Valeria Rossetti

Low CURB-65 is of limited value in deciding discharge of patients with community-acquired pneumonia

BACKGROUND The relationship between clinical judgment and indications of the CURB-65 score in deciding the site-of-care for patients with community-acquired pneumonia (CAP) has not been fully investigated. The aim of this study was to evaluate reasons for hospitalization of CAP patients with CURB-65 score of 0 and 1. METHODS An observational, retrospective study of consecutive CAP patients was performed at the Fondazione Cà Granda, Milan, Italy, between January 2005 and December 2006. The medical records of hospitalized patients with CAP having a CURB-65 score of 0 and 1 were identified and reviewed to determine whether there existed a clinical basis to justify hospitalization. RESULTS Among the 580 patients included in the study, 218 were classified with a CURB-65 score of 0 or 1. Among those, 127 were hospitalized, and reasons that justified hospitalization were found in 104 (83%) patients. Main reasons for hospitalization included the presence of hypoxemia on admission (35%), failure of outpatient therapy (14%) and the presence of cardiovascular events on admission (9.7%). Used as the sole indicator for inappropriate hospitalization, the CURB-65 score had a poor positive predictive value of 52%. CONCLUSIONS Although the CURB-65 has been proposed as a tool to guide the site of care decision by international guidelines, this score is not ideal by itself, and should not be regarded as providing decision support information if a score of 0 and 1 is present. In CAP patients with CURB-65 scores of 0 or 1, further evaluations should be performed and completed by clinical judgment.

Short- and long- term effects of cigarette smoke exposure on glutathione homeostasis in human bronchial epithelial cells.

Background: Cigarette smoke extract (CSE), a model for studying the effects of tobacco smoke in vivo and in vitro, induces cell oxidative stress and affects the antioxidative glutathione system. We evaluated the impact of CSE on airway epithelial cells and the possible cytoprotective effect of the mucolitic drug S-carboximethilcysteine lysine salt (S-CMC-Lys). Methods: Reduced glutathione (GSH) and reactive oxygen species (ROS) intracellular levels were evaluated by fluorimetry in human bronchial epithelial cells (16-HBE) and the expression and activity of enzymes of the GSH metabolic pathway were investigated by RT-PCR, Western blot and colorimetric assays. Results: CSE significantly increased cell mortality in a time and dose dependent manner, via an apoptosis-independent pathway. Short-term (3 hours) CSE exposure induced an increase in ROS levels and a GSH intracellular concentration drop. In parallel, the expression of glutathione peroxidases 2 and 3, glutathione reductase and glutamate-cysteine-ligase was increased. S-CMC-Lys was effective in counteracting these effects. Conclusion: CSE affects ROS levels, GSH concentration and GSH enzymes pathway. These effects can be to some extent reversed by S-CMC-Lys, that could represent a therapeutic tool to counteract CSE induced oxidative cellular injuries.

ICln: A New Regulator of Non-Erythroid 4.1R Localisation and Function

To optimise the efficiency of cell machinery, cells can use the same protein (often called a hub protein) to participate in different cell functions by simply changing its target molecules. There are large data sets describing protein-protein interactions (“interactome”) but they frequently fail to consider the functional significance of the interactions themselves. We studied the interaction between two potential hub proteins, ICln and 4.1R (in the form of its two splicing variants 4.1R80 and 4.1R135), which are involved in such crucial cell functions as proliferation, RNA processing, cytoskeleton organisation and volume regulation. The sub-cellular localisation and role of native and chimeric 4.1R over-expressed proteins in human embryonic kidney (HEK) 293 cells were examined. ICln interacts with both 4.1R80 and 4.1R135 and its over-expression displaces 4.1R from the membrane regions, thus affecting 4.1R interaction with ß-actin. It was found that 4.1R80 and 4.1R135 are differently involved in regulating the swelling activated anion current (ICl,swell) upon hypotonic shock, a condition under which both isoforms are dislocated from the membrane region and thus contribute to ICl,swell current regulation. Both 4.1R isoforms are also differently involved in regulating cell morphology, and ICln counteracts their effects. The findings of this study confirm that 4.1R plays a role in cell volume regulation and cell morphology and indicate that ICln is a new negative regulator of 4.1R functions.