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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Severe acute pancreatitis (SAP) is a highly morbid acute digestive disorder linked to pyroptosis. N-acetyltransferase 10 (NAT10) facilitates the production of N4-acetylcytidine (ac4C) modifications in mRNA, thereby contributing to the progression of various diseases. However, the specific role of NAT10 in SAP remains to be elucidated. ⋯ Moreover, NAT10 knockdown alleviated pancreatic tissue pathology, mitigated SAP severity, and suppressed pyroptosis in an SAP rat model. Collectively, these results demonstrate that NAT10 exacerbates pancreatic injury in SAP by promoting pyroptosis through ac4C modification of NLRP3, thereby enhancing its expression. These findings suggest a potential novel therapeutic target for SAP.
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In recent years, it has become apparent that fibrinolytic dysfunction and endotheliopathy develop in up to 40% of patients during the first hours following thermal injury and are associated with poor outcomes and increased resuscitation requirements. Rapidly following burn injury, the fibrinolytic system is activated, with activation generally greater with increased severity of injury. Very high plasma concentrations of plasmin-antiplasmin complex (marker of activation) have been associated with mortality. ⋯ Here we review the incidence and effects of these responses after burn injury and explore mechanisms and potential interactions with the early inflammatory response. Available data from burn and nonburn trauma suggest that the fibrinolytic, endothelial, and inflammatory systems interact extensively and that dysregulation in one may exacerbate dysregulation in the others. This raises the possibility that successful treatment of one may favorably impact the others.
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Background: Acute infections and sepsis are a leading cause of death. These patients are primarily encountered at the emergency department (ED), where early assessment for sepsis is necessary to improve outcome. In sepsis, the inflammatory response causes several characteristic pathophysiological changes, including a dysregulated and generalized activation of the endothelium. ⋯ Results : For sepsis, E-selectin and ICAM-1 both showed an area under the receiver operating characteristic (AUROC) of 0.62, lower than procalcitonin with 0.77 (both P < 0.01) and lactate with 0.73 ( P = 0.030 and 0.046, respectively), but similar to CRP with 0.60 ( P = 0.758 and 0.876, respectively). For 28-day in-hospital mortality among patients with infection, ICAM-1 performed best with an AUROC of 0.75. Conclusions : Despite promising results in small studies and specific cohorts, particularly in intensive care units, this large-scale evaluation of four endothelial biomarkers highlights their limited diagnostic utility in a broader inclusion setup design at the earliest possible time point of evaluation.
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Background : The interrelation between the plasma proteome and plasma metabolome with sepsis presents a multifaceted dynamic that necessitates further research to elucidate the underlying causal mechanisms. Methods : Our investigation used public genome-wide association study data to explore the relationships among the plasma proteome, metabolome, and sepsis, considering different sepsis subgroup. Initially, two-sample Mendelian randomization established causal connections between the plasma proteome and metabolome with sepsis. ⋯ Further scrutiny revealed that this plasma metabolite notably augments the abundance of ICAM5 protein ( P value = 3.52E-04, OR = 1.11, 95% CI = 1.04-1.17), devoid of any detected heterogeneity, pleiotropy, or reverse causality. Mediated Mendelian randomization revealed ICAM5 mediated 11.9% of 1,2,3-benzenetriol sulfate (2)'s total effect on sepsis progression. Conclusion : This study details the causal link between the plasma proteome and metabolome with sepsis, highlighting the roles of ICAM5 and 1,2,3-benzenetriol sulfate (2) in sepsis progression, both independently and through crosstalk.
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Comparative Study
Comparison of continuous vital signs data analysis versus venous lactate for the prediction of lifesaving interventions in patients with traumatic shock.
Introduction: The prehospital environment is fraught with operational constraints, making it difficult to assess the need for resources such as lifesaving interventions (LSI) for adults with traumatic injuries. While invasive methods such as lactate have been found to be highly predictive for estimating injury severity and resource requirements, noninvasive methods, to include continuous vital signs ( VS ), have the potential to provide prognostic information that can be quickly acquired, interpreted, and incorporated into decision making. In this work, we hypothesized that an analysis of continuous VS would have predictive capacity comparable to lactate and other laboratory tests for the prediction of injury severity, need for LSIs and intensive care unit admission. ⋯ The model using all laboratory data yielded the highest sensitivity and sensitivity (AUROC, 0.77; 95% CI, 0.74-0.81). Discussion: The results from this study suggest that continuous VS obtained from autonomous monitors in an aeromedical environment may be helpful for predicting LSIs and the critical care requirements for traumatically injured adults. The collection and use of noninvasively obtained physiological data during the early stages of prehospital care may be useful for in developing user-friendly early warning systems for identifying potentially unstable trauma patients.