Search Results (22,111)

Transcatheter aortic valve implantation (TAVI) has transformed the management of severe aortic stenosis (AS), evolving from a therapy reserved for inoperable patients to a viable treatment across the spectrum of surgical risk. This success has stimulated innovation in transcatheter therapies for other valvular heart diseases, including aortic regurgitation (AR). In contrast to AS, AR is characterised by heterogeneous aetiologies, absence of annular calcification, larger and more elliptical annular dimensions, and concomitant aortopathy. These challenges have limited the efficacy and safety of conventional transcatheter aortic valves (TAVs), use of which in pure native AR is associated with high rates of valve embolisation, significant residual regurgitation, permanent pacemaker implantation, and mortality. The development of dedicated TAVs designed specifically for the treatment of AR has addressed many of these anatomical challenges. The JenaValve Trilogy and J-Valve systems incorporate leaflet-grasping mechanisms that enable secure anchoring independent of calcification, resulting in transformation of procedural and clinical outcomes. Recent prospective registry data, including the landmark ALIGN-AR trial, demonstrate high technical and procedural success rates, low residual regurgitation, acceptable safety profiles, and meaningful improvements in functional status and ventricular remodelling. These data have informed contemporary guideline updates, with the 2025 European Society of Cardiology (ESC)/European Association of Cardiothoracic Surgery (EACTS) Guidelines for the management of valvular heart disease issuing the first conditional recommendation for TAVI in selected patients with severe AR and the National Institute for Health and Care Excellence (NICE) recommending TAVI for native AR in patients for whom surgical AVR is not available or is high risk. This review summarises the clinical implications of AR, examines current guideline recommendations for management, and critically appraises the evidence supporting transcatheter treatment strategies. Full article

Background/Objectives: Peritoneal metastasis represents the most frequent and prognostically unfavorable metastatic pattern in gastric cancer, largely due to limited sensitivity of conventional imaging, delayed diagnosis, and insufficient response assessment. The aim of this review is to provide an overview of the current evidence on the diagnosis and treatment of gastric cancer with peritoneal metastases and to address current treatment limitations and options. Methods: This review was designed as a narrative review and is based on an extensive literature search in established databases. Results: Systemic chemotherapy remains the cornerstone of palliative treatment, improving the survival and quality of life compared with the best supportive care; however, outcomes in peritoneally metastatic disease remain poor. Advances in molecularly targeted and immune-based therapies have extended survival in selected patient populations, yet favorable molecular profiles are mainly unknown in peritoneal metastases. Staging laparoscopy and semi-quantitative assessment using the Peritoneal Cancer Index (PCI) are therefore essential for accurate diagnosis, prognostication, and treatment selection. Growing evidence from retrospective studies, multi-institutional cohorts, and selected randomized trials suggests that a multimodal approach—combining systemic therapy with intraperitoneal or bidirectional chemotherapy—may improve survival and quality of life. In carefully selected patients whose primary gastric tumor and peritoneal lesions respond to systemic treatment, complete cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) may further enhance outcomes and, in rare cases, achieve long-term survival. These potential benefits appear to be limited to highly selected patients with a low peritoneal tumor burden (PCI ≤ 6–7), positive cytology, good performance status, controlled extraperitoneal disease, and a high likelihood of achieving complete macroscopic cytoreduction (CC-0). Conclusions: Although the treatment intent in metastatic gastric cancer remains primarily palliative, carefully selected patients with limited peritoneal metastases may benefit from intensified multimodal treatment strategies when managed in specialized centers. Interdisciplinary evaluation, accurate staging, and individualized treatment planning are essential to optimize outcomes in this challenging disease setting. Full article

IgA nephropathy is the most common primary glomerulonephritis worldwide and a leading cause of chronic kidney disease and kidney failure, with geographic and ancestral variation and a course ranging from asymptomatic urinary abnormalities to progressive loss of kidney function. This narrative review links the multi-hit model to risk stratification, biomarkers, current management, and emerging therapies, and highlights implementation gaps. Risk assessment is longitudinal, prioritizing proteinuria and estimated glomerular filtration rate trajectories and integrating Oxford MEST-C, prediction tools, and biomarker and multi-omics approaches, while recognizing limitations in histologic reproducibility and model calibration. Current management is anchored in optimized supportive care aimed at sustained proteinuria reduction and kidney protection, including intensive blood pressure control with maximal tolerated renin–angiotensin system blockade, dietary sodium restriction and lifestyle measures, and sodium–glucose co-transporter 2 inhibitors for eligible patients. For selected higher-risk patients with persistent proteinuria despite optimized supportive care, immunomodulatory strategies are discussed, including systemic corticosteroids and targeted-release budesonide (Nefecon), emphasizing structured toxicity risk mitigation and cautioning against assuming interchangeability among alternative oral budesonide formulations. Emerging therapies are organized around mechanism-aligned targets across the BAFF/APRIL axis, complement pathways, and endothelin-based approaches, with growing interest in sequencing and combination regimens layered on supportive care. Key gaps include reliance on surrogate endpoints, limited long-term durability and safety data, and uneven evidence for special populations. Full article

Chordoma is a rare malignant neoplasm of the axial skeleton, arising from notochordal remnants. No approved systemic therapies exist, and the 10-year overall survival is below 60%. Accurate molecular and pathological classification is a prerequisite for improved prognostication and the identification of actionable therapeutic targets; however, molecular classification of chordoma remains significantly less advanced than that of other neoplasms. This narrative review synthesizes proposed classification frameworks for chordoma across histological, radiological, surgical, genomic, epigenomic, transcriptomic, and proteomic domains. PubMed and CENTRAL were searched on 1 February 2026 using five queries: ‘chordoma classification’, ‘chordoma DNA sequencing’, ‘chordoma RNA sequencing’, ‘chordoma methylation’, and ‘chordoma copy number’. Original research articles describing more than one patient and reporting a classification or subtyping framework were included; review articles, case reports, and non-English publications were excluded. Sample size and the use of a validation dataset were identified for each study. Results were synthesized qualitatively. A total of 108 studies encompassing 6349 individuals were included. Across six domains, four cross-cutting themes with prognostic and potential theranostic value emerged: copy number alterations, particularly CDKN2A/B loss; SWI/SNF complex dysfunction; stroma–tumor ratio; and immune microenvironment heterogeneity. Full article

Epstein–Barr virus (EBV)-positive primary central nervous system lymphoma (PCNSL) is a rare entity typically associated with profound immunosuppression, most commonly in transplant recipients or individuals with HIV. We report a case of EBV-positive PCNSL arising in a 75-year-old male with myasthenia gravis receiving chronic mycophenolate mofetil (MMF) therapy outside the transplant setting. The patient presented with progressive neurological deficits, and brain magnetic resonance imaging demonstrated multiple enhancing lesions. Stereotactic biopsy revealed diffuse large B-cell lymphoma of non–germinal center subtype with immunoblastic features and EBV-encoded RNA (EBER) positivity, confirming EBV-positive PCNSL. MMF was discontinued, and the patient was treated with rituximab and high-dose methotrexate, resulting in stable disease. This case highlights that prolonged MMF therapy may confer sufficient immunosuppression to permit EBV-driven lymphoproliferative disease even in non-transplant patients. Early recognition, withdrawal of immunosuppression, and initiation of methotrexate-based chemotherapy can lead to favorable outcomes. Full article

This study investigates shared molecular mechanisms between pyoderma gangrenosum (PG) and inflammatory bowel disease (IBD) and systematically evaluates the therapeutic potential of JAK inhibitors targeting this pathway. Despite the clear clinical comorbidity, the core inflammatory pathways driving cross-tissue associations between the two diseases remain unclear. Furthermore, systematic mechanistic evidence is lacking regarding whether JAK inhibitors act by regulating shared pathological pathways in patients with comorbidities. To address this, this study integrated PG skin and IBD intestinal transcriptome data, single-cell transcriptomic data, and genome-wide association study (GWAS) meta-data from public databases. It employed a multi-level computational biology approach combining Mendelian randomization, weighted gene co-expression network analysis, protein interaction network construction, molecular docking simulations, and system dynamics modeling. The results revealed that genetic analysis confirmed IBD as a causal risk factor for PG, precisely identifying six shared genetic loci. Transcriptomic analysis identified a cross-tissue conserved inflammatory module centered on the JAK-STAT pathway, with JAK2 and STAT3 identified as network hubs. Molecular docking predicted high affinity of baricitinib for both JAK1 and JAK2, while system dynamics modeling demonstrated that its intervention effectively suppresses signaling in the shared inflammatory network. This study reveals the molecular basis of the “gut–skin axis” comorbidity between PG and IBD from a multi-omics integration perspective. It provides predictive computational evidence for the use of JAK inhibitors in targeted comorbidity therapy. Baricitinib is identified as a particularly promising candidate. These findings advance the transition from empirical drug use to mechanism-guided precision treatment strategies. Although this study provides multiscale computational simulation evidence, the lack of direct experimental validation of these predicted results necessitates further confirmation through in vitro and in vivo experiments. Full article

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with onset typically in early adulthood and the potential for long-term disability. Current therapies are initiated after symptom onset and do not address early disease triggers, highlighting the need for preventive strategies. Epstein–Barr virus (EBV) infection has emerged as the strongest candidate upstream factor in MS development. This narrative review provides a focused and critical synthesis of current evidence, with particular emphasis on the prevention perspective and the conceptual framing of MS as a potentially infection-driven disease. We integrate epidemiological, immunological, and mechanistic data while explicitly addressing key uncertainties and limitations in causal interpretation. Longitudinal studies indicate that EBV infection precedes MS onset in most cases and is associated with a markedly increased risk following seroconversion. However, EBV infection alone is not sufficient to cause MS. Proposed mechanisms include immune dysregulation and molecular mimicry, though key uncertainties remain. Based on current evidence, EBV represents a promising but unproven target for MS prevention. Future strategies may include prevention of EBV infection or infectious mononucleosis, alongside improved risk stratification and long-term studies to assess the impact of EBV-targeted interventions on MS incidence. Full article

Background: The aim of this study is to determine the prevalence of malnutrition, frailty, and cachexia in patients with different cancer subtypes undergoing oncological treatment using various screening scales and to evaluate the distribution of these conditions by geriatric age groups. Methods: This cross-sectional study included 4595 patients with different cancer subtypes undergoing oncological treatment. Nutritional status was assessed using the Mini Nutritional Assessment—Short (MNA-S) form; frailty was evaluated with the Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight (FRAIL) scale; and cachexia was determined based on >5% weight loss in the last 6 months or a body mass index (BMI) < 20 kg/m², together with an additional >2% weight loss. Patients were divided into two groups by geriatric age. Results: A total of 36% of the patients included in the study were geriatric (≥65 years old). The prevalence of malnutrition, frailty, and cachexia in the general population was determined to be 40%, 45%, and 44%, respectively. All three conditions were found to be statistically significantly more prevalent in the geriatric age group (p < 0.001 for all comparisons). Conclusions: It was determined that the prevalence of malnutrition, frailty, and cachexia was high in cancer patients receiving systemic oncological treatments including chemotherapy, hormonal therapy, targeted therapy, and immunotherapy; these syndromes are significantly more common, particularly in the geriatric patient group. Full article

Ulcerative colitis (UC) is a complex chronic inflammatory bowel disease, and its pathogenesis is closely related to immune imbalance, intestinal flora disorder and intestinal barrier damage. In recent years, a novel form of programmed cell death, PANoptosis, has been confirmed to play a core role in the pathological process of UC. PANoptosis is driven by the PANoptosome complex, which is assembled by key molecules such as ZBP1, NLRP3, and RIPK1, which can simultaneously activate pyroptosis, apoptosis, and necroptosis. This not only leads to damage to the intestinal epithelial barrier, but it also aggravates the dysfunction of immune cells by releasing a large amount of pro-inflammatory cytokines and damage-associated molecular patterns (DAMPs), thus forming a vicious cycle of “cell death and inflammation”. Given the complexity of the PANoptosis signaling network, the efficacy of single-target inhibitors is limited. This review systematically expounds the mechanism of action of PANoptosis in UC and focuses on discussing multi-target combination treatment strategies represented by smart hydrogels loaded with multiple inhibitors (such as MCC950, GSK772, VX-765, disulfiram, etc.). This strategy achieves synergy through “vertical blocking” and “horizontal coverage”, and in combination with targeted delivery to the lesion, provides a highly promising innovative direction for fundamentally breaking the pathological cycle of UC. Future research should focus on the development of new inhibitors, the optimization of delivery systems, and in-depth clinical translation to promote this strategy as a breakthrough therapy for refractory UC. Full article

Iron-based nanoparticles, particularly iron oxide nanostructures (IONPs), have emerged as versatile and clinically relevant platforms for drug delivery and theranostic applications. Among these, superparamagnetic iron oxide nanoparticles (SPIONs), including magnetite (Fe₃O₄) and maghemite (γ-Fe₂O₃), are the most extensively investigated due to their biocompatibility, magnetic responsiveness, and established safety profiles. Their unique superparamagnetic behavior enables external magnetic-field-guided targeting, magnetic resonance imaging (MRI) contrast enhancement, and magnetically triggered hyperthermia, enabling simultaneous diagnosis and therapy. Surface functionalization with polymers, silica, lipids, peptides, and biomolecules further improves colloidal stability, circulation time, targeting specificity, and controlled drug release. Core–shell architectures and multifunctional hybrid systems have expanded the therapeutic scope of iron nanoparticles, integrating chemotherapy, gene delivery, photothermal therapy, and Fenton reaction–mediated catalytic therapy. Despite promising preclinical outcomes, challenges remain regarding long-term biosafety, oxidative stress induction, biodistribution, large-scale reproducibility, and regulatory translation. This review summarizes the physicochemical properties, synthesis strategies, surface-engineering approaches, drug-loading mechanisms, and biomedical applications of iron-based nanoparticles, highlighting recent advances in multifunctional and peptide-functionalized systems. Critical considerations for clinical translation and future perspectives in precision nanomedicine are also discussed. Full article

Modern dentistry increasingly relies on light-curing units (LCUs) and lasers in essential clinical procedures such as composite resin polymerization, caries treatment, and periodontal therapy. This review aims to outline the evolution of light-emitting technologies and to assess their potential biological risks, with particular emphasis on effects on the visual system, oral tissues, and microbiome. The development of curing devices is presented chronologically, from the first-generation ultraviolet (UV-A) lamps introduced in the 1970s to current light-emitting diode (LED-LCU) systems and dental lasers (e.g., Er:YAG, Nd:YAG). The progressive increase in light intensity—now exceeding 3000 mW/cm²—has shortened curing times but simultaneously raised safety concerns. Major hazards include the so-called blue-light hazard, where exposure to high-energy visible (HEV) blue light may accelerate macular degeneration, and temperature elevations in the pulp chamber, which may damage the dentin–pulp complex. Laser radiation also exerts significant microbiological effects: Er:YAG and diode lasers demonstrate bactericidal activity against biofilms and oral pathogens (e.g., P. gingivalis), although therapeutic outcomes depend on wavelength, dose, and exposure time. Suboptimal parameters may lead to microbiome disturbances, whereas low-level laser therapy (LLLT; 600–1200 nm) supports tissue regeneration and helps restore microbial balance. The individualization of irradiation parameters, combined with thorough theoretical knowledge, operator expertise, and technical understanding of LCUs and lasers, is essential for maximizing clinical benefits while minimizing health risks and preserving oral microbiome homeostasis. Full article

Wound healing research has advanced through nanotechnology-based delivery systems that enhance the stability and therapeutic potential of bioactive compounds. Resveratrol, a natural polyphenol with antioxidant and anti-inflammatory properties, shows promise for wound healing but is limited by poor bioavailability. This study investigates the efficacy of nano-liposome-encapsulated resveratrol in enhancing skin wound repair in adult zebrafish (Danio rerio). Using a laser-based ablation method, precise full-thickness skin wounds were induced and monitored over 50 days. Resveratrol-loaded liposomes were prepared and orally administered via gavage to facilitate systemic exposure. Compared to the control and blank liposome groups, resveratrol liposome treatment significantly accelerated wound closure, achieving earlier healing milestones (25%, 50%, and 75%). The zebrafish model provided a regenerative platform for real-time evaluation of nanomedicine-based therapies. This study demonstrates the wound healing effects of resveratrol and liposomal encapsulation, offering a targeted, systemically administered strategy for advanced systemic healing and highlighting zebrafish as a valuable model for preclinical regenerative medicine research. Full article

Background/Objectives: Early neurological deterioration (END) is a frequent and clinically relevant complication in patients with a single small subcortical infarction (SSI), including lacunar infarction and branch atheromatous disease (BAD). Despite initially mild symptoms, END occurs in approximately 20–25% of cases and is strongly associated with poor functional outcomes. However, definitions, mechanisms, predictors, and therapeutic strategies remain heterogeneous. This review aims to synthesize current evidence regarding the incidence, pathophysiology, predictors, and management of END in SSI. Methods: We performed a narrative review of published studies addressing END in patients with lacunar stroke or SSI. We analyzed data on END definitions and incidence, imaging and clinical predictors, proposed pathophysiological mechanisms, and preventive and rescue therapeutic strategies. Results: END definitions vary across studies, most commonly defined as a ≥2-point increase in the National Institutes of Health Stroke Scale within 48–72 h. Hemodynamic compromise due to proximal perforator pathology, particularly in BAD, appears central to END development. Advanced imaging studies demonstrate perfusion abnormalities beyond the infarct core, supporting the concept of a “lacunar penumbra.” Lesion topology, proximal infarct patterns, parent artery plaques, larger infarct size, and vertical extension are consistent imaging predictors. Clinical factors such as diabetes mellitus, higher baseline severity, systemic inflammation, and increased arterial stiffness further modulate risk. Preventive strategies, including early dual antiplatelet therapy and intensified antithrombotic regimens, show promising signals, while induced hypertension may benefit selected patients as a rescue therapy. However, evidence remains largely observational or derived from subgroup analyses. Conclusions: END in SSI is a multifactorial and potentially modifiable process driven by interactions between proximal vascular pathology, hemodynamic failure, and tissue vulnerability. Standardized definitions, MRI-based phenotyping, and mechanism-driven trials are needed to optimize risk stratification and develop targeted preventive and rescue strategies. Full article

Accurate distinction between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) remains the key local staging problem in bladder cancer because treatment intensity, timing of radical therapy, and suitability for bladder-preserving strategies all depend on it. Multiparametric magnetic resonance imaging (mpMRI) and the Vesical Imaging-Reporting and Data System (VI-RADS) now provide a standardized imaging framework for local staging and increasingly support MRI-first clinical pathways. Artificial intelligence (AI) has emerged as an additional decision-support layer, but the evidence base remains methodologically uneven. In this structured narrative review, we synthesized peer-reviewed literature from January 2020 to March 2026, while retaining foundational VI-RADS studies from 2018 to 2019, and prioritized guideline documents, meta-analyses, prospective cohorts, multicenter and externally validated AI studies, response-assessment studies, and papers addressing implementation and reporting quality. Current evidence shows that radiomics and deep learning models can achieve high discrimination for MIBC detection on MRI, and that the most plausible incremental value of AI lies in equivocal VI-RADS lesions, reader support outside high-volume expert settings, and multimodal risk stratification. However, most studies remain retrospective, highly selected, segmentation-dependent, and vulnerable to reference-standard bias, domain shift, and poor calibration. This review therefore emphasizes several translational issues that are often underreported: lesion-level versus patient-level inference, the distortive effect of TURBT-based labels, the need to evaluate false-negative consequences in VI-RADS 3 tumors, and the distinction between diagnostic support and broader pathway redesign. We also discuss response assessment, nacVI-RADS, segmentation automation, multicenter and federated infrastructure, workflow ownership, and the limits of imaging-only models in a biologically heterogeneous disease. The most credible near-term role of AI is not autonomous diagnosis, but augmentation of standardized mpMRI and VI-RADS within multidisciplinary care. Future progress will depend on prospective utility studies, site-held-out validation, transparent reporting, and the integration of imaging with molecular and cellular heterogeneity through radiogenomic and multi-omics approaches. Full article

Steroid-sensitive cancers (e.g., breast, ovarian, uterine, and prostate cancers) are difficult to control and frequently metastasize to lymph nodes, bone, or lung. Although endocrine research has greatly advanced our identification of the direct roles of steroid sex hormones such as androgens and estrogens on tumor cells in promoting metastasis or recurrence (e.g., treatment with gonadotropin releasing hormone agonists/antagonists, aromatase inhibitors, and estrogen and androgen receptor antagonists), mechanistic insight regarding indirect effects of steroid hormones, including how the innate immune system responds to cancer and is influenced by steroid hormones, is lacking. Despite technological advances in engineering more robust adaptive immunity to combat tumor growth (e.g., CART or checkpoint inhibitors), there remains a relative lack of investigation into the role of innate immunity as a key defense system. Here we discuss recent studies that highlight the significance of neutrophils and their response to tumorigenic conditions with or without steroid hormones in animal models of cancer. We will describe relationships between steroid hormones and neutrophils, with a specific focus on neutrophil extracellular traps (NETs), and how these interactions modulate tumor growth and invasion. Together, these data indicate that combinatorial regulation of both innate and adaptive immunity in the context of tumorigenesis may improve outcomes in cancer therapies. Full article