Amyloid Biomarker Predictive of Mortality in Non-STEMI Heart Attack

MedicalResearch.com Interview with:

Prof. Dr. med. Konstantinos Stellos,MD, FAHA, FESC Cardiovascular Research Centre, Institute of Genetic Medicine Newcastle upon Tyne United Kingdom

Prof. Stellos

Prof. Dr. med. Konstantinos Stellos,MD, FAHA, FESC
Cardiovascular Research Centre, Institute of Genetic Medicine
Newcastle upon Tyne
United Kingdom

MedicalResearch.com: What is the background for this study?

 

Response: Risk stratification of patients with a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains a major challenge in clinical cardiology. Risk stratification is important to identify patients at high risk, to whom an early coronary intervention with optimal adjunctive medical therapy shall be applied to reduce that risk. Conversely, it is equally important to identify patients at low risk, to whom a potentially hazardous invasive therapy or a multi-drug administration shall be avoided. Current ACC/AHA and ESC guidelines agree in a standardized approach that uses Global Registry of Acute Coronary Events (GRACE) score, a well validated scoring system, to calculate a patient’s risk and guide triage and management decisions.

Amyloid-β (Aβ) 1-40 and 1-42 peptides (Aβ40 and Aβ42), are proteolytic fragments of a larger protein, the amyloid precursor protein (APP) cleaved by β- and γ-secretases, found in typical brain amyloid deposits in Alzheimer’s disease. Many lines of evidence support a role of Aβ40 in cardiovascular disease as a peptide with pro-inflammatory and pro-thrombotic properties. Most cardiovascular risk factors seem to affect APP metabolism and thus, Aβ production and its soluble circulating APP770 isoform are elevated in patients with ACS_ENREF_15, suggesting a role for Aβ40 in the triggering and outcome of ACS in stable CAD patients. Although vascular inflammation is considered as a hallmark in the pathophysiologic pathways of coronary artery disease (CAD) and novel mechanisms are continuously recognized in its pathogenesis, no inflammatory marker is currently recommended for risk stratification of patients with NSTE-ACS individually or as a component of the GRACE score. This may partly explain the moderate discriminative ability of GRACE score in some studies, especially in older patients and those after early percutaneous coronary intervention (PCI).

In this retrospective study, we used data from two independent prospective cohorts, the Heidelberg study (n=1,145) and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation, n=734) study and determined the clinical prognostic and reclassification value of baseline circulating Aβ40 levels in the prediction of mortality over the GRACE risk score in patients with NSTE-ACS across a median follow-up of 21.9 ( Heidelberg cohort) and 24.9 months (APACE cohort), respectively.

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Can a Pill Plus Infrared Light Replace Mammograms?

MedicalResearch.com Interview with:

Greg Thurber, PhD Assistant Professor Department of Chemical Engineering Assistant Professor Department of Biomedical Engineering University of Michigan 

Dr. Thurber

Greg Thurber, PhD
Assistant Professor
Department of Chemical Engineering
Assistant Professor
Department of Biomedical Engineering
University of Michigan 

MedicalResearch.com: What is the background for this study?

Response: Most current disease screening strategies rely on either blood tests, where the physician can obtain information on specific disease molecules but has no idea where they originated in the body, or anatomical imaging, where the physician can see changes in the structure of tissues but doesn’t have any molecular information. We wanted to develop a method that could provide both molecular information and an image of where these molecules were located. We know from decades of research in cancer that this is a molecular disease, so providing molecular information to the physician will help improve detection and diagnosis. Breast cancer screening provides an excellent opportunity to apply this approach to improve detection. Currently, estimates indicate that we are overspending $4 billion per year on the overdiagnosis and overtreatment of breast cancer because we cannot accurately determine which patients need treatment and which can be safely monitored with no intervention. Despite this problem with overdiagnosis, however, screening saves lives…we simply need a better way.

Molecular imaging has the capability of providing both molecular information and the location within the body. However, most of these techniques are expensive and use ionizing radiation, meaning there is a small risk of actually causing cancer. This is not acceptable for screening large numbers of otherwise healthy patients. To avoid this risk and provide a safe, inexpensive, and relatively easy method for patients to undergo screening, we decided to develop near-infrared fluorescent imaging agents that can be taken as a pill. The goal is for the patient to simply take a pill a day or two before their visit, and then the physician shines near-infrared light on the breast tissue to detect tumors where they ‘light up’ by giving off a different color of light.

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Sciatica: Biomarker Demonstrates Inflammation, Not Just Compression of Nerve Roots

MedicalResearch.com Interview with:

“osteopathic treatment for sciatica” by betterhealthosteopathy is licensed under PDM 3.0Daniel Albrecht, PhD
Research Fellow in Radiology, Harvard Medical School
Research Fellow, Massachusetts General Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A great deal of preclinical work in animal models of pain has established that activation of peripheral immune cells or, in the central nervous system (brain and spinal cord), immune cells called “glia” (microglia and astrocytes) play a key role in the establishment and/or maintenance of persistent pain. For instance, if you pharmacologically block activation of these cells in the nervous system, you are able to reduce/inhibit/prevent pain behaviors, e.g. in animals who have received a nerve injury.

This observation is very exciting, because it suggests that blocking neuroinflammation may be a viable way of treating pain. However, the evidence linking human chronic pain with neuroinflammation has so far been limited.

In this study we show, for the first time, that patients with chronic sciatica (that is, back pain that shoots down the leg) demonstrate elevations in the levels of a protein called the translocator protein (TSPO) in the spinal cord and in the nerve roots.

Because TSPO is a marker of neuroinflammation, our results suggest that sciatica is associated with neuroinflammation.

While on average patients do show elevations in the levels of the TSPO, we also saw significant variability across individuals. Importantly, patients that show stronger elevations (in the nerve roots) were those who benefit the most from receiving a local anti-inflammatory treatment (epidural spinal injection). This makes sense: patients whose nerve roots are inflamed benefit from an anti-inflammatory treatment. Those whose nerve roots aren’t inflamed, don’t receive the same benefit. In the latter case, the source of the inflammation and pain may not be the nerve roots, but may be the spinal cord, or, as we showed in a previous paper (Loggia et al., Brain 2015), the brain.  Continue reading

Specific Types of Inflammation Tied to Cardiovascular Disease

MedicalResearch.com Interview with:

Dr. Karl T. Kelsey, MD, MOH Professor of Epidemiology and Pathology and Laboratory Medicine Fellow, Collegium Ramazzini Providence, R.I. 02912

Dr. Kelsey

Dr. Karl T. Kelsey, MD, MOH
Professor of Epidemiology and Pathology and Laboratory Medicine
Fellow, Collegium Ramazzini
Providence, R.I. 02912

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: ​There is a large literature suggesting that the ratio of neutrophils to lymphocytes (the neutrophil to lymphocyte ratio or NLR) in the peripheral blood at the time of diagnosis is robustly predictive ​of outcome in acute cardiovascular disease.

We were curious to know if the peripheral blood profile and this ratio was a feature of the disease process, since, to our knowledge, this had not been investigated in a prospective study.  Hence, we used the resources of 2 prospective studies to assess this question, the Jackson Heart Study and the Normative Aging Study.  In both cases, the NLR predicted all cause mortality and, in the Jackson Heart Study, where we had well adjudicated outcomes, the NLR predicted various specific cardiovascular outcomes as well. Interestingly, the outcome was also modified by a well known genetic polymorphism of African origin that results in a relative neutropenia.

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Liquid Biopsy Can Guide Radiation Therapy in Early Stage Breast Cancer

MedicalResearch.com Interview with:

Chelain Goodman, MD PhD PGY-3, Radiation Oncology Northwestern University Chicago, IL 60611

Dr. Goodman

Chelain Goodman, MD PhD
PGY-3, Radiation Oncology
Northwestern University
Chicago, IL 60611

MedicalResearch.com: What is the background for this study?

Response: Circulating tumor cells are cancer cells that are shed from the primary tumor into the peripheral blood stream and are hypothesized to be one of the first steps in the initiation of metastatic progression. Prospective studies have demonstrated that approximately 15-25% of patients with early-stage breast cancer can be found to have at least one circulating tumor cell in a small sample of their blood. Currently, all patients with early-stage invasive breast cancer who undergo breast conserving surgery receive adjuvant radiation therapy. In these analyses, we wanted to determine whether presence of circulating tumor cells may be predictive of benefit of radiation therapy following surgery.

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RNA-based Blood Test Can Detect Fibromyalgia

MedicalResearch.com interview with:

Dr. Chase Spurlock, PhD CEO, IQuity, Specialty Diagnostic Technologies Faculty, Vanderbilt University Medical Center

Dr. Chase Spurlock

Dr. Chase Spurlock, PhD
CEO, 
IQuitySpecialty Diagnostic Technologies
Faculty, Vanderbilt University Medical Center

Dr. Spurlock discusses IQuity’s release of IsolateFibromyalgia, the first RNA-based blood test to detect fibromyalgia.

MedicalResearch.com: What is the background for this test? Would you briefly explain what fibromyalgia is, whom it affects and why it has been difficult to definitely diagnosis? 

Dr. Spurlock: We developed the IsolateFibromyalgia™ test using our established RNA assay platform, IQIsolate™, to help clinicians receive timely and accurate information. This technology has evolved from over a decade of research at Vanderbilt University and continues at IQuity funded by both the National Institutes of Health (NIH) as well as private investors. We discovered that differences in RNA expression patterns could be detected in patients with a variety of human conditions spanning infection to more complex inflammatory diseases. With our focus on autoimmune disease, we identified and validated RNAs capable of distinguishing multiple sclerosis, IBS, Crohn’s, ulcerative colitis and fibromyalgia syndrome. In the case of fibromyalgia, our research involved almost 600 subjects including healthy individuals, patients with endocrine conditions, dermatologic conditions and rheumatologic diseases — rheumatoid arthritis, Sjogren’s syndrome and systemic lupus erythematosus. Reported sensitivity and specificity of this assay is 92 percent and 96 percent, respectively.

Fibromyalgia syndrome is characterized by widespread musculoskeletal pain often initially localized to the neck and shoulders. Patients typically describe pain throughout the muscles but may also report pain in the joints. Furthermore, fibromyalgia is usually accompanied by fatigue as well as cognitive disturbance. Patients most afflicted are women between ages 20 and 55. Fibromyalgia affects approximately as many as 6-10 million people in the U.S.

The difficulty in reaching a definitive diagnosis lies in two important issues. First, the cause of the syndrome is unknown, and the way the condition presents and progresses can vary among patients. Secondarily, fibromyalgia syndrome mimics many other conditions due to the multiple nonspecific symptoms associated with fibromyalgia. Patients look well, there are no obvious abnormalities on physical examination other than tenderness, and laboratory and radiologic studies are normal. With no discernable abnormalities in routine clinical laboratory testing or imaging, the diagnosis is based on subjective reporting of symptoms.

The difficulties and complex nature of receiving a correct fibromyalgia diagnosis are apparent. Despite improved awareness among primary care clinicians, many continue to be uncomfortable with making this diagnosis. Fibromyalgia patients on average wait almost a year after experiencing symptoms before seeing a physician and end up visiting on average 3.7 different physicians before a diagnosis. The diagnostic journey can take years. IsolateFibromyalgia provides the clinician and patient actionable information with 94 percent accuracy.

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Low-Intensity PSA-Based Screening Does Not Reduce Prostate Cancer Deaths

MedicalResearch.com Interview with:

Richard Martin Professor of Clinical Epidemiology Head of Section, Clinical Epidemiology & Public Health Population Health Sciences Bristol Medical School 

Prof. Martin

Richard Martin
Professor of Clinical Epidemiology
Head of Section, Clinical Epidemiology & Public Health
Population Health Sciences
Bristol Medical School 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Screening for prostate cancer using the PSA test aims to detect prostate cancer at an early stage, before symptoms develop, when treatment can be offered that may avoid the risks of advanced cancer or may extend life.

Evidence from a large European trial suggests that PSA screening at 2 to 4 yearly intervals could reduce prostate-cancer deaths by 20%. after 13 years of follow-up. However, there are problems with the accuracy of the PSA test and potential harmful consequences. In particular, using the PSA test to screen for prostate cancer results in some tested men being diagnosed with low-risk, harmless cancers that are unlikely to progress or require treatment.  This problem may be particularly exacerbated when using repeated PSA testing as a screening strategy.

The CAP trial offered a one-off PSA test to men aged 50-69 years in the UK. The goal of this low-intensity, one-off PSA testing was to avoid unnecessary screening while still identifying men with high risk, aggressive cancers for whom screening and early detection can reduce morbidity and mortality. However, we found that after an average 10-years of follow-up, the PSA test still detected too many low-risk prostate cancers, while also missing cancers that did need treatment. After an average 10-years of follow-up, the group who had been screened had the same percentage of men dying from prostate cancer as those who had not been screened (0.29%).  Continue reading

Autoantibodies Generated By Zika Virus May Explain Some Consequences of Infection

MedicalResearch.com Interview with:

Slobodan Paessler, D.V.M., Ph.D. Associate Professor, Department of Pathology; Director, Galveston National Laboratory Preclinical Studies Core;  Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity; Member, Center for Biodefense & Emerging Infectious Diseases University of Texas Medical Branch  Galveston, TX

Dr. Paessler

Slobodan Paessler, D.V.M., Ph.D.
Professor, Department of Pathology;
Director, Galveston National Laboratory Preclinical Studies Core;
Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity;
Member, Center for Biodefense & Emerging Infectious Diseases
University of Texas Medical Branch
Galveston, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika virus infection is associated with various developmental issues for human embryos such as reduced head growth, reduced brain tissue growth, and damage to brain or eyes. We wanted to better understand if some of these birth defects are caused directly by the Zika virus or maybe by the host response to infection.

In our study we demonstrate that the Zika virus infection induces autoimmune response against the C1q protein. This protein is a very important immune protein as well as one of the essential proteins for healthy brain development. Attacking the C1q protein upon exposure with the Zika virus could contribute to the development of autoimmune disorders and birth defects.  Continue reading

Genetic Variant of p53 Associated With Poor Breast Cancer Survival

MedicalResearch.com Interview with:
Maureen E. Murphy, Ph.D.
Program Leader and Professor
Molecular and Cellular Oncogenesis and
Subhasree Basu PhD
Postdoctoral researcher
The Wistar Institute
Philadelphia, PA 19104

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Unlike most other genes that are intimately involved in the cause of cancer, the p53 gene displays considerable genetic variation; in other words, p53 is unusual among cancer genes in that the amino acids in p53 protein can frequently differ amongst different populations and ethnic groups. Additionally, unlike most other tumor suppressor genes, when p53 is mutated in a tumor, as it is in 50% of human cancers, that mutant protein now has a positive function in cancer progression, changing tumor metabolism and promoting tumor metastasis.

In this study, the authors analyze for the first time the impact of a common genetic variant in p53 (single nucleotide polymorphism, or SNP) in the ability of mutant p53 to promote tumor metabolism and metastasis, and they find significant differences.  Continue reading

CTC Blood Test Can Reduce Unnecessary Prostate Biopsies in PSA ‘Gray-Zone’

MedicalResearch.com Interview with:
https://cellmaxlife.com/Atul Sharan
Co-Founder & CEO at CellMax 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Approximately 30 million men in the United States take the Prostate-Specific Antigen (PSA) screening test. Recent studies published in the Annals of Internal Medicine have established that PSA screenings have resulted in reduced mortality from prostate cancer. However, the problem with the PSA test is that many patients will receive indeterminate results. Only one in five of patients who have taken the test will have a positive biopsy for prostate cancer, but 33 percent of these patients could suffer from biopsy related side effects, and 1 percent will require hospitalization.

This study showed that the CellMax CTC blood test can predict which patients in the gray zone will need/have a positive prostate biopsy with a much lower false positive rate than current standard of care tests, potentially reducing unnecessary biopsies in this group by up to 90 percent. At the same time, the sensitivity of this test at 80 percent was comparable to the current standard of care tests, meaning this test was also accurate in ruling out biopsy in patients. 

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