***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This study was design ed to evaluate the effects of enriching an essential amino acid ( EAA ) mixture with leucine on muscle protein metabolism in elderly and young individuals . Four ( 2 elderly and 2 young ) groups were studied before and after ingestion of 6.7 g of EAAs . EAAs were based on the composition of whey protein [ 26 % leucine ( 26 % Leu ) ] or were enriched in leucine [ 41 % leucine ( 41 % Leu ) ] . A primed , continuous infusion of L-[ring-2H5]phenylalanine was used together with vastus lateralis muscle biopsies and leg arteriovenous blood sample s for the determinations of fractional synthetic rate ( FSR ) and balance of muscle protein . FSR increased following amino acid ingestion in both the 26 % ( basal : 0.048 + /- 0.005%/h ; post-EAA : 0.063 + /- 0.007%/h ) and the 41 % ( basal : 0.036 + /- 0.004%/h ; post-EAA : 0.051 + /- 0.007%/h ) Leu young groups ( P < 0.05 ) . In contrast , in the elderly , FSR did not increase following ingestion of 26 % Leu EAA ( basal : 0.044 + /- 0.003%/h ; post-EAA : 0.049 + /- 0.006%/h ; P > 0.05 ) but did increase following ingestion of 41 % Leu EAA ( basal : 0.038 + /- 0.007%/h ; post-EAA : 0.056 + /- 0.008%/h ; P < 0.05 ) . Similar to the FSR responses , the mean response of muscle phenylalanine net balance , a reflection of muscle protein balance , was improved ( P < 0.05 ) in all groups , with the exception of the 26 % Leu elderly group . We conclude that increasing the proportion of leucine in a mixture of EAA can reverse an attenuated response of muscle protein synthesis in elderly but does not result in further stimulation of muscle protein synthesis in young subjects Proper r and omisation means little if investigators can not include all r and omised participants in the primary analysis . Participants might ignore follow-up , leave town , or take aspartame when instructed to take aspirin . Exclusions before r and omisation do not bias the treatment comparison , but they can hurt generalisability . Eligibility criteria for a trial should be clear , specific , and applied before r and omisation . Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested . In principle , assessment of exclusions after r and omisation is simple : none are allowed . For the primary analysis , all participants enrolled should be included and analysed as part of the original group assigned ( an intent-to-treat analysis ) . In reality , however , losses frequently occur . Investigators should , therefore , commit adequate re sources to develop and implement procedures to maximise retention of participants . Moreover , research ers should provide clear , explicit information on the progress of all r and omised participants through the trial by use of , for instance , a trial profile . Investigators can also do secondary analyses on , for instance , per- protocol or as-treated participants . Such analyses should be described as secondary and non-r and omised comparisons . Mish and ling of exclusions causes serious method ological difficulties . Unfortunately , some explanations for mish and ling exclusions intuitively appeal to readers , disguising the seriousness of the issues . Creative mismanagement of exclusions can undermine trial validity BACKGROUND To describe the prevalence of sarcopenia in ambulatory patients with heart failure with preserved ejection fraction ( HFpEF ) and its relation to reduced exercise capacity , muscle strength , and quality of life ( QoL ) . METHODS AND RESULTS A total of 117 symptomatic out patients with HFpEF were prospect ively enrolled in Germany , Engl and , and Slovenia as part of the Studies Investigating Co-morbidities Aggravating Heart Failure ( SICA-HF ) .  Appendicular skeletal muscle ( ASM ) mass ( the sum of muscle mass in both arms and legs ) was assessed by DEXA . Echocardiography , 6-minute walk testing ( 6-MWT ) , muscle strength assessment , spiroergometry and QoL evaluation using EQ-5D Question naire were performed . Sarcopenia was defined as ASM 2 st and ard deviations below the mean of a healthy reference group aged 18 - 40years . Patients were divided into 3 groups according to the E/e ' value : ≤8 , 9 - 14 , and ≥15 . Sarcopenia was detected in 19.7 % of all patients . These patients performed worse during 6-MWT ( 404±116 vs. 307±145 m , p=0.003 ) and showed lower absolute peak oxygen consumption ( 1579±474 vs. 1211±442mL/min , p<0.05 ) . Both ASM and muscle strength were lowest in patients with E/e ' > 15 ( p<0.05 ) . Higher values of muscle strength/ASM were associated with a better QoL ( r=0.5 , p<0.0005 ) . Logistic regression showed ASM to be independently associated with reduced distance walked during the 6-MWT adjusted for NYHA , height , left atrium diameter , ferritin and forced expiratory volume in 1s ( FEV1 ) ( odds ratio 1.2 , p=0.02 ) . CONCLUSION Sarcopenia affects a clinical ly relevant proportion of patients with HFpEF  . Low ASM is strongly linked to reduced muscle strength , exercise capacity and QoL in these patients Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more AIMS To assess the prevalence and clinical impact of reductions in the skeletal muscle mass of patients with chronic heart failure ( HF ) . Chronic HF is accompanied by co-morbidities that influence the quality of life and outcomes . METHODS AND RESULTS We prospect ively enrolled 200 patients with chronic HF . The appendicular skeletal muscle mass of the arms and the legs combined , was assessed by dual energy X-ray absorptiometry . We analysed the muscle strength in arms and legs , and all patients underwent a 6-min walk test , a 4-m walk test , and spiroergometry testing . Muscle wasting was defined as the appendicular muscle mass 2 SD below the mean of a healthy reference group of adults aged 18 - 40 years , as suggested for the diagnosis of muscle wasting in healthy ageing ( sarcopenia ) . Muscle wasting was detected in 39 ( 19.5 % ) subjects . Patients with muscle wasting had significantly lower values for h and grip and quadriceps strength as well as lower total peak oxygen consumption ( peakVO2 , 1173 ± 433 vs. 1622 ± 456 mL/min ) , lower exercise time ( 7.7 ± 3.8 vs. 10.22 ± 3.0 min , both P < 0.001 ) , and lower left ventricular ejection fraction ( LVEF , P = 0.05 ) than patients without . The distance walked during 6 min and the gait speed during the 4-m walk were lower in patients with muscle wasting ( both P < 0.05 ) . Serum levels of interleukin-6 were significantly elevated in patients with muscle wasting ( P = 0.001 ) . Logistic regression showed muscle wasting to be independently associated with reduced peak VO2 adjusted for age , sex , New York Heart Association class , haemoglobin , LVEF , distance walked in 6 minutes , and the number of co-morbidities ( odds ratio 6.53 , p = 0.01 ) . CONCLUSION Muscle wasting is a frequent co-morbidity among patients with chronic HF . Patients with muscle wasting present with reduced exercise capacity and muscle strength , and advanced disease Background —Skeletal muscle dysfunction and exercise intolerance are clinical hallmarks of patients with heart failure . These have been linked to a progressive catabolic state , skeletal muscle inflammation , and impaired oxidative metabolism . Previous studies suggest beneficial effects of & ohgr;-3 polyunsaturated fatty acids and glutamine on exercise performance and muscle protein balance . Methods and Results —In a r and omized double-blind , placebo-controlled trial , 31 patients with heart failure were r and omized to either L-alanyl-L-glutamine ( 8 g/d ) and polyunsaturated fatty acid ( 6.5 g/d ) or placebo ( safflower oil and milk powder ) for 3 months .  Cardiopulmonary exercise testing , dual-energy x-ray absorptiometry , 6-minute walk test , h and grip strength , functional muscle testing , echocardiography , and quality of life and lateral quadriceps muscle biopsy  were performed at baseline and at follow-up . Oxidative capacity and metabolic gene expression were analyzed on muscle biopsies . No differences in muscle function , echocardiography , 6-minute walk test , or h and grip strength and a nonsignificant increase in peak VO2 in the treatment group were found . Lean body mass increased and quality of life improved in the active treatment group . Molecular analysis revealed no differences in muscle fiber composition , fiber cross-sectional area , gene expression of metabolic marker genes ( PGC1&agr ; , CPT1 , PDK4 , and GLUT4 ) , and skeletal muscle oxidative capacity . Conclusions —The combined supplementation of L-alanyl-L-glutamine and polyunsaturated fatty acid did not improve exercise performance or muscle function but increased lean body mass and quality of life in patients with chronic stable heart failure . These findings suggest potentially beneficial effects of high-dose nutritional polyunsaturated fatty acids and amino acid supplementations in patients with chronic stable heart failure . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01534663 BACKGROUND & AIMS Heart Failure ( HF ) is a complex syndrome , which can include the physiological , neural hormonal and metabolic complications known as " Cardiac Cachexia " ( CC ) . In the development of CC there is a release of catabolic cytokines ( Tumor Necrosis Factor-α , interleukins 1 and 6 ) that cause a decrease of fat free mass and fat mass . These changes in body composition might be reversed with a therapeutic combination of resistance exercise and branched chain amino acid supplementation ( BCAA ) . AIM Evaluate changes in body composition after a resistance exercise program and BCAA supplementation in patients with HF . METHODS In a r and omized clinical trial with 3 month of follow-up anthropometric body composition analysis and stress tests were evaluated at the beginning and in the end of the study . Patients were divided into two groups ; the experimental group performed the resistance exercise program and received 10 g/day BCAA supplementation , and the control group only performed the resistance exercise program . Both groups were provided with individualized diets and conventional medical treatment . RESULTS Changes were found in hip circumference between the groups ( p = 0.02 ) , and muscle strength was increased in the experimental group ( 8 % ) and the control group ( 11.4 % ) with no difference between them . METS and VO2Max also increased in experimental and control groups ( 16.6 % and 50.1 % respectively ) . Regarding changes in symptoms , improvements in fatigue ( 45.4 % ) , decubitus intolerance ( 21.8 % ) and dyspnea ( 25.4 % ) were observed in the overall sample . CONCLUSION Improvements in physical and functional capacities are attributed to resistance exercise program but not to the BCAA supplementation . CLINICAL TRIALS IDENTIFIER NCT02240511 
    Output:
    
Data from 167 patients with CHF suggest that protein and /or EAA supplementation does not improve strength , but may increase six-minute walk test distance , muscle mass and QoL. The limited quality of the studies makes firm conclusions difficult , however protein and /or EAA supplementation may improve important outcome measures related to sarcopenia .