ASCO, Author Interviews, Biomarkers, Breast Cancer / 30.05.2020

MedicalResearch.com Interview with: Francois-Clement Bidard, MD PhD Head of Breast Cancer Group, Institut Curie Professor of Med. Oncology, UVSQ/Paris MedicalResearch.com: What is the background for this study? Response: A timely question is how to optimize the endocrine therapy of ER+ HER2- metastatic breast cancers? Aromatase inhibitors (AI) are currently the standard of care in first line, in combination with CDK4/6 inhibitors. Mutations in the estrogen receptor gene (ESR1) can be detected in up to 40% of AI-resistant metastatic breast cancers, but no data was available in the current first line setting (AI combined to CDK4/6 inhibitor). This exploratory study of the first line PADA-1 study reports on the detection rate of ESR1 mutations in cell-free DNA from an “AI-sensitive” population (with no metastatic relapse during adjuvant AI therapy), before the start of therapy (at inclusion). As expected, we found a low prevalence of 3.2% in the general population (N=1,017 patients included). The prevalence of ESR1 mutations among subgroups appeared primarily driven by the type of adjuvant endocrine therapy: patients with prior exposure to adjuvant therapy with AI displayed the highest prevalence of ESR1 mutations (7.1%), followed by patients with no prior adjuvant endocrine therapy (mostly de novo stage IV; ESR1 mutation prevalence: 2.4%). Patients who received adjuvant endocrine therapy with no AI (e.g. tamoxifen only) had the lowest ESR1 mutation prevalence (1.2%). (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, MD Anderson, Pharmaceutical Companies / 09.05.2020

MedicalResearch.com Interview with: David S Hong, M.D MD Anderson Department of Investigational Cancer Therapeutics Division of Cancer Medicine University of Texas MedicalResearch.com: What is the background for this study? Response: Larotrectinib is a first-in-class, CNS active, oral TRK inhibitor exclusively designed to treat tumors with an NTRK gene fusion and does not have secondary targets. In previous presentations and published in The Lancet Oncology, larotrectinib demonstrated robust tumor-agnostic efficacy in an integrated dataset of 159 adult and pediatric patients with TRK fusion cancer across three clinical trials (Feb 2019 data cut-off date). In these studies, the objective response rate (ORR), according to investigator assessment, was 79% (95% confidence interval [CI], 72 – 85%), with a complete response rate of 16%. In this analysis presented at AACR 2020, we sought to evaluate the outcomes in patients from the integrated data set based on different baseline characteristics, including prior lines of therapy and Eastern Cooperative Oncology Group (ECOG) performance status. ECOG measures how the disease impacts a patient. ECOG describes a patient’s level of functioning with a numbering scale (0-5) so physicians can uniformly describe a patient’s ability to care for themselves, daily activity and physical activity (selfcare, walking, working, etc). (more…)
Author Interviews, Biomarkers, Gastrointestinal Disease / 28.03.2020

MedicalResearch.com Interview with: Jean-Frederic Colombel MD The Henry D Janowitz Division of Gastroenterology Icahn School of Medicine at Mount Sina New York, NY 10029, USA MedicalResearch.com: What is the background for this study? Response: The goals of therapy in Crohn’s disease have shifted from mere control of symptoms also called clinical remission towards combination of clinical and endoscopic remission also called deep remission which is now considered as the new therapeutic “target”. However it has yet to be proven that targeting deep remission instead of clinical remission is able to stop the progression of Crohn’s disease towards bowel damage, complications and hospitalizations. This study is a post-hoc analysis of the CALM trial that was published in The Lancet in 2018 where newly diagnosed patients were randomized to escalate therapy based on symptoms only (control arm) or based on a combination of symptoms and two biomarkers namely C-reactive protein in blood and calprotectin in stools (tight control arm). (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, 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…)
Author Interviews, Biomarkers, Heart Disease, JAMA, UCLA / 09.01.2020

MedicalResearch.com Interview with: Olujimi A. Ajijola, MD, PhD Neurocardiology Research Center of Excellence Cardiac Arrhythmia Center University of California, Los Angeles MedicalResearch.com: What is the background for this study? Response: It hadn’t been understood why some people with basic heart failure might live longer than others despite receiving the same medications and medical device therapy. Through this research we set out to determine whether a biomarker of the nervous system could help explain the difference. This study revealed a biomarker that can specifically predict which patients with “stable” heart failure have a higher risk of dying within one to three years. (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, Cancer Research / 21.12.2019

MedicalResearch.com Interview with: https://www.kariusdx.com/ Dr. Asim Ahmed MD co-author of the study Senior medical director at Karius  MedicalResearch.com: What is the background for this study? Would you briefly explain the basis of the Karius Test? Response: The Karius Test is a non-invasive blood test that uses next-generation sequencing of microbial cell-free DNA to rapidly detect over 1,400 bacteria, DNA viruses, fungi, and other pathogens. Doctors primarily use the test to detect specific causative pathogens, complicated pneumonia, cardiovascular infections, and infections in immunocompromised hosts. The Karius Test is transforming how doctors diagnose infectious diseases by helping doctors identify the precise pathogens infecting patients. The Karius Test offers a higher diagnostic yield and faster time-to-diagnosis than conventional tests - with the potential to eliminate invasive diagnostic procedures like biopsies. (more…)
Author Interviews, Biomarkers, Hematology, Transplantation / 09.12.2019

MedicalResearch.com Interview with: Hrishikesh Srinagesh MD The Tisch Cancer Institute at Mount Sinai MedicalResearch.com: What is the background for this study? Response: Graft-versus-host disease (GVHD) is the leading cause of non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT). Acute GVHD occurs in approximately 50% of HCT patients and targets the skin, liver, and gastrointestinal tract primarily. The change in clinical symptoms (e.g. reduction in volume of diarrhea) is used as the primary endpoint in most trials of acute GVHD treatment, but more accurate metrics are needed to predict long-term survival. Over the past decade, the Mount Sinai Acute GVHD International Consortium (MAGIC) has studied two biomarkers important in GVHD pathogenesis: suppressor of tumorigenesis 2 (ST2) and regenerating islet-derived 3 alpha (REG3). These proteins are shed into the bloodstream when the gastrointestinal tract is damaged during GVHD, the most lethal form of acute GVHD. The concentrations of ST2 and REG3 can be used generate an individual’s estimated probability of 6 month NRM known as the MAGIC Algorithm Probability (MAP). Our study evaluated whether the MAP measured at the start of GVHD treatment and four weeks later could predict long-term survival and we compared the MAP to clinical response after four weeks, the gold standard of response.  (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, Biomarkers, Schizophrenia / 29.10.2019

MedicalResearch.com Interview with: Dr.  Takeo Yoshikawa MD PhD RIKEN Center for Brain Science Japan MedicalResearch.com: What is the background for this study? What are the main findings?
  • Currently available drugs for schizophrenia are the dopamine D2 receptor blockers. These compounds were serendipitously discovered over half-century ago. But about 30% of schizophrenia are resistant to the dopamine D2 receptor blockers. In spite of these conditions, pharmaceutical companies have abandoned the development of new drugs. This is because we do not know the principle of drug design.
  • Therefore, we need to understand the molecular underpinning of as-yet unknown schizophrenia pathophysiology. Schizophrenia is diagnosed by only patients’ symptoms, not by biological examination. To search for biological underpinning for schizophrenia using experimental animals, we thought that we should examine an endophenotype (biological trait) relevant to schizophrenia. Then we targeted prepulse (PPI) performance.
  • Here, dampened PPI is considered as a biological marker of psychiatric disorders, typically of schizophrenia. Importantly, PPI can be measured using the same behavioral paradigm between experimental animals and human.
  • C57BL/6 (B6) inbred mouse shows higher (better) prepulse inhibition (PPI) performance, while C3H/He (C3H) inbred mouse shows lowered (worse ) PPI. We premised that C3H mouse is “schizophrenia-prone” and B6 is not. To know the molecular basis for differential PPI levels between the two inbred mouse strains, we performed comprehensive protein expression level analysis (proteomics analysis) using the brains of B6 and C3H mice.
  • The expression levels of Mpst, a hydrogen sulfide (H2S)-producing enzyme, is elevated in C3H mouse compared to B6 mouse. Biochemical analysis also supported the elevated H2S production in C3H mouse compared to B6.
  • The examination of human samples including postmortem brains, iPS-derived neural stem cells (neurospheres) and hair follicle cells, gave evidence that H2S production system is indeed up-regulated in schizophrenia.
(more…)
Author Interviews, Biomarkers, JAMA, Pediatrics / 09.09.2019

MedicalResearch.com Interview with: Elizabeth D. Kantor, PhD MPH Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center NY, NY MedicalResearch.com: What is the background for this study? Response: There has been recent interest in understanding how exposures in childhood and adolescence relate to later-life health outcomes. Although inflammation is thought to play a role in the etiology of various diseases, little is known about the long-term implications of inflammation in early life. We therefore sought to evaluate how erythrocyte sedimentation rate (ESR), a marker of inflammation, measured among ostensibly healthy men in late adolescence, relates to subsequent cause-specific mortality. We found that men with high inflammation in late adolescence experienced increased mortality due to cancer and cardiovascular disease. (more…)
Author Interviews, Biomarkers, Brain Injury, Emergency Care, Pediatrics / 31.08.2019

MedicalResearch.com Interview with: Linda Papa, MD Emergency Physicians of Central Florida Orlando Health Orlando, Florida  MedicalResearch.com: What is the background for this study? Response: In 2018 serum biomarkers Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) were FDA-approved in adults to detect abnormalities on CT scan in mild to moderate traumatic brain injury. However, they have not been approved to detect concussion and they have not been approved for use in children. Previous studies have focused on detecting lesions on CT in more severely injured patients. However, not having brain lesions on a CT scan does not mean there is no brain injury or concussion. Therefore, this study focused on patients with concussion who looked well and likely had normal-appearing CT scans of the brain. This study includes THREE groups of trauma patients:
  • 1) those with concussion,
  • 2) those who hit their head but had no symptoms (subconcussive), and
  • 3) those who injured their bones but did not hit their head (no concussion).
There is a group of individuals with head trauma who have been significantly understudied, and in whom biomarkers are rarely, if at all, examined. These are people who experience head trauma without symptoms of concussion. They may be classified as having “no injury” or they may represent milder forms of concussion that do not elicit the typical signs or symptoms associated with concussion and are referred to as “subconcussive” injuries.  (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, NEJM, Pulmonary Disease / 11.07.2019

MedicalResearch.com Interview with: Dr. Chris Butler,, BA MBChB DCH CCH MD FRCGP (Hon)FFPH FMedSci Professor of Primary Care Nuffield Department of Primary Care Health Sciences, Professorial Fellow at Trinity College Clinical Director Primary Care Clinical Trials Unit University of Oxford  MedicalResearch.com: What is the background for this study? Response: More than a million people in the UK have COPD, which is a lung condition associated with smoking and other environmental pollutants. People living with the condition often experience exacerbations, or flare-ups, and when this happens, three out of four are prescribed antibiotics. However, two-thirds of these flare-ups are not caused by bacterial infections and antibiotics often do not benefit patients. A simple finger-prick blood test could help prevent unnecessary prescribing of antibiotics for people with the lung condition chronic obstructive pulmonary disease (COPD).  The finger-prick test measures the amount of C- reactive protein (CRP) - a marker of inflammation that rises rapidly in the blood in response to serious infections. People with a COPD flare-up who have a low CRP level in the blood appear to receive little benefit from antibiotic treatment. The General Practitioner (GP) use of a C-Reactive Protein (CRP) Point of Care Test (POCT) to help target antibiotic prescribing to patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) who are most likely to benefit (The PACE Study) determined whether the using a POCT CRP to guide antibiotic treatment decisions for acute exacerbations of COPD reduced antibiotic use without harming patients. (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…)
ALS, Alzheimer's - Dementia, Author Interviews, Biomarkers, JAMA, Multiple Sclerosis / 27.06.2019

MedicalResearch.com Interview with: Charlotte E. Teunissen, PhD Neurochemistry Laboratory, Department of Clinical Chemistry VU University Medical Centre, Neuroscience Campus Amsterdam Amsterdam, the Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Several reports have shown increased in NfL in various neurological disorders, separately. We wanted to know how the levels are in these disorders relative to each other. Moreover, some reports showed absence of age effects in Multiple Sclerosis (MS) patients, which is normally present in controls. So, we thought that it would be good to study age effects in a large group of controls, and if these effects are absent in other diseases, similarly as in MS. (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, 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, OBGYNE / 20.03.2019

MedicalResearch.com Interview with: Dr. Kara Rood MD Maternal-fetal Medicine Physician The Ohio State University Wexner Medical Center MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This is a simple, rapid, non-invasive test for early recognition of preeclampsia.  MedicalResearch.com: What should readers take away from your report? Response: Aid in timely diagnosis to help provide closer observations to pregnancies with complicated by preeclampsia, to prevent the devastating adverse pregnancies outcomes for mom's and babies that can occur when pregnancies become complicated by preeclampsia. (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…)