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Sepsis and Nosocomial Infection: Patient Characteristics, Mechanisms, and Modulation.

ABSTRACT: Sepsis is a leading cause of death worldwide. After initial trials modulating the hyperinflammatory phase of sepsis failed, generations of researchers have focused on evaluating hypo-inflammatory immune phenotypes. The main goal has been to develop prognostic biomarkers and therapies to reduce organ dysfunction, nosocomial infection, and death. The depressed host defense in sepsis has been characterized by broad cellular reprogramming including lymphocyte exhaustion, apoptosis, and depressed cytokine responses. Despite major advances in this field, our understanding of the dynamics of the septic host response and the balance of inflammatory and anti-inflammatory cellular programs remains limited. This review aims to summarize the epidemiology of nosocomial infections and characteristic immune responses associated with sepsis, as well as immunostimulatory therapies currently under clinical investigation.

SUBMITTER: Denstaedt SJ

PROVIDER: S-EPMC6232897 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Sepsis and Nosocomial Infection: Patient Characteristics, Mechanisms, and Modulation.

Denstaedt Scott J SJ Singer Benjamin H BH Standiford Theodore J TJ

Frontiers in immunology 20181023

Sepsis is a leading cause of death worldwide. After initial trials modulating the hyperinflammatory phase of sepsis failed, generations of researchers have focused on evaluating hypo-inflammatory immune phenotypes. The main goal has been to develop prognostic biomarkers and therapies to reduce organ dysfunction, nosocomial infection, and death. The depressed host defense in sepsis has been characterized by broad cellular reprogramming including lymphocyte exhaustion, apoptosis, and depressed cyt ...[more]

PMID: 30459764

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Project description:ObjectiveThe primary objective of this study was to determine the correlation between procalcitonin values and illness severity by evaluating the degree of end organ dysfunction using the Sequential Organ Failure Assessment score, length of stay and the severity of sepsis (sepsis alone vs. septic shock), The hypothesis that procalcitonin values would be higher in sicker patients was formulated before data collection began. Secondary outcomes studied in relation to procalcitonin levels included infection characteristics such as the site of infection, microbial agent and dialysis dependent CKD.DesignUnblinded retrospective cohort study. September 2014-December 2016.Setting364 patients with a diagnosis of sepsis or severe sepsis who were admitted to the general medical ward and ICU at Methodist Medical Center and Proctor Hospital in Peoria, Illinois, USA.ResultsThis study demonstrates the following: Weak positive correlation between procalcitonin and SOFA score. Negligible correlation with length of stay. Higher values in patients who died than in patients who survived to discharge (p = 0.058). Sensitivity and specificity of procalcitonin for septic shock was 63 and 65% respectively. Sites typically infected by gram negative bacteria have higher procalcitonin values than sites infected by gram positive bacteria (p = 0.03). Higher procalcitonin in bacteremia than non-bacteremic infections (p = 0.004). Higher procalcitonin in dialysis-dependent CKD patients (p = 0.020).ConclusionsProcalcitonin has a higher specificity for bacterial infections than other acute phase reactants. Although initial procalcitonin value may be helpful in the determination of illness severity, it is not always a reliable prognostic indicator and carries little significance as a standalone value. Procalcitonin values may be influenced by preexisting comorbid conditions such as chronic kidney disease, which are associated with higher procalcitonin values at baseline. Procalcitonin can provide invaluable information when viewed as one piece of a clinical puzzle, and is most powerful when the interpreting physician is aware of how values are influenced by the different clinical scenarios presented in this article.

Project description:Immunologic responses during sepsis vary significantly among patients and evolve over the course of illness. Sepsis has a direct impact on the immune system due to adverse alteration of the production, maturation, function, and apoptosis of immune cells. Dysregulation in both the innate and adaptive immune responses during sepsis leads to a range of phenotypes consisting of both hyperinflammation and immunosuppression that can result in immunoparalysis. In this review, we discuss components of immune dysregulation in sepsis, biomarkers and functional immune assays to aid in immunophenotyping patients, and evolving immunomodulatory therapies. Important research gaps for the future include: (1) Defining how age, host factors including prior exposures, and genetics impact the trajectory of sepsis in children, (2) Developing tools for rapid assessment of immune function in sepsis, and (3) Assessing how evolving pediatric sepsis endotypes respond differently to immunomodulation. Although multiple promising immunomodulatory agents exist or are in development, access to rapid immunophenotyping will be needed to identify which children are most likely to benefit from which therapy. Advancements in the ability to perform multidimensional endotyping will be key to developing a personalized approach to children with sepsis. IMPACT: Immunologic responses during sepsis vary significantly among patients and evolve over the course of illness. The resulting spectrum of immunoparalysis that can occur due to sepsis can increase morbidity and mortality in children and adults. This narrative review summarizes the current literature surrounding biomarkers and functional immunologic assays for immune dysregulation in sepsis, with a focus on immunomodulatory therapies that have been evaluated in sepsis. A precision approach toward diagnostic endotyping and therapeutics, including gene expression, will allow for optimal clinical trials to evaluate the efficacy of individualized and targeted treatments for pediatric sepsis.

Dataset Information

Sepsis and Nosocomial Infection: Patient Characteristics, Mechanisms, and Modulation.

Publications

Sepsis and Nosocomial Infection: Patient Characteristics, Mechanisms, and Modulation.

Similar Datasets

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