Department of Medicine, Uniformed Services University, Bethesda, MD.
United States Army Institute of Surgical Research, JBSA Fort Sam Houston, TX.
Shock. 2023 Feb 1;59(2):294-299. doi: 10.1097/SHK.0000000000002025. Epub 2022 Nov 3.
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.
败血症是烧伤患者急性复苏后死亡的主要原因。临床标准对烧伤诱导的败血症的诊断价值有限，因此难以诊断。已经检查了蛋白质生物标志物（例如降钙素原），但效果有限。我们旨在探索与线粒体（线粒体 DNA [mtDNA]）和外周血单核细胞（PBMC）线粒体功能相关的其他生物标志物，以用于烧伤患者败血症的诊断。
我们对一项单中心前瞻性观察性研究的受试者（n = 10 名健康志愿者，n = 24 名烧伤患者）进行了随访分析，以检查 mtDNA 和 PBMC 呼吸测定的诊断价值。患者无论是否存在败血症均被纳入研究，并进行纵向随访。根据经验性临床标准将患者样本分类为败血症或非败血症。将分离的 PBMC 加载到高分辨率呼吸计中，并使用基于 PCR 的测定法测量循环 mtDNA。还比较了序贯器官衰竭评估（SOFA）标准。
SOFA 标准比较败血症与之前/非败血症患者，烧伤败血症患者的心率显著升高（P = 0.012），平均动脉压显著降低（P = 0.039）。与健康志愿者（P < 0.0001）和非败血症患者（P < 0.0001）相比，败血症烧伤患者的 mtDNA 显着升高，而健康志愿者和非败血症烧伤患者之间没有显着差异（P = 0.187）。mtDNA 的 ROC 曲线下面积（AUC）为 0.685（95%置信区间为 0.50-0.86）。对于 PBMC 呼吸测定，与健康志愿者相比，烧伤患者表现出常规呼吸和最大呼吸潜能增加。然而，非败血症和败血症患者样本之间没有差异。亚分析显示，在败血症诊断后，PBMC 呼吸测定的死亡率存在显着差异，其中幸存者的常规呼吸（P = 0.003）和最大呼吸（P = 0.011）均高于非幸存者。
我们的研究结果表明，mtDNA 可能对烧伤败血症具有诊断价值，而 PBMC 呼吸测定在烧伤中特异性升高，但在预测死亡率方面可能具有价值。需要更大的、多中心的研究来进一步验证 mtDNA 和 PBMC 呼吸测定作为烧伤患者败血症预后和结局的生物标志物的诊断价值。
