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.

Oct 14, 2018 @ 12:36 pm

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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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Liquid Biopsy Using Circulating Tumor DNA Can Predict Treatment Response in Large B-Cell Lymphoma

MedicalResearch.com Interview with:
Dr. David Kurtz, MD/PhD, Instructor and
Dr. Ash Alizadeh MD/PhD, Associate Professor
Division of Oncology, Department of Medicine
Stanford University Medical Center 

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

Response: This work investigates the utility of circulating tumor DNA – a type of liquid biopsy – in diffuse large B-cell lymphoma, the most common blood cancer in adults.

Liquid biopsies are an emerging technology to track cancers from a simple blood draw. Here, using a cohort of over 200 patients from 6 centers across North America and Europe, we asked if circulating tumor DNA could be used to detect lymphoma in patients, and more importantly, could it be used to identify responders and non-responders.  Continue reading

Clinical Chemistry Score Helps Rule Out Diagnosis of Heart Attack

MedicalResearch.com Interview with:

Peter Kavsak, PhD, FCACB, FAACC, FCCS Professor, Pathology and Molecular Medicine McMaster University 

Prof.. Kavsak

Peter Kavsak, PhD, FCACB, FAACC, FCCS
Professor, Pathology and Molecular Medicine
McMaster University 

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

Response: For patients who present to the hospital with symptoms suggestive of acute coronary syndrome (ACS) the preferred blood test to help physicians in making a diagnosis is cardiac troponin.

Recent studies have demonstrated that a very low or undetectable cardiac troponin level when measured with the newest generation of blood tests (i.e., the high-sensitivity cardiac troponin tests) in this population may rule-out myocardial infarction (MI or a heart attack) on the initial blood sample collected in the emergency department, thus enabling a faster decision and foregoing the need for subsequent serial measurements of cardiac troponin over several hours as recommended by the guidelines. The problem with this approach, however, is that using high-sensitivity cardiac troponin alone to do this has not reliably been demonstrated to achieve a sensitivity >99% for detecting MI, which is the estimate that most physicians in this setting consider as safe for discharge.

Our study goal was to compare the diagnostic performance of a simple laboratory algorithm using common blood tests (i.e., a clinical chemistry score (CCS) consisting of glucose, estimated glomerular filtration rate (eGFR), and either high-sensitivity cardiac troponin I or T) to high-sensitivity cardiac troponin alone for predicting MI or death within the first month following the initial blood work. Continue reading

Gastric Cancer: Gene Mutation Predictive of Response to Immunotherapy

MedicalResearch.com Interview with:

Wei Zhang, Ph.D. Hanes and Willis Family Professor in Cancer Director Cancer Genomics and Precision Oncology Wake Forest Baptist Comprehensive Cancer Center Winston-Salem, NC  27157-1082

Prof. Zhang

Wei Zhang, Ph.D.
Hanes and Willis Family Professor in Cancer
Director
Cancer Genomics and Precision Oncology
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, NC  27157-1082

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

Response: Gastric cancer is a leading cause of cancer-related death worldwide. Infection by the Helicobacter pylori is the major cause of gastric cancer, which accounts for more than 60% of cases. Despite progress in helicobacter pylori eradication and early cancer diagnosis, the five-year survival rate of gastric cancer remains less than 30%. Gastric cancer is one of the most common cancer types in Asia but the incidence for gastric cancer has seen a steadily increase in the United States in recent years.

Immunotherapy treatment has shown remarkable benefit for some cancer patients whereas others experience toxicities. It is important to identify markers that help oncologists decide which patient would benefit from this promising new treatment strategy. It has been suggested that gastric cancer that is positive for Epstein-Barr Virus is likely more responsive to immunotherapy but only about 10% of gastric cancer patients belong to this category. More potential markers are urgently needed for clinical practice.

There is accumulating evidence that high tumor mutation load, which means there are high numbers of gene mutations in the tumor, can provide a signal to activate immune response systems thus rendering tumors more sensitive to immunotherapy.

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New Biomarkers Predictive of Atrial Fibrillation Outcome

MedicalResearch.com Interview with:

John D Horowitz, MBBS, PhD. Director of Cardiology/Clinical Pharmacology Queen Elizabeth Hospital University of Adelaide Australia

Dr. Horowitz

John D Horowitz, MBBS, PhD.
Director of Cardiology/Clinical Pharmacology
Queen Elizabeth Hospital
University of Adelaide
Australia 

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

Response:  Atrial fibrillation (AF) describes intermittent or permanent episodes of irregular pulse, due to rapid electrical activity within the atria (filling chambers) of the heart. During AF, the atria quiver, rather than contract, and the response of the ventricles is often rapid, resulting in palpitations and an increased risk of development of heart failure. AF may occur at any age, but is most common in ageing patients (typically over 75 years). The primary importance of AF is that it markedly increases the risk of thrombus formation in the atrium, with the resultant problem that these thrombi may dislodge (embolise), and commonly block arteries in the brain, causing strokes. Hence patients with AF are usually treated with anticoagulants.

Although AF often occurs in patients with prior damage to their hearts and atrial distension, there has been evidence for about the past 8 years that AF also is caused, at least in part, by inflammatory changes: two components have been identified as possible causes for this inflammation: lack of nitric oxide (NO) effect[ NO is  an anti-inflammatory chemical formed by all tissues in the body],  and excess activity of the pro-inflammatory enzyme myeloperoxidase (MPO).  High concentrations of ADMA, which inhibits NO formation, may result from effects of MPO on tissues. SDMA, which is closely related to ADMA, also exerts pro-inflammatory effects and tends to suppress NO formation.

The currently reported study began with the design of the ARISTOTLE trial, an investigation of the (then) novel anticoagulant apixaban as an alternative to warfarin therapy, as a means of preventing strokes in patients with AF. It was elected to perform a substudy to investigate the potential role of ADMA and SDMA as modulators of risk in patients with atrial fibrillation.

This substudy, performed in just over 5000 patients from the ARISTOTLE trial, essentially asked two questions:

(1) There are several indices of stroke risk in patients with atrial fibrillation, such as the CHADS2 score. These all rely on patient characteristics (eg age, presence of diabetes) rather than chemical changes. We postulated that there would be a direct relationship between clinically based risk scores and ADMA/SDMA concentrations.

(2) More ambitiously, we postulated that ADMA and SDMA concentrations would represent INDEPENDENT risk markers for major adverse effects in atrial fibrillation patients on anticoagulant treatment, namely stroke, major bleeding and risk of mortality. 

ADMA/SDMA concentrations were determined in Adelaide, Australia, while statistical analyses were performed in Uppsala, Sweden.

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Specific Microbial Signatures Differentiate Chronic Coughs in Children

MedicalResearch.com Interview with:

Dr. Mikhail Kazachkov MD Director of Pediatric Pulmonology Hassenfeld Children’s Hospital NYU Langone Medical Center

Dr. Kazachkov

Dr. Mikhail Kazachkov MD
Director of Pediatric Pulmonology
Hassenfeld Children’s Hospital
NYU Langone Medical Center 

MedicalResearch.com: What is the background for this study? How common is the problem of chronic cough in children?  Is it more common in children with allergies, asthma or reflux?

Response: Chronic cough is one of the leading causes of pediatric referrals to subspecialty physicians.  Its prevalence in the general pediatric population may approach 3% (Galassi et al, Epidemiol. Prev. 2005;29,Suppl.:9–13).

It is important to recognize that the main causes of chronic cough in children are completely different for those in adults.  Specifically, gastroesophageal reflux and postnasal drip are not considered to be important causes of cough in children.  Cough variant asthma, although is a common cause of cough in adults, does not seem to be frequently diagnosed and a cause of chronic cough in children.

The main cause of chronic wet cough in children is protracted bacterial bronchitis (Chang et al, Chest. 2017 Apr;151:884-890).  It is important to recognize that neurologically impaired children have completely different pathogenesis of chronic cough, which is mostly related to aspiration into the lower airway and development of aspiration-related lung disease.

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Novel Mechanisms and Clinical Aspects for an Aggressive Prostate Cancer Risk Locus Uncovered

MedicalResearch.com Interview with:

Gong-Hong Wei, PhD Professor, Academy Research Fellow Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu University of Oulu, Finland

Dr. Gong-Hong Wei,

Gong-Hong Wei, PhD
Professor, Academy Research Fellow
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu
University of Oulu, Finland

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

Response: Prostate cancer is the second most common cancer and the fifth leading cause of cancer-related death in men, with more than 1,100,000 new cases diagnosed and 300,000 deaths yearly around the globe. Among the risk factors for prostate cancer development, the genetic heritability of prostate cancer has been reported near 60%. Over the past decade, genome-wide association studies have identified more than 150 independent single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, we know very little mechanisms accounting for these associations.

SNP rs11672691 at the chromosome 19q13 locus has been found not only associated with prostate cancer risk but also aggressiveness, a form of prostate cancer often with worse prognosis and eventually progression to incurable stage. However, how this genomic variant accounts for prostate cancer severity remains totally unknown. Here we found the association of rs11672691 with additional clinical features of aggressive prostate cancer in an independent cohort of patients with prostate cancer, and discovered a rs11672691-mediated gene regulatory network including several novel genes, HOXA2, CEACAM21 and PCAT19, likely causing prostate cancer progression to incurable stage. In particular, the risk G (guanine) allele of rs11672691 was associated with higher RNA levels of PCAT19 and CEACAM21, and poor prognosis in prostate cancer patients. Rs11672691 G allele enhances chromatin binding of HOXA2 to regulate the expression of CEACAM21 and PCAT19. Using the CRISPR-Cas9 genome editing method, we revealed that rs11672691 genotype directly influence HOXA2 in regulating PCAT19 and CEACAM21 expression, and prostate cancer cellular phenotype.

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Non-Invasive Liquid Biopsy Can Detect Deep Seated Infections

MedicalResearch.com Interview with:

David K. Hong, M.D. VP Medical Affairs and Clinical Development at Karius

Dr. Hong


David K. Hong, M.D.

VP Medical Affairs and Clinical Development at Karius

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

Response: Invasive fungal infections (IFI) are a cause of significant mortality and morbidity in immunocompromised patients. The diagnosis of IFIs is challenging, and often requires an invasive biopsy in order to identify the causal pathogen. There is a need for non-invasive methods of fungal identification to help guide targeted anti-fungal therapy.

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Gene Biomarker Can Predict Brain Tumor Patients Who Have Better Outcomes

MedicalResearch.com Interview with:

Arnab Chakravarti MD Professor and Chair of Radiation Oncology Arthur G. James Cancer Hospital and Richard J. Solove Research Institute The Ohio State University Comprehensive Cancer Center

Dr. Chakravarti

Arnab Chakravarti MD
Professor and Chair of Radiation Oncology
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
The Ohio State University Comprehensive Cancer Center

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

Response: Historically, the treatment for grade two gliomas has been a black box without really a standard-of-care therapy. In the past, it was really dealer’s choice, where it was based upon physician and patient preference. Either radiation alone, radiation plus chemotherapy, or chemotherapy alone, there wasn’t really any data to guide therapeutic decision-making. Then about three years ago the landmark study RTOG 9802 was published, which demonstrated a survival benefit with the addition of chemotherapy to radiation versus radiation alone. That became the standard of care for the treatment of grade two gliomas.

One of the tricky issues with regards to these tumors is that there’s a wide range of outcomes.

There are patients that succumb to disease within months, others that live decades. It’s very
important to personalize care for the individual patient and that’s why biomarkers, prognostic and predictive biomarkers are so important. The 9802 study showed us for the general population of patients that the addition of chemotherapy to radiation improved outcomes versus radiation alone.

The patient population that was selected for our study were the high-risk low-grade glioma
patients. Patients who are generally over the age of 40, tumor sizes that exceeded 6 cm in terms of maximum dimension, tumors that invaded the corpus callosum, astrocytic histology of patients with neurological symptoms. These are typically the patients that were included in the study. Really the main objective of this study was to determine the efficacy of treatment compared to historical controls. Continue reading

Biomarker Procalcitonin Offered Limited Benefit Over Clinical Judgement In Antibiotic Prescribing Patterns

MedicalResearch.com Interview with:

David T. Huang, MD, MPH Associate Professor, Critical Care Medicine, Emergency Medicine, Clinical and Translational Science Director, MACRO (Multidisciplinary Acute Care Research Organization) Director, CRISMA Administrative Core (Clinical Research, Investigation, and Systems Modeling of Acute illness) University of Pittsburgh

Dr. David Huang

David T. Huang, MD, MPH
Associate Professor, Critical Care Medicine, Emergency Medicine, Clinical and Translational Science
Director, MACRO (Multidisciplinary Acute Care Research Organization)
Director, CRISMA Administrative Core (Clinical Research, Investigation, and Systems Modeling of Acute illness)
University of Pittsburgh

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

Response: The overuse of antibiotics has become a serious threat to global public health, causing antibiotic resistance and increasing health care costs. Physicians have long known that antibiotics are usually unnecessary for acute bronchitis and for some other cases of lower respiratory tract infections, and that antibiotics treat only bacterial infections, not viral. But in daily practice, many physicians often prescribe them.

Previous research had reported that using a biomarker blood test and following an antibiotic guideline tied to the test results could reduce antibiotic use in lower respiratory tract infections. In February 2017, the U.S. Food and Drug Administration approved the biomarker test that measures procalcitonin – a peptide that typically increases in bacterial infections, but not viral.

We conducted the Procalcitonin Antibiotic Consensus Trial (ProACT) trial to evaluate whether a procalcitonin antibiotic prescribing guideline, implemented for the treatment of suspected lower respiratory tract infection with reproducible strategies, would result in less exposure to antibiotics than usual care, without a significantly higher rate of adverse events.

The ProACT trial involved 14 predominately urban academic hospitals. We enrolled 1,656 adult patients who presented to the hospital emergency department and were initially diagnosed with a lower respiratory tract infection. All the patients were tested for their procalcitonin levels, but the results were shared only with the physicians of the patients randomly assigned to procalcitonin-guided antibiotic prescription.

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Trial of Antibody Immunotherapy in Parkinson’s Disease

MedicalResearch.com Interview with:

Joseph Jankovic, MD Professor of Neurology  Distinguished Chair in Movement Disorders  Director, Parkinson’s Disease Center  and Movement Disorders Clinic  Department of Neurology                                    Baylor College of Medicine  Baylor St. Luke’s Medical Center at the McNair Campus Houston, TX 77030-4202

Dr. Jankovic

Joseph Jankovic, MD
Professor of Neurology
Distinguished Chair in Movement Disorders
Director, Parkinson’s Disease Center
and Movement Disorders Clinic
Department of Neurology
Baylor College of Medicine
Baylor St. Luke’s Medical Center at the McNair Campus
Houston, TX 77030-4202

 

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

  • First demonstration of an anti-α-synuclein antibody immunotherapy in patients with Parkinson’s Disease.
  • Robust target engagement led to mean reduction of up to 97% in serum free α-synuclein levels.
  • Central Nervous System penetration is supported by a dose-dependent increase in PRX002/RG7935 levels in Cerebral Spinal Fluid.
  • All dose levels of PRX002/RG7935 had acceptable safety and tolerability profiles, meeting the primary objective of this study
  • Data support ongoing PASADENA Phase 2 clinical study of PRX002/RG7935 (NCT03100149)  

Citation:

Jankovic J, Goodman I, Safirstein B, et al. Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti–α-Synuclein Monoclonal Antibody, in Patients With Parkinson DiseaseA Randomized Clinical TrialJAMA Neurol. Published online June 18, 2018. doi:10.1001/jamaneurol.2018.1487 

 

 

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Fewer Re-infarctions With hs Troponin To Assess Heart Attacks

MedicalResearch.com Interview with:

Martin J Holzmann MD, PhD

Dr. Holzmann

Martin J Holzmann MD, PhD
Functional Area of Emergency Medicine
Department of Internal Medicine,
Solna, Karolinska Institutet
Stockholm, Sweden

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

Response: We wanted to investigate how the introduction of the new high-sensitivity cardiac troponin T (hs-cTnT) assay affected incidence of myocardial infarction (MI) use of coronary angiography, cardiac revascularizations, and prognosis in patients with myocardial infarction.

We found that the incidence of MI increased by approximately 5%, with no change in mortality, but with an 11% reduced risk of reinfarctions, and a small increase in coronary angiographies, and cardiac revascularizations by 16%, and 13%, respectively.  Continue reading

Synovial tissue profiling in autoantibody positive at risk individuals reveals gene signatures associated with later development of rheumatoid arthritis

MedicalResearch.com Interview with:

Dr. Lisa van Baarsen PhD Principal Investigator at the Amsterdam Rheumatology and Immunology Cente Academic Medical Center the Netherlands.

Dr. van Baarsen

Dr. Lisa van Baarsen PhD
Principal Investigator at the Amsterdam Rheumatology and Immunology Cente
Academic Medical Center
the Netherlands 

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

Response: The discovery that autoantibodies can be present years before the onset of clinical symptoms of rheumatoid arthritis (RA) enables us to study autoantibody positive individuals who are at risk of developing RA. In patients with established disease the target tissue of RA, the synovial joints, is characterized by cellular infiltration and inflammation. Moreover, successful therapy decreases this synovial inflammation. In the past, our department already showed (PMID: 21177292; PMID: 24574210) that in autoantibody positive at risk individuals there is no overt cellular infiltration present in the synovium.

In the current study we performed a so called discovery-based approach to investigate at a genome-wide gene expression level (using microarrays) whether the synovium is altered at a molecular level before onset of rheumatoid arthritis.

Our molecular and microscopic studies on synovial biopsies obtained from autoantibody positive individuals indeed revealed interesting differences between those at risk individuals who developed disease after follow up and those who did not. Continue reading

PDL1 Amplification Linked To Positive Response to Checkpoint Blockers

MedicalResearch.com Interview with

Aaron Goodman, MD Hematologist/Medical Oncologist Assistant Professor of Medicine UC San Diego Health

Dr. Goodman

Aaron Goodman, MD
Hematologist/Medical Oncologist
Assistant Professor of Medicine
UC San Diego Health 

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

Response: Response rates to PD-1/PD-L1 blockade in solid tumors are reported at 10-20%.  Remarkably, response rates of 65% to 87% have been reported in patients with refractory classical Hodgkin lymphoma treated with checkpoint inhibitors.

In nodular sclerosing Hodgkin lymphoma, amplification of the chromosomal region 9p24.1, which contains the genes PD-L1 (CD274)PDCD1LG2 (PD-L2)and JAK2, is directly correlated with increased expression of these proteins on Reed–Sternberg cells.

Overall, 105 of 108 (97%) biopsies from patients with newly diagnosed classical Hodgkin lymphoma have increased PD-L1 and PDCD1LG2 copy numbers.  The prevalence and utility of PD-L1amplification as a response biomarker to PD-1/PD-L1 blockade is unknown in other tumors.

We sought to determine the prevalence and utility of PD-L1 amplification as a response biomarker to PD-1/PD-L1 blockade in solid tumors.  Continue reading