LPA Gene Variants Linked To Cardiac Events Despite Statins

MedicalResearch.com Interview with:

Wei-Qi Wei, MD, PhD Assistant Professor Department of Biomedical Informatics Vanderbilt University Nashville, TN 37203

Dr. Wei-Qi Wei

Wei-Qi Wei, MD, PhD
Assistant Professor
Department of Biomedical Informatics
Vanderbilt University
Nashville, TN 37203

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

Response: The study was motived by the clinical observation that some patients develop coronary heart disease events despite taking statins, one of our most effective drugs to reduce cardiovascular risk. We collected data within the eMERGE network of people taking statins and monitored them for development of coronary heart disease events over time.  We  conducted a genome-wide association study of those with events compared to those without events.

Our results showed that single nucleotide polymorphisms (SNPs) on the LPA gene were associated with a significantly increased risk of coronary heart disease events. Individuals with the variant were 50% more likely to have an event. More importantly, even among patients who achieved ideal on-treatment LDL cholesterol levels (<70 mg/dL), the association remained statistically significant.

We then did a phenome-wide association study to see if other diseases or conditions were associated with these LPAvariants. The major associated conditions were all cardiovascular. This sort of study can highlight potential other indications for a drug targeting this pathway and suggest potential adverse events that might be experienced from targeting this pathway. Clearly, more and larger studies will be needed to truly understand the potential risks and benefits of a future drug targeting this pathway.  Continue reading

RNA-based Blood Test Can Detect Fibromyalgia

MedicalResearch.com interview with:

Dr. Chase Spurlock, PhD CEO, IQuity, Specialty Diagnostic Technologies Faculty, Vanderbilt University Medical Center

Dr. Chase Spurlock

Dr. Chase Spurlock, PhD
CEO, 
IQuitySpecialty Diagnostic Technologies
Faculty, Vanderbilt University Medical Center

Dr. Spurlock discusses IQuity’s release of IsolateFibromyalgia, the first RNA-based blood test to detect fibromyalgia.

MedicalResearch.com: What is the background for this test? Would you briefly explain what fibromyalgia is, whom it affects and why it has been difficult to definitely diagnosis? 

Dr. Spurlock: We developed the IsolateFibromyalgia™ test using our established RNA assay platform, IQIsolate™, to help clinicians receive timely and accurate information. This technology has evolved from over a decade of research at Vanderbilt University and continues at IQuity funded by both the National Institutes of Health (NIH) as well as private investors. We discovered that differences in RNA expression patterns could be detected in patients with a variety of human conditions spanning infection to more complex inflammatory diseases. With our focus on autoimmune disease, we identified and validated RNAs capable of distinguishing multiple sclerosis, IBS, Crohn’s, ulcerative colitis and fibromyalgia syndrome. In the case of fibromyalgia, our research involved almost 600 subjects including healthy individuals, patients with endocrine conditions, dermatologic conditions and rheumatologic diseases — rheumatoid arthritis, Sjogren’s syndrome and systemic lupus erythematosus. Reported sensitivity and specificity of this assay is 92 percent and 96 percent, respectively.

Fibromyalgia syndrome is characterized by widespread musculoskeletal pain often initially localized to the neck and shoulders. Patients typically describe pain throughout the muscles but may also report pain in the joints. Furthermore, fibromyalgia is usually accompanied by fatigue as well as cognitive disturbance. Patients most afflicted are women between ages 20 and 55. Fibromyalgia affects approximately as many as 6-10 million people in the U.S.

The difficulty in reaching a definitive diagnosis lies in two important issues. First, the cause of the syndrome is unknown, and the way the condition presents and progresses can vary among patients. Secondarily, fibromyalgia syndrome mimics many other conditions due to the multiple nonspecific symptoms associated with fibromyalgia. Patients look well, there are no obvious abnormalities on physical examination other than tenderness, and laboratory and radiologic studies are normal. With no discernable abnormalities in routine clinical laboratory testing or imaging, the diagnosis is based on subjective reporting of symptoms.

The difficulties and complex nature of receiving a correct fibromyalgia diagnosis are apparent. Despite improved awareness among primary care clinicians, many continue to be uncomfortable with making this diagnosis. Fibromyalgia patients on average wait almost a year after experiencing symptoms before seeing a physician and end up visiting on average 3.7 different physicians before a diagnosis. The diagnostic journey can take years. IsolateFibromyalgia provides the clinician and patient actionable information with 94 percent accuracy.

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Balanced IV Fluids Can Reduce Kidney Damage and Death in Critically Ill Patients

MedicalResearch.com Interview with:

Todd W. Rice, MD, MSc Associate Professor of Medicine Director, Vanderbilt University Hospital Medical Intensive Care Unit Division of Allergy, Pulmonary, and Critical Care Medicine Nashville, TN  

Dr. Rice

Todd W. Rice, MD, MSc
Associate Professor of Medicine
Director, Vanderbilt University Hospital Medical Intensive Care Unit
Division of Allergy, Pulmonary, and Critical Care Medicine
Nashville, TN  

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

Response: Our study (called the SMART study) evaluates the effects of different types of intravenous fluids used in practice in critically ill patients.  It is very similar to the companion study (called the SALT-ED study and published in the same issue) which compares the effects of different types of intravenous fluids on non-critically ill patients admitted to the hospital.  Saline is the most commonly used intravenous fluid in critically ill patients.  It contains higher levels of sodium and chloride than are present in the human blood.  Balanced fluids contain levels of sodium and chloride closer to those seen in human blood.

Large observational studies and studies in animals have suggested that the higher sodium and chloride content in saline may cause or worsen damage to the kidney or cause death.  Only a few large studies have been done in humans and the results are a bit inconclusive.

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For Most Patients Balanced IV Fluids Better Than Saline

MedicalResearch.com Interview with:

Wesley H. Self, MD, MPH Associate Professor Department of Emergency Medicine Vanderbilt University Medical Center Nashville, TN 

Dr. Self

Wesley H. Self, MD, MPH
Associate Professor
Department of Emergency Medicine
Vanderbilt University Medical Center
Nashville, TN  

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

Response: Doctors have been giving IV fluids to patients for more than 100 years. The most common IV fluid during this time has been saline; it has high levels of sodium and chloride in it (similar to table salt).  Balanced fluids are an alternative type of IV fluid that has lower levels of sodium and chloride that are more similar to human blood.

Our studies were designed to see if treating patients with these balanced fluids resulted in better outcomes than saline.  We found that patients treated with balanced fluids had lower rates of death and kidney damage than patients treated with saline.

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Balovaptan Has Potential to Improve Social Interaction and Communication in Autism Spectrum Disorder

MedicalResearch.com Interview with:

Dr Kevin Sanders, MD Principle Medical Director-Product Development Neuroscience Assistant Professor, Departments of Psychiatry and Pediatrics Vanderbilt University

Dr. Sanders

Dr Kevin Sanders, MD
Principle Medical Director-Product Development Neuroscience
Assistant Professor, Departments of Psychiatry and Pediatrics
Vanderbilt University 

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

Response: The FDA has granted Roche Breakthrough Therapy Designation for its investigational oral medicine balovaptan (previously known as RG7314), a vasopressin 1a (V1a) receptor antagonist for individuals with autism spectrum disorder (ASD).

FDA Breakthrough Therapy Designation for balovaptan is primarily based on efficacy findings in the VANILLA (Vasopressin ANtagonist to Improve sociaL communication in Autism) study, a Phase II trial of balovaptan in adults with ASD. Trial results were first presented at the International Congress for Autism Research (IMFAR) in May 2017. Treatment effects were observed on the Vineland-II (secondary endpoint) and also demonstrated that balovaptan was safe and well tolerated by the subjects in the study. The Vineland-II is a scale that measures socialization, communication and daily living skills. This data was presented to the FDA and is part of the basis of the Breakthrough Designation.  Continue reading

Opioids For Pain Can Exacerbate Pneumococcal Infections

MedicalResearch.com Interview with:

Andrew Wiese, PhD Postdoctoral Research Fellow, Department of Health Policy Vanderbilt University Medical Center

Dr. Wiese

Andrew Wiese, PhD
Postdoctoral Research Fellow
Department of Health Policy
Vanderbilt University Medical Center

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

Response: As opioid use has increased in the U.S., the safety of prescription opioids has come under further scrutiny.

In animal studies, use of certain opioids has been associated with increased susceptibility to bacterial infections, including infectious due to Streptococcus pneumoniae, the pathogen that causes invasive pneumococcal disease. Invasive pneumococcal disease includes bacteremia, meningitis, and invasive pneumonia, all of which are associated with high mortality. Although those associations have been well established in animal experiments, it is important to understand the risk of serious infections among humans taking prescription opioid analgesics.

We found that prescription opioid use is associated with a significantly increased risk for laboratory-confirmed invasive pneumococcal diseases, and that this association was strongest for opioids used at high doses, those classified as high potency and long-acting formulations.

The data also showed that opioids previously described as immunosuppressive in prior experimental studies conducted in animals had the strongest association with invasive pneumococcal diseases in humans. Continue reading

Shifting Attention Causes Momentary Brain Freeze

MedicalResearch.com Interview with:

Alex Maier, PhD Assistant Professor of Psychology Assistant Professor of Ophthalmology and Visual Science Vanderbilt University

Dr. Maier

Alex Maier, PhD
Assistant Professor of Psychology
Assistant Professor of Ophthalmology and Visual Science
Vanderbilt University

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

Response: We were interested in finding out about how the brain shifts attention from one location to another. We knew that when we attend a certain location, brain activity increases in a specific way. This increase in activity is how we perform better when we use attention. What we knew less about is what happens when attention moves between locations.

To our surprise, we found that there is a brief moment in between these attentional enhancements, while attention moves from one location to another, where the brain does the complete opposite and decreases its activity. Shifting attention thus has a brief negative effect on our brain’s ability to process information about the world around us.

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FDG-PET Scans of Lung Nodules Should Be Interpreted With Caution

MedicalResearch.com Interview with:

PET Scan Vanderbilt Health

PET Scan Vanderbilt Health

Amelia W. Maiga, MD MPH
Vanderbilt General Surgery Resident
VA Quality Scholar, TVHS

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

Response: Positron emission tomography (PET) combined with fludeoxyglucose F18 (FDG) is currently recommended for the noninvasive diagnosis of lung nodules suspicious for lung cancer. Our investigation adds to growing evidence that FDG-PET scans should be interpreted with caution in the diagnosis of lung cancer. Misdiagnosis of lung lesions driven by FDG-PET avidity can lead to unnecessary tests and surgeries for patients, along with potentially additional complications and mortality.

To estimate FDG-PET diagnostic accuracy, we conducted a multi-center retrospective cohort study. The seven cohorts originating from Tennessee, Arizona, Massachusetts and Virginia together comprised 1188 nodules, 81 percent of which were malignant. Smaller nodules were missed by FDG-PET imaging. Surprisingly, negative PET scans were also not reliable indicators of the absence of disease, especially in patients with smaller nodules or who are known to have a high probability of lung cancer prior to the FDG-PET test.

Our study supports a previous meta-analyses that found FDG-PET to be less reliable in regions of the country where fungal lung diseases are endemic. The most common fungal lung diseases in the United States are histoplasmosis, coccidioidomycosis and blastomycosis. All three fungi reside in soils. Histoplasmosis and blastomycosis are common across much of the Mississippi, Ohio and Missouri river valleys and coccidioidomycosis is prevalent in the southwestern U.S. These infections generate inflamed nodules in the lungs (granulomas), which can be mistaken for cancerous lesions by imaging.

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Borderline Pulmonary Hypertension Patients Often Progress To Overt Disease

MedicalResearch.com Interview with:

Dr. Evan L. Brittain, MD Assistant Professor of Medicine Vanderbilt University School of Medicine

Dr. Brittain

Dr. Evan L. Brittain, MD
Assistant Professor of Medicine
Vanderbilt University School of Medicine

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

Response: The purpose of this study was to determine whether pulmonary pressure values below the diagnostic threshold for pulmonary hypertension (25mmHg) are associated with an increased risk of mortality. We studied over 4,000 consecutive individuals referred for right heart catheterization, the “gold-standard” procedure for measuring pulmonary pressure. We found that borderline levels of mean pulmonary pressure (19-24mmHg) were common, representing 18% of all patients referred for this procedure. Borderline mean pulmonary pressure values were also associated with 31% increase in mortality after accounting for many other clinical factors. Finally, we found that most of the patients with borderline pulmonary hypertension who underwent repeat catheterization often progressed to overt pulmonary hypertension.

This study suggests that patients with borderline pulmonary hypertension should be considered an at-risk group.

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Low CD4 Count Linked To Heart Failure in HIV Patients

MedicalResearch.com Interview with:
Matthew S Freiberg, MD, MSc
Associate Professor of Medicine, Division of Cardiovascular Medicine
Vanderbilt Translational and Clinical Cardiovascular Research Center

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

Response:  HIV infected people are living longer and are at risk for cardiovascular diseases. While acute myocardial infarction has been studied and the increased risk of Acute Myocardial Infarction (AMI) among HIV+ people compared to uninfected people is well documented, there are less data describing the risk of HIV and different types of heart failure, including reduced and preserved ejection fraction heart failure. Understanding more about the link between HIV and different types of HF is important because reduced and preserved ejection fraction heart failure differ with respect to underlying mechanism, treatment, and prognosis. Moreover, as cardiovascular care has improved, HIV infected people who experience an AMI are likely to survive but may live with a damaged heart. Understanding more about the link between HIV and heart failure may help providers and their patients prevent or reduce the impact of HF on the HIV community.

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Excess Zinc May Predispose to C.diff By Altering Gut Microbiome

MedicalResearch.com Interview with:

Eric P Skaar, Ph.D., MPH Director, Division of Molecular Pathogenesis Ernest W. Goodpasture Professor of Pathology Vice Chair for Basic Research, Department of Pathology, Microbiology, and Immunology Vanderbilt University School of Medicine

Dr. Eric P Skaar,

Eric P Skaar, Ph.D., MPH
Director, Division of Molecular Pathogenesis
Ernest W. Goodpasture Professor of Pathology
Vice Chair for Basic Research, Department of Pathology, Microbiology, and Immunology
Vanderbilt University School of Medicine

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

Response: Nutrient metals are known to be a critical driver of the outcome of host-pathogen interactions, and C. difficile is the most common cause of hospital-acquired infections. C. difficile infection typically occurs following antibiotic-mediated disruption of the healthy microbiome. We were interested in learning how nutrient metals can shape the microbiome and impact the outcome of Clostridium difficile infection.

We found that excess zinc alters the structure of the microbiome and increases the severity of C. difficile infection in mice.

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HIV Patients With Depression Have Greater Risk of Myocardial Infarction

MedicalResearch.com Interview with:
Matthew S Freiberg, MD, MSc
Cardiovascular Medicine Division, Vanderbilt University School of Medicine
Tennessee Valley Geriatric Research Education and Clinical Center, Nashville  TN
Tasneem Khambaty, PhD
Department of Psychology, University of Miami, Coral Gables, Florida
Jesse C. Stewart, PhD
Department of Psychology, Indiana University–Purdue University , Indianapolis, Indianapolis

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

Response: Due to highly effective antiretroviral therapy, people with HIV are living longer. Unfortunately, these HIV-infected individuals remain at a higher risk for other chronic diseases, with cardiovascular disease (CVD) being one of the leading cause of death in this population. In the general population, depressive disorders, such as major depressive disorder (MDD) and dysthymic disorder, are associated with increased risk of new-onset CVD. Given that roughly 24-40% of HIV-infected individuals have a depressive disorder, we examined whether MDD and dysthymic disorder are also associated with an increased risk of new-onset CVD in people with HIV.
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Vanderbilt Free Colonoscopies For Uninsured Detected Some Early Cancers and Was Cost Neutral

MedicalResearch.com Interview with:
Erica R. H. Sutton, MD
Assistant Professor
Department of Surgery, General
Vanderbilt

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

Response: Colorectal cancer is one of the most preventable diseases that we face; however, despite the great strides that we have made in the realm of early detection, many people still do not undergo screenings. We sought to increase the availability of screenings to those in our community who are at high risk for colorectal cancer and uninsured by providing free colonoscopies to them and to examine the cost-effectiveness of this intervention. Over a 12-month period, 682 uninsured people underwent screening colonoscopies, and 9 cancers were detected. Compared to the Surveillance, Epidemiology, and End Results (SEER) registry, our patient population included more early-stage cancers, and our program was found to be cost-neutral.

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Adjuvant Chemotherapy Improves Survival After Pancreatic Cancer Resection

MedicalResearch.com Interview with:

Alexander A. Parikh, M.D., M.P.H. Associate Professor of Surgery Director of Hepatobiliary, Pancreatic and GI Surgical Oncology Director, Vanderbilt Pancreas Center Vanderbilt University Medical Center Nashville, TN

Dr. Alexander Parikh

Alexander A. Parikh, M.D., M.P.H.
Associate Professor of Surgery
Director of Hepatobiliary, Pancreatic and GI Surgical Oncology
Director, Vanderbilt Pancreas Center
Vanderbilt University Medical Center
Nashville, TN

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

Dr. Parikh: Although adjuvant chemotherapy has been proven to increase survival after successful resection of pancreatic cancer and has become the standard of care worldwide, the use of adjuvant chemoradiation is more controversial. The vast majority of randomized trials have failed to show a significant improvement in survival with the use of chemoradiation after pancreatic cancer resection. Furthermore, our own report from the multi-institutional Central Pancreatic Consortium (CPC) published several years ago failed to show a benefit in the use of chemoradiation except in high-risk groups such as lymph node positive disease.

The purpose of the current study was to investigate the patterns of recurrence with the use of adjuvant chemotherapy or chemoradiation in hopes of explaining some of these differences. It was our hypothesis that systemic chemotherapy would prevent distant recurrence (and perhaps local) while chemoradiation would only prevent local recurrence and thereby have less impact on overall survival.

MedicalResearch.com: What are the main findings?

Dr. Parikh: The main findings demonstrated that adjuvant chemotherapy led to an improvement in both local and distant recurrence with a corresponding improvement in overall survival while chemoradiation only led to an improvement in local recurrence but not distant nor overall survival.

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10% of ICU Patients At Risk of Developing PTSD

Mayur Patel, MD, MPH, FACS Assistant Professor of Surgery & Neurosurgery Vanderbilt University Medical Center Staff Surgeon and Surgical Intensivist Nashville VA Medical Center

Dr. Mayur Patel

MedicalResearch.com Interview with:
Mayur Patel, MD, MPH, FACS
Assistant Professor of Surgery & Neurosurgery
Vanderbilt University Medical Center
Staff Surgeon and Surgical Intensivist
Nashville VA Medical Center

Medical Research: What is the background for this study?

Dr. Patel: Post-traumatic stress disorder (PTSD) can occur in patients after the traumatizing events of critical illness. Survivors of critical illness have reported PTSD symptoms months to even years after critical illness, possibly related to nightmare-like experiences, safety restraints creating communication barriers, and protective mechanical ventilation causing feelings of breathlessness and fear of imminent death. But, the epidemiology of PTSD after critical illness is unclear with wide ranging estimates (0-64%) and largely fails to distinguish past PTSD from new PTSD specifically resulting from the critical care experience.

Our study provides estimates on new cases of PTSD stemming specifically from the ICU experience. Pre-existing PTSD has rarely been systematically assessed in prior cohorts, and our work took extra effort to distinguish pre-existing PTSD from new PTSD cases. Civilian populations have dominated the literature of PTSD after critical illness, and this research is the first to also include the expanding and aging Veteran population.  Continue reading