MedicalResearch.com: Medical Research Exclusive Interviews July 20 2015

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
July 20 2015
For Informational Purposes Only: Not for Specific Medical Advice.

Medical Disclaimer | Terms and Conditions
• The contents of the MedicalResearch.com Site, such as text, graphics, images, and
other material contained on the MedicalResearch.com Site ("Content") are for
informational purposes only. The Content is not intended to be a substitute for
professional medical advice, diagnosis, or treatment. Always seek the advice of
your physician or other qualified health provider with any questions you may have
regarding a medical condition. Never disregard professional medical advice or
delay in seeking it because of something you have read on the Hemodialysis.com
Site!
• If you think you may have a medical emergency, call your doctor or 911
immediately. MedicalResearch.com does not recommend or endorse any specific
tests, physicians, products, procedures, opinions, or other information that may be
mentioned on the Site. Reliance on any information provided by
MedicalResearch.com or other Eminent Domains Inc (EDI) websites, EDI
employees, others appearing on the Site at the invitation of MedicalResearch.com
or EDI, or other visitors to the Site is solely at your own risk.
• The Site may contain health- or medical-related materials that are sexually explicit.
If you find these materials offensive, you may not want to use our Site. The Site
and the Content are provided on an "as is" basis.
Read more interviews on
MedicalResearch.com

Can a Low Methionine Diet Starve Triple-Negative Breast Cancer?
MedicalResearch.com Interview with:
Dr. Vincent L. Cryns MD
Chief of the Division of Endocrinology, Diabetes and Metabolism Department of Medicine
University of Wisconsin Carbone Cancer Center
University of Wisconsin School of Medicine and Public Health Madison, Wisconsin
• Medical Research: What is the background for this study? What are the main findings?
• Dr. Cryns: It’s been known for quite some time that many tumors are highly vulnerable to
deficiencies in certain amino acids such as methionine, causing tumor cells to stop growing or
die. What’s been missing is a molecular explanation for these effects that would allow us
incorporate this approach into a rationally designed clinical trial. In our work, we have
demonstrated that “starving” triple-negative breast cancer cells of methionine uncovers a
“fatal flaw” by increasing the expression of a cell death receptor (TRAIL-R2) that we can
activate with a therapeutic antibody to efficiently kill the tumor cells. What’s especially
exciting is that we can use a specific diet to metabolically prime cancer cells to respond to a
targeted cancer therapy.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

• Medical Research: What should clinicians and patients take away from your report?
• Dr. Cryns: We hope that our laboratory study will guide the way for a clinical trial of a low
methionine diet in combination with a TRAIL-R2 antibody in patients with clinically aggressive
triple-negative breast cancer. Unfortunately, patients with triple-negative breast cancer have
limited treatment options beyond standard surgery, radiation and chemotherapy.

• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Cryns: A critical first step to determine the feasibility of this approach in patients would
be to do a small clinical trial in breast cancer patients to see if a low-methionine diet does
indeed increase the expression of the TRAIL-R2 receptor in their breast tumors. This would
provide a strong rationale for combining a low-methionine diet with a therapeutic TRAIL-R2
antibody in a clinical trial.
• Citation:
• Clin Cancer Res. 2015 Jun 15;21(12):2780-91. doi: 10.1158/1078-0432.CCR-14-2792. Epub
2015 Feb 27.
• Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer
Cells by Enhancing TRAIL Receptor-2 Expression.
• Strekalova E1, Malin D1, Good DM1, Cryns VL2.

Space Station Provides Ideal Environment For Study of Multiple Medical Research Issues
Patrick O’Neill CASIS Communications Manager and
Tara Ruttley Ph.D. NASA Staff Scientist
NASA Office of the Chief Scientist
• Editor’s note: CASIS, the four year old Center for the Advancement of Science in Space,
presented an informative update and display at the Biotech Conference 2015, in Philadelphia
June 2015.
• CASIS, the manager of the International Space Station U.S. National Laboratory, facilitates
space-based research for the good of mankind. To accomplish it’s goal of ‘driving scientific
inquiry toward developing groundbreaking new technologies and products’, CASIS has at its
disposal Seed Money, Expertise, Access to Launch, Administrative Support and Educational
Outreach.
• Mr. O’Neill and Dr. Ruttley spoke with MedicalResearch.com about the work CASIS is doing
and the opportunities CASIS is creating for entrepreneurs, educators and scientists.
• MedicalResearch: Why don’t you tell us a little about the background for CASIS?
• Response: The mission of NASA is space exploration, while the complementary mission of
CASIS is to use ISS (the International Space Station) to better life on earth. CASIS is the non-
profit arm of NASA that recruits, selects and manages the scientific research projects
conducted on the space station.

• MedicalResearch: What is unique about the ISS environment? What is attractive about
conducting research in that setting?
• Response: The microgravity (weightlessness), extreme conditions and low earth orbit provide
an ideal environment for many research questions, including materials testing, crystal
growth, systems dynamics, and combustion.
• From a biological standpoint, the microgravity environment is unique for the study of three-
dimensional aggregation of cells, bone density and muscle wasting, aging, protein growth
including monoclonal antibodies, STEM cell research and microbiology.

•
MedicalResearch: Can you tell us some about some of the ongoing research on the ISS?
• Response: Several of many on-board experiments include:
• 1: A yearlong twin study with homozygous twins, Scott and Mark Kelly. Astronaut Scott Kelly
will spend a year in space (March 2015-March 2016) while his brother, Mark Kelly, a retired
astronaut, will live his life on earth. The investigation will focus on “analysis of human
molecular responses to the physical, physiological and environmental stressors associated
with human spaceflight”.
• 2. Bone density loss and muscle wasting are problems associated with weightlessness and
space flight. They are also common problems linked to aging here on earth. In the past,
Amgen conducted research on its drug Prolia (denosumab) for osteoporosis on the ISS.
• One unique ongoing study by Lenore Rasmussen, Ph.D. and colleagues from the Princeton
Plasma Physics Laboratory, is attempting to develop synthetic muscle for both robotic and
human prosthetic use. Temperature and radiation resistant synthetic muscle may be used to
build hands that could work in places unsafe for humans, such as potential nuclear disasters.

• 3. The Fruit Fly Lab has “the combined capabilities of artificial gravity, day/night lighting,
video observation, tissue preservation and the ability to separate multiple generations of
flies”. The current fruit fly experiments are focusing on how spaceflight affects the immune
system’s response to infection.
• 4. The Fluid Shifts study, is examining the effects of fluids (blood and water) shifting in an
astronaut’s head during flight. What is learned from the Fluid Shifts research may be
applicable to patients with brain swelling from a variety of causes.
Response: Human monoclonal antibody studies: Merck Research Laboratories is capitalizing on
the fact that “Protein crystals grown in microgravity can reach much larger sizes and more perfect
structures than those grown on Earth, where gravity interferes with their formation”. Merck is
investigating a monoclonal antibody for potential use in autoimmune disease.

• MedicalResearch: How are supplies transported to the space station?
• Response: The Space X Dragon is a free-flying spacecraft that delivers both cargo and people
to the international space station. The ISS also had 3D printing equipment to replace worn or
provide new tools as needed.
• MedicalResearch.com: What is the educational mission of CASIS?
• Response: The educational mission of CASIS is to equip educators to be able to excite their
students in the pursuit of knowledge about their home, Earth and space. It is a major goal of
CASIS to provide STEM educators with the resources they need to inform and encourage
their students in the pursuit of a science education. CASIS actively recruits experimental
proposals from students and at the present time has 30-40 ongoing student-triggered
experiments on the space station.

• More information as CASIS can be found here:
• 1: Results of microgravity studies are featured on the Nature journal Microgravity.
• 2. CASIS website
• 3. CASIS Fact Sheet for Researchers

Acne Causing Bacteria Killed By Nitric Oxide Generated From Nanoparticles
MedicalResearch.com Interview with: Adam Friedman, MD, FAAD
Associate Professor of Dermatology Residency Program Director
Director of Translational Research Department of Dermatology
George Washington School of Medicine and Health Sciences
Medical Research: What is the background for this study? What are the main findings?
Dr. Friedman: Acne vulgaris is one of the most common skin disease that affects approximately 40-50
million people in the United States. Acne’s multifactorial etiology, resulting from a mix of androgen-
induced elevations in sebum production, abnormal follicular epithelial desquamation and proliferation,
hypercolonization of Propionibacterium acnes and host inflammatory reactions, make treatment often
times challenging. In looking at the topical therapeutic armament for Acne Vulgaris, which includes
benzoyl peroxide, salicyclic acid, topical antibiotics such as clindamycin, and retinoids, all suffer from
various related side effects including irritation, erythema, dryness, peeling and scaling, bacterial
resistance, and resulting dyschromia from the associated irritation in patients of darker skin types.
These adverse events often serve as major limiting factors influencing patient compliance and
ultimately impacting efficacy. Therefore new treatments which target all of the complexities of acne are
needed, especially given we have not had anything really new brought to market in years. Here, we
looked to biology for the answer. Our bodies generate Nitric Oxide, a diatomic lipid loving gaseous
molecule, to perform a broad range of biological activities, including but not limited to killing
bacteria/fungi/viruses and inhibiting inflammation – key elements in Acne. Its action however is very
short lived and therefore using Nitric Oxide as a treatment is difficult as one would need a delivery
system that would allow for continued and controlled release. Enter nanotechnology. We designed
exceedingly small particles (of note, 1 nanometer = 1 billionth of a meter) which allow for the
generation of nitric oxide gas from nitrite salt, and will only release the gas when exposed to moisture
over time. The size of the particles also enables them to better interact with their environment, i.e.
cells, pathogens, improving their activity as compared to large sized treatments

In this study, we showed that the nitric oxide generating/releasing nano particles effectively
killed the organism, P. acnes but was not toxic to both human skin cells and a live vertebrae
model (embryonic zebra fish). More importantly, we found that the nano particles inhibits the
activation of a newly recognized but exceedingly important inflammatory pathway that is directly
tied to the formation of an acne lesion, called the NLRP3 inflammasome. Research has shown
that our bodies already regulate this pathway with nitric oxide, and therefore once again, we are
looking to biology for answers. As opposed to a drug that may only have one target,
the nanoparticles inhibited multiple components/elements of the inflammasome pathway, giving
some insight into its potential as a treatment for acne as well as other inflammatory diseases.

• Dr. Friedman I think one theme of this paper is targeted medicine: Elucidating the
the underpinnings of disease, correlating with normal physiology, and creating a therapy
based on this understanding. This has been the modern template for many new therapies for
a broad range of diseases from cancer to psoriasis. Having a strong grasp on the biology
allows the practitioner to both use medication off label based on their mechanism as well as
help guide the development of new therapies. Focusing more on the paper, I think a
broader appreciation of nanotechnology, specifically nanomedicine is important as there is
limitless potential to both improve the sustainability and efficacy of established medications
and allow for the delivery of unstable or previously undeliverable agents like nitric oxide.

this study?
• Dr. Friedman: The next steps for this research is clinical trials. There are currently no great
animal models for acne so very often once the standard quality assurance and safety studies
are complete, one can enter the clinical space. We are currently working towards
commercializing this technology through a company named Nano BioMed inc, and hope to
move this into the clinical space with great speed.
• In terms of broader future research initiatives, a better understanding of how or if both old
and new drugs effect the inflammasome pathway is an important step in the right direction
as this is clearly an important target.
• Citation:
• Nitric Oxide Releasing Nanoparticles Prevent Propionibacterium acnes Induced Inflammation
by both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune
Response.
• Min Qin1, Angelo Landriscina2, Jamie Rosen2, Gabrielle Wei1, Stephanie Kao1, William Olcott1,
George W Agak1, Karin Blecher Paz2, Josephine Bonventre3, Alicea Clendaniel3,
Stacey Harper3,4, Brandon Adler2, Aimee Krausz2, Joel Friedman5, Joshua Nosanchuk6,7,
Jenny Kim1,8 and Adam J Friedman2,5,9
• Journal of Investigative Dermatology accepted article preview 14 July 2015; doi:
10.1038/jid.2015.277

Cost-Effective Clinical Pathway Determined Hospitalized Patients’ Risk of Sleep Apnea
Sunil Sharma, M.D
Associate professor of pulmonary medicine
Sidney Kimmel Medical College at Thomas Jefferson University
Dr. Sharma: Obstructive sleep apnea (OSA) is a highly prevalent disorder with significant
cardiovascular implications. In this condition the patient may repeatedly quit breathing during
sleep, sometimes hundreds of times, leading to loss of oxygen and frequent arousals throughout
the night. OSA has been associated with high blood pressure, congestive heart failure, coronary
artery disease, arrhythmias and stroke, among other conditions. While overall awareness is
improving, the condition is under-recognized in hospitalized patients. Due to multiple co-morbid
conditions these patients may be at higher risk for complications. Recent studies have also shown
that early recognition of OSA in hospitalized patients may reduce readmission rates. In our study,
we used a simple and cost-effective clinical pathway to determine high-risk patients. Of the 149
patient’s determined to be high risk by our protocol, 128 (87%) were confirmed with the
diagnosis by a polysomnography (gold standard test). Furthermore, data derived from a simple
and cost-effective oxygen measuring device (pulse-oximeter) was found to co-relate well with the
polysomnography.

Cost-Effective Clinical Pathway Determined Hospitalized Patients’ Risk of Sleep Apnea
Sunil Sharma, M.D
Associate professor of pulmonary medicine
Sidney Kimmel Medical College at Thomas Jefferson University
• Dr. Sharma: Obstructive sleep apnea is common but under-recognized condition in
hospitalized patients. Not only can it increase risk of complications in these patients but early
recognition and treatment has been found to reduce readmission rates. Clinicians should
have a high index of suspicion and develop simple protocols to screen their patients in the
hospital.
this study?
• Dr. Sharma: This is data from a single, tertiary care teaching hospital. To confirm that these
clinical pathways are applicable in all settings a multi-centric study is recommended.
• Citation:
• Obstructive Sleep Apnea in Obese Hospitalized Patients: A Single Center Experience
• Sunil Sharma, MD1; Paul J. Mather, MD2; Jimmy T. Efird, PhD, MSc3,4; Daron Kahn, MD1; Kristin
Y. Shiue, MPH3,4; Mohammed Cheema, MD1; Raymond Malloy, RRT1; Stuart F. Quan, MD5,6
• Journal of Clinical Sleep Medicine Volume: 11 Number: 07
http://dx.doi.org/10.5664/jcsm.4842

Genetic Testing Can Detect, Protect Patients Prone To Thoracic Aortic Aneurysm
John A. Elefteriades, MD
William W.L. Glenn Professor of Surgery Chief of Cardiothoracic Surgery
Director, Aortic Institute at Yale-New Haven
Yale University School of Medicine
Dr. Elefteriades: The race to map the human genome was declared completed in 2003, at a
cost of 3 billion dollars for the international collaborative university group and 300 million
dollars for Craig Venter at Celera. Whole exome sequencing can now be performed at a cost
of only several thousand dollars per individual. So, whole exome sequencing (also called Next
Generation Sequencing) can now be applied to understand and treat diseases of many organ
systems.
• In this study, we applied whole exome sequencing to study over 100 patients with thoracic
aneurysm.
• In the late 1990s, both Dr. Diana Milewicz in Texas and our group at Yale had determined that
many thoracic aortic aneurysms were genetically transmitted. Dr. Milewicz went on to
identify many of the causative mutations. In this study, we were able to look, by whole
exome sequencing performed on saliva, for all 21 mutations known to cause thoracic aortic
aneurysm–all at one time in one comprehensive genetic test. We were able to protect
patients with the most serious discovered mutations by early surgery, the need for which
could not otherwise have been apparent.

• Dr. Elefteriades: A comprehensive test for the genetic underpinnings of thoracic aortic
aneurysm is now available. This is accomplished via whole exome sequencing (Next
Generation Sequencing).
• It can be extremely important for patients and their family members to have this testing
done. Firstly, personalized care (including early surgery) can be performed for individuals with
the most dangerous mutations (genetic alterations).
• Secondly, if a mutation is indeed found, then a simple test on family members can determine
which relatives will be vulnerable to thoracic aortic aneurysm and which are completely
spared. The ones who are genetically spared can “forget” about the possibility of aneurysm
disease, “like it never happened”

this study?
• Dr. Elefteriades: Widespread application of whole exome sequencing for thoracic aortic
aneurysm will expand our roster of causative mutations rapidly and dramatically. We envision
a “dictionary” or “encyclopedia” of mutations causing thoracic aneurysm that will number in
the hundreds or thousands very soon.
• Thoracic aortic aneurysm is a silent disease, lethal if not detected. Detection by genetic
means will save vulnerable lives by permitting identification of disease and effective surgical
therapy.
• Citation:
• Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting
• Bulat A. Ziganshin, Allison E. Bailey, Celinez Coons, Daniel Dykas, Paris Charilaou, Lokman H.
Tanriverdi, Lucy Liu, Maryann Tranquilli, Allen E. Bale, John A. Elefteriades
• DOI: http://dx.doi.org/10.1016/j.athoracsur.2015.04.106
Publication stage: In Press Corrected Proof
Published online: July 15 2015

Health Lifestyle Reduces Risk of Atrial Fibrillation
Carl “Chip” Lavie MD, FACC FACP, FCCP
Medical Director, Cardiac Rehabilitation and Prevention Director, Exercise Laboratories John Ochsner Heart and Vascular Institute
Professor of Medicine
Ochsner Clinical School-UQ School of Medicine
Dr. Lavie: This was a review of the literature on this topic.The main findings are that various
lifestyle choices, including obesity, hypertension, metabolic syndrome/diabetes, obstructive
sleep apnea , moderate and high alcohol intakes, and sedentary lifestyle but also very high
exercise doses are all associated with increased risk of atrial fibrillation (AF).
• Dr. Lavie: Patients can reduce their risk of atrial fibrillation by keeping alcohol doses low (<2
drinks per day for large size people and only 1 per day for smaller body sizes),preventing
obesity and especially severe obesity or by losing weight, especially > 10% on severe obesity,
controlling blood pressure and sugar, treating sleep apnea, and performing regular physical
activity/exercise but avoiding prolonged exercise.

Health Lifestyle Reduces Risk of Atrial Fibrillation
Carl “Chip” Lavie MD, FACC FACP, FCCP
Medical Director, Cardiac Rehabilitation and Prevention Director, Exercise Laboratories John Ochsner Heart and Vascular Institute
Professor of Medicine
Ochsner Clinical School-UQ School of Medicine
this study?
• Dr. Lavie: Future studies are needed to determine the optimal non-phamacologic programs
to reduce atrial fibrillation risk.
• Citation:
• Healthy Lifestyle Interventions to Combat Noncommunicable Disease-A Novel
Nonhierarchical Connectivity Model for Key Stakeholders: A Policy Statement From the
American Heart Association, European Society of Cardiology, European Association for
Cardiovascular Prevention and Rehabilitation, and American College of Preventive Medicine.
• Arena R, Guazzi M, Lianov L, Whitsel L, Berra K, Lavie CJ, Kaminsky L, Williams M, Hivert MF,
Franklin NC, Myers J, Dengel D, Lloyd-Jones DM, Pinto FJ, Cosentino F, Halle M, Gielen S,
Dendale P, Niebauer J, Pelliccia A, Giannuzzi P, Corra U, Piepoli MF, Guthrie G, Shurney D.
• Mayo Clin Proc. 2015 Jun 26. pii: S0025-6196(15)00349-3. doi:
10.1016/j.mayocp.2015.05.001.

Combination Targeted Therapy Promising For Difficult Peripheral T-Cell Lymphoma
Dr Yeow Tee Goh MBBS
Department of Haematology
Singapore General Hospital
Republic of Singapore
Dr. Goh: Relapsed or refractory peripheral T-cell lymphoma after conventional chemotherapy is
associated with a very poor prognosis and there is currently no recommendation on the standard
approach to helping these patients. Novel targeted treatments for relapsed or refractory
peripheral T-cell lymphoma such as romidepsin, pralatrexate, belinostat, and brentuximab
vedotin has been approved by the US Food and Drug Administration (FDA) based on the results of
their Phase II studies. With the exception of the remarkable efficacy of brentuximab vedotin in
systemic anaplastic large cell lymphoma (86% of patients responding to treatment), the efficacy
of romidepsin, pralatrexate, and belinostat in relapsed or refractory peripheral T-cell lymphoma is
only modest with objective response rates between 25% and 29%. To our knowledge, no other
clinical study has reported on the use of novel combination of targeted agents in in relapsed or
refractory peripheral T-cell lymphoma. In our study, Of 23 patients assessable for responses, 10
(43%, 95% CI 23–63) patients had an objective response, of which 5 were complete responses.
The combined proteasome and histone deacetylase inhibitor treatment shows promising activity
for patients with peripheral T-cell lymphoma.

• Dr. Goh: Peripheral T-cell lymphoma is clinically heterogeneous and associated with a very
poor prognosis. There is an unmet need to improve the effectiveness of currently approved
novel agents to induce remission and reduce disease burden to enable stem-cell
transplantation. Our data compare favorably with the modest single-agent activities of novel
targeted compounds and ours is the first study to show that the combination of two novel
agents is safe, feasible, and promising in peripheral T-cell lymphoma. Our findings validate
data from abundant preclinical studies suggesting that a combination approach is synergistic.

this study?
• Dr. Goh: The identification of synergistic novel combinations pre-clinically and the translation
to clinical studies represents the most rational way forward in harnessing the full potential of
novel agents in peripheral T-cell lymphoma. This approach will certainly fill the emergent
need for improved treatment strategies in these patients. Studies involving larger pools of
patients would be required for further validation of the efficacy of proteasome and histone
deacetylase inhibitor combination treatment for peripheral T-cell lymphoma patients.
Optimum dosing schedules and dose combinations of various proteasome and histone
deacetylase inhibitors combinations should be explored to further harness the full potential
of such novel agents in peripheral T-cell lymphoma .

Antidepressants Plus NSAIDS May Increase Risk of Bleeding in Brain
Byung-Joo Park, MD, MPH, PhD Professor
Department of Preventive Medicine
Seoul National University College of Medicine
Response: Antidepressants and NSAIDs are each thought to increase the risk of abnormal
bleeding. However, previous studies found neither antidepressants nor NSAIDs alone to be
associated with an increased risk of intracranial haemorrhage. Our research found that combined
use of NSADIs in antidepressant users showed the increased relative risk of intracranial
haemorrhage risk within the initial 30-days of combined use.

• Response: For the clinicians, special attention should be paid for the antidepressant users
when they additionally start the NSAIDs prescription. Monitoring bleeding risk is particularly
needed at the initial combined use of both medicines. For the patients who have been taking
antidepressants, in case they need additional NSAIDs, they should tell doctors considering
the possibility of drug-drug interaction which can induce intracranial haemorrhage.

this study?
• Response: Present study was focused on the antidepressants users, and the differential risk
according to the type of antidepressants. Future research would be needed whether the type
of NSAIDs such as Cox2 selective vs. non-selective affects the risk associated with combined
use of antidepressant. Considering the frequent OTC use of NSAIDs, record linkage study
using health insurance database with pharmacy database would produce better results.
• Citation:
• Shin Ju-Young, Park Mi-Ju, Lee Shin Haeng, Choi So-Hyun, Kim Mi-Hee, Choi Nam-Kyong et al.
Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal
anti-inflammatory drugs: nationwide propensity score matched study 2015; 351 :h3517

Study Finds Increased Hospitalizations Near Marcellus Shale Fracking Wells
Reynold A. Panettieri, Jr., M.D.
Robert L. Mayock and David A. Cooper Professor of Medicine
Pulmonary, Allergy & Critical Care Division Director, Airways Biology Initiative
Deputy Director, Center of Excellence in Environmental Toxicology
• Dr. Panettieri: Over the past ten years in the US, unconventional gas and oil drilling (hydraulic
fracturing) to generate natural gas has markedly increased. In areas with hydraulic fracturing,
there is a large increase in truck traffic, noise and potential air and water
pollution. Accordingly, residents may experience health consequences from such
exposures. We questioned whether proximity to active wells increases hospitalization rates
in residents. To address this question, we reviewed all hospitalizations in two counties in
Pennsylvania, namely, Bradford and Susquehanna Counties, that experienced a meteoric
increase in active wells. In comparison, Wayne County, where there is a moratorium on
hydraulic fracturing, is demographically identical to Bradford and Susquehanna Counties and
served as a control population. Having examined the 25 most common reasons for admission
to the hospital, we determined that cardiovascular hospitalizations as well as neurologic,
dermatologic and cancer hospitalizations were associated with living closer to active
wells. These data represent some of the first studies to associate active well drilling with
hospitalizations in the United States.

• Dr. Panettieri: Our data supports the concept that hydraulic fracturing and proximity to active
wells may increase the risk for hospitalization for cardiovascular and other
diseases. Although our study can only associate active well density with hospitalizations, we
posit that air, water and noise pollution as well as aberrant stress responses may contribute
to the health consequences. Further, the economic value of hydraulic fracturing should
account for the potential of increased hospitalizations and health care associated with this
activity.

this study?
• Dr. Panettieri: Since this study can only associate active well drilling with hospitalizations,
further studies are necessary to identify the specific diseases that are manifested with
proximity to active well drilling. Other studies should examine whether emergency
department and outpatient visits also correlate with proximity to active wells to understand
the comprehensive consequences of hydraulic fracturing on health care utilization.
• Citation:
• Thomas Jemielita, George L. Gerton, Matthew Neidell, Steven Chillrud, Beizhan Yan, Martin
Stute, Marilyn Howarth, Pouné Saberi, Nicholas Fausti, Trevor M. Penning, Jason Roy,
Kathleen J. Propert, Reynold A. Panettieri Jr. Unconventional Gas and Oil Drilling Is Associated
with Increased Hospital Utilization Rates. PLoS One, 2015 DOI:
10.1371/journal.pone.0131093

Patients With Lower Health Literacy May Find Electronic Health Care Portals Challenging
Dr. Courtney Lyles Ph.D.
Assistant Professor
UCSF School of Medicine
Dr. Lyles: In our commentary
(http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001852), we
describe the Meaningful Use program sponsored by the federal government to incentivize
healthcare systems to implement electronic health records (EHRs). This Meaningful Use program
also includes financial incentives for healthcare systems who can get substantial proportions of
their patient population to access their electronic health records – that is, by logging into an
online patient portal website to view medical information like lab results or immunization lists or
to perform a healthcare task like requesting a medication refill or messaging their
provider. Because there are billions of dollars at stake in this program for EHR implementation,
there is a lot of attention on this issue right now. Many thought leaders are discussing how we
can transform healthcare by digitizing medical information and connecting with patients in their
everyday life outside of office or hospital visits. Portals are key to a lot of changes we might make
in healthcare delivery in an attempt to increase convenience and satisfaction for
patients. Perhaps most importantly, these online portal websites are also one of the first health
technologies that will be relatively uniformly distributed across healthcare settings, from private
doctor’s offices to public clinics/hospitals serving vulnerable patient populations.

Assistant Professor
However, our main message is that we in the medical and healthcare fields should be paying
more attention to how patients are able to understand and use the information provided through
portal websites. There is a lot of evidence that patients who have lower education/income, are
from racial/ethnic minority groups, or have limited health literacy are significantly less likely to
use the existing portal websites. There is also evidence that portal websites are not extremely
usable or accessible, which is an additional barrier for those with communication barriers like
lower literacy or limited English proficiency. Therefore, we don’t want widespread EHR
implementation to result in only the most well-resourced individuals gaining the potential
benefits of portal access.

Assistant Professor
• Dr. Lyles: Hopefully clinicians and patients can read our paper and think about the utility of
the existing portal websites in their setting, and come up with recommendations for better
design and functionality. Delivering health data to patients is a goal that most providers and
patients agree is critical to delivering truly patient-centered care. But providing data that is
not always easily accessed, understood, or acted upon is not ideal.

Assistant Professor
this study?
• Dr. Lyles: We put forth several recommendations in the paper for next steps. From a
research perspective, we believe it is critical to produce generalizable health communication
knowledge about the best ways to display and communication complex health information
for patients with a spectrum of literacy, numeracy, and English language skills. Making
information clearer will benefit not only those with communication challenges, but for all
patients looking to best comprehend and actively manage their healthcare treatment
decisions.
• Citation:
• Connecting the Dots: Health Information Technology Expansion and Health Disparities
• Courtney Lyles , Dean Schillinger, Urmimala Sarkar
• Published: July 14, 2015
• DOI: 10.1371/journal.pmed.1001852

Atrial Fibrillation Increases Risk of Stroke After TAVR
Medical Research Interview with:
Prof. Johan Bosmans
Interventional cardiologist
University Hospital Antwerp, Wilrijkstraat 10, 2650,
Edegem, Belgium
• MedicalResearch: What is the background for this study? What are the main findings?
• Prof. Bosmans : Transcatheter aortic valve replacement (TAVR) has become standard of care
for patients who cannot undergo surgery. With this, it is important to ensure that the risks
associated with TAVR be fully understood, and if possible prevented. Even at this stage of the
adoption of TAVR, large trials continue to provide information to the clinician about how to
select the right patients to ensure the best possible outcomes. The ADVANCE Study is a
prospective, multicenter study that evaluated the use of TAVR in 1015 patients at 44
experienced TAVR centers, which was designed to reflect routine clinical practice.
• We know that the risk of serious adverse events, such as stroke or transient ischemic attack
(TIA), in post-TAVR patients can vary based on the timing before and after the procedure. A
patient’s baseline demographics and medical history can affect their risk of procedure-related
events as well as long-term outcomes. The manipulations required crossing the aortic valve
and appropriately positioning any type of TAV has been thought to be related to procedural
stroke events. Therefore, we performed a multivariable analysis looking for predictors of
stroke – or stroke and TIA at 3 unique time periods (periprocedural, early and late) following
TAVR.

Prof. Johan Bosmans
Edegem, Belgium
The most striking result from our analyses was that we were not able to identify any predictors
of periprocedural (either during the procedure or on the day after) stroke, illustrating this very
multifactorial etiology. We were able to show that being female, experiencing acute kidney injury
or a major vascular complication positively predicted stroke during the early (2-30 days post
procedure) time period. When we combined the outcome of stroke or TIA, we found that a
history of prior atrial fibrillation (AF) was also a predictor. The only late predictor (day 31-730
post-procedure) of stroke was a history of coronary artery bypass grafting, which could reflect
the patients’ risk of vascular disease.

Prof. Johan Bosmans
Edegem, Belgium
• MedicalResearch: What should clinicians and patients take away from your report?
• Prof. Bosmans : We identified predictors of stroke, or stroke or TIA that can aid the clinician
in their screening and assessment of patients with symptomatic aortic stenosis that may
benefit from TAVR. Early predictors included both medical history and procedural outcomes
as predictors. It is common knowledge that the presence of Atrial Fibrillation is associated
with increased stroke risk; therefore this outcome only supports common clinical practice.
The procedural predictors can be managed by optimizing renal status and ensuring that
vascular access is well managed, or by using newer, lower profile TAV systems. Since
approximately 40% of patients treated with TAVR had a history of CABG, additional testing
could be performed to ensure the patients cerebrovascular status is optimal for the
procedure.

Prof. Johan Bosmans
Edegem, Belgium
• MedicalResearch: What recommendations do you have for future research as a result of this
study?
• Prof. Bosmans : Our results are based on TAVR procedures performed at experienced sites, as each
center was required to have performed at least 40 procedures before being allowed to participate
in the study. What could be interesting would be to apply a similar predictor model, with the
different inputs for the different time periods, to other studies of similar patients based on risk
profiles, and without the limitation of the experience requirement.
• Our study suggests that a history of Atrial Fibrillation may be an important risk factor for
neurological events (stroke/TIA) early after TAVR. These results strongly suggest that, in order to
reduce neurological complications after TAVR, anticoagulation therapy should be started
immediately after diagnosis of the AF episode and continued for several months. No clear
guidelines actually exist on anticoagulation therapy following short episodes of postoperative AF.
However, patients undergoing TAVR are at high risk for thromboembolism in case of atrial
arrhythmia and a more aggressive antithrombotic treatment should probably be implemented in
these cases. Although dual antiplatelet therapy with aspirin and clopidogrel has been empirically
recommended following TAVR, future randomized studies will have to evaluate the more
appropriate antithrombotic treatment following these procedures and the potential role for
systematic anticoagulant therapy either with warfarin or direct thrombin inhibitors in this setting.
• Citation:
• Bosmans J, Bleiziffer S, Gerckens U, et al. The Incidence and Predictors of Early- and Mid-Term
Clinically Relevant Neurological Events After Transcatheter Aortic Valve Replacement in Real-World
Patients. J Am Coll Cardiol. 2015;66(3):209-217. doi:10.1016/j.jacc.2015.05.025.

RNA in Sperm Could Be Biomarkers of Male Fertility
MedicalResearch.com Interview with: Stephen A. Krawetz, Ph.D.
Associate Director C.S. Mott Center for Human Growth and Development,
Charlotte B. Failing Professor of Fetal Therapy and Diagnosis,
Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics,
Wayne State University School of Medicine,
Dr. Krawetz: The current study developed over approximately the past 20 years of work in my
laboratory. In the mid 1990s, along with David Miller, we independently discovered that sperm
contain RNA. This was followed by our joint publication in The Lancet that began to describe the
RNAs in normal fertile males along with our paper in Nature that showed that RNA was delivered
to the oocyte at fertilization. Following these studies we assessed the ability of RNAs to be used
as markers of morphologically abnormal sperm (teratozoospermia). My laboratory then had the
opportunity to explore the complexity of the population of sperm RNAs using Next Generation
Sequencing. We recently began the translation of this work from the bench to bedside which
takes us to the current paper in Science Translational Medicine that was a multi-institutional
collaborative effort. Members of the team include Dr. Meritxell Jodar, Edward Sendler, Robert
Goodrich, from my laboratory, along with Dr. Clifford L. Librach, Dr. Sergey I. Moskovtsev, and
Sonja Swanson – CReATe Fertility Center, University of Toronto; Dr. Russ Hauser -Harvard
University and Dr. Michael P. Diamond, Georgia Regents University. Here we tackled the issue of
idiopathic infertility, that is, unknown infertility, since the couple appears normal in all
respects. We specifically framed our study as the contribution of the male and female as a
couple towards the birth of a healthy child focusing on male idiopathic infertility within the
setting of a Reproductive Clinic. Representative publications from my laboratory that outline this
part of my research program appear below.

• 1) Jodar, M., Sendler, E., Moskovtsev, S. Librach, C., Goodrich, R., Swanson, S., Hauser,
R., Diamond, M. and Krawetz, S.A. (2015) Absence of sperm RNA elements correlates with
idiopathic male infertility. Science Translational Medicine, 7(295):295re6.
• 2) Sendler, E., Johnson, G.D., Mao, S., Goodrich, R.J., Diamond, M.P., Hauser, R., and
Krawetz, S.A. (2013) Stability, Delivery and Functions of Human Sperm RNAs at
Fertilization. Nucleic Acids Research 41:4104-4117. PMID: 23471003
• 3) Platts, A.E., Dix, D. J., Chemes, H.E., Thompson, K.E., Goodrich, R., Rockett, J. C.,
Rawe, V.Y., Quintana, S., Diamond, M.P., Strader, L.F. and Krawetz, S.A. (2007) Success and
failure in human spermatogenesis as revealed by teratozoospermic RNAs. Human Molecular
Genetics. 16:763-773. PMID: 17327269
• 4) Ostermeier, G.C., Miller, D., Huntriss, J.D., Diamond, M.P. and Krawetz, S.A. (2004)
Delivering spermatozoan RNA to the oocyte. Nature 429:154. PMID: 15141202
• 5) Ostermeier, G.C., Dix, D.J., Miller, D., Khatri, P. and Krawetz, S.A. (2002) Spermatozoal
RNA profiles of normal fertile men. The Lancet. 360:773-777. PMID: 12241836

Medical Research: What are the main findings?
Dr. Krawetz: With the use of RNA-Seq (RNA sequencing) we defined a series of 648 RNA
elements in a series of males from couples presenting with idiopathic infertility (both the male
and female appear normal but sought reproductive care) – yet within the first spermatogenic
cycle successfully conceived, resulting in the birth of a healthy child. These RNAs correspond to
exon-sized regions of the genome that we have termed elements. Using this set of elements we
were then able to identify two groups. The first in which all the elements were present and the
second in which at least one element was absent. When all the elements were present the birth
of a healthy child could most often be achieved with minimal intervention. When at least one
element was absent the use of ART (Assisted Reproductive Technology) was required to achieve
the birth of a healthy child. This suggested that the elements we defined could serve as
biomarkers for male fecundity.

• How this may help couples trying to conceive and have a baby:
• Dr. Krawetz: It is our goal to use this technology to reduce both the time to live birth of a
healthy child and cost when couples seek infertility treatment so as to reduce the stress on
the couple. It is our hope that by identifying the extent of Dad’s contribution, the
responsibility for setting the course for the birth of a healthy child can now be more equally
shared. Upon validation this discovery may help to identify those couples who may benefit
from ART and those couples who may be successful with minimal intervention.

this study?
• Dr. Krawetz: At present the test is experimental since sperm RNA analysis is technically
challenging. It is being automated so that in the next short while it may become part of a
routine examination as we move towards Personalized and Precision Medicine. The next step
before we can make this test generally available is to secure the necessary funding so that we
may expand this study to a prospective blinded trial.
• Citation:
• Jodar, E. Sendler, S. I. Moskovtsev, C. L. Librach, R. Goodrich, S. Swanson, R. Hauser, M. P.
Diamond, S. A. Krawetz. Absence of sperm RNA elements correlates with idiopathic male
infertility. Science Translational Medicine, 2015; 7 (295): 295re6 DOI:
10.1126/scitranslmed.aab1287

Gene Therapy May Stop Blindness From Retinitis Pigmentosa
Professor Robert E MacLaren MB ChB DPhil FRCOphth FRCS
Nuffield Laboratory of Ophthalmology
Nuffield Department of Clinical Neurosciences
Oxford Biomedical Research Centre, University of Oxford,
Prof. MacLaren: The study shows that gene therapy can be used to release a protein in the eye
that arrests the development of retinitis pigmentosa, a blinding disease caused by degeneration
of the retina. The study was performed in mice which had a similar genetic defect to that found in
humans with the disease. The mice also had fluorescent green “glow in the dark” light sensing
cells known as cones, which we could see and count by looking into the eye – like counting stars
in the night sky. By counting the green fluorescent cones we were able to work out the exact
dose of gene therapy needed to keep these cells alive indefinitely. The study was funded by Fight
for Sight, a UK charity that supports finding cures for eye diseases.

Gene Therapy May Stop Blindness From Retinitis Pigmentosa
Professor Robert E MacLaren MB ChB DPhil FRCOphth FRCS
Nuffield Laboratory of Ophthalmology
Nuffield Department of Clinical Neurosciences
Oxford Biomedical Research Centre, University of Oxford,
• Prof. MacLaren: Gene therapy has great promise in treating retinitis pigmentosa but we are
only just entering clinical trials and there is a lot more to do before it becomes an approved
treatment.
this study?
• Prof. MacLaren: We need to know more about how the protein induced by the gene therapy
works. The protein is known as ciliary neurotrophic factor (CNTF) and has been in clinical
trials before but some toxic effects were seen. It may be more stable when delivered at a
lower dose using gene therapy, or the route of administration may be critical to the success
with retinitis pigmentosa. We now have sufficient data to start designing a clinical trial.
• Citation:
• Mol Ther. 2015 Apr 21. doi: 10.1038/mt.2015.68. [Epub ahead of print]
• CNTF Gene Therapy Confers Lifelong Neuroprotection in a Mouse Model of Human Retinitis
Pigmentosa.
• Lipinski DM1, Barnard AR2, Singh MS2, Martin C3, Lee EJ4, Davies WI5, MacLaren RE6.

Increased Leisure Time Sitting Raises Cancer Risk
Alpa Patel, PHD
Strategic Director, CPS-3
American Cancer Society, Inc.
Atlanta, GA 30303
Dr. Patel: Using information from more than 146,000 men and women (69,260 men and 77,462
women) who were cancer-free and enrolled in the American Cancer Society Cancer Prevention
Study II Nutrition Cohort, we examined the association between leisure time spent sitting and
cancer risk. Study participants were followed from 1992 through 2009, during which time 18,555
men and 12,236 women were diagnosed with cancer. We found longer leisure-time spent sitting
was associated with a 10 percent higher risk of cancer in women after adjustment for physical
activity, BMI, and other factors. The association in women was primarily due to invasive breast
cancer, ovarian cancer, and multiple myeloma. No association was apparent in men.

Increased Leisure Time Sitting Raises Cancer Risk
Alpa Patel, PHD
Strategic Director, CPS-3
American Cancer Society, Inc.
Atlanta, GA 30303
• Dr. Patel: These findings add to the growing body of scientific evidence that prolonged sitting
is harmful to your overall health. Given the high rate of sedentary time in the U.S. any efforts
to decrease sitting time can have broad public health benefit.
this study?
• Dr. Patel: American Cancer Society guidelines for cancer prevention currently recommend
reducing sitting time when possible. We need to conduct additional research to better
understand the differences in associations between men and women as well as to quantify
how much (or little) individuals should sit to prevent these negative health effects.
• Citation:
• Leisure-time spent sitting and site-specific cancer incidence in a large US cohort
Alpa V. Patel, Janet S. Hildebrand, Peter T. Campbell, Lauren R. Teras, Lynette L Craft, Marjorie
L. McCullough, and Susan M. Gapstur
• Cancer Epidemiol Biomarkers Prev cebp.0237.2015; Published OnlineFirst June 30, 2015;
doi:10.1158/1055-9965.EPI-15-0237

Why Do Dilute Bleach Baths Improve Atopic Dermatitis?
Adam Friedman, MD, FAAD
Director of Translational Research
Department of Dermatology
• Dr. Friedman: Given pruritus is not only a hallmark symptom of atopic dermatitis, and in fact
is even part of the diagnostic criteria, we sought to evaluate whether factors known to cause
itch or inhibit said pruritogens in other disease states are over or under expressed in skin
from patients diagnosed with atopic dermatitis. Over the past 10 years considerable
attention has been paid to the complexity of the immune dysregulation and plethora of
inflammatory and neurogenic factors involved in the activity and progression of this
disease. Our study showed significant differences between atopic dermatitis skin and normal
skin. Specifically, we found significantly elevated levels of several well-known components of
both the inflammatory and pruritus cascade including interleukin-2, BLT1 (the receptor for
leukotriene B4, recently implicated in atopic dermatitis), 5-lipoxygenase and Matrix
Metalloproteinase-7. Interestingly, for the first time to our knowledge, α-2 macroglobulin,
a ubiquitous protein found in the skin that binds a host of proteases, growth factors (TGF-b,
PDGF, b-NGF) and inflammatory cytokines (TNF-α, IL-1b, IL-2, IL-6, IL-8), was found to be
significant unregulated in atopic skin. Because it has a known an important role in the
modulation of inflammation, as its binding acts to inhibit the majority of these mediators,
this overexpression may in fact be a compensatory mechanism for ongoing disease.
Importantly, when activated through chloramination by, for example, bleach, it can very
effeectively scavenge these pro-inflammatory mediators. Thus leading to the second goal of
this study.

One of the driving forces for selecting the various “itch or anti-itch factors” is that all can be
augmented by hypochlorous acid, which is what bleach disassociates into when mixed with
water. Bleach baths have been used for years as an adjuvant to treatment in atopic
dermatitis. When mixed with water, sodium hypochlorite (NaOCL) produces hypochlorous acid
(HOCl), a compound stable between pH 3 and 6. HOCl is known to have antimicrobial properties,
and therefore it was believed that bleach baths lowered bacterial burden on the skin and
prevented and treated localized skin infections and colonization by organisms such as
Staphylococcus aureus. Recent studies have found that HOCl intact has potent anti-inflammatory
properties, and therefore we sought to expand this data by evaluating whether factors
augmented by HOCl are overexposed in atopic dermatitis skin, giving some insight into how
bleach bathes or HOCl products may aid in disease and symptom management.

• Dr. Friedman: I hope these findings encourage and give physicians confidence to utilize
bleach bathes and HOCl products in their management of atopic dermatitis. It is but one part
of our armament, one which has significant data supporting its use. When used correctly,
meaning the correct concentration and pH, HOCl may have a potent effect on itch through its
interference with the studied factors as well as activation of α-2 macroglobulin.

this study?
• Dr. Friedman: I think this study is hopefully a stimulus for prospective clinical trials. Further
research may elucidate the intricacies of HOCl and other oxidative substances’ role in these
pathways, and therapeutic strategies for minimizing their pruritogenic potential. Atopic
dermatitis (AD) is a chronic dermatologic disorder affecting 10-20% of children in the first
decade of life, with about two-thirds having persistent disease into adulthood – it’s not going
anywhere and therefore we need better and more innovative ways to manage it
• Citation:
• Identifying new biologic targets in atopic dermatitis (AD): A retrospective histologic analysis
• Angelo Landriscina, BAJamie Rosen, BA Joseph Albanese, MD Bijal Amin, MD Adam J.
Friedman, MD
• DOI: http://dx.doi.org/10.1016/j.jaad.2015.06.036
• JAAD Published Online: July 10, 2015

Evaluating Liver Fat On Cardiac CT Helps Predict Risk vs Benefit of Statin Therapy
Venkatesh L. Murthy, MD, PhD, FACC, FASNC
University of Michigan
and Dr. Ravi Shah MD
Beth Israel Deaconess Medical Center
•
MedicalResearch: What is the background for this study?
• Response: Recent changes recommend statin therapy for cardiovascular risk reduction in an
increasingly large number of Americans. Conversely, a number of studies have identified an
increased risk of diabetes with statin treatment. Thus, there is increasing need for tools to
target statin therapy to those with a favorable risk-benefit profile.

•
• MedicalResearch: What are the main findings?
• Response: In our study, we analyzed data from 3,153 individuals from the Multi-Ethnic Study
of Atherosclerosis who underwent CT scanning at baseline for assessment of calcium score.
The CT scans were analyzed to assess liver attenuation as a measure of the amount of liver
fat. We demonstrated that high liver fat doubled the risk of diabetes over a median of 9 years
of follow-up. Importantly, statin therapy also doubled the risk of diabetes. The two together
had an additive effect, even after adjusting for BMI, age, gender, family history of diabetes,
waist circumference, lipids, hsCRP and exercise habits. As in prior studies, the risk of
cardiovascular disease (CVD) events increased with increasing calcium score, as has
previously been shown in MESA and in other studies.
• We then divided the cohort into six groups based on calcium score (0, 1-100 and >100) and
liver fat (low/high). Using published data from meta-analyses of statin trials, we computed
the number needed to treat to prevent one hard CVD event for statin therapy. Using data
from our study, we computed the number needed to harm to cause one additional case of
diabetes from statin therapy. The numbers needed to treat with ranged from 29-40 for
calcium score of >100 to 218-252 for calcium score of 0. Conversely, the numbers needed to
harm were approximately 63-68 for those with low liver fat versus 22-24 for those with high
liver fat. Thus the combination of calcium score and liver fat assessment, from a single
standard calcium score scan, allows for physicians to provide better assessment of risk and
benefit of statins in discussion with their patients.

• Response: While it is well established that calcium score scans can help personalize CVD risk
assessment and select optimal patients for statin therapy based on identifying those with
greatest potential for benefit, a simple evaluation of the portion of the liver which is seen at
the edges of the scan can help physicians assess the risks of statin therapy as well. Although
not every patient needs this type of scan, when a calcium score is ordered, assessment of
liver fat may be a no or low cost additional assessment with additional clinically important
information.

• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Response: Exploration of the mechanisms whereby statins and liver fat may contribute to
diabetes remains a very active area of investigation. We also do not yet have definitive
evidence that a strategy of using calcium score combined with liver fat will optimize the
balance of cardiovascular and diabetes risks or is cost effective.
• Citation:
• Liver Fat, Statin Use, and Incident Diabetes: The Multi-Ethnic Study of Atherosclerosis
• AtherosclerosisIn Press, Accepted Manuscript, Available online 15 July 2015
• Ravi V. Shah, Matthew A. Allison, Joao A.C. Lima, David A. Bluemke, Siddique A. Abbasi,
Pamela Ouyang, Michael Jerosch-Herold, Jingzhong Ding, Matthew J. Budoff, Venkatesh L.
Murthy

Genetic Risk Score Did Not Predict Recurring Events After Myocardial Infarction
Christopher Labos MD CM, MSc FRCPC
Division of Epidemiology, Biostatistics and Occupational Health
McGill University Montreal, Quebec
Canada
Response: There have been great advances in the field of genetics in recent years. Especially in
cardiology, a number of genetic variants have been identified that are associated with
cardiovascular disease. But it is not clear how useful these variants are in terms of predicting
future evens in patients that have already suffered a myocardial infarction. What we found in our
study is that a genetic risk score composed of the 30 most common genetic variants associated
with cardiovascular diseases was not useful in predicting recurrent events in the first year after a
patient suffered a myocardial infarction.

Canada
• Response: While genetics is clearly important for the development of atherosclerosis over
the long-term, ordering a genetic panel in patients after an myocardial infarction is not likely
to provide any new useful information in the short-term beyond what physicians can get
from asking about standard risk factors in the post-ACS setting. So a genetic risk score would
not necessarily change treatment approaches in the early post-ACS setting for the patient.

Canada
this study?
• Response: It will be interesting to see if other researchers can find utility for using a genetic
risk score in certain subgroups of patients or in longer follow-up periods where the
mechanism of disease may be different. A recent study suggests that people with a high
genetic risk score may have more benefit from lipid-lowering from statins which, if replicated
by other groups, would have important clinical implications for using a genetic profile after an
ACS. It will also be important to re-examine the issue as new genetic variants are discovered
in the future that may provide additional predictive capacity.
• Citation:
• Utility of a Genetic Risk Score to Predict Recurrent Cardiovascular Events 1 Year After an
Acute Coronary Syndrome: A Pooled Analysis of the RISCA, PRAXY, and TRIUMPH Cohorts
• Atherosclerosis Available online 17 July 2015
• Christopher Labos, Sara C. Martinez, Rui Hao Leo Wang, Petra A. Lenzini, Louise Pilote, Peter
Bogaty, James M. Brophy, James C. Engert, Sharon Cresci, George Thanassoulis

• MedicalResearch: What is the background for this study?
• Response: Recent changes recommend statin therapy for cardiovascular risk reduction in an
increasingly large number of Americans. Conversely, a number of studies have identified an
increased risk of diabetes with statin treatment. Thus, there is increasing need for tools to
target statin therapy to those with a favorable risk-benefit profile.

• Response: In our study, we analyzed data from 3,153 individuals from the Multi-Ethnic Study
of Atherosclerosis who underwent CT scanning at baseline for assessment of calcium score.
The CT scans were analyzed to assess liver attenuation as a measure of the amount of liver
fat. We demonstrated that high liver fat doubled the risk of diabetes over a median of 9 years
of follow-up. Importantly, statin therapy also doubled the risk of diabetes. The two together
had an additive effect, even after adjusting for BMI, age, gender, family history of diabetes,
waist circumference, lipids, hsCRP and exercise habits. As in prior studies, the risk of
cardiovascular disease (CVD) events increased with increasing calcium score, as has
previously been shown in MESA and in other studies.
• We then divided the cohort into six groups based on calcium score (0, 1-100 and >100) and
liver fat (low/high). Using published data from meta-analyses of statin trials, we computed
the number needed to treat to prevent one hard CVD event for statin therapy. Using data
from our study, we computed the number needed to harm to cause one additional case of
diabetes from statin therapy. The numbers needed to treat with ranged from 29-40 for
calcium score of >100 to 218-252 for calcium score of 0. Conversely, the numbers needed to
harm were approximately 63-68 for those with low liver fat versus 22-24 for those with high
liver fat. Thus the combination of calcium score and liver fat assessment, from a single
standard calcium score scan, allows for physicians to provide better assessment of risk and
benefit of statins in discussion with their patients.

Why do Asian Americans Live So Much Longer Than Other Ethnic Groups?
Francesco Acciai
Department of Sociology
Pennsylvania State University
University Park, PA
• Response : Life expectancy in the United States varies greatly by race. Asian–Americans enjoy
the greatest longevity, with a nearly 8 year mortality advantage on whites
• Response : Life expectancy in the United States varies greatly by race. Asian–Americans enjoy
the greatest longevity, with a nearly 8 year mortality advantage on whites. This advantage
can derive from two separate processes. One, from a more favorable allocation of causes of
death (incidence effect); i.e. from the fact that Asians tend to die of causes that strike on
average at older ages while avoiding causes of death that afflict the young. Two, they can die
of the same causes of death, but at an older age (age effect). By using the age-incidence
decomposition method we are able to distinguish and quantify these contributions to the 7.8
year gap in life expectancy between Asians and whites.

Francesco Acciai
University Park, PA
• Response: Nearly 90% (or 6.9 years) of this gap is attributable to the fact that Asians tend to
outlive whites regardless of the cause of death (age effect). The causes that contribute the
most to the gap are heart disease (24%) and cancers (18%). The incidence effect accounts for
the remaining 0.9 years of the Asian-white gap in life expectancy. Moreover, sex-specific
analyses show that men contribute somewhat more to the gap than women do (55% vs
45%), primarily because Asian–white differences in mortality are greater among men than
among women with respect to suicide, traffic accidents and accidental poisoning.

Francesco Acciai
University Park, PA
this study?
•
Response: Since Asians and whites generally succumb to the same causes of death,
researchers can focus on why Asian victims tend to outlive white victims. Are there any
individual (e.g. health behaviors) or contextual (e.g. family network) factors that contribute to
the Asian mortality advantage? Is the onset of disease delayed for Asians, or do they live
longer while in poor health? Studies of mortality gaps, then, need to be juxtaposed with
studies of morbidity gaps. Future research should also make use of the heterogeneity of
Asian-Americans themselves (their country of origin, generation, length of time in the USA
and so on) as leverage for understanding the exceptional life expectancy of Asian-Americans.
Lastly, nativity data should be routinely transferred from death certificates to data archives to
permit the comparison of US-born and foreign-born Asians. The best studies will compare
those data with data from countries of origin to test more directly the idea that Asians live
longer in America because of self-selection, that is, the Asians who move to America tend to
be healthier than those who do not migrate.

Francesco Acciai
University Park, PA
• Response : The fact that Asians in America live so much longer than other Americans
suggests that the longevity of other groups can be increased. Clinicians should be aware of
this difference, and they should be especially alert to differences in the life style and habits of
Asians that might account for their longer lifespans. Once researchers and clinicians have a
better understanding of the protective factors that contribute to Asian longevity, clinicians
should disseminate this knowledge so that patients know not only that living a longer (and
healthier) life is possible, but also the actions that are most likely to help them achieve this
goal.
• Citation:
• Pinpointing the sources of the Asian mortality advantage in the USA
• Francesco Acciai, Aggie J Noah, Glenn Firebaugh
• J Epidemiol Community Health jech-2015-205623Published Online First: 1 June 2015
doi:10.1136/jech-2015-205623

Small Subset of Cells Make HER2+ Breast Cancer Resistant To Treatment
Niels de Jonge, Ph.D
Head of the Innovative Electron Microscopy group
German Cancer Research Center (DKFZ) in Heidelberg
University of Freiburg
Response: HER2 membrane proteins play a special role in certain types of breast cancer:
amplified levels of HER2 drive unrestricted cell growth. HER2-tailored antibody-based
therapeutics aim to prevent cancer cell growth. However, two-thirds of HER2 positive breast
cancer patients develop resistance against HER2-targeting drugs. The reason for this is not
yet understood. We now found out, that HER2 dimers appeared to be absent from a small
sub-population of resting SKBR3 breast cancer cells. This small subpopulation may have self-
renewing properties that are resistant to HER2-antibody therapy and thus able to seed new
tumor growth.

• Response: With our new analytical capabilities to study the functional state of HER2 at he
sub-cellular level, we provide a novel approach to study the functioning of HER2 proteins and
obtained data not discovered before with existing methods. Possibly, research on the effect
of HER2-targeting drugs using this new method, will lead to a better understanding of the
causes of drug resistance. The effect of medication can now be examined in a new way, which
may possible result in a better therapy with less drug resistance against breast cancer.

this study?
• Response: We aim to study the effect of HER2-targeting drugs on breast cancer cells, and in
particular plan to examine small sub-populations of cells, for example, cancer stem cells. As
found in our published study, small sub-populations of cells exist with a different behavior of
HER2. An exciting question is thus if small sub-populations also exhibit a different response to
these drugs.
• Citation:
• B. Peckys, U. Korf, N. de Jonge. Local variations of HER2 dimerization in breast cancer cells
discovered by correlative fluorescence and liquid electron microscopy. Science Advances,
2015; 1 (6): e1500165 DOI: 10.1126/sciadv.1500165

Unhealthy Weight Linked To Poor Pregnancy Outcomes
Maya Tabet, MS Graduate Research Assistant
Saint Louis University
College for Public Health and Social Justice
Department of Epidemiology St. Louis, MO 63104
• Response: The majority of women in the U.S. have an unhealthy weight before they start
pregnancy, most of them being overweight or obese. It is well-known that having an
unhealthy weight before pregnancy increases the likelihood of having adverse outcomes for
the mother and baby. However, this study is the first to examine the likelihood of adverse
outcomes in a second pregnancy among women who had an unhealthy weight before a first
pregnancy that had no complications.

• Response: Our study involved 121,049 women in Missouri who delivered their first 2
singleton pregnancies between 1989 and 2005. Findings revealed that women who were
underweight before a first uncomplicated pregnancy had a 20% increased likelihood of
having a shorter gestation and a 40% increased likelihood of having a small baby for
gestational age in the second pregnancy, as compared to women who had a healthy weight
before their first pregnancy.
• Also, women who were obese before a first uncomplicated pregnancy had a 55% increased
likelihood of having a large baby for gestational age, a 156% increased likelihood of having
preeclampsia, and an 85% increased likelihood of having a cesarean delivery. Babies born to
these women also had a 37% increased likelihood of dying in the first 28 days of their life.

• Response: Second-time mothers who had an unhealthy weight when they started their first
pregnancy have an increased likelihood of poor pregnancy outcomes even when their first
pregnancy was uncomplicated. In addition, some of the risk remains even if they reached a
normal weight by their second pregnancy.
• Health professionals should counsel women of reproductive age on the potential pregnancy
complications that an unhealthy weight may engender. Women who had a suboptimal weight
before their first pregnancy should be monitored for complications in their subsequent
pregnancies even if they had no complications in their first pregnancy or if they reached a
healthy weight by their second pregnancy.

this study?
• Response: Our finding that starting pregnancy with an unhealthy weight could pose problems
in subsequent pregnancies carries considerable public health implications and is of great
clinical significance.
• Future research should explore the mechanism by which an unhealthy weight in a first
uncomplicated pregnancy may increase the risk of adverse outcomes in a second pregnancy.
• Citation:
• Am J Obstet Gynecol. 2015 Jun 20. pii: S0002-9378(15)00631-6. doi:
10.1016/j.ajog.2015.06.031. [Epub ahead of print]
• Prepregnancy body mass index in a first uncomplicated pregnancy and outcomes of a second
pregnancy.
• Tabet M1, Flick LH2, Tuuli MG3, Macones GA3, Chang JJ2.

Soda Linked To Higher Risk of Diabetes, Regardless of Obesity Status
MedicalResearch.com Interview with: Dr. Fumiaki Imamura Ph.D.
MRC Epidemiology Unit
University of Cambridge
Dr. Imamura: Soft drink consumption is associated with risk of diabetes, but whether or not the
association persists after controlling for obesity status is not known. Diet drinks and fruit juice
may be good alternatives to soft drinks. However, while obese individuals may consume diet
drinks or fruit juice instead of sugar-sweetened soft drinks, evidence was weak to determine
whether or not consuming these beverages is associated with risk of diabetes.

MedicalResearch.com: Medical Research Exclusive Interviews July 20 2015

MedicalResearch.com: Medical Research Exclusive Interviews July 20 2015

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (10)

Similar to MedicalResearch.com: Medical Research Exclusive Interviews July 20 2015

Similar to MedicalResearch.com: Medical Research Exclusive Interviews July 20 2015 (20)

More from Marie Benz MD FAAD

More from Marie Benz MD FAAD (18)

Recently uploaded

Recently uploaded (20)

MedicalResearch.com: Medical Research Exclusive Interviews July 20 2015