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Lederle F.A.,Veterans Affairs Medical Center
New England Journal of Medicine | Year: 2012

BACKGROUND: Whether elective endovascular repair of abdominal aortic aneurysm reduces long-term morbidity and mortality, as compared with traditional open repair, remains uncertain. METHODS: We randomly assigned 881 patients with asymptomatic abdominal aortic aneurysms who were candidates for both procedures to either endovascular repair (444) or open repair (437) and followed them for up to 9 years (mean, 5.2). Patients were selected from 42 Veterans Affairs medical centers and were 49 years of age or older at the time of registration. RESULTS: More than 95% of the patients underwent the assigned repair. For the primary outcome of all-cause mortality, 146 deaths occurred in each group (hazard ratio with endovascular repair versus open repair, 0.97; 95% confidence interval [CI], 0.77 to 1.22; P = 0.81). The previously reported reduction in perioperative mortality with endovascular repair was sustained at 2 years (hazard ratio, 0.63; 95% CI, 0.40 to 0.98; P = 0.04) and at 3 years (hazard ratio, 0.72; 95% CI, 0.51 to 1.00; P = 0.05) but not thereafter. There were 10 aneurysm-related deaths in the endovascular-repair group (2.3%) versus 16 in the open-repair group (3.7%) (P = 0.22). Six aneurysm ruptures were confirmed in the endovascular-repair group versus none in the open-repair group (P = 0.03). A significant interaction was observed between age and type of treatment (P = 0.006); survival was increased among patients under 70 years of age in the endovascular-repair group but tended to be better among those 70 years of age or older in the open-repair group. CONCLUSIONS: Endovascular repair and open repair resulted in similar long-term survival. The perioperative survival advantage with endovascular repair was sustained for several years, but rupture after repair remained a concern. Endovascular repair led to increased long-term survival among younger patients but not among older patients, for whom a greater benefit from the endovascular approach had been expected. (Funded by the Department of Veterans Affairs Office of Research and Development; OVER ClinicalTrials.gov number, NCT00094575). Copyright © 2012 Massachusetts Medical Society.

Lanska D.J.,Veterans Affairs Medical Center
Neurology | Year: 2013

Objective: To analyze the contributions of American photographer Eadweard Muybridge (1830-1904) and Philadelphia neurologist Francis Dercum (1856-1931) toward creating the first motion-picture sequences of patients with neurologic disorders. Background: In the late 1870s and 1880s, prior to the development of movie cameras or projectors, Muybridge photographed sequential images of people and animals in motion, using arrays of sequentially triggered single-image cameras and multilens cameras. Methods: Examination of published writings and photographic sequences by Muybridge and Dercum, and primary source documents, including letters from Dercum. Results: In 1885, Philadelphia neurologist Francis Dercum (1856-1931) collaborated with Muybridge at the University of Pennsylvania to photograph sequential images of patients with various neurologic disorders involving abnormal movements. Subjects were recruited from the neurology services of the University Hospital and the Philadelphia Hospital. Muybridge and Dercum photographed patients with tabes dorsalis, hemiparesis, paraparesis, athetotic cerebral palsy, lead encephalopathy, congenital hydrocephalus with diparesis, poliomyelitis, pseudoseizures, psychogenic movement disorder, and other conditions. Conclusions: These are the first motion-picture sequences of neurologic disorders ever filmed, and provide an important visual archive and teaching resource for neurologic disorders that were prevalent in the late 19th century. © 2013 American Academy of Neurology.

Lederle F.A.,Veterans Affairs Medical Center
European Journal of Vascular and Endovascular Surgery | Year: 2012

In a 1997 report of a large abdominal aortic aneurysm (AAA) screening study, we observed a negative association between diabetes and AAA. Although this was not previously described and negative associations between diseases are rare, the credibility of the finding was supported by consistent results in several previous studies and by the absence of an obvious artifactual explanation. Since that time, a variety of studies of AAA diagnosis, both by screening and prospective clinical follow-up, have confirmed the finding. Other studies have reported slower aneurysm enlargement and fewer repairs for rupture in diabetics. The seeming protective effect of diabetes for AAA contrasts with its causal role in occlusive vascular disease and so provides a strong challenge to the traditional view of AAA as a manifestation of atherosclerosis. Research focused on a protective effect of diabetes has already increased our understanding of the etiology of AAA, and might eventually pave the way for new therapies to slow AAA progression. © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Carabello B.A.,Veterans Affairs Medical Center
Circulation Research | Year: 2013

Aortic stenosis is perhaps the most common of all valvular heart diseases in the developed nations of the world. Once primarily caused by rheumatic fever, the most common pathogenesis today is an active inflammatory process with some features that are similar to atherosclerosis. Because of this shift, the age at onset of severe obstruction has changed from the sixth decade 50 years ago to the eighth decade in most individuals today. The onset of symptoms remains a key determinant of outcome, although the later age at onset may make it difficult to discern if aortic stenosis or other age-related comorbidities is the cause of the symptoms. Once symptoms of aortic stenosis develop, life expectancy is shortened to ≈3 years unless the mechanical obstruction to left ventricular outflow is relieved by aortic valve replacement. Traditionally performed during cardiac surgery, aortic valve replacement now may be performed safely and effectively using transcatheter techniques, potentially revolutionizing the approach to this potentially fatal disease. © 2013 American Heart Association, Inc.

Unemo M.,Orebro University | Shafer W.M.,Emory University | Shafer W.M.,Veterans Affairs Medical Center
Clinical Microbiology Reviews | Year: 2014

Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor- made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection. © 2014, American Society for Microbiology. All Rights Reserved.

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