Donor-specific Cell-Free DNA as a Biomarker in Solid Organ Transplantation. A Systematic Review

Background There is increasing interest in the use of noninvasive biomarkers to reduce the risks posed by invasive biopsy for monitoring of solid organ transplants (SOT). One such promising marker is the presence of donor-derived cell-free DNA (dd-cfDNA) in the urine or blood of transplant recipients. Methods We systematically reviewed the published literature investigating the use of cfDNA in monitoring of graft health following SOT. Electronic databases were searched for studies relating cfDNA fraction or levels to clinical outcomes, and data including measures of diagnostic test accuracy (DTA) were extracted. Narrative analysis was performed. Results 95 manuscripts from 47 studies met the inclusion criteria (18 kidney, 7 liver, 11 heart, 1 kidney-pancreas, 5 lung, and 5 multiorgan). The majority were retrospective and prospective cohort studies, with 19 reporting DTA data. Multiple techniques for measuring dd-cfDNA were reported, including many not requiring a donor sample. dd-cfDNA falls rapidly within 2 weeks, with baseline levels varying by organ type. Levels are elevated in the presence of allograft injury, including acute rejection (AR) and infection, and return to baseline following successful treatment. Elevation of cfDNA levels are seen in advance of clinically apparent organ injury. Discriminatory power was greatest for higher grades of T cell mediated and antibody-mediated AR, with high negative predictive values. Conclusions cfDNA is a promising biomarker for monitoring the health of solid-organ transplants. Future studies will need to define how it can be used in routine clinical practice and determine clinical benefit with routine prospective monitoring. Corresponding Author: Simon R Knight, Oxford Transplant Centre, Nuffield Department of Surgical Sciences, Churchill Hospital, Old Road, Headington, OX3 7LE, United Kingdom. Tel: +44 (0) 1865 227131. E-mail: simon.knight@nds.ox.ac.uk Authorship SK conceived the study, authored the study protocol, developed and performed literature searches, screened references, analysed the data and wrote the manuscript. AT participated in study design, screened references, analysed the data and participated in the writing of the manuscript. MLF participated in study design and participated in the writing of the manuscript. Disclosures The authors declare no conflicts of interest relating to the content of this article. Funding This study received no external sources of funding. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A worldwide survey of Live liver donor selection policies at 24 centers with a combined experience of 19 009 adult living donor liver transplants

Background While surgical technique in LDLT has evolved with a focus on donor safety and recipient challenges, the donor selection criteria remain considerably disparate. Methods A questionnaire on donor selection was sent to 41 centers worldwide. 24 centers with a combined experience of 19009 LDLTs responded. Results Centers were categorized into predominantly LDLT (18) or DDLT (6), and high (10) or low volume (14) centers. At the majority of centers, the minimum acceptable GRWR was 1 features of metabolic syndrome. On biopsy, all considered macrovesicular and 50% considered microvesicular steatosis important. Nearly all (92%) rejected donors for early fibrosis, and minority for nonspecific granuloma or mild inflammation. Most anatomical anomalies except portal vein type D/E were acceptable at high volume centers. There was no standard policy for pre or peroperative cholangiogram. Conclusions This first large live liver donor survey provides insight into donor selection practices that may aid standardization between centers, with potential expansion of the donor pool without compromising safety. Corresponding author: Dr. AS Soin, Chairman, Chief Liver Transplant and Hepatobiliary Surgeon, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Haryana 122001, India. e-mail IDs: absoin@gmail.com, arvinder.soin@medanta.org Authorship Page 1 Dr. Arvinder Singh Soin. FRCS. Chairman, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Haryana 122001, India. e-mail ID: absoin@gmail.com. 2. Dr. Rohan Jagat Chaudhary. MS. Associate Consultant, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Haryana 122001, India. e-mail ID: rohanjc1@gmail.com. 3. Dr. Hirak Pahari. MS. Fellow, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Haryana 122001, India. e-mail ID: hirak.pahari@gmail.com. 4. Dr. Elizabeth Pomfret. MD. Division of Transplant Surgery, University of Colorado School of Medicine, 1635 Aurora Court, Aurora, CO, 80045, USA. E-mail ID: elizabeth.pomfret@ucdenver.edu Contributions: AS Soin: Conception of the work; data analysis and interpretation. Drafting the work, critical revision for important intellectual content and final approval of the version to be published. R J Chaudhary: Data acquisition, analysis and interpretation, drafting and final approval. H Pahari: Data acquisition, analysis and interpretation, drafting and final approval. E A Pomfret: Conception, critical revision and final approval of the version to be published. Disclosures: None. No conflict of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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High-flow oxygen via tracheostomy facilitates weaning from prolonged mechanical ventilation in patients with restrictive pulmonary dysfunction: two case reports

Weaning from prolonged mechanical ventilation is extremely difficult in tracheostomized patients with restrictive pulmonary dysfunction. High-flow oxygen via tracheostomy supplies heated and humidified oxygen ...

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Facets of Innate Immunity to Viral Infection

Viral Immunology, Ahead of Print.


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Understanding the Role of Antiviral Cytokines and Chemokines on Neural Stem/Progenitor Cell Activity and Survival

Viral Immunology, Ahead of Print.


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