The 11 reference contexts in paper M. Surbatovic , V. Raffay , J. Jevdjic , S. Radakovic , M. Jevtic , N. Filipovic , Z. Popovic , N. Cutura , Z. Fiser , M. Surbatovic , V. Raffay , J Jevdjic , S. Radakovic , M. Jevtic , N. Filipovic , Z Popovic , N. Cutura , Z. Fiser (2008) “Роль фактора некроза опухоли-альфа в прогнозировании тяжести и исхода сепсиса у пациентов неотложного отделения с системным воспалением // Tumor Necrosis Factor-a In Emergency Department Patients with Systemic Inflammation as a Predictor of Severity and Outcome of Sepsis” / spz:neicon:reanimatology:651

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    (platelet count <100 000); hyperbilirubinaemia (plasma total bilirubin >2 mg/dL; tissue perfusion variable: hyperlactataemia (>2 mmol/L); haemodynamic variables: arterial hypotension (systolic blood pressure decrease >40 mmHg). Septic shock is defined as acute circulatory failure induced by sepsis with hypotension despite adequate fluid resuscitation
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    . Currently the most recent definition of the International Consensus Conference, Paris, France, April 2006, does not require the presence of hypotension. Instead, the definition of shock as «failure to deliver and/or utilize adequate amounts of oxygen» may include, but is not limited to the presence of hypotension.
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    Shock is defined as a circulatory and cellular dysfunction, manifested by markers of hypoperfusion such as elevated blood lactate, decreased central venous oxygen saturation (ScvO2) or SvO2, with or without hypotension
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    . Multiorganic dysfunction syndrome (MODS) is defined as the presence of two or more altered organ functions in an acutely ill patient, when homeostasis cannot be maintained without intervention. Frequently, the presentation and clinical course of infected ED patients is not as distinct as the definitions of severe sepsis and septic shock would suggest.
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    Some of the new approaches to management of severe sepsis and septic shock (early goal directed therapy — EGDT) appear to be time dependent, suggesting a «golden hour» and «silver day» perspective to the management of this disorder, giving the ED a more important role in the care of these patients
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    . Most recent studies of pathophysiology of sepsis-induced MODS support EGDT approach and reveal that a critical limitation of tissue oxygenation delivery due to macrocirculatory or microcirculatory failure may play a role, but only in the early phase of the disease process before resuscitation has been initiated, in the first several hours.
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    Nonetheless, a growing body of evidence suggests that MODS may develop during sepsis mainly as a consequence of impaired cellular oxygen utilization as a result of mitochondrial dysfunction
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    . Cytokines are key family of effector molecules that coordinate the innate and acquired host antimicrobial defense responses in sepsis. The cytokine family of messenger molecules comprises tumor necrosis factor (TNF), interleukins, chemokines, interferons and colony stimulating factors.
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    It is a potent inducer of apoptosis of inflammatory cells, fibroblasts and myocytes. TNF-αis pyrogenic cytokine; it causes anorexia and can induce shock by decreasing vascular resistance, causing capillary leak and depressing myocardial function
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    . The purpose of this retrospective study was to determine whether the levels of TNF-α, proximal inflammatory mediator, in patients presenting to the ED and admitted to the ICU with sepsis are associated with the progression to severe sepsis, septic shock or death.
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    Although multiple studies of acute myocardial infarction, trauma and stroke have been translated into improved outcomes by applying diagnosis and therapy at the most proximal stage of hospital presentation (before ICU arrival), this approach to the sepsis patient has been lacking
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    . Sepsis is essentially an exaggerated inflammatory response. It is best understood in relation to endotoxin, component of the cell walls of Gram negative bacteria. Events may also be triggered by exotoxin release from Gram positive bacteria, by other microbial products or by elements of the complement system.
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    As a result of this interaction, pro-inflammatory cytokines such as TNF-αand the interleukins are released from the activated mononuclear cells. The cytokines are responsible for majority of clinical features of sepsis
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    . More than 80 biological markers of sepsis (e.g., C-reactive protein, interleukin-6, procalcitonin, protein C) were investigated both for their diagnostic and prognostic capabilities. In general, presence of these markers has been associated with increasing morbidity and mortality.
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    Cytokines were associated with sepsis and its prognosis in critical care patients but were not extensively studied in ED patients. Several studies have produced conflicting results regarding the circulating levels of cytokines and severity and outcome of sepsis in ICU patients. Contrary to some authors
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    , who found that high serum TNF-αlevels correlate positively with the severity of sepsis and fatal outcome, we showed in our investigation that patients with septic shock and fatal outcome had very low serum TNF-α levels.
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    One of our previous studies has shown that there is correlation between TNF-αand severity and outcome in combat casualties from blast or explosive trauma with or without secondary sepsis
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    ; mean values of TNF-αwere 17-fold higher in trauma and sepsis group; 2.2-fold higher in survivors (p<0.01) but were 43,5-fold higher in MODS group (p<0.01) contrary to our findings in this study that patients with septic shock had serum TNF-α191,5-fold lower than those in group with severe sepsis.
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    For the purpose of comparison, MODS corresponds to septic shock in our present study. Florence Riche with co-authors found, as did we in our study, that in patients with abdominal septic shock high serum TNF levels were associated with increased survival
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    . The high serum level of TNF may reflect the efficacy of peritoneal inflammatory response against abdominal sepsis. In several other studies, low levels of TNF-αwere detected in various patients in ED [14, 15].
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    The high serum level of TNF may reflect the efficacy of peritoneal inflammatory response against abdominal sepsis. In several other studies, low levels of TNF-αwere detected in various patients in ED
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    [14, 15]
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    . The timing of ОБЩАЯ РЕАНИМАТОЛОГИЯ, 2008, IV; 517 all_5_end.qxd 02.10.2008 17:03 Page 18 www.niiorramn.ru measurement of the proinflammatory cytokines from the onset of the disease is of great importance.
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