Evidence map›Paper›PMID 28851355›Full record

Observational studyBMC medical genomics2017

Integrative model of leukocyte genomics and organ dysfunction in heart failure patients requiring mechanical circulatory support: a prospective observational study.

Nicholas Wisniewski, Galyna Bondar, Christoph Rau, Jay Chittoor, Eleanor Chang, Azadeh Esmaeili, Martin Cadeiras, Mario Deng

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in BMC medical genomics, 2017. 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
–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

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.

  1. Article
  2. Multi-dimensional COVID-19 short- and long-term outcome prediction algorithm.Expert review of precision medicine and drug development · 2020
    Article
  3. Review
  4. Article
  5. 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

8 authors.

Nicholas WisniewskiDepartment of Medicine, Division of Cardiology, University of California Los Angeles, 100 UCLA Medical Plaza, Suite 630, Los Angeles, California, 90095, USA. nw@ucla.edu.
Galyna BondarDepartment of Medicine, Division of Cardiology, University of California Los Angeles, 100 UCLA Medical Plaza, Suite 630, Los Angeles, California, 90095, USA.
Christoph RauDepartment of Anesthesiology, Division of Molecular Medicine, University of California Los Angeles, 100 UCLA Medical Plaza, Suite 630, Los Angeles, California, 90095, USA.
Jay ChittoorDepartment of Medicine, Division of Cardiology, University of California Los Angeles, 100 UCLA Medical Plaza, Suite 630, Los Angeles, California, 90095, USA.
Eleanor ChangDepartment of Medicine, Division of Cardiology, University of California Los Angeles, 100 UCLA Medical Plaza, Suite 630, Los Angeles, California, 90095, USA.
Azadeh EsmaeiliDepartment of Medicine, Division of Cardiology, University of California Los Angeles, 100 UCLA Medical Plaza, Suite 630, Los Angeles, California, 90095, USA.
Martin CadeirasDepartment of Medicine, Division of Cardiology, University of California Los Angeles, 100 UCLA Medical Plaza, Suite 630, Los Angeles, California, 90095, USA.
Mario DengDepartment of Medicine, Division of Cardiology, University of California Los Angeles, 100 UCLA Medical Plaza, Suite 630, Los Angeles, California, 90095, USA. mdeng@mednet.ucla.edu.

Funding

Systems Approach to Unraveling the Genetic Basis of Heart FailureR01HL114437 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DENG, MARIO C., KARMA, ALAIN S · 2013 to 2016
$4.7M
Multidimensional Molecular Biomarkers of MultiOrgan Dysfunction after MCS TherapyR21HL120040 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DENG, MARIO C. · 2014 to 2015
$421k
NHLBI NIH HHS R01 HL114437NHLBI NIH HHS R21 HL120040
6 · The paper itself

Abstract

backgroundThe implantation of mechanical circulatory support devices in heart failure patients is associated with a systemic inflammatory response, potentially leading to death from multiple organ dysfunction syndrome. Previous studies point to the involvement of many mechanisms, but an integrative hypothesis does not yet exist. Using time-dependent whole-genome mRNA expression in circulating leukocytes, we constructed a systems-model to improve mechanistic understanding and prediction of adverse outcomes.

methodsWe sampled peripheral blood mononuclear cells from 22 consecutive patients undergoing mechanical circulatory support device (MCS) surgery, at 5 timepoints: day -1 preoperative, and postoperative days 1, 3, 5, and 8. Clinical phenotyping was performed using 12 clinical parameters, 2 organ dysfunction scoring systems, and survival outcomes. We constructed a strictly phenotype-driven time-dependent non-supervised systems-representation using weighted gene co-expression network analysis, and annotated eigengenes using gene ontology, pathway, and transcription factor binding site enrichment analyses. Genes and eigengenes were mapped to the clinical phenotype using a linear mixed-effect model, with Cox models also fit at each timepoint to survival outcomes.

resultsWe inferred a 19-module network, in which most module eigengenes correlated with at least one aspect of the clinical phenotype. We observed a response of advanced heart failure patients to surgery orchestrated into stages: first, activation of the innate immune response, followed by anti-inflammation, and finally reparative processes such as mitosis, coagulation, and apoptosis. Eigengenes related to red blood cell production and extracellular matrix degradation became predictors of survival late in the timecourse corresponding to multiorgan dysfunction and disseminated intravascular coagulation.

conclusionsOur model provides an integrative representation of leukocyte biology during the systemic inflammatory response following MCS device implantation. It demonstrates consistency with previous hypotheses, identifying a number of known mechanisms. At the same time, it suggests novel hypotheses about time-specific targets.

Indexed as

Gene Expression ProfilingGenomicsAdultAgedFemaleGene Regulatory NetworksHeart FailureHumansLeukocytes, MononuclearMaleMiddle AgedMultiple Organ FailurePhenotypeProspective StudiesHeart failureIntegrative modelLeukocyte genomicsMechanical circulatory supportOrgan dysfunction

Identifiers

PMID28851355
PMCPMC5576384

What OpenQuestion holds

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LicenceCC BY
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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.