Author Interviews, BMJ, Cost of Health Care, Diabetes, Mayo Clinic / 09.12.2015

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). (more…)
Author Interviews, Brain Injury, Mayo Clinic, Neurological Disorders / 02.12.2015

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. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Electronic Records, Infections, Mayo Clinic / 26.10.2015

MedicalResearch.com Interview with: Dr. Pablo 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. (more…)
Author Interviews, C. difficile, Gastrointestinal Disease, Mayo Clinic, Microbiome, Transplantation / 22.10.2015

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.. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research, JNCI, Mayo Clinic, Race/Ethnic Diversity / 05.10.2015

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. (more…)
Author Interviews, Kidney Disease, Mayo Clinic, Sugar / 30.09.2015

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. (more…)
Author Interviews, Biomarkers, Mayo Clinic, Melanoma / 17.09.2015

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 S. Dronca, 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. (more…)
Author Interviews, Gout, Heart Disease, Kidney Disease, Mayo Clinic / 14.09.2015

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. (more…)
Author Interviews, Mayo Clinic, Thyroid / 09.09.2015

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. (more…)
Author Interviews, Kidney Disease, Mayo Clinic, Radiology / 11.08.2015

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. (more…)
Author Interviews, Mayo Clinic, Opiods, Tobacco Research / 10.07.2015

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. (more…)
Author Interviews, Biomarkers, Cancer Research, Mayo Clinic, MD Anderson, Nature / 18.06.2015

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. (more…)
ASCO, Author Interviews, Journal Clinical Oncology, Mayo Clinic / 31.05.2015

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. (more…)
ALS, Author Interviews, Mayo Clinic, Science / 28.05.2015

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. (more…)
Author Interviews, Heart Disease, Mayo Clinic, Psychological Science / 01.05.2015

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. (more…)
Author Interviews, Cancer Research, Mayo Clinic / 15.04.2015

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. (more…)
Author Interviews, Gender Differences, Kidney Disease, Kidney Stones, Mayo Clinic / 30.03.2015

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. (more…)
Author Interviews, Kidney Stones, Mayo Clinic / 27.03.2015

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. (more…)
Alzheimer's - Dementia, Author Interviews, Mayo Clinic / 25.03.2015

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. (more…)
Author Interviews, Heart Disease, Mayo Clinic, Outcomes & Safety / 11.03.2015

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. (more…)
Author Interviews, Cost of Health Care, Critical Care - Intensive Care - ICUs, Mayo Clinic, Outcomes & Safety, Pediatrics, Pediatrics / 11.03.2015

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). (more…)
AHA Journals, Author Interviews, Heart Disease, Mayo Clinic, Women's Heart Health / 28.02.2015

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. (more…)
Author Interviews, JAMA, Lung Cancer, Mayo Clinic / 24.02.2015

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. (more…)
Author Interviews, Mayo Clinic, Nature, Pancreatic / 24.02.2015

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. (more…)
Author Interviews, JAMA, Mayo Clinic, Smoking / 17.02.2015

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. (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, Mayo Clinic / 30.01.2015

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). (more…)
Author Interviews, Heart Disease, Mayo Clinic, Testosterone / 27.01.2015

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. (more…)
Author Interviews, Breast Cancer, Mayo Clinic, NEJM / 03.01.2015

MedicalResearch.com Interview with: Dr. Lynn C. Hartmann MD Professor of Oncology, Mayo Clinic Associate Director for Education of the Mayo Clinic Cancer Center. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Women with atypical hyperplasia of the breast – which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern – have been considered a “high risk” group of women, but the extent of their risk has not been clearly defined. As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them. Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up. This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort). This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women. Medical Research: What should clinicians and patients take away from your report? Dr. Hartmann: There are about 100,000 US women each year diagnosed with atypical hyperplasia via breast biopsy. Although strictly speaking, atypical hyperplasia is a benign finding, it is associated with a sizable risk of a later breast cancer. Physicians from numerous disciplines care for women with high-risk benign breast issues, including gynecologists, family physicians, internists, surgeons and oncologists. These practitioners, and the patients themselves, need information about the absolute risk of breast cancer occurring over time after a diagnosis of atypical hyperplasia. This information is provided in the NEJM report. Also, current guidelines should be updated to include this high-risk population and specifics about their absolute risk, and that the risk level qualifies these patients for screening MRI. Moreover, from the standpoint of risk reduction, four previously conducted breast cancer prevention trials included women with atypical hyperplasia. These trials used hormonal therapies (anti-estrogens) and showed that, in women with atypical hyperplasia, the use of such medications could lower the risk of a later breast cancer by 50% or more. Yet, other research has shown that women are quite reluctant to take such medications, primarily because of fear of side effects. In the NEJM report, we detail specific numbers of side effects that actually occurred in women who used these anti-estrogens (as opposed to the number of side effects seen in women taking placebo) and show that most of the side effects occurred quite uncommonly. Thus, we hope that the combination of information provided in this report on (i) actual risks of breast cancer and (ii) actual risks of side effects will help patients and practitioners make informed decisions on the best treatment approaches for women with atypical hyperplasia. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Hartmann: First, women with atypical hyperplasia should be included in future prospective trials of novel imaging strategies (they were not included in trials of MRI, which had been limited to women with hereditary risk). Second, efforts should continue to predict which women with atypical hyperplasia are at highest risk, especially in the first 5-10 years after their biopsy, so they can be cared for optimally. Our research team, and others, continue to study the underlying molecular pathways that drive the progression from atypical hyperplasia to cancer; identifying such processes would not only aid in risk prediction but also identify driving pathways that could be blocked pharmaceutically. Citation: upcoming NEJM publication discussing: Women with Atypical Hyperplasia are at Higher Risk of Breast Cancer MedicalResearch.com Interview with: Dr. Lynn C. Hartmann MD Professor of Oncology, Mayo Clinic Associate Director for Education of the Mayo Clinic Cancer Center. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Women with atypical hyperplasia of the breast – which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern  – have been considered a “high risk” group of women, but the extent of their risk has not been clearly defined.  As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them.  Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up.  This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort).  This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women. (more…)
Author Interviews, Breast Cancer, JNCI, Mayo Clinic / 14.12.2014

Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo ClinicMedicalResearch.com Interview with: Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo Clinic Medical Research: What is the background for this study? What are the main findings? Dr. Goetz: There has been conflicting data with regard to the importance of metabolism as measured by CYP2D6 genetic variation.   Two large “negative” studies were reported simultaneously in 2012 and these were referenced by guidelines that CYP2D6 should not be used to select hormonal therapy.   Our findings demonstrated that these studies were flawed in part based on analytical validity issues.  In short, the use of tumor tissue to derive CYP2D6 germline genotype leads to genotyping error in up to 45% of samples. (more…)
Author Interviews, Heart Disease, Mayo Clinic, Outcomes & Safety / 14.12.2014

Atsushi Sorita, MD, MPH Mayo Clinic, Division of Preventive Medicine Rochester, MN 55905.MedicalResearch.com Interview with: Atsushi Sorita, MD, MPH Mayo Clinic, Division of Preventive Medicine Rochester, MN 55905.   Medical Research: What is the background for this study? What are the main findings? Dr. Sorita: Prior studies have suggested that patients with heart attack who are admitted during off-hours (weekends, nights and holidays) have higher risk of death when compared with patients admitted during regular hours. In our study, we found that patients undergoing percutaneous coronary interventions for heart attack who were admitted during off-hours did not have higher mortality or readmission rates as compared with ones admitted during regular hours at a highly-integrated academic center in the United States. (more…)