Biomarkers of cell damage, neutrophil and macrophage activation associated with in-hospital mortality in geriatric COVID-19 patients.

BACKGROUND: The risk for symptomatic COVID-19 requiring hospitalization is higher in the older population. The course of the disease in hospitalised older patients may show significant variation, from mild to severe illness, ultimately leading to death in the most critical cases. The analysis of circulating biomolecules involved in mechanisms of inflammation, cell damage and innate immunity could lead to identify new biomarkers of COVID-19 severity, aimed to improve the clinical management of subjects at higher risk of severe outcomes. In a cohort of COVID-19 geriatric patients (n= 156) who required hospitalization we analysed, on-admission, a series of circulating biomarkers related to neutrophil activation (neutrophil elastase, LL-37), macrophage activation (sCD163) and cell damage (nuclear cfDNA, mithocondrial cfDNA and nuclear cfDNA integrity). The above reported biomarkers were tested for their association with in-hospital mortality and with clinical, inflammatory and routine hematological parameters. Aim of the study was to unravel prognostic parameters for risk stratification of COVID-19 patients. RESULTS: Lower n-cfDNA integrity, higher neutrophil elastase and higher sCD163 levels were significantly associated with an increased risk of in-hospital decease. Median (IQR) values observed in discharged vs. deceased patients were: 0.50 (0.30-0.72) vs. 0.33 (0.22-0.62) for n-cfDNA integrity; 94.0 (47.7-154.0) ng/ml vs. 115.7 (84.2-212.7) ng/ml for neutrophil elastase; 614.0 (370.0-821.0) ng/ml vs. 787.0 (560.0-1304.0) ng/ml for sCD163. The analysis of survival curves in patients stratified for tertiles of each biomarker showed that patients with n-cfDNA integrity < 0.32 or sCD163 in the range 492-811 ng/ml had higher risk of in-hospital decease than, respectively, patients with higher n-cfDNA integrity or lower sCD163. These associations were further confirmed in multivariate models adjusted for age, sex and outcome-related clinical variables. In these models also high levels of neutrophil elastase (>150 ng/ml) appeared to be independent predictor of in-hospital death. An additional analysis of neutrophil elastase in patients stratified for n-cfDNA integrity levels was conducted to better describe the association of the studied parameters with the outcome. CONCLUSIONS: On the whole, biomarkers of cell-free DNA integrity, neutrophil and macrophage activation might provide a valuable contribution to identify geriatric patients with high risk of COVID-19 in-hospital mortality.

Underprescription of medications in older adults: causes, consequences and solutions-a narrative review.

PURPOSE: Under-prescription is defined as the omission of a medication that is indicated for the treatment of a condition or a disease, without any valid reason for not prescribing it. The aim of this review is to provide an updated overview of under-prescription, summarizing the available evidence concerning its prevalence, causes, consequences and potential interventions to reduce it. METHODS: A PubMed search was performed, using the following keywords: under-prescription; under-treatment; prescribing omission; older adults; polypharmacy; cardiovascular drugs; osteoporosis; anticoagulant. The list of articles was evaluated by two authors who selected the most relevant of them. The reference lists of retrieved articles were screened for additional pertinent studies. RESULTS: Although several pharmacological therapies are safe and effective in older patients, under-prescription remains widespread in the older population, with a prevalence ranging from 22 to 70%. Several drugs are underused, including cardiovascular, oral anticoagulant and anti-osteoporotic drugs. Many factors are associated with under-prescription, e.g. multi-morbidity, polypharmacy, dementia, frailty, risk of adverse drug events, absence of specific clinical trials in older patients and economic factors. Under-prescription is associated with negative consequences, such as higher risk of cardiovascular events, worsening disability, hospitalization and death. The implementation of explicit criteria for under-prescription, the use of the comprehensive geriatric assessment by geriatricians, and the involvement of a clinical pharmacist seem to be promising options to reduce under-prescription. CONCLUSION: Under-prescription remains widespread in the older population. Further studies should be performed, to provide a better comprehension of this phenomenon and to confirm the efficacy of corrective interventions.

Key Messages for a Frailty Prevention and Management Policy in Europe from the ADVANTAGE JOINT ACTION Consortium.

In the 2015 Ageing Report, the European Commission (EC) and the Economic Policy Committee stated that coping with the challenge posed by an ageing population will require determined policy action in Europe, particularly in reforming pension, health care and long-term care systems. The concern for this situation motivated the EC, the Parliament and many of the Member States (MS) to co-fund, in the 2015 call of the Third European Health Programme of the European Union 2014-2020, the first Joint Action (JA) on the prevention of frailty. ADVANTAGE JA brings together 33 partners from 22 MSs for 3 years. It aims to build a common understanding on frailty to be used in the MSs by policy makers and other stakeholders involved in the management, both at individual and population level, of older people who are frail or at risk for developing frailty throughout the European Union (EU). It is a formidable challenge but also a great opportunity for concerted action resulting in fostering effective and successful policies in frailty prevention and management in the participating MS. The Consortium has 2 years of hard work ahead to contribute to the needed change for frailty related disability free Europe. The first practical step towards this aim was the preparation of a document: the State of the Art on Frailty Report to support an overview of evidence of what works and what does not work on frailty prevention and management. Subsequently, this will be reflected in the advice that the JA will give to policy makers at MS level. Overall, these messages intend to be an instrument of added value to advocate for policy driven decisions on frailty prevention and management in the JA participating MSs and subsequently towards a frailty related disability free older population in Europe. The aim of this paper is to describe ADVANTAGE JA general structure, approach and recommendations towards a European health and social policy which will support frailty prevention in the participating MS.

Selenium Concentrations and Mortality among Community-Dwelling Older Adults: Results from IlSIRENTE Study.

BACKGROUND: Selenium has a wide range of pleiotropic effects, influencing redox homeostasis, thyroid hormone metabolism, and protecting from oxidative stress and inflammation. Serum selenium levels are reduced in the older population. OBJECTIVES: to investigate the association of serum selenium levels with all-cause mortality in a sample of community-dwelling older adults. DESIGN AND SETTING: Data are from the 'Invecchiamento e Longevità nel Sirente' (Aging and Longevity in the Sirente geographic area, ilSIRENTE) study, a prospective cohort study that collected information on individuals aged 80 years and older living in an Italian mountain community (n=347). The main outcome was risk of death after ten years of follow-up. PARTICIPANTS AND MEASUREMENTS: Participants were classified according to the median value of selenium (105.3 µg/L) in two groups: high selenium and low selenium. RESULTS: A total of 248 deaths occurred during a 10-year follow-up. In the unadjusted model, low levels of selenium was associated with increased mortality (HR, 0.66; 95% CI 0.51-0.85). After adjusting for potential confounders the relationship remained significant (HR, 0.71; 95% CI 0.54-0.92). CONCLUSIONS: Low serum levels of selenium are associated with reduced survival in elderly, independently of age and other clinical and functional variables.

My Mind Project: the effects of cognitive training for elderly-the study protocol of a prospective randomized intervention study.

BACKGROUND: Cognitive decline and dementia represent a key problem for public health as they heavily impair social functioning and independent living. The development of new strategies to support recommendations for patients and their caregivers may represent an outstanding step forward. AIMS: To describe the study protocol and methods of "My Mind Project: the effect of cognitive training for elderly" (Grant No. 154/GR-2009-1584108), which investigates, by the use of a multidisciplinary approach, the effects of a comprehensive cognitive training programme on performances in aged subjects with mild-moderate Alzheimer's disease, mild cognitive impairment and normal cognitive functioning. METHODS: The study is a prospective randomized intervention for the assessment of cognitive training effects in three groups of elderly subjects with different cognitive status. A total of 321 elderly people were enrolled in Marche Region, Italy. Each subject was randomly assigned to an experimental group or to a control group. Cognitive performances and biochemical blood markers have also been analysed before cognitive training (baseline), immediately after termination (follow-up 1), after 6 months (follow-up 2) and after 2 years (follow-up 3). DISCUSSION: The results will be useful to identify some efficient programmes for the enhancement of cognitive performance in elderly with and without cognitive decline. CONCLUSION: The application of a non-pharmacological approach in the treatment of elderly with cognitive disorders could have a profound impact on National Health Service.

Inappropriate Use of Proton Pump Inhibitors in Elderly Patients Discharged from Acute Care Hospitals.

BACKGROUND: Proton-pump inhibitors (PPI) are extensively prescribed in older patients. However, little information is available on factors associated to PPI prescribing patterns among older patients discharged from hospital. OBJECTIVE: To evaluate the appropriateness and clinical correlates of PPI prescription at discharge in a population of 1081 older patients discharged from acute care Italian hospitals. DESIGN: We used data from the CRiteria to Assess Appropriate Medication Use among Elderly Complex Patients (CRIME) study, a multicenter observational study. The appropriateness of PPI prescriptions was defined according to the Italian Medicines Agency (AIFA) rules. Correlates of overprescribing (i.e prescribing without recognized AIFA indications) and underprescribing (i.e. not prescribing despite the presence of recognized AIFA indications) were investigated by logistic regression analysis. RESULTS: Overprescribing was observed in 30% of patients receiving PPIs at discharge. Underprescribing was observed in 11% of patients not receiving PPIs at discharge. Overprescribing of PPIs at discharge was negatively associated with age (OR=0.88, 95%CI=0.85-0.91), depression (OR=0.58, 95%CI=0.35-0.96), use of aspirin (OR=0.03, 95%CI=0.02-0.06) and systemic corticosteroids (OR=0.02, 95%CI=0.01-0.04). The negative association with number of medications (OR=0.95, 95%CI=0.88-1.03) and overall comorbidities (OR=0.92, 95%CI=0.83-1.02) was nearly significant. Conversely, older age (OR=1.09, 95%CI=1.04-1.14), use of aspirin (OR=24.0, 95%CI=11.5-49.8) and systemic corticosteroids (OR=19.3, 95%CI=11.5-49.8) and overall comorbidities (OR=1.22, 95%CI=1.04-1.42) were independent correlates of underprescribing. CONCLUSION: Overprescribing of PPIs is more frequent in younger patients with lower burden of depression, whilst underprescribing is characterized by older age and greater burden of comorbidity and polypharmacy. Hospitalization should be considered as a clue to identify inappropriate use of PPIs and improve appropriateness of prescribing.

The impact of drug interactions and polypharmacy on antimicrobial therapy in the elderly.

Infectious diseases are more prevalent in older people than in younger adults, and represent a major healthcare issue in older populations. Indeed, infections in the elderly are often associated with higher morbidity and mortality, and may present atypically. Additionally, older patients are generally treated with polypharmacy regimens, which increase the likelihood of drug-drug interactions when the prescription of an antimicrobial agent is needed. A progressive impairment in the functional reserve of multiple organs may affect either pharmacokinetics or pharmacodynamics during aging. Changes in body composition occurring with advancing age, reduced liver mass and perfusion, and reduced renal excretion may affect either pharmacokinetics or pharmacodynamics. These issues need to be taken into account when prescribing antimicrobial agents to older complex patients taking multiple drugs. Interventions aimed at improving the appropriateness and safety of antimicrobial prescriptions have been proposed. Educational interventions targeting physicians may improve antimicrobial prescriptions. Antimicrobial stewardship programmes have been found to reduce the length of hospital stay and improve safety in hospitalized patients, and their use in long-term care facilities is worth testing. Computerized prescription and decision support systems, as well as interventions aimed at improving antimicrobial agents dosage in relation to kidney function, may also help to reduce the burden of interactions and inherent costs.

Treating cancer and no-cancer pain in older and oldest old patients.

Pain is one of the most frequent reasons for consultations in general practice, presenting either alone or associated with some comorbidity. In all care settings for older and oldest old patients, a gap exists between best-practice recommendations and current clinical practice. Clinical manifestations of persistent pain are often complex and multifactorial in the frail population, so the approach to pain management in older persons differs from that for younger people. The purpose of this review is to describe the best approach to assess and manage persistent cancer and no-cancer pain in the elderly, to explain the principles of pain treatment in this so often frail and complex population and compare the different drugs that should be used or avoided in older and oldest old patients considering the agerelated physiologic changes. Considerable emphasis is placed on conditions more common in the elderly such as neuropathic pain or typical subsets of the aging population such as the assessment of pain in people with dementia.

Diagnosing and treating depression in older and oldest old.

Depression is very common in older people and it is associated with negative consequences such as functional decline, increased morbidity and mortality and higher healthcare costs. Despite this, it is still underdiagnosed and undertreated and the issue is particularly relevant for people older than 80 years. The main reasons for underdiagnosis are: atypical presentation, concomitant cognitive decline, inadequate diagnostic tools, and prejudice that depression is a normal part of ageing. On the other hand, the main reasons for undertreatment are: multimorbidity, concerns about adverse events and drug interactions, lack of confidence in the efficacy and safety of pharmacological and non-pharmacological treatments in the oldest old depressed patients, who are underrepresented in clinical studies. The new antidepressants are the drugs most frequently used, due to their perceived more favorable safety profile than older antidepressants. Psychotherapy is equally effective but less frequently used and should request some adaptive strategies for the peculiarities of octogenarians. Electroconvulsive therapy is limited to severe psychotic late-life depression resistant to other treatments. In light of the heterogeneity of people aged 80 years and over, with multiple and different medical, functional, socioeconomic problems, a multidimensional approach is probably the most suitable both for diagnosis and treatment, in order to develop an individualized care plan. These considerations should guide the formulation of future research studies, specifically tailored for the oldest depressed patients.

Diabetes-related quality of life is enhanced by glycaemic improvement in older people.

AIMS: To investigate the validity and reliability of the Audit of Diabetes-Dependent Quality of Life instrument in older Italians with diabetes and to test the association of diabetes-related quality of life with glycaemic control over time. METHODS: A total of 558 outpatients with Type 2 diabetes from the Diabetic Unit of the Italian National Research Centre on Aging Hospital in Ancona were enrolled to complete questionnaires (Audit of Diabetes-Dependent Quality of Life-19 and the Short-Form-12), and to undergo clinical and biochemical testing at baseline and at 12 months of follow-up. The overall impact of diabetes using the average weighted impact score from the Audit of Diabetes-Dependent Quality of Life questionnaire was calculated. Participants were categorized according to this score as having either less or more negative diabetes-related quality of life. RESULTS: Participants had a mean ± SD age of 67.7 ± 9.2 years and 51.8% were male. Factor analysis and Cronbach's coefficient of internal consistency (Cronbach's α = 0.931) confirmed that the 19 domain-specific Audit of Diabetes-Dependent Quality of Life items could be combined into a single scale in this Italian population. The impact score correlated with the physical (r = 0.275; P < 0.001) and mental components (r = 0.291; P < 0.001) of the Short-Form-12 questionnaire. Significant differences were found according to diabetic complications in specific Audit of Diabetes-Dependent Quality of Life items and impact scores. Insulin use had a greater association with a more negative quality of life compared with other antidiabetic agents. A multivariate linear regression model with restricted linear spline application showed that the relationship between HbA1c and impact score was not linear and that the change in the impact score was associated with improved glycaemic control in those with a less negative diabetes-related quality of life at 12 months. CONCLUSIONS: The Audit of Diabetes-Dependent Quality of Life-19 is a valid tool for measuring the impact of diabetes on quality of life in older Italians. Perception of diabetes-related quality of life is associated with glycaemic control over time.

Non-invasive measurement of brain temperature using radiometric thermometry: experimental validation and clinical observations in asphyxiated newborns.

BACKGROUND: Therapeutic hypothermia (HT) has been shown to decrease death and severe disability in infants with hypoxic-ischemic encephalopathy (HIE). Rectal temperature (RT) is used to determine the temperature set-points for treatment with HT, however experimental studies have shown significant differences between RT and brain temperature during HT. Knowledge of actual brain temperature during HT might allow better determination of optimal degree of cooling and improve outcomes. OBJECTIVES: To compare measurements of brain temperature obtained by non-invasive radiometric thermometry (RadT) to direct tissue measurements in an experimental model of HT, and to use RadT in newborn infants with HIE undergoing HT. STUDY DESIGN: RadT measurements of brain temperature were compared to fiber optic (Luxtron) thermometry measurements placed at a depth of 1.5 centimeters into the brain of cooled miniswine. Following validation studies, brain RadT and RT measurements were continuously recorded in thirty infants with HIE during HT and rewarming. RESULTS: RadT and Luxtron probe temperatures were comparable in miniswine throughout a temperature range similar to therapeutic HT. RadT measurements of brain temperature were higher than RT in 60% of infants with HIE undergoing HT. Higher RadT measurements compared to RT were associated with cerebral white matter abnormalities (p = 0.01). CONCLUSIONS: RadT provides a safe, passive and non-invasive way to measure brain temperature that can be used in the clinical setting. RadT may be helpful in determining the optimal degree of cooling and identifying infants at highest risk of brain injury.

Physical performance measures and polypharmacy among hospitalized older adults: results from the CRIME study.

OBJECTIVE: To investigate the association of polypharmacy and physical performance measures in a sample of elderly patients aged ≥65 years admitted to acute care hospitals. DESIGN, SETTING AND PARTICIPANTS: Prospective study conducted among 1123 hospitalized older adults participating to the CRiteria to Assess Appropriate Medication Use among Elderly Complex Patients (CRIME) project. MEASUREMENTS: Physical performance was measured at hospital admission by the 4-meter walking speed (WS) and the grip strength (GS). Polypharmacy was defined as the use of ≥10 drugs during hospital stay. RESULTS: Mean age of 1123 participants was 81.5±7.4 years and 576 (51.3%) were on polypharmacy. Prevalence of polypharmacy was higher in patients with low WS and GS. After adjusting for potential confounders, participants in the highest tertile of WS were less likely to be on polypharmacy as compared with those in the lowest tertile (OR 0.58; 95% CI 0.35 - 0.96). Similarly, participants in the highest tertile of GS had a significantly lower likelihood of polypharmacy as compared with those in the lowest tertile (OR 0.55; 95% CI 0.36 - 0.84). When examined as continuous variables, WS and GS were inversely associated with polypharmacy (WS: OR 0.77 per 1 SD increment; 95% CI 0.60 - 0.98; GS: OR 0.71 per 1 SD increment; 95% CI 0.56 - 0.90). CONCLUSION: Among hospitalized older adults WS and GS are inversely related to polypharmacy. These measures should be incorporated in standard assessment of in-hospital patients.

Relationship between use of proton pump inhibitors and IGF system in older subjects.

OBJECTIVES: to investigate the effects of proton pump inhibitors (PPIs) on the insulin-like-growth factor 1(IGF-1) system in the elderly. DESIGN: cross-sectional. SETTING: InCHIANTI study. PARTICIPANTS: 938 older subjects (536 women, 402 men, mean age 75.7±7.4 years). MEASUREMENTS: complete data on age, sex, BMI, liver function, medications, dietary intake, IGF-1, IGF-binding protein-1 and -3 (IGFBP-1, IGFBP-3). RESULTS: Participants were categorized by PPI use, identifying 903 PPI non users and 35 users. After adjusting for age, male PPI users (107.0 ± 69.6 vs. 127.1 ± 55.8, p<0.001) and female PPI users (87.6 ± 29.1 vs. 107.6 ± 52.3, p=0.03) had lower IGF-1 levels than non-users. IGFBP-1 levels were similar in the two groups in both sexes. In whole population, after adjustment for age and sex, PPI users had lower IGF-1 levels 81.9 [61.1-113.8] than non-users 110 [77.8-148.6], p=0.02. After further adjustment for BMI, albumin, liver function, C-reactive protein, Interleukin-6, number of medications, ACE-inhibitors use, caloric intake, protein intake, physical activity, glycemia, and IGFBP-1, the use of PPIs remained significantly and negatively associated with IGF-1 levels (ß±SE = -19.60±9.83, p=0.045). CONCLUSION: Use of PPIs was independently and negatively associated with IGF-1 levels.

Human apolipoprotein E4 modulates the expression of Pin1, Sirtuin 1, and Presenilin 1 in brain regions of targeted replacement apoE mice.

The apolipoprotein E4 (apoE4) allele is consistently associated with increased risk for Alzheimer's disease (AD). We investigated the molecular mechanism of this susceptibility by analyzing the levels of genes involved in AD pathogenesis in transgenic mice expressing human apoE3 or apoE4 isoforms. mRNA and protein levels of Pin1, Sirtuin 1 (Sirt1), Presenilin 1 (PS1), and pro-Brain-derived Neurotrophic Factor (BDNF) were analyzed in brain regions affected by neuropathological changes in AD. Pin1 mRNA was significantly higher in the hippocampus of apoE4 mice than in apoE3 controls, whereas lower expression was detected in the entorhinal and parietal cortices. Reduced Pin1 levels may increase neurofibrillary degeneration and amyloidogenic processes, while compensatory mechanisms may take place in the hippocampus to balance spatial memory deficits. Sirt1 levels were significantly reduced in the frontal cortex of apoE4 mice. Sirt1 reduction may hinder its protective role against the formation of plaques and tangles and diminish its anti-inflammatory actions. Sirt1 decrease may also play a role in apoE4-associated memory impairments. Moreover, in apoE4 mice PS1 mRNA levels were lower in the frontal cortex. Lower PS1 expression may hamper γ-secretase function, thus affecting amyloid precursor protein processing. Pro-BDNF mRNA levels did not differ between apoE3 and apoE4 mice in any region analyzed. This study showed dysregulated expression of Pin1, Sirt1, and PS1 genes in different cerebral areas of apoE4 mice, suggesting that these changes may play a role in the mechanism of AD vulnerability.

Milk fat globule epidermal growth factor 8 (MFG-E8): a novel protein in the mammalian endometrium with putative roles in implantation and placentation.

OBJECTIVES: MFG-E8 is a novel endometrial protein with conserved functions in tissue remodeling and angiogenesis in non-uterine tissues. Our aims were: 1. To examine the presence of MFG-E8 protein in the human endometrium during the window of implantation, in human endometrial cell lines, in human placental tissue at different gestational ages, and in murine implantation sites during early gestation; and 2. To study the regulation of MFG-E8 mRNA expression in mice implantation sites. STUDY DESIGN: MFG-E8 protein and its receptor integrin αvß3 were detected by immunostaining in human endometrial biopsies obtained from normal volunteers, in human endometrial cell lines (epithelial: Ishikawa and HEC-1A, stromal: HESC, and endothelial: HEEC), in human products of conception from all trimesters of gestation, and in murine implantation and inter-implantation sites dissected on days 5 and 8 post-coitus. MFG-E8 gene expression was assessed by RT-PCR. MAIN OUTCOME MEASURES: Immunohistochemical determination of MFG-E8 in endometrium and products of conception as well as relative MFG-E8 mRNA expression in mice implantation sites. RESULTS: MFG-E8 protein was present almost exclusively in the epithelial compartment of human endometrium. It was also expressed in the cytotrophoblasts and syncytiotrophoblasts outlining chorionic villi of the human placenta at all trimesters of gestation, and in murine implantation sites. MFG-E8 mRNA was significantly up-regulated in murine implantation sites and with increased gestational age. CONCLUSIONS: MFG-E8 expression in the endometrial epithelium as well as in chorionic villi suggests its possible role in endometrial reorganization during the receptive phase and in events related to normal pregnancy in mammals.

Screening for frailty in elderly emergency department patients by using the Identification of Seniors At Risk (ISAR).

OBJECTIVES: Frail older adults are at an increased risk for adverse outcomes after an Emergency Department (ED) visit. Comprehensive geriatric assessment (CGA) has been proposed to screen for frailty in the ED, but it is difficult to carry out. We tested whether a CGA-based approach using the Identification of Seniors At Risk (ISAR) screening tool was associated with the brief deficit accumulation index (DAI) of frailty. DESIGN: Prospective observational study. SETTING: Two urban EDs in Italy. PARTICIPANTS: A cohort of 200 elderly (≥65 years) ED patients. MEASUREMENTS: Identifiers, triage, clinical and social data along with the administration of ISAR. CGA was performed using: Charlson Index, Short Portable Mental Status Questionnaire and Katz's ADL. Follow-up data at 30 and 180 days included: mortality, ED revisit, hospital admission, and functional decline. Frailty was defined according to a brief DAI. Logistic regression evaluated the consistency of the frailty definition; ROC curves evaluated ISAR ability in identifying frailty. RESULTS: Frailty was present in 117 (58.5%) subjects and predicted ED revisit and frequent ED return, hospitalization and 6-month mortality. ISAR had an AUC of 0.92 (95%CI 0.88-0.96, p<0.0001) in identifying frail elders in the ED and using a cut-off of 2 showed 94% sensitivity and 63% specificity. CONCLUSION: ISAR is a useful screening tool for frailty and identifies elderly patients at risk of adverse outcomes after an ED visit. ISAR can also be used to select high-risk patients more likely to benefit from a geriatric approach or intervention, independently of admission or discharge.

Effects of anorexia on mortality among older adults receiving home care: an observation study.

PURPOSE: We describe the prevalence of secondary anorexia in a population of older people living in community and receiving home care. In addition, we examined the relationship between secondary anorexia and mortality. METHODS: We analyzed data from a large collaborative observational study group, the Italian Silver Network Home Care project, that collected data on patients admitted to home care programs. A total of twelve Home Health Agencies participated in such project evaluating the implementation of the Minimum Data Set for Home Care (MDS-HC) instrument. A total of 2757 patients were enrolled in the present study. The main outcome measures were the prevalence of anorexia, weight loss and survival. RESULTS: More than 25% (744 subjects) of the study sample suffered from anorexia. During a mean follow-up of 10 months from initial MDS-HC assessment, 468 patients (17%) died. There was uneven distribution of the risk. After adjusting for age, gender and for all other possible risk factors for death (living alone, physical and cognitive disability, behavior problems, urinary incontinence, pressure ulcer, hearing impairment, congestive heart failure, hypertension, depression, diabetes, renal failure, cancer), subjects with anorexia were more likely to die relative to patients without anorexia (RR, 1.83; 95% CI 1.45-2.31). Even though the risk of mortality was higher among subjects suffering from anorexia and weight loss, the anorexia per se was associated with higher risk compared with subjects without anorexia (RR, 1.45; 95% CI 1.01-2.19). CONCLUSIONS: Anorexia is associated with a significant higher risk of all-cause mortality. The present findings support the possibility that anorexia has an independent effect on survival even among old people receiving home care.

Discovering pathways of sarcopenia in older adults: a role for insulin resistance on mitochondria dysfunction.

The precise cause of sarcopenia, skeletal muscle loss and strength, in older persons is unknown. However, there is a strong evidence for muscle loss due to insulin resistance as well as mitochondrial dysfunction over aging. Considering that epidemiological studies have underlined that insulin resistance may have a specific role on skeletal muscle fibre atrophy and mitochondrial dysfunction has also been extensively shown to have a pivotal role on muscle loss in older persons, a combined pathway may not be ruled out. Considering that there is growing evidence for an insulin-related pathway on mitochondrial signaling, we hypothesize that a high degree of insulin resistance will be associated with the development of sarcopenia through specific alterations on mitochondrial functioning. This paper will highlight recent reviews regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance. We will specifically emphasize possible steps involved in sarcopenia over aging, including potential biomolecular mechanisms of insulin resistance on mitochondrial functioning.

Frailty and muscle metabolism dysregulation in the elderly.

The frailty syndrome is increasingly recognized by geriatricians to identify elders at an extreme risk of adverse health outcomes. The physiological changes that result in frailty are complex and up to now have been extremely difficult to characterize due to the frequent coexistence of acute and chronic illness. Frailty is characterized by an decline in the functional reserve with several alterations in diverse physiological systems, including lower energy metabolism, decreased skeletal muscle mass and quality, altered hormonal and inflammatory functions. This altered network leads to an extreme vulnerability for disease, functional dependency, hospitalization and death. One of the most important core components of the frailty syndrome is a decreased reserve in skeletal muscle functioning which is clinically characterized by a loss in muscle mass and strength (sarcopenia), in walking performance and in endurance associated with a perception of exhaustion and fatigue. There are a number of physiological changes that occur in senescent muscle tissues that have a critical effect on body metabolism. The causes of sarcopenia are multi-factorial and can include disuse, changing hormonal function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies. In this review, we will explore the dysregulation of some biological mechanisms that may contribute to the pathophysiology of the frailty syndrome through age-related changes in skeletal muscle mass and function.

Persistent ex vivo low number and functional in vitro recovery of circulating gammadelta T cells after removal of a cutaneous primary melanoma.

We recently described gammadelta T cells alterations in patients with a cutaneous primary melanoma. To evaluate whether gammadelta T cells alterations persisted after melanoma removal, we performed a follow-up study comparing the number and function of gammadelta T lymphocytes from 19 subjects, 4 years after the removal of a cutaneous primary melanoma, with the data obtained in the same subjects before the surgical intervention and with control donors. The number of circulating gammadelta(+) T cells after melanoma removal was not recovered to the levels found in controls. gammadelta(+) T cells producing TNF-alpha or IFN-gamma were increased after melanoma removal in comparison with the same subjects before surgical intervention or with control donors. After in vitro culture, both the percentage and the expansion of gammadelta T cells were recovered to the values found in controls. In conclusion, the functional capacity of gammadelta T cells was in vitro recovered after melanoma removal, whereas their ex vivo number remained at lower levels than control donors.