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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Aim: To identify and describe microcirculatory dysfunction (MD) in severe COVID-19 cases. Methods: This prospective, cohort study evaluated microvascular function in COVID-19 patients with acute respiratory failure not requiring mechanical ventilation and compared it with that of non-COVID-19 intensive care unit (ICU)-matched controls. A validation cohort included healthy, comorbidity-free patients. ⋯ 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. Trial registration : Clinical-Trials.gov (NCT04773899).
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Objective: This study aimed to explore the clinical application of three-dimensional arterial spin labeling (3D-ASL) and diffusion-weighted magnetic resonance imaging (DWI) in transient ischemic attacks. Methods: Forty patients with transient cerebral ischemia in our hospital were selected and included from July 2020 to March 2022. All subjects were detected by DWI and 3D-ASL technology. ⋯ There was a significant difference in the attack frequency of patients with transient cerebral ischemia with different perfusion ( P < 0.05). There was a significant difference in attack frequency between patients with transient ischemic attack and patients without vascular stenosis ( P < 0.05). Conclusion: 3D-ASL and DWI technology have higher diagnostic efficiency for transient cerebral ischemia.
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Hemorrhagic shock (HS) is a life-threatening condition with high mortality rates despite current treatments. This study investigated whether targeted temperature management (TTM) could improve outcomes by modulating inflammation and protecting organs following HS. Using a rat model of HS, TTM was applied at 33°C and 36°C after fluid resuscitation. ⋯ Cytokine array analysis confirmed reduced levels of proinflammatory cytokines with TTM at 36°C. These results collectively highlight the potential of TTM at 36°C as a therapeutic approach to improve outcomes in HS. By addressing multiple aspects of injury and inflammation, including modulation of macrophage responses and cytokine profiles, TTM at 36°C offers promising implications for critical care management after HS, potentially reducing mortality and improving patient recovery.
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Objective : Vascular endothelial cells (ECs) sense and respond to both trauma factors (histone proteins) and sepsis signals (bacterial lipopolysaccharide, LPS) with elevations in calcium (Ca 2+ ), but it is not clear if the patterns of activation are similar or different. We hypothesized that within seconds of exposure, histones but not LPS would produce a large EC Ca 2+ response. We also hypothesized that histones would produce different spatio-temporal patterns of Ca 2+ events in veins than in arteries. ⋯ Exposure of ECs to histones or LPS both increased gene expression, but different mRNAs were induced. Conclusions : LPS and histones activate ECs through mechanisms that are distinct and additive; only histones produce large aberrant Ca 2+ events. ECs in arteries and veins display different patterns of Ca 2+ responses to histones.
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Background: 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. ⋯ This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multiorgan damage and lethality resulting from cecal ligation and puncture. Conclusions: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy.