Evidence map›Paper›PMID 36730076›Full record

Trial reportThe journal of trauma and acute care surgery2023

A proteomic analysis of NETosis in trauma: Emergence of serpinB1 as a key player.

Terry R Schaid, Ian LaCroix, Kirk C Hansen, Angelo D'Alessandro, Ernest E Moore, Angela Sauaia, Monika Dzieciatkowska, Margot DeBot, Alexis L Cralley, Otto Thielen and 7 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in The journal of trauma and acute care surgery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 2 pooled it
–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

6 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Obesity influences the biological response to injury: a multi-omics analysis.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025
    Article
  6. 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

17 authors.

Terry R SchaidFrom the Department of Surgery/Trauma Research Center (T.R.S.Jr, E.E.M., A.S., M.D.B., O.T., W.H., S.M., A.B., K.J., C.C.S., M.J.C.), Department of Biochemistry and Molecular Genetics (I.L.C., K.C.H., A.D'A., M.D., C.E.), University of Colorado Denver, School of Medicine, Aurora; Department of Surgery (E.E.M., A.L.C.), Denver Health Medical Center, Denver; Department of Health Systems, Management, and Policy (A.S.), University of Colorado Denver, School of Medicine, Aurora; Vitalant Research Institute (C.C.S.), Denver; and Department of Pediatrics (C.C.S.), University of Colorado Denver, School of Medicine, Aurora, CO.
Ian LaCroix
Kirk C Hansen
Angelo D'Alessandro
Ernest E Moore
Angela Sauaia
Monika Dzieciatkowska
Margot DeBot
Alexis L Cralley
Otto Thielen
William Hallas
Christopher Erickson
Sanchayita Mitra
Anirban Banerjee
Kenneth Jones
Christopher C Silliman
Mitchell J Cohen

Funding

Analysis and Characterization of Trauma-Induced CoagulopathyUM1HL120877 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI MORRISSEY, JAMES H., WISNIEWSKI, STEPHEN R · 2013 to 2019
$26.6M
Trauma Reprograms CellsP50GM049222 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI BANERJEE, ANIRBAN · 1993 to 2017
$26.1M
Resuscitation Strategies for Achieving Thrombo-inflammatory HomeostasisRM1GM131968 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI COHEN, MITCHELL, D'ALESSANDRO, ANGELO · 2019 to 2023
$11.3M
The Impact of Oxidative Stress on Erythocyte BiologyR01HL148151 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI D'ALESSANDRO, ANGELO, KARAFIN, MATTHEW S · 2019 to 2022
$8.9M
Mechanisms of Trauma-Induced CoagulopathyT32GM008315 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Mitchell Cohen, ELIZABETH J. KOVACS · 1991 to 2026
$7.1M
The role of ferroptosis in red cell aging in vivo and in vitroR01HL146442 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Angelo D'Alessandro, Adam N. Goldfarb · 2019 to 2026
$5.4M
Quadrupole-Orbitrap Mass SpectrometerS10OD021641 · OD · UNIVERSITY OF COLORADO DENVER · PI HANSEN, KIRK C · 2017 to 2017
$600k
NHLBI NIH HHS R01 HL146442NHLBI NIH HHS R01 HL148151NHLBI NIH HHS UM1 HL120877NIGMS NIH HHS P50 GM049222NIGMS NIH HHS RM1 GM131968NIGMS NIH HHS T32 GM008315NIH HHS S10 OD021641
6 · The paper itself

Abstract

backgroundRelease of neutrophil extracellular traps (NETosis) may mediate postinjury organ dysfunction, but mechanisms remain unclear. The intracellular serine protease inhibitor (serpin) B1 is vital to neutrophil function and has been shown to restrict NETosis in inflammatory settings. In this study, we used discovery proteomics to identify the proteomic signature of trauma-induced NETosis. We hypothesized that serpinB1 would be a major component of this NET protein profile and associated with adverse outcomes.

methodsThis was a post hoc analysis of data collected as part of the COMBAT randomized clinical trial. Blood was collected from injured patients at a single Level I Trauma Center. Proteomic analyses were performed through targeted liquid chromatography coupled with mass spectrometry. Abundances of serpinB1 and known NETosis markers were analyzed with patient and injury characteristics, clinical data, and outcomes.

resultsSerpinB1 levels on emergency department (ED) arrival were significantly correlated with proteomic markers of NETosis, including core histones, transketolase, and S100A8/A9 proteins. More severely injured patients had elevated serpinB1 and NETosis markers on ED arrival. Levels of serpinB1 and top NETosis markers were significantly elevated on ED arrival in nonsurvivors and patients with fewer ventilator- and ICU-free days. In proteome-wide receiver operating characteristic analysis, serpinB1 was consistently among the top proteins associated with adverse outcomes. Among NETosis markers, levels of serpinB1 early in the patient's course exhibited the greatest separation between patients with fewer and greater ventilator- and ICU-free days. Gene Ontology analysis of top predictors of adverse outcomes further supports NETosis as a potential mediator of postinjury organ dysfunction.

conclusionWe have identified a proteomic signature of trauma-induced NETosis, and NETosis is an early process following severe injury that may mediate organ dysfunction. In addition, serpinB1 is a major component of this NET protein profile that may serve as an early marker of excessive NETosis after injury.

Indexed as

ProteomicsSerpinsHistonesHumansMultiple Organ FailureNeutrophilsHistonesSERPINB1 protein, humanSerpins

Identifiers

PMID36730076
PMCPMC9974543

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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.