Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06513689
Status:
COMPLETED
Last Update Posted:
None
First Post:
2024-07-16
Brief Title:
The Oxford Pleural Infection Endotyping Study
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Pleural Fluid Proteomics From Patients With Pleural Infection Shows Signatures of Diverse Neutrophilic Responses The Oxford Pleural Infection Endotyping Study TORPIDS 2
Status:
COMPLETED
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TORPIDS-2
Brief Summary:
Pleural infection is a severe disease with increasing incidence worldwide The subphenotypes of pleural infection remain unknownWe designed a study to endotype the disease and assess the association between patient phenotype microbiology and clinical outcome
We subjected 80 pleural fluid samples to unlabelled mass spectrometry
Pathway analysis of the differentially expressed proteins identified the neutrophil degranulation glycolysis pentose phosphate pathway and the liver and retinoid X receptors LXR-RXR activation Higher neutrophil degranulation was associated with increased glycolysis and pentose phosphate activation
Pleural infection patients exhibit proteomic signatures indicating diverse responses of neutrophil mediated immunity glycolysis and pentose phosphate activation
We subjected 80 pleural fluid samples to unlabelled mass spectrometry
Pathway analysis of the differentially expressed proteins identified the neutrophil degranulation glycolysis pentose phosphate pathway and the liver and retinoid X receptors LXR-RXR activation Higher neutrophil degranulation was associated with increased glycolysis and pentose phosphate activation
Pleural infection patients exhibit proteomic signatures indicating diverse responses of neutrophil mediated immunity glycolysis and pentose phosphate activation
Detailed Description:
Pleural infection is a common and severe disease with increasing incidence worldwide The endotypes of pleural infection remain unknown A better understanding of patient variation in underlying biological response to infection may lead to improved treatments and clinical outcomes We designed a study with the aim to endotype the disease and assess the association between patient phenotype microbiology and clinical outcome
We subjected 80 pleural fluid samples from the PILOT study a prospective study on pleural infection to unlabelled mass spectrometry Proteins were retained if they were detected in at least 50 of the samples resulting in a total of 449 proteins Unsupervised hierarchical clustering and UMAP analyses were used to cluster samples Spearman and exact Fischers methods were used for correlation assessment and protein expression was correlated with clinical outcomes
UMAP plotting separated the samples in to two different and distinct cohorts Pathway analysis of the differentially expressed proteins identified neutrophil degranulation glycolysis the pentose phosphate pathway and the liver and retinoid X receptors LXR-RXR activation Higher neutrophil degranulation was associated with increased glycolysis and pentose phosphate activation Specimens dominated by Streptococcus Pneumoniae exhibited high neutrophil degranulation Increased activity of the LXR-RXR pathway was associated with better survival
Pleural infection patients exhibit proteomic signatures indicating diverse responses of neutrophil mediated immunity glycolysis and pentose phosphate activation which were associated with microbiology Therapeutic targeting the LXR-XRX pathway with agonists may improve survival
We subjected 80 pleural fluid samples from the PILOT study a prospective study on pleural infection to unlabelled mass spectrometry Proteins were retained if they were detected in at least 50 of the samples resulting in a total of 449 proteins Unsupervised hierarchical clustering and UMAP analyses were used to cluster samples Spearman and exact Fischers methods were used for correlation assessment and protein expression was correlated with clinical outcomes
UMAP plotting separated the samples in to two different and distinct cohorts Pathway analysis of the differentially expressed proteins identified neutrophil degranulation glycolysis the pentose phosphate pathway and the liver and retinoid X receptors LXR-RXR activation Higher neutrophil degranulation was associated with increased glycolysis and pentose phosphate activation Specimens dominated by Streptococcus Pneumoniae exhibited high neutrophil degranulation Increased activity of the LXR-RXR pathway was associated with better survival
Pleural infection patients exhibit proteomic signatures indicating diverse responses of neutrophil mediated immunity glycolysis and pentose phosphate activation which were associated with microbiology Therapeutic targeting the LXR-XRX pathway with agonists may improve survival
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None