Evidence map›Paper›PMID 35349828›Full record

ArticleEBioMedicine2022

Coagulation factor protein abundance in the pre-septic state predicts coagulopathic activities that arise during late-stage murine sepsis.

Douglas M Heithoff, Genaro Pimienta, Scott P Mahan, Won Ho Yang, Dzung T Le, John K House, Jamey D Marth, Jeffrey W Smith, Michael J Mahan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

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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

9 authors at 6 institutions in 3 countries.

Douglas M HeithoffDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara CA 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA 93106, USA.
Genaro PimientaCancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Scott P MahanDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara CA 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA 93106, USA; Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis CA 95616, USA.
Won Ho YangDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara CA 93106, USA; Glycosylation Network Research Center and Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea; Infectious and Inflammatory Diseases Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Dzung T LeDepartment of Pathology, University of California, La Jolla, San Diego, CA 92093, USA.
John K HouseFaculty of Science, Sydney School of Veterinary Science, The University of Sydney, Camden, New South Wales 2570, Australia.
Jamey D MarthDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara CA 93106, USA; Infectious and Inflammatory Diseases Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Jeffrey W SmithCancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Michael J MahanDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara CA 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA 93106, USA. Electronic address: mahan@ucsb.edu.
Discovery Institute · USUniversity of California, Santa Barbara · USSanford Burnham Prebys Medical Discovery Institute · USUniversity of California, Davis · USUniversity of California, San Diego · USUniversity of Sydney · AU

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE · 1985 to 2026
$107.2M
Protein Glycosylation in the Coagulopathy and Inflammation of SepsisP01HL131474 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MARTH, JAMEY · 2016 to 2025
$26.2M
NCI NIH HHS P30 CA030199NHLBI NIH HHS P01 HL131474
6 · The paper itself

Abstract

backgroundAlthough sepsis accounts for 1 in 5 deaths globally, few molecular therapies exist for this condition. The development of effective biomarkers and treatments for sepsis requires a more complete understanding of host responses and pathogenic mechanisms at early stages of disease to minimize host-driven pathology.

methodsAn alternative to the current symptom-based approach used to diagnose sepsis is a precise assessment of blood proteomic changes during the onset and progression of Salmonella Typhimurium (ST) murine sepsis.

findingsA distinct pattern of coagulation factor protein abundance was identified in the pre-septic state- prior to overt disease symptoms or bacteremia- that was predictive of the dysregulation of fibrinolytic and anti-coagulant activities and resultant consumptive coagulopathy during ST murine sepsis. Moreover, the changes in protein abundance observed generally have the same directionality (increased or decreased abundance) reported for human sepsis. Significant overlap of ST coagulopathic activities was observed in Gram-negative Escherichia coli- but not in Gram-positive staphylococcal or pneumococcal murine sepsis models. Treatment with matrix metalloprotease inhibitors prevented aberrant inflammatory and coagulopathic activities post-ST infection and increased survival. Antibiotic treatment regimens initiated after specific changes arise in the plasma proteome post-ST infection were predictive of an increase in disease relapse and death after cessation of antibiotic treatment.

interpretationAltered blood proteomics provides a platform to develop rapid and easy-to-perform tests to predict sepsis for early intervention via biomarker incorporation into existing blood tests prompted by patient presentation with general malaise, and to stratify Gram-negative and Gram-positive infections for appropriate treatment. Antibiotics are less effective in microbial clearance when initiated after the onset of altered blood proteomics as evidenced by increased disease relapse and death after termination of antibiotic therapy. Treatment failure is potentially due to altered bacterial / host-responses and associated increased host-driven pathology, providing insight into why delays in antibiotic administration in human sepsis are associated with increased risk for death. Delayed treatment may thus require prolonged therapy for microbial clearance despite the prevailing notion of antibiotic de-escalation and shortened courses of antibiotics to improve drug stewardship.

fundingNational Institutes of Health, U.S. Army.

Indexed as

BacteremiaPneumococcal InfectionsSepsisAnimalsAnti-Bacterial AgentsBiomarkersBlood Coagulation FactorsHumansMiceProteomicsRecurrenceAnti-Bacterial AgentsBiomarkersBlood Coagulation FactorsCoagulopathyFactor XIMatrix metalloprotease inhibitorSepsisSepsis diagnosisSepsis treatment

Identifiers

PMID35349828
PMCPMC8965145
OpenAlexW4220730825

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.