MedicalResearch.com: Medical Research Exclusive Interviews June 6 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
June 6 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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Dietary Fiber May Reduce Risk Of Diabetes
MedicalResearch.com Interview with:
Dagfinn Aune, PhD student
Norwegian University of Science and Technology and
Imperial College London
Medical Research: What is the background for this study? What are the main findings?
Response: There are more than 360 million people worldwide that are affected by diabetes, and
this number is projected to increase to more than 550 million by 2030, with serious
consequences for the health and economy of both developed and developing countries. While
previous research has found an association between increased dietary fibre intake and a reduced
risk of developing type 2 diabetes, most of these data come from the United States, and amounts
and sources of fiber intake differ substantially between countries. In this article the we evaluated
the associations between total fiber as well as fiber from cereal, fruit, and vegetable sources, and
new-onset type 2 diabetes in a large European cohort across eight countries, in the EPIC-InterAct
Study (and included 12403 type 2 diabetes cases and 16835 sub-cohort members). We also
conducted a meta-analysis where we combined the data from this study with those from 18
other independent studies from across the globe.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

• We found that participants with the highest total fiber intake (more than 26 g/day) had an
18% lower risk of developing diabetes compared to those with the lowest total fiber intake
(less than 19g/day), after adjusting for the effect of other lifestyle and dietary factors. When
the results were adjusted for body mass index (BMI) as a marker of obesity, higher total fiber
intake was found to be no longer associated with a lower risk of developing diabetes,
suggesting that the beneficial association with fiber intake may be mediated at least in part
by BMI. In other words, dietary fiber may help people maintain a healthy weight, which in
turn reduces the chances of developing type 2 diabetes.
• In a meta-analysis of the EPIC-InterAct study and 18 other independent studies (>41000 type
2 diabetes cases) we found that the risk was reduced by 9% for each 10 g/day increase in
total fiber intake and 25% for each 10 g/day increase in cereal fiber intake. There was no
statistically significant association between fruit or vegetable fiber intake and diabetes.

• Medical Research: What should clinicians and patients take away from your report?
• Response: The current study suggest that people can reduce their risk of type 2 diabetes by
increasing fiber intake. Since the association appeared to be driven mostly by cereal fiber
intake, increasing intake of cereal fiber may be particularly important to reduce the risk of
type 2 diabetes. Previous research has suggested that a high intake of whole grains may
reduce type 2 diabetes risk and the current findings on cereal fiber are consistent with these
findings.

• Medical Research: What recommendations do you have for future research as a result of
this study?
• Response: Any additional studies could further investigate the association between fiber
intake and types of fiber and diabetes risk in different geographic locations as well as further
try to clarify the mechanisms by which fiber may reduce diabetes risk.
• Citation:
• The InterAct Consortium. Dietary fibre and incidence of type 2 diabetes in eight European
countries: the EPIC-InterAct Study and a meta-analysis of prospective studies. Diabetologia,
May 2015 DOI: 10.1007/s00125-015-3585-9

Smartphone-Based Vision Test For Community-Based Evaluations
Andrew Bastawrous, MRCOphth
International Centre for Eye Health, Clinical Research Department
London School of Hygiene and Tropical Medicine (LSHTM), London, England
• Medical Research: What is the background for this study? What are the main findings?
Dr. Bastawrous: As part of my PhD with the International Centre for Eye Health at the
London School of Hygiene & Tropical Medicine, I led the follow-up of a major cohort study of
eye disease [http://www.biomedcentral.com/1471-2415/14/60] following up 5,000 people in
100 different locations across the Great Rift Valley in Kenya. It was really challenging, two-
thirds of the locations had no road access or electricity and we were carrying over £100,000
worth of fragile eye equipment and a team of 15 people in two vans to be able to carry out
high quality measures of eye disease and answer some important questions for planning eye
services.
• What we found was that in the most difficult to reach locations we would find lots of people
waiting to see us who had been unnecessarily blind from preventable/treatable diseases.
Despite the locations having no roads, electricity and often no water, nearly all the locations
had good phone signal.
• Together with a brilliant team of developers, engineers and ophthalmologists we developed a
suite of smartphone based tests to see if we could replace some of the standard equipment
being used, in the hope that we could make it more portable and easier for non-specialists to
perform so that ultimately the most high-risk individuals could be reached and treated.

• This paper describes one of those tests, the visual acuity test – Peek Acuity.
• Our field workers tested patients in their own homes using a standard card based Snellen
chart (the type of vision test most non-ophthalmic healthcare workers are familiar with and
has been the most commonly used acuity test for several decades now) and Peek Acuity. The
same tests were repeated by the same healthcare worker in the clinic the following day as
well as a reference standard vision test (LogMAR ETDRS) performed by an eye trained clinical
officer.
• This allowed us to perform “test re-test”, a measure of a tests repeatability. i.e. if you have
the same test at two separate time points we would expect the the measures to be very
close. We found that for both Peek Acuity and Snellen they were highly repeatable. An
advantage of Snellen is the speed of the test, Peek Acuity came out slightly quicker overall.
We also found when compared to the reference standard test, Peek Acuity was highly
comparable and within a clinically acceptable limit of difference.

• Dr. Bastawrous: What should clinicians and patients take away from your report?
• Dr. Bastawrous: Vision testing is a crucial part of an ophthalmic examination and we
demonstrated that it was possible to create a test that was independent of language (i.e. you
don’t need to recognise English letters), it could be performed by non eye care workers, is
more objective than standard vision tests as the examiner records the patients responses
through gestures (swiping and shaking) without needing to know if the patient is giving the
correct answer. The result is presented in the examiners preferred notation (LogMAR, Snellen
metric or imperial) and we are able to the simulate the patients vision over a live video feed
using SightSim(TM) to share the result in a more meaningful way.
• However, a sight test alone, whichever way it is performed will not lead patients receiving
eye treatment, if it is integrated in to a health system it can make up an important
component of a visually impaired patient being identified. We are currently trialing systems
that support automated referral and SMS reminders as well as incorporating other
smartphone based tests (retinal and lens examinations, visual fields, colour and contrast).

this study?
• Response: Future research should include using the test in different populations across
different handsets in real world scenarios. We have recently completed a randomised control
trial for a school screening program in Kenya where teachers screened over 20,000 children
for visual impairment in schools. We hope to have the results of this later this year.
• Peek Acuity will be freely available from the Google Play store once it has completed
certification as a medical device (CE Class I) and will follow on iOS soon after. If you want to
stay updated on releases please sign up to our newsletter at www.peekvision.org
• Peek is a Portable Eye Examination Kit that uses smartphones to test eyes easily and
affordably anywhere in the world. It has been developed through a collaboration between
the London School of Hygiene & Tropical Medicine, the University of Strathclyde and the NHS
Glasgow Centre for Ophthalmic Research.
• Citation:
• Bastawrous A, Rono HK, Livingstone IT, et al. Development and Validation of a Smartphone-
Based Visual Acuity Test (Peek Acuity) for Clinical Practice and Community-Based Fieldwork.
JAMA Ophthalmol. Published online May 28, 2015. doi:10.1001/jamaophthalmol.2015.1468.

Circulating Tumor Test May Identify Breast Cancer Patients Who Will Not Benefit From Endocrine Therapy
Daniel F. Hayes, M.D.Stuart B. Padnos Professor of Breast Cancer Research
University of Michigan Comprehensive Cancer Center
Ann Arbor MI
Dr. Hayes: We have developed a circulating tumor cell endocrine therapy index that we
hypothesize will identify patients with estrogen receptor positive metastatic breast cancer but
who will not benefit from endocrine (anti-estrogen) therapy. We can now semi-quantifiably
measure er as well as bcl2, her2, and ki67 in a highly accurate and reproducible fashion. We are
now conducting a multi-institutional prospective trial in North America (the Circulating Tumor
Cell-Endocrine Therapy COMETI study) to determine if our hypothesis is correct.

Ann Arbor MI
• Dr. Hayes: Currently, the Circulating Tumor Cell-Endocrine Therapy has no role in standard
clinical practice. If validated, we would hope it could be used to make clinical decisions
regarding use of endocrine therapy or not.

Ann Arbor MI
this study?
• Dr. Hayes: the COMETI trial is ongoing. We also propose that ctc-phenotyping (such as the
ctc-eti) will complement the exciting new field of circulating cell free tumor plasma dna
analysis for mutations that may be important in driving cancer behavior.
• Citation:
• Development of Circulating Tumor Cell-Endocrine Therapy Index in Patients with Hormone
Receptor–Positive Breast Cancer
• Costanza Paoletti, Maria C. Muñiz, Dafydd G. Thomas, Kent A. Griffith, Kelley M. Kidwell,
Nahomi Tokudome, Martha E. Brown, Kimberly Aung, M. Craig Miller, Dorothy L. Blossom,
Anne F. Schott, N. Lynn Henry, James M. Rae, Mark C. Connelly, David A. Chianese, and Daniel
F. Hayes
• Clin Cancer Res June 1, 2015 21:2487-2498; Published OnlineFirst November 7, 2014;
doi:10.1158/1078-0432.CCR-14-1913

State Strategies Have Had Limited Effect On Organ Donations For Transplantation
Paula Chatterjee, MD, MPH
Department of Medicine, Brigham and Women’s Hospital
Harvard Medical School Boston, Massachusetts
Dr. Chatterjee: Thousands of patients die every year due to organ shortages. Finding ways to
address this public health issue is critical. States have designed a variety of strategies to
promote organ donation and transplantation, however we don’t know if any of these
strategies have been successful. The goal of our study was to try to figure out which
strategies have been most successful in terms of increasing organ donation and
transplantation.
• We found that states have implemented a wide and creative set of strategies, but
unfortunately, it seems that these strategies have had almost no effect on increasing organ
donation and transplantation. In states that adopted these strategies compared to those that
did not, the rates of donation and transplantation increased at nearly the same rate over the
past two decades. The only strategy that seemed to have a small effect was when states
created revenue pools dedicated toward organ donation activities.

• Dr. Chatterjee: We think the main takeaway is that we need new strategies to bridge the gap
between the number of people waiting for organs and the number of organ donors in this
country. It may be that different populations respond to these strategies differently, and
states may need to take a more targeted approach when it comes to promoting organ
donation. This may differ greatly from state to state, or even from community to community,
but it will likely be important to pursue a granular approach.

this study?
• Dr. Chatterjee: Future work should aim to better identify what exactly is done with state-
based revenue pools designed to promote donation. Revenue pools are often made up of
voluntary contributions from individuals and groups to fund activities related to donor
recruitment (such as community outreach, worksite campaigns, hospital-based
interventions). The specific uses of these funds remain unknown. It will be important to
understand how much this strategy varies from state-to-state, and whether certain uses of
these funds more successful than others. With more information on a local context, we may
be better able to identify successful strategies.
• Citation:
• Chatterjee P, Venkataramani AS, Vijayan A, Wellen JR, Martin EG. The Effect of State Policies
on Organ Donation and Transplantation in the United States. JAMA Intern Med. Published
online June 01, 2015. doi:10.1001/jamainternmed.2015.2194.

Diabetic Foot Disease and Amputations Vary By Ethnicity
Tom E. Robinson
School of Population Health
University of Auckland, New Zealand
• Response: Diabetic foot disease affects up to 50% of people with diabetes and lower limb
amputation is a serious complication that has a great impact both on patient quality of life
and healthcare costs. Foot complications are however potentially preventable with good
diabetes and foot care and early intervention. There is international evidence of unexplained
ethnic variations in the incidence of lower limb amputation. This study found that ethnicity
was strongly associated with risk of lower limb amputation. For example, New Zealand Maori
people with diabetes have 63% higher rates of lower limb amputations and this increased risk
is not altered by controlling for a range of demographic and clinical risk factors. Asian New
Zealander’s have much lower risks of amputation but this may, at least in part, be explained
by the ‘healthy migrant effect’.
• Response: These findings support targeted early intervention for ethnic groups at risk.
Clinicians, researchers and decision makers in other countries need to consider whether such
inequalities also exist in their own communities.

Diabetic Foot Disease and Amputations Vary By Ethnicity
Tom E. Robinson
School of Population Health
University of Auckland, New Zealand
this study?
• Response: More research needs to be undertaken to try to understand the causes of
increased amputation rates in ethnic groups at risk so effective interventions may be
planned.
• Citation:
• Ethnicity and risk of lower limb amputation in people with Type 2 diabetes: a prospective
cohort study
• E. Robinson, T. Kenealy,M. Garrett, D. Bramley2, P. L. Drury3 and C. R. Elley1
• Diabetic Medicine DOI: 10.1111/dme.12807

ACA Enrollees More Likely To Use Medicines For Hepatitis and HIV
MedicalResearch.com Interview with: Julie M. Donohue, Ph.D.
Associate professor and Vice Chair for Research
Graduate School of Public Health Department of Health Policy and Management
University of Pittsburgh
Dr. Donohue: We looked at data on medication use from January through September 2014 on 1
million Affordable Care Act-established marketplace insurance plan enrollees. Our analysis found
that among people who enrolled in individual marketplaces, those who enrolled earlier were
older and used more medication than later enrollees. Marketplace enrollees, as a whole, had
lower average drug spending per person and were less likely to use most medication classes than
patients enrolled in employer-sponsored health insurance. However, marketplace enrollees were
much more likely to use medicines for hepatitis C and for HIV, which is particularly important
given the general concerns about the rising costs of these medications for consumers.

• Dr. Donohue: The results of our study are perhaps more significant in terms of guiding policy
decisions. The insights gained by our analysis have implications for the marketing of ACA
insurance plans, benefit design and out-of-pocket costs, as well as public health ramifications,
such as expanding treatment for infectious diseases like HIV and hepatitis C. Our findings also
show that the ACA marketplaces staved off early concerns about skyrocketing insurance
premiums by successfully attracting younger, healthier enrollees to offset higher costs from
older, less healthy people.

this study?
• Dr. Donohue: From a public health perspective, our analysis indicates that the ACA is
successfully helping more vulnerable populations with lower incomes gain access to
medications needed to treat chronic and acute conditions. Given the unprecedented
expansion of insurance coverage with the ACA, close monitoring of its impact must continue.
• Citation:
• Early Marketplace Enrollees Were Older And Used More Medication Than Later Enrollees;
Marketplaces Pooled Risk
• Julie M. Donohue, Eros Papademetriou, Rochelle R. Henderson, Sharon Glave Frazee,
Christine Eibner, Andrew W. Mulcahy, Ateev Mehrotra, Shivum Bharill, Can Cui, Bradley D.
Stein, and Walid F. Gellad
• Health Aff 10.1377/hlthaff.2015.0016; published ahead of print May 27, 2015,
doi:10.1377/hlthaff.2015.0016

Severely Injured Patients Do Better In High Level Trauma Centers
Huiyun Xiang, M.D., M.P.H.
Center for Pediatric Trauma Research
The Research Institute at Nationwide Children’s Hospital Columbus, OH
Response: In the United States trauma system, the most severe injuries ideally should receive
definitive treatment at level I or level II trauma centers, while less severe injuries should
receive treatment at level III or nontrauma centers. “Undertriage” occurs when a severe
injury receives definitive treatment at a lower level trauma center instead of a level I or level
II trauma center. But no study had used nationally representative data to evaluate mortality
outcomes of undertriage at nontrauma centers.
• Our study found detrimental consequences associated with undertriage at nontrauma
centers. There was a significant reduction in the odds of emergency department (ED) death –
by approximately half – in severely injured trauma patients who were properly triaged to a
level I or level II trauma center versus those who were undertriaged to a nontrauma center.
We also found that patients with moderate injuries may not have a reduction in the odds of
ED death when triaged to a level I or level II trauma center instead of a nontrauma center.
That suggests a possible threshold of injury severity when triaging trauma patients.

• Response: It is critically important that a severely injured trauma patient be properly triaged
to a level I or level II trauma center. There is proof that odds of ED mortality decrease
substantially when that happens. Improving triage protocols, accommodating additional
trauma victims at high level trauma centers and/or improving the response of nontrauma
centers to major trauma may produce better outcomes.

this study?
• Response: A previous study found that level I and level II trauma centers would have to
expand major trauma capacity by more than 51% to accommodate all trauma patients with
moderate to severe trauma. That is likely not feasible. Those high level trauma centers would
only have to expand severe trauma capacity by 6.2%, however, to accommodate all trauma
patients with severe trauma. The feasibility of that increase should be studied further.
• Citation:
• Comparative Study of ED Mortality Risk of US Trauma Patients Treated at Level I & Level II vs.
Nontrauma Centers
• Vickers, Brian P. et al.
• The American Journal of Emergency Medicine Published Online: May 15, 2015
DOI: http://dx.doi.org/10.1016/j.ajem.2015.05.010

Post Menopausal Hormones Improve Mood But Not Cognition
MedicalResearch.com Interview with: Dr.Carey Gleason Ph.D
School of Medicine and Public Health, University of Wisconsin
Geriatric Research, Education and Clinical Center
William S. Middleton Memorial Veterans Hospital
Wisconsin Alzheimer’s Disease Research Center, Madison, Wisconsin
• Dr. Gleason: In this response I refer to hormone therapy (HT), which was formally called
hormone “replacement” therapy. In particular, we examined menopausal HT, i.e., the use of
HT during the menopausal transition to address menopausal symptoms.
Dr. Gleason: The WHI Memory Study (WHIMS) suggested that HT was associated with
cognitive harm for women age 65 and older. In contrast, we found that the cognitive
performance of women randomized to receive menopausal hormone therapy did not differ
from that of women randomized to receive the placebo. On a measure of mood states,
women treated with conjugated equine estrogens showed improvements compared to those
on placebo.

• Dr. Gleason: If a woman chooses to manage her menopausal symptoms with hormone
therapy, she can be reassured that she is not harming her cognition. Moreover, she may also
experience some mood benefits.

this study?
• Dr. Gleason: It would be beneficial to follow the women in the KEEPS-Cog to evaluate the
long-term effects of menopausal hormone therapy used during the transition period. There is
a school of thought that there is a “critical window” for HT, during which HT exposure may be
most beneficial for the brain. This is supported by basic science data. It has been proposed
that the women enrolled in the WHIMS were given hormone therapy outside of the critical
window, thus accounting for the unexpected finding of harm for some women. In contrast,
women enrolled in the KEEPS-Cog were given HT during the critical window; follow-up would
allow us to test this hypothetical critical window.
• Citation:
• PLoS Med. 2015 Jun 2;12(6):e1001833. doi: 10.1371/journal.pmed.1001833. eCollection
2015.
• Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women:
Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study.
• Gleason CE1, Dowling NM2, Wharton W3, Manson JE4, Miller VM5, Atwood CS1, Brinton EA6,
Cedars MI7, Lobo RA8, Merriam GR9, Neal-Perry G10, Santoro NF11, Taylor HS12, Black DM13,
Budoff MJ14, Hodis HN15, Naftolin F16, Harman SM17, Asthana S1.

Sun Sensitive, Skin Cancer Prone Patients Responsive To Prevention Messages
Catherine M. Olsen, PhD
Population Health Department
QIMR Berghofer Medical Research Institute, Queensland, Austra
• MedicalResearch: What is the background for this study?
• Dr. Olsen: Effective skin cancer control requires two strategies: regular sun protection to
prevent new cancers from occurring and early detection assisted by periodic skin
examinations. The aim of our study was to describe the prevalence and predictive factors for
sun protection and skin examination practices of adults in Queensland, Australia, a region
that experiences the highest rates of skin cancer in the world. We were particularly
interested in whether sun protection and skin examination practices differed between those
with and without a previously confirmed melanoma and/or treatment for other skin lesions.
• MedicalResearch: What are the main findings?
• Dr. Olsen: The prevalence of both sun protection and skin examination practices was
generally high in this large cohort of people who experience high levels of ambient sun
exposure.
• People who had been diagnosed with a melanoma or other skin lesion were more likely than
those without to report sun protection practices including regular use of sunscreen and
wearing hats.
• The strongest predictor of sun protection practices was having a sun-sensitive skin type, and
the strongest predictor of skin examination practices was having many moles and/or a family
history of melanoma.

Sun Sensitive, Skin Cancer Prone Patients Responsive To Prevention Messages
Catherine M. Olsen, PhD
Population Health Department
QIMR Berghofer Medical Research Institute, Queensland, Austra
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Olsen: Sun protection and skin examinations practices were most frequent among those
with a history of treated skin lesions or sun-sensitive skin types, suggesting that these groups
are receptive to primary and secondary prevention messages.
• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Olsen: Continued public health efforts are needed to promote sun protection and skin
examination practices. Further research should examine attitudes and beliefs regarding these
behaviours in order that public health guidance is delivered effectively.
• Citation:
• Olsen CM, Thompson BS, Green AC, Neale RE, Whiteman DC, for the QSkin Sun and Health
Study Group. Sun Protection and Skin Examination Practices in a Setting of High Ambient
Solar Radiation: A Population-Based Cohort Study. JAMA Dermatol.Published online June 03,
2015. doi:10.1001/jamadermatol.2015.0739.

Myriad Presents Data on Expanded Cancer Genetics and Chemotherapy Susceptibility Testing
MedicalResearch.com spoke with Dr. Jonathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago.
Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at
Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center.
Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke
University Medical Center in Durham, NC, where he also completed his residency and fellowship
training.
• MedicalResearch.com: Can you tell us a little more about your background? How did you come to
work at Myriad?
• Dr. Lancaster: My background and interests lie at the intersection of patient care and the molecular
and genetic understanding of cancer. I completed my MD and Ph.D. in molecular genetics at the
University of Wales, and then came to Duke for a research fellowship and residency training in
Obstetrics & Gynecology. I spent twelve years as a gynecology-oncology surgeon.
• At the Moffitt Cancer Center, I ran a research lab attempting to understand the molecular and
genetic underpinnings of ovarian cancer development and progression. Our translation research
attempted to identify markers, or microRNAs, that help predict ovarian tumors’ response to
chemotherapeutic agents.
• I also have experience in the management and financial issues facing medicine and health care.
While at Moffitt, I was president of the 350-member Moffitt Medical Group, deputy physician-in-
chief and director of the Center for Women's Oncology.
• The opportunity at Myriad Genetics allows me to utilize my experience in all three interests, clinical
care, research and management, to contribute to a broader mission of cancer treatment and
prevention.

• MedicalResearch.com: What studies are being presented at ASCO this year by Myriad
associated researchers?
• Dr. Lancaster: There are 19 abstracts presented by Myriad at ASCO 2015, which is a
testament to the emphasis Myriad places on basic and translational research (Myriad
reinvests $300-400 of the proceeds from every clinical test performed into research). The
studies center around two main themes:
• 1: An enhanced panel of genes, called MyRisk, to test for increased risk of hereditary cancers.
• 2: The use of Homologous Recombination Deficiency (HRD) testing and score, called
MyChoice, which helps clinicians determine which patients may respond best to some
chemotherapeutic agents.

• MedicalResearch.com: What does the MyRisk panel offer over and above the information
learned from BRAC1/2 testing? Why should a patient or clinician want this testing
performed?
• Dr. Lancaster: The MyRisk panel tests for 25 state-of-the-art genes with the goal of
determining who may be at increased risk for certain malignancies even if they are BRAC1/2
negative. The typical patient is one who has a family history of cancer but may have been told
she doesn’t have the ‘breast cancer gene’ because she is BRAC1/2 negative. We now know
that up to 50% of these patients may carry other genes that make them more susceptible to
cancer. Panel testing allows clinicians to identify many more patients at risk for cancer who
would have been missed with more traditional BRAC1/2 testing alone.

• MedicalResearch.com: Let’s say a patient has a mutation in one or more the genes in the
panel. What can she, or her provider, do about it?
• Dr. Lancaster: Identification of a genetic susceptibility to cancer allows the patient to have
more control over the direction of her/his health care efforts and enables the clinician to
practice more precise medicine. For some patients, there is a relief that they don’t carry any
of the enhanced risk genes. For those who do, the knowledge allows the patient to be pro-
active.
• There are three broad categories of prevention strategies:
• Enhanced screening, not just with mammography but also with targeted imaging such as
MRI, biopsies and clinical assessments.
• Preventative medications such as Tamoxifen, which has shown breast cancer risk reduction,
and Oral Contraception, which when taken for five years has been linked to a decreased risk
of ovarian cancer.
• Risk-reducing surgery at an appropriate time for an individual patient, including removal of at
high-risk organs such as breasts, ovaries and tubes.

• MedicalResearch: What is your experience with insurance coverage for genetic panel
testing?
• Dr. Lancaster: There is always a tension between care providers and insurers as new
technology is introduced. The insurance companies naturally would like to know that patients
are receiving real value for their health care dollar and require evidence that the test or
procedure is efficacious. That is one of the important benefits of meetings such as ASCO, in
that providers can demonstrate support for novel and advanced technologies. Panel
technology is employed by most geneticists and is here for stay. We need both the medical
and insurance communities to be supportive of their use for the benefit of their patients.

• MedicalResearch: What is a Homologous Recombination Deficiency (HRD) score? How does
this help a clinician treat a patient with breast or ovarian cancer?
• Dr. Lancaster: In essence, HRD deficiency detects cells with a decreased ability to repair DNA.
Tumor cells with a high HRD score are more likely to be killed by chemotherapeutic agents
aimed at damaging DNA.
• Because tumor cells turn over or reproduce more quickly than other cells, cancers with a high
HRD score are killed at a higher rate than normal cells and thus the patient may experience
more benefit with fewer side effects.
• The Myriad Homologous Recombination Deficiency score range of 0-100 results from the
sum of three ‘fingerprints’ or components:
• LOH: Loss Of Heterozygosity
• TAI: Telomeric Allelic Imbalance
• LST: Large Scale-state Transitions
• A score > 42 indicates a high loss of the Homologous Recombination mechanism or a
Homologous Recombination deficiency, indicating the cells a have limited ability to repair
damaged DNA.

• MedicalResearch: How is a high HRD score useful to the clinician?
• Dr. Lancaster: Two classes of chemotherapeutic agents are known to specifically cause an increase
in DNA breakage: PARP inhibitors and Platinum based chemotherapeutic agents such as cisplatin.
• 1. PARP inhibitors are a growing class of medications that rely on the impaired ability of tumor cells
to repair DNA as the PARP1 protein is important in repairing single-strand DNA breaks.
• The US Food and Drug Administration approved the first PARP inhibitor, in December 2014:
AstraZeneca's Lynparza (olaparib), as a treatment for advanced ovarian cancer patients who have
BRCA mutated tumors.
• 2. In the study presented at this meeting by Dr. Gunter Von Minckwitz, HRD scoring was able to
predict response to neoadjuvant anthracycline and taxane containing chemotherapy in Triple
Negative Breast Cancer.
• (Podium Presentation (Abstract 1004): Prediction of Pathological Complete Response (pCR) by
Homologous Recombination Deficiency (HRD) after Carboplatin-Containing Neoadjuvant
Chemotherapy in Patients With TNBC: Results from GeparSixto. Lead investigator: Gunter Von
Minckwitz, German Breast Group).
• In summary, HRD scoring gives the patient and the clinician a more informed choice as to whether
certain chemotherapeutic agents have a likelihood of success against their particular cancer.

• MedicalResearch: What are you looking forward to in your new position at Myriad?
• Dr. Lancaster: Several things:
• 1: There is real excitement for a paradigm change in the potential of HRD scoring to identify
which patients will benefit from the class of PARP inhibitors and other chemotherapeutic
choices.
• 2: Myriad’s enhanced genetic panels have and will allow more patients to take greater control
of their health care by understanding their predisposition to disease and treatment options.
• 3: I believe Myriad is at an important flexion point in transitioning from a ‘genetic testing
company’ to a Precision Prevention Medicine organization, enabling patients and clinicians to
take advantage of technological advances in translational genetics.

• Citations: Representative Abstracts from ASCO 2015
• myRISK
• Podium Presentation S100BC: Predisposing Germline Mutations in High-Grade ER+HER2-
Breast Cancer Patients Diagnosed <50 Years Of Age. Lead investigator: Judy Garber, MD,
Dana-Farber Cancer Institute
• Poster Board # 181: A study of triple-negative breast cancer patients tested with a 25-gene
panel of hereditary cancer genes. Lead investigator: John Sandbach, M.D., Texas Oncology
Austin
• Poster Board # 338: Outcomes Of Clinical Testing For 50,000 Patients Utilizing A Panel Of 25
Genes Associated With Increased Risk For Breast, Ovarian, Colorectal, Endometrial, Gastric,
Pancreatic, Melanoma & Prostate Cancers. Lead investigator: Eric Rosenthal, Ph.D., and
Myriad Genetic Laboratories
• Poster Board # 357: Multi-Gene Panel Testing In An Unselected Endometrial Cancer
Cohort. Lead investigator: Kari Ring, M.D., MD Anderson Cancer Center

• myCHOICE HRD
• Podium Presentation (Abstract 1004): Prediction of Pathological Complete Response (pCR)
by Homologous Recombination Deficiency (HRD) after Carboplatin-Containing Neoadjuvant
Chemotherapy in Patients With TNBC: Results from GeparSixto. Lead investigator: Gunter
Von Minckwitz, German Breast Group
• Poster Discussion (Poster Board # 132): Combined Homologous Recombination Deficiency
(HRD) Scores and Response to Neoadjuvant Platinum-Based Chemotherapy in Triple Negative
and/or BRCA 1/2 Mutation-Associated Breast Cancer. Lead investigator: Melinda Telli, M.D.,
Stanford University School of Medicine.
• Poster Board # 90: Homologous Recombination Deficiency (HRD) Score Enriches for
Niraparib Sensitive High Grade Ovarian Tumors. Lead investigator: Keith Wilcoxen, Ph.D.,
Tesaro, Inc.
• [wysija_form id="3"]

Pain From Sciatica Not Helped By Oral Steroids
Harley Goldberg, DO
Physical Medicine and Rehabilitation
Kaiser Permanente
Dr. Goldberg: This is the first large-scale randomized, double-blind, placebo-controlled
clinical trial of oral steroids for acute radiculopathy, commonly called sciatica, associated with
a herniated lumbar disk.
• Lumbar radiculopathy (or pain down the leg in a lumbar nerve root distribution) is a common
source of pain and disability for many adults. It is thought that inflammation from a disk
herniation is responsible for many of the symptoms, so giving a powerful anti-inflammatory,
such as steroid medication, might help relieve sciatica symptoms quickly. Prior research has
shown that lumbar diskectomy does not affect the one year outcome for most patients, and
epidural steroid injections do not have strong support by clinical trials. If the use of epidural
steroids injections is based on application of steroid anti-inflammatory to the affected nerve
root(s), perhaps an oral steroid can have affect. Although oral steroids are used by many
physicians and have been included in some clinical guidelines, no large-scale clinical trials of
oral steroids for sciatica have been conducted before.
• Our study found that among patients with acute radiculopathy associated with a herniated
lumbar disk, a short course of oral steroids resulted in only modest improvement in function
and no significant improvement in pain.

Harley Goldberg, DO
Kaiser Permanente
•
Medical Research: What should clinicians and patients take away from your report?
• Dr. Goldberg: For many years, physicians have given their patients these short courses of
steroids under the assumption that they are highly effective for many or most patients. We
now know that may not be true and that most patients given oral steroids will do just as well
with a placebo.
• Each patient with acute radiculopathy (sciatica) will need to weigh the benefits and risks of
taking a short course of oral steroids with their physician. The value of this research lies in
being able to provide patients and physicians with hard evidence so that they can have a
meaningful and informed discussion about balancing the relative benefits and risks
associated with using a short course of oral steroids for acute radiculopathy in the context of
other treatment options.

Harley Goldberg, DO
Kaiser Permanente
this study?
• Dr. Goldberg: We will further evaluate our data set, to assess indications for any further
research questions. More work is needed to identify which patients will have significant
benefit from non-invasive therapies for acute radiculopathy associated with a herniated
lumbar disk.
• Looking more broadly, this study showcases the power and potential of evidence-based
research. I would encourage other researchers to test other common medical practices that
are based on anecdotal evidence to see if they hold up.
• Citation:
• Goldberg H, Firtch W, Tyburski M, et al. Oral Steroids for Acute Radiculopathy Due to a
Herniated Lumbar Disk: A Randomized Clinical Trial. JAMA. 2015;313(19):1915-1923.
doi:10.1001/jama.2015.4468.

Paring Easy Aerobics With Fast Paced Cognitive Tasks May Improve Exercise Intensity
Dr. Lori P. Altmann
Department of Speech, Language, and Hearing Sciences
Center for Movement Disorders and Neurorestoration
University of Florida, Gainesville, Florida
Dr. Altmann: There are a multitude of studies from our labs and others examining the effects of doing a variety of different
cognitive tasks while walking or while maintaining postural control, and the results across studies are consistent—motor
performance usually declines. These “dual task effects” are exaggerated in healthy older adults, and are even more
pronounced in people with Parkinson disease (PD). Our study investigated dual task effects during cycling in healthy older
adults and people with Parkinson disease. In contrast to most studies of this type which typically contrast dual task effects
of two cognitive tasks, we used an array of 12 cognitive tasks of graded difficulty, from very very easy to extremely
difficult. One of our primary goals was to establish that the dual task effects were directly related to the difficulty of the
cognitive task.
• Our primary findings were that, instead of cycling slower when doing various cognitive task, both groups of participants sped
up, and the amount they sped up was directly related to the difficulty of cognitive tasks. In the easiest task, cycling speed
increased by an average of about 25%, With some participants actually doubling their single task speed. There was no
evidence that this increase in cycling speed came as a result of prioritizing cycling over the cognitive tasks, as scores on the
cognitive tasks either remained the same or got slightly better. Interestingly, people with Parkinson disease still showed
faster cycling during the easiest tasks, but did not benefit as much from the dual task as the healthy adults.
• We attribute our findings to arousal that is triggered by both the cycling and the cognitive tasks which increases attentional
resources that can be used for both motor and cognitive processing. We believe the findings haven’t been documented
before because most studies use gait or balance as the motor tasks, and these are much more difficult tasks that demand
more attentional resources, leading to the typical findings of dual task costs instead of dual task benefits. The decrease in
dual task benefits experienced by people with Parkinson disease, we believe, is due to the effects of Parkinson disease on
neurotransmitters. Both cognitive and physiological arousal increase the production of dopamine and norepinephrine in the
brain, and disease processes in Parkinson disease interfere with production of these neurotransmitters, thus limiting
arousal-based increases in attentional resources.

Dr. Lori P. Altmann
• Dr. Altmann: Participants seemed relatively unaware of their increased intensity of exercise
during the easy cognitive tasks. We believe that pairing easy motor tasks like cycling with
easy, engaging, fast-paced cognitive tasks could increase the intensity of exercise in healthy
older adults and other populations, leading to increased physiological and cognitive benefits.

Dr. Lori P. Altmann
this study?
• Dr. Altmann: Future research needs to explore how concomitant cognitive tasks of differing
difficulty interact with different types of aerobic exercise, such as using an elliptical trainer or
walking on a treadmill. This is currently under investigation in our lab.
• In general, we need to test whether exercise programs that include cognitive distraction, such
as exercise using interactive video games, may actually encourage greater effort from
patients, and thus lead to greater health and cognitive benefits of the exercise.
• Citation:
• Unexpected Dual Task Benefits on Cycling in Parkinson Disease and Healthy Adults: A Neuro-
Behavioral Model
• Lori J. P. Altmann , Elizabeth Stegemöller, Audrey A. Hazamy, Jonathan P. Wilson, Michael S.
Okun, Nikolaus R. McFarland, Aparna Wagle Shukla, Chris J. Hass
• Published: May 13, 2015
• DOI: 10.1371/journal.pone.0125470

Coronary CT Angiography Can Detect Soft Coronary Plaque In Asymptomatic Patients
David A. Bluemke, MD, PhD, MsB, FAHA, FACR
Director Radiology and Imaging Sciences Senior Investigator,
National Institute of Biomedical Imaging and Bioengineering
Adjunct Investigator, NLBI, NIDDK
• Dr. Bluemke: Most knowledge about the extent of coronary disease is from high risk patients
who have coronary angiograms. Yet most individuals are symptomatic and have lower
cardiovascular risk, and would not undergo a coronary angiogram.
• Coronary CT angiography can be used to evaluate the extent of plaque in low or moderate
risk individuals. The most concerning type of plaque is “soft plaque”, which can increase or
rupture over time.
• Using coronary CT, all coronary plaque throughout the entire heart was measured.
Importantly, the amount of soft plaque was uniquely associated with risk factors such as LDL,
diabetes, and hypertension.

• Dr. Bluemke: Calcium scores provide a measure of risk, but all coronary plaque can now be
assessed nearly as rapidly, while displaying a full picture of the coronary plaque. Non calcified
plaque extent is closely tied to risk factors, and is the component of plaque that can rupture
or can be treated.

this study?
• Dr. Bluemke: An important issue is the extent to which soft plaque changes over time. In
particular, if a patient is treated for many years with statins, effective treatment is expected
to be associated with less soft plaque. Studies to assess these effects are underway.
• Citation:
• Karen Rodriguez, Alan C. Kwan, Shenghan Lai, João A. C. Lima, Davis Vigneault, Veit Sandfort,
Puskar Pattanayak, Mark A. Ahlman, Marissa Mallek, Christopher T. Sibley, David A. Bluemke.
Coronary Plaque Burden at Coronary CT Angiography in Asymptomatic Men and Women.
Radiology, 2015; 142551 DOI: 10.1148/radiol.2015142551

Treatment For Small Kidney Cancers Has Evolved
Wiliam C. Huang, MD FACS
Associate Professor of Urology
Division of Urologic Oncology
NYU Langone Medical Center/Perlmutter Cancer Institute
• Dr. Huang: The presentation of kidney cancers has dramatically evolved over the past two
decades with most kidney cancers being incidentally diagnosed at an early stage. We have
begun to recognize that at this small size (< 4 cm), the tumors are frequently indolent in
nature and some are completely benign. Consequently, the management options for these
small cancers have expanded and evolved. Whereas the entire removal of the kidney was
the treatment of choice in the past, alternative options including removal or ablation of the
tumor-bearing portion of the kidney has become increasingly utilized. Similar to other early
stage cancers, watchful waiting or observation is also becoming a reasonable treatment
option.
• We used the most recent SEER-Medicare Data (2001 – 2009) to evaluate the management
trends and outcomes of small kidney cancers in the new millennium. We believe that this is
an important study as it provides important and practical findings, which are useful to both
clinical researches as well as practicing physicians.

• Dr. Huang: Clinicians and patients alike should note that the treatment paradigm for small
kidneys cancers has evolved. Nephron-sparing surgery is now the most common treatment
and appears to provide an overall and cancer-specific survival benefit over other options.
Nonetheless, the risk of cancer related death is low in older patients with small kidney
cancers regardless of treatment type, so non-surgical management is an acceptable option
for some patients. Despite this findings, use of non-surgical treatment remains low.

this study?
• Dr. Huang: In the future, we will need to prospectively validate the findings from this
population based study. Additionally, we will need to find novel methods of identifying which
tumors are likely to remain indolent and which tumor will move on to become lethal.

Treatment With Eribulin Is Step Forward for Advanced Soft Tissue Sarcomas
Professor Patrick Schöffski
Head, Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospital
Leuven, KU Leuven, Belgium
• MedicalResearch: What are the key points of the study?
• Professor Schöffski: This is the first and only randomised controlled trial of a single agent
systemic therapy to demonstrate an improvement in overall survival in people previously
treated for advanced soft tissue sarcomas. The study met its primary objective for overall
survival benefit (OS) for investigational use in patients treated with eribulin compared to
dacarbazine. Median OS for eribulin was 13.5 months versus 11.5 months for dacarbazine
representing a significant benefit, meaning that patients treated with eribulin may have a
23% reduction in the risk of death. Furthermore, an additional study endpoint included
progression-free survival (PFS) at 12 weeks. While there was a numerical difference between
arms favouring eribulin versus dacarbazine (33% vs 29%) this was not statistically significant.
Median PFS was 2.6 months in both arms.

• MedicalResearch: What is the key conclusion?
• Professor Schöffski: The key conclusion in this investigational study is that eribulin represents
an important breakthrough for clinicians and a significant step forward for patients living with
advanced soft tissue sarcomas, who currently face few treatment options and a poor
prognosis. Eribulin has shown an overall survival benefit against an active comparator, which
is significant.

• MedicalResearch: Any impact on clinical practice or future studies?
• Professor Schöffski: The result of this investigational study is important because it is the first study to
show any extension of survival with a drug treatment in soft tissue sarcoma, and is a robust, randomised
phase 3 trial. I cannot comment on what the sponsor company (Eisai) will do next with eribulin in soft
tissue sarcomas, but my personal opinion is that the drug is a powerful and important potential new
treatment option and warrants further work to bring it closer to patients.
•
• Citation: Presened at 2015 ASCO meeting
• Randomized, open-label, multicenter, phase III study of eribulin versus dacarbazine in patients (pts) with
leiomyosarcoma (LMS) and adipocytic sarcoma
• J Clin Oncol 33, 2015 (suppl; abstr LBA10502)
• Author(s):
• Patrick Schöffski, Robert G. Maki, Antoine Italiano, Hans Gelderblom, Giovanni Grignani, Veridiana Pires De
Camargo, Sebastian Bauer, Sun Young Rha, Sant P. Chawla, Jean-Yves Blay, Peter Hohenberger, David R.
D’Adamo, Benjamin Wang, Bartosz Chmielowski, Axel Le Cesne, George D. Demetri, Shreyaskumar Patel;
University Hospital Leuven, Leuven, Belgium; Mount Sinai Medical Center, New York, NY; CLCC Institut
Bergonié, Bordeaux, France; Leiden University Medical Center, Leiden, Netherlands; Fondazione del
Piemonte per l’Oncologia IRCC, Candiolo, Italy; Hospital Sírio-Libanês, São Paulo, Brazil; West German
Cancer Center, Essen, Germany; Severance Hospital, Seoul, South Korea; Sarcoma Oncology Center, Santa
Monica, CA; Université Claude Bernard & Centre Léon Bérard, Lyon, France; Mannheim University Medical
Center, Mannheim, Germany; Eisai Inc, Woodcliff Lake, NJ; Eisai, Woodcliff Lake, NJ; UCLA Jonsson
Comprehensive Cancer Center, Los Angeles, CA; Institut Gustave Roussy, Villejuif, France; Dana-Farber
Cancer Institute and Harvard Medical School, Boston, MA; The University of Texas MD Anderson Cancer
Center, Houston, TX

Childhood Bullying Linked To Depression In Young Adulthood
MedicalResearch.com Interview with: Dr. Lucy Bowes Ph.D
Leverhulme Early Career Research Fellow
Fellow of Magdalen College
Department of Experimental Psychology
University of Oxford Oxford
Response: Major depression is a severe mental illness, and a leading contributor to the global burden of
disease. Rates of depression begin to rise in the teenage years, though the reasons for this remain unclear.
Peers become particularly important during this time, and victimisation by peers or “bullying” has been
proposed as one potentially modifiable risk factor for depression. There are robust findings that peer
victimisation in childhood is associated with short-term internalizing symptoms, however it remains
unclear whether victimization in the teenage years is associated with major depression. Only a relatively
small number of longitudinal studies have prospectively investigated victimisation in relation to
depression meeting diagnostic criteria in late adolescence or adulthood. Limitations of these studies
include poor measures of bullying, lack of adjustment for key confounders such as baseline emotional and
behavioral difficulties and child maltreatment.
• Our prospective cohort observational study, published in The BMJ, used detailed self-report data on peer
victimisation at 13 years from 6,719 participants of the ALSPAC or ‘Children of the 90s’ study. The outcome
was depression at 18 years, measured using a self-administered computerised version of the Clinical
Interview Schedule Revised, CIS-R (data available for 3,898 participants). We adjusted for a range of
confounders including baseline emotional and behavioral problems, family background and other risk
factors. Of the 683 children who reported frequent victimisation at 13 years, 101 (14.8%) were depressed
at 18 years. Of the 1,446 children reporting some victimisation, 103 (7.1%) were depressed, and of the
1,769 children reporting no victimisation at 13 years, 98 (5.5%) were depressed. Children who were
frequently victimized had over a two-fold increase in odds of depression compared with children who
were not victimized by peers. This association was slightly reduced when adjusting for key confounders.
The population attributable fraction suggested that 29% of depression at 18 could be explained by peer
victimisation if this were a causal relationship.

• Response: Our findings suggest that a substantial proportion of the burden of depression in
the early adult years may be attributed to peer victimization, assuming that this is a causal
relationship. There are effective interventions to reduce peer victimization, particularly in
secondary schools, and these should be refined and evaluated to determine whether this
reduces rates of depression.

this study?
• Response: Our findings support those of other studies showing a link between bullying and
later mental health difficulties. We now need to focus on the mechanisms by which being
bullied leads to depression in some individuals but not in others. There are effective
interventions at the school-level for reducing overall rates of victimization, and these could
be complemented by interventions to support vulnerable children who have experienced
bullying and reduce the likelihood that they will go on to develop depression.
• Citation:
• Peer victimisation during adolescence and its impact on depression in early adulthood:
prospective cohort study in the United Kingdom
• BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h2469 (Published 02 June 2015) Cite this
as: BMJ 2015;350:h2469

HCV Viral Load Testing Not Useful As Measure of New Hepatitis C Drug Effectiveness
Shyamasundaran Kottilil MBBS, PhD
Division of Infectious Diseases, Institute of Human Virology
University of Maryland, Baltimore
Laboratory of Immunoregulation
National Institute of Allergy and Infectious Diseases
Dr. Kottilil: During treatment with interferon-based therapies, hepatitis C viral load levels
were clinically useful as on-therapy markers of treatment outcome. However, the standard-
of-care for HCV treatment has recently evolved from interferon-based regimens to short-
duration, all-oral, direct-acting antiviral (DAA) therapies. Therefore, it is important that we re-
evaluate the utility of HCV viral loads during DAA regimens in guiding clinical decision-
making.
• We found that Hepatitis C viral loads on treatment and at end of treatment were not
predictive of treatment success versus relapse with DAA therapy. Contrary to our experience
with interferon-containing regimens, low levels of quantifiable HCV RNA at end of treatment
did not preclude treatment success.

• Dr. Kottilil: Clinicians and patients should be aware that frequent monitoring of Hepatitis C
RNA levels during therapy may have little utility in guiding treatment duration. Additionally,
detectable or low-level quantifiable viremia at end of treatment does not signify treatment
failure or necessitate the extension of therapy. However, monitoring Hepatitis C viral levels
on treatment for adherence on study medications is important.

this study?
• Dr. Kottilil: One of the limitations of our study was our small and selective patient population.
Therefore, we recommend further analysis of the predictive ability of Hepatitis C RNA levels
for treatment outcome in larger DAA trials.
• Citation:
• Clin Infect Dis. 2015 Jun 15;60(12):1743-51. doi: 10.1093/cid/civ170. Epub 2015 Mar 2.
• Utility of hepatitis C viral load monitoring on direct-acting antiviral therapy.
• Sidharthan S1, Kohli A1, Sims Z1, Nelson A2, Osinusi A3, Masur H1, Kottilil S2.

Fructose Linked To Weight Gain and Reduced Physical Activity
Catarina Rendeiro Ph.D.
Post-doctoral Research Associate
Rhodes lab University of Illinois
Urbana, Illinois
Dr. Rendeiro: The motivation for this study emerges in the context of understanding the link
between sugar intake, particularly fructose, and the rising obesity epidemic that we are currently
facing. Overeating and lack of physical activity certainly play major roles in obesity, but the
sources of calories are also important. Fructose, a simple monosaccharide found in fruit and
vegetables, and composing half of sucrose (i.e., table sugar), has been on the increase in Western
diets. In our rodent study, 18% of dietary calories were derived from sugar, either fructose or
glucose. This level is similar to typical American diets. However, the fructose diet resulted in
increased weight gain and fat deposition and reduced physical activity even though food intake
was similar between the two groups. It is also important to note that our animals were
consuming their regular amount of calories, not overeating. Only the source of sugar was
different between experimental groups, and still calorie-for-calorie, fructose caused greater
weight gain and less physical activity than glucose

Urbana, Illinois
• Dr. Rendeiro: First of all, it is important to restate that the consumption of added sugars
through soft drinks and other processed foods should be kept to a minimum in our diets,
regardless of the type of sugar. The American Heart Association recommends a maximum of
5% daily calories derived from added sugars, but in the US, intake of added sugar can reach
three to four times that recommendation.
• Our study further suggests that at those unhealthy levels of sugar intake (18% of dietary
calories derived from sugar), consuming fructose results in more fat accumulation, weight
gain and physical inactivity. If the goal is to promote weight loss and physical activity, it could
be useful to consider minimizing the amount of food with added fructose that is consumed.
In the end, consuming a calorically-appropriate diet, including fresh fruits and vegetables,
and maintaining an active lifestyle are extremely important.

Urbana, Illinois
this study?
• Dr. Rendeiro: Future work should examine the extent to which fructose, calorie-for-calorie,
may impact neurological function as compared to glucose. In our study, we did not find any
differences in the brain or behavior outcomes as a result of fructose intake, but we only
investigated the growth of new neurons and performance on a few learning and memory
tasks. We also only supplemented the animals with fructose for 10 weeks, so it is possible
that any potential negative effects in brain function might emerge after longer exposures to
fructose.
• Citation:
• Catarina Rendeiro, Ashley M. Masnik, Jonathan G. Mun, Kristy Du, Diana Clark, Ryan N. Dilger,
Anna C. Dilger, Justin S. Rhodes. Fructose decreases physical activity and increases body fat
without affecting hippocampal neurogenesis and learning relative to an isocaloric glucose
diet. Scientific Reports, 2015; 5: 9589 DOI: 10.1038/srep09589

Individualized Sunitinib Dosing Improved Response Rate in Renal Cell Cancer
Georg A. Bjarnason, MD, FRCP(C)
The Anna-Liisa Farquharson Chair in Renal Cell Cancer Research
Associate Professor, Faculty of Medicine, University of Toronto Division of Medical Oncology, Sunnybrook Odette Cancer Centre
Toronto, ONT, Canada
Medical Research: What is the background for this study?
Dr. Bjarnason: Higher sunitinib drug exposure is associated with better response
(RR), progression free (PFS) and overall survival (OS). Retrospective data show poorer PFS and OS
in patients with minimum toxicity on the 28 day (d)/14 d schedule vs patients needing
dose/schedule changes. We hypothesized that toxicity-driven dose/schedule changes would
optimize drug exposure.

• Medical Research: What are the main findings?
Dr. Bjarnason: The main findings of this report include:
• Individualized Sunitinib therapy is safe and feasible in a multicenter setting (13 study canters).
• Response rates (CR+PR+ SD rate of 89.2%) are among the best for any tyrosine-kinase
inhibitor (TKI) in renal cell cancer with implications for dosing of sunitinib in other indications
and for the dosing of other TKI’s. Only 10% of patients were refractory to Sunitinib. This has
been around 20% in other studies.3. Dose intensity was improved in 65% of patients vs. the
standard dosing schema for Sunitinib. 20% of patients were dose escalated, and much fewer
patients needed dose reductions or stopped due to toxicity.
• The primary endpoint is PFS and the data are too early for this but: 37/102 (36.3%) patients
have been on therapy longer than the 8.5 Mo PFS in the EFFECT comparator trial and
25/83 (30.1%) of these patients are still on therapy. For 49 patients with CR+PR the median
time on therapy is 14.3 months (29 patients (59%) still on treatment). For 42 patients
with standard treatment the median time in therapy is 6.8 months (15 patients (34%) still on
treatment).

• Dr. Bjarnason: Many oncologists are already using alternate schedules for sunitinib because
of the toxicity associated with the standard 4/2 schedule. These data provide them with an
algorithm for individualized sunitinib therapy that is safe and associated with a very good
response rate and time on therapy.

• Medical Research: What recommendations do you have for future research as a result of this study?
• Dr. Bjarnason: The safety and activity of other targeted drugs might be optimized by individualizing
therapy based on toxicity.
• Citation:
• Presented at 2015 ASCO Meeting:
• Phase II study of individualized sunitinib as first-line therapy for metastatic renal cell cancer
• J Clin Oncol 33, 2015 (suppl; abstr 4555)
• Author(s):
• Georg A. Bjarnason, Jennifer J. Knox, Christian K. Kollmannsberger, Denis Soulieres, D. Scott Ernst, Christina
M. Canil, Eric Winquist, Pawel Zalewski, Sebastien J. Hotte, Scott A. North, Daniel Yick Chin Heng, Robyn
Jane Macfarlane, Peter M. Venner, Ian Tannock, Anil Kapoor, Bernhard J. Eigl, Aaron Richard Hansen, Piotr
Czaykowski, Ben Boyd, Naveen S. Basappa; Sunnybrook Odette Cancer Centre, University of Toronto,
Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, University of Toronto,
Toronto, ON, Canada; BC Cancer Agency, Vancouver Cancer Centre, Vancouver, BC, Canada; Centre
Hospitalier de l’Université de Montréal, Montreal, QC, Canada; London Regional Cancer Centre, London,
ON, Canada; Ottawa Reg Cancer Centre, Manotick, ON, Canada; London Health Sciences Centre, London,
ON, Canada; Lakeridge Health, Oshawa, ON, Canada; Juravinski Cancer Centre, Hamilton, ON, Canada;
Cross Cancer Institute, Edmonton, AB, Canada; Tom Baker Cancer Center, University of Calgary, Calgary, AB,
Canada; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada; Cross Cancer Inst, Edmonton, AB,
Canada; Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; BC Cancer Agency,
Vancouver, BC, Canada; Princess Margaret Hospital, Toronto, ON, Canada; CancerCare Manitoba,
Winnipeg, MB, Canada; Ozmosis Research Inc, Toronto, ON, Canada

Common Bacteria May Be One Cause of Type II Diabetes
MedicalResearch.com Interview with: Patrick M. Schlievert Ph.D
Professor and Chair
Department of Microbiology
Carver College of Medicine
Iowa City Iowa 52242
• Medical Research: What is the background for this study? Dr. Schlievert:
• As people become obese and enter pre-diabetes type II, there is a gut microbiome shift in bacteria
from Bacteroidetes to Firmicutes. A dominant pathogenic Firmicute in humans is Staphylococcus
aureus.
• As people become obese, their skin becomes wetter due to enhanced sweating upon exertion and
the presence of more skin folds. These, plus mucous membranes have enhanced Staphylococcus
aureus numbers, such that 100% of people become colonized and numbers of the bacterium rise to
1013 per person. This number of bacteria is like a cubic inch of margarine spread across the skin and
mucous membranes.
• All pathogenic Staphylococcus aureus bacteria make and secrete a family of toxins called
superantigens, including toxic shock syndrome toxin and staphylococcal enterotoxins. In high
amounts (0.1 μg/human), these toxins can be lethal, causing toxic shock syndrome. At lower
concentrations, the same superantigen toxins cause total body inflammation without lethality.
• In order to show that a microbes causes human disease, it is necessary to fulfill Koch’s postulates:
– Must associate human symptoms with a particular disease,
– Must isolate a potentially causative bacterium that is always present when the disease is present.
– Must produce the disease in an experimental animal.
– Must re-isolate the microbe from the experimental animal and re-cause the disease in another animal.

Professor and Chair
• Medical Research: What are the main findings?
• Dr. Schlievert: We have fulfilled Koch’s postulates, showing that Staphylococcus aureus and its
superantigen toxins cause type II diabetes.
•
Medical Research: What should clinicians and patients take away from your report?
• Dr. Schlievert:
• A common bacterium, Staphylococcus aureus, is one cause of type II diabetes.
• Staphylococcus aureus, including MRSA, can rise to very high numbers in and on obese persons,
leading to elevated blood glucose and insulin resistance, the defining findings in type II diabetes.
• Some type II diabetic, and most type I diabetic patients, will have serious problems with the
Staphylococcus aureus due to superantigen toxin production.
• Type II diabetic patients should change their lifestyles, such that if they are obese, they lose weight
to reduce excess sweating in skin folds, thereby controlling the numbers of Staphylococcus aureus
in and on their bodies.
• Who would have guessed that Staphylococcus aureus could do this? It reminds me of Helicobacter
and ulcers…who would have thought?
• In serious cases, Physicians may try multiple antibiotics and IVIG to help control the diabetes.

Professor and Chair
this study?
• Dr. Schlievert:
• We are developing a novel antimicrobial that kills Staphylococcus aureus on contact. There is
no chance of bacterial development of resistance to this antimicrobial. Similarly, the
antimicrobial is anti-inflammatory. Type II diabetes has a significant chronic inflammation
component caused by staphylococcal superantigen toxin. Both killing and prevention of
inflammation can be obtained by this novel antimicrobial.
• Ultimately, vaccination is important. We have developed a vaccine that includes toxoids (non-
active toxins) of superantigens. We expect this vaccine to be tested in humans within the
next year or two. This vaccine could be used to immunize all humans against staphylococcal
diseases.
• Citation:
• Bao G. Vu, Christopher S. Stach, Katarina Kulhankova, Wilmara Salgado-Pabón, Aloysius J.
Klingelhutz, Patrick M. Schlievert. Chronic Superantigen Exposure Induces Systemic
Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits:
Possible Role in Diabetes. mBio, 2015; 6 (2): e02554-14 DOI: 10.1128/mBio.02554-14

Over 1/3 HIV Patients Who Develop Opportunistic Infection Die Within Five Years
Sandra Schwarcz, MD
Senior HIV epidemiologist
San Francisco Department of Public Health
Dr. Schwarcz: AIDS opportunistic illnesses continue to occur despite effective antiretroviral
therapy. Although previous studies examined survival following a diagnosis of an opportunistic
illness, there are few recent reports that are population-based. The San Francisco Department of
Public Health has the only population-level data on the occurrence of and survival following
opportunistic illnesses and use of antiretroviral therapy among persons reported with HIV in the
United States. By measuring survival following the occurrence of opportunistic illnesses, we were
able to document that survival following opportunistic illnesses has improved with better HIV
treatment. However, opportunistic illnesses continue to occur and carry substantial mortality risk.
Even in this era of effective HIV therapy, we found that 35% of persons who developed an
opportunistic illness died within five years of their diagnosis and some opportunistic illnesses
such as brain lymphoma and progressive multifocal leukoencephalopathy remain highly lethal.

Sandra Schwarcz, MD
• Dr. Schwarcz: Patients who are diagnosed earlier in the course of HIV disease and who
receive prompt HIV care and treatment, including antiretroviral therapy have the best chance
of avoiding opportunistic illnesses. Clinicians should provide HIV testing routinely for patients
who may be at risk of infection and provide prompt treatment for their disease along with
counseling regarding the importance of medication adherence. Clinicians should monitor
their patients for response to therapy and the occurrence of HIV-related and HIV-non-related
morbidities.

Sandra Schwarcz, MD
this study?
• Dr. Schwarcz: Additional research regarding prevention and treatment of AIDS-related
opportunistic illnesses is needed to improve survival.
• Journal References:
• Sandra Schwarcz et al. Mortality Risk After AIDS-De fi ning Opportunistic Illness Among HIV-
Infected Persons — San Francisco, 1981 – 2012. Journal of Infectious Diseases., June 2015
DOI: 10.1093/infdis/jiv235
• Henry Masur, and Sarah W. Read. Opportunistic Infections and Mortality: Still Room for
Improvement. Journal of Infectious Diseases, June 2015 DOI: 10.1093/infdis/jiv236

First X-Chromosome Related Cause of Male Infertility Identified
Alexander N Yatsenko, MD, PhD Assistant Professor,
Department of OBGYN and Reproductive Science, Magee-Womens Research Institute,
University of Pittsburgh, PA
Pittsburgh, PA 15213
Dr. Yatsenko: The known causes of male infertility not due to physical obstruction are usually
because of sex-chromosome defects, such as deletions of the Y chromosome or duplication
of the entire X chromosome in Klinefelter syndrome. Eight times out of 10, conventional
genetic testing doesn’t reveal a chromosomal problem and infertility is considered idiopathic.
We wanted to try to find other genetic reasons for the problem.
• We found a deletion in part of the DNA coding of the testis-expressed gene 11 (TEX11) on the
X-chromosome, which men inherit from their mothers. The alteration caused meiotic arrest,
meaning the precursor cells could not properly undergo meiosis. We also found similar TEX11
gene mutations and meiotic arrest in two out of 49 men diagnosed with idiopathic
azoospermia in Pittsburgh or at a Poland infertility clinic, and in five out of 240 infertile men
assessed at a collaborating Andrology clinic in Muenster, Germany. These genetic findings
were confirmed on protein level using patients’ testis biopsies.

First X-Chromosome Related Cause of Male Infertility Identified
Alexander N Yatsenko, MD, PhD Assistant Professor,
Department of OBGYN and Reproductive Science, Magee-Womens Research Institute,
University of Pittsburgh, PA
Pittsburgh, PA 15213
• Dr. Yatsenko: It is first major genetic cause of male infertility related to X-chromosome gene.
Unlike autosomal chromosomes that all people have by pairs, men have only one X
chromosome and they are vulnerable to any X-linked genetic defect inherited or acquired de-
novo. This gives us something else (new) to look for when couples come to us and the man is
found to be infertile. We can help explain why it happened, instead of leaving our patients
wondering. This knowledge could be utilized for clinical genetic testing of infertile male with
absent sperm in their semen. Since it can explain infertility in only a fraction of patients, we
want to identify other mutations that can lead to abnormal sperm production.

MedicalResearch.com: Medical Research Exclusive Interviews June 6 2015

MedicalResearch.com: Medical Research Exclusive Interviews June 6 2015

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MedicalResearch.com: Medical Research Exclusive Interviews June 6 2015