American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2019
Classifying Amyotrophic Lateral Sclerosis Patients by Changes in Forced Vital Capacity: A Group-Based Trajectory Analysis.
Rationale: A model for stratifying progression of respiratory muscle weakness in amyotrophic lateral sclerosis (ALS) would identify disease mechanisms and phenotypes suitable for future investigations. This study sought to categorize progression of FVC after presentation to an outpatient ALS clinic. Objectives: To identify clinical phenotypes of ALS respiratory progression based on FVC trajectories over time. ⋯ We found that projected group membership predicted respiratory insufficiency in the PRO-ACT cohort (concordance statistic = 0.78, 95% CI, 0.76-0.79). Conclusions: We derived a group-based trajectory model for FVC progression in ALS, which validated against the outcome of respiratory insufficiency in an external cohort. Future studies may focus on patients predicted to be rapid progressors.
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Am. J. Respir. Crit. Care Med. · Dec 2019
Inflammation without Vascular Leakage. Science Fiction No Longer?
Vascular leakage is a characteristic of critical illnesses such as septic shock and acute respiratory distress syndrome. It results in hypotension and tissue edema and contributes to organ dysfunction. It has long been taught that increased vascular permeability is a natural consequence of inflammation; in particular, many clinicians believe that it occurs inevitably during leukocyte recruitment to a site of infection. ⋯ The molecular mechanisms underpinning these processes-allowing leukocytes to exit the circulation without increasing vascular permeability-are starting to be elucidated and establish vascular leakage as a viable therapeutic target. Several preclinical studies indicate that vascular leakage can be reduced without impairing cytokine production, leukocyte recruitment, and pathogen clearance. The realization that leukocyte traffic and vascular permeability can be regulated separately should spur development of therapies that decrease vascular leakage and tissue edema without compromising the immune response.