CytoSorb在烧伤合并脓毒性休克及急性肾损伤患者接受连续性肾脏替代治疗时,可有效降低与乳酸升高相关的革兰阴性菌来源群体感应分子水平
CytoSorb in burn patients with septic shock and acute kidney injury on continuous kidney replacement therapy efficiently reduces the levels of Gram-negative-derived quorum-sensing molecules associated with lactate increases.
Filippo Mariano, Marta Leporati, Nicolo' Carpenito, Alberto Mella, Maria Cristina Di Vico, Phumzile Skosana, Anna Pensa, Nadia Depetris, Daniela Risso, Roberto Gambino, Domenico Cosseddu, Massimo Navissano, Luigi Biancone
摘要(中文译文)
革兰阴性菌产生的群体感应(QS)分子调控毒力及宿主-病原体相互作用,但其在人类感染性休克中的全身性作用在很大程度上仍未被探索。我们假设QS分子可在伴有感染性休克相关急性肾损伤(SA-AKI)的烧伤患者循环中检测到,与疾病严重程度相关,并可通过体外治疗清除。在这项观察性初步研究中,采用HPLC-MS/MS对12例接受连续性肾脏替代治疗(CKRT)和CytoSorb血液吸附的难治性感染性休克合并SA-AKI烧伤患者血浆中八种革兰阴性菌来源的QS分子浓度进行了定量检测。在23个研究滤器的24小时治疗过程中,连续采集血样(0、0.5、6、12和24小时)。评估了吸附柱和血液滤器对QS分子的清除情况,并探讨了基线QS分子水平与全身乳酸浓度之间的关联。在检测的8种QS分子中,C6-高丝氨酸内酯、3-羟基-C12-HSL、C7-PQS、HQNO、HHQ和C9-PQS在全身血浆中可检测到,而3-氧代-酰基-高丝氨酸内酯(3-氧代-C10/3-氧代-C12)低于定量下限。CytoSorb诱导C6-HSH、3-OH-C12-HSL和C7-PQS血浆QS分子浓度出现显著的早期降低,而血液滤器对QS分子的清除率可忽略不计(< 4 ml/min)。吸附后在后来的时间点出现部分反弹,与12小时后吸附剂饱和及解吸一致。基线乳酸水平与QS分子3-OH-C12-HSL(r = 0.76818,p < 0.002)和C7-PQS(r = 0.64961,p < 0.03)的相对血浆浓度呈显著正相关,在选定的铜绿假单胞菌血流感染患者中,这两种QS分子的关联仍然显著稳健(分别为r = 0.87698,p < 0.02和r = 0.55547,p < 0.03)。革兰阴性菌QS分子可在伴有SA-AKI的烧伤患者全身循环中检测到,与全身乳酸浓度相关,并可通过血液吸附清除,但不能通过血液滤器清除。这些发现支持细菌通讯信号在危重症中潜在的病理生理作用,以及血液吸附作为危重症潜在治疗靶点的可能性。
Abstract
Quorum-sensing (QS) molecules produced by Gram-negative bacteria regulate virulence and host-pathogen interactions, but their systemic role in human septic shock remains largely unexplored. We hypothesized that QS molecules are detectable in the circulation of burn patients with septic-shock-associated acute kidney injury (SA-AKI), are associated with disease severity, and are amenable to removal by extracorporeal treatment. In this observational pilot study, plasma concentrations of eight Gram-negative-derived QS molecules were quantified by HPLC-MS/MS in 12 burn patients with refractory septic shock and SA-AKI on continuous kidney replacement therapy (CKRT) and CytoSorb hemoadsorption. Serial blood samples (0, 0.5, 6, 12, and 24 h) were collected during the 24-hour sessions of the 23 studied cartridges. QS molecule removal by the sorbent cartridge and hemofilter was assessed, and associations between baseline QS molecule levels and systemic lactate concentrations were explored. Out of 8 QS molecules tested, C6-homoserine lactone, 3-hydroxy-C12-HSL, C7-PQS, HQNO, HHQ, and C9-PQS were detectable in systemic plasma, whereas 3-oxo-acyl-homoserine lactones (3-oxo-C10/3-oxo-C12) were below the limit of quantification. Cytosorb induced a significant early reduction in plasma QS molecule concentrations of C6-HSH, 3-OH-C12-HSL, and C7-PQS, whereas hemofilter clearance of QS molecules was negligible (< 4 ml/min). Adsorption was followed by partial rebound at later time points, consistent with sorbent saturation and desorption after 12 h. Baseline lactate levels showed a significant positive correlation with the relative plasma concentrations of QS molecules 3-OH-C12-HSL (r = 0.76818, p < 0.002) and C7-PQS (r = 0.64961, p < 0.03), an association that remained significantly robust for both QS molecules in selected patients with Pseudomonas aeruginosa bloodstream infection (r = 0.87698, p < 0.02 and r = 0.55547, p < 0.03, respectively). Gram-negative QS molecules are detectable in the systemic circulation of burn patients with SA-AKI, are associated with systemic lactate concentrations, and can be removed by hemoadsorption but not by the hemofilter. These findings support a potential pathophysiological role of bacterial communication signals in critical illness, and a potential therapeutic target of hemoadsorption in critical illness.
如何引用
AMAFilippo Mariano, Marta Leporati, Nicolo' Carpenito, Alberto Mella, Maria Cristina Di Vico, Phumzile Skosana, et al. CytoSorb in burn patients with septic shock and acute kidney injury on continuous kidney replacement therapy efficiently reduces the levels of Gram-negative-derived quorum-sensing molecules associated with lactate increases.. Burns : journal of the International Society for Burn Injuries. 2026; doi:10.1016/j.burns.2026.108105.
APAFilippo Mariano, Marta Leporati, Nicolo' Carpenito, Alberto Mella, Maria Cristina Di Vico, Phumzile Skosana, et al (2026). CytoSorb in burn patients with septic shock and acute kidney injury on continuous kidney replacement therapy efficiently reduces the levels of Gram-negative-derived quorum-sensing molecules associated with lactate increases.. Burns : journal of the International Society for Burn Injuries. https://doi.org/10.1016/j.burns.2026.108105
GB/T 7714Filippo Mariano, Marta Leporati, Nicolo' Carpenito, Alberto Mella, Maria Cristina Di Vico, Phumzile Skosana, et al. CytoSorb in burn patients with septic shock and acute kidney injury on continuous kidney replacement therapy efficiently reduces the levels of Gram-negative-derived quorum-sensing molecules associated with lactate increases.[J]. Burns : journal of the International Society for Burn Injuries, 2026 doi:10.1016/j.burns.2026.108105.
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