Evidence map›Paper›PMID 42274989›Full record

ArticleIntensive care medicine experimental2026

Mass cytometry reveals complex neutrophil heterogeneity in patients with severe sepsis.

Patricia D A Lima, Christina Yu, Miranda Hunt, Francois Lamontagne, Neill K J Adhikari, John C Marshall, Charles C T Hindmarch, David M Maslove

Abstract read
In one paragraph

Article in Intensive care medicine experimental, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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.

Patricia D A LimaQueen's Cardiopulmonary Unit, Queen's University, Kingston, ON, Canada.
Christina YuQueen's Cardiopulmonary Unit, Queen's University, Kingston, ON, Canada.
Miranda HuntDepartment of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
Francois LamontagneDepartment of Medicine, Université de Sherbroooke, Sherbrooke, QC, Canada.
Neill K J AdhikariDepartment of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
John C MarshallInterdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
Charles C T HindmarchQueen's Cardiopulmonary Unit, Queen's University, Kingston, ON, Canada.
David M MasloveDepartment of Critical Care Medicine, Queen's University, Kingston, ON, Canada. david.maslove@queensu.ca.ORCID http://orcid.org/0000-0002-0765-7158

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleSepsis is a state of life-threatening organ dysfunction in the setting of infection. It is biologically heterogeneous, as evidenced by whole blood transcriptomic analyses that reveal distinct molecular subtypes based on gene expression. At the cellular level, sepsis is primarily mediated by neutrophils, a leukocyte population increasingly recognized as heterogeneous across several domains. We sought to further characterize neutrophil heterogeneity by identifying neutrophil subsets in critically ill patients with severe sepsis based on multidimensional mass cytometry analysis.

methodsWe generated time series mass cytometry (CyTOF) data from whole blood samples taken from 17 patients with sepsis admitted to an intensive care unit who were enrolled in a randomized controlled trial of high-dose vitamin C. We analyzed these data using unsupervised machine learning techniques to identify distinct neutrophil subtypes. We characterized the resulting subtypes and described their changes over time.

resultsWe analyzed approximately 1.5 million cytometry events gated as neutrophils. We identified five clusters that reveal complex heterogeneity across multiple neutrophil markers of maturation and activation including olfactomedin-4 (OLFM4), CD177, glucose transporter 1 (GLUT1), CD16, and lipocalin-2. The two dominant clusters differed primarily in the abundance of OLFM4, a neutrophil granule protein. Between Day 1 and Day 7, there was an increased proportion of neutrophils in the dominant OLFM4-expressing cluster, a difference primarily driven by increased abundance of OLFM4 in the placebo group, but not the vitamin C group.

conclusionsOur findings point to complex multidimensional heterogeneity among neutrophils in sepsis, thereby extending the current concept of neutrophil heterogeneity with new data from critically ill patients with sepsis derived from mass cytometry. Variation in the temporal differences in cluster proportions between treatment arms may suggest opportunities for precision sepsis treatment.

Indexed as

CyTOFInnate immunityMass cytometryNeutrophilsPrecision medicineSepsis

Identifiers

PMID42274989
PMCPMC13260518

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.