MedicalResearch.com Interview with:
Dr. Quoc-Dien Trinh MD
Assistant Professor, Harvard Medical School
Brigham and Williams HospitalMedical Research: Please briefly explain the potential benefits and harms of PSA testing, the rationale for screening all men, and the reason U.S. guidelines now recommend against routine screening. Response: The goal of cancer screening is to detect the disease early, and consequently treat it before it becomes more aggressive and spread to other parts of the body (which ultimately leads to death). However, cancer screening may lead to overdiagnosis (detecting cancers that would not have been a problem for a while) and overtreatment. The latter is a problem for prostate cancer, because surgery and radiation therapy (the currently accepted first-line treatments for localized prostate cancer) have significant long-term adverse effects on sexual and urinary function.
I wouldn't say that 'US' guidelines are against screening. Many professional societies continue to recommend some form of joint decision-making with regard to PSA screening. the USPSTF recommends against screening for all - they argue that the harms mentioned above outweigh the benefits.
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MedicalResearch.com Interview with:
Joseph Yeboah MD, MS
Heart and Vascular Center of Excellence
Assistant Professor, Cardiology
Maya Angelou Center for Health Equity
Epidemiology & Prevention
Wake Forest University School of MedicineMedical Research: What is the background for this study? What are the main findings?
Dr. Yeboah: In 2013 the American College of Cardiology/American Heart Association introduced a new way of atherosclerotic cardiovascular disease (ASCVD) risk assessment. The document also recommended the use of additional risk markers including coronary artery calcium (CAC), ankle brachial index, high sensitivity C-reactive protein, family history of ASCVD, to refine ASCVD risk assessment for primary prevention. The goal of this study was to assess the utility of these recommended additional risk markers for primary ASCVD risk assessment in the most ethnically diverse prospective cohort in the USA. We found that among the additional risk markers considered in this analysis, only coronary artery calcium modestly improved primary ASCVD risk assessment.
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MedicalResearch.com Interview with:
Douglas A. Corley, MD, PhD
Gastroenterologist and Research Scientist III
Division of Research
Kaiser Permanente
Oakland, CAMedical Research: What is the background for this study? What are the main findings?
Dr. Corley: Colorectal cancer is a leading cause of cancer death in the United States, so understanding how cancer screening tests for this cancer are used and if they are effective is extremely important.
There are two commonly used tests for colorectal cancer screening in the United States: colonoscopy and fecal immunochemical tests (also known as "FIT"). Colonoscopy requires a bowel preparation to clean you out and is invasive but, if normal, it is done infrequently (every ten years).
FIT is simple to do at home but, to be most effective, needs to be done every year. This has the advantage of potentially picking up cancers that grow between tests. There are few studies that have looked at how well FIT picks up cancers when used year after year. If a test picks up most cancers, it is said to be very "sensitive" for picking up cancer. Most studies only looked at 1 or 2 years of use for how well FITdetected cancers. It is possible that the first year of use may "clear out" most of the easily detectable cancers and that FIT might not work as well in subsequent years.
This very large study over several years at Kaisier Permanente, where we use both colonoscopy and FIT for colorectal cancer screening, looked at whether FIT worked as well at detecting cancer in years 3 and 4 as it did the first time someone used it.
We found that the sensitivity was highest in the first year, likely from clearing out cancers that were there for a while and easily detected, but that in subsequent years the sensitivity, though 5-10% lower, remained high. Also, most people who started with FIT continued doing it, suggesting that it is both feasible and effective for colorectal cancer screening.
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MedicalResearch.com Interview with:R. Jeffrey Karnes MD
Department of Urology, Mayo Clinic,
Rochester, MN 55905 MedicalResearch: What is the background for this study? What are the main findings?
Dr. Karnes: Cancer recurrence following radical prostatectomy is a concern for men undergoing definitive surgical treatment for prostate cancer. Approximately 20-35% of patients develop a rising prostate specific antigen following radical prostatectomy for clinically localized prostate cancer. PSA monitoring is an important tool for cancer surveillance; however, a standard PSA cutpoint to indicate biochemical recurrence has yet to be established. Over 60 different definitions have been described in literature. This variation creates confusion for the patients and clinicians. By studying a large group of patients who underwent radical prostatectomy at Mayo Clinic, we found that a PSA cutpoint of 0.4 ng/mL is the optimal definition for biochemical recurrence. (more…)
MedicalResearch.com Interview with:
Stefan Verlohren, MD, PhD
Consultant and Senior Lecturer
Maternal-Fetal Medicine
Klinik für Geburtsmedizin / Department of Obstetrics
Charité Campus Mitte
BerlinMedical Research: What is the background for this study? What are the main findings?
Dr. Verlohren: Preeclampsia affects 2–5% of pregnancies worldwide, and is a potentially life threatening syndrome for both mother and child. Treatment options for preeclampsia are very limited, with delivery being the only ‘cure’; however, early detection and monitoring are beneficial for improving maternal and fetal outcomes. Development of preeclampsia is very difficult to predict: its clinical presentation is variable and its signs and symptoms overlap with other conditions. There has been an unmet medical need for improved prediction of preeclampsia, i.e. predicting which women will develop preeclampsia and which will not. Women with suspected preeclampsia are often hospitalized until preeclampsia and related adverse outcomes are ruled out. Others who require hospitalization may be overlooked because their symptoms were nonspecific (e.g. headache).
Preeclampsia has been linked with impaired function of the placenta. Placental development is highly dependent on blood vessel formation; before and during preeclampsia, levels of molecules involved in blood vessel inhibition or growth are altered in the maternal bloodstream. In particular, soluble fms-like tyrosine kinase-1 (sFlt-1) (a molecule that inhibits blood vessel growth) is increased and placental growth factor (PlGF) (a molecule that encourages blood vessel growth) is decreased. This study has established that the ratio of these two molecules (sFlt-1:PlGF) can be used to predict whether preeclampsia will develop or not.
The sFlt-1:PlGF ratio can be calculated with a blood test (the Elecsys® sFlt-1 immunoassay and Elecsys®PlGF immunoassay). PROGNOSIS has validated the sFlt-1:PlGF ratio cutoff level of 38 for prediction of preeclampsia. For women with suspected preeclampsia, the Elecsys® immunoassay sFlt-1:PlGF ratio of 38 or below has a high negative predictive value to rule out preeclampsia or adverse fetal outcomes in the next week. A Elecsys® immunoassay sFlt-1:PlGF ratio of more than 38 indicates that preeclampsia or fetal adverse outcomes may develop in the next four weeks. In conjunction with other diagnostic and clinical information, the Elecsys® immunoassay sFlt-1:PlGF ratio can be used to guide patient management.
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MedicalResearch.com Interview with:
Florence Leclercq, MD, PhD
Department of Cardiology
Arnaud de Villeneuve Hospital
University hospital of Montpellier
Montpellier,France
Medical Research: What is the background for this study? What are the main findings?
Response: Patients with history of coronary artery disease (CAD) are considered as a population with high risk of further coronary events. However, frequent pre-existing ECG changes observed in these patients result in difficulty interpreting new ECG aspects in case of chest discomfort. Furthermore, anxiety frequently induced non-cardiac causes of chest pain in these patients, leading to unjustified admission to cardiology units. Moreover, levels of troponin are usually higher in patients with previous CAD compared to patients without history of angina, resulting in difficulty interpreting baseline values in this population. Conversely, copeptin may be influenced by the severity of myocardial ischemia and resulting endogenous stress, and could be a useful additional marker to exclude severe coronary stenosis in high-risk patients with recent chest pain.
This propective monocentric study evaluates the incremental value of copeptin associated with high-sensitivity cardiac T troponin (hs-cTnT) to exclude severe coronary stenosis in 96 patients with coronary artery disease (CAD) and acute chest pain.
Mean age of patients was 60 +/- 13.8 years and the mean time between chest pain onset and blood samples of copeptin was 4.2 +/-2.7 hours. According to clinical decision, coronary angiography was performed in 71 patients (73.9 %) and severe stenosis diagnosed in 14 of them (14.6%). No ischemia was detected on SPECT imaging (n=25). Among the 69 patients with a negative kinetic of hs-cTnT and a negative baseline copeptin, 5 (7.4%) had a severe stenosis (NPV 0.93; 95% CI: 0.87-0.99), 4 of them related to in-stent restenosis (NPV for exclusion of native coronary stenosis: 0.98; 95% CI: 0.93-1).
We can conclude that in patients with preexisting CAD, and once Acute Myocardial Infarction (AMI) is excluded, copeptin increases the NPV of hs-cTnT to rule out severe coronary stenosis or significant myocardial ischemia. Coronary stenosis not detected with this strategy concerned exclusively in-stent restenosisor stenosis related to infarcted -related coronary artery without myocardial viability.
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MedicalResearch.com Interview with:
Justin A. Ezekowitz, MBBCh MSc
Associate Professor, University of Alberta
Co-Director, Canadian VIGOUR Centre
Cardiologist and Director, Heart Function Clinic
Nariman Sepehrvand, MD
Research Fellow & Graduate Student
Mazankowski Alberta Heart Institute
University of Alberta Edmonton, CanadaMedical Research: What is the background for this study? Dr. Ezekowitz: Major practice guidelines recommend the use of natriuretic peptide (NP) testing for diagnosing acute heart failure (HF) in emergency departments (ED). Despite these guidelines, the majority of healthcare regions all around the world (except for the United States and New Zealand) have restricted access to NP testing due to concerns over cost to healthcare systems. In the province of Alberta, Canada, however, a province-wide access to NP testing was provided for all EDs in 2012. This study investigates the factors that are related to the utilization of NP testing in EDs.
Medical Research: What are the main findings?
Dr. Ezekowitz: There was a substantial geographic variation in testing for NPs, despite having a single payer system and the universal availability of NP testing in Alberta. Several factors (including male sex, some comorbidities like prior heart failure, urban residence, type of care provider and ED clinical volume) influenced the utilization of testing for NPs in routine ED practice.
Interestingly, patients with heart failure who were tested for NPs at ED, had a higher rate of hospital admission and lower 7 day and 90 day repeat ED visit rates compared to those who were not tested.
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MedicalResearch.com Interview with:
Leo McHugh, Ph.D.
Director, Bioinformatics
Immunexpress
Seattle, WashingtonMedical Research: What is the background for this study? What are the main findings?
Dr. McHugh: Sepsis is the leading cause of child mortality in the world, and in developing countries kills more adults than breast cancer, prostate cancer and HIV combined. Approximately 30% of people admitted to ICU have sepsis, and up to 50% of these patients die. It’s a major cost burden also, costing the US health system $17 billion per year. The best way to reduce costs and improve patient outcomes is to detect sepsis early and with confidence, so that appropriate treatments can be applied. Each hour delay in the detection of sepsis has been reported to correspond to an 8% increase in mortality. So the need for a rapid and accurate diagnostic is recognized. Traditional methods rely on detection of the specific pathogen causing the infection, and these methods often take more than 24 hours, and find a pathogen in only 30% of clinically confirmed cases because they’re trying to detect a minuscule amount of pathogen or pathogenic product in the blood. Our approach was to use the host’s own immune system, which is highly tuned to respond to the presence of pathogens. Around 30% of all genes are dysregulated in sepsis, so there is a huge signal base to draw from. The trick with using multi marker host response is to pick out the specific combination of gene expression patterns that cover the broad range of patients that present with sepsis and who may present either early or late in the episode, thus with different gene activation patterns.
This paper describes a simple combination of such genes that can be used to detect sepsis and performs over the full range of patients irrespective of stage of infection or severity of infection. In it’s current format, the test is manual and takes 4-6 hours, and is a great advance on the current tools, however the methods we’ve used are specifically designed to meet requirements to port this assay onto a fully automated Point of Care platform that could deliver a result in under 90 minutes.
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MedicalResearch.com Interview with:
Wenjun Ju, Ph.D., M.S.
Research Assistant Professor, Internal Medicine
Matthias Kretzler, M.D.Professor, Internal Medicine, Nephrology
Research Professor, Computational Medicine and Biology
University of Michigan Health SystemMedical Research: What is the background for this study? What are the main findings?
Response: Chronic kidney disease (CKD) is a global health issue that affects approximately 15% of the global population.. While not all patients with CKD will progress to end-stage kidney disease (ESKD), those that do tend to advance quickly and require dialysis or kidney transplant. They are also at an increased risk of death from cardiovascular disease.
According to the International Society of Nephrology, treatment of CKD, including medical management, dialysis and kidney transplant, is very costly. In the U.S. alone, therapy for CKD is likely to exceed $48 billion per year, and the ESKD program consumes 6.7 percent of the total Medicare budget to care for less than 1 percent of the covered population. In China, the disease will cost the economy the equivalent of $558 billion in the U.S. over the next decade.
Early identification of patients that are more likely to experience end-stage kidney disease is an urgent, unmet clinical need. Currently, kidney biopsy is required to determine diagnosis and prognosis of kidney disease. This procedure is costly, carries a low, but significant health risk, and has limited ability to predict the future course of kidney disease.
Together with the European Renal cDNA Bank and the Peking University Institute of Nephrology, the University of Michigan team identified epidermal growth factor (EGF) as a promising candidate for prediction of kidney function loss while analyzing transcriptomic data derived from kidney tissue biopsies of CKD patients across Europe and the U.S. We then validated the findings in urine samples from more than 940 patients in North America, Europe and China, and found that a decrease in urinary EGF protein concentration is an early sign of diminishing kidney function and pinpoints the at-risk patient population.
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MedicalResearch.com Interview with:
Lori Daniels, MD, MAS, FACC
Professor of Medicine
Director, Coronary Care Unit
UCSD Division of Cardiology
Sulpizio Cardiovascular Center
La Jolla, CAMedical Research: What is the background for this study?
Dr. Daniels: A large number of individuals who are at risk for developing cardiovascular disease (CVD) may not be identified as “at risk” by traditional screening methods. Blood-based biomarkers provide a possible way, in conjunction with traditional risk factor screening, to assess risk in individuals. Two such biomarkers which are gaining widespread attention are NT-proBNP and cardiac troponin T (TnT). NT-proBNP is secreted by cardiac muscle cells in response to stretch, while TnT is consider a marker of cardiac cellular damage. Previous studies have shown that each of these markers is associated with long-term risk of cardiovascular outcomes in the general population. Race and ethnicity have been shown to affect the levels of these markers, and whether these markers are equally predictive of future cardiovascular risk in various ethnic groups has not been well studied.
The Multi-Ethnic Study of Atherosclerosis (MESA) is an NIH-funded, multicenter, prospective, population-based study of white, black, Hispanic, and Chinese individuals without clinical CVD at baseline. Participants had blood drawn at a baseline study visit in 2000-2002, and again several years later, in 2004-2005. They have been followed for the development of CVD since then.
The purpose of this study was to learn whether NT-proBNP (single and serial measures) and TnT are predictive of incident cardiovascular disease in a diverse cohort of 5592 participants from the MESA. We also wanted to learn whether the addition of these biomarkers to established CVD risk prediction scores, including the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Pooled Cohort Risk Equation and the Framingham Risk Score, could improve performance of the risk score.
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MedicalResearch.com Interview with:
Ron Rogers
Executive Vice President, Corporate Communications
Spokesman, Myriad Genetics, Inc.
Salt Lake City, Utah 84108
Medical Research: What is the background for the MBDA test? What types of biomarkers are included in the score?
Response: Vectra DA is an advanced blood test for adults with rheumatoid arthritis (RA). It helps you and your doctor better understand your rheumatoid arthritis disease activity. Vectra DA blood test for RA gives physicians a more complete look at your disease activity by measuring 12 markers of RA disease activity. Some other tests, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR or “sed rate”), only measure one marker.
Vectra DA test scores can help track your disease activity over time with an objective measure that complements your doctor’s exam and your own assessment. Patients with high Vectra DA scores have 7-fold higher risk for rheumatoid arthritis-related joint damage than patients with low or moderate Vectra DA scores.
You can learn more about the specific biomarkers at: http://vectrada.com/health-care-professionals/biomarkers/
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MedicalResearch.com Interview with:
Van K. Morris, M.D.
Assistant Professor, GI Medical Oncology
University of Texas – M.D. Anderson Cancer Center
Houston, TX 77030Medical Research: What is the background for this study? What are the main findings?
Dr. Van K Morris: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer. Patients were enrolled in a phase I clinical trial with the BRAF inhibitor vemurafenib, the anti-EGFR antibody cetuximab, and irinotecan. Blood samples were collected every two weeks with each dose, and plasma was analyzed for changes in the fraction of mutant BRAF V600E allele relative to wild-type BRAF allele with time. Trends in circulating free DNA (cfDNA) changes were compared with radiographic changes by RECIST 1.1 criteria to examine this technique as a marker for response to therapy.
For patients who had a response radiographically, drastic reductions in the BRAF V600E allele fraction were observed even after two weeks of starting therapy, well before the first restaging scan. Patients who did not have responses radiographically had less dramatic changes relative to baseline in the BRAF V600E allele fraction. This technique analyzing cfDNA from plasma was validated using two different approaches – digital droplet PCR and next-generation sequencing by Guardant Health. Sequencing of cfDNA was also compared in pretreatment and post-progression samples, and novel mutations in MEK1 and GNAS were observed uniquely in post-progression samples.
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MedicalResearch.com Interview with:
Robert B. Lochhead PhD
Clinical Fellow in Medicine Division of Rheumatology, Allergy & Immunology
Massachusetts General Hospital
Harvard Medical School, Boston, MA
Medical Research: What is the background for this study? What are the main findings?
Dr. Lochhead: Lyme arthritis (LA), caused by the tick-borne spirochete Borrelia burgdorferi, usually resolves appropriately with antibiotic treatment, called antibiotic-responsive Lyme arthritis. However, in some patients, arthritis persists for months or years after spirochetal killing with oral and IV antibiotic therapy, called antibiotic-refractory Lyme arthritis. Synovial lesions in these patients show marked synovial proliferation, inflammation, and vascularization, accompanied by autoimmune T and B cell responses. MicroRNAs (miRNAs) regulate many biological processes including inflammation, immune responses, and cell proliferation, and are effective biomarkers that may reveal molecular mechanisms of disease. Our objective here was to identify extracellular miRNAs (ex-miRNAs) in synovial fluid (SF) that distinguish regulated (responsive) from dysregulated (refractory) immune responses in Lyme arthritis, thereby providing insights into underlying biological processes and potential diagnostic biomarkers to distinguish between these disease courses.
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MedicalResearch.com Interview with:
Bakhos A. Tannous, Ph.D
Associate Professor of Neurology
Harvard Medical School
Director, Experimental Therapeutics and Molecular Imaging Lab Director, Interdepartmental Neuroscience Center
Director, MGH Viral Vector Development Facility
Massachusetts General Hospital
Charlestown, MA 02129
Medical Research: What is the background for this study? What are the main findings?
Dr. Tannous: In recent years, it has become apparent that, in addition to their role in promoting blood clotting, platelets take up protein and RNA molecules from tumors, possibly playing a role in tumor growth and metastasis. Working with our collaborators Dr. Thomas Wurdinger and Pieter Wesseling at the VU Medical Center, Amsterdam, the Netherlands, we found that the RNA profiles of tumor-educated platelets – those that have taken up molecules shed by tumors – can
(1) distinguish healthy individuals and patients with six different types of cancer,
(2) determine the location of the primary tumor and
(3) identify tumors carrying mutations that can guide therapeutic decision making and personalized medicine.
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MedicalResearch.com Interview with:
Dr. Johannes Kettunen
Computational Medicine, Institute of Health Sciences, University of Oulu
National Institute for Health and Welfare, Helsinki
NMR Metabolomics Laboratory, School of Pharmacy,
University of Eastern Finland,
Kuopio Finland
Medical Research: What is the background for this study? What are the main findings?
Dr. Kettunen: The initial discovery of the mortality biomarkers was made 1.5 years ago when we published the first paper describing four biomarkers indicative of 5-year mortality in two cohorts totaling over 17 000 population based samples (http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001606). We wanted to understand the molecular background of the strongest mortality predictor and this is how the current study was started. Here, The network was enriched with defense response genes and we had an idea to test if the biomarker was predictive of future severe infections. We were able to show that chronic inflammation creates extra stress to immune system and predisposes to future infections.
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MedicalResearch.com Interview with:
Ajay Goel, Ph.D. Investigator/Professor
Director, Center for Gastrointestinal Research
Director, Center for Epigenetics, Cancer Prevention and Cancer Genomics
Baylor Research Institute and Charles A. Sammons Cancer Center
Baylor University Medical Center
Dallas, TX 75246
Medical Research: What is the background for this study? What are the main findings?
Dr. Goel: Colorectal cancer (CRC) remains one of the most common and lethal malignancies worldwide, and is the second leading cause of cancer-related deaths in the United States. Although there are some improvements in cancer treatments, such as development of novel chemotherapeutic drugs and technical advances in invasive treatment for metastatic lesion, there is a clear need for prognostic biomarkers that can identify high-risk patients, who can benefit from intensive post-treatment surveillance protocols for early detection of recurrence.
Small nucleolar RNAs (snoRNAs) are one of the largest groups of single-stranded small ncRNAs, and in the past, snoRNAs were recognized for housekeeping functions due to their roles in rRNA maturation, while causing a relatively low impact on cellular homeostasis. However, recent evidence has revealed a new and previously unrecognized role of snoRNAs in the control of cell fate and oncogenesis in various cancers.
The main finding of this study is to firstly demonstrate the clinical impact of snoRNA expression as a predictive biomarker of recurrence and poor prognosis in patients with Colorectal cancer. This study for the first time showed that higher levels of SNORA42 were associated with overall and disease-free survival, and emerged as a risk factor for the return of cancer in another part of the body. It was also correlated with high risk of recurrence and shorter survival in a smaller sample of bowel cancer patients in early stages of their disease.
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MedicalResearch.com Interview with:
Dr. Wilson Tang MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine
Case Western Reserve University
Director of the Center for Clinical Genomics
Cleveland ClinicMedical Research: What is the background for this study? What are the main findings?
Dr. Tang: Renal impairment has long been associated with worse outcomes in acute heart failure. Administration of diuretic therapy often obscures accurate assessment of renal function by urine output. Despite extensive literature suggesting the poor outcomes in those with a rise in creatinine following treatment, recent data has suggested that in the presence of effective diuresis, this phenomenon likely represents hemoconcentration and azotemia rather than acute kidney injury. We observed that using a novel and sensitive biomarker that identified acute kidney injury, specific to tubular injury, we can identify those at higher risk of adverse outcomes in patents admitted for acute heart failure. However, after adjusting for standard risk factors, the prognostic value was clearly attenuated.
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MedicalResearch.com Interview with:
Michael P. Sherman, MD, FAAP
Professor, Department of Child Health
University of Missouri - Columbia
Women's and Children's Hospital
Columbia, Missouri 65201
Medical Research: What is the background for this study?
Dr. Sherman: We understand eosinophils are inflammatory cells in the lung during asthma attacks. Publications in a Nature journal described how eosinophils come to the lung after airway injury. Since the lung and intestine have the same embryonic source, we theorized that eosinophils would rise in the blood after the onset of necrotizing enterocolitis in preterm human infants. We correctly predicted that a rise in blood eosinophils would predict later complications from this disease.
Medical Research: What are the main findings?
Dr. Sherman: We found that within two days of disease onset infants could have a rise in eosinophils greater than 5% of the total white blood cell count. If this increase persisted for five or more days, the infant was at risk for later medical or surgical complications including feeding problems, bowel blockage, or intestinal rupture Area under the curve = 0.97, CI: .92-1.0). The babies having this finding were smaller and more premature.
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MedicalResearch.com Interview with:
Jane E. Salmon, MDDivision of Rheumatology
Hospital for Special Surgery, and
Weill Cornell Medical College, New York, NYMedical Research: Background on lupus and antiphospholipid antibodies - what are they?Dr. Salmon: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease that predominantly affects women and presents during their childbearing years. In SLE, the immune system which normally protects one from infection, turns reacts against the self and can cause damage of multiple organs.
Antiphospholipid antibodies (APL) occur in some people with SLE and some without SLE. They are autoantibodies that can damage the placenta and cause arterial and venous thromboses. Patients with APL can have fetal deaths, miscarriages, preeclampsia and/or growth restricted babies.
Pregnancy in patients with SLE, particularly those with antiphospholipid antibodies (APL), and in patients with APL alone, is associated with an increased risk for maternal and fetal morbidity due to preeclampsia (PE) and insufficient placental support of the developing fetus. PE and placental insufficiency are, in turn, associated with adverse pregnancy outcomes (APOs), including maternal complications of PE, intrauterine fetal death, and fetal growth restriction, as well as indicated preterm delivery. Given that APOs affect over one fifth of pregnancies in SLE and/or APL, the ability to identify patients early in pregnancy who are destined for poor outcomes would significantly impact care of this high risk population.
Medical Research: Two bullets about your PROMISSE study:
Dr. Salmon: The PROMISSE Study (Predictors of pRegnancy Outcome: bioMarker In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus). PROMISSE is the largest multi-center, multi-ethnic and multi-racial study to prospectively assess the frequency of APO, clinical, laboratory and biomarker variables that predict APO, in women with SLE and/or APL with inactive or mild/ moderate activity at conception.
Pregnant patients with SLE and/or APL were enrolled at <12 weeks gestation into PROMISSE between September 2003 and August 2013 at 7 sites (n=497) along with matched healthy controls (n=207) and followed every month of pregnancy.(more…)
MedicalResearch.com Interview with:
Dr. Roxana S. Dronca, M.D
Assistant Professor of Oncology
Assistant Program Director of Hematology-Oncology Fellowship
Mayo Clinic College of Medicine
Rochester, MinnesotaMedical Research: What is the background for this study? What are the main findings?
Dr. Dronca: We previously showed that Bim (BCL-2-interacting mediator of cell death ) is a downstream signaling molecule of PD-1 pathway reflecting the degree of PD-1 interaction with its ligand PD-L1 (unpublished data).
In the current study we found that patients who experienced clinical benefit (CR/PR/SD) after 4 cycles of anti-PD1 therapy had higher frequency of Bim+ PD-1+ T-killer cells in the peripheral blood at baseline compared to patients with radiographic progression, likely reflecting an abundant PD-1 interaction with its tumor-associated ligand PD-L1 (B7-H1). In addition, the frequencies of Bim+ PD-1+ CD8 T cells decreased significantly after the first 3 months of treatment in responders compared to nonresponders, indicating tumor regression and therefore less PD-1 engagement with tumor-associated PD-L1.
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MedicalResearch.com Interview with:
Kenneth R. Shroyer, MD, PhD
The Marvin Kuschner Professor and Chair
Department of Pathology
Stony Brook Medicine
Stony Brook, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Shroyer: Patients that appear to have the same type of cancer often respond very differently to treatment; while some patients appear to go into long-term regression or are cured, others follow a rapid downhill course and ultimately die of their disease. This suggests that there are fundamental differences between tumors at the biologic level that are not detected by current clinical measures.
In this study, we report the unexpected finding that cancer patients that have high levels of a protein called Keratin 17 (K17) have decreased long-term survival when compared to patients that express little to no K17 in their tumors. In addition, we found that K17 enters the nucleus of tumor cells to mediate the degradation of the master regulator of cell division and tumor growth key tumor suppressor protein, p27. Furthermore, we identified that K17 increases the resistance of tumor cells to chemotherapy.
These are critical findings because this is the first report that a keratin is an oncoprotein that can enter the nucleus to promote the development of cancer and resistance to chemotherapy.
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MedicalResearch.com Interview with:
Jenny Permuth Wey, PhD, MS
Assistant Member
Departments of Cancer Epidemiology and Gastrointestinal Oncology
Moffitt Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Wey: Pancreatic cancer is one of the deadliest cancers world-wide. It is currently the fourth leading cause of cancer-related deaths in the United States, and is predicted to become the second leading cause by 2030. Currently there are no accurate methods to diagnose pancreatic cancer early when a patient may be eligible for surgery to remove the tumor and hopefully survive longer. To beat this disease, early detection is key, and our team has dedicated efforts to studying pancreatic cancer in its ‘precancerous’ state because we and other researchers believe that the identification and treatment of precancerous pancreatic lesions offers a promising strategy to reduce the number of people losing their lives to this disease.
Similar to how colon polyps can progress into colon cancer, we now know that certain types of pancreatic cystic lesions can progress into pancreatic cancer. Pancreatic cancer precursors/pre-cancers known as intraductal papillary mucinous neoplasms (IPMNs) account for nearly one-half of the estimated 150,000 asymptomatic pancreatic cysts detected as ‘incidental findings’ on computed tomography (CT) scans or magnetic resonance imaging (MRI) scans each year during the clinical work-up for an unrelated condition. Imaging alone cannot reliably distinguish between benign, pre-cancerous, and cancerous cysts, and cannot differentiate ‘low-risk’intraductal papillary mucinous neoplasms' (defined as low- or moderate-grade disease) that can be monitored from ‘high-risk’ IPMNs (defined as high-grade or invasive disease) that should be surgically removed. The decision to undergo pancreatic surgery is not trivial for the patient and medical team since pancreatic surgery can be associated with an estimated 40% chance of complications and a 4% chance of death. Noninvasive tests are needed to accurately detect precancerous lesions of the pancreas so that personalized risk assessment and care can be provided.
microRNAs (miRNAs) are small molecules that act as ‘master-regulators’ of cancer-related processes in the body. One of the main purposes of our ‘proof of principle’ study was to measure miRNAs in the blood and determine whether a set of miRNAs could distinguish patients with IPMNs from healthy individuals. We then sought to determine whether a set of miRNAs could distinguish patients known to have ‘low-risk’ IPMNs from those with ‘high-risk’ IPMNs. We show that new, relatively inexpensive digital technology could reliably measure miRNAs in blood plasma (the pale yellow liquid component of blood) from individuals newly-diagnosed with pancreatic cancer precursors (IPMNs) and healthy individuals. Thirty miRNAs out of 800 tested showed higher levels in IPMN patients compared to healthy individuals, providing a preliminary ‘miRNA signature’ that may be found only in people with early pancreatic disease, suggesting it could serve as an early diagnostic tool. Furthermore, we also provide preliminary data to suggest that a 5-miRNA signature can partially distinguish high-risk IPMNs that warrant resection from low-risk IPMNs that can be watched. This is important clinically because it would be opportune to personalize care such that high-risk IPMNs that warrant resection are properly identified while individuals with low-risk IPMNs are spared the substantial risks of mortality and morbidity associated with overtreatment from unnecessary surgery.
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MedicalResearch.com Interview with:
Stuart Gordon, M.D.
Director of Hepatology at Henry Ford Hospital
Detroit, Michigan
Medical Research: What is the background for this study? What are the main findings?
Dr. Gordon: The U.S. Centers for Disease Control and Prevention’s Division of Viral Hepatitis estimates 2.7 to 3.9 million people in the United States currently suffer from chronic hepatitis C. But, unfortunately, many of these patients may be unaware of the severity of their liver damage. We looked at evidence of cirrhosis among hepatitis C patients by examining four different parameters: ICD9 codes; liver biopsy reports; evidence of liver failure; and the FIB-4 test, an easily calculated biomarker. By using all four indicators of cirrhosis, we found a far higher prevalence of cirrhosis than would be indicated by any one method.
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MedicalResearch.com Interview with:
Jorg Dietrich, MBA MMSc MD PhD
Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program
Massachusetts General Hospital Cancer Center
Assistant Professor of Neurology
Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Dietrich: Understanding the adverse effects associated with cancer therapy is an important issue in oncology. Specifically, management of acute and delayed neurotoxicity of chemotherapy and radiation in brain cancer patients has been challenging. There is an unmet clinical need to better characterize the effects of standard cancer therapy on the normal brain and to identify patients at risk of developing neurotoxicity. In this regard, identifying novel biomarkers of neurotoxicity is essential to develop strategies to protect the brain and promote repair of treatment-induced damage.
In this study, we demonstrate that standard chemotherapy and radiation in patients treated for glioblastoma is associated with progressive brain volume loss and damage to gray matter – the area of the brain that contains most neurons.
A cohort of 14 patients underwent sequential magnetic resonance imaging studies prior to, during and following standard chemoradiation to characterize the pattern of structural changes that occur as a consequence of treatment.
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MedicalResearch.com Interview with:
Tatjana Crnogorac-Jurcevic MD PhD
Reader Centre for Molecular Oncology
Barts Cancer Institute, Queen Mary
University of London
London UKMedical Research: What is the background for this study? What are the main findings?Dr. Crnogorac-Jurcevic: Pancreatic adenocarcinoma (PDAC) is one of the most difficult cancers to detect. More than 80% of patients usually present at a late stage, with either locally advanced or with already metastatic disease. This is one of the major reasons for a bleak prognosis of this malignancy, which is typically 3-6 months and with <5% five-year survival. However, if patients are diagnosed with stage II disease, the survival rate is 20%, and at stage I, in patients with very small tumours, the five-year survival can increase up to 60%.
In order to find biomarkers for early detection of this disease, we have performed in depth GeLC/MS/MS (SDS-PAGE-liquid chromatography-tandem mass spectrometry) analysis of 18 proteomes of urine samples collected from healthy controls, chronic pancreatitis, and patients with Pancreatic adenocarcinoma and obtained around 1500 non-redundant proteins. From these, three proteins, LYVE-1, REG1A, and TFF1, were selected for further analysis based on their known biological functions and statistical difference in comparisons of the experimental groups. These biomarkers were subsequently validated using ELISA assays in a multicenter cohort of urine samples: 87 from healthy people, 92 from patients with chronic pancreatitis, and 192 from PDAC patients.
Multiple logistic regression was then applied: when comparing Pancreatic adenocarcinoma with healthy urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the three biomarkers combined into a panel were 0.89 (95% confidence interval: 0.84–0.94) in the training dataset (70% of the data) and 0.92 (95% confidence interval: 0.86–0.98) in the validation dataset (30% of the data). When the results from the analysis of PDAC stage I–II (n=71) urine samples were compared with the healthy urine specimens, the panel achieved AUCs of 0.90 (95% confidence interval: 0.84–0.96) and 0.93 (95% confidence interval: 0.84–1.00) in the training and validation datasets, respectively. In comparison to matching plasma CA19.9 values, the only Pancreatic adenocarcinoma biomarker in widespread clinical use (albeit mostly for monitoring of the disease), the panel achieved a higher AUC of 0.97 (95% confidence interval: 0.94–0.99) than CA19.9 (AUC 1/4 0.88; 95% confidence interval: 0.81–0.95, P=0.005). When combined with CA19.9, increased AUC of 0.99 (95% confidence interval: 0.97–1.00, P=0.04) was achieved, but this was not seen in a panel combined with plasma CA19.9 in stage I–IIA PDAC (n =17) vs. healthy sample comparison.
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MedicalResearch.com Interview with: Misha A. Rosenbach, MD
Assistant Professor of Dermatology at the Hospital of the University of Pennsylvania
Assistant Professor of Dermatology in Medicine
Medical Research: What is the background for this study? What are the main findings?Dr. Rosenbach: Sarcoidosis is an inflammatory disease of unknown etiology where genetically susceptible patients develop multi-organ granulomatous inflammation in response to an as-yet unidentified stimulus. Patients with sarcoidosis typically have granulomatous inflammation in their lungs, but the second most commonly affected organ is the skin; the eyes, lymph nodes, liver, heart, brain, and other organs can be affected as well. Patients with sarcoidosis can experience a few disease trajectories; some spontaneously recover, while others have persistent, active inflammation, whereas another group can experience inflammation which leads to scarring and fibrosis. It can be challenging to distinguish these cohorts of patients based on their lungs alone.
The skin is much easier to evaluate, as it is right there on the surface, and can be examined by physicians without resorting to invasive tests or radiography. At Penn, we developed a novel cutaneous sarcoidosis assessment tool, called the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI), which is designed to accurately measure how inflamed skin sarcoid lesions are in a given patient, as well as describing which type of cutaneous lesion patients’ have. The CSAMI has in previously studies been shown to be reliable when used by dermatologists, with excellent inter-rater and intra-rater reproducibility.
In this study, we had a group of Pulmonologists, Rheumatologists, and Dermatologists (representing the groups of physicians who most commonly care for patients with sarcoidosis, especially if there is skin involvement) evaluate a group of patients with cutaneous sarcoidosis, using the CSAMI and another sarcoidosis activity instrument, the SASI, which has also previously been used to measure skin sarcoidosis activity in a number of settings. We were able to demonstrate that these cutaneous scoring tools are reliable and reproducible and able to accurately measure cutaneous sarcoidosis disease activity in a variety of patients with a range of skin disease severity. We also compared the physician scores to patients’ own evaluations of their disease, and showed that the CSAMI (physician impression of disease) correlated well with patients’ own perception of their disease activity and severity.
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MedicalResearch.com Interview with: Dr Stephen Chan DM, FRCR, FRCP
Consultant Oncologist Breast and Gynaecological Cancers
Nottingham University Hospitals Trust
Honorary Professor at the University of Nottingham
Visiting Professor of Cancer Medicine at Nottingham Trent University
MedicalResearch: What is the background for this study? What are the main findings?Dr. Chan: Worldwide each year 1.68 million women are diagnosed with breast cancer and more than half a million die from the disease. Of these new cases around 12% will be classified as triple negative breast cancer (TNBC), meaning that tumour cells from these patients do not show any of the three established clinical markers that can be treated with targeted therapies. These drugs are used in addition to standard chemotherapy to improve the chance of a good treatment response, leading to prolonged disease free survival. Without these additional treatment options triple negative patients are forced to depend entirely on chemotherapy to treat their cancer.
Traditionally the sensitivity of a cancer to different types of chemotherapy has been categorised is based on a tumours tissue of origin and stage. There is currently no predictive marker of response that would allow chemotherapy treatment to be tailored to individual patients. With this information a clinician can predict which patients would benefit most from a particular chemotherapy and switch any who would do poorly to an alternative. The result would be a shift to increased treatment efficacy, while avoiding toxicity from ineffective treatment, which would in turn also reduce the cost to the health service. This need is particularly acute in triple negative breast cancer cases where chemotherapy is the cornerstone of treatment.
In collaboration with researchers based at Nottingham Trent University our group has been successful in finding new markers, which can predict how a patient will respond to chemotherapy treatment. One of these is HAGE (DDX43), a DEAD box RNA helicase. We have found that high HAGE expression predicts good respond to one of the main first line chemotherapy drugs, called anthracycline (Tarek MA Abdel-Fatah et al, April 2014). Our recent work (Tarek MA Abdel-Fatah, 2015) has shown that the predictive value is strong in triple negative breast cancer cases.
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MedicalResearch.com Interview with:
Lac Tran, MD
Division of Nephrology and Hypertension
Kaiser Permanente Los Angeles Medical Center
Los Angeles, CA
Medical Research: What is the background for this study? What are the main findings?Dr. Tran: Abnormal serum phosphorus levels have been associated with adverse cardiovascular outcomes and progression to renal failure. Given phosphorus’s important biological roles in cellular replication and bone mineral metabolism, we sought to investigate the association between phosphorus levels and anemia in normal kidney function and early chronic kidney disease.
Our study is a population-based study among a large racially/ethnically diverse population within the Kaiser Permanente Southern California health system.
Among 155, 974 individuals, 4.1% had moderate anemia and 12.9% had mild anemia. We found that phosphorus levels greater than 3.5 mg/dL and less than 2.0 mg/dL showed a greater likelihood for moderate anemia. Every 0.5 mg/dL phosphorus level increase demonstrated a 16% greater likelihood for moderate anemia. The highest phosphorus tertile of our population had a 26% greater likelihood for anemia compared to the middle tertile. We also found that female sex, Asian race, diabetes, low albumin, and low iron saturation were risk factors for anemia.
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MedicalResearch.com Interview with:
Frederick Korley MD Ph.DJohns Hopkins University School of Medicine
Emergency Medicine
Baltimore, Maryland
Medical Research: What is the background for this study?
Dr. Korley: Each year, millions of Americans are evaluated in emergency departments for traumatic brain injuries. Currently the only test available for diagnosing traumatic brain injury is a brain CT scan. Brain CT scans accurately identify bleeding in the brain from trauma. However, they are unable to identify damage to brain cells. Approximately 90% of patients with traumatic brain injury have no bleeding in the brain and therefore have unremarkable brain CT scans. However, these patients typically have damaged brain cells and they continue to suffer headaches, dizziness, attention and memory deficits, sleep problems among others for months after their injury and can’t figure out why. Therefore new tests are needed to identify traumatic brain injury patients with damaged brain cells and especially those who are likely to have persistent traumatic brain injury-related symptoms for months after injury. If you or any one in your family has sustained a brain injury in an accident, you might want to get in touch someone similar to this Personal Injury Lawyer St. Louis or a law firm more local to your area, who might be able to look into your case.
Medical Research: What are the main findings?
Dr. Korley: Our study determined that the blood levels of a protein called brain derived neurotrophic factor (BDNF) can help predict whether a patient will continue to have symptoms related to traumatic brain injury at six 6 months after injury, even if they had an unremarkable brain CT scan.
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MedicalResearch.com Interview with:
Dr. Heinrich Thaler
Trauma Hospital Meidling
Vienna Austria
Medical Research: What is the background for this study?Dr. Thaler: An increased prevalence of minor head injuries in elderly patients combined with the frequent use of platelet aggregation inhibitors resulted in increased hospital admissions and cranial computed tomography. We undertook the study with the aim to reduce the workload of medical staff and costs as well as the radiation burden in the management of patients with mild head injuries.
Medical Research: What are the main findings?Dr. Thaler: S 100B is a reliable negative predictor in elderly patients and/or in patients on platelet aggregation inhibitors to rule out an intracranial hemorrhage after minor head injury (S100B is an astroglial derived protein detectable in serum in the case of cerebral tissue damage). The negative predictive value of S100B is 99,6%. We conclude that S100B levels below 0.105 µg/L can accurately predict a normal cranial computed tomography after minor head injury in older patients and those on antiplatelet medication. Additionally we found no increased risk for intracranial hemorrhage in older patients or in patients receiving antiplatelet therapy.
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