Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU.
| Title: | Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU. |
|---|---|
| Authors: | Miller RR 3rd; 1 Intermountain Medical Center, Murray, Utah.; 2 University of Utah School of Medicine, Salt Lake City, Utah.; Lopansri BK; 1 Intermountain Medical Center, Murray, Utah.; 2 University of Utah School of Medicine, Salt Lake City, Utah.; Burke JP; 1 Intermountain Medical Center, Murray, Utah.; 2 University of Utah School of Medicine, Salt Lake City, Utah.; Levy M; 3 Brown University, Providence, Rhode Island.; Opal S; 3 Brown University, Providence, Rhode Island.; Rothman RE; 4 Johns Hopkins University School of Medicine, Baltimore, Maryland.; D'Alessio FR; 4 Johns Hopkins University School of Medicine, Baltimore, Maryland.; Sidhaye VK; 4 Johns Hopkins University School of Medicine, Baltimore, Maryland.; Aggarwal NR; 4 Johns Hopkins University School of Medicine, Baltimore, Maryland.; Balk R; 5 Rush Medical College and Rush University Medical Center, Chicago, Illinois.; Greenberg JA; 5 Rush Medical College and Rush University Medical Center, Chicago, Illinois.; Yoder M; 5 Rush Medical College and Rush University Medical Center, Chicago, Illinois.; Patel G; 5 Rush Medical College and Rush University Medical Center, Chicago, Illinois.; Gilbert E; 6 Loyola University Medical Center, Maywood, Illinois.; Afshar M; 6 Loyola University Medical Center, Maywood, Illinois.; Parada JP; 6 Loyola University Medical Center, Maywood, Illinois.; Martin GS; 7 Grady Memorial Hospital and Emory University School of Medicine, Atlanta, Georgia.; Esper AM; 7 Grady Memorial Hospital and Emory University School of Medicine, Atlanta, Georgia.; Kempker JA; 7 Grady Memorial Hospital and Emory University School of Medicine, Atlanta, Georgia.; Narasimhan M; 8 Northwell Healthcare, New Hyde Park, New York.; Tsegaye A; 8 Northwell Healthcare, New Hyde Park, New York.; Hahn S; 8 Northwell Healthcare, New Hyde Park, New York.; Mayo P; 8 Northwell Healthcare, New Hyde Park, New York.; van der Poll T; 9 Academic Medical Center, Amsterdam-Zuidoost, the Netherlands.; Schultz MJ; 9 Academic Medical Center, Amsterdam-Zuidoost, the Netherlands.; Scicluna BP; 9 Academic Medical Center, Amsterdam-Zuidoost, the Netherlands.; Klein Klouwenberg P; 10 Department of Intensive Care, University Medical Center Utrecht, Utrecht, the Netherlands; and.; Rapisarda A; 11 Immunexpress Inc., Seattle, Washington.; Seldon TA; 11 Immunexpress Inc., Seattle, Washington.; McHugh LC; 11 Immunexpress Inc., Seattle, Washington.; Yager TD; 11 Immunexpress Inc., Seattle, Washington.; Cermelli S; 11 Immunexpress Inc., Seattle, Washington.; Sampson D; 11 Immunexpress Inc., Seattle, Washington.; Rothwell V; 11 Immunexpress Inc., Seattle, Washington.; Newman R; 11 Immunexpress Inc., Seattle, Washington.; Bhide S; 11 Immunexpress Inc., Seattle, Washington.; Fox BA; 11 Immunexpress Inc., Seattle, Washington.; Kirk JT; 11 Immunexpress Inc., Seattle, Washington.; Navalkar K; 11 Immunexpress Inc., Seattle, Washington.; Davis RF; 11 Immunexpress Inc., Seattle, Washington.; Brandon RA; 11 Immunexpress Inc., Seattle, Washington.; Brandon RB; 11 Immunexpress Inc., Seattle, Washington. |
| Source: | American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2018 Oct 01; Vol. 198 (7), pp. 903-913. |
| Publication Type: | Journal Article; Multicenter Study; Observational Study; Research Support, Non-U.S. Gov't; Validation Study |
| Language: | English |
| Journal Info: | Publisher: American Thoracic Society Country of Publication: England NLM ID: 9421642 Publication Model: Print Cited Medium: Internet ISSN: 1535-4970 (Electronic) Linking ISSN: 1073449X NLM ISO Abbreviation: Am J Respir Crit Care Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2000- : New York, NY : American Thoracic Society; Original Publication: New York, NY : American Lung Association, c1994- |
| MeSH Terms: | Intensive Care Units*; Critical Care/*methods ; Sepsis/*diagnosis ; Serum Bactericidal Test/*methods ; Systemic Inflammatory Response Syndrome/*diagnosis; Sepsis/blood ; Systemic Inflammatory Response Syndrome/blood ; Adult ; Aged ; Cohort Studies ; Critical Illness ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Netherlands ; Prospective Studies ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; United States |
| Abstract: | Rationale: A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility.; Objectives: This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults.; Methods: The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts.; Measurements and Main Results: In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity.; Conclusions: SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502). |
| Comments: | Comment in: Am J Respir Crit Care Med. 2018 Oct 1;198(7):832-833. doi: 10.1164/rccm.201804-0684ED.. (PMID: 29676931); Erratum in: Am J Respir Crit Care Med. 2020 Jul 1;202(1):155. doi: 10.1164/rccm.v202erratum2.. (PMID: 32609017) |
| References: | Crit Care. 2010;14(4):R159. (PMID: 20731880); J Crit Care. 2015 Feb;30(1):218.e7-12. (PMID: 25263339); Eur J Clin Invest. 2015 Aug;45(8):815-23. (PMID: 26046926); PLoS One. 2013 Dec 11;8(12):e82946. (PMID: 24349403); BMC Med Inform Decis Mak. 2011 Jun 22;11:45. (PMID: 21696604); EBioMedicine. 2016 Apr;6:114-125. (PMID: 27211554); JAMA. 2016 Aug 23-30;316(8):846-57. (PMID: 27552618); JAMA. 2016 Aug 23-30;316(8):835-45. (PMID: 27552617); PLoS Med. 2016 May 17;13(5):e1002022. (PMID: 27187803); PLoS Med. 2015 Dec 08;12(12):e1001916. (PMID: 26645559); PLoS One. 2015 Mar 18;10(3):e0120012. (PMID: 25785720); Crit Care Med. 2015 Nov;43(11):2283-91. (PMID: 26327198); PLoS One. 2013 May 29;8(5):e62323. (PMID: 23734173); Chest. 2010 Jul;138(1):121-9. (PMID: 20299634); Curr Opin Infect Dis. 2013 Apr;26(2):140-50. (PMID: 23411419); BMC Bioinformatics. 2011 Mar 17;12:77. (PMID: 21414208); Antimicrob Agents Chemother. 2015 Oct;59(10):6494-500. (PMID: 26239984); J Crit Care. 2013 Dec;28(6):970-4. (PMID: 24216331); Crit Care Med. 2013 Oct;41(10):2373-8. (PMID: 23921277); N Engl J Med. 2015 Apr 23;372(17):1629-38. (PMID: 25776936); Trends Mol Med. 2014 Apr;20(4):204-13. (PMID: 24548661); Caspian J Intern Med. 2013 Spring;4(2):627-35. (PMID: 24009950); Am J Respir Crit Care Med. 2017 Aug 1;196(3):328-339. (PMID: 28036233); Clin Infect Dis. 2010 Aug 1;51 Suppl 1:S59-66. (PMID: 20597674); Lancet. 2010 Jan 16;375(9710):224-30. (PMID: 20004964); Crit Care Med. 2017 Apr;45(4):e418-e425. (PMID: 27655322); Biometrics. 1988 Sep;44(3):837-45. (PMID: 3203132); BMJ. 2016 Jan 25;352:i6. (PMID: 26810254); Sci Transl Med. 2015 May 13;7(287):287ra71. (PMID: 25972003); Genome Med. 2014 Nov 26;6(11):111. (PMID: 25538794); BMJ. 2015 Oct 28;351:h5527. (PMID: 26511519) |
| Grant Information: | K08 HS025240 United States HS AHRQ HHS; KL2 TR002381 United States TR NCATS NIH HHS; R01 HL124099 United States HL NHLBI NIH HHS; UL1 TR002378 United States TR NCATS NIH HHS |
| Contributed Indexing: | Keywords: RT-qPCR; classifier; infection; inflammation; sepsis |
| Molecular Sequence: | ClinicalTrials.gov NCT01905033; NCT02127502 |
| Entry Date(s): | Date Created: 20180407 Date Completed: 20190911 Latest Revision: 20260505 |
| Update Code: | 20260505 |
| PubMed Central ID: | PMC6835074 |
| DOI: | 10.1164/rccm.201712-2472OC |
| PMID: | 29624409 |
| Database: | MEDLINE |
Journal Article; Multicenter Study; Observational Study; Research Support, Non-U.S. Gov't; Validation Study