Search Results (799)

Background/Objectives: The Lancet Commission proposes a new obesity definition that combines body mass index (BMI) with anthropometric measurements to distinguish adipose tissue excess more effectively. This study aims to determine the prevalence of obesity based on the new definition and to examine cardiometabolic risk factors and lifestyle habits across different obesity phenotypes in the urban population of Lithuania. Methods: This study was conducted among residents of Kaunas city from 2020 to 2024. A total of 3426 adults aged 25–69 years (57.1% of the random sample) were participated. Three individuals were excluded due to missing anthropometric data. Participants were categorized into three phenotypes: (1) no obesity (BMI < 30 kg/m² and no or one elevated anthropometric measure, (2) anthropometric-only obesity (BMI < 30 kg/m² and at least 2 elevated anthropometric measures), and (3) BMI-plus-anthropometric obesity (BMI ≥ 30 kg/m² plus at least one elevated anthropometric measure or BMI ≥ 40 kg/m²). Standardized anthropometric, biochemical, and clinical measurements were collected, along with self-reported dietary habits and leisure-time physical activity. Results: Anthropometric-only obesity was highly prevalent, affecting 36.1% of males and 22.7% of females (p < 0.05). The prevalence of BMI-plus-anthropometric obesity was 24.1% among males and 21.4% among females. Individuals with anthropometric-only obesity had significantly higher odds of metabolic syndrome (OR 8.64; 95% CI 6.97–10.71), diabetes (OR 3.01; 95% CI 1.72–5.25), coronary heart disease (OR 1.48; 95% CI 1.12–1.97), and several lipid abnormalities compared with those without obesity. The highest cardiometabolic risk was observed in the BMI-plus-anthropometric obesity group. Greater adiposity was associated with higher intake of red meat, junk foods, and sugary drinks, while physical activity levels declined across obesity categories. Conclusions: Anthropometric-only obesity is a common and metabolically adverse phenotype that cannot be detected using BMI alone. A new obesity definition enhances identification of high-risk individuals and supports targeted prevention strategies. Full article

Background and Clinical Significance: Giant sphenoid wing meningiomas are generally viewed as skull base masses that compress frontal centers and their respective pathways gradually enough to cause a dysexecutive–apathetic syndrome, which can mimic primary neurodegenerative disease. The aim of this report is to illustrate how bedside phenotyping and multimodal imaging can disclose similar clinical presentations as surgically treatable network lesions. Case Presentation: An independent, right-handed older female developed an incremental, two-year decline of her ability to perform executive functions, extreme apathy, lack of instrumental functioning, and a frontal-based gait disturbance, culminating in a first generalized seizure and a newly acquired left-sided upper extremity pyramidal sign. Standardized neuropsychological evaluation revealed a predominant frontal-based dysexecutive profile with intact core language skills, similar to behavioral-variant frontotemporal dementia (bvFTD). MRI demonstrated a large, right fronto-temporo-basal extra-axial tumor attached to the sphenoid wing with homogeneous postcontrast enhancement, significant vasogenic edema within the frontal projection pathways, and a marked midline displacement of structures with an open venous pathway. With the use of a skull-base flattening pterional craniotomy with early devascularization followed by staged internal debulking, arachnoid preserving dissection, and conservative venous preservation, the surgeon accomplished a Simpson Grade I resection. Sequential improvements in the patient’s frontal “re-awakening” were demonstrated through postoperative improvements on standardized stroke, cognitive and functional assessment scales that correlated well with persistent decompression and symmetric ventricles on follow-up images. Conclusions: This case illustrates the possibility of a non-dominant sphenoid wing meningioma resulting in a pseudo-degenerative frontal syndrome and its potential for reversal if recognized as a network lesion and treated with tailored, venous-sparing skull-base surgery. Contrast-enhanced imaging and routine frontal testing in atypical “dementia” presentations may aid in identifying additional patients with potentially surgically remediable cases. Full article

The hospital-at-home (HaH) model delivers hospital-level care to patients in their homes, with point-of-care ultrasonography (PoCUS) serving as a cornerstone diagnostic tool for respiratory illnesses such as pneumonia. This review—the third in a series—addresses the prognostic, synchronous, and potential overdiagnostic concerns of lung ultrasound (LUS) in managing pneumonia within HaH settings. LUS offers advantages of safety and repeatability, allowing clinicians to identify “red flag” sonographic findings that signal complicated or severe disease, including pleural line abnormalities, fluid bronchograms, absent Doppler perfusion, or poor diaphragmatic motion. Serial LUS examinations correlate closely with clinical recovery, showing progressive resolution of consolidations, B-lines, and pleural effusions, and thus provide a non-invasive method for monitoring therapeutic response. Compared with chest radiography, LUS demonstrates superior sensitivity in detecting pneumonia, pleural effusion, and interstitial syndromes across pediatric and adult populations. However, specificity may decline in tuberculosis-endemic or obese populations due to technical limitations and overlapping imaging patterns. Overdiagnosis remains a concern, as highly sensitive ultrasonography may identify minor or clinically irrelevant lesions, potentially leading to overtreatment. To mitigate this, PoCUS should be applied in parallel with conventional diagnostics and integrated into comprehensive clinical assessment. Standardized training, multi-zone scanning protocols, and structured image acquisition are recommended to improve reproducibility and inter-operator consistency. Full article

Background/Objectives: Gut dysbiosis in Chronic Fatigue Syndrome (CFS) drives low-grade inflammation and shifts tryptophan metabolism toward neurotoxic pathways. The causal link between bacterial translocation, kynurenine pathway dysregulation, and symptom severity remains under-defined. We evaluated the impact of a high-concentration multi-strain probiotic on the “gut-kynurenine axis” and clinical status in CFS patients with co-morbid IBS-U and confirmed dysbiosis. Methods: Forty female patients with confirmed dysbiosis (GA-map™ Dysbiosis Index > 2) received the CDS22 formula (450 billion CFU/day) for 12 weeks. We compared urinary tryptophan metabolite profiles (LC-MS/MS), gut dysbiosis markers (3-indoxyl sulfate), and fatigue severity (FSS) against 40 age-matched healthy controls. Results: Baseline analysis revealed profound metabolic perturbations: elevated bacterial proteolytic markers (3-IS), substrate depletion (low tryptophan), and a neurotoxic signature (high quinolinic acid [QA], low kynurenic acid [KYNA]). Following the intervention, fatigue scores declined by 40.3%, with 97.5% of patients reaching the remission threshold (FSS < 36). Biochemically, 3-IS levels decreased to the range observed in healthy controls and attenuated xanthurenic acid levels. Although absolute QA concentrations remained elevated compared to controls, the neuroprotective KYNA/QA ratio increased significantly (+45%). Increased systemic tryptophan availability correlated directly with clinical symptom reduction (Spearman’s rho = −0.36, p = 0.024). Conclusions: The CDS22 formulation was associated with a restoration of intestinal eubiosis and functional tryptophan partitioning. Clinical remission coincides with a metabolic shift favoring neuroprotection (increased KYNA/QA ratio), validating the gut–kynurenine axis as a modifiable therapeutic target. Peripheral metabolic improvement relative to the healthy baseline appeared sufficient for symptom relief in this specific phenotype, despite incomplete clearance of neurotoxic metabolites. Full article

Background: Acute kidney injury (AKI) is increasingly recognised in children with acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C), yet the long-term renal consequences in younger paediatric populations remain unclear. Most studies focus on acute illness or mixed-age cohorts, with limited data specific to children aged 0–12 years. Objectives: This study aimed to systematically identify, evaluate, and synthesise evidence on post-acute (≥30 days) and long-term (≥90 days) kidney outcomes following SARS-CoV-2 infection or MIS-C in children aged 0–12 years, including chronic kidney disease (CKD), eGFR decline, proteinuria, haematuria, hypertension, and need for kidney replacement therapy. Methods: We searched MEDLINE, Embase, CINAHL, and PubMed (December 2019–30 November 2025), following PRISMA 2020 guidelines and a registered PROSPERO protocol (CRD420251241949). Observational studies reporting kidney outcomes ≥30 days post-infection in children aged 0–12 years were included. Risk of bias was assessed using the Newcastle–Ottawa Scale or ROBINS-I. Owing to heterogeneity and absence of ≥3 comparable datasets, a narrative synthesis was performed. Results: Seven studies met inclusion criteria (five MIS-C cohorts, two acute COVID-19 cohorts). Only a subset provided extractable data specific to children aged 0–12 years. Follow-up ranged from 30 days to 12 months; four studies reported outcomes ≥ 180 days. Across all studies, no incident CKD, sustained eGFR decline, or kidney replacement therapy were reported among children completing long-term follow-up; however, most long-term outcome data were derived from MIS-C cohorts with median ages around 8–11 years that included some adolescents, rather than exclusively children aged 0–12 years. One MIS-C study reported long-term hypertension in 14% of children. A cross-sectional Italian cohort of mild COVID-19 demonstrated hyperfiltration, proteinuria, and microhaematuria at ~3 months, though chronicity could not be assessed due to absence of baseline values. A large US EHR-based cohort identified increased CKD risk after COVID-19 in the broader < 21-year population; however, 0–12-year-specific event counts were not reported, preventing quantitative synthesis for young children. Conclusions: Evidence on long-term kidney outcomes after SARS-CoV-2 infection in children aged 0–12 years remains limited, and only a small subset of studies provided extractable, age-specific data. On the other hand, MIS-C cohorts generally show favourable renal recovery, small sample sizes, lack of control groups, and short follow-up restrict confidence in these findings. Large paediatric EHR studies suggest potential long-term renal risk in broader paediatric populations, highlighting the need for age-stratified, prospective cohorts with serial eGFR, urine studies, and blood pressure assessments. Until definitive evidence emerges, structured renal follow-up may be warranted for children with AKI or MIS-C during COVID-19. Full article

Background: Carpal tunnel syndrome (CTS) is a common peripheral neuropathy with increasing prevalence and economic burden. This study aimed to analyze recent trends in CTS treatment patterns, healthcare utilization, and costs within the dualized healthcare system in Korea, using nationwide claim data. Methods: This cross-sectional study used data from the Korean Health Insurance Review and Assessment Service National Patient Sample (HIRA-NPS) between 2010 and 2017. Patients with a primary diagnosis of CTS (KCD-10: G56.0) were included. Descriptive analyses were performed to examine trends in patient characteristics, healthcare utilization, treatment patterns, and medical costs in Western and Korean medicine. Results: A total of 29,112 patients with CTS were analyzed. In Western medicine, diagnostic tests accounted for the highest expenditure, particularly X-ray, nerve conduction studies, and electromyography. Over time, X-ray utilization increased, while nerve conduction and electromyography tests decreased. The proportion of surgical treatment declined from 11.28% in 2010 to 8.55% in 2017, whereas Korean medicine use increased from 9.41% to 15.08%, mainly consisting of acupuncture and related procedures. Conclusions: Korea exhibited a lower CTS surgery rate than other countries, alongside a rising trend in Korean medicine utilization. These findings underscore the distinctive dual healthcare system in Korea and highlight the need for prospective studies to assess the long-term effectiveness of Korean medicine-based conservative treatments. Additionally, the results may inform national health policy decisions, including insurance coverage and resource allocation for CTS management. Full article

Acute kidney injury (AKI) is a critical clinical syndrome characterized by a rapid decline in renal function, frequently resulting from ischemia, nephrotoxicity, or sepsis. It represents a major global health burden due to its high morbidity and mortality and its strong association with progression to chronic kidney disease. In this study, we identified a novel small-molecule TLR4 inhibitor, DB03476, via structure-based virtual screening targeting the intracellular TIR domain of murine Tlr4. Molecular dynamics simulations confirmed that DB03476 stabilizes Tlr4 without altering its global conformation. In a murine ischemia–reperfusion-induced AKI model, DB03476 administration significantly attenuated renal inflammation, macrophage infiltration, and apoptosis and suppressed the TLR4/MyD88/NF-κB pathway. Moreover, DB03476 exhibited cross-species efficacy by binding conserved residues in human TLR4 with high affinity. Functional validation using human kidney organoids confirmed its protective effects against inflammatory challenge. These results demonstrate DB03476 as a promising therapeutic agent for AKI through selective inhibition of TLR4-mediated inflammatory responses. Full article

(1) Background: Globe-sparing radiotherapy is widely utilised in the treatment of uveal melanoma, but often results in complications requiring vitreoretinal intervention. The outcomes of secondary vitrectomy remain unclear. A multidisciplinary approach involving vitreoretinal and ocular oncology specialists is essential to managing complications. (2) Methods: We reviewed 1794 patients treated with radiotherapy for uveal melanoma between 2012 and 2022. In total, 70 patients underwent secondary vitrectomy after primary radiotherapy treatment. The outcomes included overall tumour control and visual outcome. (3) Results: Complications requiring vitrectomy were more common after proton-beam radiotherapy than plaque brachytherapy (5.4% versus 3.0%). Common indications included vitreous haemorrhage (39%) and retinal detachment/toxic tumour syndrome (31%). The affected tumours were larger, more often ciliary body in origin, and associated with a worse prognosis. Vitrectomy patients had higher rates of enucleation (9% versus 3%), metastasis (16% versus 6%), and visual decline (average 0.60 LogMAR), with limited visual improvement (≥3-line gain in 13%). Proton-beam patients had worse outcomes than plaque brachytherapy patients. (4) Conclusions: Vitreoretinal complications after uveal melanoma radiotherapy are rare, but timely treatment by those with experience may enable patients to keep their eye in situations where enucleation would be the only alternative. Patients and clinicians must understand the risks of complications to make informed decisions about treatment plans, with vitreoretinal surgeons and ocular oncologists key to outcomes. Full article

Vitamin D is well established for its skeletal effects, being a cornerstone of several endocrine disorders. In recent years, it has come under investigation as a potential disease-modifying drug in several endocrine disorders through its immune modulatory and anti-tumorigenic action, particularly in thyroid disease, gynecologic disorders, and general fertility. Vitamin D supplementation is well established in the treatment of osteoporosis, osteomalacia, hypoparathyroidism, and primary hyperparathyroidism. In autoimmune thyroid disease, there is a negative correlation between 25(OH)D3 levels and prevalence. Currently available data are inconclusive on supplementation as a disease-modifying treatment. In Hashimoto’s thyroiditis, while some found improved thyroid function, a decline in progression, and antibody titers, these findings were not consistent, and some found no improvements. Painless postpartum thyroiditis severely lacks evidence. Interventional studies failed to demonstrate benefits in Graves’ disease. The literature consistently reports lower vitamin D levels in infertility, polycystic ovarian syndrome (PCOS), and endometriosis. In PCOS, data suggest that vitamin D supplementation is beneficial; however, results in exact benefits vary and there is no consensus on dosing. Current guidelines support supplementation as part of preconception nutritional care. In general, for female infertility and endometriosis, the results are conflicting, with a lack of high-quality evidence. The literature suggests there is a possible benefit regarding sperm motility, but not in testosterone levels for males. In conclusion, while in vitro studies and animal models are promising, the available evidence is often contradictory, with high heterogeneity in study designs and populations. Our paper highlights the need for further high-quality research to resolve current controversies. Full article

Fabry disease (FD) is an X-linked lysosomal disorder caused by GLA mutations, typically associated with glycosphingolipid accumulation and a wide phenotypic spectrum. The p.R112H variant is generally linked to a non-classic predominantly renal phenotype with mild biochemical abnormalities and slow progression. We report the case of a young woman carrying the R112H mutation who exhibited early-onset kidney involvement and unusually rapid progression to end-stage renal disease. Clinical history, serial evaluations, and kidney biopsy findings initially supported a diagnosis of Fabry nephropathy; however, re-evaluation of the native kidney biopsy revealed marked remodeling and multilamellation of the glomerular basement membrane, suggesting Alport-like lesions. Subsequent genetic testing confirmed a heterozygous pathogenic COL4A4 variant (G912R), indicating coexistence of Fabry disease and autosomal dominant Alport syndrome. This dual genetic condition likely accounted for the accelerated decline in kidney function, in contrast with the typically mild phenotype associated with R112H. Our literature review indicates that coexistence of these two inherited nephropathies has not previously been confirmed either histologically or genetically. This case underscores the importance of integrating genetic and ultrastructural assessment in patients with atypical or rapidly progressive renal disease Full article

Background/Objectives: We evaluated Goreisan, a traditional Chinese medicine, for its effects on nephrotic syndrome in a rat model. Methods: Male Sprague–Dawley rats underwent right nephrectomy at 5 weeks of age, followed by adriamycin administration (5 mg/kg) at 6 and 8 weeks of age to induce nephrotic syndrome. At 10 weeks, rats were divided into three groups: vehicle (control), Goreisan 0.5 g/kg (GL), and Goreisan 1.0 g/kg (GH). Goreisan was administered daily for 4 weeks. At 14 weeks, blood, urine, mRNA expressions, and kidney histopathology were analyzed. Data were analyzed using one-way ANOVA followed by Tukey–Kramer post hoc testing. Results: Goreisan prevented worsening kidney function, with reduced glomerular and tubulointerstitial damage, lower systemic and intrarenal 8-hydroxy-2′-deoxyguanosine levels, and lower plasma aldosterone levels and expression of intrarenal renin–angiotensin–aldosterone system (RAAS)-related factors. Urine volume significantly increased in GL and GH groups compared with the control group. In the GH group, urine volume increased markedly (Δ urine volume: 10.0 ± 2.6 mL/day), whereas it tended to decrease in the Vehicle group (Δ urine volume: −1.3 ± 2.5 mL/day). Urine osmolality was lower in the GH group, with a larger decrease in Δ urine osmolality (−616.3 ± 132.8 mOsm/L). These changes occurred without an increase in urinary sodium excretion, suggesting an aquaretic effect independent of natriuresis. Creatinine clearance (CCr/kg) declined markedly in the Vehicle group but was significantly preserved in the GH group (Δ CCr/kg: −2.2 ± 0.19 vs. −0.7 ± 0.28), indicating renoprotective effects. No differences were found in serum arginine–vasopressin levels. Real-time PCR and immunohistochemical staining showed no significant differences in aquaporin (AQP) mRNA expression (AQP1, AQP2, AQP3, and AQP4), but AQP2 localization to the apical membrane in the collecting ducts was reduced with Goreisan treatment. Conclusions: Goreisan demonstrates kidney-protective and diuretic effects in nephrotic syndrome, potentially through reducing systemic oxidative stress, modulating RAAS activation, and altering AQP2 trafficking. Full article

Background: Metabolic syndrome (MetS) is linked to brain degeneration and Alzheimer’s disease (AD). Women, especially during menopausal transition, show increased susceptibility to AD-related brain changes. This study investigated the sex-specific neurostructural impact of MetS on brain regions vulnerable to AD. Methods: This cross-sectional study analyzed data from 500 participants (303 women, 197 men) from the Baependi Heart Study cohort, Brazil. High-resolution T1-weighted MRI scans were used for volumetric analysis of AD-related regions of interest (ROIs). Non-parametric quantile regression models compared ROI volumes between MetS and Non-MetS groups, stratified by sex and age (median split), adjusting for age and education. Results: No significant differences in ROI volume were observed between the MetS and Non-MetS groups in men. In women, findings were age-dependent. The younger cohort (≤48 years) with MetS exhibited significantly smaller left hippocampal volume (p = 0.02) and a trend toward smaller left middle temporal gyrus volume (p = 0.05) compared to Non-MetS. The older cohort (>48 years) with MetS showed a significantly larger right amygdala volume (p < 0.001). Furthermore, age-related volume decline in the hippocampus and middle temporal gyrus was significant in Non-MetS women but not in women with MetS, suggesting that MetS may be a confounding factor in age-related neurodegeneration. Conclusions: MetS is associated with sex-specific alterations in AD-vulnerable brain structures. In women, MetS may influence medial temporal lobe atrophy pre-menopause, and is linked to amygdala enlargement post-menopause. These exploratory results generate the hypothesis that MetS may uniquely predispose women to AD-related neurodegeneration, which requires critical longitudinal confirmation. Full article

Background/Objectives: This study evaluated the impact of the COVID-19 pandemic on trends of acute coronary syndrome hospitalizations, all-cause deaths, and ischemic heart disease (IHD) deaths in Allegheny County, Pennsylvania. Methods: Inpatient hospital records from two hospital systems within Allegheny County, Pennsylvania, were aggregated from January 2017 to November 2020. The primary diagnoses were acute myocardial infarction (AMI) and unstable angina. The Pennsylvania Department of Health provided all-cause and IHD death counts for the same period. We compared absolute percentage changes in admissions by year (March–November) and trends by age-specific groups (<45, 45–64, 65–74, ≥75) from the pre-pandemic (January 2017–February 2020) to pandemic (March 2020–November 2020) period using an interrupted time-series analysis. Results: There were 11,913 AMI hospitalizations pre-pandemic and 2170 AMI hospitalizations during the pandemic period. AMI hospitalizations decreased by 14.8% and unstable angina hospitalizations decreased by 30.7% during the pandemic compared to 2019, with the largest decreases occurring in those aged ≥75. Total mortality increased by 9.2%, and IHD mortality increased by 2.4%. About 80% of the increase in deaths was due to COVID-19, and approximately 75% of deaths occurred in those aged ≥75 and in long-term care facility residents. Conclusions: The COVID-19 pandemic did not markedly alter the longitudinal declining trend of AMI hospitalizations and IHD deaths in Allegheny County. Full article

Background: Wolfram syndrome (WS) is an ultrarare neuroendocrine disorder caused by pathogenic variants in WFS1, frequently leading to progressive neurological, autonomic, and cognitive impairment. Anticipating neurological trajectories remains challenging due to marked phenotypic variability and limited genotype–phenotype data. Methods: Forty-five genetically confirmed patients with WS were evaluated between 1998 and 2024 in Spain. All WFS1 variants were systematically classified by exon, zygosity, protein-level functional impact, and predicted wolframin production (Classes 0–3). Machine learning models (Random Forests with engineered gene–gene interaction terms) were applied to predict neurological manifestations and identify the strongest genetic determinants of symptom severity. Results: Neurological involvement was present in 93% of patients. The most prevalent manifestations were absence of gag reflex (67%), gait instability (64%), dysphagia (60%), and sialorrhea (60%), followed by dysmetria (56%), impaired tandem gait (53%), anosmia (44%), dysarthria (44%), and adiadochokinesia (42%). Most symptoms emerged in early adulthood (23–26 years), whereas cognitive decline occurred later (29.9 ± 12.2 years). Homozygosity for truncating variants—particularly c.409_424dup16 (Val142fsX110)—and complete loss of wolframin production (Class 0; 67–83% across symptoms) were the strongest predictors of early and severe neurological involvement. Machine learning models achieved high discrimination for ataxia, gait instability, and absent gag reflex (AUC 0.63–0.86; calibrated AUC up to 0.97), identifying Mut1_Protein_Class and Mut2_Protein_Class as dominant predictors across all phenotypes, followed by coherent secondary effects from zygosity × exon interaction terms (Prod_mgm). Conclusions: Integrating detailed genetic classification with machine learning methods enables accurate prediction of neurological outcomes in WS. Protein-level dysfunction and allele interaction structure are the principal drivers of neurological vulnerability. This framework enhances precision diagnosis and offers a foundation for individualized surveillance, clinical risk stratification, and future therapeutic trial design in WFS1-related disorders. Full article

Objective: Cardiovascular diseases have a high prevalence among the elderly, together with frailty syndrome, and both conditions negatively affect quality of life and limit patient autonomy. This study aimed to explore potential relationships between cardiovascular and metabolic parameters, renal function, and frailty domains to identify potential intervention targets. Methods: A cross-sectional study was conducted between January 2024 and April 2025 at the National Institute of Gerontology and Geriatrics “Ana Aslan”, including 359 patients aged over 40 years. Demographic, anthropometric, and clinical data were collected through interviews, medical records, and standardized assessments of frailty components (weakness, exhaustion, slow gait, balance impairment, reduced activity, cognitive decline, and weight loss), as well as cardiovascular diseases and comorbidities. Results: Most participants were aged 65–79 years. ROC curve identified triglycerides as a good indicator of both alcohol consumption (AUC = 0.631, p = 0.042) and smoking status (AUC = 0.676, p = 0.004), while HDL cholesterol showed an inverse association with smoking status (AUC = 0.356, p = 0.019). Reduced renal function was significantly associated with smoking status, balance, gait impairment, and reduced functional mobility. The Up and Go Test indicated a good discriminatory ability for renal function decline (AUC = 0.656, p < 0.001). Muscle strength, MMSE, and Tinetti scores showed inverse associations with renal function. Conclusions: Renal impairment appears to be a reliable indicator across multiple frailty domains, acting as an accelerator of frailty progression. Triglycerides reflect lifestyle-related factors, while the Up and Go Test may serve as a practical screening tool for renal dysfunction in frail older adults. These findings suggest the need to adapt traditional cardiovascular risk management to the frail geriatric population. Full article