Mesenchymal Stem Cell Therapy for Aging Frailty Assessment for frailty is useful for predicting morbidity in elderly patients undergoing colorectal cancer resection whose comorbidities are already optimized. Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial Frailty Intervention Trial (FIT) Frailty as a predictor of surgical outcomes in older patients. Screening for frailty: criteria and predictors of outcomes. Reduced cerebellar gray matter is a neural signature of physical frailty Frailty predicts increased hospital and six-month healthcare cost following colorectal surgery in older adults. Frailty in Older Adults Undergoing Aortic Valve Replacement: The FRAILTY-AVR Study. Redefining Geriatric Preoperative Assessment Using Frailty, Disability and Co-Morbidity The association between anorexia of aging and physical frailty: Results from the national center for geriatrics and gerontology's study of geriatric syndromes. Comparing the Prognostic Accuracy for All-Cause Mortality of Frailty Instruments: A Multicentre 1-Year Follow-Up in Hospitalized Older Patients Mesenchymal Stem Cells for Frailty? Frailty syndrome diagnosed according to the Study of Osteoporotic Fractures (SOF) criteria and adverse health outcomes among community-dwelling older outpatients in Italy. A one-year prospective cohort study. The prevalence of frailty syndrome in an older population from Spain. The Toledo study for healthy aging A pilot trial to predict frailty syndrome: The Japanese Health Research Volunteer Study Frailty and delayed graft function in kidney transplant recipients. Frailty: emergence and consequences in women aged 65 and older in the Women's Health Initiative Observational Study. Development of an easy prognostic score for frailty outcomes in the aged. Dietary quality is related to frailty in community-dwelling older adults. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial Too frail for surgery? Initial results of a large multidisciplinary prospective study examining preoperative variables predictive of poor surgical outcomes. The frailty syndrome and mortality among very old patients with symptomatic severe aortic stenosis under different treatments. Older People's Quality of Life (OPQOL) scores and adverse health outcomes at a one-year follow-up. A prospective cohort study on older outpatients living in the community in Italy
Chronic diseases and degenerative conditions are strongly linked with the geriatric syndrome of frailty and account for a disproportionate percentage of the health care budget . Frailty increases the risk of falls , hospitalization , institutionalization , disability , and death . By definition , frailty syndrome is characterized by declines in lean body mass , strength , endurance , balance , gait speed , activity and energy levels , and organ physiologic reserve . Collectively , these changes lead to the loss of homeostasis and capability to withst and stressors and result ing vulnerabilities . There is a strong link between frailty , inflammation , and the impaired ability to repair tissue injury due to decreases in endogenous stem cell production . Although exercise and nutritional supplementation provide benefit to frail patients , there are currently no specific therapies for frailty . Bone marrow-derived allogeneic mesenchymal stem cells ( MSCs ) provide therapeutic benefits in heart failure patients irrespective of age . MSCs contribute to cellular repair and tissue regeneration through their multilineage differentiation capacity , immunomodulatory , and anti-inflammatory effects , homing and migratory capacity to injury sites , and stimulatory effect on endogenous tissue progenitors . The advantages of using MSCs as a therapeutic strategy include st and ardization of isolation and culture expansion techniques and safety in allogeneic transplantation . Based on this evidence , we performed a r and omized , double-blinded , dose-finding study in elderly , frail individuals and showed that intravenously delivered allogeneic MSCs are safe and produce significant improvements in physical performance measures and inflammatory biomarkers . We thus propose that frailty can be treated and the link between frailty and chronic inflammation offers a potential therapeutic target , addressable by cell therapy BACKGROUND The clinical syndrome of frailty identified through the assessment of weight loss , gait speed , grip strength , physical activity , and physical exhaustion has been used to identify patients with reduced reserves . We hypothesized that frailty is useful in predicting adverse outcomes in optimized elective elderly colorectal surgery patients . METHODS A prospect i ve study was conducted at 2 centers ( Singapore and Japan ) . All patients over 75 years of age undergoing colorectal resection were assessed for the presence of the syndrome of frailty .  All these patients had already had their comorbidities optimized for surgery . The outcome measure was postoperative major complications ( defined as Clavien-Dindo type II and above complications ) . RESULTS Eighty-three patients were studied from February 2008 to April 2010 . The mean age was 81.5 years ( range 75 - 93 years ) . The mean comorbidity index was 3.37 ( range 0 - 11 ) . Twenty-six ( 31.3 % ) patients were an American Society of Anesthesiologists ( ASA ) score of 3 and above . Chi-square analysis revealed that the odds ratio of postoperative major complications was 4.083 ( 95 % confidence interval , 1.433 - 11.638 ) when the patient satisfied the criteria for frailty . Albumin < 35 , ASA > 3 , comorbidity index > 5 , and Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity ( POSSUM ) scores were not predictive of postoperative major complications . CONCLUSIONS Preliminary findings show that frailty is a potent adjunctive tool of predicting postoperative morbidity . Frailty can be used to identify elderly patients needing further optimization before major surgery Background Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems . Amino acid deficiency , including L-carnitine , has been proposed to be associated with its pathophysiology . Nevertheless , the efficacy of L-carnitine supplementation on frailty status has not been documented . Thus , this study aim ed to determine the effect of 10-week L-carnitine supplement ( 1.5 g/day ) on frailty status and its biomarkers and also physical function , cognition , and nutritional status among prefrail older adults in Klang Valley , Malaysia . Methodology This study is a r and omized , double-blind , placebo-controlled clinical trial conducted among 50 prefrail subjects r and omized into two groups ( 26 in L-carnitine group and 24 in placebo group ) . Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit , selected frailty biomarkers ( interleukin-6 , tumor necrosis factor-alpha , and insulin-like growth factor-1 ) , physical function , cognitive function , nutritional status and biochemical profile . Results The results indicated that the mean scores of Frailty Index score and h and grip test were significantly improved in subjects supplemented with L-carnitine ( P<0.05 for both parameters ) as compared to no change in the placebo group . Based on Fried criteria , four subjects ( three from the L-carnitine group and one from the control group ) transited from prefrail status to robust after the intervention . Conclusion L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults Background Frailty is a term commonly used to describe the condition of an older person who has chronic health problems , has lost functional abilities and is likely to deteriorate further . However , despite its common use , only a small number of studies have attempted to define the syndrome of frailty and measure its prevalence . The criteria Fried and colleagues used to define the frailty syndrome will be used in this study ( i.e. weight loss , fatigue , decreased grip strength , slow gait speed , and low physical activity ) . Previous studies have shown that clinical outcomes for frail older people can be improved using multi-factorial interventions such as comprehensive geriatric assessment , and single interventions such as exercise programs or nutritional supplementation , but no interventions have been developed to specifically reverse the syndrome of frailty . We have developed a multidisciplinary intervention that specifically targets frailty as defined by Fried et al. We aim to establish the effects of this intervention on frailty , mobility , hospitalisation and institutionalisation in frail older people . Methods and Design A single centre r and omised controlled trial comparing a multidisciplinary intervention with usual care . The intervention will target identified characteristics of frailty , functional limitations , nutritional status , falls risk , psychological issues and management of chronic health conditions .  Two hundred and thirty people aged 70 and over who meet the Fried definition of frailty will be recruited from clients of the aged care service of a metropolitan hospital . Participants will be followed for a 12-month period . Discussion This research is an important step in the examination of specifically targeted frailty interventions . This project will assess whether an intervention specifically targeting frailty can be implemented , and whether it is effective when compared to usual care . If successful , the study will establish a new approach to the treatment of older people at risk of further functional decline and institutionalisation . The strategies to be examined are readily transferable to routine clinical practice and are applicable broadly in the setting of aged care health services . Trial Registration Australian New Zeal and Clinical Trails Registry : ACTRN12608000250336 BACKGROUND Preoperative risk assessment is important yet inexact in older patients because physiologic reserves are difficult to measure . Frailty is thought to estimate physiologic reserves , although its use has not been evaluated in surgical patients . We design ed a study to determine if frailty predicts surgical complications and enhances current perioperative risk models . STUDY DESIGN We prospect ively measured frailty in 594 patients ( age 65 years or older ) presenting to a university hospital for elective surgery between July 2005 and July 2006 . Frailty was classified using a vali date d scale ( 0 to 5 ) that included weakness , weight loss , exhaustion , low physical activity , and slowed walking speed . Patients scoring 4 to 5 were classified as frail , 2 to 3 were intermediately frail , and 0 to 1 were nonfrail . Main outcomes measures were 30-day surgical complications , length of stay , and discharge disposition . Multiple logistic regression ( complications and discharge ) and negative binomial regression ( length of stay ) were done to analyze frailty and postoperative outcomes associations . RESULTS Preoperative frailty was associated with an increased risk for postoperative complications ( intermediately frail : odds ratio [ OR ] 2.06 ; 95 % CI 1.18 - 3.60 ; frail : OR 2.54 ; 95 % CI 1.12 - 5.77 ) , length of stay ( intermediately frail : incidence rate ratio 1.49 ; 95 % CI 1.24 - 1.80 ; frail : incidence rate ratio 1.69 ; 95 % CI 1.28 - 2.23 ) , and discharge to a skilled or assisted-living facility after previously living at home ( intermediately frail : OR 3.16 ; 95 % CI 1.0 - 9.99 ; frail : OR 20.48 ; 95 % CI 5.54 - 75.68 ) . Frailty improved predictive power ( p < 0.01 ) of each risk index ( ie , American Society of Anesthesiologists , Lee , and Eagle scores ) . CONCLUSIONS Frailty independently predicts postoperative complications , length of stay , and discharge to a skilled or assisted-living facility in older surgical patients and enhances conventional risk models . Assessing frailty using a st and ardized definition can help patients and physicians make more informed decisions OBJECTIVE To determine the reliability of rapid screening by clinical ly derived geriatric criteria in predicting outcomes of elderly hospitalized patients . DESIGN Prospect i ve cohort study of 985 patients screened at the time of hospital admission and followed for 1 year with respect to the outcomes of mortality , hospital readmission , and nursing home utilization . SETTING Palo Alto Veterans Affairs Medical Center , a tertiary care teaching hospital . SUBJECTS Male patients 65 years of age and older admitted to the Medical and Surgical services during the period from October 1 , 1985 through September 30 , 1986 . RESULTS Patients were grouped by specific screening criteria into three groups of increasing frailty : Independent , Frail , and Severely Impaired . Each criterion focused on a geriatric condition and was design ed to serve as a marker for frailty . Increasing frailty was significantly correlated with increasing length of hospital stay ( P less than 0.0001 ) , nursing home utilization ( P less than 0.0001 ) , and mortality ( P less than 0.0001 ) . Multivariate analyses revealed that the clinical groups were more predictive of mortality and nursing home utilization than were age or Diagnosis-Related Groups ( DRGs ) . Rehospitalization was unrelated to age , clinical group , or DRG , suggesting that utilization may not be driven by the clinical factors measured in this study . CONCLUSIONS Rapid clinical screening using specific geriatric criteria is effective in identifying frail older subjects at risk for mortality and nursing home utilization . Our findings suggest that geriatric syndromes are more predictive of adverse outcomes than diagnosis per se . This well operationalized screening process is inexpensive as well as effective and could easily be introduced into other hospital setting Physical frailty has been recognized as a clinical syndrome result ing from declines in various physiological systems ; however , the role of the central nervous system in the pathophysiology of frailty remains unclear . The I‐Lan Longitudinal Aging Study r and omly sample d community‐dwelling people aged 50 or older for a brain magnetic resonance imaging study . All participants were assessed for frailty status ( robust , prefrail , and frail ) based on the presence of five frailty components : slow walking speed , muscle weakness , low physical activity , exhaustion and weight loss ( Fried criteria ) . Gray matter volume ( GMV ) changes associated with frailty status and individual frailty components were examined . Overall , 456 participants ( 64.0 ± 8.5 years , 47.6 % women ) were included in this study . The prefrail ( n = 178 , 39.0 % ) and frail ( n = 19 , 4.2 % ) subjects were grouped for analysis . The prefrail – frail group showed reduced GMV , compared to the robust group ( n = 259 , 56.8 % ) , in the cerebellum , hippocampi , middle frontal gyri , and several other cerebral regions ( corrected P < 0.05 ) . Each frailty component was associated with GMV changes in functionally related brain areas . Hierarchical cluster analysis categorized these components into three subsets . Motor‐related components , including weakness , low activity , and slowness , comprised one subset with a common cerebellar involvement . Exhaustion and weight loss were the other two subsets without cerebellar changes . To conclude , physical frailty is associated with a decreased reserve in specific brain regions , especially cerebellum . Further longitudinal studies are needed to explore if the cerebellum‐ and noncerebellum‐based frailty components reflect a distinctive future risk for developing frailty . Hum Brain Mapp 36:3666–3676 , 2015 . © 2015 Wiley Periodicals , BACKGROUND The purpose of this study was to determine the relationship of frailty and 6-month postoperative costs . METHODS Subjects aged ≥ 65 years undergoing elective colorectal operations were enrolled in a prospect i ve observational study . Frailty was assessed by a vali date d measure of function , cognition , nutrition , comorbidity burden , and geriatric syndromes . Frailty was quantified by summing the number of positive characteristics in each subject . RESULTS Sixty subjects ( mean age , 75 ± 8 years ) were studied . Inpatient mortality was 2 % ( n = 1 ) . Overall , 40 % of subjects ( n = 24 ) were considered nonfrail , 22 % ( n = 13 ) were prefrail , and 38 % ( n = 22 ) were frail . With advancing frailty , hospital costs increased ( P < .001 ) and costs from discharge to 6-months increased ( P < .001 ) . Higher degrees of frailty were related to increased rates of discharge institutionalization ( P < .001 ) and 30-day readmission ( P = .044 ) . CONCLUSIONS A simple , brief preoperative frailty assessment accurately forecasts increased surgical hospital costs and postdischarge to 6-month healthcare costs after colorectal operations in older adults BACKGROUND Frailty is a geriatric syndrome that diminishes the potential for functional recovery after a  transcatheter aortic valve replacement ( TAVR ) or surgical aortic valve replacement ( SAVR )  procedure ; however , its integration in clinical practice has been limited by a lack of consensus on how to measure it . OBJECTIVES This study sought to compare the incremental predictive value of 7 different frailty scales to predict poor outcomes following TAVR or SAVR . METHODS A prospect i ve cohort of older adults undergoing TAVR or SAVR was assembled at 14 centers in 3 countries from 2012 to 2016 . The following frailty scales were compared : Fried , Fried+ , Rockwood , Short Physical Performance Battery , Bern , Columbia , and the Essential Frailty Toolset ( EFT ) . Outcomes of interest were all-cause mortality and disability 1 year after the procedure . RESULTS The cohort was composed of 1,020 patients with a median age of 82 years . Depending on the scale used , the prevalence of frailty ranged from 26 % to 68 % . Frailty as measured by the EFT was the strongest predictor of death at 1 year ( adjusted odds ratio [ OR ] : 3.72 ; 95 % confidence interval [ CI ] : 2.54 to 5.45 ) with a C-statistic improvement of 0.071 ( p < 0.001 ) and integrated discrimination improvement of 0.067 ( p < 0.001 ) . Moreover , the EFT was the strongest predictor of worsening disability at 1 year ( adjusted OR : 2.13 ; 95 % CI : 1.57 to 2.87 ) and death at 30 days ( adjusted OR : 3.29 ; 95 % CI : 1.73 to 6.26 ) . CONCLUSIONS Frailty is a risk factor for death and disability  following TAVR and SAVR . A brief 4-item scale encompassing lower-extremity weakness , cognitive impairment , anemia , and hypoalbuminemia outperformed other frailty scales and is recommended for use in this setting . ( Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions ; NCT01845207 ) Objectives : ( 1 ) Determine the relationship of geriatric assessment markers to 6-month postoperative mortality in elderly patients . ( 2 ) Create a clinical prediction rule using geriatric markers from preoperative assessment . Background : Geriatric surgery patients have unique physiologic vulnerability requiring preoperative assessment beyond the traditional evaluation of older adults . The constellation of frailty , disability and comorbidity predict poor outcomes in elderly hospitalized patients . Methods : Prospect ively , subjects ≥65 years undergoing a major operation requiring postoperative intensive care unit admission were enrolled . Preoperative geriatric assessment s included  : Mini-Cog Test ( cognition ) , albumin , having fallen in the past 6-months , hematocrit , Katz Score ( function ) , and Charlson Index ( comorbidities )  . Outcome measures included 6-month mortality ( primary ) and postdischarge institutionalization ( secondary ) . Results : One hundred ten subjects ( age 74 ± 6 years ) were studied . Six-month mortality was 15 % ( 16/110 ) . Preoperative markers related to 6-month mortality included : impaired cognition ( P < 0.01 ) , recent falls ( P < 0.01 ) , lower albumin ( P < 0.01 ) , greater anemia ( P < 0.01 ) , functional dependence ( P < 0.01 ) , and increased comorbidities ( P < 0.01 ) . Similar statistical relationships were found for all 6 markers and postdischarge institutionalization . Logistic regression identified any functional dependence ( odds ratio 13.9 ) as the strongest predictor of 6-month mortality . Four or more markers in any one patient predicted 6-month mortality with a sensitivity of 81 % ( 13/16 ) and specificity of 86 % ( 81/94 ) . Conclusions : Geriatric assessment markers for frailty , disability and comorbidity predict 6-month postoperative mortality and postdischarge institutionalization . The preoperative presence of ≥4 geriatric-specific markers has high sensitivity and specificity for 6-month mortality . Preoperative assessment using geriatric-specific markers is a substantial paradigm shift from the traditional preoperative evaluation of older adults OBJECTIVES The present study examined the association between anorexia of aging and physical frailty among older people . STUDY DESIGN An observational , cross-sectional cohort design was used with a sample of 4417 elderly Japanese citizens living in a community setting . MAIN OUTCOME MEASURES Frailty was operationalized as the following frailty components : slowness , weakness , exhaustion , low level of physical activity , and weight loss . Participants were grouped as non-frail , pre-frail , and frail , and categorized as anorexic or not using question naire cutoff scores . Measured covariates were as follows : sociodemographic variables , medical history , life style , body mass index , blood nutrition data , self-rated health , depressive symptoms , and cognitive function . RESULTS The prevalence of anorexia of aging in each group was as follows : non-frail , 7.9 % ; pre-frail , 14.8 % ; frail , 21.2 % ( P for trend<0.001 ) . After adjusting for all covariates , independent associations were identified between anorexia of aging and slowness ( OR 1.42 , 95 % CI : 1.14 - 1.75 , P=0.002 ) , exhaustion ( OR 1.39 , 95 % CI : 1.11 - 1.74 , P=0.004 ) and weight loss ( OR 1.37 , 95 % CI : 1.05 - 1.79 , P=0.019 ) , but not weakness or low level of physical activity . CONCLUSIONS Anorexia of aging is importantly associated with frailty and the following frailty components : slowness , exhaustion , and weight loss . Future research should prospect ively examine frailty 's causal connection with anorexia of aging Background Frailty is a dynamic age-related condition of increased vulnerability characterized by declines across multiple physiologic systems and associated with an increased risk of death . We compared the predictive accuracy for one-month and one-year all-cause mortality of four frailty instruments in a large population of hospitalized older patients in a prospect i ve multicentre cohort study . Methods and Findings On 2033 hospitalized patients aged ≥65 years from twenty Italian geriatric units , we calculated the frailty indexes derived from the Study of Osteoporotic Fractures ( FI-SOF ) , based on the cumulative deficits model ( FI-CD ) , based on a comprehensive geriatric assessment ( FI-CGA ) , and the Multidimensional Prognostic Index ( MPI ) .  The overall mortality rates were 8.6 % after one-month and 24.9 % after one-year follow-up . All frailty instruments were significantly associated with one-month and one-year all-cause mortality . The areas under the receiver operating characteristic ( ROC ) curves estimated from age- and sex-adjusted logistic regression models , accounting for clustering due to centre effect , showed that the MPI had a significant higher discriminatory accuracy than FI-SOF , FI-CD , and FI-CGA after one month ( areas under the ROC curves : FI-SOF = 0.685 vs. FI-CD = 0.738 vs. FI-CGA = 0.724 vs. MPI = 0.765 , p<0.0001 ) and one year of follow-up ( areas under the ROC curves : FI-SOF = 0.694 vs. FI-CD = 0.729 vs. FI-CGA = 0.727 vs. MPI = 0.750 , p<0.0001 ) . The MPI showed a significant higher discriminatory power for predicting one-year mortality also in hospitalized older patients without functional limitations , without cognitive impairment , malnourished , with increased comorbidity , and with a high number of drugs . Conclusions All frailty instruments were significantly associated with short- and long-term all-cause mortality , but MPI demonstrated a significant higher predictive power than other frailty instruments in hospitalized older patients Frailty is a medical syndrome associated with advancing age characterized by reduced functional reserve , strength , endurance , and susceptibility to infection associated with high morbidity , hospitalization , and death . Nonspecific interventions to improve the healthspan of affected patients include physical therapy , exercise , improved nutrition , etc . Among the hallmarks of aging , depletion of stem cells with result ant compromise of regeneration and repair of tissues informs a rational stem cell-based replacement strategy . This hypothesis has been evaluated in a r and omized , double-blind , placebo-controlled clinical trial utilizing human allogeneic mesenchymal stem cells ( allo-hMSCs ) , a facile , scalable stem cell replacement therapy . Intravenous infusion of 100 or 200 million allo-hMSCs was deemed safe in aged frail individuals . However , modest improvement outcomes were limited to the lower dose , a finding that remains difficult to explain . Future studies are definitely warranted given the magnitude of this increasingly important medical syndrome The easy-to-apply SOF criteria for frailty were recently vali date d in studies conducted in the U.S. only . In order to determine the ability of the SOF criteria to predict adverse health outcomes at a one-year follow-up in a sample of older out patients in Italy we carried out a prospect i ve cohort study on 265 community-dwelling out patients aged 65 + ( mean age 81.5 years ) consecutively referred to a geriatric clinic . At baseline participants underwent a comprehensive geriatric assessment ( CGA ) including evaluation of their frailty status according to the SOF criteria . At a one-year follow-up , between June and December 2010 , we investigated nursing home placement and death in all participants as well as any fall , any admission to the emergency department ( ED ) , any hospitalization and a greater disability among the subset of subjects still living at home . One year after the visit 231 subjects were still living at home ( 87.2 % ) , 9 had been placed in a nursing home ( 3.4 % ) and 25 had died ( 9.4 % ) . Frailty was associated with a greater risk of falls ( odds ratio [ OR ] 2.01 , 95 % confidence interval [ CI ] 1.05 - 3.83 , p=0.035 ) , hospitalization ( OR 2.08 , 95 % CI 1.02 - 4.24 , p=0.045 ) and death ( OR 3.07 , 95 % 1.02 - 4.24 , p=0.045 ) after correction for demographic characteristics , comorbidity including dementia and depression , socioeconomic position and severe disability . Thus , in an older outpatient population in Italy the frailty syndrome diagnosed according to the SOF criteria was an independent predictor of several adverse health outcomes Objective To assess the prevalence of the frailty syndrome and its associated variables among the older adult population in the province of Toledo ( Spain ) . Methods Data were taken from the Toledo Study for Healthy Aging , a population -based study conducted on 2,488 individuals aged 65 years and older . Study participants were selected by a two-stage r and om sampling from the municipal census of Toledo , covering both institutionalized and community dwelling persons from rural and urban setting s. Data were collected from 2006 to 2009 , and included information on social support , activities of daily living , comorbidity , physical activity , quality of life , depressive symptoms , and cognitive function . In addition , a nurse collected  anthropometric data  , conducted tests of physical performance ( walk speed , upper and lower extremities strength , and the st and - and -sit from a chair test ) and obtained a blood sample . The diagnosis of the frailty syndrome was based on the Fried criteria ( weakness , low speed , low physical activity , exhaustion , and weight loss ) . Results In total , 41.8 % ( 95 % confidence interval [ CI ] 39.4–44.2 % ) of the study participants were prefrail , and 8.4 % ( 95 % CI 7.1–9.8 % ) were frail . There were no differences in the prevalence of frailty by sex , level of education , occupation , marital status , or place of residence . The frequency of the frailty syndrome increased with age , and was higher in those with disability , depression , hip fracture and other comorbidity , such as cardiovascular disease and disorders of the central nervous system . Conclusions The prevalence of the frailty syndrome in older Spanish adults is high and similar to that reported in other population s in the Mediterranean basin Most definitions of frailty utilize US population s in their development . The concept of frailty has not been well studied in Japan , which has the largest percentage of older patients ( per capita ) in the world . We created a 5-year prospect i ve cohort study of community-dwelling older Japanese adults . Participants were not frail at baseline , based on our definition adapted from the Canadian Study for Health and Aging Clinical Frailty Scale . Participants underwent a comprehensive geriatric assessment ( CGA ) at baseline , and final assessment s were either in person or via mailed survey .  We enrolled 407 individuals ( 184 men , mean age 78 ± 4 years ; 223 women , mean age 77 ± 4 years ) . Sixty-five participants met criteria for frailty by the end of the study . In univariate analyses , eighteen separate parameters were associated with frailty , some of which included : age , gender , h and grip , timed walk , systolic blood pressure , pulse pressure , cognitive status , living alone , and hearing deficits . In multivariate analyses , the following elements remained associated with frailty : timed walk , pulse pressure , cognition deficits and hearing deficits . We established cut-off points for timed walk ( 5m/3s ) and pulse pressure ( 60 mmHg ) . We then created a simple additive score for these four factors ( present = 1 ; absent = 0 ) . A score of 0 had a 93 % negative predictive value for frailty while a score of 4 had a 70 % positive predictive value . While further study is needed , this work creates an easy-to-administer tool that may be generalizable to other population The ability to predict outcomes following a kidney transplant is limited by the complex physiologic decline of kidney failure , a latent factor that is difficult to capture using conventional comorbidity assessment . The frailty phenotype is a recently described inflammatory state of increased vulnerability to stressors result ing from decreased physiologic reserve and dysregulation of multiple physiologic systems . We hypothesized that frailty would be associated with delayed graft function , based on putative associations between inflammatory cytokines and graft dysfunction . We prospect ively measured  frailty  in 183 kidney transplant recipients between December 2008 and April 2010 . Independent associations between frailty and delayed graft function were analyzed using modified Poisson regression . Preoperative frailty was independently associated with a 1.94-fold increased risk for delayed graft function ( 95 % CI , 1.13 - 3.36 ; P = .02 ) . The assessment of frailty may provide further insights into the pathophysiology of allograft dysfunction and may improve our ability to preoperatively risk-stratify kidney transplant recipients OBJECTIVES To define frailty using simple indicators ; to identify risk factors for frailty as targets for prevention ; and to investigate the predictive validity of this frailty classification for death , hospitalization , hip fracture , and activity of daily living ( ADL ) disability . DESIGN Prospect i ve study , the Women 's Health Initiative Observational Study . SETTING Forty U.S. clinical centers . PARTICIPANTS Forty thous and six hundred fifty-seven women aged 65 to 79 at baseline . MEASUREMENTS Components of frailty included self-reported muscle weakness/impaired walking , exhaustion , low physical activity , and unintended weight loss between baseline and 3 years of follow-up . Death , hip fractures , ADL disability , and hospitalizations were ascertained during an average of 5.9 years of follow-up . RESULTS Baseline frailty was classified in 16.3 % of participants , and incident frailty at 3-years was 14.8 % . Older age , chronic conditions , smoking , and depressive symptom score were positively associated with incident frailty , whereas income , moderate alcohol use , living alone , and self-reported health were inversely associated . Being underweight , overweight , or obese all carried significantly higher risk of frailty than normal weight . Baseline frailty independently predicted risk of death ( hazard ratio (HR)=1.71 , 95 % confidence interval (CI)=1.48 - 1.97 ) , hip fracture ( HR=1.57 , 95 % CI=1.11 - 2.20 ) , ADL disability ( odds ratio (OR)=3.15 , 95 % CI=2.47 - 4.02 ) , and hospitalizations ( OR=1.95 , 95 % CI=1.72 - 2.22 ) after adjustment for demographic characteristics , health behaviors , disability , and comorbid conditions . CONCLUSION These results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women . Underweight , obesity , smoking , and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention BACKGROUND identification of frailty is recommended in geriatric practice . However , there is a lack of frailty scores combining easy-to-collect predictors from multiple domains . OBJECTIVE to develop a frailty score including only self-reported information and easy-to-perform st and ardised measurements recommended in routine geriatric practice . DESIGN prospect i ve population -based study . SETTING / PARTICIPANTS included 1,007 Italian subjects aged 65 and over . MEASUREMENTS seventeen baseline possible mortality predictors from several domains , 4-year risk of mortality and other adverse health outcomes associated with frailty [ fractures , hospitalisation , and new and worsening activities of daily living ( ADL ) disability ] . METHODS a multivariate Cox model was used to identify the best sub-group of independent predictors and to develop a mortality prognostic score , defined as the number of adverse predictors present . Logistic regression was used to verify whether the score also predicted risk of other frailty outcomes in the cohort survivors . RESULTS nine independent mortality predictors were identified . Among subjects with score > or =3 , each one point increase in the score was associated with a doubling in mortality risk and , among survivors , with an increased risk of all the other adverse health outcomes . CONCLUSIONS nine easy-to-collect predictors may identify aged people at increased risk of adverse health outcomes associated with frailty BACKGROUND The etiology of the geriatric syndrome frailty is multifactorial . Besides hormonal and inflammatory processes , nutritional influences may be of major relevance . In this cross-sectional study , the association between dietary quality and frailty was investigated . METHODS In 192 community-dwelling older volunteers ( > 75 years ) , an interview-based food frequency question naire was used to assess nutritional data . A Mediterranean diet ( MED ) score ( maximum 9 points ) was used to evaluate dietary quality . Frailty was defined as the presence of at least three and prefrailty as the presence of one or two of the following criteria : weight loss , exhaustion , low physical activity , low h and grip strength , and slow walking speed . Older adults without any of these attributes were defined as " nonfrail " Binomial logistic regression analysis was used to assess the risk of being frail ( vs prefrail and nonfrail ) in each quartile ( vs lowest quartile ) of the MED score . RESULTS The mean ( SD ) age of the participants was 83 ( 4 ) years ; 41.1 % were prefrail and 15.1 % were frail . The risk of being frail was significantly reduced in the highest quartile of the MED score ( OR 0.26 ; 95 % CI 0.07 - 0.98 ) . CONCLUSIONS A healthy dietary pattern is associated with a lower risk of being frail . Larger , prospect i ve and interventional studies are needed to clarify the association between dietary quality and frailty Abstract Background Aging frailty , characterized by decreased physical and immunological functioning , is associated with stem cell depletion . Human allogeneic mesenchymal stem cells ( allo-hMSCs ) exert immunomodulatory effects and promote tissue repair . Methods This is a r and omized , double-blinded , dose-finding study of intravenous allo-hMSCs ( 100 or 200-million [ M ] ) vs placebo delivered to patients ( n = 30 , mean age 75.5 ± 7.3 ) with frailty . The primary endpoint was incidence of treatment-emergent serious adverse events ( TE-SAEs ) at 1-month postinfusion . Secondary endpoints included physical performance , patient-reported outcomes , and immune markers of frailty measured at 6 months postinfusion . Results No therapy-related TE-SAEs occurred at 1 month . Physical performance improved preferentially in the 100M-group ; immunologic improvement occurred in both the 100M- and 200M-groups . The 6-minute walk test , short physical performance exam , and forced expiratory volume in 1 second improved in the 100M-group ( p = .01 ) , not in the 200M- or placebo groups . The female sexual quality of life question naire improved in the 100M-group ( p = .03 ) . Serum TNF-α levels decreased in the 100M-group ( p = .03 ) . B cell intracellular TNF-α improved in both the 100M- ( p < .0001 ) and 200M-groups ( p = .002 ) as well as between groups compared to placebo ( p = .003 and p = .039 , respectively ) . Early and late activated T-cells were also reduced by MSC therapy . Conclusion Intravenous allo-hMSCs were safe in individuals with aging frailty . Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers , both of which characterize the frailty syndrome . Given the excellent safety and efficacy profiles demonstrated in this study , larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder . Clinical Trial Registration www . clinical trials.gov : CRATUS ( # NCT02065245 ) BACKGROUND The decision as to whether a patient can tolerate surgery is often subjective and can misjudge a patient 's true physiologic state . The concept of frailty is an important assessment tool in the geriatric medical population , but has only recently gained attention in surgical patients . Frailty potentially represents a measureable phenotype , which , if quantified with a st and ardized protocol , could reliably estimate the risk of adverse surgical outcomes . STUDY DESIGN Frailty was prospect ively evaluated in the clinic setting in patients consenting for major general , oncologic , and urologic procedures . Evaluation included an  established assessment tool ( Hopkins Frailty Score ) , self-administered question naires , clinical assessment of performance status , and biochemical measures .  Primary outcome was 30-day postoperative complications . RESULTS There were 189 patients evaluated : 117 from urology , 52 from surgical oncology , and 20 from general surgery clinics . Mean age was 62 years , 59.8 % were male , and 71.4 % were Caucasian . Patients who scored intermediately frail or frail on the Hopkins Frailty Score were more likely to experience postoperative complications ( odds ratio [ OR ] 2.07 , 95 % CI 1.05 to 4.08 , p = 0.036 ) . Of all other preoperative assessment tools , only higher hemoglobin ( p = 0.033 ) had a significant association and was protective for 30-day complications . CONCLUSIONS The aggregate score of patients as " intermediately frail or frail " on the Hopkins Frailty Score was predictive of a patient experiencing a postoperative complication . This preoperative assessment tool may prove beneficial when weighing the risks and benefits of surgery , allowing objective data to guide surgical decision-making and patient counseling BACKGROUND The role of frailty as a prognostic factor in non-selected patients with symptomatic severe aortic stenosis ( SAS ) is still uncertain . This study aims to examine the association between the frailty syndrome and mortality among very old patients with symptomatic SAS , and to assess whether the association varies with the type of SAS treatment . METHODS AND RESULTS Prospect i ve study of 606 patients aged ≥75years with symptomatic SAS , recruited from February 2010 to January 2015 , who were followed up through June 2015 . At baseline , frailty was defined as having at least three of the following five criteria : muscle weakness , slow gait speed , low physical activity , exhaustion , and unintentional weight loss . Statistical analyses were performed with multivariate Cox regression . At baseline , 49.3 % patients were frail . During a mean follow-up of 98weeks , 35.3 % of patients died . The hazard ratio ( 95 % confidence interval ) of mortality among frail versus non-frail patients was 1.83 ( 1.33 - 2.51 ) . The corresponding results were 1.58 ( 1.09 - 2.28 ) among patients under medical treatment , 3.06 ( 1.25 - 7.50 ) in those with transcatheter aortic valve replacement , and 1.97 ( 0.83 - 4.67 ) in those with surgical aortic valve replacement , p for interaction=0.21 . When the frailty criteria were considered separately , mortality was also higher among patients with slow gait speed [ 1.52 ( 1.05 - 2.19 ) ] or low physical activity [ 1.35 ( 1.00 - 1.85 ) ] . CONCLUSIONS Frailty is associated with increased mortality among patients with symptomatic SAS , and this association does not vary with the type of SAS treatment . Future studies evaluating the benefits of different treatments in SAS patients should account for baseline frailty Background There is limited knowledge on the ability of a poor quality of life ( QOL ) and  health-related QOL ( HRQOL ) to predict mortality and other adverse health events , independently of the frailty syndrome and other confounders , in older people living in the community and not selected on the basis of specific chronic conditions . Aim of this study was to evaluate the ability of the overall QOL and of the HRQOL to predict several adverse health outcomes at a one-year follow-up in an older outpatient population living in the community . Methods We carried out a prospect i ve cohort study on 210 community-dwelling out patients aged 65 + ( mean age 81.2 yrs ) consecutively referred to a geriatric clinic in Milan , Italy . At baseline participants underwent a comprehensive geriatric assessment including evaluation of overall QOL and HRQOL by means of the Older People 's Quality of Life ( OPQOL ) question naire . At a one-year follow-up , between June and December 2010 , we investigated nursing home placement and death in all 210 participants as well as any fall , any admission to the emergency department ( ED ) , any hospitalisation and greater functional dependence among the subset of subjects still living at home . Results One year after the visit 187 subjects were still living at home ( 89 % ) while 7 had been placed in a nursing home ( 3.3 % ) and 16 had died ( 7.7 % ) . At multiple logistic regression analyses the lowest score-based quartile of the OPQOL total score at baseline was independently associated with a greater risk of any fall and any ED admission . Also , the lowest score-based quartile of the health-related OPQOL sub-score was associated with a greater risk of any fall as well as of nursing home placement ( odds ratio [ OR ] 10.03 , 95 % confidence interval [ CI ] 1.25 - 80.54 , P = 0.030 ) and death ( OR 4.23 , 95 % CI 1.06 - 16.81 , P = 0.041 ) . The correlation with the latter two health outcomes was found after correction for age , sex , education , income , living conditions , comorbidity , disability and the frailty syndrome . Conclusions In an older outpatient population in Italy the OPQOL total score and its health-related sub-score were independent predictors of several adverse health outcomes at one year . Notably , poor HRQOL predicted both nursing home placement and death even after correction for the frailty syndrome . These findings support and enhance the prognostic relevance of QOL measures
RESULTS Severity of frailty syndrome significantly correlated with post-surgical mortality rates and with many although not all post-surgical complications .
These relationships emerge in different type of surgical procedures and patients ' features .
BACKGROUND Frailty is a geriatric syndrome characterized by the clinical presentation of identifiable physical alterations and decreased physiological reserve .
The assessment of frailty syndrome has been recently related with post-surgical outcomes and overall mortality in older individuals .