Air Travel and Venous Thromboembolism: A Systematic Review

CONTEXT: Despite multiple attempts to document and quantify the danger of venous thromboembolism (VTE) following prolonged travel, there is still uncertainty about the magnitude of risk and what can be done to lower it. OBJECTIVES: To review the methodologic strength of the literature, estimate the risk of travel-related VTE, evaluate the efficacy of preventive treatments, and develop evidence-based recommendations for practice. DATA SOURCES: Studies identified from MEDLINE from 1966 through December 2005, supplemented by a review of the Cochrane Central Registry of Controlled Trials, the Database of Abstracts of Reviews of Effects, and relevant bibliographies. STUDY SELECTION: We included all clinical studies that either reported primary data concerning travel as a risk factor for VTE or tested preventive measures for travel-related VTE. DATA EXTRACTION AND ANALYSIS: Two reviewers reviewed each study independently to assess inclusion criteria, classify research design, and rate methodologic features. The effect of methodologic differences, VTE risk, and travel duration on VTE rate was evaluated using a logistic regression model. DATA SYNTHESIS: Twenty-four published reports, totaling 25 studies, met inclusion criteria (6 case-control studies, 10 cohort studies, and 9 randomized controlled trials). Method of screening for VTE [screening ultrasound compared to usual clinical care, odds ratio (OR) 390], outcome measure [all VTE compared to pulmonary embolism (PE) only, OR 21], duration of travel (<6 hours compared to 6–8 hours, OR 0.011), and clinical risk (“higher” risk travelers compared to “lower,” OR 3.6) were significantly related to VTE rate. Clinical VTE after prolonged travel is rare [27 PE per million flights diagnosed through usual clinical care, 0.05% symptomatic deep venous thrombosis (DVT) diagnosed through screening ultrasounds], but asymptomatic thrombi of uncertain clinical significance are more common. Graduated compression stockings prevented travel-related VTE (P < 0.05 in 4 of 6 studies), aspirin did not, and low-molecular-weight heparin (LMWH) showed a trend toward efficacy in one study. CONCLUSIONS: All travelers, regardless of VTE risk, should avoid dehydration and frequently exercise leg muscles. Travelers on a flight of less than 6 hours and those with no known risk factors for VTE, regardless of the duration of the flight, do not need DVT prophylaxis. Travelers with 1 or more risk factors for VTE should consider graduated compression stockings and/or LMWH for flights longer than 6 hours

Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells

Nearly 70% of breast cancer patients with advanced disease will develop bone metastases. Once established in bone, tumor cells produce factors that cause changes in normal bone remodeling, such as parathyroid hormone-related protein (PTHrP). While enhanced expression of PTHrP is known to stimulate osteoclasts to resorb bone, the environmental factors driving tumor cells to express PTHrP in the early stages of development of metastatic bone disease are unknown. In this study, we have shown that tumor cells known to metastasize to bone respond to 2D substrates with rigidities comparable to that of the bone microenvironment by increasing expression and production of PTHrP. The cellular response is regulated by Rho-dependent actomyosin contractility mediated by TGF-ß signaling. Inhibition of Rho-associated kinase (ROCK) using both pharmacological and genetic approaches decreased PTHrP expression. Furthermore, cells expressing a dominant negative form of the TGF-ß receptor did not respond to substrate rigidity, and inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-ß. These observations suggest a role for the differential rigidity of the mineralized bone microenvironment in early stages of tumor-induced osteolysis, which is especially important in metastatic cancer since many cancers (such as those of the breast and lung) preferentially metastasize to bone

ACC/AHA/ASE 2003 Guideline Update for the Clinical Application of Echocardiography: Summary Article: A Report of the American College of Cardiology/American HeartAssociation Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography)

"The previous guideline for the use of echocardiography was published in March 1997. Since that time, there have been significant advances in the technology of echocardiography and growth in its clinical use and in the scientific evidence leading to recommendations for its proper use. Each section has been reviewed and updated in evidence tables, and where appropriate, changes have been made in recommendations. A new section on the use of intraoperative transesophageal echocardiography (TEE) is being added to update the guidelines published by the American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists. There are extensive revisions, especially of the sections on ischemic heart disease; congestive heart failure, cardiomyopathy, and assessment of left ventricular (LV) function; and screening and echocardiography in the critically ill. There are new tables of evidence and extensive revisions in the ischemic heart disease evidence tables. Because of space limitations, only those sections and evidence tables with new recommendations will be printed in this summary article. Where there are minimal changes in a recommendation grouping, such as a change from Class IIa to Class I, only that change will be printed, not the entire set of recommendations. Advances for which the clinical applications are still being investigated, such as the use of myocardial contrast agents and three-dimensional echocardiography, will not be discussed.

Targeted Disruption of Guanylyl Cyclase-A/Natriuretic Peptide Receptor-A Gene Provokes Renal Fibrosis and Remodeling in Null Mutant Mice: Role of Proinflammatory Cytokines

Binding of atrial and brain natriuretic peptides to guanylyl cyclase-A/natriuretic peptide receptor-A produces second messenger cGMP, which plays an important role in maintaining renal and cardiovascular homeostasis. Mice carrying a targeted disruption of the Npr1 gene coding for guanylyl cyclase-A/natriuretic peptide receptor-A exhibit changes that are similar to those that occur in untreated human hypertension, including elevated blood pressure, cardiac hypertrophy, and congestive heart failure. The objective of this study was to determine whether disruption of the Npr1 gene in mice provokes kidney fibrosis, remodeling, and derangement. We found that systemic disruption of the Npr1 gene causes increased renal tubular damage characterized by dilation, flattening of epithelium, and expansion of interstitial spaces in Npr1−/− (0-copy) mice. Significant increases occurred in the expression levels of TNF-α (4-fold), IL-6 (4.5-fold), and TGF-β1 (2-fold) in 0-copy null mutant mice compared with 2-copy wild-type mice. An increased epithelial-to-mesenchymal transition indicated by increased expression of α-smooth muscle actin, was observed in Npr1−/− mouse kidneys. Treatment with captopril and losartan showed a 38 and 46% attenuation in fibrosis and 30 and 42% reduction in α-smooth muscle actin immunoexpression, respectively, in 1-copy and 0-copy mice compared with 2-copy mice. Although bendroflumethiazide treatment did not show any effect. The present results demonstrate that the disruption of Npr1 gene activates proinflammatory cytokines leading to fibrosis, hypertrophic growth, and remodeling of the kidneys of mutant mice