Critical care medicine
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Critical care medicine · Jul 2014
Computed Tomography-Defined Abdominal Adiposity Is Associated With Acute Kidney Injury in Critically Ill Trauma Patients.
Higher body mass index is associated with increased risk of acute kidney injury after major trauma. Since body mass index is nonspecific, reflecting lean, fluid, and adipose mass, we evaluated the use of CT to determine if abdominal adiposity underlies the body mass index-acute kidney injury association. ⋯ Quantitation of abdominal adiposity using CT scans obtained for clinical reasons is feasible and highly reliable in critically ill trauma patients. Abdominal adiposity is independently associated with acute kidney injury in this population, confirming that excess adipose tissue contributes to the body mass index-acute kidney injury association. Further studies of the potential mechanisms linking adiposity with acute kidney injury are warranted.
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Critical care medicine · Jul 2014
The Next Generation of Sepsis Clinical Trial Designs: What Is Next After the Demise of Recombinant Human Activated Protein C?
The developmental pipeline for novel therapeutics to treat sepsis has diminished to a trickle compared to previous years of sepsis research. While enormous strides have been made in understanding the basic molecular mechanisms that underlie the pathophysiology of sepsis, a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit. The only antisepsis agent to successfully complete a phase III clinical trial was human recumbent activated protein C. This drug was taken off the market after a follow-up placebo-controlled trial (human recombinant activated Protein C Worldwide Evaluation of Severe Sepsis and septic Shock [PROWESS SHOCK]) failed to replicate the favorable results of the initial registration trial performed ten years earlier. We must critically reevaluate our basic approach to the preclinical and clinical evaluation of new sepsis therapies. ⋯ We need to improve our ability to define appropriate molecular targets for preclinical development and develop better methods to determine the clinical value of novel sepsis agents. Clinical trials must have realistic sample sizes and meaningful endpoints. Biomarker-driven studies should be considered to categorize specific "at risk" populations most likely to benefit from a new treatment. Innovations in clinical trial design such as parallel crossover design, alternative endpoints, or adaptive trials should be pursued to improve the outlook for future interventional trials in sepsis.
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Critical care medicine · Jul 2014
Early Administration of Hydrocortisone Replacement After the Advent of Septic Shock: Impact on Survival and Immune Response.
To investigate the impact of early initiation of hydrocortisone therapy on the clinical course of septic shock and on cytokine release. ⋯ In patients receiving hydrocortisone for septic shock, early initiation of treatment was associated with improved survival. This treatment was also associated with attenuated stimulation of tumor necrosis factor-α.