All right, we'll go ahead and get started. Thank you everyone for coming this morning. It's really my privilege to introduce speakers from my favorite grand rounds of the year, which is the year in review for graduating research residents. And thank you for all the work that you've done both clinically for us, especially the fellows, but the department as a whole. And for all the exciting academic work you've done a knowledge you've contributed to. So thanks for that. I'm going to go ahead and introduce some doctors. We have today doctors, two Zali, two and Moscow, it's a I'm going to introduce everyone at the beginning. I'm going to come up and give presentations and then we'll do we'll save maybe harbor all questions for the end please on a certain clarifying questions and we'll get some comments from mentors and questions at the end. We'll plan to do it that way. But that being said, I'll start by introducing our first speaker, Dr. Priyanka Chu. So as many of you know, she's a general surgery resident of Austin University and has done really outstanding work with the care team. In particular, under the mentorship of Dr. Jacek and Dr. Modi, contributing to our knowledge about intestinal failure. As she's won a number of accolades along the way, as she was awarded the Society of University Surgeons Resident Research Scholar Award, which is very prestigious and competitive. And as well as I'll say the case of the year competition of Boston's surgical society last year before Dr. Fallin restored our honor. So with her grant funding from the S.U.S. Dr. Chu under the Capprajic to understand medication and nutrition adherence for adolescents and young adults within intestinal failure, I really enjoyed hearing about her innovative approach using multiple multi-disciplinary research methods that we've talked about over the last few years and it's really fun to hear about and see her actually push such a completion for an idea that really wasn't totally main stream but making that her own, getting funding for it and then really being persistent and achieving that. So we'll look forward to hearing about her work this morning. Dr. Sean Azadi is up next. He came to us as general surgery resident from Oregon Health and Science University and he has worked extensively with the S.O.F.A.G. Latreja and Airway team under the mentorship of Dr. Zandeha and Demarie. Dr. Zande racked up awards at the national meeting circuit bringing back first place awards from New England surgical society, APSA and Harvard research day going from local to regional and national and winning accolades at each step. Perhaps most importantly we have incorporated his work into our routine practice. So he has published evidence for primary tricute pexia at the time of the S.O.F.A.G. Latreja repair which we all understand here but disseminating that throughout the country and world and more recently for his use of vocal cord ultrasound in place of fiber optic exams for the evaluation of vocal cord function and recurrent learned gel nerve injury 10 minutes ago I was in the ICU and just like we do every day talking about getting vocal cord ultrasounds like completely especially for the patients completely changed things made things a little bit less invasive and that's extremely important and wonderful. Dr. Zande's helped me through an enormous and inordinate number of call shifts that we've happened to share in the last two years and I really appreciate all of this from Dr. Donacou. So she's a general surgery resident at Zucker's school medicine at Hofstra University. She is an innovator and mentored by Dr. Zli Demarian Kim. She's made enormous rides in areas of clinical care that most physicians most surgeons most of us take for granted and don't consider. So most pervasively she's helped to develop surgical smudges that reduces the risk of adhesion formation and gotten to see a prototype of that and have been very impressed with it and it's an exciting development that in hindsight seems so obvious but it's that kind of thing that can be really impactful. The other device innovation that she's working on is a perting device that I wouldn't be surprised if we see it commonly used in adult pediatric ICU's around the country and world in a few years. She's also helped to fellows immensely with her excellent clinical work, ever willingness to help with case coverage and scrubbing out on cases to build up her operative experience and we thank her for that. And last but not least Dr. Camila Musguita is a she's a general surgery resident across the street at Beth Israel Deakinis Medical Center and has worked extensively in the lab translating her previous experience in cardiac surgical research on mitochondrial transplantation into now developing new expertise in both trans-anionic stem cell therapy or as we know the acronym trace it and trans-anionic fetal immunotherapy traffic under the mentorship of Dr. Fraza. So I'm no expert in these topics apart from what I've learned from her impressive research presentations both here and nationally but it's self-evident that she's really pushed forward a challenging basic science work field and methodology and publish 10 basic science papers on just those two methods in the last two years which is an incredible amount of work. I really look forward to being exposed more to her work this morning and thank you for all your help these last two years. So with that we'll start with Dr. Jim. Thank you. Good morning everyone. I'm my talk. I'm in the making of the first project. All right. Hello everyone. I am Priyanka. I'm Dr. Jacksick and Dr. Modes, one of their research fellows and working with the Center for Advanced Intestinal Rehabilitation. Since it would be impossible to cover two years of fellowship in an eight to ten minute talk, I'd like to present to you my very first project that I worked on and the very last project that is still ongoing. The first project that I'll share with you is from a collaboration with Vaughn. This is a nonprofit organization that Dr. Modi and Dr. Jacksick have been working with three years. It has over a thousand niggus around the world contributing data to it and it is unique in that the data is all entered manually by a labor of love from individuals at huge sites. So for here it's Emily and I and therefore it's prospectively and clinically collected. Vaughn captures 95% of all VLVW infants in the United States so the data that we're working with can be considered population level data. Our first project was comparing healthcare needs and extremely low birth weight infants with neck and spontaneous intestinal perforation. As we know neck and sif are GI emergencies more common in the premature and low birth weight VUNA because of that we focused on ELVW neonates and we know that in this ELVW population neck and sif have quite high mortality so neck is known to have a greater mortality than sif. Existing data shows that despite this mortality difference both groups have similarly high short-term morbidity at discharge from their initial hospitalization and we also know that neck has increased long-term morbidity which is especially clear when we look at neurodevelopmental disability. This long-term information is not quite as clear for sif. So to address this knowledge gap we looked at ELVW neonates from 59 North American niggus that were all part of the Vaughn network. We looked at three groups those of lack-rotomy confirmed neck, sif and those without neck or sif. Our primary outcome was severe neurodevelopmental disability at two year follow-up and our secondary outcomes were growth morbidity with weight less than the 10th percentile as follow-up and other markers of increased healthcare needs. We had 6,391 ELVW infants in the cohort and when we compared neck to sif directly we found no significant differences in any of their outcomes. We then compared neck and sif patients to our controls those without either diagnosis and I'll focus on those which meant significance. When we compared infants with neck to the controls we found that there was a greater risk of severe neurodevelopmental disability, re-his hospitalization and post-discharge surgery. When we compared sif to the control we also found a greater risk of post-discharge surgery. Though that was the only one for sif that meant significance you can see that everywhere on this forest plot where neck had an increased risk of an outcome sif trends towards significance in that area as well. This show that overall neck had increased long-term morbidity that fits with the current literature but we now know that sif also has increased healthcare needs which allows us to better counsel parents of infants with sif and to consider allocating greater resources to long-term care. Well that was such gears to my biggest project that I spelled the bulk of my time here working on and that is still ongoing. This is medication and nutrition adherence like R& mentioned in adolescents and young adults with intestinal failure and this is the project that as you mentioned we were able to get the Society of University Surgeons Resident Research Award to support. So most of us here at Boston Children s are familiar with our intestinal failure patients so I won't go too much into the definitions other than to point out that intestinal failure encompasses a heterogeneous group of conditions as you can see here which makes the true incidence difficult to quantify. But we have a very large center here as you all know and we follow 330 patients annually about 140 of whom are adolescents and young adults and about a third of whom are on home PN. Intestinal failure was previously almost always fatal but with the advent of parental nutrition and improvements in interdisciplinary care survival of intestinal failure in the United States has gone over to 90 percent with our center having a five-year survival of 98.5 percent. While we've made major strides in survival the impact to the patient and the caregiver is still enormous. For those on PN the median hours per week of direct medical care is estimated to be nearly 30 hours per week. The economic burden of intestinal failure is also noteworthy with estimates of over 500,000 dollars in medical expenses in the first year of life and upwards of a million dollars over five years. As more of these patients are reaching adolescents it's important to consider that it's a transitional point in child development with increasing driver independence, hopefully responsibility and with those changes also comes a well-documented time of medication non-adherence as seen in other chronic diseases. On a personal note I was diagnosed with celiac disease and grave disease as a teenager and young adult and I became very aware of the burden of chronic disease. I then came here to work in our intestinal rehabilitation clinic and I met a lot of great teenagers. My very first patient was this great 12-year-old who due to a lot of his social issues had to do a lot of his care for himself so he was responsible for his own medications he was responsible for making sure he took his formula and it really pulled me kind of the impact that this disease and other chronic illnesses have on our teenagers. So with my personal experience and with the patients that I've seen here in the care clinic it sparked my interest to develop this study which is the first of its kind to develop to study adherence and intestinal failure. So we developed a cross-sectional mix method study. We included patients diagnosed with intestinal failure who are between the ages of 10 and 24 which are the WHO definitions of adolescents and young adult and who are prescribed at least one medication supplement or nutritional component. Our primary aim is simply just to quantify their medication and nutrition non-acherence. Our secondary aims are to identify disease or health related risk factors for that non-acherence and then we also want to identify their barriers so their social condition and that's what we're going to be doing with a qualitative analysis. Our first aim is measured by a self-reported non-acherence. We have to use a self-report because unfortunately there's no one biomarker, no drug assay, no route of medication or even one way that they fill their medications for us to be able to use more of a direct measure. And so we quantify non-acherence by using this measure here which is the modification of an existing instrument the medication adherence measure. So we asked them to consider an average week in their life. We refill out all of their medications and go through each one one by one and ask them how many they think they miss on average splitting between weekday and weekends. We remind them of how frequently they're supposed to be taking them as long as prompts to remind them of their schedules. By asking non-acherence our purposes to minimize our desirability bias by normalizing the fact that pretty much people are not perfectly adherent. I mean I usually start off by saying I didn't take my vitamin D today either so reminding them that you know it's normal to not take your medication every day so hopefully that'll minimize some of the bias that we introduced by talking to them about this topic. We'll then calculate a percent non-acherence based on what they were prescribed at their last visit so 0 percent non-acherent means that they are completely adherent. A little bit backwards. We repeat this process for enteral and ventral nutrition. Aim two is our evaluation risk factors from a combination of chart review and demographic survey. So we'll use the percent non-acherence calculated in the first aim to create cutoffs for our initial analysis. And for our qualitative assessment of barriers we're performing purposeful selection rather than randomize selection to identify a subset of patients in each of these groups. So we feel like each of those boxes are probably a slightly different experience and we want to get to understand each of those experiences of our patients. These patients have been invited for a compensated follow-up semi-structured telephone interview. So here's the preliminary data we have as of last night, I say I'm crunching it. So we screened 104 patients so far. We recruited 75. The mean age of the patients that we've recruited is 15.3 years old ranging from 10 to 24 so our full range of our population. We have 44 male patients and 31 female patients. The majority of the patients in our cohort are white 69.3 percent. About a third identifies Hispanic identity. 96 percent speak English at home although there's a variety of other languages represented as well. 96 percent of our patients have insurance and 74.6 percent report that all of their medications are covered by insurance and about a quarter have home nursing services. So these are the etiology that our patients have that led to their intestinal failures. So the majority that we've recruited so far have gastroschesis about a third followed by atreasia and surgical neck. Most of our patients have other comorbid conditions most commonly eosinophilic astrophagitis or chronic kidney disease. We have about a third who have a central line and a little more than half who have entral access with a G or a GJ2. When we look at our distribution of our patients by their percent entral nutritious most of the patients in our group are entraliatonomous so completely 100 percent on entral formula that's 64 percent. 18 percent are on mostly PN which we define as less than 25 percent of their entral calories are their calories coming from entral nutrition. Now the meat of it when we look at their medication regimen so we included not just what we prescribe but what they get prescribed overall to get a sense of their full regimen. The median prescribed number of medications for our patient population is six medications ranging from one medication to 11. What I found to be really interesting is when we look at their number of medication administrations in a week so how many times they have to take something the median is 56 administrations in a week ranging from seven which is just one daily medication to 155 was our highest that we've had so far. When we ask them who is primarily responsible for making sure that their patient takes their medications the majority of patients said that it's responsible adults in their life. There's a good number here who did it in a combination of the parent patient and the adult but it still seems that a lot of them are relying on their adult responsible person to help them. At what age did the patient take responsibility if they did the median age for that was 13 but ranging from eight years old to 19. When we look at our percent medication not adherence so far as you can see the graph is pretty skewed this is a histogram. Most fall between zero to 10 percent not adherent so that means almost completely adherent if you kind of flip it and the median percent adherence is 19 percent but you can see there's a broad range we have some who are almost 100 percent non adherent so it's interesting to kind of see you know where our patients fall in this and then our our second aim of looking at the risk factors will help us get a sense of why people fall into one bucket or the other. When we look at our integral and PN regimens we had about 60 percent of our patients who are on some amount of entral formula and about a third of our patients who are on PN lipid or IV fluids. When we asked who is responsible for making sure the patient takes their entral nutrition this skewed a little closer more towards the patient but still a lot of our our patients are relying on a responsible adult to help them and again they most take their responsibility around 13 years old but the range widened here to seven years old up to 20 years old at what age they start taking responsibility for their nutrition. For PN this is pretty much skewed towards the adult almost all of them have a responsible adult who takes care of their PN for them this probably due to the fact that it's you know a sterile procedure to be able to connect to your central line and it's a little more complex than you know taking formula or medication but for those who do take the responsibility themselves it usually happens around the age of 15 or 16 and we in our care clinic do that with a lot of training before people transition to the child doing it. Again the percent non-atherence for entral nutrition really skews towards the left is you can see here most being almost completely adherent I didn't even bother making a histogram for PN because almost a hundred percent of patients are adherent with their PN as that has pretty significant implications if you're not. So the next steps the qualitative interviews are still ongoing right now and then we're planning to do our survey analysis for the risk factors as well as transcribing the interviews and coding for PNs but I'd really like to thank everyone who was part of this team but also everyone who's here in this room for all of your support during these past two years it's been an incredible learning experience I you know didn't expect to gain all the knowledge that I did but I feel like I made huge strides in that and I really owe that to all of you here and I just wanted to say thank you for that. Hello everyone thank you for the opportunity to present as many of you guys know I'm the clinical research fellow for the Asophadial and Arway treatment center we'll start with a little bit about who am I well who am I I am a product of the Texas public education system yes this is how we actually view the map of the United States I was born and raised in Dallas Texas before going to the University of Texas at Austin to play football and then making my way more south to UT RGB to get my medical education before realizing I needed to get out of Texas so I went to Oregon to OHSU for my general surgery residency and then made it out here to Boston and I was super excited two years ago when doctors in that has called me to let me know that I would be the eat fellow I was really looking forward to put my taste buds to work and learn about the cuisine of Boston but little that I know that eat did not stand for eating but rather it stood for the Asophadial and Arway treatment center where we deal with pathologies of the Asophagus the Arway and the Great Vessels and it was about this time two years ago when doctors in that has told me a story and I'll represent the story as little Jimmy and little Jimmy although fictitious in name was a condition that we see not infrequently at the eat center and that had to do with vocal fold movement impairment or recurrent laryngeal nerve injury and just imagine this you do in a soft adrenal treat repair in a child and have a great anastomosis but unfortunately the child is never able to use that because they constantly aspirate due to that nerve injury resulting in vocal fold movement impairment and have a lifelong of G tube feeds so being the curious investigator that I was I took to the literature and said hmm what does the literature say about this well unfortunately the literature says that this really isn't a thing mainly because it hasn't been looked at or research no one's screening for it some say it happens as little as 0 to 1% and the cardiac literature it says maybe it happens as much as 20% but either way we wanted to take a look at this with our own population given that we were already screening this page these these patients so our first project was to do exactly that investigate the true prevalence of vocal fold movement impairment in our patients here at our eat center at that time we did a single center retrospective review from 2017 to 2021 where we looked at almost 400 patients and unsurprising to us but surprising to the rest of the country we saw that almost one in four of these patients were diagnosed with the VFMI mostly unilateral and despite classic teaching that we should be on to look out for symptoms such as dysphonia strider and hoarseness almost half of our patients did not exhibit that way mainly with signs of either asymptomatic or with micro aspirations and at resurgery put patients at a greater odds for this so at this point we've proven out that screening works and is effective because this occurs but in regards to screening how can we broaden this at that time only the flexible air and goscopy was the gold standard for screening this and I won't show the video but in case you haven't seen a flexible and goscopy in a child it's not a pretty picture and in addition to this our ORL colleagues can be burdened with doing this procedure so we set out to investigate if ultrasound could be utilized to broaden our screening paradigm so we wanted to evaluate the diagnostic accuracy of doing a laryngeal ultrasound compared to the flexible laryn goscopy to diagnose vocal fold movement impairment this time we did a prospective single center single blinded cohort study from 2021 to 2023 where we had 87 paired evaluations of this and again we had great results as our overall agreement between laryngeoscopy and ultrasound was 98.8% again proving to us that this could be utilized as a screening method but we didn't stop there we now made this protocol here at Boston Children's Hospital where we teamed up with our ORL and our radiology colleagues to make this first line for our screening for vocal fold movement impairments so now all patients undergo laryngeal ultrasound for their screening and if they need either confirmation or they have other airway of pathology that needs to be evaluated then they'll undergo their flexible laryngeoscopy so we're building out this strategy we've proved that the screening works we've now brought into our screening paradigm but let's get back to the basics how can we just prevent this from happening in the first place so we looked at intraoperative nerve monitoring something that we were routinely using in our patients and intraoperative nerve monitoring was primarily built for adults and so we had to go back to the drawing board and redefine how we geriatric this and put this together and this is a series of pictures showing us taking the adult versions of these nerve monitors cutting off strips and putting them on the smaller sized ET tubes that we utilized and neonates in infants but again this technology had not been proven out for children so we studied that we evaluated the rates of vocal fold movement impairment in those with and without intraoperative nerve monitoring and we did this in our retrospective fashion from 2018 to 2023 to go along this journey with us we'll start in 2018 when we really began routinely screening our patients represented by the blue bar graph and although we screened about half of our patients at our center we had an injury rate of 16% in 2019 we increased our screening rates along with adding selective nerve monitoring in our high-risk patients and at this time our injury increased to 24% but starting in 2020 as we then brought in nerve monitoring routinely to all our cases we saw our injury rates decline to most recently being as low as 7% in 2023 and after logistic regression nerve monitoring remained significantly associated with a reduced risk of VFMI I really think that this story starting with a singular patient and then eventually ending up being this nerve preservation package that we do now at Boston Children's Hospital is truly a testament to the work of the EAT Center and embodies the research that I've been able to do here as it embodies how we do research moreover I was able to participate in a number of other projects what from book chapters to educational projects but this slide is really to say thank you to my co-fellows as you can see I assimilated quite well to this group they were instrumental in the work that I was able to do here none of these projects would have been able to done without them I was able also to travel to a number of national international conferences this is my way of saying thank you to the department I couldn't have done this without your support both financially and mainly financially but but in addition to that I really want to take a moment to talk about some of the other projects that I was able to complete I was able to get my MPH and clinical effectiveness here thanks to being awarded the Zuckerman Fellowship which provided full tuition I was a surgical education and research fellow with the ASE where I'm building out a pilot curriculum with Dr. Scott at Southwestern and Dr. Buck Miller allowed me graciously to be on her app so well in this committee probably the least of all was meeting a medical consultant for Grayson Atomy for season 19 if you will watch this I may be in the season finale it was a fun time despite they only made me a scrubberner so with all that being said I want to take a special moment to say thank you to doctors in Dejas you can see that he still doesn't like hugs constantly pushing me away but not only have I found a great mentor but I found a great friend that I know will have many more moments together yes people would snap lovely photos of us and creeping on us but also I want to say a special thank you to my parents and my brother who are here in the crowd they've truly been my rock and people that I look up to constantly thank you to them I wouldn't be where I am without them and in case you're wondering my brother is definitely my smarter half so thank you all I'm not in college on all righty good morning everyone I'm Donna I'm the second year research fellow and the surgical innovations lab under the mentorship of Dr. Eliza Lee Dr. Ferg DeMiri and Dr. Humvee Kim thank you for the honor of sharing our work today I fixed two representative projects to highlight the breadth of the work I've done over the past two years a focus first on my innovations work with the creation of a novel patient pruning device and then transition to my clinical work in the nasic field of pediatric transplant disparities to summarize from positioning improves clinical outcomes and critically ill patients with ARDS however the practice of pruning patients is labor intensive cumbersome and dangerous for both patients and providers currently six to eight providers are needed to prone one patient which is shown in the picture on the right we conceptualize a patient prone positioning device to improve the pruning process our our proposed solution is an inexpensive inflatable device that would allow the safe and easy rotation of critically ill patients in the ICU with as few as three providers here's a schematic summarizing our initial concept key features include an inflatable wrap on a low friction sheet to allow easy rotation between the supine and prone position the wrap should be removable to allow easy patient access and be able to remain partially inflated to reduce pressure injury we made several prototypes to turn our vision into a reality our initial prototype was very simple to attach both inflatable tubes made of nylon from the neck to the feet a basic somatic is shown here on the left and here is the video of the prototype in action oh all righty well we learned a lot from our first testing session as you can see first we were successful improving our concept of a pruning device i would allow us to easily turn a patient with two to three providers it was also very easy to deflate the device in case of an emergency however because there was no set cavity inside the device the pressure exerted on the body made it difficult to get adequate venous return additionally because our legs are lighter than our torso test objects tended to float with their heads down and legs up within the device so with all this in mind we went back to the drawing board for prototype number two this time instead of one single human in each half of the device each piece has three sections that fill to create a cavity within to allow better venous return we also shortened the device to only go up to the knees so that there would be better balancing to prevent the head from going down and here's the video of this prototype in action how do you feel? if you guys it's enough so if you guys come over here and I'll go warm up just grab these pads and start lifting in hey then we're really hoping to put straps on it oh, we're going to use your fingers to get a little bit of that one two three you all right? oh yeah it's a great one we're going to use the one two three we're going to use the wow well sorry go ahead im going to keep going okay what I like as you take the top off and you take the medication for the end change i'll take the rest of the device I love that i really do overall this second prototype was also a success we found that the six chambers saw the venous return issue by creating a set cavity within the device we were also still able to inflate and deflate the device fairly easily however because the device now has six chambers which created areas of flatness it was harder to roll than the first prototype we were able to overcome this by having users pull on areas of redundancy where the fabric was welded together but users had difficulty accessing them because there were sometimes under the patient while our first two prototypes were more homegrown we decided to move forward with a contract research organization archimetic to partner with us for future development on the right is a schematic of prototype number three in this iteration several key concepts were developed and implemented first a duvet covered design made of a slippery low friction material with individual insurmable inflatable chambers second an outer layer of seven bladders per side filled to a higher pressure to create a rigid outer shell third an additional lower pressure layer of two inner bladders per side used for patient centering and cushioning and to accommodate for different size patients these would allow us to maintain a cavity within the device to ensure venous return while also allowing us to create a rigid outer shell without areas of flatness to impede rotation here's the video of our third and most recent prototype yeah yeah yeah maybe that's the question right so there's handles underneath the handle and yes we're going to have more handles I wouldn't have any more handles for this because there's 12 more to call not Dr. Demiri inside okay yeah and I'll grab the other hand wait that's it I just be prone I'm prone how do you feel that's a great wow that was so easy yeah currently we're in the process of performing and user testing at Boston Children's and at the adult hospitals across the street today we have surveyed 24 providers across disciplines we ask users to rate their experiences with promoting using existing methods shown on the top as well as with our device shown on the bottom when asked how easy it was to prone patients in terms of force required with 1 being less force and 9 being more force users felt that significantly less force was required to perform the pruning process with our device compared to existing methods when asked how safe it was to prone patients with 1 being more safe and 9 being less safe users felt that pruning with our device was significantly safer compared to existing methods the response to our device is quite positive with 100% of users feeling that the device would improve the provider pruning experience all users felt that the device would improve the patient care would use this product in a clinical setting and would recommend this product to other providers overall we were very happy with our latest prototype and encouraged by the results of our user testing we're currently in the process of filing for additional IP for our latest device prototype as well as working on a business plan and the next iteration of the device next I'm going to transition to my work in pediatric transplant disparities looking at the effect of citizenship status on access to pediatric liver and kidney transplantation transplantation is a life-saving treatment of choice for patients with end-stage liver and kidney disease however, berries transplantation includes socioeconomic status, race, and citizenship transplantation of non-US citizens remains controversial due to ethical concerns in recent years the Affordable Care Act has greatly improved general access to transplantation though adoption varies by state existing work on the Affordable Care Act's effects on have focused on results while the sex on pediatric patients have not been well characterized the aim of this study is to evaluate national trends in weightless and transplant activity and non-US citizen resident children with a focus on regional differences we obtained pediatric liver and kidney transplant data from the OPTN and SRTR as well as population rates of pediatric non-citizen residents from the US Census Bureau from 2012 to 2022 data on patient demographics, transplant activity, and citizenship status were compared between US citizens and non-citizen residents in our study we defined non-citizen residents as they're defined by the OPTN as non-citizens of the United States for which the United States is a primary place of residence without factoring whether they have documentation or authorization we first analyzed national rates of pediatric liver and kidney transplant activity from 2012 to 2022 for liver transplant on average 713 pediatric patients were added to the liver transplant weightless every year with 544 liver transplantation procedures performed annually of these non-citizen residents comprise 1.5% of both liver weightless additions shown on the left and liver transplant procedures shown on the right these trends remained stable over the study period with no significant changes in weightless or transplant activity nationwide similarly for kidney transplants on average 1,039 pediatric patients were added to the kidney transplant weightless annually with 742 transplant procedures performed of these non-citizen residents comprise 3.3% of kidney weightless additions shown on the left and 2.9% of kidney transplant procedures shown on the right again these trends remained stable over the study period with no significant changes in weightless or transplant activity nationwide after establishing that national trends of transplantation for non-citizen residents for overall unchanging in the last decade we then wanted to know if there were regional differences in transplantation across country on the map here the median annual rate of non-citizen resident transplants activity is shown for each region with red representing the lowest rates of activity for liver rates of non-citizen resident weightless additions and transplantation both differed significantly between regions and for kidney rates of non-citizen resident weightless additions in transplantation again both differed significantly between regions next we wanted to know whether or not differences in transplantation were a result of population differences to answer this question we created the comparative transplant activity rate which is the difference between a region's rate of non-citizen resident transplantation activity and the corresponding population rate of that region's non-citizen residents a negative comparative rate indicates a lower rate of transplantation activity compared to the population the underlying assumption here is that in an equitable world the transplantation rate of non-citizen residents would be equal to their representative proportionate in the population and the comparative rate would be close to zero so graphs here depict the comparative transplant activity rate for liver weightless again on the left and liver transplants on the right for liver the median comparative weightless and transplant rate 1.33 and 1.1 negative 1.33 and negative 1.34 percent the same data is depicted here in the bottom on in-heat map form with darker red indicating a higher negative rate and darker green indicating a higher positive rate differences in comparative liver weightless and transplant rates were both significant across unis regions for kidney the median comparative weightless rate on the left was 0.27 percent in the median comparative transplant rate on the right was 0.31 percent differences in comparative kidney weightless and transplant rates were also both significant across unis regions meaning that overall for both kidney and liver even when counting for population differences between regions rates of transplantation activity for non-citizen resident with significantly different between regions so to summarize national trans and transplantation activity amongst non-citizen resident children have remained stable over the last decade despite a tensed outstanding healthcare coverage there's significant variation in transplant activity between unis regions during our study period independent of population differences future work should re examine national and regional trends and compare the results to our baseline which is our study is the first of its kind to look at this in pediatric transplant patients overall our work underscores the need for targeted interventions to improve the health of all children regardless of the citizenship status of the child and their parents thank you everyone for your time and your attention and especially huge thank you to my team of colleagues and mentors without none of this would have been possible and to my husband Richard who's sitting right there so good morning and thank you for the opportunity to share my work with you in Dr. Fouselab over the last three years our lab pioneered three novel trans-amniotic fetal therapies for variety of diseases the first is called tracet or trans-amniotic stem cell therapy this involves injection of amniotic fully derived item mesenchymal or hematopoietic stem cells to treat fetal pathologies we didn't expand it to traffic or trans-amniotic fetal immunotherapy in which immunoglobulins are delivered to the fetus recently we have expanded to train it or trans-amniotic nucleic acid therapy initially attempted with mRNA as a therapeutic agent I have been fortunate to work on many projects utilizing all three trans-amniotic therapies to summarize my projects my main focus is on train it which me and Dr. Fouselab have developed when I first came to the lab and these are some projects I booked on here are my various projects with tracet in which we investigated how donor cells traffic both prenatally and postnatally we studied them in a model of IUGR and we even studied genetically modified stem cells I have also worked on multiple traffic projects and my fellowship even allowed me to expand beyond basic translational research in our lab to more clinical projects with Dr. Bakmiller or Dr. Muni as well as to be able to help my co-philos with some of their own projects in their labs I'm going to focus more on my research with mRNA for proteine replacement there are many advantages to mRNA therapies for example mRNA translation occurs in cytoplasm without insertion into the genome therefore presents with minimal lutegenesis and it uses entogenesis cells machinery with natural post translational modifications to produce final and effective final protein product our initial studies with train it using mRNA encoding for firefly ocifrase have shown that encapsulated mRNA delivered to the amniotic fluid can traffic via the amnioposityl interface to the fetal circulation besides being simply swallowed or aspirated these established an effective minimally invasive strategy of fetal mRNA delivery for proteine replacement at multiple anatomical sites I have selected few projects to be illustrative of work we have accomplished first focusing on syphacane proteins projects Boulminer syphacant is a complex lipoprotein mixture it reduces Boulminer surface tension and therefore allows for adequate gas exchange syphacane proteins play a central role in syphacane function especially syphacane protein B and syphacane protein C syphacane simply becomes ineffective in the absence of these proteins respiratory distress syndrome of pre-maternity is very common and it is known to be directly linked to syphacane deficiency including SPB and SPC leading to significant morbidity and mortality congenital mutation in a gene for syphacane proteins can also cause severe respiratory diseases in our first studies we saw to determine whether exogenous and encapsulated mRNA and coding for syphacane protein B and syphacane protein C could be incorporated and translated by the fetal length after after simple trans amniotic administration initially in a healthier at model we were also interested to see the differences in the effects of this syphacane proteins mRNA either injected in combination or as isolated injections as a strategy used to enhance syphacane production prior to birth a custom made human SPB and SPC mRNA were commercially obtained the final sequence included proprietary nucleotide sequence optimization five and cap-1 addition and three and evoldation with polyethyl to enhance mRNA stability translational efficiency and to decrease mRNA immunogenicity to minimize degradation following the liver in vivo the mRNA were encapsulated by self-assembling lipid and polymer into lipopolyplex the successful encapsulation of mRNAs by lipopolyplex particles was confirmed to be in 90s percentages by fluorescence SA rat fetuses were divided into four grooves and received either isolated human SPB mRNA isolated human SPC mRNA or combination of syphacane proteins mRNA lipopolyplexes on gestational day 17 control could be receiving lipopolyplexes only without any mRNA to control for interspersed homology of the syphacane protein was also added then a daily time point until term defeated lengths were analyzed for the presence of humans syphacane proteins by ELISA and levels of phosphatidylcholine a surrogate of overall syphacane production were measured in amniotic fluid when controlled by mRNA free injections the human syphacane protein B protein was detected in SPB mRNA group in orange only at E18 and E19 whereas in SPB plus SPC mRNA group in blue it was detected at every preterm time point as well as in all preterm fetuses combined which you can see on the graph on the right on the other hand when controlled by mRNA free injections the human SPC protein was detected in SPC mRNA group in yellow only at E18 Amniotic fluid phosphatidylcholine levels were significantly increased in SPC mRNA and SPC plus SPB mRNA groups compared to controls in the preterm period graph on the right there were variable significant differences in the amniotic fluid phosphatidylcholine levels between the groups at each time point which you can see on the graph on the left. The studies concluded that both syphacane protein B and syphacane protein C mRNA can be incorporated and translated by fetal rank following trinet and combined delivery of both syphacane protein B plus syphacane protein C mRNA can enhance syphacane production prior to term when compared with isolated mRNA deliveries therefore transamyotic mRNA delivery could become a practical novel strategy for perinatal syphacane protein replacement. We are now working on animal model of pre-maternity with decreased pulmonary syphacane levels to evaluate trinet. As expected fetal red lungs are extremely fragile and not able to withstand cannulation and functional assessment. However we had success with cannulation of E21 lungs in which syphacane levels are still not at the normal level. We can evaluate the lung with 28 gauge pre-micape however the fetal lungs can only tolerate functional assessment but obtained by obtaining only single pvl measurement. On the picture you can see my own created lung machine basically utilizing just manometer and syringe to inflate and deflate the lungs. These are representative pvlubs from the premature fetal red lungs with and without syphacane proteins mRNA delivered into amniotic fleet showing that lower pressures are needed in the lungs which receives syphacane proteins mRNA to keep the lung open at the same volume as the lung without mRNA. Although these are very preliminary experiments they show already very encouraging results. Briefly we also apply similar concept to other diseases such as hemophilia A and perinatal vaccination. Hemophilia A is genetic disease with mutation in a gene coding for pro-cogulant factor A. In cents with hemophilia A are at increased risk of intra-cranial hemorrhage and other life-threatening bleeding complications especially during birth. Following intra-amniotic delivery of encapsulated human factor A and mRNA we have shown that when controlled by mRNA-3 injections fetal serum human factor A levels were significantly higher overall in mRNA group picking at E20. The same concept was also applied to assess train-ed for active perinatal vaccination as perinatal infections remained the main cause of neonatal morbidity and mortality reading to over 500,000 deaths worldwide every year. We first analyzed the immune response to encapsulation mRNA including for human cytomegalovirus antigen. Western blood of term placenta confirmed successful mRNA translation into human searing to likeoprotein B antigen. No human CMV likeoprotein B antigen-specific IgG antibodies were detected in the serum of any term fetuses which was four days following intra-analytic mRNA immunization. However, significantly increased serum levels of antigen-specific antibodies were present in mRNA PAPS 7 and 14 days following birth when controlled by mRNA-3 injections. These are just brief examples of train-ed potential and I'm excited to see where all these and next research in Dr. Fauza continues. And I'm extremely grateful to all the people listed here to all my co-fellows, to all my interns and to entire Boston Children's Department. Thank you. Wow. I think these very brief presentations and we've had the opportunity to see you all present in some of the forms really highlight what spectacular opportunities you make for yourselves along with your mentors. I'm going to ask if any of the mentors so I want to come in. I echo Dr. Fishman and I was able to follow all follow-up for review fairly closely and I can attest to the fact that you've all left your personal signatures in your respective matters works. As to Camilla whom I met her directly, she made it look easy but these were very challenging projects which she faced with great boys and grace very consistently. Besides trace it and traffic she was actually responsible for introducing the mRNA arm to our lab. She led all but one of the mRNA projects and all the very first ones. And for that work she was recognized with awards from the International Fiddle Medicine and Surgery Society and the American College of Surgeons. And as Dr. Fishman said, she represented us very well at the multitude of meetings. So Camilla has been a joy having you. I could not be more proud or grateful. Thank you very much and thank you all. The same thing I echo, everything that's been said, you've all done a great job and we're all very proud of you and your parents and those family members here in the audience are also very proud of you. I think it's been a learn experience for all of us including me, mentoring you, Sean, has been fantastic. I think you took a topic that at first glance was not sexy and maybe boring or maybe like seem unimportant to the other multitude of complications we may have. Be really shine the light and something that means a lot to families and to parents and to patients and did something about it that is immediately tangible to improve the outcomes of these kids. So that's I think a great satisfaction for everybody that worked with you and should be for you as well. And at the same time you had fun doing it and you showed how talking about it raises awareness and we've seen a wave of interest in doing this in other centers. And so I only envision that to be the beginning of more benefit for more kids. So thank you. I wanted to congratulate all of you. I think one of the things I've noticed over the last couple of years with your cohort is just how much of a team you all are and I think that's been great to see. You've all done outstanding work. You've represented us well at all of the meetings both locally, nationally and internationally and I would just want to congratulate you all. Donna, thanks for taking the risk on the innovation fellowship. It is a risky fellowship. And I think you've done outstanding job leading our group. You certainly have a penchant for making new names and acronyms. And in fact you've changed the name of our fellowship. It's no longer a fellowship. It's a lab, a surgical innovations lab. And you spent many nights and weekends doing weird things for us. This is just a small fraction of the strange things that we did. And I'm fairly certain that your work will result in improving patient care in the future. So thank you for your hard work. I look forward to watching your career develop and keep innovating. And by the way, Donna is a epic expert. She worked there for two years. So if anyone has questions after June 1st, she's happy to help you, Dr. Lilai. Thanks. I was briefly echo what I was saying. It's been so much fun working with all of y'all. I think one of the things that I grew up on, these many of these things have been my favorite grain rounds because we've been working with you guys so much for the past several years. One of the things I love about you guys is that you've created a culture of fun with research. Seeing you guys all work together. And it's been really a joy seeing you guys present. Donna, you're an amazing leader. And I hope everyone realizes that every step of the innovation path is uncharted waters. And so it takes someone with courage as Hungbe said, but also the ability to keep a team together and to create a culture of innovation. And so Donna, thank you for doing that. I'll cap off by just saying it's been great to get to know all of you and have you be part of our team. Certainly you have enriched our education program here tremendously through your active participation in our weekly learning sessions. And I agree with what some said that your groups camaraderie and the amount of fun you bring to not just those sessions, but to all the work that you've done here for us. And what us has been tremendous and I think has been unique in what I've seen over the years. Rianca, great job of course, but I think what you're talk today highlighted for all of us and certainly for me is just you're not only bright and you're not only humble, but you are you bring a tremendous EQ to everything you do. And I think that informs and highlights the work that you do and your medication here in study, which I don't know how how much people realize how unique it is and how much work you put into developing it. And I think it just goes to show how collaborative you are, how much you rallied at everybody from the NPs and social worker in our clinic to Dr. Williams to help you learn, serve methodology completely. And to getting a grant from the SUS, it's all been tremendous. We really look forward to seeing your future career and fall in all your future successes. Congratulations. I think I'll be last. I agree with everything that you know, parameters have said that I think that you guys have been a really fun group to work with and that's been clinically. And with sort of the wonderful culture you've created with research and and collaboration and learning from each other in helping develop new projects. Donna, you're not just a mentee at this point in time, you're a friend and I'm not going to lie, I was terrified a lot of times mentoring you because I felt like a first-time parent. I really see that I was going to take you off into the woods and we weren't going to be productive or we're going to waste a lot of time and I stressed a lot about that but I appreciate you teaching me as well how to be hopefully a good mentor and setting up I think a really good and interesting research space that's going to be informative for policy moving forward and develop some new statistical like methods that really you helped drive. And that's a testament to you and your curiosity in taking a project and really just running with it and and I can't wait to you're not getting rid of me and I cannot wait to see what your your career and your progress where you go. Anybody else? I think it is self-evident that the future of pediatric surgery is very bright in the hands of you your colleagues just ahead of you those following you and we have more to hear from it's really the extraordinary it was a pleasure to watch you all grow and develop and help honestly help our programs grow and develop. You are along with our clinical trainees much of the lifeblood of our department and we're really honored to have your participation in our efforts and the care of our children and the future innovations that come that we'll see over the lifetime of your careers when we're just sitting and sharing you on. Congratulations to all of you and we are very excited to watch your careers as they develop.
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