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St. Louis, MO, United States

Gandillon R.,John Cochran Medical Center
Journal of Clinical Engineering | Year: 2013

Through recent efforts aimed toward standardization of nomenclature for medical devices, the Veteran's Health Administration is now able to leverage a large set of equipment histories to investigate the reliability and usability of particular devices. This type of analysis led to the realization of obvious distinctions between the 4 major manufacturers of infusion pumps, both in failure and use error rates. More importantly, cost and time burdens associated with these failures and errors were calculated, and these numbers show the possible savings associated with using reliability and usability data as a contributing factor in medical equipment acquisitions. Copyright © 2013 Lippincott Williams & Wilkins.

Onken M.D.,University of Washington | Winkler A.E.,University of Washington | Kanchi K.-L.,University of Washington | Chalivendra V.,University of Washington | And 10 more authors.
Clinical Cancer Research | Year: 2014

Purpose: Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison of carcinogen-induced murine and human OSCCs with indolent or metastatic growth yielded results with surprising translational relevance. Experimental Design: Murine OSCC cell lines were subjected to next-generation sequencing (NGS) to define their mutational landscape, to define novel candidate cancer genes, and to assess for parallels with known drivers in human OSCC. Expression arrays identified a mouse metastasis signature, and we assessed its representation in four independent human datasets comprising 324 patients using weighted voting and gene set enrichment analysis. Kaplan-Meier analysis and multivariate Cox proportional hazards modeling were used to stratify outcomes. A quantitative real-time PCR assay based on the mouse signature coupled to a machine-learning algorithm was developed and used to stratify an independent set of 31 patients with respect to metastatic lymphadenopathy. Results: NGS revealed conservation of human driver pathway mutations in mouse OSCC, including in Trp53, mitogen-activated protein kinase, phosphoinositide 3-kinase, NOTCH, JAK/STAT, and Fat1-4. Moreover, comparative analysis between The Cancer Genome Atlas and mouse samples defined AKAP9, MED12L , and MYH6 as novel putative cancer genes. Expression analysis identified a transcriptional signature predicting aggressiveness and clinical outcomes, which were validated in four independent human OSCC datasets. Finally, we harnessed the translational potential of this signature by creating a clinically feasible assay that stratified patients with OSCC with a 93.5% accuracy. Conclusions: These data demonstrate surprising cross-species genomic conservation that has translational relevance for human oral squamous cell cancer. ©2014 AACR.

Klein A.J.,John Cochran Medical Center | Pinto D.S.,Beth Israel Deaconess Medical Center | Gray B.H.,University of South Carolina | Jaff M.R.,Harvard University | And 2 more authors.
Catheterization and Cardiovascular Interventions | Year: 2014

Successful endovascular intervention for femoral-popliteal (FP) arterial disease provides relief of claudication and offers limb-salvage in cases of critical limb ischemia. Technologies and operator technique have evolved to the point where we may now provide effective endovascular therapy for a spectrum of lesions, patients, and clinical scenarios. Endovascular treatment of this segment offers a significant alternative to surgical revascularization, and may confer improved safety for a wide range of patients, not solely those deemed high surgical risk. Although endovascular therapy of the FP segment has historically been hampered by high rates of restenosis, emerging technologies including drug-eluting stents, drug-coated balloons, and perhaps bio-absorbable stent platforms, provide future hope for more durable patency in complex disease. By combining lessons learned from clinical trials, international trends in clinical practice, and insights regarding emerging technologies, we may appropriately tailor our application of endovascular therapy to provide optimal care to our patients. This document was developed to guide physicians in the clinical decision-making related to the contemporary application of endovascular intervention among patients with FP arterial disease. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Kramer J.R.,Houston VA Health Services Research and 38 | Kramer J.R.,Baylor College of Medicine | Hachem C.Y.,Saint Louis University | Kanwal F.,John Cochran Medical Center | And 5 more authors.
Hepatology | Year: 2011

Coinfection with hepatitis A virus (HAV) or hepatitis B virus (HBV) in patients with chronic hepatitis C virus (HCV) is associated with increased morbidity and mortality. The Center for Medicare and Medicaid Services has identified HAV and HBV vaccination as a priority area for quality measurement in HCV. It is unclear to what extent patients with HCV meet these recommendations. We used national data from the Department of Veterans Affairs HCV Clinical Case Registry to evaluate the prevalence and predictors of meeting the quality measure (QM) of receiving vaccination or documented immunity to HAV and HBV in patients with chronic HCV. We identified 88,456 patients who had overall vaccination rates of 21.9% and 20.7% for HBV and HAV, respectively. The QM rates were 57.0% and 45.5% for HBV and HAV, respectively. Patients who were nonwhite or who had elevated alanine aminotransferase levels, cirrhosis, or human immunodeficiency virus were more likely to meet the HBV QM. Factors related to HCV care were also determinants of meeting the HBV QM. These factors included receiving a specialist consult, genotype testing, or HCV treatment. Patients who were older, had psychosis, and had a higher comorbidity score were less likely to meet the HBV QM. With a few exceptions, similar variables were related to meeting the HAV QM. The incidence of superinfection with acute HBV and HAV was low, but it was significantly lower in patients who received vaccination than in those who did not. Conclusion: Quality measure rates for HAV and HBV are suboptimal for patients with chronic HCV. In addition, several patient-related factors and receiving HCV-related care are associated with a higher likelihood of meeting QMs. © 2010 American Association for the Study of Liver Diseases.

Settembre C.,Telethon Institute of Genetics and Medicine | Settembre C.,Baylor College of Medicine | Diwan A.,University of Washington | Diwan A.,John Cochran Medical Center | And 2 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2014

OBJECTIVE - Recent reports of a proatherogenic phenotype in mice with macrophage-specific autophagy deficiency have renewed interest in the role of the autophagy-lysosomal system in atherosclerosis. Lysosomes have the unique ability to process both exogenous material, including lipids and autophagy-derived cargo such as dysfunctional proteins/organelles. We aimed to understand the effects of an atherogenic lipid environment on macrophage lysosomes and to evaluate novel ways to modulate this system. APPROACH AND RESULTS - Using a variety of complementary techniques, we show that oxidized low-density lipoproteins and cholesterol crystals, commonly encountered lipid species in atherosclerosis, lead to profound lysosomal dysfunction in cultured macrophages. Disruptions in lysosomal pH, proteolytic capacity, membrane integrity, and morphology are readily seen. Using flow cytometry, we find that macrophages isolated from atherosclerotic plaques also display features of lysosome dysfunction. We then investigated whether enhancing lysosomal function can be beneficial. Transcription factor EB (TFEB) is the only known transcription factor that is a master regulator of lysosomal biogenesis although its role in macrophages has not been studied. Lysosomal stress induced by chloroquine or atherogenic lipids leads to TFEB nuclear translocation and activation of lysosomal and autophagy genes. TFEB overexpression in macrophages further augments this prodegradative response and rescues several deleterious effects seen with atherogenic lipid loading as evidenced by blunted lysosomal dysfunction, reduced secretion of the proinflammatory cytokine interleukin-1β, enhanced cholesterol efflux, and decreased polyubiquitinated protein aggregation. CONCLUSIONS - Taken together, these data demonstrate that lysosomal function is markedly impaired in atherosclerosis and suggest that induction of a lysosomal biogenesis program in macrophages has antiatherogenic effects. © 2014 American Heart Association, Inc.

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