started. So our first speaker today is a Simucumilade graduate of UC Berkeley who went onto the University of Michigan where she would obtain her medical degree as well as a master's degree in clinical research from the Michigan School of Public Health. Prior to starting her time with us, she would begin her residency in general surgery at the Brigham and Winds Hospital. She's a recipient of multiple grant's day back to 2012 including a current NIHF 32 Research Award. And her public education history is equally impressive and honestly reads like an early career attending rather than a trainee. Today she'll be talking with us about her work under PI Dr. Sean Ringell and the ACS and his quick pediatric antimicrobials due to regiaf collaborative. Please join me in welcoming Dr. Catherine Hay. Thank you for the introduction. As you'll know, I'm one of the general surgery residents from Brigham and Winds Hospital in a research fellow in Dr. Ringell's lab. This is a snapshot of my time in the Health Services Research Fellowship. I've been very fortunate to work on a variety of topics spanning antimicrobial prophylaxis, umbilical hernias, acutopenocytas and quality improvement. Due to the tiny limitations today, I like to focus on a few topics that have emerged out of the ACS NISQIP antimicrobial stewardship collaborative. While antimicrobial prophylaxis is necessary to mitigate SSI risk, overuse of prophylaxis is associated with antimicrobial resistance and adverse events such as antimicrobial associate colitis and acute kidney injury. With these considerations, we identified three projects that we consider to be high priorities within pediatric surgery. The first two projects aim to identify areas where improvements in prophylaxis are most needed. This includes both for antimicrobial stewardship and for SSI prevention. The last project represents the first multi-center study within general pediatric surgery demonstrating lack of benefit of post-operative prophylaxis, which we consider to be the highest priority in antimicrobial stewardship. To answer these questions, we use the ACS NISQIP pediatric, which is a comparative quality data platform with data from 160 hospitals. SSI events are collected via standardized definitions and a robust chart review process. RISCA-justed Bencharring Performance Reports are distributed semi-annually to all hospitals. The data from these projects are generated from 92 hospitals who collected supplemental antibiotic prophylaxis data as part of the antimicrobial stewardship collaborative. This collaborative was established with the intensive establishing utilization benchmarks and evidence-based guidelines for antibiotic prophylaxis. Prophylaxis data included number and type of agents, timing relative to incision, and duration for elective procedures. Prophylaxis were further grouped based on organ system involved. The pediatric health information system or FIS database was used to calculate relative procedure volume. The FIS is an administrative database that uses data from 49 U.S. children's hospitals. Use of a data set other than the NISQIP pediatric to calculate procedure volume was necessary, given that NISQIP pediatric represents a sample rather than comprehensive assessment of each hospital's case load. Subjected by our first study was to evaluate rates of SSI and the relative contribution of different procedures to the overall SSI burden to determine a prioritization framework for SSI prevention. SSI rates were obtained from the NISQIP pediatric database. SSI burden was then established by multiplying the NISQIP derived SSI rates by the case volume data from FIS. Procedures were then ranked. Over 11,000 patients were included for estimation of rates and over 83,000 patients for estimation of procedure volume. Guest Rossini was the most commonly performed procedure called the small bowel and colorectal procedures. These figures illustrate rates in burden associated with SSI, with rates on the Y axis and burden on the X axis. The bubble size represents the relative case volume. The overall rate of SSI was 2.8%. EATS repair and small bowel procedures had the greatest rates and the highest burden was associated with small bowel and Guest Rossini procedures. These next slides break up SSI into incisional and organ space SSI. The overall rate of incisional SSI was 2.3%. The highest rates were associated with Guest Rossini closure and small bowel procedures and the highest burden with Guest Rossini and small bowel procedures. The overall rate of organ space SSI was 0.5%. The highest rates were attributable to EATS repair and colorectal procedures and the highest burden was small bowel and colorectal procedures. In conclusion, the majority of SSI burden can be attributable to a small handful of procedures. These procedures should be considered high priorities for SSI prevention. The next project we performed was aimed to identify the rates and burden associated with under and over-utilization to identify areas for antimicrobial stewardship and SSI prevention. We define over-utilization as continuation of antibiotics for gradients 24 hours postoperatively using clean procedures without implants and use of overly broad spectrum agents. We define under-utilization as administration post-incision omission and clean contaminated cases and use of overly narrow spectrum antibiotics. Mysutilization rates were calculated from the NISCO pediatric database and misutilization burden was then estimated by multiplying NISCOPE derived misutilization rates by case-loin data from this. Procedures with higher rates and burden of over-utilization were considered to be greater opportunities for antimicrobial stewardship and procedures with greater rates and burden of under-utilization were considered to have the greatest opportunities for SSI prevention. Over 9,000 patients were included from NISCOPE protectlation of rates in over 83,000 per phase for case-loin estimates. This slide demonstrates rates and burden associated with over-utilization with rates on the Y axis and burden on the X axis. The overall rate of over-utilization was 35 percent and the highest rates were as suitable to colosectomy and ovarian and nexel procedures and the highest burden was associated with small bowel and colosectomy procedures. The overall rate of under-utilization was 14 percent and the highest rates were associated with colorectal and variatic procedures and the greatest burden was associated with colorectal and gastrocymone procedures. This slide represents the greatest opportunities for process improvement within pediatric surgery based on overall number of misutilization cases. The greatest opportunities for antimicrobial stewardship include avoiding anaerobic coverage for small bowel cases and avoiding profile axis for elective colosectomy. The greatest opportunities for SSI prevention include including anaerobic coverage for colorectal cases. In conclusion, misutilization can be also attributable to small handful of procedures and these procedures should be considered high priorities for antimicrobial stewardship and SSI prevention. The last project we like to present looks at examining whether hospitals that were higher users of post-operative prophylaxis had lower rates of SSI. To evaluate the relationship between SSI and post-operative prophylaxis, we calculated adjusted odds ratios for each of these measures after adjusting for differences in comorbidity profiles and procedure mix. We then used the Pearson correlation coefficients to assess the relationship between adjusted odds ratios for SSI's and post-operative prophylaxis. Over 40,000 patients were included in this study, this time from all six major surgical sub-specialties. These figures demonstrate the relationship between SSI's and post-operative prophylaxis. Each dot represents one single hospital with the Y-axis representing post-operative prophylaxis utilization and the Y-axis representing the SSI's and the X-axis representing the post-operative prophylaxis utilization. As you can see here, there was negligible correlation between use of post-operative prophylaxis and SSI rates, both for any post-operative prophylaxis on the left and for extended prophylaxis greater than 24 hours on the right. We further found a lack of correlation between post-operative prophylaxis and SSI on the level of both incisional and organ space SSI's. Finally, we demonstrated a lack of correlation between post-operative prophylaxis and SSI's on all six major surgical specialties. In conclusion, hospitals with more extensive use of post-operative prophylaxis did not have lower SSI rates as compared to hospitals with lower rates of post-operative prophylaxis use. These findings further support national and international guidelines recommending against the use of post-operative prophylaxis. Projects that are currently in the final stages of development include evaluating the exact same relationship between SSI's and post-operative prophylaxis this time on the individual procedure level as well as exploring hospital level association between SSI outcomes and adverse event rates and overall misstualization and a global scale with all the measures. I like to thank Dr. Rangel, our research lab and the ACS NISCO pediatric for all their support in making these these projects possible. On a more personal level, I like to also thank everybody at Boston Children's Hospital, including the faculty, fellows, and APPs for their mentorship guidance and support from engineer to the day with your guidance that become a better surgeon, researcher, person. It's been a privilege to learn from you all. Thank you very much and I look forward to your questions. Our next speaker obtained her bachelor's degree from the University of Notre Dame, followed by medical school in New Orleans at the LSU School of Medicine. She began her surgical residency at St. Elizabeth's before transitioning to research time here at Boston Children's Welsh Shew will complete not only her research time but also as an MPH candidate at the Harvard School of Public Health. While her research productivity, much like all of our wonderful fellows today is impressive, I really want to highlight her precision dedication to service and global health with service projects entered in Haiti, Ghana, Thailand, and going as far back as 2010 where she served as a camp counselor for pediatric burn survivors. I'm happy to introduce Dr. Abby Noss who's going to talk with us today about her time in the program in global surgery and social change at the Harvard Medical Center. Good morning everyone. My research years have been a little different than most. My first year I spent primarily under Dr. Mooney at the program in global surgery and social change or PGSSE before spending my second year with Dr. Faza and obtaining my MPH at Harvard Chan. I will start with a very limited overview of my work at PGSSE. These are several of the leading faculty spaces on the Brazil team at PGSSE, a team that relies on the Brazilian faculty and students who make up this group. Our team has a number of gender equity projects, one where we evaluated women representation on editorial boards of surgical, anesthesia, and obstetric journals in Latin America and which we found gross under representation of women. Since many of the faculty are pediatric surgeons, we also just finished a project that was a cross-sectional national survey of 25% of all pediatric surgeons in Brazil, assessing the delivery of congenital pediatric surgical care under Brazil's system of universal healthcare coverage, which serves about 70% of the population. We evaluated differences in delivery and barriers to care between public and private sectors. In the last project listed, we analyzed publicly available data, noting a current uptrain and reported non-external trauma in children under five. Another pediatric project we've been working on is developing a global trauma, resuscitation, and kids course, or G-TRIC, a simulation-based training developed by the Royal College of Position and Surgeons of Canada, which many of you are probably familiar with. The purpose of this study was to assess the efficacy of G-TRIC to inform future expansion across low and middle income countries. We conducted a two-day simulation-based course in Belo Horizonte in October of 2022. Initial findings on the knowledge assessment and self-evaluation demonstrated an increase in mean scores and perceived improved knowledge for all components of trauma management. We want to more closely address cost, language and resource barriers to implementing, protocolized trauma training in LMI-Cs, aiming to improve outcomes and equity and trauma care globally. The last major piece of the global surgery program I co-lead this year is the Coast for Climate of Sectorics, Anacisa, and Surgery Team, which is a collaborative effort between PGSSC and CSPH at the Brigham. If healthcare were a country, it would be the fifth largest emitter in the world. Surgery being particularly energy intensive. Our group is focused on developing research and policy recommendations to support environmentally sustainable and climate-ready surgical care delivery globally. Projects for this group cover quite a range, some are advocacy focused, such as a panel we presented this year at the CUGA's Conference in D.C. on the intersection of climate justice and surgical systems strengthening. Others are more technical projects like the one we're working on in the Pacific Island countries and territories and collaboration with health authorities there. We are working to develop climate modicals for tropical cyclone risk with associated waves when storm surge and extreme rainfall and overlaying this modeling with population data and vulnerability mapping to inform health infrastructure prioritization for policy makers. Now onto a brief overview of my time in the lab. As many of you know, there are three main novel therapies that have been developed in Dr. Fawz's lab over the years. Transminiotic fetal immunotherapy, transamniotic nucleic acid therapy, and transamniotic stem cell therapy. The latter two of which train it and trace it, we will discuss as they relate to my projects today. Once we discovered the trace and injections of donor cells into the amniotic fluid had a homogenous routing via the placenta, we expanded trace it to internal defects and diseases of the placenta. We initially studied intrauterine growth restriction, a very common pathology affecting 8% of pregnancies and representing the second leading cause of infant mortality. It's a condition caused by placental insufficiency mainly associated with placental inflammation and ischemia, causing poor nutrient transfer to the fetus. For IUDR, we use a well-established model, exposing rat dams to cyclic hypoxia for the final week of pregnancy. In recent experiments from our lab, we found that compared to normal fetuses, fetal weights were significantly decreased in all groups, except for the trace it primed group, which had normal weight, similar to healthy non-IUDR moms. Placental efficiency or the ratio between fetal and placental weights was also significantly decreased in all hypoxia group, but normalized in both trace it groups to that of healthy non-IUDR moms. Several benefits of trace it and fetal neurological and cardiopulmonary developments were also demonstrated. These findings provided the basis for my initial project, which was an experiment designed to test our hypothesis that amniotic mesenchymal stem cells are consumed in the setting of IUDR, reflecting an amniotic cellular response to the disease. In my experiments, we have control healthy non-IUDR rats and IUDR rats that are in cyclic hypoxia, again at Q12 hours at 10.5% O2. I harvested the fetal amniotic fluid at E21 or just prior to term in both groups. Once we harvested fluid, we used known markers for MSUs to stay in the fluid and identified cells expressing CD44 and CD29 as amniotic fluid mesenchymal stem cells. CD45 served as a hematoclinic cell exclusion marker. DAPI was then used as a standard cell viability marker. We then used precision count beads to determine absolute cell count. These beads are fluorescent particles about 10 micrometers that can be detected across a broad range of wavelengths. In our initial findings, placental efficiency was significantly lower in the IUDR group compared to controls, confirming reproduction of the disease model. There was no significant difference in the median individual amniotic fluid volumes between groups. IUDR fetuses had lower densities of both total live cells as well as live MSUs in the amniotic fluid. There was no difference in the ratio of MSUs per live cells between IUDR and controls. None of these analysis were affected by accounting or not for nesting a fetuses within the same mom. There was a significant decrease in the total number of MSUs in the IUDR group versus controls. This is a sample of the flow cytometry profiling from an IUDR rat on the left and a healthy rat on the right. You see in the healthy rat compared to the IUDR rat, the larger number of total cells indicated by the colored dots. The last photo on each set, DNH, indicate the MSU population of interest, which is circled. We concluded that amniotic fluid mesenchymal stem cells appear to be consumed in the setting of IUDR, providing further biological evidence for trace hit as a potential novel treatment for intrauterine growth restriction. Amniotic cell profiling may also carry a prognostic value. We have also been working this year on trainit for alpha-1 antitripsum replacement. Alpha-1 antitripsum deficiency is an underrecognized autosomal code omnihereditary disorder, characterized by low serum levels of alpha-1 antitripsum, a serine protein inhibitor encoded by the Serpina lunging, with over 150 known mutations. Disease creates a predisposition for pulmonary infezima in adults and for liver disease and severe variants. In various severe disease, it can present a scolisatic hepatitis as a newborn, and in the most rare in severe cases, can require liver transplant. Providence of alpha-1 antitripsum deficiency varies considerably between countries, but it's estimated that more than 3 million people worldwide have a leal combination associated with severe disease. Infezima of alpha-1 antitripsum presents an adulthood and think of it like toxic loss of function, resulting from the imbalance between the neutral alastase and the lastase inhibitor alpha-1 antitripsum, which protects against proteolytic degradation of alastin. Think of the liver pathology as toxic gain, a function resulting from the accumulation within the hepatocyte of unscreated variant alpha-1 antitripsum protein. For most patients, we treat the disease as a port of care, avoiding smoking and bronchodilators. Besides sung and liver transplant and various severe disease, there's also augmentation with human alpha-1 antitripsum protein pooled from sera, which is only reserved for patients with severe lung disease. Early detection of alpha-1 antitripsum would help patients with behavioral change, but technical feasibility and cost of population-based screening remains problematic. In our trained experimental design, we aim to determine the efficacy of the delivery of a trans-emionic alpha-1 antitripsum mRNA injection by assessing for the production of alpha-1 antitripsum protein and its product alastase and a healthy rap model. We plan to focus on the areas of disease pathology, including the lungs and liver, utilizing gross morphometrics, ELISA and histology. In this experiment, we injected healthy rats with either just the capsule for the mRNA, called lipopolyplex, but without the mRNA as a control, versus human alpha-antitripsum mRNA-like epolyplex. We then harvested moms at varying time points, E18, 19, 20, and 21. For testing, we focused on the lung and liver and using ELISA that detects the human alpha-antitripsum produced by the mRNA. Blood from E21 fetuses was analyzed for liver function tests to indicate any liver damage caused by the mRNA. Overall, fetal first survival was 79%, and significantly higher in the mRNA group. When controlled by mRNA-free injections, there was evidence of human alpha-antitripsum production and the fetal lungs at all four daily time points. The level of alpha-antitripsum and the lungs were highest at E18 and tended to decrease their actor, stabilizing one day before and at term. Human alpha-antitripsum was detected in the fetal liver only at E20, with levels significantly higher in the control group at E19 and 21, suggesting possible interspecies homology manifesting at the anatomical site. Term liver functions were comparable between the groups. Our initial conclusions are that encapsulated exogenous mRNA, including for human alpha-antitripsum, can be incorporated and translated by fetal lung cells, following simple and inter-amnotic injection and a healthy rap model. Fetal hepatic incorporation and translation remains to be determined in a model with minimal to no human homology. I'd like to thank you for your time today, and specifically to address my gratitude to the Boston Children's Hospital Department of Surgery and to my mentor, Dr. Fowze and Dr. Mooney, additionally to my co-fellow and lab, Camilla plus Ena and Ashlyn, Dr. John Merer for his support in global surgery, Dr. Smith-2 and Ronjan with the Flow Lab into the lab interns, Taran and Shuki. Thank you. This is a graduate from Stanford University with the Bachelor in Science and a minor in studiart from 2014. She then went on to the University of Colorado School of Medicine, where she completed her medical degree as a presidential merit scholarship recipient, and then went on to residency and surgery at the Cleveland Clinic in Ohio. She has multiple peer-reviewed publications and national presentations during her time here at Boston Children's and her PI, Dr. Pratima Nandavada, and having had the opportunity to work with her closely on the clinical site, I can say that she's a compassionate physician without sending clinical judgment. I am pleased to introduce Dr. Lorraine Rinkong-Kruz, who will be instructing us on the role of tight junction proteins in herchvarine disease. Thank you for the opportunity to present my work over the last two years with you this morning. Herchvarine disease is the developmental disorder of the interrac nervous system, with parasympathetic egg angling doses and the distal gut resulting in functional obstruction and dilation proximally. The treatment is surgical resection of the egg anglionic colon. However, as many as 30 to 50 percent of patients may continue to experience dysmotility and herchfrungs associated enterocolitis with their sturdiness of bowel function for years to come. The cause of this long term morbidity is not well understood, which led us to ask, why do some patients with herchfrung disease continue to have dysmotility and enterocolitis despite removal of the egg anglionic bowel. In addition to the well-established neuroenteric component, intestinal barrier dysfunction has been proposed as a possible risk factor for the susceptibility to enterocolitis and dysmotility. Tight junction proteins regulate intestinal permeability by two routes, the poor and the leak pathway. The poor pathway is regulated by clotting proteins and the leak pathways controlled by interactions of MLCK1 and occluding. A third route is the unrestricted route which occurs during damage and cell loss. This is not regulated by tight junctions and is unselective. The overarching goal in our lab is to identify if there are ways to improve gut barrier dysfunction in children with herchfrung disease using therapeutics that target tight junction proteins. We hypothesized that there were differences in tight junction proteins between children with herchfrung disease and those without. Toward that aim, we sought to quantify levels of tight junction protein expression in this cohort. We started with a retrospective analysis of protein expression in children with herchfrung disease compared to controls. Colonic surgical resection specimens from 29 patients with herchfrung disease were obtained from the pathology department, including the egg anglionic and ganglionic segments. Colorectal biopsies from 16-H matched patients undergoing full thickness rectal biopsies for constipation were used as controls. We stained for multiple tight junction proteins shown here on the right using multiplexin unohistochemistry. These proteins were selected for their known roles in GI diseases. We focused first on the poor pathway. These next few slides are all going to be set up the same data comparison of the pooled cohort on the left and a representative slide of the experimental condition on the right. Either control, herchbrung ganglionic colon, or herchbrung egg anglionic colon. Dappy stains nucleane blue with the stain of interest in red. Florescence intensity of each protein was normalized to 0-1. We can see that clotting 2 is downregulated in both the ganglionic and egg anglionic tissue compared to control. Additionally, there were no differences between the ganglionic and egg anglionic segments. Likewise, when we look at clotting 15, we again see reduced levels of expression in both the ganglionic and egg anglionic colonic specimens as compared to the control, with no significant differences detected between the ganglionic and egg anglionic segments. The other proteins involved in the poor pathway were not affected, moving on to the leak pathway. Acluded expression was decreased in the ganglionic and egg anglionic segments compared to the control with no differences seen between the ganglionic and egg anglionic segments. Other key proteins involved in the leak pathway include 0-1, 0-2, which were not affected. Structural proteins, including e-cat hearing, did not have their levels affected. In summary, expression of tight junction proteins clotting 2, clotting 15, and occluding are decreased in the ganglionic and egg anglionic herchbrung colonic segments relative to controls at the time of pull-through. But what role do these proteins play in the pathogenesis of the disease? We know that clotting 2 and clotting 15 form pericellular sodium and water channels that are size selective and contribute to lumenol hydration. Prior work has demonstrated that clotting 2 knockout mice stressed with infection or immune mediated colitis developed fecal dehydration and intestinal obstruction independent of the severity of the colitis. Conversely, clotting 2 over expression increases fecal water content and protects against chemical colitis. This led us to the hypothesis that reduced expression of clotting 2 and clotting 15 contribute to the pathogenesis of constipation in patients with herchbrung disease and may increase the susceptibility to post-operative anal colitis. To explore this, we have transitioned to a mirroring model in order to understand the temporal expression of tight junction proteins before and after the development of anal colitis. The endothelan receptor B knockout mouse develops short segment egg anglionosis that closely resembles human disease. These mice develop proximal obstruction and enteral colitis that is fatal by four weeks of life. The homozygate knockout mouse is easily identifiable by the white coat color and progressively enlarging abdomen due to egg anglionosis and leading to mega colon seen here in panels A and B. Heterozygates were bred to generate wild type, heterozygate and knockout litter mates. Each group was sacrificed at three time points, 7, 14 and 21 days and we gathered tissue including small bowel, colon, spleen, as well as phenotypic data for comparison. Phenotypic data included body length, abdominal girth, and weight. We saw a decrease in weight in the disease group apparent from week one from which the scohoort never recovered. Traditional H&E slides from the colonic specimens were then used for semi-phonotative histologic scoring of colitis using a previously validated scale for this particular mouse model. Despite no outward signs of colitis, histologic colitis is apparent even from week one. In order to correlate our mouse model with human data, we're in the process of recapitulating the multiplex and immunofluorescence stains as well as quantifying cell populations. Small bowel and colonic samples have been collected and sat frozen for each group at each time point and we're currently performing protein analyses, bulk RNA sequencing, and QPCR analysis in order to help define the colic transcript film shifts during disease evolution. As a functional analysis of the impact of protein expression changes on epithelial permeability, we adapted an established juvenile permeability model to the colon. This protocol uses three separate probes of three different sizes specific to each of the permeability pathways. After closed loop perfusion through the colon, blood is collected and by analyzing the levels and the ratios of these three probes, it's possible to discriminate between pathways as the mechanism underlying the changes in intestinal permeability in vivo. With these data, we'll be able to correlate tight junction protein expression to epithelial permeability as the disease progresses. Lastly, we're in the process of establishing a prospective tissue repository to evaluate the relationship between patient symptoms and intestinal morphometry and outcomes. Starting this past January, for patients undergoing pull-through for herch-front disease, we began to collect excess tissue at the time of surgery with the goal of archiving tissue for RNA, protein, and histologic analyses. In addition, tissue was cryopreserved for the development of organoids, which you see here on the right. We have created tissue derived organoids from three patients so far and we'll be staining them for clotting proteins in the coming months. We will also be performing trans-epithelial electrical resistance measurements as a way to measure permeability. Patient derived organoids display similar characteristics and morphology to the human tissue that they're derived from in constitute a valuable system to study abnormal gastrointestinal physiology. In addition to the work that I've shared with you today, these are some of the other projects that I've worked on over the past two years. I want to express a very big thank you to everyone who's helped me and contributed to my work over the past few years, and I'd like to extend my deepest gratitude to my mentor, Pratina Nandavada. I was a little nervous to join a lab being its first research fellow, but helping build a lab with you from a ground up has undoubtedly made me a better surgeon scientist. With your guidance, I know that I've grown tremendously both personally and professionally, so thank you from the bottom of my heart. Our final guest today is a cum laude biomedical engineering graduate from Northwestern University, who went on to complete her medical training at the University of Illinois, Chicago College of Medicine. There she was selected as one of the inaugural students within the UIC Innovation and Medicine, where she would complete her capstone development project on a novel protective covering for mobile devices within sterile clinical settings. Her background and research projectivities speak to her passion for changing the way that clinicians interface with technology. I really wanted to come up with a clever equipment here about the Dr. Nina Scalise-Something device that we're all going to be using 20 years, but I honestly couldn't think of something novel to talk about, and I think that that speaks to what makes a true innovator like Dr. Scalise, so special. And today we're going to be hearing about her time as a surgical innovator here at Boston Children's. Thank you for that introduction. All right, good morning. Thank you to the department for the honor to present some of the highlights from my past couple of years as a surgical innovation. Research fellow here under the mentorship of Drs. Kim, Demeri, and Lee. I think the flavor of the fellowship is best captured by showcasing the variety of what we've been up to over the last couple of years. Here's a list of the project I'll cover today, most of which are clinically based, but all of which are rooted in a question that gets at the disruption and hopefully improvement of the current way of thinking about a particular problem, in other words, innovation. I'd be remiss if I didn't have a slide to picked the innovation lifecycle in this talk. This is adapted from the Stanford biodesign curriculum. The point here is that the process is very cyclical and iterative, starting with the process of needs identification, combing the landscape for existing solutions, and working through various concepts and prototyping until you reach a stage where things like intellectual property and regulatory strategy come into play. So we'll start with the way we always do with a question. What would you do for a sprained ankle to relieve the pain? This is not a trick question. You apply some ice. The topical ice has actually been shown to reduce pain scores and opioid use and adults with midline abdominal incisions. Also has been proven in orthopedic GYN and in Inuital Heria procedures. So we asked the question, can topical cold therapy serve as an adjunct for incisional pain in children after abdominal surgery and in the analogous way? We partnered with Bragg Polarcare who provided the ice machine shown here that circulate cold ice water to the pad that supplied to the skin. It's often used after orthopedic surgery and laparoscopic appendectomy was chosen as a common abdominal surgery in children. So we conducted a randomized control trial with 58 patients randomized to two groups. Half got the standard of care pain medications post-operatively and half got the standard of care plus the cold therapy system with the pad applied to their abdomen for at least 48 hours post-operatively as much as the patient was able to tolerate. Surveys were distributed electronically on the first three post-operative days mostly to the patient's parents. Primary outcome was numeric pain scores and the secondary outcomes included morphine male equivalents administered postoperatively hospital length of stay and patient satisfaction scores. In Inuital the outcome from this trial was that the cold therapy patients in our group did not have significantly lower pain scores or an archotic usage which when they did receive narcotics which which was actually infrequent. However, patients and parents who did receive the device rated their satisfaction with it very high and listed cold therapy as a contributing factor to their pain relief and at least 50% of respondents on post-operative days 1 through 3 it was 71 74 and 50%. So where do we go from here with these results? So given the patients did report subjective pain improvement with the cold therapy, we may see the desired outcome if applying the same technique to patients with larger incisions so full laparotomy for example in patients with longer expected lengths of stay or higher than expected narcotic requirements compared to a lap api. We're also working on future development of wound dressings with cold integration in order to deliver this technology directly to the wound. Next I'll discuss our button battery ingestion project. So kids are always putting things in their mouths that don't belong. Sometimes unfortunately they're swallowing them and this has harmful effects. There's been increased awareness surrounding the hazards of button battery ingestion clinically and recently in the media. This is what a typical film looks like for those of us who've been on call and seeing this come come into the ER when the battery blodged in the osophagus. So what we did is we asked can we predict which children will have a severe outcome from a button battery ingestion and will need advanced level care like endoscopy or pediatric surgery. We collected data on a large set of button battery ingestions treated here at children over the 13 year period. It was 143 patients which turned out to be the largest single institution analysis of these patients and our question was what factors determine whether a child will have a severe outcome and a severe outcome in our study was determined by the list of bulleted criteria here like deeper circumferential erosion, metastinitis, vascular or airway injury or the eventual development of a structure. Busy slide here but we'll just highlight a few of the key findings. So kids with severe outcomes, the ones on the last slide were more likely to be younger so particularly less than three years old. Transferred from an outside hospital symptomatic at presentation have an unwitnised ingestion have swallowed a large battery and a large battery is one over two centimeters and have the battery lodged in the osophagus as opposed to somewhere else distal in the GI tract. In multivariate analysis three factors were identified as the most significant predictors of a severe outcome. Having a battery in the osophagus in an initial image the battery size being over two centimeters and being symptomatic on initial presentation. If you had all three the predicted probability of the severe outcome was nearly 90 percent. Next steps are to utilize the score and validate it in in current patients. This project was presented at last year's ipeg and published in journal pediatric surgery. Next I'll move on to our teeth assinur gastropexae project. So the standard technique used here for left g tubes is the buried trans abdominal u-stitch which is depicted on the left and teeth assinurs are shown on the right and have been adopted here as an alternate option for some patients with thicker abdominal walls. When it be more challenging to basically track that track a needle through the abdominal wall and abdomen and stomach and back out of those layers the needles often too short and patients with thicker abdominal walls. I'd also like to highlight that some that the teeth assinurs have external bolsters that rest on the skin where the sutures tied around and in order to secure them and these have often led to skin issues in our patients and so we were thinking how is how is the way we could utilize this technology without the burden of those of those bolsters. So how can we achieve a secure gastropexae using the teeth assinur technique without the unwanted effects and side effects of those of those bolsters. So before I go into our study in more detail I think a video animation better to fix this paired teeth assinur approach that we'll be talking about. So this is a schematic of where the teeth assinurs are delivered in relation to the G-tube site. So you can see the first fastener being inserted through the sub-Q fascia and stomach wall and the anchor is being deployed. The second fastener is being inserted through the same incision as the first and now we'll see the second set of fasteners being inserted through the incision on the opposite side. The G-tube's been inserted by a weldingers technique and the upper and lower pairs of fasteners are tied together bearing the knot and the subcutaneous tissues. The idea is to insert the four fasteners through the stomach and a square configuration to achieve a secure fixation is shown here. So we did a rectuspectus study comparing the PTF or paired teeth assinur approach to the buried usage gastropexy in a matched patient population. Pologies if you can't see this but there's a there's one one paired teeth assinur patient for every two control buried transadaminal usage patients. Standard G-tube cases the controls use more laparoscopic ports on average to compare to the PTF cases though the median operative times were not significantly different between the two groups. Median gastroasomy tube length was significantly longer in the PTF group it was too sent not very much but it was significant two centimeters compared to 1.7 centimeters in the control which reflects the thicker abdominal walls in these cases. There were no statistically significant difference in 30-day complication rates between the control and PTF groups and complications included things like tube dislodgment, parotonitis, bleeding, infection, so major and minor complications. There were no difference in those rates between the two groups. So the take-home here where that the PTF technique is indeed safe and efficient means of gastropexy without the bolsters and pediatric laparoscopic gastroasomy. The technique uses fewer trocars overall and provides a similar safety profile and is advantageous in patients with thicker abdominal walls. Moving on now to a more hands-on practical project from the clinic. So our Chess wall program here is you know large influx of Pectus X-Govottom patients who are treated at least initially nonoperatively with the vacuum bell therapy. The current standard of measuring severity of these effects is the halor index which we're all familiar with and this is shown in a CT image in the center. It's often required by insurances with CT scan for surgical approval but the method is imperfect and can be skewed by chest wall shape and is often and requires radiation via CT scan or x-ray. The image on the right is manual Pectus X-Govottom depth measurement using a ruler in a straight edge that goes across the test at the deepest part of the depression to get to get a depth measurement. This is often done in clinic. It looks pretty primitive that this is actually pretty reliable when done by the same provider consistently with patients. So we ask the question is there a non-invasive and non-radiating way to reliably monitor such patients with Pectus X-Govottom during their treatment with vacuum bell therapy and during any treatment in general. So indeed there is and we've been utilizing in our clinic now the Rodan M40 white light scanner that provides 3D topographic images of the Chess wall to light weight portable USB devices shown on the left and the big accomplishment of this project honestly was securing one of these scanners for our own Chess wall clinic. We were utilizing that that belonged to the Bosphorathotic and Presetics Department. So we were taking our patients there to be scanned. Now we have our own scanner, our own software right in our clinic and we're able to to deliver that for patients. And it's the process is shown on the right. It's a one minute essentially circumferential torso scan standing about a foot away from the patient. And this is already used in FDA approved actually for Plasia Cefeli helmets and torso molds for first schooliosis braces. So the output of the scan is something with like what's shown on the left here this 3D kind of external topographic image. And what can we glean from this? So basically we can get a 2D slice through the chest and calculate what's an ex known as an external halor index. It was initially named after a couple of the authors that first described it. But the the essential measurements are the media lateral over the anterior posterior dimensions. And this is all external. So it includes all of the soft tissue. It's not just a bony dimension like that would come from a standard halor index. And in recent literature this external halor index was shown to have a strong correlation with the traditional halor index in Pectus X-Govatum. So here's a couple of representative images from one of our clinic patients actually with moderate to severe Pectus X-Govatum. And you can see the 2D cross-sectional slice through that scan that was done. And particular in the image on the right we were able to construct a white light scan funnel depth. That's the dimension that's attempted to be shown here in this red line by calculating the distance from the deepest point of the depression basically to a coronal plane that's across the anterior most point of the patient's chest. We're calling it white light scan funnel depth. So here's apologies for the incomplete views. But here's some correlation studies that we had done in comparison to groups that previously reported on this. So when we looked at halor index versus the white light scan external halor index our correlation was not as strong as the as the previous groups who reported on this. It was stronger when we looked at the manual Pectus X-Govatum depth when compared to white light scan halor index external halor index. So we're basically looking at what would be the best way to report severity in these kids that's most reliable using the white light scan. What we found was actually the most reliable was this white light scan funnel depth that red line in the picture a couple of slides ago compared to the manual Pectus X-Govatum depth. These two were very highly correlated with the providers that were doing our measurements and us who were calculating these dimensions from the white light scan. So that's very promising going forward. And we're also excited to be doing work to be doing work with vacuum bell compliance tracking and monitoring as well and going forward. Okay. Moving on one of the projects that we're working on also is leveraging the wealth of data from our PDF Transplant Center. So this graph shows the percentage of kids excavated in the OR immediately after liver transplant versus years over time. Before 2005, essentially everyone stayed intubated after surgery. So why was this? Why do patients, why do we keep patients intubated after a liver transplant? This could be for a variety of reasons, right? Are they too sick, too asodotic? Are they too tiny? Too paralyzed? Is their belly closed too tight at the end of the case? Could be for a variety of reasons. So we saw it to review our center's experience with immediate activation following liver transplant to determine characteristics that would be predictive of a successful excavation and the effect that that has on postoperative outcomes. We took a retrospective look at all patients from 2005 to 2022 who received a liver containing graft but excluded those that who also received a lung transplant or who were chronically vent dependent prior to surgery. And we looked at a number of factors in the preop, intraop and postop settings that are listed in the panels on the right. Basically, the conclusion from all of this work was that early excavation in the operating room after liver transplant is indeed safe in children and not associated with an increased risk of re-intivation or postoperative complications like hepatic artery or portal vein frombosis or graft failure. The parameters that wound up being statistically significant were being in the ICU preoperatively before your transplant, having a higher meld or pelt score which is indicative of being thicker prior to your operation, having a longer total operative time and longer to cold ischemia time, being transfused intraop products. So these include Paxels, FFP and platelets, all of those were statistically significant and requiring vasopressor support postoperatively. So all of those were statistically correlated with a deep tendency for delayed excavation. So sometime after the operation in the ICU and that in turn was significantly correlated with increased ICU length of stay, total hospital length of stay and hospital costs. Finally, last but definitely not least is our project relating to polyvinyl alcohol or pva sponges to reduce intraabdominal infections. So literature has suggested that linked and fibers that leachos are the goss sponges and towels in the operating room can actually lead to inflammatory cell reaction that causes intraabdominal adhesions. So especially common in the in the peritoneum and in the pelvis and this has been previously reported in the literature. So knowing this, why are we still using cotton goss sponges in the operating room if it's known to be a contributing factor to adhesions that were harvested adhesion tissue? We think we can do better and so we proposing a polyvinyl alcohol or pva sponge that is biocompatible. It's naturally non-linting in our highly absorbent material that's actually already FDA approved in many areas in the medical space to essentially replace a to replace the way that we use cotton in in the operating room. It comes in a wide variety of porcises and configurations. So where have we seen pva? We've seen it in household cleaning products on the left. It's an ingredient in the sham wow where most of us surgical residents have seen it is the white sponge in the vac in the wound vac systems and this is the white sponge. It's equipped to go against bowel as compared to the last one. It's also a component in neuropatties and nasal packing and ophthalmology spheres. It's hidden everywhere in the medical space. So our goal is to investigate whether using a pva sponge as a packing material leads to a reduction in intra-dominolification formation compared to standard goss sponges using a mouse laparotomy model. So in this experiment each group of mice underwent an x-lap on day zero and the mice underwent a serial packing protocol with either cotton gauze and equally sized pva instrument wipe which is supposed to simulate the pva sponge or no packing which was our sham group. And the abdomens were closed after removal of the packing and anywhere from post-update 13 to 15 we targeted two weeks. The mice underwent were sacrificed and underwent necrocies during which blinded observers graded the degree of adhesions formed in each group of mice. Briefly this is just the score that the observers were using that rated the adhesions on tenacity type and extent. So basically how dense and how vascular the adhesions were the maximum score here was 12 so it's four in each of those three categories. So our goal after doing some initial pilot studies during my first year was eventually to show a 50% reduction in average adhesions score with the pva sponge compared to a gauze sponge packing. We needed 63 mice per group to adequately power this and we're actually wrapping up the conclusion of those operations this week. And we also are currently now harvesting histological and we're collecting tissue samples for histological evaluation as well. So we haven't actually shown this before in prior lab talks. This is some preliminary data with just under a hundred mice so far. Like I said we're completing the remainder this week but we have very promising results so far that suggest that the median being adhesions scores in the gauze group are more than double actually those that of the pva pva group. It's where we've shown so far a 63% reduction in those adhesions scores and we're actually overpowered to to show this so far. And the sham group was hovering somewhere just above the just above the pva group but we're continuing to analyze these results currently. Our next steps in this whole process are to develop a surgical mated pva with a commercial partner to be used in further laboratory and clinical testing. And ultimately to mimic the properties that surgeons are comparable with and come to expect with cotton gauzes to eventually ease the adaptation of this in clinically used. And with all that I'd like to conclude and thank the surgical innovation team. My mentors, Drs. Ken DiMiri and we as was hopefully evident in this talk that scholarship has been nothing if not a collaborative effort with all of you. And particularly thanks for pushing us always throughout this process. Thanks for letting us take over your offices very frequently these days. To my rock star co-pellow and brand Donna for all of her support and to Alex and all of the prior surgical innovation alum and fellows and to the Department of Surgery for Continuing Supportive Work and all the other teams that we collaborated with. Thank you. Thank you. Wow. Thank you all. I Dr. Shember and I were just lamenting over how the future of pH surgery is is so dim. Between the last group presentations, the group presentations are ongoing research and it is extraordinarily bright. It is spectacular. We have a long history and have been blessed with so many people, some of who are generic. In fact, we've been doing this kind of work. But it is extraordinary group. We are because of the breadth of our group. We don't have so much time. You guys did a spectacular job of respecting each other's time. I want to open it up for comments. There's a whole bunch of mentors for all of you and I want to open it up for brief comments by anybody, the many mentors who might like to speak for any questions. Yeah, I don't remember the last time that I had a fellow for only one year in large part because it's very challenging to learn what is required and do something meaningful in that such a small amount of time. But Abby managed to do just that. She faced those challenges with grace with boys and has completed very important projects in the respective areas which I think would be recognized as such by the medical community. So, Abby, I congratulate you. I'm very grateful to you and look forward to following your path. Nina, congratulations. It's been such a joy working with you. I remember when Nina first reached out about the Innovation Fellowship. She said that was what she wanted to do. Despite, I remember saying it's a very unstructured experience and in that soil certain types of people will blossom and Nina has completely blossomed. One of the hardest, one of the challenging parts of pediatric surgery is the range of things we have to be good at as pediatric surgeons. And the Nina has shown as you saw today that she's able to handle a very wide range of things. She's going to go and expert in multiple fields during these past two years and I'm going to show her work ethic, creativity and scope. So, congratulations. I want to thank all of you and all the former fellows for all your hard work for the department. I think I've worked with many of you clinically and been my pleasure to help train you all. Nina, great job. Great work in the lab carrying this team for the last two years. And I look forward to following your career. Keep innovating. Thanks. Grava, thanks. Well, Catherine, what can I say? I think Patrick's introduction probably speaks at all in terms of just what an incredible researcher you have been a continue to be. And I have to say, unfortunately, there's only 10 minutes, I guess, per talk. And so we didn't get a chance to hear from all the other projects. But what many folks don't know is the incredible amount of leadership and organizational skills that were involved with the NIH grant that we didn't even hear about and working with 400 pediatric practice groups to obtain their records and chart review and developing an NOP pathway to try to figure out what happens to all these kids with in the local hurry is how they bounce to the system. And the leadership skills that you exhibited in organizational skills to get those folks on board with this project in terms of realizing how important it is, I think that it was probably a bigger accomplishment than even all the other great stuff you've done. And so I think this is a hallmark of just a future, very successful HSR researcher and I just can't wait to see what you do with your career. And it's been a privilege and an honor to be part of your education and training. So thanks again for all you've accomplished. It really looked forward to seeing what happens in the future. Lorraine, so first I just really want to thank you for taking a chance on working with me because it's always a gamble when you're working with a brand new lab or brand new scientists and I have to say, you know, we were partners way more than I was your mentor and you were my fellow and I think it shows in the work. What you know, you don't see here is how much this work reflects Lorraine's ability to build relationships with others and work in teams because when you're a new attending on top of a new scientist, my schedule was all over the place and she just figured out how to find me, how to get things done together. And even more importantly, how to lean on Jerry Turner, who is our collaborator's team to really fill in the gaps and learn the skills you need to learn. And I think that was the secret to your success. It's a tremendous amount. I know it may not feel that way, but it's a tremendous amount of work that you've accomplished in just two years, really an hour and a half and have laid the foundation for a lot of fellows who are coming after you. So thank you so much for all that. Very proud. I think that I miss any of the mentors. I think that comment that that Dr. Nadevine made reflects upon all of the experiences our faculty are the second biggest beneficiaries of this, of the opportunities that are manifest in the breadth of the research experience and the apartment. We hope that the research fellows are the primary beneficiaries, but the fact in that there is a bunch of busy surgeons who have an incredible opportunity to have the best and the brightest to work with them and to make to make us shine. And that's not lost upon us. So thank you to all of you. We are out of time for questions from everybody else because of the richness of our group. And I want to thank you all, all those of you who spoke this time and last time in those to come. It is just incredible to have the opportunity to learn from all of you and to work with all of you. So thank you all so much. I would ask the mentors and the people who spoke today to hang up for some photographs. Thank you all. Thank you all. You should return off the screen. Can we take a quick look dark? You want the screen up? Yeah. Can I keep the screen going? I'm just going to leave. I was thinking about this. If it was a huge bar, I'd have to look up and I was like, damn, it's going to be there. When I was like my last, like, of like a hub ring spot, like on the, all my size notes are from my slides. That's it. I know I was thinking about that. How are you doing, still going on and chocolate? It's okay. And it's pumpkin. Oh, crispy. Truezub Isa. and behind that internet and<|pt|> No, we're in the olden... Yeah, you got me in the sky.
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