Asthma, Author Interviews, Biomarkers / 12.06.2018

MedicalResearch.com Interview with: Dr. Supinda Bunyavanich MD Pediatric Allergy and Immunology Physician and researcher at the Icahn School of Medicine. MedicalResearch.com: What is the background for this study? What are the main findings?  Response: In this study, we report on an accurate asthma biomarker we have developed based on a simple nasal brush. Nasal Brush-based Classifier of Asthma Asthma is a chronic respiratory disease that affects 10% of children and adults in the U.S. Mild to moderate asthma can be difficult to diagnose because symptoms change over time and can be complicated by other respiratory conditions. Given the high prevalence of asthma, there is high potential impact of improved diagnostic tools on reducing morbidity and mortality from asthma. Current diagnostic tools for asthma, including spirometry and bronchoscopy, require specialized equipment and expertise to operate properly. Many individuals, particularly young children, have difficulty with pulmonary function testing because it requires, coordinated, forced breaths into a device. Spirometry results are unreliable when done with poor technique. Bronchoscopy is not practical for mild to moderate symptoms. For these reasons, asthma is often diagnosed and managed based on self-reporting of symptoms  This can be unreliable, resulting in repeated doctor visits and even trips to the ER. Thus, a biomarker test for asthma that is easy to implement and interpret is highly desirable for the diagnosis and management of asthma. (more…)
Author Interviews, Biomarkers, Orthopedics / 06.06.2018

MedicalResearch.com Interview with: Rick Sumner, PhD, FAAA The Mary Lou Bell McGrew Presidential Professor for Medical Research Chair, Department of Cell & Molecular Medicine (formerly, Anatomy and Cell Biology) Rush University Medical Center Chicago, IL  60612   MedicalResearch.com: What is the background for this study? What are the main findings? Response: The main cause of failure for total hip replacements is implant loosening which is often a consequence of particle-induced peri-implant osteolysis. Unfortunately, this condition is usually not diagnosed until it has progressed to the point of needing a revision surgery. We discovered two biomarkers that may be useful for identifying at risk patients much earlier than is currently possible. (more…)
Author Interviews, Biomarkers, Prostate Cancer / 03.06.2018

MedicalResearch.com Interview with: James T. Kearns, MD Clinical Fellow, Department of Urology University of Washington School of Medicine Seattle, WA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The effects of the USPSTF recommendation against prostate cancer screening had not been fully characterized among a younger population, particularly with respect to downstream effects such as prostate biopsy, prostate cancer diagnosis, and treatment for prostate cancer. We found that PSA testing decreased in the years surrounding the USPSTF recommendation, but we also found a larger proportionate decrease in prostate biopsy, prostate cancer diagnosis, and use of surgery or radiation for the treatment of prostate cancer. (more…)
Annals Internal Medicine, Author Interviews, Biomarkers, Heart Disease / 22.05.2018

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Biomarkers, Breast Cancer, Technology, University of Michigan / 16.05.2018

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Biomarkers, Brigham & Women's - Harvard, Orthopedics, Pain Research / 11.05.2018

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.  (more…)
Author Interviews, Biomarkers, Heart Disease, JAMA, Race/Ethnic Diversity / 04.05.2018

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 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. (more…)
Author Interviews, Biomarkers, Breast Cancer, JAMA, Radiation Therapy / 03.05.2018

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Biomarkers, Rheumatology, Vanderbilt / 13.03.2018

MedicalResearch.com interview with: Dr. Chase Spurlock, PhD CEO, IQuity, Specialty 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. (more…)
Author Interviews, Biomarkers, Prostate Cancer / 07.03.2018

MedicalResearch.com Interview with: 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%).  (more…)
Author Interviews, Biomarkers, Neurological Disorders, University Texas, Zika / 07.03.2018

MedicalResearch.com Interview with: 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.  (more…)
Author Interviews, Biomarkers, Breast Cancer, Cancer Research, Genetic Research / 26.02.2018

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.  (more…)
ASCO, Author Interviews, Biomarkers, Prostate Cancer / 20.02.2018

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.  (more…)
Author Interviews, Biomarkers, Cancer Research, Gastrointestinal Disease, UT Southwestern / 09.02.2018

MedicalResearch.com Interview with: Amit Singal MD MS David Bruton Jr. Professor in Clinical Cancer Research Associate Professor of Medicine Medical Director of Liver Tumor Program Clinical Chief of Hepatology University of Texas Southwestern  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Hepatocellular carcinoma, the most common form of primary liver cancer, often has a very poor prognosis because most cancers are found at a late stage when curative treatment is not available. However, if the cancer is found early, curative therapies are possible and patients can typically live longer than 5 years. There is currently debate how at-risk patients with chronic liver disease should be screened - with an abdominal ultrasound alone or using a combination of abdominal ultrasound and a blood test called alpha fetoprotein. Many professional societies have traditionally recommended the former, i.e. ultrasound alone, given few data showing a benefit of adding alpha fetoprotein. Our study examines all available literature examining this question and found using the two tests in combination significantly increases the likelihood of finding the cancer at an early stage. Whereas abdominal ultrasound misses over half of all cancers, using it in combination with alpha fetoprotein can detect two-thirds of cancers at an early stage. (more…)
Author Interviews, Biomarkers, CT Scanning, MRI, Prostate Cancer / 07.02.2018

MedicalResearch.com Interview with: Jeremie Calais PhD Ahmanson Translational Imaging Division UCLA Nuclear Medicine Department Los Angeles, CA 90095Jeremie Calais MD Ahmanson Translational Imaging Division UCLA Nuclear Medicine Department Los Angeles, CA 90095  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The only curative treatment for recurrent prostate cancer after radical prostatectomy is salvage radiotherapy. Unfortunately, current standard imaging modalities are too insensitive to visualize the location of the recurrence until it is too late. As a result, salvage radiotherapy is directed to areas only suspected to harbor the recurrence based upon a "best guess" approach according to standard guidelines that define radiotherapy treatment volumes. PSMA PET/CT is a new imaging technique with sensitivity sufficient to detect and localize the recurrent prostate cancer early enough to potentially guide salvage radiotherapy. The first sign of prostate cancer recurrence is a rising PSA. For salvage radiotherapy to be successful, it should be initiated before the PSA rises above 1 ng/mL, and ideally, closer to 0.2 ng/mL or lower. PSMA PET/CT localizes sites of prostate cancer recurrence in up to 70% of patients with low PSA, below < 1.0. In the US it is not yet FDA approved and currently only used for research purposes. In our current study we included 270 patients with early recurrence of prostate cancer after surgery from Germany and UCLA,  we found that 20 % of the patients had at least one lesion detected by  PSMA PET/CT which was NOT covered by the standard radiation fields. Obviously, salvage radiotherapy is only curative if recurrent disease is completely encompassed by the radiotherapy fields and would have failed in these patients. (more…)
ASCO, Author Interviews, Biomarkers, Cancer Research, Gastrointestinal Disease / 02.02.2018

MedicalResearch.com Interview with: Dr. Ana Vivancos PhD, Principal Investigator Cancer Genomics Group Vall d'Hebron Institute of Oncology (VHIO Barcelona  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study was designed to address a key issue in liquid biopsy testing: analytical sensitivity. We know that mutations in plasma of mCRC patients show a wide range in their allelic frequencies (0.01-90%), the biological basis for which remains unclear. We also know that around 35% of cases show very low mutant allele fractions (MAFs), < 1%, therefore highlighting the need of using high sensitivity techniques in the routine lab in order to properly detect mutations. We have compared two different testing methods that are being used in liquid biopsy: Digital PCR (OncoBEAM RAS test, BEAMing) with a limit of detection of 0.02% vs qPCR (Idylla ctKRAS test, Biocartis) with an analytical sensitivity of 1%. Our findings indicate that detection sensitivity decreases for the qPCR based method in cases with low MAF (<1%) and more so when MAF values are very low (<0.01%). (more…)
Author Interviews, Biomarkers, BMJ, Genetic Research, Prostate Cancer, UCSD / 29.01.2018

MedicalResearch.com Interview with: “DNA” by Caroline Davis2010 is licensed under CC BY 2.0Tyler Seibert, MD, PhD Radiation Oncology Center for Multimodal Imaging & Genetics UC San Diego MedicalResearch.com: What is the background for this study? Response: Prostate cancer is an extremely common condition in men. Many die from it each year, and many others live with debilitating pain caused by prostate cancer. Screening for prostate cancer with prostate-specific antigen (PSA) testing can be effective, but there are concerns with the test.
  • First, screening everyone gives a large proportion of false-positive results, and those men end up undergoing unnecessary procedures such as prostate biopsy. S
  • econd, a significant portion of men who develop prostate cancer will develop a slow-growing form of the disease that is likely not life-threatening and may not require treatment. These concerns have led to a drop in prostate cancer screening. But avoiding screening leaves a large number of men vulnerable to diagnosis of an aggressive prostate cancer at a later stage, when it is more difficult—or impossible—to be cured. Doctors are left to guess which of their patients are at risk of aggressive disease and at which age they need to start screening those patients.
Our study sought to develop a tool to provide men and their doctors with objective, personalized information about each man’s risk of prostate cancer. Based on the man’s genetics, we wanted to predict the risk of aggressive prostate cancer and at what age in his life that risk becomes elevated. (more…)
Author Interviews, Biomarkers, Melanoma, Nature / 17.01.2018

MedicalResearch.com Interview with: Daniel S. Peeper, PhD Professor of Functional Oncogenomics (VUmc) Member of Oncode Institute Head, Division of Molecular Oncology & Immunology Chair, Scientific Faculty Council Chair, Translational Research Board The Netherlands Cancer Institute Amsterdam The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: BRAF mutant melanomas are now commonly treated with either immunotherapy or with the combination of BRAFi + MEKi. Recent clinical trials showed that combination checkpoint blockade gives 58% 3 year survival for advanced melanoma. For BRAF+MEKi these numbers are somewhat less impressive. Our study relates to the latter setting. Clearly, most patients treated with this combination do not experience a durable clinical benefit. We showed previously that resistance to these inhibitors is commonly associated with a striking increase in the number of AXL+ cells; this is the rationale for the current study.  (more…)
Author Interviews, Biomarkers, Heart Disease, JACC / 16.01.2018

MedicalResearch.com Interview with: Nick West MA MD FRCP FESC FACC Chief Medical Officer PlaqueTec Ltd MedicalResearch.com: What is the background for the Liquid Biopsy System and this study? Response: Despite huge advances in the diagnosis and treatment of coronary artery disease, this form of cardiovascular disease remains as the world’s number one cause of death. Although interventions such as coronary angioplasty and cholesterol lowering with statins have improved morbidity, patients still experience high rates of recurrent cardiovascular events. Various technologies have been applied to predict future patient events with limited success, such as ‘virtual histology’ intravascular ultrasound (VH-IVUS) in the PROSPECT study (Stone GW et al. N Engl J Med 2011; 364: 226-235). Many experts acknowledge that imaging alone may be insufficient to gauge risk, and that the utility of a more biological endpoint may be more appropriate. This supposition is supported by recent data that added endothelial shear stress estimation to the PROSPECT data and significantly improved subsequent event prediction (Stone PH et al. JACC Cardiovascular Imaging 2017; Sep 18 epub ahead of print). Coronary artery disease has long been recognised to be underpinned by an inflammatory pathogenesis, and it is bioactive molecules (growth factors, cytokines etc) within the vasculature that affect plaque growth, transformation and vulnerability to rupture, resulting in myocardial infarction. Measuring these biomolecules in situ is challenging owing to an inability to reliably sample from the ‘boundary layer’ – a slower-moving circumferential stratum of blood adjacent to the endothelial surface that does not mix with the general bulk flow. The PlaqueTec Liquid Biopsy System™ (LBS) was designed specifically to sample from the boundary layer at four sites simultaneously within the coronary artery, where biomolecules released from plaques are likely to be most concentrated. With the LBS, we can also detect small gradients of released molecules by simultaneously collecting blood both upstream and downstream of individual plaques. The LBS has demonstrated safety and feasibility in preclinical and preliminary clinical studies, and was awarded a CE mark in Europe as a dedicated coronary blood sampling device in 2014. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers, JAMA, MRI / 12.01.2018

MedicalResearch.com Interview with: Miguel A. Santos-Santos, MD Department of Neurology, Memory and Aging Center University of California San Francisco Autonomous University of Barcelona, Cerdanyola del Valles, Spain MedicalResearch.com: What is the background for this study? Response: Primary progressive aphasia (PPA) is a clinically and pathologically heterogeneous (generally Frontotemporal lobar degeneration [FTLD, generally tau or tdp proteinopathies] or Alzheimer’s disease [AD] pathology) condition in which language impairment is the predominant cause of functional impairment during the initial phases of disease. Classification of PPA cases into clinical-anatomical phenotypes is of great importance because they are linked to different prevalence of underlying pathology and prediction of this pathology during life is of critical importance due to the proximity of molecule-specific therapies. The 2011 international consensus diagnostic criteria established a classification scheme for the three most common variants (the semantic [svPPA], non-fluent/agrammatic [nfvPPA], and logopenic [lvPPA]) of PPA and represent a collective effort to increase comparability between studies and improve the reliability of clinicopathologic correlations compared to the previous semantic dementia and progressive non-fluent aphasia criteria included in the 1998 consensus FTLD clinical diagnostic criteria. Since their publication, a few studies have reported amyloid imaging and pathological results in PPA, however most of these studies are retrospective in nature and the prevalence of FTLD and Alzheimer’s disease pathological findings or biomarkers in each variant has been inconsistent across the literature, therefore prospective validation with biomarker and autopsy data remains scarce and highly necessary. (more…)
Author Interviews, Biomarkers, Gastrointestinal Disease / 26.11.2017

MedicalResearch.com Interview with: Iquity IncChase Spurlock, PhD, CEO of IQuity Inc. and Thomas M. Aune, PhD, Co-Founder of IQuity Inc. MedicalResearch.com: Why did you develop IsolateIBS-IBD? Response: Isolate IBS-IBD arose from work started at Vanderbilt University, which found that autoimmune diseases exhibit distinct RNA patterns in blood and that these patterns often are specific for a particular disease. In our longitudinal and cross-sectional studies of many human conditions that span both autoimmune and non-autoimmune disease categories, we found that differences detected at the level of RNA can provide an accurate snapshot of a person’s disease. Using RNA, we can tell at a very early stage if a pattern exists that indicates a specific disease. With this information, providers can initiate treatment plans sooner and have an additional tool in their toolbox when making diagnostic determinations. We developed this test because the symptoms of IBS and IBD are very similar, which can make it difficult and time-consuming for doctors to achieve an accurate diagnosis. IsolateIBS-IBD helps providers distinguish between the two conditions. It shouldn’t be viewed as a replacement or stand-alone test — doctors still need to use it in conjunction with clinical observation combined with traditional tests and procedures like a CT scan or endoscopic examination of the colon — but it can dramatically speed the diagnostic process. IQuity delivers results to providers within seven days of receiving the patient’s sample in the laboratory, allowing doctors to begin discussing a course of treatment as soon as possible.  (more…)
Author Interviews, Biomarkers, JAMA, Stroke / 23.11.2017

MedicalResearch.com Interview with: Pankaj Arora MD, FAHA Assistant Professor, Cardiology Division University of Alabama at Birmingham Section Editor, Circulation: Cardiovascular Genetics American Heart Association  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Natriuretic peptides are hormones produced by the heart in response to increased wall stress in the atria and ventricles. It is well known that blacks have increased prevalence of cardiovascular disease which contributes to racial disparities in outcomes. In the current work, we tested the hypothesis that black race is a natriuretic peptide deficiency state using a stratified random cohort of 4,415 participants selected from the REGARDS study (a national population-based cohort study evaluating racial and geographic disparities in stroke in US adults aged ≥45 years of age or older). Next, we looked for published results on the percentage difference in N-terminal proB-type NP (NTproBNP) levels by race in participants free of cardiovascular disease from other population cohorts. Lastly, we explored whether association of natriuretic peptides with all-cause mortality and CV mortality in apparently healthy individuals from REGARDS differs by race. We found that in multivariable adjustment, NTproBNP levels were up to 27% lower in black individuals as compared with white individuals in the REGARDS study. We pooled our results and found that in meta-analysis of the 3 cohorts, NTproBNP levels were 35% lower in black individuals than white individuals (more than 13,000 individuals in total). Lastly, we found that the higher NTproBNP levels were associated with higher incidence of all-cause mortality, and cardiovascular mortality in healthy blacks and white individuals, and this association did not differ by race. (more…)
Author Interviews, Biomarkers, Brain Injury, JAMA / 21.11.2017

MedicalResearch.com Interview with: Dr. Steven D. Hicks,  M.D., Ph.D Penn State Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous research has shown that small epigenetic molecules called microRNAs are altered in the blood after a traumatic brain injury. Our own pilot research showed that microRNAs were also changed in the saliva after brain injury and that some of these changes mirrored changes in cerebrospinal fluid. In this study we investigated whether salivary microRNA patterns after a concussion could be used to predict the duration and character of symptoms one month after injury. We found that levels of five microRNAs predicted presence of symptoms one month later with greater accuracy (~85%) than standard surveys of symptom burden (~65%). Interestingly, one of the predictive salivary microRNAs (miR-320c) targets pathways involved in synaptic plasticity and was significantly correlated with attention difficulties one month after concussive injury.   (more…)
Author Interviews, Biomarkers, Heart Disease, JAMA / 14.11.2017

MedicalResearch.com Interview with: Dr Andrew R. Chapman BHF Clinical Research Fellow University of Edinburgh Chancellors Building Edinburgh  MedicalResearch.com: What is the background for this study? What are the main findings? Response: High-sensitivity cardiac troponin tests allow accurate measurement of cardiac troponin in the bloodstream. Currently, guidelines recommend we evaluate patients with suspected myocardial infarction using these tests, by looking for levels which are above the upper reference limit (99th centile). These troponin measurements are taken on arrival, and often repeated after admission to hospital up to six hours later. When levels are below this limit, the diagnosis of myocardial infarction is ruled out. However, using such a high limit in patients on arrival to hospital may not be safe, as lower risk stratification thresholds has been shown to reduce missed events,  and in these patients admission to hospital for repeat testing may not be necessary. However, there is no consensus as to the optimal threshold for use in practice. In a worldwide study of 23,000 patients from 9 countries, we have shown when high-sensitivity cardiac troponin I concentrations are below a risk stratification threshold of 5 ng/L at presentation, patients are at extremely low risk of myocardial infarction or cardiac death at 30 days, with fewer than 1 in 200 patients missed. Importantly, this threshold identifies almost 50% of all patients as low risk after a single blood test. As admission or observation of these patients is estimated to cost as much as $11 billion per year in the United States, this strategy has major potential to improve the efficiency of our practice. (more…)
Author Interviews, Biomarkers, Brain Injury, Lancet / 09.11.2017

MedicalResearch.com Interview with: Prof.dr. J van der Naalt PhD Department of Neurology University Medical Center Groningen Groningen, The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Mild traumatic brain injury occurs frequently and is one of the leading cause of morbidity in adults worldwide. It is a major social-economic problem with one in three patients had persistent complaints several months after injury that interfere with resumption of daily activities and work. One of the most important questions concerns the finding that some patients recover without complaints and others do not after sustaining a mild traumatic brain injury. In a follow-up study with more than 1000 participants we found that personality factors are a major factor in the recovery process. In particular coping, that is the way patients adapt to persistent complaints, is important next to emotional distress and impact of the injury. In an add-on study with fMRI we found that in the early phase after injury, the interaction between specific brain networks was temporarily changed. However, when regarding persistent posttraumatic complaints , specific personality characteristics significantly determine long term outcome. (more…)
Author Interviews, Biomarkers, Flu - Influenza, Infections / 01.11.2017

MedicalResearch.com Interview with: Ana Falcón Department of Molecular and Cellular Biology National Center for Biotechnology Spanish National Research Council (CNB-CSIC) Madrid, Spain MedicalResearch.com: What is the background for this study? Response: Influenza A virus (IAV) infection can be severe or even lethal in toddlers, the elderly and patients with certain medical conditions. Infection of apparently healthy individuals nonetheless accounts for many severe disease cases and deaths, suggesting that viruses with increased pathogenicity co-circulate with pandemic or epidemic viruses. IAV virulence and pathogenesis are dependent on complex, multigenic mechanisms involving the viral genetic characteristics, the host conditions, the virus-host interactions, and the host response to the infection. Influenza virus pathogenicity has been studied in depth for many years, and several amino acid changes have been identified as virulence determinants, however, a general pathogenicity determinant has not been characterized. A proportion of influenza virus particles have defective genome RNAs (Defective Viral Genomes-DVGs) due to internal deletions of viral segments. The DVGs have the 3’ and 5’ ends of the parental RNA segments, and most have a single, large central deletion that generates viral RNAs of 180–1000 nucleotides. The presence of DVGs potentiates the host response in cultured cells and in animal models and leads to attenuated infection, possibly through recognition of double-stranded RNA by receptors that activate antiviral signaling cascades. (more…)
Author Interviews, Biomarkers, Heart Disease, JACC, Karolinski Institute / 25.10.2017

MedicalResearch.com Interview with: Martin Holzmann PhD Department of Medicine Functional Area of Emergency Medicine, Karolinska University Hospital, Huddinge Stockholm, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: There has been a few studies in the general population that indicate that subjects with detectable and elevated high-sensitivity troponin T (hs-cTnT) levels have an increased risk of death and cardiovascular disease. However, in clinical practice troponins are not used for anything else than to rule in or rule out myocardial infarction in the emergency department. In addition, in a previous publication we have shown that patients with persistently elevated troponin levels are rarely investigated or followed-up to exclude heart disease. Therefore, we wanted to investigate how the association between different levels of hs-cTnT are associated with outcomes in patients with chest pain but no MI or other acute reasons for having an acutely elevated troponin level. (more…)
Author Interviews, Biomarkers, Prostate Cancer / 24.10.2017

MedicalResearch.com Interview with: Zahava Berkowitz, MSPH, MSc Statistician Division of Cancer Prevention and Control Centers for Disease Control and Prevention MedicalResearch.com: What is the background for this study? Response: The US Preventive Services Task Force 2017 draft prostate cancer screening recommendations  suggest that clinicians inform men aged 55–69 years about the potential benefits and harms of PSA-based screening for prostate cancer. The CDC conducted an analysis using the National Health Interview Surveys in 2005, 2008, 2010, 2013, and 2015 to describe trends in the receipt of routine PSA testing in the past year by age group (40–54, 55–69, ≥70 years) and by risk group. We compared routine PSA screening among higher risk men (defined as African American men or men with a family history of prostate cancer) with other men. The analysis was conducted because CDC wanted to examine how the guidelines affect men at higher risk. The 2017 guideline did not include specific guidelines for African American men who have a higher incidence of prostate cancer than white men, more likely to develop prostate cancer at a young age, more likely to have a high-risk diagnosis and die from prostate cancer. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers, JAMA, Personalized Medicine / 17.10.2017

MedicalResearch.com Interview with: Ingrid S. van Maurik, MSc Department of Neurology and Alzheimer Center Department of Epidemiology and Biostatistics Amsterdam Neuroscience VU University Medical Center Amsterdam, the Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: CSF and MRI biomarkers are increasingly used in clinical practice, but their diagnostic and prognostic value is not perfect. Furthermore, criteria do not specify how to deal with conflicting or borderline results, or how to take patient characteristics into account. Therefore, optimal use of these biomarkers in clinical practice remains challenging. As part of the ABIDE project, we constructed biomarker-based prognostic models (CSF, MRI and combined) that enable prediction of future Alzheimer’s disease, or any type of dementia, in individual patients with mild cognitive impairment. When using these models, any value can be entered for the variables, resulting in personalized probabilities with confidence intervals. (more…)