE-2 independently predicted 1-year MACE (HR 1.24, p = 0.019). Conclusions: Functional frailty and cognitive impairment add prognostic value beyond conventional comparator models, whereas HALP does not. Brief functional and cognitive screening may help Heart Teams identify patients who need closer peri-procedural optimisation, rehabilitation planning, and discharge support rather than relying on surgical risk scores alone. Full article

Background: Continuity of care for rheumatoid arthritis patients within regional networks enables stable long-term clinical data collection, despite chronic rheumatologist shortages in Japan. We determined 5-year drug survival and discontinuation reasons for eight biological disease-modifying antirheumatic drugs (bDMARDs) using a regional multicenter registry. Methods: We retrospectively analyzed 1182 patients initiating their first (naïve, n = 784) or subsequent (switch, n = 398) bDMARD between May 2001 and August 2022 across five institutions. The primary endpoint (5-year drug survival) and secondary endpoints (discontinuation risk factors and cumulative incidence of reasons) were evaluated using Kaplan–Meier curves, Cox proportional hazards, and Fine & Gray models. Results: Baseline characteristics varied significantly among bDMARDs. Five-year drug survival in the naïve cohort ranged from tocilizumab (50.8%) to golimumab (22.6%); in the switch cohort, from abatacept (42.6%) to infliximab (10.0%). In multivariable Cox analysis of naïve patients, male sex (hazard ratio [HR] = 1.49, 95% confidence interval [CI] = 1.09–2.02), lower baseline 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) (HR = 0.90, 95% CI = 0.82–0.99), and absence of methotrexate co-therapy (HR = 0.73, 95% CI = 0.55–0.97) predicted discontinuation. The lower baseline DAS28-ESR association potentially reflects successful courses toward intentional cessation following remission. Discontinuations were attributed to inadequate response (27.1%), non-adverse events (25.3%), and adverse events (17.3%). Conclusions: Tocilizumab and abatacept demonstrated the highest retention rates in biologic-naïve and switch cohorts, respectively. Early, individualized drug selection and dose optimization are crucial to maximizing long-term bDMARD effectiveness before switching. Full article

Chronic obstructive pulmonary disease (COPD) is a major contributor to global respiratory morbidity and exhibits substantial sex- and gender-related differences in incidence, phenotype, pathophysiology, and outcomes across the life course. Historically regarded as a predominantly male disease due to higher smoking rates, COPD is now increasingly recognized among women, reflecting changing exposure patterns and enhanced diagnostic attention. Moreover, evidence indicates that women may be more biologically susceptible to the harmful effects of tobacco smoke and often develop COPD at younger ages. Clinical manifestations also differ, with women more frequently reporting dyspnea, anxiety, and depression, whereas men may exhibit more cough and sputum production. Imaging studies suggest that airway-predominant disease is more common in women, while men are more likely to demonstrate emphysema-predominant patterns. Furthermore, women face an increased risk of exacerbation, yet they are more likely to experience underdiagnosis or misdiagnosis. Treatment responses and comorbidity patterns also show sex- and gender-related variations. Despite these differences, most clinical guidelines and therapeutic strategies do not differentiate by sex and gender, highlighting a gap in personalized COPD management. Overall, growing evidence underscores the importance of incorporating sex and gender as biological and sociocultural variables in COPD research, diagnosis, and treatment. Recognizing sex/gender-specific risk profiles, symptom patterns, and disease phenotypes may improve early detection and enable more targeted, effective interventions. This narrative synthesis, derived from a meticulous search in PubMed and the critical selection of 74 articles from the 448 identified originally, integrates evidence from guideline statements, registry studies, mechanistic and preclinical research, imaging and physiology investigations, systematic reviews, and randomized controlled trials that report sex- and gender-disaggregated data. Full article

Background: Posterior cruciate ligament reconstruction (PCLR) remains one of the most technically demanding procedures in knee ligament surgery, with complication rates considerably higher than those observed for other arthroscopic procedures. Residual laxity, arthrofibrosis, neurovascular injury, tunnel-related complications, and heterotopic ossification (HO) represent the most frequent adverse events. With increasing surgical volumes and complexity—particularly in multiligament knee injuries (MLKIs)—structured, evidence-based strategies for complication avoidance are essential. The objective of this review is to provide a comprehensive, evidence-based overview of the main complications associated with PCLR and to propose a structured, reproducible protocol for complication prevention integrating current literature and high-volume institutional experience. Methods: A narrative review of the literature was conducted using PubMed and Google Scholar to identify clinical, biomechanical, and systematic studies on PCLR complications published between 2010 and 2025. Overall, 58 studies were screened and 33 were included for qualitative synthesis. Among the included studies, the level of evidence was Level I in five systematic reviews/meta-analyses, Level III–IV in seven observational clinical studies and registries, and Level V in biomechanical studies, narrative reviews, and expert consensus reports. In parallel, the recommendations were informed by the cumulative experience of a high-volume tertiary referral center with 187 PCLR procedures performed between 2010 and 2025 (136 MLKI, 51 isolated). Results: Evidence identifies several key predictors of postoperative complications: low posterior tibial slope (<6.54°), small graft diameter (<7.0 mm), untreated posterolateral corner insufficiency, excessive tibial tunnel angle, and surgical trauma at the “killer turn.” Neurovascular complications primarily arise during tibial tunnel instrumentation, with knee hyperflexion (>90°) significantly improving safety. Suture tape augmentation (STA) reduces graft elongation by 45–58% and is associated with improved biomechanical stability without increasing complication rates. Early controlled motion is critical to prevent arthrofibrosis, whereas HO—affecting up to 45% of MLKI patients—requires delayed surgical excision after maturation. Conclusions: Optimal outcomes after PCLR derive from a structured, complication-focused approach encompassing anatomical risk assessment, meticulous tunnel planning, neurovascular protection, biological augmentation, and disciplined postoperative rehabilitation. Adoption of standardized protocols—particularly in MLKIs—can substantially reduce the incidence of adverse events and improve long-term knee stability. Full article