Next Article in Journal
Screening for Early Signs of Paternal Perinatal Affective Disorder in Expectant Fathers: A Cluster Analysis Approach
Next Article in Special Issue
Individualized Hemodynamic Management in Sepsis
Previous Article in Journal
Preoperative Predicting the WHO/ISUP Nuclear Grade of Clear Cell Renal Cell Carcinoma by Computed Tomography-Based Radiomics Features
Previous Article in Special Issue
Presepsin as a Potential Prognostic Marker for Sepsis According to Actual Practice Guidelines
Article

A 33-mRNA Classifier Is Able to Produce Inflammopathic, Adaptive, and Coagulopathic Endotypes with Prognostic Significance: The Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis (ORANGES) Trial

1
Department of Critical Care, Department of Nephrology, Community Medical Center, Toms River, NJ 08755, USA
2
Department of Nephrology, Jersey Shore University Medical Center, Hackensack Meridian School of Medicine at Seton Hall Neptune, Nutley, NJ 07110, USA
3
Department of Pharmacy, Community Medical Center, Toms River, NJ 08755, USA
4
Inflammatix, Inc., Burlingame, CA 94010, USA
5
Department of Medicine Section of Nephrology, University of Illinois at Chicago, Chicago, IL 60612, USA
6
Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA
7
School of Pharmacy & Health Sciences, Fairleigh Dickinson University, Florham Park, NJ 07932, USA
8
Department of Pharmacy, Monmouth Medical Center Southern Campus, Lakewood, NJ 08701, USA
*
Authors to whom correspondence should be addressed.
J. Pers. Med. 2021, 11(1), 9; https://doi.org/10.3390/jpm11010009
Received: 10 November 2020 / Revised: 3 December 2020 / Accepted: 20 December 2020 / Published: 23 December 2020
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Patients with Sepsis)
Background: Retrospective analysis of the transcriptomic host response in sepsis has demonstrated that sepsis can be separated into three endotypes—inflammatory (IE), adaptive (AE), and coagulopathic (CE), which have demonstrated prognostic significance. We undertook a prospective transcriptomic host response analysis in a subgroup of patients enrolled in the Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis (ORANGES) trial. Methods: Blood was obtained from 51 patients and profiled using a pre-established 33-mRNA classifier to determine sepsis endotypes. Endotypes were compared to therapy subgroups and clinical outcomes. Results: We redemonstrated a statistically significant difference in mortality between IE, AE, and CE patients, with CE patients demonstrating the highest mortality (40%), and AE patients the lowest mortality (5%, p = 0.032). A higher CE score was a predictor of mortality; coronary artery disease (CAD) and elevated CE scores were associated with an increase in mortality (CAD: HR = 12.3, 95% CI 1.5–101; CE score: HR = 15.5 95% CI 1.15–211). Kaplan–Meier (KM) analysis of the entire cohort (n = 51) demonstrated a decrease survival in the CE group, p = 0.026. KM survival analysis of hydrocortisone, ascorbic acid, and thiamine (HAT) therapy and control patients not receiving steroids (n = 45) showed CE and IE was associated with a decrease in survival (p = 0.003); of interest, there was no difference in survival in CE patients after stratifying by HAT therapy (p = 0.18). These findings suggest a possible treatment effect of corticosteroids, HAT therapy, endotype, and outcome. Conclusion: This subset of patients from the ORANGES trial confirmed previous retrospective findings that a 33-mRNA classifier can group patients into IE, AE, and CE endotypes having prognostic significance. A novel finding of this study identifying an association between endotype and corticosteroid therapy warrants further study in support of future diagnostic use of the endotyping classifier. View Full-Text
Keywords: sepsis; septic shock; HAT therapy; vitamin c; endotyping; coagulopathic; hydrocortisone; thiamine; ascorbic acid sepsis; septic shock; HAT therapy; vitamin c; endotyping; coagulopathic; hydrocortisone; thiamine; ascorbic acid
Show Figures

Figure 1

MDPI and ACS Style

Iglesias, J.; Vassallo, A.V.; Liesenfeld, O.; Levine, J.S.; Patel, V.V.; Sullivan, J.B.; Cavanaugh, J.B.; Elbaga, Y.; Sweeney, T.E. A 33-mRNA Classifier Is Able to Produce Inflammopathic, Adaptive, and Coagulopathic Endotypes with Prognostic Significance: The Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis (ORANGES) Trial. J. Pers. Med. 2021, 11, 9. https://doi.org/10.3390/jpm11010009

AMA Style

Iglesias J, Vassallo AV, Liesenfeld O, Levine JS, Patel VV, Sullivan JB, Cavanaugh JB, Elbaga Y, Sweeney TE. A 33-mRNA Classifier Is Able to Produce Inflammopathic, Adaptive, and Coagulopathic Endotypes with Prognostic Significance: The Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis (ORANGES) Trial. Journal of Personalized Medicine. 2021; 11(1):9. https://doi.org/10.3390/jpm11010009

Chicago/Turabian Style

Iglesias, Jose, Andrew V. Vassallo, Oliver Liesenfeld, Jerrold S. Levine, Vishal V. Patel, Jesse B. Sullivan, Joseph B. Cavanaugh, Yasmine Elbaga, and Timothy E. Sweeney. 2021. "A 33-mRNA Classifier Is Able to Produce Inflammopathic, Adaptive, and Coagulopathic Endotypes with Prognostic Significance: The Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis (ORANGES) Trial" Journal of Personalized Medicine 11, no. 1: 9. https://doi.org/10.3390/jpm11010009

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop