Author Interviews, Biomarkers, Breast Cancer, Technology, University of Michigan / 16.05.2018

MedicalResearch.com Interview with: [caption id="attachment_41768" align="alignleft" width="200"]Greg Thurber, PhD Assistant Professor Department of Chemical Engineering Assistant Professor Department of Biomedical Engineering University of Michigan  Dr. Thurber[/caption] 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.
Author Interviews / 09.05.2018

MedicalResearch.com Interview with: Ryo Nagashio, Ph.D. Department of Molecular Diagnostics School of Allied Health Sciences, Kitasato University Japan. MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Lung cancer is the leading cause of cancer deaths in both men and women in the United States and worldwide. The disease is associated with a poor prognosis because most lung cancers are only diagnosed at an advanced stage. The identification of patients at an early stage of cancer when it can be treated surgically is extremely important to improve prognosis. Current biomarkers for lung cancer include carcinoma embryonic antigen (CEA), sialyl Lewis X antigen (SLX), SCC antigen, and cytokeratin fragment (CYFRA) 21-1, but these are not sensitive enough to detect tumors early. The results of our study provide evidence that the CKAP4 protein may be a novel early sero-diagnostic marker for lung cancer. Across disease stages I-IV, the sensitivities of serum CEA, CYFRA, and SCCa are reported with 30-52, 17-82, and 24-39 percent, respectively. In this study, the sensitivity of serum CKAP4 was 81 percent in the training set and 69 percent in the validation set. These rates are higher than those of the current sero-diagnostic markers. Furthermore, the sensitivity of serum CKAP4 was also high even in stage I non-small cell lung cancer.
Author Interviews, Biomarkers, Heart Disease, JAMA, Race/Ethnic Diversity / 04.05.2018

MedicalResearch.com Interview with: [caption id="attachment_41395" align="alignleft" width="200"]Dr. Karl T. Kelsey, MD, MOH Professor of Epidemiology and Pathology and Laboratory Medicine Fellow, Collegium Ramazzini Providence, R.I. 02912 Dr. Kelsey[/caption] 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.
Author Interviews, Biomarkers, Breast Cancer, JAMA, Radiation Therapy / 03.05.2018

MedicalResearch.com Interview with: [caption id="attachment_41471" align="alignleft" width="130"]Chelain Goodman, MD PhD PGY-3, Radiation Oncology Northwestern University Chicago, IL 60611 Dr. Goodman[/caption] 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.
Author Interviews, Breast Cancer, JNCI, UT Southwestern / 16.04.2018

MedicalResearch.com Interview with: Yingfei Wang, Ph.D. and Weibo Luo, Ph.D. Department of Pathology UT Southwestern Medical Center Dallas TX 75390 MedicalResearch.com: What is the background for this study? Response: Breast cancer is the most commonly diagnosed cancer in women. Tumor metastasis is frequently found in breast cancer patients and causes more than 90% of cancer death. There is currently no cure for this deadly disease. We have known that breast tumor is not supplied with sufficient oxygen (a phenomenon known as hypoxia), which makes breast cancer cells more aggressive and may be responsible for tumor recurrence, metastasis, and therapy resistance. Hypoxia-inducible factor (HIF) is a master regulator frequently detected in the hypoxic regions and switches on many oncogenes needed for breast cancer cells to grow and spread around the body. The role of HIF in gene regulation is precisely controlled and shutting down of HIF’s activity would be a promising strategy for the treatment of metastatic breast cancer.
Author Interviews, Biomarkers, Rheumatology, Vanderbilt / 13.03.2018

MedicalResearch.com interview with: [caption id="attachment_40533" align="alignleft" width="200"]Dr. Chase Spurlock, PhD CEO, IQuity, Specialty Diagnostic Technologies Faculty, Vanderbilt University Medical Center Dr. Chase Spurlock[/caption] 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.
Author Interviews, Biomarkers, Prostate Cancer / 07.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40377" align="alignleft" width="150"]Richard Martin Professor of Clinical Epidemiology Head of Section, Clinical Epidemiology & Public Health Population Health Sciences Bristol Medical School  Prof. Martin[/caption] 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%). 
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. 
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. 
Author Interviews, Biomarkers, Cancer Research, Gastrointestinal Disease, UT Southwestern / 09.02.2018

MedicalResearch.com Interview with: [caption id="attachment_39939" align="alignleft" width="200"]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 Dr. Amit Singal[/caption] 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.
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.
ASCO, Author Interviews, Biomarkers, Cancer Research, Gastrointestinal Disease / 02.02.2018

MedicalResearch.com Interview with: [caption id="attachment_39796" align="alignleft" width="200"]Dr. Ana Vivancos, Principal Investigator Cancer Genomics Group Vall d'Hebron Institute of Oncology (VHIO Barcelona  Dr. Ana Vivancos[/caption] 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%).
Author Interviews, Autism, Nature / 20.01.2018

[caption id="attachment_39400" align="alignleft" width="133"]Indiana University graduate student Di Wu poses for a portrait in Swain Hall on Friday, Dec. 22, 2017. Di Wu credit: James Brosher[/caption] MedicalResearch.com Interview with: Di Wu, Msc PhD candidate at Indiana University Graduate Research Assistant Department of Physics Indiana University Bloomington Linked-in: www.linkedin.com/in/di-wu-3a197373  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Current clinical diagnosis and evaluations of Autism Spectrum Disorder (ASD). has remained subjective in nature. There is a need to have objective assessments for the disorder. We discovered in this study an important motion feature that was unknown before. This feature provides a clear screening of ASD. It gave a remarkable quantitative connection between the way children with ASD move and their psychiatric scores, like the IQ score and the Vineland Adaptive Behavior Scale. This connection we captured suggests that the motor feature may be an essential core feature characterizing ASD deficits, as well as neurodevelopment in general.
Author Interviews, Biomarkers, Heart Disease, JACC / 16.01.2018

MedicalResearch.com Interview with: [caption id="attachment_39310" align="alignleft" width="300"]The PlaqueTec Liquid Biopsy System™ (LBS) The PlaqueTec Liquid Biopsy System™ (LBS)[/caption] 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.
Author Interviews, Heart Disease / 19.12.2017

MedicalResearch.com Interview with: [caption id="attachment_38914" align="alignleft" width="140"]David A. Bluemke, MD PhD, MsB Professor, Radiology Editor in Chief (2018), Radiology University of Wisconsin-Madison, School of Medicine and Public Health Madison WI 53792 Dr. Bluemke[/caption] David A. Bluemke, MD PhD, MsB Professor, Radiology Editor in Chief (2018), Radiology University of Wisconsin-Madison, School of Medicine and Public Health Madison WI 53792  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Heart failure is expected to markedly increase in the United States, because of the aging population (https://www.ncbi.nlm.nih.gov/pubmed/23616602. For patients with congestive heart failure, NT-proBNP is an excellent marker of disease severity. The presence of elevated levels of NT-proBNP also predicts future cardiac events. For individuals who do not have clinically diagnosed heart failure, the significance of small elevations in NT-proBNP is not known. We hypothesized that these small elevations were related to subclinical elevations in myocardial wall stress. However, in patients with advanced heart disease, we do know that greater myocardial wall stress is associated with histological evidence of fibrosis --- i.e., replacement of myocardial muscle by greater fibrotic tissue. New techniques using MRI can find evidence of expansion of the space between myocytes (the extracellular volume). The most common cause of this expansion is diffuse myocardial fibrosis/ collagen deposition. Using MRI to detect myocardial fibrosis is an advance because MRI is non-invasive (we would not otherwise perform myocardial biopsy for patients without clinically evident disease). Thus we can use MRI to probe the actual composition of myocardial tissue. Using MRI, we found evidence that individuals in the community (in the MESA study) who had small elevations of NT-proBNP also have evidence of myocardial fibrosis.   The mean NT-proBNP levels in the MESA study (1,334 study subjects) was 65 pg/ml. That level is considered to be normal; levels of NT-proBNP of 1200 pg/ ml or greater are found in patients with congestive heart failure. Of note, the relationship between elevations of NT-proBNP and myocardial fibrosis were independent of multiple risk factors such as age, gender, smoking status, blood pressure, cholesterol levels and diabetes. That is, if the NT-proBNP level was slightly higher (for example, due to increased wall stress), then MRI found an association with greater myocardial fibrosis.
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. 
Author Interviews, Biomarkers, JAMA, Stroke / 23.11.2017

MedicalResearch.com Interview with: [caption id="attachment_38470" align="alignleft" width="149"]Pankaj Arora MD, FAHA Assistant Professor, Cardiology Division University of Alabama at Birmingham Section Editor, Circulation: Cardiovascular Genetics American Heart Association Dr. Arora[/caption] 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.
Author Interviews, Biomarkers, Brain Injury, JAMA / 21.11.2017

MedicalResearch.com Interview with: [caption id="attachment_38373" align="alignleft" width="153"]Dr. Steven D. Hicks,  M.D., Ph.D Penn State Health Dr. Hicks[/caption] 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.  
Author Interviews, Biomarkers, Heart Disease, JAMA / 14.11.2017

MedicalResearch.com Interview with: [caption id="attachment_38279" align="alignleft" width="112"]Dr Andrew R. Chapman BHF Clinical Research Fellow University of Edinburgh Chancellors Building Edinburgh  Dr. Chapman[/caption] 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.
Author Interviews, Biomarkers, Brain Injury, Lancet / 09.11.2017

MedicalResearch.com Interview with: [caption id="attachment_38107" align="alignleft" width="200"]Prof.dr. J van der Naalt PhD Department of Neurology University Medical Center Groningen Groningen, The Netherlands Prof J van der Naalt[/caption] 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.
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.
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.
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.
Author Interviews, Biomarkers, Brain Injury, JAMA / 01.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36257" align="alignleft" width="200"]Dr-Adrian-Harel.jpg Dr. Adrian Harel[/caption] Dr. Adrian Harel, PhD Chief Executive Officer Medicortex Finland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Every 15 seconds, someone in the United States suffers a new head injury. Of the 2.5M people treated in hospital emergency rooms each year, 80,000 become permanently disabled because of TBI. Currently, there are no reliable diagnostic tests to assess the presence or severity of an injury on-site, nor are there any pharmaceutical therapies that could stop the secondary injury from spreading. Accurate diagnostics would benefit especially mild cases of TBI (concussions), which, if occurring repeatedly, may cause neurodegenerative conditions such as Chronic Traumatic Encephalopathy (which is typical for athletes in NFL and Ice-hockey). We have performed extensive preclinical research comparing fluid biopsies from normal and injured lab animals. The results showed some unique biomarkers released as a biodegradation products after head injury. The data served as the basis and confirmation for our patent applications to protect the biomarker concept. Medicortex has completed a clinical proof-of-concept trial in collaboration with Turku University Hospital (Tyks). Samples from 12 TBI patients and 12 healthy volunteers were collected and analyzed for the presence and for the level of the biomarker in state-of-the-art laboratories. The study demonstrated the diagnostic potential of the new biomarker in humans and it confirmed the prior preclinical findings. This was a significant milestone for Medicortex.
Author Interviews, Biomarkers, Critical Care - Intensive Care - ICUs, PLoS, Surgical Research / 27.07.2017

MedicalResearch.com Interview with: [caption id="attachment_36177" align="alignleft" width="200"]Dr. Joanna Shepherd Centre for Trauma Sciences Blizard Institute Queen Mary, University of London Dr. Shepherd[/caption] Dr. Joanna Shepherd Centre for Trauma Sciences Blizard Institute Queen Mary, University of London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Recent advances in resuscitation and treatment of life-threatening critical injuries means that patients with previously unsurvivable injuries are now surviving to reach hospital.  However, many of these patients develop Multiple Organ Dysfunction Syndrome (MODS), which is a failure of several organs including the lung, heart, kidney, and liver. We studied immune cell genes in the blood of critically injured patients within the first few minutes to hours after injury, a period called the ‘hyperacute window’. We found a small and specific response to critical injury during this window that then evolved into a widespread immune reaction by 24 hours.  The development of MODS was linked to changes in the hyperacute window, with central roles for innate immune cells (including natural killer cells and neutrophils) and biological pathways associated with cell death and survival.  By 24 hours after injury, there was widespread immune activation present in all critically injured patients, but the MODS signal had either reversed or disappeared.
Author Interviews, Biomarkers, Brain Injury / 10.07.2017

MedicalResearch.com Interview with: [caption id="attachment_35842" align="alignleft" width="200"]Dr Lisa J Hill PhD Institute of Inflammation and Ageing Research Fellow Neuroscience and Ophthalmology Institute of Inflammation and Ageing College of Medical and Dental Sciences University of Birmingham UK Dr. Hill[/caption] Dr Lisa J Hill PhD Institute of Inflammation and Ageing Research Fellow Neuroscience and Ophthalmology Institute of Inflammation and Ageing College of Medical and Dental Sciences University of Birmingham UK  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Traumatic brain injury (TBI) is the leading cause of death and disability among young adults and, according to the World Health Organization, by 2020 TBI will become the world’s leading cause of neurological disability across all age groups.  Early and correct diagnosis of traumatic brain injury is one of the most challenging aspects faced by clinicians. Being able to detect compounds in the blood that help to determine how severe the brain injury is would be of great benefit to patients and aid in their treatment.  Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins.  The discovery of reliable biomarkers for the management of TBI would improve clinical interventions. We collected blood samples from 30 injured patients within the first hour of injury prior to the patient arriving at hospital and analysed them. Analysis of protein biomarkers from blood taken within the first hour of injury has never been carried out until now. We used a panel of 92 inflammation-associated human proteins when analysing the blood samples. The analysis identified three inflammatory proteins, known as CST5, AXIN1 and TRAIL, as novel biomarkers of TBI.
AACR, Author Interviews, Biomarkers, Cancer Research, Prostate Cancer / 15.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35328" align="alignleft" width="138"]Dr. Yong-Jie Lu Reader in Medical Oncology Centre for Molecular Oncology Barts Cancer Institute - a CR-UK Centre of Excellence Queen Mary University of London John Vane Science Centre, Charterhouse Square, LONDON Dr. Yong-Jie Lu[/caption] Dr. Yong-Jie Lu MBBS, MD, PhD Reader in Medical Oncology Centre for Molecular Oncology Barts Cancer Institute - a CR-UK Centre of Excellence Queen Mary University of London John Vane Science Centre, Charterhouse Square London MedicalResearch.com: What is the background for this study? Response: Identifying/monitoring the occurrence of metastasis and the prediction of the length that a patient may survive with a prostate cancer is critical for doctors to select the proper treatment, aiming to achieve the best control of the cancer with a balance of quality of life. Currently this is achieved mainly by analysing the cancer tissues acquired through very invasive procedures or by expensive imaging techniques, most of which expose the patient to toxic radioactive materials. Circulating tumour cells (CTCs), which play a key role in the metastasis process, have been shown for their potential to be used for cancer prognosis by a simple blood sample analysis. However, previous CTC studies mainly detect the epithelial type of CTCs. Using the ParsortixTM (ANGLE plc) cell-size and deformability based CTC isolation system, we analysed not only epithelial CTCs, but also CTCs with epithelial-mesenchymal transition (EMT), a cellular process associated with cancer invasion and metastasis.
Author Interviews, Biomarkers, Heart Disease, Lipids / 12.06.2017

MedicalResearch.com Interview with: Amane Harada, PhD Senior Researcher Central Research Laboratories, Sysmex Corporation Kobe, Japan Ryuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of MedicineRyuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of Medicine Kobe, Japan  MedicalResearch.com: What is the background for this study? Response: High-density lipoprotein (HDL) exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative functions as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become “dysfunctional” HDL under pathological conditions. Recent studies have demonstrated that cholesterol efflux capacity of HDL is a better predictor of CVD than HDL-C, suggesting that not only the quantity, but also the quality of HDL may significantly modulate and predict the progression of cardiovascular disease. However, the conventional procedure for efflux capacity assay requires radiolabeling and cells, and the procedures are time consuming. Therefore, its clinical application is impractical. To solve those problems, we have recently developed a new assay system to evaluate the capacity of HDL to accept cholesterol, named “uptake capacity”.
Author Interviews, Biomarkers, Pediatrics, Pulmonary Disease / 07.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35124" align="alignleft" width="133"]Jegen Kandasamy MD Division of Neonatology Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program University of Alabama at Birmingham Birmingham, Alabama Dr. Kandasamy[/caption] Jegen Kandasamy MD Division of Neonatology Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program University of Alabama at Birmingham Birmingham, Alabama  MedicalResearch.com: What is the background for this study? Response: Preterm infants, especially those that are born with a birth weight of 750 grams or less, are prone to a lung disease called bronchopulmonary dysplasia (BPD) because the development of lungs in these infants takes place in an environment that has more oxygen than that available in utero. Recently, pulmonary blood vessel growth and function has been hypothesized to play a causal role in the pathogenesis of BPD. Vascular endothelial cell function has been shown to affect hyperoxia-induced lung damage in animal studies. An important source of human vascular endothelial cells is the umbilical cord of newborn infants. These human umbilical venous endothelial cells (HUVEC) have been used to measure endothelial cell function in various diseases but never in diseases related to the newborn infants from whom they were derived. In addition, the mitochondria in various cells in our body respond to oxygen toxicity by creating, as well as consuming, reactive oxygen species (ROS) that mediate most of the effects of oxygen-induced damage. Therefore, we designed this study to measure mitochondrial function in vascular endothelial cells obtained from the umbilical cords of prematurely born infants at the time of their birth. We then compared these mitochondrial functional measures between infants who later died or developed BPD versus those who survived without BPD.
Author Interviews, Biomarkers, Prostate Cancer, Urology / 17.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34627" align="alignleft" width="159"]Eric A. Klein, MD</strong> Chairman, Glickman Urological and Kidney Institute Cleveland Clinic Dr. Klein[/caption] Eric A. Klein, MD Chairman, Glickman Urological and Kidney Institute Cleveland Clinic MedicalResearch.com: Which of these results did you find most interesting or surprising? Response: What’s most interesting is that the IsoPSA assay redefines how PSA is measured, which links it more closely to the underlying biology of cancer. Current assays measure only the concentration of PSA, which can be affected by conditions other than cancer – BPH most commonly, but also infection and inflammation – which limits its diagnostic accuracy for finding cancer. Its been known for several decades that PSA exists in multiple different forms in the bloodstream in patients with prostate cancer. These novel molecules arise because cancer cells have deranged cellular metabolism that result in the generation of new species of PSA, making their measurement more tightly linked to the presence or absence of cancer and even the presence of high grade cancer (where cellular metabolism is even more disordered). The IsoPSA assay is the first assay to measure all of these isoforms and thus has better diagnostic accuracy for cancer.
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