Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study

Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify...
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Autor*in:	Brian J. Anderson [verfasserIn] Carolyn S. Calfee [verfasserIn] Kathleen D. Liu [verfasserIn] John P. Reilly [verfasserIn] Kirsten N. Kangelaris [verfasserIn] Michael G. S. Shashaty [verfasserIn] Aili L. Lazaar [verfasserIn] Andrew I. Bayliffe [verfasserIn] Robert J. Gallop [verfasserIn] Todd A. Miano [verfasserIn] Thomas G. Dunn [verfasserIn] Erik Johansson [verfasserIn] Jason Abbott [verfasserIn] Alejandra Jauregui [verfasserIn] Thomas Deiss [verfasserIn] Kathryn Vessel [verfasserIn] Annika Belzer [verfasserIn] Hanjing Zhuo [verfasserIn] Michael A. Matthay [verfasserIn] Nuala J. Meyer [verfasserIn] Jason D. Christie [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Sepsis Tumor necrosis factor receptors Interleukin-8 Angiopoietin-2 Biomarkers Prognostic enrichment

Übergeordnetes Werk:	In: Critical Care - BMC, 2015, 23(2019), 1, Seite 9
Übergeordnetes Werk:	volume:23 ; year:2019 ; number:1 ; pages:9

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13054-019-2684-2

Katalog-ID:	DOAJ058712135

Internformat


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520			\|a Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration < 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration < 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level < 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.
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653		0	\|a Medical emergencies. Critical care. Intensive care. First aid
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700	0		\|a Kathleen D. Liu \|e verfasserin \|4 aut
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700	0		\|a Michael G. S. Shashaty \|e verfasserin \|4 aut
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allfields	10.1186/s13054-019-2684-2 doi (DE-627)DOAJ058712135 (DE-599)DOAJ96e48863d23e4cd690b1a7438e01c591 DE-627 ger DE-627 rakwb eng RC86-88.9 Brian J. Anderson verfasserin aut Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration < 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration < 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level < 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials. Sepsis Tumor necrosis factor receptors Interleukin-8 Angiopoietin-2 Biomarkers Prognostic enrichment Medical emergencies. Critical care. Intensive care. First aid Carolyn S. Calfee verfasserin aut Kathleen D. Liu verfasserin aut John P. Reilly verfasserin aut Kirsten N. Kangelaris verfasserin aut Michael G. S. Shashaty verfasserin aut Aili L. Lazaar verfasserin aut Andrew I. Bayliffe verfasserin aut Robert J. Gallop verfasserin aut Todd A. Miano verfasserin aut Thomas G. Dunn verfasserin aut Erik Johansson verfasserin aut Jason Abbott verfasserin aut Alejandra Jauregui verfasserin aut Thomas Deiss verfasserin aut Kathryn Vessel verfasserin aut Annika Belzer verfasserin aut Hanjing Zhuo verfasserin aut Michael A. Matthay verfasserin aut Nuala J. Meyer verfasserin aut Jason D. Christie verfasserin aut In Critical Care BMC, 2015 23(2019), 1, Seite 9 (DE-627)331258269 (DE-600)2051256-9 1466609X nnns volume:23 year:2019 number:1 pages:9 https://doi.org/10.1186/s13054-019-2684-2 kostenfrei https://doaj.org/article/96e48863d23e4cd690b1a7438e01c591 kostenfrei https://doi.org/10.1186/s13054-019-2684-2 kostenfrei https://doaj.org/toc/1364-8535 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2019 1 9
spelling	10.1186/s13054-019-2684-2 doi (DE-627)DOAJ058712135 (DE-599)DOAJ96e48863d23e4cd690b1a7438e01c591 DE-627 ger DE-627 rakwb eng RC86-88.9 Brian J. Anderson verfasserin aut Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration < 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration < 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level < 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials. Sepsis Tumor necrosis factor receptors Interleukin-8 Angiopoietin-2 Biomarkers Prognostic enrichment Medical emergencies. Critical care. Intensive care. First aid Carolyn S. Calfee verfasserin aut Kathleen D. Liu verfasserin aut John P. Reilly verfasserin aut Kirsten N. Kangelaris verfasserin aut Michael G. S. Shashaty verfasserin aut Aili L. Lazaar verfasserin aut Andrew I. Bayliffe verfasserin aut Robert J. Gallop verfasserin aut Todd A. Miano verfasserin aut Thomas G. Dunn verfasserin aut Erik Johansson verfasserin aut Jason Abbott verfasserin aut Alejandra Jauregui verfasserin aut Thomas Deiss verfasserin aut Kathryn Vessel verfasserin aut Annika Belzer verfasserin aut Hanjing Zhuo verfasserin aut Michael A. Matthay verfasserin aut Nuala J. Meyer verfasserin aut Jason D. Christie verfasserin aut In Critical Care BMC, 2015 23(2019), 1, Seite 9 (DE-627)331258269 (DE-600)2051256-9 1466609X nnns volume:23 year:2019 number:1 pages:9 https://doi.org/10.1186/s13054-019-2684-2 kostenfrei https://doaj.org/article/96e48863d23e4cd690b1a7438e01c591 kostenfrei https://doi.org/10.1186/s13054-019-2684-2 kostenfrei https://doaj.org/toc/1364-8535 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2019 1 9
allfields_unstemmed	10.1186/s13054-019-2684-2 doi (DE-627)DOAJ058712135 (DE-599)DOAJ96e48863d23e4cd690b1a7438e01c591 DE-627 ger DE-627 rakwb eng RC86-88.9 Brian J. Anderson verfasserin aut Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration < 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration < 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level < 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials. Sepsis Tumor necrosis factor receptors Interleukin-8 Angiopoietin-2 Biomarkers Prognostic enrichment Medical emergencies. Critical care. Intensive care. First aid Carolyn S. Calfee verfasserin aut Kathleen D. Liu verfasserin aut John P. Reilly verfasserin aut Kirsten N. Kangelaris verfasserin aut Michael G. S. Shashaty verfasserin aut Aili L. Lazaar verfasserin aut Andrew I. Bayliffe verfasserin aut Robert J. Gallop verfasserin aut Todd A. Miano verfasserin aut Thomas G. Dunn verfasserin aut Erik Johansson verfasserin aut Jason Abbott verfasserin aut Alejandra Jauregui verfasserin aut Thomas Deiss verfasserin aut Kathryn Vessel verfasserin aut Annika Belzer verfasserin aut Hanjing Zhuo verfasserin aut Michael A. Matthay verfasserin aut Nuala J. Meyer verfasserin aut Jason D. Christie verfasserin aut In Critical Care BMC, 2015 23(2019), 1, Seite 9 (DE-627)331258269 (DE-600)2051256-9 1466609X nnns volume:23 year:2019 number:1 pages:9 https://doi.org/10.1186/s13054-019-2684-2 kostenfrei https://doaj.org/article/96e48863d23e4cd690b1a7438e01c591 kostenfrei https://doi.org/10.1186/s13054-019-2684-2 kostenfrei https://doaj.org/toc/1364-8535 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2019 1 9
allfieldsGer	10.1186/s13054-019-2684-2 doi (DE-627)DOAJ058712135 (DE-599)DOAJ96e48863d23e4cd690b1a7438e01c591 DE-627 ger DE-627 rakwb eng RC86-88.9 Brian J. Anderson verfasserin aut Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration < 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration < 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level < 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials. Sepsis Tumor necrosis factor receptors Interleukin-8 Angiopoietin-2 Biomarkers Prognostic enrichment Medical emergencies. Critical care. Intensive care. First aid Carolyn S. Calfee verfasserin aut Kathleen D. Liu verfasserin aut John P. Reilly verfasserin aut Kirsten N. Kangelaris verfasserin aut Michael G. S. Shashaty verfasserin aut Aili L. Lazaar verfasserin aut Andrew I. Bayliffe verfasserin aut Robert J. Gallop verfasserin aut Todd A. Miano verfasserin aut Thomas G. Dunn verfasserin aut Erik Johansson verfasserin aut Jason Abbott verfasserin aut Alejandra Jauregui verfasserin aut Thomas Deiss verfasserin aut Kathryn Vessel verfasserin aut Annika Belzer verfasserin aut Hanjing Zhuo verfasserin aut Michael A. Matthay verfasserin aut Nuala J. Meyer verfasserin aut Jason D. Christie verfasserin aut In Critical Care BMC, 2015 23(2019), 1, Seite 9 (DE-627)331258269 (DE-600)2051256-9 1466609X nnns volume:23 year:2019 number:1 pages:9 https://doi.org/10.1186/s13054-019-2684-2 kostenfrei https://doaj.org/article/96e48863d23e4cd690b1a7438e01c591 kostenfrei https://doi.org/10.1186/s13054-019-2684-2 kostenfrei https://doaj.org/toc/1364-8535 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2019 1 9
allfieldsSound	10.1186/s13054-019-2684-2 doi (DE-627)DOAJ058712135 (DE-599)DOAJ96e48863d23e4cd690b1a7438e01c591 DE-627 ger DE-627 rakwb eng RC86-88.9 Brian J. Anderson verfasserin aut Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration < 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration < 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level < 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials. Sepsis Tumor necrosis factor receptors Interleukin-8 Angiopoietin-2 Biomarkers Prognostic enrichment Medical emergencies. Critical care. Intensive care. First aid Carolyn S. Calfee verfasserin aut Kathleen D. Liu verfasserin aut John P. Reilly verfasserin aut Kirsten N. Kangelaris verfasserin aut Michael G. S. Shashaty verfasserin aut Aili L. Lazaar verfasserin aut Andrew I. Bayliffe verfasserin aut Robert J. Gallop verfasserin aut Todd A. Miano verfasserin aut Thomas G. Dunn verfasserin aut Erik Johansson verfasserin aut Jason Abbott verfasserin aut Alejandra Jauregui verfasserin aut Thomas Deiss verfasserin aut Kathryn Vessel verfasserin aut Annika Belzer verfasserin aut Hanjing Zhuo verfasserin aut Michael A. Matthay verfasserin aut Nuala J. Meyer verfasserin aut Jason D. Christie verfasserin aut In Critical Care BMC, 2015 23(2019), 1, Seite 9 (DE-627)331258269 (DE-600)2051256-9 1466609X nnns volume:23 year:2019 number:1 pages:9 https://doi.org/10.1186/s13054-019-2684-2 kostenfrei https://doaj.org/article/96e48863d23e4cd690b1a7438e01c591 kostenfrei https://doi.org/10.1186/s13054-019-2684-2 kostenfrei https://doaj.org/toc/1364-8535 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2019 1 9
language	English
source	In Critical Care 23(2019), 1, Seite 9 volume:23 year:2019 number:1 pages:9
sourceStr	In Critical Care 23(2019), 1, Seite 9 volume:23 year:2019 number:1 pages:9
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Sepsis Tumor necrosis factor receptors Interleukin-8 Angiopoietin-2 Biomarkers Prognostic enrichment Medical emergencies. Critical care. Intensive care. First aid
isfreeaccess_bool	true
container_title	Critical Care
authorswithroles_txt_mv	Brian J. Anderson @@aut@@ Carolyn S. Calfee @@aut@@ Kathleen D. Liu @@aut@@ John P. Reilly @@aut@@ Kirsten N. Kangelaris @@aut@@ Michael G. S. Shashaty @@aut@@ Aili L. Lazaar @@aut@@ Andrew I. Bayliffe @@aut@@ Robert J. Gallop @@aut@@ Todd A. Miano @@aut@@ Thomas G. Dunn @@aut@@ Erik Johansson @@aut@@ Jason Abbott @@aut@@ Alejandra Jauregui @@aut@@ Thomas Deiss @@aut@@ Kathryn Vessel @@aut@@ Annika Belzer @@aut@@ Hanjing Zhuo @@aut@@ Michael A. Matthay @@aut@@ Nuala J. Meyer @@aut@@ Jason D. Christie @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	331258269
id	DOAJ058712135
language_de	englisch
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Anderson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration < 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration < 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level < 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. 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callnumber-first	R - Medicine
author	Brian J. Anderson
spellingShingle	Brian J. Anderson misc RC86-88.9 misc Sepsis misc Tumor necrosis factor receptors misc Interleukin-8 misc Angiopoietin-2 misc Biomarkers misc Prognostic enrichment misc Medical emergencies. Critical care. Intensive care. First aid Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study
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topic_title	RC86-88.9 Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study Sepsis Tumor necrosis factor receptors Interleukin-8 Angiopoietin-2 Biomarkers Prognostic enrichment
topic	misc RC86-88.9 misc Sepsis misc Tumor necrosis factor receptors misc Interleukin-8 misc Angiopoietin-2 misc Biomarkers misc Prognostic enrichment misc Medical emergencies. Critical care. Intensive care. First aid
topic_unstemmed	misc RC86-88.9 misc Sepsis misc Tumor necrosis factor receptors misc Interleukin-8 misc Angiopoietin-2 misc Biomarkers misc Prognostic enrichment misc Medical emergencies. Critical care. Intensive care. First aid
topic_browse	misc RC86-88.9 misc Sepsis misc Tumor necrosis factor receptors misc Interleukin-8 misc Angiopoietin-2 misc Biomarkers misc Prognostic enrichment misc Medical emergencies. Critical care. Intensive care. First aid
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title	Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study
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title_full	Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study
author_sort	Brian J. Anderson
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author_browse	Brian J. Anderson Carolyn S. Calfee Kathleen D. Liu John P. Reilly Kirsten N. Kangelaris Michael G. S. Shashaty Aili L. Lazaar Andrew I. Bayliffe Robert J. Gallop Todd A. Miano Thomas G. Dunn Erik Johansson Jason Abbott Alejandra Jauregui Thomas Deiss Kathryn Vessel Annika Belzer Hanjing Zhuo Michael A. Matthay Nuala J. Meyer Jason D. Christie
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author-letter	Brian J. Anderson
doi_str_mv	10.1186/s13054-019-2684-2
author2-role	verfasserin
title_sort	plasma stnfr1 and il8 for prognostic enrichment in sepsis trials: a prospective cohort study
callnumber	RC86-88.9
title_auth	Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study
abstract	Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration < 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration < 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level < 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.
abstractGer	Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration < 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration < 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level < 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.
abstract_unstemmed	Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration < 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration < 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level < 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.
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container_issue	1
title_short	Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study
url	https://doi.org/10.1186/s13054-019-2684-2 https://doaj.org/article/96e48863d23e4cd690b1a7438e01c591 https://doaj.org/toc/1364-8535
remote_bool	true
author2	Carolyn S. Calfee Kathleen D. Liu John P. Reilly Kirsten N. Kangelaris Michael G. S. Shashaty Aili L. Lazaar Andrew I. Bayliffe Robert J. Gallop Todd A. Miano Thomas G. Dunn Erik Johansson Jason Abbott Alejandra Jauregui Thomas Deiss Kathryn Vessel Annika Belzer Hanjing Zhuo Michael A. Matthay Nuala J. Meyer Jason D. Christie
author2Str	Carolyn S. Calfee Kathleen D. Liu John P. Reilly Kirsten N. Kangelaris Michael G. S. Shashaty Aili L. Lazaar Andrew I. Bayliffe Robert J. Gallop Todd A. Miano Thomas G. Dunn Erik Johansson Jason Abbott Alejandra Jauregui Thomas Deiss Kathryn Vessel Annika Belzer Hanjing Zhuo Michael A. Matthay Nuala J. Meyer Jason D. Christie
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up_date	2024-07-03T19:39:08.157Z
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