Hector R Wong1,2, Timothy E Sweeney3,4, Kimberly W Hart5, Purvesh Khatri3,4, Christopher J Lindsell5. 1. Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Cincinnati, OH. 2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH. 3. Stanford Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Palo Alto, CA. 4. Division of Biomedical Informatics Research, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA. 5. Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH.
Abstract
OBJECTIVES: Recent transcriptomic studies describe two subgroups of adults with sepsis differentiated by a sepsis response signature. The implied biology and related clinical associations are comparable with recently reported pediatric sepsis endotypes, labeled "A" and "B." We classified adults with sepsis using the pediatric endotyping strategy and the sepsis response signature and determined how endotype assignment, sepsis response signature membership, and age interact with respect to mortality. DESIGN: Retrospective analysis of publically available transcriptomic data representing critically ill adults with sepsis from which the sepsis response signature groups were derived and validated. SETTING: Multiple ICUs. PATIENTS: Adults with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Transcriptomic data were conormalized into a single dataset yielding 549 unique cases with sepsis response signature assignments. Each subject was assigned to endotype A or B using the expression data for the 100 endotyping genes. There were 163 subjects (30%) assigned to endotype A and 386 to endotype B. There was a weak, positive correlation between endotype assignment and sepsis response signature membership. Mortality rates were similar between patients assigned endotype A and those assigned endotype B. A multivariable logistic regression model fit to endotype assignment, sepsis response signature membership, age, and the respective two-way interactions revealed that endotype A, sepsis response signature 1 membership, older age, and the interactions between them were associated with mortality. Subjects coassigned to endotype A, and sepsis response signature 1 had the highest mortality. CONCLUSIONS: Combining the pediatric endotyping strategy with sepsis response signature membership might provide complementary, age-dependent, biological, and prognostic information.
OBJECTIVES: Recent transcriptomic studies describe two subgroups of adults with sepsis differentiated by a sepsis response signature. The implied biology and related clinical associations are comparable with recently reported pediatricsepsis endotypes, labeled "A" and "B." We classified adults with sepsis using the pediatric endotyping strategy and the sepsis response signature and determined how endotype assignment, sepsis response signature membership, and age interact with respect to mortality. DESIGN: Retrospective analysis of publically available transcriptomic data representing critically ill adults with sepsis from which the sepsis response signature groups were derived and validated. SETTING: Multiple ICUs. PATIENTS: Adults with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Transcriptomic data were conormalized into a single dataset yielding 549 unique cases with sepsis response signature assignments. Each subject was assigned to endotype A or B using the expression data for the 100 endotyping genes. There were 163 subjects (30%) assigned to endotype A and 386 to endotype B. There was a weak, positive correlation between endotype assignment and sepsis response signature membership. Mortality rates were similar between patients assigned endotype A and those assigned endotype B. A multivariable logistic regression model fit to endotype assignment, sepsis response signature membership, age, and the respective two-way interactions revealed that endotype A, sepsis response signature 1 membership, older age, and the interactions between them were associated with mortality. Subjects coassigned to endotype A, and sepsis response signature 1 had the highest mortality. CONCLUSIONS: Combining the pediatric endotyping strategy with sepsis response signature membership might provide complementary, age-dependent, biological, and prognostic information.
Authors: Hector R Wong; Natalie Z Cvijanovich; Geoffrey L Allen; Neal J Thomas; Robert J Freishtat; Nick Anas; Keith Meyer; Paul A Checchia; Richard Lin; Thomas P Shanley; Michael T Bigham; Derek S Wheeler; Lesley A Doughty; Ken Tegtmeyer; Sue E Poynter; Jennifer M Kaplan; Ranjit S Chima; Erika Stalets; Rajit K Basu; Brian M Varisco; Frederick E Barr Journal: Crit Care Med Date: 2011-11 Impact factor: 7.598
Authors: Hector R Wong; Derek S Wheeler; Ken Tegtmeyer; Sue E Poynter; Jennifer M Kaplan; Ranjit S Chima; Erika Stalets; Rajit K Basu; Lesley A Doughty Journal: Crit Care Med Date: 2010-10 Impact factor: 7.598
Authors: Hector R Wong; Natalie Z Cvijanovich; Nick Anas; Geoffrey L Allen; Neal J Thomas; Michael T Bigham; Scott L Weiss; Julie Fitzgerald; Paul A Checchia; Keith Meyer; Thomas P Shanley; Michael Quasney; Mark Hall; Rainer Gedeit; Robert J Freishtat; Jeffrey Nowak; Raj S Shekhar; Shira Gertz; Emily Dawson; Kelli Howard; Kelli Harmon; Eileen Beckman; Erin Frank; Christopher J Lindsell Journal: Am J Respir Crit Care Med Date: 2015-02-01 Impact factor: 21.405
Authors: Katie L Burnham; Emma E Davenport; Jayachandran Radhakrishnan; Peter Humburg; Anthony C Gordon; Paula Hutton; Eduardo Svoren-Jabalera; Christopher Garrard; Adrian V S Hill; Charles J Hinds; Julian C Knight Journal: Am J Respir Crit Care Med Date: 2017-08-01 Impact factor: 21.405
Authors: Hector R Wong; Natalie Cvijanovich; Richard Lin; Geoffrey L Allen; Neal J Thomas; Douglas F Willson; Robert J Freishtat; Nick Anas; Keith Meyer; Paul A Checchia; Marie Monaco; Kelli Odom; Thomas P Shanley Journal: BMC Med Date: 2009-07-22 Impact factor: 8.775
Authors: Emma E Davenport; Katie L Burnham; Jayachandran Radhakrishnan; Peter Humburg; Paula Hutton; Tara C Mills; Anna Rautanen; Anthony C Gordon; Christopher Garrard; Adrian V S Hill; Charles J Hinds; Julian C Knight Journal: Lancet Respir Med Date: 2016-02-23 Impact factor: 102.642
Authors: Sivasubramanium V Bhavani; Kyle A Carey; Emily R Gilbert; Majid Afshar; Philip A Verhoef; Matthew M Churpek Journal: Am J Respir Crit Care Med Date: 2019-08-01 Impact factor: 21.405
Authors: Kimberley M DeMerle; Derek C Angus; J Kenneth Baillie; Emily Brant; Carolyn S Calfee; Joseph Carcillo; Chung-Chou H Chang; Robert Dickson; Idris Evans; Anthony C Gordon; Jason Kennedy; Julian C Knight; Christopher J Lindsell; Vincent Liu; John C Marshall; Adrienne G Randolph; Brendon P Scicluna; Manu Shankar-Hari; Nathan I Shapiro; Timothy E Sweeney; Victor B Talisa; Benjamin Tang; B Taylor Thompson; Ephraim L Tsalik; Tom van der Poll; Lonneke A van Vught; Hector R Wong; Sachin Yende; Huiying Zhao; Christopher W Seymour Journal: Crit Care Med Date: 2021-05-01 Impact factor: 7.598
Authors: Christopher W Seymour; Samantha J Kerti; Anthony J Lewis; Jason Kennedy; Emily Brant; John E Griepentrog; Xianghong Zhang; Derek C Angus; Chung-Chou H Chang; Matthew R Rosengart Journal: Crit Care Date: 2019-11-28 Impact factor: 9.097