Racial Differences in Plasma Biomarker May Partially Explain Stroke Disparities

MedicalResearch.com Interview with:

Pankaj Arora MD, FAHA Assistant Professor, Cardiology Division University of Alabama at Birmingham Section Editor, Circulation: Cardiovascular Genetics American Heart Association

Dr. Arora

Pankaj Arora MD, FAHA
Assistant Professor, Cardiology Division
University of Alabama at Birmingham
Section Editor, Circulation: Cardiovascular Genetics
American Heart Association 

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

Response: Natriuretic peptides are hormones produced by the heart in response to increased wall stress in the atria and ventricles. It is well known that blacks have increased prevalence of cardiovascular disease which contributes to racial disparities in outcomes.

In the current work, we tested the hypothesis that black race is a natriuretic peptide deficiency state using a stratified random cohort of 4,415 participants selected from the REGARDS study (a national population-based cohort study evaluating racial and geographic disparities in stroke in US adults aged ≥45 years of age or older). Next, we looked for published results on the percentage difference in N-terminal proB-type NP (NTproBNP) levels by race in participants free of cardiovascular disease from other population cohorts. Lastly, we explored whether association of natriuretic peptides with all-cause mortality and CV mortality in apparently healthy individuals from REGARDS differs by race.

We found that in multivariable adjustment, NTproBNP levels were up to 27% lower in black individuals as compared with white individuals in the REGARDS study. We pooled our results and found that in meta-analysis of the 3 cohorts, NTproBNP levels were 35% lower in black individuals than white individuals (more than 13,000 individuals in total). Lastly, we found that the higher NTproBNP levels were associated with higher incidence of all-cause mortality, and cardiovascular mortality in healthy blacks and white individuals, and this association did not differ by race.

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Micro RNAs in Saliva May Predict Severity of Concussion Injuries

MedicalResearch.com Interview with:

Dr. Steven D. Hicks,  M.D., Ph.D Penn State Health

Dr. Hicks

Dr. Steven D. Hicks,  M.D., Ph.D
Penn State Health

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

Response: Previous research has shown that small epigenetic molecules called microRNAs are altered in the blood after a traumatic brain injury. Our own pilot research showed that microRNAs were also changed in the saliva after brain injury and that some of these changes mirrored changes in cerebrospinal fluid. In this study we investigated whether salivary microRNA patterns after a concussion could be used to predict the duration and character of symptoms one month after injury.

We found that levels of five microRNAs predicted presence of symptoms one month later with greater accuracy (~85%) than standard surveys of symptom burden (~65%). Interestingly, one of the predictive salivary microRNAs (miR-320c) targets pathways involved in synaptic plasticity and was significantly correlated with attention difficulties one month after concussive injury.   Continue reading

High-Sensitivity Cardiac Troponin I Can Identify Low Risk Chest Pain Patients

MedicalResearch.com Interview with:

Dr Andrew R. Chapman BHF Clinical Research Fellow University of Edinburgh Chancellors Building Edinburgh 

Dr. Chapman

Dr Andrew R. Chapman
BHF Clinical Research Fellow
University of Edinburgh
Chancellors Building
Edinburgh 

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

Response: High-sensitivity cardiac troponin tests allow accurate measurement of cardiac troponin in the bloodstream. Currently, guidelines recommend we evaluate patients with suspected myocardial infarction using these tests, by looking for levels which are above the upper reference limit (99th centile). These troponin measurements are taken on arrival, and often repeated after admission to hospital up to six hours later. When levels are below this limit, the diagnosis of myocardial infarction is ruled out. However, using such a high limit in patients on arrival to hospital may not be safe, as lower risk stratification thresholds has been shown to reduce missed events,  and in these patients admission to hospital for repeat testing may not be necessary. However, there is no consensus as to the optimal threshold for use in practice.

In a worldwide study of 23,000 patients from 9 countries, we have shown when high-sensitivity cardiac troponin I concentrations are below a risk stratification threshold of 5 ng/L at presentation, patients are at extremely low risk of myocardial infarction or cardiac death at 30 days, with fewer than 1 in 200 patients missed. Importantly, this threshold identifies almost 50% of all patients as low risk after a single blood test. As admission or observation of these patients is estimated to cost as much as $11 billion per year in the United States, this strategy has major potential to improve the efficiency of our practice.

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Personality Changes Can Signal Incomplete Recovery After Traumatic Brain Injury

MedicalResearch.com Interview with:

Prof.dr. J van der Naalt PhD Department of Neurology University Medical Center Groningen Groningen, The Netherlands

Prof J van der Naalt

Prof.dr. J van der Naalt PhD
Department of Neurology University Medical Center Groningen
Groningen, The Netherlands

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

Response: Mild traumatic brain injury occurs frequently and is one of the leading cause of morbidity in adults worldwide. It is a major social-economic problem with one in three patients had persistent complaints several months after injury that interfere with resumption of daily activities and work.

One of the most important questions concerns the finding that some patients recover without complaints and others do not after sustaining a mild traumatic brain injury. In a follow-up study with more than 1000 participants we found that personality factors are a major factor in the recovery process. In particular coping, that is the way patients adapt to persistent complaints, is important next to emotional distress and impact of the injury.

In an add-on study with fMRI we found that in the early phase after injury, the interaction between specific brain networks was temporarily changed. However, when regarding persistent posttraumatic complaints , specific personality characteristics significantly determine long term outcome.

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Defective Viral Genomes May Indicate Greater Flu Virus Severity

MedicalResearch.com Interview with:
Ana Falcón
Department of Molecular and Cellular Biology
National Center for Biotechnology
Spanish National Research Council (CNB-CSIC)
Madrid, Spain

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

Response: Influenza A virus (IAV) infection can be severe or even lethal in toddlers, the elderly and patients with certain medical conditions. Infection of apparently healthy individuals nonetheless accounts for many severe disease cases and deaths, suggesting that viruses with increased pathogenicity co-circulate with pandemic or epidemic viruses.

IAV virulence and pathogenesis are dependent on complex, multigenic mechanisms involving the viral genetic characteristics, the host conditions, the virus-host interactions, and the host response to the infection. Influenza virus pathogenicity has been studied in depth for many years, and several amino acid changes have been identified as virulence determinants, however, a general pathogenicity determinant has not been characterized.

A proportion of influenza virus particles have defective genome RNAs (Defective Viral Genomes-DVGs) due to internal deletions of viral segments. The DVGs have the 3’ and 5’ ends of the parental RNA segments, and most have a single, large central deletion that generates viral RNAs of 180–1000 nucleotides. The presence of DVGs potentiates the host response in cultured cells and in animal models and leads to attenuated infection, possibly through recognition of double-stranded RNA by receptors that activate antiviral signaling cascades.

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Any Detectable High-Sensitivity Cardiac Troponin T Level Associated With Adverse Outcomes

MedicalResearch.com Interview with:
Martin Holzmann PhD

Department of Medicine
Functional Area of Emergency Medicine,
Karolinska University Hospital, Huddinge
Stockholm, Sweden

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

Response: There has been a few studies in the general population that indicate that subjects with detectable and elevated high-sensitivity troponin T (hs-cTnT) levels have an increased risk of death and cardiovascular disease. However, in clinical practice troponins are not used for anything else than to rule in or rule out myocardial infarction in the emergency department. In addition, in a previous publication we have shown that patients with persistently elevated troponin levels are rarely investigated or followed-up to exclude heart disease. Therefore, we wanted to investigate how the association between different levels of hs-cTnT are associated with outcomes in patients with chest pain but no MI or other acute reasons for having an acutely elevated troponin level.

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Refined Biomarker Model Can Guage Risk of Alzheimer’s In Patients With Mild Cognitive Impairment

MedicalResearch.com Interview with:
Ingrid S. van Maurik, MSc
Department of Neurology and Alzheimer Center
Department of Epidemiology and Biostatistics
Amsterdam Neuroscience
VU University Medical Center
Amsterdam, the Netherlands

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

Response: CSF and MRI biomarkers are increasingly used in clinical practice, but their diagnostic and prognostic value is not perfect. Furthermore, criteria do not specify how to deal with conflicting or borderline results, or how to take patient characteristics into account. Therefore, optimal use of these biomarkers in clinical practice remains challenging.

As part of the ABIDE project, we constructed biomarker-based prognostic models (CSF, MRI and combined) that enable prediction of future Alzheimer’s disease, or any type of dementia, in individual patients with mild cognitive impairment. When using these models, any value can be entered for the variables, resulting in personalized probabilities with confidence intervals.

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New Biomarker Has Potential For Sideline Diagnosis of Traumatic Brain Injury

MedicalResearch.com Interview with:

Dr-Adrian-Harel.jpg

Dr. Adrian Harel

Dr. Adrian Harel, PhD
Chief Executive Officer
Medicortex Finland

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

Response: Every 15 seconds, someone in the United States suffers a new head injury. Of the 2.5M people treated in hospital emergency rooms each year, 80,000 become permanently disabled because of TBI. Currently, there are no reliable diagnostic tests to assess the presence or severity of an injury on-site, nor are there any pharmaceutical therapies that could stop the secondary injury from spreading. Accurate diagnostics would benefit especially mild cases of TBI (concussions), which, if occurring repeatedly, may cause neurodegenerative conditions such as Chronic Traumatic Encephalopathy (which is typical for athletes in NFL and Ice-hockey).

We have performed extensive preclinical research comparing fluid biopsies from normal and injured lab animals. The results showed some unique biomarkers released as a biodegradation products after head injury. The data served as the basis and confirmation for our patent applications to protect the biomarker concept.

Medicortex has completed a clinical proof-of-concept trial in collaboration with Turku University Hospital (Tyks). Samples from 12 TBI patients and 12 healthy volunteers were collected and analyzed for the presence and for the level of the biomarker in state-of-the-art laboratories. The study demonstrated the diagnostic potential of the new biomarker in humans and it confirmed the prior preclinical findings. This was a significant milestone for Medicortex.

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Blood Biomarkers Signal Multiple Organ Dysfunction Syndrome After Critical Injuries

MedicalResearch.com Interview with:

Dr. Joanna Shepherd Centre for Trauma Sciences Blizard Institute Queen Mary, University of London

Dr. Shepherd

Dr. Joanna Shepherd
Centre for Trauma Sciences
Blizard Institute
Queen Mary, University of London

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

Response: Recent advances in resuscitation and treatment of life-threatening critical injuries means that patients with previously unsurvivable injuries are now surviving to reach hospital.  However, many of these patients develop Multiple Organ Dysfunction Syndrome (MODS), which is a failure of several organs including the lung, heart, kidney, and liver.

We studied immune cell genes in the blood of critically injured patients within the first few minutes to hours after injury, a period called the ‘hyperacute window’. We found a small and specific response to critical injury during this window that then evolved into a widespread immune reaction by 24 hours.  The development of MODS was linked to changes in the hyperacute window, with central roles for innate immune cells (including natural killer cells and neutrophils) and biological pathways associated with cell death and survival.  By 24 hours after injury, there was widespread immune activation present in all critically injured patients, but the MODS signal had either reversed or disappeared.

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An Ultra-Early Inflammatory Biomarker of Traumatic Brain Injury

MedicalResearch.com Interview with:

Dr Lisa J Hill PhD Institute of Inflammation and Ageing Research Fellow Neuroscience and Ophthalmology Institute of Inflammation and Ageing College of Medical and Dental Sciences University of Birmingham UK

Dr. Hill

Dr Lisa J Hill PhD
Institute of Inflammation and Ageing
Research Fellow
Neuroscience and Ophthalmology
Institute of Inflammation and Ageing
College of Medical and Dental Sciences
University of Birmingham UK 

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

Response: Traumatic brain injury (TBI) is the leading cause of death and disability among young adults and, according to the World Health Organization, by 2020 TBI will become the world’s leading cause of neurological disability across all age groups.  Early and correct diagnosis of traumatic brain injury is one of the most challenging aspects faced by clinicians. Being able to detect compounds in the blood that help to determine how severe the brain injury is would be of great benefit to patients and aid in their treatment.  Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins.  The discovery of reliable biomarkers for the management of TBI would improve clinical interventions.

We collected blood samples from 30 injured patients within the first hour of injury prior to the patient arriving at hospital and analysed them. Analysis of protein biomarkers from blood taken within the first hour of injury has never been carried out until now. We used a panel of 92 inflammation-associated human proteins when analysing the blood samples. The analysis identified three inflammatory proteins, known as CST5AXIN1 and TRAIL, as novel biomarkers of TBI.

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Circulating Cell Scoring System Identifies High Risk Prostate Cancer

MedicalResearch.com Interview with:

Dr. Yong-Jie Lu Reader in Medical Oncology Centre for Molecular Oncology Barts Cancer Institute - a CR-UK Centre of Excellence Queen Mary University of London John Vane Science Centre, Charterhouse Square, LONDON

Dr. Yong-Jie Lu

Dr. Yong-Jie Lu MBBS, MD, PhD
Reader in Medical Oncology
Centre for Molecular Oncology
Barts Cancer Institute – a CR-UK Centre of Excellence
Queen Mary University of London
John Vane Science Centre, Charterhouse Square
London

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

Response: Identifying/monitoring the occurrence of metastasis and the prediction of the length that a patient may survive with a prostate cancer is critical for doctors to select the proper treatment, aiming to achieve the best control of the cancer with a balance of quality of life. Currently this is achieved mainly by analysing the cancer tissues acquired through very invasive procedures or by expensive imaging techniques, most of which expose the patient to toxic radioactive materials.

Circulating tumour cells (CTCs), which play a key role in the metastasis process, have been shown for their potential to be used for cancer prognosis by a simple blood sample analysis. However, previous CTC studies mainly detect the epithelial type of CTCs. Using the ParsortixTM (ANGLE plc) cell-size and deformability based CTC isolation system, we analysed not only epithelial CTCs, but also CTCs with epithelial-mesenchymal transition (EMT), a cellular process associated with cancer invasion and metastasis.

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Cholesterol Uptake Capacity, a New Indicator of HDL Functionality, for Cardiovascular Risk Stratification in the Real World.

MedicalResearch.com Interview with:
Amane Harada, PhD
Senior Researcher
Central Research Laboratories, Sysmex Corporation
Kobe, Japan

Ryuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of MedicineRyuji Toh, MD, PhD
Associate Professor
Division of Evidence-based Laboratory Medicine
Kobe University Graduate School of Medicine
Kobe, Japan 


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

Response: High-density lipoprotein (HDL) exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative functions as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become “dysfunctional” HDL under pathological conditions.

Recent studies have demonstrated that cholesterol efflux capacity of HDL is a better predictor of CVD than HDL-C, suggesting that not only the quantity, but also the quality of HDL may significantly modulate and predict the progression of cardiovascular disease.

However, the conventional procedure for efflux capacity assay requires radiolabeling and cells, and the procedures are time consuming. Therefore, its clinical application is impractical.

To solve those problems, we have recently developed a new assay system to evaluate the capacity of HDL to accept cholesterol, named “uptake capacity”.

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Vascular Biomarker Predicts Death or Pulmonary Morbidity in Premature Infants

MedicalResearch.com Interview with:

Jegen Kandasamy MD Division of Neonatology Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program University of Alabama at Birmingham Birmingham, Alabama

Dr. Kandasamy

Jegen Kandasamy MD
Division of Neonatology
Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program
University of Alabama at Birmingham
Birmingham, Alabama 

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

Response: Preterm infants, especially those that are born with a birth weight of 750 grams or less, are prone to a lung disease called bronchopulmonary dysplasia (BPD) because the development of lungs in these infants takes place in an environment that has more oxygen than that available in utero. Recently, pulmonary blood vessel growth and function has been hypothesized to play a causal role in the pathogenesis of BPD. Vascular endothelial cell function has been shown to affect hyperoxia-induced lung damage in animal studies. An important source of human vascular endothelial cells is the umbilical cord of newborn infants. These human umbilical venous endothelial cells (HUVEC) have been used to measure endothelial cell function in various diseases but never in diseases related to the newborn infants from whom they were derived.

In addition, the mitochondria in various cells in our body respond to oxygen toxicity by creating, as well as consuming, reactive oxygen species (ROS) that mediate most of the effects of oxygen-induced damage. Therefore, we designed this study to measure mitochondrial function in vascular endothelial cells obtained from the umbilical cords of prematurely born infants at the time of their birth. We then compared these mitochondrial functional measures between infants who later died or developed BPD versus those who survived without BPD.

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New Prostate Cancer Specific Assay May Reduce Need For Biopsies

MedicalResearch.com Interview with:

Eric A. Klein, MD</strong> Chairman, Glickman Urological and Kidney Institute Cleveland Clinic

Dr. Klein

Eric A. Klein, MD
Chairman, Glickman Urological and Kidney Institute
Cleveland Clinic

MedicalResearch.com: Which of these results did you find most interesting or surprising?

Response: What’s most interesting is that the IsoPSA assay redefines how PSA is measured, which links it more closely to the underlying biology of cancer. Current assays measure only the concentration of PSA, which can be affected by conditions other than cancer – BPH most commonly, but also infection and inflammation – which limits its diagnostic accuracy for finding cancer. Its been known for several decades that PSA exists in multiple different forms in the bloodstream in patients with prostate cancer.

These novel molecules arise because cancer cells have deranged cellular metabolism that result in the generation of new species of PSA, making their measurement more tightly linked to the presence or absence of cancer and even the presence of high grade cancer (where cellular metabolism is even more disordered).

The IsoPSA assay is the first assay to measure all of these isoforms and thus has better diagnostic accuracy for cancer.

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TeloView Measures Genomic Stability To Predict Disease Aggressiveness

MedicalResearch.com Interview with:

3D SignaturesJason Flowerday, CEO
Director of 3D Signatures 

MedicalResearch.com: What is the background for 3D Signatures?

Response: 3D Signatures, and its clinical lab tests, which incorporate its proprietary TeloViewTM software analytics, is the culmination of over 20 years of ground-breaking research conducted by Dr. Sabine Mai and her colleagues. It is the only technology in the world that quantifies genomic instability, which is the hallmark of cancer and other proliferative diseases at the whole-cell level.

By measuring the degree of genomic instability from different tissues, TeloViewTM has produced clinically actionable distinctions in the stage of disease, rate of progression of disease, drug efficacy, and drug toxicity. The technology is well developed and supported by 22 clinical studies on over 2,000 patients on 13 different cancers including Alzheimer’s disease. The results have been exceptional and represent a universal biomarker platform across all disease areas that the company has investigated to date.

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Saliva Test Can Predict Concussion Duration in Children

MedicalResearch.com Interview with:

Steven Daniel Hicks, MD, PhD Assistant Professor, Division of Academic General Pediatrics College of Medicine Penn State Health

Dr. Hicks

Steven Daniel Hicks, MD, PhD
Assistant Professor, Division of Academic General Pediatrics
College of Medicine
Penn State Health

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

Response: There are about 3 million concussions in the US each year and the majority occur in children. Parents of children with concussions commonly cite length of recovery as a major concern, but pediatricians have no objective or accurate tests for addressing this concern.

Our research group previously identified small regulatory molecules called microRNAs that were altered in both the spinal fluid and saliva in children with traumatic brain injuries. In this study we investigated whether those microRNAs could predict duration of concussion symptoms. In 52 children with concussion we found a set of microRNAs that predict whether concussion symptoms would last beyond one month with over 80% accuracy. This was significantly more accurate than survey based tools such as the sports concussion assessment tool or a modified concussion clinical risk score. Interestingly, the microRNAs with predictive accuracy targeted pathways involved in brain repair and showed correlations with specific concussion symptoms.

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Granzyme B Probe Plus PET Scanning Helps Determine Response To Immunotherapy

MedicalResearch.com Interview with:

Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School

Dr. Ben Larimer

Ben Larimer, PhD research fellow in lab of
Umar Mahmood, MD, PhD

Massachusetts General Hospital
Professor, Radiology, Harvard Medical School

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

Response:
Although immunotherapies such as checkpoint inhibitors have revolutionized cancer treatment, unfortunately they only work in a minority of patients. This means that most people who are put on a checkpoint inhibitor will not benefit but still have the increased risk of side effects. They also lose time they could have spent on other therapies. The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not greatly improves individual patient care and helps accelerate the development of new therapies.

The main purpose of our study was to find a way to separate immunotherapy responders from non-responders at the earliest time point possible, and develop an imaging probe that would allow us to distinguish this non-invasively.

Granzyme B is a protein that immune cells use to actually kill their target. They keep it locked up in special compartments until they get the right signal to kill, after which they release it along with another protein called perforin that allows it to go inside of tumor cells and kill them. We designed a probe that only binds to granzyme B after it is released from immune cells, so that we could directly measure immune cell killing. We then attached it to a radioactive atom that quickly decays, so we could use PET scanning to noninvasively image the entire body to see where immune cells were actively releasing tumor-killing granzyme B.

We took genetically identical mice and gave them identical cancer and then treated every mouse with checkpoint inhibitors, which we knew would result in roughly half of the mice responding, but we wouldn’t know which ones until their tumors began to shrink. A little over a week after giving therapy to the mice, and before any of the tumors started to shrink, we injected our imaging probe and performed PET scans. When we looked at the mice by PET imaging, they fell into two groups. One group had high PET uptake, meaning high levels of granzyme B in the tumors, the other group had low levels of PET signal in the tumors. When we then followed out the two groups, all of the mice with high granzyme B PET uptake ended up responding to the therapy and their tumors subsequently disappeared, whereas those with low uptake had their tumors continue to grow.

We were very excited about this and so we expanded our collaboration with co-authors Keith Flaherty and Genevieve Boland to get patient samples from patients who were on checkpoint inhibitor therapy to see if the same pattern held true in humans. When we looked at the human melanoma tumor samples we saw the same pattern, high secreted granzyme levels in responders and much lower levels in non-responders.

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New Platform Aims To Improve Cancer Markers Braf p.V600E/K Mutations

MedicalResearch.com Interview with:

Thurai Moorthy Ph.D.</strong> President, MultiGEN Diagnostics Greensboro, NC 27405

Dr. Moorthy

Thurai Moorthy Ph.D.
President, MultiGEN Diagnostics
Greensboro, NC 27405

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

Response: As more cancer related genetic markers are reported, there is a need for appropriate molecular tests to meet clinical expectations. These expectations include detection at very low amount in a heterogeneous cell population, such as Formalin Fixed Paraffin embedded (FFPE) tumor biopsies.

Braf p.V600E/K mutations are cancer-specific markers found in a variety of cancers. There are several drugs in use, and more drugs are being developed, which are prescribed only to those patients whose tumor carries either of these (Braf p.V600E/K) mutations.

Hence, detection of Braf p. V600E/K is critical in the treatment of cancer patients. In this regard, we developed a new platform technology, Allele Specific Multiplex Sequencing (ASMS, for the detection of cancer markers from biopsy samples. As a demonstration project, we tested the new platform technology for the detection of Braf p.V600E/K using tumor samples (FFPE) previously tested by two presently used methods.

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Rapid Rule-Out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement

MedicalResearch.com Interview with:
Martin P. Than, MBBS
Emergency Department, Christchurch Hospital and
Dr John W Pickering, PhD
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 New Zealand

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

Response: Patients being investigated for possible acute coronary syndrome comprise one of the largest groups of patients presenting to emergency rooms. Troponin assays have developed such that they can now measure with greater accuracy much lower concentrations of troponin. A large retrospective registry based study and a couple of smaller prospective studies suggested that patients with a very low concentrations of troponin T (below the current limit of detection of 5 ng/L) measured with Roche Diagnostic’s high-sensitivity troponin T (hsTnT) assay on presentation to the emergency department (ie single blood draw) are very unlikely to be having a myocardial infarction (MI).

Our study gathers the current best evidence for using concentrations below the limit of detection in conjunction with no evidence of new ischaemia on ECG to safely risk stratify patients to a very low-risk group for MI and, therefore, potentially identify patients safe for early discharge.

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Pre-Clinical Study of Tbit™ System for Detection of Traumatic Brain Injury

MedicalResearch.com Interview with:

Sergey A. Dryga, PhD, MBA Chief Scientific Officer BioDirection, Inc.

Dr. Sergey Dryga

Sergey A. Dryga, PhD, MBA
Chief Scientific Officer
BioDirection, Inc. 

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

Response: When patients have suffered a head injury, they typically undergo a series of subjective cognitive tests to confirm a diagnosis of a concussion or other traumatic brain injury. In many cases these tests are inaccurate and inconsistent, increasing the risk of misdiagnosis. In other cases, patients may undergo an unnecessary CT scan, which is costly and exposes them to radiation. Early, objective diagnostic testing of patients who have experienced a head injury can support more rapid and appropriate treatment decisions while potentially reducing the use of unnecessary CT scans or other forms of intervention.

We know that protein biomarkers, including S100 calcium binding protein beta (S100β) and glial fibrillary acidic protein (GFAP), are released from the brain into the bloodstream immediately following a concussion or other traumatic brain injury. The Tbit™ System is a new medical device based on a nanotechnology biosensor that rapidly detects and accurately measures these protein biomarkers. The system includes a disposable cartridge and portable analyzer designed for testing using a single drop of blood at the earliest stages of a concussion.

This pre-clinical study was designed to evaluate the ability of the Tbit System to screen traumatic brain injury patients for a CT positive or CT negative test. Frozen plasma samples were collected from a total of 100 patients who had undergone CT scans post hospital admission. The Tbit System demonstrated 100% sensitivity with no false negative results, and a 41% specificity level.

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First Diagnostic Blood Test for Coronary Artery Plaque Detection

MedicalResearch.com Interview with:

Szilard Voros, MD, FACC, FSCCT, FAHA CEO of Global Genomics Group

Dr. Voros

Szilard Voros, MD, FACC, FSCCT, FAHA
CEO of Global Genomics Group 

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

Response: Atherosclerotic coronary artery disease (ASCAD) is the leading cause of death and morbidity in the United States and worldwide, despite relatively successful medical therapies such as statins, like Zocor or Lipitor. A significant majority of patients with ASCAD present with sudden cardiac arrest, and the clinical evaluation of those patients who present with chest pain to their physicians is very inefficient. Based on current clinical guidelines, patients who present to their physician with complaints of new onset chest pain or its equivalent, such as exertional dyspnea should be assessed for the probability of the presence of significant ASCAD based on simple clinical predictors. Approximately 60% of such patients have an intermediate probability, and they are typically referred for initial non-invasive evaluation, such as a stress test with cardiac imaging, or for some other type of non-invasive test. Strikingly, no more that 5% of such stress tests performed in the United States are actually positive, and even when patients with positive stress test are taken for invasive coronary angiography, no more than 40% have significant ASCAD.

A blood test that could serve as first step, as a “gatekeeper”, to non-invasive evaluation, would be highly desirable. Global Genomics Group, or G3, has performed one of the largest, unbiased, mass-spectrometry-based discovery studies in over 1,000 patients who underwent detailed cardiac CT to assess the presence or absence of ASCAD, by measuring over 1,000 metabolites from the blood. Using sophisticated bioinformatics tools, the researchers identified 8 important metabolites that were significantly abnormal in patients with ASCAD, and generated a biomarker signature for the detection of ASCAD based on those analytes, called “knowPLAQUETM”. The biomarker signature was generated in approximately 800 subjects, and was validated in an independent set of approximately 400 subjects, showing an area under the curve (“AUC”) of 0.82 for the diagnosis of Atherosclerotic coronary artery disease. This biomarker signature can be adapted relatively easily on commercial mass spectrometry platforms, and the researchers anticipate that this signature may be available for physicians to use by 2018. In addition to its diagnostic power, this biomarker signature also has uncovered important biological insights for the development of ASCAD, which can be leveraged for therapeutic purposes.

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Biomarker VCAM-1 Associated With New Onset Atrial Fibrillation

MedicalResearch.com Interview with:
Stefan Kiechl, MD and
Karin Willeit, MD
Department of Neurology
Medical University Innsbruck
Innsbruck, Austria 

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

Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major contributor to thromboembolic stroke and population morbidity and mortality. Aside from well-established risk factors such as age, heart failure, and hypertension, inflammation has been suggested to play a significant role in the pathogenesis of AF. This is evidenced by histologic studies that found marked inflammatory infiltrates in atrial biopsies of AF patients and by epidemiological studies demonstrating an association of circulatory inflammation markers with incident AF. Of note, an increased endocardial expression of vascular intercellular adhesion molecule 1 (VCAM-1), a mediator of leukocyte trafficking, during rapid atrial pacing was demonstrated which was shown to contribute to an inflammatory and prothrombotic environment within atrial tissue.

Because it is still unclear whether inflammation related to AF is primarily a systemic or localized phenomenon, we sought to examine the association of 13 baseline inflammation markers with incident atrial fibrillation in the prospective population-based Bruneck Study and to replicate key findings in a second cohort, the SAPHIR Study.

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ALS: Urinary p75ECD as a Prognostic, Disease Progression, and Pharmacodynamic Biomarker

MedicalResearch.com Interview with:

Mary-Louise Rogers, PhD Senior Research Fellow, Lab Head, Motor Neurone Disease and Neurotrophic Research Laboratory, Department of Human Physiology, Centre for Neuroscience, Flinders University, School of Medicine, South Australia, Australia

Dr. Rogers

Mary-Louise Rogers, PhD
Senior Research Fellow, Lab Head,
Motor Neurone Disease and Neurotrophic Research Laboratory,
Department of Human Physiology,
Centre for Neuroscience,
Flinders University, School of Medicine,
South Australia, Australia

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

Response: ALS is a fatal neurodegenerative disease in which motor neurons, cells that control muscle activity such as walking, talking and breathing, gradually die off, resulting in paralysis. There is no cure for ALS.

In a groundbreaking study published in the journal Neurology, and led by Mary-Louise Rogers, Ph.D., senior research fellow at Flinders University, Australia, and Michael Benatar, M.D., Ph.D, University of Miami, Miller School of Medicine,  have identified concentrations of p75ECD, the extracellular domain on the common neurotrophin receptor p75, as the first biological fluid-based biomarker for ALS progression. .

Neurotrophin receptor p75 is a growth factor receptor for neurotrophins whom promote the survival of nerve cells. Under normal circumstances, it is highly expressed on motor neurons during development but decreases after birth. Following nerve injury, however, the expression of p75 is increased and the extracellular domain of p75 is detectable in urine. Dr Rogers and her Doctoral student Stephanie Shepheard hypothesized and then showed, that p75ECD is excreted into the urine of SOD1 mice, the most commonly used animal model of ALS. These findings empowered further investigation of p75ECD, showing raised levels in the urine of patients with ALS and that it might have potential as an ALS biomarker.

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Gene “Decorations” Can Serve as Blood Biomarkers To Detect Cancer

MedicalResearch.com Interview with:

Kun Zhang, PhD Professor UCSD Department of Bioengineering La Jolla, CA 92093-0412

Dr. Kun Zhang

Kun Zhang, PhD
Professor
UCSD Department of Bioengineering
La Jolla, CA 92093-0412

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

Response: We have been interested in a type of chemical modification on the DNA, called CpG methylation, for years. This is like a decoration of DNA molecules that is specific to the cell type or tissue type. We were particularly interested in studying how such decoration spread along the DNA molecules. In this study, we did a very comprehensive search of the entire human genome for various human cell types and tissue types, and found close to 150,000 regions (called MHB in this study) in which adjacent CpG share the same decoration. We then went on to find out how many of such regions are unique to each normal cell/tissue type, and how many are specific to cancers. Then we took some of these highly informative regions as “biomarkers”, and showed that we can detect the absence or presence of cancer, and, in the latter case, where the tumor grow, in a patient’s blood.

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Sleep Duration and Exhaled Nitric Oxide in Asthma and Health Adults

MedicalResearch.com Interview with:
Rauno Joks, MD

Associate Professor of Clinical Medicine
Chief, Division of Allergy & Immunology
Program Director, Allergy &Immunology Fellowship
SUNY Downstate Medical Center

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

Response: There are circadian and circannular patterns to many diseases, including allergy and asthma. Humans spend roughly one-third of their lifetimes asleep. Your immune system never sleeps, but shifts its activity when you sleep.

It is known that asthma disease activity can be worse at night – the reasons for this are complex, and may involve changes in allergic responses.

We found, in a preliminary study of both adults with and without asthma, that longer duration of nighttime sleep was associated with lower levels of exhaled nitric oxide, a biomarker which is elevated in exhaled breath of those with allergic asthma. This may carry over into the afternoon as well, but the sample size was too small to fully conclude that.

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Genetic Defect in DNA Repair Enzyme Linked to Prostate Cancer

MedicalResearch.com Interview with:
G. Andrés Cisneros, Ph.D.

Associate Professor
Department of Chemistry Center for Advanced Scientific Computing and Modeling, University of North Texas

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

Response: The accurate maintenance of DNA is crucial, if DNA damage is not addressed it can lead to various diseases including cancer. Therefore, the question arises about what happens if enzymes in charge of DNA repair are themselves mutated. We previously developed a method to perform targeted searches for cancer-related SNPs on genes of interest called HyDn-SNP-S. This method was applied to find prostate-cancer SNPs on DNA dealkylases in the ALKB family of enzymes.

Our results uncovered a particular mutation on ALKBH7, R191Q, that is significantly associated with prostate cancer. Subsequent computer simulations and experiments indicate that this cancer mutation results in a decreased ability of ALKBH7 to bind its co-factor, thus impeding its ability to perform its native function.

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Prostate Cancer: Genetic Biomarker Predicts Response To Androgen Deprivation Therapy

MedicalResearch.com Interview with:

Neeraj Agarwal, MD Associate Professor, Division of Oncology, Department of Medicine University of Utah School of Medicine

Dr. Neeraj Agarwal

Neeraj Agarwal, MD
Associate Professor, Division of Oncology, Department of Medicine
University of Utah School of Medicine

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

Response: Biomarkers predicting response to cancer therapy help guide physicians personalize medicine. Significant advances have been made in the development of therapeutic biomarkers in various malignancies, but not in prostate cancer. Dr. Nima Sharifi’s group at the Cleveland Clinic recently discovered that a germline inherited polymorphic variant (1245A→C) in the HSD3B1 gene correlates with shorter duration of response to androgen deprivation therapy (ADT) in hormone sensitive prostate cancer (HSPC). HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen.

The authors found that the variant allele of HSD3B1 led to decreased progression-free survival in a dose-dependent manner in post-prostatectomy biochemical recurrence and metastatic HSPC (mHSPC). These results needed external validation before application in the clinic. In our study, we sought to provide the first independent validation of these results in patients with mHSPC.

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Roles of Angiotensin Peptides and Recombinant Human ACE2 in Heart Failure

MedicalResearch.com Interview with:

Gavin Y Oudit, MD, PhD, FRCPC Associate Professor, Department of Medicine, University of Alberta Clinician-Scientist, Mazankowski Alberta Heart Institute Canada Research Chair in Heart Failure Division of Cardiology, 2C2 Walter Mackenzie Health Sciences Centre Edmonton, Alberta

Dr. Gavin Oudit

Gavin Y Oudit, MD, PhD, FRCPC
Associate Professor, Department of Medicine, University of Alberta
Clinician-Scientist
Mazankowski Alberta Heart Institute
Canada Research Chair in Heart Failure
Division of Cardiology
Edmonton, Alberta

Heart specialist Gavin Oudit and his research team discovered a molecule — angiotensin converting enzyme 2 (ACE2)—that works to restore balance to the pathways responsible for chronic and acute heart failure, including in hearts from patients with advanced heart failure who underwent heart transplants.

In developing the new drug, Oudit and his team discovered to an extent not seen before how the renin-angiotensin system (RAS), which regulates the body’s sodium balance, fluid volume, and blood pressure, is at play in both acute and chronic heart failure. In collaboration with Dr. Oudit, recombinant human ACE2 was made by Apeiron Biologics, purchased by GlaxoSmithKline, and has recently completed phase II clinical trial.

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New ‘Blood Biopsies’ with Experimental Device to Speed Cancer Diagnosis and Predict Disease Spread

MedicalResearch.com Interview with:

Edwin Posadas, MD, FACP, KM Director, Translational Oncology Program Medical Director, Urologic Oncology Program Samuel Oschin Comprehensive Cancer Institute

Dr. Edwin Posadas

Edwin Posadas, MD, FACP, KM
Director, Translational Oncology Program
Medical Director, Urologic Oncology Program
Samuel Oschin Comprehensive Cancer Institute
Clinical Chief, Division of Hematology/Oncology
Associate Professor, Department of Medicine
Cedars-Sinai

MedicalResearch.com: What is the background for this study? What are the main findings of your work so far?

Response: The technology we are using is called a NanoVelcro assay. This is a nanotechnology that can be used to isolate rare cells and cell-like particles in the blood stream. We have focused the use of the NanoVelcro on isolating circulating tumor cells (or CTCs). This technology is about 10 times more sensitive than that currently used in clinics. More importantly, because of some modification in our approach, we can now not only capture CTCs, but also examine them under the microscope and even analyze them using advanced molecular techniques. In this way, we take a classic and modern approach to our work.

We firmly believe that there is much to be learned by studying the shapes of these CTCs. We in the cancer field have long known that shape and cellular function are intimately related. In fact, a young pathologist in our group readily recognized that patients with the most aggressive cancers had CTCs with small nuclei, which we verified in a larger study. We are now exploring the importance of these shape variations in CTCs by coupling this classic microscopy-driven approach with RNA characterizations, giving us insight into the molecular nature of the CTC. My collaborator, UCLA Professor Hsian-Rong Tseng, PhD, is a brilliant engineer who has found ways of altering the system to allow us to capture and release live cells for analysis. By using this system, we believe that one day we may be able to avoid performing invasive tissue biopsies to study a cancer.

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New Blood Test May Screen For ATTR Cardiac Amyloidosis

MedicalResearch.com Interview with:

Frederick L. Ruberg, MD Director, Cardiovascular Medicine Fellowship Training Program Director, Pilot Grants Program, Boston University Clinical and Translational Science Institute Director, Advanced Cardiac Imaging Program Section of Cardiovascular Medicine, Department of Medicine Department of Radiology Boston Medical Center

Dr. Frederick Ruberg

Frederick L. Ruberg, MD
Director, Cardiovascular Medicine Fellowship Training Program
Director, Pilot Grants Program, Boston University Clinical and Translational Science Institute
Director, Advanced Cardiac Imaging Program
Section of Cardiovascular Medicine
Department of Medicine
Department of Radiology
Boston Medical Center 

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

Response: ATTR cardiac amyloidosis is an under-recognized cause of congestive heart failure in older adults that results from the deposition of misfolded TTR protein in the heart. One cause of ATTR cardiac amyloidosis is a genetic abnormality, inherited from an affected patient’s parent, that causes the protein TTR to misfold. The most common genetically inherited cause of ATTR amyloidosis in the US is called Val122Ile (V122I), named for the specific mutation in the TTR gene, that is seen in approximately 3.5% of US African Americans. ATTR cardiac amyloidosis was once an untreatable disease, but now new drugs are in different stages of clinical trial testing. Thus, recognition is important to get patients on the right treatments.

One of the principal reasons why the disease is under-recognized is that doctors don’t have proven and available diagnostic tests that can be applied in the outpatient clinic. This study demonstrated that a new point-of-care diagnostic test, using measurement of a blood protein called retinol binding protein 4 (RBP4) and other standard of care test information, can accurately diagnose ATTR cardiac amyloidosis. We demonstrated the validity of this test in two separate cohorts of patients with proven ATTR cardiac amyloidosis due to the Val122Ile mutation and control patients with heart failure but without amyloidosis.

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Gene Variant That Controls Tumor Metabolism Linked To Breast Cancer Risk

MedicalResearch.com Interview with:

Ulrich Pfeffer, PhD Head of the Functional Genomics lab IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro Genova, Italy

Dr. Ulrich Pfeffer

Ulrich Pfeffer, PhD
Head of the Functional Genomics lab

IRCCS AOU San Martino – IST Istituto Nazionale per la Ricerca sul Cancro
Genova, Italy

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

Response: In recent years our knowledge on genetic variants that are associated with the risk to develop breast cancer has grown substantially. In addition to the two breast cancer genes, BRCA1 and BRCA2 we know approximately 100 other genes that are present in the population in two variants. In the presence of a single of these variants the breast cancer risk is slightly increased and several variants together determine a significant increase in risk. We also know that certain variants are associated with specific subtypes of breast cancer such as the estrogen receptor positive breast cancer.

We show in our work for the first time that some of these variants are more frequent in breast cancers that carry a specific somatic, non-inherited, mutation. In particular, we show this for the most frequent somatic mutation in breast cancer, PIK3CA, a gene involved in the control of tumor metabolism and many other aspects, a fundamental gene. The knowledge of this association tells us a lot on cancer biology. But most important, it might help to design specific prevention strategies. Since when you carry a germline allele that is associated with a specific somatic mutation you know your risk of a specific molecular type of breast cancer and eventually you can do something specific to prevent it.

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Elevated Lactate Linked To Increased Mortality in Children With Sepsis

MedicalResearch.com Interview with:

Halden F. Scott MD, Assistant Professor Departments of Pediatrics and Emergency Medicine University of Colorado School of Medicine

Dr. Halden F. Scott

Halden F. Scott MD, Assistant Professor
Departments of Pediatrics and Emergency Medicine
University of Colorado School of Medicine

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

Response: Sepsis, a dysregulated immune response to infection, is a leading cause of death for children. Survival depends on rapid diagnosis and timely delivery of life-saving resuscitative care, including fluids and antibiotics. However, it can be challenging to make an early diagnosis of sepsis in children.

Millions of children present for emergency care of infection and fever every year, most of whom will not develop sepsis. Tools that assist providers in distinguishing the sickest children with infection at an early stage could enable the early delivery of life-saving treatments.

Lactate is a clinically-available laboratory test that has played a critical role in improving the diagnosis and treatment of sepsis in adults. Sepsis may cause lactate levels to rise in the blood during sepsis, through reduced delivery of oxygen to the tissues, as well as through changes in how energy is produced and in how lactate is cleared by the kidney and liver. Data about lactate in pediatric sepsis, particularly early levels and whether it is associated with mortality, have been limited.

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Our Biomarker Signature Can Predict How Well We Are Aging

MedicalResearch.com Interview with:

Paola Sebastiani PhD Department of Biostatistics Boston University School of Public Health Boston, MA 02118

Dr. Paola Sebastiani

Paola Sebastiani PhD
Department of Biostatistics
Boston University School of Public Health
Boston, MA 02118

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

Response: Human life expectancy has increased steadily in the last century and has led to a growth of the elderly population and a need for prevention strategies and interventions that promote healthy aging.

A challenge in assessing the effect of such interventions is ‘what to measure’ because people can age very differently from one another. Our study used 19 blood biomarkers that include for example cholesterol level and hemoglobin A1C to discover 26 biological signatures of aging in approximately 4,700 participants of the Long Life Family Study. These signatures are essentially patterns of values of the 19 biomarkers and we showed that one of these signatures is associated with better physical and cognitive functions, and reduced risk for disease and mortality compared to the most common signature in the study. Additional signatures predict varying risk for diabetes, cardiovascular and other aging-related diseases. We replicated these results in an independent data set. The associations of these biomarker signatures with physical and cognitive functions, and risk for morbidity and mortality support the conclusion that they capture different form of biological aging.

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CSF Biomarker May Signal Progression of Clinically Isolated Syndrome to MS

MedicalResearch.com Interview with:

Prof Rogier Q Hintzen Neurologist/immunologist Head MS Centre ErasMS Dept of Neurology Erasmus MC, PB 2040 Rotterdam

Prof Rogier Q Hintzen

Prof Rogier Q Hintzen
Neurologist/immunologist
Head MS Centre ErasMS
Dept of Neurology
Erasmus MC, Rotterdam

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

Response: Years ago, we identified soluble (s) CD27 as a biomarker for T cell activation in body fluids, as part of my PhD study. (J Immunol. 1991 Jul 1;147(1):29-35.)
As we presume the neuropathology seen in MS is guided by T cells we were interested to be able to quantify the activity of such cells in a given patient.
Cerebrospinal fluid (CSF) is as close as we can get to the site of the disease process in MS, therefore we focus on biomarkers in this compartment.
We found clearly elevated levels of sCD27 in CSF of Multiple Sclerosis patients versus non-inflammatory controls.

In this study we investigated whether at the moment of first attack of suspected Multiple Sclerosis, quantification of CSF sCD27 can predict further progression in to a diagnosis of MS and whether sCD27 levels are correlated with later attack frequency. Indeed, we found that high sCD27 measured at this early stage predicts a more rapid diagnosis of Multiple Sclerosis and a more aggressive disease course.

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Biomarker sST2 Predicts All-Cause and Cardiac Death in Heart Failure Patients

MedicalResearch.com Interview with:

Prof. Michele Emdin, MD, PhD, FESC Associate Professor of Cardiovascular Medicine Institute of Life Sciences Scuola Superiore Sant'Anna - Sant'Anna School of Advanced Studies Director, Cardiology & Cardiovascular Medicine Division Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica

Prof. Michele Emdin

Prof. Michele Emdin, MD, PhD, FESC
Associate Professor of Cardiovascular Medicine
Director, Cardiology & Cardiovascular Medicine Division
Fondazione Toscana Gabriele Monasterio
per la Ricerca Medica e di Sanità Pubblica
CNR-Regione Toscana with the collaboration of
Dr. Alberto Aimo, MD
Institute of Life Sciences
Scuola Superiore Sant’Anna – Sant’Anna School of Advanced Studies
Pisa, Italy

MedicalResearch.com: What is the background for these meta-analyses?

Response: Soluble suppression of tumorigenicity 2 (sST2) is a novel and promising biomarker of heart failure (HF). It has been extensively studied in both stable chronic (CHF) and acute HF (AHF), demonstrating substantial potential as a predictor of prognosis in both settings (Dieplinger et al., 2015).

An International Consensus Panel (Januzzi et al., 2015) and latest American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines (Yancy et al., 2013) support the use of sST2 assay for risk stratification in both CHF and AHF patients. By contrast, European Society of Cardiology guidelines do not provide specific recommendations on sST2 (Ponikowski et al., 2016). Because of ambiguity due to discordant conclusions and to the absence of a thorough revision of the literature and of rigorous meta-analyses of published studies up-to-date, we felt it worthwhile to carefully examine and meta-analyze evidence supporting measurement of sST2, in order to assess the prognostic role of this biomarker in CHF and AHF. Most of the groups originally publishing on the topic all over the world and representing the Gotha of clinical research on cardiovascular biomarker, accepted to directly contribute allowing the main Authors to achieve novel information by a guided statistical reappraisal, The final results furnish clinically significant support to the use of sST2 as a risk stratification tool either in the acute or in the chronic heart failure setting.

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ER-beta May Identify Breast Cancer Patients For Whom Chemotherapy is Sufficient

MedicalResearch.com Interview with:
Helena Jernström, PhD
Associate Professor in Experimental Oncology
Study Coordinator for Graduate studies Division of Oncology and Pathology
Coordinator of the programmes in statistics and epidemiology for doctoral students at the Medical Faculty, Lund University
Division of Oncology and Pathology, Department of Clinical Sciences, Lund
Lund University Cancer Center/Kamprad
Lund, Sweden

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

Response: There is a need for better predictive markers to guide selection of therapy in breast cancer patients. Estrogen receptor beta (ER-beta) may confer prognostic information beyond what is currently obtained by the established clinical markers, including ER-alpha, which is routinely evaluated.

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Lung Maturity Test Can Determine Which Premature Infants are at risk of RDS

MedicalResearch.com Interview with:

Prof. Henrik Verder Department of Pediatrics Holbaek University Hospital Denmark

Prof. Henrik Verder

Prof. Henrik Verder
Department of Pediatrics
Holbaek University Hospital
Denmark

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

Response: Respiratory Distress Syndrome (RDS) is a major cause of mortality and morbidity in premature infants. It can be effectively treated with surfactant, a therapy which reduces the effort needed to expand the lungs during inspiration and allow gas exchange to take place. Early surfactant treatment can help prevent the onset and impact of RDS, however, prophylactic treatment has been shown to be harmful and only necessary in half of all pre-term infants. This study provided data validating the efficacy of a lung maturity test (LMT) in identifying infants at risk of respiratory distress syndrome (RDS) who could benefit from early surfactant treatment.
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DNA Markers May Differentiate Heavy From Light Alcohol Users

MedicalResearch.com Interview with:
Chunyu Liu, PhD
The Population Sciences Branch, Division of Intramural Research
The Framingham Heart Study, National Heart, Lung and Blood Institute
Framingham, MA
Department of Biostatistics
Boston University School of Public Health
Boston, MA

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

Response: Excessive alcohol consumption contributes to many diseases as well as to injuries and deaths. The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Our study has identified a group of DNA markers in blood that could provide the basis for a reliable blood test to detect heavy alcohol use.

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Distinct Mutational Signatures Correlate With Increased Immune Activity in Pancreatic Cancer

MedicalResearch.com Interview with
Dr. Ashton A. Connor, MD
PanCuRx Translational Research Initiative,
Ontario Institute for Cancer Research
Dr. Steven Gallinger MD, MSC
Division of General Surgery
Toronto General Hospital
Toronto, ON

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

Response: The etiology of pancreatic ductal adenocarcinoma (i.e. “pancreatic cancer”) and the relationship between the tumour and its characteristic dense, encroaching stroma are still poorly understood.

Using whole genome sequencing in two large cohorts, we show that there are four fundamental mutational processes that give rise to pancreatic cancer.
With expression data, we also show that the interaction between the tumour and the surrounding stroma varies with the type of mutational process found in the tumour. Specifically, tumours with defective DNA repair, either homologous recombination or mismatch repair deficiency, elicited strong anti-tumour immune responses, likely due to the relatively high numbers of neoantigens in these tumours.

Individually, these concepts have been studied in other cancer types, but we are first to apply either of these to pancreatic cancer, and we also the first to integrate these two aspects of cancer biology for any tumour, to our knowledge.

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Little Change in PSA Use After Taskforce Recommendation

MedicalResearch.com Interview with:
Dr Ryan Hutchinson MD and
Yair Lotan MD

Department of Urology
University of Texas Southwestern Medical Center

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

Response: The United States Preventative Services Task Force recommendation against PSA screening generated significant controversy. Research since then has relied heavily on survey data to examine the impact of the recommendation on PSA screening practices. In a hotly charged issue such as this, such data can carry significant bias.

We examined a large, whole-institution data in the years before and after the USPSTF recommendations reflecting actual practice and found that the changes in PSA use at our institution, if any, were small. This is more consistent with behavior seen after the vast majority of practice recommendations.

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Cell Biomarkers To Distinguish Deadly From Less Aggressive HPV Oral Cancers

MedicalResearch.com Interview with:

Elizabeth Franzmann, M.D. Scientific Founder and Chief Scientific Officer Vigilant Biosciences

Dr. Elizabeth Franzmann

Elizabeth Franzmann, M.D.
Scientific Founder and Chief Scientific Officer
Vigilant Biosciences

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

Response: Head and neck cancer involves cancers of the oral cavity, oropharynx and larynx. It is difficult to treat. Part of the challenge is that it is distinguishing the patients with tumors that are going to behave aggressively from those with less aggressive disease. As a result, many patients undergo treatment that may be more intensive and morbid than they need while others need more aggressive treatment. Tissue markers associated with prognosis may be able to help clinicians differentiate patients who need more aggressive treatment from those whose treatment can be less intensive. CD44 is a cell surface glycoprotein and tumor-initiating marker. CD44 and another surface protein, EGFR, are involved in tumor extension and are associated with poor prognosis. Certain forms of Human Papillomavirus (HPV) are known to cause oropharyngeal cancer and are associated with a good prognosis. P16 is a surrogate marker for the kind of HPV that causes cancer. Understanding the relationships between how these markers are expressed in cancer tissue may direct patient treatment in the future.

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IL-33 May Be First Stand Alone Biomarker of Prostate Cancer Recurrence

MedicalResearch.com Interview with:
Iryna Saranchova MD
PhD candidate
Michael Smith Laboratories
Vancouver, BC

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

• The immune system is efficient at identifying and halting the tumour emergence at early stages. However, when metastatic (sufficient to cause death) tumour appears, the immune system is no longer able to recognize the cancer cells and control their growth and spread.
• Recent studies of solid cancers have shown considerable heterogeneity between different tumour types and several lines of evidence suggest that tumours are not only heterogeneous, but they constantly evolve during the disease progression and this often hampers the existing treatment methods.
• It means that it is important to consider each patient’s mutational changes accumulated over time in antecedent primary, metastatic lesions and/or local recurrences. This approach will help to understand the mechanism of tumour development, create a background for specific treatment modality and prevent therapeutic failure with consequent systemic relapse of the disease
• Therefore, in our project we were aiming to find possible immune markers of tumour transition from the primary stage to its metastatic form. For this purpose, we selected a special study model: two pairs of separate mouse tumour cell lines, where metastatic cells arose from the initial primary tumour.

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Parkinson’s Disease Linked To Increase in Number of Inflammatory Markers

MedicalResearch.com Interview with:

Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland

Dr. Yong Cheng

Yong Cheng, PhD, post-doc fellow
Section on Cellular Neurobiology
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland

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

Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with  Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls.

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BDNF Is Potential Biomarker For Autism Spectrum Disorder

MedicalResearch.com Interview with:

Dr. Yong Cheng, PhD Postdoctoral Fellow NIH

Dr. Yong Cheng

Dr. Yong Cheng, PhD
Postdoctoral Fellow
NIH

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

Response: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which affect about 1 in 68 children in the United States, according to data from the Centers for Disease Control and Prevention. Brain-derived neurotrophic factor (BDNF) is an important moderator in neurodevelopment and neuroplasticity, and studies have suggested the involvement of BDNF in ASD. Although some clinical studies show abnormal expression of BDNF in children with ASD, findings have been inconsistent. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood BDNF levels in children with ASD, compared with healthy peers.

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New Onset Diabetes, Especially In Lean Patients, Can Be Marker of Pancreatic Cancer

MedicalResearch.com Interview with:
Dr. Pavel Škrha
Charles University, Prague
Czech Republic

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

Response: Incidence of pancreatic cancer (PAC) is still increasing. The main problem is in the late diagnosis of the cancer. It was found, that diabetes mellitus was much more frequent in the pancreatic cancer patients than in the general population. DM can be already the first symptom of the disease (secondry T3cDM).

In our study nearly 80 % of all the pancreatic cancer patients had DM/prediabetes and it was of new-onset (less than 2 years before the cancer diagnosis) in 73 % out of them. We have measured the current marker of PAC (CA 19-9) together with serum microRNA-196 and -200 (that we have chosen in the previous pilot study). All the markers were significantly elevated in the pancreatic cancer patients, without any difference between the subgroups according to DM presence/absence. While the sensitivity of CA 19-9 alone (to detect the cancer) was 85 % (specificity 73 %), combining all the three markers improved it to 95 % (specificity 77 %). In the pancreatic cancer group, there were only six patients with T1 or T2 stage (others had an advanced stage of the disease – T3, T4). While CA 19-9 alone identified only 2 patients of them, the combined test identified all the six patients (data not shown in the poster). Continue reading

RANK signaling-blockade reduces breast cancer recurrence by inducing tumor cell differentiation

MedicalResearch.com Interview with:

Eva Gonzalez Suarez, PhD Group Leader Transformation and Metastasis lab. Cancer Epigenetics and Biology Program-PEBC Institut d'Investigació Biomédica de Bellvitge-IDIBELL Hospital Duran i Reynals Avinguda Gran Via de l'Hospitalet, L'Hospitalet de Llobregat-Barcelona-Spain

Dr. Eva Gonzalez Suarez

Eva Gonzalez Suarez, PhD
Group Leader Transformation and Metastasis lab.
Cancer Epigenetics and Biology Program-PEBC
Institut d’Investigació Biomédica de Bellvitge-IDIBELL
Hospital Duran i Reynals Avinguda Gran Via de l’Hospitalet,
L’Hospitalet de Llobregat-Barcelona-Spain

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

Response: Thousands of cancer patients worldwide are taking RANKL inhibitors for the management of bone metastasis, based on the key role of RANKL and its receptor, RANK, driving osteoclastogenesis. RANK signaling pathway acts as a paracrine mediator of progesterone in mouse and human mammary epithelium. RANK expression is associated with poor prognosis in breast cancer even though its therapeutic potential remained unknown.

Complementary genetic and pharmacological approaches demonstrate that therapeutic inhibition of RANK signaling drastically reduces the cancer stem cell pool, decreases tumor and metastasis initiation and enhances sensitivity to chemotherapy in mouse models that closely resemble the clinical disease. Mechanistically, genome wide expression analyses showed that anti-RANKL therapy promotes differentiation of tumor cells into milk-producing cells, as observed during pregnancy.

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Penn Reports Successful Pilot Study of Liquid Biopsy To Monitor Advanced Lung Cancer

MedicalResearch.com Interview with:

Erica L. Carpenter, MBA, PhD Research Assistant Professor, Department of Medicine Director, Circulating Tumor Material Laboratory Division of Hematology/Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania

Dr. Erica Carpenter

Erica L. Carpenter, MBA, PhD
Research Assistant Professor, Department of Medicine
Director, Circulating Tumor Material Laboratory
Division of Hematology/Oncology
Abramson Cancer Center
Perelman School of Medicine at the University of Pennsylvania

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

Response: The advent of precision medicine practices for cancer patients, including the use of drugs that target specific tumor mutations, has necessitated improved diagnostics with real-time molecular monitoring of patients’ tumor burden. While biopsy material, obtained surgically or through fine needle aspirate, can provide tissue for next generation sequencing (NGS) and mutation detection, this requires an invasive often painful procedure for the patient. In many cases, especially in more advanced disease when multiple metastases are present, such tissue cannot be obtained or can only be obtained from a single tumor site, thus limiting the sensitivity of tissue-based biopsy.

Here we report on a prospective cohort of 102 consecutively enrolled patients with advanced non-small lung cancer (NSCLC) for whom a non-invasive liquid biopsy was used for real-time detection of therapeutically targetable mutations. Tissue samples were only obtainable for 50 of the 102 patients, and these tissue biopsies were analyzed using a 47-gene Next Generation Sequencing (NGS) panel at Penn’s Center for Personalized Diagnostics. Concordance of results for the 50 patients who received both tests was close to 100% when the samples were obtained concurrently.

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Liquid Biopsies Hold Promise of Diagnosing Response to Chemotherapy

MedicalResearch.com Interview with:

Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010

Dr. Karen Reckamp

Karen L. Reckamp, M.D.
Associate Professor
City of Hope Comprehensive Cancer Center
Duarte, CA 91010

MedicalResearch.com: What is the background for this study? What are the main findings?
Response:
• Approximately 60% of patients with non-small cell lung cancer (NSCLC) receiving EGFR tyrosine kinase inhibitors (TKIs) will develop TKI resistance through the acquisition of the EGFR T790M mutation.
• A major challenge for assessing EGFR mutation status in advanced NSCLC is the availability of suitable biopsy tissue for molecular testing, specifically for determination of the emergence of T790M following progression on initial EGFR TKI therapy.
• The objective of this study was to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations is feasible from urine and plasma, providing comparable clinical information while potentially mitigating the issues associated with tissue biopsies.
• This blinded, retrospective study was conducted on matched tissue, urine and plasma specimens collected from 63 patients with Stage IIIB-IV NSCLC enrolled in the TIGER-X trial of rociletinib, an investigational 3rd generation tyrosine kinase inhibitor (TKI), targeting T790M.

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Storage Time Can Effect Plasma Biomarker Results

MedicalResearch.com Interview with:
Stefan Enroth, Associate Professor, PhD
Dept. of Immunology, Genetics & Pathology
Uppsala University

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

Response: One basic requirement of life science research is the quality of samples. Proper handling and rigorous biobanking of clinical samples is very important when for instance collecting samples for rare diseases, for monitoring individual variation in longitudinal studies and when conducting prospective studies of biomarkers and risk of developing for instance cardiovascular disease. In epidemiological studies using case and control cohorts, great care is taken to ensure that the cases and controls are matched in terms of for instance age, anthropometrics and lifestyle exposures such as smoking or alcohol consumption. Technical factors and sampling handling history are not as commonly used. There has been a lack of studies that systematically investigated the effects of for instance storage-time on a larger set of plasma proteins. With emerging high-throughput technologies enabling measurements of a high number of proteins simultaneously on a population level, biomarker research will enter a new era and the more knowledge we have on what factors that influence circulating biomarker levels – such as plasma proteins, the higher the chances are of finding new clinically important biomarkers for disease.

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Despite Valuable Biomarkers Clinical Evaluation Still Important in Diagnosing Heart Attack

MedicalResearch.com Interview with:

Dr. Juan Sanchis Full professor of Medicine Cardiology Department, University Clinic Hospital. Medicine Department, University of Valencia Valencia. Spain

Dr. Juan Sanchis

Dr. Juan Sanchis
Full professor of Medicine
Cardiology Department, University Clinic
Hospital. Medicine Department, University of Valencia
Valencia. Spain

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

Response: Decision making in acute chest pain in the emergency departments
remains challenging despite the introduction of new troponin assays
(high-sensitivity assays) capable of detecting any amount of
myocardial damage.

The upper limit of normality of high-sensitivity
troponin is established at the 99th percentile of a normal reference
population. This is the limit for the diagnosis of acute myocardial
infraction. Detectable troponin levels below the 99th percentile,
though non diagnostic of acute myocardial infarction, might be
considered as of uncertain significance since some patients might
still suffer from unstable angina. Undetectable troponin (far below
the 99th percentile), however, could rule out unstable angina meaning
that such patients could safely be discharged from the emergency
department according to some studies. Therefore, if this were fully
demonstrated, clinical evaluation could play a secondary role.

We investigated clinical data in comparison to undetectable
high-sensitivity troponin in patients with normal high-senstivity
troponin levels (below the 99th percentile).

The main findings indicate that clinical data can guide decision making and perform at
least equally well as undetectable high-sensitivity troponin for
ruling out unstable angina, in patients presenting at the emergency
department with chest pain and normal troponin.

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