Evidence map›Paper›PMID 31182705›Full record

ArticleAnnals of transplantation2019

Metabolomic Characterization of Human Model of Liver Rejection Identifies Aberrancies Linked to Cyclooxygenase (COX) and Nitric Oxide Synthase (NOS).

Nicholas J Skill, Campbell M Elliott, Brian Ceballos, Romil Saxena, Robert Pepin, Lisa Bettcher, Matthew Ellensberg, Daniel Raftery, Mary A Malucio, Burcin Ekser and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Annals of transplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
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  5. Observational
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

12 authors at 2 institutions in 1 country.

Nicholas J SkillDepartment of Surgery, Indiana University Medical School, Indianapolis, IN, USA.
Campbell M ElliottDepartment of Surgery, Indiana University Medical School, Indianapolis, IN, USA.
Brian CeballosDepartment of Surgery, Indiana University Medical School, Indianapolis, IN, USA.
Romil SaxenaDepartment of Pathology, Indiana University Medical School, Indianapolis, IN, USA.
Robert PepinDepartment of Anesthesiology and Pain Medicine, Northwest Metabolomics Research Center, University of Washington, Seattle, WA, USA.
Lisa BettcherDepartment of Anesthesiology and Pain Medicine, Northwest Metabolomics Research Center, University of Washington, Seattle, WA, USA.
Matthew EllensbergDepartment of Anesthesiology and Pain Medicine, Northwest Metabolomics Research Center, University of Washington, Seattle, WA, USA.
Daniel RafteryDepartment of Anesthesiology and Pain Medicine, Northwest Metabolomics Research Center, University of Washington, Seattle, WA, USA.
Mary A MalucioDepartment of Surgery, Indiana University Medical School, Indianapolis, IN, USA.
Burcin EkserDepartment of Surgery, Indiana University Medical School, Indianapolis, IN, USA.
Richard S MangusDepartment of Surgery, Indiana University Medical School, Indianapolis, IN, USA.
Chandrashekhar A KubalDepartment of Surgery, Indiana University Medical School, Indianapolis, IN, USA.
Indiana University – Purdue University Indianapolis · USUniversity of Washington · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
Multiplexed UPLC-MS/MS System for Advanced Target MetabolomicsS10OD021562 · OD · UNIVERSITY OF WASHINGTON · PI RAFTERY, DANIEL · 2016 to 2016
$596k
NCI NIH HHS P30 CA015704NIH HHS S10 OD021562
6 · The paper itself

Abstract

BACKGROUND Acute liver rejection (ALR), a significant complication of liver transplantation, burdens patients, healthcare payers, and the healthcare providers due to an increase in morbidity, cost, and resources. Despite clinical resolution, ALR is associated with an increased risk of graft loss. A unique protocol of delayed immunosuppression used in our institute provided a model to characterize metabolomic profiles in human ALR. MATERIAL AND METHODS Twenty liver allograft biopsies obtained 48 hours after liver transplantation in the absence of immunosuppression were studied. Hepatic metabolites were quantitated in these biopsies by liquid chromatography and mass spectroscopy (LC/MS). Metabolite profiles were compared among: 1) biopsies with reperfusion injury but no histological evidence of rejection (n=7), 2) biopsies with histological evidence of moderate or severe rejection (n=5), and 3) biopsies with histological evidence of mild rejection (n=8). RESULTS There were 133 metabolites consistently detected by LC/MS and these were prioritized using variable importance to projection (VIP) analysis, comparing moderate or severe rejection vs. no rejection or mild rejection using partial least squares discriminant statistical analysis (PLS-DA). Twenty metabolites were identified as progressively different. Further PLS-DA using these metabolites identified 3 metabolites (linoleic acid, γ-linolenic acid, and citrulline) which are associated with either cyclooxygenase or nitric oxide synthase functionality. CONCLUSIONS Hepatic metabolic aberrancies associated with cyclooxygenase and nitric oxide synthase function occur contemporaneous with ALR. Additional studies are required to better characterize the role of these metabolic pathways to enhance utility of the metabolomics approach in diagnosis and outcomes of ALR.

Indexed as

MetabolomicsAgedEnd Stage Liver DiseaseFemaleGraft RejectionHumansLiverLiver TransplantationMaleMiddle AgedNitric Oxide SynthaseProstaglandin-Endoperoxide SynthasesNitric Oxide SynthaseProstaglandin-Endoperoxide Synthases

Identifiers

PMID31182705
PMCPMC6582681
OpenAlexW2952186190

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.