Natural Course of Aortic Stenosis in Older Subjects: Effects of COVID-19

Objective: Both aortic stenosis (AS) and COVID-19 affect the morbidity and mortality burden among older adults. The aim of the study was to examine whether aortic stenosis (AS) affects the prognosis after SARS-CoV-2 infection and whether COVID-19 affects AS prognosis, in a cohort of older adults hospitalized with and without COVID-19. Design: Observational study. Setting and participants: Patients admitted to 9 geriatric clinics in Stockholm from March 2020 to November 2021. Methods: AS and COVID-19 diagnoses were identified by electronic health records; the outcomes were mortality at 30 days and any time during a median follow-up of 630 days. The associations between AS, COVID-19, and mortality were assessed by using Royston-Parmar models adjusting for age, sex, comorbidities, and admission waves. Results: Among 28,974 patients, 85 had concomitant AS and COVID-19, 529 had only AS, and 5033 had only COVID-19. Both at 30 days and at any time, as compared to patients without, concomitant AS and COVID-19 subjects had a higher mortality rate (438.4 per 100 py, 95% CI 296.2-648.8, and 72.9, 95% CI 53.7-99.0, respectively) and a higher death risk (adjusted HR 5.5, 95% CI 3.7-8.2; and 2.8, 95% CI 2.1-3.9). AS patients presented increased mortality HR both in the presence and absence of COVID-19 at 30 days (1.6, 95% CI 1.1-2.4; and 1.6, 95% CI 1.2-2.2, respectively) and at any time (1.6, 95% CI 1.1-2.1; 1.4, 95% CI 1.2-1.7, respectively). Conclusions and implications: AS was a significant mortality risk factor, independent of concomitant COVID-19. Careful AS management should always be pursued, even in acute and post-acute phases of COVID-19

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

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

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

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

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 Combined Muscle Ultrasound and Bioimpedentiometry Parameters for Sarcopenia Diagnosis in a Population of Hospitalized Older Adults

Background: For the study of quantitative and qualitative muscle parameters, ultrasound and bioelectric impedance analysis are reliable, non-invasive, and reproducible. The aim of this study was to test the combined role of those techniques for the diagnosis of sarcopenia in a population of hospitalized older males and females. Methods: A total of 70 subjects were recruited, including 10 healthy adults and 60 hospitalized elderly patients with a good level of independence and cooperation, with and without sarcopenia. The rectus femoris cross-sectional area (CSA), thickness, echogenicity, and compressibility were measured with ultrasound echography. The phase angles (PhAs) and skeletal muscle mass were calculated by bioimpedence analysis. The muscle quality index (MQI) was calculated as the product of CSA and PhA. Results: Muscle compressibility was greater and PhA was lower in sarcopenic when compared with non-sarcopenic subjects. The threshold values for sarcopenia diagnosis in both sexes of CSA, of PhA, and of the MQI were identified. The obtained CSA values showed an AUC of 0.852 for women and 0.867 for men, PhA of 0.792 in women and 0.898 in men, while MQI was 0.900 for women and 0.969 for men. Conclusions: The newly calculated cut-off values of CSA, PhA, and MQI predicted the presence of sarcopenia with good sensitivity and specificity values. The use of the MQI proved to be more promising than the separate use of CSA and PhA in both male and female subjects

Kawasaki disease : an epidemiological study in central Italy

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis with an acute and self-limited course. The incidence of KD differs widely among ethnic groups and is higher in the Asian population. In Italy, no recent data are available. Our purpose is to define the epidemiology of Kawasaki disease in the years 2008-2013 in children aged\u2009<\u200914 years in the Italian regions of Tuscany and Emilia Romagna through administrative data. METHODS: We studied the epidemiology of KD in the years 2008-2013 in children 0-14 years old resident in Tuscany and in Emilia Romagna regions using hospital ICD-9 discharge codes with a thorough data cleaning for duplicates. RESULTS: The distribution of the KD patients across ages was similar for the two regions with a peak in the second year of life. When considering data of the two regions together, the rate of incidence was 17.6 for 100,000 children under 5 years. For both Regions the incidence rose slightly during the study period and had a seasonal distribution, with higher incidence in spring and winter. CONCLUSION: This is the first Italian study performed through the use of administrative data. Figures are in line but slightly higher than those published in other European countries

Neurological manifestations of Kawasaki disease and multisystem inflammatory syndrome in children associated with COVID-19: A comparison of two different clinical entities

Kawasaki disease (KD) is one of the most frequent idiopathic vasculitis in children, affecting medium- and small-sized vessels. Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has recently emerged as a new systemic hyperinflammatory condition affecting children some weeks after an acute COVID-19 infection. KD and MIS-C share different aspects and differ in many others: patients affected by MIS-C are usually older, with prominent gastrointestinal manifestations, diffuse adenopathy, extensive conjunctivitis, myocardial damage, leukopenia, and thrombocytopenia at the laboratory exams. Both conditions can present neurological complications. The aim of this manuscript is to provide a narrative review of neurological involvement in KD and MIS-C. A comprehensive review literature has been performed, and the main clinical features have been analyzed, contributing to neurological differential diagnosi