Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Randomized Controlled Trial Multicenter Study
Hemoperfusion using the LPS-selective mesoporous polymeric adsorbent in septic shock: a multicenter randomized clinical trial.
Extracorporeal hemoperfusion (EHP) may improve the course and outcomes of patients with septic shock by targeting cytokines or bacterial endotoxins (lipopolysaccharide [LPS]). Here, we present the results of a multicenter randomized controlled trial ( clinicaltrials.gov/ct2/show/NCT04827407 ) to assess the efficiency and safety of Efferon LPS hemoperfusion cartridges engineered for multimodal targeting LPS, host-derived cytokine, and damage-associated molecule pattern molecules. Patients with intra-abdominal sepsis (IAS) and septic shock (Sepsis-3) were subjected to EHP procedures (n = 38). ⋯ Early 3-day mortality was significantly reduced in the Efferon LPS versus control group; however, no significant improvements in survival in 14 and 28 days were revealed. Laboratory tests showed rapidly decreased levels of LPS, procalcitonin, C-reactive protein, IL-6, creatinine, leukocytes, and neutrophils only in the Efferon LPS group. Results demonstrate that EHP with Efferon LPS is a safe procedure to abrogate septic shock and normalize clinical and pathogenically relevant biomarkers in patients with IAS.
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Background: The Society for Cardiovascular Angiography and Intervention (SCAI) Shock Classification can define shock severity. We evaluated the vasoactive-inotropic score (VIS) combined with the SCAI Shock Classification for mortality risk stratification. Methods: This was a single-center retrospective cohort analysis including Mayo Clinic cardiac intensive care unit patients from 2007 to 2015. ⋯ A gradient of in-hospital mortality was observed according to the VIS at 1 h and the increase in VIS from 1 to 24 h. Conclusions: Higher vasoactive drug requirements portend a higher risk of mortality, particularly a high VIS early after admission. The VIS provides incremental prognostic information beyond the SCAI Shock Classification, emphasizing the continuum of risk that exists across the spectrum of shock severity.
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Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled inflammation, which manifests as leukocyte infiltration and lung injury. However, the molecules that initiate this infiltration remain incompletely understood. We evaluated the effect of the nuclear alarmin IL-33 on lung damage and the immune response in LPS-induced lung injury. ⋯ We found that IL-33 promoted inflammation through NKT cells in ARDS. In summary, our results demonstrated that the IL-33/ST2 axis promotes the early uncontrolled inflammatory response in ARDS by activating and recruiting iNKT cells. Therefore, IL-33 and NKT cells may be therapeutic target molecules and immune cells, respectively, in early ARDS cytokine storms.
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Sepsis is one of the leading causes of morbidity and mortality worldwide. Monocytes seem to undergo functional reprogramming during sepsis, resulting in dysregulated host immune response. To clarify this dysregulation mechanism, we investigated three histone modifications found in promoters of genes involved in innate immune response, and associated these findings with gene transcription in septic patients. ⋯ In addition, we found moderate to strong correlation between gene transcription and the enzymes that modulate these histone modifications in the transcriptome data sets. Our study, one of the pioneering by evaluating septic patients' samples, suggests that epigenetic enzymes modulate the prevalent histone marks in promoters of genes involved in the immune-inflammatory response, altering the transcription of these specific genes during sepsis. Furthermore, nonsurviving sepsis patients have a more pronounced epigenetic dysregulation compared with survivors, suggesting a more dysfunctional response.
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Objective: The aim of the study is to explore the impact of early serum phosphate levels on the prognosis of critically ill patients with sepsis. Methods: In this retrospective large cohort study, data of patients with sepsis were obtained from the Medical Information Mart for Intensive Care IV database. Patients were retrospectively divided into a control group and three study groups according to their daily serum phosphate levels within 2 days of intensive care unit (ICU) admission. ⋯ After stratification in the hypophosphatemia group, subgroup analysis showed that only the association between the mild hypophosphatemia group and 28-day mortality reached statistical significance (hazard ratio = 0.76, 95% CI = 0.65-0.89, P = 0.001). Conclusions: Mild hypophosphatemia might improve the short-term prognosis of patients with sepsis, and hyperphosphatemia is an independent risk factor for the outcomes of septic patients. After ICU admission, the serum phosphate levels on the second day had a better independent correlation with 28-day mortality, which prompted us to reconsider the optimal timing of phosphate evaluation.