Frailty predicts outcome of partial nephrectomy and guides treatment decision towards active surveillance and tumor ablation.

PURPOSE: To examine frailty and comorbidity as predictors of outcome of nephron sparing surgery (NSS) and as decision tools for identifying candidates for active surveillance (AS) or tumor ablation (TA). METHODS: Frailty and comorbidity were assessed using the modified frailty index of the Canadian Study of Health and Aging (11-CSHA) and the age-adjusted Charlson-Comorbidity Index (aaCCI) as well as albumin and the radiological skeletal-muscle-index (SMI) in a cohort of n = 447 patients with localized renal masses. Renal tumor anatomy was classified according to the RENAL nephrometry system. Regression analyses were performed to assess predictors of surgical outcome of patients undergoing NSS as well as to identify possible influencing factors of patients undergoing alternative therapies (AS/TA). RESULTS: Overall 409 patient underwent NSS while 38 received AS or TA. Patients undergoing TA/AS were more likely to be frail or comorbid compared to patients undergoing NSS (aaCCI: p < 0.001, 11-CSHA: p < 0.001). Gender and tumor complexity did not vary between patients of different treatment approach. 11-CSHA and aaCCI were identified as independent predictors of major postoperative complications (11-CSHA ≥ 0.27: OR = 3.6, p = 0.001) and hospital re-admission (aaCCI ≥ 6: OR = 4.93, p = 0.003) in the NSS cohort. No impact was found for albumin levels and SMI. An aaCCI > 6 and/or 11-CSHA ≥ 0.27 (OR = 9.19, p < 0.001), a solitary kidney (OR = 5.43, p = 0.005) and hypoalbuminemia (OR = 4.6, p = 0.009), but not tumor complexity, were decisive factors to undergo AS or TA rather than NSS. CONCLUSION: In patients with localized renal masses, frailty and comorbidity indices can be useful to predict surgical outcome and support decision-making towards AS or TA.

Association Between Erythrocyte Levels of n-3 Polyunsaturated Fatty Acids and Risk of Frailty in Community-Dwelling Older Adults: The Korean Frailty and Aging Cohort Study.

BACKGROUND: Inflammation is a major risk factor for frailty, but n-3 polyunsaturated fatty acids (PUFA) has been suggested as an anti-inflammatory agent. The present study aimed to investigate the hypothesis that the higher erythrocyte levels of long-chain n-3 PUFA were associated with lower odds of frailty and frailty criterion. METHODS: Cross-sectional analysis from the Korean Frailty and Aging Cohort Study, a total of 1,435 people aged 70-84 years were included. Sex- and age-stratified community residents, drawn in urban and rural regions nationwide, were eligible for participation in the study. All participants were categorized as frail and nonfrail according to the Cardiovascular Health Study index. RESULTS: The likelihood of frailty was inversely associated with the erythrocyte levels of eicosapentaenoic acid (EPA; odds ratio [OR] per unit 0.33; 95% confidence interval [CI] 0.14-0.77; p for trend = .002) and docosahexaenoic acid (DHA; OR per unit 0.42; 95% CI 0.20-0.87; p for trend = .018). Among each frailty criterion, the likelihood of slow walking speed was associated with erythrocyte levels of EPA and DHA, and the likelihood of exhaustion was inversely associated with the erythrocyte levels of DHA. CONCLUSIONS: The present study showed that the frailty and frailty criterion were significantly associated with lower erythrocyte levels of long-chain n-3 PUFA, suggesting that lower n-3 PUFA could be a marker for the risk of frailty.

Use of plasma-free amino acids as biomarkers for detecting and predicting disease risk.

This paper reviews developments regarding the use of plasma-free amino acid (PFAA) profiles as biomarkers for detecting and predicting disease risk. This work was initiated and first published in 2006 and was subsequently developed by Ajinomoto Co., Inc. After commercialization in 2011, PFAA-based tests were adopted in over 1500 clinics and hospitals in Japan, and numerous clinician-led studies have been performed to validate these tests. Evidence is accumulating that PFAA profiles can be used for diabetes prediction and evaluation of frailty; in particular, decreased plasma essential amino acids could contribute to the pathophysiology of severe frailty. Integration of PFAA evaluation as a biomarker and effective essential amino acid supplementation, which improves physical and mental functions in the elderly, could facilitate the development of precision nutrition, including personalized solutions. This present review provides the background for the technology as well as more recent clinical findings, and offers future possibilities regarding the implementation of precision nutrition.

Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study.

BACKGROUND: The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients. METHODS: Seventy-seven patients consecutively hospitalized for COVID-19 in a geriatric unit were included. Intervention groups were participants regularly supplemented with vitamin D over the preceding year (Group 1), and those supplemented with vitamin D after COVID-19 diagnosis (Group 2). The comparator group involved participants having received no vitamin D supplements (Group 3). Outcomes were 14-day mortality and highest (worst) score on the ordinal scale for clinical improvement (OSCI) measured during COVID-19 acute phase. Potential confounders were age, gender, functional abilities, undernutrition, cancer, hypertension, cardiomyopathy, glycated hemoglobin, number of acute health issues at admission, hospital use of antibiotics, corticosteroids, and pharmacological treatments of respiratory disorders. RESULTS: The three groups (n = 77; mean ± SD, 88 ± 5years; 49% women) were similar at baseline (except for woman proportion, p = 0.02), as were the treatments used for COVID-19. In Group 1 (n = 29), 93.1% of COVID-19 participants survived at day 14, compared to 81.2% survivors in Group 2 (n = 16) (p = 0.33) and 68.7% survivors in Group 3 (n = 32) (p = 0.02). While considering Group 3 as reference (hazard ratio (HR) = 1), the fully-adjusted HR for 14-day mortality was HR = 0.07 (p = 0.017) for Group 1 and HR = 0.37 (p = 0.28) for Group 2. Group 1 had longer survival time than Group 3 (log-rank p = 0.015), although there was no difference between Groups 2 and 3 (log-rank p = 0.32). Group 1, but not Group 2 (p = 0.40), was associated with lower risk of OSCI score ≥5 compared to Group 3 (odds ratio = 0.08, p= 0.03). CONCLUSIONS: Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly.

Vitamin D Receptor Polymorphisms in Sex-Frailty Paradox.

The "male-female health-survival paradox" evidences that the survival advantage observed in women is linked to higher rates of disability and poor health status compared to men, a phenomenon also called the "sex-frailty paradox". The depletion of vitamin D seems to play a role in the fragilization of old persons, and genetic polymorphisms of the vitamin D receptor (VDR) gene seem to be involved in regulating the vitamin D pathway. This study correlated the VDR gene polymorphisms (FokI, ApaI, BsmiI, and TaqI) with frailty, computed by frailty index (FI), in 202 persons (127 women and 75 men, aged from 60 to 116 years), aiming to capture the involvement of vitamin D in the sex-frailty paradox. The results showed slightly higher FI (p = 0.05), lower levels of 25(OH)D (p = 0.04), and higher levels of parathyroid hormone PTH (p = 0.002) and phosphorus (p < 0.001) in women than in men. Interestingly, the ApaI minor allele (Aa + aa) showed a significant positive association with FI (p = 0.03) and a negative association with inorganic phosphorus values (p = 0.04) compared to AA genotype only in women, regardless of age. The exact mechanism and the causal role that, in old women, links ApaI polymorphism with frailty are still unclear. However, we could speculate that a specific genetic profiling, other than 25(OH)D levels, play a role in the sex-frailty paradox.

Low Vitamin D Levels and Frailty Status in Older Adults: A Systematic Review and Meta-Analysis.

Serum vitamin D deficiency is widespread among older adults and is a potential modifiable risk factor for frailty. Moreover, frailty has been suggested as an intermediate step in the association between low levels of vitamin D and mortality. Hence, we conducted a systematic review of the literature and meta-analysis to test the possible association of low concentrations of serum 25-hydroxyvitamin D (25(OH)D), a marker of vitamin D status, with frailty in later life. We reviewed cross-sectional or longitudinal studies evaluating populations of older adults and identifying frailty by a currently validated scale. Meta-analyses were restricted to cross-sectional data from studies using Fried's phenotype to identify frailty. Twenty-six studies were considered in the qualitative synthesis, and thirteen studies were included in the meta-analyses. Quantitative analyses showed significant differences in the comparisons of frail (standardized mean difference (SMD)-1.31, 95% confidence interval (CI) (-2.47, -0.15), p = 0.0271) and pre-frail (SMD-0.79, 95% CI (-1.58, -0.003), p = 0.0491) subjects vs. non-frail subjects. Sensitivity analyses reduced heterogeneity, resulting in a smaller but still highly significant between-groups difference. Results obtained indicate that lower 25(OH)D levels are significantly associated with increasing frailty severity. Future challenges include interventional studies testing the possible benefits of vitamin D supplementation in older adults to prevent/palliate frailty and its associated outcomes.

Vitamin D deficiency is highly prevalent in malnourished inpatients and associated with higher mortality: A prospective cohort study.

The impact of vitamin D deficiency on the recovery of patients with malnutrition remains undefined. Our aim was to study the prevalence of vitamin D deficiency in a well-characterized cohort of patients with malnutrition and its association with outcomes.Within this secondary analysis of a randomized controlled trial, we examined the association of vitamin D deficiency and adverse clinical outcomes over a follow-up of 180 days in hospitalized patients at risk for malnutrition. We measured 25-hydroxyvitamin D levels upon admission and defined Vitamin D deficiency when levels were <50nmol/l. The primary endpoint was 180-day mortality.The prevalence of vitamin D deficiency in our cohort of 828 patients was 58.2% (n = 482). Patients with vitamin D deficiency had increased 180-day mortality rates from 23.1% to 29.9% (odds ratio 1.42, 95% confidence interval [CI] 1.03-1.94, P = .03). When adjusting the analysis for demographics, comorbidities, and randomization, this association remained significant for the subgroup of patients not receiving vitamin D treatment (adjusted odds ratio 1.63, 95% CI 1.01-2.62, P = .04). There was no significantly lower risk for mortality in the subgroup of vitamin D deficient patients receiving vitamin D treatment compared to not receiving treatment (adjusted odds ratio 0.74, 95% CI 0.48-1.13, P = .15).Vitamin D deficiency is highly prevalent in the population of malnourished inpatients and is negatively associated with long-term mortality particularly when patients are not receiving vitamin D treatment. Our findings suggest that malnourished patients might benefit from vitamin D screening and treatment in case of deficiency.

Low 25-hydroxyvitamin D levels and the risk of frailty syndrome: a systematic review and dose-response meta-analysis.

BACKGROUND: Vitamin D deficiency and frailty are common with aging. Previous studies examining vitamin D status and frailty have produced mixed results, and in particular, the shape of the association has not been well established. We examined the association between 25-hydroxyvitamin D (25OHD) serum levels and frailty by performing a systematic review and dose-response meta-analysis. METHODS: We searched the PubMed, EMBASE and Cochrane Library databases of Elsevier through February 2017. Cross-sectional and cohort studies that reported adjusted risk ratios with 95% confidence intervals (CI) for frailty with ≥3 categories of 25OHD serum levels were selected. Data extraction was performed independently by two authors. The reported risk estimates for 25OHD categories were recalculated, employing a comprehensive trend estimation from summarized dose-response data. RESULTS: The pooled risk estimate of frailty syndrome per 25 nmol/L increment in serum 25OHD concentration was 0.88 (95% CI = 0.82-0.95, I2 = 86.8%) in the 6 cross-sectional studies and 0.89 (95% CI = 0.85-0.94, I2 = 0.0%) in the 4 prospective cohort studies. Based on the Akaike information criteria (AIC), a linear model was selected (AIC for the nonlinear model: - 5.4, AIC for the linear model: - 6.8 in the prospective cohort studies; AIC for the linear model: - 13.6, AIC for the nonlinear model: - 1.77 in the cross-sectional studies). CONCLUSIONS: This dose-response meta-analysis indicates that serum 25OHD levels are significantly and directly associated with the risk of frailty. Further studies should address the underlying mechanisms to explain this relationship and to determine whether vitamin D supplementation is effective for preventing frailty syndrome.

Vitamin D supplementation as a potential cause of U-shaped associations between vitamin D levels and negative health outcomes: a decision tree analysis for risk of frailty.

BACKGROUND: A recent controversy in vitamin D research is a "U-shaped association", with elevated disease risks at both high and low 25-hydroxyvitamin D (25 (OH) D) levels. METHODS: This is a cross-sectional study of 238 male nursing home veterans in Hawaii. Classification and regression tree (CART) analysis identified groups based on 25 (OH) D and vitamin D supplementation for frailty risk. Characteristics were examined and compared across the groups using logistic regression and receiver operating characteristic (ROC) curve analyses. RESULTS: CART analysis identified three distinct groups: vitamin D supplement users (n = 86), non-users with low vitamin D (n = 55), and non-users with high vitamin D (n = 97). Supplement users were the most frail, but had high mean 25 (OH) D of 26.6 ng/mL, which was compatible with 27.1 ng/mL in non-users with high vitamin D, while mean 25 (OH) D of non-users with low vitamin D was 11.7 ng/mL. Supplement users and non-users with low vitamin D were significantly more likely to be frail (odds ratio (OR) = 9.90, 95% CI = 2.18-44.86, p = 0.003; OR = 4.28, 95% CI = 1.44-12.68, p = 0.009, respectively), compared with non-users with low vitamin D. ROC curve analysis showed the three groups significantly predicted frailty (area under the curve = 0.73), with sensitivity of 64.4% and specificity of 76.7%, while 25 (OH) D did not predict frailty. CONCLUSIONS: In these nursing home veterans, vitamin D supplement users were the most frail but with high 25 (OH) D. This can potentially be a cause of U-shaped associations between vitamin D levels and negative health outcomes.

Malnutrition in the elderly and its effects on bone health - A review.

This article aims to provide an overview of the prevalence, causes and risk factors associated with malnutrition in the elderly. It includes the clinical consequences and economic impact of malnutrition in the elderly and in particular the osteoporotic population. It encompasses the significance of dietary protein and its effects on bone health.

Relevance of vitamin D in the pathogenesis and therapy of frailty.

PURPOSE OF REVIEW: This article reviews recently published evidence regarding the role of vitamin D in the physiopathology of physical frailty in elderly populations and its role in the management of this geriatric condition. RECENT FINDINGS: Some recent studies have found a low level of 25-hydroxyvitamin D, considered the best marker of vitamin D status, in frail individuals. All prospective studies consistently report that low vitamin D status is associated with an increased risk of becoming frail. Recent studies also suggest that the relationship between vitamin D status and frailty is largely mediated by the development of sarcopenia. Very few well designed randomized controlled trials are available that assess the effectiveness of vitamin D supplementation in the prevention or management of frailty. In the absence of specific guidelines, a minimal serum 25-hydroxyvitamin D level of 75 nmol/l is proposed for frail elderly patients by some scientific societies. The doses necessary to reach this target are between 800 and 2000 IU/day. SUMMARY: Several studies suggest a potential effect of vitamin D on physical frailty but large clinical trials are lacking at this time to provide solid evidence of clinical benefit.