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Biomarker Assessment in Suspected ACS Could be Practice-changing: BIC-8 Results

An emergency department strategy that uses two biomarkers to triage patients with suspected acute coronary syndrome (ACS) can increase the rate of early, safe hospital discharge, according to results of the Biomarkers in Cardiology 8 (BIC-8) trial.

“This biomarker strategy using a state-of-the-art quantitative troponin assay in combination with an ultrasensitive copeptin assay has the potential to change clinical practice with high patient safety,” said lead investigator Martin Möckel, MD, PhD, from Charité – Universitätsmedizin Berlin, in Berlin, Germany.

“This is the first interventional trial to study whether it is safe to discharge suspected ACS patients who test troponin and copeptin negative at admission. Using this strategy, a high proportion of patients could be discharged early, thus unnecessary treatments and resources could be saved, causing a substantial benefit for patients and health care providers.”

Emergency departments worldwide face increasing overcrowding and patients with signs and symptoms which might be caused by an acute coronary syndrome are very common, even though only around 15% of these patients are ultimately diagnosed with an acute myocardial infarction as the underlying disease, explained Dr. Möckel.

“Rapid rule-out of acute myocardial infarction (MI) is therefore a major clinical need, saving the health care system time and resources and patients unnecessary stress, anxiety and other risks associated with hospitalization.”

Current guidelines recommend that patients receive serial troponin testing to confirm that hospital discharge is appropriate, but this testing delays definitive action, he said.

“The new biomarker copeptin has been shown to be elevated in patients first presenting with acute MI, and when combined with the cardiac troponin biomarker has an excellent negative predictive value for acute MI. However, an early discharge strategy based on combining these two tests has never been assessed prospectively.”

BIC-8, a multicentre, open, randomized, controlled clinical trial included 902 patients with an initial negative troponin test to assess this strategy.

In the experimental arm (n=451), patients with a negative copeptin test (less than 10 pmol/L) were discharged into ambulant care, with a scheduled outpatient visit within 72 hours, while those with a positive copeptin test received standard treatment according to current guidelines.

Among patients in the standard arm (n=451), copeptin results were not available to treating staff and patients were treated according to current guidelines.

At 30 days of follow-up the rate of major adverse cardiovascular events (MACE) was similar in both groups (5.46% in the experimental arm vs 5.5% in the standard arm), but emergency room discharge rates were significantly higher in the experimental arm (66% vs 12%; P < 0.001).

The results support the consideration of a new treatment algorithm in low-to-intermediate risk patients with suspected ACS, said Dr. Möckel.

“Patients with a negative troponin and a negative copeptin result at admission can safely be discharged if the final clinical assessment is consistent with this decision, as long as a timely diagnostic work-up is done in the outpatient setting,” he said.

However, the clinical judgment of the treating physician is of utmost importance, he stressed.

“If his or her final clinical assessment excludes discharge due to high suspicion of ACS, perhaps due to recurrent symptoms or an updated history, the patient should not be discharged despite negative biomarker results.”

Source: EurekAlert!

HSS Uses Grant to Test New MRI Techniques & Biomarkers for Arthritis Prevention Treatments

In recent years, researchers have been frustrated because there are no tools to identify early stages of osteoarthritis and thus no good way to test therapies for preventing or slowing the disease. Now, three institutions have been awarded $1 million from the Arthritis Foundation to validate the use of new MRI (magnetic resonance imaging) techniques and newly identified biomarkers to solve this vexing problem. Hospital for Special Surgery in New York City, University of California-San Francisco (UCSF), and Mayo Clinic in Rochester, Minnesota will share the $1 million.

“There is no magic bullet for treatment of osteoarthritis yet, but once we have a potential oral drug, therapeutic injection, or surgery for treating the disease, we will need a way to identify patients who might need it and follow their response to the treatment,” said Scott Rodeo, M.D., orthopedic surgeon and co-chief of the sports medicine and shoulder service at Hospital for Special Surgery (HSS) and co-principal investigator of the tripartite grant. “Using X-rays to measure joint space narrowing is the gold standard for assessing the presence and progression of osteoarthritis, but X-rays are next to worthless for detecting the early changes of arthritis. This study will help us understand the early factors that lead to the degenerative changes in ACL (anterior cruciate ligament) injured knees.”

Acute ACL injury is a major risk factor for developing osteoarthritis. In the past several years, researchers have discovered that long before osteoarthritic changes in joint space can be detected on X-ray, biochemical changes can be detected in cartilage using newer quantitative MRI techniques. Many studies have also shown that ACL injury is associated with quantifiable changes in biochemical biomarkers that can be detected in synovial fluid (joint fluid), blood, and urine.

The Arthritis Foundation grant will be distributed over one year and then the three grant recipients have made an institutional commitment to provide annual patient follow up after that. Each institution will recruit 25 patients who are at a maximum of 14 days out from tearing their ACL. Patients will be evaluated at baseline, six weeks, six months, 12 months and yearly thereafter with traditional MRI and newer MRI techniques.

Specifically, the new quantitative MRI techniques, developed by researchers at HSS and UCSF, measure T1ρ and T2 values of articular cartilage and the meniscus. Articular cartilage is the smooth cushion that lines the end of the bones where they meet at the joints. The meniscus is a knee structure that spans and cushions the space between the joint surfaces of the thighbone and shinbone. In scientific speak, T1ρ measures proteoglycan depletion, and T2 evaluates abnormal collagen orientation. Proteoglycans are conjugates of proteins and long carbohydrate molecules joined together with sugars.

“Imagine you are playing basketball and you jump up to make a basket, your ability to withstand the load when you come down is a function of proteoglycan,” said Hollis Potter, M.D., chief of the division of magnetic resonance imaging, director of research in the Department of Radiology and Imaging at HSS. “If you pivot and throw the ball to someone else, your ability for your cartilage to withstand that load is a function of the collagen. You need both to be healthy.” Dr. Potter is the HSS site leader of the grant.

At each time point that researchers collect MRI data, they will also collect samples of synovial fluid, blood, and urine from patients and evaluate knee function using surveys such as the Knee Outcome Survey, international knee documentation committee (IKDC) evaluation forms, and Marx Activity Level. These surveys gauge whether a patient has knee impairment; the degree of symptoms such as knee swelling and pain; and how much knee impairment impacts overall well-being, daily living, work, and athletic and social activities. The majority of participants in the study will undergo ACL reconstruction, and surgeons will evaluate these patients arthroscopically at the time of the operation. Clinicians will correlate fluid biomarkers and quantitative MRI results with traditional imaging, clinical, and functional outcomes.

Osteoarthritis is an extremely heterogeneous disorder in terms of the factors that contribute to the loss of joint function. Researchers need to be able to identify where a patient is in the progression of the disease to be able to target specific processes that are responsible for the symptoms and loss of joint function.

“Not everyone who has an ACL tear will develop osteoarthritis, but some do,” said Dr. Rodeo. “The goal is to identify biomarkers that reflect alterations in the joint environment that may be predictive of developing arthritis.” Once these are identified, researchers can test therapies to slow or prevent the disease, which can be crippling and lead to disability.

“There remain many unanswered questions regarding the optimal care of patients with ACL injuries,” said Steven Goldring, M.D., Chief Scientific Officer, St. Giles Chair, Hospital for Special Surgery. “This study is a paradigm of interdisciplinary research that brings together experts in orthopedics, radiology and basic science from multiple leading medical centers with the single goal of developing the most effective therapies to improve outcomes in patients with ACL injuries. The Arthritis Foundation should be congratulated in initiating this groundbreaking program.”

ACL ruptures affect roughly 1 in 3,000 people per year in the United States alone. The cumulative population risk of an ACL injury in people between the ages of 10 and 64 years has been estimated to be 5%, but could be considerably higher. More than 175,000 ACL reconstructions are performed each year in the United States at a cost of $2 billion. Participation in sports that involve pivoting including soccer, basketball, football, and skiing put individuals at higher risk for tearing their ACL.

Source: EurekAlert!

Ruggles Family Foundation and Mr. and Mrs. Rudy L. Ruggles, Jr. Make $1.25M Donation to J. Craig Venter Institute for New Study to Identify and Elucidate Healthy Aging Biomarkers

The J. Craig Venter Institute (JCVI), a not-for-profit genomic research organization, recently announced that the Ruggles Family Foundation and Mr. and Mrs. Rudy L. Ruggles, Jr. have made a $1.25 million donation to JCVI to identify and study biomarkers associated with healthy aging. As part of the four year grant, JCVI will collaborate with the Western Connecticut Health Network (WCHN), located in Danbury, CT.

The study, conducted by a team of scientists and clinicians from JCVI and WCHN, will focus on two groups of elderly individuals aged 65 to 85 years by correlating genetics with a variety of human genomic, gut microbiome and other “omics” profiles and integrating these data with the individuals’ health record. One group will consist of healthy individuals, and the other will have individuals with a variety of diagnosed health conditions. The team will then compare the microbiome and molecular profiles of the healthy aging group with those of the non-healthy aging group to identify biomarker candidates. The investigators hope that in the future these data can be used to develop cost-effective, clinically relevant tests.

“As traditional modes of funding for science become less and less plentiful, the need for informed and supportive philanthropic donors is more important than ever. We are grateful for the support of Rudy and Sara and the Ruggles Family Foundation as this will enable us to better understand what healthy aging looks like at the genomic level,” said J. Craig Venter, Ph.D., JCVI Founder and CEO.

“The time is right for pursuing the complex question of healthy aging given the rapid advances in analytical technologies and the expanding knowledge of the human genome and microbiome and their interactions. JCVI’s capabilities in this realm are unparalleled, and I am confident that this ground breaking study will expand materially the horizons of this area of fundamental understanding,” said Rudy Ruggles, a physicist and Adjunct Professor at JCVI, who is a healthy 74 years old and a participant in this study. He is also Chairman of the Research Advisory Council of WCHN’s Biomedical Research Institute.

According to a United Nations report, in 1950 there were 205 million people worldwide aged 60 or older. By 2000 there were 606 million aged 60 or older, and they project that by 2050 this figure will reach nearly 2 billion people who are 60 or older. Understanding the elderly patient and figuring out modes of intervention to better prevent and treat disease associated with aging will continue to be an important area of research.

In addition to more comprehensively studied human genetic factors, other areas of human health and biology that influence and define healthy aging in humans are emerging. For example, a healthy microbiome (the full complement of microbes that live on and in the human body) interacts with the human immune system establishing protective activities when necessary. Low-grade chronic inflammation in humans is a risk factor for the development of more serious diseases that reduce life spans. New tools and technologies developed since the first sequencing of the human and other genomes are now allowing researchers to explore the human body in more detail than ever before, including identifying biological signatures (biomarkers) indicative and even predictive of healthy aging.

According to JCVI President Karen Nelson, Ph.D., “JCVI’s extensive knowledge in human genomics, comparative genomics and the human microbiome, coupled with the clinical expertise of WCHN, should result in new insights into healthy aging. We are excited to add this new study to our repertoire of ongoing human microbiome studies as it will enhance our knowledge in this important area of research.”

For more information on how to support the genomics research programs at JCVI, contact Katie Collins, 858-200-1847.

Source: The J. Craig Venter Institute

Nodality, Inc. Reports Promising Rheumatoid Arthritis Study Results to Predict Patient Treatment Response to TNF Inhibitors

Nodality, Inc., an innovative biotechnology company advancing discovery, development and use of transformative therapies by revealing functional systems biology, recently announced results of the Company’s comprehensive research study to identify cell markers (biomarkers) of disease activity and treatment success in rheumatoid arthritis (RA) patients. The study findings demonstrated that Nodality’s SCNP technology, which measures functional pathways at the single cell level, can be used to identify biomarkers of responsiveness to treatment with tumor necrosis factor inhibitors (TNFIs). RA affects an estimated two million Americans, and TNFIs constitute the most commonly prescribed therapy. Approximately half of patients respond to treatments such as TNFIs, leaving a substantial unmet need to identify which patients are more likely to respond to current therapies. Optimizing use of currently available therapies could potentially delay tissue damage and progression of disease.

SCNP provides the core technology foundation for Nodality’s programs dedicated to improving clinical medicine by increasing the efficiency of therapeutic R&D programs, enhancing life cycle management for commercialized drugs, and introducing new predictive diagnostics. The study results were featured in an oral presentation titled, Comparison of functional immune signaling profiles in peripheral blood mononuclear cells (PBMC) from rheumatoid arthritis (RA) patients versus healthy donors (HD) using Single Cell Network Profiling (SCNP) (Abstract W7.02.04), at the 15th International Congress of Immunology (ICI) in Milan, Italy, taking place August 22 to 27, 2013. The findings were presented by S. Louis Bridges, Jr., M.D., Ph.D., Marguerite Jones Harbert-Gene V. Ball, MD Professor of Medicine, Director, Division of Clinical Immunology and Rheumatology, University of Alabama School of Medicine.

“Nodality’s research program demonstrates the great promise and potential in gaining a better understanding of disease biology and applying this to the development of prognostic and predictive biomarkers for autoimmune diseases such as RA,” commented Alessandra Cesano, M.D., Ph.D., Chief Medical Officer of Nodality. “I look forward to the final results of this program, one of the most comprehensive of its kind. Our technology, based on immune-biology, can predict which RA patients will respond to specific therapies and reveal the mechanisms of drug resistance, thus informing alternative therapeutic strategies.”

The Nodality research program compares healthy and diseased peripheral blood cells at the single cell level, studying samples obtained through the national Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository (TETRAD). Nodality anticipates completing its research program and announcing the key findings later this year.

Laura Brege, Nodality’s President and Chief Executive Officer, stated, “ICI has provided an important opportunity to showcase one of our key programs in immunology, further validating our broadly enabling SCNP platform. This platform has led to major collaborations in immunology addressing significant unmet needs among patients, as well as new predictive diagnostic modalities in blood cancers. Ultimately, Nodality’s goal is to accelerate and make more efficient the development of new therapeutic agents for serious diseases affecting large patient populations within immunology and oncology, two areas of continuing significant unmet clinical need.”

Additional program results were featured in a second oral presentation at the ICI Congress in a presentation titled, Functional proteomic interrogation of immune cell crosstalk and the effects of cytokine-targeted inhibitors using Single Cell Network Profiling (SCNP) (Abstract W7.02.03).

Source: Nodality, Inc

Researchers Agree that Alzheimer’s Test Results Could be Released to Research Participants

A leading group of Alzheimer’s researchers contends that, as biomarkers to detect signals of the disease improve at providing clinically meaningful information, researchers will need guidance on how to constructively disclose test results and track how disclosure impacts both patients and the data collected in research studies. A survey conducted by a group including experts from the Perelman School of Medicine at the University of Pennsylvania found that a majority of Alzheimer’s researchers supported disclosure of results to study participants. The study is published online in Neurology.

“While this is not a call to immediately tell subjects their biomarker results, it does show that the field is moving to a point where experts want to share valid and meaningful results with participants,” said co-senior author Jason Karlawish, MD, professor of Medicine and Medical Ethics and Health Policy. “As we gain more data on the predictive abilities of these measurements, we will need models and methods to effectively reveal results.”

The study surveyed 139 Alzheimer’s clinical trial leaders and coordinators from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) in April 2012, just before the U.S. Food and Drug Administration approved the amyloid-binding radiotracer known as Amyvid (florbetapir). 73 percent of respondents supported disclosing amyloid imaging results to study participants with mild cognitive impairment, whereas 58 percent supported giving amyloid imaging results to those with normal cognition.

Six themes emerged from the survey, regarding participant preferences and cognition levels, researchers’ requests to develop standardized counseling procedures, participant education, and standardization of data-gathering, and concerns regarding potential harms and benefits to participants, as well as the ways disclosure could impact study results.

Currently, ADNI has a policy to not disclose results to participants, but the survey showed a growing trend of experts who would favor revising this policy. In addition to finding amyloid imaging results valuable, Alzheimer’s experts also valued other biomarker data collected in ADNI, such as spinal fluid tests, PET imaging, and other psychometric tests, suggesting that if amyloid imaging results were allowed to be disclosed, it would likely lead to disclosure of other test results.

Study: Using AD biomarker research results for clinical care [Neurology] 

Source: EurekAlert!