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Web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries

A recent randomised controlled trial failed to demonstrate a beneficial effect of recombinant human thrombomodulin (rhTM) on sepsis. However, there is still controversy in the effects of rhTM for sepsis due to the heterogeneity of the study population. We previously identified patients with a distin...

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Autores principales: Goto, Tadahiro, Kudo, Daisuke, Uchimido, Ryo, Hayakawa, Mineji, Yamakawa, Kazuma, Abe, Toshikazu, Shiraishi, Atsushi, Kushimoto, Shigeki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121613/
https://www.ncbi.nlm.nih.gov/pubmed/35590381
http://dx.doi.org/10.1186/s13054-022-04020-1
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author Goto, Tadahiro
Kudo, Daisuke
Uchimido, Ryo
Hayakawa, Mineji
Yamakawa, Kazuma
Abe, Toshikazu
Shiraishi, Atsushi
Kushimoto, Shigeki
author_facet Goto, Tadahiro
Kudo, Daisuke
Uchimido, Ryo
Hayakawa, Mineji
Yamakawa, Kazuma
Abe, Toshikazu
Shiraishi, Atsushi
Kushimoto, Shigeki
author_sort Goto, Tadahiro
collection PubMed
description A recent randomised controlled trial failed to demonstrate a beneficial effect of recombinant human thrombomodulin (rhTM) on sepsis. However, there is still controversy in the effects of rhTM for sepsis due to the heterogeneity of the study population. We previously identified patients with a distinct phenotype that could be a potential target of rhTM therapy (rhTM target phenotype). However, for application in the clinical setting, a simple tool for determining this target is necessary. Thus, using three multicentre sepsis registries, we aimed to develop and validate a machine learning model for predicting presence of the target phenotype that we previously identified for targeted rhTM therapy. The predictors were platelet count, PT-INR, fibrinogen, fibrinogen/fibrin degradation products, and D-dimer. We also implemented the model as a web-based application. Two of the three registries were used for model development (n = 3694), and the remaining registry was used for validation (n = 1184). Approximately 8–9% of patients had the rhTM target phenotype in each cohort. In the validation, the C statistic of the developed model for predicting the rhTM target phenotype was 0.996 (95% CI 0.993–0.998), with a sensitivity of 0.991 and a specificity of 0.967. Among patients who were predicted to have the potential target phenotype (predicted target patients) in the validation cohort (n = 142), rhTM use was associated with a lower in-hospital mortality (adjusted risk difference, − 31.3% [− 53.5 to − 9.1%]). The developed model was able to accurately predict the rhTM target phenotype. The model, which is available as a web-based application, could profoundly benefit clinicians and researchers investigating the heterogeneity in the treatment effects of rhTM and its mechanisms. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-022-04020-1.
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spelling pubmed-91216132022-05-21 Web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries Goto, Tadahiro Kudo, Daisuke Uchimido, Ryo Hayakawa, Mineji Yamakawa, Kazuma Abe, Toshikazu Shiraishi, Atsushi Kushimoto, Shigeki Crit Care Brief Report A recent randomised controlled trial failed to demonstrate a beneficial effect of recombinant human thrombomodulin (rhTM) on sepsis. However, there is still controversy in the effects of rhTM for sepsis due to the heterogeneity of the study population. We previously identified patients with a distinct phenotype that could be a potential target of rhTM therapy (rhTM target phenotype). However, for application in the clinical setting, a simple tool for determining this target is necessary. Thus, using three multicentre sepsis registries, we aimed to develop and validate a machine learning model for predicting presence of the target phenotype that we previously identified for targeted rhTM therapy. The predictors were platelet count, PT-INR, fibrinogen, fibrinogen/fibrin degradation products, and D-dimer. We also implemented the model as a web-based application. Two of the three registries were used for model development (n = 3694), and the remaining registry was used for validation (n = 1184). Approximately 8–9% of patients had the rhTM target phenotype in each cohort. In the validation, the C statistic of the developed model for predicting the rhTM target phenotype was 0.996 (95% CI 0.993–0.998), with a sensitivity of 0.991 and a specificity of 0.967. Among patients who were predicted to have the potential target phenotype (predicted target patients) in the validation cohort (n = 142), rhTM use was associated with a lower in-hospital mortality (adjusted risk difference, − 31.3% [− 53.5 to − 9.1%]). The developed model was able to accurately predict the rhTM target phenotype. The model, which is available as a web-based application, could profoundly benefit clinicians and researchers investigating the heterogeneity in the treatment effects of rhTM and its mechanisms. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-022-04020-1. BioMed Central 2022-05-19 /pmc/articles/PMC9121613/ /pubmed/35590381 http://dx.doi.org/10.1186/s13054-022-04020-1 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 Brief Report
Goto, Tadahiro
Kudo, Daisuke
Uchimido, Ryo
Hayakawa, Mineji
Yamakawa, Kazuma
Abe, Toshikazu
Shiraishi, Atsushi
Kushimoto, Shigeki
Web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries
title Web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries
title_full Web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries
title_fullStr Web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries
title_full_unstemmed Web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries
title_short Web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries
title_sort web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121613/
https://www.ncbi.nlm.nih.gov/pubmed/35590381
http://dx.doi.org/10.1186/s13054-022-04020-1
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