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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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.
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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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The variant single nucleotide polymorphism rs8104571 has been associated with poor outcomes following traumatic brain injury (TBI) and is most prevalent in those of African ancestry. This single nucleotide polymorphism (SNP) resides within a gene coding for the TRPM4 protein, which complexes with SUR1 protein to create a transmembrane ion channel and is believed to contribute to cellular swelling and cell death in neurological tissue. Our study evaluates the relationship between circulating TRPM4 and SUR1, rs8104571 genotype, and clinical outcome in TBI patients. ⋯ Plasma TRPM4 abundance increased with acute kidney injury severity ( P = 0.02). The association between increased plasma TRPM4 and variant rs810457 supports an underlying mechanism involving increased neuroinflammation with a subsequent increase in the leakage of TRPM4 from the central nervous system into circulation. Alternative sources of plasma TRPM4 including the kidney cannot be excluded and may play a significant role in the pathophysiology of trauma as well.