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Find video protocols related to scientific articles indexed in Pubmed.
End Stage Renal Disease Among HIV-Infected Adults in North America.
Clin. Infect. Dis.
PUBLISHED: 11-20-2014
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?HIV-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks.
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Opportunity for Offshore Wind to Reduce Future Demand for Coal-fired Power Plants in China with Consequent Savings in Emissions of CO2.
Environ. Sci. Technol.
PUBLISHED: 11-20-2014
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Although capacity credits for wind power have been embodied in power systems in the U.S. and Europe, the current planning framework for electricity in China continues to treat wind power as a non-dispatchable source with zero contribution to firm capacity. This study presents a rigorous reliability model for the electric power system evaluating capacity credits that could be recognized for offshore wind resources supplying power for Jiangsu, China, which accounts for 10% of the total electricity consumed in China. Demand for electricity in Jiangsu is projected to increase from 331 TWh in 2009 to 800 TWh by 2030. Given a wind penetration level of 60% for the future additional Jiangsu power supply, wind resources distributed along the offshore region of five coastal provinces in China (Shandong, Jiangsu, Shanghai, Zhejiang and Fujian) could earn a capacity credit of 12.9%, the fraction of installed wind capacity that should be recognized to displace coal-fired systems without violating reliability standards. In the high-coal-price scenario, with 60% wind penetration, reductions in CO2 emissions relative to a business as usual reference could be as large as 200.3 million tons of CO2 or 51.8% of the potential addition, with a cost for emissions avoided of $29.0 per ton.
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Periprosthetic Joint Infection: Modern Aspects of Prevention, Diagnosis, and Treatment.
J Knee Surg
PUBLISHED: 11-19-2014
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Periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) is a devastating complication. Despite improvements in our understanding of PJI, the prevalence of this complication has not decreased in recent years, with various authors reporting rates of 1 to 2% after primary TJA and up to 7% following revision TJA. While the volume of publications, symposiums, and presentations on PJI is vast, controversy still remains regarding the prevention, diagnosis, and treatment of patients with PJI. The purpose of this article is to provide a succinct summary of the recent literature on the diagnosis, treatment, and prevention of a PJI after TJA.
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Clinical Trials in Peripheral Vascular Disease: Pipeline and Trial Designs: An Evaluation of the ClinicalTrials.gov Database.
Circulation
PUBLISHED: 09-19-2014
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Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease).
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Do Serologic and Synovial Tests Help Diagnose Infection in Revision Hip Arthroplasty With Metal-on-metal Bearings or Corrosion?
Clin. Orthop. Relat. Res.
PUBLISHED: 08-30-2014
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The diagnosis of periprosthetic joint infection (PJI) in patients with failed metal-on-metal (MoM) bearings and corrosion reactions in hip arthroplasties can be particularly difficult, because the clinical presentation of adverse local tissue reactions may mimic that of PJI, because it can also occur concurrently with PJI, and because common laboratory tests used to diagnose PJI may be elevated in patients with MoM THAs.
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Survey of video laryngoscopy use by u.s. Critical care fellowship training programs.
Ann Am Thorac Soc
PUBLISHED: 08-30-2014
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Recent studies on video laryngoscopy have demonstrated improvements in both safety and success of endotracheal intubation in the critically ill.
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Incidence and risk factors of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma in HIV-infected individuals.
Oral Oncol.
PUBLISHED: 07-29-2014
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To examine the risk and trends of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma (HNSCC) in HIV-infected individuals and assess whether immunosuppression (measured through CD4 cell count) and other risk factors impact HNSCC risk.
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Factors contributing to risk for cancer among HIV-infected individuals, and evidence that earlier combination antiretroviral therapy will alter this risk.
Curr Opin HIV AIDS
PUBLISHED: 07-08-2014
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To critically appraise recent published literature about factors associated with cancer risk likely to be influenced by combination antiretroviral therapy (cART) in HIV-infected individuals, and the potential of earlier cART initiation to reduce this risk.
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HIV infection and incidence of ischemic stroke.
AIDS
PUBLISHED: 06-18-2014
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To determine the association of HIV infection and immunodeficiency with incidence of ischemic stroke.
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Comparative health systems research among Kaiser Permanente and other integrated delivery systems: a systematic literature review.
Perm J
PUBLISHED: 06-09-2014
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Because of rising health care costs, wide variations in quality, and increased patient complexity, the US health care system is undergoing rapid changes that include payment reform and movement toward integrated delivery systems. Well-established integrated delivery systems, such as Kaiser Permanente (KP), should work to identify the specific system-level factors that result in superior patient outcomes in response to policymakers' concerns. Comparative health systems research can provide insights into which particular aspects of the integrated delivery system result in improved care delivery.
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Non-AIDS-Defining Malignancies in the HIV-Infected Population.
Curr Infect Dis Rep
PUBLISHED: 05-22-2014
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With the advent of effective combination antiretroviral therapy, HIV infection has been transformed from a fatal disease to a chronic condition. There is renewed clinical interest in long-term morbidities, including malignancies that occur disproportionately within this population. Non-AIDS-defining cancers (NADCs) are a significant source of morbidity and mortality in the aging HIV-infected population. There are data to suggest that incidence rates are elevated among HIV-infected individuals for many cancer sites, particularly those with a confirmed or suspected infectious etiology. The complex interplay between behavioral risk factors, coexistence of viral infections, immunodeficiency and antiretroviral therapy makes it difficult to analyze why certain cancers develop more frequently in HIV-infected individuals. The challenge to clinicians caring for HIV-infected patients is to develop and implement effective means to screen, treat, and prevent NADCs in the future. This review presents data on whether NADCs are increased in the HIV-Infected population, as well as ongoing research on epidemiology, prevention and pathogenesis of this evolving aspect of the HIV epidemic.
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Prostate cancer incidence and prostate-specific antigen testing among HIV-positive and HIV-negative men.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-14-2014
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We investigated whether the reported lower incidence of prostate cancer in HIV-positive men is a result of confounding factors or reduced screening.
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The management of extensor mechanism complications in total knee arthroplasty. AAOS exhibit selection.
J Bone Joint Surg Am
PUBLISHED: 03-21-2014
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Complications involving the knee extensor mechanism and patellofemoral joint occur in 1% to 12% of patients following total knee arthroplasty and have major negative effects on patient outcomes and satisfaction. The surgeon must be aware of intraoperative, postoperative, and patient-related factors that can increase the rate of these problems. This review focuses on six of the most commonly encountered problems: patellar tendon disruption, quadriceps tendon rupture, patellar crepitus and soft-tissue impingement, periprosthetic patellar fracture, patellofemoral instability, and osteonecrosis of the patella. The goals of this report are to (1) review the relevant anatomy of the knee extensor mechanism, (2) present risk factors that may lead to extensor mechanism complications, (3) provide a diagnostic and treatment algorithm for each of the aforementioned problems, and (4) review the specific surgical techniques of Achilles tendon allograft reconstruction and synthetic mesh augmentation. Extensor mechanism disorders following total knee arthroplasty remain difficult to manage effectively. Although various surgical techniques have been used, the results in patients with a prior total knee arthroplasty are inferior to the results in the young adult without such a prior procedure. Surgical attempts at restoration of the knee extensor mechanism are usually warranted; however, the outcomes of treatment of these complications are often poor, and management of patient expectations is important.
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Fretting and corrosion in modular-neck total hip arthroplasty femoral stems.
J Bone Joint Surg Am
PUBLISHED: 03-21-2014
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During total hip arthroplasty, use of a modular femoral neck on a stemmed implant allows optimization of neck anteversion, length, and offset, resulting in more accurate balance. We performed a retrospective analysis of a consecutive cohort of patients who had undergone total hip arthroplasty with a modular-neck hip system with ceramic-on-ceramic bearings.
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Clinical correlates of red blood cell omega-3 fatty acid content in male veterans with peripheral arterial disease.
J. Vasc. Surg.
PUBLISHED: 03-04-2014
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Despite available medical therapies, patients with peripheral arterial disease (PAD) remain at high risk for cardiovascular events. The n-3 polyunsaturated fatty acids (PUFA), derived from marine sources, have been shown to improve cardiovascular mortality. The Omega-3 Index (O3I), a proportion of the n-3 PUFA eicosapentaenoic acid and docosahexaenoic acid in the red blood cell membrane, correlates with cardiovascular risk. Previous investigations have found that n-3 PUFA supplementation, fish consumption, older age, and smoking history affect the O3I in different patient populations, although similar correlations have never been explored in PAD. We hypothesized that in our PAD cohort, blood content of omega-3 fatty acids would directly and positively correlate with a history of fish oil supplementation and older age and inversely correlate with a smoking history and obesity.
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Revising an HTO or UKA to TKA: is it more like a primary TKA or a revision TKA?
J Arthroplasty
PUBLISHED: 02-18-2014
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Forty-nine patients revised from UKA to TKA and 43 from HTO to TKA were matched to 43 aseptic, both component revision TKAs (rTKA) and 97 primary TKAs. At a mean of 4.8 years, the KSS and function scores in the UKA to TKA, HTO to TKA and primary TKA cohorts were similar. Total operative times were significantly higher in the HTO to TKA and rTKA groups. LOS was shorter in the primary TKA cohort. The rate of complications and reoperations were higher in HTO to TKA and rTKA compared to UKA to TKA and primary TKA. Thus, revising an HTO and UKA both had functional outcomes more similar to a primary TKA, however, the complication rate of revising an HTO was similar to an rTKA.
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Results of custom-fit, noncemented, semiconstrained total elbow arthroplasty for inflammatory arthritis at an average of eighteen years of follow-up.
J Shoulder Elbow Surg
PUBLISHED: 02-10-2014
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The literature available on the results after noncemented total elbow arthroplasty (TEA) in inflammatory arthritis is limited.
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Vascular anatomy of the patella: implications for total knee arthroplasty surgical approaches.
Knee
PUBLISHED: 01-31-2014
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Iatrogenic disruption of the patellar vascular supply has been identified as a possible contributing factor to the commonly reported patellofemoral complications following total knee arthroplasty (TKA). We performed an anatomic cadaveric study evaluating the extra-osseous vascular anatomy of the patella, and correlated our findings to routine TKA surgical dissection to determine how to better preserve patellar vascularity.
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Disparities in the quality of HIV care when using US Department of Health and Human Services indicators.
Clin. Infect. Dis.
PUBLISHED: 01-23-2014
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We estimated US Department of Health and Human Services (DHHS)-approved human immunodeficiency virus (HIV) indicators. Among patients, 71% were retained in care, 82% were prescribed treatment, and 78% had HIV RNA ?200 copies/mL; younger adults, women, blacks, and injection drug users had poorer outcomes. Interventions are needed to reduce retention- and treatment-related disparities.
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Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-21-2014
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We sought to clarify the association of HIV infection and immunodeficiency on myocardial infarction (MI) risk.
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Vitamin D deficiency is associated with mortality and adverse vascular access outcomes in patients with end-stage renal disease.
J. Vasc. Surg.
PUBLISHED: 01-17-2014
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Plasma 25 hydroxycholecalciferol (vitamin D) deficiency has been associated with adverse cardiovascular outcomes in epidemiologic studies. Chronic kidney disease is associated with loss of 1?-hydroxylase and consequently vitamin D deficiency. We hypothesized that vitamin D deficiency was associated with increased mortality and increased vascular access failure in patients undergoing permanent vascular access for end-stage renal disease.
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Short-term physical inactivity impairs vascular function.
J. Surg. Res.
PUBLISHED: 01-16-2014
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Sedentarism, also termed physical inactivity, is an independent risk factor for cardiovascular diseases. Mechanisms thought to be involved include insulin resistance, dyslipidemia, hypertension, and increased inflammation. It is unknown whether changes in vascular and endothelial function also contribute to this excess risk. We hypothesized that short-term exposure to inactivity would lead to endothelial dysfunction, arterial stiffening, and increased vascular inflammation.
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Hepatitis C screening trends in a large integrated health system.
Am. J. Med.
PUBLISHED: 01-14-2014
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As new hepatitis C virus (HCV) therapies emerge, only 1%-12% of individuals are screened in the US for HCV infection. Presently, HCV screening trends are unknown.
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Safety and feasibility of adjunctive dexamethasone infusion into the adventitia of the femoropopliteal artery following endovascular revascularization.
J. Vasc. Surg.
PUBLISHED: 01-11-2014
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Restenosis following endovascular treatment of the femoropopliteal segment is associated with the inflammatory response produced in the artery wall at the time of the procedure. Although local drug delivery to the superficial femoral and popliteal arteries promises improved patency, data are currently limited. We hypothesized that improved percutaneous delivery of an anti-inflammatory compound into the adventitia of the femoropopliteal at the time of endovascular treatment would be safe, feasible, and decrease the inflammatory response.
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Total hip arthroplasty with acetabular reconstruction using a bulk autograft for patients with developmental dysplasia of the hip results in high loosening rates at mid-term follow-up.
Int Orthop
PUBLISHED: 01-06-2014
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Managing a deficient acetabulum in patients with developmental dysplasia of the hip (DDH) can be challenging. The purpose of the study was to determine the mid-term results of total hip arthroplasty (THA) using a bulk structural autograft for reconstruction of the acetabular roof in patients with DDH.
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The Pro-Resolving Lipid Mediator Maresin 1 (MaR1) Attenuates Inflammatory Signaling Pathways in Vascular Smooth Muscle and Endothelial Cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Inflammation and its resolution are central to vascular injury and repair. Maresins comprise a new family of bioactive lipid mediators synthesized from docosahexaenoic acid, an ?-3 polyunsaturated fatty acid. They have been found to exert anti-inflammatory and pro-resolving responses in macrophages, neutrophils and bronchial epithelial cells and impart beneficial actions in murine models of peritonitis and colitis. We investigated the impact of maresin-1 (MaR1) on tumor necrosis factor alpha (TNF-?) induced inflammatory responses in human vascular endothelial (EC) and smooth muscle cells (VSMC).
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Increased Extinction Potential of Insular Fish Populations with Reduced Life History Variation and Low Genetic Diversity.
PLoS ONE
PUBLISHED: 01-01-2014
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Theoretical work has shown that reduced phenotypic heterogeneity leads to population instability and can increase extinction potential, yet few examples exist of natural populations that illustrate how varying levels expressed diversity may influence population persistence, particularly during periods of stochastic environmental fluctuation. In this study, we assess levels of expressed variation and genetic diversity among demographically independent populations of tidewater goby (Eucyclogobius newberryi), show that reductions in both factors typically coincide, and describe how low levels of diversity contribute to the extinction risk of these isolated populations. We illustrate that, for this annual species, continuous reproduction is a safeguard against reproductive failure by any one population segment, as natural, stochastically driven salinity increases frequently result in high mortality among juvenile individuals. Several study populations deviated from the natural pattern of year-round reproduction typical for the species, rendering those with severely truncated reproductive periods vulnerable to extinction in the event of environmental fluctuation. In contrast, demographically diverse populations are more likely to persist through such periods through the continuous presence of adults with broader physiological tolerance to abrupt salinity changes. Notably, we found a significant correlation between genetic diversity and demographic variation in the study populations, which could be the result of population stressors that restrict both of these diversity measures simultaneously, or suggestive of a causative relationship between these population characteristics. These findings demonstrate the importance of biocomplexity at the population level, and assert that the maintenance of diversity contributes to population resilience and conservation of this endangered species.
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Accumulation and Connectivity of Coarse Woody Debris in Partial Harvest and Unmanaged Relict Forests.
PLoS ONE
PUBLISHED: 01-01-2014
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When a tree dies, it continues to play an important ecological role within forests. Coarse woody debris (CWD), including standing deadwood (SDW) and downed deadwood (DDW), is an important functional component of forest ecosystems, particularly for many dispersal-limited saproxylic taxa and for metapopulation dynamics across landscapes. Processes, such as natural disturbance or management, modify forest composition and structure, thereby influencing CWD abundance and distribution. Many studies have compared older forests to forests managed with even-aged silvicultural systems and observed a prolonged period of low CWD occurrence after harvesting. With fine-scale spatial data, our study compares the long-term impacts of light partial harvesting on the CWD structure of eastern deciduous hardwood forests. We mapped and inventoried DDW and SDW using variable radius plots based on a 10 m×10 m grid throughout an unmanaged, structurally-complex relict forest and two nearby forests that were partially harvested over 46 years ago. The relict stand had significantly larger individual pieces and higher accumulations of DDW and SDW than both of the partially harvested stands. Connectivity of CWD was much higher in the relict stand, which had fewer, larger patches. Larger pieces and higher proportion of decay-resistant species (e.g. Quercus spp.) in the relict forest resulted in slower decomposition, greater accumulation and increased connectivity of CWD. Partial harvests, such that occur with selection forestry, are generally considered less disruptive of ecosystem services, but this study highlights the long-term impacts of even light partial harvests on CWD stocks and distribution. When planning harvesting events, forest managers should also consider alternative methods to ensure the sustainability of deadwood resources and function.
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Design Aspects of a Case-Control Clinical Investigation of the Effect of HIV on Oral and Gastrointestinal Soluble Innate Factors and Microbes.
PLoS ONE
PUBLISHED: 01-01-2014
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The impaired host defense system in HIV infection impacts the oral and gastrointestinal microbiota and associated opportunistic infections. Antiretroviral treatment is predicted to partially restore host defenses and decrease the oral manifestation of HIV/AIDS. Well-designed longitudinal studies are needed to better understand the interactions of soluble host defense proteins with bacteria and virus in HIV/AIDS. "Crosstalk" was designed as a longitudinal study of host responses along the gastrointestinal (GI) tract and interactions between defense molecules and bacteria in HIV infection and subsequent therapy.
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Strong agreement of nationally recommended retention measures from the institute of medicine and department of health and human services.
PLoS ONE
PUBLISHED: 01-01-2014
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We sought to quantify agreement between Institute of Medicine (IOM) and Department of Health and Human Services (DHHS) retention indicators, which have not been compared in the same population, and assess clinical retention within the largest HIV cohort collaboration in the U.S.
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Dual-mobility acetabular components in total hip arthroplasty.
Am J. Orthop.
PUBLISHED: 11-27-2013
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With dislocation being one of the most serious complications of total hip arthroplasty, prevention of recurrent instability has been the driving force behind several implant designs, including large-diameter heads, metal-on-metal bearing surfaces, and constrained acetabular components. Dual-articulation acetabular component design was similarly conceived in an effort to reduce postoperative dislocation risk. This design, developed in France in 1975 and popularized in Europe, was recently approved in the United States and represents a new surgical option for United States orthopedic surgeons performing total hip arthroplasty. In this article, we review the dual-articulation design in terms of its history, biomechanical concepts, published indications, contraindications, outcomes, and complications based on more than 20 years of largely French clinical experience.
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Growing impact of restenosis on the surgical treatment of peripheral arterial disease.
J Am Heart Assoc
PUBLISHED: 11-27-2013
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Patients with peripheral arterial disease often experience treatment failure from restenosis at the site of a prior peripheral endovascular intervention (PVI) or lower extremity bypass (LEB). The impact of these treatment failures on the utilization and outcomes of secondary interventions is poorly understood.
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Adventitial Nab-Rapamycin Injection Reduces Porcine Femoral Artery Luminal Stenosis Induced by Balloon Angioplasty via Inhibition of Medial Proliferation and Adventitial Inflammation.
Circ Cardiovasc Interv
PUBLISHED: 11-12-2013
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Endovascular interventions on peripheral arteries are limited by high rates of restenosis. Our hypothesis was that adventitial injection of rapamycin nanoparticles would be safe and reduce luminal stenosis in a porcine femoral artery balloon angioplasty model.
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Invasive cervical cancer risk among HIV-infected women: a North American multicohort collaboration prospective study.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 10-30-2013
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HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic human papillomavirus infection-the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women.
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Microclimate moderates plant responses to macroclimate warming.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-28-2013
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Recent global warming is acting across marine, freshwater, and terrestrial ecosystems to favor species adapted to warmer conditions and/or reduce the abundance of cold-adapted organisms (i.e., "thermophilization" of communities). Lack of community responses to increased temperature, however, has also been reported for several taxa and regions, suggesting that "climatic lags" may be frequent. Here we show that microclimatic effects brought about by forest canopy closure can buffer biotic responses to macroclimate warming, thus explaining an apparent climatic lag. Using data from 1,409 vegetation plots in European and North American temperate forests, each surveyed at least twice over an interval of 12-67 y, we document significant thermophilization of ground-layer plant communities. These changes reflect concurrent declines in species adapted to cooler conditions and increases in species adapted to warmer conditions. However, thermophilization, particularly the increase of warm-adapted species, is attenuated in forests whose canopies have become denser, probably reflecting cooler growing-season ground temperatures via increased shading. As standing stocks of trees have increased in many temperate forests in recent decades, local microclimatic effects may commonly be moderating the impacts of macroclimate warming on forest understories. Conversely, increases in harvesting woody biomass--e.g., for bioenergy--may open forest canopies and accelerate thermophilization of temperate forest biodiversity.
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Feasibility and safety of performing outpatient unicompartmental knee arthroplasty.
Int Orthop
PUBLISHED: 10-27-2013
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Unicompartmental knee arthroplasty (UKA) has a faster short-term recovery than total knee arthroplasty (TKA). The purpose of this study was to determine the feasibility and safety of performing outpatient UKAs in a consecutive group of patients presenting with unicompartmental knee osteoarthritis.
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Single-incision chronic distal biceps tendon repair with tibialis anterior allograft.
Int Orthop
PUBLISHED: 10-21-2013
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Several techniques for chronic distal biceps tendon repair have been reported; however, the literature is sparse.
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n-3 Polyunsaturated fatty acids supplementation in peripheral artery disease: the OMEGA-PAD trial.
Vasc Med
PUBLISHED: 09-19-2013
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Despite current consensus guidelines recommending intensive cardiovascular risk factor management for peripheral artery disease (PAD), patients suffering from PAD continue to experience significant morbidity and mortality. This excess morbid burden is at least partially related to impaired vascular function and systemic inflammation. Interventions bridging this gap are critical. Dietary supplementation of n-3 polyunsaturated fatty acids (n-3 PUFA) has been shown to improve endothelial function and reduce inflammation in different cohorts, as well as to decrease cardiovascular events in secondary prevention trials in patients with coronary artery disease. Their effects in the PAD population are, however, less well understood. The OMEGA-PAD trial is a double-blinded, randomized, placebo-controlled trial that examines the impact of a high-dose, short-duration dietary oral supplementation of n-3 PUFA on vascular function and inflammation in patients with established PAD. The purpose of this article is to provide a detailed description of the design and methods of the OMEGA-PAD trial, and a summary of baseline characteristics of the cohort.
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Factors associated with primary vein graft occlusion in a multicenter trial with mandated ultrasound surveillance.
J. Vasc. Surg.
PUBLISHED: 08-27-2013
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Even in the setting of duplex ultrasound (DUS) surveillance, a significant number of lower extremity vein bypass grafts (LEVBGs) become occluded as a first event. We sought to identify factors that may contribute to these primary occlusions.
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Retention among North American HIV-infected persons in clinical care, 2000-2008.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-21-2013
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Retention in care is key to improving HIV outcomes. The goal of this study was to describe churn in patterns of entry, exit, and retention in HIV care in the United States and Canada.
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Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers.
AIDS
PUBLISHED: 08-16-2013
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To investigate the relationship between inflammatory [interleukin-6 (IL-6) and C-reactive protein (CRP)] and coagulation (D-dimer) biomarkers and cancer risk during HIV infection.
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The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Ischemia, and foot Infection (WIfI).
J. Vasc. Surg.
PUBLISHED: 08-07-2013
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Critical limb ischemia, first defined in 1982, was intended to delineate a subgroup of patients with a threatened lower extremity primarily because of chronic ischemia. It was the intent of the original authors that patients with diabetes be excluded or analyzed separately. The Fontaine and Rutherford Systems have been used to classify risk of amputation and likelihood of benefit from revascularization by subcategorizing patients into two groups: ischemic rest pain and tissue loss. Due to demographic shifts over the last 40 years, especially a dramatic rise in the incidence of diabetes mellitus and rapidly expanding techniques of revascularization, it has become increasingly difficult to perform meaningful outcomes analysis for patients with threatened limbs using these existing classification systems. Particularly in patients with diabetes, limb threat is part of a broad disease spectrum. Perfusion is only one determinant of outcome; wound extent and the presence and severity of infection also greatly impact the threat to a limb. Therefore, the Society for Vascular Surgery Lower Extremity Guidelines Committee undertook the task of creating a new classification of the threatened lower extremity that reflects these important considerations. We term this new framework, the Society for Vascular Surgery Lower Extremity Threatened Limb Classification System. Risk stratification is based on three major factors that impact amputation risk and clinical management: Wound, Ischemia, and foot Infection (WIfI). The implementation of this classification system is intended to permit more meaningful analysis of outcomes for various forms of therapy in this challenging, but heterogeneous population.
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Hepatitis C viremia and the risk of chronic kidney disease in HIV-infected individuals.
J. Infect. Dis.
PUBLISHED: 07-31-2013
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?The role of active hepatitis C virus (HCV) replication in chronic kidney disease (CKD) risk has not been clarified.
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Preferential HIV infection of CCR6+ Th17 cells is associated with higher levels of virus receptor expression and lack of CCR5 ligands.
J. Virol.
PUBLISHED: 07-31-2013
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Th17 cells are enriched in the gut mucosa and play a critical role in maintenance of the mucosal barrier and host defense against extracellular bacteria and fungal infections. During chronic human immunodeficiency virus (HIV) infection, Th17 cells were more depleted compared to Th1 cells, even when the patients had low or undetectable viremia. To investigate the differential effects of HIV infection on Th17 and Th1 cells, a culture system was used in which CCR6(+) CD4(+) T cells were sorted from healthy human peripheral blood and activated in the presence of interleukin 1? (IL-1?) and IL-23 to drive expansion of Th17 cells while maintaining Th1 cells. HIV infection of these cultures had minimal effects on Th1 cells but caused depletion of Th17 cells. Th17 loss correlated with greater levels of virus-infected cells and cell death. In identifying cellular factors contributing to higher susceptibility of Th17 cells to HIV, we compared Th17-enriched CCR6(+) and Th17-depleted CCR6(-) CD4 T cell cultures and noted that Th17-enriched CCR6(+) cells expressed higher levels of ?4?7 and bound HIV envelope in an ?4?7-dependent manner. The cells also had greater expression of CD4 and CXCR4, but not CCR5, than CCR6(-) cells. Moreover, unlike Th1 cells, Th17 cells produced little CCR5 ligand, and transfection with one of the CCR5 ligands, MIP-1? (CCL4), increased their resistance against HIV. These results indicate that features unique to Th17 cells, including higher expression of HIV receptors and lack of autocrine CCR5 ligands, are associated with enhanced permissiveness of these cells to HIV.
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Missed office visits and risk of mortality among HIV-infected subjects in a large healthcare system in the United States.
AIDS Patient Care STDS
PUBLISHED: 07-19-2013
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Linkage and retention in care soon after HIV diagnosis improves clinical outcomes. Conversely, missed visits after diagnosis are associated with increased mortality in the public care setting. We analyzed mortality among newly diagnosed HIV patients ?18 years old in a large private care setting between 01/01/1997 and 12/31/2009, comparing patients who missed visits in their first year following diagnosis (index period) with those who did not. Patients who died during the index period were excluded. Hazard ratios (HR) for association of missed visits and mortality were obtained by Cox proportional hazards regression, adjusting for patient demographics, CD4+ counts, and AIDS-defining conditions (CDC, 1993) at diagnosis. We also evaluated risk factors of missed visits by multivariable logistic regression. 2811 patients were included, of whom 65% had ?1 missed visit, and 226 patients died during follow-up. Patients with ?1 missed visit had a 71% increased mortality risk (HR=1.71, p=0.001) with 12% increased rate per missed visit (HR=1.12, p<0.001). Factors associated with missed visits were younger age (OR=1.69 compared to 60+ years), Black and Latino race/ethnicity (OR=1.54, 1.48 respectively, compared to Caucasians), injection drug use (OR=2.50 compared to men who have sex with men), and lower CD4+ (OR=1.43 for CD4+ 100-199 cells/?L, OR=1.39 for 50-99 cells/?L, and OR=1.63 for CD4+ <50 cells/?L, compared with CD4+ >500 cells/?L). In an insured patient population, missed visits in the first year of HIV care are common and associated with increased mortality. Early retention in HIV care is critical to improving outcomes.
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Peripheral artery disease and risk of cardiovascular events in patients with coronary artery disease: insights from the Heart and Soul Study.
Vasc Med
PUBLISHED: 07-08-2013
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Among patients with coronary artery disease (CAD), those with peripheral artery disease (PAD) have a greater vulnerability to cardiovascular (CV) events than those with CAD alone. In a prospective cohort study of patients with CAD, we evaluated potential mechanisms that might explain the adverse CV outcomes associated with PAD. We performed a prospective cohort study of 1018 patients with stable CAD who were recruited from 2000 to 2002. Incident symptomatic PAD events were adjudicated during a follow-up period of 7.2 ± 2.6 years. We used Cox proportional hazards models to evaluate the association between incident symptomatic PAD events and subsequent risk of CV events or death. Models were adjusted for demographics, traditional risk factors, inflammation, insulin resistance and health behaviors. Among the 1018 patients, 50 patients who did not report a history of PAD at baseline suffered incident symptomatic PAD events during the follow-up period. Those patients had a higher risk of subsequent CV events and death compared to those who did not develop PAD. After adjustment for traditional risk factors, symptomatic PAD events remained associated with a 70% increased risk of subsequent CV events (adjusted HR 1.7; 95% CI 1.0, 2.9; p = 0.04) and an 80% increased risk of death (adjusted HR 1.8; 95% CI 1.2, 2.7; p = 0.006). Inflammatory biomarkers were the strongest risk factor contributing to the excess risk. In a contemporary cohort of patients with CAD, incident symptomatic PAD events were associated with an increased risk for subsequent CV events. The increased vulnerability to CV events was partially explained by shared CV risk factors and inflammation.
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Vein graft failure.
J. Vasc. Surg.
PUBLISHED: 07-02-2013
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After the creation of an autogenous lower extremity bypass graft, the vein must undergo a series of dynamic structural changes to stabilize the arterial hemodynamic forces. These changes, which are commonly referred to as remodeling, include an inflammatory response, the development of a neointima, matrix turnover, and cellular proliferation and apoptosis. The sum total of these processes results in dramatic alterations in the physical and biomechanical attributes of the arterialized vein. The most clinically obvious and easily measured of these is lumen remodeling of the graft. However, although somewhat less precise, wall thickness, matrix composition, and endothelial changes can be measured in vivo within the healing vein graft. Recent translational work has demonstrated the clinical relevance of remodeling as it relates to vein graft patency and the systemic factors influencing it. By correlating histologic and molecular changes in the vein, insights into potential therapeutic strategies to prevent bypass failure and areas for future investigation are explored.
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Use of web-based shared medical records among patients with HIV.
Am J Manag Care
PUBLISHED: 06-04-2013
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To compare use of 7 shared electronic medical record (SMR) features by adult HIV patients.
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Complication rates after total ankle arthroplasty in one hundred consecutive prostheses.
Int Orthop
PUBLISHED: 05-16-2013
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Total ankle arthroplasty is increasingly used as an alternative to arthrodesis to treat advanced ankle arthritis. However, the outcomes and postoperative complications are poorly described.
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Characterization of the orientation and isometry of Humphreys ligament.
Knee
PUBLISHED: 04-02-2013
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The purpose of this study was to examine the effect of flexion angle on isometry and fiber obliquity of the anterior meniscofemoral ligament (Humphreys ligament (HL)).
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Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease.
J. Vasc. Surg.
PUBLISHED: 03-28-2013
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The n-3 polyunsaturated fatty acids are dietary components derived from fish oil with beneficial cardiovascular effects that may relate in part to anti-inflammatory properties. Peripheral artery disease (PAD) is characterized by a marked proinflammatory state. We hypothesized that the n-3 polyunsaturated fatty acids content of red blood cells (omega-3 index) would be correlated with biomarkers of inflammation and vascular function in a PAD cohort.
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D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury.
FASEB J.
PUBLISHED: 02-13-2013
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Recent evidence suggests that specialized lipid mediators derived from polyunsaturated fatty acids control resolution of inflammation, but little is known about resolution pathways in vascular injury. We sought to determine the actions of D-series resolvin (RvD) on vascular smooth muscle cell (VSMC) phenotype and vascular injury. Human VSMCs were treated with RvD1 and RvD2, and phenotype was assessed by proliferation, migration, monocyte adhesion, superoxide production, and gene expression assays. A rabbit model of arterial angioplasty with local delivery of RvD2 (10 nM vs. vehicle control) was employed to examine effects on vascular injury in vivo. Local generation of proresolving lipid mediators (LC-MS/MS) and expression of RvD receptors in the vessel wall were assessed. RvD1 and RvD2 produced dose-dependent inhibition of VSMC proliferation, migration, monocyte adhesion, superoxide production, and proinflammatory gene expression (IC50?0.1-1 nM). In balloon-injured rabbit arteries, cell proliferation (51%) and leukocyte recruitment (41%) were reduced at 3 d, and neointimal hyperplasia was attenuated (29%) at 28 d by RvD2. We demonstrate endogenous biosynthesis of proresolving lipid mediators and expression of receptors for RvD1 in the artery wall. RvDs broadly reduce VSMC responses and modulate vascular injury, suggesting that local activation of resolution mechanisms expedites vascular homeostasis.
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Clinical consequence of bare metal stent and stent graft failure in femoropopliteal occlusive disease.
J. Vasc. Surg.
PUBLISHED: 02-11-2013
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The optimal role for bare metal stents (BMS) or stent grafts (SG) in femoropopliteal occlusive disease (FPOD) is as of yet undefined. Understanding the clinical consequences of failure can help guide initial treatment decisions. The goal of this study was to define the nature, frequency, and risk factors for adverse clinical events related to BMS and SG failure in FPOD.
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Risk prediction of 30-day readmission after infrainguinal bypass for critical limb ischemia.
J. Vasc. Surg.
PUBLISHED: 02-06-2013
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Hospital readmission after lower extremity bypass is a large cost burden and has become a focal point for policy change directed at disease-specific bundling strategies. The purpose of this study was to evaluate rates and predictors of 30-day readmission from a large, multicenter trial data set.
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Effects of gravitational mechanical unloading in endothelial cells: association between caveolins, inflammation and adhesion molecules.
Sci Rep
PUBLISHED: 01-23-2013
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Mechanical forces including gravity affect endothelial cell (ECs) function, and have been implicated in vascular disease as well as physiologic changes associated with low gravity environments. The goal of this study was to investigate the impact of gravitational mechanical unloading on ECs phenotype as determined by patterns of gene expression. Human umbilical vascular endothelial cells were exposed to 1-gravity environment or mechanical unloading (MU) for 24 hours, with or without periods of mechanical loading (ML). MU led to a significant decrease in gene expression of several adhesion molecules and pro-inflammatory cytokines. On the contrary, eNOS, Caveolin-1 and -2 expression were significantly increased with MU. There was a decrease in the length and width of the cells with MU. Addition of ML during the MU period was sufficient to reverse the changes triggered by MU. Our results suggest that gravitational loading could dramatically affect vascular endothelial cell function.
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Critical appraisal of surgical revascularization for critical limb ischemia.
J. Vasc. Surg.
PUBLISHED: 01-23-2013
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Peripheral artery disease is growing in global prevalence and is estimated to afflict between 8 and 12 million Americans. Its most severe form, critical limb ischemia (CLI), is associated with high rates of limb loss, morbidity, and mortality. Revascularization is the cornerstone of limb preservation in CLI, and has traditionally been accomplished with open surgical bypass. Advances in catheter-based technologies, coupled with their broad dissemination among specialists, have led to major shifts in practice patterns in CLI. There is scant high-quality evidence to guide surgical decision making in this arena, and market forces have exerted profound influences. Despite this, available data suggest that the expected outcomes for both endovascular and open surgery in CLI are strongly dependent on definable patient factors such as anatomic distribution of disease, vein quality, and comorbidities. Optimal patient selection is paramount for maximizing benefit with each technique. This review summarizes some of the existing data and suggests a selective approach to revascularization in CLI, which continues to rely on vein bypass surgery as a primary option in appropriately selected patients.
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Setting high-impact clinical research priorities for the Society for Vascular Surgery.
J. Vasc. Surg.
PUBLISHED: 01-23-2013
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With the overall goal of enhancing the effectiveness and efficiency of vascular care, the Society for Vascular Surgery (SVS) recently completed a process by which it identified its top clinical research priorities to address critical gaps in knowledge guiding practitioners in prevention and treatment of vascular disease. After a survey of the SVS membership, a panel of SVS committee members and opinion leaders considered 53 distinct research questions through a structured process that resulted in identification of nine clinical issues that were felt to merit immediate attention by vascular investigators and external funding agencies. These are, in order of priority: (1) define optimal management of asymptomatic carotid stenosis, (2) compare the effectiveness of medical vs invasive treatment (open or endovascular) of vasculogenic claudication, (3) compare effectiveness of open vs endovascular infrainguinal revascularization as initial treatment of critical limb ischemia, (4) develop and compare the effectiveness of clinical strategies to reduce cardiovascular and other perioperative complications (eg, wound) after vascular intervention, (5) compare the effectiveness of strategies to enhance arteriovenous fistula maturation and durability, (6) develop best practices for management of chronic venous ulcer, (7) define optimal adjunctive medical therapy to enhance the success of lower extremity revascularization, (8) identify and evaluate medical therapy to prevent abdominal aortic aneurysm growth, and (9) evaluate ultrasound vs computed tomographic angiography surveillance after endovascular aneurysm repair.
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Clash of the microbes: lets bring back the good guys.
J. Clin. Invest.
PUBLISHED: 01-16-2013
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A 38-year-old man with a history of HIV infection virologically suppressed on antiretroviral therapy presents to his gastroenterologist for evaluation of iron deficiency anemia and weight loss. A diagnostic colonoscopy demonstrates a two-centimeter ulcerated mass in the cecum. Biopsies of the lesion return moderately differentiated adenocarcinoma that is wild type for the KRAS mutation by real-time PCR.
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Trends and disparities in antiretroviral therapy initiation and virologic suppression among newly treatment-eligible HIV-infected individuals in North America, 2001-2009.
Clin. Infect. Dis.
PUBLISHED: 01-11-2013
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Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes.
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A single nucleotide polymorphism in the p27(Kip1) gene is associated with primary patency of lower extremity vein bypass grafts.
J. Vasc. Surg.
PUBLISHED: 01-09-2013
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Factors responsible for the variability in outcomes after lower extremity vein bypass grafting (LEVBG) are poorly understood. Recent evidence has suggested that a single nucleotide polymorphism (SNP) in the promoter region of the p27(Kip1) gene, a cell-cycle regulator, is associated with coronary in-stent restenosis. We hypothesized an association with vein graft patency.
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HIV infection status, immunodeficiency, and the incidence of non-melanoma skin cancer.
J. Natl. Cancer Inst.
PUBLISHED: 01-04-2013
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Background The incidence of non-melanoma skin cancers (NMSCs), including basal cell (BCC) or squamous cell carcinoma (SCC), is not well documented among HIV-positive (HIV(+)) individuals. Methods We identified 6560 HIV(+) and 36 821 HIV-negative (HIV(-)) non-Hispanic white adults who were enrolled and followed up in Kaiser Permanente Northern California from 1996 to 2008. The first biopsy-proven NMSCs diagnosed during follow-up were identified from pathology records. Poisson models estimated rate ratios that compared HIV(+) (overall and stratified by recent CD4 T-cell counts and serum HIV RNA levels) with HIV(-) subjects and were adjusted for age, sex, smoking history, obesity diagnosis history, and census-based household income. Sensitivity analyses were adjusted for outpatient visits (ie, a proxy for screening). All statistical tests were two-sided. Results The NMSC incidence rate was 1426 and 766 per 100 000 person-years for HIV(+) and HIV(-) individuals, respectively, which corresponds with an adjusted rate ratio of 2.1 (95% confidence interval [CI] = 1.9 to 2.3). Similarly, the adjusted rate ratio for HIV(+) vs HIV(-) subjects was 2.6 (95% CI = 2.1 to 3.2) for SCCs, and it was 2.1 (95% CI = 1.8 to 2.3) for BCCs. There was a statistically significant trend of higher rate ratios with lower recent CD4 counts among HIV(+) subjects compared with HIV(-) subjects for SCCs (P trend < .001). Adjustment for number of outpatient visits did not affect the results. Conclusion HIV(+) subjects had a twofold higher incidence rate of NMSCs compared with HIV(-) subjects. SCCs but not BCCs were associated with immunodeficiency.
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Closing the Gap: Increases in Life Expectancy among Treated HIV-Positive Individuals in the United States and Canada.
PLoS ONE
PUBLISHED: 01-01-2013
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Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000-2007 in the U.S. and Canada.
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Association between U.S. State AIDS Drug Assistance Program (ADAP) Features and HIV Antiretroviral Therapy Initiation, 2001-2009.
PLoS ONE
PUBLISHED: 01-01-2013
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U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes.
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HIV infection, immunodeficiency, viral replication, and the risk of cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 11-22-2011
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Few studies have compared cancer risk between HIV-infected individuals and a demographically similar HIV-uninfected internal comparison group, adjusting for cancer risk factors.
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From wall graft to roof graft: reassessment of femoral posterior cruciate ligament positioning.
Am J. Orthop.
PUBLISHED: 10-25-2011
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In many technique guides for posterior cruciate ligament (PCL) reconstruction, the PCL is depicted on the wall of the medial femoral condyle (MFC). We hypothesized that most of the anterolateral (AL) bundle originates on the roof of the intercondylar notch (ICN), not on the wall. Using a surgical navigation system, we delineated and morphed in the computer the entire PCL footprint-the AL bundle, the posteromedial (PM) bundle, and the Humphrey ligament (HL)-of 7 fresh-frozen cadaveric specimens. A clock face was defined in the en face view, with the 12-oclock axis pointing anteriorly through the top of the notch and the roof being the region between 10 oclock and 2 oclock. The AL-bundle, PM-bundle, and HL positions were calculated in terms of this clock-face definition. Mean centroids (oclock position) over all specimens of AL bundle, PM bundle, and HL were, respectively, 10:49, 9:43, and 9:00 on the left knee and 1:11, 2:17, and 3:00 on the right knee. Mean areas were 63 mm(2) (AL bundle), 63 mm(2) (PM bundle), and 45 mm(2) (HL). In 5 of the 7 specimens tested, 100% of the AL bundle originated on the roof of the ICN. Conversely, 66% of the PM bundle and 100% of the HL inserted on the wall of the MFC rather than on the intercondylar roof. Using computer navigation software, we determined that most of the AL bundle originates on the roof of the ICN and that the PM bundle is centered near the transition between the roof and the wall of the MFC. These findings contradict the depiction in most technique guides for PCL reconstruction. Implant companies and surgeons should modify their techniques to shift PCL graft tunnels from the wall of the MFC to the roof of the ICN.
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Essential components of effective HIV care: a policy paper of the HIV Medicine Association of the Infectious Diseases Society of America and the Ryan White Medical Providers Coalition.
Clin. Infect. Dis.
PUBLISHED: 10-20-2011
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Human immunodeficiency virus (HIV) antiretroviral agents and effective HIV care management transformed HIV disease from a death sentence to a chronic condition for many in the United States. A comprehensive HIV care model was developed to meet the complex needs of HIV patients, with support from the Ryan White program, the Veterans Administration, and others. This paper identifies the essential components of an effective HIV care model. As access to health care expands under the National HIV/AIDS Strategy and the Patient Protection and Affordable Care Act, it will be critical to build upon the HIV care model to realize positive health outcomes for people with HIV infection.
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What opportunities are available for resident involvement in national orthopedic and subspecialty societies?
Orthopedics
PUBLISHED: 09-30-2011
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As physician involvement in health policy grows, there will be an increasing need for future leaders in orthopedics. Interested orthopedic residents may be unaware of opportunities for leadership involvement in professional and subspecialty organizations. This article investigates whether national and subspecialty organizations offer membership to residents, allow residents to participate in committees, and provide opportunities for scholarly activity and mentorship. The authors surveyed 20 national orthopedic professional and subspecialty societies to evaluate the availability and cost of resident membership, meeting attendance and participation, research funding, committee membership, and mentorship opportunities. Each societys Web site was reviewed, and societies were contacted by phone if further inquiry was needed. Of the 20 orthopedic societies surveyed, 11 allowed resident membership. Five of 20 societies allowed residents to serve on committees, with a total of 14 total positions for residents. Four organizations provided formalized mentorship programs to residents. Although opportunities for resident involvement in subspecialty and professional societies are available in the majority of groups surveyed, the Orthopaedic Trauma Association and American Society for Surgery of the Hand provided the most comprehensive collection of opportunities. Residents should also pursue involvement in other organizations that may be more readily accessible, such as local, state, and regional orthopedic and medical societies. Increased resident participation in these organizations may help in increasing the 14 nationally available committee positions for orthopedic residents. Our orthopedic profession and societies should encourage motivated residents to pursue involvement and leadership at the national level.
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An analysis of the hip and knee reconstruction section of the orthopaedic in-training examination.
Orthopedics
PUBLISHED: 09-10-2011
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This article analyzes the hip and knee reconstruction section of the Orthopaedic In-Training Examination (OITE). All of the hip and knee reconstruction questions from 2005 to 2009 were analyzed, and the following data were recorded: number of questions per year in the hip and knee section, total number of questions on the OITE per year, national average score by year in training, references cited, taxonomy classification of each question, topics that were tested, imaging modalities used for a given question, and treatment modalities tested. Eight percent to 9% of the questions on the OITE each year were hip and knee reconstruction-related questions. Performance improved with each year in training, but not by a statistically significant amount. The most commonly tested topics over the past 5 years were anatomy and physiology, ligament and/or gap balancing during total knee arthroplasty (TKA), surgical approaches, properties of polyethylene, periprosthetic fractures about an arthroplasty, and questions dealing with the mechanical properties of implants. In 4 out of 5 years, the majority of questions were classified as Taxonomy 1 (knowledge and recall). The bulk of the questions each year did not require the examinee to interpret a radiograph or make a treatment decision. The most common references cited were from Journal of Bone and Joint Surgery (American), followed by the Journal of Arthroplasty. This detailed analysis of the hip and knee reconstruction section of the OITE should improve resident performance, and may serve as a study tool for the OITE.
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RNA interference-mediated survivin gene knockdown induces growth arrest and reduced migration of vascular smooth muscle cells.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 08-19-2011
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Survivin (SVV) is a multifunctional protein that has been implicated in the development of neointimal hyperplasia. Nuclear SVV is essential for mitosis, whereas in mitochondria SVV has a cytoprotective function. Here, we investigated the effects of RNA interference (RNAi)-mediated SVV knockdown on cell cycle kinetics, apoptosis, migration, and gene expression in primary cultured vascular smooth muscle cells (VSMCs) from the human saphenous vein. Primary Human VSMCs were obtained from saphenous veins and cultured under standard conditions. SVV knockdown was achieved by either small interfering RNA or lentiviral transduction of short hairpin RNA, reducing SVV gene expression by quantitative PCR (>75%, P < 0.01) without a loss of cell viability. Subcellular fractionation revealed that RNAi treatment effectively targeted the nuclear SVV pool, whereas the larger mitochondrial pool was much less sensitive to transient knockdown. Both p53 and p27 protein levels were notably increased. SVV RNAi treatment significantly blocked VSMC proliferation in response to serum and PDGF-AB, arresting VSMC growth. Cell cycle analysis revealed an increased G(2)/M fraction consistent with a mitotic defect; 4,6-diamidino-2-phenylindole staining confirmed an increased frequency of polyploid and abnormal nuclei. In a transwell assay, SVV knockdown reduced migration to PDGF-AB, and actin-phalloidin staining revealed disorganized actin filaments and polygonal cell shape. However, apoptosis (DNA content and annexin V flow cytometry) was not directly induced by SVV RNAi, and sensitivity to apoptotic agonists (e.g., staurosporine and cytokines) was unchanged. In conclusion, RNAi-mediated SVV knockdown in VSMCs leads to profound cell cycle arrest at G(2)/M and impaired chemotaxis without cytotoxicity. The regulation of mitosis and apoptosis in VSMC involves differentially regulated subcellular pools of SVV. Thus, treatment of VSMC with RNAi targeting SVV might limit the response to vascular injury without destabilizing the vessel wall.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.