Search Results (486)

Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article

Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due to multi-morbidity, polypharmacy, and age-related physiological changes. Given advancements in medicine and more prolonged cumulative exposure to risk factors in the elderly population, it is likely that the prevalence of chronic kidney disease (CKD) and heart failure (HF) will continue to rise going forward. Hence, understanding the mechanisms involved in the development of CRS is paramount. There are five different CRS types—they are categorised depending on the primary organ involved the acuity of disease. The pathophysiological process behind CRS is complex, involving the interplay of many processes including hemodynamic changes, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction and vascular stiffness. The numerous diagnostic and management challenges associated with CRS are significantly further exacerbated in an elderly population. Biomarkers used to aid the diagnosis of CRS, such as serum creatinine and brain natriuretic peptide (BNP), can be challenging to interpret in the elderly population due to age-related renal senescence and multiple comorbidities. Polypharmacy can contribute to the development of CRS and therefore, before initiating treatment, coordinating a patient-centred, multi-speciality, holistic review to assess potential risks versus benefits of prescribed treatments is crucial. The overall prognosis of CRS in the elderly remains poor. Treatments are primarily directed at addressing the sequelae of the underlying aetiology, which often involves the removal of fluid through diuretics or ultrafiltration. Careful considerations when managing elderly patients with CRS is essential due to the high prevalence of frailty and functional decline. As such, in these patients, early discussions around advance care planning should be prioritised. Full article

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article

Introduction: Respiratory Syncytial Virus (RSV) infection causes seasonal respiratory illness in both children and adults, with increasing recognition of its impact in older adults with chronic comorbidities. This study aimed to characterize adult patients hospitalized with RSV infection in Switzerland and identify comorbidities linked to poor outcomes. Methods: Adults hospitalized with RSV infection between May 2022 and April 2024 at a Swiss public teaching hospital were included in this retrospective observational study. To assess the association between comorbidities and patient outcomes, separate multivariable regression analyses for each comorbidity, adjusted for age and sex, were performed. The primary composite endpoint was ’severe course’ (in-hospital death or intensive care unit (ICU) admission), secondary endpoints included in-hospital death, ICU admission, and length of stay. Results: Among 136 included patients (mean age 78, 38% male), 98% had comorbidities, most commonly cardiovascular (75.7%), respiratory (51%), and chronic kidney disease (CKD) (36.7%). Further, 18.4% experienced a severe course. The ICU admission rate was 14.0%, in-hospital mortality 6.6%, and the median hospital stay of survivors was 6 days (IQR 4–10). CKD was significantly associated with severe course (OR 2.64, p = 0.045) and in-hospital mortality (OR 11.6, p = 0.025), while immunosuppression predicted ICU admission (OR 5.7, p = 0.018). Length of stay was not linked to any comorbidities. Conclusions: In this cohort of hospitalized adults, mainly elderly individuals with chronic comorbidities were tested positive for RSV. CKD and immunosuppression were associated with severe course. Prevention strategies, including RSV vaccination, should prioritize these high-risk populations. Full article

Chronic coronary syndrome (CCS) and atrial fibrillation (AF) are prevalent cardiovascular conditions that share numerous risk factors and pathophysiological mechanisms. While clinical scores commonly used in AF—such as CHA₂DS₂VA (which includes congestive heart failure, hypertension, age ≥ 75, diabetes, stroke/TIA, vascular disease, and age 65–74), HAS-BLED (which incorporates hypertension, abnormal renal/liver function, stroke, bleeding history, labile INR, elderly age, and drug/alcohol use), and C₂HEST (incorporating coronary artery disease, COPD, hypertension, elderly age ≥ 75, systolic heart failure, and thyroid disease)—are traditionally applied to rhythm or bleeding risk prediction, their value in estimating the angiographic severity of coronary artery disease (CAD) remains underexplored. We conducted a prospective, single-center study including 131 patients with suspected stable CAD referred for coronary angiography, stratified according to coronary angiographic findings into two groups: significant coronary stenosis (S-CCS) and non-significant coronary stenosis (N-CCS). At admission, AF-related scores (CHA₂DS₂, CHA₂DS₂VA, CHA₂DS₂VA-HSF, CHA₂DS₂VA-RAF, CHA₂DS₂VA-LAF, HAS-BLED, C₂HEST, and HATCH) were calculated. CAD severity was subsequently assessed using the SYNTAX and Gensini scores. Statistical comparisons and Pearson correlation analyses were performed to evaluate the association between clinical risk scores and angiographic findings. Patients in the S-CCS group had significantly higher scores in CHA₂DS₂VA (4.09 ± 1.656 vs. 3.20 ± 1.338, p = 0.002), HAS-BLED (1.98 ± 0.760 vs. 1.36 ± 0.835, p < 0.001), CHA₂DS₂VA-HSF (6.00 ± 1.854 vs. 5.26 ± 1.712, p = 0.021), and C₂HEST (3.49 ± 1.501 vs. 2.55 ± 1.279, p < 0.001). Multivariate logistic regression identified HAS-BLED and C₂HEST as independent predictors of significant coronary lesions. A threshold value of HAS-BLED ≥ 1.5 and C₂HEST ≥ 3.5 demonstrated moderate discriminative ability (AUC = 0.694 and 0.682, respectively), with acceptable sensitivity and specificity. These scores also demonstrated moderate to strong correlations with both Gensini and SYNTAX scores. AF-related clinical scores, especially HAS-BLED and C₂HEST, may serve as practical and accessible tools for early CAD risk stratification in patients with suspected CCS. Their application in clinical practice may serve as supplementary triage tools to help prioritize patients for further diagnostic evaluation, but they are not intended to replace standard imaging or testing. Full article

Introduction: Urinary tract infections (UTIs) remain a significant public health issue worldwide, particularly affecting the geriatric population with increased morbidity and mortality. Aging-related immune changes, comorbidities, and urogenital abnormalities contribute to the higher incidence and complexity of UTIs in elderly patients. Antimicrobial resistance, especially extended-spectrum beta-lactamase (ESBL) production and carbapenem resistance, poses a major challenge in managing UTIs in this group. Methods: This retrospective, multicenter study included 776 patients aged 65 and older, hospitalized with a diagnosis of urinary tract infection between January 2019 and August 2024. Clinical, laboratory, and microbiological data were collected and analyzed. Urine samples were obtained under sterile conditions and pathogens identified using conventional and automated systems. Antibiotic susceptibility testing was performed according to CLSI standards. Logistic regression analyses were conducted to identify factors associated with ESBL production, carbapenem resistance, and mortality. Results: Among the patients, the median age was 78.9 years, with 45.5% female. ESBL production was detected in 56.8% of E. coli isolates and carbapenem resistance in 1.2%. Klebsiella species exhibited higher carbapenem resistance (37.8%). Independent predictors of ESBL production included the presence of urogenital cancer and antibiotic use within the past three months. Carbapenem resistance was associated with recent hospitalization, absence of kidney stones, and infection with non-E. coli pathogens. Mortality was independently associated with intensive care admission at presentation, altered mental status, Gram-positive infections, and comorbidities such as chronic obstructive pulmonary disease and urinary incontinence. Discussion: Our findings suggest that urinary pathogens and resistance patterns in elderly patients are similar to those in younger adults reported in the literature, highlighting the need for age-specific awareness in empiric therapy. The identification of risk factors for multidrug-resistant organisms emphasizes the importance of targeted antibiotic stewardship, especially in high-risk geriatric populations. Multicenter data contribute to regional understanding of resistance trends, aiding clinicians in optimizing management strategies for elderly patients with UTIs. Conclusions: This study highlights that E. coli and Klebsiella species are the primary causes of UTIs in the elderly, with resistance patterns similar to those seen in younger adults. The findings also contribute important data on risk factors for ESBL production and carbapenem resistance, supported by a robust patient sample. Full article

Inhaled corticosteroids (ICSs) are widely used to manage chronic respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), and human immunodeficiency virus (HIV). However, prolonged use of ICS is associated with the development of oropharyngeal candidiasis, a fungal infection primarily caused by Candida albicans, due to local immunosuppression in the oral cavity. The incidence of oropharyngeal candidiasis varies depending on geographic region, patient age, and comorbidities, with immunocompromised individuals, those with diabetes, and the elderly being particularly vulnerable. Key risk factors include high ICS doses, poor oral hygiene, and improper use of inhalers. Prevention is the cornerstone of managing oropharyngeal candidiasis associated with the chronic use of inhaled corticosteroids. Patient education on proper inhaler technique and oral hygiene is essential to reduce the risk of fungal overgrowth in the oral cavity. Additional preventive strategies include the use of spacers, mouth rinsing after inhalation, and proper denture care. In cases where these measures fail to prevent the infection, prompt detection and early intervention are crucial to prevent progression or recurrence. This narrative review aims to analyze the most effective prophylactic measures to prevent oropharyngeal candidiasis associated with the chronic use of inhaled corticosteroids, emphasizing patient education, oral hygiene, and proper use of inhalation devices. Full article

Background and Clinical Significance: Neuromyelitis optica (NMO) is a chronic demyelinating inflammatory disease of the central nervous system (CNS), mediated by autoantibodies against aquaporin-4 (AQ4) receptors. In the spectrum of NMO, other autoimmune diseases also coexist, though their association with systemic lupus erythematosus (SLE) is rare. Case Presentation: We present two cases of patients in their 70s who were diagnosed with NMO in the context of SLE. The first case concerns a 78-year-old woman with drug-induced SLE and thoracic myelitis who developed T4-level incomplete paraplegia over three weeks. The second case involves a 71-year-old woman with a history of SLE and myasthenia gravis, presenting with cervical myelitis with progressive worsening of walking and C4-level paraparesis over two months. In both cases, elevated serum anti-AQ4 titers were detected, establishing the diagnosis of NMO and differentiation from an atypical manifestation of SLE-related myelitis. High doses of intravenous corticosteroids with gradual tapering, along with cyclophosphamide, followed by rituximab, were administered in both patients. The first patient showed a poor response, while the second showed improvement. Conclusions: The coexistence of NMO with SLE is rare, but the occurrence of myelitis in patients with connective tissue diseases should raise the suspicion of NMO, especially in elderly women and several years after the diagnosis of SLE. Time to treatment is critical, as delays in treating NMO can result in cumulative and disabling damage. Full article

Peripheral artery disease (PAD) is a common vascular disorder in the elderly, often accompanied by frailty syndrome, which is associated with increased inflammation, oxidative stress, and functional decline. Nutritional strategies, particularly those involving bioactive compounds like flavonoids and omega-3 fatty acids, have been suggested as potential approaches to modulate these pathological processes. This narrative review summarizes current evidence regarding the anti-inflammatory and antioxidant effects of flavonoids and omega-3 fatty acids, and their possible roles in mitigating frailty syndrome in patients with PAD. We examine mechanistic pathways including NF-κB, AMPK, PI3K/Akt/mTOR, and Nrf2, which are implicated in chronic inflammation, endothelial dysfunction, and muscle wasting. Although studies in general and aging populations suggest beneficial effects of these compounds on vascular and muscle health, specific evidence in PAD patients remains limited. Flavonoids may reduce pro-inflammatory cytokine production and enhance antioxidant responses, while omega-3 fatty acids have shown potential in modulating inflammatory signaling and supporting vascular repair. Current data provide a basis for further investigation into the dietary modulation of frailty syndrome in PAD. Understanding the impact of these nutrients may offer insights into adjunctive strategies for improving patient outcomes. Full article

Repetitive DNA represents over 50% of the human genome and is an abundant component of circulating cell-free DNA (cfDNA). We previously showed that cfDNA levels and integrity can predict survival in elderly patients with cardiovascular disease. Here, we aimed to clarify whether a low-pass next-generation sequencing (NGS) approach can characterize the repeat content of cfDNA. Considering the bimodal distribution of cfDNA fragment lengths, we examined the occurrence of repetitive DNA subfamilies separately in dinucleosomal (>250 bp) and mononucleosomal (≤250 bp) cfDNA sequences from 24 patients admitted for heart failure. An increase in the relative abundance of Alu repetitive elements was observed in the longer fraction, while alpha satellites were enriched in the mononucleosomal fraction. The relative abundance of Alu, ALR, and L1HS DNA in the dinucleosomal fraction correlated with different prognostic biomarkers, and Alu DNA was negatively associated with the presence of chronic kidney disease comorbidity. These results, together with the observed inverse correlation between Alu DNA abundance and cfDNA integrity, suggest that the composition of plasma cfDNA could be determined by multiple mechanisms in different physio-pathological conditions. In conclusion, low-pass NGS is an inexpensive method to analyze the cfDNA repeat landscape and identify new cardiovascular disease biomarkers. Full article

Objectives: Frailty is increasingly recognized as a key determinant of surgical risk in elderly patients undergoing aortic valve replacement (AVR). This study aimed to evaluate the prognostic value of the modified Frailty Index (mFI) in a homogeneous cohort of octogenarians undergoing minimally invasive surgical AVR, to enhance risk stratification and guide surgical decision-making. Methods: We retrospectively analyzed 67 patients aged ≥ 80 years (mean 84.1 ± 3.2) who underwent isolated minimally invasive AVR. The mFI was calculated preoperatively using standardized clinical variables. Primary outcomes included 30-day mortality and perioperative complications; long-term survival was also assessed. Receiver operating characteristic (ROC) curves identified optimal mFI cut-offs. Kaplan-Meier and Cox regression analyses were used to evaluate survival and predictors of mortality. Results: The mFI demonstrated a strong prognostic accuracy. An mFI > 0.455 predicted 30-day mortality with 81.8% sensitivity and 88.4% specificity (AUC = 0.888, p < 0.001), while an mFI > 0.273 predicted perioperative complications (AUC = 0.818, p < 0.001). During a median follow-up of 51.8 ± 36.4 months, 24 patients (45.3%) died. One-year survival was 83.7%. The mFI > 0.455 was the strongest independent predictor of early mortality (HR 6.34, p = 0.001); mFI > 0.273, HFpEF with NT-proBNP > 1000 pg/mL, and chronic kidney disease were predictors of long-term mortality. Conclusions: The mFI is a simple, reproducible tool that reliably predicts early and late outcomes in very elderly patients undergoing minimally invasive AVR. Integrating frailty into preoperative evaluation may improve patient selection by prioritizing physiological over chronological age. Full article

Background and Objectives: Acute kidney injury (AKI) is common in intensive-care unit (ICU) patients and is associated with increased mortality. Elderly patients tend to have more comorbid chronic diseases and are more prone to AKI than younger populations, resulting in higher rates of hospitalization and a higher incidence of AKI. Our aim in this study was to investigate the prognostic utility of BUN/albumin ratio (BAR) in predicting mortality in elderly critically ill patients with AKI. Materials and Methods: This study was conducted retrospectively on 154 elderly patients with AKI who were admitted to the ICU between October 2023 and September 2024.Data on the following demographic, clinical, and laboratory parameters were retrospectively collected from medical cards and electronic records. Results: In the non-survivor group, among comorbidities, lung disease was higher (p < 0.05), GCS was lower, and APACHE II was higher among clinical scores (p < 0.001). In the non-survivor group, diuretic use (p = 0.03), oliguria, RRT, vasopressor requirement, sepsis, and MV rates (p < 0.001),as well as BUN, phosphate, LDH, Crp, APTT, INR, and BAR rates, were higher (all p < 0.05) and albumin was lower (p = 0.01). Cut-off values of BUN, albumin, and BAR variables according to mortality status were determined by an ROC curve analysis, as follows:48.4 for BUN (p = 0.013), 31.5 for albumin (p = 0.001), and 1.507 for BAR (p = 0.001).According to the results of the ROC analysis performed to predict in-hospital mortality, the BAR level reached an AUC value of 0.655. A BAR value above 1.507 increases mortality by 3.944 times (p = 0.023). Conclusions: BAR is a simple and accessible biomarker that may serve as a predictor of in-hospital mortality in elderly patients with AKI. Its use may aid early risk stratification and decisionmaking in the ICU. Full article

Background: Chronic lymphocytic leukemia (CLL) is a prevalent hematologic malignancy that predominantly affects elderly individuals, posing significant clinical challenges due to patient comorbidities and inherent resistance to conventional chemotherapy. The emergence of targeted therapies combining venetoclax, a selective inhibitor of the anti-apoptotic protein BCL-2, with anti-CD20 monoclonal antibodies has dramatically transformed the treatment landscape. Methods: This retrospective observational study analyzed the differential impacts of first-line venetoclax-obinutuzumab (VenO) and second-line venetoclax-rituximab (VenR) on immunoglobulin G (IgG) levels and absolute neutrophil count (ANC) in CLL patients. Results: Our findings indicate that during first-line VenO therapy, a significant improvement in ANC levels from baseline was observed, whereas patients undergoing second-line VenR therapy demonstrated limited impact on ANC and the decreasing tendency in IgG levels. Patients treated with VenR had a longer disease history and previous exposure to other treatment regimens, primarily chemoimmunotherapy, which could negatively influence immune recovery, making direct comparisons between these two treatment lines challenging. Although this observational study did not directly compare infection rates, the observed enhancement of ANC levels in patients receiving VenO suggests a potential for lower infection risk compared to pretreated VenR patients. Conclusions: These results underscore the clinical significance of considering both the treatment line and the patient’s prior therapeutic history when selecting venetoclax-based regimens for CLL. The potential association of first-line VenO with improved immunological parameters and the complex impact of prior therapies on immunological recovery with second-line VenR warrant further prospective investigation into the correlation between treatment regimen, patient history, immune function, and infectious complications. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory disease frequently accompanied by comorbid conditions that contribute to disability and worsen long-term outcomes. Among these, malnutrition and osteosarcopenia remain under-recognised. This cross-sectional study aimed to assess the prevalence of malnutrition and osteosarcopenia among elderly women with RA and explore the clinical impact of these conditions. Methods: Sixty-five women over 65 years with RA were evaluated using Global Leadership Initiative on Malnutrition (GLIM) criteria for malnutrition and EWGSOP2-based assessments for sarcopenia; bone status was measured by dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS), and three-dimensional DXA (3D-DXA). Results: Malnutrition was identified in 49.2% and osteosarcopenia in 52.3% of participants. A significant bidirectional association was observed: malnourished patients had higher rates of osteosarcopenia (65.6% vs. 34.4%; p < 0.05), and osteosarcopenic patients were more frequently malnourished (61.8% vs. 39.1%; p < 0.05). Both conditions were associated with older age, lower body mass index (BMI), impaired muscle parameters, and reduced bone mineral density. Malnourished and osteosarcopenic patients reported worse fatigue and lower physical quality of life, despite similar inflammatory activity. Significant correlations were found between muscle mass indices and bone quality metrics assessed by 3D-DXA. These findings highlight a substantial burden of malnutrition and osteosarcopenia in elderly women with RA, even with well-controlled disease despite similar inflammatory activity (mean Disease Activity Score 28: 2.8 ± 1.0; 43.1% in remission. Conclusions: There is a substantial burden of malnutrition and osteosarcopenia in elderly women with RA that support the integration of systematic nutritional and musculoskeletal screening into routine care. Future studies should evaluate age- and disease-specific mechanisms and assess the benefit of multidisciplinary strategies to prevent frailty and improve long-term outcomes. Full article

Background: Elderly patients with chronic lower respiratory diseases (CLRDs) demonstrate an increased susceptibility to complications arising from influenza. Influenza vaccination remains the most effective strategy against influenza-related diseases among elderly CLRD patients. This study aimed to evaluate the influenza vaccination status of older CLRD patients and the factors affecting influenza vaccination. Methods: Using population-based health registries, we analyzed the longitudinal uptake of influenza vaccination among elderly patients with CLRDs in Ningbo from the 2018/19 season to the 2022/23 season. A multivariate logistic regression analysis was performed to identify behavioral determinants influencing influenza vaccination among elderly CLRD patients under Ningbo’s post-pandemic free vaccination policy. Results: An average of 487,309 older patients with CLRDs were included in our analysis for each season. The influenza vaccination rate increased from 3.59% in 2018/19 to 43.32% in the 2022/23 influenza season. There was a significant increase in the proportion of timely influenza vaccinations prior to November 15, rising from 3.01% before the COVID-19 pandemic to 33.90% during the pandemic period. The multivariate logistic regression analysis indicated that both the COVID-19 pandemic and free vaccination policy significantly promoted influenza vaccine uptake. Older CLRD patients with comorbidities such as diabetes, hypertension, or cancer exhibited higher influenza vaccination coverage, whereas those who have experienced acute cardiovascular events showed a lower vaccination rate. Additionally, a prior vaccination history significantly influenced uptake. Conclusions: Despite the significant improvement in vaccination rates, coverage among elderly patients with CLRDs remains below the WHO target. Addressing this gap requires integrated interventions that combine expanding the population eligible for free vaccinations, community mobilization efforts, and effective communication regarding cardiovascular safety to mitigate vaccine hesitancy within high-risk groups. Full article