Search Results (525)

Fractional flow reserve (FFR) is a standard physiological index for guiding coronary revascularization, with a threshold of >0.80 typically used to defer intervention. However, due to its distinct anatomical and physiological features, the left anterior descending artery (LAD) often exhibits lower FFR values than non-LAD vessels for lesions of similar angiographic severity. These vessel-specific differences raise concerns about applying a uniform FFR cutoff across all coronary territories. Observational studies indicate that LAD lesions deferred at an FFR of 0.80 may have similar or better outcomes than non-LAD lesions do. LAD lesions also tend to show lower post-percutaneous coronary intervention FFR values, suggesting that vessel specific target thresholds may be more prognostically appropriate. Additionally, some evidence suggests that instantaneous wave-free ratio may offer greater prognostic value than FFR, specifically in LAD lesions, a trend not consistently seen in other arteries. In patients with acute myocardial infarction and multivessel disease, the prognostic relevance of non-culprit lesion FFR may vary by coronary territory, particularly in the LAD. This review outlines the physiological rationale and clinical evidence for vessel-specific interpretation of FFR, with a focus on the LAD, and explores its potential clinical implications and limitations. Full article

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, CTEPH remains underdiagnosed due to nonspecific symptoms and overlapping features with other forms of pulmonary hypertension. Basic Methodology: This review synthesizes data from large international registries, epidemiologic studies, translational research, and multicenter clinical trials. Key methodologies include analysis of registry data to assess incidence and risk factors, histopathological examination of lung specimens, and molecular studies investigating endothelial dysfunction and inflammatory pathways. Diagnostic modalities and treatment outcomes are evaluated through observational studies and randomized controlled trials. Recent Advances and Affected Population: Research has elucidated that CTEPH arises from incomplete resolution of pulmonary emboli, with subsequent fibrotic transformation mediated by dysregulated TGF-β/TGFBI signaling, endothelial dysfunction, and chronic inflammation. Affected populations are typically older adults, often with prior venous thromboembolism, splenectomy, or prothrombotic conditions, though up to 25% have no history of acute PE. The disease burden is substantial, with delayed diagnosis contributing to worse outcomes and higher societal costs. Microvascular arteriopathy and PAH-like lesions in non-occluded vessels further complicate the clinical picture. Conclusions: CTEPH is now recognized as a treatable disease, with multimodal therapies—surgical endarterectomy, balloon pulmonary angioplasty, and targeted pharmacotherapy—significantly improving survival and quality of life. Ongoing research into molecular mechanisms and biomarker-driven diagnostics promises earlier identification and more personalized management. Multidisciplinary care and continued translational investigation are essential to further reduce mortality and optimize outcomes for this complex patient population. Full article

Background: Vitiligo, a chronic depigmentation disorder driven by oxidative stress and immune dysregulation, remains poorly understood mechanistically. The Keap1/NRF2/ARE pathway is critical for melanocyte protection against oxidative damage; however, the role of Cullin-3 (CUL3), a scaffold for E3 ubiquitin ligases that regulate NRF2 degradation, and its interplay with inflammatory mediators in vitiligo pathogenesis are underexplored. This study investigates CUL3, NRF2, and the associated regulatory networks in vitiligo, integrating clinical profiling and computational docking to identify therapeutic targets. Methods: A case-control study compared non-segmental vitiligo patients with age-/sex-matched controls. Lesional skin biopsies were analyzed by qRT-PCR for the expression of CUL3, NRF2, miRNA-146a, FOXP3, NF-κB, IL-6, TNF-α, and P53. Molecular docking was used to evaluate vitexin’s binding affinity to Keap1, validated by root mean square deviation (RMSD) calculations. Results: Patients with vitiligo exhibited significant downregulation of CUL3 (0.27 ± 0.03 vs. 1 ± 0.58; p = 0.013), NRF2 (0.37 ± 0.26 vs. 1 ± 0.8; p = 0.001), and FOXP3 (0.09 ± 0.2 vs. 1 ± 0.3; p = 0.001), alongside the upregulation of miRNA-146a (4.7 ± 1.9 vs. 1 ± 0.8; p = 0.001), NF-κB (4.7 ± 1.9 vs. 1 ± 0.5; p = 0.001), IL-6 (2.8 ± 1.5 vs. 1 ± 0.4; p = 0.001), and TNF-α (2.2 ± 1.1 vs. 1 ± 0.3; p = 0.001). P53 showed no differential expression (p > 0.05). Docking revealed a strong binding of vitexin to Keap1 (RMSD: 0.23 Å), mirroring the binding of the control ligand CDDO-Im. Conclusions: Dysregulation of the CUL3/Keap1/NRF2 axis and elevated miRNA-146a levels correlate with vitiligo progression, suggesting a role for oxidative stress and immune imbalance. Vitexin’s high-affinity docking to Keap1 positions it as a potential modulator of the NRF2 pathway, offering novel therapeutic avenues. This study highlights the translational potential of targeting the ubiquitin–proteasome and antioxidant pathways in the management of vitiligo. Full article

Background/Objectives: Mpox re-emerged in 2022 as a global health concern. Between 2022 and 2025, Portugal experienced three distinct outbreak waves, highlighting the critical role of laboratory surveillance and public health interventions. This study describes the epidemiological trends, diagnostic performance, and key lessons learned to improve outbreak preparedness. Methods: A total of 5610 clinical samples from 2802 suspected cases were analyzed at the National Institute of Health Doutor Ricardo Jorge using real-time PCR methods. Positivity rates and viral loads (Ct values) were assessed across different clinical specimen types, including lesion, anal, oropharyngeal swabs, and urine samples. Results: Mpox was confirmed in 1202 patients. The first outbreak accounted for 79.3% of cases (n = 953), followed by a significant reduction in transmission during subsequent waves. Lesion and rectal swabs provided the highest diagnostic sensitivity (95.1% and 87.9%, respectively). Oropharyngeal swabs contributed to diagnosis in cases without visible lesions, while urine samples showed limited utility. Conclusions: This study underscores the importance of sustained laboratory surveillance and adaptive public health strategies in controlling mpox outbreaks. Optimizing specimen collection enhances diagnostic accuracy, supporting early detection. Continuous monitoring, combined with targeted vaccination and effective risk communication, is essential to prevent resurgence and ensure rapid response in non-endemic regions. Full article

Background: prostate fusion biopsies are key in the diagnosis of prostate cancer (PCa); however, the fusion imaging system is not always user-friendly or reliable. The aim of this study was to assess the feasibility, accuracy, and effectiveness of transperineal fusion biopsies performed with a novel fusion imaging device equipped with AI-driven auto-contouring. Methods: data from 148 patients who underwent MRI-targeted and systematic prostate fusion biopsy with UroFusion (Esaote) were prospectively collected. All biopsies were performed in-office, under local anaesthesia. Results: cancer detection rate was 64% overall and 56% for clinically significant PCa (csPCa, ISUP ≥ 2). PCa was detected in 35%, 65% and 84% of lesions scored as PI-RADS 3, 4 and 5, respectively. Outfield positive systematic cores were found in the contralateral lobe in one third of cases. Median device-time to obtain fusion imaging was 5 min and median biopsy duration was 15 min. Median difference in volume estimation between ultrasound and MRI auto-contouring was only 1 cc. Detection rate did not differ between experienced and novice, supervised users. Conclusions: in this initial prospective experience, fusion biopsies performed with UroFusion AI-driven auto-contouring system appeared time-efficient, accurate, well tolerated, and user-friendly, with comparable outcomes between experienced and novice users. Systematic biopsies remain highly recommended given the non-negligible rates of positive outfield cores. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease linked to fibrosis and hepatocellular carcinoma (HCC). Gut-derived lipopolysaccharide (LPS) promotes hepatic inflammation, fibrosis, and angiogenesis through toll-like receptor 4 (TLR4) signaling. This study examined the effects of rifaximin, a non-absorbable, gut-targeted antibiotic, on MASH-related liver fibrosis and early hepatocarcinogenesis, with a focus on the LPS–epiregulin–IL-8–angiogenesis axis.MASH was induced in Fischer 344 rats using a choline-deficient, L-amino acid-defined high-fat diet (CDAHFD). Rifaximin (30 mg/kg/day) was orally administered for 12 weeks. Liver histology, gene expression, intestinal permeability, LPS levels, and angiogenic markers were evaluated. Rifaximin reduced hepatic inflammation, fibrosis, hydroxyproline content, and fibrogenic gene expression. The number and size of GST-P-positive preneoplastic lesions and proliferation-related genes were decreased. Portal LPS levels and Kupffer cell activation declined, with downregulation of Lbp, Cd14, Tlr4, and inflammatory cytokines. Rifaximin decreased hepatic epiregulin and IL-8 expression, attenuated CD34-positive neovascularization, and suppressed proangiogenic gene expression, accompanied by improved intestinal barrier function and reduced gut permeability. Rifaximin mitigates MASH progression by restoring gut barrier integrity, limiting LPS translocation, and inhibiting fibrogenic and angiogenic pathways. These results suggest its potential as a chemopreventive agent in MASH-related hepatocarcinogenesis. Full article

Recent advances in technology and pharmacologic agents have significantly improved both local and systemic therapies, making the treatment of non-small cell lung cancer (NSCLC) more effective and less invasive. However, recurrence after radical resection remains a major clinical challenge. Among the various recurrence patterns, oligo-recurrence—particularly metachronous oligo-recurrence, characterized by a limited number of metastatic lesions appearing after a disease-free interval—has gained attention due to its potential for long-term survival and even cure through local therapy. Concurrently, systemic treatments have advanced with the development of molecularly targeted therapies and immune checkpoint inhibitors. Numerous studies have demonstrated their clinical efficacy, resulting in significant improvements in patient prognosis. Therefore, selecting an appropriate treatment strategy for recurrent NSCLC involves a broad spectrum of therapeutic options, including targeted therapies, immune checkpoint inhibitors, and conventional chemotherapy. Treatment decisions are particularly complex in cases of oligo-recurrence, where local therapy is feasible, making it challenging to choose the best approach from the available options. This narrative review summarizes current evidence from retrospective and ongoing prospective trials and discusses the clinical characteristics and treatment strategies for oligo-recurrent NSCLC. Full article

Background/Objectives: Multiparametric MRI (mpMRI) is widely established as the standard imaging modality for detecting clinically significant prostate cancer (csPCa), yet it can be limited by cost, accessibility, and the need for specialized radiologist interpretation. Micro-ultrasound (micro-US) has recently emerged as a more accessible alternative imaging modality. This review evaluates whether the evidence base for micro-US meets thresholds comparable to those that led to MRI’s guideline adoption, synthesizes diagnostic performance data compared to mpMRI, and outlines future research priorities to define its clinical role. Methods: A targeted literature review of PubMed, Embase, and the Cochrane Library was conducted for studies published between 2014 and May 2025 evaluating micro-US in csPCa detection. Search terms included “micro-ultrasound,” “ExactVu,” “PRI-MUS,” and related terminology. Study relevance was assessed independently by the authors. Extracted data included csPCa detection rates, modality concordance, and diagnostic accuracy, and were synthesized and, rarely, restructured to facilitate study comparisons. Results: Micro-US consistently demonstrated non-inferiority to mpMRI for csPCa detection across retrospective studies, prospective cohorts, and meta-analyses. Several studies reported discordant csPCa lesions detected by only one modality, highlighting potential complementarity. The recently published OPTIMUM randomized controlled trial offers the strongest individual-trial evidence to date in support of micro-US non-inferiority. Conclusions: Micro-US shows potential as an alternative or adjunct to mpMRI for csPCa detection. However, additional robust multicenter studies are needed to achieve the evidentiary strength that led mpMRI to distinguish itself in clinical guidelines. Full article

Brain metastases (BMs) are the most common intracranial tumors in adults. Their heterogeneity, potential multifocality, and complex biomolecular behavior pose significant diagnostic and therapeutic challenges. Artificial intelligence (AI) has the potential to revolutionize BM diagnosis by facilitating early lesion detection, precise imaging segmentation, and non-invasive molecular characterization. Machine learning (ML) and deep learning (DL) models have shown promising results in differentiating BMs from other intracranial tumors with similar imaging characteristics—such as gliomas and primary central nervous system lymphomas (PCNSLs)—and predicting tumor features (e.g., genetic mutations) that can guide individualized and targeted therapies. Intraoperatively, AI-driven systems can enable optimal tumor resection by integrating functional brain maps into preoperative imaging, thus facilitating the identification and safeguarding of eloquent brain regions through augmented reality (AR)-assisted neuronavigation. Even postoperatively, AI can be instrumental for radiotherapy planning personalization through the optimization of dose distribution, maximizing disease control while minimizing adjacent healthy tissue damage. Applications in systemic chemo- and immunotherapy include predictive insights into treatment responses; AI can analyze genomic and radiomic features to facilitate the selection of the most suitable, patient-specific treatment regimen, especially for those whose disease demonstrates specific genetic profiles such as epidermal growth factor receptor mutations (e.g., EGFR, HER2). Moreover, AI-based prognostic models can significantly ameliorate survival and recurrence risk prediction, further contributing to follow-up strategy personalization. Despite these advancements and the promising landscape, multiple challenges—including data availability and variability, decision-making interpretability, and ethical, legal, and regulatory concerns—limit the broader implementation of AI into the everyday clinical management of BMs. Future endeavors should thus prioritize the development of generalized AI models, the combination of large and diverse datasets, and the integration of clinical and molecular data into imaging, in an effort to maximally enhance the clinical application of AI in BM care and optimize patient outcomes. Full article

Objective: Burning mouth syndrome (BMS) is a chronic and often debilitating orofacial pain condition characterized by a burning sensation in the oral mucosa without clear abnormal lesions. While its etiology is considered multifactorial, the underlying pathophysiology remains unclear. This narrative review aims to synthesize existing functional magnetic resonance imaging (fMRI) studies to shed light on the central neural mechanisms contributing to BMS. Methods: A focused electronic search was conducted across the PubMed and J-STAGE databases for relevant articles published in English from January 2000 to May 2025. The review prioritized studies investigating brain structure and function using fMRI in individuals with BMS. Results: Our synthesis of the literature consistently demonstrated that the brains of individuals with BMS exhibit augmented connectivity within the medial pain system and a diminished gray matter volume in the medial prefrontal cortex (mPFC). These findings suggest a crucial role for altered brain circuitry, particularly a reduction in the output of the basal ganglia dopamine system, in the experience of BMS pain. Conclusions: The consistent fMRI findings strongly indicate that BMS involves significant functional and structural brain alterations. The observed changes in the mPFC and its connections to the basal ganglia dopamine system highlight this pathway as a potential target for both pharmacological and non-pharmacological neurological interventions for individuals with BMS. Full article

Osteoarthritis (OA) is the most common degenerative joint disease, characterized by articular cartilage degradation, synovial inflammation, and ligament lesions. Non-coding RNAs (ncRNAs) do not encode any protein products and play a fundamental role in regulating gene expression in several physiological processes, such as in the regulation of cartilage homeostasis. When deregulated, they affect the expression of genes involved in cartilage degradation and synovial inflammation, contributing to the onset and progression of OA. Oxidative stress is also involved in the pathogenesis of OA by contributing to the inflammatory response, degradation of the extracellular matrix, and induction of chondrocyte apoptosis. Studies in the literature show a reciprocal relationship between the altered expression of a number of ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and oxidative stress. The aim of this review is to highlight the role of oxidative stress, miRNAs, and lncRNAs and their cross-talk in OA in order to understand the main molecular mechanisms involved and to identify possible targets that may be useful for the identification and development of new diagnostic and therapeutic approaches for this disease. Full article

Meningiomas are the most common primary intracranial tumors in adults. For most cases, surgical resection is effective in mitigating recurrence risk. Accurate visualization of meningiomas helps radiologists assess the distribution and volume of the tumor within the brain while assisting neurosurgeons in preoperative planning. This paper introduces an innovative realistic 3D medical visualization system, namely SegR3D. It incorporates a 3D medical image segmentation pipeline, which preprocesses the data via semi-supervised learning-based multi-target segmentation to generate masks of the lesion areas. Subsequently, both the original medical images and segmentation masks are utilized as non-scalar volume data inputs into the realistic rendering pipeline. We propose a novel importance transfer function, assigning varying degrees of importance to different mask values to emphasize the areas of interest. Our rendering pipeline integrates physically based rendering with advanced illumination techniques to enhance the depiction of the structural characteristics and shapes of lesion areas. We conducted a user study involving medical practitioners to evaluate the effectiveness of SegR3D. Our experimental results indicate that SegR3D demonstrates superior efficacy in the visual analysis of meningiomas compared to conventional visualization methods. Full article

Root lesion nematodes (RLNs) are major plant parasites causing significant global yield losses in a wide range of crops. Current management strategies largely depend on synthetic nematicides, which raise environmental and human health concerns due to their broad-spectrum toxicity and persistence in the ecosystem. Volatile allelochemicals offer a promising, environmentally safer alternative due to their biodegradability and lower toxicity to mammals. In this study, we assessed the nematicidal activity of five allelochemical volatiles—dimethyl sulphide (DMS), dimethyl disulphide (DMDS), trans-cinnamaldehyde (TCA), trans-2-decenal (T2D), and trans-2-undecenal (T2U)—against Pratylenchus penetrans, using direct-contact bioassays, in comparison with the conventional nematicide oxamyl. Additionally, we assessed their environmental behaviour and toxicity profiles through in silico modelling. At 1 mg/mL, TCA, T2D, and T2U exhibited strong activity against P. penetrans, outperforming oxamyl by up to 1.6-fold, while DMS and DMDS showed reduced activity. The environmental risk assessment revealed that these compounds have a lower predicted persistence and bioaccumulation compared with oxamyl or fluopyram, a new generation nematicide. Though these findings boost the potential of these compounds as sustainable alternatives for RLN management, field validation and testing with non-target organisms remain necessary for the development of biopesticides. Nevertheless, this study emphasizes the need for an integrated risk-based assessment in the selection of nematicidal agents, warranting efficacy as well as environmental safety. Full article

Rectal cancer management necessitates a rigorous multidisciplinary strategy, emphasizing precise staging and detailed risk stratification to inform optimal therapeutic decision-making. Obtaining an accurate histological diagnosis before initiating treatment is essential. Comprehensive staging integrates clinical evaluation, thorough medical history analysis, assessment of carcinoembryonic antigen (CEA) levels, and computed tomography (CT) imaging of the abdomen and thorax. High-resolution pelvic magnetic resonance imaging (MRI), utilizing dedicated rectal protocols, is critical for identifying recurrence risks and delineating precise anatomical relationships. Endoscopic ultrasound further refines staging accuracy by determining the tumor infiltration depth in early-stage cancers, while preoperative colonoscopy effectively identifies synchronous colorectal lesions. In early-stage rectal cancers (T1–T2, N0, and M0), radical surgical resection remains the standard of care, although transanal local excision can be selectively indicated for certain T1N0 tumors. In contrast, locally advanced rectal cancers (T3, T4, and N+) characterized by microsatellite stability or proficient mismatch repair are optimally managed with total neoadjuvant therapy (TNT), which combines chemoradiotherapy with oxaliplatin-based systemic chemotherapy. Additionally, tumors exhibiting high microsatellite instability or mismatch repair deficiency respond favorably to immune checkpoint inhibitors (ICIs). The evaluation of tumor response following neoadjuvant therapy, utilizing MRI and endoscopic assessments, facilitates individualized treatment planning, including non-operative approaches for patients with confirmed complete clinical responses who comply with rigorous follow-up. Recent advancements in molecular characterization, targeted therapies, and immunotherapy highlight a significant evolution towards personalized medicine. The effective integration of these innovations requires enhanced interdisciplinary collaboration to improve patient prognosis and quality of life. Full article