Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study.
John A. Kellum,Lan Kong,Mitchell P. Fink,Lisa A. Weissfeld,Donald M. Yealy,Michael R. Pinsky,Jonathan M. Fine,Alexander Krichevsky,Russell L. Delude,Derek C. Angus +9 more
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TLDR
The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis.Abstract:
Background: Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evidence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and determine if specific patterns, including the balance of proinflammatory and anti-inflammatory markers, are associated with severe sepsis and death. Methods: This is a cohort study of 1886 subjects hospitalized with CAP through the emergency departments in 28 US academic and community hospitals. We defined severe sepsis as CAP complicated by new-onset organ dysfunction, following international consensus conference criteria. We measured plasma tumor necrosis factor, IL-6 (interleukin 6), and IL-10 levels daily for the first week and weekly thereafter. Our main outcome measures were severe sepsis and 90-day mortality. Results: A total of 583 patients developed severe sepsis (31%), of whom 149 died (26%). Systemic cytokine level elevation occurred in 82% of all subjects with CAP. Mean cytokine concentrations were highest at presentation, declined rapidly over the first few days, but remained elevated throughout the first week, beyond resolution of clinical signs of infection. Cytokine levels were highest in fatal severe sepsis and lowest in CAP with no severe sepsis. Unbalanced (high/low) cytokine patterns were unusual (4.6%) and not associated with decreased survival. Highest risk of death was with combined high levels of the proinflammatory IL-6 and anti-inflammatory IL-10 cytokine activity (hazard ratio, 20.5; 95% confidence interval, 10.8-39.0) (P.001). Conclusions: The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis. Unbalanced activation is uncommon, and mortality is highest w hen b oth p roinflammatory a nd a ntiinflammatory cytokine levels are high.read more
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Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)
Christopher W. Seymour,Vincent X. Liu,Theodore J. Iwashyna,Frank M. Brunkhorst,Thomas D. Rea,André Scherag,Gordon D. Rubenfeld,Jeremy M. Kahn,Manu Shankar-Hari,Mervyn Singer,Clifford S. Deutschman,Gabriel J. Escobar,Gabriel J. Escobar,Gabriel J. Escobar,Derek C. Angus +14 more
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Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Clinical Trial
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TL;DR: To determine whether early initiation of RRT in patients who are critically ill with AKI reduces 90-day all-cause mortality, a single-center randomized clinical trial of 231 critically ill patients with KDIGO stage 2 found that more patients in the early group recovered renal function by day 90.
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Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine.
Paul E. Marik,Stephen M. Pastores,Djillali Annane,Gianfranco Umberto Meduri,Charles L. Sprung,Wiebke Arlt,Didier Keh,Josef Briegel,Albertus Beishuizen,Ioanna Dimopoulou,Stylianos Tsagarakis,Mervyn Singer,George P. Chrousos,Gary P. Zaloga,Faran Bokhari,Michael Vogeser +15 more
TL;DR: In this paper, a multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Car to develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients.
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Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis.
Christopher W. Seymour,Jason Kennedy,Shu Wang,Chung-Chou H. Chang,Corrine F. Elliott,Zhongying Xu,Scott M. Berry,Gilles Clermont,Gregory F. Cooper,Hernando Gomez,David T. Huang,John A. Kellum,Qi Mi,Steven M. Opal,Victor B. Talisa,Tom van der Poll,Shyam Visweswaran,Yoram Vodovotz,Jeremy C. Weiss,Donald M. Yealy,Sachin Yende,Sachin Yende,Derek C. Angus +22 more
TL;DR: In this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects.
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