Molecular Patterns in Acute Pancreatitis Reflect Generalizable Endotypes of the Host Response to Systemic Injury in Humans.
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
pubmed:
4
6
2020
medline:
19
2
2022
entrez:
4
6
2020
Statut:
ppublish
Résumé
Acute Pancreatitis (AP) is sudden onset pancreas inflammation that causes systemic injury with a wide and markedly heterogeneous range of clinical consequences. Here, we hypothesized that this observed clinical diversity corresponds to diversity in molecular subtypes that can be identified in clinical and multiomics data. Observational cohort study. n = 57 for the discovery cohort (clinical, transcriptomics, proteomics, and metabolomics data) and n = 312 for the validation cohort (clinical and metabolomics data). We integrated coincident transcriptomics, proteomics, and metabolomics data at serial time points between admission to hospital and up to 48 hours after recruitment from a cohort of patients presenting with acute pancreatitis. We systematically evaluated 4 different metrics for patient similarity using unbiased mathematical, biological, and clinical measures of internal and external validity.We next compared the AP molecular endotypes with previous descriptions of endotypes in a critically ill population with acute respiratory distress syndrome (ARDS). Our results identify 4 distinct and stable AP molecular endotypes. We validated our findings in a second independent cohort of patients with AP.We observed that 2 endotypes in AP recapitulate disease endotypes previously reported in ARDS. Our results show that molecular endotypes exist in AP and reflect biological patterns that are also present in ARDS, suggesting that generalizable patterns exist in diverse presentations of critical illness.
Sections du résumé
OBJECTIVE
Acute Pancreatitis (AP) is sudden onset pancreas inflammation that causes systemic injury with a wide and markedly heterogeneous range of clinical consequences. Here, we hypothesized that this observed clinical diversity corresponds to diversity in molecular subtypes that can be identified in clinical and multiomics data.
SUMMARY BACKGROUND DATA
Observational cohort study. n = 57 for the discovery cohort (clinical, transcriptomics, proteomics, and metabolomics data) and n = 312 for the validation cohort (clinical and metabolomics data).
METHODS
We integrated coincident transcriptomics, proteomics, and metabolomics data at serial time points between admission to hospital and up to 48 hours after recruitment from a cohort of patients presenting with acute pancreatitis. We systematically evaluated 4 different metrics for patient similarity using unbiased mathematical, biological, and clinical measures of internal and external validity.We next compared the AP molecular endotypes with previous descriptions of endotypes in a critically ill population with acute respiratory distress syndrome (ARDS).
RESULTS
Our results identify 4 distinct and stable AP molecular endotypes. We validated our findings in a second independent cohort of patients with AP.We observed that 2 endotypes in AP recapitulate disease endotypes previously reported in ARDS.
CONCLUSIONS
Our results show that molecular endotypes exist in AP and reflect biological patterns that are also present in ARDS, suggesting that generalizable patterns exist in diverse presentations of critical illness.
Identifiants
pubmed: 32487804
pii: 00000658-202202000-00052
doi: 10.1097/SLA.0000000000003974
doi:
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e453-e462Subventions
Organisme : Medical Research Council
ID : MR/P008887/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 103258/Z/13/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 103258/Z/13/A
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
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