***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: 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 Objectives The interactions between nutritional supplementation and physical activity on changes in physical function among older adults remain unclear . The primary objective of this study was to examine the impact of nutritional supplementation plus structured physical activity on 400 M walk capacity in mobility-limited older adults across two sites ( Boston , USA and Stockholm , Sweden ) . Design All subjects participated in a physical activity program ( 3x/week for 24 weeks ) , involving walking , strength , balance , and flexibility exercises . Subjects were r and omized to a daily nutritional supplement ( 150kcal , 20 g whey protein , 800 IU vitamin D ) or placebo ( 30kcal , non-nutritive ) . Setting Participants were recruited from urban communities at 2 field centers in Boston MA USA and Stockholm SWE . Participants Mobility-limited ( Short Physical Performance Battery ( SPPB ) ≤9 ) and vitamin D insufficient ( serum 25(OH ) D 9 - 24 ng/ml ) older adults were recruited for this study . Measurements Primary outcome was gait speed assessed by the 400 M walk . Results : 149 subjects were r and omized into the study ( mean age=77.5±5.4 ; female=46.3 % ; mean SPPB= 7.9±1.2 ; mean 25(OH)D=18.7±6.4 ng/ml  ) . Adherence across supplement and placebo groups was similar ( 86 % and 88 % , respectively ) , and was also similar across groups for the physical activity intervention ( 75 % and 72 % , respectively ) . Both groups demonstrated an improvement in gait speed with no significant difference between those who received the nutritional supplement compared to the placebo ( 0.071 and 0.108 m/s , respectively ( p=0.06 ) ) . Similar effects in physical function were observed using the SPPB . Serum 25(OH)D increased in supplemented group compared to placebo 7.4 ng/ml versus 1.3 ng/ml respectively . Conclusion Results suggest improved gait speed following physical activity program with no further improvement with added nutritional supplementation 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 ) Circulating  osteogenic progenitor ( COP ) cells are considered as surrogates of the mesenchymal repository in the body . In this study , we hypothesized that COP cells decrease with age and that lower levels of COP cells are associated with greater frailty and disability in older persons . Using well-established clinical criteria , we quantified physical performance and disability and stratified frailty in a r and om sample of community-dwelling individuals enrolled in the Nepean Osteoporosis and Frailty ( NOF ) Study ( mean age 82.8 ; N = 77 ; 70 % female ; 27 nonfrail , 23 prefrail , and 27 frail ) . Percentage of COP cells was quantified by flow cytometry . Logistic regression models estimated the relationship between the percentage of COP cells and prevalent disability , poor physical performance , and frailty . We found that aging is associated with a significant decrease in COP cells ( p < .001 ) . Lower percentages of COP cells were associated with disability and poor physical performance ( p < .001 ) . Older adults with  COP cells  in the lower quartile were more likely to be frail ( odds ratio 2.65 , 95 % confidence interval 2.72 - 3.15 , p < .001 ) . In conclusion , COP cells in the circulation decrease with age . Lower percentages of COP cells in late life are associated with prevalent frailty and disability . Further longitudinal studies are needed to underst and COP cells as a risk stratifier , biomarker , or therapeutic target and to predict disability in frail older persons Background : There is no single generally accepted clinical definition of frailty . Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians . We aim ed to develop a tool that would be both predictive and easy to use . Methods : We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging ( CSHA ) . We followed this cohort prospect ively ; after 5 years , we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care , and correlated the results with those obtained from other established tools . Results : The CSHA Clinical Frailty Scale was highly correlated ( r = 0.80 ) with the Frailty Index . Each 1-category increment of our scale significantly increased the medium-term risks of death ( 21.2 % within about 70 mo , 95 % confidence interval [ CI ] 12.5%–30.6 % ) and entry into an institution ( 23.9 % , 95 % CI 8.8%–41.2 % ) in multivariable models that adjusted for age , sex and education . Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition , function or comorbidity in assessing risk for death ( area under the curve 0.77 for 18-month and 0.70 for 70-month mortality ) . Interpretation : Frailty is a valid and clinical ly important construct that is recognizable by physicians . Clinical judgments about frailty can yield useful predictive information OBJECTIVES To determine the independent prognostic effect of seven potential frailty criteria , including five from the Fried phenotype , on several adverse outcomes . DESIGN Prospect i ve cohort study . SETTING Greater New Haven , Connecticut . PARTICIPANTS Seven hundred fifty-four initially nondisabled , community-living persons aged 70 and older . MEASUREMENTS An assessment of seven potential frailty criteria ( slow gait speed , low physical activity , weight loss , exhaustion , weakness , cognitive impairment , and depressive symptoms ) was completed at baseline and every 18 months for 72 months . Participants were followed with monthly telephone interviews for up to 96 months to determine the occurrence of chronic disability , long-term nursing home ( NH ) stays , injurious falls , and death . RESULTS In analyses adjusted for age , sex , race , education , number of chronic conditions , and the presence of the other potential frailty criteria , three of the five Fried criteria ( slow gait speed , low physical activity , and weight loss ) were independently associated with chronic disability , long-term NH stays , and death . Slow gait speed was the strongest predictor of chronic disability ( hazard ratio (HR)=2.97 , 95 % confidence interval (CI)=2.32 - 3.80 ) and long-term NH stay ( HR=3.86 , 95 % CI=2.23 - 6.67 ) and was the only significant predictor of injurious falls ( HR=2.19 , 95 % CI=1.33 - 3.60 ) . Cognitive impairment was also associated with chronic disability ( HR=1.82 , 95 % CI=1.40 - 2.38 ) , long-term NH stay ( HR=2.64 , 95 % CI=1.75 - 3.99 ) , and death ( HR=1.54 , 95 % CI=1.13 - 2.10 ) , and the magnitude of these associations was comparable with that of weight loss . CONCLUSION The results of this study provide strong evidence to support the use of slow gait speed , low physical activity , weight loss , and cognitive impairment as key indicators of frailty while raising concerns about the value of self-reported exhaustion and muscle weakness Importance As the US population ages , the number of operations performed on elderly patients will likely increase . Frailty predicts postoperative mortality and morbidity more than age alone , thus presenting opportunities to identify the highest-risk surgical patients and improve their outcomes . Objective To examine the effect of the Frailty Screening Initiative ( FSI ) on mortality and complications by comparing the surgical outcomes of a cohort of surgical patients treated before and after implementation of the FSI . Design , Setting , and Participants This single-site , facility-wide , prospect i ve cohort quality improvement project studied all 9153 patients from a level 1b Veterans Affairs medical center who presented for major , elective , noncardiac surgery from October 1 , 2007 , to July 1 , 2014 . Interventions Assessment of preoperative frailty in all patients scheduled for elective surgery began in July 2011 . Frailty was assessed with the Risk Analysis Index ( RAI ) , and the records of all frail patients ( RAI score , ≥21 ) were flagged for administrative review by the chief of surgery ( or design ee ) before the scheduled operation . On the basis of this review , clinicians from surgery , anesthesia , critical care , and palliative care were notified of the patient ’s frailty and associated surgical risks ; if indicated , perioperative plans were modified based on team input . Main Outcomes and Measures Postoperative mortality at 30 , 180 , and 365 days . Results From October 1 , 2007 , to July 1 , 2014 , a total of 9153 patients underwent surgery ( mean [ SD ] age , 60.3 [ 13.5 ] years ; female , 653 [ 7.1 % ] ; and white , 7096 [ 79.8 % ] ) . Overall 30-day mortality decreased from 1.6 % ( 84 of 5275 patients ) to 0.7 % ( 26 of 3878 patients , P < .001 ) after FSI implementation . Improvement was greatest among frail patients ( 12.2 % [ 24 of 197 patients ] to 3.8 % [ 16 of 424 patients ] , P < .001 ) , although mortality rates also decreased among the robust patients ( 1.2 % [ 60 of 5078 patients ] to 0.3 % [ 10 of 3454 patients ] , P < .001 ) . The magnitude of improvement among frail patients increased at 180 ( 23.9 % [ 47 of 197 patients ] to 7.7 % [ 30 of 389 patients ] , P < .001 ) and 365 days ( 34.5 % [ 68 of 197 patients ] to 11.7 % [ 36 of 309 patients ] , P < .001 ) . Multivariable models revealed improved survival after FSI implementation , cont 
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We conclude that intravenous infusion of allogenic MSCs is safe , well tolerated , and preliminarily effective clinical ly .