MiR-422a promotes adipogenesis via MeCP2 downregulation in human bone marrow mesenchymal stem cells.

Methyl-CpG binding protein 2 (MeCP2) is a ubiquitous transcriptional regulator. The study of this protein has been mainly focused on the central nervous system because alterations of its expression are associated with neurological disorders such as Rett syndrome. However, young patients with Rett syndrome also suffer from osteoporosis, suggesting a role of MeCP2 in the differentiation of human bone marrow mesenchymal stromal cells (hBMSCs), the precursors of osteoblasts and adipocytes. Here, we report an in vitro downregulation of MeCP2 in hBMSCs undergoing adipogenic differentiation (AD) and in adipocytes of human and rat bone marrow tissue samples. This modulation does not depend on MeCP2 DNA methylation nor on mRNA levels but on differentially expressed miRNAs during AD. MiRNA profiling revealed that miR-422a and miR-483-5p are upregulated in hBMSC-derived adipocytes compared to their precursors. MiR-483-5p, but not miR-422a, is also up-regulated in hBMSC-derived osteoblasts, suggesting a specific role of the latter in the adipogenic process. Experimental modulation of intracellular levels of miR-422a and miR-483-5p affected MeCP2 expression through direct interaction with its 3' UTR elements, and the adipogenic process. Accordingly, the knockdown of MeCP2 in hBMSCs through MeCP2-targeting shRNA lentiviral vectors increased the levels of adipogenesis-related genes. Finally, since adipocytes released a higher amount of miR-422a in culture medium compared to hBMSCs we analyzed the levels of circulating miR-422a in patients with osteoporosis-a condition characterized by increased marrow adiposity-demonstrating that its levels are negatively correlated with T- and Z-scores. Overall, our findings suggest that miR-422a has a role in hBMSC adipogenesis by downregulating MeCP2 and its circulating levels are associated with bone mass loss in primary osteoporosis.

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.

Possible Role of Tauroursodeoxycholic Acid (TUDCA) and Antibiotic Administration in Modulating Human Gut Microbiota in Home Enteral Nutrition Therapy for the Elderly: A Case Report.

Tauroursodeoxycholic acid (TUDCA) increases the influx of primary bile acids into the gut. Results obtained on animal models suggested that Firmicutes and Proteobacteria phyla are more resistant to bile acids in rats. As part of a pilot study investigating the role of probiotics supplementation in elderly people with home enteral nutrition (HEN), a case of a 92-year-old woman with HEN is reported in the present study. She lives in a nursing home and suffers from Alzheimer's disease (AD); the patient had been prescribed TUDCA for lithiasis cholangitis. The aim of this case report is therefore to investigate whether long-term TUDCA administration may play a role in altering the patient's gut microbiota (GM) and the impact of an antibiotic therapy on the diversity of microbial species. Using next generation sequencing (NGS) analysis of the bacterial 16S ribosomal RNA (rRNA) gene a dominant shift toward Firmicutes and a remodeling in Proteobacteria abundance was observed in the woman's gut microbiota. Considering the patient's age, health status and type of diet, we would have expected to find a GM with a prevalence of Bacteroidetes phylum. This represents the first study investigating the possible TUDCA's effect on human GM.

Neutrophil-to-lymphocyte ratio (NLR) predicts mortality in hospitalized geriatric patients independent of the admission diagnosis: a multicenter prospective cohort study.

BACKGROUND: The Neutrophil-to-lymphocyte ratio (NLR) is a marker of poor prognosis in hospitalized older patients with different diseases, but there is still no consensus on the optimal cut-off value to identify older patients at high-risk of in-hospital mortality. Therefore, in this study we aimed at both validating NLR as a predictor of death in older hospitalized patients and assess whether the presence of specific acute diseases can modify its predictive value. METHODS: This prospective cohort study included 5034 hospitalizations of older patients admitted to acute care units in the context of the ReportAge study. NLR measured at admission was considered as the exposure variable, while in-hospital mortality was the outcome of the study. ROC curves with Youden's method and restricted cubic splines were used to identify the optimal NLR cut-off of increased risk. Cox proportional hazard models, stratified analyses, and Kaplan-Meier survival curves were used to analyse the association between NLR and in-hospital mortality. RESULTS: Both continuous and categorical NLR value (cut-off ≥ 7.95) predicted mortality in bivariate and multivariate prognostic models with a good predictive accuracy. The magnitude of this association was even higher in patients without sepsis, congestive heart failure, and pneumonia, and those with higher eGFR, albumin, and hemoglobin (p < 0.001). A negative multiplicative interaction was found between NLR and eGFR < 45 (p = 0.001). CONCLUSIONS: NLR at admission is a readily available and cost-effective biomarker that could improve identification of geriatric patients at high risk of death during hospital stay independent of admitting diagnosis, kidney function and hemoglobin levels.

Technologies for frailty, comorbidity, and multimorbidity in older adults: a systematic review of research designs.

BACKGROUND: Frailty, neurodegeneration and geriatric syndromes cause a significant impact at the clinical, social, and economic level, mainly in the context of the aging world. Recently, Information and Communication Technologies (ICTs), virtual reality tools, and machine learning models have been increasingly applied to the care of older patients to improve diagnosis, prognosis, and interventions. However, so far, the methodological limitations of studies in this field have prevented to generalize data to real-word. This review systematically overviews the research designs used by studies applying technologies for the assessment and treatment of aging-related syndromes in older people. METHODS: Following the PRISMA guidelines, records from PubMed, EMBASE, and Web of Science were systematically screened to select original articles in which interventional or observational designs were used to study technologies' applications in samples of frail, comorbid, or multimorbid patients. RESULTS: Thirty-four articles met the inclusion criteria. Most of the studies used diagnostic accuracy designs to test assessment procedures or retrospective cohort designs to build predictive models. A minority were randomized or non-randomized interventional studies. Quality evaluation revealed a high risk of bias for observational studies, while a low risk of bias for interventional studies. CONCLUSIONS: The majority of the reviewed articles use an observational design mainly to study diagnostic procedures and suffer from a high risk of bias. The scarce presence of methodologically robust interventional studies may suggest that the field is in its infancy. Methodological considerations will be presented on how to standardize procedures and research quality in this field.

Blood circulating bacterial DNA in hospitalized old COVID-19 patients.

BACKGROUND: Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. RESULTS: BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65-99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. CONCLUSIONS: The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.

Diabetes and factors associated with cognitive and functional decline. The screening for CKD among older people across Europe (SCOPE) study.

BACKGROUND: Type 2 diabetes mellitus (DM) in older people is a heterogeneous condition that exhibits differential characteristics in comparison with younger adults. DM increases the risk of disability, is associated with dementia and loss of function, and cognition may often be interrelated and more pronounced in older patients with DM than in those without. AIMS: Our aim was to evaluate the incidence of functional and/or cognitive impairment in older adults with and without DM, and its associated factors in DM participants. METHODS: A 2-year prospective analysis was conducted in a European multicenter prospective cohort (SCOPE study). Older community-dwelling adults (aged ≥ 75 years) underwent a comprehensive geriatric assessment. New functional and/or cognitive decline was explored. RESULTS: Of 1611 participants, 335 (22.0%) had DM at baseline. The percentage of participants scoring at least one ADL impairment and/or cognitive impairment (MMSE < 24) was similar in both groups (9.6%). Factors associated with any new disability in participants with DM in the multivariate analysis were female sex (OR 3.28, 95% CI 1.42-7.56), history of stroke (OR 4.58, 95% CI 1.64-12.7), and greater IADL dependency (OR 1.08 95% CI 1.02-1.15). DISCUSSION: Association between DM and cognitive or functional decline in outpatients of 75 years and older was not found, but factors such as female gender, history of stroke, and IADL dependency could be related. CONCLUSION: Decline in functional and cognitive status of community-dwelling older adults with DM was similar to participants without DM in a short period of 2 years of follow-up, though several clinical factors may increase its risk in this population.

Effect of Cytomegalovirus Reactivation on Inflammatory Status and Mortality of Older COVID-19 Patients.

Herpesviridae reactivation such as cytomegalovirus (CMV) has been described in severe COVID-19 (COronaVIrusDisease-2019). This study aimed to understand if CMV reactivation in older COVID-19 patients is associated with increased inflammation and in-hospital mortality. In an observational single-center cohort study, 156 geriatric COVID-19 patients were screened for CMV reactivation by RT-PCR. Participants underwent a comprehensive clinical investigation that included medical history, functional evaluation, laboratory tests and cytokine assays (TNF-α, IFN-α, IL-6, IL-10) at hospital admission. In 19 (12.2%) of 156 COVID-19 patients, CMV reactivation was detected. Multivariate Cox regression models showed that in-hospital mortality significantly increased among CMV positive patients younger than 87 years (HR: 9.94, 95% CI: 1.66-59.50). Other factors associated with in-hospital mortality were C-reactive protein (HR: 1.17, 95% CI: 1.05-1.30), neutrophil count (HR: 1.20, 95% CI: 1.01-1.42) and clinical frailty scale (HR:1.54, 95% CI: 1.04-2.28). In patients older than 87 years, neutrophil count (HR: 1.13, 95% CI: 1.05-1.21) and age (HR: 1.15, 95% CI: 1.01-1.31) were independently associated with in-hospital mortality. CMV reactivation was also correlated with increased IFN-α and TNF-α serum levels, but not with IL-6 and IL-10 serum changes. In conclusion, CMV reactivation was an independent risk factor for in-hospital mortality in COVID-19 patients younger than 87 years old, but not in nonagenarians.

Long-term changes in pulmonary function among patients surviving to COVID-19 pneumonia.

PURPOSE: The aim of this study was to assess respiratory function at the time of clinical recovery, 6 weeks, 6 months, and 12 months after discharge in patients surviving to COVID-19 pneumonia. METHODS: Our case series consisted of 13 hospitalized patients with COVID-19 pneumonia. RESULTS: Baseline pulmonary function tests were 55.7 ± 15.6 for FEV1%, 68.6 ± 16.0 for FVC%, and 1.2 ± 0.1 for FEV1/FVC%. Although pulmonary function showed a small improvement after 6 weeks, patients experienced a more significant improvement after 6 and 12 months in FEV1% (95.4 ± 13.7 and 107.2 ± 16.5, respectively; p < 0.001), FVC% (91.3 ± 14.5, and 105.9 ± 15.6, respectively; p < 0.001), and FEV1/FVC% values (1.04 ± 0.04, and 1.01 ± 0.05, respectively; p < 0.001). CONCLUSION: COVID-19 pneumonia may result in significant alterations in lung function, with a mainly restrictive pattern, partly persisting at 6 weeks after recovery from acute phase, but significantly improving during a 12-month follow-up period.

The relevance of geriatric assessments on the association between chronic kidney disease stages and mortality among older people: a secondary analysis of a multicentre cohort study.

BACKGROUND: age-adapted definition of chronic kidney disease (CKD) does not take individual risk factors into account. We aimed at investigating whether functional impairments influence CKD stage at which mortality increases among older people. METHODS: our series consisted of 2,372 outpatients aged 75 years or more enrolled in a multicentre international prospective cohort study. The study outcome was 24-month mortality. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Geriatric assessments included handgrip strength, short physical performance battery (SPPB), cognitive impairment, dependency in basic activities of daily living (BADL) and risk of malnutrition. Analysis was carried out by Cox regression, before and after stratification by individual functional impairments. Survival trees including kidney function and functional impairments were also investigated, and their predictivity assessed by C-index. RESULTS: overall, mortality was found to increase starting from eGFR = 30-44.9 ml/min/1.73 m2 (hazard ratio [HR] = 3.28, 95% confidence interval [CI] = 1.81-5.95) to ACR = 30-300 mg/g (HR = 1.96, 95%CI = 1.23-3.10). However, in survival trees, an increased risk of mortality was observed among patients with impaired handgrip and eGFR = 45-59.9 ml/min/1.73 m2, as well as patients with ACR < 30 mg/g and impaired handgrip and SPPB. Survival tree leaf node membership had greater predictive accuracy (C-index = 0.81, 95%CI = 0.78-0.84 for the eGFR survival tree and C-index = 0.77, 95%CI = 0.71-0.81 for the ACR survival tree) in comparison with that of individual measures of kidney function. CONCLUSIONS: physical performance helps to identify a proportion of patients at an increased risk of mortality despite a mild-moderate impairment in kidney function and improves predictive accuracy of individual measures of kidney function.

Transient versus stable nature of fear of falling over 24 months in community-older persons with falls- data of the EU SCOPE project on Kidney function.

BACKGROUND: Fear of falling (FoF) is an important risk factor for falls among older people. The objectives of our investigations were: a.) to present characteristics of older community-dwelling (CD) fallers with persistent or transient FoF (P-FoF or T-FoF) over 12 months, and b.) to investigate clinical predictors of P-FoF and T-FoF and c.) to explore differences between P-FoF and T-FoF. METHODS: Our series consisted of 389 older people reporting a fall or injurious fall at baseline and during 24 months follow-up participating in a multicenter prospective study. T-FoF was defined as participants reported "not at all" at baseline and "somewhat/fairly/very concerned" at follow-up, or "not at all" at follow-up, and "somewhat/fairly/very concerned" at baseline, and P-FoF was defined as participants answered "somewhat/fairly/very concerned" in both assessments at baseline and at follow-up. The association between risk factors and T-FoF or P-FoF was investigated by logistic regression analysis. RESULTS: The mean age of fallers in our sample was 79.0 years (SD 6.0), and 54.2% were females. Out of 389 older adults with a fall history at baseline, 83 participants (21.3%) did not report any FoF over time, P-FoF and T-FoF were observed in 42.7% and 35.9% of participants, respectively. After adjusting for potential confounders (e.g. age, gender), osteoporosis (OR = 2.04, 95%CI = 1.03-4.05) and impaired physical performance (OR = 2.38, 95%CI = 1.12-5.03) were significant predictors of T-FoF vs No-FoF. Osteoporosis (OR = 2.68, 95%CI = 1.31-5.48), depressive symptoms (OR = 3.54, 95%CI = 1.23-10.1) and living alone (OR = 2.44, 95%CI = 1.17-5.06) were significantly associated with P-FoF vs No-FoF. When comparing T-FoF and P-FoF, female gender (OR = 1.95, 95%CI = 1.16-3.27), BMI (OR = 1.08, 95%CI = 1.02-1.14), overall comorbidity (OR = 1.07, 95%CI = 1.02-1.13) and depression (OR = 2.55, 95%CI = 1.33-4.88) were significant predictors of P-FoF. CONCLUSIONS: T-FoF and P-FoF may be predicted by different sets of risk factors among older fallers. Thus, fallers should be screened for FoF especially when carrying specific risk factors, including female gender, osteoporosis, depression, living alone, impaired physical performance, BMI, comorbidity. These findings may be helpful in designing tailored intervention to blunt the risks related to consequence of FoF among older people experiencing falls. TRIAL REGISTRATION: The SCOPE study was registered prospectively at clinicaltrials.gov (NCT02691546; 25/02/2016).

Diabetes, sarcopenia and chronic kidney disease; the Screening for CKD among Older People across Europe (SCOPE) study.

BACKGROUND: Sarcopenia may be more present in older adults with diabetes (DM). Accordingly, we evaluated the prevalence of sarcopenia and its associated risk factors among community-dwelling older adults with DM. METHODS: A cross-sectional analysis of older people living in the community was carried out. Participants (aged 75 years and more) came from an European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test and bioelectrical impedance analysis was performed. Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate (eGFR) was calculated using Berlin Initiative Study (BIS) to define the stages of chronic kidney disease (CKD). Previous known DM was defined as physician-diagnosed DM registered in the patient's medical record or the use of DM-related medications. Hemoglobin A1c levels and specific DM therapies administered were collected. Time elapsed from the first diagnosis of DM was not collected and, therefore, was not included in the analyses. RESULTS: A total of 1,420 subjects were evaluated with a median age of 79.0 (6.0) years, of which 804 (56.6%) were women and 615 (43.3%) men; 315 (22.2%) participants had prior DM diagnosis, with a median age of 80.0 (6.0), 146 (46.3%) were women. Using EWGSOP2 definition, 150 (10.6%) participants in the SCOPE study met diagnostic criteria for sarcopenia. Participants without diabetes had more often normal results in the 3 sarcopenia components than participants with diabetes [887 (80.31%) vs. 227 (72.1%), p = 0.002], highlighting higher percentages of severe sarcopenia in participants with diabetes [27 (8.6%) vs. 58 (5.2%), p = 0.028]. Confirmed or severe sarcopenia was detected in 41 (13%) participants with diabetes and 109 (9.8%) participants without diabetes (p = 0.108). According to BIS equation, sarcopenia was not significantly more prevalent in the more advanced stages of CKD (p = 0.845). In multivariate analyses, older age (odds ratios [OR], 1.17; 95% confidence interval [CI], 1.08-1.27), and lower body mass index (OR, 0.79; 95% CI, 0.71-0.89 were associated with the presence of sarcopenia. CONCLUSIONS: One tenth of all older community-dwelling subjects have sarcopenia. Older age and being thinner, but not worse renal function, were associated with higher prevalence of sarcopenia in older older adults with diabetes.

"The Community That Takes Care of Itself": A Feasibility Study to Support Families Caring for a Loved One With Alzheimer Disease.

This pilot project was aimed at supporting those families caring at home for loved ones suffering from Alzheimer dementia. Fourteen dyads of "caregivers-loved ones with dementia" were recruited and assigned either to the experimental group (n = 7) or to the control group (n = 7). The experimental group attended a training course, an Alzheimer Café, a self-help group for caregivers, and the support from a volunteer and professional nurse in-home visits, while the control group's dyads attended a standard intervention. To investigate the effects of this integrated and interprofessional model of care, caregivers completed the Caregiver Burden Inventory and 2 ad hoc structured questions to evaluate whether quality of life of the dyads was changed. Moreover, the caregivers of the experimental group completed the Self-Assessment Single Questionnaire, version 6 (Q-UAV6). Only caregivers of the experimental group reported a significant reduction in burden and an improved quality of life of the dyad. They also showed a greater acceptance of the disease, became experts in the care of their loved ones, and improved their relationship. The creation of a service integration network of professionals, volunteers, and families has been shown to be useful in supporting those families caring at home for loved ones suffering from Alzheimer dementia.

Pulmonary function in patients surviving to COVID-19 pneumonia.

PURPOSE: The aim of our study was to assess respiratory function at the time of clinical recovery and 6 weeks after discharge in patients surviving to COVID-19 pneumonia. METHODS: Our case series consisted of 13 patients with COVID-19 pneumonia. RESULTS: At the time of clinical recovery, FEV1 (2.07 ± 0.72 L) and FVC (2.25 ± 0.86 L) were lower compared to lower limit of normality (LLN) values (2.56 ± 0.53 L, p = 0.004, and 3.31 ± 0.65 L, p < 0.001, respectively), while FEV1/FVC (0.94 ± 0.07) was higher compared to upper limit of normality (ULN) values (0.89 ± 0.01, p = 0.029). After 6 weeks pulmonary function improved but FVC was still lower than ULN (2.87 ± 0.81, p = 0.014). CONCLUSION: These findings suggest that COVID-19 pneumonia may result in clinically relevant alterations in pulmonary function tests, with a mainly restrictive pattern.

ICT technologies as new promising tools for the managing of frailty: a systematic review.

OBJECTIVES: Frailty is a major health issue as it encompasses functional decline, physical dependence, and increased mortality risk. Recent studies explored Information and Communication Technology (ICT) interventions as alternatives to manage frailty in older persons. The aim of the present systematic review was to synthesize current evidence on ICT application within the complex models of frailty care in older people. METHODS: Data sources included PubMed, PsycINFO, EMBASE and Web of Science, considering eligible those reviews on ICT application in samples of older persons formally assessed as frail. Records were screened by two independent researchers, who extracted data and appraised methodological quality of reviews and studies. RESULTS: Among the 764 retrieved papers, two systematic reviews were included. Most of the studies analyzed defined frailty considering only few components of the phenotype and used ICT to stratify different levels of frailty or to support traditional screening strategies. Assessment of frailty was the context in which ICT has been mostly tested as compared to intervention. Cost effectiveness evaluations of the ICT technologies were not reported. CONCLUSIONS: The research investigating the use of ICT in the context of frailty is still at the very beginning. Few studies strictly focused on the assessment of frailty, while intervention on frailty using ICT was rarely reported. The lack of a proper characterization of the frail condition along with the methodological limitations prevented the investigation of ICT within complex care models. Future studies are needed to effectively integrate ICT in the care of frailty in orders.

Does trail making test predict long-term prognosis in older patients with COPD?

Executive abilities are frequently impaired in patients with chronic obstructive pulmonary disease (COPD). We aimed at investigating the association between trail making test (TMT) and survival. Our series consisted of 68 stable COPD outpatients followed-up every 6 months for 52.6 ± 27.6 months. Enrolled patients underwent a baseline comprehensive neuropsychological assessment, including mini-mental state exam, attentional matrices, digit span, Rey auditory verbal learning, Rey-Osterrieth complex figure, copy drawing, tokens test, verbal fluency, category fluency, frontal assessment battery, Raven's progressive matrices, TMT-A, -B and -B-A. The association between neuropsychological deficits and overall mortality was investigated by Cox regression. During follow-up period, 41 patients (60.3%) died. After adjusting for potential confounders, TMT-B was significantly associated with mortality (HR = 2.42, 95% CI = 1.10-5.31), along with age (HR = 1.06, 95% CI = 1.0-1.13), overall comorbidity (HR = 1.29, 95% CI = 1.02-1.62) and use of noninvasive ventilation (HR = 2.16, 95% CI = 1.05-4.45). Defective TMT-B may be associated with long-term mortality in patients with stable COPD.

Design and methodology of the chronic kidney disease as a dysmetabolic determinant of disability among older people (CKD-3D) study: a multicenter cohort observational study.

BACKGROUND: Chronic kidney disease (CKD) is a common condition in older people and represents a global health issue since it increases the risk of associated comorbidities and all-cause mortality. Furthermore, older people with reduced renal function might be at higher risk for developing functional limitation and disability. Moreover, the current creatinine-based measures of renal function are influenced by several factors in older population. The aims of the CKD-3D project are to perform an observational study to expand the knowledge about CKD-disability relationship and to investigate the use of novel biomarkers of kidney function. METHODS: An observational, multicenter, prospective cohort study will be conducted in 75 + old patients consecutively admitted to acute care wards of geriatric medicine at participating hospitals. The study planned to enroll 440 patients undergoing clinical and laboratory evaluations at baseline and after 12 months. Face-to-face follow-up at 6 months and telephone follow-up at 3 and 9 months will be carried out. Comprehensive Geriatric Assessment (CGA) and the measurement of Cystatin C, Beta-Trace Protein and Beta2-Microglobulin levels will be included. DISCUSSION: This study will provide useful information to prevent CKD-related disability by collecting real-life data over 1-year period. The combined approach of CGA and the investigation of innovative existing biomarkers will make it possible to develop new recommendations and guidelines for a patient-centered approach. It is believed that such a study may lead to an improvement of knowledge on CKD in elderly patients and may also have implications in daily clinical practice and in decision-making process.

Physical performance measures and hospital outcomes among Italian older adults: results from the CRIME project.

BACKGROUND: Older adults are a complex population, at risk of adverse events during and after hospital stay. AIM: To investigate the association of walking speed (WS) and grip strength (GS) with adverse outcomes, during and after hospitalization, among older individuals admitted to acute care wards. METHODS: Multicentre observational study including 1123 adults aged ≥ 65 years admitted to acute wards in Italy. WS and GS were measured at admission and discharge. Outcomes were length-of-stay, in-hospital mortality, 1-year mortality and rehospitalisation. Length-of-stay was defined as a number of days from admission to discharge/death. RESULTS: Mean age was 81 ± 7 years, 56% were women. Compared to patients with WS ≥ 0.8 m/sec, those unable to perform or with WS < 0.8 m/sec had a higher likelihood of longer length-of-stay (OR 2.57; 95% CI 1.63-4.03 and 2.42; 95% CI 1.55-3.79) and 1-year mortality and rehospitalization (OR 1.47, 95% CI 1.07-2.01; OR 1.57, 95% CI 1.04-2.37); those unable to perform WS had a higher likelihood of in-hospital mortality (OR 9.59; 95% CI 1.23-14.57) and 1-year mortality (OR 2.60; 95% CI 1.37-4.93). Compared to good GS performers, those unable to perform had a higher likelihood of in-hospital mortality (OR 17.43; 95% CI 3.87-28.46), 1-year mortality ( OR 3.14; 95% CI 1.37-4.93) and combination of 1-year mortality and rehospitalisation (OR 1.46; 95% CI 1.01-2.12); poor GS performers had a higher likelihood of 1-year mortality (OR 1.39; 95% CI 1.03-2.35); participants unable to perform GS had a lower likelihood of rehospitalisation (OR 0.59; 95% CI 0.39-0.89). CONCLUSION: Walking speed (WS) and grip strength (GS) are easy-to-assess predictors of length-of-stay, in-hospital and post-discharge death and should be incorporated in the standard assessment of hospitalized patients.

Impact of working situation on mental and physical health for informal caregivers of older people with Alzheimer's disease in Italy. Results from the UP-TECH longitudinal study.

OBJECTIVES: This longitudinal study explores whether the working situation (no change in working hours despite care, reduction of working hours due to care or not working) moderates mental and physical health of informal caregivers of older people with Alzheimer's disease (AD) in Italy. METHODS: Data from a sample of 146 caregivers of older people with moderate AD involved in the UP-TECH trial across three waves were analysed. Multivariate analyses were used to study the association between independent variables (caregivers' work situation) and dependent variables (caregivers' psycho-physical health). In a second model, elements relating to the caregiver, the cared-for individual and the caregiving situation were added as controls. RESULTS: Being forced to reduce working hours due to care tasks or not being employed independently from care was negatively associated with informal caregiver's physical health, compared with working carers not experiencing reduction of working hours. In the extended model, this result was confirmed. In comparison with working carers not forced to reduce working hours, non-working carers experienced higher levels of caregiver burden and depression, however these results were not confirmed in the adjusted model. Other factors also emerged as important including weekly hours of care, the cared-for older individual's ADL/IADL scores and informal support network. CONCLUSIONS: Given the positive effect of labour force participation on health of informal caregivers of older people with AD, policy makers should promote their employment avoiding their forced reduction of working hours, while also putting measures in place to decrease the intensity of informal care provision.

Rehabilitation of older people with Parkinson's disease: an innovative protocol for RCT study to evaluate the potential of robotic-based technologies.

BACKGROUND: Parkinson's disease is one of the most frequent causes of disability among the older adults. It is a chronic-progressive neuro-degenerative disease, characterized by several motor disorders. Balance disorders are a symptom that involves the body axis and do not respond to dopaminergic therapy used in Parkinson's disease. Therefore, physiotherapy becomes an important intervention for the management of motor disorders. Originally, these rehabilitative approaches were based on empirical experiences, but several scientific evidences suggests that neuronal plasticity is exercise-dependent. In this context, robotic rehabilitation plays an important role because it allows to perform task-oriented exercises and to increase the number of repetitions and their intensity. This protocol study aims to evaluate the effectiveness of robotic-based intervention of the older adults with Parkinson's disease, designed to improve the gait and to reduce the risk of falling. METHODS: This study is a single-blinded randomized controlled trial. The primary outcomes are: risk of falling, gait performance and fear of falling measured through Performance-Oriented Mobility Assessment (POMA), instrumental gait analysis and Short Falls Efficacy Scale - International (FES-I), respectively. One hundred ninety-five patients with PD will be recruited and randomly divided into three groups, to receive a traditional rehabilitation program or a robotic rehabilitation using Tymo system or Walker View in addition to the traditional therapy. Assessments will be performed at baseline, at the end of treatment and 6 months, 1 year and 2 years from the end of the treatment. A 10-treatment session will be conducted, divided into 2 training sessions per week, for 5 weeks. The control group will perform traditional therapy sessions lasting 50 min. The technological intervention group will carry out 30 min of traditional therapy and 20 min of treatment with a robotic system. DISCUSSION: The final goals of the present study are to propose a new approach in the PD rehabilitation, focused on the use of robotic device, and to check the results not only at the end of the treatment but also in the long term. TRIAL REGISTRATION: NCT04087031, registration date September 12, 2019.