DIAGNOSTIC VALUE OF MITOCHONDRIAL DNA AND PERIPHERAL BLOOD MONONUCLEAR CELL RESPIROMETRY FOR BURN-RELATED SEPSIS.

Autor:	Robles MC; Department of Medicine, Uniformed Services University, Bethesda, MD., Heard TC; United States Army Institute of Surgical Research, JBSA Fort Sam Houston, TX., Chao T; United States Army Institute of Surgical Research, JBSA Fort Sam Houston, TX., Alcover K, Wagner A; United States Army Institute of Surgical Research, JBSA Fort Sam Houston, TX., Akers KS; United States Army Institute of Surgical Research, JBSA Fort Sam Houston, TX., Burmeister DM
Jazyk:	angličtina
Zdroj:	Shock (Augusta, Ga.) [Shock] 2023 Feb 01; Vol. 59 (2), pp. 294-299. Date of Electronic Publication: 2022 Nov 03.
DOI:	10.1097/SHK.0000000000002025
Abstrakt:	Abstract: Background: Sepsis is the leading cause of mortality among burn patients that survive acute resuscitation. Clinical criteria have poor diagnostic value for burn-induced sepsis, making it difficult to diagnose. Protein biomarkers (e.g., procalcitonin) have been examined with limited success. We aimed to explore other biomarkers related to mitochondria (mitochondrial DNA [mtDNA]) and mitochondrial function of peripheral blood mononuclear cells (PBMCs) for sepsis diagnosis in burn patients. Methods: We conducted a follow-up analysis of a single center, prospective observational study of subjects (n = 10 healthy volunteers, n = 24 burn patients) to examine the diagnostic value of mtDNA and PBMC respirometry. Patients were enrolled regardless of sepsis status and followed longitudinally. Patient samples were classified as septic or not based on empiric clinical criteria. Isolated PBMCs were loaded into a high-resolution respirometer, and circulating mtDNA was measured with a PCR-based assay. Sequential Organ Failure Assessment (SOFA) criteria were also compared. Results: The SOFA criteria comparing septic versus before/nonseptic patients revealed significantly higher heart rate ( P = 0.012) and lower mean arterial pressure ( P = 0.039) in burn sepsis. MtDNA was significantly elevated in septic burn patients compared with healthy volunteers ( P < 0.0001) and nonseptic patients ( P < 0.0001), with no significant difference between healthy volunteers and nonseptic burn patients ( P = 0.187). The area under the ROC curve (AUC) for mtDNA was 0.685 (95% confidence interval = 0.50-0.86). For PBMC respirometry, burn patients exhibited increased routine and maximal respiration potential compared with healthy volunteers. However, no difference was found between nonseptic and septic patient samples. A subanalysis revealed a significant mortality difference in PBMC respirometry after sepsis diagnosis, wherein survivors had higher routine respiration ( P = 0.003) and maximal respiration ( P = 0.011) compared with nonsurvivors. Conclusion: Our findings reveal that mtDNA may have diagnostic value for burn sepsis, whereas PBMC respirometry is nonspecifically elevated in burns, but may have value in mortality prognosis. A larger, multisite study is warranted for further validity of the diagnostic value of mtDNA and PBMC respirometry as biomarkers for prognosis of sepsis and outcomes in burn patients. Competing Interests: The authors report no conflicts of interest. (Copyright © 2022 by the Shock Society.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu