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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Continuous kidney replacement therapy (CKRT) is a crucial intervention for hemodynamically unstable patients with acute kidney injury (AKI). Despite the recommendations to offer a CKRT dose of 20-25 mL/kg/h, the optimal CKRT dose remains uncertain, especially whether low-dose CKRT is associated with poor outcomes. This study investigated the association between low CKRT dosage and 90-day mortality using a marginal structural model (MSM). ⋯ This study highlights the impact of methodological approaches on the association between CKRT dose and mortality and that with personalized adjustments, there may not be a lower limit of the unsafe CKRT dose. However, lower CKRT doses were initially associated with higher mortality, and adjusting for time-dependent variables nullified this association.
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To identify and describe microcirculatory dysfunction (MD) in severe COVID-19 cases. ⋯ We observed evidence of MD in COVID-19 patients through various microcirculatory parameters. This study's reproducible multimodal approach facilitates acute MD detection across multiple clinical applications. Limitations included the observational design, limited statistical power, single-time microvascular measurements, varying illness severity among groups, and possible influences of treatments and vaccinations on MD.
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Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo. ⋯ Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy.
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Sepsis is a critical medical condition characterized by a dysregulated host response to infection. Platelet abnormalities frequently manifest in sepsis patients, but the causal role of platelets in sepsis remains unclear. This study employed a bidirectional two-sample Mendelian randomization (MR) approach to investigate the causal direction between platelets and sepsis. ⋯ This study suggests a causal association between low PCT and MPV levels and increased risk of sepsis. Additionally, sepsis with a poor prognosis was causally linked to decreased PLT. These findings provide novel evidence for the causal relationship between platelet traits and sepsis.
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Sepsis, a systemic inflammation syndrome initiated by infection, poses significant challenges due to its intricate pathophysiology. T cells play a crucial role in combating infections during sepsis. Despite previous observations indicating T cell dysfunction in sepsis, reliable in-vitro detection methods were lacking, and the factors influencing these impairments remained unclear. ⋯ Short-term incubation with sepsis plasma does not directly inhibit T cell migration but instead affects T cell function by disrupting the intracellular redox environment. Improving the intracellular redox environment of sepsis patients contributes to restoring impaired migration and proliferation, with MitoQ demonstrating therapeutic potential.