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      Report from the American Society of Transplantation on frailty in solid organ transplantation

      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 4 , 10 , 12 , 1 , 13 , 14 , 15 , 16 , 1 , 1 , 17 , 18 , 15 , 19 , 20 , 4 , 21 , 22 , 21 , 23 , 12 , 24 , 4
      American Journal of Transplantation

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          A consensus conference on frailty in kidney, liver, heart, and lung transplantation sponsored by the American Society of Transplantation (AST) and endorsed by the American Society of Nephrology (ASN), the American Society of Transplant Surgeons (ASTS), and the Canadian Society of Transplantation (CST) took place on February 11, 2018 in Phoenix, Arizona. Input from the transplant community through scheduled conference calls enabled wide discussion of current concepts in frailty, exploration of best practices for frailty risk assessment of transplant candidates and for management after transplant, and development of ideas for future research. A current understanding of frailty was compiled by each of the solid organ groups and is presented in this paper. Frailty is a common entity in patients with end-stage organ disease who are awaiting organ transplantation, and affects mortality on the waitlist and in the posttransplant period. The optimal methods by which frailty should be measured in each organ group are yet to be determined, but studies are underway. Interventions to reverse frailty vary among organ groups and appear promising. This conference achieved its intent to highlight the importance of frailty in organ transplantation and to plant the seeds for further discussion and research in this field.

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          Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments.

          The medical syndrome of frailty is widely recognized, yet debate remains over how best to measure it in clinical and research settings. This study reviewed the frailty-related research literature by (a) comprehensively cataloging the wide array of instruments that have been utilized to measure frailty, and (b) systematically categorizing the different purposes and contexts of use for frailty instruments frequently cited in the research literature. We identified 67 frailty instruments total; of these, nine were highly-cited (≥ 200 citations). We randomly sampled and reviewed 545 English-language articles citing at least one highly-cited instrument. We estimated the total number of uses, and classified use into eight categories: risk assessment for adverse health outcomes (31% of all uses); etiological studies of frailty (22%); methodology studies (14%); biomarker studies (12%); inclusion/exclusion criteria (10%); estimating prevalence as primary goal (5%); clinical decision-making (2%); and interventional targeting (2%). The most common assessment context was observational studies of older community-dwelling adults. Physical Frailty Phenotype was the most used frailty instrument in the research literature, followed by the Deficit Accumulation Index and the Vulnerable Elders Survey. This study provides an empirical evaluation of the current uses of frailty instruments, which may be important to consider when selecting instruments for clinical or research purposes. We recommend careful consideration in the selection of a frailty instrument based on the intended purpose, domains captured, and how the instrument has been used in the past. Continued efforts are needed to study the validity and feasibility of these instruments.
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            Sarcopenia from mechanism to diagnosis and treatment in liver disease.

            Sarcopenia or loss of skeletal muscle mass is the major component of malnutrition and is a frequent complication in cirrhosis that adversely affects clinical outcomes. These include survival, quality of life, development of other complications and post liver transplantation survival. Radiological image analysis is currently utilized to diagnose sarcopenia in cirrhosis. Nutrient supplementation and physical activity are used to counter sarcopenia but have not been consistently effective because the underlying molecular and metabolic abnormalities persist or are not influenced by these treatments. Even though alterations in food intake, hypermetabolism, alterations in amino acid profiles, endotoxemia, accelerated starvation and decreased mobility may all contribute to sarcopenia in cirrhosis, hyperammonemia has recently gained attention as a possible mediator of the liver-muscle axis. Increased muscle ammonia causes: cataplerosis of α-ketoglutarate, increased transport of leucine in exchange for glutamine, impaired signaling by leucine, increased expression of myostatin (a transforming growth factor beta superfamily member) and an increased phosphorylation of eukaryotic initiation factor 2α. In addition, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy mediated proteolysis, also play a role. These molecular and metabolic alterations may contribute to the anabolic resistance and inadequate response to nutrient supplementation in cirrhosis. Central and skeletal muscle fatigue contributes to impaired exercise capacity and responses. Use of proteins with low ammoniagenic potential, leucine enriched amino acid supplementation, long-term ammonia lowering strategies and a combination of resistance and endurance exercise to increase muscle mass and function may target the molecular abnormalities in the muscle. Strategies targeting endotoxemia and the gut microbiome need further evaluation.
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              Frailty in Older Adults Undergoing Aortic Valve Replacement

              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.

                Author and article information

                American Journal of Transplantation
                Am J Transplant
                October 22 2018
                April 2019
                December 22 2018
                April 2019
                : 19
                : 4
                : 984-994
                [1 ]Cedars‐Sinai Smidt Heart Institute Los AngelesCalifornia
                [2 ]Weill Cornell Medicine New York New York
                [3 ]Northwestern University Chicago Illinois
                [4 ]University of California at San Francisco San FranciscoCalifornia
                [5 ]University of Texas Southwestern Medical Center Dallas Texas
                [6 ]Advocate Christ Medical Center Oak Lawn Illinois
                [7 ]Cleveland Clinic Cleveland Ohio
                [8 ]University of Arkansas Little Rock Arkansas
                [9 ]University of Pittsburgh Pittsburgh Pennsylvania
                [10 ]Baylor University Dallas Texas
                [11 ]Drexel University Philadelphia Pennsylvania
                [12 ]Mayo Clinic Rochester Minnesota
                [13 ]St. Louis University Saint Louis Missouri
                [14 ]Emory University AtlantaGeorgia
                [15 ]Johns Hopkins University Baltimore Maryland
                [16 ]Henry Ford Hospital Detroit Michigan
                [17 ]Mount Sinai Hospital New York New York
                [18 ]University of California Los AngelesCalifornia
                [19 ]Inova Heart and Vascular Institute Falls Church Virginia
                [20 ]University of Toronto Toronto OntarioCanada
                [21 ]University of Michigan Ann Arbor Michigan
                [22 ]University of Alberta Edmonton AlbertaCanada
                [23 ]Division of Transplant Surgery Brigham and Women's Hospital Harvard Medical School Boston Massachusetts
                [24 ]University of Colorado Denver Colorado
                © 2019





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