Predictors of hospital readmission rate in geriatric patients.

BACKGROUND: Hospital readmissions among older adults are associated with progressive functional worsening, increased institutionalization and mortality. AIM: Identify the main predictors of readmission in older adults. METHODS: We examined readmission predictors in 777 hospitalized subjects (mean age 84.40 ± 6.77 years) assessed with Comprehensive Geriatric Assessment (CGA), clinical, anthropometric and biochemical evaluations. Comorbidity burden was estimated by Charlson Comorbidity Index (CCI). Median follow-up was 365 days. RESULTS: 358 patients (46.1%) had a second admission within 365 days of discharge. Estimated probability of having a second admission was 0.119 (95%C.I. 0.095-0.141), 0.158 (95%C.I. 0.131-0.183), and 0.496 (95%C.I. 0.458-0.532) at 21, 30 and 356 days, respectively. Main predictors of readmission at 1 year were length of stay (LOS) > 14 days (p < 0.001), albumin level < 30 g/l (p 0.018), values of glomerular filtration rate (eGFR) < 40 ml/min (p < 0.001), systolic blood pressure < 115 mmHg (p < 0.001), CCI ≥ 6 (p < 0.001), and cardiovascular diagnoses. When the joint effects of selected prognostic variables were accounted for, LOS > 14 days, worse renal function, systolic blood pressure < 115 mmHg, higher comorbidity burden remained independently associated with higher readmission risk. DISCUSSION: Selected predictors are associated with higher readmission risk, and the relationship evolves with time. CONCLUSIONS: This study highlights the importance of performing an accurate CGA, since defined domains and variables contained in the CGA (i.e., LOS, lower albumin and systolic blood pressure, poor renal function, and greater comorbidity burden), when combined altogether, may offer a valid tool to identify the most fragile patients with clinical and functional impairment enhancing their risk of unplanned early and late readmission.

Myocardial Fibrosis and Steatosis in Patients with Aortic Stenosis: Roles of Myostatin and Ceramides.

Aortic stenosis (AS) involves progressive valve obstruction and a remodeling response of the left ventriculum (LV) with systolic and diastolic dysfunction. The roles of interstitial fibrosis and myocardial steatosis in LV dysfunction in AS have not been completely characterized. We enrolled 31 patients (19 women and 12 men) with severe AS undergoing elective aortic valve replacement. The subjects were clinically evaluated, and transthoracic echocardiography was performed pre-surgery. LV septal biopsies were obtained to assess fibrosis and apoptosis and fat deposition in myocytes (perilipin 5 (PLIN5)), or in the form of adipocytes within the heart (perilipin 1 (PLIN1)), the presence of ceramides and myostatin were assessed via immunohistochemistry. After BMI adjustment, we found a positive association between fibrosis and apoptotic cardiomyocytes, as well as fibrosis and the area covered by PLIN5. Apoptosis and PLIN5 were also significantly interrelated. LV fibrosis increased with a higher medium gradient (MG) and peak gradient (PG). Ceramides and myostatin levels were higher in patients within the higher MG and PG tertiles. In the linear regression analysis, increased fibrosis correlated with increased apoptosis and myostatin, independent from confounding factors. After adjustment for age and BMI, we found a positive relationship between PLIN5 and E/A and a negative correlation between septal S', global longitudinal strain (GLS), and fibrosis. Myostatin was inversely correlated with GLS and ejection fraction. Fibrosis and myocardial steatosis altogether contribute to ventricular dysfunction in severe AS. The association of myostatin and fibrosis with systolic dysfunction, as well as between myocardial steatosis and diastolic dysfunction, highlights potential therapeutic targets.

The Mini Sarcopenia Risk Assessment (MSRA) Questionnaire score as a predictor of skeletal muscle mass loss.

BACKGROUND: Previous studies showed a strong relationship between reduction of appendicular muscle mass and worsening disability; hence, accuracy in assessing muscle mass is considered a key feature for a sarcopenia screening tool. AIM: The aim of the study was to evaluate if the 7 items of Mini Sarcopenia Risk Assessment (MSRA) questionnaire predict muscle mass loss in a population of community-dwelling elderly subjects over a 5.5-y follow-up. METHODS: The study included 159 subjects, 92 women and 67 men aged 71.5 ± 2.2 years and with mean body mass index of 26.7 ± 4.0 kg/m2. Appendicular skeletal muscle mass (ASMM) as measured with Dual-Energy X-ray absorptiometry (DXA), was obtained at baseline and after 2 and 5.5 years of follow-up where the skeletal muscle index (SMI) was calculated. RESULTS: A significant reduction of ASMM and SMI was observed at two and 5.5 years of follow-up, in both, men and women. Repeated-measures analysis of variance (ANOVA) found a significant time effect on ASMM for both subjects with MSRA > 30 and ≤ 30 (P < 0.01 and P < 0.001). The group × time interaction was significant (P < 0.001), after even considering separately subjects with normal muscle mass and low muscle mass at baseline (P < 0.05 and P = 0.005). Similar results were obtained for SMI. Considering only the subjects with normal SMI at baseline, subjects with MSRA questionnaire ≤ 30 showed 5.7 (95% CI 1.73-19.03) higher risk of exceeding the low muscle mass threshold. CONCLUSION: In a population of community-dwelling elderly men and women, MSRA score of 30 is predictive of a steeper decline in ASMM and SMI and of a higher risk of exceeding the low muscle mass EWGSOP threshold.

Predictors of self-reported adherence to direct oral anticoagulation in a population of elderly men and women with non-valvular atrial fibrillation.

There is a general lack of studies evaluating medication adherence with self-report scales for elderly patients in treatment with direct oral anticoagulants (DOACs). The aim of the study was to assess the degree of adherence to DOAC therapy in a population of elderly outpatients aged 65 years or older affected by non-valvular atrial fibrillation (NVAF), using the 4-item Morisky Medication Adherence Scale, and to identify potential factors, including the geriatric multidimensional evaluation, which can affect adherence in the study population. A total of 103 subjects, anticoagulated with DOACs for NVAF in primary or secondary prevention, were eligible; 76 showed adequate adhesion to anticoagulant therapy, while 27 showed inadequate adherence. Participants underwent biochemical assessment and Morisky Scale, Instrumental Activities of Daily Living, CHA2DS2-VASc, HAS-BLED, mental status and nutritional evaluations were performed. 2% of subjects assumed Dabigatran at low dose, while 7.8% at standard dose, 9.7% assumed low-dose of Rivaroxaban and 30.1% at standard dose, 6.8% assumed Apixaban at low dose and 39.7% at standard dose, and finally 1% assumed Edoxaban at low dose and 2.9% at standard dose. Most subjects took the DOACs without help (80.6%), while 16 subjects were helped by a family member (15.5%) and 4 were assisted by a caregiver (3.9%). Binary logistic regression considered inappropriate adherence as a dependent variable, while age, male sex, polypharmacotherapy, cognitive decay, caregiver help for therapy assumption, duration of DOAC therapy and double daily administration were considered as independent variables. The double daily administration was an independent factor, determining inappropriate adherence with an OR of 2.88 (p = 0.048, CI 1.003-8.286).

LPS response pattern of inflammatory adipokines in an in vitro 3T3-L1 murine adipocyte model.

OBJECTIVE: In vitro 3T3-L1 mouse cells represent a reliable model to investigate the inflammatory phenotype of adipocytes activated by bacteria-derived lipopolysaccharide (LPS). In this study we have evaluated the differential expression of adipokines in response to increasing doses of LPS and various incubation times. METHODS: 3T3-L1 mouse adipocytes were treated with E. coli LPS (from 0 to 10 µg/ml) for a time course ranging from 4 to 24 h, 4 h each. A time point at 2 h was also included to highlight early activation by LPS. mRNA expression by RT-PCR on cell lysates and ELISA assays on cell culture supernatants were performed. RESULTS: Cells activated by increasing doses of LPS upregulated TNF-α expression in the first 2 h, but this expression slowed down within 6-8 h, while IL-6 expression was increasing. This reduction was also observed for CXCL12/SDF1α. Unlike IL-10, IL-6 expression was constantly upregulated by prolonging incubation with LPS. TNF-α and CXCL12 gene expression occurred early in the time-course and exhibited a second increase following the first 4-6 h of incubation with LPS. Optimal expression of most adipokines needed 6-8 h of a prolonged treatment with LPS at 37 °C. The chemokines MIP-1α/CCL3 and MIP-1ß/CCL4 were maximally expressed within the first 8 h, then significantly reduced in the following times. IL-10 expression was upregulated by low doses of LPS and downregulated by prolonging time with the bacterial endotoxin. ELISA analysis of released products generally confirmed the result from gene expression experiments. CONCLUSION: These data, while assessing previously reported results, highlighted new evidence about the time-dependency in LPS-mediated adipokine production, thus contributing to the comprehension of the inflammatory response of adipocyte.

Inflammatory profile in subcutaneous and epicardial adipose tissue in men with and without diabetes.

In recent years, evidence has emerged indicating that insulin resistance and diabetes mellitus type 2 are associated with inflammation of adipose tissue (AT). Interest has been focused on epicardial AT (EAT) because of its possible involvement with atherosclerosis and cardiovascular diseases. The aim of this study was to characterize adipocyte size and inflammatory profile in subcutaneous (SAT) and EAT among subjects with or without diabetes. Biopsies were collected from SAT and EAT in 34 men undergoing elective cardiac surgery. Weight, height, body mass index, waist circumference, as well as serum levels of glucose, insulin, lipids, adiponectin, and leptin were determined in all subjects. Adiponectin, MCP-1, and CD68 mRNA levels present within cells from AT biopsies were determined by real-time polymerase chain reaction. Adipocyte size was determined by optic microscopy and morphometry. Regarding the experimental group as a whole, gene-expression levels within EAT were significantly lower for adiponectin and higher, albeit not significantly, for MCP-1, when compared with that of SAT. In addition, adipocytes in EAT were significantly smaller than those in SAT. Subjects with diabetes showed lower adiponectin gene-expression levels in both SAT and EAT when compared with subjects without diabetes. By contrast, MCP-1 and CD68 gene-expression levels were higher in both tissue types of diabetic subjects. Adipocyte size in EAT was significantly larger in diabetic subjects than in nondiabetic subjects. Our data revealed a predominantly inflammatory profile in both SAT and EAT in subjects with diabetes in comparison with those without diabetes.

The Role of Ultrasound Muscle Parameters for Myosteatosis and Myofibrosis Measurement in Young, Older, and Obese Subjects.

OBJECTIVES: The aim of the study was to compare quantitative and qualitative ultrasound parameters between healthy young adults and post-acute hospitalized older adults with and without physical disability, as well as between normal weight and overweight/obese persons. DESIGN: Cross-sectional observational study. SETTING AND PARTICIPANTS: A total of 120 individuals were recruited: 24 healthy young adults, 24 normal weight and 24 overweight/obese community-dwelling adults, and 48 post-acute hospitalized older adults with different degrees of functional autonomy. METHODS: The rectus femoris cross-sectional area (CSA), subcutaneous adipose tissue (SCAT) thickness, echogenicity, strain elastography, and compressibility were measured with ultrasound echography. RESULTS: Post-acute older adults with a good level of autonomy showed higher echogenicity, a higher compressibility index and elastometry strain, and lower rectus femoris thickness and CSA as compared with young persons. Post-acute individuals with physical disability showed lower echogenicity and a greater stiffness compared with their still autonomous counterparts. Normal weight individuals showed lower stiffness as evaluated with elastometry and a lower SCAT thickness, as compared with individuals with age-matched overweight or obesity. From multiple regression analyses, using CSA as an independent variable, an inverse association with female sex and age was observed, explaining 16% and 51% of variance. Echogenicity was directly associated with age (34% of variance) and with the Barthel index (6% of variance). Elastometry showed association with age and body mass index (BMI), 30% and 16% of variance, respectively. Considering compressibility as a dependent variable, a direct association with age and an inverse association with BMI were observed, with 5% and 11% of variance respectively. CONCLUSIONS AND IMPLICATIONS: Muscle mass decreases with age and with physical disability. Echogenicity, which increases with age and disability level, seems to be associated with myofibrosis. Conversely, elastometry seems useful in the characterization of muscle quality in overweight or obese individuals and as a reliable indirect measure of myosteatosis.

Arterial stiffness and cardiovascular risk in patients with nephrolithiasis: a 10-year prospective study.

BACKGROUND: Nephrolithiasis is frequently associated with cardiovascular diseases. These conditions present common risk factors: systemic inflammation that promotes oxidative stress leading to arterial wall stiffening may also play a role in plaque formation predisposing to nephrolithiasis. OBJECTIVES: The aim of this study was to evaluate arterial stiffness indices at baseline and after a 10-year follow-up, in patients with nephrolithiasis compared with patients without. METHODS: A total of 82 patients (37 men; mean age 45 ±â€Š13 years) were enrolled at the Geriatrics and Nephrology Outpatient Clinic: 66 were diagnosed with nephrolithiasis, whereas the control group consisted of 16 individuals. At baseline and after 10 years, they underwent clinical evaluation and arterial stiffness measurement, such as carotid-femoral pulse wave velocity (CF-PWV), by arterial applanation tonometry. RESULTS: At baseline, when compared with the control group, patients with nephrolithiasis showed higher SBP and CF-PWV. After 10 years, patients with nephrolithiasis, but not those without, showed a significant raise in CF-PWV, even after adjustment for age and sex. In a stepwise regression model, with CF-PWV changes during the follow-up as the dependent variable, and age, sex, follow-up years, Δ mean arterial pressure, BMI, hypertension and nephrolithiasis as independent variables, nephrolithiasis was proved to be the only significant predictor of ΔCF-PWV, accounting for 6% of the variance. CONCLUSION: Our study shows higher baseline CF-PWV and greater increase in ΔCF-PWV within 10 years in individuals with nephrolithiasis than in those without, demonstrating an increased cardiovascular risk for nephrolithiasis patients.

Sarcopenia, sarcopenic obesity, and arterial stiffness among older adults.

Background: Aging is associated with a higher prevalence of sarcopenia, sarcopenic obesity (SO), and increased arterial stiffening, with possible detrimental effects on morbidity and mortality. The aim of this study was to assess the relationships between sarcopenia, SO, and different indexes of arterial stiffness in older adults. Methods: A total of 77 hospitalized patients (mean age 78.68 ± 9.65 years) were evaluated, obtaining anthropometric variables, biochemical samples, handgrip test, and body composition assessment. Arterial stiffness was evaluated by measuring both carotid-femoral pulse wave velocity (cfPWV), a proxy for central stiffness, and cardio-ankle vascular index (CAVI), as well as considering peripheral arteries. The population was sorted into four subgroups: obese, sarcopenic, SO, and controls. Results: The highest CAVI (11.31 ± 2.58) was found in sarcopenic patients. SO had the highest value of cfPWV (15.18 ± 8.44 m/s), even after adjustment for significant covariates. In multiple regressions, SO diagnosis resulted as a significant predictor of cfPWV (p = 0.03, R2 = 0.20), and sarcopenia diagnosis resulted as a predictor of CAVI (p = 0.042, R2 = 0.12). Conclusions: In conclusion, a positive correlation is found between sarcopenia, SO, and arterial stiffness among older subjects. In particular, greater central arterial stiffness is associated with SO, outlining a remarkable effect on the cardiovascular risk profile.

Cardio-Ankle Vascular Index and Aging: Differences between CAVI and CAVI0.

BACKGROUND: Cardio-ankle vascular index (CAVI) and CAVI0 (a mathematical expression derived from CAVI, supposed to be less dependent on blood pressure), can describe arterial stiffness, considering a wide proportion of the arterial tree. The aim of this study was to examine the relationship between CAVI, CAVI0 and aging, looking at the differences between the two arterial stiffness indexes. METHODS: A total of 191 patients (68 male, mean age 68.3 ± 14.4 years) referred to the Geriatric Ward and Outpatient Clinic at Verona University Hospital were included and underwent a comprehensive clinical evaluation. CAVI and CAVI0 were obtained for each. RESULTS: CAVI0 steeply rises in the elderly age strata, widening the gap between CAVI and CAVI0. An inverse relationship is evident between CAVI0 and DBP in older patients, and CAVI0 is shown to be dependent on age, DBP and age-DBP interaction (R2 = 0.508). Age modifies the effect of DBP on CAVI0, but not on CAVI. CONCLUSIONS: The real new findings of our study are that the association between CAVI0 and diastolic blood pressure (DBP) is modified by age, whereas the association between CAVI and DBP is not modified by age. From a clinical point of view, these are very important findings, as DBP decreases with aging, affecting in elderly populations the reliability of CAVI0, which strictly depends on DBP in the formula to calculate it. To monitor the effect of CV therapies, progression of CV diseases and to evaluate clinical outcomes in elderly populations, we suggest using CAVI and not CAVI0.

Senescent adipocytes as potential effectors of muscle cells dysfunction: An in vitro model.

Recently, there has been a growing body of evidence showing a negative effect of the white adipose tissue (WAT) dysfunction on the skeletal muscle function and quality. However, little is known about the effects of senescent adipocytes on muscle cells. Therefore, to explore potential mechanisms involved in age-related loss of muscle mass and function, we performed an in vitro experiment using conditioned medium obtained from cultures of mature and aged 3 T3-L1 adipocytes, as well as from cultures of dysfunctional adipocytes exposed to oxidative stress or high insulin doses, to treat C2C12 myocytes. The results from morphological measures indicated a significant decrease in diameter and fusion index of myotubes after treatment with medium of aged or stressed adipocytes. Aged and stressed adipocytes presented different morphological characteristics as well as a different gene expression profile of proinflammatory cytokines and ROS production. In myocytes treated with different adipocytes' conditioned media, we demonstrated a significant reduction of gene expression of myogenic differentiation markers as well as a significant increase of genes involved in atrophy. Finally, a significant reduction in protein synthesis as well as a significant increase of myostatin was found in muscle cells treated with medium of aged or stressed adipocytes compared to controls. In conclusion, these preliminary results suggest that aged adipocytes could influence negatively trophism, function and regenerative capacity of myocytes by a paracrine network of signaling.

The Role of Crosstalk between Adipose Cells and Myocytes in the Pathogenesis of Sarcopenic Obesity in the Elderly.

As a result of aging, body composition changes, with a decline in muscle mass and an increase in adipose tissue (AT), which reallocates from subcutaneous to visceral depots and stores ectopically in the liver, heart and muscles. Furthermore, with aging, muscle and AT, both of which have recognized endocrine activity, become dysfunctional and contribute, in the case of positive energy balance, to the development of sarcopenic obesity (SO). SO is defined as the co-existence of excess adiposity and low muscle mass and function, and its prevalence increases with age. SO is strongly associated with greater morbidity and mortality. The pathogenesis of SO is complex and multifactorial. This review focuses mainly on the role of crosstalk between age-related dysfunctional adipose and muscle cells as one of the mechanisms leading to SO. A better understanding of this mechanisms may be useful for development of prevention strategies and treatments aimed at reducing the occurrence of SO.

The Correlation of Arterial Stiffness Parameters with Aging and Comorbidity Burden.

The aim of the study was to evaluate the relationships between carotid-femoral pulse wave velocity (PVW-cf), cardio-ankle vascular index (CAVI) and CAVI0 (which is a mathematical elaboration of CAVI, theoretically less dependent on blood pressure), age and comorbidity burden. Furthermore, 183 patients (119 female, mean age 67.5 ± 14.3 years) referred to the Geriatric Ward and Outpatient Clinic at Verona University Hospital were included; demographic, clinical and blood analysis data were collected. Charlson Comorbidity Index (CCI), PVW-cf, CAVI and CAVI 0 were obtained. Significant correlations were found between CAVI, CAVI0, PVW-cf and both age (r = 0.698, r = 0.717, r = 0.410, respectively p < 0.001 for all) and CCI, (r = 0.654; r = 0.658; r = 0.448 respectively and p < 0.001 for all), still significant after adjustment for several variables. In a stepwise multiple regression model, considering several variables, CCI was the only predictor of PWV-cf, whereas age and CCI were significant predictors of both CAVI and CAVI 0. In conclusion, all arterial stiffness indexes are associated with CCI and aging; the latter correlation is more evident for CAVI and CAVI 0 than for PVW-cf. Arterial stiffness parameters can complement the characterization of patients affected by a remarkable comorbidity burden across aging; arterial stiffening might mirror the complexity of these individuals.

Arterial Stiffness, Subendocardial Impairment, and 30-Day Readmission in Heart Failure Older Patients.

Arterial stiffness and subendocardial perfusion impairment may play a significant role in heart failure (HF) outcomes. The aim of the study was to examine the main predictors of 30-day readmission in geriatric patients, hospitalized with HF, explore hemodynamical parameters, arterial stiffness indexes, and subendocardial viability ratio (SEVR). In total, 41 hospitalized patients, affected by HF, were included; they underwent clinical evaluation, routine laboratory testing, and echocardiography. At the time of admission, after the achievement of clinical stability (defined as switching from intravenous to oral diuretic therapy), and at discharge, arterial tonometry was performed to evaluate carotid-femoral pulse wave velocity (PWVcf) and SEVR (then corrected for hemoglobin concentration and oxygen saturation). Through the evaluations, a significant progressive decrease in PWVcf was described (17.79 ± 4.49, 13.54 ± 4.54, and 9.94 ± 3.73 m/s), even after adjustment for age, gender, mean arterial pressure (MAP) variation, and left ventricular ejection fraction (LVEF). A significant improvement was registered for both SEVR (83.48 ± 24.43, 97.94 ± 26.84, and 113.29 ± 38.02) and corrected SEVR (12.74 ± 4.69, 15.71 ± 5.30, and 18.55 ± 6.66) values, and it was still significant when adjusted for age, gender, MAP variation, and LVEF. After discharge, 26.8% of patients were readmitted within 30 days. In a multivariate binary logistic regression analysis, PWVcf at discharge was the only predictor of 30-day readmission (odds ratio [OR] 1.957, 95% CI 1.112-3.443). In conclusion, medical therapy seems to improve arterial stiffness and subendocardial perfusion in geriatric patients hospitalized with heart failure. Furthermore, PWVcf is a valid predictor of 30-day readmission. Its feasibility in clinical practice may provide an instrument to detect patients with HF at high risk of rehospitalization.

How does adipose tissue contribute to inflammageing?

Across aging, white adipose tissue (WAT) undergoes significant changes in quantity and distribution, with an increase in visceral adipose tissue, ectopic fat deposition and a decline in gluteofemoral subcutaneous depot. In particular, WAT becomes dysfunctional with an increase in production of inflammatory peptides and a decline of those with anti-inflammatory activity and infiltration of inflammatory cells. Moreover, dysfunction of WAT is characterized by preadipocyte differentiation decline, increased oxidative stress and mitochondrial dysfunction, reduction in vascularization and hypoxia, increased fibrosis and senescent cell accumulation. WAT changes represent an important hallmark of the aging process and may be responsible for the systemic pro-inflammatory state ("inflammageing") typical of aging itself, leading to age-related metabolic alterations. This review focuses on mechanisms linking age-related WAT changes to inflammageing.

Impaired subendocardial perfusion in patients with metabolic syndrome.

BACKGROUND: Metabolic Syndrome (MS) is associated to vascular damage, increased arterial stiffness, and impaired myocardial perfusion. Subendocardial viability ratio (SEVR) is a noninvasive estimation of myocardial workload, oxygen supply, and perfusion. The aim of the study was to describe the relation between arterial stiffness, SEVR, and cardio-metabolic risk factors. METHODS: A cohort of 55 patients, aged 59.9 ± 10.8 years, was studied; 28 subjects (50.9%) had metabolic syndrome. All patients underwent a clinical evaluation and blood venous sampling, to assess glico-lipid profile. Applanation tonometry was performed, to obtain pulse wave analysis and SEVR values. RESULTS: In the overall study population, SEVR showed negative associations with mean (r = -0.301; p = 0.026) and systolic (borderline relation, r = -0.257; p = 0.058) arterial pressure. Metabolic syndrome patients presented lower level of SEVR (p = 0.012), even after adjusting for age, sex, and mean arterial pressure (p = 0.040). Subdividing the study population by the number of metabolic syndrome components, SEVR significantly decreased as the number of Metabolic Syndrome components increased (p for trend 0.005). In a logistic backward regression analysis, both metabolic syndrome and mean arterial pressure resulted significant predictors of SEVR, accounting for 18% of variance. CONCLUSION: The reduced SEVR in metabolic syndrome patients could be an important pathophysiological determinant of the increased cardiovascular risk.

Relationships between subendocardial perfusion impairment, arterial stiffness and orthostatic hypotension in hospitalized elderly individuals.

BACKGROUND: Orthostatic hypotension is an independent risk factor for cardiovascular morbidity and mortality. Arterial stiffness has been shown to be a pathophysiological mechanism linking orthostatic hypotension and increased cardiovascular risk. This study aims to evaluate the relationship between arterial stiffness, orthostatic hypotension and subendocardial viability ratio (SEVR) and moreover to identify the main predictors of orthostatic hypotension, carotid-femoral pulse wave velocity (PWV-cf) and SEVR. METHODS: Seventy-five patients were enrolled (mean age 82.95 ±â€Š6.45) in Verona's AOUI Geriatric ward. They underwent blood pressure, heart rate, body weight measurements and also comorbidity, arterial stiffness (PWV-cf measured by applanation tonometry), SEVR and biochemical indexes. RESULTS: Prevalence of orthostatic hypotension was 46.6%. Even after adjustment for age, sex, glomerular filtration rate and mean arterial pressure, SEVR values corrected for arterial oxygen and haemoglobin content were statistically lower in orthostatic hypotension patients (P = 0.05) and PWV-cf values were statistically higher in orthostatic hypotension individuals (P = 0.042). In a binary logistic regression, PWV-cf was the only significant predictor of orthostatic hypotension (odds ratio 1.123; P = 0.039; confidence interval = 1.006--1.17).In a backward logistic regression model sex, creatinine clearance and orthostatic hypotension were significant predictors of SEVR corrected for O2 content. Mean arterial pressure, creatinine clearance and orthostatic hypotension were significant predictors of PWV-cf. CONCLUSION: This study shows that orthostatic hypotension is related to increased arterial stiffness, confirming its higher prevalence in elderly patients. Orthostatic hypotension was also associated with reduced values of corrected SEVR, showing a relevant consequence of orthostatic hypotension on subendocardial perfusion impairment.

Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence.

The dysfunction of adipose tissue with aging and the accumulation of senescent cells has been implicated in the pathophysiology of chronic diseases. Recently interventions capable of reducing the burden of senescent cells and in particular the identification of a new class of drugs termed senolytics have been object of extensive investigation. We used an in vitro model of induced senescence by treating both pre-adipocytes as well as mature adipocytes with hydrogen peroxide (H2O2) at a sub-lethal concentration for 3 h for three consecutive days, and hereafter with 20 uM quercetin at a dose that in preliminary experiments resulted to be senolytic without cytotoxicity. H2O2 treated pre-adipocytes and adipocytes showed typical senescence-associated features including increased beta-galactosidase activity (SA-ß-gal) and p21, activation of ROS and increased expression of pro-inflammatory cytokines. The treatment with quercetin in senescent pre-adipocytes and adipocytes was associated to a significant decrease in the number of the SA-ß-gal positive cells along with the suppression of ROS and of inflammatory cytokines. Besides, quercetin treatment decreased miR-155-5p expression in both models, with down-regulation of p65 and a trend toward an up-regulation of SIRT-1 in complete cell extracts. The senolytic compound quercetin could affect AT ageing by reducing senescence, induced in our in vitro model by oxidative stress. The downregulation of miRNA-155-5p, possibly through the modulation of NF-κB and SIRT-1, could have a key role in the effects of quercetin on both pre-adipocytes and adipocytes.

Sarcopenia Risk Evaluation in a Sample of Hospitalized Elderly Men and Women: Combined Use of the Mini Sarcopenia Risk Assessment (MSRA) and the SARC-F.

BACKGROUND: SARC-F and Mini Sarcopenia Risk Assessment (MSRA) questionnaires have been proposed as screening tools to identify patients at risk of sarcopenia. The aim of this study is to test the use of SARC-F and MSRA, alone and combined, as a pre-screening tool for sarcopenia in geriatric inpatients. METHODS: 152 subjects, 94 men and 58 women, aged 70 to 94, underwent muscle mass evaluation by dual energy X-ray absorptiometry (DXA), muscle strength evaluation by handgrip, and completed the MSRA, SARC-F and Activity of daily living (ADL) questionnaires. RESULTS: 66 subjects (43.4%) were classified as sarcopenic according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. The 7-item SARC-F and MRSA and 5-item MSRA showed an area under the curve (AUC) of 0.666 (95% confidence interval (CI): 0.542-0.789), 0.730 (95% CI: 0.617-0.842) and 0.710 (95% CI: 0.593-0.827), respectively. The optimal cut-off points for sarcopenia detection were determined for each questionnaire using the Youden index method. The newly calculated cut-off points were ≤25 and ≤40 for MSRA 7- and 5-items, respectively. The ideal cut-off for the SARC-F was a score ≥3. Applying this new cut-off in our study population, sensitivity and specificity of the 7-item MSRA were 0.757 and 0.651, and 0.688 and 0.679 for the 5-item MSRA, respectively. Sensitivity and specificity of SARC-F were 0.524 and 0.765, respectively. The combined use of the 7-item SARC-F and MSRA improved the accuracy in sarcopenia diagnosis, with a specificity and sensitivity of 1.00 and 0.636. CONCLUSION: 7-item SARC-F and MSRA may be co-administered in hospital wards as an easy, feasible, first-line tool to identify sarcopenic subjects.

In vitro aging of 3T3-L1 mouse adipocytes leads to altered metabolism and response to inflammation.

We used an in vitro model to evaluate the effects of cellular aging and inflammation on the gene expression and protein secretion profiles of adipocytes. 3T3-L1 mouse preadipocytes were cultured according to standard conditions and analyzed at different time points both at the basal state and after an acute stimulation with LPS. The mRNA levels of CCAAT/enhancer-binding protein (C/EBP)alpha, peroxisome proliferator-activated receptor (PPAR)gamma and S100A1 were maximal during adipocyte differentiation and then significantly decreased. The expression of the GLUT4 and IRS-1 genes peaked during differentiation and then decreased in aged cells. The mRNA levels and secretion of adiponectin, quickly rose as adipocytes matured and then declined. The mRNA levels of IL6, as well as its secretion, increased as preadipocytes matured and became old cells; a similar trend was also found for MCP-1. LPS decreased the mRNA levels of C/EBPalpha and PPARgamma at all time points, as well as those of GLUT4, IRS-1 and adiponectin. LPS significantly increased the mRNA levels of IL-6, as well as its secretion, with a similar trend also observed for MCP-1. These data suggest that aging adipocytes in vitro show a decline in pro-adipogenic signals, in genes involved in glucose metabolism and cytoskeleton maintenance and in adiponectin. These changes are paralleled by an increase in inflammatory cytokines; inflammation seems to mimic and amplify the effects of cellular aging on adipocytes.