Evidence map›Paper›PMID 40254929›Full record

ArticleXenotransplantation

Treatment of Presumptive Rejection After Orthotopic Pig-to-Baboon Cardiac Xenotransplantation.

Chace B Mitchell, Sarah J Neal, Joe H Simmons, Sriram Chitta, David K C Cooper, David C Cleveland, John D Cleveland

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Xenotransplantation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Chace B MitchellDivision of Cardiothoracic Surgery, Department of Surgery, Heart Institute, Children's Hospital of Los Angeles (CHLA), University of Southern California (USC), Los Angeles, California, USA.
Sarah J NealDepartment of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Michale E. Keeling Center for Comparative Medicine and Research, Bastrop, Texas, USA.
Joe H SimmonsDepartment of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Michale E. Keeling Center for Comparative Medicine and Research, Bastrop, Texas, USA.
Sriram ChittaDepartment of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Michale E. Keeling Center for Comparative Medicine and Research, Bastrop, Texas, USA.
David K C CooperCenter for Transplantation Sciences, Massachusetts General Hospital / Harvard Medical School, Boston, Massachusetts, USA.
David C ClevelandDivision of Cardiothoracic Surgery, Department of Surgery, Heart Institute, Children's Hospital of Los Angeles (CHLA), University of Southern California (USC), Los Angeles, California, USA.
John D ClevelandDivision of Cardiothoracic Surgery, Department of Surgery, Heart Institute, Children's Hospital of Los Angeles (CHLA), University of Southern California (USC), Los Angeles, California, USA.

Funding

Specific Pathogen Free Baboon Research Resource (SPFBRR) - Bridge Funding Administrative SupplementP40OD024628 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WILLIAM D HOPKINS · 2017 to 2026
$15.7M
The genetically engineered pig heart as a bridge to allotransplantation in infantsR33HL163718 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CLEVELAND, DAVID C · 2022 to 2023
$990k
eGenesis BiotechnologyNHLBI NIH HHS R33 HL163718NIH HHS P40 OD024628
6 · The paper itself

Abstract

backgroundSignificant progress has been made in the long-term survival of non-human primates after orthotopic gene-edited pig cardiac xenotransplantation. However, to our knowledge, there are no reports of the successful reversal of an acute rejection episode in such an experiment. We present evidence suggesting that rejection can be reversed with corticosteroids and complement inhibition.

methodsOrthotopic transplantation of a pig heart (with 69 gene-edits) was carried out in a baboon. The immunosuppressive regimen was based on CD40/CD154 T cell co-stimulation pathway blockade and rapamycin. Cardiac function remained excellent until Day 162, when there were increases in heart rate, ventricular septal wall thickness, left ventricular end-diastolic pressures (LVEDP), and troponin level, which were associated with a low serum level of rapamycin (<4 ng/mL). Anti-rejection treatment was begun with an increase in rapamycin dosage, steroid bolus therapy, two doses of a C1-esterase inhibitor, and an extra dose of the anti-CD154mAb.

resultsThere was a rapid correction of all hemodynamic parameters, and the troponin T level (which had risen to 139 ng/L) returned to pre-rejection levels. Ventricular septal thickness and LVEDP returned to pre-rejection levels after treatment. The baboon remains well with normal graft function. Baseline heart rate remains faster than before the rejection episode.

conclusionsAs we transition to the clinical application of gene-edited pig cardiac xenotransplantation, the ability to treat rejection is of vital importance. The optimal treatment for rejection remains uncertain but we suggest that systemic complement inhibition is important.

Indexed as

Graft RejectionHeart TransplantationTransplantation, HeterologousAnimalsGraft SurvivalHeterograftsImmunosuppressive AgentsPapioSirolimusSwineImmunosuppressive AgentsSirolimuscardiac xenotransplantationgenetically modified xenograftpediatricrejection

Identifiers

PMID40254929
PMCPMC13093855

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.