Articles: sepsis.
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Postsepsis early mortality is being replaced by survivors who experience either a rapid recovery and favorable hospital discharge or the development of chronic critical illness with suboptimal outcomes. The underlying immunological response that determines these clinical trajectories remains poorly defined at the transcriptomic level. ⋯ Using single-cell RNA sequencing and pathway analyses, we identified gene expression patterns between these two groups that are consistent with differences in TNF-α production based on clinical outcome. This may provide therapeutic targets for those at risk for chronic critical illness in order to improve their phenotype/endotype, morbidity, and long-term mortality.
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Background: The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury. ⋯ Similar findings were demonstrated on fibronectin, collagen I, collagen IV, and laminin, suggesting that neutrophil surface VLA-3 and CD151 are responsible for endothelial damage regardless of substrata and are likely to be operative in all bodily tissues. Conclusion: This report identifies VLA-3 and CD151 on the activated human neutrophil, which are responsible for damage to endothelial function. Targeting these molecules in vivo may demonstrate preservation of organ function during critical illness.
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Background: The association between sepsis and noninfectious respiratory diseases is well-documented, yet the specific causal link between the two remains unclear. In order to explore this relationship further, we employed a Mendelian randomization (MR) analysis utilizing data from the UK Biobank and FinnGen Biobank. Methods: We analyzed the summary statistics of a genome-wide association study summary statistics for chronic obstructive pulmonary disease (COPD), asthma, pulmonary embolism (PE), idiopathic pulmonary fibrosis (IPF), obstructive sleep apnea (OSA), lung cancer, sepsis, and sepsis-related mortality. ⋯ IPF and OSA were not significantly associated with sepsis or sepsis-related mortality ( P > 0.05). Conclusion: Our MR analysis offers new insights into potential links between noninfectious respiratory diseases and the risk of sepsis. However, additional investigation into the underlying mechanisms and clinical studies are necessary to confirm these findings.
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Background: The inability to evaluate host immunity in a rapid quantitative manner in patients with sepsis has severely hampered development of novel immune therapies. The enzyme-linked immunospot (ELISpot) assay is a functional bioassay that measures the number of cytokine-secreting cells and the relative amount of cytokine produced at the single-cell level. A key advantage of ELISpot is its excellent dynamic range enabling a more precise quantifiable assessment of host immunity. ⋯ Conclusion: ELISpot offers a unique capability to assess the functional status of both adaptive and innate immunity over time. The results presented herein demonstrate that ELISpot can also be used to detect and follow the in vivo effects of drugs to ameliorate sepsis-induced immune dysfunction. This capability would be a major advance in guiding new immune therapies in sepsis.
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Leaving university I started working for the Belgian National Radio as a journalist. I used to travel a lot and produce radio features about life abroad and how people all over the world dealt with the different challenges in society. A privileged job that I enjoyed doing for many years. ⋯ The Head of the ICU informed my husband that there was less than 5% chance to survive and if so, he could not predict what kind of damage there would be: the amount of drugs that I had been given, including noradrenaline, was so extremely high, that it became very unclear how my body would respond to it. And if, as by miracle, I would survive: what kind of damage would there be? Physical? Mental? Physical and mental? No specialist could answer those questions. But both the health care professionals and my family fought to keep me alive.