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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The global prevalence of heart failure is still growing, which imposes a heavy economic burden. The role of microRNA-146b (miR-146b) in HF remain largely unknown. This study aims to explore the role and mechanism of miR-146b in HF. ⋯ MiR-146b knockout mice showed a more pronounced decrease in cardiac function and more severe myocardial fibrosis and apoptosis than wild type. Meanwhile, over expression or repression of miR-146b in primary neonatal mouse cardiomyocytes could inhibit or upregulate HIF-1α mRNA and protein expression. Conclusion: Our study shows that miR-146b may be a protective factor for cardiomyocytes by modulating HIF-1α.
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Loss of function of the phospholipid scramblase (PLS) TMEM16F results in Scott Syndrome, a hereditary bleeding disorder generally attributed to intrinsic platelet dysfunction. The role of TMEM16F in endothelial cells, however, is not well understood. We sought to test the hypothesis that endothelial TMEM16F contributes to hemostasis by measuring bleeding time and venous clotting in endothelial-specific knockout (ECKO) mice. ⋯ Endothelial TMEM16F function is essential for normal hemostasis. ECKO of TMEM16F is sufficient to produce a coagulopathic phenotype, as shown by the prolonged bleeding time after tail transection and decreased thrombus generation in response to IVC stenosis. Because endothelial calcium events are pathologically amplified in response to trauma factors, these results suggest that TMEM16F may play a role in trauma-induced coagulopathy.
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Understanding clinical trajectories of sepsis patients is crucial for prognostication, resource planning, and to inform digital twin models of critical illness. This study aims to identify common clinical trajectories based on dynamic assessment of cardiorespiratory support using a validated electronic health record data that covers retrospective cohort of 19,177 patients with sepsis admitted to ICUs of Mayo Clinic Hospitals over eight-year period. Patient trajectories were modeled from ICU admission up to 14 days using an unsupervised machine learning two-stage clustering method based on cardiorespiratory support in ICU and hospital discharge status. ⋯ Four distinct trajectories were identified: fast recovery (27% with a mortality rate of 3.5% and median hospital LOS of 3 (IQR, 2-15) days), slow recovery (62% with a mortality rate of 3.6% and hospital LOS of 8 (IQR, 6-13) days), fast decline (4% with a mortality rate of 99.7% and hospital LOS of 1 (IQR, 0-1) day), and delayed decline (7% with a mortality rate of 97.9% and hospital LOS of 5 (IQR, 3-8) days). Distinct trajectories remained robust and were distinguished by Charlston comorbidity index, Apache III scores, day 1 and day 3 SOFA (p < 0.001 ANOVA). These findings provide a foundation for developing prediction models and digital twin decision support tools, improving both shared decision-making and resource planning.
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Trauma and hemorrhagic shock (T/HS) are associated with multiple organ injury. Antithrombin (AT) has anti-inflammatory and organ protective activity through its interaction with endothelial heparan sulfate containing a 3-O-sulfate modification. Our objective was to examine the effects of T/HS on 3-O-sulfated (3-OS) heparan sulfate expression and determine whether AT-heparan sulfate interactions are necessary for its anti-inflammatory properties. ⋯ T/HS causes pronounced reductions in pulmonary expression of 3-OS heparan sulfate, which is essential to AT's anti-thrombotic and anti-inflammatory activity. Blocking the interaction between AT and the endothelium attenuates the anti-thromboinflammatory and organ protective properties of FFP, suggesting that AT-endothelial anticoagulant function and anti-inflammatory signaling is important for organ protection during T/HS.
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Introduction: Coagulopathy following traumatic injury impairs stable blood clot formation and exacerbates mortality from hemorrhage. Understanding how these alterations impact blood clot stability is critical to improving resuscitation. Furthermore, the incorporation of machine learning algorithms to assess clinical markers, coagulation assays and biochemical assays allows us to define the contributions of these factors to mortality. ⋯ Fibrinogen, clot stiffness, D-dimer and tPA all demonstrated significant correlation to ISS. Machine-learning algorithms identified the importance of coagulation kinetics and clot structure on patient outcomes. Conclusions: Rheological markers of coagulopathy and biochemical factors are associated with injury severity and are highly predictive of mortality after trauma, providing evidence for integrated predictive models and therapeutic strategies.