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
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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Purpose: To evaluate significant risk variables for sepsis incidence and develop a predictive model for rapid screening and diagnosis of sepsis in patients from the emergency department (ED). Methods: Sepsis-related risk variables were screened based on the PIRO (Predisposition, Insult, Response, Organ dysfunction) system. Training (n = 1,272) and external validation (n = 568) datasets were collected from Peking Union Medical College Hospital (PUMCH) and Beijing Tsinghua Changgung Hospital (BTCH), respectively. ⋯ Both calibration curves of EASE in training and external validation datasets were close to the ideal model and were well-calibrated. Conclusions: The EASE model can predict and screen ED-admitted patients with sepsis. It demonstrated superior diagnostic performance and clinical application promise by external validation and in-parallel comparison with the NEWS scoring system.
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Thrombomodulin alfa (TM alfa) has been shown effective for treatment of disseminated intravascular coagulation (DIC) associated with sepsis, although the optimal therapeutic plasma concentration has not been clarified. In the present study, the plasma trough concentration of TM alfa in septic patients with DIC was determined, then the cutoff value for that concentration showing influence on treatment outcome was calculated using a receiver operating characteristic curve. With a cutoff value of 1,010, the area under the curve of the receiver operating characteristic was 0.669 (95% confidence interval, 0.530-0.808), with sensitivity of 0.458 and specificity of 0.882. ⋯ The above-cutoff group showed a significantly higher 90-day survival rate (91.7%) as compared with the below-cutoff group (63.4%) ( P = 0.017), with a hazard ratio of 0.199 (95% confidence interval, 0.045-0.871). Interestingly, the incidence of hemorrhagic adverse effects was not significantly different between the groups. Based on these results, the recommended plasma trough concentration of TM alfa for treatment of septic DIC is 1,010 ng/mL, which should minimize the risk of severe bleeding while maximizing the therapeutic effect.
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Background: The dysregulation of circular RNAs (circRNAs) is involved in various human diseases, including sepsis-induced acute lung injury (ALI). We aimed to investigate the role of circTDRD9 in the development of sepsis-induced ALI. Methods: Cell models of sepsis-induced ALI were established by treating A549 cells with LPS. ⋯ Importantly, circTDRD9 positively regulated RAB10 expression by binding to miR-223-3p. Conclusion: CircTDRD9 overexpression was closely associated with LPS-induced ALI. CircTDRD9 contributed to LPS-induced ALI partly by upregulating RAB10 via binding to miR-223-3p.
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Background: Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome, are complicated pulmonary inflammatory conditions for which standard therapeutics are still not well established. Although increasing research has indicated the anti-inflammatory, anticancer, and antioxidant effects of luteolin, especially in lung diseases, the molecular mechanisms underlying luteolin treatment remain largely unclear. Methods: The potential targets of luteolin in ALI were explored using a network pharmacology-based strategy and further validated in a clinical database. ⋯ Luteolin simply reduced systemic inflammation and lung tissue damage in septic mice. Furthermore, we blocked AKT1 expression and found luteolin reduced the degree of lung injury and affected NOS2 levels. Conclusions: As demonstrated by a network pharmacology approach, luteolin may exert an antipyroptosis effect on ALI via AKT1, NOS2, and CTSG.