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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Association between thrombomodulin and high mobility group box 1 in sepsis patients
Adriana Teixeira Rodrigues, Julia Teixeira Rodrigues, Carolina Teixeira Rodrigues, Caroline Maria de Oliveira Volpe, Fabiana Rocha-Silva, Jose Augusto Nogueira-Machado, Luiz Ronaldo Alberti
Adriana Teixeira Rodrigues, Department of Pediatrics, School of Medicine, Federal University of Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
Adriana Teixeira Rodrigues, Luiz Ronaldo Alberti, Graduation Program in Medicine/Biomedicine - Santa Casa Hospital - Education and Research, Belo Horizonte 30150-240, Minas Gerais, Brazil
Julia Teixeira Rodrigues, Department of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil
Carolina Teixeira Rodrigues, Department of Internal Medicine, Unimed Hospital, Belo Horizonte 30150-340, Minas Gerais, Brazil
Caroline Maria de Oliveira Volpe, Jose Augusto Nogueira-Machado, Department of Immunology, Graduation Program in Medicine/Biomedicine - Santa Casa Hospital - Education and Research, Belo Horizonte 30150-240, Minas Gerais, Brazil
Fabiana Rocha-Silva, Clinical Laboratory, Graduation Program in Medicine/Biomedicine - Santa Casa Hospital - Education and Research, Belo Horizonte 30150-240, Minas Gerais, Brazil
Luiz Ronaldo Alberti, Department of Surgery, School of Medicine, Federal University of Minas Gerais, Belo Horizonte 30220-000, Minas Gerais, Brazil
Author contributions: Rodrigues AT analyzed the data and wrote the manuscript; Rodrigues AT, Volpe CMO, Rocha-Silva F, Nogueira-Machado JA and Alberti LR designed the research study and corrected the manuscript; Rodrigues JT and Rodrigues CT participated to the collection of the human material (blood sample), data and corrected the manuscript; all authors have read and approve the final manuscript.
Institutional review board statement: The study and the Free and Informed Consent (FIC) form, signed by the patients or their representatives, were approved by the Institutional Review Board (IRB) of the Santa Casa Hospital - Education and Research, Belo Horizonte, Brazil, under No. 2778641, on July 20, 2018.
Informed consent statement: Informed written consent was obtained from the patient for publication of this manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at adrianatr92@gmail.com. Participants gave informed consent for data sharing.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Adriana Teixeira Rodrigues, MD, PhD, Assistant Professor, Attending Doctor, Department of Pediatrics, School of Medicine, Federal University of Minas Gerais, 190 Alfredo Balena Avenue, Belo Horizonte 30130-100, Minas Gerais, Brazil. adrianatr92@gmail.com
Received: June 16, 2020
Peer-review started: June 16, 2020
First decision: July 21, 2020
Revised: July 31, 2020
Accepted: August 24, 2020
Article in press: August 24, 2020
Published online: October 18, 2020
BACKGROUND
High mobility group box 1 (HMGB1) has been studied as a molecule associated with severe outcomes in sepsis and thrombomodulin (TM) seems to decrease HMGB1 activity.
AIM
To investigate the role of the thrombomodulin/high mobility group box 1 (T/H) ratio in patients with sepsis and their association with their clinic, testing the hypothesis that higher ratios are associated with better outcomes.
METHODS
Twenty patients diagnosed with sepsis or septic shock, according to the 2016 criteria sepsis and septic shock (Sepsis-3), were studied. Patients were followed until they left the intensive care unit or until they achieved 28 d of hospitalization (D28). The following clinical outcomes were observed: Sequential Organ Failure Assessment (SOFA) score; Need for mechanical pulmonary ventilation; Presence of septic shock; Occurrence of sepsis-induced coagulopathy; Need for renal replacement therapy (RRT); and Death.
RESULTS
The results showed that patients with SOFA scores greater than or equal to 12 points had higher serum levels of TM: 76.41 ± 29.21 pg/mL vs 37.41 ± 22.55 pg/mL among those whose SOFA scores were less than 12 points, P = 0.003. The T/H ratio was also higher in patients whose SOFA scores were greater than or equal to 12 points, P = 0.001. The T/H ratio was, on average, three times higher in patients in need of RRT (0.38 ± 0.14 vs 0.11 ± 0.09), P < 0.001.
CONCLUSION
Higher serum levels of TM and, therefore, higher T/H ratio in the first 24 h after the diagnosis of sepsis were associated with more severe disease and the need for renal replacement therapy, while those with better clinical outcomes and those who were discharged before D28 showed a tendency for lower T/H ratio values.
Core Tip: The knowledge of physiological mechanisms that lead an organism to respond to an infectious agent with such intensity is of great importance. It has been described that during sepsis, an organism produces intense inflammatory activity, caused by the action of several inflammatory mediators. High mobility group box 1 (HMGB1) has been the target of recent studies for its proinflammatory actions as well as for the possibility of having its action reduced by thrombomodulin. For this reason, this study proposed to evaluate the relationship between thrombomodulin and HMGB1 in the initial phase of sepsis and its association with clinical outcomes in sepsis patients.
