do Carmo De Stefani Fernanda, de Miranda Ana Carolina, Vesco Bruna Cassia Dal, Zanette Dalila Luciola, Marin Anelis Maria, Morello Luis Gustavo, de Menezes Igor Alexandre Côrtes
Post-graduation program, Federal University of Parana, Parana, Brazil.
Clinical Hospital, Federal University of Parana, Parana, Brazil.
Shock. 2025 Jun 30. doi: 10.1097/SHK.0000000000002661.
Sepsis heterogeneity affects the identification of high-risk patients. Outcomes in low- and middle-income countries are worse than those in developed nations. This study aimed to assess the prognostic potential of the previously described molecular endotypes, Mars1, Mars2, Mars3, and Mars4, in a Brazilian cohort with sepsis.
This prospective, multicenter, observational study identified molecular expression-based endotypes in adults from four intensive care units in Brazil. Patients on their first 24-hour diagnosis of sepsis based on the Sepsis 3 criteria were included. Health care workers were included in the control group. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify the transcripted levels of eight genes and determine the four endotypes. The primary endpoint was 28-day mortality with a secondary analysis of diagnostic accuracy. Statistical significance was set at P < 0.05.
One-hundred-sixty-eight participants and twenty-five controls were enrolled in this study. The overall mortality rate was 44%. The Mars1 group showed a higher 28-day mortality than the non-Mars1group. The log-rank test showed a worst survival probability in Mars1 subgroup (P = 0.013), and the hazard ratio was 1.78 (P = 0.017). Compared to control, area-under-the-curve (AUC) of ROC curves for diagnosing sepsis were: 0.69 for Mars1 (SD 0.62-0.77 / P = 0.0016), 0.89 for Mars2 (SD 0.85-0.94 / P < 0.0001), 0.82 for Mars3 (SD 0.75-0.88 / P < 0.0001) and 0.71 for Mars4 (SD 0.64-0.79 / P < 0.0006).
The Mars1 endotype detected by qRT-PCR was associated with worse sepsis survival in low-to middle-income countries. We also identified the Mars 2 endotype as a potential diagnostic marker for sepsis.
脓毒症异质性影响高危患者的识别。低收入和中等收入国家的脓毒症患者预后比发达国家的患者更差。本研究旨在评估先前描述的分子内型Mars1、Mars2、Mars3和Mars4在巴西脓毒症队列中的预后潜力。
这项前瞻性、多中心观察性研究在巴西四个重症监护病房的成人患者中识别基于分子表达的内型。纳入依据脓毒症3标准在诊断脓毒症的首个24小时内的患者。对照组纳入医护人员。采用定量实时聚合酶链反应（qRT-PCR）定量八个基因的转录水平并确定四种内型。主要终点为28天死亡率，并对诊断准确性进行二次分析。设定P < 0.05为具有统计学意义。
本研究纳入了168名参与者和25名对照。总体死亡率为44%。Mars1组的28天死亡率高于非Mars1组。对数秩检验显示Mars1亚组的生存概率更差（P = 0.013），风险比为1.78（P = 0.017）。与对照组相比，诊断脓毒症的ROC曲线下面积（AUC）分别为：Mars1为0.69（标准差0.62 - 0.77 / P = 0.0016），Mars2为0.89（标准差0.85 - 0.94 / P < 0.0001），Mars3为0.82（标准差0.75 - 0.88 / P < 0.0001），Mars4为0.71（标准差0.64 - 0.79 / P < 0.0006）。
通过qRT-PCR检测到的Mars1内型与低收入和中等收入国家脓毒症患者较差的生存率相关。我们还将Mars2内型鉴定为脓毒症的潜在诊断标志物。
