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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Background: Previous trials evaluated the incidence of critical illness-related corticosteroid insufficiency (CIRCI) using 250 μg adrenocorticotropic hormone (ACTH). However, this supraphysiological dose could result in false-positive levels. We aimed to determine the incidence of CIRCI in septic patients using a 1 μg ACTH stress test. ⋯ In addition, the CIRCI group had a shorter time to develop AKI and a higher probability of developing AKI (4 days and 44.6%, respectively) in comparison with the non-CIRCI group (6 days and 45.57%, respectively). Conclusion: We concluded that the CIRCI group had a lower mean survival rate and a higher incidence of AKI. We recommend the use of 1 μg ACTH test in septic shock patients to identify this subgroup of patients.
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Contrast-induced acute kidney injury (CI-AKI) is a serious and common complication in patients receiving intravenous iodinated contrast medium (CM). Clinically, congestive heart failure is the most critical risk factor for CI-AKI and always leads to renal congestion for increased central venous pressure and fluid overload. Here, we aimed to investigate a novel CI-AKI rat model based on renal congestion. ⋯ Simultaneously, Mdivi-1 alleviated oxidative stress, apoptosis, and inflammatory responses induced by CM toxicity. We concluded that renal congestion exacerbated CM toxicity and presented a novel CI-AKI rat model. Excessive mitochondrial fission plays a crucial role in CM reno-toxicity and is a promising target for preventing and treating CI-AKI.
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Background: The kidney is the most common extrapulmonary organ injured in sepsis. The current study examines the ability of aerosolized nanochemically modified tetracycline 3 (nCMT-3), a pleiotropic anti-inflammatory agent, to attenuate acute kidney injury (AKI) caused by intratracheal LPS. Methods: C57BL/6 mice received aerosolized intratracheal nCMT-3 (1 mg/kg) or saline, followed by intratracheal LPS (2.5 mg/kg) to induce acute lung injury-induced AKI. ⋯ Lipopolysaccharide-treated mice demonstrated renal injury with increased levels of inflammatory cytokines (IL-1β, IL-6), active MMP-2 and MMP-9, proapoptotic proteins (cytochrome C, Bax/Bcl-2 ratio, cleaved caspase-3), apoptotic cells, inflammasome activation (NLRP3, caspase-1), and p38 signaling. Intratracheal nCMT-3 significantly attenuated all the measured markers of renal injury, inflammation, and apoptosis. Conclusions: Pretreatment with aerosolized nCMT-3 attenuates LPS-induced AKI by inhibiting renal NLRP3 inflammasome activation, renal inflammation, and apoptosis.