Evidence map›Paper›PMID 30211758›Full record

ArticleShock (Augusta, Ga.)2019

Leukocyte Transcriptional Response in Sepsis.

Simon Skibsted, Manoj K Bhasin, Daniel J Henning, Shou Ching Jaminet, Jeffrey Lewandowski, Hans Kirkegaard, William C Aird, Nathan I Shapiro

Open access · bronzeAbstract read
In one paragraph

Article in Shock (Augusta, Ga.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. The "Self-Sacrifice" of ImmuneCells in Sepsis.Frontiers in immunology · 2022
    Review
  2. Fluid Therapy in Dogs and Cats With Sepsis.Frontiers in veterinary science · 2021
    Review
  3. What's New in Shock, August 2019?Shock (Augusta, Ga.) · 2019
    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 at 5 institutions in 2 countries.

Simon SkibstedDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Manoj K BhasinCenter for Genomics, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Daniel J HenningDivision of Emergency Medicine, University of Washington, Seattle, WA, USA.
Shou Ching JaminetCenter for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Jeffrey LewandowskiDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Hans KirkegaardCenter for Emergency Medicine Research, Aarhus University Hospital and Aarhus University, Aarhus, Denmark.
William C AirdCenter for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Nathan I ShapiroDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Center for Vascular Biology Research · USAarhus University Hospital · DKBeth Israel Deaconess Medical Center · USHarvard University · USUniversity of Washington · US

Funding

Endothelial Cell Signaling and Microcirculatory Flow in Severe SepsisR01HL091757 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SHAPIRO, NATHAN I · 2008 to 2011
$2.0M
NHLBI NIH HHS R01 HL091757
6 · The paper itself

Abstract

backgroundThe complex host response to sepsis is incompletely understood. The aim of this investigation is to use leukocyte RNA sequencing to characterize biological functions, cellular pathways, and key regulatory molecules driving sepsis pathophysiology.

methodsThis was a prospective, observational study of emergency department patients with sepsis, at an urban, academic, tertiary care center. In the derivation cohort, we collected blood at enrollment and 90 days after hospital discharge allowing each patient to serve as an internal control. We performed RNA sequencing to quantify transcriptional expression changes during sepsis and non-sepsis states. We then performed unsupervised and supervised analyses, as well as functional and pathway analyses. We selected the top down and upregulated genes and key regulatory molecules for validation. Validation occurred in a cohort of septic and non-septic using real-time PCR.

resultsThe derivation cohort included 5 patients, and RNA sequencing revealed 916 unique mRNA transcripts differentially expressed during sepsis. Among these, 673 (73%) genes were upregulated, and 243 (27%) were downregulated. Functional enrichment analysis revealed a highly dynamic downstream effect of the transcriptional activity during sepsis. Of the 43 functional cellular pathways activated during sepsis, the top pathways were closely associated with inflammation and response to infection. Validation occurred in 18 septic and 25 non-septic control patients, with 34/45 (76%) of identified genes validated. The regulatory analysis identified several key regulators of sepsis.

conclusionsHighly dynamic transcriptional activity occurs in leukocytes during sepsis, activating key cellular pathways and master regulatory molecules that drive the sepsis process.

Indexed as

AdultAgedFemaleHumansInflammationLeukocytesMaleMiddle AgedProspective StudiesReal-Time Polymerase Chain ReactionRNA, MessengerSepsisRNA, Messenger

Identifiers

PMID30211758
PMCPMC10608800
OpenAlexW2895200701

What OpenQuestion holds

Textmetadata
LicenceTDM
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.