Search Results (1,343)

Since the discovery and characterization of mesenchymal stem cells (MSC) some 40 years ago and the development of induced pluripotent stem cells (iPSC), opportunities to advance repair and potentially regenerate injured or diseased connective tissues of the musculoskeletal (MSK) system have been intensely investigated. While some advances have been made with some tissues, progress has not been as great as was hoped following the availability of such stem-like cells. Optimizing cell-biomaterial composites in vitro for features such as cell state or extracellular vesicle cargo, structure, composition, biomechanical integrity are likely to be only part of the story and optimizing the environments where such composites have been implanted has not received the same attention. Thus, implanting optimized or near optimized cell-biomaterial composites in acutely or chronically affected implantation sites can compromise the efficacy of such composites to effectively repair/regenerate MSK tissues. This may be due to inflammatory processes, alterations to the remaining tissues in the injury site during development of chronicity, waiting too long to repair residual tissue, or other host factors. Thus, success in realizing the potential of MSC and iPSC may depend, in significant part, on the environment at the implantation site. Further attention to optimizing the implantation site may enhance outcome success with long-term return to tissue function. Furthermore, heterogeneity in patient populations regarding natural factors influencing healing outcomes after injury may also require changes to clinical trial design to assess efficacy of cell therapies. Full article

Playing-related musculoskeletal pain is common among musicians and may affect performance, quality of life, and professional continuity. This exploratory cross-sectional study investigated the prevalence and characteristics of playing-related musculoskeletal pain in student and professional musicians. An anonymous survey was administered to student and professional musicians. Data were analyzed descriptively; normality was assessed using the Shapiro–Wilk test, and between-group comparisons were performed using Mann–Whitney U tests, chi-square tests, or Fisher exact tests as appropriate. Effect sizes and 95% confidence intervals were reported where possible. Ninety-seven musicians participated, including 61 students and 36 professionals. Seventy-three participants (75.3%) reported pain while playing. Compared with musicians without pain, musicians reporting pain showed numerically higher daily practice duration, weekly practice duration, and uninterrupted practice duration, but these differences were not statistically significant. Only 31 participants (32.0%) reported having consulted a physiotherapist. The associations between practice duration and pain were weak and not statistically significant after the corrected analysis. Owing to the cross-sectional design and self-reported outcomes, these findings should be interpreted cautiously and not as evidence of causality. Preventive education, workload management, and improved access to healthcare professionals with expertise in performing arts medicine may help reduce the burden of musculoskeletal symptoms in musicians. Full article

Background: Tuberculosis (TB) remains a leading cause of global morbidity and mortality, yet its impact extends far beyond microbiological cure. Many TB survivors experience persistent structural lung damage or functional impairment consistent with post-TB lung disease, while growing evidence highlights long-term non-respiratory health outcomes. Synthesizing evidence across lung and non- respiratory health outcomes, along with their risk factors, is critical to inform long-term TB care. Methods: We conducted a scoping review including systematic reviews reporting on post-TB long-term health outcomes. A search was performed in PubMed/MEDLINE on 27 July 2025, using terms related to “tuberculosis,” “systematic review,” “meta-analysis,” “sequelae” and “long-term health outcomes,” without language restrictions. Results: Nine systematic reviews met inclusion criteria. Most focused on pulmonary outcomes and consistently demonstrated that TB is associated with chronic airflow obstruction, reduced lung function, and an increased long-term risk of lung cancer, although residual confounding from environmental, clinical, and socioeconomic factors cannot be excluded. While younger adults are more prone to developing COPD after TB in high TB burden settings, older individuals face a higher risk of broader post-TB lung sequelae. Evidence suggested that TB survivors are at increased risk of non-respiratory complications. HIV co-infection, low CD4 counts, older age, pre-existing hepatitis, prior TB treatment, and hypoalbuminemia were associated with post-TB liver injury, while baseline hearing impairment and HIV co-infection increased the likelihood of post-TB hearing loss. TB was also linked to elevated risk of several non-pulmonary cancers, including oesophageal, cervical, hematological, pancreatic, and gastric malignancies, with the highest risk within the first year after TB diagnosis and persisting, though attenuated, in subsequent years. Conclusion: TB should be viewed as a chronic condition with enduring lung and non-respiratory health outcomes. TB survivors face increased risks of COPD, lung cancer, and a range of non-respiratory health outcomes, including hepatic and auditory complications, particularly among high-risk groups, such as those living with HIV infection, along with baseline hearing and hepatic impairment. Public health programmes must extend care beyond microbiological cure to include integrated, post-TB long-term monitoring of lung, hepatic and hearing across all ages, including malignancy surveillance, after baseline assessments to identify high-risk TB survivors. Future research should also elucidate risk factors for post-TB malignancy, and clarify the relationship between neurological, renal, and musculoskeletal sequelae and TB to inform evidence-based TB survivorship care. Full article

Dorsal metacarpal disease (DMD) is a common musculoskeletal injury in young racehorses, and effective non-invasive treatments remain of clinical interest. This study aimed to evaluate whether high-intensity laser therapy (HILT), which was applied as the sole intervention in horses retired from training, reduces the clinical signs of DMD compared with untreated controls. During the 2023–2024 racing seasons, 15 Arabian racehorses diagnosed with DMD were enrolled; 9 received HILT and 6 served as controls without laser therapy. The treatment protocol consisted of five daily HILT sessions followed by five sessions administered every other day. Thermographic, orthopedic, and radiographic examinations of the third metacarpal bones were performed before and after the treatment period in both groups, with additional thermographic and clinical assessments conducted throughout therapy. The results showed that horses treated with HILT did not exhibit a significant reduction in pain and lameness accompanied by thermographic changes consistent with decreased inflammation. These findings indicate that HILT did not alleviate clinical signs associated with DMD in the affected horses; however, further controlled studies are required to determine its effect on tissue healing processes and to optimize treatment duration. Full article

Osteosarcopenia, which is the coexistence of sarcopenia and osteoporosis, is being increasingly recognized as a systemic musculoskeletal aging syndrome. However, shared molecular regulators of bone–muscle deterioration remain unclear. In this study, we integrated bulk transcriptomic datasets from sarcopenic skeletal muscle and osteoporosis peripheral blood mononuclear cells to identify shared differentially expressed genes, followed by two-sample Mendelian randomization using osteoporosis genome-wide association study summary statistics to prioritize genes with potential causal relevance. Furthermore, diagnostic performance, functional enrichment, immune infiltration, single-cell RNA sequencing, regulatory network reconstruction, compound prediction, and siRNA-mediated validation were conducted in C2C12 and MC3T3-E1 cells. Overall, 122 shared differentially expressed genes were preliminarily screened, and KAZN and SUPT3H were tentatively proposed as candidate genes genetically associated with osteoporosis risk. Both genes were upregulated in the disease groups and exhibited weak to modest diagnostic performance. Furthermore, Kazn or Supt3h knockdown promoted myogenic differentiation in C2C12 cells as well as osteogenic differentiation and mineralization in MC3T3-E1 cells, supporting their roles as negative regulators of lineage differentiation. Moreover, functional analyses linked KAZN mainly to mitochondrial-related programs and SUPT3H to immune signaling, whereas single-cell analyses localized these genes to stromal, progenitor, and immune-related compartments. These hypothesis-generating findings suggest that KAZN and SUPT3H participate in shared bone–muscle dysfunction and generate candidate genes and mechanistic hypotheses for subsequent functional validation and translational research. Full article

Kienböck disease, osteonecrosis of the lunate of uncertain aetiology, presents with progressive pain, stiffness, and grip loss in dominant-hand-using adults during their most productive working years, yet its rehabilitation literature has lagged behind its surgical counterpart. This narrative review synthesises current rehabilitation evidence across conservative and post-operative pathways, mapping recommendations to disease stage and to surgical procedure. Following SANRA-aligned methods with selected PRISMA 2020 transparency elements, we appraise immobilisation and orthotic management, dart-throwing-motion-plane mobilisation, sensorimotor retraining, oedema and pain control, psychosocial screening, and procedure-specific protocols that span joint-levelling osteotomy, vascularised bone grafting (including medial femoral trochlea flap), limited intercarpal arthrodeses, proximal row carpectomy, wrist denervation, and salvage arthrodesis or arthroplasty. Patient-reported, performance-based, and occupational outcome instruments are reviewed, with explicit declaration that no Kienböck-validated MCIDs exist. We also set out an integrative reference frame that cross-walks osseous, articular, and tissue-healing axes, offered as clinical orientation rather than as a validated algorithm. The most pressing evidence gaps (Kienböck-specific functional movement screens, sustained return-to-work data, and procedure-specific rehabilitation cohorts) are translated into four registered, powered, COMET-aligned trial proposals. Full article

Background: Idiopathic hypereosinophilic syndrome (iHES) is a rare disorder of persistent hypereosinophilia with secondary organ damage, but the full spectrum of organ involvement and the constitutional-symptom burden under systematic ascertainment remain incompletely characterised. Objectives: To describe the clinical phenotype of iHES in a large single-centre cohort, with attention to symptoms typically under-reported in observational series. Methods: We followed 72 consecutive patients with iHES at a tertiary referral centre between January 2017 and May 2025. Defined HES variants were excluded by FIP1L1-PDGFRA RT-PCR and aberrant T-cell phenotyping on flow cytometry; secondary causes were excluded clinically. Each potential organ manifestation was systematically assessed at every visit using a structured clinician-administered checklist. Wilson 95% confidence intervals (CIs) are reported for all proportions. Results: Median age at diagnosis was 45 years (interquartile range [IQR] 31–58); 83% were female. The median number of involved organ systems was 3 (IQR 2–4, range 1–6). Pulmonary (91.7%, 95% CI 83.0–96.1), sinonasal (75.0%, 95% CI 63.9–83.6), musculoskeletal (72.2%, 95% CI 61.0–81.2) and gastrointestinal (66.7%, 95% CI 55.2–76.5) involvement predominated. Constitutional symptoms—principally fatigue—were recorded in 97% of patients (95% CI 90.4–99.2) and tracked clinically with disease activity. Cardiac involvement was infrequent (8.3%, 95% CI 3.9–17.0) but uniformly severe. Conclusions: Under systematic symptom probing, constitutional features and pulmonary/sinonasal involvement were recorded more frequently in this single-centre idiopathic HES cohort than in earlier series that pooled HES variants. However, selection bias from a pulmonology and severe-asthma referral pattern, together with differences in symptom ascertainment, likely contributes to these estimates and limits their generalisability to the broader iHES population. Routine echocardiographic screening and structured assessment of fatigue and cognitive symptoms should be incorporated into iHES monitoring. Full article

Population ageing has intensified interest in biological mechanisms that influence healthspan and susceptibility to age-related diseases. Among these mechanisms, the gut microbiota has emerged as an important modulator of immune, metabolic, and neurophysiological processes involved in ageing. This narrative review critically synthesises current evidence regarding age-related alterations in gut microbiota composition and function, their relationship with inflammaging and the hallmarks of ageing, and the potential role of microbiota-targeted interventions in promoting healthy ageing. A comprehensive narrative literature search was conducted using PubMed, Scopus, and Web of Science, focusing primarily on human observational studies, longitudinal cohorts, mechanistic investigations, and interventional trials published in peer-reviewed journals between 2010 and 2025. Priority was given to studies examining older adults, frailty, longevity, and microbiota-mediated mechanisms relevant to ageing biology. Current evidence suggests that ageing is frequently associated with reduced microbial diversity, depletion of beneficial short-chain fatty acid-producing taxa, altered intestinal barrier integrity, and increased abundance of pro-inflammatory microorganisms. These alterations are linked to inflammaging and may contribute to neurodegenerative, cardiovascular, metabolic, musculoskeletal, and joint diseases, including osteoporosis, sarcopenia, rheumatoid arthritis, and osteoarthritis. However, causality remains incompletely established in humans, and substantial inter-individual variability exists. Studies of centenarians suggest that preservation of specific microbial metabolic functions may be associated with healthier ageing trajectories. Dietary interventions, particularly Mediterranean-style diets rich in fibre and polyphenols, alongside exercise, prebiotics, probiotics, and emerging microbiota-targeted therapies, show potential to modulate these pathways. Despite significant advances, major challenges remain regarding causality, reproducibility, standardisation of microbiome analyses, and personalised therapeutic implementation. Future longitudinal multi-omics studies and precision microbiome interventions will be essential to clarify the translational role of the gut microbiota in healthy ageing and age-related disease prevention. Full article

Firefighting is a high-risk occupation involving intense physical exertion and hazardous environments. Occupational exposures, including combustion byproducts, contribute to long-term cancer risk and acute burn injuries. While line-of-duty fatalities have declined, substantial morbidity remains, particularly among female and wildland firefighters who have historically been underrepresented in research. A narrative review was conducted using PubMed, Scopus, and Google Scholar to identify relevant studies published after 2010. Search terms included firefighter, fatality, injury, cardiovascular disease, occupational exposure, cancer, wildland, and female. Articles were synthesized using the NIOSH Hierarchy of Controls framework. Cardiovascular events and overexertion remain leading contributors to line-of-duty deaths, while non-fatal injuries are commonly musculoskeletal. Occupational exposures, related to dermal absorption of toxins and improper use of protective equipment, contribute to burn injuries and may increase long-term cancer risk. Wildland firefighters face risks in the expanding wildland-urban interface, such as prolonged smoke exposure and extended exertion, which may elevate cardiopulmonary and cancer risks. Female firefighters face challenges related to ergonomic mismatch with protective equipment primarily designed for male body dimensions. Firefighters face health risks from a variety of environmental and operational factors. Risk mitigation must transition from a reliance on PPE to higher-level engineering and administrative controls. Future research should prioritize longitudinal health tracking and standardized equipment for diverse fire service populations. Full article

Background/Objectives: Celiac disease (CD) is an immune-mediated enteropathy with gastrointestinal and extraintestinal manifestations. In primary care, recognition can be delayed when psychiatric symptoms, arthralgia, thyroid dysfunction, alcohol exposure, and liver-test abnormalities coexist. This case report describes a confounder-aware diagnostic approach to histologically confirmed CD in a patient with a multifactorial primary-care presentation. Methods: We report a single-patient, de-identified reflective case from routine family medicine practice, organized according to CARE case-report principles. Results: A woman in her early sixties with hypothyroidism and glaucoma presented with new low mood, anhedonia, somnolence, generalized anxiety, increased alcohol intake, poor appetite, weight loss, abdominal bloating, diarrhea, flatulence, and polyarthralgia. Initial investigations, including celiac serology obtained before gluten-free diet advice, showed mild anemia, marked hyperferritinemia, severe cholestatic and hepatocellular liver-test abnormalities, uncontrolled hypothyroidism, and strongly positive tissue transglutaminase IgA (>250 kIU/L; reference 0.0–14.9). Radiographs showed mild osteoarthritis and osteopenia without erosive arthropathy. Computed tomography excluded malignancy but showed severe diffuse hepatic steatosis and mild pancreatic atrophy. Mirtazapine was started at the index visit; after the initial laboratory results, gluten-free diet advice, alcohol-reduction counseling, and levothyroxine adjustment were undertaken. During the diagnostic episode, small-bowel biopsy demonstrated moderate-to-severe crypt hyperplastic villous atrophy with increased intraepithelial lymphocytes, and gastric biopsies showed no significant pathology; the histology was consistent with CD. Symptoms improved substantially. Longer-term objective follow-up showed persistent but improved celiac serology (tTG-IgA 49.4 kIU/L), normalization of thyroid-stimulating hormone, partial improvement in gamma-glutamyl transferase, which remained elevated, and a later iron-deficiency pattern with persistent anemia. Conclusions: This case supports targeted CD testing when anxiety or depressive symptoms occur alongside gastrointestinal symptoms, weight loss, arthralgia, hypothyroidism or documented thyroid autoimmunity, anemia, osteopenia, or liver-test abnormalities. Histology and repeat serology confirmed the diagnosis, but the psychiatric and hepatic manifestations still require cautious interpretation because hypothyroidism, alcohol exposure, steatotic liver disease, and simultaneous treatments also shaped the clinical course. Full article

Background and Objectives: Oral health is a key but often overlooked component of healthy aging and functional wellbeing in older adults. Population aging, multimorbidity, and social determinants of health interact in order to shape oral disease patterns, particularly in primary care settings. Understanding age- and sex-specific distributions of oral diseases is essential for informing integrated public health strategies aimed at promoting healthy aging. Materials and Methods: We conducted a cross-sectional population-based analysis using the SIMEF primary care database, including 7386 adults aged 60 years and older, who were attended between January and December 2022. Oral diseases were identified using ICD-10 codes K00–K14. Prevalence estimates were calculated by life decade and sex. Associations were assessed using chi-square tests and sex-stratified analyses. Results: The overall prevalence of oral diseases was 5.2%, with a significant and progressive decline across age groups, from 6.5% in sexagenarians to 1.6% in nonagenarians (p < 0.001). The most prevalent conditions were disorders of teeth and supporting structures (2.6%, 95% confidence interval [95% CI] 2.3–3.0), dentofacial anomalies (2.2%, 95% CI 1.8–2.5), and dental caries (1.7%, 95% CI 1.4–2.0). Women showed a slightly higher prevalence of selected oral and mucosal conditions. Among older adults with oral diseases (n = 384), the most frequent comorbidities were hypertension (40.4% 95% CI 35.7–45.3), type 2 diabetes (29.2% 95% CI 24.7–33.8), and dyslipidemia (21.1% 95% CI 17.2–25.3), with marked sex-specific differences in endocrine, urinary, musculoskeletal, and mental health conditions. Conclusions: Oral disease burden in older adults decreases with advancing age but remains strongly linked to cardiometabolic and systemic comorbidities, reflecting shared risk factors relevant to healthy aging. The observed age- and sex-specific patterns underscore the need to integrate oral health into primary care and public health policies targeting aging populations, supporting comprehensive and equitable strategies for healthy longevity. Full article

Background/Objectives: Knee injuries and overuse-related disorders are common among athletes participating in jumping sports such as handball and basketball. Musculoskeletal ultrasonography is increasingly used for the assessment of knee pathology; however, evidence regarding the prevalence and clinical relevance of ultrasonographic abnormalities in young athletes remains limited. The aim of this study was to investigate the prevalence of ultrasonographic knee abnormalities in young male handball and basketball athletes and to examine their association with pain intensity. Methods: A cross-sectional observational study was conducted between June 2025 and June 2026 and included 69 competitive male athletes (35 handball players and 34 basketball players). All participants underwent bilateral knee ultrasonographic examination using a standardized assessment protocol and completed a questionnaire regarding demographic and training characteristics. Knee pain intensity was evaluated using the Visual Analogue Scale (VAS). Comparisons between sports were performed using χ² and t-tests, while associations between participant-level ultrasonographic findings and pain were evaluated using independent-samples t-tests (or Mann–Whitney U tests, as appropriate), with Cohen’s d effect sizes and exploratory multivariable linear regression. Sensitivity analyses stratified by sport were additionally performed. Results: Patellar tendinopathy was the most prevalent ultrasonographic abnormality (21.0%), followed by medial meniscal abnormality (15.9%) and infrapatellar bursitis (13.0%). Athletes with patellar tendinopathy, medial meniscal abnormality, or infrapatellar bursitis had significantly higher VAS pain scores than athletes without the corresponding ultrasonographic abnormality. Patellar tendinopathy demonstrated the strongest association with participant-reported pain (VAS: 4.1 ± 1.3; Cohen’s d = 1.24; p < 0.001). Handball athletes exhibited a significantly higher prevalence of patellar tendinopathy than basketball athletes (34.3% vs. 11.8%; OR = 3.90, 95% CI: 1.09–13.95; p = 0.027). In multivariable regression analysis adjusted for age, BMI, sport type, previous knee injury, and weekly training volume, patellar tendinopathy (β = 1.34, p < 0.001), medial meniscal abnormality (β = 0.70, p = 0.017), and infrapatellar bursitis (β = 0.54, p = 0.046) remained independently associated with higher pain scores. The regression model explained 39% of the variance in VAS pain scores (R² = 0.39). Conclusions: Ultrasonographic knee abnormalities are common among young male handball and basketball athletes and are significantly associated with pain intensity. Because ultrasonography has limited ability to characterize intra-articular pathology, particularly the menisci, the ultrasonographic abnormalities identified in this study should not be interpreted as definitive diagnoses, and MRI remains the reference imaging modality when comprehensive evaluation of intra-articular pathology is clinically indicated. Patellar tendinopathy was the most prevalent ultrasonographic abnormality and was most strongly associated with pain intensity. These findings support the use of musculoskeletal ultrasonography as a complementary imaging modality alongside clinical assessment in the evaluation of symptomatic athletes. However, prospective longitudinal studies are required to determine whether these ultrasonographic abnormalities have prognostic value for future pain, functional limitation, or time-loss injury. Full article

Introduction: Pain is one of the most common reasons why patients seek medical care, and chronic pain is now recognized as a major health problem worldwide. Better understanding of pain mechanisms has shown the importance of distinguishing nociceptive, neuropathic, and nociplastic pain in order to choose the most effective treatment. In recent years, topical analgesics have gained increasing attention because they can provide pain relief directly at the site of application while reducing systemic exposure and the risk of adverse effects. This is especially important in older adults, patients with multiple diseases, and those exposed to polypharmacy. Methods: This narrative review presents the current knowledge on the pharmacology, efficacy, and safety of topical drugs used in pain treatment. Particular attention is given to topical non-steroidal anti-inflammatory drugs (NSAIDs), lidocaine, capsaicin, menthol, and camphor. The review also discusses newer and less established therapies used mainly in neuropathic pain, including topical ketamine, amitriptyline, phenytoin, gabapentin, and clonidine. A structured, non-systematic literature search was conducted using the PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar databases to identify studies evaluating the efficacy and safety of topical analgesic therapies. Results: Current evidence supports topical NSAIDs as first-line therapy for localized musculoskeletal pain and osteoarthritis, while lidocaine and high-concentration capsaicin patches are effective options in focal neuropathic pain. Although several newer topical therapies show promising results, more high-quality clinical studies are still needed. Overall, topical analgesia is an important part of multimodal pain management because it combines analgesic efficacy with a better safety profile compared with many systemic therapies. Conclusions: Taking the aspects discussed in this paper into account, it seems justified to search for new drug combinations that would contribute to effective pain therapy with topical agents. It is recognized that a multimodal approach to pain management, which utilizes drugs with different mechanisms of action, can increase efficacy and reduce the systemic adverse events of the drugs used. The effective and safe treatment of patients with pain, especially neuropathic pain, despite emerging new clinical trials, remains a challenge for clinicians. Full article

Background and Objectives: Knee osteoarthritis (OA) is a prevalent musculoskeletal disorder. This study aims to assess the hip-knee-ankle anatomical alignment in patients with OA at different stages. Materials and Methods: Radiological images of 200 OA patients were analyzed to measure parameters such as femoral and tibial lengths (both anatomical and mechanical), abductor length, hip center length, femoral offset, collum femoris length, and shaft angle using ImageJ software (version 1.53k; National Institutes of Health, Bethesda, MD, USA). Results: The female-to-male ratio was 2.17:1. Male participants exhibited greater values for femoral and tibial lengths, abductor length, hip center length, femoral offset, collum femoris length, and collum femoris shaft angle, whereas females showed higher Q angle, hip–knee–ankle angle, mechanical lateral distal femoral angle, mechanical medial proximal tibial angle, and femoral angle measurements. Significant differences in both linear and angular parameters were observed among age groups. Q angle, hip–knee–ankle angle, femoral mechanical axis shaft angle, plateau angle, and ankle tilt angle values were significantly higher in individuals aged 62–75 years. According to Kellgren–Lawrence staging, significant increases were observed in Q angle, hip–knee–ankle angle, femoral mechanical axis shaft angle, plateau angle, and ankle tilt angle in advanced-stage disease (Stage 4) (p < 0.05). Although mechanical lateral distal femoral angle, femoral Q angle, tibial Q angle, condylar plateau angle, and tibiotalar angle showed numerical differences across disease stages, these findings did not reach statistical significance. Conclusions: Comprehensive assessment of lower-extremity alignment may provide complementary information regarding biomechanical changes associated with knee osteoarthritis progression and could support individualized clinical follow-up and treatment planning. Full article

Background: Gender differences in aging among people with HIV (PWH) remain poorly characterized. Women with HIV (WWH) may experience more complex aging trajectories, due to the interplay of biological, clinical, and psychosocial factors. In this context, we aimed to investigate gender-specific determinants of frailty among older people with HIV, with a particular focus on women, to better inform tailored clinical care. Methods: Cross-sectional analysis of the Over50 Cohort, including PWH aged ≥50 years from two tertiary hospitals in Spain. Participants underwent a comprehensive geriatric assessment across demographic, clinical, functional, cognitive, psychological, and social domains. Gender-stratified multivariable analyses examined frailty (by Fried criteria) and associated factors. Results: Among 588 participants, 139 (23.6%) were cisgender WWH. Despite younger age and better immune status, WWH showed higher prevalence of frailty (17% vs. 9%), musculoskeletal disease (47% vs. 28%), depressive symptoms (45% vs. 30%), sleep disturbances (10% vs. 5%), and cognitive complaints (23% vs. 11%). Men with HIV (MWH) more frequently had cardiovascular (48% vs. 35%) and renal disease (22% vs. 15%). In multivariable models, frailty in WWH was independently associated with musculoskeletal disease (OR 3.85), cognitive impairment (OR 3.21), depressive symptoms (OR 2.67), and malnutrition (OR 2.14). In MWH, frailty was associated with musculoskeletal disease, cognitive impairment, malnutrition, and older age. Conclusions: Frailty exhibits gender-specific patterns: a multidimensional phenotype in WWH versus age-driven in MWH, supporting tailored, gender-responsive care integrating geriatric, mental, and musculoskeletal health. Full article