Search Results (360)

The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has transformed significantly with the advent of triplet therapy involving androgen deprivation therapy (ADT), docetaxel, and androgen receptor signalling inhibitors (ARSIs). While clinical guidelines increasingly support early intensification, real-world practice remains challenged by patient heterogeneity, evolving evidence, and limited consensus on treatment sequencing. This narrative review integrates evidence from landmark trials, clinical guidelines, and expert insights from oncologists managing mHSPC in India. Findings affirm that triplet therapy, particularly with darolutamide, improves survival in high-volume disease and underscores the need for personalized treatment based on disease burden, comorbidities, and genomic profiles. The review also highlights gaps in real-world data, sequencing strategies, and biomarker-driven therapy, reinforcing the need for precision medicine and locally relevant evidence to guide treatment. Ultimately, optimizing mHSPC management requires harmonizing guideline-based approaches with individualized, real-world decision making to improve patient outcomes. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Background/Objectives: Senior nurses in Taiwan shoulder layered responsibilities shaped by professional roles, gendered expectations, and family duty. Although Taiwan faces a persistent shortage of experienced clinical nurses, limited research has explored how long-serving nurses sustain identity and commitment across decades of caregiving. This study examines how senior staff nurses understand their journeys of becoming—and remaining—nurses within a culturally and emotionally complex landscape. Methods: Interviews were conducted between May 2019 and September 2023 in locations chosen by participants, with most sessions face-to-face and others undertaken via video conferencing during COVID-19. This narrative inquiry involved in-depth, multi-session interviews with five female senior staff nurses born in the 1970s to early 1980s. Each participant reflected on her life and career, supported by co-constructed “nursing life lines.” Thematic narrative analysis was conducted using McCormack’s five-lens framework and Riessman’s model, with ethical rigor ensured through reflexive journaling and participant validation. Results: Three overarching themes emerged: (1) inner strength and endurance, highlighting silent resilience and the ethical weight of caregiving; (2) support and responsibility in relationships, revealing the influence of family, faith, and relational duty; and (3) role navigation and professional identity, showing how nurses revisit meaning, self-understanding, and tensions across time. Participants described emotionally powerful moments, identity re-connection, and cultural values that shaped their paths. Conclusions: These narratives offer a relational and culturally embedded understanding of what it means to sustain a career in nursing. Narrative inquiry created space for reflection, meaning-making, and voice in a system where such voices are often unheard. Identity was not static—it was lived, reshaped, and held in story. Full article

Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, driven by advances in two complementary strategies: organotypic in vitro spermatogenesis (IVS), which aims to complete spermatogenesis ex vivo using native testicular tissue, and in vitro gametogenesis (IVG), which seeks to generate male gametes de novo from pluripotent or reprogrammed somatic stem cells. To evaluate the current landscape and future potential of these approaches, a narrative, semi-systematic literature search was conducted in PubMed and Scopus for the period January 2010 to February 2025. Additionally, landmark studies published prior to 2010 that contributed foundational knowledge in spermatogenesis and testicular tissue modeling were reviewed to provide historical context. This narrative review synthesizes multidisciplinary evidence from cell biology, tissue engineering, and translational medicine to benchmark IVS and IVG technologies against species-specific developmental milestones, ranging from rodent models to non-human primates and emerging human systems. Key challenges—such as the reconstitution of the blood–testis barrier, stage-specific endocrine signaling, and epigenetic reprogramming—are discussed alongside critical performance metrics of various platforms, including air–liquid interface slice cultures, three-dimensional organoids, microfluidic “testis-on-chip” devices, and stem cell-derived gametogenic protocols. Particular attention is given to clinical applicability in contexts such as NOA, oncofertility preservation in prepubertal patients, genetic syndromes, and reprocutive scenarios involving same-sex or unpartnered individuals. Safety, regulatory, and ethical considerations are critically appraised, and a translational framework is outlined that emphasizes biomimetic scaffold design, multi-omics-guided media optimization, and rigorous genomic and epigenomic quality control. While the generation of functionally mature sperm in vitro remains unachieved, converging progress in animal models and early human systems suggests that clinically revelant IVS and IVG applications are approaching feasibility, offering a paradigm shift in reproductive medicine. Full article

Hypertrophic cardiomyopathy (HCM) is a prevalent and often underdiagnosed genetic cardiac disorder characterized by left ventricular hypertrophy and, in many cases, dynamic left ventricular outflow tract obstruction (LVOTO). The development of cardiac myosin inhibitors (CMIs) represents an emerging therapeutic approach in the pharmacological management of obstructive HCM (oHCM). This review offers an integrated and up-to-date synthesis of the cardiac myosin inhibitor class, with a focus on mavacamten, aficamten, and the broader landscape of emerging agents. It also highlights recent clinical trial outcomes, pharmacokinetic and pharmacogenetic considerations, and potential future directions in therapy. Furthermore, we incorporate the most recent data up to May 2025, including late-breaking trial results and real-world safety findings, aiming to provide clinicians with a practical and comprehensive perspective on this evolving drug class. A narrative review was conducted by systematically searching PubMed, Scopus, Google Scholar, and ClinicalTrials.gov for English-language articles and trials published between January 2016 and May 2025. Keywords included “cardiac myosin inhibitor”, mavacamten”, “aficamten”, “MYK-224”, and “hypertrophic cardiomyopathy.” Inclusion criteria encompassed clinical trials and comprehensive reviews specifically addressing CMIs in cardiac applications. CMIs such as mavacamten and aficamten have demonstrated significant clinical benefits in reducing LVOT gradients, improving exercise capacity, and alleviating symptoms in patients with oHCM. Mavacamten is currently approved for clinical use, while aficamten is in advanced regulatory review. Comparative data suggest potential advantages of aficamten in the onset of action, pharmacokinetic profile, and tolerability. Emerging evidence supports the exploration of CMIs in pediatric populations, heart failure with preserved ejection fraction (HFpEF), and non-obstructive HCM (nHCM), although results are still preliminary. Cardiac myosin inhibitors offer a novel, pathophysiology-targeted approach to managing oHCM. While mavacamten has established efficacy, next-generation agents like aficamten may offer improved safety and versatility. Further long-term studies are needed to clarify their role across broader patient populations. Full article

Background: Chronic Kidney Disease (CKD) is a major global health issue, with diabetes being its primary cause and cardiovascular disease contributing significantly to patient mortality. Recently, two classes of medications—sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—have shown promise in protecting both kidney and heart health beyond their effects on blood sugar control. Methods: We conducted a narrative review summarizing the findings of different clinical trials and mechanistic studies evaluating the effect of SGLT2i and GLP-1 RAs on kidney function, cardiovascular outcomes, and overall disease progression in patients with CKD and DKD. Results: SGLT2i significantly mitigate kidney injury by restoring tubuloglomerular feedback, reducing intraglomerular hypertension, and attenuating inflammation, fibrosis, and oxidative stress. GLP-1 RAs complement these effects by enhancing endothelial function, promoting weight and blood pressure control, and exerting direct anti-inflammatory and anti-fibrotic actions on renal tissues. Landmark trials—CREDENCE, DAPA-CKD, and EMPA-KIDNEY—demonstrate that SGLT2i reduce the risk of kidney failure and renal or cardiovascular death by 25–40% in both diabetic and non-diabetic CKD populations. Likewise, trials such as LEADER, SUSTAIN, and AWARD-7 confirm that GLP-1 RAs slow renal function decline and improve cardiovascular outcomes. Early evidence suggests that using both drugs together may offer even greater benefits through multiple mechanisms. Conclusions: SGLT2i and GLP-1 RAs have redefined the therapeutic landscape of CKD by offering organ-protective benefits that extend beyond glycemic control. Whether used individually or in combination, these agents represent a paradigm shift toward integrated cardiorenal-metabolic care. A deeper understanding of their mechanisms and clinical utility in both diabetic and non-diabetic populations can inform evidence-based strategies to slow disease progression, reduce cardiovascular risk, and improve long-term patient outcomes in CKD. Full article

Transcranial direct current stimulation (tDCS) can modulate cortical excitability in a polarity-specific manner, yet identical protocols often produce inconsistent outcomes across sessions or individuals. This narrative review proposes that much of this variability arises from the brain’s intrinsic temporal landscape. Integrating evidence from chronobiology, sleep research, and non-invasive brain stimulation, we argue that tDCS produces reliable, polarity-specific after-effects only within a circadian–homeostatic “window of efficacy”. On the circadian (Process C) axis, intrinsic alertness, membrane depolarisation, and glutamatergic gain rise in the late biological morning and early evening, whereas pre-dawn phases are marked by reduced excitability and heightened inhibition. On the homeostatic (Process S) axis, consolidated sleep renormalises synaptic weights, widening the capacity for further potentiation, whereas prolonged wakefulness saturates plasticity and can even reverse the usual anodal/cathodal polarity rules. Human stimulation studies mirror this two-process fingerprint: sleep deprivation abolishes anodal long-term-potentiation-like effects and converts cathodal inhibition into facilitation, while stimulating at each participant’s chronotype-aligned (phase-aligned) peak time amplifies and prolongs after-effects even under equal sleep pressure. From these observations we derive practical recommendations: (i) schedule excitatory tDCS after restorative sleep and near the individual wake-maintenance zone; (ii) avoid sessions at high sleep pressure or circadian troughs; (iii) log melatonin phase, chronotype, recent sleep and, where feasible, core temperature; and (iv) consider mild pre-heating or time-restricted feeding as physiological primers. By viewing Borbély’s two-process model and allied metabolic clocks as adjustable knobs for plasticity engineering, this review provides a conceptual scaffold for personalised, time-sensitive tDCS protocols that could improve reproducibility in research and therapeutic gain in the clinic. Full article

Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare and biologically distinct subset of urothelial malignancies, comprising approximately 5–10% of urothelial cancers. UTUC presents unique diagnostic and therapeutic challenges, with both a higher likelihood of invasive disease at presentation and a less favorable prognosis compared to urothelial carcinoma of the bladder. Current treatment strategies for UTUC are largely derived from bladder cancer studies, underscoring the need for UTUC-directed research. This review provides a comprehensive overview of UTUC, encompassing diagnostic approaches, systemic and intraluminal therapies, surgical management, and future directions. Methods: A narrative review was conducted synthesizing evidence from guideline-based recommendations, retrospective and prospective clinical studies, and ongoing trials focused on UTUC. Results: Neoadjuvant cisplatin-based chemotherapy is increasingly preferred in UTUC due to the risk of postoperative renal impairment that may preclude adjuvant cisplatin use. Surgical management includes kidney-sparing approaches and radical nephroureterectomy (RNU), with selection guided by tumor risk and patient comorbidities. While endoscopic management (EM) preserves renal function, it carries a higher recurrence and surveillance burden; RNU remains standard for high-risk cases. Systemic therapy for advanced and metastatic UTUC mirrors that of bladder urothelial carcinoma. Enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy over chemotherapy in the EV-302 trial, with improved response rate, progression-free survival, and overall survival across subgroups, including UTUC. For patients ineligible for EV, the CheckMate-901 study supported first-line chemoimmunotherapy with gemcitabine, cisplatin, and nivolumab. Further systemic therapy strategies include maintenance avelumab post-chemotherapy (JAVELIN Bladder 100), targeted therapies such as erdafitinib (THOR trial), and trastuzumab deruxtecan (DESTINY-PanTumor02) in FGFR2/3-altered and HER2-positive disease, respectively. Conclusions: Historically, the therapeutic landscape of UTUC has been extrapolated from bladder cancer; however, ongoing research specific to UTUC is deriving more precise regimens involving the use of immune checkpoint inhibitors, antibody–drug conjugates, and biomarker-driven therapies. Full article

Oligometastatic non-small-cell lung cancer (OMD-NSCLC) has emerged as a biologically and clinically distinct subtype of advanced disease, characterized by limited metastatic burden and a more indolent course. In this narrative review, we examine the current definition of OMD-NSCLC, diagnostic tests, possible biomarkers, and current therapeutic strategies. Biological insights highlight the role of microRNAs in differentiating true oligometastatic state from polymetastatic disease. The main local ablative therapies (LAT) include surgery and radiotherapy. The integration of LAT with systemic therapies has been explored in clinical trials, yielding promising but occasionally inconsistent results. As the therapeutic landscape of OMD-NSCLC patients continues to evolve, refining definitions, identifying predictive biomarkers, and individualizing care are essential steps toward achieving the potential of radical-intent therapy. Full article

This study delivers a rigorous and in-depth bibliometric examination of 693 scholarly publications addressing the intersection of metaverse technologies and banking, retrieved from the Web of Science Core Collection. Through advanced scientometric tools, including VOSviewer and Bibliometrix, the research systematically unpacks the evolving intellectual and thematic contours of this interdisciplinary frontier. The co-occurrence analysis of keywords reveals a landscape shaped by seven core thematic clusters, encompassing immersive user environments, digital infrastructure, experiential design, and ethical considerations. Factorial analysis uncovers a marked bifurcation between experience-driven narratives and technology-centric frameworks, with integrative concepts such as technology, information, and consumption serving as conceptual bridges. Network visualizations of authorship patterns point to the emergence of high-density collaboration clusters, particularly centered around influential contributors such as Dwivedi and Ooi, while regional distribution patterns indicate a tri-continental dominance led by Asia, North America, and Western Europe. Temporal analysis identifies a significant surge in academic interest beginning in 2022, aligning with increased institutional and commercial experimentation in virtual financial platforms. Our findings argue that the incorporation of metaverse paradigms into banking is not merely a technological shift but a systemic transformation in progress—one that blurs the boundaries between speculative innovation and tangible implementation. This work contributes foundational insights for future inquiry into digital finance systems, algorithmic governance, trust architecture, and the wider socio-economic consequences of banking in virtualized environments. Whether a genuine leap toward financial evolution or a sophisticated illusion, the metaverse in banking must now be treated as a systemic phenomenon worthy of serious scrutiny. Full article

Russia’s invasion of Ukraine has profoundly altered the global geopolitical landscape. Owing to its geographical proximity, the conflict has had a considerable impact on Europe. Marked by the professionalisation and democratisation of technology, it has underscored the growing significance of hybrid warfare, in which disinformation and propaganda serve as additional instruments of war. Within this context, the aim of this article is to examine the characteristics of false information related to the war between Russia and Ukraine in four European countries between 2022 and 2023. To this end, a content analysis of 297 hoaxes was conducted across eight fact-checking platforms, complemented by ten in-depth interviews with specialised professionals. The findings indicate that disinformation is characterised by viral audiovisual hoaxes, particularly on Facebook and X (formerly Twitter), with a notable surge in disinformation flows at the onset of the invasion. In the early months, misleading content predominantly consisted of decontextualised images of the conflict, whereas a year later, the focus shifted to narratives concerning international support and alliances. The primary objective of this disinformation is to polarise public opinion against a perceived common enemy. The conclusions provide a broader and more nuanced understanding of wartime disinformation within the European context. Full article

Background: The landscape of antimicrobial therapy is undergoing a profound transformation; the contemporary arsenal of antimicrobials, particularly those with extended half-lives and enhanced tissue penetration, necessitates critically reassessing these traditional paradigms. The growing emphasis on antimicrobial stewardship programs has underscored the importance of optimizing antimicrobial agents to minimize the development and spread of resistance. Shorter treatment durations, when clinically appropriate, represent a key strategy in this endeavor. Methods: This narrative review provides a comprehensive synthesis of current evidence on the duration of antimicrobial therapy, with a particular focus on the clinical and pharmacological implications of novel agents, including long-acting formulations. Results: We critically examine the pharmacokinetic and pharmacodynamic properties of these agents, evaluate the opportunities and limitations associated with treatment shortening strategies, and underscore the pivotal role of antimicrobial stewardship in optimizing therapeutic outcomes within an increasingly complex and evolving landscape. Conclusions: The future of antimicrobial therapy lies in a personalized approach, where treatment decisions are tailored to the individual patient, but detailed clinical trials are necessary to evaluate these approaches. Full article

Obesity is a chronic, relapsing disease with multifactorial origins and significant global health implications. Historically, bariatric surgery has been the most effective intervention for achieving sustained weight loss and metabolic improvement, especially in individuals with moderate to severe obesity. However, the therapeutic landscape is rapidly evolving. Recent advances in pharmacotherapy—including GLP-1 receptor agonists, dual and triple incretin agonists, and amylin-based combination therapies—have demonstrated unprecedented efficacy, with some agents inducing 15–25% weight loss, approaching outcomes once exclusive to surgical intervention. These developments challenge the continued applicability of existing bariatric surgery criteria, which were established in an era of limited medical alternatives. In this narrative review, we examine the evolution of surgical eligibility thresholds and critically assess the potential role of novel pharmacotherapies in redefining treatment algorithms. By comparing the efficacy, safety, metabolic benefits, and cost-effectiveness of surgery versus next-generation drugs, we explore whether a more stepwise, pharmacotherapy-first approach may now be justified, particularly in patients with BMI 30–40 kg/m². We also discuss future directions in obesity management, including personalized treatment strategies, perioperative drug use, and the integration of pharmacologic agents into long-term care pathways. As the field advances, a paradigm shift toward individualized, minimally invasive interventions appears inevitable—necessitating a timely re-evaluation of current bariatric surgery guidelines to reflect the expanding potential of medical therapy. Full article

Background: Refractory ventricular fibrillation (RVF) is a life-threatening condition characterized by the persistence of ventricular fibrillation despite multiple defibrillation attempts. It represents a critical challenge in out-of-hospital cardiac arrest management, with poor survival outcomes and limited guidance from current resuscitation guidelines. In recent years, alternative defibrillation strategies (ADSs), including dual sequential external defibrillation (DSED) and vector change defibrillation (VCD), have emerged as potential interventions to improve defibrillation success and patient outcomes. However, their clinical utility remains debated due to heterogeneous evidence and limited high-quality data. Methods: This narrative review explores the current landscape of ADSs in patients with RVF. MEDLINE, Google Scholar, the World Health Organization, LitCovid NLM, EMBASE, CINAHL Plus, and the Cochrane Library were examined from their inception to April 2025. Results: The available literature is dominated by retrospective studies and case series, with only one randomized controlled trial (DOSE-VF). This trial demonstrated improved survival to hospital discharge with ADSs compared to standard defibrillation. DSED was associated with higher rates of return of spontaneous circulation and favorable neurological outcomes. However, subsequent meta-analyses have produced inconsistent results, largely due to the heterogeneity of the included studies. The absence of sex-, gender-, and ethnicity-specific analyses further limits the generalizability of the findings. In addition, practical barriers, such as equipment availability, pose significant challenges to implementation. Conclusions: ADSs represent a promising yet still-evolving approach to the management of RVF, with DSED showing the most consistent signal of benefit. Further high-quality research is required to enhance generalizability and generate more definitive, high-level evidence. Full article

Background: Since the 1980s, numerous case reports have explored the use of intramuscular botulinum toxin (BoNT) for Complex Regional Pain Syndrome (CRPS), with significant variation in rationale, dosing, guidance techniques, and outcome measures. This narrative review aims to summarize published evidence on the use of intramuscular BoNT in patients with CRPS, including studies using earlier terminology such as reflex sympathetic dystrophy (RSD). Given the heterogeneous and largely anecdotal nature of the literature, this review is intended to map the existing landscape rather than conduct a formal analysis. Methods: The PubMed and EMBASE databases were searched in August 2024 using terms related to CRPS and botulinum toxin. Following abstract and full-text screening, 25 publications were included. Results: The included studies span single case reports, case series, and small cohorts, encompassing at least 96 individual CRPS patients treated with intramuscular BoNT. Reported outcomes were heterogeneous, and key treatment parameters—such as toxin type, target muscles, guidance technique, and dosing—were inconsistently reported. Conclusion: The evidence for intramuscular BoNT in CRPS remains limited and heterogeneous, preventing firm conclusions on its efficacy or safety. Its use may be considered in select cases, particularly those with disabling or painful focal dystonia or myofascial pain, but standardized prospective studies are needed to clarify its clinical role. Full article