Ayush Kumar, a third-year medical student from the University of Massachusetts Chan Medical School, is the winner of the 2024 AMA Research Challenge and will be awarded the grand prize of $10,000, presented by Laurel Road.

• Poster: Enhancing the Radiosensitivity of Triple-negative Breast Cancer by Targeting VEGF/Neuropilin-2 (PDF)
• Topic: Basic Science
• School: University of Massachusetts Chan Medical School

The judges announced the winner on Feb. 20 at the conclusion of the virtual research presentations from the finalists.

AMA President Bruce A. Scott, MD

Aditya Kotla

• Poster: A Survey on Disabilities and Disability Awareness in General Surgery Residents in the US (PDF)
• Topic: Medical Education
• School: Carver College of Medicine—The University of Iowa

Ayush Kumar

• Poster: Enhancing the Radiosensitivity of Triple-negative Breast Cancer by Targeting VEGF/Neuropilin-2 (PDF)
• Topic: Basic Science
• School: University of Massachusetts Chan Medical School

Darwin Kwok

• Poster: Tumor-wide RNA Splicing Aberrations Generate Immunogenic Public Neoantigens Across Cancers (PDF)
• Topic: Basic Science
• School: University of California San Francisco School of Medicine

Ashley Newsholme

• Poster: Major Adverse Cardiovascular and Limb Events Post Tibial vs Femoropopliteal Angioplasty​ (PDF)
• Topic: Basic Science
• School: FIU Herbert Wertheim College of Medicine

Phoebe Yu, MD, MPH

• Poster: Upper Airway Stimulation for Adolescents with Down Syndrome and Obstructive Sleep Apnea (PDF)
• Topic: Clinical and Transitional Research
• School: Sleep medicine/otolaryngology fellow—University of Pennsylvania

Kirsten Bibbins-Domingo, MD, PhD, MAS

Editor-in-chief, JAMA® and the JAMA Network™

Frederick Chen, MD, MPH

AMA chief health & science officer

Sanjay Desai, MD, MACP

AMA chief academic officer

Dr. Scott: On behalf of the American Medical Association, welcome to the 2024 AMA Research Challenge. I'm Dr. Bruce Scott, president of the AMA, and your host for today's exciting event. For more than two decades, the AMA Research Challenge has been the main event for showcasing the best in research conducted by medical students and residents. 

Today, when our judges select this year's winner, that tradition continues. The AMA Research Challenge is the largest event of its kind in the country, and for the fourth year in a row, the winner will take home a $10,000 grand prize, provided by Laurel Road. Laurel Road offers customized financial solutions to our AMA members, and we're thrilled that they are once again presenting the grand prize here today. Thank you, Laurel Road, for supporting our next generation of physicians. 

This year's challenge has generated a record-breaking level of participation and interest with the road to today's exciting finals, beginning last summer. We started with over 1,300 submissions, with 939 selected for presentation in our virtual poster symposium. The top 50 posters then advanced to the semifinals where they were scored by judges and AMA members. Which brings us to today's five finalists, an extraordinary group whose work represents the innovative thinking needed to continue driving medicine forward. 

Please join me in wishing them all good luck as they compete for the AMA Research Challenge's $10,000 grand prize. In this final round of the Research Challenge, each finalist will have five minutes to present their research to our panel of judges, who will then determine our winner. Let's meet our distinguished judges. 

First, Dr. Kirsten Bibbins-Domingo, the editor-in-chief of JAMA® and the JAMA Network™. Dr. Freddy Chen, the AMA's chief health and science officer, and Dr. Sanjay Desai, the AMA's chief academic officer. Welcome, and thank you, judges, for being here today. 

Now let's meet our incredible finalists who are ready to compete for this year's grand prize. Our first finalist is Aditya Kotla, a second-year medical student at Carver College of Medicine at the University of Iowa. Aditya, what inspired you to go to medical school? 

Kotla: That's a great question. I think for me, medicine is a really wonderful blend of scientific inquiry as well as an artistic element. I had an artistic background growing up, and being able to pay attention to details is something that I think is important in medicine, particularly to the patient's story and how I can use what I learned from their story, as well as the stuff I've learned in medical school and the scientific evidence, to put together a very tailored and individualized plan for the patient. And I think the harmony between science and art is what really inspired me to go into medicine. 

Dr. Scott: Well, Aditya, that's a really interesting story. And our second finalist is Ayush Kumar. Ayush is a third-year medical student at the University of Massachusetts Medical School. Ayush, what keeps you motivated? 

Kumar: Absolutely. So, as an MD-PhD student, one of the great aspects of that career is that sometimes, whether you're in the clinic and doing the med school type of things, that can be stressful. But it's a nice way to go to the PhD side and find a way to relieve that stress, whether it's talking with colleagues, reading papers, and it also works vice versa. Sometimes, there are days in the lab where the results aren't coming as you expected, but you go back to the clinic and you understand how your research could impact other people's lives. That makes you really excited and motivated to continue in this pathway moving forward. 

Dr. Scott: Well, that makes a lot of sense. Thanks for being here, Ayush. Next, Darwin Kwok, a first-year medical student at the University of California, San Francisco School of Medicine. Darwin, what inspired you to get involved in research? 

Kwok: Thank you. That's a great question. So, when I was a undergraduate in Carnegie Mellon, my father was actually diagnosed with a vestibular schwannoma, and that sparked my interest in understanding the disease a lot more. When I did research with my undergraduate PIs, and also my PIs during my gap years, I realized that immunotherapy was a fantastic way of treating cancers that otherwise would require very invasive procedures. So I spent the next few years of my career studying immunotherapies, T-cell based, cell-based immunotherapies, and understanding how these approaches can actually better treatments for these very, very difficult-to-treat cancer types. 

Dr. Scott: Well thank you for sharing your story, Darwin. It's great to have you here. Now let's welcome Ashley Newsholme, a fourth-year medical student at Florida International University's Herbert Wertheim College of Medicine. Ashley, what are your plans after you graduate medical school? 

Newsholme: After graduating, I will be pursuing emergency medicine residency. I really enjoy community outreach and street medicine, and I hope to continue my efforts throughout my career. 

Dr. Scott: Well, best of luck with emergency medicine. That's a great specialty. Thank you, Ashley. And our final contestant, Phoebe Yu, is an MD and a sleep medicine otolaryngology fellow at the University of Pennsylvania. Dr. Yu, what was your inspiration to get involved in clinical research? 

Dr. Yu: Thank you. So I was inspired to get involved in clinical research because of its direct impact on patient outcomes. I'm a surgical trainee, so there's a tendency to show pictures and anecdotes, but there really is a need for rigorous research methods to be able to assess our outcomes, especially if we're offering an invasive therapy for patients. Ultimately, my desire to be involved in clinical research came from a desire to be able to better serve my patients. 

Dr. Scott: Well, great. Thank you, Phoebe. That makes a lot of sense. Thank you to all of our finalists for being here today. Good luck, everyone. Now let the AMA Research Challenge begin, as we hear from each of our finalists. First up is Aditya Kotla. 

Kotla: Hello, my name is Aditya Kotla, and I'm an MD candidate at the University of Iowa Carver College of Medicine. I'm excited to share my research examining the prevalence of disabilities among general surgery residents in the U.S., and the barriers they face in disclosing disabilities within their programs. 

The Center for Disease Control and Prevention, as well as the American Disability Association, define a disability as any condition of the body or mind that substantially affects one's performance in one or more major life activities. Around 25% of adults in the U.S. live with a disability, and mental health conditions are the leading cause. 

Despite the American College of Graduate Medical Education and the American Association of Medical Colleges requiring residency programs to maintain a policy on disability and provide accommodations consistent with that policy, many people with disabilities do not disclose their conditions, particularly in the context of medical training. The goal of this study was to assess the prevalence of disabilities in general surgery residency programs and identify barriers that prevent residents from reporting their disabilities. 

This study was a cross-sectional cohort study that surveyed 198 general surgery residents across urban, suburban and rural residency programs in the U.S. The survey consisted of 33 multiple choice questions on demographics, disability status, disclosure practices, use of accommodations, and disability policies and training. The survey ran from February to April of 2024, and the responses were analyzed to identify trends and patterns related to disabilities in general surgery residency programs. 

Of the 198 residents, around 11% reported having a physical disability, approximately 20% reported having mental disabilities, and around 1% had both physical and mental disabilities. A majority did not have a disability. Notably, 24% of residents who disclosed a disability were diagnosed during their residency, and over 80% of residents with disabilities reported that their condition impacted their ability to work as a resident, with many requiring accommodations such as assistive technologies or adjusted work schedules. 

One of the most striking findings was that 63% of residents with disabilities did not disclose their condition to their program directors. The primary reasons for non-disclosure included fear of discrimination, perceived legitimacy of the disability, personal choice and the burden of proof. Many residents reported concerns about being judged negatively or facing a conflict of interest in their evaluations if they disclosed their disability to their program directors. 

The study also uncovered a significant lack of disability awareness and training within the residency programs. Over half of non-disabled residents had no prior training on how to interact with people with disabilities. Additionally, 72% of residents reported that disability was not addressed at all during the residency application process, and 75% were unaware of their program's disability policies. 

A majority of residents agreed that disability training should be integrated into the residency curriculum. Overall, the findings of the study indicate that disability is a significant issue among general surgery residents, but it remains underreported due to stigma and institutional barriers. The stigma surrounding disability, particularly mental health conditions, may stem from long-held societal biases about disability, which in turn affects how residents perceive their ability to disclose and request accommodations. 

In general surgery residency, a field known for intense workloads and stress, the lack of disability policies and support systems exacerbates the challenges faced by residents with disabilities. Prior studies have evaluated the compliance of 50 accredited graduate medical institutions with the ACGME and AAMC requirements and discovered that although 68% did maintain a disability policy, most of these policies did not fully align with the AAMC considerations, and less than half of these policies were even made publicly available. 

With this evidence, there is a clear need for better disability education and more transparency about policies and resources. A more proactive approach to incorporating disability support into the residency process would begin with the residency application process, and would likely reduce barriers to disclosure. It's also essential to ensure that disability resources are visible and that residents feel supported when making accommodation requests. 

In conclusion, this study highlights the need for reform and the way general surgery residency programs address disability. And with a significant proportion of residents reporting disabilities and facing barriers to disclosure, it's crucial that programs not only improve their disability policies, but also provide comprehensive training and awareness. These changes can lead to a more inclusive environment, increasing diversity within the surgical workforce, and ultimately improving patient care. By addressing these disparities, residency programs can better support their residents and contribute to a more equitable health care system. Thank you. 

Dr. Scott: Well, thank you, Aditya. And now our judges for their comments. Dr. Bibbins-Domingo, why don't you lead us off? 

Dr. Bibbins-Domingo: Well, what I really appreciated was that we have research on graduate medical education included amongst the finalists here. I think that type of research is so important for gaining new insights that hopefully will improve―continue to improve―how we educate physicians. 

Dr. Desai: I agree completely. I think there's so much need for more data in graduate medical education, and I think that this research in particular, it really uncovered or exposed the reality that our residents face the same conditions that occur in general population. The other thing that I think this highlighted for me is that policy is not enough. Aditya mentioned that there are policies to have residents trained in these particular―and to have support for those that have disabilities, but it's not happening. And so we need to move beyond policy to culture change. And I think that's the long arc that we're all in. And this type of data is what's necessary for us to get there quickly. 

Dr. Chen: Yeah. I mean, the topic is such an important one, but it's also such a challenging topic for medical education in general, especially in residency programs. So I appreciate that. I would have liked to see a little bit more detail about these types of disabilities because there is such a range of disability and there's such a range of how programs have to respond to disabilities and accommodations. 

The other piece would be―is recognizing that it's part of a continuum. And even though some of these disabilities may be relatively new, a lot of them have been there since medical school for our learners, and so how that part of the continuum connects to graduate medical education, those are interesting and challenging questions, I think. 

Dr. Desai: Actually, the last point that you made highlights also for me, that I think, where should this training occur? Because these disabilities were likely in place before they entered residency program. So should we move this all upstream? And is the focus really in medical school or even before that for us to really have an effect on the culture? 

Dr. Bibbins-Domingo: Well, with all good research, more research is needed. 

Dr. Scott: Well, great feedback, judges. And I think we're off to a good start. Next up is Ayush Kumar. 

Kumar: Hello everyone, my name is Ayush Kumar. I'm an MD-PhD student at UMass Chan Medical School. My work focuses on triple negative breast cancer, or TNBC, which is highly aggressive and unfortunately has a poor prognosis for patients. A major reason for this is the lack of targeted treatment options and a reliance on more conventional therapeutic strategies. 

Currently, radiation therapy is the last line of defense to prevent recurrence in breast cancer patients. However, it is not as effective in the context of TNBC. Radiosensitizers such as DNA repair inhibitors or immune checkpoint blockade have had variable effects in the clinic. Therefore, it is critical to identify tumor intrinsic factors of TNBC that drive radioresistance. 

To accomplish this, I'd like to direct your attention to my methods section, where I screened for TNBC-specific surface markers that modulate radio sensitivity. Then we developed a targeted treatment option for a specific surface marker called a monoclonal antibody, that could modulate radio sensitivity, followed by using molecular tools to identify the signaling pathways that change when given this antibody and promote radiosensitivity. 

But to start, we first used public databases with RNA sequencing information from TNBC tumors and normal mammary tissue before and after radiotherapy. There were 22 surface protein genes that were highly upregulated in response to radiotherapy in tumors, but were not expressed in normal mammary tissue, making them strong therapeutic targets. 

Of those genes, five of them showed a correlation with patient outcome. One of the top candidates we identified was neuropilin-2, or NRP2. As a transmembrane protein receptor that is associated with a poor prognosis in patients, is enriched upon increasing radiation dose, and is not expressed in normal mammary tissue. Normally, neuropilin-2 binds with its ligand VEGF to induce cancer stem cell properties. Thus, we developed an antibody that can inhibit the binding of VEGF neuropilin-2, which I'll refer to now as anti-neuropilin-2. 

We had a radioresistant TNBC organoid that became sensitive to radiation when we gave anti-neuropilin-2. We also assessed the efficacy of anti-neuropilin-2 with radiation in mouse tumors. And as shown by the tumor growth curve, double treatment significantly delayed tumor growth compared to either treatment alone. 

Moreover, we optimized the radiation regimen with antibody treatment that promoted tumor regression. The orange boxes show the five mice given radiation with anti-neuropilin-2 all saw a decrease in tumor sizes, whereas the other mice continued to have tumor growth. The mechanism responsible for the enhanced radiosensitivity with anti-neuropilin-2 involved turning off the antioxidant machinery of the cancer cells via the transcription factor NRF2. 

As seen in the immunofluorescent images, at baseline, the green signal, or NRF2, is localized in the blue area or the nucleus, suggesting higher activity. However, when treating with anti-neuropilin-2, the NRF2 signal in the nucleus diminishes and this is reflected by a decrease in expression of the three NRF2 target genes shown below. 

To conclude, we were able to accomplish two things. One, we identified the mechanism by which neuropilin-2 expressing cells within TNBC tumors counteract radiotherapy. And two, we have an antibody that shows to be very effective in enhancing the radiosensitivity of TNBC. Together, we hope to take one step forward in making a new novel therapeutic for TNBC patients. Thank you. 

Dr. Scott: Very interesting research. Thank you, Ayush. OK, judges, time for your comments. Dr. Chen, let's start with you this time. 

Dr. Chen: Boy, that was such a fabulous presentation. I feel like I could sit and listen to him all day. I think he did such a nice job presenting the flow. I mean, I'm not a big basic science person, and for me to be able to follow that and understand it, I think, is a huge win. I really enjoyed hearing the amount of science that went into this work and how it really also highlights just so much of the innovation and development that's happened in this field so far. 

Dr. Desai: Yeah, no, I agree. I think listening to somebody at his tenure in medical education present, identifying the clinical question, and then beyond that, understanding the science, his facility with that science, creating the experiments. And then I think, as you highlighted so eloquently, the capacity to communicate that in this type of presentation, I think is unique. And I think I look forward to how this will move forward into more basic research, but also into translational and hopefully eventually reach patients. 

Dr. Bibbins-Domingo: Yeah, I mean, I think he's working in such an interesting area. This is really transforming how we think about cancer therapies, really being able to target our treatments more precisely to the specific issues related to the tumor. And then understanding when it doesn't work, what is it about the cancer cells that we can discover in order to optimize the treatment further? And in addition to the great way he describes this, I think he's working in a really fascinating area. And so it'll be exciting to see what comes next. 

Dr. Scott: Well thank you, judges. Obviously a very important area of research. Let's get to our next contestant, Darwin Kwok. 

Kwok: Hi, my name is Darwin Kwok, and I'm a first year medical student at UCSF in the Okada and Costello labs. It is my pleasure to share with you my work on the discovery of tumor-wide splicing derived neoantigens for cell-based immunotherapy. As a brief background, immunotherapies have revolutionized cancer treatment. But its benefits are limited in cancers such as glioblastomas and gliomas due to low somatic mutational burden and high intratumoral heterogeneity. 

Taken together, this prompted us to look towards RNA splicing as a promising source of neoantigen production, as a 2018 cancer cell paper demonstrated that tumors exhibit more splicing abnormalities compared to normal tissues. As such, we hypothesized that cancer-specific splicing could provide tumor-wide and public immunotherapy targets. To accomplish this, we developed a unique platform called SNP. 

Here, we characterized splicing isoforms from TCGA/RNA sequencing data, characterized their intratumoral heterogeneity via our in-house spatially mapped data set, and identified TCR clones that targeted HLA displayed neoantigens. We defined neojunctions as splicing events that are non-annotated in other databases, publicly found in 10% of each tumor cohort, and cancer-specific, meaning that they're found in less than 1% of a normal tissue database called GTEx. 

Thousands of neojunctions were identified, yet there's a subset of which that were expressed in multiple cancer types, indicating the potential of generating an off-the-shelf therapy. After identifying these neojunctions, we wanted to then evaluate the intratumoral heterogeneity using multi-site biopsies from individual tumors. 

With this method we identified many neojunctions found across the whole tumor landscape. However, to achieve a much higher resolution, our team developed a data set of 56 glioma patients where each tumor undergoes 10 maximally distanced and spatially mapped resections. With this analysis, we can characterize how conservative a neojunction is, and a distinct subset of these were found tumor-wide in not just one patient, but in multiple patients. 

From these neojunctions, we can predict peptide candidates that are processed and presented by HLA. Most prediction algorithms typically score peptides solely on their binding affinity to HLA molecules. However, before even binding to HLA, the n-mers would need to be properly cleaved out by the proteasome. In our approach, we utilized two independent algorithms to evaluate both properties of proteasomal processing and HLA binding to identify strong candidates. 

We take the candidates that scored in the top 1% of both algorithms, which allows us to generate a list of high confidence targets for in-vitro validation. From these top scoring candidates, we used in-vitro sensitization and 10x single cell sequencing to identify TCR clones specific to two neoantigens derived from neojunctions in the GNAS and P22 genes. 

CD8-positive T-cells transfected with these TCRs demonstrated reactivity against HLA presented neoantigens at concentrations as low as 1 picomolar. T-cells recognizing the GNAS neojunction can also be detected in the peripheral blood of glioma patients, which indicates a degree of memory development. In collaboration with the Klebanoff Lab at MSKCC, we confirmed endogenous neojunction processing and HLA presentation. Mass spectrometry detected HLA-A2 bound GNAS from unmodified GBM cell lines, which demonstrated that the neojunctions are endogenously processed and their physiological levels of expression is sufficient for detectable presentation. 

These findings led us to evaluate T-cell mediated cytotoxicity, and we successfully demonstrated that TCR engineered T-cells can mount a tumor-killing immune response. Finally, we wanted to investigate mechanisms that drive neojunction production. IDH mutations in gliomas were previously suggested to be associated with increased neojunction expression, but when you further stratify the IDH mutant subtypes into astrocytomas and oligodendrogliomas, you can see that the oligos have even more elevated neojunction expression. 

Oligos are molecularly characterized by the codeletion of chromosomes 1p and 19q. From differential gene analysis, we noticed that elevated expression of splicing related genes in IDH mutant tumors, but also the loss of expression of those located on 1p and 19q in oligodendrogliomas, led to basically an increase in the number of the neojunctions that we found. When we performed CRISPRi knockdown of selected splicing genes, such as CELF2 and SNRPD2, and SF3A3, we actually see a corresponding upregulation or downregulation of associated neojunctions. 

While most studies highlight the importance of splicing factor mutations and generating neojunctions, we show that simply changing the expression of normal splicing factors is enough to modulate aberrant splicing. Altogether, our work discovered a new class of tumor-wide neoantigens that can be targeted by engineered T-cells. We've also demonstrated that dysregulated splicing factor expression is sufficient in sculpting the neojunction landscape. 

Hopefully, these findings will be the start of many exciting new discoveries in the world of cell-based immune therapies. Thank you very much. 

Dr. Scott: Well, thank you, Darwin. Another impressive presentation. It's time to hear from our judges. Dr. Desai, why don't you lead us off this time? 

Dr. Desai: Sure. I think, again, another impressive foundational science. Someone participating and engaging in research and discovery that seems far beyond the tenure of Darwin's training. The other thing that really came across to me was his palpable enthusiasm. I think it was so wonderful, wonderful to feel that. 

And the last thing I experienced was there's just so much there, and it's hard. I think it's challenging to communicate that much science. And it reveals the complexity of the experiments, the ambitious experiments that our students are conducting. 

Dr. Chen: Yeah. I mean, first of all, I'll just say he had me at oligodendroglioma. No, but it is complex. It's really tough to do a 30-second elevator speech or explain it to your grandmother. And that's one of the challenges of this competition, right, is making sure that people can follow the line of logic. 

And so I certainly found the more times I heard it, every time, I would get something more and more out of it. But it is quite complicated. 

Dr. Bibbins-Domingo: Yeah. I mean, I think he's really working in one of the worst cancers that we have, glioblastoma, and trying to identify ways in which one of the most impressive therapies that we have could better address the therapeutic needs in this particular cancer. And yes, he's starting at the discovery phase, and the discovery phase is much more open-ended. But I agree, I think he's both enthusiastic; the results are impressive. I think they also highlight all of the ways in which our ability to computationally take so much data and then identify new mechanisms that might be applicable, I think is great. 

It sort of reminds me how much we have the opportunity to learn when a therapy doesn't work for a particular tumor, and then go back to the foundational sciences to really identify other things that we might do, and that interplay of the clinical insights as well as the foundational mechanisms is where I think the most interesting science is happening right now. 

Dr. Desai: I think the other reaction I had is listening to Darwin, it's undoubtedly the case that he benefits from such sophisticated and strong, dedicated mentorship. 

Dr. Bibbins-Domingo: Absolutely. 

Dr. Desai: And it reminds me of the need for us to really invest in students in this foundational science and in discovery, so that we can reach these benefits that we're excited to hear more about. 

Dr. Scott: Great comments, judges. I can tell it's going to be a tough decision to pick a winner here tonight. Next up, we have Ashley Newsholme. 

Newsholme: Hello. My name is Ashley Newsholme, and I'm a fourth-year medical student at Florida International University's Herbert Wertheim College of Medicine. Today, I'll be presenting this study done along with my colleagues, Amina Namrouti and Nicole Moscoso, titled Major Adverse Cardiovascular and Limb Events Post Tibial versus Femoropopliteal Angioplasty. 

Both femoropopliteal and tibial angioplasty are commonly used procedures to achieve revascularization in the setting of chronic peripheral artery disease or acute limb-threatening ischemia. Our study assessed whether adults who underwent either femoropopliteal or tibial angioplasty had different 30-day post-procedural outcomes. 

We conducted a retrospective cohort study with data from over 8,000 patients in the National Surgical Quality Improvement program data set. We included adults who underwent either femoropopliteal or tibial angioplasty, and our two major outcomes were major adverse coronary events, or MACE, and major adverse limb events, or MALE. MACE was defined as myocardial infarction or stroke and death. MALE was defined as amputation and intervention of the treated segment. We controlled for confounders like age, sex, ethnicity, diabetes and dialysis. 

Data was analyzed using a logistic regression model, yielding odds ratios and 95% confidence intervals. Of the 8,319 participants that were included in the study, 71% underwent femoropopliteal angioplasty, while 29% underwent tibial angioplasty. As seen in figure 1, we found no significant difference in the post-procedural 30-day outcomes of femoropopliteal versus tibial angioplasty. 

Figure 2 displays the incidence of MACE, MALE, or no significant outcome by procedure type. The incidence of MALE was 7% in the femoropopliteal and 8% in tibial angioplasty. This was not statistically significant in either crude or multivariable adjustment. The incidence of MACE was 2.5% in femoropopliteal and 3.3% in tibial angioplasty. This was statistically significant in crude analysis, but lost significance after multivariable adjustment. 

Incidentally, we noted that pre-procedural ABI measurement and dialysis were found to increase the risk of both MALE and MACE, with dialysis having over 30% increased risk of MALE and an almost three-fold increased risk of MACE. The findings suggest that the choice between femoropopliteal and tibial angioplasty may not significantly impact short term outcomes, thus suggesting that procedure selection may be based on physician preference and patient comorbidities. 

Further research, especially clinical trials, is needed to clarify the racial, ethnic and comorbid disparities present in procedure selection and post-procedural outcomes. Thank you for your attention. 

Dr. Scott: Well, thank you so much, Ashley. Judges, back to you. Dr. Bibbins-Domingo, let's start off with you again. 

Dr. Bibbins-Domingo: Well, I'll tell you what I liked about this. So she's using a really large database of surgical outcomes. It's a national database. That's how she has a study of more than 8,000 procedures. And those databases are developed so that we can look at patterns of outcomes from surgical procedures. And they also turn out to be a great way for somebody early in their career to get started doing research, to start to ask a question that hopefully she observed in the context of her own early pursuits of clinical care. 

And I thought she told us very nicely about the question she has and then making use of these publicly available databases to actually start to explore this. And that's oftentimes, I think, the first step to really getting a research career going that's grounded in the type of clinical pursuits that you're engaged in. 

Dr. Chen: Yeah, I really liked the clinical aspect of this. I would have liked to hear a little bit more about what really prompted this question. What is that piece of it? I want to appreciate negative findings, that not all research turns into a clear piece there. 

But at the same time, I think, for example, the multivariate model―it would have been interesting to hear a little bit more sort of about what went into that and what we learned from this piece. 

Dr. Desai: Yeah. I think picking up on the negative findings, I think that what impressed me is that she found a clinical question that had relevance to clinical practice. And having a negative finding still informs patients and trainees and clinicians that are performing this surgery, knowing now that one is not objectively superior to the other, but to take that into account and looking at the patients and looking at their training environment and what they feel comfortable with. So that in itself, I think, again, answering something that has practical implications, I found very interesting. 

Dr. Chen: And you always have to remember too, with these large data sets, because they are essentially cohorts, there's not a control and there's not a randomization piece of it. So you've got to weigh sort of those pros and cons when you look at that type of research. 

Dr. Bibbins-Domingo: Absolutely, yeah. 

Dr. Scott: Thank you, judges, again, for very insightful comments. Now on to our final presentation from Dr. Phoebe Yu. 

Dr. Yu: Today, we'll be talking about our work looking at upper airway stimulation for adolescents with Down syndrome and obstructive sleep apnea. Obstructive sleep apnea, or OSA, is a common condition of airway collapse during sleep and is associated with health sequelae, including cardiovascular and neurobehavioral morbidity. 

Neurobehavioral morbidity is especially relevant to special needs and vulnerable populations like children with Down syndrome, where the prevalence of OSA is as high as 80%. Yet, children with Down syndrome have had limited therapy options for OSA. 

Adenotonsillectomy is the first line treatment, but less than a third of these children have complete resolution after adenotonsillectomy alone. Many require subsequent CPAP or continuous positive airway pressure, which often has low adherence due to poor patient tolerance and coincident sensory disorders. 

Upper airway stimulation is a novel surgery to place an implant that stimulates the hypoglossal nerve to open the airway during sleep. It has shown efficacy as a therapy for CPAP intolerant adults with OSA, but prior to this study, had not been investigated in a pediatric population. We conducted a single arm phase I trial of upper airway stimulation in 42 adolescents with Down syndrome at five different sites. Inclusion criteria were adolescents aged 10 to 21 years old with persistent severe OSA, which is defined as an apnea hypopnea index, or AHI, of at least 10 events an hour after adenotonsillectomy.

Participants also had to be intolerant to CPAP or have a tracheostomy, and they had to have a sleep endoscopy pattern that showed a favorable pattern of collapse, meaning there was no circumferential palatal collapse. Participants were excluded if they had a central apnea contribution over 25% or a body mass index over the 95th percentile. 

Our study protocol involves surgery to implant the device, activation of the device one month after surgery, and then follow-up assessments with subjective outcomes and objective polysomnography that was done at 1, 2, 6 and 12 months postoperatively. The pre-specified primary outcome was the change in the AHI 12 months after surgery, and we defined treatment success as a 50% decrease from the baseline AHI, based on SuRe Criteria that was modified for a pediatric population. 

In terms of results, 67% of the participants were male with a mean age of 15.1 years old. For objective sleep outcomes, we found that there was a significant improvement in the sleep apnea severity, with a mean decrease in the AHI by 12.9 events an hour. 65.9% of patients were treatment responders 12 months after surgery, meaning they had an over 50% decrease in AHI. 

Participants also had meaningful clinical improvements in subjective outcomes. The OSA-18 quality of life survey improved by an average of 34.8 points, with 77.8% of patients having a moderate or large improvement in quality of life. Similarly, there are significant improvements in the Epworth Sleepiness Scale by an average of 5.1 points. 

There was an acceptable adverse event profile, with the most common complication being temporary oral discomfort. Four patients had readmissions and two patients had reoperations, one for an extruded device, and the other for a revision of the sensing lead. There were no adverse events that led to permanent injury or life-threatening illness. 

Finally, there were high rates of adherence, with the mean nightly therapy duration of nine hours, and 95.2% of patients using the device at least four hours a night. 

In summary, we found that upper airway stimulation was a safe and effective therapy for adolescent patients with Down syndrome and OSA. The patients had objective and subjective improvements, excellent adherence and acceptable adverse event profile a year after surgery. Limitations of our study are that it was a single arm study that did not have an untreated control group, and we did not include younger children in the study. 

Strengths of our study include that we had multiple sites and central review of sleep endoscopy videos and polysomnography results. Overall, our results describe a novel therapy for a population that has thus far had limited options. Our data led to FDA approval for this indication in March of 2023. Based on our promising results, there are a number of centers across the United States that are now starting to offer upper airway stimulation for children with Down syndrome, and our goal is to assess the outcomes as the therapy becomes more widespread, as well as to look more specifically at neurocognitive outcomes like expressive language. Thank you. 

Dr. Scott: Well thank you, Phoebe. As a fellow otolaryngologist, I actually understood most of your presentation. Let's go to the judges. What are your comments? Dr. Chen, kick us off. 

Dr. Chen: Yeah, super interesting to see a study, a clinical study, at this kind of phase 1 level, and for a population that really is underserved and has particular special needs. I took note of the really particular selection criteria. And so you've got to think about how that's going to get used in real life practice. But at the same time, I also really appreciated not just the sort of objective measures of outcomes, but the quality of life measures that were in the study. 

Dr. Bibbins-Domingo: Yeah. I mean, I think the thing that I'm always struck by is how few studies we have in adolescent and in younger children. And for this condition, for this population, doing studies in adolescence, as she's done, is critical. But we oftentimes don't think of it. It's a lot easier, we want to protect younger populations. But it is important to also have good science to guide therapies in the younger age. And so to be able to do this study and to have it actually affect the regulatory environment to approve this treatment I think is really, really commendable. 

Dr. Desai: Yeah, as a pulmonologist studying OSA but in adults, it was really interesting to hear how prevalent this condition is in this population. And it's a clever approach to a treatment that seems to have really wonderful adherence and clinical impact. And so I think having that meaningful impact clinically on a population that, as you mentioned, may be underserved and certainly in investigation is, I think, really useful. 

The other is that this is a five site study, which I think, again, for somebody at this tenure to take a device and move it to phase 1 and then have five sites and enroll patients I thought was impressive. It is important, I think, as she highlights, to test this against other standards and to do more prospective research now that it is approved in the clinical environment and used presumably more broadly. 

Dr. Bibbins-Domingo: Absolutely. 

Dr. Scott: Thank you, judges, for your comments on her presentation and your discussion on all five of our incredible presentations. And congratulations to all five finalists for your outstanding research and presentations. 

Now let's go back to our judges, who face a difficult decision as they choose this year's winner. Judges, let's get your final thoughts on crowning our 2024 AMA Research Challenge winner. Dr. Desai, let's start with you. 

Dr. Desai: Wow, is my first reaction. Difficult decision, I think, is an understatement here. I am so impressed with all of these presentations and actually quite humbled as well. I think just thinking back to where I was at the stage they are at now, this was not even in the realm of imagination for me to be able to conduct this and then actually do the research, communicate it in a way that's been demonstrated today. 

And the other part that impresses me is the breadth of science that we saw today. We saw clinical research. We saw foundational science. We saw survey-based results. We saw prospective device investigation. So that breadth is impressive from the group that we had today. I found it very interesting. 

Dr. Bibbins-Domingo: Yeah, I totally agree. I totally agree. I think that the breadth is certainly going to make it challenging on us to make, because the science is so different in each of these cases. But I'm heartened because we need those early in their career to be interested in a breadth of types of science, because I think it will―from medical education to very mechanistic science―I think that's going to be important. 

Another feature I think that we're going to have to consider as we evaluate is just their ability to communicate their science. And I would say, we had five outstanding presentations there. And I think they really speak to not just doing great science, but actually communicating to a broad audience about what the findings mean and why the question is important. 

Dr. Chen: Yeah, absolutely. Again, I'll echo Dr. Scott's piece about how difficult this decision is. We see this a lot in research competitions where you're like, well, what's more important, brain cancer or breast cancer? And it's not about that. And it can't be about that. But really, what it is, is an appreciation for science and how important high quality science is, how important research is and the educational piece of this. 

Because at this stage of their career sort of exposing folks, I think we saw some really great examples of clinical research and of foundational basic science research. And tying all of them together, especially for this competition, is this piece around how do you communicate and present results? How do you represent your work appropriately? And how do you make it relevant to your audience and make it meaningful in that way? And so those are all the things going through my mind, for sure. 

Dr. Desai: I just wanted to pick up on the theme of communication that both of you raised. And I think sometimes, we think of communication in scientific sessions, and how do you explain this to an investigator or to another scientist? And I think what I heard both of you say, and what I'm hearing from the presentations today, is the need to communicate also to the public, because to patients and to those that will benefit from this science, if we can't explain our science to them and the impact and the meaningfulness of this research, then it won't have the dissemination that we want it to have. And I think all five presentations today, really, the presenters thought about that. And I think they were capable of presenting the story in a way that I think was enjoyable to hear. 

The last piece I'm thinking about is that none of this research occurs by individuals alone. They happen because there are teams. And the presentations today and how the exemplar nature of them all, and of the science itself, I think, is a reflection of the investment that mentors are making in our students and in these five students, certainly in particular. And I'm impressed and grateful for that as well. 

Dr. Bibbins-Domingo: Yeah, I totally agree. And medical education is full of really outstanding physicians teaching those coming up through medical, undergraduate or graduate medical education. And I think those who are also working in that specific area of getting clinical scientists, physicians to be scientists and to ask questions, and also, frankly, to mentor through the communication aspects, is really wonderful. And it can be a challenge. I think you do that because you love it because it is also investing in the next generation. But as you suggest, it's really so critical. 

Dr. Scott: Well, judges, these were certainly five fantastic presentations on some incredible research. But now you have to pick a winner. We're going to give you a few minutes and then come back to you for your final decision. 

OK, judges, it's time to get your final thoughts on the winner of the 2024 AMA Research Challenge. Judges? 

Dr. Chen: Well, I will say, Dr. Scott, you are correct. It was a very difficult decision. First, let me just say congratulations to all of our finalists on your fine work, your excellent presentations, and congratulations as well to your medical schools and your mentors. For our final decision, I'm going to turn it over to Dr. Bibbins-Domingo. 

Dr. Bibbins-Domingo: Well, the deliberations were challenging, but in the end, the judges were unanimous, and the winner of the 2024 AMA Research Challenge is Ayush Kumar from UMass Chan Medical School, for his study of triple negative breast cancer and biomarkers of radiosensitivity. We were impressed both by the science and the importance of the question, as well as the very clear presentation of the very interesting results, so congratulations. 

Dr. Scott: Thank you, judges. What an amazing group of presentations. That had to be a difficult decision. Thank you again for joining us today. 

And now we've come to the exciting moment where we get to tell the winner the big news, live. Let's bring in Ayush Kumar. 

Hi, Ayush, it's Dr. Bruce Scott, the president of the AMA. How are you doing today? 

Kumar: I'm good. How are you? 

Dr. Scott: Well, we've finished with the judges here. And they had just one more question that we needed to ask you. And so what we need to know is, how does it feel to be the winner of the AMA Research Challenge? 

Kumar: Oh, wow. That is awesome to hear. I'm so thankful for this award and this honor. Wow, I'm super happy, definitely at a loss for words. 

Dr. Scott: Well, congratulations, and a $10,000 grand prize. How's that feel? 

Kumar: That feels really good to hear. And it's sort of surreal as well. Thank you so much. 

Dr. Scott: So I'm curious, when you first entered this competition, did you ever think that you would leave as the big winner? 

Kumar: No, it definitely wasn't something that I thought at the top of my mind. I just wanted to do a good job practicing my presentation skills and share what of the research I was able to accomplish. So definitely did not think that when I first applied, but I'm glad that it turned out this way. 

Dr. Scott: Well, your research was impressive and your presentation was incredible. There were a lot of other great presentations as well, but you stood out among the group, so congratulations. Now, I know research is a team effort. Is there anyone you'd like to give a special shout-out to from your team? 

Kumar: Absolutely. My thesis advisor, Dr. Mercurio, has been someone in my corner throughout this whole process, supporting me, my ideas, and I wouldn't be here in this position without him today, so definitely a big shout out to him. 

Dr. Scott: Well, fantastic. And I want to thank all those who support the research efforts of our aspiring students. And so we're so very fortunate to have Laurel Road provide the grand prize and to provide services to our AMA members. Have you thought about what you're going to do with the money? 

Kumar: Oh, that's a good question. I haven't really thought about it that much, but I definitely will reward myself and maybe the lab members that have helped me up to this point. So maybe a nice dinner would be something that we all deserve for this. So thank you so much for this opportunity. 

Dr. Scott: Well, certainly. Thank you very much for being with us here today. And thank you again, and congratulations. Please continue your journey in research. We're excited to see what you'll accomplish in the future. 

Kumar: Thank you so much. I appreciate it. 

Dr. Scott: Have a great day. 

Kumar: You as well. 

Dr. Scott: Congratulations to our finalists and to our 2024 AMA Research Challenge winner, Ayush Kumar. Such an impressive and innovative body of work was demonstrated here today and throughout this year's challenge. On behalf of the entire AMA, thank you to all our participants, co-authors, and mentors for your contribution to research and this year's projects. 

Again, a huge thank you to Laurel Road for presenting our grand prize and offering customized financial solutions to our AMA members. As a final thought to close the event, let us continue to recognize and support the vital role of research in medicine. It's research that moves medicine forward. It's research that drives innovation, new methodologies and treatments that results in better outcomes for our patients. It's research that makes us better physicians. Thank you for joining us and being part of this great event.