The Medical I.B.I.S., Issue 7, 2019 by The Medical I.B.I.S.

University Universityof ofMiami Miami

Miller MillerSchool Schoolof ofMedicine Medicine

Volume Volume77 Spring Spring2019 2019

Message from President

Frenk

As a university president with a long career in public health, I believe the wellbeing of our students at the Leonard M. Miller School of Medicine is of paramount importance as we pursue our vision for the future of the University of Miami. A healthy student body provides a strong foundation for our continued excellence and relevance in scientific research, clinical care, and service to our local, hemispheric, and global communty.

I know firsthand how difficult it can be to achieve a healthy balance between rigorous academic studies and our personal lives. Therefore, our University leadership team makes it a priority to address the physical, mental, and emotional wellbeing of our students. Our holistic strategy, which is based on the principles of public health, includes the interrelated areas of promotion, prevention, and protection. Promotion involves our ongoing initiatives to empower students to lead healthy lifestyles, such as facilitating physical activity, stress reduction, and mindfulness, as well contributing their time to charitable and civic organizations. Our second principle, prevention, means adapting specific measures to address risk factors that can lead to disease, while the third principle of protection involves taking a proactive approach to reducing social isolation and physical harm. With the continued support of our Miller School faculty and staff, our medical student researchers will be well prepared to find a healthy balance in their own lives, so they can continue to make meaningful contributions to medical research and care in the future. I congratulate the Medical I.B.I.S. staff for addressing this vital issue.

Julio Frenk, MD, MPH, PhD President, University of Miami

spring 2019 | The Medical I.B.I.S.

Message from

dean

Ford My first months as dean of the University of Miami Leonard M. Miller School of Medicine have been an extraordinary experience, and I am grateful for the warm welcome that I have received from our medical students, faculty and staff.

Through countless one-on-one meetings and several town hall meetings, I have received valuable ideas and suggestions on a wide range of timely issues, including the importance of supporting the health and wellbeing of our students in their personal lives as well as their academic careers. I look forward to turning those listening sessions into action! One of my goals is to establish pre-eminence in scientific research and promote the translation of discoveries into interventions that will transform lives, build healthier communities, and improve health globally. Therefore, it is my pleasure to present this seventh annual edition of The Medical I.B.I.S., the University of Miami Miller School of Medicine student-produced research publication.

From the design of the first cardiopulmonary simulator (â&#x20AC;&#x153;Harveyâ&#x20AC;?), to our seminal contributions in the field of cellular therapeutics, the Miller School remains at the forefront of advances in scientific research and translational medicine. Since my arrival, I have constantly been inspired by the many contributions made by our student researchers to advance our knowledge of medicine and improve patient care here and around the world. Together, we will build a culture of innovation and excellence at the Miller School in support of the next generation of world-class researchers and physicians.

Henri R. Ford, MD, MHA Dean and Chief Academic Officer, UMMSOM

The Medical I.B.I.S. | spring 2019

The I.B.I.S. Masthead Editor-in-Chief Hardik Patel Senior Editors Tom Boyle Dylan Greif A. Mariquit Lu Lily Zhang

Gonzalez, Rakitina, Patel, Lu, Zheng

Selection Committee Chair Jeff Wu Selection Committee Ryan Gallo Olivia Gardner Jeffrey Lowell Brandon Rosen Brooke Sama Ahmed Yousef Layout Managing Editor Alison Zheng

Lowell, Ahmed

Layout Team Rhiya Mittal Victoria Rea-Wilson Publishing Team Aarabhi Rajagopal Ahmed Yousef

Rea-Wilson, Zheng, Mittal

spring 2019 | The Medical I.B.I.S.

Section Editors Jacqueline Baikovitz Alexandra DeBose-Scarlett Aarabhi Rajagopal Gautam Shrivastva Logan Stone Saradadevi Thanikachalam

Photography Managing Editor Daisy Gonzalez Photography Team Daniela Cosio Kerry O’Sullivan Sara Pengelley Emily Ramos Nicole Souza Erin Wolfe Wolfe, Pengelley, Gonzalez, Cosio, O’Sullivan

Writing Managing Editor Jenny Rakitina Writers Jacqueline Baikovitz Brett Colbert Kyrra Engle Amoghavarsha Havanur Mackenzie Jones Sai Polineni Victoria Rea-Wilson Gautam Shrivastva Jay-Shing Wang Erin Wolfe

Jones, Wang, Rea-Wilson, Colbert, Rakitina, Shrivastva, Havanur, Stone, O’Sullivan, Polineni, Baikovitz, Engle

- THE 2018-2019 I.B.I.S. MASTHEAD -

The Medical I.B.I.S. | spring 2019

TABLE of 8

Contents

Researcherâ&#x20AC;&#x2122;s Guide to Research Tools Sai Polineni

Effects of PRP-1 on ALDHHIGH Cancer Stem Cells and Wnt/B-catenin Pathway in Human JJ012 Chondrosarcoma Cells Aaron Hoyt

Surgical Treatment of Symptomatic Foreign Body Injections to the Male Genitalia Carissa Patete

PRAME as an Independent Biomarker for Metastasis in Uveal Melanoma Matthew G. Field

SDF-1a is a Novel Biomarker of Mesenchymal Stem Cell Efficacy in Patients with Dilated Cardiomyopathy Courtney Premer

Low Fat Diet Improves Quality of Life and Alters Gut Micobriome and Metabalome in Ulcerative Colitis Patients Matthew Phillips

spring 2019 | The Medical I.B.I.S.

THE MEDICAL I.B.I.S

Spring 2019 Vol 7, Issue 1

Discrepancies in Chemotherapy and Radiation Start Times for Non-Small Cell Lung Cancer Patients Joseph Quintana

Initial Implementation of an Enhanced Recovery After Surgery G. Damian Brusko

Assessing Connection to Resources and Barriers to Access through Evaluation of Community Resource Connection Tool Sarah Simko & Heather Farthing

17 20

Determining the Effectiveness of a Novel, Digital Pendant and Voice Reminder Platform on Increasing Infant Immunization Adhesion Logan Stone

Eliminating Barriers for Diabetic Eyecare with a Fundus-On-Phone Camera, Artificial Intelligence, and Telemedicine Rajika Jindani

The Medical I.B.I.S. is published by the University of Miami Miller School of Medicine Student Government

The Medical I.B.I.S. | spring 2019

data toxic infile “tox dlm=”,”; input life son $ trea $; run;

A Researcher’s Guide to Research Tools

By Sai Polineni

here’s a wonderful article published in Statistics in Medicine in 1987 (PubMed ID: 3576014) that presents the results of a nine-question multiple choice questionnaire to “a random sample of Danish doctors to assess their knowledge of elementary statistical expressions”. Naturally, as seems to be the case with studies of this sort, the authors concluded that most doctors possessed such a poor grasp of the most basic statistical concepts that they cannot be expected to properly evaluate the statistical methods and conclusions presented in medical journals. Rather than chalk this up as a shortcoming unique to Danish physicians of the 1980s, a quick PubMed search reveals these findings to be commonplace around the world.1 The point of this article is not to lament the fact that medical students and physicians seem to forget biostatistics faster than they forget the most esoteric anatomic facts because, honestly, it is rather easy to relearn most biostatistics principles quickly. After you learn basic biostatistics once, you are only a quick internet search, 8 pages of First Aid, or one helpful biostatistician away from remembering things again. Rather, the point of this article is to tell you what do with that knowledge. Yes, you can differentiate when to use a ChiSquare vs a Fisher’s Exact vs a One- or Two-Sided T-test but how do you use them? It’s fine and dandy to know that multivariate analysis of continuous variables requires linear regression, but what software do you use to do that regression? Let’s paint a picture: you are a medical student who has been assigned a summer chart review project that requires you to go thru 1000 charts, 500 of which are for patients with a certain genetic mutation and 500 for patients who lack the mutation. You collect demographic, family, social, and medical information. Your research hypothesis is that the presence of the genetic mutation increases risk of a specific disease outcome.2 You have somehow managed to complete all 1000 chart reviews and emerged on the other side of your summer a bit dazed and confused. Your PI is thrilled with your work and suggests that if you are willing to do the statistical analysis and write the first draft of the manuscript, you would be placed as the first author. You are thrilled as you’ve heard that having your name as first-author on a research paper is the bee’s knees. How should you proceed?

data toxic; infile “toxic.dat” spring 2019 | The Medical I.B.I.S. dlm=”,”;

First, you should compile all your data onto a single Excel file. Excel is built to handle both small and large datasets and, before any statistical analysis can begin, you must have your data in one location to more easily run analyses. The second step in your methodology is the most important one: which

proc anova toxic; class pois treatment; model life son treatm poison*tre run;

“I would pick one program... and become good at it.”

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statistical software should you use? In brief, the five most common statistical software packages are R, Stata, SPSS, SAS, and Excel. There are others, but most medical research is done using one of these 5 packages or their derivatives (JMP is a tamer version of SAS), so it is to your advantage to become familiar with one of these. In this author’s opinion, Excel, while a great tool to use as you’re collecting data, is a bit difficult and cumbersome to use for high-end medical research so it has been left out of the accompanying table comparing the software packages.

proc reg data=crack model lo age / p; output o =crackreg r=resid; run;

Picking the right software really comes down to how deep you anticipate diving into medical research in medical school and beyond. There are several reasons for picking R or Stata over easier to use programs like SPSS and JMP: (1) they allow you greater independence in conducting statistical analyses on subsets of your population and even designing your own algorithms, (2) they allow you greater ability to generate and edit figures that you may wish to include on posters or manuscripts, and (3) they are tailored towards biostatistics research (Stata especially so) and thus have the capacity to run complex survey designs and diagnostics that would be useful in medical research but may not be commonly used in other fields. However, they also require far more time to learn and, if you don’t expect to become heavily involved in research, might not be worth the time commitment as SPSS and JMP will carry you far, or at least to a biostatistician who can do the more complex analy-

proc plot data=crack plot load*age=” pred*age=” overlay; run;

class poison treatment; model life = poi-

input id age load; datalines; 1 20 11.45

data chisq input df; chirat = c v(.995,df) v(.005,df) datalines;

proc reg dat model load p;

oxic; “toxic.dat” ”; life poitreatment ses for you if necessary. In an ideal world, you would programs, I would pick one program – Stata if you are become familiar with two different programs but, given that you don’t have time to breathe in med school much less indulge your craving for statistical software

nova data=-

poison ent; life = poieatment *treatment;

rack; t id age

lines; 0 11.45 0 10.42 0 11.14 5 10.84 5 11.17

eg rack; l load = p; ut outreg p=pred d;

lot rackreg;

ge=”*” ge=”+”/ y;

hisq; df; = cin,df)/cin,df); nes;

data=crack; oad = age /

interested in a career in academic medicine and SPSS if you just want to know enough to confidently send that manuscript to your PI – and become good at it.

Choose the Right Program for You R

Stata

SPSS

SAS JMP

Price

Free. Open source

Varies. $198 for a lifetime license of Stata/IC

Varies. 6 or 12-month rental. Usually <$100

Free. Obtain via University Software Download

Subjective Ease of Use

- Many free to download algorithms and stats packages built by other users - Very flexible. Gives the user great leeway to specify and modify their variables and statistical tests

-Many, many free to download algorithms and stats packages built by other users -Very flexible. Gives the user great leeway to specify and modify their variables and statistical tests -Fast

-Very similar to Excel -Easy for beginners to pick up -“Point and Click” and “Drag and Drop” type of analyses -Very good for ANOVA analyses

-SAS JMP is an easier to use version of SAS -“Point and Click” and “Drag and Drop” type of analyses

-Requires specific coding language inputs to run analyses -Learning the coding language will take time

-Requires specific coding language inputs to run analyses -Learning the coding language will take time -Very good for non-ANOVA analyses -Pricy but $198 for a perpetual license is not a bad deal

-Less flexibility in modifying data -Has the fewest number of statistical procedures out of these 4 programs -Pricy

-Few people use it -It can be cumbersome to move data files from or to JMP from other statistical programs

r-project.org

stata.org

(1-10, 1 is easiest)

Pros

Cons

Website

ibm.com/us-en/marketplace/spss-statistics-gradpack/

it.miami.edu/a-z-listing/sas/index.html

Index 1. If you want to see how you’d stack up against the Danish doctors of yesteryear, the questionnaire is listed in the Methods section of the aforementioned paper and the answers are in the Appendix. To find the paper, search PubMed for 3576014. 2. Recognize that though this may sound like a case-control study, it is actually a retrospective cohort as you are first partitioning people by exposure and then calculating risk of disease. If it was case-control, you would have partitioned by disease outcome and then checked odds of exposure i.e. genetic mutation.

proc plot data=crack-

input df; chirat = cinv(.995,df)/cinv(.005,df);

The Medical I.B.I.S. | spring 2019 proc plot data=chisq;

PRP-1 eliminates ALDHhigh cancer stem cell population and regulates aberrant Wnt/β-catenin pathway in human JJ02 chondrosarcoma cells

hat mechanisms allow cancer stem cells to self-renew? How would targeting those mechanisms play out for patients? These questions drive cutting-edge cancer research today. Chondrosarcomas, rare cancers affecting the bone, have been particularly puzzling because of their resistance to both chemotherapy and radiation. Third year MD student Aaron Hoyt explored these questions over the past year while working in UMMSM’s Musculoskeletal Oncology Signal Transduction Laboratory with mentor Karina Galoian, PhD, research Associate Professor in the Department of Orthopaedic Surgery. The team investigated how stem cell populations in lines of chondrosarcoma cells react to proline-rich polypetide-1 (PRP-1), a neurosecretory peptide with previously demonstrated anti-cancer properties by the laboratory. This peptide was originally isolated from the hypothalamus of the brain that was described previously by the principal investigator and collaborators. Recently, the team confirmed prior research demonstrating aldehyde dehydrogenase (ALDH) as a stem cell marker in chondrosarcoma. Through flow cytometry, the laboratory found that PRP-1 eliminated stem cell populations in chondrosarcoma cells as evidenced by low ALDH activity compared to high ALDH levels in untreated chondrosarcoma cells. Hoping to build on this promising finding, Aaron conducted a literature search and found a link between the Wnt signaling pathway and ALDH. With Dr. Galoian’s mentorship, Aaron devised a project aimed at characterizing the Wnt/β-Catenin signaling pathway’s interaction with PRP-1 treatment in JJ012 human chondrosarcoma cell lines. This insight could prove particularly useful for bone cancer research; while the Wnt/β-Catenin signaling pathway is well characterized in colon cancer and many other carcinomas (epithelial cell derived) to activate carcinogenesis, recent literature in bone cancer (mesenchymal

10 spring 2019 | The Medical I.B.I.S.

by Gautam Shrivastava

derived) suggests the Wnt/β-Catenin signaling pathway might be reversed. Building on this previous research, Aaron’s study sought to shed light on Wnt/β-Catenin activity in chondrosarcoma cells through use of different methods, namely a Wnt/β-catenin gene PCR array, western blots and immunocytochemistry. Unsorted JJ012 chondrosarcoma cells and chondrosarcoma stem cells demonstrated downregulation of the Wnt/β-catenin pathway, consistent with recent literature suggesting sarcomas arise from mesenchymal stem cells via inactivation of this pathway. Interestingly, Aaron found treatment with PRP-1 resulted not only in the elimination of cancer stem cells, but also led to Wnt/β-Catenin activation. This bolsters the assertion that mesenchymal tumors might have an opposite role for the Wnt/β-Catenin pathway when compared the pathway’s role in activation and progression of carcinomas. Additionally, this study provides further evidence of the anti-cancer property of PRP-1 in chondrosarcoma with downregulation of two vital oncogenes: Cyclin D2, an important cell cycle progression gene, and matrix metalloproteinase 7, which confers the ability to metastasize. These findings contribute significantly to broader efforts uncover ways to eliminate cancer stem cells, the seed that allows cancers to self-renew. The PRP-1 peptide also holds special promise as a potential therapeutic modality for chondrosarcoma, a condition only amenable to surgery and otherwise plagued by limited treatment options in later stages. Future directions for the laboratory include extending its application to animal models, human chondrosarcoma biopsies, and other types of bone tumors. Aaron hopes to present these results at conferences in the upcoming year and a manuscript is submitted for review with a peer-reviewed journal. With future plans to pursue a career in orthopaedic surgery with active involvement in research, Aaron was grateful for the opportunity to lead this project from inception to completion and for the team

Aaron Hoyt MD, 2020

Other Interests: Soccer, golf, fitness training His dog Bolt Dean’s Cup V.P. of OSIG Anatomy T.A. Tutor for Academic Societies Future Goals: Orthopaedic Surgery

Surgical Treatment of Symptomatic Foreign Body Injections to the Male Genitalia by Victoria Rea-Wilson

lective plastic surgery has become increasingly common globally and in Miami. Unfortunately, as the number of elective plastic surgeries rises, so too does the number of reconstructive surgeries needed to address the adverse outcomes of elective surgeries. For example, the cosmetic enhancement of the penis through foreign body injections, usually silicone, has left patients with foreign body reactions featuring short term adverse effects and long term consequences. After the pain, edema, and erythema that can come in the short term following the procedure, many patients suffer granulomas, dyspareunia, painful erections, de-pigmentation, and scarring, leading some patients to feel regret and guilt becauses of their decision.

“Fixing [the granuloma] helps,” according to Carissa Patete,

a MD candidate in UMMSM’s class of 2020. While shadowing Dr. Christopher Salgado at UHealth’s Department of Plastic & Reconstructive Surgery, Carissa has observed and assisted in the long-term follow up of three patients who have received the novel use of autologous dermal fat grafts to reconstruct the penile shaft following excision of siliconomas. Autologous dermal fat grafts have been used to reconstruct other parts of the body, and the application to penile reconstruction has so far been promising in Dr. Salgado’s patients. Carissa reports that the patients have been pleased with the results of their procedure and that their quality of life has improved. Unlike skin grafts that cannot restore volume to the shaft or fat grafts that can result in scarring and nodules, Carissa explains that dermal fat grafts provide aesthetically pleasing and pain-free re-

Carissa Patete MD, 2020

Mentor: Christopher J. Salgado, MD Other Interests: President of SSIG, President of Plastic Surgery Interest Group, MSAT leader, enjoys painting and screen printing Future Goals: Plastic Surgery

sults without the scarring or strictures associated with other reconstructive procedures. Carissa says that “patients are pleased and happy” with the aesthetic and functional results of their dermal fat grafts, as they are able to once again have “erections and intercourse without pain.” Recently, Carissa submitted an article she co-authored about the longitudinal follow-up of these three patients. She plans to continue assisting Dr. Salgado with follow-up and collecting data as more patients receive this reconstructive surgery. Carissa has found the “hands-on” clinical aspects of this research enjoyable, and the immediate results that improve patient’s lives has been “really rewarding” for her. She will continue to shadow and eventually go into this complex and artistic field. Plastic surgery, she explains, is a field that has “no one set way” to do each procedure, because each patient is unique, which requires “creativity and visualization” on the part of the surgeon. Carissa hopes to be one of these plastic surgeons who “really make[s] a difference in [their] patient’s lives” as she has seen Dr. Salgado do with these reconstructive surgeries.

Creativity

& Visualization The Medical I.B.I.S. | spring 2019

PRAME as an Independent Biomarker for Metastasis in Class 1 Uveal Melanoma By Amogh Havanur

Matthew Field, MD, PhD 2019 Honors/Presentations: Presenter, Annual Meeting of American Association of Cancer Research, April 2015, Philadelphia, PA. Recipient, Louis J Elsas Award Biochemical Genetics, John T. MacDonald Foundation (2016) Mentors: J. William Harbour, MD Future Goals: Ophthalmology

Publication: Field, M. G., Decatur, C. L., Kurtenbach, S., Gezgin, G., Van Der Velden, P. A., Jager, M. J., ... & Harbour, J. W. (2016). PRAME as an independent biomarker for metastasis in uveal melanoma. Clinical cancer research, 22(5), 1234-1242. PMID: 26933176 Other Interests: Creator, CCS Student Mentor Program for Bioinformatics, The Medical I.B.I.S, MD, PhD Representative, Biomedical Graduate Student Government

efore Matthew Field arrived at UMMSM in 2010 to pursue his MD-PhD, he spent two years conducting research in the visual sciences. “I loved working with the patients, seeing how much they appreciated their eyesight,” he recalls.

Class 1 tumors were low-risk, deemed unlikely to metastasize—to spread to other tissues—whereas Class 2 tumors were high-risk, with metastasis considered highly likely. The DecisionDx-UM, Dr. Harbour’s clinically validated 12gene test for classifying UM tumors, has since become a routine prognostic tool for clinicians around the country.

This passion for ophthalmology made him a natural fit for the lab of Dr. J. William Harbour, the Director of Ocular Oncology at the Bascom Palmer Eye Institute. One of Dr. Harbour’s primary research interests involves uveal melanomas (UM), a type of cancer in ocular melanocytes, which produce pigment responsible for eye color.

Upon further follow-up, however, it became apparent that metastasis nevertheless occurred in roughly 10% of “low-risk” Class 1 UM tumor patients. In the fall of 2013 Dr. Harbour asked Matt, who had just joined his lab, to investigate further. Matt began by analyzing data from 108 patients with UM whose tumors, collected over the past fifteen years as part of Harbour’s prior research, had been biopsied and designated as Class 1 tumors by the DecisionDx-UM tool.

In the past Dr. Harbour had demonstrated that based on their genetic expression profiles, UM tumors could be separated into two broad risk categories: Class 1 and Class 2.

12 spring 2019 | The Medical I.B.I.S.

Early results indicated that he and Dr. Harbour onto some-

thing. A preliminary principal component analysis of mRNA expression of the 12 genes incorporated into the DecisionDx-UM divided the Class 1 tumors into two new subgroups: Class 1 tumors that had remained benign and Class 1 tumors that had metastasized. This in turn demonstrated that there was a statistically significant genetic difference between Class 1PRAME+ and Class 1PRAME+ tumors. Next, to uncover specific biomarkers of metastasis, Matt conducted a genome-wide transcriptomic analysis of 13 Class 1 UM patients—5 of which had metastasized, 8 of which had remained benign. In doing so, he made a crucial discovery: patients with Class 1 metastatic tumors appeared to express abnormally high levels of a gene called PRAME (Preferentially Expressed Antigen in Melanoma). PRAME belongs to a class of genes known as cancer/testis antigens, which are activated briefly during embryonic germ cell development and then typically

“

It’s very exciting to be involved in the clinical care of a patient, use that information to ask a research question that you can answer in your laboratory, and then use that information to bring it back to clinic.

”

remain unexpressed in most adult tissues. However, certain cancers can re-express them, driving tumor progression. Subsequent analysis revealed that PRAME was by far the most highly overexpressed gene in Class 1 metastatic tumors.

rupts the regulatory mechanisms that ocular melanocyte cells employ in order to maintain chromosomal integrity, which then encourages the irregular chromosomal gains and losses that are highly associated with tumorigenesis. He and Dr. Harbour are collaborating with international researchers to develop new innovate cancer immunotherapies that attack PRAME which could potentially prevent the progression of Class 1 UM tumors into metastasis. Meanwhile, thanks to Matt’s research the Decision-DX-UM test used nationwide by clinicians has since been updated to include a test for PRAME, resulting in two new diagnostic subcategories: Class 1PRAME+ and Class 1PRAME—, each with their distinct prognostic profiles. Upon graduation next year, Matt intends to start his ophthalmology residency, and will likely pursue a fellowship after that. As an MD-PhD student, he finds great value in translational research, which integrates basic science with clinical application: “It’s very exciting to be involved in the clinical care of a patient, use that information to ask a research question that you can answer in your laboratory, and then use that information to bring it back to clinic. It’s bedside-to-bench-to-bedside.” Devising tailored interventions in order to exploit a disease’s unique genetic fingerprints is the essence of the precision-based approach that Matt believes will soon be the future of medicine. “This work with molecular profiling is important in helping to determine ideal therapies,” he suggests. “I don’t think we’re quite there yet. But we’re currently identifying the relevant genetic alterations—and developing targeted therapies for these alterations is really going to drive personalized medicine in the future.”

Emboldened, Matt analyzed 64 Class 1 tumors—39 Class 1PRAME+ and 25 Class 1PRAME— patients—and plotted the incidence of metastasis of the two groups at fiveyear follow-up. Of the Class 1PRAME+ patients, 38% had metastasized at five years. Astonishingly, however, every single one of the Class 1PRAME— patients had remained metastasis-free at 5 years. This convinced Matt that he had successfully implicated PRAME for its role as a biomarker for Class 1 UM Metastasis. In 2015, Matt presented his findings at the annual meeting of the American Association for Cancer Research. A year later he was first author of the paper, published by his lab in Clinical Cancer Research, which first introduced PRAME’s role in the metastasis of Class 1 UM tumors. On the basis of this paper, the National Cancer Institute awarded him a prestigious F30 fellowship grant to continue investigating PRAME’s functional role in the progression of UM. Currently, Matt’s working hypothesis is that PRAME dis-

The Medical I.B.I.S. | spring 2019

SDF-1a is a Novel Biomarker of Mesenchymal Stem Cell Efficacy in Patients with Dilated Cardiomyopathy

By Kyrra Engle

hen President George W. Bush issued an executive order banning federal funding for newly created human embryonic stem cell lines in 2001, stem cell research in America was indefinitely stalled. However, 5 years later, this changed when Shimnya Yamanaka and his graduate student, Kazutoshi Takahashi, scientists at Kyoto University, developed a technique to “reprogram” adult cells into a pluripotent state.

While the dysfunction of endothelial cells that underlies the pathophysiology of HF has been well characterized, the specific signaling pathways responsible for stimulating endothelial cell turnover and function following tissue damage are largely unknown. Pre-clinical trials have shown that injecting mesenchymal stem cells (MSCs) in animals with induced HF can improve endothelial function. However, therapeutic use of MSC to treat HF in clinical trials has had mixed results.

This technique gave researchers the ability to harness the power of pluripotency using a patient’s own cells, with the expectation that medicine would be revolutionized by the creation of powerful, novel “personalized” treatments for a range of diseases. Ten years later, thanks to research being done on heart failure (HF) at the Interdisciplinary Stem Cell Institute (ISCI) at UMMSM, it seems stem cells may finally deliver on that promise.

The use of MSCs has been further complicated by the different sources that exist. Currently, there are two sources of MSCs in clinical trials: autologous MSCs, from the patient, and allogeneic MSCs, from a healthy donor. Additionally, the ideal source for MSCs is still widely debated. MSCs are considered relatively safe for patients because they do not have MHC II receptors. which can trigger graft versus host disease. Still, some researchers are concerned about the potential long-term effects of introducing foreign stem cells into a patient’s body. In clinical trials, autologous MSCs have shown mixed results in treating HF, with some trials showing great efficacy and others showing negative results using a variety of clinical parameters. Now, new research done by Courtney Premer, Ph.D. and others at ISCI may explain why.

In the United States, heart failure persists as the leading cause of morbidity and mortality, where the heart becomes unable to pump enough blood and oxygen to support vital organs in the body. The second most common cause of HF is nonischemic cardiomyopathy (NICM), a broad category of conditions in which the left ventricle becomes enlarged, dilated, and weak for reasons other than coronary heart disease or a heart attack. For one third of these NICM patients, the reason is unknown and referred to as idiopathic dilated cardiomyopathy (DCM). Treatment options for HF patients, including those with DCM, are limited. In most cases, HF patients are given medications intended to minimize further damage to the heart and extend their life. Until the recent introduction of stem cell therapy, cardiac transplantation was the only treatment available to HF patients that provided them with new cardiac tissue. Researchers have been able to obtain stem cells from patients relatively easily for a while now. However, ensuring these cells go to a specific location when injected into a patient’s heart and repair any damaged tissue has remained a challenge. One issue has been a lack of knowledge regarding the complex processes that regulate stem cell activity.

14 spring 2019 | The Medical I.B.I.S.

“This was a really exciting finding! It opens the doors for a paradigm shift in the type of cells we use, with the potential of one day having a donor stem cell bank for patients.” As part of POSEIDON-DCM, a larger phase I/II randomized pilot study conducted at ISCI, DCM patients were randomized to receive either autologous MSCs or allogeneic MSCs. Premer et al. then compared endothelial function and vasodilation among the two groups before and three months after treatment. Specifically, endothelial function was calculated by the growth of the patient’s endothelial cells in culture (EPC-colony forming units, EPC-CFUs), and vasodilation was measured by the patient’s brachial artery diameter (flow-mediated vasodilation, FMD). Surprisingly, Premer et al. found that DCM patients who received alloge-

neic MSCs had significantly higher EPC-CFUs (12 ± 4 vs. 6 ± 5, P = 0.015) and a significantly greater change in FMD from baseline (Δ3.7 ± 3%, P = 0.0002 vs. Δ-0.46 ± 3%) on average. To understand the biological mechanism that made allogeneic cells more effective in restoring endothelial function in DCM patients, Premer et al. looked at systemic levels of inflammation and the release of inflammatory and paracrine factors, including stromal derived factor-1α (SDF-1α) from the allogeneic and autologous MSCs. A growing body of research suggests that SDF-1α may play a critical role in honing endothelial cells to the site of repair. Premer et al. hypothesized that lower levels of SDF-1α released by the autologous MSCs, as compared to the allogeneic MSCs, may explain their inability to improve endothelial cell function. Surprisingly, the results showed that the autologous MSCs were not producing less SDF-1α in vitro than allogeneic MSCs. In fact, the autologous MSCs(n=11) in vitro secreted strikingly higher levels of SDF-1α than allogeneic MSCs [76.0 (63.7, 100.9) vs. 22.8 (7.2, 43.5) pg/mL, P=0.0002]. Despite this, Premer et al. found that DCM patients who received allogeneic MSCs had significantly greater endothelial function 3 months after treatment than DCM patients who received autologous MSCs. Furthermore, SDF-1α release from MSCs and levels of systemic inflammatory factors from patients after 3 months of treatment, correlated with endothelial function (EPC-CFUs) in both treatment groups. Together, these results challenge the widely held belief that increased SDF-1α is associated with better therapeutic efficacy. Instead, they suggest that levels of SDF1α that are too high may actually be associated with a worse therapeutic outcome. Most importantly, this study broadens our understanding of SDF-1α’s role in cardiac repair and provides researchers with a biomarker that could be used to determine the potential effectiveness of stem cell therapy for patients with HF in the future.

Courtney Premer, PhD; MD 2021 Honors: American Heart Association Predoctoral Fellowship; New Investigator Travel Award, BCVS Mentor: Joshua N. Hare, MD, FACC, FAHA Other

Interests: Medical Students in Action, Debbie Project, COATS, Academic Society Trainer, Deans Cup, Beats Per Minute, Running, Biking, Swimming

Future Goals: Emergency Medicine

*Premer and Hare reported having a material and methods patent for endothelial dysfunction

The Medical I.B.I.S. | spring 2019

Low fat diet improves quality of life and alters gut microbiome and metabolome in ulcerative colitis patients By Brett Colbert

pproximately 1.3 million Americans suffer from ulcerative colitis (UC), a form of inflammatory bowel disease localized to the colon. Though the exact cause of UC is not well understood, it is thought to be an autoimmune disease in which the mucosa of the colon is damaged by the patient’s own immune system. Current therapies include the use of both steroidal and non-steroidal anti-inflammatory drugs, as well as biologics to selective modulate the immune system. These treatment options are effective at maintaining remission of symptoms, but patients always ask their physicians about what dietary changes they should make. The answer they most often receive is that there are no conclusive studies on the topic yet and as such the physician cannot offer any suggestions Matthew Phillips, currently in his final year of the MD/PhD program at UMMSM, conducted research in Dr. Maria Abreu, MD’s lab seeking to change that paradigm. investigating the effects of a low-fat diet on patients with UC. Subjects with UC in remission and a flare up in the last 18 months would be given two isocaloric diets for 4 weeks with a 2 week wash out period in between. One diet would be the standard American diet (SAD) in which 35-40% of calories comes from fat, and the other would be a low fat diet (LFD) with only 10% of calories from fat. This study, the first of its kind, distribut-

“‘What should I be eating?’”

Matthew Phillips MD/PhD, 2019

Honors: 3 conference presentations Mentor: Maria Abreu, MD Future Goals: Infectious disease physician-scientist

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ed three catered meals a day, to all the participants to ensure fidelity to the diets. Participants completed the Inflammatory Bowel Disease Questionnaire (IBDQ) before and after each of the diets in order to assess changes in self-reported quality of life. Stool, rectal swabs, and blood samples were also taken before and after the first diet, after the wash out period, and after the second diet to monitor markers of inflammation, as well as any concomitant changes in the gut microbiome. To date, the study has had 13 participants complete both diets and quality of life has been shown to improve on the LFD according to the IBDQ. Additionally, the microbiome has been observed to change between diets with a healthier, more diverse set of microbes seen with the LFD. All these data suggest that physicians may be able to propose LFD to their UC patients to help improve quality of life. Matthew says the next steps of this project will be to enroll more subjects and to transplant the microbiomes associated with each diet into germ-free mice to examine whether the microbiome is the cause of the changes in the inflammatory response between diets. Matthew is graduating this spring with his MD/PhD and hopes to pursue a career in infectious disease and research. Matthew was part of the Medical IBIS’s founding group and we are grateful that he decided to round out that aspect of his medical school experience by providing his research for an article in this edition.

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Discrepancies in Chemotherapy and Radiation Start Times for Non-Small Cell Lung Cancer Patients By Jacqueline Baikovitz

Joseph Quintana MD, 2019 Honors: North Miami Dade Medical Scholarship Foundation, Scholarship Recipient, Alpha Omega Alpha Society Member.

Other Interests: San Juan Bosco Clinic, Operation Veteran Engagement – VP of Music Therapy Future Plans: Internal Medicine

oseph Quintana, a 4th year medical student, aims to reduce health disparities by addressing discrepancies involving the start times of lung cancer treatment in order to maximize survival and improve health outcomes. He has enjoyed working with Raphael Yechieli, MD, Assistant Professor of Radiation Oncology, on this project. Joseph was curious about whether racial and ethnic disparities exist in radiation and chemotherapy start times for non-small cell lung cancer patients. Treatment guidelines indicate that radiation and chemotherapy should be initiated concurrently, and Joseph looked at whether patients were undergoing simultaneous treatment or discordant treatment where radiation therapy was given before chemotherapy or chemotherapy before radiation. Joseph stressed the importance of concurrent start times when saying, “Cancer is very difficult to treat. Studies are done in very controlled environments, and we can maximize patient survival if we can get closer to these environments.” Joseph chose to conduct his research on non-small cell lung cancer as it is primarily treated using both modalities. He also noted the importance of studying lung cancer as it is the second most prevalent cancer in the United States with approximately 234,000 cases being diagnosed each year in the U.S. according to the National Cancer Institute. Joseph found that non-Hispanic blacks had a higher risk of discordant start times. He also found that Hispan-

ic patients were more likely to experience concordant therapy. Joseph also compared treatment start times between patients at the University of Miami Hospital, a private academic hospital, and at Jackson Memorial Hospital, a county hospital. Patients at the University of Miami Hospital were more likely to undergo concordant therapy start times in comparison to patients at Jackson. Joseph mentioned that “This is an opportunity for us to think about why there is discordant care. How are we going to improve these discrepancies in the delivery of treatment? Our research served as the first step in the solution. We identified this problem and are bringing awareness to it. We want to conduct follow up studies to find out why these disparities exist and figure out how to implement strategies to fix them.” Joseph presented his research at the ASTRO (American Society of Radiation Oncology) national conference in October in San Antonio, TX. He plans to continue to work on reducing health disparities and has especially been motivated by his Cuban heritage. He has shown his devotion to overcoming health disparities by volunteering at the San Juan Bosco Clinic where the majority of the patients are Hispanic immigrants, and he looks forward to making sure that people from all backgrounds receive the best medical care. Joseph is grateful to Haley Perlow and Vincent Cassidy for their hard work and important contributions to this project.

The Medical I.B.I.S. | spring 2019

Initial Implementation of an Enhanced Recovery After Surgery (ERAS) Protocol for Lumbar Spinal Fusion By Erin Wolfe

pine surgery is one of the most common and most costly neurosurgical procedures. For lumbar spinal fusion procedures, Enhanced Recovery After Surgery (ERAS) protocols have the potential to address problems resulting from an aging patient population, high costs, increases in rates of surgery, and notoriety as a painful surgical procedure. ERAS protocols are multimodal care pathways that serve to optimize patient outcomes. Throughout the entire surgical process, a multidisciplinary medical team uses a variety of methods and a patient-centered approach to reduce the stress of the operation and improve patient outcomes. ERAS programs have been successfully implemented throughout the world across multiple surgical disciplines. However, standardized ERAS protocols are limited in the field of neurosurgery. Damian Brusko, MD 2020, works alongside Dr. Michael Wang, MD, FACS, the Chief of Neurosurgery at the University of Miami Hospital (UMH), to develop, implement, and evaluate the first neurosurgical ERAS protocol for lumbar spinal fusion. They are working in conjunction with the International ERAS Society to write the first international ERAS guidelines for spine surgery. Damian says, “I believe that it’s an incredibly powerful tool. It has been used in other countries and other specialties and has had amazing results” Spine care at UMH requires a multidisciplinary team of medical professionals to provide spine patients with a full spectrum of care. Because ERAS also requires a multidisciplinary approach, Damien believes, “ERAS protocols transition very well to spine surgery, where the severe pain, long length of stay, and high costs can all be remedied by ERAS.” This initiative could ultimately reshape standards of practice within spine surgery. Damian holds a long-standing interest in neuroscience, having conducted research in a basic science cerebrovascular laboratory for nearly three years as an undergraduate student at the University of Miami (UM). As a medical student, Damian transitioned to clinical research in the Department of Neurological Surgery. He began working with Dr. Wang on the first ERAS protocol for lumbar spinal fusion during the developmental stages of the study.

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The research team set out to implement one of the first ERAS protocols in spine surgery at UMH and to compare their results to those reported in other specialties. The ERAS protocol implementation entailed the initial iteration of a “bottom-up” approach, in which implementation of three interventions was provider-driven and targeted to specific key elements of enhanced recovery, including postoperative pain control, patient monitoring, and early ambulation. Beginning in March 2018 at UMH, 34 patients in the ERAS cohort underwent posterior, one-to-three level, lumbar fusion surgery. Spine surgeons Dr. Wang, Dr. Glen Manzano, and Dr. Allan Levi, MD, PhD, FACS, Chairman of the Department of Neurological Surgery at the University of Miami Miller School of Medicine and

“It’s a win-win-win for the patient, surgeon, and hospital”

Chief of Neurosurgery and Jackson Memorial Hospital, performed three different surgical interventions: Patients received an intraoperative injection of liposomal bupivacaine, immediate postoperative infusion of onegram intravenous acetaminophen, and daily postoperative visits from the multidisciplinary ERAS care team. Damian and a second-year medical student, Julie Heger, MD 2021, constituted the ERAS care team. In addition to the surgeon and residents rounding on the patient, the ERAS care team rounded on patients in the ERAS cohort in order to check on their status, monitor their pain levels, and provide comfort, measures which may improve patient outcomes and satisfaction. Following the implementation of three interventions to the spine program at UMH, ERAS patients experienced less pain and exhibited earlier mobilization during hospitalization compared to the control group. ERAS patients walked significantly greater distances with physical therapy, used significantly less pain medication, and had a significant de-

Damian Brusko, MD 2020

Honor for this project: Presentation at second annual ERAS Congress in November, previous publications for the full ERAS study

Other interests: Vice President of NSIG, COATS, George Paff teaching awards committee (Co Chair)

Mentor: Michael Wang, MD, FACS

Future goals: Neurological surgery, continue clinical research in the field of neurological surgery

crease in pain scores on several postoperative days. ERAS patients also had a decreased length of stay. The results of the ERAS study will provide support for the implementation of this type of care pathway for spine surgery, and will guide future efforts to improve outcomes and limit post-operative morbidity in patients undergoing spine surgery. For Damian, postoperative rounding and speaking with patients immediately after surgery was one of the most rewarding aspects of working on the study. He felt that he made the most impact as a member of the ERAS care team and was able to observe patients’ remarkable change in quality of life. Patients went from experiencing a great deal of pain prior to surgery to feeling relief from pain and excitement at their ability to walk pain-free again. Damian will be presenting the results of this study at the second annual ERAS Congress. He is thankful to Dr. Wang, Dr. Levi and Dr. Manzano for

their commitment to the ERAS implementation initiative. Damian has been able to successfully balance research with academics due to his strong time management capabilities, which he learned from his father at a young age. He also maintains a balance between his personal life and academics, pursuing hobbies such as golf, reading, DJing, and spending time with family and friends. Damian attributes his success in pursuing his interest in the field of neurological surgery to personal commitment to his interest in the field and to mentorship from Dr. Wang. Damian hopes to continue advocating for implementation of neurosurgical ERAS protocols. He explains, “it’s a win-win-win for the patient, surgeon, and hospital”and hopes that the use of ERAS protocols ultimately becomes a standardized approach widespread in spine surgery.

The Medical I.B.I.S. | spring 2019

Assessing Connection to Resources and Barriers to Access Through Evaluation of Community Resource Connection Tool at the San Juan Bosco Clinic By Mackenzie Jones Sarah Simko MD, MPH 2019 & Heather Farthing MD, MPH 2020not pictured

Sarah Simko Other Interests: Health Hospitals 4 U, Drug Development Interest Group, Logistics Coordinator for San Juan Bosco Clinic, Doctor’s Note, Women in Medicine Club Future Goals: OB/GYN and Gynecologic Oncology

Heather Farthing Other Interests: Health Hospitals 4 U, Women in Medicine Club, Roller Derby Future Goals: Emergency Medicine Mentor: Dr. Erin Kobetz, PhD, MPH

arah Simko and Heather Farthing’s implementation and research study of a Community Resource Connection Tool epitomizes the benefits that can come from an integration of medicine and public health. As volunteers for the student-run clinic at San Juan Bosco (SJBC) in Allapattah, Miami, Sarah and Heather noticed that many of the pati ents in the clinic were unable to receive complete and proper care due to social needs. Each night at the clinic, they would get to know patients who were doing everything they could to take charge of their own health but were held back by a lack of access to transportation, mental health services, legal counsel, nutritious food and more. Recognizing that the mission of SJBC should be to improve the health of their patients from all angles, they decided to gather a team to design a resource that would connect patients to resources that could address their non-medical health needs. The team included full-time master’s in public health

students, Spanish-fluent MD and MD/MPH students, clinic directors, and members of the DOCS group.

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The Social Needs Assessment Tool works by taking information provided by the patient, such as social needs identified by a series of screening questions, and generating a list of resources that will address those needs at sites near the patient’s home. Once a Social Needs Assessment Provider (aka SNAP) at San Juan Bosco Clinic has used the program to identify the most important needs of the patient and has a list of the accessible resources, they use a motivational interviewing technique to encourage patients to access resources and improve their overall health. The tool also has the capacity to screen for high impact/ high risk needs, including homelessness, domestic violence, human trafficking, and suicide. Since it was decided that this conversation should be a process separate from the clinical visit, more time is devoted to counseling the

patient on the importance of accessing the resources, as well as other important medical topics that aren’t often given enough time in appointments with physicians such as nutritional recommendations and advanced directives. After the initial meeting, the SNAPs follow up with patients two to four weeks later by telephone to determine whether the patient was able to access resources and why or why not.

clinic, they hope to eventually offer the program to the day clinic as well. The model may also be adapted for use in other community health project such as the Sylvester Comprehensive Cancer Center mobile van for cancer screenings. In fact, Sarah, who is interested in going into gynecologic oncology, hopes she can one day use the model in her own practice.

The program took approximately one year to design and set-up within the volunteer clinic. Eleven months after the program was implemented, Sarah and Heather conducted a study to evaluate the process and identify ways to improve it. Forty patients were enrolled by SNAPs, and twenty-two of those patients were reached for follow-up. Seven of those twenty-two reported that they had successfully benefited from one or more health resources provid-

Sarah and Heather credit much of the program’s success to each other and the team at San Juan Bosco. A fellow medical student, Dan O’Shea, inspired them to begin looking for resources in the community. Berta Cabrera and Luz Gallardo, the executive director and clinic coordinator at San Juan Bosco, have supported them each step of the way.

The model may also be adapted for use in other community health projects... ed by the SNAPs. Even more patients had benefited from nutritional counseling and advanced directive education during the initial SNAP meeting itself and from connections to non-health resources such as voter registration. Importantly, one goal of the project was to be mindful that the patient population is particularly vulnerable and to avoid collecting data on patients solely for publication purposes. Instead, data collection is used by the clinic to design future interventions and to apply for grant funding. Sarah and Heather hope that the SNAP program didn’t just help the patients directly. The ultimate goal is that the devotion of time and energy to the upstream barriers to patients’ healthcare will create a shift in the mindset of the clinic. The SNAP program will hopefully serve as a constant reminder to providers to consider the social factors impacting their patients in addition to medical issues. One benefit of the project was the ability to incorporate best practice and ensure that each patient is treated with the respect they deserve. For example, the screen uses updated language surrounding gender, sexuality, and sexual assault. Heather found this aspect of the project to be particularly educational for her future career. She hopes to be an emergency medicine physician, where small interventions such as a short human trafficking screen can have a huge impact on patient care. Even though the project has already undergone a number of improvements, Sarah and Heather have plans to use their research findings and observations to continue expanding the program and increasing the number of patients who are connected to resources. While the program curr ently only runs during the evening student-run

Dr. Erin Kobetz PhD, MPH has been their faculty mentor advising them on what was needed to achieve their goals. Two medical students, Isabel Penabad and Yanelys Fernandez, coordinated the team of SNAPs and two MPH students, Daphne and Francelia Eckembrecher validated the local health resources. The project has taken almost three years so far and still has a long way to go, but the work has motivated Sarah and Heather through the most difficult parts of medical school. The opportunity to collaborate with so many people who strive to improve the healthcare of patients is uplifting and gives them hope for the future of medicine.

Interested in volunteering at the San Juan Bosco Clinic? Visit: https://umdocs.mededu.miami.edu/projects/ clinics/sjb-clinic/

The Medical I.B.I.S. | spring 2019

Evaluating a Novel Digital Pendant and Voice Reminder Platform to Increase Immunization By Jay-Shin Wang Compliance in Rural India

ealthcare delivery is challenging enough in urban setting, where many already fail to receive adequate care due to poverty or limited access to care. These challenges of healthcare delivery are only confounded in a rural setting, where poverty persists and facilities are not only even rarer, but often temporary. These increased challenges are reflected in health outcomes: in rural India immunization coverage is low and leads to increased rates of child mortality from preventable illnesses. This was the problem Logan Stone, a second year MD/MPH, wanted to tackle through the Khushi Baby pendant program. The idea was introduced to him by his undergraduate roommate at Yale, and their work together developing the Khushi Baby program recently yielded a publication in Vaccine November of last year. The Khushi baby program distributes a pendant that can be worn around the neck of a child currently undergoing the 3 part DTP (diphtheria, tetanus, pertussis) vaccine. The pendant is design is unique, because the color choice of the thread and the shape of the pendant were meant to evoke cultural symbols associated with warding off evil spirits to protect the health of the wearer. The pendant additionally contained an NFC device, which could be scanned by a healthcare worker to access the wearer’s immunization record. This record was stored in a cloud server accessible through the Khushi Baby app, which is compatible with other health record systems. At the study’s outset, it was believed the Khushi Baby pendant would help increase vaccination compliance: it would provide a visible reminder to get the remaining shots in the series in addition to providing a durable record for the healthcare official so the patient would be recorded as complete. Its design choice further ties into the secondary objectives of the study, which were to evaluate its social impact: did the pendant evoke community discussion and promote awareness of vaccination?

22 spring 2019 | The Medical I.B.I.S.

Logan worked with a local non-profit, Seva Mandir to evaluate whether the Khushi baby pendant intervention increased vaccination rates. Seva Mandir runs 96 camps servicing 108 villages in the Udaipur region of India, a region that has historically low rates of vaccination. Children who were of age to receive the DTP vaccination series and had not yet completed it were eligible to be enrolled in the study with parental consent. The aims of the study were explained to the parent, usually the mother, who expressed consent through a fingerprint. Enrollment and data collection for the study ran from August 2015 to February 2016. Depending on which camp enrolled the subject, they would receive either an NFC sticker to be attached to their government issued vaccination record card, a Khushi baby pendant, or a Khushi baby pendant with voice call reminders. The NFC sticker arm functioned as a control, because the intervention Logan was studying was the pendant itself when worn by a patient, not the vaccination record accessed through the NFC.

“IN

RURAL INDIA I M M U N I Z AT I O N COVERAGE IS LOW AND LEADS TO INCREASED RATES OF CHILD MORTALITY FROM PREVENTABLE ILLNESSES”

“

Our work in Udaipur during our first RCT was fundamental in understanding the challenges of prospective research in the region. We observed that the digital pendant was well received and promoted discussion regarding positive health behaviors with infant immunization.

”

Logan D. Stone MD/MPH, 2021 Yale University Thorne Prize

Other Interests: Editor for Medical IBIS DOCS Fair volunteer Orthopedics research on midfoot fracture outcomes Tennis

At the start of the study, a survey was distributed to see how many persons were vaccinated within the community as a baseline. As patients completed their vaccination series, they were given another survey to evaluate their feelings about the Khushi baby pendant. Patients who failed the primary outcome of completing the DTP series were still included in the final analysis so the results would not be overstated. To Logan’s dismay, the study did not yield the primary outcomes he wanted. In fact, there was no statistically significant difference in vaccination rates between the three arms of the study. However, the study noted significant differences in the secondary outcomes of the study. Patients who had the pendant reported more satisfied in comparison to the control, increased community discussion, and increased vaccination visibility to the grandmothers and fathers of the child. These social consequences are significant, Logan says, to improving vaccination rates. He believes if this project is followed longitudinally, it will create its own social context and social reward for vaccination compliance. For example, others may see that babies who had the Khushi baby pendant grew up

to be healthier and pursue the program, increasing their contact with the healthcare system. The more normalized it becomes to use the Khushi baby program, the more social pressure exists to conform to vaccination guidelines. Furthermore, Logan acknowledges the study design was flawed in many ways. For one, only around half the patients who were supposed to receive voice call reminders were actually called. Assigning test subjects to each arm of the study by camp, rather than individually, also limited how well he could generalize his results as the sample populations did not resemble each other. Not only that, the sample size was also small, which further lowers the study’s power and limits how well he could generalize the results. These concerns are currently being addressed in a follow up study that Logan anticipates will be his MPH capstone project. For this follow up study, he is working with local Indian government to collect data and promote the Khushi baby pendant program at public health subcenters. He is passionate about Khushi baby, and intends to follow wherever the project may lead him.

The Medical I.B.I.S. | spring 2019

Diabetic Retinopathy Screening in Juiz de Fora, Brazil by Victoria Rea-Wilson

rtificial Intelligence in medicine is still new in the field, but it has shown promise, especially in screening high risk populations. Population Health Scholar Rajika Jindani, MS, a second year in the MD/MPH program at UMMSM, saw first hand how important AI screening can be. This summer, Rajika established in Juiz de Fora, Brazil a screening program at a diabetes clinic using a Remedio non-mydriatic Fundus on Phone camera, an easy use camera that does not require dilation of patient’s eyes, and the EyePACS system, a program that uses cloud technology and an algorithm with 98% sensitivity to grade images of the retina, as well as a portal for ophthalmologists to view the images and confirm the results. The Fundus on Phone camera and EyePACS technology is therefore well-suited to screening diabetic retinopathy in primary care setting for patients that do not have access to specialized care. Rajika was able to obtain one of these cameras as a donation from EyePACS to establish this screening program for diabetic retinopathy.

technology to identify the problem. Overall, Rajika collected data from 50 patients during this time and the screening is being continued by medical students from Universidade Federal Juiz de Fora. The AI detected signs of diabetic retinopathy in almost half of these patients, and 13 were flagged for urgent referral to an ophthalmologist. With telemedicine, these patients were able to be seen by specialists in an expedited manner. Rajika’s project was facilitated by her mentor Dr. Alberto Barcelo, MD, MSc, who was able to help her establish connections in Juiz de Fora through his work with University Federal de Juiz De Fora. During the summer, Rajika trained six Brazilian medical students in the EyePACS system, which will hopefully allow this promising program to continue in the future. Rajika speaks very highly of her “bright and interesting” Brazilian counterparts, claiming “they helped [her] more than [she] helped them.” Rajika plans on staying in contact with them and continuing to follow this program as it evolves.

Early in the progression of the disease, diabetic patients with retinopathy do not present with any outstanding problems with their vision, and “by the time they have symptoms it’s too late,” Rajika explained. Time is critical, and in a city like Juiz de Fora with only one ophthalmologist for nearly 500 thousand citizens, waiting a year between scheduling an appointment and actually seeing the doctor, and then another year to receive results, is not an option. And in emergencies, technology like the Fundus on Phone can really make a difference. During her time at the clinic, Rajika encountered a patient with a retinal tear who was able to see an ophthalmologist within two weeks because of the help of AI

Rajika Jindani, MS

MD/MPH, 2021 Population Health Scholar Award Recipient 2018 Rajika is an Admissions Ambassador, a member of the Ophthalmology Interest Club, is assisting with ENT research, consults at an Ed Tech start-up, serves on the Women in Surgery Committee for the Florida Chapter of the American College of Surgeons, and is also involved in DOCS for her second year, this year as an alternate Ophthalmology Station Manager. She is interested in global health.

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A letter from the Editor-in-Chief Dear Readers, I hope you enjoyed reading the 7th edition of the Medical IBIS produced by the talented medical students from the University of Miami Leonard M. Miller School of Medicine (UMMSM)! The Miller School of Medicine is home to exciting research opportunities such as the Miami Project to Cure Paralysis and the Bascom Palmer Eye Institute among countless others. The Medical IBIS is purposed to highlight the groundbreaking research conducted by the medical students at UMMSM. This year we also dedicate the 7th edition of the Medical IBIS to the importance of medical student mental health and wellbeing.

Hardik Patel MD/MPH, 2021

In addition to acting as Editor-in-Chief for the Medical I.B.I.S., Hardik also leads a student-run wound care clinic at the IDEA Exchange.

Medical school challenges students to push themselves and can commonly lead to burnout. Burnout might be especially prevalent in students who conduct basic science, clinical, or public health research projects in addition to their medical coursework. In this edition of the Medical IBIS, we sought to capture a holistic view of the humans behind the medical research and provide a glimpse into how they maintain their wellbeing. My hope is that the Medical IBIS will serve as platform to stimulate conversations about burnout and lead to meaningful changes to promote medical student wellness. Thank you for reading the Medical IBIS, Hardik P. Patel Editor-in-Chief Medical I.B.I.S.

The Medical I.B.I.S. | spring 2019

About the Cover

The ibis has long been associated with science and medicine. The Ancient Egyptians imagined their god of wisdom, magic, and science with the head of an ibis and named him Djehuty, which literally means “he who is like an ibis.” Today we know him as Thoth because of the Ancient Greeks. In addition to inventing writing and science, Thoth gave mankind medicine according to the Ancient Egyptians. It is very fitting that University of Miami Miller School of Medicine named its research magazine after the ibis. The Ancient Egyptians investigated science and medicine. While most of their discoveries have since been refuted, I would like to honor their early contributions to this field, especially in this edition dedicated to Mental Wellness and Wellbeing in medical students. Unlike many civilizations historically, the Ancient Egyptians recognized the importance of mental wellness and how it could impact health. For example, in the Ebers Papyrus (circa 1500 BCE) features discussion of dementia and depression as conditions that require medicine and not just religious interventions. For mental well-being, the Ebers Papyrus recommends playing music, attending concerts, dancing, and painting, some of which I have chosen to feature on the back cover. I would like to thank fellow ‘cane Mark Wethli, BFA ‘71 and MFA ‘73, who helped me hone my artistic abilities at Bowdoin College.

Victoria “Vic” Rea-Wilson MD/MPH, 2021 Vic likes interdisciplinary and multidisciplinary approaches to medicine and life.

26 spring 2019 | The Medical I.B.I.S.

Questions? Comments?

You can reach us at medicalibis@gmail.com

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Digital Ibis

Connect with us at: https://www.facebook.com/MedicalIBIS/ http://medicalibis.weebly.com

Artistic rendering of the great banyan tree on UMMSM campus.

Photo credit: Daisy Gonzales, Digital editing: Victoria Rea-Wilson

The Medical I.B.I.S. | spring 2019

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