Ettore Capoluongo

Sarcopenia as a risk factor for falls in elderly individuals: Results from the ilSIRENTE study

BACKGROUND & AIMS Sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals. We evaluated the relationship between sarcopenia and 2-year risk of falls in a population of persons aged 80 years or older. METHODS Data are from the baseline and follow-up evaluations of the Aging and Longevity Study in the Sirente Geographic Area (ilSIRENTE Study) (n=260). According to the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia was diagnosed in presence of low muscle mass (mid-arm muscle circumference) plus either low muscle strength (hand grip) or low physical performance (4-m walking speed). The primary outcome measure was the incident falls during the follow-up period of 2 years. The relationship between sarcopenia and incident falls was estimated by deriving hazard ratios (HRs) from multiple logistic regression models considering the dependent variable of interest at least one fall during the follow-up period. RESULTS Sixty-six participants (25.4%) were identified as affected by sarcopenia. Eighteen out of 66 (27.3%) participants with sarcopenia and 19 out of 194 (9.8%) without sarcopenia reported incident falls during the two-year follow-up of the study (p<0.001). After adjusting for age, gender, cognitive impairment, ADL impairment, sensory impairments, BMI, depression, physical activity, cholesterol, stroke, diabetes, number of medications, and C-reactive protein, participants with sarcopenia had a higher risk of incident falls compared with non sarcopenic subjects (adjusted hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.25-8.29). CONCLUSIONS The present study suggests that sarcopenia - assessed using the EWGSOP algorithm - is highly prevalent among elderly persons without gender differences (25%). Sarcopenic participants were over three times more likely to fall during a follow-up period of 2 years relative to non sarcopenic individuals, regardless of age, gender and other confounding factors.

Sarcopenia and mortality risk in frail older persons aged 80 years and older: results from ilSIRENTE study

BACKGROUND AND AIMS sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals. We evaluated the impact of sarcopenia on the risk of all-cause death in a population of frail older persons living in community. METHODS we analysed data from the Aging and Longevity Study, a prospective cohort study that collected data on all subjects aged 80 years and older residing in the Sirente geographic area (n = 364). The present analysis was conducted among those subjects who were between 80 and 85 years of age at the time of the baseline assessment (n = 197). The main outcome measure was all-cause mortality over 7-year follow-up. According to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria, the diagnosis of sarcopenia required the documentation of low muscle mass and the documentation of either low muscle strength or low physical performance. Cox proportional regression models were used to estimate crude and adjusted hazard ratios and 95% confidence intervals of death by the presence of sarcopenia. RESULTS using the EWGSOP-suggested criteria, 43 subjects with sarcopenia (21.8%) were identified. During the 7-year follow-up, 29 (67.4%) participants died among subjects with sarcopenia compared with 63 subjects (41.2%) without sarcopenia (P < 0.001). After adjusting for potential confounders including age, gender, education, activities of daily living (ADL) impairment, body mass index, hypertension, congestive heart failure, chronic obstructive pulmonary disease, number of diseases, TNF-α, participants with sarcopenia had a higher risk of death for all causes compared with non-sarcopenic subjects (HR: 2.32, 95% CI: 1.01-5.43). CONCLUSIONS our results obtained from a representative sample of very old and frail subjects show that sarcopenia is associated with mortality, independently of age and other clinical and functional variables.

Insulin-Like Growth Factor-1 as a Vascular Protective Factor

Recent advances in cardiology have focused on proliferation and regeneration as potential cardiovascular defense mechanisms. Within this framework, growth factors are acquiring increasing importance; insulin-like growth factor-1 (IGF-1) emerges among them for its versatile pleiotropic actions. This review provides a current perspective on IGF-1 and vascular disease. The IGF-1 system is dynamic and complex,1,2 involving at least 6 IGF-1–binding proteins (IGFBP-1 through -6) and several binding protein–related proteases,1 including pregnancy-associated plasma protein-A (PAPP-A). The latter promotes IGF-1 bioavailability by cleaving IGFBP-4 and -5.3 Acute coronary syndromes have been associated with raised PAPP-A concentrations in blood, leading to the interpretation that PAPP-A may enhance the risk of coronary artery disease through increased IGF-1 in vascular tissues.4 Recent results, however, suggest a different relation between IGF-1 and ischemic syndromes. Indirect data have supported the concept that IGF-1 may be atherogenetic because it can induce vascular smooth muscle cell (VSMC) proliferation in vitro.5 Early studies on VSMCs from human and rabbit atherosclerotic arteries showed enhanced staining for IGF-1 and its receptor6,7 compared with normal tissues,7 with further enhancement after experimental angioplasty.7 Thus, IGF-1 has been considered a promoter of arterial obstructive lesions8; an alternative possibility, however (consistent with the higher IGF-1 expression after angioplasty), is that IGF-1 initiates a survival pathway aimed at compensating local vascular cell apoptosis (see sections III.C.3 and III.C.4). Randomized trials of the somatostatin analogue, angiopeptin, have been performed in the setting of postangioplasty restenosis and heart transplant vasculopathy to assess the possible benefits of lowering IGF-1 levels.9 Somatostatin analogues, however, have multiple actions: They reduce growth hormone (GH) release and the serum concentrations of other growth factors (epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, and vascular endothelial growth factor [VEGF]) in addition to IGF-1,10,11 …

Granulocyte colony‐stimulating factor promotes the generation of regulatory DC through induction of IL‐10 and IFN‐α

We have recently demonstrated that G‐CSF promotes the generation of human T regulatory (TREG) type 1 cells. In this study, we investigated whether the immunomodulatory effects of G‐CSF might be mediated by DC. CD14+ monocytes were cultured with serum collected after clinical administration of G‐CSF (post‐G), which contained high amounts of IL‐10 and IFN‐α. Similar to incompletely matured DC, monocytes nurtured with post‐G serum acquired a DC‐like morphology, expressed high levels of costimulatory molecules and HLA‐DR, and exhibited diminished IL‐12p70 release and poor allostimulatory capacity. Importantly, post‐G DC‐like cells were insensitive to maturation stimuli. As shown by neutralization studies, IFN‐α and, even more pronounced, IL‐10 contained in post‐G serum inhibited IL‐12p70 release by post‐G DC‐like cells. Furthermore, phenotypic and functional features of post‐G DC‐like cells were replicated by culturing post‐G monocytes with exogenous IL‐10 and IFN‐α. Post‐G DC‐like cells promoted Ag‐specific hyporesponsiveness in naive allogeneic CD4+ T cells and orchestrated a TREG response that was dependent on secreted TGFβ1 and IL‐10. Finally, neutralization of IL‐10 and IFN‐α contained in post‐G serum translated into abrogation of the regulatory features of post‐G DC‐like cells. This novel mechanism of immune regulation effected by G‐CSF might be therapeutically exploited for tolerance induction in autoimmune disorders.

Midarm muscle circumference, physical performance and mortality: results from the aging and longevity study in the Sirente geographic area (ilSIRENTE study).

BACKGROUND & AIMS Sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals. We evaluated the relationship between midarm muscle circumference (MAMC) and physical performance, muscle strength, functional status and survival in persons aged 80 years or older. METHODS Data are from the baseline evaluation of the Aging and Longevity Study in the Sirente Geographic Area (ilSIRENTE Study) (n = 357). MAMC was calculated taking into account the mid upper arm circumference and the triceps skinfold thickness of the right arm. Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4-m walking speed test, the balance test and the chair stand test. Analyses of covariance were performed to evaluate the relationship between different MAMC levels and physical function. Cox proportional regression models were used to estimate crude and adjusted hazard ratios and 95% confidence intervals of death by MAMC levels. RESULTS After adjustment for potential confounders - which included age, gender, living alone, sensory impairments (hearing and vision), body mass index, albumin and cholesterol - physical performance and function (which were measured using the 4-m walking speed test, the Short Physical Performance Battery score, the hand grip strength), improved significantly as MAMC increased. Compared with those in the low MAMC tertile, subjects in the high MAMC tertile had a lower risk of death (adjusted hazard ratio (HR) 0.45; 95% Confidence Interval (CI) 0.23-0.87). CONCLUSIONS The present study suggests that among community-dwelling old-old subjects muscle mass may be positively related to functional performance and survival.

Disability, More than multimorbidity, was predictive of mortality among older persons aged 80 years and older.

OBJECTIVE In this study, we evaluate the impact of disability and multimorbidity on the risk of all-cause death in a population of frail older persons living in community. STUDY DESIGN AND SETTING We analyzed data from the Aging and Longevity Study in the Sirente geographic area, a prospective cohort study that collected data on all subjects aged 80 years and older (n=364). The main outcome measure was all-cause mortality over 4-year follow-up. RESULTS A total of 150 deaths occurred. Sixty-seven subjects (44.6%) died in the nondisabled group compared with 83 subjects (55.3%) in the disabled group (P<0.01). Thirty-nine subjects (31.7%) died among subjects without multimorbidity compared with 111 subjects (46.0%) with two or more diseases (P<0.01). When examining the combined effect of multimorbidity and disability, the effect of disability on the risk of death was higher than that of multimorbidity. After adjusting for potential confounders, relative to those without disability and multimorbidity, disabled subjects showed an increased risk of death when multimorbidity was associated (hazard ratio [HR]=3.91; 95% confidence interval [CI]=1.53-10.00) and in absence of multimorbidity (HR=2.36; 95% CI=0.63-8.83). CONCLUSION Our results show that disability exerts an important influence on mortality, independently of age and other clinical and functional variables.

Glucose-6-phosphate Dehydrogenase Laboratory Assay: How, When, and Why?

Glucose 6‐phosphate dehydrogenase (G6PD) deficiency is the most common defect of red blood cells. Although some different laboratory techniques or methods are employed for the biochemical screening, a strict relationship between biochemists, clinicians, and molecular biologists is necessary for a definitive diagnosis. This article represents an overview on the current laboratory tests finalized to the screening or to the definitive diagnosis of G6PD‐deficiency, underlying the problems regarding the biochemical and molecular identification of heterozygote females other than those regarding the standardization of the clinical and laboratory diagnostic procedures. Finally, this review is aimed to give a flow‐chart for the complete diagnostic approach of G6PD‐deficiency.

Calf circumference, frailty and physical performance among older adults living in the community

BACKGROUND & AIMS Lean body mass loss has been indicated as a reliable marker of frailty and poor physical performance among older individuals. We evaluated the relationship between calf circumference and frailty, physical performance, muscle strength, and functional status in persons aged 80 years or older. METHODS Data are from the baseline evaluation of the Aging and Longevity Study in the Sirente geographic area (ilSIRENTE Study) (n = 357). The calf circumference was measured at the point of greatest circumference. Frailty was categorized according to the present of slow gait speed, weakness, weight loss, energy expenditure and exhaustion. Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4-m walking speed test, the balance test and the chair stand test. Analyses of covariance were performed to evaluate the relationship between different calf circumference and physical function. RESULTS After adjustment for potential confounders, which included age, gender, education, body mass index, sensory impairments, cerebrovascular diseases, albumin, reactive C protein, interleukine-6, and cholesterol, physical performance (SPPB score: 7.27 versus 6.18, p = 0.02) and muscle strength (Hand Grip: 32 kg versus 28 kg, p = 0.03) measures significantly improved as calf circumference increased. The frailty index score was significantly lower among subjects with higher calf circumference (1.66 versus 2.17, p = 0.01). CONCLUSIONS The present study suggests that among community-dwelling older people, calf circumference may be positively related to lower frailty index and higher functional performance. As such, calf circumference is a valuable tool for guiding public health policy and clinical decisions.

Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: A HuGE-GSEC review

The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/index.html). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9–3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9–1.1). The meta-analysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-ORm2/m2: 1.9, 95% confidence interval: 1.4–2.7; Pooled ORm2m2: 2.0, 95% confidence interval: 1.3–3.1; ORm1m2 or [infi]m2m2: 1.3, 95% confidence interval: 1.1–1.6). The association was present for the CYP1A1 (exon 7) polymorphism (ORVal/Val: 2.2, 95% confidence interval: 1.1–4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer.

Interleukin-6, C-Reactive Protein, and Tumor Necrosis Factor-Alpha as Predictors of Mortality in Frail, Community-Living Elderly Individuals

To investigate whether interleukin‐6 (IL‐6), C‐reactive protein (CRP) and tumor necrosis factor‐alpha (TNF‐α) protein levels predict all‐cause mortality in older persons living in the community.