Off-pump coronary artery bypass surgery is associated with worse arterial and saphenous vein graft patency and less effective revascularization: Results from the veterans affairs randomized on/off bypass (ROOBY) trial
Hattler B.,University of Denver |
Messenger J.C.,University of Denver |
Shroyer A.L.,Northport Veterans Affairs Medical Center |
Collins J.F.,Cooperative Studies Program Coordinating Center |
And 5 more authors.
Circulation | Year: 2012
Background-The Department of Veterans Affairs Randomized On/Off Bypass (ROOBY) trial compared clinical and angiographic outcomes in off-pump versus on-pump coronary artery bypass graft (CABG) surgery to ascertain the relative efficacy of the 2 techniques. Methods and Results-From February 2002 to May 2007, the ROOBY trial randomized 2203 patients to off-pump versus on-pump CABG. Follow-up angiography was obtained in 685 off-pump (62%) and 685 on-pump (62%) patients. Angiograms were analyzed (blinded to treatment) for FitzGibbon classification (A=widely patent, B=flow limited, O=occluded) and effective revascularization. Effective revascularization was defined as follows: All 3 major coronary territories with significant disease were revascularized by a FitzGibbon A-quality graft to the major diseased artery, and there were no new postanastomotic lesions. Off-pump CABG resulted in lower FitzGibbon A patency rates than on-pump CABG for arterial conduits (85.8% versus 91.4%; P=0.003) and saphenous vein grafts (72.7% versus 80.4%; P<0.001). Fewer off-pump patients were effectively revascularized (50.1% versus 63.9% on-pump; P<0.001). Within each major coronary territory, effective revascularization was worse off pump than on pump (all P≤0.001). The 1-year adverse cardiac event rate was 16.4% in patients with ineffective revascularization versus 5.9% in patients with effective revascularization (P<0.001). Conclusions-Off-pump CABG resulted in significantly lower FitzGibbon A patency for arterial and saphenous vein graft conduits and less effective revascularization than on-pump CABG. At 1 year, patients with less effective revascularization had higher adverse event rates. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00032630. © 2012 American Heart Association, Inc.
Choi E.,Northport Veterans Affairs Medical Center
American Journal of Health-System Pharmacy | Year: 2012
Purpose. The pharmacology and pharmacokinetics of the antidepressant vilazodone (approved for U.S. marketing in 2011) are reviewed, with an emphasis on efficacy and safety data from Phase III clinical trials. Summary. Vilazodone (marketed as Viibryd by Forest Pharmaceuticals) is a dualacting serotonergic agent that combines the antidepressant effects of a selective serotonin-reuptake inhibitor (SSRI) with partial serotonin (5-HT)1A-receptor agonist activity. In two published eight-week Phase III trials involving a total of 878 adults with major depressive disorder (MDD), vilazodone use was found to yield significant symptomatic improvements relative to placebo use, as determined by mean changes from baseline in scores on the Hamilton Depression Rating Scale and other widely used clinical assessment instruments. Vilazodone hydrochloride therapy should be initiated at a dosage of 10 mg once daily and incrementally adjusted over 14 days to the recommended target daily dose of 40 mg; for optimal bioavailability and effectiveness, it should be taken after a light or high-fat meal. The adverse effects most commonly reported in clinical trials of vilazodone were diarrhea, nausea, vomiting, and insomnia. Conclusion. Vilazodone is an efficacious and safe new antidepressant for the treatment of MDD. Its relatively high cost and adverse-effect profile, as well as a lack of data demonstrating that vilazodone can produce long-term MDD remission and offer significant advantages over the current standard of care, may limit the usefulness of vilazodone in clinical practice. Copyright © 2012, American Society of Health-System Pharmacists, Inc. All rights reserved.
Lu Z.,State University of New York at Stony Brook |
Wu C.-Y.C.,State University of New York at Stony Brook |
Jiang Y.-P.,State University of New York at Stony Brook |
Ballou L.M.,State University of New York at Stony Brook |
And 4 more authors.
Science Translational Medicine | Year: 2012
Many drugs, including some commonly used medications, can cause abnormal heart rhythms and sudden death, as manifest by a prolonged QT interval in the electrocardiogram. Cardiac arrhythmias caused by drug-induced long QT syndrome are thought to result mainly from reductions in the delayed rectifier potassium ion (K +) current I Kr. Here, we report a mechanism for drug-induced QT prolongation that involves changes in multiple ion currents caused by a decrease in phosphoinositide 3-kinase (PI3K) signaling. Treatment of canine cardiac myocytes with inhibitors of tyrosine kinases or PI3Ks caused an increase in action potential duration that was reversed by intracellular infusion of phosphatidylinositol 3,4,5-trisphosphate. The inhibitors decreased the delayed rectifier K + currents I Kr and I Ks, the L-type calcium ion (Ca 2+) current I Ca,L, and the peak sodium ion (Na +) current I Na and increased the persistent Na + current I NaP. Computer modeling of the canine ventricular action potential showed that the drug-induced change in any one current accounted for less than 50% of the increase in action potential duration. Mouse hearts lacking the PI3K p110α catalytic subunit exhibited a prolonged action potential and QT interval that were at least partly a result of an increase in / NaP. These results indicate that down-regulation of PI3K signaling directly or indirectly via tyrosine kinase inhibition prolongs the QT interval by affecting multiple ion channels. This mechanism may explain why some tyrosine kinase inhibitors in clinical use are associated with increased risk of life-threatening arrhythmias.
Dou Z.,State University of New York at Stony Brook |
Pan J.-A.,State University of New York at Stony Brook |
Dbouk H.A.,Yeshiva University |
Ballou L.M.,State University of New York at Stony Brook |
And 9 more authors.
Molecular Cell | Year: 2013
Autophagy is an evolutionarily conserved membrane trafficking process. Induction of autophagy in response to nutrient limitation or cellular stress occurs by similar mechanisms in organisms from yeast to mammals. Unlike yeast, metazoan cells rely more on growth factor signaling for a wide variety of cellular activities including nutrient uptake. How growth factor availability regulates autophagy is poorly understood. Here we show that, upon growth factor limitation, the p110β catalytic subunit of the class IA phosphoinositide 3-kinases (PI3Ks) dissociates from growth factor receptor complexes and increases its interaction with the small GTPase Rab5. This p110β-Rab5 association maintains Rab5 in its guanosine triphosphate (GTP)-bound state and enhances the Rab5-Vps34 interaction that promotes autophagy. p110β mutants that fail to interact with Rab5 are defective in autophagy promotion. Hence, in mammalian cells, p110β acts as a molecular sensor for growth factor availability and induces autophagy by activating a Rab5-mediated signaling cascade. © 2013 Elsevier Inc.
Truman J.-P.,Health Science University |
Garcia-Barros M.,Health Science University |
Obeid L.M.,Northport Veterans Affairs Medical Center |
Obeid L.M.,Health Science University |
Hannun Y.A.,State University of New York at Stony Brook
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2014
Traditional methods of cancer treatment are limited in their efficacy due to both inherent and acquired factors. Many different studies have shown that the generation of ceramide in response to cytotoxic therapy is generally an important step leading to cell death. Cancer cells employ different methods to both limit ceramide generation and to remove ceramide in order to become resistant to treatment. Furthermore, sphingosine kinase activity, which phosphorylates sphingosine the product of ceramide hydrolysis, has been linked to multidrug resistance, and can act as a strong survival factor. This review will examine several of the most frequently used cancer therapies and their effect on both ceramide generation and the mechanisms employed to remove it. The development and use of inhibitors of sphingosine kinase will be focused upon as an example of how targeting sphingolipid metabolism may provide an effective means to improve treatment response rates and reduce associated treatment toxicity. This article is part of a Special Issue entitled Tools to study lipid functions. © 2013 Elsevier B.V.
Cavanagh M.F.,Northport Veterans Affairs Medical Center |
Lane D.S.,Stony Brook University Medical Center |
Messina C.R.,Stony Brook University Medical Center |
Anderson J.C.,White River Junction Medical Center
Cancer | Year: 2013
BACKGROUND One of 5 nationally funded Centers for Disease Control and Prevention Colorectal Cancer (CRC) Screening Demonstration Programs, Project SCOPE, was conducted at an academic medical center and provided colonoscopy screening at no cost to underserved minority patients from local community health centers. METHODS Established barriers to CRC screening (eg, financial, language, transportation) among the target population were addressed through clinical coordination of care by key project staff. The use of a clinician with a patient navigator allowed for the performance of precolonoscopy "telephone visits" instead of office visits to the gastroenterologist in virtually all patients. The clinician elicited information relevant to making screening decisions (eg, past medical and surgical history, focused review of systems, medication/supplement use, CRC screening history). The patient navigator reduced barriers, including, but not limited to, scheduling, transportation, and physical navigation of the medical center on the day of colonoscopy. RESULTS Preprogram preparation was vital in laying groundwork for the project, yet enhancements to the program were ongoing throughout the screening period. Detailed referral forms from primary care physicians, coupled with information obtained during telephone interviews, facilitated high colonoscopy completion rates and excellent patient satisfaction. Similarly valuable was the employment of a bilingual patient navigator, who provided practical and emotional patient support. CONCLUSIONS Academic medical centers can be efficient models for providing CRC screening to disadvantaged populations. Coordination of care by a preventive medicine department, directing the recruitment, scheduling, prescreening education, and the evaluation and preparation of target populations had an overall positive effect on CRC screening with colonoscopy among patients from a community health center. Cancer 2013;119(15 suppl):2894-904. © 2013 American Cancer Society.
News Article | December 22, 2016
NORTHPORT, N.Y.--(BUSINESS WIRE)--The Northport Veterans Affairs Medical Center (NVAMC) recently completed the replacement of its cooling towers and related chiller plant systems under a federal contract task order awarded in July to National Grid. ConEdison Solutions, a national energy services company, served as prime contractor to National Grid in completion of the project. While incurring no upfront construction expenses, the medical complex expects to reduce its electricity consumption costs by approximately $90,000 per year, while reaping $1 million per year in savings by eliminating rental costs associated with the use of temporary equipment. The 277-acre medical campus consists of a main hospital building and numerous support buildings, providing a full complement of healthcare services to the area’s veteran community. “The Northport Veterans Affairs Medical Center is committed to serving the healthcare needs of Long Island’s veterans in a way that delivers the highest quality of care while remaining mindful of the need to invest our resources in an efficient way,” said Philip Moschitta, Director. “We are grateful to National Grid and ConEdison Solutions for acting swiftly to deliver a long-term, money-saving solution to our center’s cooling and infrastructure needs.” “National Grid congratulates the staff at the Northport VA Medical Center. This is the latest in a series of energy savings and environmentally superior projects at the facility. National Grid is proud to have contributed to making this one of the most energy efficient major medical facilities we serve and to have helped substantially lower its carbon footprint and operating costs,” said Kiel Costella, Manager, Community and Customer Management for National Grid. “As an experienced energy services company with a long history of supporting federal agencies in energy upgrades, our company was proud to have the opportunity to extend our support to the region’s veterans,” said Mark Noyes, President and CEO of ConEdison Solutions. “America’s veterans deserve the best-possible facilities for medical care, and it was gratifying that our company was able to devise a solution to the VA’s cooling and chiller challenges that will both boost the patient environment and the quality of care, while also saving money.” Upon completion and formal acceptance of the project by NVAMC management, the installed equipment becomes property of the U.S. government. At that point, the federal government begins paying for the construction and all other construction-related costs using the annual savings generated by the equipment installations and upgrades. The savings take into account the money saved by reduction of energy costs, reduction of operations and maintenance costs and the elimination of costs, such as rental fees. Under the terms of the Federal Utility Energy Services Contract, ConEdison Solutions’ duties included design, construction, commissioning and measurement and verification of energy savings associated with replacement of the hospital’s cooling towers. In addition to replacing the rooftop towers, ConEdison Solutions also replaced existing vertical risers, four existing condenser water pumps, four existing chilled water pumps, a condenser and chilled water piping connecting the equipment cited above, and a chiller plant controls system. ConEdison Solutions installed equipment with a longer service lifespan that, when paired with an energy-efficient controls system and state of the art engineering design, will improve system performance and overall patient and staff comfort.
Snider A.J.,Northport Veterans Affairs Medical Center |
Snider A.J.,Health Science University
International Journal of Clinical Rheumatology | Year: 2013
Sphingolipids and their metabolizing enzymes are beginning to be recognized as critical mediators in biological processes, specifically in inflammation and autoimmunity. Sphingosine kinases (SKs) and their lipid product sphingosine-1-phosphate (S1P) play essential roles in inflammatory signaling processes, as well as disease development and progression. SKs can be activated by numerous growth factors and cytokines, including TNF-α and IL-1β, leading to the generation of S1P. S1P exerts its biological effects on intracellular and extracellular targets, such as S1P receptors. In addition to roles in inflammatory signaling pathways SKs, S1P and S1P receptors have been implicated in immune cell function and trafficking, specifically in lymphocytes. This review will discuss the contribution of the bioactive sphingolipid S1P, its generating enzyme SK, and its cell surface receptors in the inflammatory and autoimmune diseases systemic lupus erythematosus, arthritis and inflammatory bowel disease. © 2013 Future Medicine Ltd.
Hunanyan A.S.,Northport Veterans Affairs Medical Center |
Petrosyan H.A.,Northport Veterans Affairs Medical Center |
Alessi V.,Northport Veterans Affairs Medical Center |
Arvanian V.L.,Northport Veterans Affairs Medical Center
Journal of Neurophysiology | Year: 2013
Transmission through descending pathways to lumbar motoneurons, although important for voluntary walking in humans and rats, has not been fully understood at the cellular level in contusion models. Major descending pathways innervating lumbar motoneurons include those at corticospinal tract (CST) and ventrolateral funiculus (VLF). We examined transmission and plasticity at synaptic pathways from dorsal (d)CST and VLF to individual motoneurons located in ventral horn and interneurons located in dorsomedial gray matter at lumbar segments after thoracic chronic contusion in adult anesthetized rats. To accomplish this, we used intracellular electrophysiological recordings and performed acute focal spinal lesions during the recordings. We directly demonstrate that after thoracic T10 chronic contusion the disrupted dCST axons spontaneously form new synaptic contacts with individual motoneurons, extending around the contusion cavity, through spared ventrolateral white matter. These detour synaptic connections are very weak, and strengthening these connections in order to improve function may be a target for therapeutic interventions after spinal cord injury (SCI). We found that degradation of scar-related chondroitin sulfate proteoglycans with the enzyme chondroitinase ABC (ChABC) combined with adeno-associated viral (AAV) vector-mediated prolonged delivery of neurotrophin NT-3 (AAV-NT3) strengthened these spontaneously formed connections in contused spinal cord. Moreover, ChABC/ AAV-NT3 treatment induced the appearance of additional detour synaptic pathways innervating dorsomedial interneurons. Improved transmission in ChABC/AAV-NT3-treated animals was associated with increased immunoreactivity of 5-HT-positive fibers in lumbar dorsal and ventral horns. Improved locomotor function assessed with automated CatWalk highlights the physiological significance of these novel connections. © 2013 the American Physiological Society.
Walsh-Irwin C.,Northport Veterans Affairs Medical Center
AACN Advanced Critical Care | Year: 2012
Brugada syndrome can lead to lethal cardiac arrhythmias and is often difficult to diagnose because the ECG can be masked. Abnormal STsegment changes in the precordial leads should be recognized and investigated further. A good history of any syncopal episodes as well as a family history of SCD in young family members can be instrumental in helping identify patients at risk. Patients younger than 45 years with symptoms or with a family history of SCD are predictors of poor outcomes. 13 Psychosocial support and referral to an electrophysiologist, as well as genetic counseling, should be considered. © 2012, AACN.