Sunnybrook Research Institute

Toronto, Canada

Sunnybrook Research Institute

Toronto, Canada

Sunnybrook Research Institute is the research component of Sunnybrook Health science Centre in Toronto, Ontario. It is one of the largest research centres in Canada, second only to the University Health Network within the Toronto Academic Health science Centre Network. SRI is fully affiliated with the University of Toronto.Conducting over $100 million in research every year, SRI is home to a number of breakthroughs that have transformed health care. The research institute supports the activities of over 200 scientists and clinician-scientists, over 200 research associates, engineers, physicists and technicians and over 300 students and trainees that works in 250,000 square feet of state-of-the-art research space in northeastern Toronto. They work to prevent disease and develop treatments that enhance and extend life. These aims derive from SRI’s core vision: to achieve discovery and its translation into clinic to set best practices. Wikipedia.

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News Article | May 22, 2017
Site: www.eurekalert.org

ATS 2017, WASHINGTON, DC-- Obstructive sleep apnea (OSA) may increase the risk of developing atrial fibrillation (AF), according to new research presented at the ATS 2017 International Conference. OSA is characterized by repetitive episodes of shallow or paused breathing during sleep that lead to a drop in blood oxygen level and disrupted sleep. AF is one of the most common cardiac arrhythmias characterized by a rapid and irregular heart beat that can lead to stroke and related heart problems. "There is strong biologic plausibility that obstructive sleep apnea may increase the risk of developing atrial fibrillation through a number of mechanisms," said lead author Tetyana Kendzerska, MD, PhD, assistant professor of medicine at the University of Ottawa in Canada. "There is emerging evidence from animals and smaller studies in humans that OSA may increase the chances of developing AF through oxidative stress, increased sympathetic activity, metabolic abnormalities, endothelial dysfunction and cardiac stretch from intrathoracic pressure swings." Researchers in Canada reviewed the records of 8,256 adults (average age 47) referred with suspected OSA, but free of any physician-diagnosed heart rate abnormalities, including AF at baseline. Participants were followed for up to 13 years. During that time, 173 developed AF resulting in hospitalization. Before controlling for established risk factors for AF, the researchers found that measures of OSA severity such as the number of times an individual partially or completely stopped breathing per hour of sleep and sleep time spent with oxygen saturation lower than normal ( Those who developed AF were more likely to be older, current or former smokers and have a high level of comorbidities. After adjusting for these and other known risk factors, the authors found that oxygen desaturation in sleep, but not the number of times an individual stops breathing, remained a significant predictor of AF hospitalizations. They also found the association between oxygen desaturation and AF hospitalization was stronger in women than men. "Other studies have shown that women with sleep apnea are at greater risk of cardiovascular consequences, including mortality," said senior author Richard S. Leung, MD, PhD, assistant professor of medicine at the University of Toronto. "Greater endothelial dysfunction, higher propensity to develop pulmonary and systemic hypertension and impaired heart rate responses to autonomic challenges in women with OSA may explain these findings, but further studies are needed to confirm this finding and understand the potential mechanisms." In their primary analysis, the researchers did not include hypertension. "Hypertension may be the causal pathway between OSA and AF, so including it might have diminished the association between OSA and AF," Dr. Kendzerska said. "However, in our secondary analysis, we did control for hypertension, and the association between oxygen desaturation and AF remained significant, suggesting that OSA can directly cause AF without the intermediate step of developing hypertension." Study limitations include not having data on adherence to continuous positive air pressure (CPAP) treatment for OSA and whether a participant's hypertension was being treated or not. The authors are now analyzing data connecting OSA to emergency department visits for AF. Sleep Apnea Increases the Risk of New Onset Atrial Fibrillation: A Clinical Cohort Study Authors: T. Kendzerska1, A.S. Gershon2, C. Atzema2, G. Hawker1, R. Leung3; 1University of Toronto - Toronto, ON/CA,2Institute for Clinical Evaluative Sciences, Sunnybrook Research Institute - Toronto, ON/CA, 3St. Michael's Hospital - Toronto, ON/CA RATIONALE: Evidence for a causal relationship between obstructive sleep apnea (OSA) and atrial fibrillation (AF) is limited and conflicting. In subjects free of any arrhythmias at baseline, we examined the association between the severity of OSA and incident AF controlling for known risk factors such as age, sex, smoking status, alcohol dependency/intoxication, prior congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and pulmonary embolism/infarction. Since there is a possible causal relationship between OSA and hypertension, hypertension is in the causal pathway between OSA and AF. Thus, including hypertension in a model would diminish a true association. METHODS: Clinical data on all adults referred with suspected OSA who underwent a first diagnostic sleep study at a large urban academic hospital (Toronto, Canada) between 1994 and 2010 linked to provincial health administrative data from 1991 to 2015 were included. Individuals with any diagnosis of arrhythmias at baseline were excluded. Our primary outcome was incident hospitalization with AF. Cox regressions were used to investigate the longitudinal association between OSA and hospitalized AF. RESULTS: In total, 8,256 subjects were included in our analyses: median age of 47 years, 62% men, median AHI of 15 events per hour, and 28% had AHI>30. Over a median follow-up of 10 years (IQR: 7 - 13 years), 173 participants (2.1%) were hospitalized with AF. Participants with hospitalized AF in follow-up were more likely to be older, men, current or ex-smokers, had a higher level of comorbidities, and more severe OSA as measured by apnea-hypopnea index (AHI) or degree of nocturnal oxygen desaturation. In univariate analyses, AHI > 30 vs. AHI ?30 events/ hour and ? 10 vs. CONCLUSIONS: In a large clinical cohort with suspected OSA free of any arrhythmias at baseline, sleep time spent with oxygen desaturation Figure 1. Results from Cox regression presented as hazard ratios and 95% confidence interval. Session: B98 OSA and Coronary Artery Disease: Are We Save-ing Lives? Abstract Presentation Time: Monday, May 22, 3:15 p.m. ET Location: Walter E. Washington Convention Center, Room 152A-B (Middle Bldg., Street Level)


Systems and methods for generating imaging biomarkers that indicate detectability or conspicuity of lesions that may be present in mammographic images are provided. In general, a task-based measure of a signal-to-noise ratio (SNR) measurement of a detection task is computed over a number of small regions-of-interest (ROIs) in an image, and the computed parameter is used to predict what detection rates should be if a lesion was present in the image. As such, the computed parameter can be used to define an imaging biomarker that is a masking measure that indicates the degree of conspicuity of lesions that may be present in a given a mammographic image.


Patent
Spidertech Inc. and Sunnybrook Research Institute | Date: 2015-08-21

A wound care tape includes a sterile high-stretch strip of woven material having a first face and an opposed second face. A sterile adhesive is on the first face in a discontinuous pattern, whereby a set of spaced apart adhesive-covered portions of the first face are covered by the adhesive, and a set of spaced apart adhesive-free portions of the first face are free of the adhesive.


Patent
Novartis and Sunnybrook Research Institute | Date: 2016-10-12

The present invention relates to a method of treating breast cancer in a human and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a breast cancer treatment method that includes administering 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide, or a pharmaceutically acceptable salt thereof, and (S)-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3,4:6,7] indolizino [1,2-b]quinoline-3,14-(4H,12H)-dione, or a pharmaceutically acceptable salt thereof, to a human in need thereof.


Patent
Sunnybrook Research Institute | Date: 2017-01-04

A system and method for performing a medical procedure is provided. The system includes a device having a shaft that generally extends from a proximal end to a distal end along a longitudinal axis. The distal end of the device is configured to identify a topographical profile of a lumen, wherein the topographical profile is determined by traversing the device a distance along the longitudinal axis of the lumen. The device also includes at least one of a plurality of projections movably coupled to the distal end and configured to provide a coupling with the lumen by extending in a direction substantially orthogonal to the longitudinal axis, and at least one radiopaque marker coupled to the distal end and designed to provide a contrast during imaging of the device.


High-dose glucocorticoids (GCs) can be a useful treatment for aggressive forms of chronic lymphocytic leukemia (CLL). However, their mechanism of action is not well understood, and resistance to GCs is inevitable. In a minimal, serum-free culture system, the synthetic GC dexamethasone (DEX) was found to decrease the metabolic activity of CLL cells, indicated by down-regulation of pyruvate kinase M2 (PKM2) expression and activity, decreased levels of pyruvate and its metabolites, and loss of mitochondrial membrane potential. This metabolic restriction was associated with decreased size and death of some of the tumor cells in the population. Concomitant plasma membrane damage increased killing of CLL cells by DEX. However, the nuclear receptor peroxisome proliferator activated receptor α (PPARα), which regulates fatty acid oxidation, was also increased by DEX, and adipocyte-derived lipids, lipoproteins, and propionic acid protected CLL cells from DEX. PPARα and fatty acid oxidation enzyme inhibitors increased DEX-mediated killing of CLL cells in vitro and clearance of CLL xenografts in vivo. These findings suggest that GCs prevent tumor cells from generating the energy needed to repair membrane damage, fatty acid oxidation is a mechanism of resistance to GC-mediated cytotoxicity, and PPARα inhibition is a strategy to improve the therapeutic efficacy of GCs.


Kerbel R.S.,Sunnybrook Research Institute
Journal of Mammary Gland Biology and Neoplasia | Year: 2012

Viewed as a whole, the aggregate outcomes of a number of positive randomized phase III clinical trial results evaluating the VEGF-pathway targeting antiangiogenic drug bevacizumab, with or without concurrent chemotherapy, in metastatic breast cancer patients have been disappointingly modest. In the case of antiangiogenic tyrosine kinase inhibitors (TKIs) the results have been negative. Nevertheless, several findings indicate antiangiogenic drugs, especially bevacizumab, are active and can lead to demonstrable clinical benefit in some patients, thus stimulating research into developing strategies to significantly improve their efficacy and reduce toxicity. Some of these initiatives include: 1) discovery and validation of predictive markers that can prospectively identify patients more likely to benefit from antiangiogenic therapy; 2) recognition that the nature of the chemotherapy partner or backbone can strongly impact outcomes when combined with antiangiogenic drugs such as bevacizumab, and thus developing what may be improved combination chemotherapy partner regimens, e.g. metronomic chemotherapy; 3) evaluating prospectively in more depth whether subtypes of the disease - especially triple negative or inflammatory breast cancer - are more responsive to antiangiogenic therapy than other subtypes; 4) evaluating new agents that inhibit angiogenesis in a VEGF-independent manner and other types of drug that can be effectively combined with antiangiogenics, e.g. c-met inhibitors; 5) uncovering the basis of resistance or relapse/progression on the therapy with antiangiogenic drugs; 6) development of improved predictive preclinical breast cancer models for therapy testing, e.g. treatment of mice with established multi-organ breast cancer metastatic disease or genetically engineered mouse models of breast cancer, or mice bearing patient derived breast cancer tissue xenografts. © 2012 Springer Science+Business Media, LLC.


Patent
Sunnybrook Research Institute | Date: 2016-06-15

Intravascular imaging catheters are provided that include a distal sheath portion having a lumen that is configured to optionally receive a guidewire or an imaging assembly. The distal sheath portion may be configured to have dimensions such that when a guidewire is inserted through the lumen and extends through a distal exit port, the distal sheath portion may be employed as a microcatheter. External tissue may be imaged at a location at or near the distal end of the catheter, enabling, for example, the controlled imaging of a total occlusion, and the positioning of the distal end (and guidewire) within a true lumen associated with a total occlusion. A structural stop may be provided at or near the distal end of the distal sheath portion to prohibit extension of the imaging assembly out of the distal exit port, while permitting the extension of the guidewire through the distal exit port.


Patent
Sunnybrook Research Institute | Date: 2015-02-26

A system and method for performing a medical procedure is provided. The system includes a device having a shaft that generally extends from a proximal end to a distal end along a longitudinal axis. The distal end of the device is configured to identify a topographical profile of a lumen, wherein the topographical profile is determined by traversing the device a distance along the longitudinal axis of the lumen. The device also includes at least one of a plurality of projections movably coupled to the distal end and configured to provide a coupling with the lumen by extending in a direction substantially orthogonal to the longitudinal axis, and at least one radiopaque marker coupled to the distal end and designed to provide a contrast during imaging of the device.


Patent
Sunnybrook Research Institute | Date: 2016-04-05

The present application provides a multilayer lateral mode coupling method for phased array construction and transducer devices built accordingly. This disclosure describes and demonstrates that the electrical impedance of a phased array can be substantially reduced and readily controlled to be close to the source impedance. The fabrication process is relatively simple and inexpensive. In addition, the elements are robust for use in 1.5, 2, 3 or other dimensional configurations, over an extended period of operation, without structural failure, and providing a high power output required for imaging and/or medical therapy applications.

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