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News Article | May 17, 2017
Site: www.eurekalert.org

CLEVELAND - Results from the DAWN stroke trial presented at the European Stroke Organization Conference (ESOC) provide compelling evidence that selected patients suffering a major ischemic stroke recovered significantly better with mechanical retrieval of the blood clot with medical therapy compared with medical therapy alone when initiated past the current guidelines of within 6 hours and up to 24 hours of the stroke. University Hospitals Cleveland Medical Center was one of the top seven recruiting sites in the multi-site study that enrolled a total of 206 patients in the nation. The results showed that patients treated with the retrieval system, known as mechanical thrombectomy, had significantly decreased post-stroke disability and improved functional independence at 90 days compared to medical management alone. "This is incredible," said Cathy Sila, MD, Director of UH's Comprehensive Stroke Center, and principal investigator of the study at the UH site. "Almost half of the patients (48.6 percent) receiving the thrombectomy therapy had a good outcome at 90 days after treatment--defined as the patients being independent in activities of daily living--as opposed to only 13.1 percent of the patients treated medically or with clot-busting drugs alone. This 35 percent difference may be higher than any level of benefit from any stroke trial." "Not only did the patients treated with mechanical thrombectomy dramatically improve during hospitalization, sometimes being able to walk and be discharged to home, but there was also a much lower risk of subsequent neurological worsening because of the poor blood flow to the brain," said Dr. Sila. "The number of patients needed to treat to achieve a good outcome was 2.8. This is a much greater chance of response than what was seen in trials that did not routinely use advanced brain imaging to guide treatment," she said. "We have long believed in the usefulness of MRI scans to define appropriateness of treatment. UH had been using a similar MRI protocol since 2010, five years before the DAWN trial began in 2015." Anthony Furlan, MD, Chairman of the Department of Neurology at UH and Case Western Reserve University School of Medicine, was on the DAWN study's steering committee and helped write the study protocol. "These results provide physicians who treat stroke with evidence of the benefits of thrombectomy even when administered out as far as 24 hours, and should help to make decisions clearer as to which patients to treat," said Dr. Furlan. "These positive outcomes of the DAWN trial represent a major change in patient selection for endovascular therapy for stroke," he said. In the study, researchers used neuroimaging to determine which patients would likely benefit from the procedure. According to Dr. Sila, they would examine how much brain tissue had suffered irreversible damage and how much might be able to be saved. If the amount of damaged tissue were no bigger than the size of a small apricot, researchers believed the patient could benefit from the therapy. Neuro-interventionists would then use a mechanical stent retriever called the Trevo Retriever to remove the blood clot, followed by treatment with the clot-busting medication. The study had been stopped earlier this year after an FDA-approved planned interim review by the independent Data Safety Monitoring Board (DSMB) of data from the first 200 patients enrolled nationally because there was such a dramatic difference between the two arms of the study. The study had been designed to enroll up to a maximum of 500 patients. Dr. Sila said that in Northeast Ohio, we have about 18,000 strokes per year. Stroke survivors commonly experience devastating disabilities and loss of independence due to impaired movement, paralysis, loss of speech and memory. Randomized clinical data has proven the benefit of mechanical thrombectomy with stent retrievers in helping patients with large vessel occlusion strokes, but these devices have only been indicated to reduce disability if used within six hours of stroke onset. "For patients presenting with stroke symptoms beyond six hours, the benefit of clot retrieval using a stent retriever was unknown," said Dr. Furlan. "Now we have evidence that for patients who present to the hospital outside of the six hour time window could have a better chance for an independent life with improved clinical outcomes. Although this is great news, earlier treatment is always better because with stroke 'time is brain.'" The study was supported by Stryker, which produces the Trevo Retriever, a tiny stent-shaped medical device that is attached to a thin wire. The retriever is designed to ensnare the blood clot to remove it from a blood vessel. UH is working with Case Western Reserve University to develop the Cleveland Brain Health Initiative, linking this kind of leading edge neuroscience work from CWRU, UH, Cleveland Clinic, MetroHealth Medical Center and the Louis Stokes Cleveland VA Medical Center to advance progress therapy and treatment of devastating neurological diseases. A video of a UH patient who was in the DAWN trial at: http://www. The DAWN trial is an international, multi-center, blinded endpoint assessment, randomized study. The purpose of the study is to demonstrate superior clinical outcomes at 90 days with Stryker's Trevo Retriever plus medical management compared to medical management alone in appropriately selected patients treated six to 24 hours after last seen well. The Trevo Retriever indication within the DAWN Trial is currently approved for investigational use only by the U.S. Food and Drug Administration in the United States under an Investigational Device Exemption (IDE) study approval. Founded in 1866, University Hospitals serves the needs of patients through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to UHhospitals.org. The Trevo Retriever is a tiny stent-shaped medical device that is attached to a thin wire. In a minimally invasive procedure that utilizes X-ray, the physician navigates the retriever from the femoral artery (located in the upper leg) to the blocked blood artery in the brain. The retriever is designed to ensnare the blood clot and remove it from the body. Originally cleared by the FDA in 2012 for the revascularization of patients experiencing ischemic stroke, the Trevo Retriever has been used in thousands of patients worldwide. Stryker's Trevo Retriever was the only mechanical thrombectomy device used in this trial. An animation of Stryker's Trevo Retriever is available here: https:/ An ischemic stroke occurs when an artery in the brain becomes blocked by a blood clot or other substance such as plaque, a fatty material. Blood vessels carry blood, oxygen and nutrients throughout the body and to the brain. When the brain is deprived of blood and oxygen, it fails to work properly. Depending on the severity of the stroke and the area of the brain affected, loss of brain function or death may occur. According to the World Heart Federation, ischemic stroke contributes to nearly six million deaths around the globe. Stryker is one of the world's leading medical technology companies and, together with our customers, we are driven to make healthcare better. The Company offers a diverse array of innovative products and services in Orthopedics, Medical and Surgical, and Neurotechnology and Spine that help improve patient and hospital outcomes. Stryker is active in over 100 countries around the world. Please contact us for more information at http://www.


CLEVELAND (June 13, 2017) -- A University Hospitals Seidman Cancer Center (UH) study shows TempTraq®, a patented, wearable, Bluetooth® continuous temperature monitor in the form of a soft, comfortable patch, can detect a rise in body temperature up to 180 minutes earlier, in a majority of patient cases, than the current standard-of-care (SOC) method. Earlier fever detection empowers clinicians to intervene faster. The promising results were published in the Journal of Clinical Oncology in conjunction with the ASCO Annual Meeting, which took place last week in Chicago. "This temperature monitoring patch has the potential to improve clinical outcomes for patients undergoing stem cell transplant and intensive chemotherapy for hematological malignancies by identifying neutropenic fever and beginning clinical interventions sooner," said Dr. Ehsan Malek, MD, UH Seidman Cancer Center. "We are looking forward to the next step in our research--implementing this temperature patch in the outpatient stem cell transplant setting." Unlike other devices and methods that provide physicians with only one point of data and offer no continuous monitoring or alerts, this patented device is the ideal, non-invasive, solution for doctors and nurses who need a continuous, smarter way to track, log and respond to fevers quickly. "It has been very exciting for our project team, the bedside nursing staff, and our patients to see this device working in real time," said Nina Dambrosio, MSN CNP, UH Seidman Cancer Center. To study this continuous, real-time method of body temperature measurement, UH tested the feasibility of monitoring body temperature for patients specifically undergoing stem cell transplant or intensive chemotherapy for leukemia. The patches were applied every 24 hours on 10 neutropenic patients throughout their hospital stays. Body temperature was recorded remotely with TempTraq in 10 minute intervals totaling 14,342 temperature measurements, vs the current standard SOC of one measurement every 4 hours. Though it wasn't tested in this study, Blue Spark's TempTraq Connect, a secure, HIPAA-compliant service supported by the Google Healthcare Cloud Platform, will allow the patches to integrate directly with hospital central monitoring systems and electronic health records (EHR) to safely and securely store patient health care data. Nurses can then view the temperature in their system as frequently as needed and can receive real-time audible or visual temperature change alerts at patient bedsides and/or through the central nursing station. Plus, no more waking patients to take their temperatures, and the hygienic, single-use, disposable design eliminates the hassle, time and cost of sterilizing the device between uses. The TempTraq system is scalable and can support a single hospital or a multi-hospital/physician group healthcare system. For more information on TempTraq or the results of this study, please visit http://www. . Headquartered in Westlake, Ohio, Blue Spark Technologies, Inc. is the leader in developing thin, flexible, printed power solutions for printed electronic systems, including solutions developed utilizing their thin, flexible proprietary battery technology. Blue Spark Technologies' latest innovation, TempTraq®, is the only Bluetooth®, wearable temperature monitor in the form of a soft, comfortable patch that continuously, safely and comfortably, monitors body temperature for up to 72 hours and sends alerts to Apple® or Android™ compatible mobile devices. The company's TempTraq Connect HIPAA-compliant service supported by Google Healthcare Cloud Platform allows parents and caregivers to monitor body temperature from anywhere. It also allows direct integration with health care provider electronic health records (EHR) systems and central nursing stations, providing a secure method of storing patient health care data. Founded in 1866, University Hospitals serves the needs of patients through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to UHhospitals.org.


News Article | May 31, 2017
Site: www.eurekalert.org

It may be possible to disrupt harmful blood clots in people at risk for heart attack or stroke without increasing their risk of bleeding, according to a new study published in Nature Communications. The new research out of University Hospitals (UH) Cleveland Medical Center, Case Western Reserve University School of Medicine, and the Cleveland Clinic reveals a previously unknown cell receptor interaction that, when manipulated with therapeutic molecules, safely prevents blood clots. Approximately 100,000 Americans die annually from blood clots, or thrombosis, according to the Centers for Disease Control and Prevention. "We have found a new thrombosis target that does not increase bleeding risk," said senior author Daniel I. Simon, MD, President, UH Cleveland Medical Center, Herman K. Hellerstein Chair of Cardiovascular Research, and Professor of Medicine at Case Western Reserve School of Medicine. "Our discovery indicates that you can identify a new pathway and target that mediates blood clotting, but does not affect our body's natural processes to stop bleeding, called hemostasis." The new pathway centers around a pair of protein receptors that help certain cells interact in inflammation and thrombosis. One receptor--Mac-1--is found on the surfaces of white blood cells recruited to sites of blood vessel injury, and the other--GPIbα--resides on the surfaces of platelets that form clots. When the receptors interact, they trigger cascades of signals that amplify both inflammation and clotting. Mac-1 binding to GPIbα also broadly regulates inflammation in laboratory models of kidney disease, vasculitis, and multiple sclerosis. Simon and colleagues discovered the interaction causes large and small artery clots in mice, but can be blocked by an antibody or a new, therapeutic small molecule that binds to the Mac-1 receptor. The researchers showed genetically engineered mice either without the Mac-1 receptor or with a mutant form could not bind GPIbα on platelets. As a result, the mice had delayed blood clot formation in response to artery injury. Mice exposed to the interfering antibody or small molecule were also unable to form the kinds of blood clots that can lead to stroke or heart attack. While the results showed the Mac-1-GPIbα receptor duo is required for harmful clots, the researchers discovered blocking their interaction with the small molecule had no effect on bleeding risk. Mice exposed to the molecule were still able to successfully stop minor bleeding, like tail cuts, and maintain normal blood coagulation and platelet function. The findings could lead to new medications that stave off heart attacks and strokes without harmful side effects, like excessive bleeding. "Current anti-clotting drugs (anticoagulants, such as warfarin, Xarelto/rivaroxaban, Eliquis/apixaban) and antiplatelet agents (aspirin, Plavix/clopdigorel, Brilinta/ticagrelor) are effective in reducing heart attack and stroke, but are associated with increased bleeding and transfusion," said Dr. Simon. "We have learned that bleeding and transfusion complications are equally as bad from a prognosis standpoint as heart attack or stroke." Simon and colleagues are now pursuing pre-clinical studies using antibodies to further test this novel technology, which according to Dr. Simon "is jointly owned by Case Western Reserve University and University Hospitals, has been licensed to BioMotiv, and is the basis for NEWCO Sujana Biotech." Simon co-founded Sujana Biotech with the study's lead author Yunmei Wang, PhD, Assistant Professor of Cardiovascular Medicine at Case Western Reserve University School of Medicine, and fellow senior author Edward Plow, PhD, Chair of Molecular Cardiology and The Robert C. Tarazi, MD, Endowed Chair in Heart and Hypertension Research at Cleveland Clinic Lerner Research Institute. This work was supported by National Institutes of Health grants to E.P. (P01HL073311 and R01 HL096062) and D.I.S. (R37 HL57506 and R01 HL126645) and a Harrington Discovery Institute Consortium Scholar Award to D.I.S. Founded in 1866, University Hospitals serves the needs of over 1 million patients per year through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, dermatology, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to UHhospitals.org. For more information about Case Western Reserve University School of Medicine, please visit: http://case. .


Vuilleumier P.,University of Geneva | Vuilleumier P.,University Hospitals Geneva Medical Center
Current Opinion in Neurology | Year: 2015

Purpose of review: It is increasingly recognized that affective values associated with visual stimuli can influence visual perception, attention, and eye movements. Recent research has begun to uncover the brain mechanisms mediating these phenomena. The present review summarizes the main paradigms and findings demonstrating emotional and motivational influences on visual processing. Recent findings: Several pathways have been identified for enhancing neural responses of cortical visual areas to stimuli with intrinsic emotional value (e.g., facial expressions, social scenes, and others), including projections from the amygdala and ascending modulatory neurotransmitter systems from the brainstem. These pathways can guide attention and gaze to emotionally salient information with either negative (threatening) or positive (rewarding) associations. In addition, abundant research in recent years suggests that probabilistic reward learning can lead to powerful biases in visual attention and saccade control through subcortical pathways connecting visual areas with basal ganglia and superior colliculus. Time-resolved neuroimaging using electroencephalography or magnetoencephalography has begun to tackle the time course of these effects, and can now be complemented by neuroimaging and neurophysiology recordings in monkey. Summary: These findings have implications for understanding and assessing affective biases in perception and attention in patients with psychiatric disorders, such as phobias, depression, and addiction, but also open new avenues for rehabilitation in neurological patients with attention disorders. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Kaufmann S.H.,Max Planck Institute for Infection Biology | Hussey G.,University of Cape Town | Lambert P.-H.,University Hospitals Geneva Medical Center
The Lancet | Year: 2010

New vaccines are urgently needed if we want to reach the goal of substantially reducing the incidence of tuberculosis by 2050. Despite a steady increase in funding over the past decade, there is still a striking financial shortfall for vaccine research and development for tuberculosis. Yet, around ten vaccine candidates have left the laboratory stage and entered clinical trials. These vaccines are either aimed at replacing the present vaccine, BCG, or at enhancing immunity induced by BCG. However, these pre-exposure candidates are designed for prevention of disease and will therefore neither eradicate the pathogen, nor prevent stable infection. Long-term vaccination strategies need to target these more ambitious goals. Even though vaccine development will have a price, the return of investment will greatly exceed original costs. © 2010 Elsevier Ltd. All rights reserved.


Cosson P.,University Hospitals Geneva Medical Center | Perrin J.,University Hospitals Geneva Medical Center | Bonifacino J.S.,U.S. National Institutes of Health
Trends in Cell Biology | Year: 2013

The transmembrane domains (TMDs) of integral membrane proteins have emerged as major determinants of intracellular localization and transport in the secretory and endocytic pathways. Unlike sorting signals in cytosolic domains, TMD sorting determinants are not conserved amino acid sequences but physical properties such as the length and hydrophilicity of the transmembrane span. The underlying sorting machinery is still poorly characterized, but several mechanisms have been proposed, including TMD recognition by transmembrane sorting receptors and partitioning into membrane lipid domains. Here we review the nature of TMD sorting determinants and how they may dictate transmembrane protein localization and transport. © 2013 Elsevier Ltd.


Dayer J.M.,University Hospitals Geneva Medical Center
Rheumatology (Oxford, England) | Year: 2010

RA is a chronic, debilitating disease in which articular inflammation and joint destruction are accompanied by systemic manifestations including anaemia, fatigue and osteoporosis. IL-6 is expressed abundantly in the SF of RA patients and is thought to mediate many of the local and systemic effects of this disease. Unlike a number of other cytokines, IL-6 can activate cells through both membrane-bound (IL-6R) and soluble receptors (sIL-6R), thus widening the number of cell types responsive to this cytokine. Indeed, trans-signalling, where IL-6 binds to the sIL-6R, homodimerizes with glycoprotein 130 subunits and induces signal transduction, has been found to play a key role in acute and chronic inflammation. Elevated levels of IL-6 and sIL-6R in the SF of RA patients can increase the risk of joint destruction and, at the joint level, IL-6/sIL-6R can stimulate pannus development through increased VEGF expression and increase bone resorption as a result of osteoclastogenesis. Systemic effects of IL-6, albeit through conventional or trans-signalling, include regulation of acute-phase protein synthesis, as well as hepcidin production and stimulation of the hypothalamo-pituitary-adrenal axis, the latter two actions potentially leading to anaemia and fatigue, respectively. This review aims to provide an insight into the biological effects of IL-6 in RA, examining how IL-6 can induce the articular and systemic effects of this disease.


Cvetkovic-Lopes V.,University Hospitals Geneva Medical Center
PloS one | Year: 2010

In a previous study we proposed that the depolarized state of the wake-promoting hypocretin/orexin (hcrt/orx) neurons was independent of synaptic inputs as it persisted in tetrodotoxin and low calcium/high magnesium solutions. Here we show first that these cells are hyperpolarized when external sodium is lowered, suggesting that non-selective cation channels (NSCCs) could be involved. As canonical transient receptor channels (TRPCs) are known to form NSCCs, we looked for TRPCs subunits using single-cell RT-PCR and found that TRPC6 mRNA was detectable in a small minority, TRPC1, TRPC3 and TRPC7 in a majority and TRPC4 and 5 in the vast majority (∼90%) of hcrt/orx neurons. Using intracellular applications of TRPC antibodies against subunits known to form NSCCs, we then found that only TRPC5 antibodies elicited an outward current, together with hyperpolarization and inhibition of the cells. These effects were blocked by co-application of a TRPC5 antigen peptide. Voltage-clamp ramps in the presence or absence of TRPC5 antibodies indicated the presence of a current with a reversal potential close to -15 mV. Application of the non-selective TRPC channel blocker, flufenamic acid, had a similar effect, which could be occluded in cells pre-loaded with TRPC5 antibodies. Finally, using the same TRPC5 antibodies we found that most hcrt/orx cells show immunostaining for the TRPC5 subunit. These results suggest that hcrt/orx neurons are endowed with a constitutively active non-selective cation current which depends on TRPC channels containing the TRPC5 subunit and which is responsible for the depolarized and active state of these cells.


Saurat J.-H.,University Hospitals Geneva Medical Center
Dermatology | Year: 2015

The sequence of events and mechanisms leading to the development of the primary acne lesion, the comedone, is revisited. Recent knowledge obtained both from lineage tracing experiments in the mouse and the pilosebaceous response to xenobiotics in humans provides robust models for further understanding key biological events at the cellular roots of comedogenesis. The focus is set on the LRIG1+ sebaceous stem cells in the isthmus of the pilosebaceous duct. The master switch that transforms a normally functioning sebaceous gland into a microcomedone and the hierarchy of factors involved in this process are reviewed. The key strategic target in acne care appears to be the naïve pilosebaceous follicle that is not involved yet in the acne cycle. The prevention of the comedone switch implies that the key switching factors are adequately controlled in the long term. © 2015 The Author(s) Published by S. Karger AG, Basel.


Sallusto F.,University Hospitals Geneva Medical Center
Annual Review of Immunology | Year: 2016

CD4+ T helper (Th) cells play a central role in the adaptive immune response by providing help to B cells and cytotoxic T cells and by releasing different types of cytokines in tissues to mediate protection against a wide range of pathogenic microorganisms. These functions are performed by different types of Th cells endowed with distinct migratory capacities and effector functions. Here we discuss how studies of the human T cell response to microbes have advanced our understanding of Th cell functional heterogeneity, in particular with the discovery of a distinct Th1 subset involved in the response to Mycobacteria and the characterization of two types of Th17 cells specific for extracellular bacteria or fungi. We also review new approaches to dissect at the clonal level the human CD4+ T cell response induced by pathogens or vaccines that have revealed an unexpected degree of intraclonal diversification and propose a progressive and selective model of CD4+ T cell differentiation. Copyright © 2016 by Annual Reviews. All rights reserved.

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