Single Measurement of High-Sensitivity Troponin To Assess Myocardial Infarction Risk

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

Dr. Apple

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.

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Fingerprick Biomarker Test Can Reduce Use of Antibiotics in COPD Flares

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

Dr. Butler

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.

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What Are the Negative Risk Markers for Cardiovascular Events in the Elderly?

MedicalResearch.com Interview with:

Martin Bødtker Mortensen, læge PhD Afdelingen for Hjertesygdomme Aarhus Universitetshospital Danmark

Dr. Mortensen

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.

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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurologic Diseases

MedicalResearch.com Interview with:

Charlotte E. Teunissen,

Prof. Teunissen

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.

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COLVERA™ Blood Test Provides Improved Effectiveness Detecting Recurrence of Colorectal Cancer

MedicalResearch.com Interview with:

Lawrence LaPointe, Ph.D. Chief Innovation Officer Clinical Genomics Bridgewater, New Jersey 

Dr. LaPointe

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. 

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Metagenomic Sequencing Enhanced Diagnosis of Meningitis and Encephalitis Infections

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

Dr. Chiu

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.

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Accumulation of Metabolite M-2 Predicts Overall Survival of Chemorefractory Metastatic Colorectal Cancer Patients Treated with Regorafenib (Stivarga®)

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).  Continue reading

Circulating DNA Can Indicate Melanoma Treatment Failure

MedicalResearch.com Interview with:

David Polsky, MD, PhDDermatologist and Director of the Digmented Lesion Service

Dr. Polsky

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.

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Circulating Tumor DNA Linked to Recurrence After Colon Cancer Surgery

MedicalResearch.com Interview with:

Louise OlssonSenior researcherDepartment of Molecular Medicine and SurgeryColorectal SurgeryKarolinski InstituteStockholm, Sweden

Dr. Olsson

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.

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Amyloid and Tau Biomarkers Help Distinguish Alzheimer’s from Other Forms of Mild Cognitive Impairment

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].

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Multiple Sclerosis: Elevated IgG Linked to Risk of More Severe Disease

MedicalResearch.com Interview with:

Prof. Bernhard Hemmer MD PhDDirector of the Neurology ClinicTechnische Universität München

Prof. Hemmer

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. Continue reading

Fetal Haptoglobin as Potential Biomaker for Increased Risk of Cerebral Palsy

MedicalResearch.com Interview with:

MedicalResearch.com Interview with:Catalin S. Buhimschi MD, MMS, MBAProfessor of Obstetrics and GynecologyDivision of Maternal Fetal MedicineDirector of ObstetricsDepartment of Obstetrics and GynecologyChicago, IL, 60612

Dr. Buhimschi

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.

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Simple Urine Test May Allow Pregnant Women to Detect Preeclampsia at Home

MedicalResearch.com Interview with:

Dr. Kara Rood MDMaternal-fetal Medicine PhysicianThe Ohio State University Wexner Medical Center

Dr. Rood

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.

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Do Elevated Troponins Always Indicate a Heart Attack?

MedicalResearch.com Interview with:

Prof. Nick Curzen  BM(Hons) PhD FRCPProfessor of Interventional Cardiology/Consultant CardiologistUniversity Hospital SouthamptonSouthampton

Prof. Curzen

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.  Continue reading

Non-Small Cell Lung Cancer: Liquid Biopsy Pinpoints Treatment Options

MedicalResearch.com Interview with:

Vassiliki Papadimitrakopoulou, MDProfessor of MedicineDepartment of Thoracic/Head and Neck Medical OncologyMD Anderson Cancer Center in Houston

Dr. Papadimitrakopoulou

Vassiliki Papadimitrakopoulou, MD
Professor of Medicine
Department of Thoracic/Head and Neck Medical Oncology
MD Anderson Cancer Center in Houston

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

Response: 30% of patients with newly diagnosed advanced NSCLC can be treated successfully with targeted therapies, often yielding higher response rates than chemotherapy or immune checkpoint inhibitors. Selecting first-line therapy for patients with NSCLC requires assessment of an expanding list of guideline-recommended genomic biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET amplification and exon 14 skipping, and ERBB2, with NTRK newly added)

Standard-of-care (SOC) testing relies on tissue, which is limited by biopsy-related risks, specimen insufficiency, and lab processing duration, which hamper timely optimal treatment selection

–          NILE is a large, prospective, multicenter, head-to-head study of SOC tissue-based genomic testing to plasma-based comprehensive cfDNA genomic testing (Guardant360®). For the four biomarkers with FDA approved therapies, up to 34% of patients were tested by SOC tissue testing versus 95% with cfDNA testing. NILE met its primary endpoint – cfDNA performed similar to tissue in the detection of guideline-recommended biomarkers and cfDNA results were delivered significantly faster than SOC tissue testing (median 9 days vs. 15 days).Using cfDNA testing first, 87% of patients with a guideline-recommended biomarker would have been detected, compared to 67% if SOC tissue testing was first.

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Lung Cancer: Screening Model Including Low-Dose CT Can Improve Risk Prediction

MedicalResearch.com Interview with:

Martin C. Tammemägi   PhDSenior Scientist | Cancer Care Ontario | Prevention & Cancer Control | Scientific Lead | Lung Cancer Screening Pilot for People at High RiskProfessor (Epidemiology) | Brock University | Department of Health SciencesOntario  Canada

Dr. Tammemägi

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. Continue reading

First Blood Test To Predict Lung Transplant Rejection

MedicalResearch.com Interview with:

Sean Agbor-Enoh, M.D., Ph.D. Co-Director/Staff Clinician Laboratory of Transplantation Genomics National Heart, Lung, and Blood Institute National Institutes of Health

Dr. Agbor-Enoh

Sean Agbor-Enoh, M.D., Ph.D.
Co-Director/Staff Clinician
Laboratory of Transplantation Genomics
National Heart, Lung, and Blood Institute
National Institutes of Health

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

Response: People who receive organ transplants may develop acute or chronic rejection, in which the body’s immune system attacks the transplanted organ. While acute rejection is treatable and reversible, chronic rejection is not and remains the most common cause for organ transplant loss. Lung transplant recipients have the shortest survival rates among patients who get solid organ transplantation of any kind—only about half live past five years. This poor survival rate among lung transplant recipients is due in part to a high incidence of chronic rejection. Existing tools for detecting signs of rejection, such as biopsy, either require the removal of small amounts of lung tissue or are not sensitive enough to discern the severity of the rejection.

Building upon earlier work, our research team developed a simple blood test that can detect when a newly transplanted lung is being rejected by a patient, even when no outward signs of the rejection are evident.  The test could make it possible for doctors to intervene faster to prevent or slow down so-called chronic rejection—which is severe, irreversible, and often deadly—in those first critical months after lung transplantation. This same test might also be useful for monitoring rejection in other types of organ transplants.

Called the donor-derived cell-free DNA test, the experimental test begins with obtaining a few blood droplets taken from the arm of the transplant recipient. A special set of machines then sorts the DNA fragments in the blood sample, and in combination with computer analysis, determines whether the fragments are from the recipient or the donor and how many of each type are present.  Because injured or dying cells from the donor release lots of donor DNA fragments into the bloodstream compared to normal donor cells, higher amounts of donor DNA indicate a higher risk for transplant rejection in the recipient.

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CTCA Reports Thousands of Patients Have Had Treatment Based On Precision Biomarkers

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

Dr. Alvarez

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.”

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Advanced Prostate Cancer: Androgen-Receptor Testing May Guide Selection of Treatment

MedicalResearch.com Interview with:

Diagram_showing_prostate_cancer_that_has_spread_to_the_bones_CRUK_183.svg.png

Prostate cancer that has metastasized to the bone: Wikipedia Image

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.

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Panel of Salivary RNA Biomarkers Could Identify Autism

MedicalResearch.com Interview with:

Steven D. Hicks, M.D.,Ph.D Department of Pediatrics Penn State College of Medicine Hershey, PA

Dr. Hicks

Steven D. Hicks, M.D.,Ph.D
Department of Pediatrics
Penn State College of Medicine
Hershey, PA

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

Response: Since autism has both genetic and environmental underpinnings, my colleagues and I suspected that transcriptional elements (e.g. regulatory RNA molecules) might be different in the saliva of children with autism compared to peers without autism. We used a non-biased approach to analyze saliva from 372 children, and allowed machine learning techniques to inform which RNA elements best predicted autism status. To our surprise, microbial RNA levels and human RNA levels were equally powerful in predicting which children had autism. This may be because some children with autism eat restricted diets, resist tooth brushing, or put foreign objects in their mouths. The end result was a panel of 32 RNAs (20 human and 12 bacterial) that identified autism with 87% accuracy. Interestingly, when we tested the panel in a completely separate set of 84 children (including children from a different geographic region) the accuracy remained 88%. 

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New Biomarker Allows ‘Liquid Biopsy’ of Heart Muscle

MedicalResearch.com Interview with:

Robin M. Shaw, MD, PhD Wasserman Foundation Chair in Cardiology in honor of S. Rexford Kennamer MD Division of Cardiology, Smidt Heart Institute Department of Medicine, Cedars-Sinai Medical Center, Division of Cardiology, Department of Medicine University of California, Los Angeles, California

Dr. Shaw

Robin M. Shaw, MD, PhD
Wasserman Foundation Chair in Cardiology
in honor of S. Rexford Kennamer MD
Division of Cardiology, Smidt Heart Institute
Department of Medicine, Cedars-Sinai Medical Center,
Division of Cardiology, Department of Medicine
University of California,
Los Angeles, California

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

Response: At present, doctors do not have a clinical tool that assesses the biochemical health of heart muscle.  Biomarkers are available that tests the amount of fluid in the heart, and whether a heart is overloaded (which can be resolved with diuretics).  However, we don’t have biomarkers that assess the state of heart muscle itself.  As a result, doctors can use biomarkers to determine whether, when a patient has trouble breathing, there is heart failure present.

However, biomarkers do not work when the patient does not have symptoms or when we already know the patient has heart failure and are trying to make clinical management decisions about the condition.

Current biomarkers also don’t work to assess the health of the heart before symptoms develop which is to detect cellular changes in muscle before overall heart function is impaired. The new biomarker, CS, address the above unmet needs.  CS is based on cBIN1 which is a heart muscle protein that is essential for the heart to both contract and relax.  cBIN1 decrease when hearts are stressed such as in heart failure.  cBIN1 is also released into the blood stream, so it can be detected from a simple blood draw.  CS is determined from the inverse of cBIN1, so low cBIN1 in blood will give a high CS signal.  A low cBIN1, or a high CS, indicates failing heart muscle, and an increased likelihood for being admitted to the hospital with acute heart failure within the next twelve months.  Continue reading

Gene Signature Blood Test Can Diagnose TB and Treatment Response

MedicalResearch.com Interview with:
"Mycobacterium tuberculosis Bacteria, the Cause of TB" by NIAID is licensed under CC BY 2.0Purvesh Khatri, Ph.D.
Associate Professor
Stanford Institute for Immunity, Transplantation and Infection (ITI)
Stanford Center for Biomedical Informatics Research (BMIR)
Department of Medicine
Stanford University
Stanford, CA 94305

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

Response: We have previously described a 3-gene signature for distinguishing patients with active tuberculosis (ATB) from those with other diseases, latent mycobacterium tuberculosis (LTB) infection, and healthy controls (Sweeney et al. Lancet Respir Med 2016).

The current study in JAMA Network Open is a follow up study to validate the 3-gene signature in 3 additional independent cohorts that were prospectively collected.

Using these 3 cohorts we have now showed that the 3-gene signature

(1) can identify patients with LTB that will progress to ATB about 6 months prior to diagnosis of active tuberculosis.

(2) can identify patients with ATB in active screening, and

(3) can identify patients with ATB at diagnosis that have higher likelihood of persistent lung inflammation due to subclinical ATB at the end of treatment.  Continue reading

Computer Algorithm Can Distinguish Dangerous From Manageable Prostate Cancer

MedicalResearch.com Interview with:

Davide Pellacani Ph.D. Postdoctoral Fellow, Eaves' Lab Terry Fox Laboratory, BC Cancer Research Centre Vancouver, BC

Dr. Pellacani

Davide Pellacani Ph.D.
Postdoctoral Fellow, Eaves’ Lab
Terry Fox Laboratory,
BC Cancer Research Centre
Vancouver, BC

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

Response: Prostate cancer is characterized by frequent DNA methylation changes compared to normal tissue. Nevertheless, understanding which of those changes lead to the acquisition of malignant proprieties is complicated by the predominance of cells with luminal features in prostate cancers.

In this study we generated DNA methylation maps of two distinct cell populations found within prostate cancer samples (called basal and luminal) and their normal counterparts. These datasets clearly showed that many of the common DNA methylation changes found in prostate cancer are present in luminal cells from both cancer and normal tissues. These changes are not necessarily cancer-specific, and are likely due to the bias associated with analyzing tissues in bulk, where most cancer cells have luminal-like features.

We used these datasets to derive two cancer-specific and phenotype-independent DNA methylation signatures: one specific to prostate cancer luminal cells, and one composed of changes measured in both luminal and basal cancer cells.

We then validated the potential clinical utility of these signatures by testing their ability to distinguish prostate cancer from normal samples, and tumours that have already escaped the prostate from those that have not, using the publicly available dataset from The Cancer Genome Atlas.

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Endometriosis: Biomarker May Allow Personalized Approach to Treatment

MedicalResearch.com Interview with:

Valerie A. Flores, MD Clinical Instructor Division of Reproductive Endocrinology & Infertility Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of Medicine - Yale New Haven Hospital

Dr. Flores

Valerie A. Flores, MD
Clinical Instructor
Division of Reproductive Endocrinology & Infertility
Department of Obstetrics, Gynecology & Reproductive Sciences
Yale School of Medicine – Yale New Haven Hospital

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

Response: Endometriosis is a debilitating gynecologic disease that affects 1 in 10 reproductive-aged women, causing pain and infertility.  It is a hormonally dependent disorder— estrogens promote growth of endometriosis, while progesterone inhibits estrogen-dependent proliferation. Although progestin-based therapies (including combined oral contraceptives) are first-line therapy in the management of endometriosis-associated pain, response to progestins is variable and currently unpredictable.

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TumorScan May Become a Universal Screening Blood Test For Cancer

MedicalResearch.com Interview with:

Professor Diana Anderson Established Chair in Biomedical Sciences The University of Bradford Richmond Road Bradford West Yorkshire

Prof Anderson

Prof. Diana Anderson
Established Chair in Biomedical Sciences
The University of Bradford Richmond Road Bradford West Yorkshire

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

Response: I have worked in this field for over 40 years both as a research scientist in industry and as a university-based researcher. It has always been my ambition to develop a relatively simple and affordable test to predict if a person is sensitive to cancer. In fact, in 1974, I was appointed as Head of Mutagenesis Studies at ICI’s Central Toxicology Laboratory in Manchester, UK, and I was looking at developing a short-term test to predict cancer even back then.

Our ‘universal’ cancer test is different from other ‘universal’ tests being developed, because ours is not looking for a specific biomarker or mutation. Ours is a generic test for cancer in an individual, regardless of any underlying mechanism that’s causing their cancer.

It is known that levels of damage to the DNA in the cellular genome can correlate with cancer and this is what we set out to investigate with the Comet assay.

Of the available tests to detect damage to the genome the Comet assay is very straightforward. This assay was primarily developed as a method to measure DNA damage. Briefly, cells are embedded in agarose on a microscope slide and lysed to remove membranes leaving supercoiled DNA loops, breaks in which after alkaline treatment and alkaline electrophoresis move towards a positive charge. The DNA is stained with a fluorescent dye and visualised by fluorescent microscopy. The image is like Haley‘s comet and the greater number of breaks the greater is the migration to the anode and the greater the damage.  Continue reading

New Point-of-Care Troponin Assay Can Rapidly Rule Out Heart Attack

MedicalResearch.com Interview with:

Dr John W Pickering, BSc(Hons), PhD, BA(Hons) Associate Professor , Senior Research Fellow in Acute Care Emergency Care Foundation, Canterbury Medical Research Foundation, Canterbury District Health Board |  Christchurch Hospital Research Associate Professor | Department of Medicine University of Otago Christchurch

Prof. Pickering

Dr John W Pickering, BSc(Hons), PhD, BA(Hons)
Associate Professor , Senior Research Fellow in Acute Care
Emergency Care Foundation, Canterbury Medical Research Foundation, Canterbury District Health Board |  Christchurch Hospital
Research Associate Professor | Department of Medicine
University of Otago Christchurch

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

Response: The assessment of patients with suspected myocardial infarction is one of the most common tasks in the emergency department. Most patients assessed (80 to 98% depending on the health system) are ultimate not diagnosed with an MI.   High-sensitivity troponin assays have been shown to have sufficient precision at low concentrations to allow very early rule-out of myocardial infarction. However, these are lab-based assays which typically result in a delay from blood sampling before the result is available and the physician is able to return to a patient to make a decision to release the patient or undertake further investigation. Point-of-care assays provide results much quicker, but have to-date not had the analytical characteristics that allow precise measurements at low concentrations.

In this pilot study we demonstrated that a single measurement with a new point-of-care assay (TnI-Nx; Abbott Point of Care) which can measure low troponin concentrations, could safely be used to rule-out myocardial infarction a large proportion of patients (57%). The performance was at least comparable to the high-sensitivity troponin I assay, if not a little better (44%).

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MidLife PSA Can Risk-Stratify Prostate Cancer in African American Men

MedicalResearch.com Interview with:

Mark Preston, MD, MPH Associate Surgeon, Brigham and Women's Hospital Assistant Professor of Surgery, Harvard Medical School Brigham and Women's Hospital Department of Surgery, Urology Boston, MA

Dr. Preston

Mark Preston, MD, MPH
Associate Surgeon, Brigham and Women’s Hospital
Assistant Professor of Surgery, Harvard Medical School
Brigham and Women’s Hospital
Department of Surgery, Urology
Boston, MA
MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Black men are at significantly increased risk of developing and dying from prostate cancer. Unfortunately, there is limited research on screening strategies in this high-risk population. In this original investigation, we studied how baseline PSA levels measured in midlife predict later risk of aggressive prostate cancer in a population of black men. This study used stored blood samples and over a decade of follow-up in the Southern Community Cohort Study, an on-going cohort study with the highest representation of black men in the U.S.

We demonstrated that PSA levels in midlife very strongly predict future aggressive prostate cancer. Our data identify subgroups of black men who have widely divergent long-term risk of aggressive prostate cancer based on baseline PSA during midlife. We suggest that these groups could benefit from screening intervals tailored to their actual magnitude of disease risk.

These important findings build on our previous work on baseline PSA and subsequent risk of lethal prostate cancer in mainly white men, which was published in the Journal of Clinical Oncology in August 2016. 

MedicalResearch.com: What should readers take away from your report? 

Response: One strategy for improving PSA screening is to do an earlier measurement of PSA during midlife (aged 40-55). PSA levels during midlife have been shown by our group and others to strongly predict long-term risk of prostate cancer, particularly risk of aggressive disease, in now both black and white men.

This baseline PSA level during midlife can be used to risk-stratify PSA screening, targeting higher risk men for screening in order to diagnosis and treat them early while an opportunity exists for cure.  In addition, men at low risk could safely be screened less frequently. As a result, much of the benefit of PSA screening on prostate cancer mortality could be maintained, while overdiagnosis and overtreatment would be reduced.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Prospective studies of a risk stratified screening program should be conducted.  We are also studying ways to further improve risk prediction and to explore biologic mechanisms why a midlife PSA is so predictive.

Disclosures. I have no disclosures. Disclosures for other authors are listed in the manuscript.

Citation:

Eur Urol. 2018 Sep 17. pii: S0302-2838(18)30627-4. doi: 10.1016/j.eururo.2018.08.032. [Epub ahead of print]

Baseline Prostate-specific Antigen Level in Midlife and Aggressive Prostate Cancer in Black Men.

Preston MA1, Gerke T2, Carlsson SV3, Signorello L4, Sjoberg DD5, Markt SC6, Kibel AS7, Trinh QD7, Steinwandel M8, Blot W9, Vickers AJ5, Lilja H10, Mucci LA6, Wilson KM11.

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Proteomics Leads to Discovery of Ovarian Cancer Protein Biomarker

MedicalResearch.com Interview with:

Site of Ovarian Cancer - Wikipedia Image

Site of Ovarian Cancer – Wikipedia Image

Fabian Coscia PhD
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, German and
Ernst Lengyel MD PhD
Department of Obstetrics and Gynecology
Section of Gynecologic Oncology
University of Chicago, Chicago, IL 


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

Response: Ovarian cancer is a very aggressive disease. Only one in six patients survives more than 10 years after the first diagnosis. This high mortality is primarily because the disease is usually detected late in its course, when the tumor has already spread from the ovaries to the surrounding organs in the abdomen.

In an interdisciplinary collaboration between the Max Planck Institute of Biochemistry in Martinsried, Munich, the University of Chicago and the University of Copenhagen, we performed deep tissue proteomics on archived biobank material to identify drivers of long-term patient survival.  Continue reading

IMPRES Score Predicts Melanoma Response to Immunotherapy

MedicalResearch.com Interview with:

Melanoma CDC/ Carl Washington, M.D., Emory Univ. School of Medicine; Mona Saraiya, MD, MPH

This image depicts the gross appearance of a cutaneous pigmented lesion, which had been diagnosed as superficial spreading malignant melanoma (SSMM).  Reminder: Melanoma can take many forms. Not all look like this. Have your skin examined for skin cancer.

Dr. Noam Auslander PhD
National Cancer institute and the Center for Bioinformatics and Computational Biology University of Maryland, College Park

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

Response: Immunotherapy – specifically immune checkpoint blockage (ICB) therapy – has been shown to be very effective in treating melanoma. However, only some patients with advanced tumors currently benefit from ICB therapies, while others are completely resistant and hence can be spared from the associated side effects and costs. Hence, predicting which patients are most likely to respond is an important challenge that can have great clinical benefits.   Continue reading

Serial Liquid Biopsies May Predict Response to Colon Cancer Treatment

MedicalResearch.com Interview with:

Andrea Sottoriva, PhD, MSc Reader in Cancer Evolutionary Dynamics | Evolutionary Genomics & Modelling Lab Centre for Evolution and Cancer | The Institute of Cancer Research London

Dr. Sottoriva

Dr. Andrea Sottoriva, PhD
Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom


MedicalResearch.com: What is the background for this study?
Would you briefly explain what is meant by a liquid biopsy?


Response:
Cetuximab is a targeted treatment available for metastatic colorectal cancer patients. Unfortunately, although many patients benefit from Cetuximab, after an initial response to the treatment many patients relapse and become resistant to the drug.

We know that this resistance is due to the tumour evolving and adapting to therapy. Liquid biopsies allow to look for residual cancer DNA in the blood of a patient and hence monitor the emergence of resistance over time. We used blood samples take every 4 weeks (quite frequently for this type of study) to monitor the evolution of the cancers under treatment and see if there were some measurements that would predict if and when patients will relapse.

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