Evidence map›Paper›PMID 35787933›Full record

ArticleTransplant immunology2022

Will previous palliative surgery for congenital heart disease be detrimental to subsequent pig heart xenotransplantation?

Max Oscherwitz, Huy Quoc Nguyen, Syed Sikandar Raza, David C Cleveland, Luz A Padilla, Robert A Sorabella, David Ayares, Kathryn Maxwell, Leslie A Rhodes, David K C Cooper and 1 more

Open access · greenAbstract read
In one paragraph

Article in Transplant immunology, 2022. 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
0.2field-weighted citation impact, top 47% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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 citations in OpenAlex.

  1. Article
  2. Article
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

11 authors at 2 institutions in 1 country.

Max OscherwitzXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Huy Quoc NguyenXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Syed Sikandar RazaXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
David C ClevelandDivision of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Luz A PadillaDivision of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Robert A SorabellaDivision of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
David AyaresRevivicor, Blacksburg, VA, USA.
Kathryn MaxwellDivision of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Leslie A RhodesDepartment of Pediatric Cardiology, Division of Critical Care, University of Alabama at Birmingham, Birmingham, AL, USA.
David K C CooperXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Hidetaka HaraXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: harahjp@icloud.com.
University of Alabama at Birmingham · USXenotran (United States) · US

Funding

Prolonging life-supported pig kidney and heart graft survival in baboons by suppressing inflammationU19AI090959 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MOHIUDDIN, MUHAMMAD M · 2010 to 2024
$26.3M
Training In Cardiovascular Physiology & PharmacologyT32HL007444 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Ju Chen, Robert Scott Ross · 1985 to 2026
$11.1M
UCSD PRIDE Faculty Development Program in Cardiovascular SciencesR25HL145817 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Robert Scott Ross, Joann Trejo · 2019 to 2026
$3.3M
Short-Term Research Experiences Advancing Medical Students (STREAMS)T35DK116670 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI HERBERT CHEN, Daniel I Chu · 2019 to 2026
$371k
NHLBI NIH HHS R25 HL145817NHLBI NIH HHS T32 HL007444NIAID NIH HHS U19 AI090959NIDDK NIH HHS T35 DK116670
6 · The paper itself

Abstract

introductionPig heart xenotransplantation might act as a bridge in infants with complex congenital heart disease (CHD) until a deceased human donor heart becomes available. Infants develop antibodies to wild-type (WT, i.e., genetically-unmodified) pig cells, but rarely to cells in which expression of the 3 known carbohydrate xenoantigens has been deleted by genetic engineering (triple-knockout [TKO] pigs). Our objective was to test sera from children who had undergone palliative surgery for complex CHD (and who potentially might need a pig heart transplant) to determine whether they had serum cytotoxic antibodies against TKO pig cells.

methodsSera were obtained from children with CHD undergoing Glenn or Fontan operation (n = 14) and healthy adults (n = 8, as controls). All of the children had complex CHD and had undergone some form of cardiac surgery. Seven had received human blood transfusions and 3 bovine pericardial patch grafts. IgM and IgG binding to WT and TKO pig red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry, and killing of PBMCs by a complement-dependent cytotoxicity assay.

resultsAlmost all children and adults demonstrated relatively high IgM/IgG binding to WT RBCs, but minimal binding to TKO RBCs (p < 0.0001 vs WT), although IgG binding was greater in children than adults (p < 0.01). All sera showed IgM/IgG binding to WT PBMCs, but this was much lower to TKO PBMCs (p < 0.0001 vs WT) and was greater in children than in adults (p < 0.05). Binding to both WT and TKO PBMCs was greater than to RBCs. Mean serum cytotoxicity to WT PBMCs was 90% in both children and adults, whereas to TKO PBMCs it was only 20% and < 5%, respectively. The sera from 6/14 (43%) children were cytotoxic to TKO PBMCs, but no adult sera were cytotoxic.

conclusionsAlthough no children had high levels of antibodies to TKO RBCs, 13/14 demonstrated antibodies to TKO PBMCs, in 6 of these showed mild cytotoxicity. As no adults had cytotoxic antibodies to TKO PBMCs, the higher incidence in children may possibly be associated with their exposure to previous cardiac surgery and biological products. However, the numbers were too small to determine the influence of such past exposures. Before considering pig heart xenotransplantation for children with CHD, testing for antibody binding may be warranted.

Indexed as

Heart Defects, CongenitalHeart TransplantationAnimalsAnimals, Genetically ModifiedCattleHumansImmunoglobulin GImmunoglobulin MInfantLeukocytes, MononuclearPalliative CareSwineTissue DonorsTransplantation, HeterologousImmunoglobulin GImmunoglobulin MChildrenGenetically-engineered pigHeartPalliative cardiac surgeryXenotransplantation

Identifiers

PMID35787933
PMCPMC9762890
OpenAlexW4283803118

What OpenQuestion holds

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Registered trials

None linked

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.