THE MEDICAL I.B.I.S. INVESTIGATION OF BASIC
University of Miami
Miller School of Medicine VOLUME 5 ISSUE 1 SPRING 2017
The students at the University of Miami Miller School of Medicine are among the nation’s most extraordinary individuals, committed to advancing research and extending health care to all corners of our community. I am honored to be included in this issue of The Medical I.B.I.S., an impressive showcase of the dedication of our students to advancing medical science.
The aspirations that guide our vision for the future of the University of Miami – to become the hemispheric, excellent, relevant and exemplary university – will be realized through the imagination and discoveries of our students. Connecting that curiosity and excitement across our schools and disciplines will extend the impact of our work to transform lives throughout the Americas and beyond.
I look forward to seeing the growing connections of our brilliant medical students with students and faculty throughout the University. The results of their interactions, as well as their research described in this book, will improve the quality of life of our patients and patients everywhere. For that, I am deeply grateful.
Julio Frenk, M.D., Ph.D. President, University of Miami
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It is my pleasure to present the fifth issue of The Medical I.B.I.S., the University of Miami Miller School of Medicine student-produced research publication, which features outstanding examples of research conducted by our medical students.
Nowhere is the synergy of enthusiastic and intelligent students combined with committed and remarkable faculty better demonstrated than in publications like this. Furthermore, the Miller School of Medicine commitment to research, which aims to improve the lives of our patients and the care they receive, is evident throughout the pages of this publication. The combination of intellectual curiosity, a remarkable patient population and a terrific group of faculty creates an outstanding demonstration of the Schoolâ€™s commitment to transform lives through education, research and service.
The research presented in these pages is truly impressive. It spans the environment of inquiry from the basic research laboratory to the bedside. As the Interim Dean of the Miller School of Medicine, I am proud to see our students, just at the beginning of their research and clinical careers, starting to make contributions that will improve the care of the patients who entrust us with the privilege and responsibility to improve and maintain their health and wellbeing.
As the Dean, it makes me proud to see our students excel in research, as their work will bring great value to our community in South Florida, the U.S., the Americas and the entire world.
Laurence B. Gardner, M.D., M.A.C.P. Dean, University of Miami Miller School of Medicine
Spring 2017 THE MEDICAL I.B.I.S. 3
THE MEDICAL I.B.I.S.
Editor-In-Chief Tom Boyle Managing Editor Lily Zhang Senior Editors Laura Bloom Nikesh Doshi Kevin Moore Reshma Muppala Muppala, Boyle, Zhang, Doshi
Selection Committee Chair Michael Durante Selection Committee Michelle Caunca Matt Field Olivia Gardner Patrick Staropoli Shuo-chieh Wu Director of Layout Anjanique Mariquit Lu Director of Photography Alexander Bode
Caunca, Staropoli, Durante, Wu, Gardner
Photography Assistant Nicole Lin Publishing Editor Aarabhi Rajagopal
Special Thanks to:
Lu, Rajagopal, Boucekkine, Thanikachalam
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Section Editors Houda Boucekkine Emily Chen Cathy Cichon Saradadevi Thanikachalam Genevieve Wiehl Writers David Feldman Ryan Gallo Dylan Greif John Paul George Kolcun Nathan McKenty Santiago Montana Amit Patel Dylan Petkus Catherine Zaw
Faculty Advisor Emmanuel Thomas, M.D., Ph.D. Advisory Board Alex J. Mechaber, M.D.
The Medical I.B.I.S. is published by the University of Miami Miller School of Medicine Student Government. We reserve the right to edit any submissions, solicited or unsolicted, for publication. This magazine is the work of University of Miami medical students, and the University of Miami is not responsible for its contents. Perspectives expressed by authors do not necessarily reflect the opinions of the University of Miami. We retain the right to reprint contributions, both text and graphics, in future issues as well as a non-exclusive right to reproduce these in electronic form.
Gallo, McKenty, Zaw, Greif, Feldman, Kolcun
The Medical I.B.I.S. welcomes comments and feedback. Please send questions and comments to email@example.com.
Special Thanks to:
The 2017 Medical I.B.I.S. Masthead
Spring 2017 THE MEDICAL I.B.I.S. 5
12 Katyayini Aribindi Comparative Profiles of Cholesterols between Normotensive and Hypertensive States in DBA/2J Mouse Aqueous Humor
Research in Residency
Zika in Pregnancy: The Miami Experience
How to Get Involved and What to Expect
Endothelial/Descemetâ€™s Membrane Thickening as a Sign for the Diagnosis of Corneal Graft Rejection
Genetics of Anti-TNF Therapy in Inflammatory Bowel Disease
Interaction of Otopathogenic Staphylococcus aureus with Human Middle-ear Epithelial Cells
6 THE MEDICAL I.B.I.S. Spring 2017
18 Outcomes-Based Evaluation of a Pediatric Nutritional Recuperation Program in Cartagena, Colombia
Telemedicine Broadening Access to Care for Complex Cancer Cases
Healthy Skin for Everyone: Addressing Skin Cancer Disparities in Underserved, Uninsured and Minority Communities
Post-Ischemic Whole Body Vibration Reduces Inflammation in the Brain of Middle-aged Female Rats
Distance Between Uveal Melanoma and Optic Disc Margin: The Best Predictor of Radiation-Induced Complications from Iodine-125 Plaque Brachytherapy
Experienced Career Researchers Provide Words to Live By
Sleep Duration is Associated with Depression Symptoms in the Northern Manhattan Study
24 Gabrielle Hodgins The Power of the Placebo Effect in a PTSD Clinical Trial
Spring 2017 THE MEDICAL I.B.I.S. 7
Zika in Pregnancy:
STUDENT RESEARCHER Colette Tse MD/MPH 2019 by Santiago Montana
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The Miami Experience Zika virus is a new and enigmatic pathogen that piqued the world’s interest in 2016, setting off an unparalleled wave of infectious disease research and political rumbling. The virus was first discovered in 1947 in Uganda and is a member of the family Flaviviridae, which includes the well-known Dengue, yellow fever, and West Nile viruses. Zika can spread through mosquito bites, sexual contact, and vertical transmission, but rarely produces bothersome symptoms in adults. For this reason, research into the virus remained relatively quiet for the last half century. Between 1947 and 2006, there were only 14 recorded cases of Zika infection in humans worldwide. In 2007, the first Zika outbreak occurred in The Pacific island of Yap. Later, in 2013 and 2014, four more Zika outbreaks struck in other Pacific islands, and researchers began to recognize a relationship between Zika virus and severe congenital malformations. In 2016, a study published in the New England Journal of Medicine established definitively that Zika infection during pregnancy could cause severe congenital defects in newborns.
Colette Tse is a second-year MD/MPH student who has been working to investigate the effects of the virus with Dr. Christine Curry, M.D., Ph.D., an Assistant Professor of Obstetrics and Gynecology who is spearheading UMMSM’s response to the virus. Specifically, Colette has been tracking outcomes of pregnancies in which the mothers have confirmed Zika infections. Colette first cultivated an interest in infectious diseases as an undergraduate at UC Berkeley, where she majored in molecular and cellular biology with an emphasis in infectious disease. In addition, Colette is interested in obstetrics and gynecology as a potential career. When she spoke with Dr. Curry regarding the opportunity to investigate Zika infections in Miami, the project sounded like the perfect marriage of three of her greatest interests: ob-gyn, population health, and infectious diseases. Colette is currently helping to conduct a retrospective review of all pregnant women who were tested for Zika virus while they were patients at Jackson Memorial Hospital or University of Miami Hospital. As of now, the team has reviewed the charts of 1,345 patients meeting those criteria. Among them, 67 have tested positive for Zika. Within the cohort, 33 children have been born to infected mothers and 2 of those children have confirmed congenital abnormalities: one with microcephaly and intracranial calcifications and one with intracranial calcifications and retinal hypopigmentation. In addition to data gathering, Colette and the clinical team ensure that the Zika-positive mothers receive adequate perinatal care, and that the virus is tracked through birth. Additionally, the researchers coordinate with pediatric infectious disease spe-
cialists to ensure newborns have adequate follow-up care. An important aspect of the project is that it is still in its early phase, and there are many births to come and follow-up visits to be conducted. Collette is hopeful that her work will help the local and global medical communities gather valuable information about the full spectrum of Zika virus’ effects on pregnancies.
Colette believes that one of the most important clinical lessons from her experience has been observing the weaknesses of various testing modalities. Outside of the CDC headquarters in Atlanta, there are only two tests for Zika virus: an IgM antibody test and a test for viral RNA called PCR. Both tests are far from perfect. The PCR is only useful within two weeks of infection, when there is substantial viral material circulating in a patient’s blood. The IgM antibody test often loses its effectiveness 3 months after infection. Both tests leave the door open for false negatives – test results that show no virus when, in fact, an individual is infected. The implications are massive because prompt testing is essential for accurate results and quickly connecting families to adequate care. Colette and other researchers are hopeful that better tests will become available soon. In addition to gaining direct insight into the disease, Colette has grown tremendously as a researcher and future physician through conducting this project. By being on the front line of the outbreak in south Florida, Colette was able to observe how the Department of Health, the Centers for Disease Control, local and state governments, hospitals, and researchers all collaborated to care for patients after the initial outbreak. She has gained firsthand experience and can recognize the strengths and weaknesses of our healthcare infrastructure as it pertains to responding to emerging diseases. She understands the hurdles that stand between undiagnosed patients and adequate care. Because of these deficiencies in diagnosis and care, she is excited at the prospect of continuing to aid patients at the frontline of this new disease in Florida, and to have learned about some new and fascinating ways she can apply her MPH degree in the future.
Colette is eager to continue working on this project during the remainder of her time in Miami. Currently, the team plans on continuing testing and patient follow-up care. Additionally, future goals include evaluating the economic impact of Zika virus and further improving screening methods. Colette presented her research findings at the American Medical Association Research Symposium in November 2016. She has more presentations scheduled in the near future so that she can continue to spread the word about this emerging disease.
Spring 2017 THE MEDICAL I.B.I.S. 9
Endothelial/Descemet’s Membrane Thickening as a Sign for the Diagnosis of
Corneal Graft Rejection An In and Ex Vivo Study by Ryan Gallo
The most commonly transplanted human tissue is the cornea, the eye’s outermost transparent layer. Transplants can restore vision to people who have a damaged or diseased cornea by replacing theirs with healthy donor tissue. However, approximately 50% of patients receiving the 120,000 corneal grafts performed worldwide annually undergo a rejection event in which their immune systems attack the donor cornea. One in four corneal grafts fail within three years, and while repeated surgeries are utilized, rejection risk increases with each subsequent graft. STUDENT RESEARCHER Ryan VanDenBerg MD 2017
Honors Presented at the American Academy of Ophthalmology Education Symposium in Chicago, IL in October 2016
Mentor Dr. Mohamed F. Abou Shousha, M.D., FRCS, Ph.D.
Other Interests Cancer, biomedical engineering
Future Goals Improve healthcare through technology
Damage from rejection events can be minimized if treatment begins promptly; however, predicting and identifying rejection are major challenges. Ryan VanDenBerg, a fourth-year medical student and researcher, sought to address this problem by identifying the histopathological changes underlying corneal graft rejection with light microscopy and advanced imaging technology. Since September 2015, Ryan has worked under the guidance of Dr. Mohamed F. Abou Shousha, M.D., FRCS, Ph.D., Assistant Professor of Clinical Ophthalmology, Cornea and External Disease at Bascom Palmer Eye Institute. Given his engineering background, Ryan was initially attracted to this work because of how he could apply novel technologies to solve critical medical problems. Ryan’s research focused on understanding the histopathological changes in the Endothelial/Descemet’s membrane complex (En/ DM), which is a collection of discrete supportive tissue layers in the cornea. First, he utilized light microscopy as the standard to diagnose corneal graft rejection. In those same patients, images were obtained using high definition optical coherence tomography (HD-OCT), which demonstrated that the En/DM thickens in cases of rejection. The next task was to evaluate which layers of the En/DM contributed to the overall thickening. This phase of the study was performed ex vivo because the Descemet's membrane, endothelium, and retrocorneal membrane that constitute the En/DM thickness cannot be individually differentiated by HD-OCT. Ryan found that the overall En/DM thickening was solely a result of Descemet’s membrane thickening and not the endothelium or retrocorneal membrane. Overall, these results support that En/DM thickening measured by HD-OCT is diagnostic of corneal graft rejection. This has the potential to greatly aid in the diagnosis and early management of graft rejection.
For Ryan, the most enjoyable aspect of this study was to see the scientific method from start to finish. He presented his findings at the prestigious Cornea Society Education Symposium in October 2016. As for future plans, Ryan states, “In whatever medical field I decide to go into, I plan to continue to look for ways to implement advanced technologies with medical care to improve patient outcomes.”
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120,000 ESTIMATED # OF CORNEAL GRAFTS PERFORMED WORLDWIDE ANNUALLY
ESTIMATED % OF CORNEAL GRAFTS THAT UNDERGO A REJECTION EVENT
1 in 4
ESTIMATED PROPORTION OF CORNEAL GRAFTS THAT FAIL WITHIN THREE YEARS
Interaction of Otopathogenic
Staphylococcus aureus with Human Middle Ear Epithelial Cells by Ryan Gallo
NUMBER OF PEOPLE WORLDWIDE WITH HEARING LOSS FROM CSOM
ANNUAL DEATHS WORLDWIDE FROM CSOM
ESTIMATED BURDEN OF CASES IN UNDERDEVELOPED NATIONS
Otitis media (OM), the most common type of ear infection, is a major global health burden that affects more than 80% of children by age three. The chronic form of OM, chronic suppurative otitis media (CSOM), can damage auditory hair cells and lead to hearing loss. This progression is a serious concern for affected children because it can have significant consequences on language, psychosocial and cognitive development. Although it is known that Staphylococcus aureus and Pseudomonas aeruginosa are the predominant bacterial pathogens that cause CSOM, the molecular mechanisms that enable S. aureus to cause CSOM are still unknown. This knowledge gap has hindered the development of effective therapeutic strategies against the disease.
Second-year medical student Luca H. Debs is currently working alongside Dr. Xue Zhong Liu, M.D., Ph.D., FACS and Dr. Rahul Mittal, Ph.D., to investigate the mechanisms that cause CSOM. Luca was eager to get involved in translational research upon beginning his medical school training, and since the fall of 2015 has been able to do just that in Dr. Zhong Liu’s laboratory. The team’s assets include Dr. Zhong Liu’s knowledge as a leader in the field of otolaryngology and Dr. Mittal’s experience as a research scientist. Working together with them, Luca has been able to help investigate the underlying mechanisms of CSOM with the ultimate goal of developing more effective therapies.
Luca is currently studying how otopathogenic S. aureus isolated from CSOM patients interacts with human middle ear epithelial cells (HMEECs). He and the rest of his team have demonstrated that S. aureus requires microtubules, which are filamentous proteins that help give cells structure, to invade HMEECs and initiate disease. At the site of bacterial entry, the research team also observed aberrant accumulations of cholesterol. The addition of various compounds such as actin polymerization inhibitors (which prevent microtubule formation) and cholesterol-depleting agents to the HMEECs before infection with S. aureus were shown to significantly decrease bacterial invasion. “Seeing such a dramatic decrease in invasion was very motivating and gives hope for future treatments,” Luca says.
STUDENT RESEARCHER Luca H. Debs MD 2019
Honors Selected for Eastern Atlantic Student Research Forum
Xue Zhong Liu, M.D., Ph.D. Rahul Mittal, Ph.D.
Plastic surgery, cardiothoracic surgery
Future Goals Academic surgery
With these novel observations, the team is now examining how S. aureus and cholesterol interact within HMEECs. They are also focusing on the innate immune system’s response to S. aureus invasion. Luca says that a better understanding of the infectious characteristics of S. aureus and the underlying mechanisms of CSOM will lead to novel therapeutic targets. He is very excited by the potential this research has for improving patients’ health. This excitement has motivated Luca to continue translational research in his future medical career. In the meantime, he looks forward to improving the field’s understanding of CSOM pathogenesis and to developing his own scientific investigative skills further.
Spring 2017 THE MEDICAL I.B.I.S. 11
Comparative Profiles of Cholesterols Between Normotensive and Hypertensive States in DBA/2J Mouse Aqueous Humor by Dylan Petkus
Conducting research can be one of the most rewarding experiences at the University of Miami Miller School of Medicine. Delving into a scientific project can put students at the forefront of cutting-edge discoveries. Many students find interests during research that launch their careers. A lucky few also meet lifelong mentors and friends along the way. Katyayini Aribindi, a fourthyear medical student and four-time I.B.I.S. honoree is one of the lucky students who has experienced all of the above.
Katyayini has devoted her research career at UMMSM to investigating glaucoma, which is the leading cause of blindness in the world and affects 3 million individuals in the United States alone. Glaucoma is a disease of optic nerve damage traditionally characterized by increased intraocular pressure. Intraocular pressure is determined by the amount of aqueous humor within the hollow globe of the eye. A healthy amount of aqueous humor, and thereby normal intraocular pressure, is maintained by outflow through a trabecular meshwork at the base of the cornea. However, draining can be affected if the trabecular meshwork becomes rigid. Research in human cadavers has revealed that the lipid content of aqueous humor is associated with trabecular meshwork stiffness and glaucoma, but the directionality of the relationship remains unclear. Katyayini has worked to determine if increased intraocular pressure can be predicted by aquesous humor lipid profiles in rodents. Katyayini’s search for answers was hindered by a major obstacle: the rodent eye provides too dilute of a lipid profile to be analyzed by conventional mass spectrometry. In human aqueous humor, lipids are present in the micromolar range or greater. Typical mass spectrometry techniques can assess profiles in this range, providing the resolution needed to identify nearly 100 components including cholesterols, sphingomyelins, phosphotidylcholine, and many more. Rodent aqueous humor, in contrast, only contains lipid concentrations in the picomolar range, one-million times lower than the threshold required for accurate analysis. Unphased by this challenge, Katyayini began her investigatation by improving the resolution of mass spectrometry. Mass spectrometry allows researchers to visualize and identify the molecules present in a sample based on mass-to-charge ratios. The resolution of mass spectrometry is typically sufficient when compounds differ by dozens of atoms, which was not enough for Katyayini’s needs. She required a resolution for compounds that differ by only a few atoms. This need for extreme resolution led her to incorporate a process known as chip-based infusion to enhance mass spectrometry resolution. Put simply, chip-based infusion separates compounds based on charge and sprays this mixture into the mass spectrometer. Applying this preliminary separation is a cutting-edge techinque that provided the resolution Katyayini needed. Armed with the proper analytical method, Katyayini returned to the question of intraocular pressure and cholesterol profiles. To
12 THE MEDICAL I.B.I.S. Spring 2017
this end, a DBA/2J mouse model was used to analyze aqeuous humor cholesterol profiles in mice with normal and high intraocular pressures. The aqueous humor was extracted via paracentesis, and lipids were extracted prior to analysis with a TSQ Quantum Access Max triple quadrupole mass spectrometer with Triversa Nanomate apparatus utilizing precursor ion scan mode as part of the analytical method described above.
Analysis revealed that the cholesterol profiles of mice with normal and high intraocular pressures shared 50 cholesterol species. Mice with normal intraocular pressure displayed 3 unique cholesterol species.The greatest difference between the groups was that mice with high intraocular pressures displayed 40% less total cholesterol relative to the normal intraocular pressure group. These results suggest that a reduction in aqueous humor cholesterol may drive glaucoma through increases in intraocular pressure. This finding is the first step in the long journey towards identifying the mechanism that drives changes in aqueous humor cholesterol profiles and how this affects intraocular pressure. Elucidation of this mechanism will then allow for the development of pharmalogical interventions for glaucoma. Such news can dramatically improve patient outcomes as effective glaucoma treatments currently rely on costly and invasive surgical procedures.
On the road towards these findings, Katyayini also discovered the importance of mentorship working alongside Dr. Sanjoy Bhattacharya, Ph.D., or as Katyayini calls him, “Dr. B.” Dr. Bhattacharya has played an instrumental role in Katyayini’s academic and personal development since she entered his lab as a freshman at the University of Miami. Dr. Bhattacharya took Katyayini under his wing and showed her the ropes of scientific research. As a result, Katyayini has developed into one of the most impressive student researchers on the UMMSM campus. Not only has Dr. Bhattacharya bestowed his research knowledge to Katyayini, but also his life experience. Katyayini has learned so many important personal lessons from Dr. Bhattacharya that she freely refers to him as her “research dad.” In addition to her scientific and personal development, Katyayini has garnered several other scientific accolades. She has presented at several conferences, including the International Society for Eye Research. Her work has been published in Biochemie, Current Eye Research, and Investigative Opthalmology and Visual Science. Currently, Katyayini is looking forward to the results of residency applications. Although she has devoted her scientific career to ophthalmology, she hopes to land a residency in internal medicine. Wherever Katyayini goes for residency, she will undoubtedly continue to thrive in both scientific and medical realms.
STUDENT RESEARCHER Katyayini Aribindi MD 2017 Honors Presented at ISER (San Francisco, California, July, 2014) Published in Biochimie, October 2014.
Sanjoy Bhattacharya, PhD, M.Tech
Other Interests President of medical humanities interest group
Future Goals Internal medicine residency
Labor Research Omnia During Vincit Residency "Find something you
to work on"
Walter Jermakowicz, MD, PhD is in his fifth year of residency. Walter’s current projects include novel therapies for epilepsy, Parkinson’s disease, and traumatic brain injury. His joint training in medicine and laboratory research provides a valuable perspective in evaluating the scope and quality of research available to residents.
How do you find projects during residency? Between the responsibilities of internship and feeling burnt-out after my PhD, I was less engaged in research as a junior resident. With time, though, the interest came back. I was fortunate that the faculty here encouraged me to take on projects. That led to most of my current work.
I had always heard that surgery was a poor choice if I wanted to do research – that could not be more wrong. There is an abundance of private funding in surgical specialties and potential for great collaborations. There is money out there for good ideas. Here at UM, we have two years of dedicated research time. I used one year to complete an in-folded clinical fellowship; this year I am working in a lab. Our program lets you pursue your passions; I enjoy that freedom. This university also has great interdisciplinary work; some of my projects span basic science, psychology, neurology, and neurosurgery. That is the future of research. Why is resident-driven research important? To an extent it depends on your field: some specialties essentially require research time, others are more lenient. If you pursue a career in academia, the benefits are obvious. But talking about private practice, healthcare reimbursements are becoming increasingly linked to outcomes. With a strong research background, you’re more likely to keep your practice current. This easily translates to better outcomes, a win for physicians and patients.
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How useful is the PhD? I think the best part was earning the degree. The practice in scientific writing, statistics, and following through on projects was indispensible. It took extra time, but I enjoyed the work and it was worth it to me.
I don’t think everyone needs a PhD to incorporate research into a career. You need training, whether in the form of time off or just during medical school. You need the trial and error to learn what works, and just practice at it, like any other skill. Any last words of advice? Find something you love to work on. Having a few papers in one field is stronger than having many papers in many fields. It shows commitment, and you get a mastery of the subject you will not find if you spread your work too thin. The work becomes more enjoyable.
by John Paul Kolcun The modern medical student may feel an impulse familiar to academics worldwide: publish, publish, publish. However, while most academics seek that ever-elusive tenure, the medical student works toward a residency match. Thus, for us students, publication pressure is a drive to begin our careers in the field of our choosing.
Once we match though, what is the next step? Do we bid the bench goodbye, delete SPSS and R, and vow to never look at another spreadsheet? Or is there a place for research in residency, even while juggling hospital duties, board exams, and home life? To explore these questions, I sat down with two residents at our institution. Each has a unique research background, but equal passion and motivation.
Why promote resident research? The medical school I attended lacked the degree of research activity we have at UM, so I entered residency without a clear vision of what an academic project should be. After a few years’ experience, I think I have developed the skills necessary to be academically productive. I learned from numerous mentors here who took the time to teach me techniques and how to approach a research problem. I want to be that resource for younger residents. You’re so busy as a junior resident, it is important to have someone to guide you through those years. Part of that is incorporating research activity into your work. When you reach the senior years, you have the experience, resources, and relationships required to conduct research effectively.
"You should always have a project
hanging over your head." Timur Urakov, MD is also a fifth-year resi-
dent. His current work includes basic science investigation of drug-delivery materials, applications of robotics and brain-machine interfacing, and many clinical projects. One of his primary interests is encouraging younger residents and medical students to seek research opportunities.
How does research now affect your career? There are trade-offs in everything. Every year of training – a fellowship, incorporated research years in the program, etc. – has tangible correlates (for example, an extra year with an attending level salary). So is a research year really worth that much money? Unless your work saves lives or changes the field, maybe not. But the goal in residency is to give you as many tools as possible. The experience of conducting research is more important than completing any single project, because it becomes a skill you carry forward. So, these projects are not just lines on a CV; they represent the ability to do more work in the future. Any last words of advice? Research is not just the work you do, it’s a mindset. You become continuously part of the process because you’re thinking of new ways to solve old problems and you’re looking for applications no one else has noticed. At a student’s level, you should take any project offered, because even a bad project will teach you something. You should always have a project hanging over your head.
Spring 2017 THE MEDICAL I.B.I.S. 15
Genetics and Anti-TNF Therapy in
Bowel Disease by David Feldman
STUDENT RESEARCHER Chethan Ramprasad MD 2017
Crohn’s Disease and Ulcerative Colitis, two forms of inflammatory bowel disease (IBD), currently affect over 1 million people in the United States. A condition characterized by chronic intestinal inflammation, IBD is neither preventable nor medically curable. Therapies are improving, but patients must cope with lifelong consequences of the disease and frequent interaction with the healthcare system. In fact, these patients account for a total of 700,000 physician visits and 100,000 hospitalizations each year. 80% of those affected will endure surgical procedures during their lifetimes. While physicians cannot currently erase the disease, they can alter its course by applying the information acquired from various basic, translational and clinical research studies. With the help of researchers and clinicians from the Crohn’s and Colitis Center at the University of Miami Miller School of Medicine, significant strides are being made in the management and treatment of patients with IBD. One research project that was developed at the Center for Crohn’s and Colitis by Dr. Oriana Damas, an Assistant Professor of Medicine, and Chethan Ramprasad, a fourth-year medical student, explores the role of genetics in determining disease course and treatment response. Currently, physicians focus on relieving symptoms, minimizing complications and maintaining inflammatory remission when treating patients with IBD. Critical for achieving these goals are anti-inflammatory, chemotherapeutic, and biologic immunosuppressant medications. Effective management with these drugs is complicated by high costs, toxicity, and relapses. The shortcoming in treatment have led researchers to investigate the potential role of genetics in the pathophysiology of IBD in order to better understand individual susceptibilities and ultimately improve prevention and treatment efforts for these patients. While at least 160 genetic loci have been identified in IBD, and genome-wide significant thresholds have been validated, these genetic findings have not yet produced widespread changes in clinical management. Hoping to build on the existing medical literature regarding IBD and genetic risk, Chethan and his research colleagues conducted a retrospective cohort study that reviewed IBD patient charts to better correlate individual genetic predisposition to biologic
therapy response and disease remission. From the charts, the researchers extracted data on disease duration, medication history, use of biologic therapy, remission status, surgical status and other advanced gastrointestinal markers. Combining this data with the previously published genetic data documenting the 160 risk alleles for IBD, genetic risk scores were calculated for each patient. In a multivariate adjusted analysis, they concluded that a limited subset of IBD variants may be useful for predicting disease course, including response to medications. Risk scores based on genetic testing may play a role in predicting relapses, which themselves predict long term outcomes in patients with IBD. While many medical fields successfully employ risk stratification in guiding therapy, IBD research is evolving so rapidly that research findings are outpacing physician’s ability to translate the new information into clinical recommendations. Chethan and Dr. Damas identified genetic testing, which has recently become more affordable and accessible for both physicians and patients, as a possible resource to improve the outcomes for patients with IBD. If genetic risk scores can predict the type of therapy needed, the patient response to therapy, and the likelihood for needing surgery in patients with IBD, the economic burden and prognostic difficulties that these patients pose on their healthcare system and provider can be drastically reduced.
Inspired by the groundbreaking research and world-renowned faculty at the Crohn’s and Colitis Center in Miami, Chethan hopes to someday lead research as an academic gastroenterologist and contribute to future solutions in the field of IBD. If the implications of this study are expanded on and utilized in clinical practice, patients with IBD may benefit from individualized evaluations focused on quantifying genetic risk and determining optimal management strategies. Although Chethan recognizes that the results of this study are only a small step towards the larger improvements needed in patients with IBD, he is excited to continue conducting translational research that he can apply to his practice as a future physician.
Spring 2017 THE MEDICAL I.B.I.S. 17
Outcomes-Based Evaluation of a
Pediatric Nutritional Recuperation Program in Cartagena, Colombia by Amit Patel
Even before she began her project in Cartagena, Columbia, MD/ MPH student Michelle Picon knew she wanted to do something to help the Latino populations. After working with Mexican immigrants in Oakland and with the Latino population at the San Juan Bosco clinic, Michelle decided she felt most comfortable and most effective when working with those communities. When her mentor, Dr. Eric Hecht, M.D., MSPH, suggested the Juanfe Foundation to her, she quickly identified with their mission: to help adolescent mothers and poor children break the cycle of poverty through holistic interventions. In particular, Michelle was excited about their work providing job training, education, psychosocial support and primary care to young moms. After learning about the foundation she said, â€œIf I had dreamt up an organization, this would be it.â€? She therefore applied for and received a Fulbright Grant in order to conduct research with them in Cartagena. Upon arriving in Cartagena, Michelle determined that the Foundation was doing a great deal on the social side, but was overlooking some opportunities on the clinical front. After looking at the available data and resources, she concluded that the best
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way to help the organization would be to perform a retrospective study of their pediatric nutritional recuperation effort. The goal of the program was to improve the health of sick and malnourished children by providing nutritional counseling and food. However, the impact of the program could not be quantified because no one had been tracking the outcomes. Altogether, Michelle analyzed the data collected on 274 children in the program over the course of 16 months using WHO measurements, including their height by age z-score (HAZ) and weight-height z-score (WHZ).
At the end of her study, Michelle found that, on average, patients missed 51% of their appointments and the program had an attrition rate of 56.9%. She also observed that chronic malnutrition, lower respiratory tract infections and congenital malformations predicted the lowest rate of HAZ improvement among participants. Children with low birth weights and chronic malnutrition, and those born to mothers that were adolescent, uneducated, or unemployed were the least likely to improve their WHZ scores. These results suggested that the program, in its existing form, was not serving its purpose. Michelle probed further and determined
STUDENT RESEARCHER Michelle Picon MD/MPH 2017
Honors Fullbright Presented at the National Conference for the International Academy for Pediatrics
Mentor Dr. Eric Hecht, MD, MSPH
Other Interests San Juan Bosco- Director of Public Relations Regional Campus DOCS Board Medical Students in Action
that requiring appointments with nutritionists would improve outcomes dramatically. Mandating one meeting with a nutritionist increased the probability of HAZ score improvement by 79%, while adherence to 90% of nutrition appointments by participants resulted in a 79% improvement in their WHZ score.
When Michelle presented the findings of her research for the first time, she felt nervous. On a stage in front of an assembly of many of the workers and leaders of the Juanfe Foundation, she had to suggest that their current efforts were not achieving desired goals. According to Michelle’s findings, there was no statistically significant reduction in morbidity among the children. Thankfully, the foundation was receptive to her findings. They realized that they needed to make changes if they were going to improve the health of their city. They told Michelle, “We felt like we were blindfolded the whole time”, and made a commitment to making their programs more effective.
Thanks to Michelle’s efforts, the Juanfe Foundation was able to identify ways to better serve their community. They implemented Michelle’s suggestions for the pediatric nutritional recuperation effort, and went further by adopting a more clinical mindset in assessing their programs. They built a state-of-the-art NICU that directly decreased infant mortality and hired a physician to head the administrative center in order to ensure clinical outcomes are tracked on an ongoing basis.
For Michelle, the experience provided the opportunity to see the impact research can make on improving social outcomes. In the future, Michelle hopes to use her clinical insight from her research to advocate for her future patients. Michelle says this goal is what draws her to the field of obstetrics and gynecology. Michelle notes that there are many social and cultural challenges that impact obgyn patients, and she hopes her experiences can help her traverse these obstacles to provide the best care possible.
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Telemedicine Broadening Access to Care for Complex Cancer Cases by David Feldman
STUDENT RESEARCHER Joshua Jue MD 2018
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The implementation of electronic health (eHealth) has grown increasingly important in recent years as technological advancements have helped physicians improve patient outcomes and satisfaction across the United States. One form of eHealth that many academic centers throughout the country have utilized to provide advanced care to surrounding rural areas is telemedicine, which leverages video telecommunication to connect doctors with patients who are physically or financially unable to visit specialized academic and private health centers.
hotel cost savings of $155,000. In addition, surveys of patient participants showed high satisfaction regarding time and cost savings, and positive approval ratings of their relationships with the surgeon. While reviewing the results of the trial after its completion in the Fall of 2016, Joshua and his research team were excited about telecommunication’s ability to effectively expand physician access beyond an in-person medical visit and to provide widespread access to highly specialized care for patients living in rural communities.
Starting in 2012, Josh and his research colleagues began enrolling patients in his telemedicine trial, where patients engaged in video telecommunication visits from their local VA Healthcare System with the surgical oncologist in Miami. The surgical oncologist was aided by a nurse practitioner who was present with the patient to perform a physical exam and any other technical procedures. The only time patients were required to visit the surgical oncologist in Miami was for the surgery itself, with all pre- and post-operative care occurring at the patients’ local facility. For each patient, the researchers calculated the mileage and travel cost savings, and assessed patient satisfaction with the program using a positively and negatively keyed survey. A total of 296 patients engaged in 755 visits during the 2-year study. The majority of the patients received operations, with the most common being for neoplasms of the colon, liver, and pancreas. Throughout the course of the study, patients were spared 213,000 travel miles, which translated into travel and
Interested in becoming a surgeon, Josh is encouraged by today’s surgeons’ ability to reach patients all over the world and extend their skills beyond the operating room and office. He has truly enjoyed speaking with patients enrolled in his trial about their experiences and the impact of receiving specialized care through telecommunication. He understands that improvements in access to medical care cannot only improve the outcomes and satisfaction among patients, but also help reduce the overwhelming economic burden that patients with complex diseases experience personally and bring to health systems. With webcams and internet access cheaper than ever, and Medicaid agreeing to reimburse physicians for certain telehealth services in 47 states, surgeon-directed telemedicine has the potential to advance the “iron triangle of healthcare” – greater access, improved quality, and lower cost – to new heights. As evidenced by this trial, surgical oncologists can appropriately manage patients with cancer through video telecommunication, and thus save patients the time and money required for in-person medical visits. During an enthusiastic conversation about his research and the future implications, Josh stated, “I hope to utilize the experiences acquired during this trial to inform others worldwide of our ability to change the way we provide medical care for patients by leveraging technologies like telemedicine and video consultation.”
At the University of Miami Miller School of Medicine, Joshua Jue, a third-year MD student, and his mentor Dr. Seth Spector, the Chief of Surgery at the Miami VA Healthcare System, studied the feasibility and effectiveness of an innovative Surgeon-Directed Tele-Oncology (SDTO) program that provides specialized care to patients at their local health centers throughout south and central Florida. Growing up in a small town in Northern California, Joshua was always frustrated with the sacrifices his mother made during his childhood when he required specialized care at distant health centers. When he was told about a project for providing additional resources for medically underserved areas outside of large urban healthcare systems, he was immediately intrigued. The project tested the ability of SDTO to provide specialized surgical services and care to historically underserved patient populations living tens to hundreds of miles away from quality surgical oncology care. Joshua and his research team sought to determine if video tele-communication consultation with a surgical oncologist based in the Miami VA would reduce the economic and physical burden of traveling long distances, without compromising the quality of care and patient satisfaction reported for in-person visits.
Besides bringing immediate benefit to patients enrolled in this trial, the results of Josh’s research project had broader implications. By utilizing a system that supports the SDTO program, any patient with access to internet and video conferencing can receive medical consultation. Although cancer cases requiring surgical intervention are projected to increase by 50% from 2000 to 2020, and will primarily be managed by general surgeons, many cases will still require the expertise of specialized surgeons. In fact, prior studies have shown that specialized surgeons yield significantly improved outcomes when patients require more complex procedures. However, less than 8% of counties in America have surgical oncologists practicing locally as defined by the Society of Surgical Oncology, which underscores the need to expand the reach of technological advancements to rural medical facilities using video telecommunication.
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Post-Ischemic Whole Body Vibration Reduces Inflammation in the Brain of Middle-aged Female Rats by Dylan Petkus The widespread incidence of strokes in the aging population demands the development of new treatments for stroke victims, especially aging women. After menopause, women’s estrogen levels drop, and the protective effects of estrogen on the cardiovascular system and the brain fade. Removing this protective hormone may explain the elevated risk of stroke and stroke complications in post-menopausal women when compared to men of the same age. There is a heated search for interventions that can help prevent strokes or improve outcomes after they occur.
STUDENT RESEARCHER Marc Schatz MD 2019
Marc Schatz, a second-year medical student, works alongside Dr. Helen Bramlett, Ph.D., Professor of Neurological Surgery, to contribute to the search for better therapies. Specifically, their team has investigated the potential for a novel technique called whole body vibration, or WBV, to improve recovery of post-menopausal stroke victims. WBV is a promising potential treatment for several reasons. First, WBV simulates many of the mechanical forces of exercise, which benefits recent stroke victims who are unable to exercise themselves. Second, WBV reduces systemic inflammation, which is a key operator in post-stroke damage. Lastly, WBV could theoretically be incorporated into existing hospital equipment, such as with vibrating hospital beds.
Marc tested WBV using a special rodent model for post-menopausal women. First, strokes were induced via transient occlusion of the middle cerebral artery, the blood vessel most commonly implicated in strokes. Then the animals either received WBV or no treatment at all. Rats in the WBV group received two 15-minute WBV sessions, 5 days per week, for 30 days. On days 7, 15, and 30 of the study, neurological function was assessed with tests for post-stroke neurological deficits and motor coordination. Lastly, brain tissue was evaluated in terms of tissue volume, inflammatory activity, and neurotrophic factors – those factors which encourage tissue survival. The results of this novel study were impressive. WBV reduced damaged tissue volume, a surrogate of brain function, in the rats’ brains by nearly half. The WBV group also enjoyed more freedom from neurological deficits by day 7 and improved motor coordination by day 15. The treatment also attenuated inflammatory activation and increased neurotrophic factors.
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Marc was able to participate in this groundbreaking research all while while balancing the demands of his MD curriculum. For example, Marc maximized his time by listening to lectures and reviewing notes in between experiments. He says that, more than anything, the dual responsibilities complement each other. As he approaches his clinical years, he’s pleased to know the research has advanced his knowledge and interest in neurology.
LET T ME OFFER YOU SOME
E ADVICE FREE by Santiago Montana We asked researchers at various phases in their training for the best piece of advice they had received, and what character traits younger researchers should develop now. We hope you can find passion and encouragement in their words.
PATIENCE Be gentle and patient with yourself, and your progress. Spe-
cifically, be patient if you feel like you lack knowledge or skills, and let that feeling strengthen your drive to work and deepen your hunger to learn. Also be patient with others… “To do research, we need to wade into ignorance… being totally fine with [feeling ignorant] as long as we learn something each time [is crucial]. Being comfortable with feeling ignorant is how big discoveries are made.” “So you need to be patient with yourself, and with the science. Being patient also helps you avoid taking shortcuts that might harm the quality of your work! And finally, patience helps you deal with some of those ... more difficult colleagues.”
HUMILITY Humility as a particularly important virtue in research was a
theme that came up frequently. Numerous researchers saw staying humble as a vehicle to success because it would help a researcher accept failure and being wrong. Additionally, several people saw it as an essential mechanism for producing good science, as humility helps protect a researcher from the dangerous perception of being infallible. “There is no room for one's ego in science and that we must remain humble in the face of the unknown. This advice has provided me with solace and guidance as I confront both failure and success in the lab."
BALANCE Other important pieces of advice centered on balancing our
passion for our work with skepticism and objectivity. One researcher summed this up nicely:
“Sometimes it can be better to work on something that interests you, but that you can also keep some distance from – so that you remain objective and your science isn’t compromised.”
MOTIVATION Finally cultivating curiosity in various research areas and ar-
eas of medicine is an invaluable trait for a successful research career. Further it allows a person to engage with other people in more meaningful and insightful ways.
“One of the most important traits aspiring investigators should be cultivating is intellectual curiosity. Asking “how” and “why” we know the knowledge…even questioning if we really “know” the knowledge at all... Generating knowledge requires creativity that can’t be cultivated by only learning what is “required” so reading outside your field is super important." “[Researchers] need to be self-motivated; to want to do the next experiment, to find out the next result… There will not be some one looking over their shoulder telling them what to do and when to do it. In my opinion, the really successful investigators are those that are innately curious and want to know why things work the way they do – and are willing and motivated enough to do the actual work.”
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The Power of the Placebo Effect in a PTSD Clinical Trial by Dylan Greif
Despite advances in scientific and public understanding, mental illnesses continue to carry negative connotations that can limit care. As a result, the impact of many psychiatric diseases continues to grow. Out of the top ten causes of death in the United States, suicide is the only cause that continues to rise. Moreover, depression is projected to be the largest psychiatric cost to our economy by 2020. In all, approximately 60% of patients who enter a medical clinic carry a psychiatric comorbidity.
Contrary to popular belief, it is not the ability to recognize mental illnesses that is lacking, rather it is the inability to get effective, targeted therapies to market. For drugs to receive FDA approval they must be more efficacious than the placebo, a benchmark that has been instrumental in the history of medicine, but poses unique challenges in mental health. Gabrielle Hodgins, a third-year medical student at the Miller School of Medicine uncovered some powerful findings about the placebo effect while investigating post-traumatic stress disorder (PTSD). Gabrielle discovered a passion for psychiatry shortly after entering UMMSM. She volunteered and shadowed in mental health clinics and developed contacts. She found a passion for interacting with psychiatry patients, and wanted to address the fact that some conditions lack effective drugs and promising clinical trials. An area that stands out to her as particularly neglected is PTSD in women. Along with her mentor Dr. Philip Harvey, Ph.D., she tested the effects of a corticotrophin-releasing hormone (CRH) antagonist on patients with PTSD. Early studies suggested that CRH antagonists had great potential to help patients with PTSD.
The methods were as follows: women with PTSD were randomized in a 1:1 ratio to six weeks of double-blind treatment with either the experimental drug or a placebo. All subjects completed clinical and functional assessments before and at five weeks into the treatment period. Clinical assessments performed at those times included the Clinician-Administered PTSD Scale, the Montgomery-Asberg Depression Rating Scale and self-reporting of symptoms. To supplement self-re-
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ported and clinician-reported measures, a cognitive battery test and performance-based skills assessment were administered to assess neuropsychological impairment.
The results of the trial were unexpected. The experimental drug produced measurable improvements in participants, but so did the placebo. There was no significant difference between the two groups. The response to placebo was highest according to clinician and patient-reported measurements. The neuropsychological-based cognitive test performances also improved in the placebo group to a degree rarely seen in clinical trials. Even more impressive was that only 10% of patients presented with scores at follow up that were worse than baseline. Since patients with PTSD tend to show depressed IQ scores compared to healthy patients with similar demographics, if one looked at these results and thought that they were medically induced, a CRH antagonist drug would be headed full-speed to market. Faced with statistically insignificant results, Gabrielle and her research team were left with a conundrum. The performance-based exams were meant to obviate self-reported placebo effects, but they, too, improved in the placebo arm. Was it fair to conclude that the CRH antagonist is worthless? Not exactly.
STUDENT RESEARCHER Gabrielle Hodgins MD 2018
Gabrielle attributed the results to deficiencies in not the drug itself, but rather in the clinical procedures and examinations involved in mental illness drug trials. Patients with minimal previous experience in performance-based physiological assessments became more familiar and more comfortable during their follow ups, which can inflate their apparent responses to therapy. Another weakness of the study leading to enormous placebo effect may have been that patients in the trial did not have many treatment options prior, and the trial may have induced psychological responses that enhanced or became the basis for the placebo effect. The challenges in this study are not unique: schizophrenia patients in recent drug trials in Boston showed similar effects, namely a significant increase in placebo related cognitive function. Such comparisons show similar patterns and are cause for further exploration. Gabrielle was invited to the American College of Neuro-
psychopharmacology Conference later this year to share the results and implications of her study.
Rather than being discouraged by the results of the drug trial, Gabrielleâ€™s passion for research has continued to swell. She is motivated to not only reveal the science behind developing efficacious drugs for patients with PTSD, but also to re-examine the basic structure of drug trials and possible targets for reform. She believes her work can help impact marginalized populations with mental illnesses that currently have limited treatment options. Gabrielle hopes to become a child and adolescent psychiatrist here at the University of Miami Miller School of Medicine where she has been able to collaborate with faculty and mentors, and where she will be able to continue towards her goal of implementing early intervention in psychiatric conditions.
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Healthy Skin for Everyone: Addressing Skin Cancer Disparities in Underserved, Uninsured and Minority Communities by Amit Patel
During her second year of medical school, Audrey Jacobsen encountered a patient with locally invasive basal cell carcinoma, a type of skin cancer that frequently occurs on the face. In this case, the carcinoma had progressed so far that it had invaded the patient’s eye socket. It was treatable, but the patient was homeless and could not afford the medication. The only other option was removal of the eye. Determined to avoid this option, the medical team successfully secured treatment for the man through patient advocacy. Thanks to their efforts, the patient made a full recovery. Although the success of this case was inspiring, Audrey saw deeper issues and realized that early detection of the carcinoma would have caught it before it progressed so far. She saw an opportunity to apply public health in order to bridge this disparity in medicine and catch skin cancers at earlier stages. Fortunately, Audrey has an extensive background in public health to guide her. She studied public health in Tanzania and Vietnam and has interned in a hospital in Ghana. Her public health capstone project from the previous year looked at the prevalence of hypertension in Haiti. As a result, she felt well prepared to take on this new project.
Under the guidance of Dr. Robert Kirsner and Dr. John Strasswimmer, Audrey developed the "Healthy Skin For Everyone" initiative. The goal of the program was to bridge disparities in medicine by developing education initiatives about skin health for underserved communities. The initiative was a multi-step project based at the Caridad Center, one of the largest free clinics in the country. Before implementing the project, Audrey first needed to complete a needs assessment of the target population .
Ultimately, Audrey was able to enroll and survey 206 participants from the community. 58.2% of the participants reported that they never or rarely conducted self skin tests. 20.7% of the participants believed “people with dark skin cannot get skin cancer.” These findings demonstrated a clear need for a community-based initiative to provide education and implement preventative practices. Once Audrey identified these needs, she worked to develop a community-based skin cancer education workshop that could be used to increase public awareness of relevant issues surrounding melanoma, the deadliest of the skin cancers. In conjunction with the Caridad Center and her mentors, Audrey implemented the “Healthy Skin for Everyone” program to increase awareness of risk factors and to teach people how to perform self-skin test. To ensure the programs could be disseminated to the greatest
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number of people, Audrey also helped train community health workers to conduct the educational programs themselves.
At the completion of the program, 114 community members were meaningfully educated. Audrey measured “meaningful education” by (1) the ability to conduct selfskin exams and (2) increased knowledge of risk factors. In total, 19 community health workers were trained to conduct the educational programs that were implemented in the community. Upon completion of the project, Audrey compiled and published the programs used in the “Healthy Skin for Everyone” initiative. By disseminating her methods, Audrey ensured communities all over the world would be able to use the same programs that had proven successful in the community around the Caridad Center. On the path to establishing this program, Audrey came across a great deal of challenges. Both the research and program development presented a vast array of logistical challenges and uncontrollable variables. Notable challenges included finding physical space, recruiting patients, following-up with participants, and determining measures of success. In addition to these logistical challenges, the many stakeholders in the project constantly tried to push the project in different directions. The research team, the clinic, the donors, and the school all had their own goals, and Audrey had to work to satisfy the goals of each of those groups. Despite all of these challenges, Audrey says she was driven forward by the hard work and passion of the community health workers who were so dedicated to helping their communities. With the support of her team, she managed to execute an initiative that would help reduce the burden of disease on the community, and set up the foundation to assist communities all over the world.
STUDENT RESEARCHER Audrey Jacobsen MD/MPH 2017 Mentors Dr. Robert Kirsner Dr. John Strasswimmer
Camillus Health Concern Lotus House Logistics Manager Caneshare
Future Goals Dermatology
Outside of the tangible community benefits, the “Healthy Skin for Everyone” initiative has seen success through awards and recognition. The pharmaceutical company Pfizer and the American Academy of Dermatology awarded $65,000 to help fund the project. The project has been presented at three conferences and has been featured on Fox News. In the future, Audrey hopes to help expand the initiative into other communities. A prime element of this is her plan to develop online training programs to make adoption of the initiative as seamless as possible. She also hopes to expand the project and develop programs to cover a wider variety of detectable skin issues.
Going forward, Audrey plans to pursue a residency in dermatology. For the rest of her career, she also plans to work in public health and academic medicine in order to address disparities in medicine. She hopes by working in both of these fields, she can help bridge the gap between research and the public. A primary goal for her is to help tackle the logistical issues that prevent the expansion of public health initiatives into underserved communities. Audrey is spurred by the hope that initiatives such as “Healthy Skin for Everyone” will ensure stories such as the one about the homeless man who nearly lost his eye will be replaced with happier tales of healthy communities.
STUDENT RESEARCHER Chris Dermarkarian MD 2017
Distance Between Uveal Melanoma and Optic Disc Margin: The Best Predictor of Radiation-Induced Complications from Iodine-125 Plaque Brachytherapy by Nathan McKenty
1 in 10 people has a mole in the back of the eye
Chris Dermarkarian is one of the most recognizable characters on The Miller School of Medicine's campus. The bow-tie-wearing, four-time Class of 2017 President is one of those cheerful people who will cross the entire library just to give you a high five (and maybe talk about the supposedly unparalleled greatness of his alma mater, Duke University). While scrolling through his prolific Snapchat history, you would hardly know he was working behind the scenes to prevent blindness in patients with ocular cancer at the Bascom Palmer Eye Institute. Alongside Bascom Palmerâ€™s Dr. J. William Harbour, M.D. and fellow fourth-year student Erin Ong, Chris investigated uveal melanoma, one of the most common primary tumors of the eye. Uveal
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melanoma often develops from pigmented cells in the iris, ciliary body, or uvea of the eye. In the not-so-distant past, surgical removal of the entire eye (enucleation) was the standard treatment, but today, brachytherapy is the preferred method of treatment. In brachytherapy, tiny plaques of radioactive material such as Iodine-125 are surgically placed into the eye to deliver local radiation to the tumor. This treatment spares the globe of the eye and has similar survival outcomes as total removal. However, about 47% of patients will develop complications from brachytherapy, the most serious of which is the loss of vision through radiation damage to the optic nerve or macula. Not only are these complications sight-threatening, but they are unfortunately irreversible.
A current problem with these therapies is that predicting which patients will suffer complications is extremely difficult. If clinicians were better able to identify those patients, they could be triaged to different therapeutic approaches. Chris's work sought to find new predictors of radiation risks through statistical analysis of patient outcomes. The chance of developing either radiation maculopathy or optic neuropathy was evaluated according to age, gender, tumor characteristics, and the components of the plaques used during treatment. His group's predictive model revealed
Honors Official Selection:
AMA Research Symposium
Eastern-Atlantic Student Research Forum
Mentor Dr. J.W. Harbour, MD
that the most important determinant of complications is the actual position of the tumor in the eye – 4.5 millimeters away from the optic nerve is the ‘sweet spot’ for preventing complications of brachytherapy. Tumors greater than this distance away from the optic nerve showed a reduced incidence of complications, even as long as 60-months post-treatment. Surprisingly, the size and the height of the tumor or the age or gender of the patient had minimal influence on the chances of developing radiation maculopathy or optic neuropathy. With this project, Chris and his fellow researchers have developed a simple, practical guide that can be utilized to help predict patient outcomes. Chris' research experience at UMMSM has changed his career and the way he envisions his future. While he had not originally considered pursuing ophthalmology or oncology earlier in his medical career, he recently matched at Baylor College of Medicine for Ophthalmology. Inspired by his experiences at Miami and his love of being a leader and teacher, Chris wants to continue working in an academic environment. He is hopeful to continue his work in ocular oncology as he pursues additional training as an ophthalmologist, clinical educator, and perhaps a research mentor to future medical students.
Other Interests Student Government Medical Education
Future Goals Ocular oncology, specializing in the retina
"My mentor, Dr. Harbour, is really one of the top experts in this field, and one of the radiation oncology residents brought me onto his team. That chance encounter? It ended up making me fall in love with ophthalmology. My advice to others is to put yourself out there and be flexible! Don't get discouraged if a project turns out differently than you expected. Research is a very time consuming process, and you have to be ready to adapt when new research questions come up!" Chris, who has also conducted research through the Interdisciplinary Stem Cell Institute and Sylvester Comprehensive Cancer Center, beams when praising the research environment here at UM. "I think in the past few years, UMMSM has created something really special. The leadership put huge effort into bringing the top researchers here. Think about all the unique research centers we have, like Bascom Palmer, Ryder Trauma, the Project the Cure Paralysis, and the Interdisciplinary Stem Cell Institute. Our research faculty are cutting edge, very approachable, and they want medical students to help them. It's just a question of: do you want to be a part of that journey?"
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Sleep Duration and
in Multiethnic Populations by Catherine Zaw
Sleep disturbances are some of the most common and relatable health issues across populations, and paired with mental health, they make up increasing numbers of chronic disease prevalence in the United States. In fact, sleep disturbances are seen in up to 70 percent of clinically depressed patients — both short and long sleep durations are associated with depressive symptoms and cerebrovascular risk factors. While this information may not seem surprising, there is actually very limited research evaluating depression in older multi-ethnic cohorts. Doing the research on these populations is precisely what Suzanne Lippman, a third-year medical student at UMMSM, is doing to advance neurological research. Lippman is currently working with Dr. Alberto Ramos, M.D., an epidemiologist at the Northern Manhattan Study (NOMAS) lab at the McKnight Brain Institute. Born and raised in South Florida, Suzanne has always been interested in the brain, graduating from the University of Miami with a neuroscience degree. Two years ago, as an undergraduate, Suzanne began research with NOMAS, a National Institute for Neurological Disorders and Stroke (NINDS)-funded study, well-known for following a cohort from Washington Heights in Northern Manhattan since 1990 — a largely Hispanic, Black and elderly population.
Upon beginning, she was quickly encouraged by other investigators in the lab to take on her own project, which empowered her to take on her own independent project. “That was really cool and I started thinking about what was interesting to me and what could be testable, and I began looking at old papers to see what kind of research we’d done before and what research we were missing.” After reviewing her lab’s past publications and conducting an extensive outside literature review, she realized there was a significant lack of studies and evidence pertaining to the relationship between sleep and depressive symptoms — especially in non-white populations. Suzanne recognized that the population data collected from the NOMAS cohort would be able to fill the gap in that information, and
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this field is going to explode in the next five or ten years as we learn more.”
STUDENT RESEARCHER Suzanne Lippman MD 2018
she set to work.
While the NOMAS study was primarily built to study stroke and stroke risk factors among the older multi-ethnic community in New York City, the existing data included both sleep patterns — short (<6 hours), intermediate (6-9 hours), and long (>9 hours) — as well as indications of depression, using screening tools like the Center for Epidemiologic Studies Depression Scale (CES-D) or reporting of patient use of antidepressants. This allowed Suzanne to investigate the association between sleep duration and symptoms of depression. “[Our research team] originally hypothesized that both short and long sleep duration would be associated with depressive symptoms,” Suzanne explains. “While our study didn’t show a correlation with long sleep duration, we found a significant correlation between short sleep duration and depressive symptoms.”
In fact, within the patients that had depression at baseline, compared to those reporting intermediate sleep, those reporting short sleep reported more depressive symptoms (OR 1.8 with a 95 percent confidence interval), after adjustment for demographic, behavioral, and vascular risk factors.
While Suzanne states that her study findings may not seem particularly surprising, the investigation of sleep and depression associations in older, multi-ethnic populations is pivotal. As a result, she has been able to present her abstract to a variety of conferences, including the 2016 American Academy of Neurology conference at Vancouver, Canada, as well as Eastern-Atlantic Student Research Forum (ESRF) at University of Miami last March. According to Suzanne, her research has reaffirmed her desire to specialize in neurology or psychiatry. With the amount of support and resources that she has received here, she feels more compelled to continue her research and her exploration in these fields. Although she didn’t expect to put so much time into her research, she states that she hasn’t felt overwhelmed and that she hopes to apply her future research into her clinical practice. In the long run, Suzanne wants to contribute to improving psychological and neurological care for patients, explaining that there is still a lot to learn.
“We know so little about the brain — new research comes out all the time about how closely mental health is tied to neuroscience,” she says, citing research that associates depression with pro-inflammatory cytokines in the body that are related to similar sources of inflammation in sleep. “I think this field is going to explode in the next five or ten years as we learn more,” she says. “It’s a really exciting time to be in neuroscience research.”
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