Temporal Cytokine Profiles in Severely Burned Patients: A Comparison of Adults and Children

Finnerty, Celeste C.; Jeschke, Marc G.; Herndon, David N.; Gamelli, Richard L.; Gibran, Nicole S.; Klein, Matthew B.; Silver, Geoff; Arnoldo, Brett D.; Remick, Daniel G.; Tompkins, Ronald G.

doi:10.2119/2007-00132.finnerty

Cited by 154 publications

(133 citation statements)

References 23 publications

(27 reference statements)

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“…Lower sepsis in pediatric patients may also be attributable to differences in the inflammatory response after burn. Finnerty et al(9)have shown that the inflammatory response differs between adult and pediatric burn patients, with the latter havinglessinflammatory stress. This suggeststhat hyper-inflammation leads to a higher incidence of sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…Inclusion criteria were as follows:age of 0–99years, admissionto a participating hospital no later than96 hours postburn, >20% TBSA burns with the need for at least one surgical intervention. All hospitals followedstandard operating procedures set forth by the burn patient-oriented research core(9, 10). Each subject or a family member provided written informed consent before study participation.…”

Section: Methodsmentioning

confidence: 99%

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Morbidity and Survival Probability in Burn Patients in Modern Burn Care*

Jeschke

Pinto

Kraft

et al. 2015

Critical Care Medicine

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173

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Objective Characterizing burn sizes that are associated with an increased risk of mortality and morbidity is critical because it would allow identifying patients who might derive the greatest benefit from individualized, experimental, or innovative therapies. Although scores have been established to predict mortality, few data addressing other outcomes exist. The objective of this study was to determine burn sizes that are associated with increased mortality and morbidity after burn. Design and Patients Burn patients were prospectively enrolled as part of the multicenter prospective cohort study, Inflammation and the Host Response to Injury Glue Grant, with the following inclusion criteria: 0–99 years of age, admission within 96 hours after injury, and >20% total body surface area burns requiring at least one surgical intervention. Setting Six major burn centers in North America. Measurements and Main Results Burn size cutoff values were determined for mortality, burn wound infection (at least two infections), sepsis (as defined by ABA sepsis criteria), pneumonia, acute respiratory distress syndrome, and multiple organ failure (DENVER2 score >3) for both children (<16 years) and adults (16–65 years). Five-hundred seventy-three patients were enrolled, of which 226 patients were children. Twenty-three patients were older than 65 years and were excluded from the cutoff analysis. In children, the cutoff burn size for mortality, sepsis, infection, and multiple organ failure was approximately 60% total body surface area burned. In adults, the cutoff for these outcomes was lower, at approximately 40% total body surface area burned. Conclusions In the modern burn care setting, adults with over 40% total body surface area burned and children with over 60% total body surface area burned are at high risk for morbidity and mortality, even in highly specialized centers.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Morbidity and Survival Probability in Burn Patients in Modern Burn Care*

Jeschke

Pinto

Kraft

et al. 2015

Critical Care Medicine

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173

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“…It remains to be established how strongly (if at all) this particular age disparity can influence the studied responses in mice and humans. However, the role of age should not be minimized as differential age-dependent outcomes and responses in the immuno-inflammatory compartment were demonstrated in pediatric versus adult patients with trauma (36; 37), burns (38;39), endotoxemia (40) and infections (41;42) as well as in corresponding mouse models (43-46). Of note, although not directly pertinent to data analyzed in the study by Seok and colleagues (3) (as leukocytes from septic patients were not analyzed), age is a major mismatch in the mouse-to-human comparison of data from sepsis syndromes; while a majority of human septic patients are old, preclinical sepsis models (including the most relevant) typically rely on young mice (47).…”

Section: Lost In Translation: What Does the Pnas Study Really Say?mentioning

confidence: 99%

Abandon the Mouse Research Ship? Not Just Yet!

Osuchowski¹,

Remick

Lederer

et al. 2014

Shock

129

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Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiological alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly-publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without over-interpretation. Hopefully a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.

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“…Other factors have also been shown to be elevated after burn injury. These include pro-inflammatory factors, such as IFN-g, IL-10, IL-17, IL-4, IL-6, IL-8, eotaxin, granulocyte colony-stimulating factor (G-CSF), IL-13, IL-15, IP-10, MCP-1 and MIP-1a, which are differentially elevated in the peripheral blood of adults and children with burns (Finnerty et al 2008). Finnerty et al (2008) have suggested that such differences may provide insight into the higher rates of morbidity and into the development of potentially differential therapeutic treatments in adults compared with children suffering from major burn injuries.…”

Section: Can Epcs Be Mobilized Into the Circulation By Angiogenic Facmentioning

confidence: 99%

Human endothelial stem/progenitor cells, angiogenic factors and vascular repair

Watt

Athanassopoulos

Harris

et al. 2010

J. R. Soc. Interface.

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Neovascularization or new blood vessel formation is of utmost importance not only for tissue and organ development and for tissue repair and regeneration, but also for pathological processes, such as tumour development. Despite this, the endothelial lineage, its origin, and the regulation of endothelial development and function either intrinsically from stem cells or extrinsically by proangiogenic supporting cells and other elements within local and specific microenvironmental niches are still not fully understood. There can be no doubt that for most tissues and organs, revascularization represents the holy grail for tissue repair, with autologous endothelial stem/progenitor cells, their proangiogenic counterparts and the products of these cells all being attractive targets for therapeutic intervention. Historically, a great deal of controversy has surrounded the identification and origin of cells and factors that contribute to revascularization, the use of such cells or their products as biomarkers to predict and monitor tissue damage and repair or tumour progression and therapeutic responses, and indeed their efficacy in revascularizing and repairing damaged tissues. Here, we will review the role of endothelial progenitor cells and of supporting proangiogenic cells and their products, principally in humans, as diagnostic and therapeutic agents for wound repair and tissue regeneration.

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Temporal Cytokine Profiles in Severely Burned Patients: A Comparison of Adults and Children

Cited by 154 publications

References 23 publications

Morbidity and Survival Probability in Burn Patients in Modern Burn Care*

Morbidity and Survival Probability in Burn Patients in Modern Burn Care*

Abandon the Mouse Research Ship? Not Just Yet!

Human endothelial stem/progenitor cells, angiogenic factors and vascular repair

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