Evidence map›Paper›PMID 32549246›Full record

ArticleJournal of clinical medicine2020

Tryptophan Metabolism via the Kynurenine Pathway: Implications for Graft Optimization during Machine Perfusion.

Anna Zhang, Cailah Carroll, Siavash Raigani, Negin Karimian, Viola Huang, Sonal Nagpal, Irene Beijert, Robert J Porte, Martin Yarmush, Korkut Uygun and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal of clinical medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. 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 4 institutions in 2 countries.

Anna ZhangCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Cailah CarrollCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Siavash RaiganiCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Negin KarimianCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Viola HuangCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Sonal NagpalCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Irene BeijertCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Robert J PorteDivision of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen 9700, 9713 GZ Groningen, The Netherlands.
Martin YarmushCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Korkut UygunCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Heidi YehDivision of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Harvard University · USUniversity Medical Center Groningen · NLRutgers, The State University of New Jersey · USTufts University · US

Funding

Metabolic Modeling for Cadaveric Organ ResuscitationR01DK096075 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI UYGUN, KORKUT, YEH, HEIDI · 2012 to 2022
$3.9M
Expanding the Liver Transplant Organ Pool through Ex Vivo Liver PerfusionR01DK107875 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MARKMANN, JAMES FRANCIS, UYGUN, KORKUT · 2016 to 2020
$2.8M
NIDDK NIH HHS R01 DK096075NIDDK NIH HHS R01DK096075NIDDK NIH HHS R01 DK107875NIDDK NIH HHS R01DK107875
6 · The paper itself

Abstract

Access to liver transplantation continues to be hindered by the severe organ shortage. Extended-criteria donor livers could be used to expand the donor pool but are prone to ischemia-reperfusion injury (IRI) and post-transplant graft dysfunction. Ex situ machine perfusion may be used as a platform to rehabilitate discarded or extended-criteria livers prior to transplantation, though there is a lack of data guiding the utilization of different perfusion modalities and therapeutics. Since amino acid derivatives involved in inflammatory and antioxidant pathways are critical in IRI, we analyzed differences in amino acid metabolism in seven discarded non-steatotic human livers during normothermic- (NMP) and subnormothermic-machine perfusion (SNMP) using data from untargeted metabolomic profiling. We found notable differences in tryptophan, histamine, and glutathione metabolism. Greater tryptophan metabolism via the kynurenine pathway during NMP was indicated by significantly higher kynurenine and kynurenate tissue concentrations compared to pre-perfusion levels. Livers undergoing SNMP demonstrated impaired glutathione synthesis indicated by depletion of reduced and oxidized glutathione tissue concentrations. Notably, ATP and energy charge ratios were greater in livers during SNMP compared to NMP. Given these findings, several targeted therapeutic interventions are proposed to mitigate IRI during liver machine perfusion and optimize marginal liver grafts during SNMP and NMP.

Indexed as

ex situ perfusionglutathionehistaminekynurenineliver transplantmachine perfusionmetabolomicsnormothermicsubnormothermictryptophan

Identifiers

PMID32549246
PMCPMC7355886
OpenAlexW3035349426

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.