Search Results (5,095)

Background: Age- and cancer-related sarcopenia and malnutrition are common in older patients with colorectal cancer (CRC) and may negatively influence treatment tolerance and prognosis. However, the comparative prognostic value of post-chemotherapy changes in CT-based body composition parameters at the third lumbar vertebra (L3) and the twelfth thoracic vertebra (T12) levels, and their associations with nutritional indices, remain unclear. This study aimed to examine and compare the prognostic relevance of post-chemotherapy body composition changes at L3 and T12 and to assess their relationship with nutritional indices in older patients with metastatic CRC (mCRC). Methods: This retrospective study included 87 older patients with mCRC. Baseline and ~3-month follow-up CT scans were analyzed at L3 and T12 using 3D Slicer to quantify skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), visceral-to-subcutaneous fat ratio (VSR), and intramuscular adipose tissue index (IMATI). Changes (Δ) in CT-derived body composition after chemotherapy were calculated as percentage change using ((follow-up − baseline)/baseline) × 100. Prognostic Nutritional Index (PNI) and Geriatric Nutritional Index (GNRI), which are established nutritional assessment tools, were calculated from baseline laboratory/anthropometric data. Agreement between T12 and L3 was assessed, and associations with grade ≥3 toxicity, progression-free survival (PFS), and overall survival (OS) were evaluated using multivariable models and ROC analyses. Results: Mean age was 69.0 ± 4.5 years (59 male/28 female), and 26.4% developed grade ≥3 adverse events. Over 3 months, mean SMI declined significantly at both L3 (46.7 ± 8.8 → 42.8 ± 9.8 cm²/m²) and T12 (34.6 ± 8.2 → 31.6 ± 8.1 cm²/m²) (p < 0.001 for both), accompanied by decreases in VATI and VSR; T12-IMATI increased significantly. Baseline PNI showed a weak positive correlation with L3-SMI (r = 0.302, p = 0.033), whereas GNRI showed moderate correlations with SMI at L3 (r = 0.502, p < 0.001) and T12 (r = 0.317, p = 0.025) and was associated with longitudinal changes in muscle metrics. T12-SMI consistently yielded lower values than L3-SMI, and agreement varied by compartment (best for SATI; weakest for VSR). Lower GNRI and greater L3-SMI loss were independently associated with grade ≥3 toxicity; ΔL3-SMI showed the highest discrimination (AUC = 0.79, 95% CI = 0.69–0.87, p < 0.001; cut-off >5.1% loss). All patients progressed (median PFS 7.6 months); mortality was 82.8% (median follow-up: 25 months). In multivariable analysis, PFS, CRP, GNRI, and ΔL3-SMI remained independently associated with OS. ΔL3-SMI provided the strongest mortality discrimination (AUC = 0.85, 95% CI = 0.74–0.94, p < 0.001; cut-off >10.4% loss), while ΔIMATI was also informative (AUC = 0.71, 95% CI = 0.59–0.82, p = 0.023). Conclusions: In older patients with mCRC, early post-chemotherapy skeletal muscle loss—particularly at the L3 level—showed the strongest prognostic association with severe toxicity and mortality. GNRI provided complementary prognostic information as a marker of baseline immunonutritional reserve. Although T12-derived measurements were correlated with L3-derived values, systematic bias suggests that they should not be interpreted interchangeably for longitudinal risk stratification. Full article

Atherosclerosis, the leading global cause of death, is a chronic inflammatory vascular disease with higher prevalence and earlier onset in men than in women. This study aims to investigate sex differences in the atherogenic endothelial phenotype during early atherosclerosis processes by providing the first comprehensive analysis of hormone-independent responses in human umbilical vein endothelial cells (HUVECs) from opposite-sex twins. HUVECs underwent pro-inflammatory stimulation with TNF-α and supernatant from activated pro-inflammatory THP-1 cells, revealing distinct sex-specific patterns: mRNA expression of focal adhesion proteins talin-I, vinculin, FAK, and α1-actinin increased significantly only in male cells, while paxillin showed elevated mRNA and protein levels in both sexes. Male HUVECs exhibited stronger induction of cell adhesion molecule VCAM-1, pro-inflammatory cytokine IL-1β, and proangiogenic factors Flt-3L, G-CSF, and PDGF-AA, whereas IL-22 secretion was exclusively upregulated in female cells. These sex differences in levels of focal adhesion, adhesion molecules, and cytokine profiles uncover the mechanistic backgrounds of the atherogenic endothelial phenotype, independent of systemic hormones. The findings emphasize cellular sex as a critical biological variable in early atherosclerosis and vascular inflammation. Full article

Cardiovascular disease (CVD) and cancer frequently coexist in older patients, posing significant challenges in clinical management due to overlapping risk factors and treatment-related complications. This narrative review summarizes current knowledge on the epidemiology, shared pathophysiological mechanisms and clinical impact of neoplastic comorbidities in older adults with cardiovascular diseases. It highlights the increased mortality, morbidity and diminished quality of life resulting from the coexistence of these conditions. The review also discusses personalized management strategies, emphasizing comprehensive geriatric and cardiac assessments, and tailoring oncologic treatments to minimize cardiotoxicity, as well as the role of prevention and rehabilitation programs. As the population ages and cancer survival improves, integrated cardio-oncology care adapted to older adults becomes increasingly essential to optimize outcomes and preserve functional status. Full article

The objective was to expand community-based dementia screening across diverse settings in Brunei and evaluate the prevalence of risk factors, cognitive symptoms and factors associated with suspected cognitive impairment using the Mini-COG. Cross-sectional community screening was conducted across community and healthcare settings among adults aged 60 years and older, or aged 50 years and older with dementia risk factors. Participants completed a structured questionnaire on demographics, dementia risk factors and cognitive symptoms, followed by the Mini-COG. Multivariable logistic regression was used to examine factors associated with suspected cognitive impairment. A total of 1358 participants were included, with a median age of 60 years, and 63.5% were female. Two-thirds had hypertension, over half had hypercholesterolaemia and over one-third had diabetes mellitus. The most commonly reported symptoms were misplacing things (42.6%), forgetfulness (32.5%) and visuospatial difficulties (24.2%). Among those with symptoms, 14.5% reported worsening symptoms and 12.0% had impaired activities of daily living. From the Mini-COG, 14.4% had suspected cognitive impairment. Multivariable analysis revealed that older age (adjusted OR 1.06 per year, p < 0.001) and education level (adjusted OR 2.25 for primary versus tertiary, p = 0.007) were independently associated with Mini-COG impairment, while vascular risk factors showed no significant associations. Community-based dementia screening using a brief questionnaire and the Mini-COG was feasible across multiple settings in Brunei. There was a high prevalence of vascular risk factors and cognitive symptoms. Age and educational attainment were stronger predictors of abnormal Mini-COG results compared to vascular risk factors in this study. These findings support opportunistic screening in healthcare and community settings, and an emphasis on public education on dementia symptoms and risk reduction. Full article

Background: Sarcopenia is an age-related syndrome characterized by progressive loss of skeletal muscle mass and strength, representing a major contributor to disability and increased mortality in older adults. Current diagnostic frameworks increasingly emphasize muscle quality alongside quantity, creating a clinical need for bedside tools that can objectively assess muscle mechanical properties. Shear-wave elastography (SWE), an ultrasound-based technique that quantifies muscle stiffness, has emerged as a promising biomechanical biomarker of muscle quality. Aim: This narrative review evaluates the evidence supporting SWE for assessing muscle quality and its association with aging, sarcopenia, and functional outcomes. Methods: We searched PubMed, Embase, and Web of Science (from January 2010 to December 2025) using terms related to elastography and sarcopenia. Based on relevance and methodological quality, approximately 50 key studies were selected for in-depth discussion and synthesis. Synthesis: Observational studies consistently demonstrate that SWE detects age-related reductions in muscle stiffness, which correlate significantly with declines in muscle strength and physical performance. Unlike conventional B-mode ultrasound, which primarily provides morphological parameters, SWE directly reflects intrinsic tissue mechanics, enabling more direct assessment of muscle quality. In high-risk populations such as patients with type 2 diabetes, reduced muscle stiffness is also associated with sarcopenia and poor functional outcomes. However, reported stiffness trends with aging remain heterogeneous, and validated diagnostic thresholds are lacking. Stiffness changes vary by muscle group, acquisition protocol, and loading state. Clinical implementation is currently limited by inter-device variability, operator dependence, and sensitivity to muscle loading conditions. Conclusions: Current evidence suggests that SWE holds promise as an adjunctive research tool for assessing muscle quality and risk stratification, but it is not yet ready for standalone clinical diagnosis due to methodological heterogeneity, lack of validated cutoffs, and limited longitudinal data. Future large-scale, longitudinal, multicenter studies with standardized protocols are needed to establish its definitive diagnostic utility. Full article

Background: Our study retrospectively investigated the therapeutic effects of SGLT2 inhibitors on multiple outcomes in patients with Type 2 Diabetes, capitalizing on the agent’s proven benefits in glycemic, cardiovascular, and renal systems. Methods: This retrospective cohort study investigated a total of 200 patients with T2DM, 100 SGLT2I-treated and 100 treated without SGLT2Is. Clinical data were retrieved from the electronic health record system of the hospital. Patients were followed for more than 6 months to assess the effects of SGLT2Is on metabolic, biochemical, and renal parameters. Results: In the SGLT2I-treated cohort, a higher prevalence of males, non-geriatrics, and comorbidities such as HF and ASCVD was observed with greater use of concomitant medications (beta-blockers, antithrombotics, antilipidemics). SGLT2I treatments show a greater reduction in FBG (control: −6.3 mg/dL vs. treatment: −24.2 mg/dL; p ≤ 0.05), HbA1c (control: −0.093% vs. treatment: −0.76%; p ≤ 0.001), weight (control: −0.6 kg vs. treatment: −3.6 kg; p ≤ 0.001), SBP (control: 5.8 mmHg vs. treatment: −9.2 mmHg; p ≤ 0.001), and DBP (control: 2.2 mmHg vs. treatment: −4.7 mmHg; p ≤ 0.05) compared to the control group. The analysis of the mean change in eGFR showed no statistically significant difference in both groups. The SGLT2I’s safety profile was favorable, with no difference in adverse events and no cases of euglycemic ketoacidosis or Fournier’s gangrene. Conclusions: In this study, SGLT2Is demonstrated strong clinical efficacy in improving multiple cardiometabolic parameters without compromising patient safety in short-term follow-up. Large-scale and long-term real-world studies are needed to monitor the long-term safety profile, characterize the incidence of rare adverse events in general clinical practice, and validate results from this study. Full article

Agonists of the G protein-coupled receptor TGR5 have long been sought-after for their metabolic benefits. Intestinal TGR5 activation induces secretion of the antidiabetic hormone GLP-1, which can systemically improve diabetes phenotypes in multiple organs. However, no TGR5 agonist drug candidate has succeeded in clinical trials due to their low potency and unwanted side effects. A challenge in the field has been the development of TGR5 agonists that are non-toxic, long-acting, and have functional selectivity for G protein-biased agonism. In this study, we propose a systematic pipeline for engineering optimal TGR5 agonists with antidiabetic properties. This pipeline is interdisciplinary, combining in silico, in vitro, and in vivo assays to design and validate drug candidates. We identify 2 lead compounds that outline the necessary beneficial properties for a successful TGR5 agonist against diabetes. We uncover the molecular mechanisms that allow TGR5 agonists to induce the transcription of their target, TGR5, in intestinal enteroendocrine cells. Lastly, we investigate the molecular interactions of our lead candidates in the TGR5 binding pocket to identify optimal parameters for stability and biological activity. Our strategy for TGR5 agonist design and evaluation has the potential to guide the discovery process for targeted TGR5 therapeutics for metabolic diseases. Full article

Human endogenous retroviruses (HERVs), remnants of ancient germline infections, constitute ~8% of the human genome. Although mostly silenced, these elements can be expressed and play physiological or pathological roles. We investigated HERV expression dynamics, proviral load, and systemic inflammatory status in young and older adults, as well as the impact of regular physical exercise. PBMC and serum samples were collected from 30 young controls (YC), 30 inactive older adults (INAC) and 30 regularly exercising older adults (REG). Expression of HERV-W, -K, -H, Syncytin-1 and -2 was assessed by qPCR using the −2ΔΔCt method, and proviral load (HERV-W, -K, -H) was estimated by relative copy number. Serum cytokines (IL-1β, IL-6, IL-17, TNF-α, IFN-γ, IL-10) were quantified by ELISA. Statistical significance was set at p < 0.05. INAC participants showed higher proviral load of HERV-K, -W and -H compared to YC (p = 0.025), but overall lower HERV expression, except for HERV-K. REG presented increased expression of HERV-W (~1.5-fold, p < 0.0001), HERV-H (~1.8-fold, p < 0.0001; higher than YC p = 0.01), HERV-K (vs. YC p = 0.02) and Syncytin-1 (~1.4-fold vs. INAC and YC, p < 0.01). HERV-K was the most upregulated element in INAC. HERV-W and HERV-H expression were strongly correlated in all groups. INAC showed a pro-inflammatory profile, with elevated IL-6/IL-10, IL-1β/IL-10, and IFN-γ/IL-10 ratios. Older adults exhibit higher HERV proviral load, suggesting possible age-related insertions. Regular physical exercise modulates HERV expression, whereas inactivity is associated with reduced expression and increased inflammation. HERV-W and HERV-H maintain coordinated expression across ages, indicating interplay between inflammatory balance, aging, and retroviral activity. Full article

Global population aging has led to a substantial increase in the number of older adults receiving long-term pharmacological treatment, often involving polypharmacy. Long-term medication use is often linked to negative oral health outcomes, such as xerostomia, periodontal disease, dental caries, and changes in the oral microbiome, even if it is necessary for treating systemic conditions. The general health, nutritional state, and quality of life of elderly people are all significantly impacted by these diseases. This narrative review integrates recent data on biological causes, genetic vulnerability, and public health consequences to investigate oral self-care as a preventive strategy in older persons on medication. The effects of long-term medication therapy on oral tissues, salivary function, inflammatory responses, and microbial balance are given special attention, as is the role of genetic variants linked to immunological and inflammatory pathways on individual variability. The review also evaluates oral self-care interventions aimed at reducing medication-related oral complications, such as the use of fluoride, mechanical plaque control measures, and caregiver-assisted oral care practices. Oral self-care is viewed from a public health perspective as a scalable and affordable strategy for reducing oral health disparities in older populations. The results highlight the significance of preventative, individualized, and integrated oral health interventions within larger healthcare frameworks for older persons taking long-term medications. Full article

The ratio of high-sensitivity C-reactive protein (hs-CRP) to Serum albumin (SA) (hs-CRP/SA) is emerging as a new potential biomarker capable of stratifying cardiovascular risk in patients with chronic HF (CHF), particularly the risk of major adverse cardiovascular events (MACEs). Objectives: The aim of this study was to evaluate the long-term prognostic value of the hs-CRP/SA ratio on the risk of MACEs in a population of outpatients with CHF. Methods: In this retrospective observational study, 500 patients were enrolled and were stratified into two groups based on the median value of the hs-CRP/SA ratio: 249 patients with hs-CRP/SA < 1.19 and 251 patients with hs-CRP/SA ≥ 1.19. Results: During median follow-up of 5.2 years, 3.6 MACEs/100 patients/year were detected; patients with hs-CRP/SA ≥ 1.19 had a MACE incidence of 5.9 events per 100 patient-years, compared with 1.2 events per 100 patient-years in those with hs-CRP/AS < 1.19 (p < 0.001). Multivariate analysis confirmed that hs-CRP/SA ≥ 1.19 was associated with an approximately 6.5-fold increased risk of new MACEs (HR 6.513, 95% CI 3.928–10.797; p < 0.001). Conclusions: The hs-CRP/SA ratio is confirmed as a powerful prognostic marker in patients with CHF, associated with a significantly increased risk of MACEs. Full article

Background/Objectives: Endometrial cancer is one of the most common malignancies of the female reproductive system. Fortunately, risk-adapted therapy offers a promising chance of recovery, even from locally advanced disease. In particular, older patients with higher risk factors benefit markedly from adjuvant radiotherapy with or without chemotherapy. Nevertheless, this also carries a risk of higher cumulative toxicity thereafter. Although this phenomenon has been observed in older patients, it has not yet been adequately evaluated. Methods: This retrospective study compared the clinical features of patients receiving adjuvant radiotherapy with or without sequential chemotherapy or radiotherapy with concomitant chemotherapy between 2011 and 2023. The cohort was divided into two groups: patients over 65 years old and those under 65. Results: 100 patients received adjuvant radiotherapy at our center between 2011 and 2023. The mean age of patients was 66.87 years. We observed that neither diabetes, obesity, concurrent, sequential chemotherapy, nor para-aortic field irradiation was associated with an increased incidence of acute radiogenic side effects such as cystitis, diarrhea, proctitis, radiodermatitis, nausea, or vaginal dryness according to CTCAE ≥ 2 (all p > 0.50). No difference was found between the two groups in terms of the incidence of radiotherapy-associated toxicity. Conclusions: We found no increase in toxicity in elderly patients after adjuvant radiotherapy with or without chemotherapy. Full article

The remarkable evolution of oncological therapies has dramatically improved cancer survival rates but has simultaneously introduced a significant burden of cardiovascular complications. Cardio-oncology has emerged as a critical multidisciplinary field focused on mitigating the “collateral damage” of life-saving anticancer treatments, ranging from traditional chemotherapeutics to novel immunotherapies. This review provides a comprehensive analysis of the pathophysiological mechanisms, clinical phenotypes, and evolving management strategies for cancer therapy-related cardiac dysfunction (CTRCD). An extensive synthesis of the current literature was conducted, focusing on the molecular pathways of cardiotoxicity, including Topoisomerase IIβ inhibition by anthracyclines, HER2 signaling disruption by targeted agents, and immune-mediated myocarditis triggered by checkpoint inhibitors (ICIs). Cardiotoxicity is increasingly recognized as a spectrum of phenotypes. Heart failure with reduced ejection fraction (HFrEF) remains a primary concern with cytotoxic agents, while heart failure with preserved ejection fraction (HFpEF) is emerging as a critical complication of radiation therapy and tyrosine kinase inhibitors (TKIs). The integration of advanced diagnostic tools—specifically Global Longitudinal Strain (GLS) and Cardiac Magnetic Resonance (CMR) mapping—has shifted the clinical focus toward subclinical detection. Furthermore, pivotal clinical trials such as PRADA and SUCCOUR have validated early pharmacological prophylaxis and strain-guided interventions. Emerging challenges, including the management of CAR-T cell-induced cytokine release syndrome and the specific cardiovascular needs of pediatric and geriatric populations, are also explored. The future of cardio-oncology lies in precision medicine, leveraging genomic profiling and artificial intelligence to identify high-risk individuals. A proactive, multidisciplinary approach is essential to ensure that the success of modern oncology is not compromised by irreversible cardiovascular morbidity. Full article

Background: Advanced heart failure (HF) in very old patients follows an unpredictable trajectory marked by recurrent decompensations, progressive functional decline, and high mortality. In this population, decision-making regarding goals of care and treatment proportionality is particularly complex due to multimorbidity, frailty, cognitive vulnerability, and prognostic uncertainty, and remains insufficiently addressed by conventional disease-centred heart failure pathways. Methods: This narrative review synthesizes current evidence from heart-failure guidelines, geriatric medicine, and palliative care literature to propose a cardiogeriatric framework for end-of-life decision-making in advanced HF. Results: In older adults, functional decline and geriatric vulnerability often progress independently of cardiac parameters, limiting the relevance of prognosis-based thresholds. The palliative turning point should be understood as a multidimensional process resulting from converging cardiological, geriatric, organizational, and patient-reported signals. Therapeutic decisions should be guided by proportionality between expected benefit, treatment burden, and patient priorities. Longitudinal, iterative communication is essential to align care with evolving goals. Conclusions: A cardiogeriatric approach integrating cardiology, geriatrics, and palliative principles supports timely palliative integration, shared decision-making, and coordinated care in very old patients with advanced HF. Full article

Background/Objectives: During the last decades, there has been a growing interest in and knowledge of the relationship between adverse childhood experiences (ACEs) or stressful life events and health issues in younger and adult populations. However, less is known in older populations. This narrative review aimed to summarize cross-syndrome studies on the relationship between life course exposure to adversity (e.g., ACEs, discrimination, famine, adult violence) and geriatric syndromes (e.g., dementia, frailty, falls, depression), with the primary intention of providing a descriptive mapping of the evidence and identifying gaps. Methods: We searched PubMed for articles published between 2015 and 2026 using specific keywords. Results: We included 84 studies. There is substantial variability in the exposure measures used (e.g., for ACEs, from one question to more than 30) and in the outcomes (e.g., different diagnostic criteria for dementia or frailty). Conclusions: Our synthesis showed that ACEs, stressful events, and other adversity measures are usually associated with greater probabilities of the occurrence of geriatric syndromes such as dementia, frailty, depression, falls, low muscle strength, multimorbidity, and functional decline. There are also some reports for mediators, depression being the most common, that may partially explain those associations. Full article

Background: Fermented dairy foods, such as yogurt and cheese, contain bioactive components that differ from those in non-dairy foods, but their associations with depression and dementia risk in later life remain unclear. Methods: We analyzed data from the Sydney Memory and Ageing Study, a community-dwelling cohort of adults aged 70–90 years, to examine associations between dairy intake and depressive symptoms (Geriatric Depression Scale-15), psychological distress (Kessler-10), and incident depression (physician diagnosis or antidepressant use) and dementia (DSM-IV criteria). Intake of yogurt, cheese, and non-fermented milk was assessed at baseline using a validated food-frequency questionnaire. Longitudinal associations were examined using Fine–Gray competing-risks models that accounted for death; cross-sectional associations were also assessed. Results: Among 966 participants (mean age: 78.3; 55.5% women), compared with no consumption, higher yogurt intake (one standard serving) was significantly associated with lower depressive symptom scores (adjusted β: −0.37 and −0.39 for quartiles 3–4 (mean: 88.5–164 g/day), and so was low-fat cheese intake (mean: 13.2 g/day) (adjusted β: −0.35). Over a mean follow-up of 3.3 years, 120 incident cases of depression and 68 deaths occurred: higher yogurt intake and low-fat cheese consumption (versus non-consumption) were associated with lower risk of depression (adjusted subdistribution hazard ratios 0.41 [95% CI 0.19–0.88] and 0.40 [0.21–0.78], respectively). No significant associations were observed for psychological distress, cognition, or incident dementia (a mean follow-up of 5.2 years, 100 incident cases, and 153 deaths); no associations were observed for regular cheese or milk intake. Conclusions: These findings suggest a potential role for fermented dairy foods, particularly yogurt and low-fat cheese intake, but not non-fermented milk, in mental well-being in later life. Full article