Search Results (2,608)

Early diagnosis of ovarian cancer remains one of the most important unmet needs in gynecologic oncology because survival is strongly stage-dependent and most patients still present with disseminated disease. Conventional non-invasive tools, particularly CA-125, transvaginal ultrasound, and composite triage algorithms, remain clinically useful but are limited by suboptimal sensitivity for stage I disease and by reduced specificity in premenopausal women and in benign inflammatory or endometriosis-associated conditions. Circulating tumor DNA (ctDNA) has therefore emerged as a candidate biomarker capable of extending liquid biopsy beyond conventional serology. In ovarian cancer, however, ctDNA implementation is constrained by low tumor shedding in early-stage disease, marked biologic heterogeneity across histotypes, clonal hematopoiesis-related background noise, and major pre-analytical and analytical sources of variability. This narrative review, informed by structured searches of PubMed, Scopus, and Web of Science, examines the evolving evidence for ctDNA mutations, methylation-based assays, multi-omic platforms, and machine-learning models across three distinct clinical contexts: population screening, preoperative triage of adnexal masses, and post-treatment assessment of molecular residual disease. We also discuss positive predictive value, false-positive harms, health-economic implications, standardization initiatives, and ongoing prospective studies. Overall, current evidence suggests that the most plausible near-term role for liquid biopsy in ovarian cancer is not as a universal stand-alone screening test, but as an integrated component of risk stratification and disease-monitoring frameworks that combine molecular signals with clinicopathologic and imaging data. Full article

Dementia caregiving represents a major public health challenge, with spousal caregivers assuming the greatest burden. Spouses, themselves typically older adults, provide high intensity, long-term, and largely unpaid care across all stages of cognitive decline. Despite their central role in dementia care, the health consequences experienced by spousal caregivers remain insufficiently characterized in the literature and inadequately addressed in clinical and public health practice. This structured narrative review synthesizes current evidence on the multidimensional impact of dementia caregiving on the physical, psychological, cognitive, social, and financial health of spousal caregivers. It further contextualizes these consequences within the trajectory of dementia progression, and identifies interventions, support systems, and policy considerations necessary to mitigate caregiver burden. Spousal caregivers experience disproportionate burden due to continuous, escalating responsibilities that often mirror the progressive deterioration of their partners. Emotional burdens, including uncertainty during pre-diagnostic stages, role strain, conflict, loss of intimacy, and anticipatory grief. Physically, spouses endure musculoskeletal strain, sleep disruption, poor nutrition, and heightened frailty risk. Psychologically, spousal caregivers exhibit elevated rates of depression, anxiety, loneliness, and stress-related disorders. Socially, caregivers experience substantial isolation, stigma, and erosion of social networks. Financial hardship, including early retirement, reduced employment, and uncompensated care hours, further exacerbate stress. Evidence suggests that chronic caregiving stress contributes to biological changes such as immune dysregulation, inflammation, acceleration, aging, and potential cognitive decline in caregivers themselves. Caregiver burden influences patient outcomes as evidenced by increased emergency department use, falls, and earlier institutionalization in persons with dementia whose caregiver is subjected to a high burden. Current care models rarely include routine, caregiver assessment or structured guidance following diagnosis, resulting in substantial unmet needs. Effective mitigation requires integrated, stage-sensitive interventions, including psychosocial support, caregiver education, respite services, culturally tailored programs, and digital health tools, alongside broader policy reforms to reduce financial and structural barriers. Full article

GM1 gangliosidosis and Morquio B are rare lysosomal storage disorders (LSDs) with significant unmet medical needs. These disorders result from mutations in the galactosidase beta 1 (GLB1) gene, leading to impaired β-galactosidase (β-Gal) activity and toxic substrate accumulation. The lack of approved disease-modifying therapies for GM1 gangliosidosis and Morquio B, along with the challenges of achieving effective central nervous system delivery, has driven interest in small-molecule pharmacological chaperones (PCs) to restore β-Gal stability and function. Using Gain Therapeutics’ Magellan™ platform, a novel allosteric binding site on β-Gal was identified, enabling the discovery of a new class of Structurally Targeted Allosteric Regulators (STARs). Medicinal chemistry optimization produced a structurally unique STAR compound series, demonstrating broad β-Gal stabilizing effects. The therapeutic potential of these compounds was evaluated in vitro using a canine fibroblast model of GM1 gangliosidosis, where they were shown to significantly reduce toxic GM1 ganglioside accumulation. Immunocytochemistry-based assays confirmed substrate clearance and provided reliable structure–activity relationships, guiding further compound development. Notably, STARs achieved greater substrate clearance than the competitive PC N-nonyl-deoxygalactonojirimycin (NN-DGJ) under the conditions tested, as demonstrated by immunocytochemistry-based assays. While these findings are encouraging, further in vivo studies are required to validate the therapeutic efficacy of these few STAR compounds, particularly in addressing the neurodegenerative aspects of GM1 gangliosidosis. This study underscores the potential of the Magellan platform in identifying STAR molecules and provides a strong foundation for further optimization and preclinical validation in GLB1-related disorders, particularly GM1 gangliosidosis. Full article

Background: Migraine in older adults represents an increasingly relevant yet underrecognized clinical challenge in aging societies, where multimorbidity, frailty, and polypharmacy complicate both diagnosis and management. Although traditionally considered a disorder of younger individuals, migraine frequently persists or presents after the age of 60 with atypical features, contributing to diagnostic uncertainty. Methods: This narrative review, conducted in accordance with the SANRA principles, aims to provide a comprehensive overview of the epidemiology, clinical presentation, pathophysiology, and management of migraine in older adults, with particular emphasis on age-related complexities, therapeutic challenges, and unmet clinical needs. Results: Migraine in this population often presents with atypical or misleading features, such as aura without headache, vestibular symptoms, or overlap with cerebrovascular conditions, leading to delayed or incorrect diagnoses. The burden of disease is substantial, affecting physical function, mobility, cognition, emotional well-being, and social participation, and is further amplified by comorbid conditions including cardiovascular and metabolic disorders, mood disturbances, and chronic pain syndromes. Aging-related neurobiological changes, such as impaired pain modulation, endothelial dysfunction, and neuroinflammation, may influence disease expression and treatment response. Therapeutic management is challenged by contraindications, increased susceptibility to adverse drug effects, and the complexity of polypharmacy, highlighting the importance of individualized and non-pharmacological approaches. Conclusions: Migraine in older adults is a significant but often overlooked contributor to disability and reduced quality of life. Improved recognition of its unique clinical features and age-specific vulnerabilities is essential to optimize patient-centered care. Future research should prioritize the inclusion of older populations and the development of tailored, safe, and effective management strategies. Full article

Background: Adults with disabilities living in low-resource communities experience persistent inequities in access to healthcare, mental health services, and community participation. However, qualitative data capturing lived experiences in the Deep South remain limited. This study aimed to identify priority needs among adults with mobility disabilities residing in economically distressed communities near Birmingham, Alabama, to inform future telehealth programming. Methods: Fifteen adults (mean age = 60 ± 10 years), predominantly African American and female, completed semi-structured phone interviews exploring basic needs, neighborhood accessibility, health priorities, and perceived supports. Interviews were audio-recorded, transcribed verbatim, and analyzed using Braun and Clarke’s six-phase thematic analysis. Results: Five themes emerged: (1) seeking stability amid severe mental health strain and inadequate supports; (2) constrained food environments shaped by cost, location, and safety; (3) feeling forgotten: systemic neglect and restricted participation in community life; (4) physical health deprioritized by competing needs and structural barriers; and (5) remote support as a viable but unrealized option. Participants described how safety concerns, transportation barriers, and rising food costs constrained daily functioning, while unmet mental health needs compounded isolation. Despite widespread cardiometabolic disease, immediate needs related to mental health, food, and housing consistently superseded physical health. Mental health support was identified as the most feasible area for remote delivery, though poor awareness of available resources limited engagement with any service model. Conclusions: Findings demonstrate that disability-related disparities in low-resource communities are driven largely by structural and environmental factors rather than individual choice. Telehealth and mobile-based services may provide a feasible access strategy for mental health and supportive care in under-resourced settings, particularly when integrated with broader community supports. Addressing foundational needs is essential for advancing health equity among people with disabilities in the Southeast. Full article

Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease characterized by marked clinical heterogeneity. While the genetic architecture underlying disease susceptibility is well established, the role of genetic factors in shaping disease prognosis remains clearly defined. In this structured narrative review, we examine available evidence on genetic contribution to key MS prognostic domains. This includes clinical outcomes, such as age at onset, relapse rate, disability progression, neurological sequelae, and cognitive impairment. We also consider radiological measures like brain and spinal cord lesion burden, gadolinium-enhancing lesions, and atrophy, as well as laboratory biomarkers, such as oligoclonal bands and Immunoglobulin G (IgG) index. Overall, current evidence suggests that genetic influences on prognosis are modest and highly heterogeneous. Only a limited number of associations—primarily from genome-wide association studies (GWAS)—have shown consistent replication, whereas many reported findings come from small candidate-gene studies and remain unconfirmed. Among these, the largest GWAS on age-related Multiple Sclerosis Severity Score (MSSS) identified a locus in the DYSF–ZNF638 region reaching genome-wide significance. The strongest evidence from GWAS relates to relapse rate, magnetic resonance imaging (MRI) measures (e.g., thalamic atrophy) and intrathecal IgG synthesis, the latter also reaching genome-wide significance. Interpretation of genotype–phenotype associations is further limited by small sample sizes, limited replication, heterogeneity in study design with the predominance of candidate-gene approaches, variability in outcome definitions, treatment exposure, and population ancestry. These limitations currently preclude the routine use of genetic markers for prognostic stratification in clinical practice. Larger studies and collaborative genetic consortia efforts are needed to improve statistical power and reproducibility. Additionally, emerging epigenetic studies may provide valuable insights into prognosis and disease management. Understanding which genetic factors can predict diverse MS courses could enhance patient management and enable personalized treatment approaches. Full article

Background: Unhoused individuals face disproportionately high rates of preventable chronic disease due to fragmented access to care and prolonged exposure to environmental stressors. Street medicine programs offer a mobile, low-barrier model to assess and address these unmet needs. Despite well-documented disparities, no publications in the current literature provide numerically specific screening recommendation guidelines tailored to unhoused populations. This study fills that gap using clinical data from Street Medicine Phoenix (SMP), a mobile healthcare initiative serving urban Arizona. Methods: We retrospectively reviewed 1322 clinical encounters recorded by SMP between August 2023 and October 2024. Diagnoses and treatments were manually categorized. Blood pressure (BP) and glucose values were analyzed using descriptive statistics and compared against national norms (CDC 50th percentile and ADA guidelines). Kruskal–Wallis and Dunn’s tests assessed age-based differences, while chi-square and Mann–Whitney U tests examined glucose patterns. Results: The mean patient age was 51.4 years; 34.5% identified as female. Cardiovascular issues (39.4%) and routine screenings (39.6%) were most frequently documented. Systolic and diastolic BP values were significantly elevated across all age groups except those 60+, with even the 18–39 group showing median systolic BP above CDC norms (124.0 mmHg). Among 60 patients with fasting glucose data, 41.4% met ADA criteria for diabetes, and 10.7% of those without a known diagnosis had diabetic-range values. Conclusions: Our findings suggest that cardiometabolic disease may emerge earlier and more aggressively among unhoused individuals than in the general U.S. population, reflecting patterns of accelerated biological aging. The elevation of cohort-based BP percentiles suggests that current national benchmarks may underrepresent clinical risk in this group. We propose initiating blood pressure screening at age 18 and fasting glucose screening by age 35 in unhoused individuals—adaptations of existing USPSTF recommendations based on cohort-specific trends. These screening thresholds can be feasibly implemented in street medicine settings to promote earlier detection and improve long-term health outcomes. Full article

Early-stage healthcare innovation depends on systematic unmet need discovery, a process constrained by time and multidisciplinary coordination. We developed BioDesign Agent, a multi-agent debate framework built on LangGraph to augment the identify phase of design thinking. The system assigns expert roles, clinical, engineering, human factors, regulatory, business, intellectual property, and patient access, to digital agents engaging in structured debate and scoring. Applied to antimicrobial resistance risk prediction, the agent surfaced diverse perspectives, refined need statements, and produced prioritized evaluations. Multi-agent debate yielded more differentiation, richer trade-off analysis, and more actionable insights compared with ChatGPT oss:20b only baselines, demonstrating how structured AI-assisted debate can accelerate healthcare need discovery and complement human-driven biodesign with scalable front-end innovation support. Full article

Background: Malnutrition is a clinically relevant yet often under-recognized complication of inflammatory bowel diseases (IBD). Evidence from non-hospitalized patients remains limited. This study provides a descriptive analysis of indicators of nutritional risk among members of the Italian IBD patients’ association and explores the association with symptoms, clinical characteristics, and access to nutritional care. Methods: A cross-sectional survey was conducted on 705 IBD patients. The questionnaire incorporated all the items required to assess nutritional risk included in the Malnutrition Universal Screening Tool (MUST) and its association with other clinical parameters. Results: Overall, 43.0% of respondents were found to be at moderate or high risk of malnutrition based on the MUST. A low BMI was observed in 25.6% of patients with CD and 22.1% of those with UC. Additionally, unintentional weight loss (UWL) occurred in 24.5% and 23.7% of CD and UC patients, respectively. In total, 30% of patients reported restricting their diet because they were afraid certain foods would worsen their symptoms. Gastrointestinal symptoms were significantly associated with MUST ≥ 2. Only 21.7% of participants reported receiving nutritional counselling. A total of 67.3% of subjects already at high nutritional risk (MUST ≥ 2) have never received any dietary recommendations. Conclusions: In this community sample of IBD patients, a considerable proportion reported indicators compatible with nutritional risk. These findings are not generalized to the general IBD population due to the dissemination through a patient association, but highlight gaps in outpatient nutritional assessment and patient education. Structured, accessible nutritional support may help address these unmet needs. Full article

Financial literacy is critical for individual well-being and sustainable economic development, yet significant gaps remain among Portuguese young adults. Using a two-phase design, this study combines a diagnostic assessment and multi-criteria decision analysis to identify and prioritise effective financial education strategies. In Phase 1, a diagnostic questionnaire administered to 172 first-year university students revealed pronounced deficiencies in core financial concepts. Only 29.1% correctly answered a question on compound interest, and almost half were unable to understand the concept of inflation. Additionally, 62.8% reported low exposure to financial education during compulsory schooling, and 59.9% strongly agreed that it should be included in the mandatory curriculum, indicating both unmet need and strong receptiveness. Phase 2 employed the Analytic Hierarchy Process (AHP) to evaluate five educational alternatives across four criteria. Engagement and motivation (0.32) and knowledge acquisition (0.31) were prioritised over behavioural impact (0.22) and accessibility (0.15). Based on expert assessments weighted by student preferences, in-person courses emerged as the most effective strategy (0.42), substantially outperforming online courses (0.22), videos and digital content (0.14), books (0.13), and games (0.10). The findings point to the need for policy-driven integration of structured, educator-led financial education within formal curricula, supported by approaches that prioritise active engagement and knowledge acquisition over convenience, with digital tools serving as complements rather than replacements. Full article

Background/Objectives: Previous research has shown that mental disorders are common in the general population in Latvia, while access to specialised psychiatric services is limited, particularly in rural areas. General practitioners, therefore, have a crucial role in the early detection and management of these conditions. Previous studies and national initiatives have highlighted an unmet need for continuing education in psychiatry tailored to the Latvian primary care context. In response, the first Latvian telementoring programme, the “ECHO School of Psychiatry” (Extension for Community Healthcare Outcomes, ECHO), was launched in 2023 to enhance general practitioners’ competencies and decision-making in mental healthcare. This study explored general practitioners’ experiences and perceptions of participation in the programme and its perceived impact on their practice, using a qualitative approach. Methods: Thirteen women general practitioners who had participated in the programme between October 2023 and February 2025 were recruited using voluntary response sampling, via email invitations from programme coordinators. Individual semi-structured interviews were conducted remotely between May and September 2025, audio-recorded, transcribed verbatim, and the resulting transcripts were analysed thematically using an inductive approach, supported by NVivo software. Data collection continued until no new themes emerged. Results: Four main themes emerged from the thematic analysis: (1) participants’ perceptions of the structure and educational value of the programme; (2) perceived impact of the programme on clinical practice and decision-making; (3) programme limitations in addressing professional isolation and fostering collaboration; (4) suggestions for programme improvement. Themes illustrate participants’ perceptions of the programme’s value, its impact on practice, and recommendations for further development. Conclusions: This study provides insights into the strengths and areas for improvement of the “ECHO School of Psychiatry” as perceived by general practitioners. It also acknowledges current challenges in primary care, such as limited access to specialists and professional isolation. Full article

Lymphedema is a chronic condition marked by swelling in the body’s soft tissues due to impaired or damaged lymphatic function. Lymphedema is estimated to affect about 1 in 1000 in the United States and 1.4 per 1000 based on two European studies. Lymphedema diagnosis relies on clinical visual assessment by physicians, and the quantitative evaluation of lymphatic function is not widely employed due to the lack of standardized and validated metrics. Lymphoscintigraphy is considered the practical gold standard for evaluating lymphedema. With the emergence of advanced surgical therapies, there is a growing demand for quantitative evaluation metrics to objectively evaluate treatment response. To address this unmet need, we reviewed various methods of quantitative lymphoscintigraphy (qLSG) that were used for assessing lymphedema. We found that multiple qLSG approaches have been described. Moreover, the protocols vary widely in terms of tracer type, injection route, dosage, and exercise interventions. We compared the quantitative assessment strategies and highlighted the approaches that may help provide a more objective lymphedema diagnosis and follow-up. Full article

Background: Chronic Obstructive Pulmonary Disease (COPD) remains a leading cause of emergency department (ED) presentation, hospitalisation, and preventable healthcare utilisation worldwide. Although guidelines advocate coordinated, preventative, and community-based management, care within ED settings often remains reactive and crisis-driven. Nurses occupy a central role in COPD management; however, the experiential dimensions of nursing practice and its contribution to improving patient outcomes are insufficiently understood. Objectives: To explore the lived experiences of patients, nurses and medical officers regarding COPD presentations to the ED, with particular focus on the nursing role in assessment, coordination, education, and identification of unmet and comorbid care needs. Methods: A qualitative phenomenological approach was undertaken across three regional Australian EDs. Purposive sampling recruited patients presenting with acute exacerbations of COPD and nursing and medical officers involved in their care. Semi-structured interviews were conducted and transcribed verbatim. Data were analysed using Braun and Clarke’s thematic analysis framework, supported by reflexive discussion and audit trails to enhance rigour. Results: Six interrelated themes were identified: (1) nursing within a “crisis first” model of care; (2) holistic assessment and translation of complexity; (3) education and care coordination as preventative nursing work; (4) relational care and therapeutic connection; (5) nurses as sentinels for undiagnosed comorbidities, particularly obstructive sleep apnoea; and (6) system pressures constraining optimal nursing practice. Participants consistently described nurses as the clinicians who stabilised acute episodes, interpreted contextual risks, coordinated services, and provided relational and educational support, yet whose preventative contributions were limited by time and organisational demands. Conclusions: ED nurses function as critical integrators between acute stabilisation and chronic disease management for patients with COPD. Formalising nurse-led assessment, education, coordination, and sleep-disordered breathing screening may reduce avoidable ED presentations and enhance patient-centred outcomes. Investment in structured nursing models represents a key opportunity for improving COPD care delivery. Full article

As population aging accelerates, the demand for high-quality end-of-life (EOL) care continues to rise. However, a substantial proportion of patients with terminal cancer still experience death in acute-care hospitals without adequate palliative care. Consultative palliative care (CPC) represents a feasible model for delivering palliative care without requiring dedicated inpatient units, yet evidence evaluating its clinical impact remains limited. In this study, we developed a structured hospital-based CPC model tailored to the Korean healthcare system, the Korea Holistic Optimized Palliative care for End-of-life (K-HOPE) model, and prospectively evaluated its clinical impact. K-HOPE was delivered by an interdisciplinary CPC team in a tertiary hospital. Unmet needs were assessed using the Integrated Palliative care Outcome Scale (IPOS), and longitudinal changes were analyzed using mixed-effects models for repeated measures. Among patients who died during hospitalization, quality of death was evaluated using the Good Death Scale (GDS). A total of 84 patients with terminal cancer received K-HOPE. The total IPOS score significantly decreased over time (β = −10.4, 95% CI −12.8 to −8.0; p < 0.001), indicating reduced overall burden and unmet needs. Significant improvements were observed in psychological distress (p = 0.010) and communication and information needs (p < 0.001), whereas changes in physical symptoms and practical concerns were not statistically significant. Among 22 patients who died during hospitalization, 59.1% achieved a good quality of death (GDS ≥ 12). Longer duration of CPC involvement was significantly associated with higher quality of death and remained an independent predictor in multivariable analysis. These findings suggest that the K-HOPE CPC model improves communication and overall EOL care experiences among hospitalized patients with terminal cancer, indicating that meaningful improvements in EOL care can occur even during short periods of CPC involvement. Structured CPC integrated into routine oncology practice represents a feasible strategy for improving EOL care in tertiary hospitals, and a standardized CPC framework may enhance the consistency and reproducibility of care delivery within the Korean healthcare system. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) commonly arises from oral potentially malignant disorders (OPMDs), yet reliable molecular biomarkers that predict malignant transformation remain scarce. Because epithelial carcinogenesis follows similar multistep trajectories across multiple organs, pan-cancer transcriptional analyses may reveal conserved pathways relevant to early oral tumorigenesis. This study aimed to identify shared transcriptional signatures across carcinomas and evaluate their applicability to precancerous-to-carcinoma progression. Methods: Bulk RNA-seq data from five carcinomas (lung, colon, breast, prostate, and head and neck squamous cell carcinoma, HNSCC) were obtained from TCGA to identify shared differentially expressed genes (DEGs) (|log₂FC| ≥ 2; FDR < 0.05). Functional enrichment, clustering, and gene–pathway network analyses characterized conserved biological processes. Independent GEO datasets containing premalignant and malignant samples, including OPMD and OSCC cohorts, were examined to assess early-stage relevance. Results: A conserved 45-gene signature was identified, enriched for transcriptional regulation, chromatin organization, and RNA polymerase II-mediated processes. Regulatory hubs, including ZIC5, MYBL2, ONECUT2, POU4F1, and PDX1, and strong upregulation of cancer-testis antigens (MAGEA3, MAGEA6, MAGEC2) were notable. Integration with premalignant datasets revealed 13 genes consistently dysregulated across early lesions, involving pathways such as cell differentiation, apoptosis, and lipid transport. Several genes remained altered from normal tissue through OPMD to OSCC, supporting their potential as stable biomarkers. Conclusions: This study identifies conserved transcriptional programs shared across epithelial cancers and detectable in OPMDs. These findings highlight promising biomarker and regulatory candidates for improving early detection and risk stratification of oral precancer, addressing a critical unmet need in OSCC prevention and clinical management. Full article