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Development and validation of a cellular host response test as an early diagnostic for sepsis

Sepsis must be diagnosed quickly to avoid morbidity and mortality. However, the clinical manifestations of sepsis are highly variable and emergency department (ED) clinicians often must make rapid, impactful decisions before laboratory results are known. We previously developed a technique that allo...

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Autores principales: Guillou, Lionel, Sheybani, Roya, Jensen, Anne E., Di Carlo, Dino, Caffery, Terrell S., Thomas, Christopher B., Shah, Ajay M., Tse, Henry T. K., O’Neal, Hollis R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049231/
https://www.ncbi.nlm.nih.gov/pubmed/33857126
http://dx.doi.org/10.1371/journal.pone.0246980
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author Guillou, Lionel
Sheybani, Roya
Jensen, Anne E.
Di Carlo, Dino
Caffery, Terrell S.
Thomas, Christopher B.
Shah, Ajay M.
Tse, Henry T. K.
O’Neal, Hollis R.
author_facet Guillou, Lionel
Sheybani, Roya
Jensen, Anne E.
Di Carlo, Dino
Caffery, Terrell S.
Thomas, Christopher B.
Shah, Ajay M.
Tse, Henry T. K.
O’Neal, Hollis R.
author_sort Guillou, Lionel
collection PubMed
description Sepsis must be diagnosed quickly to avoid morbidity and mortality. However, the clinical manifestations of sepsis are highly variable and emergency department (ED) clinicians often must make rapid, impactful decisions before laboratory results are known. We previously developed a technique that allows the measurement of the biophysical properties of white blood cells as they are stretched through a microfluidic channel. In this study we describe and validate the resultant output as a model and score—the IntelliSep Index (ISI)—that aids in the diagnosis of sepsis in patients with suspected or confirmed infection from a single blood draw performed at the time of ED presentation. By applying this technique to a high acuity cohort with a 23.5% sepsis incidence (n = 307), we defined specific metrics—the aspect ratio and visco-elastic inertial response—that are more sensitive than cell size or cell count in predicting disease severity. The final model was trained and cross-validated on the high acuity cohort, and the performance and generalizability of the model was evaluated on a separate low acuity cohort with a 6.4% sepsis incidence (n = 94) and healthy donors (n = 72). For easier clinical interpretation, the ISI is divided into three interpretation bands of Green, Yellow, and Red that correspond to increasing disease severity. The ISI agreed with the diagnosis established by retrospective physician adjudication, and accurately identified subjects with severe illness as measured by SOFA, APACHE-II, hospital-free days, and intensive care unit admission. Measured using routinely collected blood samples, with a short run-time and no requirement for patient or laboratory information, the ISI is well suited to aid ED clinicians in rapidly diagnosing sepsis.
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spelling pubmed-80492312021-04-21 Development and validation of a cellular host response test as an early diagnostic for sepsis Guillou, Lionel Sheybani, Roya Jensen, Anne E. Di Carlo, Dino Caffery, Terrell S. Thomas, Christopher B. Shah, Ajay M. Tse, Henry T. K. O’Neal, Hollis R. PLoS One Research Article Sepsis must be diagnosed quickly to avoid morbidity and mortality. However, the clinical manifestations of sepsis are highly variable and emergency department (ED) clinicians often must make rapid, impactful decisions before laboratory results are known. We previously developed a technique that allows the measurement of the biophysical properties of white blood cells as they are stretched through a microfluidic channel. In this study we describe and validate the resultant output as a model and score—the IntelliSep Index (ISI)—that aids in the diagnosis of sepsis in patients with suspected or confirmed infection from a single blood draw performed at the time of ED presentation. By applying this technique to a high acuity cohort with a 23.5% sepsis incidence (n = 307), we defined specific metrics—the aspect ratio and visco-elastic inertial response—that are more sensitive than cell size or cell count in predicting disease severity. The final model was trained and cross-validated on the high acuity cohort, and the performance and generalizability of the model was evaluated on a separate low acuity cohort with a 6.4% sepsis incidence (n = 94) and healthy donors (n = 72). For easier clinical interpretation, the ISI is divided into three interpretation bands of Green, Yellow, and Red that correspond to increasing disease severity. The ISI agreed with the diagnosis established by retrospective physician adjudication, and accurately identified subjects with severe illness as measured by SOFA, APACHE-II, hospital-free days, and intensive care unit admission. Measured using routinely collected blood samples, with a short run-time and no requirement for patient or laboratory information, the ISI is well suited to aid ED clinicians in rapidly diagnosing sepsis. Public Library of Science 2021-04-15 /pmc/articles/PMC8049231/ /pubmed/33857126 http://dx.doi.org/10.1371/journal.pone.0246980 Text en © 2021 Guillou et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Guillou, Lionel
Sheybani, Roya
Jensen, Anne E.
Di Carlo, Dino
Caffery, Terrell S.
Thomas, Christopher B.
Shah, Ajay M.
Tse, Henry T. K.
O’Neal, Hollis R.
Development and validation of a cellular host response test as an early diagnostic for sepsis
title Development and validation of a cellular host response test as an early diagnostic for sepsis
title_full Development and validation of a cellular host response test as an early diagnostic for sepsis
title_fullStr Development and validation of a cellular host response test as an early diagnostic for sepsis
title_full_unstemmed Development and validation of a cellular host response test as an early diagnostic for sepsis
title_short Development and validation of a cellular host response test as an early diagnostic for sepsis
title_sort development and validation of a cellular host response test as an early diagnostic for sepsis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049231/
https://www.ncbi.nlm.nih.gov/pubmed/33857126
http://dx.doi.org/10.1371/journal.pone.0246980
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