Vasopressin-Inhibitor Tolvaptan Reduces Kidney Function Decline in Polycystic Kidney Disease

MedicalResearch.com Interview with:
Dr. TorresVicente E. Torres, M.D., Ph.D.

Director of the Mayo Clinic Translational Polycystic Kidney Disease (PKD) Center

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

Response: Experimental work pioneered by Dr. Jared Grantham showed that cyclic AMP, an intracellular signaling molecule, promotes the development and growth of cysts. Vasopressin, a hormone produced by the pituitary gland, stimulates the production of cyclic AMP in the collecting ducts, from which most cysts derive in autosomal dominant polycystic kidney disease (ADPKD). While this effect of vasopressin is necessary for the kidneys to concentrate and reduce the volume of urine, it promotes the development and growth of cysts in patients with ADPKD. Dr. Vincent Gattone realized that inhibiting the action of vasopressin could be protective in polycystic kidney disease. Work in our and other laboratories confirmed that suppression of vasopressin production, release or action reduces cyst burden, protects kidney function, and prolongs survival in rodent models of the disease.

This experimental work provided a strong rationale for clinical trials of tolvaptan, a vasopressin V2 receptor antagonist. Tolvaptan reduced the rate of kidney growth in the TEMPO 3:4 trial, in patients with early ADPKD. It also reduced the rate of decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), from 10.1 to 6.8 mL/min/1.73 m2 over three years. The eGFR benefit was maintained during two additional years when all the patients were treated with tolvaptan in an open label extension of the TEMPO 3:4 trial (TEMPO 4:4). Safety laboratory tests performed every four months showed elevations of liver transaminases in blood in 4.4% of tolvaptan and 1% of placebo-treated patients. Three of 1,271 tolvaptan-treated patients during TEMPO 3:4 and TEMPO 4:4 had evidence of potentially serious drug-induced liver injury. These abnormalities occurred all within the first 18 months of exposure to tolvaptan.

Based on the TEMPO 3:4 results, tolvaptan was approved for the treatment of rapidly progressive ADPKD in Japan, Canada, European Union, Switzerland and South Korea. In the United States, the Food and Drug Administration requested additional data to further evaluate the efficacy and safety of this drug. The REPRISE trial was performed to determine the efficacy and safety of tolvaptan in patients with later stage ADPKD.

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Liraglutide (SAXENDA) May Lead To Weight Loss By Slowing Stomach Emptying

MedicalResearch.com Interview with:

Prof Michael Camilleri, MD Gastroenterologist, Professor of Medicine, Pharmacology and Physiology at Mayo Clinic Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Mayo Clinic, Rochester, MN

Prof. Camilleri

Prof Michael Camilleri, MD
Gastroenterologist, Professor of Medicine, Pharmacology and Physiology at Mayo Clinic
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER)
Mayo Clinic, Rochester, MN

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

Response: Liraglutide is approved for treatment of obesity; the precise mechanisms for the beneficial weight loss are unclear. We are interested to learn whether it is possible to identify people who are more likely to benefit from this treatment.

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Blocking Gherlin May Be Key To Preventing Weight Gain After Dieting

MedicalResearch.com Interview with:

Dr. W. Stephen Brimijoin PhD Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic, Rochester, MN 55905

Dr. Brimijoin

Dr. W. Stephen Brimijoin PhD
Department of Molecular Pharmacology and Experimental Therapeutics
Mayo Clinic, Rochester, MN 55905

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

Response: The background for this study was:

1) Ordinary C57 black mice readily become obese when given unrestricted access to high-fat mouse chow.

2) If the obese mice are put on a forced calorie restricted diet they will regain their previous normal healthy weight.  However, if they are given unrestricted access to their previous “normal” low-fat mouse chow, they will rebound into obesity.  This effect can be seen as a model of human obesity and the difficulties that formerly obese men and women face in maintaining healthy body mass gained after dieting.

3) The literature on obesity provided reason to believe that this self-defeating behavioral cycle involves ghrelin, the so-called “hunger hormone.”

4) We had recently shown that the plasma enzyme called “butyrylcholinesterase” was a key regulator of active ghrelin. Therefore, it seemed plausible that raising enzyme levels would reduce ghrelin and, in turn, would blunt food craving.

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In Accordance With Guidelines, Fewer Low Risk Patients Receiving Antibiotics Before Dental Procedures

MedicalResearch.com Interview with:

Daniel C. DeSimone, M.D.</strong> Infectious Diseases Fellowship, Year 2 Mayo Clinic

Dr. DeSimone

Daniel C. DeSimone, M.D.
Infectious Diseases Fellowship, Year 2
Mayo Clinic

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

Response: For over 50 years, the American Heart Association (AHA) has recommended antibiotics to be given to patients with certain cardiac conditions prior to invasive dental procedures (dental cleanings, extractions, root canals) with the hope to prevent infective endocarditis–a potentially deadly infection of the heart valves. Prevention of this infection was preferred to treatment of an established infection due to its high morbidity and mortality rates. However, in 2007, experts found that there was very little, if any, evidence that showed antibiotics prophylaxis prevented infective endocarditis prior to invasive dental procedures. Given this, the AHA revised its guidelines, significant reducing the number of patients where antibiotic prophylaxis would be given–as routine daily activities such as chewing food, tooth brushing, and flossing were much more likely to cause infective endocarditis than a single dental procedure.

For over 50 years, patients with cardiac conditions that placed them at “moderate risk” and/or “high risk” were to receive antibiotics prior to dental procedures. In 2007, the “moderate risk” group were to no longer receive antibiotic prophylaxis. This is a significantly large proportion of patients–approximately 90% of all patients who would have received antibiotic prophylaxis. Given the drastic changes made in 2007, there was concern among the medical and dental communities about whether we were leaving patients “unprotected” and at risk for infective endocarditis. Thankfully, several population based studies from our group and others across the United States have not shown an increase in the rate of infective endocarditis. However, the question remained, “Are providers following the 2007 AHA guidelines?” and “Are patients still receiving antibiotics prior to dental procedures when its no longer indicated by the guidelines?”.

This was the main focus of our paper. We were able to go into the local dental offices and at the same time, have full access to their medical records. Every dental visit between 2005 and 2015 at their dental office was reviewed; the type of dental visit, whether they received antibiotic prophylaxis or not. In addition, we could confirm their cardiac conditions that would place them at “moderate risk” or “high risk” compared to the general population.

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Patients With Clostridium difficile Infections Should Have Need For Gastric Acid Suppression Reassessed

MedicalResearch.com Interview with:

Sahil Khanna,

Dr. Sahil Khanna

Sahil Khanna, M.B.B.S. MS
Division of Gastroenterology and Hepatology
Mayo Clinic, Rochester, Minnesota

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

Response: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea and has recently shown increasing incidence especially in the community. Novel risk factors for CDI development include the use of gastric acid suppression medication, presence of systemic comorbid conditions, C difficile carriage in water and food sources, amongst others.

Gastric acid suppression medications such as proton-pump inhibitors (PPIs) and histamine-2 receptor blockers (H2Bs) are commonly prescribed and consumed over the counter for gastroesophageal reflux disease, peptic ulcer disease, or functional dyspepsia, but they are also sometimes prescribed for unnecessary indications, which leads to overuse of these medications. Recurrent CDI after a primary infection is a major problem, with the risk being as high as 50% to 60% after 3 or more Clostridium difficile infections. Data on the association between acid suppression and recurrent CDI are conflicting and therefore we performed a systematic review and meta-analysis to study the association between the use of gastric acid suppression medications and the risk of recurrent CDI.

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Effect of SSRIs and Depression On Revisions After Hip or Knee Replacement

MedicalResearch.com Interview with:

Hilal Maradit Kremers, M.D. M.Sc.   Associate Professor of Epidemiology Mayo Clinic College of Medicine

Dr. Hilal Maradit Kremers

Hilal Maradit Kremers, M.D. M.Sc. 
Associate Professor of Epidemiology
Mayo Clinic College of Medicine 

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

Response: Depression and mood disorders are common comorbidities in patients undergoing total hip and total knee arthroplasty.  Based on previous research, there is evidence to suggest presence of depression in arthroplasty patients is associated with worse functional and clinical outcomes, such as complications, readmissions and mortality.  Although the mechanisms are poorly understood, it is important to identify strategies to effectively manage perioperative depression in an effort to improve arthroplasty outcomes.  One potential strategy is effective medical treatment of underlying depression which can potentially improve depression symptoms, thereby surgical outcomes.

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New Recording System Enables Identification of Complex Cardiac Arrhythmias

MedicalResearch.com Interview with:

Jay Millerhagen

Jay Millerhagen

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

Response: Journal of the American College of Cardiology (JACC): Clinical Electrophysiology (JACC CEP) publication entitled, “Novel Electrophysiology Recording System Enables Specific Visualization of the Purkinje Network and Other High-Frequency Signals” reports important findings obtained using BioSig Technologies’ PURE EP System during a series of pre-clinical studies conducted at Mayo Clinic in Rochester, Minnesota. These studies are part of a company-funded Advanced Research Program announced on March 28, 2016. The JACC CEP manuscript provides an excellent example of the PURE EP System’s ability to record challenging high frequency signals known as Purkinje potentials. These signals are of great interest to electrophysiologists when assessing arrhythmia syndromes dependent on the Purkinje network.

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Thyroid Hormone Treatment In Pregnant Women With Subclinical Hypothyroidism

MedicalResearch.com Interview with:

Dr. Spyridoula Maraka Assistant professor of medicine Division of Endocrinology and Metabolism Center for Osteoporosis and Metabolic Bone Diseases University of Arkansas for Medical Sciences and the Central Arkansas Veterans Health Care System Little Rock Arkansas

Dr. Spyridoula Maraka

Dr. Spyridoula Maraka
Assistant professor of medicine
Division of Endocrinology and Metabolism
Center for Osteoporosis and Metabolic Bone Diseases
University of Arkansas for Medical Sciences and
Central Arkansas Veterans Health Care System
Little Rock Arkansas

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

Response: Subclinical hypothyroidism, a mild thyroid dysfunction, has been associated in pregnancy with multiple adverse outcomes. Our aim was to estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism.

Using a large national US dataset, we identified 5,405 pregnant women diagnosed with subclinical hypothyroidism. Of these, 843 women, with an average pretreatment TSH concentration of 4.8 milli-international units per liter, were treated with thyroid hormone. The remaining 4,562, with an average pretreatment TSH concentration of 3.3 milli-international units per liter, were not treated.

Compared with the untreated group, treated women were 38 percent less likely to experience pregnancy loss. However, they were more likely to experience a preterm delivery, gestational diabetes or preeclampsia. Moreover, the benefit of thyroid hormone treatment on pregnancy loss was seen only among women with higher TSH levels (4.1 to 10 mIU/L) before treatment. We also found that for women with lower levels of TSH (2.5–4.0 mIU/L), the risk of gestational hypertension was significantly higher for treated women than for untreated women.

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5ARIs Found Not Linked To Increased Prostate Cancer Mortality

MedicalResearch.com Interview with:

Lauren P. Wallner, PhD, MPH Assistant Professor, Departments of Medicine and Epidemiology, University of Michigan Adjunct Investigator, Kaiser Permanente Southern California North Campus Research Complex Ann Arbor, MI

Dr. Lauren P. Wallner

Lauren P. Wallner, PhD, MPH
Assistant Professor, Departments of Medicine and Epidemiology, University of Michigan
Adjunct Investigator
Kaiser Permanente Southern California
North Campus Research Complex
Ann Arbor, MI

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

Response: 5 alpha-reductase inhibitors (5ARIs) are often used for the management of lower urinary tract symptoms in men. Two prior clinical trials found 5ARIs also reduced the risk of prostate cancer, but there was an increase in more aggressive (Gleason 7-10) cancers among the men who were diagnosed. Thus, concerns over whether 5ARIs may increase the risk of prostate cancer death have limited their use in the prevention of prostate cancer, which remains controversial. To address the safety of 5ARIs for the primary prevention of prostate cancer, we conducted a large population-based study of over 200,000 men in community practice settings of over a 19 year observation period to assess whether 5ARI use (as compared to alpha-blocker use) was associated with prostate cancer mortality.

Our results suggest that 5ARI use was not associated with an increased risk of prostate cancer mortality when compared to alpha-blocker use.

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What Interventions Can Reduce Epidemic Physician Burnout?

MedicalResearch.com Interview with:

Colin P. West, MD, PhD, FACP  Divisions of General Internal Medicine and Biomedical Statistics and Informatics Departments of Internal Medicine and Health Sciences Research Mayo Clinic

Dr. Colin West

Colin P. West, MD, PhD, FACP
Divisions of General Internal Medicine and Biomedical Statistics and Informatics
Departments of Internal Medicine and Health Sciences Research
Mayo Clinic

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

Response: Physician burnout has reached epidemic levels, as documented in national studies of both physicians in training and practicing physicians demonstrating burnout rates in excess of 50%. Consequences include negative effects on patient care, professionalism, physicians’ own care and safety, and the viability of health-care systems. We conducted a systematic review and meta-analysis to better understand the quality and outcomes of the literature on approaches to prevent and reduce burnout.

We identified 2617 articles, of which 15 randomized trials including 716 physicians and 37 cohort studies including 2914 physicians met inclusion criteria. Across interventions, overall burnout rates decreased from 54% to 44%, emotional exhaustion score decreased from 23.82 points to 21.17 points, and depersonalization score decreased from 9.05 to 8.41. High emotional exhaustion rates decreased from 38% to 24% and high depersonalization rates decreased from 38% to 34%.

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Chronic Subthreshold Cortical Stimulation to Treat Resistant Focal Epilepsy.

MedicalResearch.com Interview with:

Brian Nils Lundstrom, MD, PhD Department of Neurology Mayo Clinic Rochester, Minnesota

Dr. Brian Lundstrom

Brian Nils Lundstrom, MD, PhD
Department of Neurology
Mayo Clinic
Rochester, Minnesota

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

Response: About as many people have drug-resistant focal epilepsy as have multiple sclerosis, and treatment options are limited.

This study describes an alternative treatment option that has proven very helpful for the majority of participants. Electrical stimulation is delivered continuously via implanted electrodes to the region of brain where seizures start. The electrical stimulation decreases the seizure-related discharges from the brain, and for about 40% of patients their disabling seizures were completely stopped.

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Quality Performance Measures Should Include Hypoglycemia Assessments

MedicalResearch.com Interview with:

Victor M. Montori, MD Mayo Clinic

Dr. Victor Montori

Victor M. Montori, MD MSc
Knowledge and Evaluation Research Unit in Endocrinology
Mayo Clinic, Rochester, Minnesota

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

Response: Hypoglycemia can acutely disrupt patients’ lives through symptoms ranging from bothersome to life-threatening; worsen quality of life; and hinder medication adherence and glycemic control. Hypoglycemia is now known to increase risk of mortality, cognitive impairment, and cardiovascular events. In order to improve the quality of diabetes care, healthcare organizations use publicly reported performance measures for quality measurement and improvement, and pay-for-performance initiatives. The degree to which existing performance measures are aligned with guidelines, particularly in regard to hypoglycemia avoidance, is uncertain.

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Healthy Eating in Adolescence Sets Pattern For Less Weight Gain As Young Adult

MedicalResearch.com Interview with:

David R. Jacobs, Jr., PhD Mayo Professor of Public Health Division of Epidemiology and Community Health, School of Public Health University of Minnesota Minneapolis MN 55454-1075

Dr. David R. Jacobs, Jr.

David R. Jacobs, Jr., PhD
Mayo Professor of Public Health
Division of Epidemiology and Community Health, School of Public Health
University of Minnesota
Minneapolis MN 55454-1075

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

Response: Project EAT (Eating and Activity in Teens and Young Adults) is on ongoing longitudinal study which began by screening middle and secondary school students in the Minneapolis and St Paul Metropolitan are. Students were the 11-18 years old (average age 15), then followed up at average ages 20 and 25. We had devised an eating pattern in about 2006, which
a) predicts a lot of things in several different studies (including total mortality in the Iowa Women’s Health Study) and b) looks a great deal like the recently released 2015 Dietary Guidelines for Americans (DGA).

We call our diet pattern A Priori Diet Quality Score (APDQS) and think of it as close to or in the style of a Mediterranean/prudent/healthy diet.

We hypothesized that this pattern would be associated with lower weight (in general with better long term health, but the focus in Project EAT was weight and BMI), probably least so at age 15. The minimal hypothesized effect in adolescence relates to the very large energy expenditure in adolescent growth years; we thought that diet composition would be less important for body weight at that time than energy intake (and APDQS is about diet composition).

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Estrogen Patch in Newly Postmenopausal Women May Reduce Alzheimer’s Risk

MedicalResearch.com Interview with:

Kejal Kantarci, M.D. M.S. Professor of Radiology Division of Neuroradiology

Dr. Kejal Kantarci

Kejal Kantarci, M.D. M.S.
Professor of Radiology
Division of Neuroradiology

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

Response: A rapid decline in estrogen with menopause may be associated with an increased risk of Alzheimer’s disease risk in women. This study was conducted in newly postmenopausal women who received 17β-Estradiol via a skin patch or conjugated equine estrogen orally or placebo.

Those who received 17β-Estradiol patch had reduced β-amyloid deposits, the plaques found in the brains of people with Alzheimer’s disease, three years after the end of the hormone therapies.

In the study, women with APOE e4 — one form of the most common gene associated with late-onset Alzheimer’s disease — who received the 17β-Estradiol patch had lower levels of β-amyloid deposits than those who received placebo.

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Functional Medicine Plan Treats Fatigue, Stress and Digestive Issues in Women

MedicalResearch.com Interview with:

SUSANNE M. CUTSHALL, APRN, CNS, D.N.P. Division of General Internal Medicine Mayo Clinic, Rochester, MN

Susanne Cutshall

SUSANNE M. CUTSHALL, APRN, CNS, D.N.P.
Division of General Internal Medicine
Mayo Clinic, Rochester, MN

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

Response: Several years ago a group of practitioners from the Mayo Clinic, including Sue Cutshall and Larry Bergstrom took my functional medicine training program that I teach through The Kalish Institute. They were interested in researching the effectiveness of the functional medicine techniques I’ve developed over the last twenty years, so we embarked on this study together. The study showed women on the program experienced increased energy, were better able to handle stress and had less physical pain. Additional information gathered from follow-up testing, but not reported in the formal study, showed a significant improvement in digestive health as well.

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Intensive Glucose Control Still Attempted in Frail Patients, Risking Hypoglycemia

MedicalResearch.com Interview with:

Rozalina McCoy, M.D Assistant Professor of Medicine Division of Primary Care Internal Medicine Department of Medicine Mayo Clinic Rochester

Dr. Rozalina McCoy

Rozalina McCoy, M.D
Assistant Professor of Medicine
Division of Primary Care Internal Medicine
Department of Medicine
Mayo Clinic Rochester

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

Dr. McCoy: Hypoglycemia is a serious potential complication of diabetes treatment; it worsens quality of life and has been associated with cardiovascular events, dementia, and even death. Most professional societies recommend targeting HbA1C levels less than 6.5% or 7%, with individualized treatment targets based on patient age, other medical conditions, and risk of hypoglycemia with therapy. Treating patients to very low HbA1c levels is not likely to improve their health, especially not in the short-term, but can cause serious harms such as hypoglycemia. The goal of our study was to assess how frequently patients with type 2 diabetes are treated intensively, focusing specifically on patients who are elderly or have serious chronic conditions such as dementia, kidney disease including dialysis need, heart disease, stroke, lung disease, and cancer. Moreover, while prior studies have suggested that intensive treatment may be common, there was no strong evidence that intensive treatment does in fact increase risk of hypoglycemia. Our study was designed specifically to assess this risk.

We examined medical claims, pharmacy fill data, and laboratory results of 31,542 adults with stable and controlled type 2 diabetes who were included in the OptumLabs™ Data Warehouse between 2001 and 2013. None of the patients were treated with insulin or had prior episodes of severe hypoglycemia, both known risk factors for future hypoglycemic events. None of the patients had obvious indications for very tight glycemic control, such as pregnancy.

“Intensive treatment” was defined as being treated with more glucose-lowering medications than clinical guidelines consider to be necessary given their HbA1C level. Patients whose HbA1C was less than 5.6 percent (diabetes is defined by HbA1C 6.5 percent or higher) were considered intensively treated if they were taking any medications. Patients with HbA1C in the “pre-diabetes” range, 5.7-6.4 percent, were considered to be intensively treated if using two or more medications at the time of the test, or if started on additional medications after the test, because current guidelines consider patients with HbA1C less than 6.5 percent to already be optimally controlled. For patients with HbA1C of 6.5-6.9 percent the sole criteria for intensive treatment was treatment intensification with two or more drugs or insulin.

The patients were separated by whether they were considered clinically complex (based on the definition by the American Geriatrics Society)—75 years of age or older; or having end-stage kidney disease, dementia; or with three or more serious chronic conditions. This distinction has been made to help identify patients for whom adding glucose-lowering medications is more likely to lead to treatment-related adverse events, including hypoglycemia, while not providing substantial long-term benefit.

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Multiple Chronic Conditions Accumulating Over Time Lead To Frailty

MedicalResearch.com Interview with:

Alanna Chamberlain, PhD Assistant Professor of Epidemiology Mayo Clinic College of Medicin

Dr. Alanna Chamberlain

Alanna Chamberlain, PhD
Assistant Professor of Epidemiology
Mayo Clinic College of Medicine

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

Dr. Chamberlain: The number of elderly individuals in the US will double by the year 2050 and these individuals will become increasingly frail as they get older. Frailty has been recognized by doctors and researchers as an important contributor to poor health and declines in quality of life among older adults. However, it is difficult to measure frailty because it’s not due to a single condition. Instead, multiple health problems tend to accumulate over time until a person becomes increasingly frail. It is important to understand how frailty develops as patients age and how changes in frailty are related to outcomes. To address these questions, we followed individuals over 8 years to identify changes in frailty over time, to describe how people cluster (follow similar trajectories of frailty over time), and to examine how these changes relate to emergency department visits, hospitalizations, and death in a large population from Olmsted County, MN.

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Intellectual Activity May Delay Onset of Alzheimer’s Dementia

MedicalResearch.com Interview with:

Prashanthi Vemuri, PhD Mayo Clinic Rochester, Minnesota

Dr. Prashanthi Vemuri

Prashanthi Vemuri, PhD
Mayo Clinic
Rochester, Minnesota 

Medical Research: What is the background for this study? What are the main findings?

Dr. Vemuri: Lifetime Intellectual enrichment has been found to delay the symptoms of dementia but the impact on brain changes due to Alzheimer’s disease has been poorly understood. In this study we studied the impact of lifetime intellectual enrichment (education, occupation, and midlife cognitive activities) on the brain changes related to Alzheimer’s disease. We obtained serial imaging on 393 individuals from a population based sample. We found that in majority of the individuals, there were minimal effects of intellectual enrichment on brain changes due to Alzheimer’s disease. However in those with higher genetic risk of Alzheimer’s, lifetime intellectual enrichment had a protective effect on the brain.

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Carotid Stenosis for Stroke Prevention: Both Surgery and Stenting Give Long Lasting Results

MedicalResearch.com Interview with:

Thomas G. Brott, M.D. Professor of neurology and director for research and The Eugene and Marcia Applebaum Professor of Neurosciences and James C. and Sarah K. Kennedy Dean for Research. Mayo Clinic in Jacksonville, Fla

Dr. Thomas Brott

Thomas G. Brott, M.D.
Professor of neurology and director for research and
The Eugene and Marcia Applebaum Professor of Neurosciences and James C. and Sarah K. Kennedy Dean for Research.
Mayo Clinic in Jacksonville, Fla

Medical Research: What is the background for this study? What are the main findings?

Dr. Brott: Revascularization for carotid artery stenosis is the accepted treatment for symptomatic patients with >50% stenosis and for asymptomatic patients with >70% stenosis.  The original CREST report in 2010 showed both surgery and stenting were the safe methods to treat severe carotid stenosis.  But the follow-up averaged 2.5 years and Medicare-age patients live for an average of 18-20 years.  These patients and their families needed to know if surgery and stenting are durable in preventing stroke.

CREST was designed to answer the questions of clinical and anatomic durability for the long-run.

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Midlife Weight Loss Linked to Mild Cognitive Impairment

Rosebud O. Roberts, M.B., Ch.B. Mayo Clinic Rochester, Minn.

Dr. Rosebud Roberts

MedicalResearch.com Interview with:
Rosebud O. Roberts, M.B., Ch.B.
Mayo Clinic
Rochester, Minn. 

Medical Research: What is the background for this study?

Dr. Roberts: Decline in weight has been observed 10-20 years prior to onset of dementia. We wanted to study whether this decline also occurs for mild cognitive impairment (an intermediate stage in the progression from normal cognition to dementia).

Medical Research: What are the main findings?

Dr. Roberts: The main finding was that there was indeed a decline in weight (from the maximum weight in midlife to weight assessed in late life) was associated with a increased risk of mild cognitive impairment.

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Thermal Ablation Can Treat Some Focal Melanoma Metastases

Dr. Mariah White

Mariah L. White

MedicalResearch.com Interview with:
Mariah L. White, MD

Department of Radiology
Mayo Clinic
Rochester, MN 55905

Medical Research: What is the background for this study?

Dr. White: Stage IV (metastatic) melanoma carries a poor prognosis with median survival of 6 to 10 months, claiming over 9000 lives per year in the United States. There is evidence that aggressive focal treatment in patients with oligometastatic disease with complete eradication of all clinical disease can result in durable remissions and potentially improve overall survival. Oligometastatic disease is typically defined as metastatic disease limited to 5 or fewer lesions. Thermal ablation is an alternative local management strategy to resection of limited sites of distant spread.  Similar to surgical management of oligometastatic disease it can be used in conjunction with systemic medical therapy or as an alternative in those patients where SMT is not well tolerated or unable to achieve complete remission.

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Study Identifies PSA Level Most Likely To Predict Prostate Cancer Recurrence

R. Jeffrey Karnes MD Department of Urology, Mayo Clinic, Rochester, MN 55905

Dr. R. Jeffrey Karnes

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.
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Frailty Linked To Lower Survival in Lung Transplant Patients

Cassie Kennedy, M.D. Pulmonology and Critical Care Medicine Mayo Clinic

Dr. Cassie Kennedy

MedicalResearch.com Interview with:
Cassie Kennedy, M.D.
Pulmonology and Critical Care Medicine
Mayo Clinic 

Medical Research: What is the background for this study?

Dr. Kennedy: Lung transplant is a surgical procedure that can offer extended life expectancy and improved quality of life to selected patients with end-stage lung disease. However there are about 1700 patients awaiting lung transplant at any given time in the United States because transplant recipients far exceed potential donors.  In addition, even with carefully chosen candidates, lung transplant recipients live on average about 5.5 years.  It is therefore very important for transplant physicians to choose patients who will receive the most benefit from their lung transplant.

Frailty (defined as an increased vulnerability to adverse health outcomes) has typically been a subjective consideration by transplant physicians when choosing lung transplant candidates.  The emergence of more objective and reproducible frailty measures from the geriatric literature present an opportunity to study the prevalence of frailty in lung transplant (despite that subjective screening) and to determine whether the presence of frailty has any impact on patient outcomes.

Medical Research: What are the main findings?

Dr. Kennedy: Frailty is quite common –46 percent of our patient cohort was frail by the Frailty Deficit Index. We also saw a significant association between frailty and worsened survival following lung transplantation: one-year survival rate for frail patients was 71.7 percent, compared to 92.9 percent for patients who were not frail. At three years this difference in survival persisted–the survival rate for frail patients was 41.3 percent, compared to 66.1 percent for patients who were not frail.

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Overtesting in Stable Diabetes Leads To Overtreatment

Rozalina G. McCoy, M.D. Senior Associate Consultant Division of Primary Care Internal Medicine Assistant Professor of Medicine Mayo Clinic

Dr. McCoy

MedicalResearch.com Interview with:
Rozalina G. McCoy, M.D
.
Senior Associate Consultant
Division of Primary Care Internal Medicine
Assistant Professor of Medicine
Mayo Clinic

Medical Research: What is the background for this study? What are the main findings?

Dr. McCoy: Blood glucose monitoring is an integral component of managing diabetes.  Glycosylated hemoglobin (HbA1c) is a measure of average glycemia over approximately 3 months, and is used in routine clinical practice to monitor and adjust treatment with glucose-lowering medications.  However, monitoring and treatment protocols are not well defined by professional societies and regulatory bodies; while lower thresholds of testing frequencies are often discussed, the upper boundaries are rarely mentioned.  Most agree that for adult patients who are not using insulin, have stable glycemic control within the recommended targets, and have no history of severe hypoglycemia or hyperglycemia, checking once or twice a year should suffice. Yet in practice, there is a much higher prevalence of excess testing.  We believe that such over-testing results in redundancy and waste, adding unnecessary costs and burdens for patients and the health care system.

We therefore conducted a large retrospective study among 31,545 adults across the U.S. with stable and controlled type 2 diabetes who had HbA1c less than 7% without use of insulin and without documented severe hypoglycemia or hyperglycemia.  We found that 55% of patients had their HbA1c checked 3-4 times per year, and 6% had it checked 5 times a year or more.  Such excessive testing had additional harms as well – we found that excessive testing was associated with greater risk of treatment intensification despite the fact that all patients in the study already met glycemic targets by having HbA1c under 7%.  Indeed, treatment was intensified by addition of more glucose lowering drugs or insulin in 8.4% of patients (comprising 13%, 9%, and 7% of those tested 5 or more times per year; 3-4 times per year; and 1-2 times per year, respectively).

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Chronic Traumatic Encephalopathy Found In Brains of Non-Professional Athletes

Kevin Bieniek

Kevin Bieniek

MedicalResearch.com Interview with:
Kevin Bieniek B.Sc.

Biology and Psychology
Neuroscience researcher
Mayo Clinic’s campus in Florida. 

Medical Research: What is the background for this study? What are the main findings?

Response:  Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury often sustained through contact sports and military blast exposure.  While CTE was first described in boxers in the 1920s, to date many descriptions of CTE have been made in high-profile professional athletes, but the frequency of Chronic traumatic encephalopathy pathology in athletes with more modest contact sports participation is unknown.  For this study, researchers at the Mayo Clinic in Jacksonville, FL examined the Mayo Clinic Brain Bank, one of the largest brain banks of neurodegenerative diseases.  In searching through medical records of over 1,700 patients, 66 individuals with clinically-documented contact sports participation were identified.  Of these 66 former athletes, 21 or 32% had pathologic changes in their brains consistent with CTE.  By comparison, none of 198 control individuals that did not have contact sports documentation in their medical records (including 66 women) had CTE pathology.  These results have been recently published in the December issue of the journal Acta Neuropathologica <<hyperlink: http://www.springer.com/medicine/pathology/journal/401.

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Electronic Alerts Improved Sepsis Care and Outcomes

Dr. Pablo Moreno Franco Assistant Professor of Medicine MAYO Clinic

Dr. Franco

MedicalResearch.com Interview with:
DrPablo Moreno Franco MD
Assistant Professor of Medicine
MAYO Clinic

Medical Research: What is the background for this study? What are the main findings?

Dr. Pablo Franco: Early alerts and prompt management of patient with severe sepsis and septic shock (SS/S) starting in the emergency department (ED) have been shown to improve mortality and other pertinent outcomes. With this in mind, we formed a multidisciplinary sepsis and shock response team (SSRT) in September 2013. Automated electronic sniffer alerted ED providers for possible sepsis and when S/SS was identified, they were encouraged to activate SSRT.

SSRT-Compliance-Study-Cohort Two blinded reviewers retrospectively abstracted data on clinical trajectory and outcomes of all patients with sepsis and SS/S admitted at a single academic medical center between September 2013 and September 2014. Given importance of timely recognition and interventions in S/SS, we specifically focused on 2 periods: 0-4 hours and 4-12 hours after hospital admission. Additionally, we compared the compliance to “standard of care” between the SSRT pre-implementation period and the study period.

There were 167 patients admitted with sepsis, among which there were 3 SSRT activations and sepsis mortality was 3.6%. There were 176 patients with SS, SSRT was called in 42 (23%) and SS mortality was 8.5%. CCS was involved in 66 patients and mortality was 6.9% if SSRT was activated, versus 21.6% if SSRT was not activated. There were 76 patients with septic shock, SSRT was called in 44 (57%) and septic shock mortality was 25%. Critical Care Service (CCS) was involved in 68 patients and mortality rates with and without SSRT were 30.9% and 15.4%, respectively. The all-or-none compliance with applicable goals of resuscitation improved from the baseline 0% to over 50% at the study period end. Overall observed/expected sepsis mortality index improved from 1.38 pre-SSRT to 0.68 post-SSRT implementation.

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Microbiome Signature Can Predict Risk of C. difficile Treatment Failure

Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic

Dr. Sahil Khanna

MedicalResearch.com Interview with:
Dr. Sahil Khanna MBBS
Assistant Professor of Medicine
Mayo Clinic

Medical Research: What is the background for this study? What are the main findings?

Response: C. difficile infection patients are at a high risk of complications such as treatment failure. Gut microbiota signatures associated with CDI have been described but it is unclear if differences in gut microbiota play a role in response to therapy. No studies have identified predictors of treatment failure and we aimed to identified gut microbiota signatures to predict response to treatment for primary C. difficile . While there were no clinical predictors of treatment response, there were increases in certain genera in patients with successful treatment response in the fecal samples at initial diagnosis compared to non-responders. A risk index built from this panel of microbes highly differentiated between patients based on response and ROC curve analysis showed that this risk index was a strong predictor of treatment response, with a high area under the curve of 0.83..

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Young Black Colon Cancer Patients Have Greater Risk of Recurrence

Harry H. Yoon, MD Mayo Clinic Rochester, MN 55905MedicalResearch.com Interview with:
Harry H. Yoon, MD
Mayo Clinic
Rochester, MN 55905

Medical Research: What is the background for this study? What are the main findings?

Dr. Yoon: In the U.S., the survival of patients with colon cancer is known to differ by race, with individuals of black race having worse outcomes than those of white race.

However, it has been difficult to tease apart why the differences in survival exist.

It is generally believed that social or other non-biologic factors (eg, decreased access to care, suboptimal treatment) contribute to the discrepancy.  It’s also known that differences in the general medical condition of patients could affect how long a patient lives.

However, it is unknown whether there are race-based differences in the biology of colon tumors themselves.  This biology can be reflected in the genetic composition of tumors, as well as by whether and how quickly the cancer returns after the patient has undergone surgery and chemotherapy.

In addition, it is unknown whether race-based differences in biology may be related to the age of the patient at the time of diagnosis.  Blacks with colorectal cancer typically have an earlier age of onset than whites do.

A major barrier to addressing these questions are that there are very few large populations of colon cancer patients where everyone had the same disease stage and received uniform treatment, and where patients were monitored for years afterward specifically to see whether the cancer returned.  It is much harder to measure whether cancer has returned (ie, cancer recurrence), as compared to simply knowing whether a patient is alive or dead.  This difference is important, because knowing about cancer recurrence sheds more light on cancer biology than only knowing about patient survival, since many factors unrelated to cancer biology (eg., heart disease) can affect whether a person is alive or dead.

The most reliable data on cancer recurrence (not just patient survival) generally comes from patients who have enrolled in a clinical trial.  In the Alliance N0147 trial, all patients had the same cancer stage (ie, stage III), underwent surgery and received standard of care chemotherapy (ie, “FOLFOX”) after surgery.  Patients had uniform, periodic monitoring after chemotherapy to see if the cancer returned.

In other words, examining racial outcomes in this cohort largely eliminates some of the key factors (eg, decreased access to care, suboptimal treatment) that are believed to contribute to racial discrepancies, and provides a unique opportunity to determine if differences in cancer biology between races may exist.

This study was done to see if colon cancers are genetically different based on race, and whether race-based differences exist in cancer recurrence rates.

The study found that tumors from whites, blacks, and Asians were different in terms of the frequency of mutations in two key cancer-related genes, BRAF and KRAS.  Tumors from whites were twice as likely to have mutated BRAF (14% in whites compared to 6% in Asians and 6% in blacks).  Tumors from blacks had the highest frequency of KRAS mutations (44% in blacks compared to 28% in Asians and 35% in whites).  Tumors from Asians were the mostly likely to have normal copies of both genes (67% in Asians compared to 50% in blacks and 51% in whites).

Next, the study found that the colon cancers among blacks had more than double the risk of cancer recurrence, compared to whites.  However, this discrepancy was only evident among young patients (ie, aged less than 50 years).  Almost 50% of younger black patients experienced colon cancer recurrence within 5 years, compared to ~30% of black patients over age 50, or compared to white or Asian patients regardless of age. The worse outcome among young blacks remained evident even after adjusting for many potential confounding factors, such as tumor grade, the number of malignant nodes, or the presence of BRAF or KRASmutations.  Because this question was examined in a clinical trial cohort of uniform stage and treatment, the role of multiple important potential confounders was diminished.

To our knowledge, this is the first report indicating that colon cancers from young black individuals have a higher chance of relapsing after surgery and chemotherapy, compared to those from white individuals.

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Sugar Sweetened Soda Linked To Chronic Kidney Disease

Wisit Cheungpasitporn, MD Nephrology Fellow Departments of Nephrology and Hypertension Mayo Clinic, Rochester, MNMedicalResearch.com Interview with:
Wisit Cheungpasitporn, MD
Nephrology Fellow
Departments of Nephrology and Hypertension
Program director: Suzanne Norby, MD
Co-authors: Charat Thongprayoon, MD, Oisin A O’Corragain, MD, Peter J Edmonds, BS, Wonngarm Kittanamongkolchai, MD, Stephen B Erickson, MD
Project mentor: Stephen B. Erickson, MD Departments of Nephrology and Hypertension
Mayo Clinic, Rochester, MN

Medical Research: What is the background for this study?

Dr. Cheungpasitporn: High-fructose corn syrup consumption in the form of sugar-sweetened soda has dramatically increased worldwide and associated with risk factors for chronic kidney disease (CKD) including diabetes mellitus (DM) and metabolic syndrome. Recently, artificial sweeteners have become commonly used in soda marketed as ‘diet’ alternatives. Recent studies have demonstrated that diet soda consumption may also be associated with weight gain, metabolic syndrome and cardiovascular disease. The risks of CKD in individuals with sugar-sweetened or diet soda consumption, however, were conflicting. We therefore conducted a meta-analysis to assess the associations between CKD and the consumption of sugar sweetened and diet soda. The findings of our study were recently published in Nephrology (Carlton). 2014; 19(12):791-7.

Medical Research: What are the main findings?

Dr. Cheungpasitporn: Five studies (2 prospective cohort studies, 2 cross-sectional studies and a case-control study) were included in our analysis of the association between consumption of sugar-sweetened soda (≥1-2 drinks of sugary soda/day) and CKD. We found an overall 1.58-fold increase CKD risk in individuals who regularly consumed sugar-sweetened soda with the pooled risk ratio (RR) of 1.58 (95% CI 1.00–2.49). Four studies (2 prospective cohort studies, a cross-sectional studies and a case-control study) were included to assess the association between CKD and diet soda consumption (≥1-2 drinks of diet soda/day). Despite a trend of chronic kidney disease risk in individuals with diet soda consumption with the pooled RR of 1.33 (95% CI 0.82–2.15), this association was not statistically significant.

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Cell Death Biomarker May Help Predict Melanoma PD-1 Responders

Dr. Roxana S. Dronca, M.D Assistant Professor of Oncology Assistant Program Director of Hematology-Oncology Fellowship Mayo Clinic College of Medicine Rochester, Minnesota MedicalResearch.com Interview with:
Dr. Roxana SDronca, M.D
Assistant Professor of Oncology
Assistant Program Director of Hematology-Oncology Fellowship
Mayo Clinic College of Medicine
Rochester, Minnesota 

Medical 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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Elevated Uric Acid Correlates With High Risk of Acute Kidney Injury

Wisit Cheungpasitporn, MD Nephrology Fellow Departments of Nephrology and Hypertension Mayo Clinic, Rochester, MMedicalResearch.com Interview with:
Wisit Cheungpasitporn, MD
Nephrology Fellow
Departments of Nephrology and Hypertension
Mayo Clinic, Rochester, MN
Program director: Suzanne Norby, MD
Co-authors: Charat Thongprayoon, MD, Andrew M. Harrison, BS and Stephen B. Erickson, MD
Project mentors: Stephen B. Erickson, MD Departments of Nephrology and Hypertension
Mayo Clinic, Rochester, MN

 

Medical Research: What is the background for this study?

Dr. Cheungpasitporn: Uric acid has been linked to acute kidney injury (AKI) through crystal-dependent pathways and crystal-independent mechanisms, including reduced renal blood flow and glomerular filtration rate. Serum uric acid measurement has recently been examined as a marker for early AKI detection, especially in the setting of postoperative AKI following cardiovascular surgery. The effect of admission serum uric acid levels on the risk of in-hospital AKI in the general hospitalized patients, however, was unclear. Thus, we conducted a study to assess the risk of AKI in all hospitalized patients across different serum uric acid levels. The findings of our study data were recently published in Clinical Kidney Journal.

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Excessive Diagnosis of Small Thyroid Cancers May Bring More Harm and Than Good

Juan P. Brito Campana, MBBS Division of Diabetes, Endocrinology, Metabolism, and Nutrition, Department of Medicine Mayo Clinic , Rochester, MinnesotaMedicalResearch.com Interview with:
Juan P. Brito Campana, MBBS
Division of Diabetes, Endocrinology, Metabolism, and Nutrition, Department of Medicine
Mayo Clinic , Rochester, Minnesota

Medical Research: What is the background for this study?

Dr. Brito: The occurrence of thyroid cancer is increasing faster than any other cancer in the United States. If this trend continues, thyroid cancer will become the third most frequent cancer in women in the next five years. Despite this increase, death related to thyroid cancer has not increased.  The reason is that the majority of the new cases of thyroid cancer are small papillary thyroid cancers. These cancers are the most benign variant of thyroid cancer and most patients diagnosed with this type of cancer never experience any symptoms or other negative effects. To better understand how these new cases of thyroid cancer are diagnosed we studied every case of thyroid cancer diagnosed in Olmsted, County, MN from 1935-2012.

Medical Research: What are the main findings?

Dr. Brito: We found that almost half the new cases of thyroid cancer were found among people who did not have any symptoms related to thyroid cancer. The most frequent reasons for identifying these patients presenting were review of thyroid tissue removed for benign conditions; incidental discovery during an imaging test ; and investigations of patients with symptoms or palpable nodules that were clearly not associated with thyroid cancer, but triggered the use of imaging tests of the neck.

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CT Scan IV Contrast Not Linked With AKI or Emergent Dialysis, Even In Patients With Impaired Kidney Function

MedicalResearJennifer S. McDonald Ph.D Assistant Professor Department of Radiology Mayo Clinicch.com Interview with:
Jennifer S. McDonald Ph.D
Assistant Professor
Department of Radiology
Mayo Clinic

Medical Research: What is the background for this study? What are the main findings?

Dr. McDonald: Our research group is interested in studying contrast-induced nephropathy (CIN), which is the development of acute kidney injury following administration of iodinated contrast material. Iodinated contrast material is frequently administered during CT examinations. Recent publications, including those by our group, suggest that the incidence of contrast-induced nephropathy has been overestimated by prior, uncontrolled studies. The purpose of our study was to better evaluate the incidence and severity of CIN in patients with diminished renal function (eGFR < 60 ml/min/1.73m2). In the current article, we performed a controlled retrospective study comparing patients who received a contrast-enhanced CT scan at our institution to patients who received an unenhanced CT scan. We used propensity score analysis that incorporated numerous variables to match contrast recipients and control patients with similar clinical characteristics. After performing this analysis, we found that the rate of AKI, emergent dialysis, and short-term mortality was similar between contrast recipients and control patients.

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Substance Abuse and Tobacco Linked To Longer Term Opioid Use

W. Michael Hooten, M.D Professor of Anesthesiology Mayo ClinicMedicalResearch.com Interview with:
W. Michael Hooten, M.D

Professor of Anesthesiology
Mayo Clinic

Medical Research: What is the background for this study?

Dr. Hooten: The purpose of the study was to investigate a gap in knowledge related to the progression of short-term opioid use to longer-term use.

Medical Research: What are the main findings?

Dr. Hooten: The main findings are that a history of substance abuse or tobacco use is associated with the progression from short-term to a longer-term pattern of opioid prescribing.

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Epigenetic Profiling Of Tumor Metastases May Improve Therapeutic Options

Eric Jonasch, MD Associate Professor Department of Genitourinary Medical Oncology University of Texas MD Anderson Cancer Center Houston, TXMedicalResearch.com Interview with:
Eric Jonasch, MD
Associate Professor Department of Genitourinary Medical Oncology
University of Texas MD Anderson Cancer Center
Houston, TX

and

Dr. Thai H. Ho, MD Ph.D. Department of Oncology Mayo Clinic Scottsdale ArizonaDr. Thai H. Ho, MD Ph.D.
Department of Oncology
Mayo Clinic Scottsdale Arizona

Medical Research: What is the background for this study? What are the main findings?

Response: The blueprints of a cell are encoded in DNA strands (its genome) which are highly compressed in order to fit into a tiny cell. The reading (called the epigenome) of these DNA ‘blueprints’ determines whether that cell will develop into a kidney cell or another type of cell. However, in cancer, errors occur either in the blueprints themselves or the cell makes mistakes in reading the blueprints. Cancers of the kidney affect more than 61,000 patients annually and over 13,000 patients die annually, making it one of the top 10 leading causes of cancer deaths. Studies have revealed that mutations occur in genes that regulate how our DNA ‘blueprints’ are compacted in greater than >50% of kidney cancers, making these genes as a group the most frequently mutated. In our study, we identified that these errors that initially arise in an early kidney cancer lead to propagation of these same errors in metastases, a phenomenon in which the cancer has spread to another organ and is a major cause of death. Furthermore, we generated a detailed map of these epigenomic changes in patient-derived tumors.

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Pacritinib Improved Disease Control In Myelofibrosis and Reduced Need For Blood Transfusions

Ruben A. Mesa, MD, FACP Consultant Hematologist Chair, Division of Hematology & Medical Oncology Deputy Director, Mayo Clinic Cancer Center Professor of Medicine Mayo Clinic Cancer Center NCI Designated Comprehensive Cancer Center Scottsdale, AZMedicalResearch.com Interview with:
Ruben A. Mesa, MD, FACP
Consultant Hematologist
Chair, Division of Hematology & Medical Oncology
Deputy Director, Mayo Clinic Cancer Center
Professor of Medicine Mayo Clinic Cancer Center
NCI Designated Comprehensive Cancer Center
Scottsdale, AZ

Medical Research: What is the background for this study? What are the main findings?

Dr. Mesa: Myelofibrosis is a rare and chronic blood cancer associated with significantly reduced quality of life and shortened survival. In patients with this disease, spleen enlargement (splenomegaly) is a very common and debilitating symptom – and as the disease progresses, the body slows production of important blood cells.

The results presented at ASCO were from the PERSIST-1 study, which is a Phase 3 registration-directed trial designed to compare pacritinib — an investigational oral multikinase inhibitor with specificity for JAK2 and FLT3 – to best available therapy (exclusive of a JAK inhibitor) in patients with myelofibrosis — regardless of their platelet counts.  Data from this study showed that compared to best available therapy, pacritinib resulted in a significantly higher proportion of patients with spleen volume reduction and control of disease-related symptoms, regardless of platelet levels at the time of enrollment.

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Mayo Researchers Develop Mouse Model To Study ALS and Frontotemporal Dementia

Dr. Leonard Petrucelli Ph.D Mayo Clinic Jacksonville, FL 32224MedicalResearch.com Interview with:
Dr. Leonard Petrucelli Ph.D
Mayo Clinic
Jacksonville, FL 32224

MedicalResearch: What is the background for this study?

Dr. Petrucelli: According to the ALS Association, more than 30,000 Americans live with amyotrophic lateral sclerosis (ALS), a condition that destroys motor neuron cells that control essential muscle activity such as speaking, walking, breathing and swallowing. After Alzheimer’s disease, frontotemporal dementia (FTD) is the most common form of early onset dementia. It is characterized by changes in personality, behavior, and language due to loss of neurons in the brain’s frontal lobe. Once considered rare, frontotemporal dementia is now thought to account for up to 10 to 15 percent of all dementia cases, according to the Alzheimer’s Association.

In 2011, Mayo investigator Rosa Rademakers, Ph.D., identified the most common genetic mutation known to cause ALS and FTD, namely a repeat expansion in the gene C9ORF72. The C9ORF72 repeat expansion leads to the generation of toxic RNA species that form abnormal foci, as well as inclusions of c9RAN proteins in affected cells in the central nervous system. Prior to this research study lead by Leonard Petrucelli, Chair of the Department of Neuroscience at the Mayo Clinic Florida, no animal model existed that fully recapitulated the known clinicopathological features of what is now collectively referred to as c9FTD/ALS. Without such an animal it has remained difficult to identify important mechanisms by which the repeat expansion leads to neurodegeneration and putative therapeutic targets that may mitigate disease in patients where currently there are no curative treatments.

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Depression, Illicit Drug Use Linked To Readmissions After LVAD Placement

Shannon M. Dunlay, M.D. M.S. Advanced Heart Failure and Cardiac Transplantation Assistant Professor of Medicine and Health Care Policy and Research Mayo Clinic RochesterMedicalResearch.com Interview with:
Shannon M. Dunlay, M.D. M.S.
Advanced Heart Failure and Cardiac Transplantation
Assistant Professor of Medicine and Health Care Policy and Research
Mayo Clinic Rochester

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

Dr. Dunlay: Left ventricular assist devices (LVAD) are increasingly utilized as destination therapy (DT) in patients that are not candidates for heart transplantation. Optimal patient selection is essential in improving outcomes, but many of the factors associated with favorable outcomes remain poorly understood. It is important for us to better understand the role that psychosocial factors may play in outcomes after DT LVAD. Unlike transplant, where the limited organ supply requires choosing candidates with optimal psychosocial characteristics, DT LVAD therapy is more readily available as it does not rely on organ donors. There are no clear guidelines on what constitutes an acceptable psychosocial risk prior to DT LVAD. As a result, many programs will offer DT LVAD to candidates despite psychosocial concerns if it is felt they will otherwise benefit. Data are needed to inform programs about whether such candidates are truly at elevated risk of adverse outcomes.

In our single-center study including 131 patients, we found that several psychosocial characteristics are predictive of readmission after DT LVAD. A history of illegal drug use and depression are associated with a higher risk of readmission, while tobacco use is associated with lower readmission risk. Psychosocial characteristics were not significant predictors of death after DT LVAD.

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Which Pancreatic Cysts Carry Malignant Potential?

 Michael B. Wallace, M.D., MPH, Mayo Clinic Jacksonville, FL 32224MedicalResearch.com Interview with:
Michael B. Wallace, M.D., MPH
Mayo Clinic
Jacksonville, FL 32224

 

Medical Research: What is the background for this study?

Dr. Wallace: Since its first consideration as an independent entity in 1996,1 intraductal papillary mucinous neoplasms (IPMN) of the pancreas have been diagnosed with increasing frequency. Detection and resection of IPMN offer a unique opportunity to cure and prevent adenocarcinoma of the pancreas, an otherwise highly lethal disease. The main clinical concern related to intraductal papillary mucinous neoplasms is its wide-ranging potential for malignancy from low-risk indolent lesions to those with high incidence of malignant degeneration. It is well-established that this malignant progression varies based on the morphological subtypes. The current methods of predicting malignant potential are limited to clinical, morphological, and cyst fluid cytology and biomarker data.

Medical Research: What are the main findings?

Dr. Wallace: Of 1126 patients, 84 were diagnosed with invasive carcinoma/high-grade dysplasia and were compared to the rest of the cohort. Multivariate logistic analysis showed no statistically significant association between cancer/high-grade dysplasia and gender, age or alcohol consumption. Smoking history and body mass index was significantly related with cancer/ high-grade dysplasia. Jaundice and steatorrhea were also associated with cancer/ high-grade dysplasia; however, weight loss was not. Univariate analysis showed no association between malignancy and the cyst number/location, although a strong association was shown for cyst size. The presence/size of nodules, and main duct involvement were strongly related with malignancy.
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Kidney Stone Risk Affected By Age and Sex

MedicalResearch.com Interview with:
Majuran Perinpam, BsC

Mayo Clinic
Rochester, Minn

MedicalResearch: What is the background for this study?

Response: The four key urinary factors: Calcium, magnesium, oxalate and uric acid are all implicated in kidney stone formation. Age and sex are known to influence kidney stone risk and type (1). However the effects of demographics on excretion of the four key urinary factors are not clear. Since diet alters urinary excretions of the four factors, adjusting for this is important. During metabolic evaluation of kidney stone patients, these urinary factors are often measured in 24-hour urine samples. However, often a single adult reference range is used and the effect of demographics is rarely taken into account during the interpretation of results.

MedicalResearch: What are the main findings?

Response: From a cohort of 709 healthy individuals we found a substantial influence of age and sex on the excretion of urinary calcium. Adjusted models showed that urinary calcium, magnesium, oxalate and uric acid were all less in females, possibly explaining why kidney stones are more dominant in males (1). Also a positive association of urinary uric acid excretion with Cystatin C eGFR, but not eGFR calculated from creatinine, suggests cystatin C to possibly being involved in inflammation and hyperuricemia. But further studies are needed to investigate this.

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High Fluid Intake Reduces Risk Of New Kidney Stones

Wisit Cheungpasitporn, MD, Nephrology Fellow Program director: Suzanne Norby, MD Project mentors: Stephen B. Erickson, MD and John C. Lieske, MD Departments of Nephrology and Hypertension Mayo Clinic, Rochester, MNMedicalResearch.com Interview with:
Wisit Cheungpasitporn, MD, Nephrology Fellow
Program director: Suzanne Norby, MD
Project mentors: Stephen B. Erickson, MD
and John C. Lieske, MD
Departments of Nephrology and Hypertension
Mayo Clinic, Rochester, MN

 

MedicalResearch: What is the background for this study?

Dr.Cheungpasitporn: Kidney stones are very common urologic problems. In addition, once someone has a kidney stone, the likelihood of having another episode increases to 50% within 5 years. Increased fluid intake has been suggested as a simple strategy for kidney stone prevention. However the data on conclusions regarding the benefit, adherence and safety of high fluid intake for the primary or secondary prevention of stones were limited. Thus, we conducted this meta-analysis to evaluate the treatment effect of high fluid intake on the incidence of kidney stones, and to assess the compliance and safety of high fluid intake to prevent kidney stones. Our data presented at the National Kidney Foundation’s 2015 Spring Clinical Meetings may help improve clinicians’ ability to manage kidney stones.

MedicalResearch: What are the main findings?

Dr.Cheungpasitporn: Our meta-analysis included 9 studies with 273,954 patients. According to the findings of our study, individuals with daily high fluid intake (to achieve a urine volume of at least 2.0‒2.5 L per day) had lower risk of new kidney stones by approximately 50%. High fluid intake provided the same benefit in men and women. In addition, high fluid intake reduced the risk of recurrent kidney stones by 40%. Overall, high fluid intake is safe with low adverse events.

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Tau Protein A Key Driver Of Cognitive Decline in Alzheimer’s disease

Melissa Murray, Ph.D Assistant Professor of Neuroscience Mayo ClinicMedicalResearch.com Interview with:
Melissa Murray, Ph.D

Assistant Professor of Neuroscience
Mayo Clinic

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Murray: Our study investigates two of the hallmark brain pathologies that underlie Alzheimer’s disease, abnormally accumulated tau and amyloid proteins.  While both are integral to diagnosing Alzheimer’s disease postmortem, their exclusive relationship with cognitive decline has been debated.  Using a large series from our brain bank we found that while an increase in abnormal accumulation of both proteins shares a close relationship with a decline in cognition, tau is the key driver of decline.  This was important for us to understand as the second part of our study investigated amyloid brain scanning. We found that amyloid brain scanning closely represents amyloid deposits and not tau in postmortem brain tissue.  One particular aspect we focused on is the cutoff for what would be a amyloid-positive brain scan that indicates Alzheimer’s disease.  Our study supports that currently available cutoffs correspond to a level of amyloid accumulation that occurs before Alzheimer’s disease has too far advanced.

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‘Leadership Saves Lives’ Program Aims To Reduce Heart Attack Mortality

Dr. Leslie CurryMedicalResearch.com Interview with:
Leslie Curry PhD, MPH
Senior Research Scientist in and Lecturer in Public Health (Health Policy)
Co-Director, Robert Wood Johnson Clinical Scholars Program
Yale School of Public Health

Medical Research: What is the background for this study? What are the main findings?

Dr. Curry: Quality of care for patients with acute myocardial infarction (AMI) has improved substantially in recent years due to important investments by clinicians and policymakers; however, survival rates across U.S. Hospitals still differ greatly. Evidence suggests links between hospital organizational culture and hospital performance in care of patients with AMI. Yet few studies have attempted to shift organizational culture in order to improve performance, fewer have focused on patient outcomes, and none have addressed mortality for patients with acute myocardial infarction.  We sought to address this gap through a novel longitudinal intervention study, Leadership Saves Lives (LSL). We have a large team of people with backgrounds in nursing, medicine, health care administration and research working in 10 very diverse hospitals across the country in 10 states. All hospitals are members of the Mayo Clinic Care Network and are fully committed to saving lives of patients with heart attacks. Teams of 10-12 clinicians and administrators are devoting substantial energy, expertise and good will to this project.

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Inhaled Nitric Oxide Still Used Off-Label In Preterm Infants

Marc Ellsworth, M.D Neonatology fellow at the Mayo Clinic Children’s CenterMedicalResearch.com Interview with:
Marc Ellsworth, M.D
Neonatology fellow at the
Mayo Clinic Children’s Center

MedicalResearch: What is the background for this study?

Dr. Ellsworth: Inhaled Nitric Oxide (iNO) is a drug that has FDA approval for use in neonates >34 weeks gestational age. It is used for severe respiratory failure secondary to pulmonary hypertension. However, it has been previously shown that neonatologists have been using this medication off-label and especially in the most premature neonates. Over the last 10 years there have been multiple large studies trying to determine a clinical use (ie long term benefit) for iNO in preterm neonates (patients where there is no FDA approval for iNO use currently). Despite evidence of short term benefit (improved clinical stability) use of this drug has not been shown to improve long-term outcomes (death and chronic lung disease) in premature neonates. As a result of these findings the National Institute of Child Health and Human Development (NICHD) released a consensus guideline in 2011 indicated that available evidence did not support the routine use of iNO in preterm neonates and discouraged this use of this expensive therapy in preterm neonates. Similarly, in 2014 the American Academy of Pediatrics issued a similar statement with similar recommendations.

In 2014 a group of NICUs (collectively called the Neonatal Research Network) associated with the NICHD published a report showing that the use of Inhaled Nitric Oxide in preterm infants (ie off-label) decreased following the report in 2011.

However, I did not feel that these NICUs were representative of the United States alone as the Neonatal Research Network consists of only a handful of NICUs (~15) and is directly associated with the NICHD. As a result I wanted to get a better idea of Inhaled Nitric Oxide use in a population based study to see if the trends were similar (ie use of iNO has been decreasing) on a much larger, more representative scale. (Editorial comment: My anecdotal experience was that rates of iNO use off-label have not decreased in preterm neonates since the 2011 report).

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Many Patients With Heart Failure Report Impairment of Daily Activities

dr-shannon-dunlayMedicalResearch.com Interview with:
Shannon M. Dunlay, M.D. M.S.
Advanced Heart Failure and Cardiac Transplantation
Assistant Professor of Medicine and Health Care Policy and Research
Mayo Clinic Rochester
MedicalResearch: What is the background for this study?

Dr. Dunlay: Loss of mobility and independence can complicate the care of patients with chronic conditions such as heart failure, and can degrade their quality of life.  However, we have a very poor understanding of the burden of disability in patients with heart failure and how it impacts outcomes.  What are the main findings?  In this study, patients with heart failure were asked whether they had difficulty performing activities of daily living (ADLs)—these include normal activities that most people do in daily life such as eating, bathing, dressing, and walking.  Most patients with heart failure reported having difficulty with at least one ADL at the beginning of the study, and over 1/3 had moderate or severe difficulty with activities of daily living.  Patients who were older, female and had other chronic conditions such as diabetes, dementia and obesity had more difficulty with activities of daily living.  Patients that reported more difficulty with ADLs (worse mobility) were more likely to die and be hospitalized over time.  Some patients had a decline in function over time, and this was also predictive of worse outcomes.

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CT Lung Cancer Screening Guidelines May Miss Some At Risk

MedicalResearch.com Interview with:
David Mithun, M.D.

Division of Pulmonary and Critical Care Medicine
Mayo Clinic, Rochester, Minnesota

Medical Research: What is the background for this study?

Dr. Mithun: Lung cancer screening should be pursued for those people at highest risk who are otherwise in good enough health to be able to undergo curative intent treatment if cancer is found. The current criteria for screening recommended by the US Preventive Services Task Force of age 55-80 years, 30 pack-years of smoking, and if quit, have done so within 15 years and are based on the National Lung Screening Study (NLST).

Medical Research: What are the main findings?

Dr. Mithun: Our data was retrospective over a 28 year time period and showed that an increasing number of people who actually got cancer would not have been candidates for screening based on the current criteria.  This suggests there may be some degree of mismatch between risk as defined by the current criteria to screen and those who developed cancer.  An increasing number of those who would not have been candidates for screening yet got lung cancer were among those who quit smoking 15 years or longer.
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Signaling Pathways That Lead Pancreatic Cancer Identified

Peter Storz, Ph.D. Associate Professor & Consultant Department of Cancer Biology Mayo Clinic Jacksonville, FL 32224MedicalResearch.com Interview with:
Peter Storz, Ph.D.
Associate Professor & Consultant Department of Cancer Biology
Mayo Clinic
Jacksonville, FL 32224

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Storz:   Our study focuses on cellular signaling mechanisms that lead to the initiation of pancreatic cancer. After acquisition of an oncogenic mutation of Kras, pancreatic acinar cells can undergo a transdifferentiation process to a phenotype that gives rise to pancreatic intraepithelial lesions (PanINs). These lesions then can further progress to pancreatic cancer.

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Varenicline – Chantix – Helped More Smokers Quit Gradually

Jon Ebbert, M.D. Associate director for research Mayo Clinic Nicotine Dependence CenterMedicalResearch.com Interview with:
Jon Ebbert, M.D.

Associate director for research
Mayo Clinic Nicotine Dependence Center

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Ebbert: Some cigarette smokers prefer to reduce the number cigarettes that they smoke before quitting smoking completely. Previous studies have evaluated the use of nicotine replacement therapy and one smaller study looked at varenicline to help smokers quit through smoking reduction. We wanted to conduct a larger study with varenicline using a longer duration of treatment.

We enrolled cigarette smokers who had no intention of quitting in the next month but who were willing to reduce the number of cigarettes they smoked while working toward a quit attempt in the next 3 months.

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New Mayo Model Better Predicts Breast Cancer Risk After Benign Biopsy

MedicalResearch.com Interview with:
Dr.  Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester.Dr.  Amy C. Degnim MD
Professor of Surgery
Mayo Clinic, Rochester.

Medical Research: What is the background for this study? What are the main findings?

Dr. Hartmann: Approximately 1 million women in the US every year have a breast biopsy that shows benign findings. We have found that the specific features of the breast tissue seen under the microscope can help to predict the risk of breast cancer in the future.  We developed a mathematical formula to calculate breast cancer risk based on the features seen in the biopsy tissue (named the BBD-BC model).  We found that using these microscopic features provides more accurate predictions of risk than the previous standard- the Breast Cancer Risk Assessment Tool (BCRAT).

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Low Levels of Testosterone May Raise Risk of Heart Disease

Abraham Morgentaler, MD Director and Founder Men’s Health BostonMedicalResearch.com Interview with:
Abraham Morgentaler, MD

Director and Founder
Men’s Health Boston

Medical Research: What is the background for this study? What are the main findings?

Response: There has been  tremendous media attention over the last 15 months to two retrospective studies that reported increased cardiovascular risks with testosterone. Those reports anchored a variety of stories critical of testosterone therapy for non-scientific reasons, such as alleged dangers of direct-to-consumer advertising.  In this review we investigated the two recent studies in depth, as well as the broader literature regarding testosterone and cardiovascular issues. One primary finding was that the studies alleging risk were remarkably weak and flawed- one reported low rates of MI and had no control group, and the other had such large data errors (nearly 10% of the all-male population turned out to be female!) that 29 medical societies have called for its retraction. In contrast, there is substantial literature suggesting that testosterone therapy, or naturally occurring higher levels of testosterone, is protective against atherosclerosis, and mortality.  Several small randomized controlled trials in men with known heart disease- angina and congestive heart failure- have even shown benefits for men that received testosterone compared with placebo.

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