American journal of respiratory and critical care medicine
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Pivotal sepsis clinical trials and preclinical research in 2012 are reviewed. For interventions ranging from synthetic complex starch solutions to recombinant human activated protein C, large multicenter randomized controlled trials generally failed to show benefit and some even demonstrated harm in the intervention group. In smaller innovative clinical trials simple interventions such as external cooling to control fever and biomarker-guided weaning from mechanical ventilation found potential benefit. ⋯ Additional publications explore the key leukocyte subsets acting in sepsis, highlighting the underappreciated role of helper T-cell type 2-related pathways. Cellular remnants in the form of microparticles contribute to coagulopathy and further organ dysfunction. As a consequence, we suggest that sepsis may be the paradigm disease or condition requiring personalized care first to discover and validate new therapies and second to increase survival.
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Am. J. Respir. Crit. Care Med. · Jun 2013
ReviewImmunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change?
Sepsis is the leading cause of death in the intensive care unit and ranks in the top 10 causes of death in general worldwide. Proinflammatory mediators are related to symptoms observed early in patients with sepsis, such as fever and hemodynamic instability. ⋯ In this Critical Care Perspective we give an overview of the pathophysiology of sepsis, with a focus on immunosuppressive mechanisms that play an important role in outcome. In addition, we present an appraisal of the recent advances in immunotherapy as an adjunctive treatment for sepsis.
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Am. J. Respir. Crit. Care Med. · Jun 2013
Impact of delay in clinical presentation on the diagnostic management and prognosis of patients with suspected pulmonary embolism.
The nonspecific clinical presentation of pulmonary embolism (PE) frequently leads to delay in its diagnosis. ⋯ PE can be safely excluded based on a clinical decision rule and D-dimer testing in patients with a delayed clinical presentation. A delayed presentation for patients who survived acute PE was associated with a more central PE location, although this did not affect the clinical outcome at 3 months.
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Am. J. Respir. Crit. Care Med. · Jun 2013
Randomized Controlled TrialRandomized placebo-controlled trial to evaluate chronic dosing effects of propranolol in asthma.
Unblinded studies have shown improvements in airway hyperresponsiveness with chronic nadolol in steroid-naive patients with asthma. ⋯ This is the first placebo-controlled study to assess the effects of chronic nonselective β-blockade in asthma, showing no significant effect of propranolol compared with placebo on either methacholine or histamine airway hyperresponsiveness and no change in ACQ or AQLQ. Clinical trial registered with www.clinicaltrials.gov (NCT01074853).
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Am. J. Respir. Crit. Care Med. · Jun 2013
ReviewThe decision to extubate in the intensive care unit.
The day of extubation is a critical time during an intensive care unit (ICU) stay. Extubation is usually decided after a weaning readiness test involving spontaneous breathing on a T-piece or low levels of ventilatory assist. Extubation failure occurs in 10 to 20% of patients and is associated with extremely poor outcomes, including high mortality rates of 25 to 50%. ⋯ Strategies for identifying patients at high risk for extubation failure are essential to improve the management of weaning and extubation. Two preventive measures may prove beneficial, although their exact role needs confirmation: one is noninvasive ventilation after extubation in high-risk or hypercapnic patients, and the other is steroid administration several hours before extubation. These measures might help to prevent postextubation respiratory distress in selected patient subgroups.