Genetically Elevated BMI Raises Risks of Hypertension and Diabetes

MedicalResearch.com Interview with:

Brendan Keating D.Phil Assistant Professor, Dept of Pediatrics and Surgery, University of Pennsylvania Lead Clinical Data Analyst, Center for Applied Genomics Children's Hospital of Philadelphia,Brendan Keating D.Phil
Assistant Professor, Dept of Pediatrics and Surgery, University of Pennsylvania
Lead Clinical Data Analyst, Center for Applied Genomics
Children’s Hospital of Philadelphia

Michael V. Holmes, MD, PhD, MSc, BSc, MRCP Transplant Surgery Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAMichael V. Holmes, MD, PhD, MSc, BSc, MRCP
Transplant Surgery
Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA


MedicalResearch.com: What are the main findings of the study?

Answer: We found that individuals with a genetically-elevated BMI had higher
blood pressure, inflammatory markers, metabolic markers and a higher
risk of type 2 diabetes, although there was little correlation with
coronary heart disease in this study population of over 34,500
European-descent individuals of whom over 6,000 had coronary heart
disease.
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Hospital Mortality: Association With Nurses’ Work Load and Education

Professor Linda H Aiken PhD, FAAN, FRCN, RN Claire M. Fagin Leadership Professor in Nursing, Professor of Sociology Director of the Center for Health Outcomes and Policy Research Center for Health Outcomes and Policy Research University of Pennsylvania School of NursingMedicalResearch.com Interview with:
Professor Linda H Aiken PhD, FAAN, FRCN, RN
Claire M. Fagin Leadership Professor in Nursing, Professor of Sociology
Director of the Center for Health Outcomes and Policy Research
Center for Health Outcomes and Policy Research
University of Pennsylvania School of Nursing

MedicalResearch.com: Austerity measures and health-system redesign to minimise hospital expenditures risk adversely affecting patient outcomes. Against that backdrop, can you start by letting us know the background of the study?

 Prof. Aiken: European Surgical Outcomes Study in 28 countries showed higher than necessary deaths after surgery.

A comparable study in the US showed that despite the nation spending hundreds of millions of dollars on improving patient safety, there were no improvements in adverse outcomes after surgery in US hospitals between 2000 and 2009.  Clearly it is time to consider new solutions to improving hospital care for surgical patients, who make up a large proportion of all hospital admissions.  Our study was designed to determine whether there are risks for patients of reducing hospital nurse staffing, and what, if any, are the benefits to patients of moving to a more educated nurse workforce. Continue reading

After Outgrowing One Food Allergy, Some Patients Develop Second Allergic Reaction to Same Food

Jonathan M. Spergel, M.D., Ph.D. The Children's Hospital of Philadelphia Chief, Allergy Section Co-director, Center for Pediatric Eosinophilic Disorders Associate Professor of Pediatrics Perelman School of Medicine at the University of PennsylvaniaMedicalResearch.com Interview with:
Jonathan M. Spergel, M.D., Ph.D.
The Children’s Hospital of Philadelphia
Chief, Allergy Section
Associate Professor of Pediatrics
Perelman School of Medicine at the University of Pennsylvania

MedicalResearch.com: What are the main findings of the study?

Dr. Spergel: We were examining patients with Eosinophilic Esophagitis, an unique food allergy of the esophagus.   We found a subset of patients, who in the past had IgE mediated reaction to the food (hives, anaphylaxis) and had outgrown it.  Two-three years after outgrowing the food, then the patients developed Eosinophilic Esophagitis to the same food.
MedicalResearch.com: Were any of the findings unexpected?

Dr. Spergel: Yes, this finding indicated two important things:

  1. You can get two different reactions to the same food.
  2. The mechanism of the reactions for IgE-mediated reactions and Eosinophilic Esophagitis are different.

MedicalResearch.com:  What should clinicians and patients take away from your report?

Dr. Spergel: For patients and clinician, if someone has outgrown the food allergy.  But, then gets new symptoms, it could be the food that they had outgrown.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Spergel:  This research raises two important questions.

  1. How often does this happen?  How many patients that outgrown their food allergy will develop a different reaction to the same food?
  2. Is there a better to treat patients with Eosinophilc Esophagitis or food allergy due to this difference in mechanism?

Citation:

Maggadottir et al, “Development of Eosinophilic Esophagitis to Food after Development of IgE Tolerance to the Same Food, abstract 990, presented March 2, 2014 at the AAAAI Annual Meeting.

Gene Modifies Response to Topiramate in Heavy Drinkers

Henry R. Kranzler, MD Professor, Department of Psychiatry Director of the Center for Studies of Addiction. University of Pennsylvania Perelman School of Medicine, PhiladelphiaMedicalResearch.com Interview with:
Henry R. Kranzler, MD
Professor, Department of Psychiatry
Director of the Center for Studies of Addiction.
University of Pennsylvania Perelman School of Medicine, Philadelphia

MedicalResearch.com: What are the main findings of the study?

Dr. Kranzler: The study had two main findings:

  • First, topiramate, at a maximal dosage of 200 mg/day, which is lower than the 300 mg/day used in prior treatment trials, substantially reduced the frequency of heavy drinking and increased the frequency of abstinent days more than placebo. The lower dosage was well tolerated.
  • Second, a variant in a gene that encodes a receptor subunit that binds topiramate moderated the response to topiramate. That is, C-allele homozygotes in the single nucleotide polymorphism rs2832407 in GRIK1, the gene encoding the GluK1 subunit of the kainate receptor, were the subgroup that accounted for the effects of topiramate on heavy drinking. This has important implications for the personalized treatment of alcohol use disorder, in that 40% of people of European ancestry have this genotype and, if confirmed, these findings would make it possible to screen people genetically to select an effective treatment.

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Teledermatololgy As Triage Tool For Dermatology Hospital Consultation

Dr. Misha A. Rosenbach Assistant Professor of Dermatology Hospital of the University of Pennsylvania Section Editor, JAMA Dermatology Patient PageMedicalResearch.com Interview with:
Dr. Misha A. Rosenbach
Assistant Professor of Dermatology Hospital of the University of Pennsylvania Section Editor,
JAMA Dermatology Patient Page

MedicalResearch.com: What are the main findings of the study? Dr. Rosenbach: There is strong agreement between teledermatologists and in-person dermatologists when evaluating inpatients at a tertiary care academic hospital.  The primary aim of this study was to assess telederm as a triage tool.  Many dermatologists are not full-time hospitalists, but work in private practice or clinics which may be remote from affiliated hospitals.  The goal was to evaluate whether teledermatology could help those providers assess the acuity of inpatient consults.  There was strong concordance. Continue reading

Costs of Health Care: Teaching Medical Residents How to Provide Cost-Conscious Care

Mitesh Patel, MD, MBA RWJF Clinical Scholar, University of Pennsylvania Mitesh Patel, MD, MBA is a Robert Wood Johnson Clinical Scholar the University of Pennsylvania and primary care physician at the Philadelphia VA Medical CenterMedicalResearch.com Interview with:
Mitesh Patel, MD, MBA
RWJF Clinical Scholar, University of Pennsylvania
Mitesh Patel, MD, MBA is a Robert Wood Johnson Clinical Scholar the University of Pennsylvania and primary care physician at the Philadelphia VA Medical Center

MedicalResearch.com: What are the main findings of the study?

Dr. Patel: We evaluated survey responses from nearly 300 internal medicine residency programs directors to assess whether residency programs were teaching residents the fundamental concepts of practicing high-value, cost-conscious care.  We found that 85% of program directors feel that graduate medical education has a responsibility to help curtail the rising costs of health care.  Despite this, about 6 out of every 7 internal medicine residency programs have not yet adopted a formal curriculum teaching new physicians these important concepts.
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Medical School Minority Faculty Not Markedly Increased by Development Programs

James Guevara, MD, MPH Associate Professor of Pediatrics & Epidemiology Senior Diversity Search Advisor, Perelman School of Medicine University of Pennsylvania,Director of Interdisciplinary Initiatives PolicyLab: Center to Bridge Research, Practice, & Policy The Children's Hospital of Philadelphia,Philadelphia, PA  19104MedicalResearch.com Interview with:
James Guevara, MD, MPH
Associate Professor of Pediatrics & Epidemiology
Senior Diversity Search Advisor, Perelman School of Medicine
University of Pennsylvania,Director of Interdisciplinary Initiatives
PolicyLab: Center to Bridge Research, Practice, & Policy
The Children’s Hospital of Philadelphia,Philadelphia, PA  19104

MedicalResearch.com: What did the study attempt to address?

Dr. Guevara: Medical schools have sought to build more diverse faculty in their institutions through faculty development programs targeted to underrepresented minority faculty members. This study was conduct by THE CHILDREN’S HOSPITAL OF PHILADELPHIA’S POLICYLAB  and The University of Pennsylvania and sought to determine if there was an association between minority faculty development programs and the representation, recruitment, and promotion of underrepresented minority faculty.
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Electronic Medical Records: Tool to Identify Readmission Risk

Craig A Umscheid, MD, MSCE, FACP Assistant Professor of Medicine and Epidemiology Director, Center for Evidence-based Practice Medical Director, Clinical Decision Support Chair, Department of Medicine Quality Committee Senior Associate Director, ECRI-Penn AHRQ Evidence-based Practice Center University of Pennsylvania Philadelphia, PA 19104MedicalResearch.com Interview with:
Craig A Umscheid, MD, MSCE, FACP
Assistant Professor of Medicine and Epidemiology
Director, Center for Evidence-based Practice
Medical Director, Clinical Decision Support
Chair, Department of Medicine Quality Committee
Senior Associate Director, ECRI-Penn AHRQ Evidence-based Practice Center
University of Pennsylvania Philadelphia, PA 19104

MedicalResearch.com: What are the main findings of the study?

Dr. Umscheid: We developed and successfully deployed into the electronic health record of the University of Pennsylvania Health System an automated prediction tool which identifies newly admitted patients who are at risk for readmission within 30 days of discharge.  Using local data, we found that having been admitted to the hospital two or more times in the 12 months prior to admission was the best way to predict which patients are at risk for being readmitted in the 30 days after discharge. Using this finding, our automated tool identifies patients who are “high risk” for readmission and creates a “flag” in their electronic health record (EHR). The flag appears next to the patient’s name in a column titled “readmission risk.” The flag can be double-clicked to display detailed information relevant to discharge planning.  In a one year prospective validation of the tool, we found that patients who triggered the readmission alert were subsequently readmitted 31 percent of the time. When an alert was not triggered, patients were readmitted only 11 percent of the time.  There was no evidence for an effect of the intervention on 30-day all-cause readmission rates in the 12-month period after implementation.
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Yoga and Effect on Menopause Symptoms

MedicalResearch.com Interview with:
Katherine Newton, PhD
Senior Investigator at Group Health Research Institute in Seattle

MedicalResearch.com: What are the main findings of the study?

Answer: We found that when women took a 12-week yoga class and practiced yoga at home, they had significantly less insomnia than did women who did not. This was the only statistically significant finding in this MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) Network randomized controlled trial. We also found that being in the yoga class did not decrease the number of hot flashes or night sweats. Yoga  was linked to better sleep quality and less depression—but  these effects were not statistically significant. In separate papers, published slightly earlier, our MsFLASH group reported that a non-yoga exercise program seemed linked to slightly improved sleep and less insomnia and depression—but these effects were not statistically significant. And an omega-3 (fish oil) supplement was not linked to any improvement in hot flashes, night sweats, sleep, or mood.

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Lung Cancer: Calcineurin Pathway Helps Enable Metastases

Sandra Ryeom, PhD, Assistant professor of Cancer Biology, Perelman School of Medicine, University of Pennsylvania
MedicalResearch.com Interview with:
Sandra Ryeom, PhD,
Assistant professor of Cancer Biology,
Perelman School of Medicine, University of Pennsylvania


MedicalResearch.com: What are the main findings of the study?

Answer: We identified an important pathway (calcineurin-NFAT-Angiopoeitin2) in the vasculature of early metastatic lung lesions that is critical for promoting lung metastases.

MedicalResearch.com: Were any of the findings unexpected?

Answer: Since there is limited understanding of regulation of tumor angiogenesis at metastatic sites, identification of the calcineurin pathway and a newly identified target of calcineurin-NFAT signaling  was all unexpected.
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Parkinson’s Disease: ApoA1 may be a Protection Marker

Alice Chen-Plotkin, MD Assistant Professor Department of Neurology University of Pennsylvania School of Medicine MedicalResearch.com: Interview with Alice Chen-Plotkin, MD
Assistant Professor
Department of Neurology
University of Pennsylvania School of Medicine

 


MedicalResearch.com: What are the main findings of the study?

Answer: Parkinson’s disease (PD) is an incurable neurodegenerative disease.  Many neurons die, but the neurons that make dopamine (dopaminergic neurons) are particularly vulnerable.  We think that the disease actually starts well before the time when people show clinical symptoms.  We were therefore interested in finding proteins from the blood that correlated with better or worse dopaminergic neuron integrity.  Since it’s hard to access the dopaminergic neurons directly, we looked at a tracer that labels the ends of the dopaminergic neurons in people who do not have Parkinson’s disease but are at high risk for developing it, and we also looked at the age at onset of PD in people who are already symptomatic.  Screening just under 100 different proteins from the blood, we found that higher plasma levels of apolipoprotein A1 (ApoA1) were correlated with better tracer uptake in the people who did not yet have PD, and with older ages at onset in the people who already had PD.  These data suggest that plasma ApoA1 may be a marker for PD risk, with higher levels being relatively protective.

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Chronic Kidney Disease: Novel variants of APOL1 gene may play a role in susceptibility

MedicalResearch.com Interview with:

Dr. Wen-Ya Ko, Ph.D. Postdoctoral Fellow, First author of the paper  Department of Genetics School of Medicine University of Pennsylvania 426 Clinical Research Building 415 Curie Boulevard Philadelphia, PA 19104-6145Dr. Wen-Ya Ko, Ph.D.
Postdoctoral Fellow, First author of the paper

Department of Genetics
School of Medicine
University of Pennsylvania
426 Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104-6145

Dr. Sarah Tishkoff, Ph.D., Senior author of the paper  David and Lyn Silfen University Professor Departments of Genetics and Biology School of Medicine School of Arts and Sciences University of PennsylvaniaDr. Sarah Tishkoff, Ph.D., Senior author of the paper

David and Lyn Silfen University Professor
Departments of Genetics and Biology
School of Medicine
School of Arts and Sciences
University of Pennsylvania

MedicalResearch.com: What are the main findings of the study?



Answer: In humans the APOL1 gene codes for Apolipoprotein L1, a major component of the trypanolytic factor in serum.  The APOL1 gene harbors two risk alleles (G1 and G2) associated with chronic kidney disease (CKD) among individuals of recent African ancestry. We studied APOL1 across genetically and geographically diverse ethnic groups in Africa. We have discovered a number of novel variants at the APOL1 functional domains that are required to lyse trypanosome parasites inside human blood vessels.

We further identified signatures of natural selection influencing the pattern of variation on chromosomes carrying some of these variants. In particular, we have identified a haplotype (a cluster of genetic variants linked along a short region of a chromosome), termed G3, that has evolved adaptively in the Fulani population who have been practicing cattle herding which has been historically documented as early as in the medieval ages (but which could have begun thousands of years earlier).  Many of the novel variants discovered in this study are candidates to play a role conferring protection against trypanosomiasis and/or to play a role in susceptibility of CKD in humans.
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Intestinal Virus Populations Huge and Rapidly Changing

MedicalResearch.com Interview with Frederic D. Bushman, Ph.D.  Professor, Department of Microbiology Department of Microbiology Perelman School of Medicine University of Pennsylvania 426A Johnson Pavilion 3610 Hamilton Walk Philadelphia, PA 19104MedicalResearch.com Interview with Frederic D. Bushman, Ph.D.

Professor, Department of Microbiology
Department of Microbiology
Perelman School of Medicine
University of Pennsylvania
426A Johnson Pavilion 3610 Hamilton Walk
Philadelphia, PA 19104

 

MedicalResearch.com: What are the main findings of the study?

Dr. Bushman: Viral populations in the human gut are huge, and some of the viruses change rapidly over time.
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Alcohol dependence and PTSD: Simultaneous Treatment Improves Outcomes

MedicalResearch.com Interview with Edna B. Foa, PhD
Department of Psychiatry, University of Pennsylvania, Philadelphia

MedicalResearch.com: What are the main findings of the study?

Dr. Foa: Naltrexone was effective in decreasing the percentage of days drinking in people with alcohol dependence and posttraumatic stress disorder during active treatment.  Six months after treatment discontinuation, participants who received prolonged exposure therapy for PTSD drank less than those who did not receive prolonged exposure.  Participants who received a combined treatment of prolonged exposure and naltrexone had the lowest drinking level after six-month treatment discontinuation. The main message of the study is that simultaneous treatment of alcohol dependence and PTSD yield superior outcome than each treatment alone. Importantly, the findings indicated that prolonged exposure therapy was not associated with increased drinking or alcohol craving, a concern that has been voiced by some investigators. In fact, reduction in PTSD severity and drinking was evident for all four treatment groups. This finding contradicts that common view that trauma-focuses therapy is contraindicated for individuals with alcohol dependence and PTSD, because it may exacerbate PTSD symptoms and thereby lead to increased alcohol use. Continue reading

TAp73, a molecular relative of p53 Tumor Suppressor Protein, gives tumor cells a growth advantage

MedicalResearch.com Interview with: Xiaolu Yang, Ph.D.MedicalResearch.com Interview with:
Xiaolu Yang, Ph.D.
Professor of Cancer Biology at the Perelman School of Medicine
University of Pennsylvania
and the Abramson Family Cancer Research Institute,

MedicalResearch.com: What are the main findings of the study?

Dr. Yang: TAp73 is a structural homologue of the preeminent tumor suppressor p53, but its role in tumorigenesis has been unclear. In this study, we show that TAp73 supports the proliferation of tumor cells. Mechanistically, TAp73 activates the expression of glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme in the pentose phosphate pathway. This function of TAp73 is required for maintaining a robust biosynthesis and anti-oxidant defense in tumor cells. These finding connects TAp73 to oncogenic growth and suggest that G6PD may be a valuable target for tumor therapy.

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Sleep Duration as a Predictor of Moderate/High (vs Low) Suicide Risk in Insomnia

MedicalResearch.com eInterview with:

Linden Oliver, MA, Clinical Research Coordinator
University of Pennsylvania Behavioral Sleep Medicine Research Program Philadelphia, Pa

MedicalResearch.com: What are the main findings of the study?

Answer: We found that less sleep is associated with greater suicide risk in those with insomnia. Specifically, we looked at suicide risk in people with insomnia, and also asked how much sleep they got in the past month. In those with some suicide risk, the likelihood of being high risk (versus low risk) decreased by 72% for every hour of sleep that person reported getting at night.

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Relationship of Early-Onset Baldness to Prostate Cancer in African-American Men

MEDICALRESEARCH.COM INTERVIEW WITH

Charnita Zeigler-Johnson, Ph.D., M.P.H.
Research Assistant Professor CCEB
University of Pennsylvania

MEDICALRESEARCH.COM: What are the main findings of the study?

Dr. Zeigler-Johnson: The main findings of the study are:

  • Younger African-American men diagnosed with advanced prostate cancer at an early age (under the age of 60) are more likely to have had a personal history of early-onset baldness (baldness by age 30.)
  • For older patients, this is not necessarily the case, and future studies will need to focus on which factors place men in this age group at risk for prostate cancer.
    Continue reading

Alzheimer’s plaques in PET brain scans identify future cognitive decline

Alzheimer’s plaques in PET brain scans identify future cognitive decline

DURHAM, N.C. – Among patients with mild or no cognitive impairment, brain scans using a new radioactive dye can detect early evidence of Alzheimer’s disease that may predict future decline, according to a multi-center study led by researchers at Duke University Medical Center.

The finding is published online July 11, 2012, in the journal Neurology, the medical journal of the American Academy of Neurology. It expands on smaller studies demonstrating that early detection of tell-tale plaques could be a predictive tool to help guide care and treatment decisions for patients with Alzheimer’s disease.

“Even at a short follow-up of 18 months we can see how the presence of amyloid plaques affects cognitive function,” said P. Murali Doraiswamy, M.D., professor of psychiatry at Duke who co-led the study with R. Edward Coleman, M.D., professor of radiology at Duke . “Most people who come to the doctor with mild impairment really want to know the short-term prognosis and potential long-term effect.”

Doraiswamy said such knowledge also has some pitfalls. There is no cure for Alzheimer’s disease, which afflicts 5.4 million people in the United States and is the sixth-leading cause of death among U.S. adults. But he said numerous drugs are being investigated, and identifying earlier disease would improve research into their potential benefits and speed new discoveries, while also enhancing care and treatment of current patients.

In the Neurology study, 151 people who had enrolled in a multi-center test of a new radioactive dye called florbetapir (Amyvid) were recruited to participate in a 36-month analysis. Of those participants, 69 had normal cognitive function at the start of the study, 51 had been diagnosed with mild impairment, and 31 had Alzheimer’s dementia.

All completed cognitive tests and underwent a brain scan using Positron Emission Tomography, or PET imaging. The technology uses radioactive tracers designed to highlight specific tissue to create a three-dimensional picture of an organ or a biological function.

The dye used in the study, florbetapir, was recently approved by the U.S. Food and Drug Administration for PET imaging of the brain to estimate beta-amyloid plaque density in patients who are being evaluated for cognitive impairment. It binds to the amyloid plaques that characterize Alzheimer’s disease, providing a window into the brain to see if the plaques have formed, and how extensively.

Patients in the study were reassessed with additional cognitive exams at 18 months and 36 months. At the 18-month point, patients with mild cognitive impairment who had PET evidence of plaque at the trial’s start worsened to a great degree on cognitive tests than patients who had no evidence of plaque at the trial’s start. Twenty-nine percent of the plaque-positive patients in this group developed Alzheimer’s dementia, compared to 10 percent who started with no plaque.

Cognitively normal patients with a plaque-positive PET scan at the start of the study also showed more mental decline at 18 months compared to those who were negative for plaque.

The study additionally found that people with negative scans reversed from minimally impaired to normal more often than people with positive PET scan, suggesting test anxiety or concentration problems could have affected their initial performance.

“For the most part we have been blind about who would progress and who wouldn’t, so this approach is a step toward having a biomarker that predicts risk of decline in people who are experiencing cognitive impairment,” Doraiswamy said.

He said the study’s results provide initial data that needs to be verified by additional research. Final, 36-month data from the study has been completed and will be presented at the Alzheimer’s Association International Conference this week in Vancouver, Canada. Doraiswamy also cautioned that florbetapir is currently not approved to predict the development of dementia or other neurologic conditions and stressed that it should not be used as a screening tool in otherwise normal or minimally impaired people. Likewise, a positive scan is not necessarily diagnostic for Alzheimer’s by itself.

###

In addition to Doraiswamy and Coleman (who died in June), study authors included; Reisa A. Sperling and Keith A. Johnson of Massachusetts General Hospital, Boston Medical School; Eric M. Reiman of Banner Alzheimer’s Institute; Mat D. Davis of the University of Pennsylvania; Michael Grundman of Global R&D Partners and the University of California, San Diego; Marwan N. Sabbagh of Banner-Sun Health Research Institute; Carl H. Sadowsky of Nova SE University; Adam S. Fleisher of Banner Alzheimer’s Institute and UCSD; and Alan Carpenter, Christopher M. Clark (deceased), Abhinay D. Joshi, Mark A. Mintun, Daniel M. Skovronsky, and Michael J. Pontecorvo of Avid Radiopharmaceuticals.

Alzheimer's plaques in PET brain scans identify future cognitive decline

Caption: PET images using florbetapir dye to highlight beta-amyloid plaques show (A), a cognitively normal subject; (B) an amyloid-positive patient with Alzheimer’s disease; (C) a patient with mild cognitive impairment; and (D) a patient with mild cognitive impairment who progressed to dementia during the study.
Credit: Slide courtesy of the journal Neurology.

2 genetic variations predict second cancers after radiation for children with Hodgkin lymphoma

A genome-wide association study published in the August issue of Nature Medicine has found two tiny genetic variations that can predict which patients with Hodgkin’s lymphoma are most likely to develop radiation-induced second cancers years after treatment. Knowing in advance who is at risk could help physicians tailor treatment to reduce the risks for patients who are most susceptible to long-term damage.

Hodgkin’s lymphoma is one of the most treatable cancers, with more than 90 percent of patients surviving after a combination of radiation and chemotherapy. But nearly 20 percent of patients treated as children develop a second cancer within 30 years. The younger the patients are when treated and the higher the radiation dose, the greater the risk. This late side effect of treatment is the second leading cause of death for long-term Hodgkin’s survivors.

“This finding means we can better identify children who are most susceptible to radiation-induced cancers before treatment begins and modify their care to prevent this serious long-term complication,” said Kenan Onel, MD, PhD, associate professor of pediatrics and senior author of the study. “Luckily our options for Hodgkin’s are broad enough that we can find ways to control the initial disease without relying on radiation therapy.”

“This is also a triumph for genome-wide association studies,” he added. “Many previous GWAS studies found multiple genetic differences, with each of them playing only a modest role, with minimal impact on clinical management. In this study, which focused on the interaction between genes and a very specific environmental factor—cancer long after radiation therapy—a small number of genetic differences produced a very big impact.”

Onel and colleagues analyzed the genomes of 178 Hodgkin’s patients who had been treated between the ages of 8 and 20 with chemotherapy and radiation therapy. Within 30 years after treatment, 96 of them had developed second cancers and 82 had not.

When they scanned each patient’s genome, focusing on 665,313 tiny genetic variations known as single nucleotide polymorphisms, they found three variations that appeared far more often in patients with second cancers. When they repeated the study using a different set of patients—62 cases with second cancers and 71 without—two of the three markers were significant.

Those two markers were both from a small region known as 21q on chromosome 6. Both are positioned near a gene known as PRDM1.

The genetic variations closely associated with increased cancer risk, and with each other, appeared to decrease activation of the PRMD1 gene. They had no detectable effect any other genes. Cells with the protective version of both markers expressed PRDM1 after being exposed to radiation. Cells with the variants linked to subsequent cancers did not produce any PRDM1.

Previous studies have found that PRDM1 is involved in a variety of fundamental cellular processes, including proliferation, differentiation and apoptosis—which can all go awry in cancer. The gene’s activity is lost in many cancer types.

In Onel’s small samples, only three percent of patients with both of the protective variants developed second cancers within 30 years; nearly 33 percent of those with both of the high-risk variations did.

“Taken together,” the authors note, “our findings support a novel role for PRDM1 as a radiation-responsive tumor suppressor.” PRMD1 may be important for understanding the causes of second cancers in survivors of pediatric Hodgkin’s lymphoma as well as in other cancer patients treated with radiation therapy.”

This study should also “bring some optimism” back to genome-wide association studies, Onel added. Most previous cancer-related markers found through GWAS have been “of little clinical value for predicting risk, response to therapy or survival.” But by incorporating environmental exposure, such as radiation therapy, into genomic investigations, “much of the missing heritability can be revealed,” he said. “By folding in the environmental component, we were able to ask a more targeted question. This approach could improve our ability to integrate genomics into routine cancer care.”

###

The National Institutes of Health, the American Cancer Society, American Lebanese Syrian Associated Charities, the Leukemia Lymphoma Society, the Breast Cancer Research Foundation, the Cancer Research Foundation, and the University of Chicago Comprehensive Cancer Center supported this research.

Additional authors include Timothy Best, Andrew Skol, Sarah Jackson, Olufunmilayo Olopade and Stephanie Huang of the University of Chicago; Dalin Li, Thomas Mack, Wendy Cozen and David Conti of University of Southern California; Kenneth Offit and Thomas Kirchhoff of Memorial Sloan Kettering Cancer Center; Yutaka Yasui of the University of Alberta; Smita Bhatia of City of Hope; Louise Strong of the MD Anderson Cancer Center; Susan Domchek and Katherine Nathanson of the University of Pennsylvania; and Leslie Robison of St Jude Children’s Research Hospital.

Optimism associated with lower risk of having stroke

American Heart Association Rapid Access Journal Report

Study Highlights:
• A large-scale observational study shows that optimism is associated with lower risk of stroke.
• On a 16-point scale, each point increase in optimism correlated with a 9 percent reduction in stroke risk.
• This study adds to the increasing body of research on the health benefits of optimism.

DALLAS, July 21, 2011 — A positive outlook on life might lower your risk of having a stroke, according to new research reported in Stroke: Journal of the American Heart Association.

In an observational study, a nationally representative group of 6,044 adults over age 50 rated their optimism levels on a 16-point scale. Each point increase in optimism corresponded to a 9 percent decrease in acute stroke risk over a two-year follow-up period.

“Our work suggests that people who expect the best things in life actively take steps to promote health,” said Eric Kim, study lead author and a clinical psychology doctoral student at the University of Michigan.

Optimism is the expectation that more good things, rather than bad, will happen.

Previous research has shown that an optimistic attitude is associated with better heart health outcomes and enhanced immune-system functioning, among other positive effects.

The study is the first to discover a correlation between optimism and stroke. Previous research has shown that low pessimism and temporary positive emotions are linked to lower stroke risk.
Researchers analyzed self-reported stroke and psychological data from the ongoing Health and Retirement Study, collected between 2006 and 2008. Participants were stroke-free at the beginning of the study.

Researchers measured optimism levels with the modified Life Orientation Test-Revised, a widely used assessment tool in which participants rank their responses on a numeric scale.

The team used logistic regression analysis to establish the association between optimism and stroke and adjusted for factors that might affect stroke risk, including chronic illness, self-reported health and sociodemographic, behavioral, biological and psychological conditions.

“Optimism seems to have a swift impact on stroke,” said Kim, noting that researchers followed participants for only two years.
The protective effect of optimism may primarily be due to behavioral choices that people make, such as taking vitamins, eating a healthy diet and exercising, researchers said. However, some evidence suggests positive thinking might have a strictly biological impact as well.

Stroke is the No. 3 killer in the United States, behind heart disease and cancer, and a leading cause of disability.

Co-authors of the study are Nansook Park, Ph.D., and Christopher Peterson, Ph.D. Author disclosures are on the manuscript.

The Robert Wood Johnson Foundation’s Pioneer Portfolio funded a part of the study through the Positive Psychology Center of the University of Pennsylvania.

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Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association’s policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.americanheart.org/corporatefunding.

NR11– 1100 (Stroke/Kim)
• For more on stroke, visit the American Stroke Association.