Gene Expression Signatures in Blood that Predict Mortality in a West African Sepsis Cohort Define Host Response Phenotypes
Josh G. ChenowethCarlo ColantuoniDeborah A. StriegelJoost BrandsmaRittal MethaPaul W. BlairSubramaniam KrishnanPavol GenzorMichael ConsidineLeslie CopeAudrey C. KnightAnissa N. ElayadiAnne T. FoxRonna HertzanoAndrew G. LetiziaAlex Owusu‐OforiDaniel AnsongGeorge OduroKevin L. SchullyDanielle V. Clark
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Uploaded documents are in support of the manuscript and contain: Gene-level quantitation values (transcripts per million - TPM) for the 573 subjects described in the study Metadata with basic information about 573 study subjectsKeywords:
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In sepsis-3, in contrast with sepsis-1, the definition “systemic inflammatory response” has been replaced with “dysregulated host response”, and “systemic inflammatory response syndrome” (SIRS) has been replaced with “sequential organ failure assessment” (SOFA). Although the definition of sepsis has changed, the debate regarding its nature is ongoing. What are the fundamental processes controlling sepsis-induced inflammation, immunosuppression, or organ failure? In this review, we discuss the heterogeneity of sepsis-3 and address the central role of inflammation in the pathogenesis of sepsis. An unbalanced pro- and anti-inflammatory response, inflammatory resolution disorder, and persistent inflammation play important roles in the acute and/or chronic phases of sepsis. Moreover, powerful links exist between inflammation and other host responses (such as the neuroendocrine response, coagulation, and immunosuppression). We suggest that a comprehensive evaluation of the role of the inflammatory response will improve our understanding of the heterogeneity of sepsis.
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Sepsis is the leading cause of death in critically ill patients and is the most common risk factor for the development of acute lung injury in medical patients. Initially investigators hypothesized that an excessive proinflammatory response contributed to the pathogenesis of sepsis. However, this hypothesis overlooked the beneficial effects of proinflammatory mediators and the detrimental effects of an excessive anti-inflammatory response. This has led to a new hypothesis where sepsis is characterized by imbalances of the pro- and anti-inflammatory responses, with tissue injury the result of an excessive proinflammatory response and impaired pulmonary host defense the result of an excessive anti-inflammatory response. This article reviews clinical studies and animal models which show that sepsis results in an impaired lung host response to bacteria. Information in this article should provide the reader with an increased understanding of the pathogenesis of sepsis and the realization that new therapeutic strategies for sepsis need to take into account the need to balance pro- and anti-inflammatory responses to maintain pulmonary host defenses and prevent the development of acute lung injury.
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The differential roles of infection as a microbial phenomenon and sepsis as a host response were studied in 210 critically ill surgical patients. Infections occurred in 41.4% of all cases and in 82% of nonsurviving patients. Both infection and the expression of a septic response, measured as a sepsis score, were associated with significantly increased intensive care unit morbidity and mortality. Nonsurviving patients with infection had significantly higher sepsis scores than did survivors. Nonsurvivors with sepsis, on the other hand, did not differ from survivors with respect to any variable reflecting infection but did have higher mean sepsis scores. Maximum sepsis scores and sepsis scores on the day of death were similar in patients dying without infection and those dying with uncontrolled infection. The magnitude of the host septic response, independent of the presence, bacteriologic characteristics, or control of infection, is an important determinant of outcome in critical surgical illness.
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Sepsis is a syndrome of life-threatening organ dysfunction caused by a dysregulated host response to infection. Neutrophils are essential players in the host defense against invading pathogens. This review provides an overview of neutrophils dysfunction and the underlying mechanism in the sepsis. Several investigations have shown that impairment of neutrophil migration to the site of infection occurs during sepsis, resulting in an inability of the host to eliminate the infection. On the other hand, the neutrophil accumulation contributes to tissue damage and organ dysfunction during sepsis. This review summarizes the role and the potential mechanism of neutrophils in the sepsis. Neutrophils play an important role in the development of sepsis. Thus, its specific mechanisms need to be further studied and explored to give full play to its proper medical value.
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Sepsis; Neutrophil migration; Organ dysfunction
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Sepsis,a kind of systemic infection,caused by bacteria that invading the blood,is one of leading causes of death in clinic.Understanding the mechanism of sepsis will provides us with novel strategy to prevent and treat sepsis.Here,we review the recent study on the role of microorganisms and host genetic background in the development of sepsis.
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Sepsis is a syndrome characterized by life-threatening organ dysfunction caused by the dysregulated host response to an infection. Sepsis, especially septic shock and multiple organ dysfunction is a medical emergency associated with high morbidity, high mortality, and prolonged after-effects. Over the past 20 years, regulatory T cells (Tregs) have been a key topic of focus in all stages of sepsis research. Tregs play a controversial role in sepsis based on their heterogeneous characteristics, complex organ/tissue-specific patterns in the host, the multi-dimensional heterogeneous syndrome of sepsis, the different types of pathogenic microbiology, and even different types of laboratory research models and clinical research methods. In the context of sepsis, Tregs may be considered both angels and demons. We propose that the symptoms and signs of sepsis can be attenuated by regulating Tregs. This review summarizes the controversial roles and Treg checkpoints in sepsis.
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The most recent definition of sepsis in human medicine can be summarized as organ dysfunction caused by a dysregulated host response to infection. In equine medicine, although no consensus definition is available, sepsis is commonly described as a dysregulated host systemic inflammatory response to infection. Defense against host infection is the primary role of innate immune cells known as neutrophils. Neutrophils also contribute to host injury during sepsis, making them important potential targets for sepsis prevention, diagnosis and treatment. This review will discuss history and updates regarding sepsis and the systemic inflammatory response syndrome (SIRS), as well evidence for the role neutrophils play in sepsis. Future identification of clinically relevant sepsis diagnosis and therapy depends on a more thorough understanding of disease pathogenesis across species. To gain this understanding, there is a critical need for research that utilizes a clearly defined, and consistently applied, classification system for patients diagnosed with, and at risk of developing, sepsis.
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