MAY 28, 2020 10:00 AM PDT

In situ immune profiling of heart transplant biopsies improves diagnostic accuracy and rejection risk stratification

Sponsored by: Akoya Biosciences
C.E. Credits: P.A.C.E. CE Florida CE
  • Physician, Advanced Heart Failure and Transplant Medicine, University of Pennsylvania
      My research focuses on applying computer-assisted analytical methods to multidimensional diagnostic data in order to enhance the understanding of human cardiovascular disease. With clinical training in cardiovascular medicine and scientific training in translational research, my research aims to identify appropriate populations and experimental designs for introducing innovative diagnostic and analytical approaches into clinical care.

      Specific areas of interest include computational morphologic analysis of human heart tissue, in-situ molecular diagnostics, and comprehensive characterizations of the role of inflammation and immune cell populations in diseases of the cardiovascular systems. In recent years, I have participated in research characterizing inflammatory markers and immune cell signatures in diseases of the heart and vasculature. I have served as a co-investigator on a prospective clinical trial investigating a targeted tissue sampling and advanced tissue characterization in patients with new- and recent-onset cardiomyopathy. I have also led multiple projects using machine learning computer-vision technologies to identify quantitative morphologic features which strongly predict important patient outcomes in native and transplanted heart tissue samples. My goal is to integrate automated morpho-molecular analysis pipelines with genomic and transcriptomic data to improve prediction and biological characterization of important patient outcomes.

    DATE:  May 28, 2020
    TIME:   10:00am PT, 1:00pm ET
    Cardiac allograft rejection is a serious concern in transplant medicine, conferring an increased risk of acute graft failure and adverse patient outcomes. The guideline-directed histologic grading of biopsy tissues for rejection surveillance has modest diagnostic performance, correlating poorly with the clinical trajectory of concurrent rejection events and offering minimal information about future rejection risk. These limitations expose patients to an immediate potential risk of over- or under-treating for rejection, while also imposing a rigid, protocolized rejection surveillance and immunosuppression weaning strategy that appears outdated in an era of precision medicine.
    These findings highlight the limitations of the current guideline-recommended biopsy grading standard, while supporting the diagnostic and prognostic importance of the PD1/PD-L1 checkpoint system and regulatory T-cells in cardiac allografts. We believe that the results of this proof-of-concept work will lead to a rethinking of rejection surveillance protocols for heart transplant patients, and may represent an initial step towards identifying molecular targets for immunotherapeutics in transplant medicine.
    Learning Objectives:
    • Outline the limitations of conventional histologic rejection grading in heart transplant medicine, and how this affects patient outcomes.
    • Outline the potential of in-situ immune-phenotyping for improving diagnostic accuracy and rejection risk stratification.



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