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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Objective: We sought to identify potential drivers behind resuscitative endovascular balloon occlusion of the aorta (REBOA) induced reperfusion coagulopathy using novel proteomic methods. Background: Coagulopathy associated with REBOA is poorly defined. The REBOA Zone 1 provokes hepatic and intestinal ischemia that may alter coagulation factor production and lead to molecular pathway alterations that compromises hemostasis. ⋯ Zone 3 2.4%, P < 0.05). In the proteomics and ELISA results, REBOA Zone 1 was associated with significant decreases in coagulation factor XI and coagulation factor II, and significant elevations of active tissue plasminogen activator, plasmin-antiplasmin complex complexes, and syndecan-1 (P < 0.05). Conclusion: REBOA Zone 1 alters circulating mediators of clot formation, clot lysis, and increases plasma levels of known markers of endotheliopathy, leading to a reperfusion-induced coagulopathy compared with REBOA Zone 3 and no REBOA.
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Randomized Controlled Trial
Prolonged mechanical ventilation in acute respiratory distress syndrome.
Purpose: Trajectory of acute respiratory distress syndrome (ARDS) spans from rapidly improving cases to cases receiving prolonged mechanical ventilation (PMV). We attempted to estimate temporal trends of prevalence and mortality of PMV and to identify risk factors associated with mortality of patients with ARDS receiving PMV. Methods: We performed a secondary analysis of individual patient data from six randomized controlled clinical trials conducted by the ARDS Network. ⋯ Ninety-day mortality of patients receiving PMV did not change over time ( R2 = 0.271, P = 0.290) and remained as high as 36.8%. Ιn the three most recent trials, risk factors associated with mortality among the 250 patients with ARDS receiving PMV included age, malignancy, pneumonia as the cause of ARDS, coagulation dysfunction, and hepatic dysfunction during the first 21 days after trial enrollment. Conclusion: Although prevalence of PMV among patients enrolled in ARDS Network trials gradually declined, mortality did not change. Risk factors associated with mortality were mostly nonmodifiable.
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Background: Resuscitative balloon occlusion of the aorta (REBOA) is an endovascular hemostasis method used for the management of traumatic abdominal and pelvic hemorrhages. However, REBOA-associated ischemia-reperfusion injury complication limits its blocking time. We hypothesized that mild therapeutic hypothermia would relieve ischemia-reperfusion injury caused by prolonged zone 1 REBOA. ⋯ In the hypothermia group, prothrombin time at 120 and 180 min was significantly longer than that at baseline (all P < 0.05). Compared with the control, animals in the hypothermia group showed slighter pathological injury of the distal organs and significantly lower overall injury score (all P < 0.05). Conclusions: Mild therapeutic hypothermia during prolonged zone 1 REBOA offered extraordinary distal organ preservation and decreased metabolic acidosis.
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Randomized Controlled Trial
Chronic ethanol use worsens gut permeability and alters tight junction expression in a murine sepsis model.
Alcohol use disorder is associated with increased mortality in septic patients. Murine studies demonstrate that ethanol/sepsis is associated with changes in gut integrity. This study examined intestinal permeability after ethanol/sepsis and investigated mechanisms responsible for alterations in barrier function. ⋯ The frequency of CD4 + cells expressing TNF and IL-17A and the frequency of CD8 + cells expressing IFN-γ in Peyer's Patches were also increased in ethanol/CLP. Thus, there is an ethanol-specific worsening of gut barrier function after CLP that impacts all pathways of intestinal permeability, mediated, in part, via changes to the tight junction. Differences in the host response in the setting of chronic alcohol use may play a role in future precision medicine approaches toward the treatment of sepsis.
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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.