Yeah Oh I you. That's a lot. All right. Uh, good morning, everyone, and welcome to surgical grand rounds. Uh, this morning, it's my distinct and unequivocal pleasure. To introduce, uh, two of our research fellows, uh, uh, with whom I've, uh, we've all had the chance to work over the past few years. Um, I'll introduce them both and they'll speak uh sequentially. So, Gabriel Ramos Gonzalez is a research fellow in Doctor Kim's laboratory, uh, and the Boston Children's Hospital first surgical innovation fellow. Originally from Puerto Rico, he completed a bachelor's in Science at Boston College prior to returning to Puerto Rico to complete an MD at the Ponce School of Medicine. He went on to St. Luke's Hospital also in Ponce for his general surgery residency where he's currently a PGY 2. Uh, during his time here, he's represented Boston Children's at the American Academy of Pediatrics, uh, Massachusetts chapter at the American College of Surgeons, and the American Transplant Congress. He has been awarded the best clinical project in the 6th edition of the Harvard Surgical Research Day. He'll be returning to St. Luke's Hospital in Puerto Rico to complete his final 3 years of general surgery residency. Uh, Charles Hong is a 2-year research fellow in Doctor Jacki's laboratory and has also been actively involved in the care clinic. He's originally from Hong Kong and first moved to the US to study biochemistry at Georgetown University. Subsequently, he went on to obtain his MD from Washington University in St. Louis and is in the midst of general surgery residency at NYU. Where he has completed his PGY 2 year. During his time here at Boston Children's, he has represented the Department of Surgery at the American Academy of Pediatrics and the American Pediatric Surgical Association. He was also awarded the Rosencrantz Award for Best Poster Presentation at the 2017 AAP section on surgery. He'll be returning to NYU to complete the 3 remaining years of his general surgery residency this coming academic year. Uh, on a personal note, I will just say that it's always been a pleasure to work with, uh, both of these two, residents. They're, uh, industrious without question. Uh, I've had a chance to work with them in the OR as well. Um, and so it's a real pleasure to welcome them, uh, each to the podium today. Welcome. Thank you everyone for the opportunity to discuss our work. I'll try to cover multiple projects from different genres, but I won't have time to talk about all of them. As you know, I work in Doctor Jacki's lab, and so most projects are related to intestinal failure and nutrition. So the first project I'd like to start with is a continuation of efforts from prior Jacki research fellows in extra luminal distraction enterogenesis. Since bowel length is such a key determinant in the potential for weaning off PM in pediatric intestinal failure, there's been a lot of research into bowel lengthening using mechanical force. In this paper from 2015, Spike Dolly rats underwent Ro and Y isolation of 10 centimeter segment of small intestine, and then this isolated limb was then wrapped around a shaped memory polymer, which is a sheet that's rolled into a cylinder and expands radially upon exposure to moisture and heat. As this device expands over time, you see that the bowel gets stretched, and then this was allowed to occur over a two-week period in this initial study. In this pilot feasibility study, a significant increase in the length of the stretch segment was achieved, and mucosal damage was not observed. The next steps that I then undertook was to try different rates of expansion and over different amounts of time. The thought was that a slower rate of stretch might reduce adhesions and that the 2 week time point used in a prior study may not be ideal for re-exploration in clinical practice. So our collaborator helped us devise two shaped memory polymers with different expansion rates by altering the chemical composition, and you see below there this is the fast and the slow ones, each with a different chemical composition. The graph shows that shows the percent increase in diameter over time in vitro for the fast device under full saline submersion and then also under dry conditions. And then for the slow device also under full saline submersion versus dry conditions, and these were all at 37 °C. The expected amount of expansion in the peritoneum would be somewhere in between full saline submersion and dry conditions. We plan to look at the 3 and 6 week time points for these. So here are some of the, uh, the representative route photos of the shape memory polymer in situ. You can see the, uh, the rune, isolated rune Y limb wrapped around the device, and here is a picture of the shape memory polymer close up. So we had an end of 32 sprake dolly rats split into 4 groups based on different device and different time points. There was one mortality where an animal was euthanized on post-op day one for distress and was found to have a segmental lovulus. So overall, the devices had a very high degree of variability in terms of expansion. At the 3 week time point, there was actually no difference in expansion between the fast and the slow devices, and at the 6 week time point, the fast device had expanded more. But the more important take home here were the complications we saw. So most notably, there was a significantly higher rate of device erosion at the 6 week time point regardless of which device type was implanted. And in some cases it had completely eroded intraluminally, though oddly for the most part these animals remained well appearing. And so at this point, further refinements to device are needed. And for the next steps, we are exploring the use of a softer, expandable uh material that comes in a shape of a solid cylinder and it's, and it's degradable. So we'll be working more on that with our collaborator. Uh, the next, uh, the next translational project I'd like to talk about explores the relationship between citrulline and immune function and intestinal failure. The initial idea of this project was inspired by the recent discovery of TTC-7A mutations that were responsible for hereditary multiple intestinal atresias and also acquired atresias, along with combined immunodeficiency. Patients with this rare condition. have immunodeficiency characterized by severe T cell lymphopenia with variable B and NK cell uh defects. They also have intestinal failure secondary to multiple intestinal atresias with also very abnormal intestinal mucosa uh in the remaining bowel and are then have lifelong PN dependence. I believe many of us know this patient who has this mutation and has actually done very well after receiving a bone marrow transplant followed by a multi-visceral transplant. So inspired by this link between immunodeficiency and intestinal failure, renorilain connected, uh, conducted this retrospective study of 70 infants with severe intestinal failure treated here between 2009 and 2016. So we found that 34% of these infants had a positive SKIT screen on their newborn screen, and the rates of positive screen were similar across different intestinal failure etiologies. And so a little more on the cis screen is it, it measures these T cell receptor excision circles or tracks shown here on the, in the graphic on the right. These are non-chromosomal circular DNA that are formed as an excisional byproduct of successful T cell receptor rearrangement during T-cell development. So they are markers of newly produced T cells from the thymus and are measured through PCR. Absence of trek suggests very low thymic output of T cells. And so here you see the median trek count for an examined cohort is actually less than 252, which is the cutoff for a positive screen, uh, skid screen in Massachusetts. The general newborn population median is about 1500. And so to reiterate, the positive skid screen rate in this group of 70 patients was 34%, whereas in the general population it's typically 0.3%. Of these, a third of these patients who have a positive schizocreen, half of them had a further workup with flow cytometry, and among these, there were 8 patients with severe T cell lymphopenia, just CD3 counts less than 1500 cells, and, uh, 3 of these were patients with TTC7A mutations. And this rate of severe T-cell lymphopenia is also much higher than what's expected in a NICU population. And so, in, and then, next, in the entire court, we looked at patients who had available plasma citrine levels and there were 45 of them. And just as a reminder, citrulline is a non-protein amino acid that's primarily made by enterocytes, and it is a commonly used marker uh for enterocyte mass intestinal failure and very low citrine levels can mean a worse prognosis for coming off PM. When we compared the median plasma citrillen levels that were measured while on PN between patients who had severe T-cell lymphopenia and those who didn't, the patients with severe T-cell lymphopenia had significantly lower plasma citrulline levels. And so based on these clinical observations, we hypothesize that low citrulline levels in pediatric intestinal failure may be a mechanism contributing to impaired immune function, and we have two different animal models ongoing to explore this. In the first model, we used a custom-made compound called glycolipalo, and this compound is selectively taken up into enterocytes and inhibits ornithine transcarbamalase, which is shown here, and that's the enzyme that catalyzes the conversion of ornithine to citrulline, uh, and this would therefore inhibit intestinal synthesis of citruline. This compound was actually first described in the 1980s where it was given to rats in their drinking water and it led to impaired growth and also reduction of plasma citrune levels, which he also arginine levels which were all prevented with citrullin supplementation. So we performed pilot studies of giving different concentrations of glycolipilote in drinking water to C57BL6 3-week-old male mice over 2 weeks. Unfortunately we didn't see any difference in plasma citrulline levels compared to control mice that received plain drinking water. We also didn't see any differences in food intake, water intake, or weight gain. And then when we, and then the next steps, we retested this compound and there was some degradation, unfortunately. It's since been remade and we're ready to try again. We also had a uh surgical model. We did 50% distal small bowel resection in sprag dolly rats to suppress plasma citrine levels. And here in the bottom, we do see um successful fasting plasma citrullin suppression with, uh, within the resection group both at the 6-week and 8-week time points, and there is um low variability within each group as well. And then both groups have similar weight gain per day and food and water intake per day when normalized for body weight. Uh, we didn't see any differences in thymic and spleen weights. Fortunately, the, the more exciting part with the, uh, flow cytometry to look at T cell populations has been in troubleshooting mode. Uh, moving forward, our lab will plan to continue exploring this hypothesis with both animal models. Next, I'd like to switch gears and talk about some of the clinical database projects I've been involved with, uh, namely the Vermont Oxford Network, which is a nonprofit voluntary collaboration of healthcare professionals that aims to improve, uh, neonatal care. So a big part of Vaughn's efforts in improving neonatal care are these multi-center databases that it maintains. There is a very low birth rate database from over 750 North American centers. They expanded database from over 350 North American centers captures the both VLBWA patients and also non-VLBWA infants admitted to those NICUs. And then the ELBW follow-up database consists of over 50 North American centers which do health and neurodental assessments of surviving ELBW infants at 18 to 24 months corrected age. We've had lots of research collaborations with Vaughn over the past 15 years, examining neonatal surgical outcomes, and these have all been very fruitful. So my first project aimed to examine postnatal growth in surviving ELBD infants with a history of neck compared to those without a history of neck. And so in this study, we used prospectively collected data from 46 Vaughn Centers participating in the ELBW Follow-up Center uh project uh between 2000 and 2013. And as you can see, it covers a wide variety of regions within the US, maybe a little sparse in the mountain states. And in terms of the definitions we use, the, the Vaughn definition of neck requires at least one clinical sign and one radiographic sign as listed here, and this would be consistent with at least a Bell stage 2 neck. For surgical neck, we use the definition of undergoing laparotomy or perineal drainage for neck or SIP. And then our primary outcomes of interest were presence of severe growth failure, discharge, and at follow-up with severe growth failure defined as less than 3rd percentile weight for age. So there were over 9000 infants without neck, 416 with medical neck, and 462 with surgical neck who underwent evaluation and follow-up. So we found high rates of severe growth failure at discharge, with the surgical neck population most severely affected at 61%. At follow-up of median 20 months corrected age, the rates of um severe growth failure were similar between all three groups, but still about 25% of all EWW infants had severe growth failure regardless of neck status. On multivariate analysis, predictors of severe growth failure followed included small for gestational age at birth, chronic lung disease, severe IVH or cystic PVL, severe growth failure discharge, and tube feeding after discharge. Next status and assessed caregiver socioeconomic characteristics were not predictive. So based on these data, we concluded that ELBW infants with a history of neck are at higher risk for severe growth failure at discharge, particularly those with surgical neck. While we do see signs of catch-up growth among infants with a history of neck, a significant portion of infants still have severe growth failure at follow-up. And even in light of catch-up growth, the potential long-term consequences of acute malnutrition during infancy cannot be overlooked, since this has been shown in literature to be associated with negative neurodevelopmental outcomes later in life. And lastly, the presence of these predictors for severe growth failure at 18 to 24 months corrected age, uh, may warrant support strategies that are tailored to these infants' unique nutritional needs. The next Vaughan project was conceived in response to recent studies that have had conflicting findings on the relationship between surgical volume and outcomes in gastroschisis. So we thought, we sought to further examine the impact of disease-specific surgical volume in early hospital trans and outcomes in gastroschisis. We use data collected prospectively on over 4600 infants with gastroschisis born in 2009 to 2015 and were treated at 159 Vaughn expanded database uh US centers that all had neonatal surgical capabilities. The centers were divided into tersciles based on the number of gastroschisis re uh repairs performed per year, and the breakdown is as shown. Uh, at the low volume centers, they performed a medium of 1 gastroschisis repair per year. The medium volume centers, it was 4 per year, and at high volume centers, it was 9 per year. Infants born less than 1500 g or transferred after gastroschisis repair were excluded. So we saw differences in both patient characteristics and management based on center volume and transfer status. Infants treated at high volume centers were more likely to have intestinal trasia or be outborn, and, and they were less likely to be born via C-section. This suggests that the high volume centers may see sicker infants and have different delivery practices. One quarter of the cohort was outborn, and these infants had lower rates of C-section and higher rates of surgical feeding tube placement, the latter, which also suggests that these transfer infants may be sicker or they have greater exposure to caregivers or centers that place more surgical feeding tubes. Importantly, high volume center status was not associated with differences in mortality, sepsis, or length of stay on multivariate analysis. Outborn status was independently associated with longer length of stay, but not mortality or sepsis. Not surprisingly, other variables in the multivariate model such as prematurity, atresia, other congenital anomalies, and bowel resection have more of an impact on outcomes. So from the study, we concluded that routine delivery acts or transfers to high volume centers for gastroschisis may not be warranted. However, given the equivalent outcomes with seemingly sicker patients at higher volume centers, further research into patient characteristics that might predict benefit from care at higher volume centers is needed. While staying on the topic of gastroschisis, I'd like to move on to some uh clinical retrospective reviews. Uh, we conceived this study based on the finding from another Vaug project, which found that gastroschisis babies, when they're born, about 1/3 of them are small for gestational age, but by discharge, over 50% of them are less than 10th percentile weight for age. So we wanted to look at our own data and we sought to describe nutrition delivery and growth in infants with gastroschisis, and I try to identify factors associated with poor growth. So this is a single center retrospective review of neonates admitted to our NICU within one week of life and underwent gastroschisis closure here between 2010 and 2015. Our primary outcomes were weight for HC scores at discharge and one year corrected age using the fentan and WHO growth curves, and also to look at time to enter autonomy. We identified 60 patients and looking at the entire cohort from birth to discharge, you see there is a big range of weight for HD scores, but there is a significant drop in weight for HD scores from birth to discharge. There were 34 patients who had uh growth data up to one year, and those who had follow-up were more likely to be male, and they were more likely to be sicker with higher rates of bowel resection, neck, longer length of stay, and greater pee independence. But their birth and discharge weight Z scores are actually similar to the infants who did not have fallout. So looking at just these 34, uh, up to one year, you see there is a decrease in weight for HD score from birth to discharge just like the whole cohort. And then there was a significant increase in weight for H Z score from discharge to one year, such that there was no difference between birth and one year. We then did a multivariate analysis to look at variables independently associated with lower discharge rate for AZ and, and also a greater decrease in weight for HZ score from birth to discharge. The, these, the independent predictors for lower discharge weight for HZ were prematurity, lower birth weight for HZ, collabsy, and longer ICU stay. Uh, whereas the independent predictors for a greater decrease in weight for HZ score from birth to discharge were prematurity, CLBsy, and higher birth weight for HZ. Of note, the time to enteral feeding and initiation, the pent dependence uh days and also whether they were on two feeds or discharge were not associated with uh either of these uh outcomes of interest. So even though these, uh, the nutritional factors I just mentioned, um, did not pan out in predicting weight for HD score, we're still interested in further examining uh PN dependence since that is related to clumsy risk, cholestasis, intestinal failure, and uh overall length of stay as well. So this graph plots the percentage of our cohort still on parental nutrition over time up to one year. And you can see our median time to enter uh enter autonomy is 36 days, which we'll see is actually a little on the higher side, and we had 14 patients or nearly a quarter who are on PN for 90 days or greater, which is the criteria we use here for severe intestinal failure. Here I've, uh, compared data from our institution to what I was able to extract from a fi study that involved 37 PS hospitals spanning 2005 to 2013. What's notable is we do, we do have a, a much longer PN days and length of stay compared to the physical cohort. And one might be, one might be tempted to say that the patients we see are sicker at baseline, but, uh, based on the data I could uh extract from that paper, um, that, that doesn't seem to be the case. So we did a multivariate Koch regression analysis to try to identify the factors independently associated with prolonged PN dependence. And here we found that prematurity, stage repair, any atresia, and clamsy were all independently associated with longer time to enter autonomy, while interestingly time to initiation was not. Other studies have reported that earlier time to initiation of EM is associate associated with shorter PNA, but I think most likely the short um being able to start into nutrition early may be a marker for milder disease severity. So from these data, we can conclude that poor growth is common among neonatal hospitalization for gastroschisis infants. And prematurity and lapsy are the strongest predictors for poor weight growth. So lapsy prevention is a very important target for reducing growth morbidity. Uh, unfortunately, optimal nutritional management strategies are still unclear at this time. We do see that stage closure associated with longer PN duration, though there are likely confounders that we haven't been able to control for. And then importantly, we've also identified potential room for improvement as seen in our longer PN days and length of stay. Shifting back to reviewing our data specific to care patients, uh, many of you may have noticed that in the past 2 years, we've been performing a lot more fiber scans to look at liver fibrosis in our patients. And here we have set out to the diagnostic utility of using, uh, vibration control transient elastography, which is a term that more accurately describes what fibroscan is. Some background on VCTE in terms of how it's done. In very brief terms, it measures tissue stiffness. So here you, you see a probe that contains both an ultrasound transducer and also a mechanical vibrating device. The operator places a probe in between ribs so as to get a clear window into the liver, uh, in the right upper quadrant, and then uses a mode ultrasound to locate a part of the liver that's about 3 to 6 centimeters below the skin surface and free of large vascular structures. So once they've selected the imaging area, the mechanical vibrating device, uh, sends a kind of a vibrating punch, uh, on the body surface to generate shear waves, and the shear waves propagate through the tissue. The same probe can then measure the speed of the shear waves, which can be converted to a liver stiffness measurement that's reported in Kilopascals. This is not a painful procedure at all, and it can be done relatively quickly. And then once we have a uh liver stiffness measurement, there are these nomograms that are used in interpreting, uh, in assigning a corresponding meta fibrosis score. Um, and as you can see, there are different nomograms for different liver pathologies. There really has not been one validated for pediatric intestinal failure associated with liver disease, and typically the one for chronic cholestatic diseases is used. So we did a single center retrospective review. Thus far, 70 patients have undergone 75 fibro scans. Most have only had one, but since the non-invasive nature of the study provides an an advantage over a liver biopsy, the goal is to perform these serially. As you can see, we have been able to assess patients with a wide variety of underlying causes for intestinal failure, and the majority of these patients are still Pin dependent. So we, we wanted to compare FibroScan to what's considered gold standard, which is liver biopsy. So we focused on 16 patients who had a liver biopsy obtained within 1 year of FibroScan and a median of 0.6 months in between. These patients tended to be younger and were more likely and were less likely to be Caucasian compared to the less of the cohort. So on the X axis is uh the, for the metavi fibrosis scores. F0 means no fibrosis and F4 is cirrhosis. We set out to see how well liver stiffness measurements can differentiate mild fibrosis or F0 and F1, from moderate to severe fibrosis or F0 to F4. You can see there is a wide range of KPAs for the F2 to F4 group, but you do see there's good separation between the two. We performed a receiver operating characteristic curve analysis, plotting the uh true positive rate as a function of the false positive rate to help identify an optimal cut point to differentiate between mild and uh versus moderate to severe fibrosis. So we, we found that a liver stiffness measurement of at least 6 KPA uh provided an area under the ROC curve of 0.883, which is quite good, uh, with a sensitivity of 80% and specificity of 100%. So based on our early experience with fibro scan and pediatric intestinal failure, we see that liver stiffness measurement as determined by BCTE can distinguish mild from moderate to severe liver fibrosis, uh, as determined by liver biopsy. So this will allow serial non-invasive monitoring of liver injury in pediatric intestinal failure patients. While we were discussing uh this non-invasive assessment in pediatric, I felt, I just wanted to briefly mention a clinical prospective study that's been in a holding pattern, awaiting administrative approval for some time. So several generations ago in Dr. Jackik's lab, it was shown using an IV-13C methionine breath test, uh, that it's feasible in the pediatric IL population and as a measure of hepatic mitochondrial methionine metabolism, the results did correlate with the established methods of assessment used in. Intestinal failure associated liver disease. This graphic just summarizes how breath testing works. In stable isotope breath testing, we're trying to assess a metabolic pathway. So known quantity of a substrate labeled with 13C is administered, and this is a non-radioactive isotope. And when the metabolism of that substrate leads to CO2 production and the appropriate carbon atom is labeled as 13C, the exhalation of labeled CO2 reflects metabolism of the substrate. And so the breast samples can be collected over time after giving a substrate, and the 13C enrichment at each time point can be measured. And so this method actually directly measures metabolic capacity. And currently we have the 13 semethanine compounds stored and ready to be prepared at a compounding pharmacy, and we also have the breath analyzer. More importantly, we have received the necessary approvals from the Massachusetts Department of Public Health and Pharmacy Board, so we are getting closer and closer to enrolling patients. The last project I'd like to present are the long-term outcomes of patients seen in care clinic with ultra-short bowel syndrome due to mid-gutlobulus. This paper by Doctor Javit is very timely. They surveyed over 300 pediatric surgeons via ABSA and 288 neonatologists via AAP and uh asked them about the recommendations regarding comfort care and clinical scenarios of newborns with massive bowel loss. So in the scenario of a full-term infant with mid-gut ovules leading to minimal residual bowel. Um, 54% of providers would consider comfort care, 6, 62% of, uh, among neonatologists, and 47% among pediatric surgeons. So these survey results suggest that there is a lack of long-term data on these infants with massive bowel loss. So the aim of our study was to describe the long-term outcomes of pediatric onset ultra-short bowel syndrome due to mid-gutlobulus from our care clinic. So this is a single-center retrospective review of patients seen in care clinic um between 2010 to 2017. We included patients who had midgutlovulus with documented malrotation, less than 20% residual small bowel length for a post-conception age, and at least 90 days of PN dependence. We identified 23 patients with median onset of mid gut volumes at one day of life. We do have quite long-term data of them with um median of 8.5 years follow-up since onset, and they had a median of 9% of expected residual bowel length. Over a third of them also had gastroschisis, and as expected, most of them do not have a uh ileocecal valve or a full colon. Looking at the outcomes, there were 2 deaths in the study period, 1 while awaiting transplant and another 4 years after intestinal transplant. 5 patients underwent intestinal or multivisceral transplant and all had achieved enteral autonomy. There were 7 patients who came off PM without transplantation. And as a group, you see they have high rates of intestinal failure associated liver disease, clamsy, and a bacterial overgrowth. Specifically, 30% of them had a history of d lactic acidosis. In with the last few data points here, I wanted to try to get a sense of quality of life, which is very difficult with a retrospective study. And you can see with a median age of close to 9 years at last follow-up, over 2/3 still had a a surgical feeding tube in place. They had median 3 bowel movements per day, and then practically all school-age children were in school. Unfortunately, uh I was not able to get more detailed information in terms of neurodevelopmental status. So we honed in on a group of 18 patients who did not undergo transplant, and this is our Kaplan-Meier analysis demonstrating the achievement of enter autonomy over time among these 18 patients. When we compared the, um, when we looked at the 7 patients who came off PM without transplant, they did so after a meeting of 2 years, um, after being on PN. But from this curve, you see that there are still patients coming off PN up to 5 years afterwards. And when we compared those uh still on PM to those who came off PM within this group, the major difference was that none of the patients with gastroschisis came off PM. So in light of the survey results, uh, regarding redirection of care to comfort measures, we hope to get this data out there, um, and it will be presented in caps and coming up soon. We believe that mid-gut volvulus due to malrotation with extensive bowel loss is associated with favorable long-term survival, and that weaning from PN may be feasible even without transplantation, uh, especially in the absence of gastroschisis. And future directions for research should focus more on the quality of life and neurodevelopmental outcomes. Uh, with that, I'd just like to thank, um, all the, all my mentors and everyone who's made this a really excellent, uh, and, uh, productive research years. And I'd like to also thank, uh, our collaborators from Veron Oxford Network, the, the care clinic, and then all, all, all of my co-fellows. And also it's uh thank you to everyone that I have worked with on call who has made it a very educational and positive experience. And without all of your mentorship and guidance, uh, this would not have been as enjoyable or as productive two years. So, thank you. Uh I think uh if there are any, uh, we have time maybe for one question now and then we can, if we have time at the end, we can do some more. Any questions from the audience? Charles, thanks you for a great talk, obviously great work and it's uh impressive what a wide range of, uh, projects you've undertaken. OK, seeing none at this point. Gabriel, why don't you go ahead and then, uh, if we have some time, we'll call you back for some questions at the end. Good morning. Thank you for the opportunity to present our work in the 1st 2 years of Boston Children's Surgical Innovation Fellowship. Originally coined the Kindergarten Fellowship, the SIFF was an idea by Doctor Kim and Doctor Fishman that intended to use the inquisitive attitude of medical students and young residents to identify unmet clinical needs. In order to accomplish this goal, various departments across Boston Children's were recruited to guide fellows through the different phases of innovation. Available resources within the Harvard System and the greater Boston Innovation ecosystem were harnessed to establish a formal curriculum in innovation education. This resulted in a unique program that offers a platform for surgical residents interested in pediatric surgery to engage in innovation. While I was personally drawn to medical device development, there are opportunities to participate in digital health innovation, surgical innovation, and quality improvements. One of the things that separates Boston Children's Program to other innovation fellowships is the is the commitment to provide the fellow with clinical research experience. This gives so the opportunity to collaborate in clinical research with various clinicians and surgeons, while also helping them to enrich their curriculum for the application process. Although we aspire to establish licensing agreements and spin off startup companies, the true mission of the Surgical Innovation Fellowship is to create future surgical innovators and entrepreneurs within a collaborative environment that combines unique clinical experiences with state of the art training across digital and device platforms. In order to achieve this, we created a curriculum that exposes naive innovators like myself to all the phases of innovation and provides the necessary theory and concepts to take a project from the need to a commercial solution. The boot camp allows the fellows to start off with uh with predetermined product and get a fast-paced glimpse of the innovation process. This is followed by 6 to 8 weeks of need finding, which really goes to the essence of what the kindergarten fellowship is about. This, this followed by vetting, development, and ultimately, the bulk of the time is spent on prototyping. Internal and external courses and resources have been identified and curated to complement each of the phases of the CIF curriculum. Having access to institutes like the Harvard Catalyst and the BVIC certainly allows the fellows to acquire a wealth of information and establish a great network of innovators around the Boston ecosystem. Throughout these past two years, I've attended a wide variety of courses. The list here is just The ones that I found most useful useful. My first months at Children's were spent identifying clinical needs throughout the hospital. Here's a list of needs that we identified throughout that time and we kept adding on for the two years of my fellowship. Each of these projects was analyzed with regards to three basic innovation components, clinical need, technical feasibility, and business viability. In our first, our first project in collaboration with the innovation and digital health accelerator was a wayfinding app for the hospital. After getting lost in these halls for the first couple of weeks, it was evident that there had to be an easier way to navigate around this place. So at the height of the Pokemon Go rage, we seek to create an interactive digital platform that will help guide our patients from their car to their appointments. Unfortunately, after reaching out to several vendors for indoor navigation systems, we found out that the marketing department had already started looking into this. Despite, despite identifying a, a clinical need, this need was already being addressed by another player in the enterprise, so we decided to drop this project. Next, we turn our attention to a product we named True Fit. This project aimed at improving the assessment of whether a donor organ would fit into a recipient's cavity. By doing so, we can minimize the waste of resources from trips in which the assessment was done interpretatively. Our solution was that by creating a 3D representation of the donor's organ and the recipient's cavity, we could better assess this or the organ's fit. As it happens, there are 2 companies that are dedicated to creating 3D representation of patient scans for education and surgical planning purposes. Their technology could be harnessed to superimpose a 3D model of the donor organ in the abdominal cavity of the patient or compare its volume to that of the recipient's organ. However, the waiting time for 3D representations is over 5 days, which clearly is not applicable for transplant purposes. In light of this, a new service of 24/7 availability and rapid delivery would have to be created. Given that our problem was determining whether or not a donor organ would fit in a certain cavity, our technology would mostly be applicable to lung transplants and very young pediatric liver transplants. Early analysis of the UNOS data showed a little over 2000 lung transplants are performed every year. And as this graph shows, less than 400 liver transplants are performed in children under 5 years of age, with approximately 100 of those being split livers. We decided to abandon this project as it did not represent a viable business opportunity, given its limited market and high cost of providing service. With True Seal, we aim at solving gastrostomy tube complications. Due to complications are a common sight for all surgeons, especially among our very young patients. Dislodgements, infections, and leakage are common causes of revisits and re-interventions. Our proposed solution consisted of applying a proprietary dental implant microsurfacing technology, which has been shown to increase the binding of soft tissue to either the shaft of the G tube or a separate rocor type device through which the G tube could be inserted and or exchanged. To test this solution, we placed custom designed, customly designed titanium G tubes that were treated with a special microsurfacing into spray dolly rats. After 2 weeks, the rats were euthanized, and the G tubes were removed and blocked along with the stomach and abdominal wall. Unfortunately, this technology has not proven to increase the teacher adherence to the device and has failed to establish a reliable seal around the gastrostomy. With more than 400,000 license of adhesions operations performed in the US per year, and an estimated annual cost of $3.45 billion. Our next projects focused on trying to reduce post-operative adhesions. Many authors have tackled this problem in various ways. Lindt has been one factor associated to increased inflammation. Secondary to foreign body reaction. As this might result in an increased formation of intraabdominal adhesions, we hypothesize that by replacing cotton sponges in the OR might reduce to, might reduce this complication. The ponic vinyl alcohol or PVH rags that we use to drive cars and for all around the household quickly popped into our minds. PVA is a non-lething, biocompatible, and hydrophilic material. Sponges made out of PVA consist of a network of open pores that make them extremely absorbent. We use a mice model to test our hypothesis that PVA sponges would result in a decrease in the abdominal adhesions. A total of 3067 BL6 mice were assigned to either a control group that was irrigated with saline, cotton sponge group that had moist sponges placed in their abdomen, with a new sponge placed every 5 minutes for 15 minutes, or PVA's group that had a PVA sponge placed in the abdomen, which was irrigated and replaced every 5 minutes for 15 minutes. 2 weeks later, the mice were euthanized, and 2 blinded observers graded the adhesions. The Bigatti scale was used to assess tenacity, type, and extent of intraabdominal adhesions. Our results show that with regards to adhesion tenacity, there was a significant difference between control and cotton. However, there was no statistically significant difference between cotton and PVA or between cotton and PVA. This pattern was also true for the adhesion type and adhesion extent. Total adhesion scores showed that cotton sponges and PVA sponges were significantly associated to adhesions compared to control group, yet no significant difference was observed among the experimental groups. As cotton sponges and PVA sponges seem to be similarly associated to adhesions, the next question would be if there will be a financial incentive from replacing cotton sponges. This does not seem to be the case either, as a single 3x3 PVA sponge costs approximately 5 times as much as cotton. The marginal cost and wide availability of cotton certainly makes them appealing. However, we must also be cognizant of the large amount of cotton sponges that are wasted in each case. Could reusable PVA sponges represent a solution to minimize OR waste and improve OR workflow? This remains to be seen. One observation that we made in our experiment was that mirrors cell sponges, which hadn't, which are intended as instrument wipes, seems to cause high degree of bowel desiccation. These sponges might be too absorbent, and further experiments are required with less absorbent PVA sponges. The last project that we'll talk about today is the quick trigger, a combined cautery suction device. All of you here are used to operating in tight confined spaces that are constantly crowded with retractors, dissectors, cautery, and suction. And all have been annoyed and frustrated by the constant exchange between cautery and suction in the surgical field. In one of my first experiences looking for inefficiency in the OR with Doctor Kim, I noticed his homemade cari suction device that he had put together to address this problem. As you can see in this video, although this device seemed to satisfy an unmet need, it clearly requires much optimization to turn it into a commercial solution. The main hassle of, of this homemade solution, it's purely its static suction tip. We set out to create a single-use combined cautery and fluid suction device with a retractable suction tip. However, this solution needed to meet certain requirements in order to be a viable replacement for the current solution. It had to preserve as much as possible the outline of the current boy pen, as surgeons will be less likely to adopt it if it, it did not feel similar. It had to be inexpensive, for which it had to rely on the equipment already available in the OR. It required a robust deployment mechanism that could be triggered hundreds of times within a surgery, and a robust locking mechanism for the suction tip. Finally, the suction tip, when deployed, had to lock in place in such a way that it can be used for blunt dissection. When deciding how to power the retractable suction means, we looked into many possibilities available to us. However, we knew that the ideal choice was a mechanism that was cheap and used technology already present in the OR. This is why we chose suction as our power source. Here you have the very first proof of concept that we could use suction within a chamber to cause the translation of a piston. From there, we continued iterating with multiple prototypes in which we use a variety of mechanisms to alternate suction force between the front and the rear of a chamber that house a piston which deployed and retrieved the suction tip. By prototype 3, we felt fairly comfortable that our design was good enough to start gathering user experience feedback from surgeons and residents. One question that we were interested in answering was what will be the best type of interface for the user to activate the mechanism. We had never reached a consensus within our team as to whether a longer pads style trigger would be preferable to a precise button. However, your feedback made this very clear to our team. Another question that we asked centered on the location of the trigger button. At the moment, all of our iterations, the trigger button was on the right-hand side of the device. This posed a problem for those of you who are thumb users of the cautery pen, as the trigger button would be on the bottom, bottom part of the device. Feedback made it very evident that most users would prefer a trigger on both sides of the device, as they're constantly changing from thumb to index users of the cautery pen. Using this design it was impossible to actuate the system from both sides of the device. Thus, we went back to the drawing board. At this time, one of the things that popped into our radar was the COIDian force driver's cautery pen. Interestingly, this device had a 3rd button in between the COAG and cut buttons. Having a trigger button in a similar position will solve our problems as users will be able to actuate the suction tip regardless of whether they're thumb users or index users. This led to our 4th and most recent iteration. In this design, we created a vacuum channel that extended longitudinally from the connection to the wall suction at the back end of the device to a couple of vents in the front end. When a button is pressed in between the coag and the cut cut buttons, the vacuum channel is occluded, and all the vacuum power is delivered and diverted to the front end of the piston chamber, causing the suction tip to deploy into the field. We finally had a device that was similar in size, easy to use, adequate for thumb and index finger users alike, with a reliable deployment mechanism and a robust locking mechanism. And in light of this, we want to get more feedback. This time, we walked, we knocked on the door of of Doctor Dolnito, the chair of cardiac surgery and then successful innovator himself. His words were both motivating and a reality check to our team. He was adamant that we had taken this project as far as we could and it was time to get professional help. Thanks to Doctor Delnido, we recently partnered with SmithWise, a medical device development company. Smithwise immediately started looking into new ways to optimize the actuation mechanism, but also focused on creating a better industrial design for our device. Here, you could see some of their proposed models. We recently decided on the model here. Which includes a step up from the shaft of the device to host the cautery tip and allow the suction to deploy in parallel. Another change that we've made is have implemented into this design is moving the suction tip and the suction trigger button from the, from in between the cut and coag buttons to behind the coag button. We believe that this movement will feel more natural and lead to less finger fatigue from the user. This device is not clearly intended for sur open surgeries with moderate to high bleeding or those in which a pristine surgical field is necessary. It is true that not all, all of you will consider this device necessary for the surgeries you perform. However, there are certain areas in which we truly believe this device will offer an advantage to the surgeons. There are many smoke evacuators in the market from all major vendors, but to our knowledge, there is only one product marketed for smoke and fluid evacuation. The Remora by A&T is an add-on product to the existing cautery pen which offers a static suction. The remora does have some benefits, yet the static position of the suction complicates its use for fluid suctioning. We believe that our device offers a unique opportunity of using the suction tip as a blunt dissector, given that it extends past the cautery tip and protects the tissue from it. Also, it provides a degree of freedom in the OR as personal, uh, for the OR personnel as the assistants may perform other tasks rather than be managing the suction. This quality may prove very beneficial in the inner workings of the OR, especially in smaller hospital. And in and in ambulatory centers where OR personnel might be an issue. Even though our product mostly resembles smoke evaporators out there, we know that in order for it, for it to create a successful product, we have to compete against the traditional Bobi. Thus, we must be able to provide a product with all the aforementioned capabilities at a cost that approximates the $5 per unit rather than the $35 per unit. That it is easier said than done. Here is the timeline for the development of our device going forward. At the time, we're currently collaborating with MethW in the prototyping design phase, and we've recently filed for a provisional patent application. This is the team that made it all possible. This project has been a learning experience and a journey into the world of medical device development. Personally, it has been a blessing to share the journey with great innovative minds like Doctor Kims and Alex Yang, a bright young engineer who recently graduated from Harvard. If there's one thing that I've learned in the past 2 years, is that innovation is based on one thing, teamwork. I want to thank the great team of mentors that have put their time aside for, from their busy lives to create the CIF and give fellows like me the tools and the platforms to think differently and navigate the innovation pipeline. Without their compromise, these last two years at Children's would not have been possible. Especially, I would like to thank Doctor Kim, who took the chance on bringing me to Children's to start this program, who's worked tirelessly to see it come to fruition, and who throughout the past 2 years have always been supportive and optimistic about our work. I would also like to thank the Department of Surgery, Doctor Chamberger for giving my Flos and I the opportunity to come to a prestigious institution to follow our dreams. Doctor Fauza for his continuous commitment on research program and his multiple advice during the past two years. To all the attendings, For all the feedback that you've given our team about our ideas, and for all the many lessons learned along the way. Special thanks to the Billi and Jackson Lab, whose PIs have allowed me to collaborate on clinical projects with them and their fellows who's always been present whenever I needed help on my projects. Last but not least, I would like to thank Sean and Alec who were part of the clinical projects, and to my good friend and here Alex Yang, who took the chance to join. Join us in the Quick Trigger team and he's, and has been an invaluable asset to our group. We couldn't have done it without him. Thank you all. Are there any questions for Cabra? So we um We have to change the format this year since the change party occurs in now in July because of our tardy departure of our fellows. Um, and the research fellows are having to go back at the end of June for their, for their, uh, resumption of their, their residencies. So we've decided that the best time to make the presentations and give them their diplomas will be after they do their successful presentations, which both of you did today. At, at Grand Realm. So I'd like each of the uh mentors to say a few words about their uh mentees and then uh give them their words. So we'll start with Doctor Jackik for Charles. Uh, first of all, uh, uh, it's great to see, uh, all these people in the audience. Uh, uh, Charles, I really want to personally thank you for a truly wonderful job. Uh, I think your, uh, uh, intellect and diligence are clearly demonstrated by your productivity. Uh, however, perhaps what doesn't show is that you have a wonderful sense of humor and you have true intellectual honesty, and, uh, those are the things that, uh, I value most about you. So, uh, thank you very much, Charles, and, uh, it's a true pleasure to, uh, give you, uh, uh, uh, your, uh, book and, uh, certificate, which undoubtedly will be one of your most valued possessions. Doctor Kim Uh, let's start off by, um, congratulating both of you guys. Great, great talks today. Um, and I've worked, uh, with both of them, uh, clinically, uh, during organ procurements, um, and I wanna thank all the residents who, who helped us on those, uh, busy days and nights. Um, I know that, uh, uh, Cash and I are very, very, very thankful that you guys are around. Um, it's kind of lonely out there in the middle of the night. Um, Gabriel, I wanna thank you, um, For taking a chance on this fellowship. It's really, it's been an adventure and um you clearly showed uh one of the aspects of innovation, which is that there's way more failures than successes, um, and you really need to keep pushing through and um if an idea is um clearly not gonna work out, you got to move on. And um um I was very happy that you joined us and I think Uh, you have the right, uh, type of attitude to do this kind of work. I think it's not for everybody, and, um, uh, you've done an amazing job, uh, gotten through, um, uh, uh, to a provisional patent, which is, uh, pretty impressive, and, um, uh, uh, I think you've actually, uh, taught me way more than I've taught you. Um, so, um, clearly, uh, Uh, setting up, you know, uh, it didn't really show in this talk, but I didn't set up any of this stuff. Gabriel set it up all himself, and, um, he's, uh, uh, basically writing the book and the pathway for fellows to follow. So, um, I, I did none of that work. Uh, it was all him. Um, and, uh, lastly, I just want to thank Alex, um, who's gonna be an HMS student, um, in the fall, um, who, um, they just met over lunch one day at the Innovation Center and start talking about this, um, and it's turned into, uh, a great collaboration. So, I look forward to working with both of you in the future. Um, uh, good luck, Alex in med school. Hopefully, you'll spend some time here with us, um, and, um, good luck, Gabriel, uh, finishing your residency. Um, hopefully there's electricity back home when you get there, um, but, uh, I really appreciate your work. So thanks. So I think we can all give a final round of applause to Charles and uh Gabriel for their wonderful presentations this morning and their work for the last couple of years.
Click "Show Transcript" to view the full transcription (53934 characters)
Comments