Search

Malnutrition often affects elderly patients and significantly contributes to the reduction in healthy life expectancy, causing high morbidity and mortality. In particular, protein malnutrition is one of the determinants of frailty and sarcopenia in elderly people.To investigate the role of amino acid supplementation in senior patients we performed an open-label randomized trial and administered a particular branched-chain amino acid enriched mixture (BCAAem) or provided diet advice in 155 elderly malnourished patients. They were followed for 2 months, assessing cognitive performance by Mini Mental State Examination (MMSE), muscle mass measured by anthropometry, strength measure by hand grip and performance measured by the Timed Up and Go (TUG) test, the 30 s Chair Sit to Stand (30-s CST) test and the 4 m gait speed test. Moreover we measured oxidative stress in plasma and mitochondrial production of ATP and electron flux in peripheral blood mononuclear cells.Both groups improved in nutritional status, general health and muscle mass, strength and performance; treatment with BCAAem supplementation was more effective than simple diet advice in increasing MMSE (1.2 increase versus 0.2, p = 0.0171), ATP production (0.43 increase versus -0.1, p = 0.0001), electron flux (0.50 increase versus 0.01, p 0.0001) and in maintaining low oxidative stress. The amelioration of clinical parameters as MMSE, balance, four meter walking test were associated to increased mitochondrial function.Overall, our findings show that sustaining nutritional support might be clinically relevant in increasing physical performance in elderly malnourished patients and that the use of specific BCAAem might ameliorate also cognitive performance thanks to an amelioration of mitochondria bioenergetics.

Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p = .07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p = .17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p

Background Here we study the effect of type 2 diabetes (T2DM) on bone cell precursors, turnover and cytokines involved in the control of bone cell formation and activity. Methods We enrolled in the study 21 T2DM women and 21 non diabetic controls matched for age and body mass index (BMI). In each subject we measured bone cell precursors, Receptor Activator of Nuclear Factor κB (RANKL), Osteoprotegerin (OPG), Sclerostin (SCL) and Dickoppf-1 (DKK-1) as cytokines involved in the control of osteoblast and osteoclast formation and activity, bone density (BMD) and quality trough trabecular bone score (TBS) and bone turnover. T2DM patients and controls were compared for the analyzed variables by one way ANOVA for Gaussian ones and by Mann-Whitney or Kruskal-Wallis test for non-Gaussian variables. Results RANKL was decreased and DKK-1 increased in T2DM. Accordingly, patients with T2DM have lower bone turnover compared to controls. BMD and TBS were not significantly different from healthy controls. Bone precursor cells were more immature in T2DM. However the number of osteoclast precursors was increased and that of osteoblasts decreased. Conclusions Patients with T2DM have more immature bone cells precursors, with increased number of osteoclasts and decreased osteoblasts, confirming low bone turnover and reduced cytokines such as RANKL and DKK-1. BMD and TBS are not significantly altered in T2DM although, in contrast with other studies, this may be due to the match of patients and controls for BMI rather than age.

Hyponatremia and hypokalemia are common among elderly and have been associated with osteoporosis, we evaluate the role of these electrolytes as risk for fragility fractures. This study is divided in two parts: one retrospective and one prospective. We retrospectively collected data on urgently admitted patients for femoral fragility fractures (Fx) or for acute myocardial infarction (AMI), and patients admitted for elective hip/knee replacement surgery for osteoarthrosis (OA). Age, sex, serum sodium, potassium, creatinine, and comorbidities were recorded. We enrolled prospectively in-patients from our unit: age, sex, comorbidities, drugs, and fragility fractures were recorded. Blood electrolytes were measured. Cognitive function, nutrition, muscular strength, and balance were evaluated by standard tests. The mortality rate was recorded with a follow-up after hospital discharge. The retrospective study included 2166 subjects: 702 Fx and 1464 controls (907 AMI, 557 OA): the prevalence of hyponatremia was similar in Fx and AMI, whereas it was higher in Fx with respect to OA (p

Purpose: o report and describe cognitive impairments during lenalidomide treatment in three patients. Despite the relevant clinical impact of chemotherapy-related cognitive deficit (known as "chemobrain effect"), very few data are available in the literature. Methods: We present three subjects who developed cognitive impairment during treatment with lenalidomide. Their neuropsychological assessment was evaluated in order to better define the cognitive areas involved. For each patient medical history, drug therapy, physical examination and other instrumental tests (brain CT scan and/or MRI scan, FDG-PET and electroencephalography) were collected. Results: In all patients, we observed an homogeneous neuropsychological pattern characterized by long-term verbal and visuospatial memory deficits, and decline in attentional and executive functions. Conclusions: Lenalidomide treatments can determine severe cognitive impairments especially in elderly patients. Our data suggest the need for a careful evaluation of cognitive decline risk before and after drug administration. However, larger studies are required to confirm our findings.

Uncertainties about efficacy and safety of oral anticoagulant therapy (OAT) among older and frail medical patients with atrial fibrillation (AF) largely contribute to under-prescription of these drugs. In this prospective observational cohort study, we investigated mortality, and ischemic and hemorrhagic events, in hospital-discharged older patients with AF. Stroke and bleeding risk were evaluated using CHA2DS2-VASC and HAS-BLED scores. Comorbidity, frailty, cognitive and nutritional status and functional autonomy were evaluated using standardized scales. Independent associations between clinical variables, including OAT use, and all-cause mortality, fatal and non-fatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. Of 452 patients included (mean age 81.6 years, 54.9 % women, roughly 30 % cognitively impaired and/or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.6 and 2.8, respectively), 151 (33.4 %) died during a mean follow-up period of 300.5 days; ischemic and hemorrhagic stroke occurred in 4.0 and 0.4 % of patients, respectively, and major bleedings in 6.2 %. After multivariate analysis, OAT at discharge was associated with lower overall mortality and reduced occurrence of ischemic stroke, the first finding being confirmed in propensity score matched analysis. Among older vulnerable AF patients with high post discharge death rate, OAT was associated, among other multiple factors, with reduced mortality and lower occurrence of ischemic stroke.

Background: Acute kidney injury (AKI) incidence is reported to be 10 times higher in aged people. Related to their higher prevalence of chronic kidney disease (CKD), older patients are at high risk of toxic effects driven by drugs. Methods: The demographics, hospitalizations, visits to the Emergency Department, pharmacological therapy, and lab tests were analyzed in 71,588 individuals. Results: Data showed a higher prevalence of AKI as well as CKD in the elderly as compared to the younger group, with an associated very high mortality. A broad number of drugs was prescribed, ranging from 1 to 35, the majority being between 5 and 9 drugs. Conclusion: Elderly patients who developed AKI had a higher number of hospitalizations (underlying frailty), were more likely to progress to more severe stages of CKD and to be affected by other non-renal pathologies (associated comorbidities) and to be given heavier pharmacological prescriptions (polypharmacy).

Individuals with dementia and their families often experience poor quality of life due to patient’s behavioral and psychological symptoms. Increasing evidence has mounted on the potential role of music in improving social, emotional and cognitive skills. In the present study we aim to investigate whether a receptive music intervention might reduce apathy and depression in elderly patients with Alzheimer’s disease (AD) or vascular dementia (VaD) and improve their caregivers’ burden. Among patients attending to a Memory Clinic, we have enrolled 48 AD or VaD elderly subjects. They were divided into two groups on the basis of family agreement to musictherapy. The experimental group (n=15) was asked to listen to a 80-minute audio CD, for at least 15 minutes per day, at least once a week, for three months. The overall sample was evaluated at baseline, at week 4 and at week 12 through the Mini Mental State Examination (MMSE), the Cornel- Brown Scale QoL in Dementia (CBSQoLD) and the Apathy Evaluation Scale (AES); caregiver stress was assessed using the Caregiver Burden Inventory (CBI). Apathy and depression were significantly improved among patients treated with music interventions compared to control group (treatment effect =43.667; P

Blood pressure variability (BPV) may have prognostic implications for cardiovascular risk and cognitive decline; however, BPV has yet to be studied in old and very old people. Aim of the present study was to evaluate the extent of BPV and to identify variables associated with BPV among older subjects. A retrospective study of patients aged ≥ 65 years who underwent 24-h ambulatory blood pressure monitoring (ABPM) was carried out. Three different BPV indexes were calculated for systolic and diastolic blood pressure (SBP and DBP): standard deviation (SD), coefficient of variation (CV), and average real variability (ARV). Demographic variables and use of antihypertensive medications were considered. The study included 738 patients. Mean age was 74.8 ± 6.8 years. Mean SBP and DBP SD were 20.5 ± 4.4 and 14.6 ± 3.4 mmHg. Mean SBP and DBP CV were 16 ± 3 and 20 ± 5%. Mean SBP and DBP ARV were 15.7 ± 3.9 and 11.8 ± 3.6 mmHg. At multivariate analysis older age, female sex and uncontrolled mean blood pressure were associated with both systolic and diastolic BPV indexes. The use of calcium channel blockers and alpha-adrenergic antagonists was associated with lower systolic and diastolic BPV indexes, respectively. Among elderly subjects undergoing 24-h ABPM, we observed remarkably high indexes of BPV, which were associated with older age, female sex, and uncontrolled blood pressure values.

The purpose of this document, a result of the harmonisation and revision of Guidelines published separately by the SIMFER, SIOMMMS/SIR, and SIOT associations, is to provide practical indications based on specific levels of evidence and various grades of recommendations, drawn from available literature, for the management of osteoporosis and for the diagnosis, prevention, and treatment of fragility fractures. These indications were discussed and formally approved by the delegates of the Italian Scientific Associations involved in the project (SIE, SIGG, SIMFER, SIMG, SIMI, SIOMMMS, SIR, and SIOT). The purpose of this document, a result of the harmonisation and revision of Guidelines published separately by the SIMFER, SIOMMMS/SIR, and SIOT associations, is to provide practical indications based on specific levels of evidence and various grades of recommendations, drawn from available literature, for the management of osteoporosis and for the diagnosis, prevention, and treatment of fragility fractures. These indications were discussed and formally approved by the delegates of the Italian Scientific Associations involved in the project (SIE, SIGG, SIMFER, SIMG, SIMI, SIOMMMS, SIR, and SIOT).

We investigated the effect of bone turnover on glucose homeostasis, fat distribution and adipokine production during anabolic treatment with PTH. This is a parallel, randomized controlled, open label, trial. The randomization was done by computer generated tables to allocate treatments. Forty-six postmenopausal osteoporotic non-diabetic women were assigned to treatment with calcium and colecalcipherol with (24) or without (22) PTH 1-84. Patients were recalled after 3, 6, 12 and 18 months of treatment and markers of bone turnover, glucose metabolism, adipokine secretion and fat distribution were analyzed. Markers of bone turnover and adipokines were measured by ELISA. Glucose metabolism was evaluated by an oral glucose load test and insulin resistance and secretion were calculated. Fat and lean mass were evaluated by anthropometric measures. The effect of treatment on measured variables was analyzed by repeated measure test, and its effect on glucose was also evaluated by mediation analysis after correction for possible confounders. Twenty patients in the calcium and vitamin D groups and 19 in the group treated with PTH 1-84 completed the study. There were no significance adverse events. Treatment with PTH increases osteocalcin, both total (OC) and undercarboxylated (uOC), and decreases blood glucose, without influence on insulin secretion, resistance and pancreatic β cell function. Treatment with PTH does not influence fat distribution and adipokine production. The results of the mediation analyses suggest a total effect of PTH on blood glucose, moderately mediated by OC and to a less extent by uOC. Here we suggest that treatment with PTH influences glucose metabolism partially through its effect on bone turnover, without influence on insulin secretion, resistance, pancreatic β cell function and fat mass.

Aim To characterize elderly medical patients and identify factors associated with prolonged length of stay. Methods The present prospective observational study evaluated consecutive patients aged ≥65 years admitted in acute geriatric and medical wards. A comprehensive assessment including demographic, clinical, functional and cognitive variables was carried out. Delayed discharge was defined when patients were discharged later than the date they were deemed medically ready for discharge by physicians. The analysis was initially carried out on the total sample and subsequently according to whether hospital admission had been from home, or from intermediate or long-term facilities. Results Among 1568 patients (age 81.3 ± 7.3 years, 712 men), we observed a high prevalence of functional dependence, cognitive impairment, chronic immobilization and frailty (50%, 25%, 20% and 40%, respectively). Overall, delayed discharge occurred in 442 cases – resulting in 2637 days of prolonged hospital stay – and was independently associated with impairment in activities of daily living, frailty, high comorbidity and inappropriate admission. Among patients admitted from home (roughly 90% of the sample), delayed discharge occurred in 392 patients, and was independently associated with cognitive impairment, functional dependence, low severity of comorbidity and inappropriate admission (OR 3.39). Among patients admitted from intermediate or long-term facilities, lower cognitive impairment and greater severity of functional dependence were independently associated with prolonged stay. Conclusions Poor health conditions and high prevalence of geriatric syndromes are extremely common among older medical inpatients. Delayed discharge was mainly observed in patients admitted from home, and associated with cognitive impairment (OR 1.12) and functional dependence (OR 1.49). Geriatr Gerontol Int 2015; 16: 314–321.

The aim of this study was to evaluate differences in T helper cell sub-types and osteoclast (OCs) precursors in peripheral blood between patients affected by early rheumatoid arthritis (eRA) and healthy controls. The effect of administration of cholecalcipherol on clinical and laboratory parameters was subsequently evaluated, by a parallel, randomized double blind, placebo controlled trial. Thirty nine eRA patients and 31 age-matched controls were enrolled and compared for levels of 25OH vitamin D, T helper cell sub-types, OCs precursors including both classical and non-classical and pro-inflammatory cytokines at baseline. Eligible patients were female ≥18 years of age with a diagnosis of RA, as defined by the American College of Rheumatology 2010 criteria for

Objectives: Severe protein energy malnutrition results in muscle wasting and loss of subcutaneous tissue and has serious implications for health, recovery from illness or surgery, and hospital costs; however this condition is often underestimated and considered as one of the aspects of aging. We measure the incidence of malnutrition and its consequences on general health, physical and mental performance in a cohort of elderly patients. Study Design: This is a cross-sectional study conducted in a geriatric inpatient unit. Three hundred patients admitted to the clinic who fulfilled the inclusion criteria were enrolled. Main Outcome Measures: Nutritional status was evaluated by Mini Nutritional Assessment (MNA) questionnaire, macro and micronutrients intake, anthropometric measures and biochemical parameters. Physical and mental performances were recorded by questionnaires. Muscular strength was measured by a hand dynamometer and clinical outcomes were recorded. Results: Patients with poor nutritional status have lower physical and mental performance as respect to well nourished patients. Undernourished patients have longer hospitalization and worst outcomes. We observe a high prevalence of severe hypovitaminosis D and the intake of various micronutrients was severely unbalanced. The incidence of malnutrition was 25% (75 patients); 39% (119 patients) were at risk of malnutrition. MNA was inversely related with the length of hospital stay (R = -0.25, p = 0.012) and with Geriatric Depression Scale (GDS) (R = -0.56, p = 0.000), whereas directly related with cognitive performance measured through Mini Mental State Examination (MMSE) (R = 0.5, p = 0.000) and hand grip strength (R = 0.35, p = 0.000). Conclusions: Malnutrition significantly reduced quality of life, physical and mental performance and worsened patients’ prognosis.

We report the prevalence of osteoporosis, osteopenia, and fractures in a cohort of Italian women randomly recruited among the general population and validate the use of clinical guidelines in referring women for bone density testing. We enrolled in the study 995 healthy women (age range 45-92 years). A bone density test at the lumbar spine and femur was performed and a questionnaire on osteoporosis risk factors completed for all patients. The prevalence of osteoporosis was 33.67 %, that of osteopenia was 46.63, and 19.7 % were normal at bone density testing. Osteoporotic women were generally older and thinner, with a shorter period of estrogen exposure. The prevalence of fractures was 21.9 %, and fractured women had a lower bone density, were older, and had a longer postmenopausal period. Clinical guidelines for referring women for bone density testing performed poorly (the best performance was 68 %). This is the first study providing data on the prevalence of osteoporosis/osteopenia and of fractures in a cohort of healthy postmenopausal women. Known risk factors influence bone density and risk of fractures. The role of screening in detecting women with postmenopausal osteoporosis is far from optimal.

Osteoblasts, osteocytes, and osteoclasts (OCs) are involved in the bone production and resorption, which are crucial in bone homeostasis. OC hyperactivation plays a role in the exaggerated bone resorption of diseases such as osteoporosis, rheumatoid arthritis, and osteolytic tumor metastases. This work stems from the finding that OCs can express B7h (ICOS-Ligand), which is the ligand of the ICOS T cell costimulatory molecule. Because recent reports have shown that, in endothelial, dendritic, and tumor cells, B7h triggering modulates several activities of these cells, we analyzed the effect of B7h triggering by recombinant ICOS-Fc on OC differentiation and function. The results showed that ICOS-Fc inhibits RANKL-mediated differentiation of human monocyte-derived OC-like cells (MDOCs) by inhibiting the acquirement of the OC morphology, the CD14− cathepsin K+ phenotype, and the expression of tartrate-resistant acid phosphatase, OSCAR, NFATc1, and DC-STAMP. Moreover, ICOS-Fc induces a reversible decrease in the sizes of cells and nuclei and cathepsin K expression in mature MDOCs. Finally, ICOS-Fc inhibits the osteolytic activities of MDOCs in vitro and the development of bone loss in ovariectomized or soluble RANKL-treated mice. These findings open a novel field in the pharmacological use of agonists and antagonists of the ICOS–B7h system.

To characterize elderly medical patients and identify factors associated with prolonged length of stay.The present prospective observational study evaluated consecutive patients aged ≥65 years admitted in acute geriatric and medical wards. A comprehensive assessment including demographic, clinical, functional and cognitive variables was carried out. Delayed discharge was defined when patients were discharged later than the date they were deemed medically ready for discharge by physicians. The analysis was initially carried out on the total sample and subsequently according to whether hospital admission had been from home, or from intermediate or long-term facilities.Among 1568 patients (age 81.3 ± 7.3 years, 712 men), we observed a high prevalence of functional dependence, cognitive impairment, chronic immobilization and frailty (50%, 25%, 20% and 40%, respectively). Overall, delayed discharge occurred in 442 cases - resulting in 2637 days of prolonged hospital stay - and was independently associated with impairment in activities of daily living, frailty, high comorbidity and inappropriate admission. Among patients admitted from home (roughly 90% of the sample), delayed discharge occurred in 392 patients, and was independently associated with cognitive impairment, functional dependence, low severity of comorbidity and inappropriate admission (OR 3.39). Among patients admitted from intermediate or long-term facilities, lower cognitive impairment and greater severity of functional dependence were independently associated with prolonged stay.Poor health conditions and high prevalence of geriatric syndromes are extremely common among older medical inpatients. Delayed discharge was mainly observed in patients admitted from home, and associated with cognitive impairment (OR 1.12) and functional dependence (OR 1.49).

A follow-up program to help patients suffering from severe osteoporosis during their therapy with teriparatide or PTH(1-84) has been designed and performed. The objective of this study was to evaluate the 18-month persistence on these therapies in patients participating in the program. We enrolled 382 patients who started teriparatide or PTH(1-84) following this program and compared them with a historical cohort of 398 patients treated with the same therapies but who did not participate in any follow-up program. At the beginning of the therapy, nurses trained patients on self-injection. Patients received one phone call per week during the first month, then one phone call per month and per 3 months during the following 5 and 12 months, respectively. In every call, nurses helped patients to resolve any possible issues and collected adverse event information. The persistence rate of the group following the program was 85.6%, 8.2% higher than that of the group not following any program (77.4%). The log-rank test on persistence rates on therapy in patients enrolled and not enrolled in the program was performed; the difference was statistically significant (P = 0.006). Discontinuation in the follow-up program group occurred mainly at early stages of the treatment due to adverse events. Our results show that patients suffering from severe osteoporosis treated with teriparatide or PTH(1-84) and enrolled in a follow-up program have higher persistence rates than patients not following the program.

The fatigue life of a structure is also influenced by its size. Statistically, a bone from a large animal is expected to bear a higher risk of stress fracture if compared to the same bone from a small animal of the same species. This is not documented in the dog, where individuals can have a 40 times difference in body mass. We investigated the effect of body size on cortical bone microdamage accumulation, cortical microstructural organization (porosity, osteon area, and osteocyte lacunar density), and turnover in dogs with a wide body mass range. The aim was to understand and mathematically model how the bone tissue copes with the microdamage accumulation linked to body mass increase. Calcified transverse cortical sections of 18 canine radii of remarkably different size were examined by means of a standard bulk-staining technique and histomorphometric standard algorithms. Relationships between the investigated histomorphometric variables age, sex and mass were analyzed by general linear multivariate models and exponential equations. Type and location of microdamage and bone turnover were not influenced by body mass. Gender did not influence any parameter. Age influenced bone turnover and activation frequency. Microcrack density was influenced by bone mass. Bones had a similar microstructural organization within the same species regardless of the subject's dimension. Microdamage accumulation is inversely related to bone mass, whereas bone turnover is mass-invariant. We theorize a mass-related change in the bone fracture toughness targeted to reach an optimal unique dimensionless curve for fatigue life.

The relation between immune system, estrogen deficiency and postmenopausal bone loss is an intriguing and yet unexplained challenge of the past two decades. Here we summarize the evidences that link estrogen deficiency, T and B cells proliferation and activation, cytokines production, and bone loss with particular regard to humans.

The patients’ adherence to osteoporosis treatments is low. In our study population a history of osteoporotic fractures was associated to better compliance and persistence; however, a 12-month randomized study carried out on 816 osteoporotic women showed that providing the patients with their individual fracture risk information did not prove effective. Several drugs are currently available for the treatment of osteoporosis, but the patients’ compliance and persistence with these treatments are low. This study aimed to both analyze the adherence to oral osteoporosis medications among Italian osteoporotic patients (cross-sectional study) and evaluate if providing patients with their individual fracture risk information may improve compliance and persistence (prospective study). A total of 3379 osteoporotic patients referred as outpatients for a visit 1 year after receiving a prescription of oral osteoporosis medications for the first time, were enrolled for the retrospective study. Moreover, 816 postmenopausal women receiving an oral prescription for osteoporosis for the first time, were randomized into two groups: group 1 (managed according to standard clinical practice) and group 2 (managed with greater patient involvement and information on the individual risk of major osteoporotic fractures calculated by DeFRA algorithm). In the retrospective study, a history of osteoporotic fractures, the frequency of drug administration and a condition of being overweight/obese had a significant influence on both compliance and persistence. Of the 816 patients enrolled in the longitudinal study, 731 (374 of group 1 and 357 of group 2) attended the 1 year follow-up visit. The percentage of women with high compliance or persistence was greater in group 2 (64.2 vs. 58.1 % and 66.8 vs. 62.6 %, respectively), but without reaching any statistical significance. Although providing the patients with their individual fracture risk information was not statistically effective, further studies on additional interventions able to improve the patients’ perceived risk of fracture are warranted.

In this retrospective cohort observational study, we investigated mortality, ischemic, and hemorrhagic events in patients ≥65 years with atrial fibrillation consecutively discharged from an Acute Geriatric Ward in the period 2010 to 2013. Stroke and bleeding risk were evaluated using CHA2DS2-VASC (congestive heart failure/left ventricular dysfunction, hypertension, aged ≥75 years, diabetes mellitus, stroke/transient ischemic attack/systemic embolism, vascular disease, aged 65 to 74 years, gender category) and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) scores. Co-morbidity, cognitive status, and functional autonomy were evaluated using standardized scales. Independent associations among clinical variables, including use of vitamin K antagonist-based oral anticoagulant therapy (OAT), all-cause mortality, and fatal and nonfatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. Of 980 patients discharged (mean age 83 years, 60% women, roughly 30% cognitively impaired or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.8 and 2.1, respectively), 505 (51.5%) died during a mean follow-up period of 571 days; ischemic and hemorrhagic stroke occurred in 82 (12.3%) and 13 patients (1.3%), respectively, and major bleedings in 43 patients (4.4%). Vitamin K antagonists' use was independently associated with reduced mortality (odds ratio 0.524) and with a nonsignificant reduction in incidence of ischemic stroke, without excess in bleeding risk. Similar findings were observed in the 2 propensity score-matched cohorts of patients. In conclusion, among vulnerable patients with atrial fibrillation ≥65 years with high post-discharge death rate, OAT was associated, among other multiple factors, with reduced mortality.

We evaluated the effect of parathyroid hormone (PTH) on Wnt10b production by immune system cells in humans. We showed that bone anabolic effect of intermittent PTH treatment may be amplified by T cells through increased production of Wnt10b. Chronic increase in PTH as in primary hyperparathyroidism does not increase Wnt10b expression. The aim of this study is to assess the effect of PTH on Wnt10b production by immune system cells in humans. We assessed both the effect of intermittent PTH administration (iPTH) and of chronic PTH hypersecretion in primary hyperparathyroidism (PHP). Eighty-two women affected by post-menopausal osteoporosis were randomly assigned to treatment with calcium and vitamin D alone (22) or plus 1-84 PTH (42), or intravenous ibandronate (18). Wnt10b production by unfractioned blood nucleated cells and by T, B cells and monocytes was assessed by real-time RT-PCR and ELISA at baseline, 3, 6, 12 and 18 months of treatment. The effect of chronic elevation of PTH was evaluated in 20 patients affected by PHP at diagnosis and after surgical removal of parathyroid adenoma. WNT10b from both osteoporotic and PHP patients was compared to healthy subjects matched for age and sex. iPTH increases Wnt10b production by T cells, whereas PHP does not. After surgical restoration of normal parathyroid function, WNT10b decreases, although it is still comparable with healthy subjects’ level. Thus, chronic elevation of PTH does not significantly increase WNT10b production as respect to control. This is the first work showing the effect of both intermittent and chronic PTH increase on Wnt10b production by immune system cells. We suggest that, in humans, T cells amplified the anabolic effect of PTH on bone, by increasing Wnt10b production, which stimulates osteoblast activity.

Primary hyperparathyroidism (PHPT) is a common cause of bone loss that is modeled by continuous PTH (cPTH) infusion. Here we show that the inflammatory cytokine IL-17A is upregulated by PHPT in humans and cPTH in mice. In humans, IL-17A is normalized by parathyroidectomy. In mice, treatment with anti-IL-17A antibody and silencing of IL-17A receptor IL-17RA prevent cPTH-induced osteocytic and osteoblastic RANKL production and bone loss. Mechanistically, cPTH stimulates conventional T cell production of TNFα (TNF), which increases the differentiation of IL-17A-producing Th17 cells via TNF receptor 1 (TNFR1) signaling in CD4(+) cells. Moreover, cPTH enhances the sensitivity of naive CD4(+) cells to TNF via GαS/cAMP/Ca(2+) signaling. Accordingly, conditional deletion of GαS in CD4(+) cells and treatment with the calcium channel blocker diltiazem prevents Th17 cell expansion and blocks cPTH-induced bone loss. Neutralization of IL-17A and calcium channel blockers may thus represent novel therapeutic strategies for hyperparathyroidism.

Background and aim: The relationships between C-reactive protein (CRP) levels, adipose tissue and metabolic alterations have not been clearly established in healthy non-obese subjects. We investigated the relationships between body fat, CRP levels and metabolic variables in healthy, non-obese sons of patients affected by metabolic syndrome (MS). Methods and Results: Age, CRP and interleukin 6 (IL-6) levels, anthropometric measures (body mass index, BMI; waist circumference and waist-to-hip ratio, WHR), total and regional fat content (as determined by means of dual X-ray absorptiometry, DXA), total and LDL cholesterol, and the metabolic variables related to MS (HDL-cholesterol, triglyceride, glucose and insulin levels; the fasting insulin resistance index, FIRI; blood pressure) were evaluated in 85 healthy non-obese sons of MS patients. Linear and multiple regression analyses were used to evaluate the relationships between body fat, metabolic variables and CRP levels, and to investigate whether the association between body fat content and metabolic variables persists after adjustment for CRP levels. Body fat was associated with all of the investigated variables. CRP levels were associated with total and regional body fat, the anthropometric index of weight, age, and with some metabolic alterations (HDL-cholesterol and triglyceride levels, systolic blood pressure, and fasting insulin and LDL-cholesterol levels). The associations between total body fat and the metabolic variables did not change after adjustment for CRP levels. Total body fat was the best predictor of CRP levels (p Conclusions: In healthy, non-obese sons of MS patients, total body fat is the best predictor of CRP levels, and remains closely associated with metabolic abnormalities after adjustment for CRP levels. These findings strongly support the hypothesis that body fat is the main determinant of metabolic abnormalities and a low inflammatory state, at least in healthy subjects.

We evaluated bone mineral density (BMD) and bone turnover in 22 homozygous prepubertal beta-thalassemic patients treated with desferrioxamine. Ten patients underwent treatment with desferrioxamine for the whole study period, while 12 patients stopped desferrioxamine and were then treated with deferiprone (L1). Lumbar and femoral BMD and bone metabolism markers were examined at baseline and after 1 and 3 years of follow up. All patients were prepubertal at baseline and they all became pubertal over the 3 years of follow up. At baseline, the mean lumbar Z score value was -2.048 SD +/- 0.75; the Z score was less than -2 SD in 13 children, within -1 and -2 SD in 6, and within 0 and -1 SD in only 3 subjects. A significant BMD increase (P0.0001) was observed at both the lumbar (+8.466%/year) and the femoral level (average of +3.46%/year at neck and +5.83%/year at the intertrochanteric region) after 3 years, without any significant difference being shown between patients treated with desferrioxamine and those treated with L1. The mean Z score SD values increased to -1.957 +/- 0.975 at 1 year (not significantly different from baseline) and to -1.864 +/- 1.221 at 3 year follow up (P0.05 vs baseline); an increase in bone turnover was also observed. These findings show that low BMD, a hallmark of beta-thalassemia, improves significantly when puberty begins; this increase involves different skeletal sites, regardless of pharmacological treatment with different iron-chelating drugs.

Objective.—To assess the sensitivity of 5-HT1D receptors in chronic tension-type headache using sumatriptan as a pharmacological probe. Background.—Previous studies have suggested involvement of serotonergic systems in chronic tension-type headache (CTTH), but relevant experimental data are limited. Sumatriptan, a 5-HT1B/1D receptor agonist, stimulates the release of growth hormone (GH) and inhibits the release of ACTH, cortisol, and prolactin. These effects may be used to explore the function of serotonergic systems in vivo. Methods.—We measured GH, ACTH, cortisol and prolactin (PRL) plasma concentrations in 15 patients with chronic tension-type headache and in 18 healthy controls after subcutaneous administration of sumatriptan (6 mg) or placebo. Results.—Placebo administration had no effect on hormone concentrations. GH and PRL secretion after sumatriptan administration was significantly (P

Malnutrition is a frequent complication for elderly demented patients even if they live at their own home with the assistance of a caregiver. The present study evaluates nutritional characteristics of a population of 130 non-institutionalized demented patients. The results show that the mini nutritional assessment (MNA) total score is inversely related with the neuro-psychiatric inventory (NPI) score and that the level of cognitive impairment is related with the nutritional status: patients with mild cognitive impairment (MCI) showed a mean MNA score higher than patients affected by Alzheimer's disease (AD) or vascular dementia (VaD). Moreover, patients depressed, with hallucinations or with behavioral disturbs are more exposed to underfeeding than only cognitively impaired subjects. In conclusion, an appropriated evaluation of nutritional status could prevent and treat nutrition-related problems even in the elderly demented patients living at home.

Atypical or silent celiac disease may go undiagnosed for many years and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis. The prevalence of the latter conditions, in case of new diagnosis of celiac disease, has been evaluated in many studies but, due to the variability of epidemiologic data and patient features, the results are contradictory. The aim of this study was to evaluate bone mineral density by dual-energy X-ray absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those withT-score value T-score value. We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged >30 years, taking into account each risk factor in single patients.

iPTH increases WNT10b in T cells Our results show a marked increase in WNT10b expression in lymphoid cells during treatment with iPTH, whereas calcium and vitamin D alone has no effect; the increase is maximum after 6 months of treatment. We show that iPTH increases WNT10b production mainly by T cells. cPTH does not affect WNT10b expression In patients affected by primary hyperparatiroidism there was no significant difference in baseline expression as respect to osteoporotic, non-treated patients and surgical intervention does not modify WNT10b expression, data not shown.

Background Dickoppf-1 (DKK-1) is a negative regulator of bone formation with tumorigenic potential. The up-regulation of DKK-1 is an early event in prostate cancer (PCa) development, thus we investigated its role as a marker in the diagnosis and prognosis of PCa. Methods We retrospectively enrolled 159 patients who underwent prostate biopsy, either for elevated PSA or suspect digital rectal examination, between 2003 and 2010. During the biopsy, one serum sample was collected from all patients; PSA and DKK-1 were measured by ELISA technique. Amongst the biopsy of 159 patients 75 were affected by PCa and 84 were not the mean period of follow-up for these patients was 5 years; a new biopsy was performed in case of PCa suspicion. Results PSA performed better than DKK-1 in detecting PCa (0.63 vs 0.51 respectively). Differently from PSA DKK-1 was significantly higher in patients who developed PCa during follow-up than in cancer-free ones, thus DKK-1 performed better than PSA in detecting these patients (0.67 vs 0.55). DKK-1 was significantly lower in patients with bone metastases, whereas PSA was not significantly different in patients with different outcomes. Conclusions DKK-1 might be predictive for patients negative at first biopsy who will develop PCa and in the prognosis of bone metastases. It performed worse than PSA in the early diagnosis of Pca.

Osteoporosis is a common disease characterized by the occurrence of fragility fractures. Major osteoporotic fractures are associated with decreased quality of life and high costs.This review summarizes clinical data on raloxifene (RLX), a second generation selective estrogen-receptor modulator (SERM), currently approved for the treatment of postmenopausal osteoporosis. RLX has estrogen effects on bone and lipid profile, whereas it has anti-estrogen effects on uterus and breast cells. Its main side effects are hot flushes and venous thromboembolism. Literature searches were conducted to retrieve articles reporting RLX clinical trial data. For comparison of safety and efficacy, post-marketing studies on RLX were included.RLX is effective in reducing vertebral fracture risk in osteoporotic women, it is safe and its ability to prevent breast cancer has to be considered in the analyses of cost/effect and of the ideal candidate to this treatment. RLX has to be avoided in patients with previous history of venous thromboembolism.

Summary This study evaluates cytokines production in bone and bone marrow of patients with an osteoporotic fracture or with osteoarthritis by real time PCR, Western blot and immunohistochemistry. We demonstrate that the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in patients with osteoporotic fractures. Introduction Fragility fractures are the resultant of low bone mass and poor bone architecture typical of osteoporosis. Cytokines involved in the control of bone cell maturation and function are produced by both bone itself and bone marrow cells, but the roles of these two sources in its control and the amounts they produce are not clear. This study compares their production in patients with an osteoporotic fracture and those with osteoarthritis. Methods We evaluated 52 femoral heads from women subjected to hip-joint replacement surgery for femoral neck fractures due to low-energy trauma (37), or for osteoarthritis (15). Total RNA was extracted from both bone and bone marrow, and quantitative PCR was used to identify the receptor activator of nuclear factor kB Ligand (RANKL), osteoprotegerin (OPG), macrophagecolony stimulatingfactor (M-CSF), transforming growth factor β (TGFβ), Dickoppf-1 (DKK-1) and sclerostin (SOST) expression. Immunohisto- chemistry and Western blot were performed in order to quantify and localize in bone and bone marrow the cytokines. Results We found an increase of RANKL/OPG ratio, M- CSF, SOST and DKK-1 in fractured patients, whereas TGFβ was increased in osteoarthritic bone. Bone marrow produced greater amounts of RANKL, M-CSF and TGFβ compared to bone, whereas the production of DKK-1 and SOST was higher in bone. Conclusions We show that bone marrow cells produced the greater amount of pro-osteoclastogenic cytokines, whereas bone cells produced higher amount of osteoblast inhibitors in patients with fragility fracture, thus the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in these patients.

Introduction: The use of hospital care increases significantly with age. Older people coming to the emergency department have three to seven times higher rates of hospitalization than younger people. Hospitalization can lead to loss of independence and also need for long-term care at discharge. Methods: A prospective observational non-randomized study of elderly patients admitted to the Department of Geriatric Medicine, University of Torino, Italy, between October 2006 and May 2007. Results: The mean age of 123 subjects was 82.2±7.3 years. Among patients with dependence two weeks before admission, as reported by their caregivers, bathing, toileting and dressing were the most compromised ADL functions. In the same patients, shopping and transportation were reported as the most frequent IADL functions lost. Functional decline before hospitalization was significantly associated with a worsening in functional decline during the length of stay (RR 2.2, CI 1.05–4.66) and with discharge to a long-term facility (RR 2.1, CI 1.04–4.44). Conclusions: As functional decline two weeks before hospitalization influences hospital discharge and functional outcomes, it is certainly interesting to evaluate the impact of a dedicated early rehabilitation program for elderly patients. A well-structured program involving geriatricians, physiatricians and physiotherapists could be helpful for better short-term prognoses.

Background: Osteoporosis is a highly prevalent disease and fractures are a major cause of disability and morbidity. Aim: The purpose of this study was to characterize post-menopausal women attending osteoporosis centers in Italy, to evaluate physician management, and to determine the incidence of first osteoporotic fracture. Subjects and methods: PROTEO-1 was an observational longitudinal study with a 12-month follow-up. Data were collected from women attending osteoporosis centers. Women without prevalent fracture were eligible to enter the 1-yr follow-up phase: the clinical approach to patients according to their fracture risk profile and the incidence of fracture were recorded. Results: 4269 patients were enrolled in 80 centers in the cross-sectional phase; 34.2% had an osteoporotic fracture at baseline. Patients with prevalent fractures were older and more likely to be treated compared with non-fractured patients. The incidence of vertebral or hip fracture after 1 yr was 3.84%, regardless of the calculated risk factor profile, and was significantly higher in patients with back pain at baseline (4.2%) compared with those without back pain (2.2%; p=0.023). Generally, physicians prescribed more blood exams and drugs to patients at higher risk of fracture. Among fractured patients only 24% were properly treated; the rate of non-responders to treatment was about 4%. Conclusions: In a large, unselected sample of post-menopausal women attending osteoporosis centers, those without previous fracture were at substantial risk of future fracture, regardless of their theoretical low 10-yr fracture risk. The presence of back pain in women without previous fracture warrants close attention.

Background and aims: Caregiving can be extremely stressful, especially when patients’ ability to communicate is impaired. While the stress undergone by relatives assisting their loved ones has been widely investigated, fewer data can be found about the stress in healthcare professionals. The aim of this study is to evaluate whether a specific training course could be related to a reduction in the levels of stress of professional care-givers working with patients suffering from dementia. Methods: Work-related levels of stress of study participants were evaluated with the Staff Stress Measure Dementia Care Scale, at baseline and four months after completion of an eight-month training course. Results: We found no significant correlation between care-givers’ age, gender, marital status, years of employment or perceived economic status, and their stress levels at baseline. Patients’ characteristics were not related with care-givers’ stress at baseline. The mean level of stress was significantly reduced (34.64±4.15 vs 26.64±3.82, p