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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Myeloid differentiation 2 (MD-2) plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire MD-2 gene and to investigate their clinical relevance in patients with major trauma. A total of 726 patients with major trauma were prospectively recruited and composed of two different geographic populations (Chongqing in southwestern China and Zhejiang in eastern China). ⋯ However, only the rs11465996 polymorphism was shown to be significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma in both Chongqing and Zhejiang districts. In addition, the rs11465996 polymorphism was significantly associated with tumor necrosis factor α production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Among the three htSNPs of the entire MD-2 gene, only the rs11465996 might be used as relevant risk estimate for the development of sepsis and MOD syndrome in patients with major trauma.
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After severe tissue injury, innate immunity mounts a robust systemic inflammatory response. However, little is known about the immediate impact of multiple trauma on early complement function in humans. In the present study, we hypothesized that multiple trauma results in immediate activation, consumption, and dysfunction of the complement cascade and that the resulting severe "complementopathy" may be associated with morbidity and mortality. ⋯ Key fluid-phase inhibitors of complement, such as C4b-binding protein and factor I, were significantly diminished early after trauma. The present data indicate an almost synchronical rapid activation and dysfunction of complement, suggesting a trauma-induced complementopathy early after injury. These events may participate in the impairment of the innate immune response observed after severe trauma.
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Randomized Controlled Trial
Hemodynamic effects of intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: the prospective, randomized IABP shock trial.
We conducted the IABP Cardiogenic Shock Trial (ClinicalTrials.gov ID NCT00469248) as a prospective, randomized, monocentric clinical trial to determine the hemodynamic effects of additional intra-aortic balloon pump (IABP) treatment and its effects on severity of disease in patients with acute myocardial infarction complicated by cardiogenic shock (CS). Intra-aortic balloon pump counterpulsation is recommended in patients with CS complicating myocardial infarction. However, there are only limited randomized controlled trial data available supporting the efficacy of IABP following percutaneous coronary intervention (PCI) and its impact on hemodynamic parameters in patients with CS. ⋯ However, there were no significant differences between the IABP group and the medical-alone group. Additional IABP treatment did not result in a significant hemodynamic improvement compared with medical therapy alone in a randomized prospective trial in patients with CS following PCI. Therefore, the use and recommendation for IABP treatment in CS remain unclear.
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Myocardial injury in adult, pediatric, and newborn patients is a leading cause of mortality and morbidity. Although the underlying etiologies are different among patient populations, the sequence of initial ischemic-hypoxic injury followed by secondary myocardial reperfusion injury is relatively consistent. Overall infarct size is important because it is believed to be a key determinant of mortality. ⋯ Multiple adult animal models have demonstrated the protective effects of cyclosporine in ischemia-reperfusion. A recent human pilot clinical trial also reported reduced myocardial injury and infarct size in patients treated with cyclosporine intravenously before percutaneous coronary intervention for ST-elevation myocardial infarction. Despite the paucity of evidence of cyclosporine A demonstrating myocardial protection in pediatric and newborn patients, the existing animal experimental results are promising.
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We hypothesize that the nebulization of γ-tocopherol (g-T) in the airway of our ovine model of acute respiratory distress syndrome will effectively improve pulmonary function following burn and smoke inhalation after 96 h. Adult ewes (n = 14) were subjected to 40% total body surface area burn and were insufflated with 48 breaths of cotton smoke under deep anesthesia, in a double-blind comparative study. A customized aerosolization device continuously delivered g-T in ethanol with each breath from 3 to 48 h after the injury (g-T group, n = 6), whereas the control group (n = 5) was nebulized with only ethanol. ⋯ The following clinical parameters were improved with g-T treatment: pulmonary shunt fraction, peak and pause pressures, lung bloodless wet-to-dry weight ratios (2.9 ± 0.87 vs. 4.6 ± 1.4, P < 0.05), and bronchiolar obstruction (2.0% ± 1.1% vs. 4.6% ± 1.7%, P < 0.05). Nebulization of g-T, carried by ethanol, improved pulmonary oxygenation and markedly reduced the time necessary for assisted ventilation in burn- and smoke-injured sheep. Delivery of g-T into the lungs may be a safe, novel, and efficient approach for management of acute lung injury patients who have sustained oxidative damage to the airway.