Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma

Erika Gonzalez Rodriguez; Sisse R. Ostrowski; Jessica C. Cardenas; Lisa A. Baer; Jeffrey S. Tomasek; Hanne H. Henriksen; Jakob Stensballe; Bryan A. Cotton; John B. Holcomb; Pär I. Johansson; Charles E. Wade

doi:10.1016/j.jamcollsurg.2017.05.012

Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma

Erika Gonzalez Rodriguez^*, Sisse R. Ostrowski, Jessica C. Cardenas, Lisa A. Baer, Jeffrey S. Tomasek, Hanne H. Henriksen, Jakob Stensballe, Bryan A. Cotton, John B. Holcomb, Pär I. Johansson, Charles E. Wade

^*Corresponding author for this work

Department of Clinical Medicine

43 Citations (Scopus)

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Abstract

Background Endothelial glycocalyx breakdown elicits syndecan-1 shedding and endotheliopathy of trauma (EoT). We hypothesized that a cutoff syndecan-1 level can identify patients with endothelial dysfunction who would have poorer outcomes. Study Design We conducted a prospective observational study. Trauma patients with the highest level of activation admitted from July 2011 through September 2013 were eligible. We recorded demographics, injury type/severity (Injury Severity Score), physiology and outcomes data, and quantified syndecan-1 and soluble thrombomodulin from plasma with ELISAs. With receiver operating characteristic curve analysis, we defined EoT+ as the syndecan-1 cutoff level that maximized the sum of sensitivity and specificity (Youden index) in predicting 24-hour in-hospital mortality. We stratified by this cutoff and compared both groups. Factors associated with 30-day in-hospital mortality were assessed with multivariable logistic regression (adjusted odds ratios and 95% CIs reported). Results From receiver operating characteristic curve analysis (area under the curve = 0.71; 95% CI 0.58 to 0.84), we defined EoT+ as syndecan-1 level ≥40 ng/mL (sensitivity = 0.62, specificity = 0.73). Of the 410 patients evaluated, 34% (n = 138) were EoT+ patients, who presented with higher Injury Severity Scores (p < 0.001) and blunt trauma frequency (p = 0.016) than EoT− patients. Although EoT+ patients had lower systolic blood pressure (median 119 vs 128 mmHg; p < 0.001), base excess and hemoglobin were similar between groups. The proportion of transfused (EoT+ 71.7% vs EoT− 36.4%; p < 0.001) and deceased EoT+ patients (EoT+ 24.6% vs EoT− 12.1%; p < 0.001) was higher. EoT+ was significantly associated with 30-day in-hospital mortality (adjusted odds ratio = 2.23; 95% CI 1.22 to 4.04). Conclusions A syndecan-1 level ≥40 ng/mL identified patients with significantly worse outcomes, despite admission physiology similar to those without the condition.

Original language	English
Journal	Journal of the American College of Surgeons
Volume	225
Issue number	3
Pages (from-to)	419-427
Number of pages	9
ISSN	1072-7515
DOIs	https://doi.org/10.1016/j.jamcollsurg.2017.05.012
Publication status	Published - Sept 2017

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Gonzalez Rodriguez, E., Ostrowski, S. R., Cardenas, J. C., Baer, L. A., Tomasek, J. S., Henriksen, H. H., Stensballe, J., Cotton, B. A., Holcomb, J. B., Johansson, P. I., & Wade, C. E. (2017). Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma. Journal of the American College of Surgeons, 225(3), 419-427. https://doi.org/10.1016/j.jamcollsurg.2017.05.012

@article{9f55b908285f498d8a944c3f40c6f899,

title = "Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma",

abstract = "Background Endothelial glycocalyx breakdown elicits syndecan-1 shedding and endotheliopathy of trauma (EoT). We hypothesized that a cutoff syndecan-1 level can identify patients with endothelial dysfunction who would have poorer outcomes. Study Design We conducted a prospective observational study. Trauma patients with the highest level of activation admitted from July 2011 through September 2013 were eligible. We recorded demographics, injury type/severity (Injury Severity Score), physiology and outcomes data, and quantified syndecan-1 and soluble thrombomodulin from plasma with ELISAs. With receiver operating characteristic curve analysis, we defined EoT+ as the syndecan-1 cutoff level that maximized the sum of sensitivity and specificity (Youden index) in predicting 24-hour in-hospital mortality. We stratified by this cutoff and compared both groups. Factors associated with 30-day in-hospital mortality were assessed with multivariable logistic regression (adjusted odds ratios and 95% CIs reported). Results From receiver operating characteristic curve analysis (area under the curve = 0.71; 95% CI 0.58 to 0.84), we defined EoT+ as syndecan-1 level ≥40 ng/mL (sensitivity = 0.62, specificity = 0.73). Of the 410 patients evaluated, 34% (n = 138) were EoT+ patients, who presented with higher Injury Severity Scores (p < 0.001) and blunt trauma frequency (p = 0.016) than EoT− patients. Although EoT+ patients had lower systolic blood pressure (median 119 vs 128 mmHg; p < 0.001), base excess and hemoglobin were similar between groups. The proportion of transfused (EoT+ 71.7% vs EoT− 36.4%; p < 0.001) and deceased EoT+ patients (EoT+ 24.6% vs EoT− 12.1%; p < 0.001) was higher. EoT+ was significantly associated with 30-day in-hospital mortality (adjusted odds ratio = 2.23; 95% CI 1.22 to 4.04). Conclusions A syndecan-1 level ≥40 ng/mL identified patients with significantly worse outcomes, despite admission physiology similar to those without the condition.",

author = "{Gonzalez Rodriguez}, Erika and Ostrowski, {Sisse R.} and Cardenas, {Jessica C.} and Baer, {Lisa A.} and Tomasek, {Jeffrey S.} and Henriksen, {Hanne H.} and Jakob Stensballe and Cotton, {Bryan A.} and Holcomb, {John B.} and Johansson, {P{\"a}r I.} and Wade, {Charles E.}",

year = "2017",

month = sep,

doi = "10.1016/j.jamcollsurg.2017.05.012",

language = "English",

volume = "225",

pages = "419--427",

journal = "Journal of the American College of Surgeons",

issn = "1072-7515",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - Syndecan-1

T2 - A Quantitative Marker for the Endotheliopathy of Trauma

AU - Gonzalez Rodriguez, Erika

AU - Ostrowski, Sisse R.

AU - Cardenas, Jessica C.

AU - Baer, Lisa A.

AU - Tomasek, Jeffrey S.

AU - Henriksen, Hanne H.

AU - Stensballe, Jakob

AU - Cotton, Bryan A.

AU - Holcomb, John B.

AU - Johansson, Pär I.

AU - Wade, Charles E.

PY - 2017/9

Y1 - 2017/9

N2 - Background Endothelial glycocalyx breakdown elicits syndecan-1 shedding and endotheliopathy of trauma (EoT). We hypothesized that a cutoff syndecan-1 level can identify patients with endothelial dysfunction who would have poorer outcomes. Study Design We conducted a prospective observational study. Trauma patients with the highest level of activation admitted from July 2011 through September 2013 were eligible. We recorded demographics, injury type/severity (Injury Severity Score), physiology and outcomes data, and quantified syndecan-1 and soluble thrombomodulin from plasma with ELISAs. With receiver operating characteristic curve analysis, we defined EoT+ as the syndecan-1 cutoff level that maximized the sum of sensitivity and specificity (Youden index) in predicting 24-hour in-hospital mortality. We stratified by this cutoff and compared both groups. Factors associated with 30-day in-hospital mortality were assessed with multivariable logistic regression (adjusted odds ratios and 95% CIs reported). Results From receiver operating characteristic curve analysis (area under the curve = 0.71; 95% CI 0.58 to 0.84), we defined EoT+ as syndecan-1 level ≥40 ng/mL (sensitivity = 0.62, specificity = 0.73). Of the 410 patients evaluated, 34% (n = 138) were EoT+ patients, who presented with higher Injury Severity Scores (p < 0.001) and blunt trauma frequency (p = 0.016) than EoT− patients. Although EoT+ patients had lower systolic blood pressure (median 119 vs 128 mmHg; p < 0.001), base excess and hemoglobin were similar between groups. The proportion of transfused (EoT+ 71.7% vs EoT− 36.4%; p < 0.001) and deceased EoT+ patients (EoT+ 24.6% vs EoT− 12.1%; p < 0.001) was higher. EoT+ was significantly associated with 30-day in-hospital mortality (adjusted odds ratio = 2.23; 95% CI 1.22 to 4.04). Conclusions A syndecan-1 level ≥40 ng/mL identified patients with significantly worse outcomes, despite admission physiology similar to those without the condition.

AB - Background Endothelial glycocalyx breakdown elicits syndecan-1 shedding and endotheliopathy of trauma (EoT). We hypothesized that a cutoff syndecan-1 level can identify patients with endothelial dysfunction who would have poorer outcomes. Study Design We conducted a prospective observational study. Trauma patients with the highest level of activation admitted from July 2011 through September 2013 were eligible. We recorded demographics, injury type/severity (Injury Severity Score), physiology and outcomes data, and quantified syndecan-1 and soluble thrombomodulin from plasma with ELISAs. With receiver operating characteristic curve analysis, we defined EoT+ as the syndecan-1 cutoff level that maximized the sum of sensitivity and specificity (Youden index) in predicting 24-hour in-hospital mortality. We stratified by this cutoff and compared both groups. Factors associated with 30-day in-hospital mortality were assessed with multivariable logistic regression (adjusted odds ratios and 95% CIs reported). Results From receiver operating characteristic curve analysis (area under the curve = 0.71; 95% CI 0.58 to 0.84), we defined EoT+ as syndecan-1 level ≥40 ng/mL (sensitivity = 0.62, specificity = 0.73). Of the 410 patients evaluated, 34% (n = 138) were EoT+ patients, who presented with higher Injury Severity Scores (p < 0.001) and blunt trauma frequency (p = 0.016) than EoT− patients. Although EoT+ patients had lower systolic blood pressure (median 119 vs 128 mmHg; p < 0.001), base excess and hemoglobin were similar between groups. The proportion of transfused (EoT+ 71.7% vs EoT− 36.4%; p < 0.001) and deceased EoT+ patients (EoT+ 24.6% vs EoT− 12.1%; p < 0.001) was higher. EoT+ was significantly associated with 30-day in-hospital mortality (adjusted odds ratio = 2.23; 95% CI 1.22 to 4.04). Conclusions A syndecan-1 level ≥40 ng/mL identified patients with significantly worse outcomes, despite admission physiology similar to those without the condition.

U2 - 10.1016/j.jamcollsurg.2017.05.012

DO - 10.1016/j.jamcollsurg.2017.05.012

M3 - Journal article

C2 - 28579548

AN - SCOPUS:85020758602

SN - 1072-7515

VL - 225

SP - 419

EP - 427

JO - Journal of the American College of Surgeons

JF - Journal of the American College of Surgeons

IS - 3

ER -

Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma

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