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Background: Cardiovascular diseases are the leading cause of mortality, morbidity, and disability in the world, especially in the older adults. A relevant proportion of patients admitted to Cardiac Rehabilitation (CR) may suffer from frailty, a complex geriatric syndrome with multifactorial aetiology., Aims: The hypothesis underlying the study is that frailty complicates the management of older patients undergoing CR. The main objective is, therefore, to determine the relationship between frailty and CR outcomes in hospitalized older adults., Methods: The participants have been recruited among patients aged ≥ 65 years admitted at the hospital for CR. A Comprehensive Geriatric Assessment (CGA)-based Frailty Index (FI) was created following a standard procedure. The outcome was measured as the ratio between 6-min walk test (6MWT) distance at the end of CR and normal predicted values for a healthy adult of same age and gender, according to reference equations., Results: The study population consisted of 559 elderly patients, 387 males (69.2%), with age of 72 (69-76) years. The most frequent diagnosis at admission was ischaemic heart disease (231, 41.5%) and overall 6MWT ratio was 0.62 ± 0.21. At the multivariable regression analysis, gender, diagnosis and FI were significantly and independently associated with 6MWT ratio (p ≤ 0.0001, p ≤ 0.001 and p ≤ 0.0001, respectively), while no significant association emerged for age., Conclusion: FI resulted independently correlated to 6MWT ratio in a population of older patients undergoing in-hospital CR programs. Frailty is a multifactorial geriatric syndrome whose assessment is essential for prognostic evaluation of older patients, also in CR clinical setting., (© 2022. The Author(s).)

With ageing population the number of elderly vulnerable to abuse is expected to grow. Hospital personnel play a crucial role in identifying mistreatment. The aim of this study was to establish the level of awareness and perception of elder abuse by healthcare workers, and to understand if they are able to recognize and properly report elder abuse, as well as to identify the physical signs of abuse and neglect. A 41-question survey was administered to healthcare professionals, working in the Internal Medicine and Geriatric Wards of two different University Hospitals of Southern Italy, representative of the Italian health public system. The data collection resulted in 98 questionnaires. For the majority, neglect represents a type of abuse, whereas 40% of physicians and 37% of nurses considered this concept false. All the professionals recognized the elder abuse as a violation of the human rights, but 46.94% were not sure about the existence of standard procedures for abuse reporting/treatment. The most of the nurses and the care assistants declared they never had suspected or witnessed abuse, while few physicians stated to have suspected/witnessed abuse 1-3 times in their career. In both the suspected and witnessed cases, the healthcare personnel did not made any action, neither reported them to public authorities nor adult protective service agencies. The level of awareness and perception of elder abuse by healthcare professionals are still poor especially regarding the reporting procedures. There is still strong need for education and specific training programs on elder abuse.

T H 17 cells play important yet complex roles in cancer development and progression. We previously reported that T H 17 cells and IL-17 mediate resistance to anti-VEGF therapy by inducing recruitment of immunosuppressive and proangiogenic myeloid cells to the tumor microenvironment. Here, we demonstrate that IL-22, a key effector cytokine expressed by T H 17 cells, directly acts on endothelial cells to promote tumor angiogenesis. IL-22 induces endothelial cell proliferation, survival, and chemotaxis in vitro and neovascularization in an ex vivo mouse choroid explant model. Blockade of IL-22, with a neutralizing antibody, significantly inhibits tumor growth associated with reduced microvascular density. No synergistic effect of IL-22 with VEGF was observed. These results identify IL-22 as a potential therapeutic target for blocking tumor angiogenesis.

Diabetes mellitus (DM) and heart failure (HF) are frequent comorbidities among elderly patients. HF, a leading cause of mortality and morbidity worldwide, is characterized by sympathetic nervous system hyperactivity. The prevalence of diabetes mellitus (DM) is rapidly growing and the risk of developing HF is higher among DM patients. DM is responsible for several macro- and micro-angiopathies that contribute to the development of coronary artery disease (CAD), peripheral artery disease, retinopathy, neuropathy and diabetic nephropathy (DN) as well. Independently of CAD, chronic kidney disease (CKD) and DM increase the risk of HF. Individuals with diabetic nephropathy are likely to present a distinct pathological condition, defined as diabetic cardiomyopathy, even in the absence of hypertension or CAD, whose pathogenesis is only partially known. However, several hypotheses have been proposed to explain the mechanism of diabetic cardiomyopathy: increased oxidative stress, altered substrate metabolism, mitochondrial dysfunction, activation of renin-angiotensin-aldosterone system (RAAS), insulin resistance, and autonomic dysfunction. In this review, we will focus on the involvement of sympathetic system hyperactivity in the diabetic nephropathy.

Backround: Use of indwelling urinary catheter (IUC) in older adults has negative consequences, including delirium., Aim: This analysis, from the "Delirium Day 2015", a nationwide multicenter prevalence study, aim to evaluate the association of IUC with delirium in hospitalized and Nursing Homes (NHs) patients., Methods: Patients underwent a comprehensive geriatric assessment, including the presence of IUC; inclusion criteria were age > 65 years, being Italian speaker and providing informed consent; exclusion criteria were coma, aphasia, end-of-life status. Delirium was assessed using the 4AT test (score ≥ 4: possible delirium; scores 1-3: possible cognitive impairment)., Results: Among 1867 hospitalized patients (mean age 82.0 ± 7.5 years, 58% female), 539 (28.9%) had IUC, 429 (22.9%) delirium and 675 (36.1%) cognitive impairment. IUC was significantly associated with cognitive impairment (OR 1.60, 95% CI 1.19-2.16) and delirium (2.45, 95% CI 1.73-3.47), this latter being significant also in the subset of patients without dementia (OR 2.28, 95% CI 1.52-3.43). Inattention and impaired alertness were also independently associated with IUC. Among 1454 NHs residents (mean age 84.4 ± 7.4 years, 70.% female), 63 (4.3%) had IUC, 535 (36.8%) a 4AT score ≥ 4, and 653 (44.9%) a 4AT score 1-3. The multivariate logistic regression analysis did not show a significant association between 4AT test or its specific items with IUC, neither in the subset of patients without dementia., Discussion: We confirmed a significant association between IUC and delirium in hospitalized patients but not in NHs residents., Conclusion: Environmental and clinical factors of acute setting might contribute to IUC-associated delirium occurrence.

Aims: The purpose of this study was to examine the tools used in Italy to diagnose mild cognitive impairment (MCI)., Methods: In collaboration with the Luigi Amaducci Research Consortium, the Italian Network of Alzheimer Evaluation Units prepared a questionnaire to describe how MCI is diagnosed in the Italian Centres for cognitive disorders and dementia (CCDD)., Results: Most of the ninety-two CCDDs participating in the survey were located in hospitals (54.7%); large percentages were coordinated by neurologists (50.8%) and geriatricians (44.6%). Almost all (98.5%) used the Mini Mental State Examination to diagnose MCI; the Clock Drawing Test was also frequently used (83.9%). Other neuropsychological, imaging and biomarker tests were utilized less frequently and a wide diversity in the instruments used was noted., Conclusions: According to the results, diagnoses of MCI are based on a multitude of instruments, with major differences in the clinical assessment of geriatricians and neurologists. Standardized testing protocols, validated instruments and cut-off points need to be identified and adopted by the CCDDs for assessing MCI.

Aim: To evaluate the efficacy of multidimensional geriatric assessment (MGA/CGA) in patients over 65 years old in predicting the release of the accompaniment allowance (AA) indemnity by a Local Medico-Legal Committee (MLC-NHS) and by the National Institute of Social Security Committee (MLC-INPS)., Methods: In a longitudinal observational study, 200 Italian elder citizens requesting AA were first evaluated by MLC-NHS and later by MLC-INPS. Only MLC-INPS performed a MGA/CGA (including SPMSQ, Barthel Index, GDS-SF, and CIRS). This report was written according to the STROBE guidelines., Results: The data analysis was performed on January 2016. The evaluation by the MLC-NHS and by the MLC-INPS was in agreement in 66% of cases. In the 28%, the AA benefit was recognized by the MLC-NHS, but not by the MLC-INPS. By the multivariate analysis, the best predictors of the AA release, by the MLC-NHS, were represented by gender and the Barthel Index score. The presence of carcinoma, the Barthel Index score, and the SPMQ score were the best predictors for the AA release by MLC-INPS., Conclusions: MGA/CGA could be useful in saving financial resources reducing the risk of incorrect indemnity release. It can improve the accuracy of the impairment assessment in social security system.

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

Delirium is a severe neuropsychiatric syndrome characterized by inattention and global cognitive dysfunction in the setting of an acute medical illness, medical complication, drug intoxication, or drug withdrawal. The most important risk factors are advanced age and dementia, whereas pain, dehydration, infections, stroke, metabolic disturbances, and surgery are the most common triggering factors. Although delirium is a common clinical syndrome in different settings of care (acute care hospitals, inpatient rehabilitation facilities, nursing homes, and hospices), it often remains under-recognized, poorly understood, and inadequately managed. There exists a clear need for improved understanding to overcome cultural stereotypes, and for the development and dissemination of a comprehensive model of implementation of general good practice points. A network of Italian national scientific societies was thus convened (1) to develop a collaborative multidisciplinary initiative report on delirium in elderly hospitalized patients, (2) to focus the attention of health care personnel on prevention, diagnosis, and therapy of patients suffering from delirium, and (3) to make the health services research community and policy-makers more aware of the potential risks of this condition providing a reference for training activities and data collection.

If aging is a physiological phenomenon-as maintained by the programmed aging paradigm-it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer's disease, Parkinson's disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.

Background: Oxidative stress is strongly associated with aging and age-related diseases and plays a crucial role in endothelial dysfunction development., Aim: To better understand the molecular mechanisms of aging and stress response in humans, we examined changes to young and older human endothelial cells over time (72, 96 and 120 h), before and after H2O2-induced stress., Methods: We measured the expression of the deacetylase Sirtuin 1 (Sirt1) and its transcriptional target Forkhead box O3a (Foxo3a); TBARS, a well-known marker of overall oxidative stress, and catalase activity as index of antioxidation. Moreover, we quantified levels of cellular senescence by senescence-associated β galactosidase (SA-βgal) assay., Results: Under oxidative stress induction older cells showed a progressive decrease of Sirt1 and Foxo3a expression, persistently high TBARS levels with high, but ineffective Cat activity to counteract such levels. In addition cellular senescence drastically increased in older cells compared with Young cells both in presence and in the absence of oxidative stress., Discussion: By following the cell behavior during the time course, we can hypothesize that while in young cells an oxidative stress induction stimulated an adequate response through activation of molecular factor crucial to counteract oxidative stress, the older cells are not able to adequately adapt themselves to external stress stimuli., Conclusions: During their life, endothelial cells impair the ability to defend themselves from oxidative stress stimuli. This dysfunction involves the pathway of Sirt1 a critical regulator of oxidative stress response and cellular lifespan, underlining its crucial role in endothelial homeostasis control during aging and age-associated diseases.

Elderly abuse is still a hidden problem, often underestimated. It is much more common than the data available suggest. Unfortunately, the incidence is expected to grow with the progressive increase in the elderly population in the future. The aim was to examine the available literature in the last 5 years to define the state of art on this phenomenon, with particular regard to the nursing role in elderly abuse, focusing on the possible types of mistreatment, the motivations and preventive interventions. Articles published in the last 5 years regarding the mistreatment of the elderly were selected, by using scientifically recognized databases such as PubMed, Cochrane Library, Medline, Scopus, and Web of Knowledge. Several keywords were used for the query among which were: "elderly abuse" and "elderly abuse in nursing home". Moreover, to better understand the entity of the phenomenon, we also searched the corresponding keywords for child abuse. Considering the Scopus database, only 78 out of 1,342 published articles in the last 5 years deal with abuse of the elderly in relation to nursing, representing a very small part (5.81%) of the considered sample. Comparing the number of articles, the ratio child/elderly is equal to 1/0.04, underlying the poor interest of research on this phenomenon. Moreover, it was observed that elderly abuse in nursing homes is still underreported in both original articles and reviews. Despite the aging of the population, elderly abuse and neglect still remain hidden problems, overlooked and also underestimated in the literature.

Aging is a well-recognized risk factor for several different forms of cardiovascular disease. However, mechanisms by which aging exerts its negative effect on outcome have been only partially clarified. Numerous evidence indicate that aging is associated with alterations of several mechanisms whose integrity confers protective action on the heart and vasculature. The present review aims to focus on the beneficial effects of exercise, which plays a pivotal role in primary and secondary prevention of cardiovascular diseases, in counteracting age-related deterioration of protective mechanisms that are crucially involved in the homeostasis of cardiovascular system. In this regard, animal and human studies indicate that exercise training is able: (1) to improve the inotropic reserve of the aging heart through restoration of cardiac β-adrenergic receptor signaling; (2) to rescue the mechanism of cardiac preconditioning and angiogenesis whose integrity has been shown to confer cardioprotection against ischemia and to improve post-myocardial infarction left ventricular remodeling; (3) to counteract age-related reduction of antioxidant systems that is associated to decreased cellular resistance to reactive oxygen species accumulation. Moreover, this review also describes the molecular effects induced by different exercise training protocols (endurance vs. resistance) in the attempt to better explain what kind of exercise strategy could be more efficacious to improve cardiovascular performance in the elderly population.

Objectives: In the last decade, there has been a rapid increase in the number of elderly patients referred for cardiac surgery. Recent studies have identified risk factors for prolonged intensive care unit (ICU) stay in cardiac surgery patients. The aims of this study was to evaluate pre-operative risk factors for ICU stay longer than 3 days in a cardiac surgery elderly population, and whether prolonged ICU stay may influence disability, functional recovery and length of rehabilitation., Methods: Two hundred and fifty elderly (≥65 years) cardiac surgery patients were consecutively evaluated at enter in cardiac rehabilitation after ICU dismissal from January 2008 to July 2009. Univariate and multivariate analyses for risk factors were performed for ICU stay longer than 3 days. Thereafter, 6-minute walking test (6MWT), Barthel Index (BI), BI percent recovery and length of stay (LOS) in rehabilitation were evaluated., Results: Mean age was 72.9±4.8 yrs, 170 (68%) patients underwent cardiac surgery for coronary artery by-pass grafting (CABG), 56 (22.4%) for valve replacement and 24 (9.6%) for both CABG and valve replacement. Mean ICU stay was 1.9±1.5 days and 72 patients (28.8%) spent more than 3 days in ICU. Age, New York Heart Association class ≥3, Cumulative Illness Rating Scale (CIRS) score, prevalence of stroke and renal failure were significantly higher in patients with than in those without ICU stay ≥3 days. Off-pump CABG, Physical Activity Scale for the Elderly (PASE), BI and 6MWT were significantly lower in patients with than in those without ICU stay ≥3 days. Multivariate analysis shows that female sex, a NYHA class ≥3, CIRS and PASE score are predictors of ICU stay ≥3 days independently of age, off-pump CABG, stroke and renal failure. Multiple linear regression shows that ICU stay ≥3 days is negatively associated with 6MWT, BI at entry and BI percent recovery, whereas it is positively associated with a longer rehabilitation LOS., Conclusions: Pre-operative comprehensive assessment in the elderly could help to identify predictors of long ICU stay after cardiac surgery. This approach could help to better define the elderly cardiac surgery patients and their needs throughout the cardiac rehabilitation program in order to maximize functional capacity recovery, reducing disability and rehabilitation LOS.

Background and Aims: Elderly subjects are characterized by a high prevalence of chronic obstructive pulmonary disease (COPD) and frailty. This study examined the predictive role of frailty on long-term mortality in elderly subjects with and without COPD., Methods: The study assessed mortality after a 12-year follow-up in 489 subjects with COPD and 799 subjects without COPD, selected in 1992. Frailty was assessed according to the Frailty Staging System scores ranging from 1 to 7., Results: After 12 years' follow-up, mortality was 48.1% in subjects without and 60.7% in subjects with COPD (p<0.001). With increasing frailty, mortality increased from 41.7% to 75.1% (p for trend <0.01) in subjects without and from 54.3% to 97.0% in subjects with COPD (p for trend <0.001). Multivariate analysis showed that both COPD [hazard ratio (HR)=1.34; 95% confidence interval (95% CI)=1.02-1.81; p=0.042] and frailty score (HR=1.69 for each unit of increase; 95% CI=1.42- 2.00; p<0.001) were predictive of long-term mortality. The frailty score also increased the risk of long-term mortality by 34% in the absence of COPD (HR=1.34 for each unit of increase; 95% CI=1.02-1.81; p<0.05) and by 80% in its presence (HR=1.80 for each unit of increase; 95% CI=1.28-2.53; p<0.001)., Conclusions: Long-term mortality was higher in elderly subjects with than in those without COPD. The clinical frailty score also significantly predicted mortality in subjects without and, even more, in those with COPD. Thus, clinical frailty may be considered a new prognostic factor to identify COPD subjects at high risk of mortality.

Background and Aims: We investigated the prevalence of visual impairment (VI), its determinants and its association with Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Gross Mobility (GM) and 6-year mortality in elderly subjects. A cross-sectional survey in a large population randomly selected in 1992 with a 6-year mortality evaluation in Campania, a region in southern Italy., Methods: A random sample of 1332 elderly subjects aged 65 to 95 years (mean age 74.2 +/- 6.4), selected from the electoral rolls, was interviewed by trained physicians. Self-reported visual function, socio-demographic and clinical characteristics were recorded. Disability was assessed by measuring ability in ADL, IADL and GM., Results: VI was found to affect 34% of this population, with an age-related increase of mild and severe VI. VI affects ADL, IADL and GM disability. Age, diabetes and low educational level, but not comorbidity or hypertension, proved to be predictors of VI. Mortality increased with severity of VI in 38.1% of subjects with severe functional impairment (p < 0.001). The presence of VI was seen to increase the risk of mortality by 1.40 (95% CI 1.07-1.84), independently of age, sex, comorbidity, diabetes, hypertension or disability., Conclusions: This study demonstrates an association between visual impairment and disability in an elderly population, and the predictive effect of visual impairment on mortality independently of comorbidity. These results illustrate the need to eradicate avoidable blindness, in order to improve the quality of life and to prolong survival of the elderly.

Early stage primary human cutaneous melanoma is known to remain relatively avascular and dormant for up to a decade, after which it may give rise to more rapidly growing, vascular and metastatically- competent primary tumor. Clinical dormancy of early stage human melanomas can be recapitulated experimentally by injection of cell lines established from such tumors into nude mice. For example, WM1341B cells, which were isolated from a thin vertical growth phase (VGP) human melanoma, are non-tumorigenic in nude mice even though some of the cells remain viable for at least three weeks at the site of orthotopic injection. These cells produce little or no vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), a potent stimulator of angiogenesis. In order to determine whether their in vivo dormant behaviour may therefore be related to an inability to induce tumor angiogenesis, subpopulations of WM1341B cells were engineered to constitutively overexpress the VEGF/VPF121 isoform. This apparently single modification was sufficient to induce overt and progressively growing tumors by several independent VEGF/VPF121 producing clones, which could be largely blocked by systemic treatment of mice with a monoclonal anti-VEGF neutralizing antibody (A 4.6.1). No evidence for an autocrine mechanism of growth stimulation by VEGF was found. Taken together, these results support the notion that defective angiogenesis may, at least in part, account for dormant phenotype of some early stage primary melanomas. Since the induction of an overt tumorigenic phenotype in several VEGF/VPF transfected WM1341B clones appears to depend exclusively on their expression of VEGF/VPF, such sublines should be useful for screening the activity of known or potential VEGF/VPF ligand or VEGF/VPF receptor antagonists in an in vivo context.