MedicalResearch.com: Medical Research Exclusive Interviews May 18 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
May 18 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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Dietary Restriction Provides Benefits Beyond Weight Loss
MedicalResearch.com Interview with:
Edward “Ted” Weiss, Ph.D.
Associate Professor Department of Nutrition and Dietetics
Saint Louis University Saint Louis MO
Medical Research: What is the background for this study? What are the main findings?
Dr. Weiss: Results from one of our previous study yielded a surprising result that diet-induced
weight loss improved insulin sensitivity (major diabetes risk factor) by the same amount as
exercise induced weight loss. We thought that the exercise-induced weight loss would have
yielded benefits from the weight loss itself but also from a weight loss-independent benefit that
has been reported in other studies. One explanation for dietary restriction providing the same
benefit of exercise was that it also provides benefits besides those that are attributable to weight
loss. Our recently completed/published study was designed to evaluate this possibility and the
finding do suggest what we hypothesized… i.e. that dietary restriction provides benefits above
and beyond that which are attributable to weight loss.
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. Weiss: For individuals with excess body weight/fat, weight loss provides clear health
benefits; therefore, weight loss strategies should be discussed with and encouraged in these
patients (surprisingly, studies show that many physicians do not address this with patients).
The findings from our study add to what was already known by showing that both diet and
exercise provide benefits that don’t appear to be directly attributable to weight loss. Thus,
healthy diet and exercise behaviors should always be encouraged and pursued regardless of
whether it results in weight loss and regardless of whether weight loss is needed (for
example then people can benefit from a healthy diet and exercise).

• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Weiss: We are currently developing a study to identify the weight loss-independent
mechanisms by which dietary restriction and exercise improve insulin sensitivity. Preliminary
data from our recently published study suggest that some of the adaptations may involve
hormones that are secreted from the intestines after a meal (i.e. incretin hormones,
especially GLP-1).
• Citation:
• Diabetes Care. 2015 Apr 15. pii: dc142913. [Epub ahead of print]
• Calorie Restriction and Matched Weight Loss From Exercise: Independent and Additive
Effects on Glucoregulation and the Incretin System in Overweight Women and Men.
• Weiss EP, Albert SG, Reeds DN, Kress KS, Ezekiel UR, McDaniel JL, Patterson BW, Klein S,
Villareal DT

HPV Vaccination of Boys Can Yield Substantial Health Benefits
MedicalResearch.com Interview with: Dr. Johannes Berkhof
Department of Epidemiology and Biostatistics, VU University Medical Centre Amsterdam
Centre for Infectious Disease Control,
National Institute for Public Health and the Environment,Bilthoven, Netherlands
• Medical Research: What is the background for this study? What are the main findings?
• Response: Vaccination against the sexually transmitted human papillomavirus (HPV) is
offered free-of-charge to 12-year-old girls in the Netherlands.
There is strong evidence that HPV also causes cancer in men: the virus is associated with
cancers of the penis, anus, and oropharynx, and possibly with a small proportion of oral
cancers. A number of these cancers will be prevented because vaccination of girls leads to a
decrease of HPV in the general population and thus provides indirect protection to
heterosexual men.
• However, vaccine uptake among girls is only about 60 percent in the Netherlands. Moreover,
men who have sex with men are at increased risk of HPV-related cancer and will not be
protected by vaccination of girls.
• On the basis of data from several epidemiological studies and a dynamic model for virus
transmission, we calculated that, if the vaccine uptake is low, about 200 girls need to be
vaccinated to prevent one case of cervical cancer and 470 boys need to be vaccinated to
prevent one case of cancer in men.
• An increase in vaccine uptake in girls will decrease the HPV infection risk in heterosexual men
and if the uptake in girls is 60 percent, around 800 boys need to be vaccinated to prevent one
additional case of cancer in men.

• Response: Indirect protection of men through vaccination of girls is important to take into
account, but vaccination of boys can still yield substantial health benefits. Therefore, we
suggest policy makers to evaluate future HPV vaccination strategies not only with a single
focus on the protection of women. HPV-associated burden in men is lower than in women,
but vaccine prices have declined since market introduction that may change the perspective.
• As a general take-home message, I’d like to state that protection of men against HPV-related
cancer should be an integral part of the objective of an HPV vaccination program.

this study?
• Response: Future research should include an evaluation of the cost-effectiveness of gender-
neutral vaccination as a function of vaccine uptake among girls and vaccine price.
For countries with organized HPV immunization programs in place, a comparative analysis
contrasting gender-neutral vaccination to stimulated vaccine uptake in girls
can be very valuable to guide policy makers. Another recommendation is to delineate the
prospects of targeted HPV vaccination of men who have sex with men, as these
will likely remain at increased risk of HPV-related cancers, even if boys aged 12 will be offered
free vaccination.
• Citation:
• Direct benefit of vaccinating boys along with girls against oncogenic human
papillomavirus: bayesian evidence synthesis
• BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h2016 (Published 12 May 2015) Cite this
as: BMJ 2015;350:h2016
• Johannes A Bogaards, senior researcher, Jacco Wallinga, senior researcher, Ruud H
Brakenhoff, professor, Chris J L M Meijer, professor Johannes Berkhof, associate professor

It Really Is Harder For Some People to Lose Weight
Martin Reinhardt, MD
Postdoctoral Fellow PECRB, NIDDK, NIH
Phoenix, AZ 85016
Dr. Reinhardt: It can be very difficult for some people with obesity to lose weight despite
great efforts. There is an immense deal of individual variability in weight loss success. Beyond
differences in diet adherence, it is not clear what causes this variability in weight loss.
• Through a study conducted at our facilities at the National Institutes of Health in Phoenix,
Arizona, we have now shown that individual differences in biology – more precisely,
differences in the amount of energy bodies use during fasting – make it difficult for certain
obese people to lose weight.

Phoenix, AZ 85016
• Dr. Reinhardt: It is important to know that all volunteers, regardless of metabolism, lost a
significant amount of weight during the six-week calorie restriction period. Our study shows
that weight loss is possible despite inherent biological differences.

Phoenix, AZ 85016
this study?
• Dr. Reinhardt: To define the metabolic characteristics of the study participants, we measured
energy expenditure using a whole-room calorimeter. Only a handful of those calorimeters
exist in research centers around the world. We are currently looking for other markers that
may be more easily measured to identify people with varying metabolisms. Whether
identification of these biological traits could be harnessed to prevent weight gain remains to
be established.
• Citation:
• A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction
• Martin Reinhardt, Marie S. Thearle, Mostafa Ibrahim, Maximilian G. Hohenadel, Clifton
Bogardus, Jonathan Krakoff, and Susanne B. Votruba
• Diabetes published ahead of print May 11, 2015, doi:10.2337/db14-1881

Frequent ER Visits Linked To Prescription Drug Overdose
Joanne Brady, PhD candidate
Department of Anesthesiology, College of Physicians and Surgeons
Department of Epidemiology, Mailman School of Public Health
Columbia University, New York, NY;
Response: Prescription drug overdose is a major public health problem in the United States.
Prescription drug overdose mortality has increased dramatically over the past twenty five years.
Frequent emergency department utilization may be a marker for risk of prescription drug
overdose death. The current study assessed how frequency of emergency department visits in
the past year related to risk of subsequent prescription drug overdose death. In a cohort of
patients visiting the emergency department, patients with four or more visits to the emergency
department in the past year were at substantially higher risk for prescription drug overdose death
than patients who visited the emergency department one or fewer times. As the number of visits
to the emergency department increased from 0 – 1 to 4 or more for any reason the risk of dying
from prescription drug overdose also increased.
Medical Research: What should clinicians and patients take away from your report?
Response: Frequency of emergency department visits may be a means for identifying patients at
heightened risk of prescription drug overdose. These visits are a clinical point of contact for
providing preventative interventions, such as providing patients and their families with take-
home naloxone, referral to drug treatment or other supportive services.

Frequent ER Visits Linked To Prescription Drug Overdose
Joanne Brady, PhD candidate
Department of Anesthesiology, College of Physicians and Surgeons
Department of Epidemiology, Mailman School of Public Health
Columbia University, New York, NY;
this study?
• Response: Future studies should focus on identifying other health encounter patterns and
alternative approaches to aid vulnerable individuals who do not utilize emergency services.
• Citation:
• Emergency department utilization and subsequent prescription drug overdose death
• Brady JE1, DiMaggio CJ2, Keyes KM3, Doyle JJ4, Richardson LD5, Li G6.
• Ann Epidemiol. 2015 Apr 2. pii: S1047-2797(15)00128-3. doi:
10.1016/j.annepidem.2015.03.018. [Epub ahead of print]

Study Tests Two Dose Schedule of HPV Vaccination Against Genital Warts In Girls
Maria Blomberg Virus, Lifestyle & Genes
Danish Cancer Society Research Centre
Copenhagen, Denmark
Response: Two vaccines against human papillomavirus (HPV) were licensed almost one decade
ago. Since then multiple countries have implemented HPV vaccination programs, but many
struggle with low coverage rates. An important barrier to vaccination is the cost of the vaccines
and less developed countries also face considerable logistical challenges. Both vaccines were
administered as three dose schedules, but in early 2014 the WHO’s Strategic Advisory Group of
Experts and the European Medicines Agency reviewed the evidence of reduced dose schedules of
HPV vaccination, and subsequently recommended a two dose schedule for young girls. A
reduction of the number of doses has obvious advantages; it would lower the costs, ease
implementation of vaccination schedules and potentially increase coverage rates. Based on these
recommendations, countries around the world have reduced the dosing schedule in their HPV
vaccination programs for young girls to two doses. However, the current evidence is based
primarily on immunological studies, and because the immune correlate of protection is not
known, studies with disease endpoints are very important.

Copenhagen, Denmark
Using the biologically relevant endpoint of genital warts, this study aimed to assess the clinical
effectiveness of a two dose schedule of quadrivalent HPV vaccine compared with the standard
three-dose regimen administered at month 0, 2 and 6. We found that with the standard
vaccination schedule, completion of the three dose regimen is important to gain maximal
protection. However, the effectiveness of two doses increased significantly with increasing time
between the doses, and with an interval of approximately 6 months between dose one and two,
no differences could be found between two and three doses.

Copenhagen, Denmark
• Response: The results of this study strengthen the evidence supporting a two dose regimen
administered at month 0 and 6 for young girls. Young women, who have received the first
two doses of the quadrivalent HPV vaccine at month 0 and 2, will require a third dose to
maximize protection, whereas a 6 months interval between dose one and two seems to
provide equal effectiveness of two and three doses. The duration of the effectiveness of two
doses is, however, unknown.

Copenhagen, Denmark
this study?
• Response: Randomized, clinical dose-related studies are currently ongoing. If these studies
support a two dose schedule, it will be important to follow the long-term effectiveness,
because it is not yet known whether the duration of two and three doses differs. Long-term
protection is essential as exposure to HPV continues for several decades after vaccination. In
addition, some subgroups e.g. immunocompromised individuals or individuals with co-
morbidities may react differently to a reduced number of doses, and they should therefore
be followed up separately. These unsolved issues should also be considered for the recently
licensed ninevalent HPV vaccine.
• Citation:
• Dose-related differences in effectiveness of HPV vaccination against genital warts: a
nationwide study of 550,000 young girls
Maria Blomberg, Christian Dehlendorff, Carsten Sand, and Susanne K. Kjaer
• Clin Infect Dis. first published online May 5, 2015 doi:10.1093/cid/civ364

Extracerebral Biomarkers May Not Be Optimal For Monitoring Sports-Related Concussions
Pashtun Shahim, MD
Departement of Neurosurgery, University Hospital, Linköping, Sweden
Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology Sahlgrenska University Hospital
Response: Visinin-like protein-1 (VLP-1 or VILIP-1) is a neuronal calcium-sensor protein,
originally studied as a stroke marker and identified as a marker of neuronal injury in brain
injury models. Increased plasma and cerebrospinal fluid (CSF) VILIP-1 hase been reported in
Alzheimer’s disease, where CSF VILIP-1 correlates with CSF total tau (T-tau) and with brain
volume. Recently, using a novel ultrasensitive method to measure tau in plasma, increased
levels of plasma T-tau were found in concussed professional ice hockey players, where the
levels correlated with the resolution of post-concussive symptoms and the players returning
to play.
• The main findings of this study were that VILIP-1 did not increase significantly in serum after
sports-related concussion. However, the serum levels of VILIP-1 increased after a friendly
game without concussion, signaling extracerebral expression.

Pashtun Shahim, MD
• Response: The results of this current study provide evidence that serum VILIP-1 may not be
a useful biomarker for diagnosis and prognosis of sports-related concussion at least over the
first week.
• Moreover, the findings of this study further strengthen the notion that biomarkers that are
expressed extracerebrally may not be optimal for monitoring sports-related concussion.

Pashtun Shahim, MD
this study?
• Response: Additional studies of VILIP-1 and as yet undiscovered biomarkers will be needed
to determine their use to prospectively identify concussion and their ability to predict
prognosis.
• Citation:
• Serum visinin-like protein-1 in concussed professional ice hockey players
• Pashtun Shahim, Niklas Mattsson, Elizabeth M. Macy, Dan L. Crimmins, Jack H. Ladenson,
Henrik Zetterberg, Kaj Blennow, Yelverton Tegner
• Brain Injury : 1–5.
• Posted online on 8 May 2015.

Combining Acceleration and Skin Temperature Can Improve Accuracy of Physical Activity Monitors
Dr. Shang-Ming Zhou
Senior Lecturer in Statistical Modelling and Analytics for Epidemiology and Public Health,
Public Health Informatics Group, Health Information Research Unit (HIRU),
• Response: In medical and sport science research, body-worn accelerometers are widely used
to provide objective measurements of physical activity. However, accelerometers collect data
continuously even during periods of nonwear (i.e. periods when participants may not be
wearing their monitor, such as during sleeping). It is important to distinguish time of
sedentary behaviours (eg. watching television) from time of nonwear. The clinical
consequence of misclassification of accelerometer wear and nonwear would overestimate or
underestimate physical activity level, and mislead the interpretation of the relationship
between physical activity and health outcomes. Automated estimation of accelerometer
wear and nonwear time events is particularly desired by large cohort studies, but algorithms
for this purpose are not yet standardized and their accuracy needs to be established. This
study presents a robust method of classifying wear and nonwear time events under free
living conditions for triaxial accelerometers which combines acceleration and surface skin
temperature data.

Dr. Shang-Ming Zhou
The new findings are: Either acceleration data or skin temperature data alone is inadequate to
accurately predict wear and nonwear events in some scenarios under a free living condition; This
study provides a simple and efficient algorithm on use of short time periods of consecutive data
blocks for accurately predicting triaxial accelerometer wear and nonwear events; Combining both
types of acceleration and skin temperature data can significantly improve the accuracy of
accelerometer wear and nonwear events classification in monitoring physical activity.

Dr. Shang-Ming Zhou
• Response: Clinicians and researchers would benefit from using the reported method to
generate more accurate estimations of time spent in sedentary and active behaviours in free
living conditions, and gain correct interpretation of relationships between physical activity,
energy expenditure and health outcomes.
this study?
• Response: Clinicians and researchers would benefit from using the reported method to
generate more accurate estimations of time spent in sedentary and active behaviours in free
living conditions, and gain correct interpretation of relationships between physical activity,
energy expenditure and health outcomes.
• Citation:
• BMJ Open 2015;5:e007447 doi:10.1136/bmjopen-2014-007447
• Sports and exercise medicine
• Classification of accelerometer wear and non-wear events in seconds for monitoring free-
living physical activity
• Shang-Ming Zhou, Rebecca A Hill, Kelly Morgan, Gareth Stratton, Mike B Gravenor, Gunnar
Bijlsma,Sinead Brophy

Basic Research Of Ovarian Development May Lead To Understanding Of Ovarian Disorders
MedicalResearch.com Interview with: Humphrey Yao, Ph.D. Lead Researcher
Reproductive and Developmental Biology Laboratory
National Institute of Environmental Health Sciences (NIEHS)
National Institutes of Health (NIH)
Research Triangle Park, North Carolina
Dr. Yao: We wanted to understand how an organ forms, and what basic cell types were
needed to form an organ. So, we used a mouse ovary model system to understand the
process. The functional unit of the ovary is called the follicle, and it is made up of three types
of cells — the maturing egg, granulosa cells, and theca cells. Scientists knew where the egg
and the granulosa cells came from, but no one knew where theca cells came from. Theca
cells are important, because they allow females to produce the hormones that sustain follicle
growth. Researchers also lacked information about how the egg, granulosa cells, and theca
cells talked to each other to promote growth and maintain a healthy ovary.
• We made two discoveries. First, we answered the long-standing question of theca cell origin
by determining that they have two sources, both inside and outside of the ovary. We don’t
yet know why theca cells have two sources.
• Second, we uncovered the molecular signaling system that the egg, granulosa cells, and theca
cells use to communicate. We didn’t expect to find this three-way cellular crosstalk, but now
that we know how they signal each other, I believe we are closer to understanding how an
ovary develops and what happens when something goes wrong. Ovarian disorders, such as
premature ovarian failure and polycystic ovarian syndrome, may start when cellular
communication is altered or if the various cells fail to develop properly.

Basic Research Of Ovarian Development May Lead To Understanding Of Ovarian Disorders
MedicalResearch.com Interview with: Humphrey Yao, Ph.D. Lead Researcher
Reproductive and Developmental Biology Laboratory
National Institute of Environmental Health Sciences (NIEHS)
National Institutes of Health (NIH)
Research Triangle Park, North Carolina
• Dr. Yao: They should know that basic research using animal models provides invaluable
information that could be used to understand human biology and diseases.
this study?
• Dr. Yao: Future research should examine the two cell types that make up theca cells more
closely, and it should determine if the same holds true for humans. I
• In addition, researchers could investigate whether miscommunication or defects in the
crosstalk among the three ovarian cell types could contribute to ovarian disorders in humans.
Doing so may uncover additional roles that theca cells play in female fertility
• Citation:
• Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and
granulosa cells
• Chang Liu, Jia Peng, Martin M. Matzuk & Humphrey H.-C. Yao
• Nature Communications 6, Article number: 6934 doi:10.1038/ncomms7934
• Received 29 September 2014 Accepted16 March 2015 Published 28 April 2015

Genomic Instability Biomarker May Help Predict Treatment Response In Triple Negative Breast Cancer
MedicalResearch.com Interview with: Melinda L. Telli, M.D.
Assistant Professor of Medicine Stanford University
Division of Medical Oncology Stanford, CA 94305-5826
Response: A major goal of this study was to explore a DNA damaging chemotherapy regimen in
patients with newly diagnosed early-stage triple-negative or BRCA1/2 mutation-associated breast
cancer. This was based on the hypothesis that these types of tumors are more responsive to DNA
damaging therapeutics. A second major goal was to identify predictors of response to this
platinum-based therapy among patients with sporadic triple-negative breast cancer (TNBC).
• Overall, this study demonstrated that the non-anthracycline and non-taxane neoadjuvant regimen
of gemcitabine, carboplatin and iniparib resulted in a 36% pathologic complete response rate (pCR).
This compares favorably to pCR rates commonly observed with anthracycline and taxane-based
regimens in this group of patients. The response rate was higher among triple-negative breast
cancer patients with a germline BRCA1 or BRCA2 mutation (56%).
• Given the hypothesis of underlying DNA repair defects in sporadic triple-negative breast cancer, we
also evaluated a novel measure of genomic instability to detect the accumulation of changes in the
genomic landscape of a tumor attributable to defective homologous recombination DNA repair.
Homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in
pretreatment core breast biopsies. Very importantly, we found that the HRD-LOH assay was able to
identify patients with sporadic TNBC lacking a BRCA1 or BRCA2 mutation, but with an elevated
HRD-LOH score, who achieved a favorable pathologic response.

• Response: Our data do not have a direct impact for clinical practice today, but they strongly
suggest that patient selection based on underlying DNA repair deficiency in future
randomized trials of standard versus DNA repair defect–targeted therapy in triple-negative
breast cancer hold great promise. In particular, germline BRCA1 and BRCA2 mutation status,
as well as the HRD-LOH assay emerged as important biomarkers associated with improved
neoadjuvant response to this platinum-based regimen.

this study?
• Response: At present, three phase II randomized trials have been reported, two of which
showed an improvement in pCR rate when carboplatin is added to anthracycline and taxane-
based neoadjuvant therapy. Whether this will result in improved long-term outcomes
remains unknown. Our data support that future investigation with treatment selection based
on tumor DNA repair capacity in triple-negative breast cancer holds tremendous promise and
may be able to identify those patients who stand to gain most from a platinum-based
approach.
• Citation:
• Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-
Negative and BRCA1/2 Mutation–Associated Breast Cancer With Assessment of a Tumor-
Based Measure of Genomic Instability: PrECOG 0105
• Melinda L. Telli, Kristin C. Jensen, Shaveta Vinayak, Allison W. Kurian, Jafi A. Lipson, Patrick J.
Flaherty, Kirsten Timms, Victor Abkevich, Elizabeth A. Schackmann, Irene L. Wapnir, Robert W.
Carlson, Pei-Jen Chang, Joseph A. Sparano, Bobbie Head, Lori J. Goldstein, Barbara Haley,
Shaker R. Dakhil, Julia E. Reid, Anne-Renee Hartman, Judith Manola, and James M. Ford
• JCO JCO.2014.57.0085; published online on April 6, 2015;

Study Identifies One Pathway Cancer Cells Use To Evade Death
Katherine Aird, Ph.D.
Gene Expression and Regulation Program
The Wistar Institute, Philadelphia, PA
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Aird: Senescence is considered an important tumor suppressor mechanism. In normal
cells, activation of certain oncogenes decreases the levels of dNTPs (the building blocks of
DNA), leading to replication stress. We previously found that loss of the rate-limiting enzyme
in dNTP synthesis, ribonucleotide reductase M2 (RRM2), is the cause of this replication
stress. Restoration of RRM2 expression could rescue the loss of dNTPs and replication stress,
which overcame the senescence-associated growth arrest. Indeed, RRM2 is highly expressed
in many cancer types, including melanoma and ovarian cancer. Therefore, we found that
increased dNTP levels can overcome senescence and potentially lead to transformation of
cells and cancer.
• We next wanted to further our understanding of replication stress in the context of
senescence. In the current study, we suppressed nucleotide metabolism by decreasing RRM2
expression as a model for replication stress and then determined what proteins are
necessary for the induction of senescence. We found that loss of ATM could overcome
replication stress-induced senescence. This was due to increased dNTP levels. dNTPs were
increased due to a coordinated inactivation of p53 and activation of c-MYC by loss of ATM.
These changes at the molecular level correlate with reprogramming of cellular metabolism by
generating dNTPs. Thus, loss of ATM in the context of replication stress can change cellular
metabolism to a more cancer-like phenotype.

• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Aird: Understanding how cells overcome senescence may allow for new therapeutic
strategies to target these cells. Knowledge of these pathways may even allow for us to
prevent these cells from becoming cancer. However, it is important to stress that our
observation is just one of many potential ways cells could overcome senescence. A
comprehensive study is needed to explore ways of targeting the common threads to benefit
a larger subset of patients.

• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Aird: Here, we identified a novel pathway whereby loss of ATM, which occurs in a number
of human cancers, can overcome senescence by reprogramming cellular metabolism. It is
therefore possible that patients with loss or mutations in ATM may benefit from metabolism-
targeting therapeutics. This is the next step we will need to take to ultimately determine
whether any metabolism-targeting cancer therapeutics can be derived from our current
study.
• Citation:
• Cell Rep. 2015 May 12;11(6):893-901. doi: 10.1016/j.celrep.2015.04.014. Epub 2015 Apr 30.
• ATM Couples Replication Stress and Metabolic Reprogramming during Cellular Senescence.
• Aird KM1, Worth AJ2, Snyder NW2, Lee JV3, Sivanand S3, Liu Q4, Blair IA2, Wellen KE3, Zhang R5.

Pregnant Women Have Same Low Rate Of Adverse Surgical Outcomes As Non-Pregnant Patients
Robert A. Meguid, MD MPH FACS Assistant Professor Section of General Thoracic Surgery
Division of Cardiothoracic Surgery Department of Surgery
University of Colorado Denver | Anschutz Medical Campus
Aurora, CO 80045

Aurora, CO 80045
Dr. Meguid: The surgical literature on adverse outcomes after surgery on pregnant patients is
conflicting. We know that the majority of surgery performed on pregnant patients is not elective
(and just over 50% of it in the database studied was emergency surgery). We expected to find an
increased rate of adverse outcomes in those pregnant patients. However, when we matched the
pregnant and non-pregnant women who underwent surgery in the database, with excellent
matching on all available preoperative characteristics and on the actual operation performed, we
found similar, low rates of 30-day postoperative death and complication. In this study, pregnant
patients had undergone a broad spectrum of different types of operations, including general,
vascular, thoracic, head and neck, non-obstetric gynecologic and urologic, orthopedic,
reconstructive, and neuro-surgery. Given the concern that we as surgeons have over operating
on pregnant patients, both for the well-being of the patient and her child, our findings are
reassuring. This suggests that we as a medical profession are diligent in minimizing risk to
pregnant women who need surgery that cannot be delayed until after the child’s birth. Again,
this study faces the limitations of being unable to assess any short term harm done to the fetus
and the subsequent long term outcome of the child.

Aurora, CO 80045
• Dr. Meguid: The message of the findings of this study to clinicians and patients is that
pregnant women who must undergo surgery have a similarly low risk of adverse outcomes
(death and other complications) as comparable non-pregnant women. As we are not able to
assess the impact on the fetus using the database studied, we still advocate that elective
surgery which can safely be postponed until after pregnancy be done so

Aurora, CO 80045
this study?
• Dr. Meguid: The inclusion of specific outcomes for populations of interest (in this case, fetal
outcomes in observational databases including pregnant women) is valuable for further
refinement of questions such as the one we asked. In this era of the electronic health record,
we still record data and report outcomes by hand. We hope that in the near future, the
electronic health record can become a reliable source of clinical data for comparable studies,
opening up the door to engage in near-real time, high volume data analysis to further shape
our clinical decisions.
• Citation:
• Moore HB, Juarez-Colunga E, Bronsert M, et al. Effect of Pregnancy on Adverse Outcomes
After General Surgery. JAMA Surg. Published online May 13, 2015.
doi:10.1001/jamasurg.2015.91.

Scientists Get Closer To A Vaccine Against Allergies
MedicalResearch.com Interview with: Dr. Christine McCusker MD
Associate Professor, Department Pediatrics
Meakins-Christie Laboratories
McGill University and the MUHCRI, Montreal Quebec, Canada
Dr. McCusker: When the body is exposed to new substances, the immune system must
evaluate the “threat” and choose the type of response that will best protect the host.
Allergies and allergic asthma develop after the response to “allergens” follows the TH2-type
inflammatory pathway instead of the non-inflammatory tolerant pathway. Evidence suggests
that there is some plasticity in this “choice” and thus it may be possible to influence the
immune response to preferentially choose the tolerant pathway when exposed to allergens.
We therefore treated very young mice to a molecule designed to inhibit activation of the TH2
pathway.
• We showed that this early treatment resulted in long-lasting protection from the
development of allergies. Instead of allergic responses, vaccinated animals developed
tolerant responses to allergens and did not show any signs of allergies or
asthma. Importantly, while the influence of the treatment was long-lasting, the molecule
itself is rapidly removed from the system.

• Dr. McCusker: Allergy development results from a combination of genetic and environmental
factors. Manipulation of the immune system to promote tolerance early in life may result in
lifelong protection from allergies as the immune system “ can learn” to be tolerant of
allergens. This study we showed that early inhibition of the TH2-type pathway resulted in
immune-education towards tolerance that persisted through adulthood. Thus a vaccine that
prevents development of allergies is a very real possibility.

this study?
• Dr. McCusker: This research in animals, coupled with a recent clinical trial in infants shows
that infant immune responses can be influenced to develop in the best possible adaptive
manner to provide balance between protection from infection and tolerance. The timing of
introduction of oral and inhaled allergens is critical for promoting tolerance. Studies are
needed to further evaluate the elements essential for promoting this homeostasis to develop
strategies aimed at reducing the frequency of allergies and asthma in children.
• Citation:
• TGF-β-mediated airway tolerance to allergens induced by peptide-based immunomodulatory
mucosal vaccination
• Michael H1, Li Y1, Wang Y1, Xue D1, Shan J1, Mazer BD1, McCusker CT1.
• Mucosal Immunol. 2015 Mar 18. doi: 10.1038/mi.2015.15. [Epub ahead of print]

Hospital System Efficiently Uses MRI To Screen For Stroke and Shorten Treatment Window
Amie W. Hsia, MD
Medical Director, Comprehensive Stroke Center MedStar Washington Hospital Center
NIH Stroke Program at MWHC Associate Professor, Neurology
Dr. Hsia: Acute stroke is a common presenting problem in the emergency department. We know
that “time is brain” and that for patients experiencing an ischemic or “blockage” type of stroke,
the most common type, the sooner we can administer tPA, a clot-busting medication and the
only FDA-approved medication to treat acute stroke, the better chance for a good outcome.
Therefore, there is a goal national benchmark time of administering the drug to appropriate
acute stroke patients within 60 minutes of their arrival to the emergency department. There are
many steps that are necessary in the evaluation of an acute stroke patient in the emergency
department before tPA can be given. This includes a brain scan to make sure a patient is not
having the less common bleeding type of stroke. A CT or “CAT” scan is the typical type of brain
scan that is performed in emergency departments across the country and the world to screen a
patient before giving tPA. The primary purpose of the CT scan is to exclude bleeding; it is difficult
to visualize an early stroke on CT. Though an MRI can give more complete information including
showing the stroke as it is happening in these first few hours and though most hospitals have an
MRI scanner, an MRI takes longer to perform and has not traditionally been used in an emergency
setting.

Amie W. Hsia, MD
At the two hospitals included in this study, MedStar Washington Hospital Center in D.C. and
Suburban Hospital in Maryland, we are fortunate to serve as the sites for the NINDS intramural
stroke clinical research program and use MRI routinely to screen acute stroke patients to learn
more about stroke and develop new treatments for stroke. It is upon this foundation that we
performed independent hospital-wide quality improvement initiatives engaging multidisciplinary
committees with leadership from all the departments involved in the care of the acute stroke
patient in that critical first 60 minutes. Inspired by our colleagues at Washington University in St.
Louis led by Dr. Andria Ford who used similar methods in reducing treatment times with CT
screening, we used lean manufacturing principles to streamline our processes that include MRI
screening and dramatically reduced our treatment times from a baseline of 93 minutes down to
55 minutes while still maintaining safety. Through these efficiency improvements, we were able
to achieve a 4-fold increase in the percentage of stroke patients treated with tPA within 60
minutes.

Amie W. Hsia, MD
• Dr. Hsia: Our report can serve to dispel the myth or misconception that routinely screening
with MRI and treating acute stroke patients in under 60 minutes cannot be done. We have
clearly demonstrated that this can be done consistently and safely. Through our publication,
we aim to share with the medical community very practical details including flowchart
diagrams and a copy of the simplified MRI screening form that we now use in practice to
serve as a reference for other hospital providers interested in applying similar changes.

Amie W. Hsia, MD
this study?
• Dr. Hsia: Our study can really open the doors to more widespread use of this available MRI
technology, not only to screen acute stroke patients prior to standard tPA treatment, but also
to continue to leverage this technology as we look to identify other new treatments for
stroke. Having the more comprehensive information provided by an MRI compared to a CT
can serve as a critical tool to guide treatments that can be delivered both quickly and safely
• Citation:
• Screening with MRI for Accurate and Rapid Stroke Treatment
• Shreyansh Shah, MD,Marie Luby, PhD,Karen Poole, RN, MSN,Teresa Morella, RN,Elizabeth
Keller, BSIE, MBA,Richard T. Benson, MD, PhD,John K. Lynch, DO,Zurab Nadareishvili, MD
andAmie W. Hsia, MD
• Published online before print May 13, 2015, doi: 10.1212/WNL.0000000000001678
Neurology 10.1212/WNL.0000000000001678

Gene Expression Signatures May Help Differentiate Sepsis From Non-Infectious Inflammation
Timothy E Sweeney, MD PhD Resident, General Surgery
Postdoc, Khatri Lab, Bioinformatics
Stanford University
• Dr. Sweeney: Sepsis is defined as the presence of systemic inflammation due to infection.
Systemic inflammation can be caused from many things, such as trauma, surgery, thrombosis,
autoimmunity, etc. It can also be caused by infection. On the other hand, infection does not
necessarily cause systemic inflammation, either: a person can get a minor infection, like
strep throat, and not have a systemic response. It’s the intersection of severe inflammation (a
syndrome called SIRS) with infection that defines sepsis.
• In general surgery, we frequently see patients after traumatic injury or surgery who are
having an inflammatory response (ie, fevers, fast heart rate, high white blood cell count, etc).
But it’s not clear whether this inflammatory response is a reaction to the trauma or surgery,
or whether there might be an infection brewing that is causing the reaction. Identifying the
inflammatory response doesn’t require many special tests– it’s easy to spot. So we know
which patients have inflammation and which do not. What is difficult is determining the root
cause of the inflammation, and, in particular, whether there is an infection present that
needs treatment with antibiotics.

Stanford University
Current diagnostics for infection (not sepsis) are either slow (like blood cultures, which can take
24-72 hours to return) or not highly accurate (like procalcitonin). We sought to define a better
test that could specifically differentiate between people with sterile inflammation, and people
with inflammation due to infection (sepsis). By integrating gene expression data from multiple
publicly available cohorts, we were able to find a set of 82 genes that are significantly differently
expressed between these two groups. We then used an algorithm called a greedy forward search
to find a subset of 11 genes that were most diagnostic for sepsis.

Stanford University
• Dr. Sweeney: These findings aren’t yet available in a clinical form. We are currently in the
process of prospectively testing the diagnostic power of the 11 genes, and of their protein
products. Eventually we hope to make a test that a doctor could use to help determine
whether a patient has sepsis.

Stanford University
this study?
• Dr. Sweeney: One of our key findings is that gene expression is heavily influenced by the
recovery process. Thus, future trials should be designed to compare people with and without
infections who are at the same point in their hospital course (in other words, compare
patients with and without infection at admission, or patients who acquire an infection at
hospital day 3 to patients without infection at hospital day 3, etc). In addition, we’ve shown
that gene expression signatures in the blood do carry useful diagnostic information even for
acute illness. Further work will be necessary to develop robust point-of-care tests that can
utilize this information.
• Citation
• A comprehensive time-course–based multicohort analysis of sepsis and sterile inflammation
reveals a robust diagnostic gene set
• Timothy E. Sweeney1,2,*Aaditya Shidham2 Hector R. Wong34and Purvesh Khatri
• Sci Transl Med 13 May 2015:
Vol. 7, Issue 287, p. 287ra71
Sci. Transl. Med. DOI: 10.1126/scitranslmed.aaa5993

Texting or Talking While On Treadmill Reduces Exercise Intensity
Michael Rebold, PhD, CSCS Assistant Professor
Department of Exercise ScienceBloomsburg University Bloomsburg, PA 17815
Dr. Rebold: We assessed how common smartphone uses (texting and talking) interfere with
treadmill exercise.
• We found that when individuals use their smartphones during exercise for texting or talking,
it causes a reduction in exercise intensity.
• Dr. Rebold: Exercising at a lower intensity has been found to reduce the health benefits of
exercise and fitness improvements over time.
• These findings are important because poor cardiorespiratory fitness is associated with an
increased prevalence of cardiovascular disease risk factors, such as higher cholesterol and
blood pressure levels, which could potentially lead to premature mortality.

Texting or Talking While On Treadmill Reduces Exercise Intensity
Michael Rebold, PhD, CSCS Assistant Professor
Department of Exercise ScienceBloomsburg University Bloomsburg, PA 17815
this study?
• Dr. Rebold: Assess other modes of exercise (bike, elliptical) since treadmill exercise is not the
preferred mode of exercise for all individuals.
• Examine different age groups.
• Currently conducting similar studies at Bloomsburg University of Pennsylvania examining
specifically how much time is spent at different exercise intensities (light, moderate,
vigorous) during a bout of exercise while having a smartphone present / and also examining
how different smartphone functions (texting, talking, music) affect balance.
• Citation:
• Michael J. Rebold, Andrew Lepp, Gabriel J. Sanders, Jacob E. Barkley. The Impact of Cell
Phone Use on the Intensity and Liking of a Bout of Treadmill Exercise. PLOS ONE, 2015; 10
(5): e0125029 DOI: 10.1371/journal.pone.0125029

Low Testosterone May Affect More Than 25% of US Males
Jim Dupree, MD, MPH
Assistant Professor
Department of Urology, Division of Andrology
University of Michigan
Dr. Dupree: There are increasing discussions in the United States about testosterone therapy and
men with clinical hypogonadism (or low testosterone). Yet, to date, there have not been any
nationally-representative studies of the prevalence of low testosterone in the United
States. Using a validated national health examination program from the CDC, we found that the
national prevalence of low testosterone (serum testosterone ≤ 300 ng/dL) in adult males in the
US was 28.9%. Among other factors, men who were older, had a higher body mass index (BMI),
or had a larger waist circumference were at risk for having lower testosterone levels.

Jim Dupree, MD, MPH
Assistant Professor
• Dr. Dupree: For the first time, we now have nationally-representative data on the prevalence
of low testosterone in United States. It’s important that low testosterone alone is not used
as the sole reason for a man to seek treatment. In order for a man to start medications for
low testosterone, he should also have symptoms of low testosterone. If a man is concerned
that he has low testosterone levels (also known as clinical hypogonadism), he should speak
with his doctor about his symptoms. Patients and clinicians can also use this data to
recognizable that modifiable factors like BMI and waist circumference are likely related to
testosterone levels.

Jim Dupree, MD, MPH
Assistant Professor
this study?
• Dr. Dupree: It has been well established that low testosterone levels are a necessary but not
sufficient reason for a man to start taking medications for clinical hypogonadism. In order to
begin treatment, a man should also have symptoms consistent with hypogonadism. We were
not able to evaluate hypogonadal symptoms in our study, so future studies should work to
establish national prevalence numbers for symptoms of hypogonadism and testosterone
levels, both of which are needed to guide treatment decisions.
• Citation:
• PREVALENCE OF LOW TESTOSTERONE IN A POPULATION BASED, NATIONALLY
REPRESENTATIVE SURVEY
James Dupree*, Chang He, Dana Ohl, Ann Arbor, MI, Larry Lipshultz, Houston, TX, Aruna
Sarma, Ann Arbor, MI
American Urological AssociationSunday, May 17, 2015 1:00 PM-3:00 PM
NOMCC: 208-210
Sexual Function/Dysfunction/Andrology: Evaluation II

Should Digital Rectal Exam Still Be Used For Prostate Cancer Screening?
Ryan P. Terlecki, MD, FACS Director, Men’s Health Clinic
Director, Fellowship in Urologic Reconstruction, Prosthetic Urology, and Infertility
Director, Medical Student Education Associate Professor of Urology Wake Forest Baptist Health
Response: In recent years, the value of generalized screening for prostate cancer (PCa) in adult
men has been questioned, with several national associations recommending against the practice
in men without recognized risk factors. Screening, when performed, often consists of a blood test
for prostate specific antigen (PSA) and a digital rectal exam (DRE). Once PSA was developed as a
screening tool, we witnessed a stage migration such that observing a locally advanced cancer that
would be initially found via DRE became a rarer event. In practice, we have noticed that some
men will actually avoid a clinic visit because of the DRE. Additionally, the digital rectal exam has
limitations and is often poorly reproducible among providers. We chose to review a large body of
data to shed some light on the utility of the digital rectal exam exam. We analyzed data from the
Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening trial, to determine the ability of
the digital rectal exam to result in a diagnosis of clinically significant PCa in the setting of a normal
PSA. We found that if PSA is normal and digital rectal exam is considered abnormal, the chance of
detecting a clinically significant cancer is similar to a situation of normal DRE and normal PSA.
Also, 1,372 men would need to undergo a digital rectal exam to identify a single case of clinically
significant prostate cancer not detected by PSA.

• Response: We did find that if both PSA and DRE was abnormal, there was a higher chance of
clinically significant PCa. Thus, if a patient has abnormal PSA and is ‘on the fence’ about
having a biopsy, also having an abnormal DRE may lend more support to proceeding with the
procedure.
• The guideline from the American Urological Association (AUA) states that the literature
supporting the efficacy of DRE as a screening test to reduce deaths from prostate cancer is
too limited to draw conclusions. The panel responsible for creating the guideline stated that
they could find no evidence to support the continued use of DRE as a first line screening test.
This element of the guideline seems to be further supported by the findings of our analysis.

this study?
• Response: It should be determined if the digital rectal exam should disappear from routine
urologic management in patients without a prior history of prostate cancer. If the AUA has
already asserted that using the DRE as a first line screening tool is not supported by evidence,
research should be directed at the use of DRE in the setting of benign disease. In regard to
benign prostatic hyperplasia (BPH), decision-making is guided by patient symptoms (reflected
in the AUA symptom score) and not by the DRE, which often poorly estimates the nature of
the prostate and does not provide reliable information regarding the inner portion of the
prostate, which is most relevant to urination.
• Citation:
• American Urological Society abstract May 2015:
• Does digital rectal examination provide additional value in the era of PSA screening?: Lessons
from the PLCO study
• Cui, Tao (Winston Salem, NC); Cui, Tao; Kovell, Robert C; Kovell, Robert C; Brooks, David
C; Brooks, David C; Terlecki, Ryan P; Terlecki, Ryan P

Frequent Ejaculation Linked To Lower Prostate Cancer Risk
Jennifer R. Rider, ScD, MPH Assistant Professor of Medicine
Channing Division of Network Medicine
Brigham and Women’s Hospital and Harvard Medical School Department of Epidemiology
Harvard T.H. Chan School of Public Health
Dr. Rider: Numerous studies have investigated the potential role of sexual activity on the
development of prostate cancer. However, most of these studies have been small and
retrospective, making them more prone to bias. In addition, previous studies often relied on
proxies of exposure for sexual activity (number of sexual partners, age at first marriage, etc.),
which may not adequately measure the aspects of sexual activity that are most important for
prostate health. The current study is the largest prospective study to date on ejaculation
frequency and prostate cancer. It includes 18 years of follow up of almost 32,000 healthy men,
3839 of whom later were diagnosed with prostate cancer. We asked men about their average
monthly frequency of ejaculation between the ages of 20-29, 40-49, and in the year prior to the
questionnaire (1991). We find that frequency of ejaculation throughout life course is inversely
associated with risk of prostate cancer at all three of these time points. For instance, men who
have an average monthly ejaculation frequency of 21 or more times/moth at ages 40-49 have a
statistically significant 22% reduction in risk of developing prostate cancer compared to men with
a frequency of 4-7 times/month, adjusting for multiple dietary and lifestyle factors, and prostate
cancer screening history.

Frequent Ejaculation Linked To Lower Prostate Cancer Risk
Jennifer R. Rider, ScD, MPH Assistant Professor of Medicine
Channing Division of Network Medicine
Brigham and Women’s Hospital and Harvard Medical School Department of Epidemiology
Harvard T.H. Chan School of Public Health
• Dr. Rider: While these data are the most compelling to date on the potential benefit of
ejaculation on prostate cancer development, they are observational data and should be
interpreted somewhat cautiously. At the same time, given the lack of modifiable risk factors
for prostate cancer, the results of this study are particularly encouraging.
this study?
• Dr. Rider: The next step will be relate ejaculation to specific changes in the prostate that
could impact prostate cancer development to clarify the underlying mechanism.
• Citation:
• Presented at the American Urological Society May 2015
• Ejaculation frequency and risk of prostate cancer: updated results from the Health
Professionals Follow-up Study
• Jennifer Rider*, Kathryn Wilson, Rachel Kelly, Erika Ebot, Edward Giovannucci, Lorelei Mucci,
Boston, MA
• Funding: Prostate Cancer Foundation Young Investigator Award

Understanding PSA Controversy Does Not Deter Men From Getting Tested
Michael Fenstermaker MD
NYU School of Medicine | MD, MS | Class of 2015
Northwestern University | BA | Biochemistry, Psychology
Dr. Fenstermaker: The benefits of using prostate-specific antigen (PSA) testing to screen for
prostate cancer are uncertain. In response to this, many medical societies have recently scaled back
their recommendations for PSA screening. One common thread among these groups is that shared
decision-making should guide whether or not men get tested. Shared decision-making is a process
by which physicians and patients work together to make a medical decision that aligns with the
patient’s values and follows the best available medical evidence.
• Several studies have shown a decline in PSA testing since new guidelines have been
published. While a decrease in screening is not necessarily problematic itself, it could be an issue if
this is the result of fewer physicians discussing screening with their patients. Some experts worry
that disparities in screening could develop, such that only informed patients go on to speak with
their physicians and receive PSA testing. By analyzing data from a national survey, we had the
chance to investigate just how much men know about the controversies leading to these guidelines
changes and whether this knowledge influences PSA usage.
• Our findings show that the majority of U.S. males of screening age report that they were not
informed of many key facts important to understanding the risks and controversies surrounding PSA
testing. Of particular concern, certain vulnerable populations, such as those without regular
healthcare providers were less likely to be informed of these facts. Surprisingly, those men who had
more awareness of the controversies about PSA testing were more likely to undergo testing.

• Dr. Fenstermaker: We hope the extent to which most screening-age males are under
informed about the risks, benefits, and controversies of prostate cancer screening is eye-
opening to many physicians. Without definitive evidence that PSA screening is helpful or not,
we owe it to our patients to discuss the current controversies surrounding PSA. The
observation that PSA usage was associated with awareness is potentially concerning as well.
With shared decision-making, it is important to ensure that variations in PSA usage are the
result of patient preferences.
• Some patients may also feel shy about participating in shared decision-making. Patients
should realize that they have a say in the decision to be screened for prostate cancer. By
starting a dialog, encouraging their physician to discuss the evidence behind PSA openly, they
can reach a choice that better fits their own values.

this study?
• Dr. Fenstermaker: Strategies for better implementing shared decision-making into clinic
practice need to be developed. There is the impression that providing a comprehensive
overview of prostate cancer screening in a short clinic visit is too difficult. However, this is
where tools to assist physicians and patients, such as decision aids, may become valuable in
helping with the shared decision-making process.
• Citation:
• Presented at the 2015 American Urological Association
• Friday, May 15, 2015 1:00 PM-3:00 PM
NOMCC: 217-219
General & Epidemiological Trends & Socioeconomics: Evidence-based Medicine & Outcomes I
Funding: None
MP5-12: Understanding the Limitations of Prostate-Specific Antigen Testing Does not Deter
Men from Undergoing Prostate Cancer Screening
Michael Fenstermaker*, Stacy Loeb, Heather T. Gold, Joseph Ravenell, Danil Makarov, New
York, NY

Neuron-Specific Biomarker May Help Predict Outcome After Out-of-Hospital Cardiac Arrest
Dr Pascal Stammet
Dépt. Anesthésie-Réanimation
Centre Hospitalier de Luxembourg Luxembourg
• Dr Stammet: Patients hospitalized after an out-of-hospital cardiac arrest (OHCA) survive in
about fifty percent and nine out of ten survivors have a good functional level six months after
the arrest. However, in the early days after the cardiac arrest it is difficult to distinguish those
who will survive from those who have very severe brain damage, not compatible with life.
Biomarkers, like neuron specific enolase (NSE) have shown a prognostic value for outcome
prediction. As a consequence of the widespread use of induced hypothermia, to improve
survival and neurological function, for patients resuscitated form cardiac arrest, concerns
have arisen about the impact of body temperature on previously published cut-off values for
poor outcome. NSE has thus been questioned as a useful clinical tool. Recently, the Target
Temperature Management trial (TTM-trial) published in November 2013 in the NEJM has
shown no benefit of a target body temperature of 33°C over 36°C in patients with out-of-
hospital cardiac arrest admitted to the ICU. In the present sub-study, we have analyzed the
value of NSE to predict outcome in a cohort of 686 patients of the TTM-trial. Importantly,
serial measurements of NSE at 24, 48 and 72 hours allowed accurate outcome prediction,
with better performance than clinical and peri-arrest data alone. NSE did not significantly
differ between temperature groups meaning that clinicians can use NSE as an adjunct
prognostic tool regardless of the chosen temperature management strategy.

Dr Pascal Stammet
• Dr Stammet: High, serial and increasing NSE values over time are strongly predictive of poor
outcome after out-of-hospital cardiac arrest. The degree of targeted temperature
management does not affect significantly the levels of NSE; identical NSE cut-offs are
applicable for both temperature levels. Furthermore, biomarkers, like NSE are independent
of sedation, unlike EEG or clinical examination, which can be strongly influenced by the level
of sedative medications. One word of caution though: NSE values determined in haemolyzed
blood samples must be discarded as haemolysis interferes with NSE measurement. Finally, no
single outcome predictor should be used alone to decide on withdrawal of life supporting
therapies for an individual patient; there must always be a bundle of parameters taken into
consideration.

Dr Pascal Stammet
this study?
• Dr Stammet: As brain-derived biomarkers are generally not influenced by sedation, their
potential as outcome predictor after out-of-hospital cardiac arrest is appealing. Novel
families of biomarkers like micro-RNAs (miRNAs) are under investigation. Brain-enriched
miRNAs are released in the bloodstream after OHCA and thus may accurately reflect brain
damage. Since miRNAs are able to regulate gene expression, they could even host potential
therapeutic opportunities in the future. Therefore, this study motivates further research on
the use of brain-derived biomarkers to tailor healthcare to each individual with cardiac arrest.
• Citation:
• Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome After Out-of-
Hospital Cardiac Arrest and Targeted Temperature Management at 33°C and 36°C
• Irina Dragancea, Janneke Horn, Michael Kuiper, Hans Friberg, Susann Ullén. Jørn Wetterslev,
Jules Cranshaw, Christian Hassager, Niklas Nielsen, Tobias Cronberg, the TTM trial
investigators
• Resuscitation
• Available online 25 April 2015

Rosacea: Metronidazole Plus Modified Release 40 Mg Doxycycline Improved Moderate To Severe Disease
Warren J. Winkelman, MD, MBA, PhD, FRCPC, FAAD
Director, Medical Affairs Galderma Laboratories, L.P.
Fort Worth TX 76177
• Dr. Winkelman: Rosacea is a common dermatologic facial disorder estimated to affect 16 million
Americans. Rosacea is a chronic condition of the central face, including the nose, chin, cheeks and
forehead, and is often characterized by flare-ups and remissions. While the cause of rosacea is
unknown and there is no cure, its signs and symptoms can become markedly worse in the absence
of treatment. Rosacea can be managed with topical and oral medications, and physicians often
resort to using these medications in combination for more severe or resistant cases. Doxycycline 40
mg modified release (MR) and metronidazole 1% gel are FDA-approved oral and topical therapies,
respectively, indicated to treat the papules and pustules of rosacea. We conducted a phase 2 study
to assess the relapse rate, efficacy, and safety of doxycycline 40 mg MR compared to placebo after
an initial 12-week once-daily combination regimen of doxycycline 40 mg MR and metronidazole 1%
gel in subjects with moderate to severe disease.
Of the 235 subjects enrolled in the study, 71% were women, 94% were white, and 75% had
Fitzpatrick skin type I, II or III. The mean age was 47.4 years. The percentage of subjects who
achieved a success score of 0 (clear) or 1 (near clear) improved from 0% at baseline to 51% at week
12. Clinician’s erythema assessment scores, inflammatory lesion counts, and quality of life scores
also improved. Most subjects reported no or mild scaling, stinging/burning, and dryness. Five
adverse events were reported that were considered probably or definitely related to treatment:
fungal infection, vulvovaginal mycotic infection, pain in extremity, erythema, and skin exfoliation.

Fort Worth TX 76177
• Dr. Winkelman: A once-daily combination regimen of doxycycline 40 mg MR and
metronidazole 1% gel was observed to be efficacious, safe, and tolerable, and had a positive
effect on quality of life in subjects with moderate to severe rosacea.

Fort Worth TX 76177
this study?
• Dr. Winkelman: Future research should include long-term approaches to managing signs and
symptoms of rosacea. In addition, further examination of the pathophysiology of rosacea and
the mechanism of action of factors that trigger the onset of signs and symptoms and
exacerbate the condition will be vital in treating this chronic skin condition.
• Citation:
• Berlin J and Winkelman W. Efficacy and tolerability of oral doxycycline 40 mg modified
released with topical metronidazole 1% gel in moderate to severe rosacea. Poster presented
at 73rd Annual Meeting American Academy of Dermatology; March 20-24, 2015; San
Francisco, CA.

Poor Sleep May Contribute To Lower Urinary Tract Symptoms in Men
Alexander W. Pastuszak, MD, PhD Male Reproductive Medicine and Surgery Scott Department of Urology
Jason Malcolm Scovell Medical Student, Ofc SA-BCM Students
Baylor College of Medicine Houston, TX
Response: Sleep quality is an important component of overall health, and can both exacerbate
health issues and be impaired by health problems. Shift workers, primarily those who do not
work standard daylight shifts, are prone to sleep problems, a significant concern in light of the
fact that up to 25% of the U.S. workforce is comprised of shift workers. As men age, the
prevalence of Lower Urinary Tract Symptoms (LUTS), which include urgency, frequency, waking up
at night to urinate, and difficulties with urination, increases. Unsurprisingly, men with LUTS
report poor sleep in part due to awakening repeatedly during the night. We studied a group of
male shift workers, who we believe to be an ‘at-risk’ population, and found that not only do the
men who report worse sleep quality have worse Lower Urinary Tract Symptoms, but also men
who report difficulty falling asleep have more severe LUTS than those who do not. This latter
point is significant, given that most men with LUTS can fall asleep without difficulty, but then
awaken repeatedly throughout the night, and suggests that sleep difficulties in this population
may be resulting in Lower Urinary Tract Symptoms rather than LUTS exclusively resulting in sleep
difficulties.

• Response: Worse sleep quality in patients with regards to falling asleep, staying asleep, and
getting back to sleep once awakened is associated with more severe Lower Urinary Tract
Symptoms in our study. We cannot conclude whether poor sleep quality is exacerbating LUTS
with, although the relationship between difficulty falling asleep and more severe Lower
Urinary Tract Symptoms suggests that poor sleep may indeed be a contributing factor.

this study?
• Response: Given that sleep is important to mitigating the effects of numerous bodily
dysfunctions, and sleep optimization can be achieved through simple lifestyle interventions,
future studies investigating the causes of why patients who have more difficulty falling asleep
report more severe LUTS will be important. If poor sleep is, in fact, exacerbating LUTS, simple
changes to sleep habits may be an effective intervention to reduce LUTS. Similarly, if LUTS are
resulting in difficulty with falling asleep, aggressive treatment of these symptoms may be
important in improving sleep quality, which has such an important effect on overall health.
• Citation: Abstract Presented at the 2015 American Urological Society
• PD39-06 IMPAIRED SLEEP QUALITY PREDICTS MORE SIGNIFICANT LOWER URINARY TRACT
SYMPTOMS IN MALE SHIFT WORKERS
• Pastuszak, Alexander W. et al.
The Journal of Urology , Volume 193 , Issue 4 , e832

Testosterone Therapy Lowered Mortality In Hypogonadal Men
Ranjith Ramasamy MD
Assistant Professor of Urology
University of Miami
Medical Research: What is the background for this study?
Dr. Ramasamy: The association between testosterone supplementation therapy (TST) and
thrombotic risk in elderly men remains controversial. We evaluated the prevalence of thrombotic
events and all-cause mortality in men older than 65 years with hypogonadism treated with
testosterone therapy. We compared men treated with testosterone to an age and comorbidity
matched cohort of hypogonadal men not treated with testosterone supplementation therapy.

Ranjith Ramasamy MD
University of Miami
Medical Research: What are the main findings?
Dr. Ramasamy: No man who received testosterone supplementation therapy died, whereas 6
hypogonadal men who did not receive TST died (p=0.007). There were 4 thrombotic events (1 MI
– myocardial infarction, 2 CVA/TIA – stroke, 1 PE – pulmonary embolism) in men who received
testosterone supplementation therapy compared to 1 event (CVA/TIA) among men who did not
receive TST (p = 0.8). All the events (except one death which took place at 6 months of follow–up)
occurred 2 years or more after follow–up. Strengths of the study include long follow–up (>3
years), availability of serum testosterone levels before and after therapy and of a control group
(hypogonadal men not treated with TST) for comparison. Limitations included retrospective study
design, and a small sample size.

Ranjith Ramasamy MD
University of Miami
•
• Dr. Ramasamy: Consistent with the majority of the studies in the literature, there was increased all-
cause mortality in hypogonadal men (men with total testosterone < 300 ng/dL) not treated with
testosterone compared to men who received testosterone therapy. There was no difference in
prevalence of MI, TIA/CVA, or PE between patients who were treated with testosterone and
hypogonadal men not treated with testosterone.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Ramasamy: Long term randomized trials evaluating the benefits and risks of testosterone
therapy in elderly men is necessary.
• Citation:
• Abstract Present at the 2015 American Urology Association
• Sunday, May 17, 2015 1:00 PM-3:00 PM
NOMCC: 208-210
Sexual Function/Dysfunction/Andrology: Evaluation II
Funding: none
MP51-01: LH Suppression and Serum Testosterone is Positively Associated with Fewer Hypogonadal
Symptoms in Men on Testosterone Supplementation
Jason Scovell*, Christina Mai, Michael Mederos, Ranjith Ramasamy, Dolores Lamb, Larry Lipshultz,
Houston, TX

Iron Deficiency Anemia May Complicate Diagnosis of Diabetes
Emma English PhD
Lecturer in Healthcare Science and Academic Lead for Clinical Biochemistry
University of Nottingham, School of Medicine Royal Derby Hospital, UK
• Dr. English: HbA1c is widely used for monitoring glycaemic control in people with diabetes as
there is clear evidence that lowering HbA1c values leads to reductions in the rates of
diabetes complications. Recently the World Health Organization and the American Diabetes
Association have both advocated the use of HbA1c for the diagnosis of Type 2 diabetes at a
value of ≥48 mmol/mol (6.5%). Whilst there are many advantages to the use of HbA1c as a
diagnostic tool there are equally some significant limitations to its use. A widely cited
confounder is anaemia, however to what extent and which types of anaemia affect HbA1c
results was not clearly understood. When HbA1c was introduced as a diagnostic test in
England we received many queries from healthcare professionals asking questions such as ‘at
what level of anaemia should I not use HbA1c?’ and ‘should I routinely screen patients for
anaemia when using HbA1c? And if so, what test should I use?’. In order to answer these
questions we conducted a systematic review of the literature to determine what was known
on this subject.
• Our findings, presented in Diabetologia, suggest that iron deficiency and iron deficiency
anaemia may lead to a spuriously elevated HbA1c level, thus may lead a false positive
diagnosis of diabetes. However, non-iron deficiency anaemias can lead to an artificially lower
HbA1c and may lead to a false negative result where a diagnosis of diabetes would be
missed. There is no clear evidence to suggest at what levels anaemia can give rise to these
effects on HbA1c value and also there does not appear to be a single ideal test for identifying
patients where this could be an issue.

MedicalResearch.com: Medical Research Exclusive Interviews May 18 2015

MedicalResearch.com: Medical Research Exclusive Interviews May 18 2015

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MedicalResearch.com: Medical Research Exclusive Interviews May 18 2015