Microvesicle-Mediated Transfer of DNA Methyltransferase Proteins Results in Recipient Cell Immunosuppression

Harkless, Ryan; Singh, Kanhaiya; Christman, John W.; McCarty, Adara; Sen, Chandan K.; Wisler, Jon

doi:10.1016/j.jss.2022.10.030

Cited by 1 publication

(2 citation statements)

References 29 publications

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“…While studies support a role for genetic (243)(244)(245)(246)(247)(248) and epigenetic (249)(250)(251)(252)(253)(254)(255) factors in sepsis, the topic remains relatively unexplored. Despite years of research in this domain, we do not yet fully understand the link between genetic factors and susceptibility, severity and evolution of sepsis.…”

Section: Bts5: How Do Genetics and Epigenetics Influence The Developm...mentioning

confidence: 99%

“…Some cohort data or post hoc analyses of intervention studies suggest a link between genetic or metabolomic factors and response to therapy (206,219,(256)(257)(258). Epigenetic factors play a crucial role in various processes in sepsis from the coordination of the response to infection to inflammatory response (259,260) but also particularly contributes to the induction of immunoparalysis (249,250,252,261). The pattern (predominantly affecting immune state, coagulation or other genes) may vary on a daily basis after admission, suggesting that repeated measurements may be required (257).…”

Section: Bts5: How Do Genetics and Epigenetics Influence The Developm...mentioning

confidence: 99%

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Surviving Sepsis Campaign Research Priorities 2023

De Backer,

Deutschman,

Hellman

et al. 2024

Critical Care Medicine

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OBJECTIVES: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. DESIGN: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities. METHODS: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article. RESULTS: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis? CONCLUSIONS: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.

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