Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Tissue injury, such as burns or inflammation, can lead to the generation of oxidized lipids capable of regulating hemodynamic, pulmonary, immune, and neuronal responses. However, it is not known whether traumatic injury leads to a selective upregulation of transcripts encoding oxidative enzymes capable of generating these mediators. Here, we analyzed microarrays taken from circulating leukocytes of 187 trauma subjects compared with 97 control volunteers for changes in the expression of 105 oxidative enzymes and related receptors. ⋯ In addition, the level of expression of CYP2A7, CYP2B7P1, CYP2C19, CYP2E1, CYP4A11, CYP4F3, CYP8B1, CYP19A1, CYP20A1, CYP51A1, HMOX2, NCF1, NCF2, and NOX1 and the receptors PTGER2 and ESR2 were correlated with clinical trauma indices such as APACHE II, Max Denver Scale, and the Injury Severity Score. Demonstration of a selective alteration in expression of transcripts encoding oxidative enzymes reveals a complex molecular response to major blunt trauma in circulating leukocytes. Furthermore, the association between changes in gene expression and clinical trauma scores suggests an important role in integrating pathophysiologic responses to blunt force trauma.
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There is currently no reliable tool available to measure immune dysfunction in septic patients in the clinical setting. This proof-of-concept study assesses the potential of gene expression profiling of whole blood as a tool to monitor immune dysfunction in critically ill septic patients. Whole-blood samples were collected daily for up to 5 days from patients admitted to the intensive care unit with sepsis. ⋯ Furthermore, expression levels of these genes correlated with clinical severity, with a significantly greater degree of downregulation found in nonsurvivors compared with survivors. The results show that whole-blood gene expression analysis can capture systemic immune dysfunctions in septic patients. Our study provides an experimental basis to support further study on the use of a gene expression-based assay, to assess immunosuppression, and to guide immunotherapy in future clinical trials.
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Once established, the acute respiratory distress syndrome (ARDS) is highly resistant to treatment and retains a high mortality. We hypothesized that preemptive application of airway pressure release ventilation (APRV) in a rat model of trauma/hemorrhagic shock (T/HS) would prevent ARDS. ⋯ Our findings demonstrate that preemptive mechanical ventilation with APRV attenuates the clinical and histologic lung injury associated with T/HS. The mechanism of injury prevention is related to preservation of alveolar epithelial and endothelial integrity. These data support our hypothesis that preemptive APRV, applied using published guidelines, can prevent the development of ARDS.
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Few studies were performed to investigate the association between tissue Doppler imaging parameters about left ventricular (LV) systolic function and LV systolic asynchrony and prognosis in patients with septic shock and normal LV ejection fraction (LVEF). This prospective study was performed from January 2010 to April 2012 in a medical intensive care unit. Fifty-one patients with septic shock and LVEF greater than or equal to 50% were analyzed. ⋯ The patients with Sm-mean greater than or equal to 6.2 cm/s or Ts-SD less than 33 ms had higher 28-day mortality. In the Cox multivariate analysis, Sm-mean, Ts-SD, and mean arterial blood pressure emerged as independent predictors for 28-day mortality. We concluded that LV systolic dysfunction and systolic asynchrony assessed by tissue Doppler imaging were associated with improved 28-day all-cause mortality in patients with septic shock and normal LVEF.
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S100A12 is highly expressed, and serum levels correlate with individual disease activity in patients with inflammatory diseases. We here sought to determine the extent of S100A12 release and its soluble high-affinity receptor for advanced glycation end products (sRAGE) in patients with severe sepsis stratified to the three most common infectious sources (lungs, abdomen, and urinary tract) and to determine S100A12 and sRAGE concentrations at the site of infection during peritonitis. Two patient populations were studied: (a) 51 patients with sepsis due to (i) peritonitis (n = 12), (ii) pneumonia (n = 29), or (iii) urinary tract infection (n = 10); and (b) 17 patients with peritonitis. ⋯ In conclusion, in severe sepsis, S100A12 is released systemically irrespective of the primary source of infection. During abdominal sepsis, S100A12 release likely predominantly occurs at the site of infection. Concentrations of its high-affinity sRAGE do not change during infection or human endotoxemia.