Evidence map›Paper›PMID 38066613›Full record

ArticleCritical care (London, England)2023

Whole blood transcriptomics identifies subclasses of pediatric septic shock.

Jamie O Yang, Matt S Zinter, Matteo Pellegrini, Man Yee Wong, Kinisha Gala, Daniela Markovic, Brian Nadel, Kerui Peng, Nguyen Do, Serghei Mangul and 8 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Critical care (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01565941 (Heart And Lung Failure - Pediatric INsulin Titration Trial), which is not on this map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.2field-weighted citation impact, top 7% 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.

NCT01565941 phase3completednot on this map

Heart And Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT)

TypeinterventionalSponsorBoston Children's HospitalRan2012 to 2018Enrolled713ConditionsHeart Failure, Respiratory FailureArmsInsulin
3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 15 citations in OpenAlex.

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  17. Open Science at PLOS Pathogens.PLoS pathogens · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 2 countries.

Jamie O YangUCLA Department of Internal Medicine, David Geffen School of Medicine, Los Angeles, CA, USA.
Matt S ZinterUCSF Department of Pediatrics, San Francisco, CA, USA.
Matteo PellegriniUCLA Department of Molecular, Cell, and Developmental Biology, Los Angeles, CA, USA.
Man Yee WongDivision of Pediatric Critical Care, UCLA Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles, CA, USA.
Kinisha GalaDivision of Pediatric Critical Care, UCLA Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles, CA, USA.
Daniela MarkovicUCLA Department of Medicine Statistics Core, Los Angeles, CA, USA.
Brian NadelUSC Department of Clinical Pharmacy, USC Alfred E Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, USA.
Kerui PengUSC Department of Clinical Pharmacy, USC Alfred E Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, USA.
Nguyen DoDivision of Pediatric Critical Care, UCLA Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles, CA, USA.
Serghei MangulUSC Department of Clinical Pharmacy, USC Alfred E Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, USA.
Vinay M NadkarniDepartment of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Aaron KarlsbergUSC Department of Clinical Pharmacy, USC Alfred E Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, USA.
Dhrithi DeshpandeUSC Department of Clinical Pharmacy, USC Alfred E Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, USA.
Manish J ButteDivision of Immunology, Allergy, and Rheumatology, UCLA Department of Pediatrics, Los Angeles, CA, USA.
Lisa AsaroDepartment of Pediatrics, Division of Medical Critical Care, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Michael AgusDepartment of Pediatrics, Division of Medical Critical Care, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Anil SapruDivision of Pediatric Critical Care, UCLA Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles, CA, USA. anilsapru@g.ucla.edu.
Study Site Investigators for CAF-PINT
Mattel Children's Hospital · USLAC+USC Medical Center · USUniversity of California, Los Angeles · USBoston Children's Hospital · USChildren's Hospital of Philadelphia · USUCLA Health · US

Funding

HALF-PINT: Heart and Lung Failure - Pediatric INsulin Titration trial - CCCU01HL107681 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI AGUS, MICHAEL SD, NADKARNI, VINAY M · 2011 to 2016
$9.6M
ENHANCING THE INTERNATIONAL MOLECULAR EXCHANGE (IMEX): PROVIDING AN IMPROVED COMMUNITY-ORIENTED MOLECULAR INTERACTIONS RESOURCER01GM123126 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PELLEGRINI, MATTEO · 2018 to 2021
$2.0M
Coagulation and Fibrinolysis in Pediatric Insulin Titration TrialR01HL114484 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAPRU, ANIL · 2012 to 2015
$1.6M
Pathobiologic Transcriptional Signatures of Pulmonary Complications in Pediatric Hematopoietic Cellular TransplantationK23HL146936 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZINTER, MATTHEW SCOTT · 2020 to 2024
$980k
NHLBI NIH HHS K23HL146936NHLBI NIH HHS R01 HL114484NHLBI NIH HHS R01HL114484NHLBI NIH HHS U01HL107681NIGMS NIH HHS R01 GM123126NIGMS NIH HHS R01GM123126
6 · The paper itself

Abstract

backgroundSepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles.

methodsThe subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses.

resultsPatients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells and less diverse T cell receptor repertoires.

conclusionsTwo subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences. Trial Registration This is a secondary analysis of data generated as part of the observational CAF-PINT ancillary of the HALF-PINT study (NCT01565941). Registered March 29, 2012.

Indexed as

SepsisShock, SepticChildGene Expression ProfilingHumansObservational Studies as TopicProspective StudiesRandomized Controlled Trials as TopicTranscriptomeAdaptive immunityGene expressionRNA-SeqSepsisSubclassification

Identifiers

PMID38066613
PMCPMC10709863
OpenAlexW4389489819

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Registered trials

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.