IntroductionBacteremia is recognized as a critical condition that influences the outcome of sepsis. Although large-scale surveillance studies of bacterial species causing bacteremia have been published, the pathophysiological differences in bacteremias with different causative bacterial species remain unclear. The objective of the present study is to investigate the differences in pathophysiology and the clinical course of bacteremia caused by different bacterial species.MethodsWe reviewed the medical records of all consecutive patients admitted to the general intensive care unit (ICU) of a university teaching hospital during the eight-year period since introduction of a rapid assay for interleukin (IL)-6 blood level to routine ICU practice in May 2000. White blood cell count, C-reactive protein (CRP), IL-6 blood level, and clinical course were compared among different pathogenic bacterial species.ResultsThe 259 eligible patients, as well as 515 eligible culture-positive blood samples collected from them, were included in this study. CRP, IL-6 blood level, and mortality were significantly higher in the septic shock group (n = 57) than in the sepsis group (n = 127) (P < 0.001). The 515 eligible culture-positive blood samples harbored a total of 593 isolates of microorganisms (Gram-positive, 407; Gram-negative, 176; fungi, 10). The incidence of Gram-negative bacteremia was significantly higher in the septic shock group than in the sepsis group (P < 0.001) and in the severe sepsis group (n = 75, P < 0.01). CRP and IL-6 blood level were significantly higher in Gram-negative bacteremia (n = 176) than in Gram-positive bacteremia (n = 407) (P < 0.001, <0.0005, respectively).ConclusionsThe incidence of Gram-negative bacteremia was significantly higher in bacteremic ICU patients with septic shock than in those with sepsis or severe sepsis. Furthermore, CRP and IL-6 levels were significantly higher in Gram-negative bacteremia than in Gram-positive bacteremia. These findings suggest that differences in host responses and virulence mechanisms of different pathogenic microorganisms should be considered in treatment of bacteremic patients, and that new countermeasures beyond conventional antimicrobial medications are urgently needed.
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.
IntroductionNeurological prognostic factors after cardiopulmonary resuscitation (CPR) in patients with cardiac arrest (CA) as early and accurately as possible are urgently needed to determine therapeutic strategies after successful CPR. In particular, serum levels of protein neuron-specific enolase (NSE) and S-100B are considered promising candidates for neurological predictors, and many investigations on the clinical usefulness of these markers have been published. However, the design adopted varied from study to study, making a systematic literature review extremely difficult. The present review focuses on the following three respects for the study design: definitions of outcome, value of specificity and time points of blood sampling.MethodsA Medline search of literature published before August 2008 was performed using the following search terms: "NSE vs CA or CPR", "S100 vs CA or CPR". Publications examining the clinical usefulness of NSE or S-100B as a prognostic predictor in two outcome groups were reviewed. All publications met with inclusion criteria were classified into three groups with respect to the definitions of outcome; "dead or alive", "regained consciousness or remained comatose", and "return to independent daily life or not". The significance of differences between two outcome groups, cutoff values and predictive accuracy on each time points of blood sampling were investigated.ResultsA total of 54 papers were retrieved by the initial text search, and 24 were finally selected. In the three classified groups, most of the studies showed the significance of differences and concluded these biomarkers were useful for neurological predictor. However, in view of blood sampling points, the significance was not always detected. Nevertheless, only five studies involved uniform application of a blood sampling schedule with sampling intervals specified based on a set starting point. Specificity was not always set to 100%, therefore it is difficult to indiscriminately assess the cut-off values and its predictive accuracy of these biomarkers in this meta analysis.ConclusionsIn such circumstances, the findings of the present study should aid future investigators in examining the clinical usefulness of these markers and determination of cut-off values.
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