Prospective Testing and Redesign of a Temporal Biomarker Based Risk Model for Patients With Septic Shock: Implications for Septic Shock Biology

被引：10

作者：

Wong, Hector R. ^{[1
,2
,3
]}

Cvijanovich, Natalie Z. ^{[4
]}

Anas, Nick ^{[5
]}

Allen, Geoffrey L. ^{[6
]}

Thomas, Neal J. ^{[7
]}

Bigham, Michael T. ^{[8
]}

Weiss, Scott L. ^{[9
]}

Fitzgerald, Julie ^{[9
]}

Checchia, Paul A. ^{[10
,11
]}

Meyer, Keith ^{[12
]}

Quasney, Michael ^{[13
]}

Hall, Mark ^{[14
]}

Gedeit, Rainer ^{[15
]}

Freishtat, Robert J. ^{[16
]}

Nowak, Jeffrey ^{[17
]}

Raj, Shekhar S. ^{[18
]}

Gertz, Shira ^{[19
]}

Howard, Kelli ^{[1
,2
]}

Harmon, Kelli ^{[1
,2
]}

Lahni, Patrick ^{[1
,2
]}

Frank, Erin ^{[1
,2
]}

Hart, Kimberly W. ^{[20
]}

Lindsell, Christopher J. ^{[20
]}

机构：

[1] Cincinnati Childrens Hosp Med Ctr, Div Crit Care Med, Cincinnati, OH 45229 USA

[2] Cincinnati Childrens Res Fdn, Cincinnati, OH USA

[3] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA

[4] UCSF Benioff Childrens Hosp Oakland, Oakland, CA USA

[5] Childrens Hosp Orange Cty, Orange, CA 92668 USA

[6] Childrens Mercy Hosp, Kansas City, MO 64108 USA

[7] Penn State Hershey Childrens Hosp, Hershey, PA USA

[8] Akron Childrens Hosp, Akron, OH USA

[9] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[10] Texas Childrens Hosp, Houston, TX 77030 USA

[11] Baylor Coll Med, Houston, TX 77030 USA

[12] Miami Childrens Hosp, Miami, FL USA

[13] Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA

[14] Nationwide Childrens Hosp, Columbus, OH USA

[15] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA

[16] Childrens Natl Med Ctr, Washington, DC 20010 USA

[17] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA

[18] Riley Hosp Children, Indianapolis, IN USA

[19] Hackensack Univ, Med Ctr, Joseph M Sanzari Childrens Hosp, Hackensack, NJ USA

[20] Univ Cincinnati, Coll Med, Dept Emergency Med, Cincinnati, OH USA

来源：

EBIOMEDICINE | 2015年 / 2卷 / 12期

基金：

美国国家卫生研究院;

关键词：

Sepsis; Biomarkers; Outcome; Prediction; Modeling; Inflammation; Immune Suppression; Endotype; SEPSIS THERAPY;

D O I：

10.1016/j.ebiom.2015.11.035

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The temporal version of the pediatric sepsis biomarker risk model (tPERSEVERE) estimates the risk of a complicated course in children with septic shock based on biomarker changes from days 1 to 3 of septic shock. We validated tPERSEVERE performance in a prospective cohort, with an a priori plan to redesign tPERSEVERE if it did not perform well. Biomarkers were measured in the validation cohort (n = 168) and study subjects were classified according to tPERSEVERE. To redesign tPERSEVERE, the validation cohort and the original derivation cohort (n = 299) were combined and randomly allocated to training (n = 374) and test (n = 93) sets. tPERSEVERE was redesigned using the training set and CART methodology. tPERSEVERE performed poorly in the validation cohort, with an area under the curve (AUC) of 0.67 (95% CI: 0.58-0.75). Failure analysis revealed potential confounders related to clinical characteristics. The redesigned tPERSEVERE model had an AUC of 0.83 (0.79-0.87) and a sensitivity of 93% (68-97) for estimating the risk of a complicated course. Similar performance was seen in the test set. The classification tree segregated patients into two broad endotypes of septic shock characterized by either excessive inflammation or immune suppression. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：2087 / 2093

页数：7

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