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

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148387/1/ajt15198_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148387/2/ajt15198.pd

Physiological studies on the growth and development of the carrot, Daucus carota L.

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Frailty in heart transplantation: Report from the heart workgroup of a consensus conference on frailty

A consensus conference on frailty in solid organ transplantation took place on February 11, 2018, to discuss the latest developments in frailty, adopt a standardized approach to assessment, and generate ideas for future research. The findings and consensus of the Frailty Heart Workgroup (American Society of Transplantation\u27s Thoracic and Critical Care Community of Practice) are presented here. Frailty is defined as a clinically recognizable state of increased vulnerability resulting from aging-associated decline in reserve and function across multiple physiologic systems such that the ability to cope with every day or acute stressors is compromised. Frailty is increasingly recognized as a distinct biologic entity that can adversely affect outcomes before and after heart transplantation. A greater proportion of patients referred for heart transplantation are older and have more complex comorbidities. However, outcomes data in the pretransplant setting, particularly for younger patients, are limited. Therefore, there is a need to develop objective frailty assessment tools for risk stratification in patients with advanced heart disease. These tools will help to determine appropriate recipient selection for advanced heart disease therapies including heart transplantation and mechanical circulatory support, improve overall outcomes, and help distinguish frailty phenotypes amenable to intervention

A novel donor-derived cell-free DNA assay for the detection of acute rejection in heart transplantation

BackgroundEndomyocardial biopsy (EMB), the reference surveillance test for acute rejection (AR) in heart transplant (HTx) recipients, is invasive, costly, and shows significant interobserver variability. Recent studies indicate that donor-derived cell-free DNA (dd-cfDNA), obtained non-invasively from blood, is associated with AR and could reduce the frequency of EMB surveillance. The aim of this study was to examine the performance characteristics of a novel test for detecting AR in adult HTx recipients.MethodsPlasma samples with contemporaneous EMBs were obtained from HTx recipients. A clinically available SNP-based massively multiplexed-PCR dd-cfDNA assay was used to measure dd-cfDNA fraction. dd-cfDNA fractions were compared with EMB-defined rejection status and test performance was assessed by constructing ROC curves and calculating accuracy measures.ResultsA total of 811 samples from 223 patients with dd-cfDNA testing and contemporaneous EMB were eligible for the study. dd-cfDNA fraction was significantly higher in AR (median 0.58%, IQR, 0.13%-1.68%) compared to non-AR (median 0.04%, IQR, 0.01%-0.11%, pc < 0.001). ROC analysis produced an area under the curve (AUC-ROC) of 0.86 (95% CI, 0.77-0.96). Defining samples with dd-cfDNA fraction ≥0.15% as AR yielded 78.5% sensitivity (95% CI, 60.7%-96.3%) and 76.9% specificity (95% CI, 71.1%-82.7%). Positive and negative predictive values were 25.1% (95% CI, 18.8%-31.5%) and 97.3% (95% CI, 95.1%-99.5%) respectively, calculated using the cohort AR prevalence of 9.0% (95% CI, 5.3%-12.8%) with adjustment for repeat samples.ConclusionsThis novel dd-cfDNA test detects AR in HTx recipients with good accuracy and holds promise as a noninvasive test for AR in HTx recipients

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

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