Inflammation and sarcopenia: A systematic review and meta-analysis.

Inflammatory cytokines have been shown to prompt muscle wasting, ultimately stimulating protein catabolism and suppressing muscle synthesis. However, the possible association between inflammatory parameters and sarcopenia is poorly understood. We therefore aimed to summarize the current evidence about this topic with a meta-analysis of studies reporting serum inflammatory parameters in patients with sarcopenia vs. people without sarcopenia (controls). An electronic PubMed and Scopus search through to 09/01/2016 and meta-analysis of cross-sectional studies comparing serum levels of inflammatory cytokines between patients with sarcopenia and controls was made, calculating random-effects standardized mean differences (SMDs) ±95% confidence intervals (CIs) as the effect size. Out of 1370 initial hits, 17 studies with a total of 11249 participants (3072 with sarcopenia and 8177 without) were meta-analyzed. Sarcopenic participants had significantly higher levels of CRP (SMD=0.51; 95%CI 0.26, 0.77; p<0.0001; I2=96%) than controls. Conversely, serum IL6 levels were not significantly different (SMD=0.35; 95%CI: -0.19, 0.89; p=0.21; I2=97%) in people with sarcopenia versus controls. Sarcopenic people did not have higher levels of TNF-α than controls (SMD=0.28; 95%CI -0.26, 0.83; p=0.31; I2=97%). In conclusion, sarcopenia seems to be associated with elevated serum CRP levels; future longitudinal studies are needed to clarify this relationship.

Validation of bioelectrical impedance analysis for estimating limb lean mass in free-living Caucasian elderly people.

BACKGROUND & AIMS: Aging is characterized by a loss of limb lean mass (LLM) that can lead to physical disability and death. Regional bioelectrical impedance analysis (BIA) may be a reliable method for estimating LLM, but no prediction equations are available for elderly Caucasian subjects. The aim of this study was to develop and validate a BIA-based equation for predicting LLM in healthy elderly Caucasians, taking dual X-ray absorptiometry (DXA) as the reference method. METHODS: Using a cross-sectional design, 244 free-living healthy Caucasian subjects (117 men, 179 women) over 60 years of age were enrolled. LLM was measured with DXA (LLMDXA), and the resistance (Rz) and reactance (Xc) of each limb were measured with a regional bioelectrical impedance analyzer. A resistive index (RI) was calculated from stature in meters divided by Rz of each arm. A BIA-based multiple regression equation for predicting the lean mass (LM) of dominant and non-dominant limbs was developed using a double cross-validation technique. RESULTS: Using the sample as a whole, cross-validation resulted in an equation specific for each limb, as follows, where sex equals 1 for males, and 0 for females: LM (kg) = -0.081 + (0.061*RI) + (0.010*body weight) + (0.299*sex) for the dominant arm; LM (kg) = -0.026 + (0.014*RI) + (0.009*body weight) + (0.352*sex) for the non-dominant arm; LM (kg) = -0.462 + (0.027*RI) + (0.047*body weight) + (0.639*sex) + (0.026*Xc) for the dominant leg; and for the non-dominant leg, LM (kg) = -0.522 + (0.029*RI) + (0.045*body weight) + (0.569*sex) + (0.025*Xc). The DXA-measured and BIA-predicted LLM for each limb did not differ significantly. CONCLUSION: Our newly-developed BIA equations seem to provide a valid estimation of LLM in older Caucasian adults.

Changes in Frailty Status and Risk of Depression: Results From the Progetto Veneto Anziani Longitudinal Study.

OBJECTIVE: To evaluate whether prefrailty was associated with the risk of developing depression and if longitudinal changes in frailty status corresponded to changes in incident depression during follow up. METHODS: A population-based, prospective cohort study was conducted for 4.4 years in two separate geographic areas near the city of Padua in the Veneto Region of Northern Italy. In 891 nondepressed, nonfrail, community-dwelling Italian subjects aged ≥ 65 (46.6% men) belonging to the Progetto Veneto Anziani study, depression was defined according to the Geriatric Depression Scale and was confirmed by geriatricians skilled in psychogeriatric medicine. Prefrailty was defined by the presence of one or two criteria among the Fried criteria. RESULTS: The incidence rate of depression was 13.3% among subjects improving their frailty status at follow-up (N = 15), 15.0% in those who remained stable (N = 79), and 26.7% among worsening participants (N = 67) (p = 0.001). Prefrailty at baseline did not predict the onset of depression (HR: 0.82; 95% CI: 0.55-1.21; Wald χ2 = 0.73; df = 1; p = 0.43), but a deterioration during follow-up in at least one additional frailty criteria was associated with a significantly higher risk (HR: 1.95; 95% CI: 1.32-2.89; Wald χ2 = 5.78; df = 2; p = 0.01). Improvement in frailty status was not associated with the risk of incident depression (HR: 0.71; 95% CI: 0.35-1.42; Wald χ2 = 0.47; df = 2; p = 0.28). CONCLUSION: Our data did not offer evidence that prefrailty per se predisposes to the onset of depression, but worsening in frailty status is associated with an almost twofold increased risk of incident depression, irrespective from the initial level of impairment.

Hyperuricemia protects against low bone mineral density, osteoporosis and fractures: a systematic review and meta-analysis.

BACKGROUND: Serum uric acid (SUA) accounts for about 50% of extracellular antioxidant activity, suggesting that hyperuricemia may have a protective role in diseases characterized by high levels of oxidative stress, such as osteoporosis. We aimed to meta-analyse data regarding bone mineral density (BMD), osteoporosis and fractures in people with higher SUA vs. lower SUA concentrations. MATERIALS AND METHODS: Two investigators conducted a literature search using PubMed and Scopus, without language restrictions. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used for BMD; risk ratios (RRs) and adjusted odds ratios (ORs) for cross-sectional data. Most possible adjusted hazard ratios (HRs) were used to assess the association between baseline SUA and incident fractures. RESULTS: Of 1405 initial hits, 19 studies were eligible including a total of 55 859 participants. Subjects with higher SUA levels had significantly higher BMD values for the spine (six studies; SMD = 0·29; 95% CI: 0·22-0·35; I2 = 47%), total hip (seven studies; SMD = 0·29; 95% CI: 0·24-0·34; I2 = 33%) and femoral neck (six studies; SMD = 0·25; 95% CI: 0·16-0·34; I2 = 71%). Simple correlation analyses substantially confirmed these findings. An increase of one standard deviation in SUA levels reduced the number of new fractures at follow-up (three studies; HR = 0·83; 95% CI: 0·74-0·92; I2 = 0%). No significant differences between men and women emerged, although data about women were limited. CONCLUSIONS: Hyperuricemia was found independently associated with BMD and fractures, supporting a protective role for uric acid in bone metabolism disorders.

Extranodal Extension of Nodal Metastases Is a Poor Prognostic Indicator in Gastric Cancer: a Systematic Review and Meta-analysis.

INTRODUCTION: The extranodal extension (ENE) of nodal metastases (the extension of neoplastic cells through the nodal capsule into the perinodal soft tissue) is a histological feature that has been considered a prognostic factor in several cancers, but the role in gastric cancer was not yet investigated. We aimed to investigate the prognostic role of ENE in patients affected by gastric cancer through a systematic review and meta-analysis. MATERIAL AND METHODS: Two independent authors searched major databases until 09/30/2015 to identify studies providing data on gastric cancer patients' prognostic parameters and comparing patients with ENE (ENE+) vs intra-nodal extension (ENE-). The data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) with 95 % confidence intervals (CI), adjusted for potential confounders. RESULTS: Nine studies followed up 3250 patients with gastric cancer (1064 ENE+ and 2186 ENE-). ENE+ was associated with a significantly higher risk of all-cause mortality (RR = 1.70; 95 % CI: 1.43-2.03, I (2) = 66 %; HR = 2.14; 95 % CI: 1.66-2.75, I (2) = 0 %), cancer-specific mortality (RR = 1.59; 95 % CI: 1.42-1.79; HR = 1.52; 95 % CI: 1.19-1.96), and disease recurrence (RR = 3.43, 95 % CI: 1.80-6.54, I (2) = 0 %). DISCUSSION: Judging from our results, ENE in gastric cancer patients should be considered for prognostic purposes from the gross sample to the pathology report.

Effect of Oral Beta-Hydroxy-Beta-Methylbutyrate (HMB) Supplementation on Physical Performance in Healthy Old Women Over 65 Years: An Open Label Randomized Controlled Trial.

UNLABELLED: Although older people are particularly liable to sarcopenia, limited research is available on beta-hydroxy-beta-methylbutyrate (HMB) supplementation in this population, particularly in healthy subjects. In this parallel-group, randomized, controlled, open-label trial, we aimed to evaluate whether an oral supplement containing 1.5 g of calcium HMB for 8 weeks could improve physical performance and muscle strength parameters in a group of community-dwelling healthy older women. Eighty healthy women attending a twice-weekly mild fitness program were divided into two equal groups of 40, and 32 of the treated women and 33 control completed the study. We considered a change in the Short Physical Performance Battery (SPPB) score as the primary outcome and changes in the peak torque (PT) isometric and isokinetic strength of the lower limbs, 6-minute walking test (6MWT), handgrip strength and endurance as secondary outcomes. Body composition was assessed with dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). The mean difference between the two groups on pre-post change were finally calculated (delta) for each outcome. After 8 weeks, there were no significant differences between the groups' SPPB, handgrip strength or DXA parameters. The group treated with HMB scored significantly better than the control group for PT isokinetic flexion (delta = 1.56±1.56 Nm; p = 0.03) and extension (delta = 3.32±2.61 Nm; p = 0.03), PT isometric strength (delta = 9.74±3.90 Nm; p = 0.02), 6MWT (delta = 7.67±8.29 m; p = 0.04), handgrip endurance (delta = 21.41±16.28 s; p = 0.02), and muscle density assessed with pQCT. No serious adverse effects were reported in either group. In conclusion, a nutritional supplement containing 1.5 g of calcium HMB for 8 weeks in healthy elderly women had no significant effects on SPPB, but did significantly improve several muscle strength and physical performance parameters. TRIAL REGISTRATION: ClinicalTrials.gov NCT02118181.

Are the Recommended Dietary Allowances for Vitamins Appropriate for Elderly People?

BACKGROUND: An adequate vitamin intake is essential for a good nutritional status, especially in older women, who are more sensitive to nutritional deficiencies. The American, European and Italian Recommended Dietary Allowances (RDAs) derive mainly from studies on adults, and it is not clear whether they also apply to elderly people. Comparing the RDAs with the actual vitamin intake of a group of healthy older women could help to clarify the real needs of elderly people. OBJECTIVE: Our aim was to compare the American, European, and Italian RDAs with the actual vitamin intake of a group of healthy older women. DESIGN: This was a cross-sectional study. PARTICIPANTS: The study included 286 healthy women aged older than 65 years. MAIN OUTCOME MEASURES: For each micronutrient, the 50th percentile of the distribution of its intake was considered as the average requirement, and the corresponding calculated RDA for our sample was the average requirement×1.2, as recommended by the US Food and Nutrition Board. This calculated RDA was then compared with the American, European, and Italian RDAs. STATISTICAL ANALYSES PERFORMED: Student's t test or the Mann-Whitney test (after checking the normal distribution of the micronutrient) for continuous variables; the χ(2) test for categorical variables. RESULTS: The calculated RDA were 2,230 µg retinol equivalents for vitamin A, 2.8 µg for vitamin B-12, 0.9 mg for thiamin, 1.4 mg for riboflavin, 3.6 mg for pantothenic acid, 1.4 mg for vitamin B-6, 320 µg for folic acid, and 115 mg for vitamin C. CONCLUSIONS: Our findings suggest that the current RDAs are adequate for older women's intake of riboflavin, vitamin B-6, and folic acid, but should be raised for vitamin B-12 and for vitamin C.

Assessing appendicular skeletal muscle mass with bioelectrical impedance analysis in free-living Caucasian older adults.

BACKGROUND & AIMS: Aging is characterized by a loss of appendicular skeletal muscle mass (ASMM) leading to physical disability and death. Bioelectrical impedance analysis (BIA) is reliable in estimating ASMM but no prediction equations are available for elderly Caucasian subjects. The aim of the study was to develop and validate an equation derived from bioelectrical impedance analysis (BIA) to predict appendicular skeletal muscle mass (ASMM) in healthy Caucasian elderly subjects, taking dual X-ray absorptiometry (DXA) as the reference method, and comparing the reliability of the new equation with another BIA-based model developed by Kyle et al. (Kyle UG, Genton L, Hans D, Pichard C, 2003). METHODS: With a cross-sectional design, 296 free-living, healthy Caucasian subjects (117 men, 179 women) over 60 years of age were enrolled. Lean mass of limbs was measured with DXA to ascertain ASMM (ASMMDxA). Whole-body tetrapolar BIA was performed to measure resistance (Rz), resistance normalized for stature (RI), and reactance (Xc). The BIA multiple regression equation for predicting ASMM was developed using a double cross-validation technique. The predicted ASMM values were compared with ASMMKyle, i.e. ASMM estimates derived from the model developed by Kyle et al. (Kyle et al., 2003). RESULTS: Cross-validation resulted in a unique equation using the whole sample: ASMM (kg) = -3.964 + (0.227*RI) + (0.095*weight) + (1.384*sex) + (0.064*Xc) [R(2) = 0.92 and SEE = 1.14 kg]. In our sample, ASMMKyle differed significantly from the ASMMDxA (p < 0.0001), with a mean error of -0.97 ± 1.34 kg (5.1 ± 6.9%). Unlike the present BIA prediction equation, the Kyle et al. model showed a correlation between the bias and the mean of ASMMDxA and ASMMKyle (r = -0.406, p < 0.001). CONCLUSION: The new BIA equation provides a valid estimate of ASMM in older Caucasian adults.

Effect of oral magnesium supplementation on physical performance in healthy elderly women involved in a weekly exercise program: a randomized controlled trial.

BACKGROUND: Magnesium deficiency is associated with poor physical performance, but no trials are available on how magnesium supplementation affects elderly people's physical performance. OBJECTIVE: The aim of our study was to investigate whether 12 wk of oral magnesium supplementation can improve physical performance in healthy elderly women. DESIGN: In a parallel-group, randomized controlled trial, 139 healthy women (mean ± SD age: 71.5 ± 5.2 y) attending a mild fitness program were randomly allocated to a treatment group (300 mg Mg/d; n = 62) or a control group (no placebo or intervention; n = 77) by using a computer-generated randomization sequence, and researchers were blinded to their grouping. After assessment at baseline and again after 12 wk, the primary outcome was a change in the Short Physical Performance Battery (SPPB); secondary outcomes were changes in peak torque isometric and isokinetic strength of the lower limbs and handgrip strength. RESULTS: A total of 124 participants allocated to the treatment (n = 53) or control (n = 71) group were considered in the final analysis. At baseline, the SPPB scores did not differ between the 2 groups. After 12 wk, the treated group had a significantly better total SPPB score (Δ = 0.41 ± 0.24 points; P = 0.03), chair stand times (Δ = -1.31 ± 0.33 s; P < 0.0001), and 4-m walking speeds (Δ = 0.14 ± 0.03 m/s; P = 0.006) than did the control group. These findings were more evident in participants with a magnesium dietary intake lower than the Recommended Dietary Allowance. No significant differences emerged for the secondary outcomes investigated, and no serious adverse effects were reported. CONCLUSIONS: Daily magnesium oxide supplementation for 12 wk seems to improve physical performance in healthy elderly women. These findings suggest a role for magnesium supplementation in preventing or delaying the age-related decline in physical performance.

Role of bioelectrical impedance analysis in follow-up of hospitalized elderly patients with congestive heart failure.

BACKGROUND AND AIMS: Congestive heart failure (CHF) is characterized by high levels of B-type natriuretic peptide (BNP), expanded total body water (TBW) and extracellular water (ECW). Bioelectrical impedance analysis (BIA) has demonstrated high diagnostic accuracy in CHF but no information is available for older patients. We hypothesized that, in the follow-up of patients with CHF, body fluid changes estimated by BIA are related to BNP variations rather than with body weight. The aim of this study was to evaluate the relationship between variations in body fluid compartments, body weight and BNP in hospitalized elderly patients with decompensated CHF. METHODS: 49 elderly patients admitted to the Geriatric Department for decompensated CHF were included in the study. On admission and at discharge, all patients underwent clinical and functional assessment and BNP dosage. TBW and ECW were also determined by the BIA method. RESULTS: At discharge, all patients showed reductions in TBW (ΔTBW -2.9 ± 3.0 liters), ECW (ΔECW 1.9 ± 2.1 liters) and BNP levels (ΔBNP -219.6 ± 458.1 pg/mL). Variations in TBW and ECW were correlated with BNP changes (r=0.65 and 0.62, respectively) rather than with body weight variations and BNP changes (r=0.51). CONCLUSIONS: The stronger relationship between fluid variations determined by BIA and BNP changes may make BIA a useful method in the follow-up of decompensated CHF elderly patients.

Obstetric complications and pregnancy-related venous thromboembolism: the effect of low-molecular-weight heparin on their prevention in carriers of factor V Leiden or prothrombin G20210A mutation.

Whether the administration of low-molecular-weight heparin (LMWH) during pregnancy is effective in preventing obstetric complications and pregnancy-related venous thromboembolism (VTE) in women who are carriers of factor V Leiden (FVL) and/or prothrombin variant G20210A (PTm) is controversial. This observational study investigated the possible efficacy of pharmacological treatment with LMWH ± aspirin (ASA) in pregnancy outcomes in 1,011 pregnancies of 416 women with thrombophilia (FVL and/or PTm). Most patients were chosen on the basis of previous obstetrical complications (36%), or because of familial or personal history of venous/arterial thromboembolism (28% and 18%, respectively); 74 patients (18%) were incidentally identified. The outcome was evaluated according to the type of treatment and of the period of pregnancy when the treatment was started. After adjustment for observation before and after diagnosis of thrombophilia, previous miscarriages and VTE, parity, age and centre, we observed that LMWH had a protective effect on miscarriages (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.29-0.94) and VTE (OR 0.05, 95% CI 0.01-0.21). ASA appeared to have no effect on the prevention of obstetric complications and VTE. A nested analysis performed in 116 women with two or more obstetric complications confirmed that the highest number of live births was recorded in the group under LMWH prophylaxis (OR 0.19, 95% CI 0.05-0.75). These results suggest that LMWH prophylaxis reduces the risk of obstetric complications in carriers of FVL and/or PTm, particularly in those with previous obstetric events. Furthermore, LMWH prophylaxis reduces the risk of pregnancy-related VTE.

Gender and the risk of venous thromboembolism.

The role of gender in the causation of first and recurrent venous thromboembolism (VTE) is uncertain. The use of hormonal therapy and pregnancy has been associated with VTE in women. Epidemiological studies have described a higher incidence of first VTE in women of childbearing age. Nevertheless, no consistent differences in the overall incidence of VTE between males and females have been found. Recent studies have shown that women exhibit a lower risk of recurrent VTE than men, although these data were not confirmed in other studies that evaluated only women with idiopathic VTE. This article reviews the role of gender as a risk factor for first and recurrent VTE.