Chest
-
Acute lung injury (ALI) and ARDS fall within a spectrum of pulmonary disease that is characterized by hypoxemia, noncardiogenic pulmonary edema, and dysregulated and excessive inflammation. While mortality rates have improved with the advent of specialized ICUs and lung protective mechanical ventilation strategies, few other therapies have proven effective in the management of ARDS, which remains a significant clinical problem. Further development of biomarkers of disease severity, response to therapy, and prognosis is urgently needed. ⋯ This review will focus on the roles of matrix metalloproteinases and protein tyrosine kinases in the pathobiology of ALI in humans, and in animal models and in vitro studies. These molecules can act independently, as well as coordinately, in a feed-forward manner via activation of tyrosine kinase-regulated pathways that are pivotal in the development of ARDS. Specific signaling events involving proteolytic processing by matrix metalloproteinases that contribute to ALI, including cytokine and chemokine activation and release, neutrophil recruitment, transmigration and activation, and disruption of the intact alveolar-capillary barrier, will be explored in the context of these novel molecular pathways.
-
Advances in critical care practice have led to a substantial decline in the incidence of ARDS over the past several years. Low tidal volume ventilation, timely resuscitation and antimicrobial administration, restrictive transfusion practices, and primary prevention of aspiration and nosocomial pneumonia have likely contributed to this reduction. Despite decades of research, there is no proven pharmacologic treatment of ARDS, and mortality from ARDS remains high. ⋯ Prediction scores have been developed to identify patients at risk for ARDS, and clinical trials testing aspirin and inhaled budesonide/formoterol for ARDS prevention are ongoing. Future trials aimed at preventing ARDS face several key challenges. ARDS has not been validated as an end point for pivotal clinical trials, and caution is needed when testing toxic therapies that may prevent ARDS yet potentially increase mortality.
-
This overview will demonstrate that cough is a common and potentially expensive health-care problem. Improvement in the quality of care of those with cough has been the focus of study for a variety of disciplines in medicine. The purpose of the Cough Guideline and Expert Panel is to synthesize current knowledge in a form that will aid clinical decision-making for the diagnosis and management of cough across disciplines and also identify gaps in knowledge and treatment options.
-
Case Reports
Survival following investigational treatment of amanita mushroom poisoning: thistle or shamrock?
We report the first case, to our knowledge, of amatoxin hepatotoxicity in Iowa and explore the ethical and decisional challenges of offering an investigational treatment of a rare disease. Acute liver failure due to ingestion of amatoxin-containing mushrooms is a relatively rare entity. ⋯ We explore the pitfalls in medical decision-making experienced by both the patient and the physician in the face of ambiguity. The patient did well following silibinin infusion, but we are left uncertain as to whether the patient truly responded to treatment or was simply destined to recover.
-
Protracted bacterial bronchitis (PBB) is a common and treatable cause of chronic wet cough in children in which the mechanisms are not understood. This study investigates the IL-1 pathway and a neutrophil gene expression signature in PBB. ⋯ PBB is characterized by increased IL-1β pathway activation. IL-1β and related mediators were associated with BAL neutrophils, cough symptoms, and disease recurrence, providing insight into PBB pathogenesis.