Author Interviews, Biomarkers, Cancer Research, Science / 18.02.2021

MedicalResearch.com Interview with: Muhammed Murtaza M.B.B.S. (M.D.), Ph.D. Translational Genomics Research Institute Phoenix, AZ MedicalResearch.com: What is the background for this study? Response: Liquid biopsies and cell-free DNA analysis using blood samples have transformed cancer diagnostics in recent years. We started this project wondering whether cell-free DNA in urine is a viable alternative to blood, since urine could be collected completed non-invasively. Our very first experiment showed the lengths of DNA fragments in urine very similar across healthy individuals, leading us to wonder whether urine was actually as randomly degraded as we had previously thought. (more…)
Author Interviews, Biomarkers, COVID -19 Coronavirus / 25.01.2021

MedicalResearch.com Interview with: Marlene Cano MD. PhD. Post-Doctoral Research Fellow in Pulmonary Transplant Immunology Division of Pulmonary and Critical Care Department of Medicine Washington University/Barnes-Jewish Hospital Saint Louis, MO MedicalResearch.com: What is the background for this study? How does this test differ from other tests for COVID-19?   Response: We know COVID-19 causes a wide spectrum of disease, and that while many develop only mild uncomplicated illness, others develop severe respiratory failure, multi-organ failure and death. These patients often require prolonged hospitalization, ICU level care and even mechanical intubation for respiratory support. However, we still do not have a great way to identify which patients are likely to develop severe disease. We felt it was important to have a test that could act as sort of a ‘biomarker’ that we could measure early in COVID-19 patients and would help predict which patients would develop severe disease. From prior work, we knew that mitochondrial DNA, which are proinflammatory molecules that are released into the circulation from damaged organs could be this such ‘biomarker’. So, we measured the levels of mitochondrial DNA circulating in the plasma of patients with COVID-19 at the time they first presented to the hospital. Then we investigated if higher levels of mitochondrial DNA indeed predict the development of more severe disease. Currently there are no ‘biomarker’ tests specific for COVID-19. We do currently measure levels of other markers in the hospital that we feel might help us assess overall how sick patients may be, but these are very non-specific and assess only level of inflammation. This test instead can measure level of tissue injury. (more…)
Author Interviews, Biomarkers, Lymphoma / 14.08.2020

MedicalResearch.com Interview with: Dr. Ivana Špaková Pavol Jozef Šafárik University Košice, Slovakia MedicalResearch.com: What is the background for this study? Response:  The background is the plenty of space for studying "waste metabolites" which tell us more about the metabolism of the whole body as well as about the metabolism of the smallest compartment - cell. So we decided to study what is the difference in urine spectra (absorbance, excitation, and emission spectra) in patients with malignant melanoma and healthy subjects without positive cancer history. MedicalResearch.com: What are the main findings? Response: The main findings are "discovery" (it is not true discovery because the target molecules or metabolites are known for decades) of molecules{metabolites which together describe the stage of malignant melanoma. These findings could be used for future tracking the patient's response for treatment or for tracking the previously treated patients for malignant melanoma and are healthy at the moment of sampling. (more…)
Author Interviews, Biomarkers, COVID -19 Coronavirus / 17.07.2020

MedicalResearch.com Interview with: Abdi Ghaffari, Ph.D. Associate Professor (adjunct) Dept. of Pathology and Molecular Medicine Queen’s University MedicalResearch.com: What is the background for this study? Response: SARS-CoV-2 virus has infected millions and changed our way of life by placing nearly 3 billion people under lockdown or some form of physical isolation. In the absence of a vaccine or reliable treatment, diagnostic testing must be a pillar of public health policy to control further spread of the virus and to guide gradual removal of lockdown measures. COVID-19 antibody diagnostic tests are being increasingly used to assess the protective immunity status in the population. There are over 100 different COVID-19 antibody tests developed by companies worldwide in an effort to address this need. However, companies’ reported performance data are not always in line with the actual performance of these diagnostic tests in the real-world. In this work, we conducted a systemic review of independent studies (sponsored by academic or government institutions) that aimed to validate the performance of currently available COVID-19 antibody tests on the market.  (more…)
Author Interviews, Biomarkers, Cancer Research / 28.06.2020

MedicalResearch.com Interview with: Dr. Kathryn Lang VP, Outcomes and Evidence Guardant Health  MedicalResearch.com: What is the background for this study? Response: Despite a wide variety of screening methods available and increasing public awareness of the value of early detection, colorectal cancer (CRC) remains a leading cause of cancer-related deaths.  However nearly 1 in 3 adults in the United States  is not compliant with screening recommendations, with most citing that current screening methods are time consuming, unpleasant (stool-based testing), and in the case of colonoscopy, invasive. A blood-based CRC screening test could improve compliance rates by providing physicians with an opportunistic, in-office screening modality. However, demonstrating the clinical utility of blood-based cell-free circulating tumor DNA (ctDNA) fractions  for the detection of cancer in asymptomatic individuals has thus far been challenged by the failure to achieve clinically meaningful sensitivity and specificity thresholds due to significantly lower tumor cell-free free DNA  fractions and the increasing relevance of biological confounders. The multi-modal approach of Guardant Health’s LUNAR-2 assay (genomics, methylation and fragmentomics) coupled with advanced bioinformatic analysis and a focused approach of honing in on the unique signals of CRC  has been shown in previously reported cohorts to perform with sensitivity and specificity which satisfies the needs of clinicians in screening for CRC. (more…)
Author Interviews, Biomarkers, Diabetes, Diabetes Care, Johns Hopkins / 26.03.2020

MedicalResearch.com Interview with: Olive Tang, MD/PhD Student Johns Hopkins School of Medicine   Elizabeth Selvin, PhD, MPH Professor of Epidemiology & Medicine Director, Cardiovascular and Clinical Epidemiology Department of Epidemiology Welch Center for Prevention, Epidemiology and Clinical Research and the Johns Hopkins Bloomberg School of Public Health MedicalResearch.com: What is the background for this study? Response: The best approach to diabetes management in older adults is unclear. A new blood test called high-sensitivity troponin can detect damage to the heart, even in people without any signs or symptoms of heart disease. (more…)
Author Interviews, Columbia, Heart Disease, Mediterranean Diet, Women's Heart Health / 13.03.2020

MedicalResearch.com Interview with: Dr. Riddhi Shah, PhD AHA SFRN Postdoctoral Research Fellow Division of Cardiology Columbia University Medical Center New York, New York MedicalResearch.com: What is the background for this study? Response: The Mediterranean Diet, characterized by higher intakes of plant foods including plant proteins, monounsaturated fat, fish, and lower consumption of animal products and saturated fat, has long been associated with reduced cardiovascular risk and greater longevity, but the molecular mechanisms underlying these associations have not been fully elucidated. We evaluated associations of an Alternate Mediterranean Diet Score, reflective of adherence to this diet pattern and adapted for US populations, and its components with markers of endothelial inflammation directly measured in endothelial cells harvested from women, including oxidative stress, nuclear factor kappa B (NFκB), and endothelial nitric oxide synthase (eNOS) gene expression. (more…)
Author Interviews, Biomarkers, Lung Cancer, Stanford / 09.03.2020

MedicalResearch.com Interview with: Professor Dr. Andreas Keller Stanford University School of Medicine Office Department of Neurology and Neurological Sciences Chair for Clinical Bioinformatics Saarbrücken, Germany MedicalResearch.com: What is the background for this study? Response: Lung cancer is among the three most common cancers and the leading cause of cancer-related deaths worldwide. The overall low survival rate of patients with lung cancer calls for improved detection tools to enable better treatment options and improved patients’ outcomes. To detect lung tumors, liquid biopsy-based strategies are increasingly explored, that are biomarkers, which are identifiable in body fluids such as human blood. The clinical application of biomarkers is, however, largely hampered by the relatively small numbers of cases that have been analyzed in the majority of the preclinical studies including the studies on lung cancer.  (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers, Heart Disease / 25.02.2020

MedicalResearch.com Interview with: Prof. Konstantinos Stellos, MD, DM, MRCP, DSc, FAHA, FESC Professor of Medicine, Chair of Cardiovascular Medicine, Chair of Epitranscriptomics Lead, Vascular Biology & Medicine Theme Hon. Consultant Cardiologist, Newcastle Hospitals NHS Foundation Trust Biosciences Institute Faculty of Medical Sciences Newcastle University MedicalResearch.com: What is the background for this seminar? Can you tell us a little about how amyloid is made and stored? Response: Patients are afraid that they may die due to a heart attack - a major cause of death worldwide- or if they live long they may get dementia compromising severely their quality of life in their last years of life. Many years ago we asked the question whether there is a link between these two ageing-associated diseases. For this reason we studied the clinical value of amyloid-beta peptides in patients with coronary heart disease. We chose to study the amyloid-beta peptides, which are the cleavage product of the beta- and gamma-secretases of the mother protein amyloid precursor protein, because amyloid-beta plaques in brain is the hallmark of Alzheimer's disease. Following amyloid precursor protein (APP) gene transcription, APP is cleaved in the nonamyloidogenic pathway (plasma membrane) by α- and γ- secretases or in the amyloidogenic pathway (endosomes) by β- and γ- secretases. The later pathway generates amyloid beta (Αβ) peptides that are released extracellularly. Αβ accumulation in blood or tissues may result from enhanced production/cleavage or by impaired degradation and/or clearance. The related mechanisms are depicted in Figure 2 of our publication in JACC: http://www.onlinejacc.org/content/75/8/952  (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, McGill, Neurology, Technology / 28.01.2020

MedicalResearch.com Interview with: Yasser Iturria-Medina PhD Assistant Professor, Department of Neurology and Neurosurgery Associate member of the Ludmer Centre for Neuroinformatics and Mental Health McConnell Brain Imaging Centre McGill University MedicalResearch.com: What is the background for this study? Response: As background, two main points:
  • Almost all molecular (gene expression) analyses performed in neurodegeneration are based on snapshots data, taking at one or a few time points covering the disease's large evolution. Because neurodegenerative diseases take decades to develop, until now we didn't have a dynamical characterization of these diseases. Our study tries to overcome such limitation, proposing a data-driven methodology to study long term dynamical changes associated to disease.
Also, we still lacked robust minimally invasive and low-cost biomarkers of individual neuropathological progression. Our method is able to offer both in-vivo and post-mortem disease staging highly predictive of neuropathological and clinical alterations. (more…)
Annals Internal Medicine, Author Interviews, Biomarkers, Heart Disease / 23.12.2019

MedicalResearch.com Interview with: Dr. PJ Devereaux MD, PhD, FRCP(C) Director of the Division of Cardiology Scientific Leader Anesthesiology, Perioperative Medicine, and Surgical Research Group Population Health Research Institute McMaster University  MedicalResearch.com: What is the background for this study? Response: There is an ethical obligation to provide patients with an accurate estimation of the potential benefits of surgery and the potential risks, to facilitate informed decision making about the appropriateness of surgery.  There are two common approaches to risk estimation. First, physicians commonly use clinical risk indices.  Based upon a patient’s clinical history (e.g., history of prior heart attack or stroke) an estimate of perioperative risk is determined.  Research demonstrates that these clinical risk indices have suboptimal risk discrimination capabilities, and they will underestimate risk in many patients. The second approach that has commonly been used is to have patients undergo an expensive and time consuming non-invasive cardiac test (e.g., stress nuclear cardiac study).  Although these non-invasive cardiac tests can enhance risk estimation in some patients who will have a perioperative cardiac event, these tests more commonly exaggerate risk in patients who will not have a complication. (more…)
Author Interviews, Biomarkers, Prostate Cancer / 02.12.2019

MedicalResearch.com Interview with: Dr Jeremy Clark University of East Anglia Norwich Medical School MedicalResearch.com: What is the background for this study? Response: Earlier this year we published our pilot study which showed how useful we have found urine to be for diagnosing prostate cancer and predicting which cancers will get bigger and nastier up to 5 years later (Connell et al 2019). – Our PUR (Prostate Urine Risk) signatures separated men with low-risk cancer into two groups one of which had 8-times the rate of future development of aggressive cancer that the other. There is nothing in clinical use at present that can do this. The new development is our At-Home Urine collection system which means that we can now send out a urine collection kit to a man at home, he fills up a small pot with his first wee of the day and posts it back to us for PUR analysis. This makes the whole system so much less stressful for the patient. The idea behind it is as follows: the prostate lays just below the bladder, it is a secretory organ and these secretions carry cells and molecules from all over the prostate to the urethra which then get flushed out of the body on urination. If a cancer is present then tiny bits of the tumour are also carried with the secretions and we can detect these in the urine. As the prostate is constantly secreting the levels of biomarkers in the urethra will build up with time. Collecting from the first wee of the day means that overnight secretions can be collected which makes the analysis more sensitive and more robust. (more…)
Author Interviews, Biomarkers, Melanoma, Ophthalmology / 15.11.2019

MedicalResearch.com Interview with: Dr. Mitchell Stark, B.App.Sc (Hons), PhD NHMRC Research Fellow The University of Queensland Diamantina Institute Woolloongabba, QLD MedicalResearch.com: What is the background for this study? Response: Uveal nevi (moles) mimic the appearance of uveal melanoma and their transformation potential cannot be definitively determined without a biopsy. Moles or naevi in the eye are common but can be difficult to monitor because changes to their shape or colouring can’t always be seen as easily as on the skin. As naevi are difficult to biopsy, they are usually “monitored” at regular intervals. If there is a melanoma in the eye, then outcomes are poor for people if their cancer spreads to the liver. This study aimed to identify a “biomarker” that could be measured in patients’ blood that could be used as an early indicator of melanoma formation (from a mole) or progression to other body sites.  (more…)
Author Interviews, Cancer Research, HPV, OBGYNE / 15.08.2019

MedicalResearch.com Interview with: Marc Eloit, D.V.M, Ph.D. Pathogen Discovery Laboratory, Biology of Infection Unit, Institut Pasteur Paris, France MedicalResearch.com: What is the background for this study? Response: Human papillomaviruses (HPV) are responsible for >99% of cervical cancers. Currently, cervical cancer screening either focuses on testing for the presence of HPV or identifying abnormal cervical cells with cytology (Pap test). However, molecular diagnostic tests based on the detection of viral DNA or RNA have low positive predictive values for the identification of cancer or precancerous lesions, and analysis of cervical cells with the Pap test, even when combined with molecular detection of high-risk HPV, results in a significant number of unnecessary colposcopies. We have developed HPV RNA-Seq, a new “two-for-one” molecular diagnostic test that not only detects the type of HPV, but also identifies precancerous markers. This test is therefore designed to diagnose the riskiest forms of HPV infection, provide rapid results at moderate cost, and helps avoiding unnecessary diagnostic procedures. HPV RNA-Seq is based on the dual combination of multiplexed reverse transcription PCR (RT-PCR) and next-generation sequencing (NGS). RT-PCR is a sensitive way to detect small amounts of RNA, the genetic material that reflects the activity of the HPV genes, and NGS finely characterizes the amplified viral sequences. This enables detection of up to 16 high-risk or putative high-risk HPV in a sample as well as the presence of precancerous markers. (more…)
Author Interviews, Biomarkers, Cancer Research / 05.08.2019

MedicalResearch.com Interview with: Emeritus Professor Attila Lorincz, PhD Centre for Cancer Prevention Queen Mary University of London  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The vast majority of women with cervical lesions are not at risk for cancer, however, because there is no way to accurately identify the very small proportion of women at risk of cervical cancer a recommendation for treatment is commonly given by doctors. Surgery on women with cervical lesions is risky for future pregnancies and can cause harm to the baby. Occasionally there are also problems in physical recovery and the mental well-being of the treated women. We wanted to see if the S5 DNA methylation test could identify the women who need treatment. We ran a two-year follow-up study on 149 young women with moderate dysplasia in Finland. Our results showed that the S5 test was by far the best method to reveal which women needed treatment.  (more…)
Author Interviews, Biomarkers, Heart Disease, JACC / 17.07.2019

MedicalResearch.com Interview with: Dr. Fred Apple, PhD, DABCC Medical director,Clinical Laboratories, Clinical Chemistry, Clinical and Forensic Toxicology and Point of Care Testing, Hennepin HealthCare Principal investigator, Minneapolis Medical Research Foundation Professor, Department of Laboratory Medicine and Pathology University of Minnesota  MedicalResearch.com: What is the background for this study? Response: Few studies have addressed the role of high sensitivity cardiac troponin (hs-cTn) assays in ruling out myocardial infarction (MI) based on the measurement of a single baseline specimen in US patients presenting to the emergency department with symptoms suggestive of ischemia. Most studies have been published predicated on patients in Europe, Australia, and New Zealand. As US emergency departments have different ordering practices for using cTn in triaging patients, it is important to validate the role of hs-cTn assays in US practices to assure providers of appropriate utilization. We have published two papers using the Abbott ARCHITECT hs-cTnI assay, the same one used outside the US in clinical practice (as this assay is not yet FDA cleared) in a US cohort (clinicialtrials.gov trial: UTROPIA - Sandoval Y, Smith SW, Shah ASV, Anand A, Chapman AR, Love SA, Schulz K, Cao J, Mills NL, Apple FS. Rapid rule-out of acute myocardial injury using a single high-sensitivity cardiac troponin I measurement. Clin Chem 2017;63:369-76. Sandoval Y, Smith SW, Love SA,  Sexter A, Schulz K, Apple FS. Single high-sensitivity cardiac troponin I to rule out myocardial infarction. Am J Med 2017;130:1076-1083) that have shown similar rule out capacities predicated on clinical presentation, a normal ECG and the role of hs-cTnI testing. (more…)
Author Interviews, Biomarkers, Geriatrics, Heart Disease, JACC / 02.07.2019

MedicalResearch.com Interview with: Martin Bødtker Mortensen, læge PhD Afdelingen for Hjertesygdomme Aarhus Universitetshospital Danmark  MedicalResearch.com: What is the background for this study?   Response: The background for the study is a combination of two things: First, the proportion and number of elderly people 65 years of age or older are increasing fast worldwide. Second, given the dominant impact of age on estimated risk for cardiovascular disease, nearly all elderly individuals eventually become statin eligible under current guidelines – just because of aging alone. Thus, to limit overtreatment of elderly individuals, we wanted to find “negative” risk markers that can be used to identify elderly individuals at truly low cardiovascular risk who are less likely to benefit from statin therapy despite advancing age. (more…)
ASCO, Author Interviews, Biomarkers, Colon Cancer / 24.06.2019

MedicalResearch.com Interview with: Lawrence LaPointe, Ph.D. Chief Innovation Officer Clinical Genomics Bridgewater, New Jersey  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Colorectal cancer is a cancer of the colon and the rectum. The American Cancer Society estimates that about 1 in 21 men and 1 in 23 women in the United States will develop colorectal cancer during their lifetime. This disease is the second leading cause of cancer death in women, and the third for men. Colorectal cancer has a high 5-year recurrence rate and most likely is spread to the liver and lungs. Clinical Genomics has two decades of experience striving to save lives and reduce costs by developing easy-to-use tests for the detection of colorectal cancer. With breakthrough diagnostic tools, the company aims to offer affordable and accurate tests, supporting physicians and patients with potential life-saving knowledge about colorectal cancer. On June 3, 2019, Clinical Genomics presented research detailing breakthrough methods of colorectal cancer recurrence monitoring at the American Society of Clinical Oncology (ASCO) annual meeting in the McCormick Place Convention Center, Chicago.  (more…)
Author Interviews, Biomarkers, Genetic Research, Infections, NEJM, UCSF / 13.06.2019

MedicalResearch.com Interview with: Dr. Charles Chiu, M.D./Ph.D. Professor, Laboratory Medicine and Medicine / Infectious Diseases Director, UCSF-Abbott Viral Diagnostics and Discovery Center Associate Director, UCSF Clinical Microbiology Laboratory UCSF School of Medicine MedicalResearch.com: What is the background for this study? Would you describe what is meant by metagenomic sequencing? Response: Metagenomic next-generation sequencing (mNGS) is the use of technology to generate millions of sequence reads to diagnose infection sin patients by characterizing the full range of potential pathogens (bacteria, viruses, fungi, and parasites) in a single sample. Although shown to be a promising diagnostic tool for  infectious diseases in case reports and limited case series (Chiu and Miller Nature Reviews Genetics 20, 341-355 (2019)), to date the “real-life” utility of this approach for patient care has hitherto not been demonstrated.  This study is the first prospective, multi-center study of clinical mNGS testing for the diagnosis of neurological infections in acutely ill hospitalized patients presenting with meningitis and/or encephalitis. (more…)
Author Interviews, Bayer, Biomarkers, Colon Cancer / 05.06.2019

MedicalResearch.com Interview with: Joseph Germino, M.D., PhD Vice President US Medical Affairs Oncology Bayer Healthcare Pharmaceuticals Whippany, N.J. 07981 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R). This prospective pharmacokinetic (PK) ancillary study is part of a prospective phase II study evaluating treatment response with regorafenib in patients with chemorefractory metastatic colorectal cancer (mCRC) called TEXAN, which aimed to investigate correlations between overall survival (OS) and regorafenib, or its enterohepatic cycle-dependent active metabolites M-2 and M-5 concentrations. As measured by LC-MS/MS, the main findings showed that regorafenib, M-2 and M-5 were respectively 1.99 (1.03-2.73), 1.44 (0.89-2.49) and 1.61 (0.79-2.37) mg/L during the first cycle at day 15 (C1D15) and 1.90 (1.10-2.76), 1.29 (0.77-2.24) and 1.17 (0.45-2.42) mg/L at during the second cycle at day 15 (C2D15).  (more…)
ASCO, Author Interviews, Biomarkers, Melanoma, NYU / 02.06.2019

MedicalResearch.com Interview with: David Polsky, MD, PhD Dermatologist and Director of the Digmented Lesion Service Mahrukh M. Syeda, MS Research Associate Ronald O. Perelman Department of Dermatology NYU Langone Health MedicalResearch.com: What is the background for this study? Response: Several studies of metastatic melanoma patients have demonstrated that measuring circulating tumor DNA (ctDNA) associates with their disease burden and survival.  Generally, patients with detectable pre-treatment ctDNA levels and/or detectable ctDNA at various time intervals after starting treatment have shorter survivals than patients with lower pre-treatment or on-treatment ctDNA levels.  Studies have varied in their methods to detect ctDNA, the thresholds chosen to call a sample positive or negative, and the follow up time point for measurement, if any. In this study, we examined pre-treatment and week 4 on-treatment plasma samples from patients enrolled in Combi-D, the Phase III, randomized, double-blind trial of the BRAF and MEK inhibitors Dabrafenib and Trametinib, which led to FDA approval of the combination therapy for patients with unresectable stage III/IV melanoma. Only patients with BRAF V600E or V600K mutations identified from tumor genotyping were enrolled in the clinical trial. (more…)
Author Interviews, Biomarkers, Cancer Research, Colon Cancer, JAMA, Karolinski Institute / 13.05.2019

MedicalResearch.com Interview with: Louise Olsson MD PhD Senior researcher Department of Molecular Medicine and Surgery Colorectal Surgery Karolinski Institute Stockholm, Sweden  MedicalResearch.com: What is the background for this study? What are the main findings? Response: I read a very interesting paper back in 2006 “Detection and quantification of mutation in the plasma of patients with colorectal cancer”. Only some 60 % of patients with early colorectal cancer were detectable in this way whereas patients with stage IV disease all had a high concentration of APC mutations in their plasma. So the prospects of using the method for example, screening of primary colorectal cancer seemed limited but I thought wow, this is the test to detect recurrences and generalized disease during follow-up after surgery for colorectal cancer. After some discussion we started to collect plasma samples from patients at the hospital where I worked and that´s how my research began. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers, Neurological Disorders, Neurology, University of Pennsylvania / 08.05.2019

MedicalResearch.com Interview with: Lauren McCollum, MDCognitive and Behavioral Neurology FellowPenn Memory Center / Cognitive Neurology DivisionLauren McCollum, MD Cognitive and Behavioral Neurology Fellow Penn Memory Center / Cognitive Neurology Division MedicalResearch.com: What is the background for this study?   Response: Alzheimer’s Disease (AD) is a heterogenous condition, with considerable variability in cognitive symptoms and progression rates. One major reason for this heterogeneity is “mixed pathology,” – i.e., both AD- and non-AD pathology. Examples of non-AD pathology include cerebrovascular disease (CVD), Lewy Bodies, and TDP-43. Pathologically, Alzheimer’s Disease is defined by characteristic amyloid plaques and neurofibrillary tangles, which can be assessed for in living patients with CSF- or PET-based biomarkers for amyloid and tau, respectively. Classically, amyloid deposition begins years or even decades before pathologic tau accumulation, which is in turn associated with brain atrophy and cognitive decline. The recently developed NIA-AA “ATN” research framework allows for the classification of individuals with regard to 3 binary biomarkers: Amyloid (A), Tau (T), and Neurodegeneration (N). An individual’s ATN biomarker status indicates where along the “Alzheimer’s Disease continuum” they lie. Additionally, some ATN statuses are on the “typical AD” continuum, while others are not. Research has shown that 15-30% of cognitively normal older adults have elevated amyloid. It stands to reason that some portion of cognitively impaired individuals with elevated amyloid and neurodegeneration have something other than AD driving their neuronal injury. Within the context of the ATN research framework, this subset of people is the A+T-N+ group (i.e., people who have elevated amyloid and neurodegeneration, but are tau-negative), as amyloid alone (that is, amyloid without tau) is not thought to cause significant cognitive impairment or brain atrophy. Our hypothesis was that, compared to A+T+N+ (a set of typical-AD biomarkers), A+T-N+ have cognitive and neuroimaging profiles that deviate from a typical Alzheimer’s Disease pattern – i.e., with less memory loss and less atrophy in AD-signature regions – and may have biomarkers suggestive of alternate non-AD pathologies [e.g., white matter hyperintensities (WMHs), a marker of CVD]. (more…)
Author Interviews, Biomarkers, Multiple Sclerosis / 30.04.2019

MedicalResearch.com Interview with: Prof. Bernhard Hemmer MD PhD Director of the Neurology Clinic Technische Universität München  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The course of multiple sclerosis (MS) is still highly unpredictable and reliable markers to predict disability progression are largely missing. We found that patients with a high IgG Index, which means that the produce large amount of IgG within the CNS, have a higher risk of disease worsening during the first 4 years. I would consider patients with an elevated IgG index at a higher risk to run a more severe disease course. The marker could be used together with others to guide treatment decisions after multiple sclerosis diagnosis. (more…)
Author Interviews / 16.04.2019

MedicalResearch.com Interview with: Héctor Peinado PhD Microenvironment and Metastasis Laboratory Molecular Oncology Program Spanish National Cancer Research Center Madrid, Spain  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: In this study we detected for the first time BRAF mutation by liquid biopsy in melanoma stage III patients that underwent lymphadenectomy. We obtained a novel biofluid from the drainage implanted 24-48 hours post-lymphadenectomy, called exudative seroma, and profiled BRAF mutation in circulating free DNA and extracellular vesicles. Those patients positive for BRAF mutation in the seroma had increased risk of relapse, therefore we believe that this technique identifies patients at risk of relapse by identifying residual disease. (more…)
Author Interviews, Biomarkers, Lancet, OBGYNE, Pediatrics / 01.04.2019

MedicalResearch.com Interview with: Catalin S. Buhimschi MD, MMS, MBA Professor of Obstetrics and Gynecology Division of Maternal Fetal Medicine Director of Obstetrics Department of Obstetrics and Gynecology Chicago, IL, 60612 MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2008, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal–Fetal Medicine Units Network published the results of a randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy (CP). The results of this trial suggested that fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate to severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. As such, the search for a biomarker or a therapeutic solution to prevent CP had to continue. We are grateful to the NICHD for giving us access to the umbilical cord blood samples retrieved at the time of birth for the infants enrolled, who were also followed for 2 years postnatally. We discovered that fetus’s ability to switch-on haptoglobin (Hp) expression in response to inflammation was associated with reduction of intra-ventricular hemorrhage (IVH) and/or death, and cerebral palsy and/or death. Fetuses unable to mount such a response in-utero had an increased risk of adverse outcomes. (more…)
Author Interviews, Biomarkers, BMJ, Heart Disease / 18.03.2019

MedicalResearch.com Interview with: Prof. Nick Curzen  BM(Hons) PhD FRCP Professor of Interventional Cardiology/Consultant Cardiologist University Hospital Southampton Southampton MedicalResearch.com: What is the background for this study? Response: The commonest blood test now used to assess whether a patient has had a heart attack or not is called high sensitivity troponin (hs trop).  The test is supplied with an Upper Limit of Normal, which is based upon results from relatively healthy people.  When doctors take the hs trop, they then use this ULN to decide if the patient had has a heart attack. This study set out to see what the hs trop level is in a large number of patients attending the hospital for any reason, either inpatient or outpatient, in most of whom there was no clinical suspicion of heart attack at all.  We therefore took hs trop measurements on 20,000 consecutive patients attending our hospital and having a blood sample for any reason.  (more…)
Author Interviews, Biomarkers, CT Scanning, JAMA, Lung Cancer, Medical Imaging / 01.03.2019

MedicalResearch.com Interview with: Martin C. Tammemägi PhD Senior Scientist Cancer Care Ontario | Prevention & Cancer Control Scientific Lead Lung Cancer Screening Pilot for People at High Risk Professor (Epidemiology) | Brock University Department of Health Sciences Ontario, Canada MedicalResearch.com: What is the background for this study? Response: Some prediction models can accurately predict lung cancer risk (probability of developing lung cancer during a specified time). Good model predictors include sociodemographic, medical and exposure variables. In recent years, low dose computed tomography (LDCT) lung cancer screening has become widespread in trials, pilots, demonstration studies, and public health practice. It appears that screening results provides added valuable, independent predictive information regarding future lung cancer risk, aside from the lung cancers directly detected from the diagnostic investigations resulting from positive screens. (more…)
Author Interviews, Biomarkers, Cancer Research / 28.11.2018

MedicalResearch.com Interview with: Ricardo Alvarez MD MSc Medical Director of the Breast Cancer Center Director of Cancer Research Cancer Treatment Centers of America, CTCA Atlanta MedicalResearch.com: What is the background for this study? What are the main findings? Response: “The background of this study comes from five years of experience in one of our precision medicine programs that was launched in 2013 and this is the experience of a group of personnel from a hospital that helps physicians in five different hospitals that are a part of the CTCA network and for physicians who order a next generation sequencing test. In this particular report, we have only one vendor, and that is Foundation Medicine and we analyze three different genomic platforms, Foundation One test, Foundation Act and Foundation One Hem. In total, approximately 8,800 tests have been analyzed and that was the presentation at ESMO 2018. It’s important that the Precision Medicine Program (PMed) helps physicians to identify actionable and potentially actionable targets for the result of this test so patients can be treated with targeted therapy, and this can be done by selecting clinical trials or recommending patients to be treated off-label agents. When we say off label, meaning that they are not specifically FDA-approved drugs for this indication that we are treating.” (more…)
Author Interviews, Biomarkers, Endocrinology, Prostate Cancer / 14.11.2018

MedicalResearch.com Interview with: Vincenza Conteduca, MD, PhD Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl - IRCCS Meldola , Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: In our previous publications, we showed that the study of plasma cell-free DNA holds promise for improving treatment choice in metastatic castration-resistant prostate cancer (mCRPC). Specifically, we demonstrated that the detection in plasma of aberrations (copy number alterations and/or point somatic mutations) of androgen receptor (AR), using an easy and robust multiplex droplet digital PCR method, predicted an adverse outcome in mCRPC patients treated with second-generation AR-directed therapies (abiraterone or enzalutamide) in both settings: chemotherapy-naïve and post-docetaxel. This current multi-institution work builds on our previous discoveries. We investigated the association of androgen receptor status and survival in men treated with docetaxel. Moreover, we performed an exploratory analysis in patients treated with docetaxel or AR-directed therapies as first-line therapy. Interestingly, we observed that plasma AR-gained patients do not have a worse outcome compared to AR-normal patients when treated with docetaxel as first-line therapy. This introduces the opportunity to use plasma to select for docetaxel in preference to androgen receptor-directed therapies in AR gained mCRPC patients. (more…)