Search Results (1,111)

Menopause marks a complex biopsychosocial transition defined by the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. South Asian women tend to experience menopause earlier (45–47 years) than North American women, yet limited culturally appropriate interventions exist to address their symptoms. While hormone replacement therapy can reduce discomfort, its associated risks and limited cultural feasibility restrict its use in this population. There is a growing need to explore non-pharmacological and culturally relevant alternatives. Physical activity has been associated with potential well-being benefits during menopause. This study examined the prospective acceptability of a pedometer-based walking intervention, encouraging 10,000 steps daily, among South Asian immigrant women. The study was conducted in 2024 and completed within approximately seven months. A cross-sectional survey was conducted with 64 South Asian women aged 40–70+ years, who completed a questionnaire assessing the prospective acceptability and perceived barriers to participation. Overall, participants reported moderate to high levels of acceptability of the proposed walking intervention. Some participants perceived potential benefits for well-being; however, given the study design, effectiveness and symptom management outcomes were not assessed. Sociocultural factors—such as family responsibilities, modesty concerns, and limited access to supportive environments—were identified as potential barriers to participation. These findings suggest that a pedometer-based walking intervention may be acceptable to some South Asian immigrant women, though acceptability was not uniform and may be influenced by contextual factors, including opportunity costs. Further research using longitudinal or interventional designs is needed to evaluate feasibility, uptake, and effectiveness. Full article

Irritable bowel syndrome (IBS) is a prevalent disorder of gut–brain interaction, characterized by a substantial symptom burden, impaired quality of life, and increased healthcare use. Despite advances in diagnostic criteria and treatment strategies, many patients feel dismissed, inadequately informed, or uncertain about the nature and meaning of their symptoms; these experiences may undermine trust and reduce engagement with healthcare professionals. The aim of this narrative review is to synthesize clinical and ethical considerations and propose a patient-centered ethical framework for IBS management, positioning communication as a core therapeutic intervention. We highlight how validation, clear and non-stigmatizing explanations, transparency about uncertainty, and recognition of patient values can strengthen the therapeutic alliance, support relational autonomy, and enable shared decision-making. These elements can promote supported self-management and improve adherence to individualized dietary, behavioral, and pharmacologic strategies. In response to the central role of nutrition in IBS care, we further integrate dietary management into the ethical framework, addressing dietary assessment, first-line dietary advice, soluble fiber, the structured low-FODMAP approach, and the risks of excessive or unsupported food restriction. We further discuss how the incorporation of patient-reported outcomes (PROs) can translate patient priorities into measurable outcomes, monitor clinically meaningful changes over time, and reduce discrepancies between clinical assessment and patients’ lived experiences. Finally, we underscore the impact of stigma and uncertainty and provide practical communication approaches to support a stronger therapeutic alliance in IBS care. The integration of ethical communication, PROs, and nutrition-sensitive self-management may improve patient experience, strengthen adherence, and support individualized therapeutic strategies in IBS care. Full article

Acute exacerbation of interstitial lung disease (AE-ILD) represents sudden, severe deterioration in patients with pre-existing ILD and is associated with high morbidity and mortality. Our work presents a case series of AE-ILD in patients with idiopathic pulmonary fibrosis (IPF), idiopathic non-specific interstitial pneumonia (iNSIP), and connective tissue disease-associated ILD (CTD-ILD) managed at our institution and provides a narrative review of AE-ILD. Across cases, AE-ILD manifested as rapid progression of dyspnea and extensive ground-glass opacities (GGOs) on imaging, often triggered by infections or immune-mediated processes. Despite treatment, all cases were fatal, confirming that mortality remains high in AE-ILD. In our literature review, we focus on dysregulated innate immunity, an altered microbiome, potential microaspiration, surgical procedures, and autoantibody-mediated inflammation as triggers, as well as the risk factors for and prevalence of AE-ILD. We also examine pharmacological and non-pharmacological interventions, with particular emphasis on the role of antifibrotic agents as a key protective factor. Evidence for and against corticosteroid use in AE-IPF and non-IPF AE-ILD is discussed, highlighting the radically different treatment approach for AE in melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM)-associated ILD compared to AE-IPF. Our findings underscore the heterogeneous presentation and poor prognosis of AE-ILD, emphasizing the urgent need for standardized diagnostic criteria, risk stratification, and prospective studies with larger cohorts to establish evidence-based therapeutic strategies. Full article

Introduction: Aquatic chemical pollution is among the most worrying threats to ecosystem health. There is an ever-increasing variety of pollutant substances detected across the source-to-sea continuum, causing loss of biodiversity and ecological disequilibrium. Achieving cleaner and healthier systems relies on carrying out sustained, cost-effective, diagnosis and aquatic effects monitoring, within the adaptive management cycle. The available methods are, however, cumbersome, which creates a clear need for innovative expeditious approaches for low-cost surveillance monitoring. In the last decade, Raman Spectroscopy (RS) has gained wide recognition for application to biological questions, for its ability to uncover the complexity of molecules and their interactions. Various fields, from pharmacology to disease diagnosis and prognosis, have suffered an innovation revolution through the application of RS. In this technique inelastic light scattering of a small part of photons of an incident electromagnetic monochromatic light beam (ranging from near-infrared to visible or ultraviolet) is caused by the molecular vibration of chemical bonds. This results in shifts in energy, which indicate discrete vibrational modes of polarisable molecules, providing qualitative and quantitative assessments of the chemical composition and molecular structure of the sample. The technique shows high sensitivity, no need for sample preparation and the possibility of use in non-invasive and label-free analysis. Objective: The aim of this work is to present and discuss evidence about the application of Raman Spectroscopy (RS) to environmental diagnosis and aquatic effect monitoring of pollution. Methodology: The technique was applied to different biological models, i.e., diatoms, zebrafish embryos and larvae and freshwater snails. Quality assessments with diatoms were tested in environmental monitoring, while assessments with other models were done upon exposure to metals and organic contaminants. Results and conclusions: The Raman spectra obtained from the samples analysed comprised bands detected within the 800 to 2000 cm⁻¹ wavenumber range. These were related to bond vibrations of carbohydrates, DNA phosphate groups, proteins or CH, NH and OH stretching in lipids and proteins. Data analysis using chemometric methods clearly distinguished pollutant exposure from control sites or treatments, pointing out the potential for surveyance monitoring. The next steps include the comparison with other sensitive methods (e.g., locomotion and avoidance behaviours, omics methods) to assess efficiency and bring further mechanistic understanding. Full article

Background: Cancer pain affects approximately 44.5% of all patients with malignancy and up to 55–65% of those with advanced or metastatic disease; a substantial proportion remain inadequately controlled with conventional pharmacological approaches alone. Peripheral nerve stimulation (PNS), a minimally invasive neuromodulatory strategy, has emerged as a potential opioid-sparing analgesic option for the perioperative management of oncologic surgical patients. Objectives: This narrative review synthesizes current evidence on the application, mechanisms, clinical efficacy, safety, and integration of temporary and permanent PNS systems in cancer patients, with specific focus on cancer-specific pain syndromes, key clinical studies, opioid-sparing immunological implications, evidence quality, and directions for future research. Methods: As a narrative review, this work was structured in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) to ensure methodological transparency. A focused, non-systematic literature search of PubMed/MEDLINE, Embase, and the Cochrane Library was performed from database inception through March 2026, supplemented by hand-searching of reference lists and targeted retrieval of clinical practice guidelines. Sources were selected on the basis of relevance to PNS or closely analogous peripheral neurostimulation modalities in oncologic, perioperative, or chronic pain contexts. Evidence was synthesized narratively, with each cited study graded using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 Levels of Evidence framework to enable transparent calibration of confidence. Results: Available preliminary and largely extrapolated evidence supports PNS as a promising but not yet established useful adjunct in oncologic perioperative care; because cancer-specific data rest substantially on a single pilot study (n = 12), one retrospective review (n = 15), and extrapolation from non-cancer populations, these conclusions should be regarded as hypothesis-generating. Randomized controlled trial data from non-cancer cohorts demonstrate opioid consumption reductions of approximately 80–90% in the PAINfRE trial, while the post-amputation trial demonstrated ≥50% pain-relief responder rates and reductions in pain interference, with clinically meaningful improvements in pain and function. Oncologic-specific pilot and retrospective evidence confirms feasibility and a 58–67% success rate across diverse cancer pain subtypes. Conclusions: The opioid-sparing properties of PNS carry additional biological plausibility for preserving perioperative antitumor immune function. High-quality prospective trials specifically designed for oncologic surgical populations remain needed to establish evidence-based recommendations. Full article

Non-ST-segment elevation myocardial infarction (NSTEMI) has become the predominant form of acute coronary syndrome (ACS) and is frequently associated with multivessel coronary artery disease (MVD). Patients presenting with NSTEMI and MVD represent a particularly high-risk population characterized by advanced age, comorbidities, and an increased atherosclerotic burden. Although advances in pharmacological therapy and early invasive management have improved prognosis, the optimal revascularization strategy in this setting remains uncertain. In contrast to ST-segment elevation myocardial infarction (STEMI), where randomized controlled trials consistently support complete revascularization, evidence in NSTEMI with MVD is limited and is largely derived from observational studies and registry data. This has generated ongoing debate regarding whether complete revascularization offers superior outcomes compared with culprit-only percutaneous coronary intervention (PCI), and whether non-culprit lesions should be treated during the index procedure (immediate strategy) or in a staged manner. Current data suggest that complete PCI is generally associated with reduced recurrent ischemia, reinfarction, and repeat revascularization, with potential long-term survival benefits. However, patient comorbidities, lesion complexity, and procedural risk continue to influence outcomes, highlighting the importance of individualized decision-making. This narrative review synthesizes contemporary evidence on PCI-based revascularization strategies in NSTEMI with MVD, focusing on two central aspects: the extent of revascularization (complete versus incomplete) and the timing of intervention (single-stage versus staged). By integrating findings from registries, randomized trials and guideline recommendations, the review identifies areas of consensus, persisting uncertainties, and key evidence gaps. Ultimately, it underscores the need for large, dedicated trials to guide practice and optimize outcomes for NSTEMI patients with multivessel coronary disease. Full article

Background: Critical illness leads to profound metabolic, neuroendocrine and immune disorders that affect the prognosis of patients treated in intensive care units (ICUs). The ketogenic diet, a high-fat and low-carbohydrate eating model, is gaining increasing importance as a potential metabolic intervention in the ICU. Preliminary data suggest that the ketogenic diet (KD) may support the control of seizures in a super-refractive epileptic state (SRSE), stabilize glycemia, reduce insulin demand, and modulate the immune response in sepsis. The aim of this review was to present a synthetic presentation of the current state of knowledge regarding use of the KD in intensive care patients. Methods: The review was carried out in accordance with the guidelines of the Joanna Briggs Institute and PRISMA-ScR. PubMed, Scopus, EBSCO, Web of Science, Google Scholar and Cochrane Library databases were searched (10–19 April 2026) using the Population–Concept–Context model. Full-text observational studies, randomized trials and reviews of the use of KDs in ICU patients were included. Data extraction was performed independently by two reviewers. Results: Of the 42 publications identified, seven studies were included in the analysis. The KD was feasible and safe in both critically ill adults and children. In SRSE, most patients achieved stable ketosis within a few days, which often allowed for reduction or discontinuation of anesthetics. In sepsis, the KD led to glycemic stabilization, reduced insulin demand and reduced immune deregulation; in one study, “after day 4, none of the patients in the KD group required insulin treatment.” The KD also showed beneficial effects on cellular bioenergetics and mitochondrial function. The safety profile was acceptable and adverse reactions were manageable with appropriate monitoring. Conclusions: The KD represents a promising, non-pharmacological metabolic intervention in intensive care, particularly in the treatment of SRSE and in the stabilization of glucose metabolism in sepsis and other critical conditions. Despite the growing number of positive clinical observations, the available evidence remains limited due to small samples, heterogeneous protocols, and a lack of randomized trials. Further, well-designed prospective studies are needed to determine optimal KD implementation protocols and identify the patient populations that benefit most. Full article

Background and Objectives: Mild cognitive impairment (MCI) and dementia are prevalent public health challenges with limited pharmacological options for cognitive enhancement. Digital cognitive rehabilitative interventions (DCIs) have emerged as a promising non-pharmacological approach, offering accessibility and personalized strategies. However, their efficacy across diverse populations and contexts remains unclear. This study evaluated the effectiveness of DCIs in improving global cognitive function in individuals with MCI and dementia by comparing them to active controls and usual care. Materials and Methods: Ten databases, including Ovid-Medline, Ovid–Embase, Cochrane Library, CINAHL, Web of Science, PsycINFO, KoreaMed, KMbase, RISS, and KISS, were searched for studies published up to May 2025. Global cognitive and executive functions, along with quality of life, were assessed. Meta-analyses using Review Manager version 5.4 were conducted to evaluate global cognitive function improvements, first stratified by comparator group (active control vs. usual care) and further stratified by patient (MCI vs. dementia) and intervention (computer-based vs. virtual reality cognitive training) types. Results: This systematic review and meta-analysis analyzed 37 studies. Overall, DCIs improved global cognitive function compared to the control group (SMD = 0.44, 95% CI: 0.18, 0.69). However, subgroup analysis showed no significant effect when DCIs were compared with active controls (SMD = 0.24, 95% CI: −0.35, 0.82). Subgroup analysis showed benefits for individuals with MCI (SMD = 0.43, 95% CI: 0.16, 0.70) but yielded inconclusive results for those with dementia (SMD = 0.95, 95% CI: −0.69, 2.59). Computer-based DCIs were effective (SMD = 0.57, 95% CI: 0.20, 0.93), whereas VR-based interventions had inconsistent outcomes (SMD = 0.32, 95% CI: −0.34, 0.98). Conclusions: DCIs may improve cognitive function compared with usual care, particularly in patients with MCI. However, their added benefits overactive cognitive interventions remain uncertain. Further well-designed studies are needed to clarify the relative advantages of DCIs across patient populations and intervention formats. Full article

Introduction. Chronic non-cancer pain is highly prevalent and profoundly diminishes quality of life. While pharmacological and interventional treatments are central, its psychosocial and spiritual dimensions remain under-addressed. This pilot study assessed the feasibility of a therapist-led support group intervention for patients with chronic non-cancer pain and explored preliminary psychospiritual outcomes. Methods. A two-arm, non-randomized pilot feasibility study was conducted among 58 outpatients of a university pain management clinic in Poland. Feasibility was assessed through recruitment, retention, attendance, and safety, while preliminary psychological and spiritual outcomes were evaluated using validated self-report instruments. The intervention group (n = 29) participated in eight group sessions combining psychoeducation, mindfulness-based techniques, and supportive dialogue inspired by the Simonton Method. The control group (n = 29) received standard care. Participants completed the Numeric Rating Scale to measure pain intensity, the Satisfaction with Life Scale, the Positive and Negative Affect Schedule, the WHOQOL-BREF, the Spiritual Well-Being Scale, the Generalized Anxiety Disorder Scale, and the Patient Health Questionnaire-9. Results. The intervention was feasible in terms of physician workload; however, patients adherence varied significantly. At baseline, the control group showed a significantly higher positive affect and existential well-being than did the intervention group. In exploratory within-group analyses, participants in the intervention group showed improved positive affect and reduced anxiety (p < 0.05), whereas existential well-being showed a trend toward improvement (p < 0.06). However, the self-selection design limits causal inferences. Nevertheless, participants reported social connectedness, meaning-making, and enhanced vitality. Discussion. This pilot feasibility study provides preliminary evidence that a therapist-led support group intervention integrating psychoeducation, mindfulness, and supportive components is practicable within multidisciplinary pain management. Further research in a larger, randomized trial is needed to evaluate adherence and safety, as well as clinical effects, more rigorously. Full article

Spermatogenesis is a highly coordinated biological process in which diploid spermatogonia undergo mitotic expansion, meiotic division, and terminal differentiation into haploid spermatozoa. This process is tightly regulated by intrinsic germ cell programs and extrinsic signals from Sertoli cells within the seminiferous epithelium. Among the signaling pathways governing male germ cell development, all-trans retinoic acid (RA), a bioactive metabolite of vitamin A, has emerged as a master regulator of meiotic initiation and spermatogonial differentiation in mammals. RA functions through nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which regulate transcriptional networks essential for germ cell progression, including the activation of Stimulated by Retinoic Acid 8 (STRA8), a key determinant of meiotic entry. Intratesticular RA homeostasis is maintained by a balance between synthesis via aldehyde dehydrogenase (ALDH) enzymes and degradation by cytochrome P450 family 26 (CYP26) enzymes, ensuring precise temporal and spatial control of germ cell development. While rodent models have defined core mechanisms of RA signaling, the canine testis provides a valuable comparative and translational system due to its physiological similarity to human spermatogenesis and relevance to reproductive management. Recent studies highlight conserved RA signaling pathways in dogs, including receptor-mediated transcriptional regulation, feedback control of RA metabolism, and post-transcriptional modulation via microRNAs. Importantly, pharmacological manipulation of RA signaling can reversibly disrupt spermatogenesis, supporting its potential applications in non-hormonal male contraception. This review integrates molecular, developmental, pharmacological, and comparative evidence and presents RA signaling as a central regulatory axis of spermatogenesis with important translational applications. Full article

Background: Enterocutaneous fistulas (ECFs) and enteroatmospheric fistulas (EAFs) are rare but highly morbid complications that most commonly arise after abdominal surgery. Outcomes have improved with advances in multidisciplinary care and with increasing research on how to best manage them; however, they remain associated with significant morbidity, high mortality, and prolonged hospitalization. Optimal timing of definitive repair is unknown, with many high-volume centers waiting 6–12 months, though emerging data suggest that earlier intervention may be feasible in carefully selected patients. Given their complexity and variability in management, a comprehensive review of current evidence is needed. Methods: A narrative review of the literature was conducted with emphasis on the classification, pathophysiology, and multidisciplinary management of ECFs and EAFs. Relevant studies addressing fluid and sepsis control, nutritional optimization, wound care, pharmacologic therapies, and interventional strategies were reviewed. Results: The management of ECFs requires a staged approach focused on fluid resuscitation, sepsis control, wound management, and nutritional optimization. Spontaneous closure can occur, and is most commonly within the first two months. Nutritional optimization through enteral and/or parenteral nutrition or fistuloclysis plays a vital role in improving outcomes. Therapies such as negative pressure wound therapy, biologics, and pharmacologic agents may support spontaneous closure and fistula control. In non-healing fistulas, surgical repair remains necessary, with optimal time for surgery at least 6–12 months from fistula development. Conclusions: ECFs and EAFs remain complex surgical challenges. Outcomes have improved due to advances in nutritional support and wound management, and the emergence of minimally invasive techniques. Standardization of treatment protocols and further research into novel therapy may further enhance outcomes and limit variability in management. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for several advanced malignancies, but their use is accompanied by immune-related adverse events, including liver injury. Some cases resemble autoimmune hepatitis (AIH), although many are more accurately described as AIH-like immune-mediated hepatitis rather than classical AIH. This distinction matters, as diagnosis is often based on exclusion and management must balance hepatic recovery against interruption of potentially life-prolonging cancer therapy. This systematic review summarised the clinical phenotype, diagnostic assessment, treatment strategies, treatment response, ICI discontinuation, and rechallenge outcomes in patients with ICI-associated AIH-like liver injury. Methods: A systematic PubMed search was performed for English-language human studies reporting autoimmune hepatitis, AIH-like liver injury, or immune-mediated hepatitis following exposure to ICIs. Eligible studies included case reports, case series, retrospective cohorts, prospective cohorts, and pharmacovigilance-type studies with extractable clinical, treatment, or outcome data. Reviews, guidelines, non-original articles, animal studies, non-English publications, and reports without usable liver injury data were excluded. The review followed PRISMA principles. Risk of bias was assessed using Joanna Briggs Institute tools and summarised with ROBVIS. Given the heterogeneity of study design, diagnostic criteria, treatment definitions, and outcome reporting, formal meta-analysis was not appropriate; results were therefore synthesised descriptively. Results: Twenty-two studies were included, comprising 195 patients with ICI-associated AIH-like or immune-mediated hepatitis. Of these, 140 patients received active treatment, and 133/140 achieved clinical or biochemical recovery with varying therapies. Corticosteroids were the most frequently used first-line therapy, with recovery reported in 102/105 patients treated with corticosteroids alone. Mycophenolate mofetil was the main second-line agent for steroid-refractory disease, with response reported in 9/10 treated patients. Other therapies, including tacrolimus, azathioprine, ursodeoxycholic acid, bezafibrate, tocilizumab, basiliximab, infliximab, budesonide, and double plasma molecular adsorption system with or without plasma exchange, were described only in small numbers or isolated cases. Spontaneous recovery without pharmacological treatment was reported in 19 patients. ICI interruption or discontinuation occurred in 141 patients, and rechallenge was reported in 55 patients after recovery, with no recurrent hepatic toxicity documented in the extracted dataset. Conclusions: ICI-associated AIH-like liver injury is an important immune-related toxicity, but the available literature remains fragmented and methodologically heterogeneous. Most reported patients recovered, particularly with corticosteroids, and MMF appears to be the most consistently used escalation therapy in steroid-refractory cases. However, the strength of evidence is limited by uncontrolled designs, variable terminology, inconsistent diagnostic work-up, and non-standardised outcome definitions. Future studies should separate classical AIH from AIH-like immune-mediated hepatitis, use uniform criteria for severity and response, and report treatment denominators clearly, especially for rechallenge and steroid-refractory disease. Full article

Background/Objectives: Non-pharmacological approaches are urgently required for managing chronic pain in sickle cell disease (SCD). This multiple-method, exploratory pilot randomized trial was conducted to evaluate preliminary benefits of an in-home virtual reality (VR) intervention (EaseVRx), compared to content-matched audio attention control, for chronic pain reduction and changes to chronic pain-related outcomes in adults with SCD. Methods: Participants were randomized to VR (19) or audio (25), with 2–16 min daily modules for eight weeks, a daily pain diary survey, VR surveys, assessments of chronic pain grade and chronic pain correlates every 4 weeks for 3 months, and a qualitative interview. Analyses were conducted using quantitative and qualitative methods. Clinical Trial Registration: ClinicalTrials.gov, NCT04906707, 27 May 2021. Results: Average intervention use was 19.1 and 12.1 min per day in VR and audio, respectively. Preliminary benefits of VR included decreased pain (p = 0.002), improved pain coping (pain catastrophizing [p = 0.005] and chronic pain acceptance [p = 0.002]), and improved sleep (p = 0.009). Additionally, symptoms associated with cybersickness were significantly lower (p = 0.012) after VR use than before VR use. Among interviewees, the interventions were acceptable and helpful in managing pain, although there were some barriers and challenges to use. Conclusions: Study findings suggest that in-home VR may be a self-management resource for adults with SCD and warrants additional research. Full article

Background/Objective: Persistent dry mouth, associated with poor oral health and lower quality of life (QoL), affects approximately 20% of adults in the global population. Indicating a potential role in nutrition, Camellia sinensis tea leaves contain bioactive compounds that may help prevent and manage dry mouth. This review aimed to evaluate the effects of different tea types on salivary flow rate (SFR), salivary pH, and QoL in healthy and at-risk patients and patients with hyposalivation or xerostomia. Methods: A systematic review without meta-analysis (SWiM) was conducted. Pre-defined inclusion and exclusion criteria were applied to databases: PubMed, Scopus, Web of Science, and the Cochrane Library. Results: Eighteen studies met the eligibility criteria for inclusion in the review. Over 50% of studies investigated either black or green tea, with most conducted in healthy young adults (67%) and predominantly among females. Fifteen of the studies reported that tea intervention improved at least one outcome of interest. In general, green tea improved SFR and salivary pH more consistently than black, oolong, or matcha tea, particularly in at-risk populations and patients diagnosed with xerostomia. Conclusions: Tea consumption, particularly of green and black tea, showed a transient enhancement of salivary flow, pH, and QoL, offering a low-cost non-pharmacological approach to supporting oral health. Definitive recommendations were limited by heterogeneity in study interventions and outcome measurements, small sample sizes, and incomplete reporting of study details. However, tea’s potential as an adjunct for the prevention and management of dry mouth warrants further study in larger, well-designed studies that employ standardized protocols. Full article

Heart failure (HF) represents a major and escalating public health challenge in the aging population. Older adults with HF frequently present with coexisting conditions such as hypertension, diabetes mellitus and obesity, which substantially influence disease pathophysiology, clinical presentation, therapeutic response and prognosis. The complex interplay between HF risk factors and comorbidities complicates diagnosis, limits the applicability of guideline-directed therapies and contributes to increased symptom burden, recurrent hospitalizations, higher healthcare utilization and reduced quality of life. In this Review, we examine the mechanisms through which common risk factors and comorbidities modify HF progression and outcomes in elderly patients, highlighting their impact on disease severity and treatment effectiveness. We emphasize the need for individualized, patient-centered management strategies that move beyond a single-disease framework and incorporate multidisciplinary care models. Early identification of comorbidities tailored pharmacological and non-pharmacological interventions, and longitudinal monitoring are essential to address the dual burden of HF and multimorbidity. Finally, we discuss current knowledge gaps and future research priorities, including the need to elucidate shared pathophysiological pathways and to develop integrated therapeutic approaches. Advancing our understanding of HF in the context of aging and risk factor/comorbidity is critical for improving clinical outcomes and informing healthcare policy in this growing patient population. Full article