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A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis

BACKGROUND: Sepsis is a life-threatening organ dysfunction. A fast diagnosis is crucial for patient management. Proteins that are synthesized during the inflammatory response can be used as biomarkers, helping in a rapid clinical assessment or an early diagnosis of infection. The aim of this study w...

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Autores principales: D’Onofrio, Valentino, Heylen, Dries, Pusparum, Murih, Grondman, Inge, Vanwalleghem, Johan, Meersman, Agnes, Cartuyvels, Reinoud, Messiaen, Peter, Joosten, Leo A. B., Netea, Mihai G., Valkenborg, Dirk, Ertaylan, Gökhan, Gyssens, Inge C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905560/
https://www.ncbi.nlm.nih.gov/pubmed/35264246
http://dx.doi.org/10.1186/s40560-022-00602-x
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author D’Onofrio, Valentino
Heylen, Dries
Pusparum, Murih
Grondman, Inge
Vanwalleghem, Johan
Meersman, Agnes
Cartuyvels, Reinoud
Messiaen, Peter
Joosten, Leo A. B.
Netea, Mihai G.
Valkenborg, Dirk
Ertaylan, Gökhan
Gyssens, Inge C.
author_facet D’Onofrio, Valentino
Heylen, Dries
Pusparum, Murih
Grondman, Inge
Vanwalleghem, Johan
Meersman, Agnes
Cartuyvels, Reinoud
Messiaen, Peter
Joosten, Leo A. B.
Netea, Mihai G.
Valkenborg, Dirk
Ertaylan, Gökhan
Gyssens, Inge C.
author_sort D’Onofrio, Valentino
collection PubMed
description BACKGROUND: Sepsis is a life-threatening organ dysfunction. A fast diagnosis is crucial for patient management. Proteins that are synthesized during the inflammatory response can be used as biomarkers, helping in a rapid clinical assessment or an early diagnosis of infection. The aim of this study was to identify biomarkers of inflammation for the diagnosis and prognosis of infection in patients with suspected sepsis. METHODS: In total 406 episodes were included in a prospective cohort study. Plasma was collected from all patients with suspected sepsis, for whom blood cultures were drawn, in the emergency department (ED), the department of infectious diseases, or the haemodialysis unit on the first day of a new episode. Samples were analysed using a 92-plex proteomic panel based on a proximity extension assay with oligonucleotide-labelled antibody probe pairs (OLink, Uppsala, Sweden). Supervised and unsupervised differential expression analyses and pathway enrichment analyses were performed to search for inflammatory proteins that were different between patients with viral or bacterial sepsis and between patients with worse or less severe outcome. RESULTS: Supervised differential expression analysis revealed 21 proteins that were significantly lower in circulation of patients with viral infections compared to patients with bacterial infections. More strongly, higher expression levels were observed for 38 proteins in patients with high SOFA scores (> 4), and for 21 proteins in patients with worse outcome. These proteins are mostly involved in pathways known to be activated early in the inflammatory response. Unsupervised, hierarchical clustering confirmed that inflammatory response was more strongly related to disease severity than to aetiology. CONCLUSION: Several differentially expressed inflammatory proteins were identified that could be used as biomarkers for sepsis. These proteins are mostly related to disease severity. Within the setting of an emergency department, they could be used for outcome prediction, patient monitoring, and directing diagnostics. Trail registration number: clinicaltrial.gov identifier NCT03841162. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40560-022-00602-x.
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spelling pubmed-89055602022-03-09 A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis D’Onofrio, Valentino Heylen, Dries Pusparum, Murih Grondman, Inge Vanwalleghem, Johan Meersman, Agnes Cartuyvels, Reinoud Messiaen, Peter Joosten, Leo A. B. Netea, Mihai G. Valkenborg, Dirk Ertaylan, Gökhan Gyssens, Inge C. J Intensive Care Research BACKGROUND: Sepsis is a life-threatening organ dysfunction. A fast diagnosis is crucial for patient management. Proteins that are synthesized during the inflammatory response can be used as biomarkers, helping in a rapid clinical assessment or an early diagnosis of infection. The aim of this study was to identify biomarkers of inflammation for the diagnosis and prognosis of infection in patients with suspected sepsis. METHODS: In total 406 episodes were included in a prospective cohort study. Plasma was collected from all patients with suspected sepsis, for whom blood cultures were drawn, in the emergency department (ED), the department of infectious diseases, or the haemodialysis unit on the first day of a new episode. Samples were analysed using a 92-plex proteomic panel based on a proximity extension assay with oligonucleotide-labelled antibody probe pairs (OLink, Uppsala, Sweden). Supervised and unsupervised differential expression analyses and pathway enrichment analyses were performed to search for inflammatory proteins that were different between patients with viral or bacterial sepsis and between patients with worse or less severe outcome. RESULTS: Supervised differential expression analysis revealed 21 proteins that were significantly lower in circulation of patients with viral infections compared to patients with bacterial infections. More strongly, higher expression levels were observed for 38 proteins in patients with high SOFA scores (> 4), and for 21 proteins in patients with worse outcome. These proteins are mostly involved in pathways known to be activated early in the inflammatory response. Unsupervised, hierarchical clustering confirmed that inflammatory response was more strongly related to disease severity than to aetiology. CONCLUSION: Several differentially expressed inflammatory proteins were identified that could be used as biomarkers for sepsis. These proteins are mostly related to disease severity. Within the setting of an emergency department, they could be used for outcome prediction, patient monitoring, and directing diagnostics. Trail registration number: clinicaltrial.gov identifier NCT03841162. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40560-022-00602-x. BioMed Central 2022-03-09 /pmc/articles/PMC8905560/ /pubmed/35264246 http://dx.doi.org/10.1186/s40560-022-00602-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
D’Onofrio, Valentino
Heylen, Dries
Pusparum, Murih
Grondman, Inge
Vanwalleghem, Johan
Meersman, Agnes
Cartuyvels, Reinoud
Messiaen, Peter
Joosten, Leo A. B.
Netea, Mihai G.
Valkenborg, Dirk
Ertaylan, Gökhan
Gyssens, Inge C.
A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis
title A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis
title_full A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis
title_fullStr A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis
title_full_unstemmed A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis
title_short A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis
title_sort prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905560/
https://www.ncbi.nlm.nih.gov/pubmed/35264246
http://dx.doi.org/10.1186/s40560-022-00602-x
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