Relationship between imaging-derived parameters and circulating microRNAs to study the degree of lung involvement in hospitalized geriatric patients with COVID-19 pneumonia.

AIM: Chest computed tomography (CT) scan is useful to evaluate the type and extent of lung lesions in coronavirus disease 2019 (COVID-19) pneumonia. This study explored the association between radiological parameters and various circulating serum-derived markers, including microRNAs, in older patients with COVID-19 pneumonia. METHODS: A retrospective analysis was designed to study geriatric patients (≥75 years) with COVID-19 pneumonia, who underwent chest CT scan on admission, and for whom clinical data and serum samples were obtained. To quantify the extent of lung involvement, CT-score, the percentage of healthy lung (HL%), the percentage of ground glass opacity (GGO%), and the percentage of lung consolidation were assessed using computer-aided tools. The association of these parameters with two circulating microRNAs, miR-483-5p and miR-320b, previously identified as biomarkers of mortality risk in COVID-19 geriatric patients, was tested. RESULTS: A total of 73 patients with COVID-19 pneumonia were evaluable (median age 85 years; interquartile range 82-90 years). Among chest CT-derived parameters, the percentage of lung consolidation (HR 1.08, 95% CI 1.02-1.14), CT-score (HR 1.14, 95% CI 1.03-1.25), and HL% (HR 0.97, 95% CI 0.95-0.99) emerged as significant predictors of mortality, whereas non-significant trends toward increased mortality were observed in patients with higher GGO%. We also found a significant positive association between serum miR-483-5p and GGO% (correlation coefficient 0.28; P = 0.018) and a negative association with HL% (correlation coefficient -0.27; P = 0.023). CONCLUSIONS: Overall, the extent of lung consolidation can be confirmed as a prognostic parameter of COVID-19 pneumonia in older patients. Among various serum-derived markers, miR-483-5p can help in exploring the degree of lung involvement, due to its association with higher GGO% and lower HL%. Geriatr Gerontol Int 2024; ••: ••-••.

Biomarkers of chronic kidney disease in older individuals: navigating complexity in diagnosis.

Chronic kidney disease (CKD) in older individuals is a matter of growing concern in the field of public health across the globe. Indeed, prevalence of kidney function impairment increases with advancing age and is often exacerbated by age-induced modifications of kidney function, presence of chronic diseases such as diabetes, hypertension, and cardiovascular disorders, and increased burden related to frailty, cognitive impairment and sarcopenia. Accurate assessment of CKD in older individuals is crucial for timely intervention and management and relies heavily on biomarkers for disease diagnosis and monitoring. However, the interpretation of these biomarkers in older patients may be complex due to interplays between CKD, aging, chronic diseases and geriatric syndromes. Biomarkers such as serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria can be significantly altered by systemic inflammation, metabolic changes, and medication use commonly seen in this population. To overcome the limitations of traditional biomarkers, several innovative proteins have been investigated as potential, in this review we aimed at consolidating the existing data concerning the geriatric aspects of CKD, describing the challenges and considerations in using traditional and innovative biomarkers to assess CKD in older patients, highlighting the need for integration of the clinical context to improve biomarkers' accuracy.

Interactions between patterns of multimorbidity and functional status among hospitalized older patients: a novel approach using cluster analysis and association rule mining.

BACKGROUND: Multimorbidity (MM) is generally defined as the presence of 2 or more chronic diseases in the same patient and seems to be frequently associated with frailty and poor quality of life. However, the complex interplay between MM and functional status in hospitalized older patients has not been fully elucidated so far. Here, we implemented a 2-step approach, combining cluster analysis and association rule mining to explore how patterns of MM and disease associations change as a function of disability. METHODS: This retrospective cohort study included 3366 hospitalized older patients discharged from acute care units of Ancona and Cosenza sites of Italian National Institute on Aging (INRCA-IRCCS) between 2011 and 2017. Cluster analysis and association rule mining (ARM) were used to explore patterns of MM and disease associations in the whole population and after stratifying by dependency in activities of daily living (ADL) at discharge. Sensitivity analyses in men and women were conducted to test for robustness of study findings. RESULTS: Out of 3366 included patients, 78% were multimorbid. According to functional status, 22.2% of patients had no disability in ADL (functionally independent group), 22.7% had 1 ADL dependency (mildly dependent group), and 57.4% 2 or more ADL impaired (moderately-severely dependent group). Two main MM clusters were identified in the whole general population and in single ADL groups. ARM revealed interesting within-cluster disease associations, characterized by high lift and confidence. Specifically, in the functionally independent group, the most significant ones involved atrial fibrillation (AF)-anemia and chronic kidney disease (CKD) (lift = 2.32), followed by coronary artery disease (CAD)-AF and heart failure (HF) (lift = 2.29); in patients with moderate-severe ADL disability, the most significant ARM involved CAD-HF and AF (lift = 1.97), thyroid dysfunction and AF (lift = 1.75), cerebrovascular disease (CVD)-CAD and AF (lift = 1.55), and hypertension-anemia and CKD (lift = 1.43). CONCLUSIONS: Hospitalized older patients have high rates of MM and functional impairment. Combining cluster analysis to ARM may assist physicians in discovering unexpected disease associations in patients with different ADL status. This could be relevant in the view of individuating personalized diagnostic and therapeutic approaches, according to the modern principles of precision medicine.

Physical performance strongly predicts all-cause mortality risk in a real-world population of older diabetic patients: machine learning approach for mortality risk stratification.

Background: Prognostic risk stratification in older adults with type 2 diabetes (T2D) is important for guiding decisions concerning advance care planning. Materials and methods: A retrospective longitudinal study was conducted in a real-world sample of older diabetic patients afferent to the outpatient facilities of the Diabetology Unit of the IRCCS INRCA Hospital of Ancona (Italy). A total of 1,001 T2D patients aged more than 70 years were consecutively evaluated by a multidimensional geriatric assessment, including physical performance evaluated using the Short Physical Performance Battery (SPPB). The mortality was assessed during a 5-year follow-up. We used the automatic machine-learning (AutoML) JADBio platform to identify parsimonious mathematical models for risk stratification. Results: Of 977 subjects included in the T2D cohort, the mean age was 76.5 (SD: 4.5) years and 454 (46.5%) were men. The mean follow-up time was 53.3 (SD:15.8) months, and 209 (21.4%) patients died by the end of the follow-up. The JADBio AutoML final model included age, sex, SPPB, chronic kidney disease, myocardial ischemia, peripheral artery disease, neuropathy, and myocardial infarction. The bootstrap-corrected concordance index (c-index) for the final model was 0.726 (95% CI: 0.687-0.763) with SPPB ranked as the most important predictor. Based on the penalized Cox regression model, the risk of death per unit of time for a subject with an SPPB score lower than five points was 3.35 times that for a subject with a score higher than eight points (P-value <0.001). Conclusion: Assessment of physical performance needs to be implemented in clinical practice for risk stratification of T2D older patients.

Deterioration of Kidney Function Is Affected by Central Arterial Stiffness in Late Life.

Cardiovascular diseases affect kidney function. The aim of this study was to investigate the possible associations between hemodynamic parameters and change in kidney function in individuals aged 75 years and older. Data on hemodynamics and blood and urine samples were collected at baseline and during one-year visits. Hemodynamics were split into two groups based on median values. Changes in the estimated glomerular filtration rate (eGFR) were investigated between low and high groups for each hemodynamic parameter using analysis of variance. Changes in the albumin-creatinine ratio (ACR) were examined as binary outcomes (large increase vs. stable) using logistic regression. The population consisted of 252 participants. Participants in the high central systolic blood pressure (cSBP) group had a greater decline in eGFR than participants in the low cSBP group (-6.3% vs. -2.7%, p = 0.006). Participants in the high aortic pulse wave velocity (aPWV) group had a greater decline in eGFR than those in the low aPWV group (-6.8% vs. -2.5%, p = 0.001). Other hemodynamic parameters were not associated with eGFR changes. Hemodynamics were not associated with changes in the ACR; aPWV and cSBP appear to be predictors for eGFR decline in older age; monitoring and treatment of elevated stiffness might be helpful in order to prevent kidney function decline.

Prevalence of Sarcopenia in Chronic Heart Failure and Modulating Role of Chronic Kidney Disease.

INTRODUCTION: Sarcopenia, heart failure (HF), and chronic kidney disease (CKD) are common among the older people. Our objective was to evaluate the frequency of sarcopenia, among community-dwelling older adults with HF, possible causative factors, and the additive factor of CKD. METHODS: A cross-sectional analysis of 1,420 older people living in the community was carried out. Participants (aged 75 years and more) came from a European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test, and bioelectrical impedance analysis was performed. Previous known HF was defined as physician-diagnosed HF registered in the patient's medical record or the use of HF-related medications, regardless of left ventricular ejection fraction (LVEF). Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate was calculated using Berlin Initiative Study (BIS) to define the stages of CKD. Two-year mortality was also collected. RESULTS: A total of 226 (15.9%) participants had a prior chronic HF diagnosis, with a median age of 80.0 (5.0), and 123 (54.4%) were women. Using EWGSOP2 definition, 11.5% HF and 10.7% in non-HF participants met diagnostic criteria for sarcopenia. In multivariate analyses, only a lower body mass index (BMI) (odds ratios [OR], 0.82; 95% confidence interval [CI], 0.73-0.93) and lower short physical performance battery score (OR, 0.81; 95% CI, 0.69-0.96) were associated with sarcopenia. Patients with HF and sarcopenia have a similar all-cause mortality risk but higher 2-year cardiovascular mortality risk (p = 0.047). DISCUSSION/CONCLUSION: One out of ten community-dwelling older adults with concurrent clinical stable chronic HF, without considering LVEF, have sarcopenia. Lower BMI and poor physical performance are associated with sarcopenia in this population, but not CKD.

Appropriateness of direct oral anticoagulant prescribing in older subjects with atrial fibrillation discharged from acute medical wards.

AIMS: Knowledge on the prescriptive practice of direct oral anticoagulants (DOACs) in older subjects with atrial fibrillation (AF) hospitalized in acute medical wards is limited. This study aimed to evaluate the prevalence and appropriateness of DOAC prescriptions in hospitalized older subjects with AF, discharged from acute medical wards. METHODS: We analysed a cohort of 609 subjects with AF, aged ≥65 years (mean age 85 years) enrolled from 39 geriatric and nephrology wards in Italy. DOAC prescriptive appropriateness was evaluated according to the summary of product characteristics (smPC), 2019 Beers and STOPP criteria, and drug-drug interactions (DDIs). RESULTS: At hospital discharge, 33% of patients with AF were prescribed with DOAC, 26% with vitamin-K antagonist, while 41% did not receive any anticoagulant. Among subjects on DOAC therapy, 31% presented a violation of the smPC criteria (mainly underdosage-17%), while 48% and 18% presented a Beers/STOPP inappropriate prescription, or a DDI, respectively. Older age, lower body mass index (BMI), cancer and higher estimated glomerular filtration rate (eGFR) were independently associated with DOAC underdosage or missed prescription (age: adjusted odds ratio [aOR] 1.06, 95% confidence interval [95% CI] 1.00-1.12 for underdosage; eGFR: aOR 1.04, 95% CI 1.02-1.07 for underdosage; BMI: aOR 0.95, 95% CI 0.91-0.99 for missed prescription; cancer: aOR 1.93, 95% CI 1.19-3.13 for missed prescription). CONCLUSIONS: This study showed a suboptimal DOAC prescriptive practice in older in-patients, with frequent missed prescription and DOAC underdosage. Contrary to current recommendations, physicians appear overly concerned by bleeding risk in real-life older and frailer subjects. Strategies should be developed to promote appropriate DOAC prescription in the hospital setting.

Short physical performance battery is not associated with falls and injurious falls in older persons: longitudinal data of the SCOPE project.

INTRODUCTION: Falls and fall-related injuries in older persons are a major public health problem. Our objective was to study the predictive value of the Short Physical Performance Battery (SPPB) in the cohort of the SCOPE project on falls, injurious falls, and possible difference of prediction between indoors and outdoors falls. METHODS: For this sub-study of the SCOPE project participants reporting no falls at baseline, and survey data on falls at the 12-month and 24-month follow-up were included. Participant´s characteristics were assessed during the baseline interview and medical examinations. Falls as well as injurious falls and fall circumstances were obtained self-reported. SPPB and its association with fallers vs. no fallers at 12 and at 24 months were studied with logistic regression models. RESULTS: The 1198 participants had a median age of 79 years (77-82), and a median SPPB of 10 (8-11), with a 52.5% of female. A total of 227 and 277 falls (12- and 24- month visits, respectively) were reported. In the crude model, the SPPB sum scores (p < 0.001) as well as most single item scores were significant different between fallers and non-fallers over time. However, the association was attenuated in models adjusted for age, sex, marital status, number of medications, quality of life, handgrip strength, and muscle mass [e.g., 12 months; OR 0.94 (0.87-1.02)]. While SPPB fails to differentiate between injurious and non-injurious falls (p = 0.48), a lower SPPB score was associated with falls at home (p < 0.01) after 24 months. CONCLUSION: SBPP was not able to significantly predict the risk of falling as well as experiencing an injurious fall. TRIAL REGISTRATION: This study was registered prospectively on 25th February 2016 at clinicaltrials.gov (NCT02691546).

Neuroinflammaging: A Tight Line Between Normal Aging and Age-Related Neurodegenerative Disorders.

Aging in the healthy brain is characterized by a low-grade, chronic, and sterile inflammatory process known as neuroinflammaging. This condition, mainly consisting in an up-regulation of the inflammatory response at the brain level, contributes to the pathogenesis of age-related neurodegenerative disorders. Development of this proinflammatory state involves the interaction between genetic and environmental factors, able to induce age-related epigenetic modifications. Indeed, the exposure to environmental compounds, drugs, and infections, can contribute to epigenetic modifications of DNA methylome, histone fold proteins, and nucleosome positioning, leading to epigenetic modulation of neuroinflammatory responses. Furthermore, some epigenetic modifiers, which combine and interact during the life course, can contribute to modeling of epigenome dynamics to sustain, or dampen the neuroinflammatory phenotype. The aim of this review is to summarize current knowledge about neuroinflammaging with a particular focus on epigenetic mechanisms underlying the onset and progression of neuroinflammatory cascades in the central nervous system; furthermore, we describe some diagnostic biomarkers that may contribute to increase diagnostic accuracy and help tailor therapeutic strategies in patients with neurodegenerative diseases.

Kidney function and other associated factors of sarcopenia in community-dwelling older adults: The SCOPE study.

AIM: Sarcopenia is associated with several factors and medical conditions among older adults, though previous research has shown limitations and inconsistencies, especially regarding chronic kidney disease (CKD). We investigated the clinical and laboratory variables associated with sarcopenia and severe sarcopenia in older adults, focusing on kidney function measures. METHODS: Data from community-dwelling adults aged ≥75 years participating in the SCOPE multicenter prospective cohort study were assessed cross-sectionally. Comprehensive geriatric assessment was conducted; sociodemographic and lifestyle factors, clinical variables and comorbidities, anthropometric and bioelectrical impedance analysis, blood and urine laboratory variables were collected. EWGSOP2 revised criteria were used to define sarcopenia and its severity. Estimated glomerular filtration rate (eGFR) was calculated using creatinine and non-creatinine-based equations, and CKD stages were defined accordingly. RESULTS: 1420 participants were included, prevalence of sarcopenia was 10.6 %, and 6 % had severe sarcopenia. Multivariate logistic regression analysis showed that age [OR =1.14; 95 %CI (1.09-1.19)], body mass index (BMI) [0.83 (0.79-0.88)], disability performing instrumental activities of daily living (IADL) [2.61 (1.69-4.06)], Mini Mental State Examination (MMSE) score <24 [2.75 (1.62-4.67)], osteoporosis [2.39 (1.55-3.67)], and stage 4 CKD defined by CKD-EPIBTP-B2M, a non-creatinine-based eGFR equation [2.88 (1.11-7.49)], were independently associated with sarcopenia; as were specifically with severe sarcopenia, with more pronounced associations. CONCLUSIONS: In community-dwelling older adults, sarcopenia is a relevant condition and is associated with severe CKD, older age, IADL, cognitive impairments, osteoporosis and low BMI. These factors should be assessed for proper identification and management of older patients with sarcopenia, and even more so with severe sarcopenia.