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Muri, Switzerland

Bounameaux H.,University of Geneva | Spirk D.,Sanofi S.A. | Kucher N.,Cardiovascular Division
Swiss Medical Weekly | Year: 2011

There is a gap between knowledge and recommendations regarding venous thromboembolism (VTE) on the one hand and daily practice on the other. This fact has prompted a Swiss multidisciplinary group consisting of angiologists, haematologists, internists, and emergency medicine and pharmaceutical medicine specialists interested in VTE, the SAMEX group, to set up a series of surveys and studies that give useful insight into the situation in our country. Their projects encompassed prophylactic and therapeutic aspects of VTE, and enrolled over 7000 patients from five academic and 45 non-academic acute care hospitals and fifty-three private practices in Switzerland. This comprehensive Swiss Clinical Study Programme forms the largest database surveying current clinical patterns of VTE management in a representative sample of the Swiss patient population. Overall the programme shows a lack of thromboprophylaxis use in hospitalised at-risk medical patients, particularly in those with cancer, acute heart or respiratory failure and the elderly, as well as underprescription of extended prophylaxis beyond hospital discharge in patients undergoing major cancer surgery. In regard to VTE treatment, planning of anticoagulation duration, administration of LMWH for cancer-associated thrombosis, and the use of compression therapy for prevention of post-thrombotic syndrome in patients with symptomatic proximal DVT require improvement. In conclusion, this programme highlights insufficient awareness of venous thromboembolic disease in Switzerland, underestimation of its burden and inconsistent application of international consensus statement guidelines regarding prophylaxis and treatment adopted by the Swiss Expert Group.


Alonso A.,University of Minnesota | Bengtson L.G.S.,University of Minnesota | Maclehose R.F.,University of Minnesota | Lutsey P.L.,University of Minnesota | And 2 more authors.
Stroke | Year: 2014

BACKGROUND AND PURPOSE - : In randomized trials, patients with atrial fibrillation (AF) receiving dabigatran, a direct oral anticoagulant, had lower risk of intracranial bleeding (ICB) than those on warfarin. However, concerns exist about potential worse outcomes in dabigatran users if bleeding occurs, given the lack of approved reversal agents. Thus, we examined in-hospital mortality in AF patients with ICB being treated with dabigatran versus warfarin in a real-world population in the United States. METHODS - : We analyzed healthcare utilization claims in the Truven Health Marketscan Research Databases. The study sample included patients with AF admitted to a hospital with a primary diagnosis of ICB. Information on medications, inpatient, and outpatient diagnoses was obtained from available claims. Propensity score-adjusted risk ratios and 95% confidence intervals of in-hospital mortality comparing current users of dabigatran versus warfarin were estimated using relative risk regression. RESULTS - : Among 2391 AF patients admitted with ICB (2290 on warfarin, 101 on dabigatran), 531 died during their admission. In-hospital mortality was similar in those treated with warfarin (22%) or dabigatran (20%). Compared with warfarin users, the propensity score-adjusted risk ratio (95% confidence interval) of mortality in dabigatran users was 0.93 (0.62-1.37). Associations were similar across different ICB subtypes (intracerebral hemorrhage, subarachnoid hemorrhage, and subdural hematoma). CONCLUSIONS - : In this sample of AF patients with ICB on oral anticoagulants, dabigatran was not associated with higher in-hospital mortality compared with warfarin. Hence, reluctance to use dabigatran because of a lack of approved reversal agents is not supported by our results. © 2014 American Heart Association, Inc..


News Article
Site: www.biosciencetechnology.com

Metastasis — the spread of cancer from one part of the body to others — accounts for more than 90 percent of cancer-related deaths. Although the cells that seed metastasis and the sites they tend to travel to have been increasingly studied over the years, little has been known about how cancer migrates from a primary site, such as breast tissue, to a secondary site, such as the brain or bone marrow. A study by researchers from Harvard-affiliated Brigham and Women’s Hospital (BWH), published in Nature Communications, offers a new view of how cancer cells extend their reach, co-opting and transforming normal cells through “metastatic hijacking.” The researchers also find that in preclinical models, pharmacological intervention can stop the hijack before it starts, pointing to new therapeutic targets for preventing cancer cells from spreading. “Metastasis remains a final frontier in the search for a cure for cancer,” said Shiladitya Sengupta of BWH’s Bioengineering Division in the Department of Medicine and corresponding author of the study. “For the past five years we have studied how cancer travels to other parts of the body, and what we find is that communication is key.” “By working together, our labs have been able to gain greater insights into cell-cell communication in tumor states, which will shed new light on cancer as a disease and the promise and potential of emerging innovative therapies,” said Elazer Edelman of BWH’s Cardiovascular Division in the Department of Medicine. Sengupta, Edelman, and colleagues began with a simple experiment. In the lab, they constructed a 3-D tumor matrix, complete with endothelial cells, and added metastatic breast cancer cells. They observed that instead of adhering together to form a sphere, the metastatic breast cancer cells spread out along the model’s blood vessels. Using a scanning electron microscope, the researchers detected long, thin tubes extending outward from the cells — nanoscale bridges that connected the cancer cells to normal tissue. The researchers found that the molecular profiles of some of the normal endothelial cells had been changed, and hypothesized that microRNAs were being transferred over the bridges into the endothelial cells. Upon closer examination, they found that the transformed endothelial cells now harbored two microRNAs that previously had been implicated in metastasis. The researchers then used chemical compounds to prevent the nanoscale bridges from forming, disrupting communication between the tumor cells and endothelium. They did so in the laboratory-constructed model and also in a mouse model, finding that pharmacological agents, including docetaxel, which is used to treat metastatic breast cancer, decreased the number of nanoscale bridges the cells formed. In mice pretreated with the pharmacological agents, the researchers observed a significant decrease in metastatic tumor burden. In future studies, the researchers will look to see if ATPase inhibitors — drugs that have been studied for treating HIV-AIDS — may also be able to inhibit metastasis by preventing the bridges from forming. “Our study opens up new avenues for exploration and suggests that these nanoscale membrane bridges may represent new therapeutics in managing metastatic breast cancer,” said Sengupta, who is an assistant professor of medicine at Harvard Medical School. “We plan to continue searching for and evaluating treatments that take aim at these conduits.” Other researchers who contributed to this work include Yamicia Connor, Sarah Tekleab, Shyama Nandakumar, Cherelle Walls, Yonatan Tekleab, Amjad Husain, Or Gadish, Venkata Sabbisetti, Shelley Kaushik, Seema Sehrawat, Ashish Kulkarni, Harold Dvorak and Bruce Zetter. This work was supported by the National Institutes of Health, a Department of Defense Breast Cancer Research Program Breakthrough Award, an American Lung Association Innovator Award, and the National Institute of General Medical Sciences.


Gong Y.,Florida College | Beitelshees A.L.,Cardiovascular Division | Cooper-DeHoff R.M.,Florida College | Lobmeyer M.T.,Florida College | And 9 more authors.
Circulation: Cardiovascular Genetics | Year: 2011

Background: Although numerous single-nucleotide polymorphisms (SNPs) in chromosome 9p21 have been associated with coronary artery disease (CAD) and incident myocardial infarction (MI) in whites, there are limited and conflicting reports on the association of this locus with prognosis in whites with existing CAD and no reports in blacks or Hispanics. We investigated the hypothesis that 9p21 polymorphisms are associated with increased risk for adverse cardiovascular outcomes in patients with documented CAD. Methods and Results: We studied the association of 155 chromosome 9p21 SNPs with adverse outcomes among hypertension patients with CAD of multiple races/ethnicities in INVEST-GENES (the International Verapamil SR Trandolapril Study Genetic Substudy) (n=1460 and n=5979 for 2 SNPs) with replication testing of 4 SNPs in the INFORM (Investigation of Outcomes From Acute Coronary Syndrome) study (n=714) of patients with acute coronary syndromes. In INVEST, the haplotype comprising the risk allele for the widely reported 9p21 SNPs was associated with better prognosis in whites (odds ratio [OR], 0.72; 95% CI, 0.57 to 0.92; P=0.0085) but not in blacks (OR, 1.21; 95% CI, 0.68 to 1.24; P=0.52) or Hispanics (OR, 0.96; 95% CI, 0.65 to 1.44; P=0.86). A less commonly reported linkage disequilibrium block was associated with worse prognosis in INVEST in both whites (OR, 1.52; 95% CI, 1.20 to 1.93; P=0.0006) and blacks (OR, 4.11; 95% CI, 1.55 to 10.88; P=0.004). Conclusions: O r findings suggest that previously reported chromosome 9p21 SNPs, which predict incident CAD, are not associated with higher risk for adverse outcomes in patients with established CAD. The less commonly reported linkage disequilibrium block warrants further investigation. © 2011 American Heart Association, Inc.


Tschabrunn C.M.,Harvard University | Roujol S.,Cardiovascular Division | Nezafat R.,Cardiovascular Division | Faulkner-Jones B.,Beth Israel Deaconess Medical Center | And 3 more authors.
Heart Rhythm | Year: 2016

Background Human ventricular tachycardia (VT) after myocardial infarction usually occurs because of subendocardial reentrant circuits originating in scar tissue that borders surviving myocardial bundles. Several preclinical large animal models have been used to further study postinfarct reentrant VT, but with varied experimental methodologies and limited evaluation of the underlying substrate or induced arrhythmia mechanism. Objective We aimed to develop and characterize a swine model of scar-related reentrant VT. Methods Thirty-five Yorkshire swine underwent 180-minute occlusion of the left anterior descending coronary artery. Thirty-one animals (89%) survived the 6-8-week survival period. These animals underwent cardiac magnetic resonance imaging followed by electrophysiology study, detailed electroanatomic mapping, and histopathological analysis. Results Left ventricular (LV) ejection fraction measured using CMR imaging was 36% ± 6.6% with anteroseptal wall motion abnormality and late gadolinium enhancement across 12.5% ± 4.1% of the LV surface area. Low voltage measured using endocardial electroanatomic mapping encompassed 11.1% ± 3.5% of the LV surface area (bipolar voltage ≤1.5 mV) with anterior, anteroseptal, and anterolateral involvement. Reentrant circuits mapped were largely determined by functional rather than fix anatomical barriers, consistent with "pseudo-block" due to anisotropic conduction. Sustained monomorphic VT was induced in 28 of 31 swine (90%) (67 VTs; 2.4 ± 1.1; range 1-4) and characterized as reentry. VT circuits were subendocardial, with an arrhythmogenic substrate characterized by transmural anterior scar with varying degrees of fibrosis and myocardial fiber disarray on the septal and lateral borders. Conclusion This is a well-characterized swine model of scar-related subendocardial reentrant VT. This model can serve as the basis for further investigation in the physiology and therapeutics of humanlike postinfarction reentrant VT. © 2016 Heart Rhythm Society.

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