Evidence map›Paper›PMID 42201983›Full record

ArticleCritical care explorations2026

The Tip of the Iceberg: Pathway Biology Must Anchor the Next Generation of Critical Care Trials.

Logan R Van Nynatten, Douglas D Fraser, Tristan Look-Hong, Marat Slessarev, John Basmaji

Abstract readLetter
In one paragraph

Article in Critical care explorations, 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

5 authors.

Logan R Van NynattenDivision of Critical Care Medicine, Western University, London, ON, Canada.
Douglas D FraserDivision of Pediatric Critical Care Medicine, Western University, London, ON, Canada.
Tristan Look-HongDivision of Critical Care Medicine, Western University, London, ON, Canada.
Marat SlessarevDivision of Critical Care Medicine, Western University, London, ON, Canada.
John BasmajiDivision of Critical Care Medicine, Western University, London, ON, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Heterogeneity of treatment effect has yielded decades of negative critical care trials. Syndromic diagnoses like sepsis and acute respiratory distress syndrome mask distinct molecular programs that respond differently to the same intervention, and single biomarkers lack the resolution to capture this complexity. Recent evidence now demonstrates that each step of the enrichment pipeline, from real-time bedside endotyping to prospective endotype-matched therapy, is clinically operational. However, current approaches rely on limited biomarker panels that capture only surface-level biology. Pathway biology, examining coordinated dysregulation of molecular networks rather than isolated analytes, offers the deeper resolution needed to match patients to targeted therapies. We propose a translational pipeline integrating multiomics, pathway analysis, machine learning, and point-of-care assays to advance critical care toward pathway-focused predictive enrichment.

Indexed as

Clinical Trials as TopicCritical CareSystems BiologyBiomarkersCritical IllnessHumansMultiomicsBiomarkersbiomarkersclinical trial designcritical illnessomicspredictive enrichmentsystems biology

Identifiers

PMID42201983
PMCPMC13218767

What Socratic 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 Socratic graph.