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 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.
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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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Background: Noncompressible torso hemorrhage remains a leading cause of potentially preventable deaths. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has emerged as an adjunct temporizing hemorrhage control. The complete occlusion strategy with the ER-REBOA catheter can cause distal ischemia when used for longer than 30 min. ⋯ The partial aortic occlusion strategy was employed more often in the pREBOA-PRO group (87% vs. 33%, P < 0.05) and for longer periods (59 min vs. 50 min, P < 0.003). In contrast, AKI occurred less frequently in the pREBOA-PRO group (19% vs. 33%, P < 0.05). Conclusions: The more frequently partial and longer occlusion times in Zone 1 with the use of pREBOA-PRO resulted in lower AKI incidence suggesting that this newer device is a safer extended bridge to hemorrhage control.
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Sepsis results from a dysregulated host immune response to infection and is responsible for ~11 million deaths each year. In the laboratory, many aspects of sepsis can be replicated using a cecal ligation and puncture model, which is considered the most clinically relevant rodent model of sepsis. ⋯ Treatment of mice with 10 μg of a synthetic 68-amino acid peptide derived from an immunomodulatory molecule secreted by a parasitic worm of humans and livestock, F. hepatica , termed F. hepatica helminth defense molecule, potently suppressed the systemic inflammatory profile, protected mice against acute kidney injury, and improved survival between 48 and 72 h after procedure. These results suggest that the anti-inflammatory parasite-derived F. hepatica helminth defense molecule peptide has potential as a biotherapeutic treatment for sepsis.