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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Von Willebrand factor (VWF)-cleaving protease (ADAMTS13) cleaves ultralarge VWF (ULVWF) secreted from endothelium and by which is regulating its physiologic function. An imbalance between ULVWF secretion and ADAMTS13 level occurs in sepsis and may cause multiple organ dysfunction. We evaluated the association between the VWF-propeptide (VWF-pp)/ADAMTS13 ratio and disease severity in patients with severe sepsis or septic shock. ⋯ The VWF-pp/ADAMTS13 ratio significantly correlated with Acute Physiology and Chronic Health Evaluation II score on days 1 and 5; Sepsis-related Organ Failure Assessment score on days 1, 3, and 5; maximum Sepsis-related Organ Failure Assessment score and tumor necrosis factor α level on days 1, 3, 5, and 7; and creatinine level on days 1, 5, and 7. Patients with greater than stage 1 acute kidney injury had significantly higher VWF-pp/ADAMTS13 ratio than patients without acute kidney injury. In summary, the VWF-pp/ADAMTS13 ratio was associated with disease severity in patients with severe sepsis or septic shock and may help identify patients at risk for multiple organ dysfunction by detecting severe imbalance between ULVWF secretion and ADAMTS13 level.
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Inappropriate use of antimicrobial drugs is responsible for therapeutic failures, increased mortality rates, and the emergence of resistance. Antimicrobial activity is determined by intrinsic pharmacokinetics/pharmacodynamics concepts. In critically ill patients, an inappropriate dosing regimen can be caused by the inability of an antimicrobial drug to reach adequate concentrations at the infection site owing to alterations in the drug's pharmacokinetics caused by pathophysiological changes. Understanding these concepts and changes in PK-PD parameters that occur in intensive care unit patients is crucial for the optimization of antimicrobial therapy in these patients.
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Colloids are frequently used for fluid expansion in the intensive care unit, although its use on several clinical scenarios remains unproven of any relevant clinical benefit. The purpose of this article was to carry out a narrative review regarding the safety and efficacy of colloids in patients with sepsis and septic shock, with emphasis on the most commonly used colloids, albumin and starches. Colloids are effective fluid expanders and are able to restore the hemodynamic profile with less total volume than crystalloids. ⋯ Albumin is the only colloid solution that has proven to be safe, and its use may be considered on hypoalbuminemic patients with sepsis. Nevertheless, there are no robust data to recommend routine albumin administration in sepsis. Starch use should be avoided in patients with sepsis because of the recent findings of a multicenter randomized study until further evidence is available.
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Acute lung injury (ALI) is a severe pulmonary disease causing high numbers of fatalities worldwide. Innate immune responses are an integral part of the pathophysiologic events during ALI. Interleukin 23 (IL-23) is a proinflammatory mediator known to direct the inflammatory responses in various settings of infection, autoimmunity, and cancer. ⋯ The mouse alveolar macrophage cell line, MH-S, as well as primary alveolar macrophages displayed abundant surface expression of CD11c. Activation of these macrophages by LPS resulted in release of IL-23 in vitro. Our findings identify CD11c macrophages in the lung are likely an important source of IL-23 during ALI, which may be helpful for better understanding of this disease.
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"De-escalation therapy" is a term that suggests the need to reduce the spectrum or the number of antibiotics formerly prescribed for critical patients, upon clinical improvement and/or microorganism recovery. The major goal of this concept is the use of broad-spectrum antibiotic agents as initial drugs of choice for severe patients, instead of "reserving" the most potent agents after an inadequate clinical response, or after the microorganism is recovered. ⋯ However, the "de-escalation" component of the concept is very seldom reported, and no large clinical trial on this issue is available until today. To definitely put in practice this concept, comparative large trials must be designed and sponsored to insert this strategy at the same level of evidence of wide initial empiric antibiotic treatments.