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Northwestern University Feinberg School of Medicine
Department of Surgery

2025 Abstracts

Megan Alagna, BS

Student

Patient-reported outcomes in lower extremity amputees with peripheral artery disease
Introduction
Peripheral artery disease (PAD) is a chronic and incurable disease that can lead to lower extremity major amputation. The short- and mid-term experiences of patients who undergo major amputation for PAD are not well understood. Our objective was to investigate time-dependent changes in physical function and quality of life after major amputation in people with PAD. We hypothesized that these patient-reported outcomes would improve over time in the postoperative period.

Methods
This is a retrospective single-center study of patients who underwent lower extremity major amputation for PAD at Northwestern Memorial Hospital between 2022 and 2024. A 56-item paper survey consisted of: (1) the validated World Health Organization Quality of Life (WHO QOL) assessment for quality of life in physical health, psychological health, social relationships, and environmental health; (2) the PROMIS Short Form Physical Function and Depression assessment for mobility and depression level; and (3) questions on demographic and clinical variables. Kruskal-Wallis tests were used to assess differences in outcomes between groups and Cuzick's trend test was used to assess trends in outcomes between groups.

Results
Eighteen participants (33% female, mean age 62 ± 3 years, 56% non-White race) returned completed surveys. The survey response rate was 37%. Levels of amputation were above-knee (28%), through-knee (11%), and below-knee (61%). Participants were stratified by time since amputation into three groups: 0-6 months (22%), 7-12 months (33%), and 13-39 months (45%). Depression scores were lower for the group with the longest time since amputation (p=0.03). Scores for social relationships, environmental health, and quality of life increased as time since amputation increased, and these upward trends were significant (p=0.04, p=0.03, p=0.03, respectively). Depression scores decreased as time since amputation increased. This trend was also significant (p=0.01).

Conclusions
Among patients with PAD, as time since amputation increases, quality of life and physical function scores increase, and depression scores decrease. This work highlights the importance of providing sufficient resources for patients with PAD recovering in the first year after major amputation to adequately support their physical function and mental health.

Competition Category: Health Services Outcomes or Clinical

Mentor: Karen Ho, MD

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Brandon Applewhite, PhD

Fellow (Clinical or Postdoctoral Researcher)

Peptide-PEG DSPE Coatings for Targeted Mitochondria Delivery to the Vascular Endothelium
Introduction
The vascular endothelium is important to maintain vascular function and its dysfunction and injury is implicated in various cardiovascular diseases. Mitochondria transplantation represents a promising strategy for rescuing damaged endothelial cells and promoting vascular healing, but is challenged by poor cell specificity, limited uptake, and inadequate protection of mitochondria within the tissue environment, thereby diminishing their therapeutic potential. To address these limitations, we have developed a versatile engineering platform to modify the surface of therapeutic mitochondria with tissue/cell-specific peptides, enabling targeted delivery. We hypothesized that surface modification of isolated mitochondria with vascular injury specific peptides could improve their uptake into the endothelium following injury.

Methods
Mitochondria polymer coatings were synthesized by reacting 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-5000] (DSPE-PEG-Mal) with cysteine terminated peptides (Collagen Binding Peptide and VCAM-1 Binding Peptide) to yield DSPE-PEG-peptide conjugates. The resulting chemical product was characterized with nuclear magnetic resonance and MALDI spectroscopy. Mitochondria were isolated from IPSC-derived mesenchymal stem cells and coated by incubating with increasing amounts of DSPE-PEG-peptide. MitoTracker-labeled mitochondria were incubated with streptavidin-labeled peptide and coating efficiency was quantified via flow cytometry. Particle size was measured with dynamic light scattering. Mitochondria respiration after coating was confirmed with the Seahorse Mito Stress test. To investigate whether coating improved endothelial cell uptake, diabetic human aortic endothelial cells were incubated with mitochondria for 24 hours before imaging using confocal microscopy. Local uptake was evaluated in a rat carotid balloon injury model.

Results
DSPE-PEG-peptide conjugates were shown to colocalize with labeled mitochondria, visually confirming coating. Increasing DSPE-PEG: mitochondria ratio reduced coating efficiency (Figure 1). Average mitochondria particle diameter also decreased with increasing DSPE-PEG. Coating had no detrimental effects on mitochondria respiration. Both coated and uncoated mitochondria were shown to improve cell respiration. Mitochondria internalization was enhanced with VCAM-1 Binding Peptide after 24 hours. Histological analysis confirmed mitochondria were internalized by endothelial cells and smooth muscle cells after local catheter-guided delivery following balloon injury.

Conclusions
These results demonstrate the feasibility of using DSPE-PEG-peptide coatings to functionalize mitochondria for targeted delivery to for vascular surgery applications. Future studies will evaluate whether mitochondria transplantation can improve surgical outcomes.

Competition Category: Basic Science or Translational

Mentor: Bin Jiang, PhD

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Paola Barrios, MD, MS

Senior Resident (Clinical PGY3-5)

Association between area deprivation index (ADI), hospitalization patterns, resource utilization and healthcare costs among patients with liver cirrhosis
Introduction
Liver cirrhosis affects an estimated 2-5 million adults in the United States, with rising rates of hospitalization that signal worsening health, high readmission and mortality rates, increased healthcare costs, and significant impacts on quality of life. This study aims to examine in-hospital resource utilization and associated costs among patients with liver cirrhosis living in low- versus high-resourced environments, using the Area Deprivation Index (ADI).

Methods
A retrospective cohort study of privately insured adults with cirrhosis was performed using a large national insurer claims database from 7/2011-12/2022. Hospitalization rates, in-hospital resource utilization and cost were analyzed. ADI categories are reported (ADI 1: least deprived; ADI 5: most deprived). Multivariate analyses were adjusted for age, gender, insurance type, Charleston Comorbidity Index (CCI), and cirrhosis etiology.

Results
In 393,745 patients (mean age 63.9 years; 45.5% female; Medicare 57.6%), the most common etiologies were MASLD (36.3%) and MetALD (25.97%). The average CCI at cirrhosis diagnosis is 5.7, and mean MELD 3.0 at diagnosis is 14.1. Mean hospitalization rate is 65 hospitalizations per 100 patient years, 21.59 for compensated and 91.09 for decompensated patients. Patients in ADI 5 vs ADI 1 had 9.7% higher hospitalization rates, lower outpatient-to-inpatient visit ratio by 13.3%, and an increase in acute care visits by 50.8%. ADI 5 patients experienced 18.8% more hospital days, were 40.3% more likely to be discharged to hospice, 106.5% more likely to leave the hospital against medical advice, and underwent 12.8% fewer cirrhosis related procedures. Patients living in ADI 5 had a lower cost per hospitalization ($16,194.69 vs $17,967.15) but overall cost of care per 100-patient years was 8.7% higher ($1,359,666 vs $1,250,507). All results reached statistical significance (p <0.05).

Conclusions
Hospitalization rates are high for patients with cirrhosis, especially for patients with decompensated cirrhosis. Patients living in the least resourced geographic areas are requiring more hospitalizations, have fewer outpatient relative to inpatient visits and overall higher inpatient costs of inpatient care.

Competition Category: Health Services Outcomes or Clinical

Mentor: Daniela Ladner, MD, MPH

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Kelly Bates, BA

Student

National rates of hepatocellular carcinoma surveillance in an insured population of patients with cirrhosis
Introduction
Cirrhosis serves as a primary risk factor for developing hepatocellular carcinoma (HCC), the most common liver malignancy worldwide. HCC surveillance in patients with cirrhosis is associated with cost-effective improvements in patient outcomes. Though smaller studies have investigated HCC adherence, national rates of guideline-concordant surveillance in insured patients have not been addressed. This study aims to characterize the utilization of HCC surveillance and identify predictors associated with its use.

Methods
A retrospective cohort study of patients within a large, national insurance claims database between 2011-2020 was conducted. Adult patients with cirrhosis were identified by ICD-9/-10 codes. Patients with less than 12 months of follow up and HCC at baseline were excluded. Guidelines set by the American Association for the Study of Liver Diseases, consisting of abdominal ultrasound (US) and alpha fetoprotein (AFP) level, were used to define adherence. Abdominal magnetic resonance imaging (MRI) with contrast and abdominal computed tomography (CT) with contrast were also considered to be qualifying surveillance exams based on clinical practice. Patients were followed until the identification of HCC or disenrollment. Multivariable generalized linear mixed-effects model identified predictors of adherence.

Results
Among 86 million insured patients, 270,686 patients were included in the analysis. Patients were 52.9% male, had mean (SD) age of 63.4 (12.3) years, and had mean (SD) follow up time of 3.9 (2.5) years. The most frequent cirrhosis etiologies were metabolic dysfunction associated steatohepatitis (MASH) 95,618 (35.3%), metabolic and alcohol-associated liver disease (MetALD) 68,284 (25.4%), and hepatitis C virus (HCV) 21,084 (7.8%). The incidence of any one surveillance exam within the 6 months before, 6 months after, and 12 months after identification was 7.1%, 14.0%, and 20.8% respectively. Only 35.9% of patients ever received at least one surveillance exam. Guideline-concordant adherence was highest in the first 8 months after cirrhosis diagnosis (at most 18.3%). 117,774 (43.5%) patients were decompensated at baseline. 75,319 (27.8%) experienced decompensation and 81,737 (30.2%) saw a gastroenterologist during follow-up. Following with a gastroenterologist was a strong predictor of adherence (Odds ratio 7.21 95% confidence interval 7.18-7.25). 14,828 (5.5%) patients were diagnosed with HCC during follow-up.

Conclusions
The rate of cost-effective, guideline-adherent screening among insured patients is low. Specialty care was substantially associated with guideline-concordant adherence. Efforts to promote awareness of surveillance programs between gastroenterologists and primary care physicians are warranted.

Competition Category: Health Services Outcomes or Clinical

Mentor: Daniela Ladner, MD, MPH

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Raheem Bell, MD

Fellow (Clinical or Postdoctoral Researcher)

Utilization and timeliness of next-generation sequencing testing for patients with resected or metastatic non-small cell lung cancer: a real-world analysis.
Introduction
Comprehensive next-generation sequencing (NGS) is an evidence-based molecular testing modality used to identify actionable oncogenic drivers in tumor tissue, guiding therapy selection and improving survival in early-stage and metastatic non-small cell lung cancer (NSCLC). However, uptake of NGS in oncology practices varies. This study aimed to identify hospital-level variation in NGS testing adoption within a statewide quality improvement collaborative.

Methods
We conducted a cross-sectional analysis of patients with clinical Stage IB-IIIA NSCLC who underwent surgical resection and clinical Stage IV NSCLC sampled in 2023 across 10 academic, community, and integrated network hospitals in a statewide cancer quality improvement collaborative. Rates of NGS testing and turnaround times between biopsy date, NGS order date, NGS result date, and first treatment time were analyzed. Subsets of patients treated at facilities with in-house molecular labs or reflex molecular testing protocols were described. Multivariable logistic regression identified demographic and clinical predictors of NGS use. In a subset of patients with EGFR or ALK mutations, we evaluated tyrosine kinase inhibitor (TKI) use across hospital sites.

Results
Among 318 patients, 34.9% had clinical Stage IB-IIIA and 65.1% had clinical Stage IV lung adenocarcinoma. NGS testing was performed in 65.1% of patients, with rates ranging from 13.5% to 97.8% across sites. Facilities with in-house NGS capabilities had higher NGS rates (87.8%) compared to facilities relying on send-out testing (50.8%). Similarly, facilities with reflex molecular testing protocols demonstrated higher NGS rates (75.4%) compared to those without reflex protocols (50.4%). Among patients with EGFR or ALK mutations, 77.8% received TKI therapy, with rates ranging from 0% to 100%. Of 113 early-stage patients, 32 (28.3%) had NGS performed pre-resection, 36 (34.0%) post-resection, and 40 (37.7%) did not have NGS performed. Across all sites, the median time from biopsy to NGS order was 29 days (IQR 20-49), from order to results was 13 days (IQR 11-18), and from biopsy to treatment initiation was 42 days (IQR 31-58). Smoking status was an independent predictor of NGS use with OR 0.28 (0.13-0.61, p = 0.002).

Conclusions
Significant variation exists in NGS adoption across hospital sites in a statewide quality improvement collaborative. However, turnaround times were consistent across sites. These benchmarking data, combined with qualitative insights, can inform quality improvement interventions for underperforming sites.

Competition Category: Quality Improvement

Mentor: Nisha Mohindra, MD

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Cade Bennett, BA

Student

Surgical outcomes for patients receiving neoadjuvant Imatinib for stage I-III gastric gastrointestinal stromal tumors
Introduction
Since 2007, neoadjuvant therapy (NAT) has been recommended for gastric GISTs to promote curative-intent resection, but large cohort analysis has not been sufficiently completed to understand its benefits. We aimed to characterize the benefits of NAT on resected gastric GISTs by retrospective analysis of a large database.

Methods
We used the 2020 National Cancer Database (NCDB) to identify patients with Stage I-III GISTs from 2006-2020 who received curative-intent surgical resection after NAT or with upfront surgery (UFS). Patient and tumor characteristics were quantified. Cohorts were propensity-score matched prior to multivariate regression. Cox proportional hazards model and Kaplan-Meier curves assessed time-based survival metrics after controlling for age, sex, ethnicity, Charleson-Deyo score, year of diagnosis, node status at surgery, tumor size, and surgery type.

Results
18,654 patients were identified, in which 1,504 received NAT (8.1%) and 17,150 received UFS (91.6%). Patients treated with NAT were younger (62.8 years vs 64.7 years) and more male (50.1% vs 47.5%). NAT was more frequently used for larger tumors (12.0 cm vs 6.4 cm, p<0.001), higher grading (p = 0.031), higher Charleson-Deyo comorbidity scores (p<0.001), and more multivisceral resections (p<0.001). Cox proportional hazards model revealed no difference in overall survival between NAT and UFS (UFS: HR=0.86, 95%CI=0.76-1.01, p=0.07).

Conclusions
Our propensity-matched models suggest that neoadjuvant therapy achieves similar outcomes to up-front surgery in the setting of Stage I-III gastric GISTs. However, its increased utilization in prognostically-worse tumors may indicate a benefit to downstaging tumors and improving R0 resection.

Competition Category: Health Services Outcomes or Clinical

Mentor: Akhil Chawla, MD

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Taylor Brown, BS

Student

Modulating Sympathetic Nerve Regeneration for Vascular Remodeling in Peripheral Vascular Grafts
Introduction
Vascular grafts used for revascularization fail at unacceptably high rates, often due to the phenotypic shift and resultant over-proliferation of vascular smooth muscle cells (VSMC). Growth and maturation of sympathetic nerves and contractile VSMCs are closely linked, yet sympathetic innervation as a modulator of vascular graft remodeling remains underexplored. The goal of this work is to design perivascular therapies that modulate sympathetic nerve regeneration around vascular grafts to promote healthy remodeling. We hypothesize that perivascular delivery of neurotrophic factors such as netrin-1 and artemin will lead to sympathetic nerve regeneration around vascular grafts.

Methods
Synthetic human aortic smooth muscle cells (HAoSMC) were treated with adrenergic agonists (norepinephrine and phenylephrine) at different concentrations for seven days. Immunocytochemistry and resazurin assays were used to study viability, morphology, and phenotype. VSMC-secreted guidance cues artemin (10 ng/mL) and netrin-1 (1 µg/mL) were mixed into fibrin gels (20 mg/mL, n=4 combinations) and implanted subcutaneously in Sprague-Dawley rats for two weeks (n=3 rats). Skin tissue was harvested for histology and immunofluorescence. For sustained delivery of neurotrophic factors, poly(lactic-co-glycolic acid) (PLGA, 50:50, Mw 7-17 kDa) microspheres were generated with a water/oil/water emulsion containing 50 mg/mL bovine serum albumin with or without 20 µg netrin-1. BCA assays were used to determine drug loading and encapsulation efficiency. Human umbilical vein endothelial cells (HUVECs) were cultured with netrin-1 and assessed with resazurin and live/dead assays to establish optimal netrin-1 dosage in future microspheres.

Results
HAoSMCs demonstrate dose-dependent responses to adrenergic agonists. Initial increases in proliferation (100 nM) are reversed at high doses (100 µM) of norepinephrine but not phenylephrine. Subcutaneous tissue of rats implanted with neurotrophic factors did not demonstrate swelling or irritation, and complete gel degradation was observed at two weeks. Regions of high nuclear density near the implantation site showed no notable changes in angiogenesis (CD31+), innervation (tyrosine hydroxylase+), and inflammation (CD68+) across groups. PLGA microspheres were generated with a maximum of 5% drug loading and 23% encapsulation efficiency. Release assays demonstrated burst protein release, so further optimization is needed. HUVECs survive up to 1 µg/mL netrin-1.

Conclusions
Both insufficient and excessive nerve signaling are pathogenic to arteries, so there is a need to develop vascular therapies that can induce an ideal level of nerve signaling around peripheral bypass grafts. This work supports the development of perivascular regenerative therapies that can be applied to any vascular graft to regenerate sympathetic nerves and promote favorable

Competition Category: Basic Science or Translational

Mentor: Bin Jiang, PhD

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Mariana Bustamante Eduardo, PhD

Fellow (Clinical or Postdoctoral Researcher)

Medium-chain fatty acid exposure in non-transformed mammary glands leads to pro-tumorigenic alterations associated with aging
Introduction
The local breast environment is a fruitful resource for identifying the etiological and biological factors that contribute to the development of breast cancer (BC). Using this resource, we identified a lipid metabolism gene signature associated with Estrogen Receptor negative BC (ERnegBC) risk. Exposure of non-transformed breast cells to fatty acid (FA) induces a metabolic shift toward the serine, one-carbon, glycine and methionine pathways, engendering epigenetic plasticity, increasing reactive oxygen species (ROS), and promoting cell survival. We hypothesize that this shift results in pro-tumorigenic alterations that facilitate carcinogenesis.

Methods
Non-transformed MCF-10A cells were exposed to the medium-chain FA octanoic acid (OA) for proteomics. Human breast tissue derived microstructures exposed to ± OA were utilized for single-cell RNA-seq analysis. Cell-cell communication was analyzed using CellChat and SCPA was used for pathway analysis. Breast microstructures embedded in Matrigel and 3D mammary spheres formed from luminal and basal cells at a 1:1 ratio and embedded in Matrigel were exposed to ± OA for 7 days, followed by staining for luminal and basal markers, F-actin, and nuclei, and imaged using confocal microscopy.

Results
Differential proteomics revealed downregulation of proteins involved in extracellular matrix (ECM)-receptor interaction and focal adhesion. OA exposure modulated gene expression of epithelial and non-epithelial subtypes. In epithelial subtypes, pathway analysis showed upregulation of terms related to senescence, signal transduction, DNA repair, and metabolism, along with downregulation of terms associated with cell-cell communication and ECM. Cell-cell communication analysis indicated increased secreted signaling. Among the strongest signals identified in OA were AREG (linked to proliferation, senescence, and invasiveness), GDF15 (related to EMT, invasion, lipolysis and aging), and MDK (involved in neurogenesis, cancer progression, and aging). Cell-cell communication analysis also revealed a decreased ECM-cell interactions following OA exposure, alongside reduced cell-cell adhesions. In line with these observations, ex vivo culture of microstructures and 3D mammary spheres revealed that OA exposure alters cell-cell adhesions, compromising the basal barrier and leading to luminal cell dissemination.

Conclusions
The proportion of breast adipocytes releasing free FAs increases with age. We show that FA exposure causes changes typical of the aged mammary gland, such as elevated ROS, epigenetic alterations, downregulation of cell-cell junctions, altered ECM-receptor interactions, and increased expression of MDK and GDF15. We propose that the relese of free FAs from an increased number of breast adipocytes, potentially due to elevated GDF15-induced lipolysis during aging, is a factor that induces mammary gland remodeling, increasing vulnerability to ERnegBC.

Competition Category: Basic Science or Translational

Mentor: Susan Clare, MD, PhD

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Ani Chandrabhatla, MD

Junior Resident (Clinical PGY1-2)

Impact of donor age and ischemic time on infections after lung transplantation: a focus on age-dependent ischemic susceptibility
Introduction
Respiratory infection is a common and morbid complication after lung transplantation. The impact of donor age and ischemic time on risk of post-lung transplant respiratory infection is unclear.

Methods
We studied adults who underwent lung transplantation at a single institution (1/2018-6/2023), excluding multiorgan transplants and re-transplants. Recipient and donor characteristics and pre-, intra-, and post-operative data were collected. Recipients were stratified by donor age (< or > 40 years) and ischemic time (< or > 5.5 hours). We chose 40 years of age as a cutoff for donor age as there is progressive lung function decline and breakdown of lung epithelial function starting in the fourth decade. A cutoff of 5.5 hours was used for ischemic time as this was the median lung ischemic time reported by the International Society for Heart and Lung Transplantation.

Results
Among 288 patients who met inclusion criteria, ischemic time >5.5 hours did not impact respiratory infection rates in the donor < 40 years group. In the >40 group, infection rate was 56.3% for ischemic time < 5.5 hours and 83.3% for ischemic time > 5.5 hours (p = 0.015). In multivariate logistic regression, recipient female sex (OR = 0.47, p = 0.012) and absence of smoking (OR = 0.54, p = 0.037) were associated with reduced infection risk in the donor < 40 group. Ischemic time > 5.5 hours (OR = 4.40, p = 0.018) was the only predictor of infection in the donor > 40 group and was also associated with worse infection-free survival (p = 0.030).

Conclusions
There is unique interplay between donor age, ischemic time, and risk of post-lung transplant respiratory infection. This may be due to decreases in lung function after the fourth decade of life and implies that a “one size fits all” strategy in assessing post-transplant infection risk may not be appropriate.

Competition Category: Health Services Outcomes or Clinical

Mentor: Chitaru Kurihara, MD

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Isabel Cohen, BS

Student

A population health analysis of statewide trends in lower extremity amputation secondary to diabetes and peripheral artery disease, 2016-2023
Introduction
Lower extremity (LE) amputation is a devastating consequence of diabetes mellitus (DM) and peripheral artery disease (PAD). Recent population-based trends in above knee (AK), below knee (BK) or through foot (TF) amputations have not been fully explored. This study analyzes amputation rates and inpatient outcomes for Illinois residents from 2016 to 2023.

Methods
Hospital admissions for AK, BK, and TF amputation for Illinois residents from 2016-2023 were identified from the Illinois Hospital Association COMPdata database. Patients < 34 years, with oncology or trauma-related diagnosis codes, or isolated toe amputations were excluded. Average annual amputation rates per 100,000 by age group, sex, race and ethnicity, and zip code household poverty levels were calculated using American Community Survey estimates.

Results
There were 30,834 amputation admissions from 193 Illinois hospitals, increasing 65% from 2016 to 2023. The average annual amputation rate per 100,000 increased from 38.6 in 2016 to 68.6 in 2023. The largest overall percent increases were for males (+76.1%) and non-Hispanic Black patients (+67.5%). Patients from <5% poverty level zip codes had the largest rate increase (69.1%) during the study period. Mortality (2.5% overall) was stable, however stays of over 20 days increased from 10% to 14.0% of admissions in 2023 (P<0.001).

Conclusions
Racial, socioeconomic, and gender disparities in amputation rates appear to be increasing despite reduced smoking and therapeutic improvements reflecting increasing DM and PAD prevalence. Health systems and community partners should emphasize aggressive prevention including screening, early diagnosis, and intensive risk factor management of DM and PAD.

Competition Category: Health Services Outcomes or Clinical

Mentor: Karen Ho, MD

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Lixuan Cong, MPP

Student

Work system analysis of determinants of interprofessional communication for shock etiology diagnosis: a qualitative analysis of clinicians' perspectives
Introduction
Nearly half of people with shock will die. Lack of agreement on shock etiology among clinicians has been associated with higher death rates. Effective interprofessional communication may facilitate agreement on shock diagnosis and reduce mortality. This study sought to define how components of the clinical work system (people, environments, tools, tasks) acted as determinants of interprofessional communication in diagnosing shock etiology.

Methods
We conducted a cross-sectional qualitative study using semi-structured interviews following a Critical Incident Technique in three United States hospitals (an urban academic, a suburban community, and rural community hospital). Interviews were audio recorded, transcribed verbatim and analyzed through reflexive thematic analysis guided by the System Engineering Initiative for Patient Safety model.

Results
Twenty-eight physicians, advanced practice providers, nurses, and pharmacists were interviewed between January and May 2024. The central theme was that clinicians worked across fragmented physical, socio-organizational, and digital environments to balance the urgency to diagnose and treat shock quickly with intermediate steps to reduce diagnostic uncertainty. Analysis generated four themes: 1) incorporating multiple clinicians' expertise while managing responsibilities among them, 2) fragmented digital, physical and socio-organizational environments inadequately reflected status of shock etiology diagnosis, 3) choosing tasks differently in response to uncertainty, 4) disagreement as productive and discouraging.

Conclusions
Synchronous interprofessional communication is needed to coordinate the task and people work system components by leveraging disagreement to build consensus and reduce uncertainty of shock etiology diagnosis across all environments.

Competition Category: Health Services Outcomes or Clinical

Mentor: Anne Stey, MD

Madison Cox, BS

Student

Ultra-Sensitive Detection of Mutant KRAS in Circulating Tumor DNA Predicts Survival in Resectable Pancreatic Adenocarcinoma
Introduction
The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene is mutated in over 90% of pancreatic adenocarcinoma (PDAC). These mutations are predominantly single-base missense variants, 98% of which are found at codon 12 (G12), codon 13 (G13), or codon 61 (Q61). Numerous studies have demonstrated the clinical utility of these KRAS mutations in PDAC, more recently employing liquid biopsy technology as a preferred method to analyze tumor mutations non-invasively. This study aimed to investigate the prognostic potential of pathogenic KRAS G12, G13, or Q61 mutations detected through circulating tumor DNA (ctDNA) analysis prior to treatment initiation using an ultra-sensitive liquid biopsy panel in resectable PDAC.

Methods
Plasma samples for patients at our institution with resectable disease at diagnosis were collected prior to chemotherapy start. This study cohort included 45 patients (median age 73; 42% male and 58% female; 86.7% Non-Hispanic White, 2.2% Non-Hispanic Black, 8.9% Hispanic White, 2.2% American Indian). At diagnosis, 68.8% had resectable disease (Stage IA-IIA), 15.6% had borderline resectable disease (Stage IIB), and 15.6% had locally advanced disease (Stage III). Among these, 38 patients received 3-12 cycles of neoadjuvant chemotherapy with modified FOLFIRINOX and/or Gemcitabine/Abraxane, 27 patients received 1-8 cycles of adjuvant chemotherapy, and 29 patients underwent upfront or interval surgery with Whipple procedure or distal pancreatectomy. Baseline ctDNA was analyzed for KRAS G12/G13/Q61 mutations using the PredicineCARE liquid biopsy assay (20,000x sequencing depth) and the PredicineCARE Ultra assay (>100,000x sequencing depth), providing full KRAS gene coverage.

Results
The PredicineCARE assay identified pathogenic KRAS mutations (G12/G13/Q61) in 11 patients. Of these, 8 had co-occurring G12 and Q61 mutations. Presence of any KRAS mutation determined by CARE assay at baseline was not significantly associated with overall survival (OS) (HR 2.96, 95% CI 0.85-10.29), however, detection of a G12 mutation in specific by CARE assay in baseline ctDNA was significantly predictive of worse OS (HR 4.93, 95% CI 1.39-17.44). Co-occurrence of KRAS G12 and Q61 mutations in baseline ctDNA was also predictive of worse OS (HR 3.89, 95% CI 1.12-13.54). The PredicineCARE Ultra assay identified KRAS mutations in 7 additional patients who were mutation-negative by the standard CARE assay, demonstrating a 46% improvement in detection compared to the standard assay. Baseline KRAS G12/G13 mutations detected with the Ultra assay were predictive of OS (HR 3.71, 95% CI 1.04-13.28), in addition to demonstrating 100% concordance with the standard assay results for overlapping mutations.

Conclusions
Ultra-sensitive liquid biopsy assays, such as the PredicineCARE Ultra panel, demonstrate robust detection of pertinent mutations that support improved prognostic stratification for patients with PDAC. These findings demonstrate the potential value of advanced liquid biopsy technology in guiding treatment decisions and improving outcomes in PDAC.

Competition Category: Basic Science or Translational

Mentor: Akhil Chawla, MD

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Zaiba Shafik Dawood, MD

Student

Role of Peptidylarginine Deiminase 2 in a Murine Model of Traumatic Brain Injury
Introduction
Traumatic brain injury (TBI) is among the leading causes of death and disability worldwide. Studies have linked Peptidylarginine deiminases (PADs) with TBI outcomes. However, nonspecific PAD inhibition makes it difficult to decipher the exact role of specific PAD enzymes in neurotrauma. Since both PAD2 and PAD4 have been linked with neurodegeneration, we sought to clearly establish their roles in TBI.

Methods
Male mice (11-14 weeks) were subjected to controlled cortical impact TBI (n=5/group). Experimental groups included wildtype (WT), PAD2 knockout (PAD2-KO), PAD4 knockout (PAD4-KO), and PAD2/4 double knockout (PAD2/4-DKO). 24 hours post-TBI, frozen brain-sections were stained (Nissl and immunofluorescence) to determine lesion size and expression of PAD2 and PAD4. We also assessed the impact of PAD2-KO on neurologic severity scores (NSS, 1-8 days post TBI) and visuospatial learning using the Morris water maze test (MWM, 21-30 days post TBI).

Results
Overall, PAD2-KO and PAD2/4-DKO displayed significantly smaller brain lesion sizes than WT (p= 0.005 and 0.005 respectively) and PAD4-KO (p= 0.005 and 0.004 respectively). However, there was no significant difference in lesion size between PAD4-KO and WT (p= 0.880). Analysis of archived snRNA-seq data and immunofluorescence staining 24 hours post-TBI showed upregulation of PAD2 (primarily in astrocytes) in WT compared with sham (P=0.048), whereas PAD4 was undetectable. Guided by these results, we compared the neurological outcomes of WT with PAD2-KO TBI mice. Overall, PAD2-KO had a significantly lower NSS on post-injury days 1, 5 and 6 compared with WT TBI mice (all P<0.05). Moreover, MWM demonstrated that the cumulative noncued spatial learning was worse in WT compared with PAD2-KO (p < 0.05).

Conclusion
Our results suggest that PAD2, but not PAD4, blockade can improve outcomes following TBI, which justifies its exploration as a potential therapeutic target. Conclusion: Our results suggest the role of PAD2, but not PAD4, as a potential therapeutic target for TBI management. Further efforts are warranted to elucidate downstream mechanisms of PAD2 in the central nervous system.

Competition Category: Basic Science or Translational

Mentor: Hasan Alam, MD

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Ashley Dodd, MD MS

Senior Resident (Clinical PGY3-5)

First-in-human pilot study of broadband optical spectroscopy as noninvasive surveillance for necrotizing enterocolitis
Introduction
Necrotizing enterocolitis (NEC) lacks predictive biomarkers and objective early diagnostic criteria. A transcutaneous noninvasive system for broadband optical spectroscopy (BOS) was previously demonstrated in a mouse model of NEC to have diagnostic specificity and early predictive power. Here, in continuation of the translational development, we report a first-in-human observational study in premature infants.

Methods
An apparatus for BOS in infants was assembled comprising a handheld probe with broad-spectrum light source coupled to a laboratory-grade spectrometer (ASD LabSpec 4, Malvern Panalytical), with detection range of 350-2500 nm. Inclusion criteria were premature neonates fewer than 36 weeks of gestation without congenital cardiac conditions or abdominal wall defects.

Results
One hundred infants were enrolled over a 3-year period in two large affiliated neonatal intensive care units. Daily four-quadrant abdominal measurements were obtained in under 2 minutes at the time of routine nursing care. Neither patient harm nor impediments to clinical treatment were noted. Reliable infrared reflectance signals of intra-abdominal intestine were acquired from infants of all skin tones. Ten infants developed Bell Stage 2 (moderate) or 3 (severe) NEC during the study and another four had a spontaneous intestinal perforation or other intra-abdominal process. At the time of NEC, BOS demonstrated noticeably different visible reflectance patterns compared to measurements taken from the same infants in usual state of health.

Conclusions
BOS is a feasible, noninvasive technology for point-of-care assessment of newborn intestinal ischemia. The presence of signal changes in premature infants under 2 kg with severe NEC suggests that BOS is promising as a viable modality of early detection.

Competition Category: Health Services Outcomes or Clinical

Mentor: Seth Goldstein, MD, MPhil

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Kacie Ford, BS

Student

Fecal microbiota transfer with stool from human IBD patients results in neuroinflammation and anxiety-like behavior in mice
Introduction
Inflammatory bowel disease (IBD) is a term that describes two disorders involving chronic inflammation of the gastrointestinal tract— Chron's Disease (CD) and Ulcerative Colitis (UC). Patients with IBD have a markedly increased incidence of anxiety and depression disorders resulting in loss in quality of life as well as complicating the clinical management of IBD. Our prior data demonstrates that restoring a normal gut microbial community structure attenuates neurocognitive loss in models of brain injury and aging. Therefore, we hypothesized that an IBD-associated gut microbial community structure would induce neuroinflammation and anxiety-like phenotypes in mice.

Methods
Stool was collected from CD and UC patients with an active disease flare as well as control stool from healthy donor patients. Fecal microbiota transplant (FMT) with IBD stool, healthy donor stool, or saline vehicle was performed via oral gavage into healthy naïve C57BL/6 male mice (14 weeks old, N=15/group) every other day for 5 days. On post gavage day 7 mice underwent neurocognitive testing with zero maze to assess anxiety-like behavior. On post gavage day 9 mice were sacrificed, brains harvested, and brain cytokines assessed via a Luminex-based assay. Data was analyzed using two-way ANOVA and Tukey's multiple comparison test.

Results
Stool from IBD patients with an active flare was markedly dysbiotic as compared to the stool from healthy donor patients (5.87 vs 6.45 shannon index, p<.05). At 7 days post gavage mice underwent zero maze testing. Mice that received IBD FMT spent significantly less time in the open area of the maze as compared to mice that received healthy donor FMT (13.90% vs. 24.03% time ± 3.52% time, p<.05). Lastly, we identified increased levels of IL2 (3.60 pg/mL vs. 2.36pg/mL ± .57pg/mL) and decreased levels of IL10 (4.68 pg/mL vs. 7.10 pg/mL ± .92 pg/mL, p<.05) within the brains of mice that received IBD FMT as compared to healthy donor stool FMT.

Conclusions
We hypothesized that an IBD-associated gut microbial community structure would induce neuroinflammation and an anxiety-like phenotype in mice. We found that FMT with stool from IBD patients with an active disease flare resulted in neuroinflammation as well as a significant anxiety-like phenotype in mice. These data suggest that IBD-induced alterations in the gut microbial community structure play a mechanistic role in the neuropsychiatric complications of inflammatory bowel disease.

Competition Category: Basic Science or Translational

Mentor: Steven Schwulst, MD, FACS, FCCM

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Emily George, MD

Junior Resident (Clinical PGY1-2)

Hypotelorism in Metopic Craniosynostosis: persistent undercorrection after open fronto-orbital advancement (FOA)
Introduction
Fronto-orbital advancement (FOA) surgery aims to normalize cranial vault parameters affected in Metopic Craniosynostosis. While FOA can normalize cranial shape and alleviate brain growth restriction, hypotelorism—characterized by a narrowed interdacryon distance—is not directly addressed with standard surgical techniques. This study aims to examine the changes in interdacryon distance, and other key parameters, following traditional open FOA.

Methods
After IRB approval, this single institution study evaluated 20 patients with metopic craniosynostosis undergoing FOA. Pre- and post-operative CT scans were evaluated by institutional radiologists who measured four key parameters: Interdacryon distance, Endocranial bifrontal angle, Inter-zygomaticofrontal suture (inter-ZF) distance, and Orbital rim angles. These measurements were compared before and after surgery for each patient, as well as against age matched controls with normal cranial morphology. Patients were stratified into two groups based on the time between the repair and post operative imaging: 0-13 months (one-year group) and 13-24 months (two-year group). Student's t-test was used to assess differences between the patient groups and their respective matched controls.

Results
The average age at the time of surgery was 212 days (7 months). Both groups exhibited a persistent undercorrection of interdacryon distance despite cranial vault repair (one-year group p <0.001; two-year group p= 0.0005). Post operatively, the one-year group exhibited an average interdacryon distance that was 4mm smaller than that of age-matched controls, while the two-year group demonstrated an average reduction of 3.6mm. Inter-ZF suture distance and right orbital rim angle were found to significantly increase following repair. Endocranial bifrontal angle and left orbital rim angle changes did not approach significance.

Conclusions
Open FOA, involving remodeling of the supraorbital bandeau and frontal bones, results in improvement but not complete correction of hypotelorism when re-evaluated at one and two years postoperatively. This suggests that intrinsic developmental factors may be contributing beyond premature suture fusion. The present study challenges the assumption that hypotelorism may spontaneously improve with growth after repair. These insights play a crucial role in informing clinical decisions and optimizing surgical plans to prevent the need for additional procedures to correct this persistent deformity.

Competition Category: Health Services Outcomes or Clinical

Mentor: Arun Gosain, MD

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Isabel Gippo, MPH

Student

Development of a quality improvement toolkit bundle to improve NGS testing in a lung cancercollaborative
Introduction
Next-generation sequencing (NGS) testing is used to identify driver mutations to inform delivery of targeted therapy in non-small cell lung cancer (NSCLC), which has been shown to increase overall survival. Timely identification of molecular targets and implementation of NGS testing are varied and not standardized across cancer programs. We aimed to develop a quality improvement (QI) toolkit bundle for hospitals in a statewide cancer collaborative to improve processes surrounding NGS testing in early-stage and metastatic NSCLC.

Methods
We previously performed a mixed-methods analysis across 10 academic and community hospitals in rural and urban settings participating in a statewide cancer collaborative to identify local practice patterns, barriers, and facilitators to NGS testing, as well as establish benchmarking of process measures for NGS testing rates and turnaround times. We used these data to develop primary and secondary drivers to inform resources in a QI toolkit bundle for the QI collaborative.

Results
From the quantitative arm of the mixed-methods analysis, we identified some cancer programs with lower uptake of NGS testing and higher turnaround times between initial biopsy of tissue to initial NGS order, with approximately half of patients receiving NGS testing following surgical resection for early-stage cases. From the qualitative arm of the mixed-methods analysis, we identified three primary drivers as key domains for QI interventions in NGS testing: (1) Patient Selection, (2) Biomarker Testing Options, and (3) Best Practices & Process Improvement. Secondary drivers to support each domain were subsequently developed, which included addressing guidance on patient selection, implementation of reflex testing protocols and practices around liquid biopsy as an adjunct to tissue-based testing, tissue collection protocols emphasizing conservation of tissue, augmented use of navigators to streamline clinician referrals, guidance on using multidisciplinary teams to drive local process improvement, generating benchmarking reports for site-specific areas of improvement, and enhancing automated patient sharing of data through EHR integration among clinical stakeholders. Evidence-based resources for each secondary driver were compiled into the QI toolkit bundle.

Conclusions
We developed a QI toolkit bundle in efforts to standardize timely NGS testing for NSCLC that was informed by baseline site-level data. We are presenting this toolkit bundle and site-level baseline data as part of ongoing site visits to guide cancer programs on developing targeted QI interventions to address local process improvement.

Competition Category: Quality Improvement

Mentor: Nisha Mohindra, MD

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Yinan Guo, MD

Fellow (Clinical or Postdoctoral Researcher)

Myd88-Areg axis in Regulating Host Responses to Vascularized Composite Allotransplantation
Introduction
The rejection of Vascularized Composite Allotransplantation (VCAs) is known for being a more complicated process compared to solid organ transplant. The inherent discrepancy of immunogenicity among tissues has led to a phenomenon named “split tolerance”. The skin component, where antigen presenting cells and high levels of glycoproteins, has been viewed as highly immunogenic. When subjected to ischemic injury, the inflammation of skin grafts would fuel the immune rejection. Myd88 signaling have been documented in ischemia reperfusion injury, chronic graft dysfunction and rejection of solid organ (kidney, heart and lung) and skin transplantation. It has also been found to dampen inflammation through Amphiregulin (Areg,). Areg, an EGF receptor ligands could also be induced in recipient regulatory T cells (Tregs), which would help reduce graft rejection and fibrosis. We sought to examine the role of Myd88-AREG axis in VCA.

Methods
Full MHC-mismatched hindlimb allografts procured from BALB/c mice were subjected prolonged cold ischemic storage (4 hours at 4°C UW) and then orthotopically transplanted onto wt C57BL6, Myd88-/- C57BL6 and Trif/Myd88-/- C57BL6 was performed. Graft survival was monitored and documented. Graft, spleen and lymph node were harvested at POD1 and POD7 in designated group. H&E staining, mRNA expression and flowcytometry was performed. Cellular infiltration and proinflammatory cytokines were evaluated.

Results
The median graft survival of wt C57BL6, Myd88-/- C57BL6 and Trif Myd88-/- C57BL6 were respectively 7d, 12d and 16d (Log-rank test p<0.0001). Additional limb transplants were harvested and examined at 7 day post-transplantation. H&E staining reveals a reduced leukocyte Infiltration in Myd88 KO allografts, compared to the WTs. In addition, phenotypic analysis shows decreased CD45 and CD8 T cells but increased Regulatory T cells in limb allografts of Myd88 ko mice. To interrogate whether Myd88 differentially regulates tissue specific rejection responses, RNAs were isolated from skins and skeletal muscles of the limb grafts at d1 and d7 were analyzed for cytokine/chemokines expression. MyD88-/- Recipients exhibit a decreased mRNA expression of proinflammatory cytokines (IL-6, TNF-a, CCL3 et al) in both skin and muscles at both timepoints. Interestingly, the Areg (Amphiregulin) and CCL22 were found to be elevated in graft skin but not muscles of MyD88-/- Recipients.

Conclusions
Recipient deficiency of Myd88 has significantly reduced inflammation and extended full MHC-mismatched hindlimb graft survival. The early graft protection is associated with increased influx of Tregs that corresponds with increased CCL22 and Areg in the skin of in Myd88-/- recipient, suggesting a role of Myd88 in regulating mediated differentiation and recruitment of Treg through CCL22 and Areg. Further studies are warranted to determine precise mechanisms and potential strategy that targets Myd88-Areg axis for the improvement of VCA outcome.

Competition Category: Basic Science or Translational

Mentor: Zheng Zhang, MD

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Nicola Habash, BS

Student

Role of the β-adrenergic system in regulating arterial calcification
Introduction
Arterial calcification is a hallmark of advanced vascular disease and contributes significantly to cardiovascular morbidity and mortality. A key feature of arterial calcification is the osteogenic differentiation of vascular smooth muscle cells (VSMC), which resembles bone formation. While β2-adrenergic receptor (β2-AR) signaling is known to regulate bone remodeling through calcium deposition, its role in vascular calcification remains poorly understood. Emerging evidence suggests that β2-AR signaling inhibits aortic valve calcification, but their involvement in VSMC osteogenic differentiation has not been defined. We hypothesize that β2-AR activation inhibits the osteogenic differentiation of VSMCs and prevents calcification.

Methods
Human aortic smooth muscle cells (HASMCs) were cultured in growth media or osteogenic media for 21 days to induce calcification, with or without treatment using β-AR ligands (β-AR agonists (1 μmol/L): salmeterol, isoproterenol, an antagonist (0.3 μmol/L): CGP-20712A, or an inverse agonist (0.3 μmol/L): ICI-118551). Calcification and phenotype were assessed through immunocytochemistry staining for β1-ARs, β2-ARs, the osteogenic marker osteopontin (OPN), and the contractile marker alpha-smooth muscle actin (αSMA). Alkaline phosphatase (ALP) activity was measured with an ALP enzyme assay.

Results
Osteogenic medium significantly increased ALP activity in HASMCs compared with growth medium, confirming calcification induction. Treatment with β-AR agonists salmeterol and isoproterenol both significantly reduced ALP activity relative to the osteogenic control (P < 0.05), suggesting a protective anti-calcific effect. The β1-antagonist CGP-20712A, applied alone, produced no significant change in ALP activity, while the β2-inverse agonist ICI-118551 showed ALP levels lower than those of the osteogenic control. Co-administration of CGP-20712A with either salmeterol or isoproterenol did not diminish the agonist-mediated reduction in ALP, indicating that β1 blockade does not interfere with the anti-calcific response. Likewise, combining ICI-118551 with either agonist failed to restore ALP to osteogenic levels, suggesting that inverse agonism at β2 does not negate the protective signaling elicited by salmeterol or isoproterenol under these conditions. β-agonist treatments preserved αSMA staining and reduced OPN expression. β2-AR staining remained strong after any β-agonist treatment, whereas β1-AR signal stayed low across all groups, including controls.

Conclusions
β-AR stimulation attenuates osteogenic differentiation of HASMCs, even in the presence of β1 blockade or β2 inverse agonism. These findings suggest a protective role for β2-AR signaling in vascular calcification, potentially via non-canonical or biased β2 signaling. Future studies should investigate downstream mechanisms, including cAMP signaling and functional contractility, to assess the therapeutic potential of β-AR modulation in vascular disease

Competition Category: Basic Science or Translational

Mentor: Bin Jiang, PhD

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Atieh Hajirahimkhan, PhD

Fellow (Clinical or Postdoctoral Researcher)

Reprogramming SREBP1-dependent metabolism and inflammation using licochalcone A for preventing breast cancer
Introduction
Breast cancer (BC) risk-reducing drugs have minimal impact due to their adverse effects and low acceptance. Novel non-endocrine agents with reduced toxicity and efficacy beyond HR+ BC are needed. We recently showed that in high-risk women's breast treated with licochalcone A (LicA) ex vivo, changes in metabolism flux led to reduced proliferation, NF-kB-dependent inflammation, and SREBP1-dependent lipogenesis. Additionally, LicA suppressed the proliferation of pre-malignant and malignant breast cell lines and their xenografts in mice. Now we present confirmatory evidence that LicA prevents BC by reducing SREBP1-dependent metabolism and inflammation. We also show the promising pharmacokinetic (PK) profiles of our novel oral formulations.

Methods
We performed NanoString metabolism panel assay in MDA-MB-231 (HR-) and MCF-7 (HR+) cells treated with LicA (10 µM, 24 h) and analyzed data by ROSALIND. We also conducted Proteome Integral Solubility Alteration (PISA) proteomics and Enrichr analysis to confirm transcriptomic data and the main targets of LicA. We validated the findings with western blots. In addition, we evaluated spatiotemporal changes in cholesterol concentrations in the inner leaflet of the plasma membrane. Five proprietary novel formulations of LicA were developed and administered orally and intravenously to female BALB/c mice and Sprague-Dawley rats followed by LC-MS/MS analysis of the plasma and mammary tissue, and PK modeling.

Results
We observed significant (adj P < 0.05) upregulation of anti-inflammatory genes and proteins (up to 9-fold) such as HMOX1, and downregulation (up to 6-fold) of NF-kB-dependent inflammatory pathways such as prostaglandin E2 synthesis. We also observed significant downregulation of SREBP1-dependent lipogenesis genes and proteings ACAT2, FASN, SCD, and proliferation marker MKI67. Proteomics results further revealed a reduction in neddylation responsible for stabilizing SREBP1, and a metabolic shift from lipogenesis to the degradation of fatty acids, branched amino acids, and enhanced TCA cycle. Western blots revealed significant suppression of SREBP1 (4-fold), and the reduced phosphorylation of PI3K (5-fold) and AKT (6-fold, at Ser 473). These results were confirmed by cholesterol depletion in the inner leaflet of the plasma membrane in HR- (8-fold) and HR+ (4-fold) cells to the levels observed in normal breast cells. Our novel oral formulation of LicA, L13 showed promising PK (Cmax ≈ 6 µM, T1/2 = 26 h) suitable for BC prevention efficacy.

Conclusions
Our data suggests that reprogramming SREBP1-dependent metabolism and inflammation by LicA prevents BC regardless of HR status. We will test L13 in immunocompetent models of BC to further establish its preventive efficacy.

Competition Category: Basic Science or Translational

Mentor: Seema Khan, MD, MS

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Hyebin Han, MS

Student

Fecal microbiota transplant with youthful stool increases cellular metabolism in microglia from aged mice post-TBI.
Introduction
Traumatic brain injury (TBI) affects nearly 3 million people annually in the United States, with patients aged 65 years and over suffering increased neurocognitive outcomes than younger individuals. Aging is associated with progressive gut dysbiosis, and our prior work showed that fecal microbiota transplant (FMT) can restore gut microbial composition and reduce neuroinflammation after TBI in adult mice. However, its therapeutic value in aged TBI subjects remains unclear. We hypothesized that restoring a youthful gut microbiota would attenuate microglial activation in aged mice after TBI.

Methods
Aged C57BL/6 male mice (84 weeks old) received severe TBI or sham injury via open-head controlled cortical impact. Two hours post-injury, mice received the first of five weekly FMTs from either young (10-14 weeks; ygFMT) or aged (80-84 weeks; agFMT) donor mice. Sixty days post-injury, brains were harvested for single-cell RNA sequencing (scRNAseq), using 10x Genomics platform. Data were processed with Cell Ranger and analyzed using Seurat v5.1. Differential gene expression (DE) and pathways analyses were performed using EnrichR. Differentially expressed genes (DEGs) were identified using the Wilcoxon Rank Sum test with log2FC ≥0.5 and Bonferroni-adjusted p-value ≤0.01.

Results
After filtering, 4,000-18,000 cells per group were recovered. Unsupervised clustering identified microglia based on the high P2ry12, Cx3cr1, and Tmem119 expression. DE analysis showed no clear attenuation of microglia activation with either FMT treatment post-TBI. However, comparison of sham-ygFMT vs sham-agFMT revealed 31 DEGs in sham-ygFMT, including Apoe, a lipid-metabolizing protein associated with neurodegeneration. Of these, 24 overlapped with 63 DEGs in TBI-ygFMT vs TBI-agFMT, many related to mitochondrial metabolism (e.g., Cox8a, Cox7a2, and Cox4i1). Pathway analysis confirmed strong enrichment for oxidative phosphorylation (OXPHO, including Mitochondrial Electron Transport (FDR q = 3.75 × 10⁻⁴ and 1.96 × 10⁻⁹ in sham- and TBI-ygFMT, respectively).

Conclusions
Contrary to our hypothesis, ygFMT did not attenuate microglial activation post-TBI in aged mice, unlike our prior findings in younger animals. Nonetheless, ygFMT enhanced mitochondrial metabolism, suggesting a shift from glycolysis (characteristic of disease-associated microglia) to OXPHO. Since aging increases the DAM signature, these findings suggest that youthful gut microbiota may help re-establish microglial homeostasis in aging. FMT may therefore have therapeutic potential beyond injury, including other age-related neurological conditions.

Competition Category: Basic Science or Translational

Mentor: Steven Schwulst, MD

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Carolyn Hu, BS

Student

Using Implementation Science to increase faculty engagement with Entrustable Professional Activities
Introduction
Previous studies have shown that that faculty may “buy-in” conceptually to the idea of Entrustable Professional Activities (EPAs) and yet may not enact the behavior of completing EPA evaluations. Implementation Science (IS) is the scientific study of methods and strategies that facilitate the uptake of evidence-based practice and research into regular use. To encourage or reinforce new behavior, it is important to identify intrinsic and extrinsic influences on Capability, Opportunity, and Motivation (COM-B model). The Theoretical Domains Framework (TDF) has previously been used to identify influences on health professional behavior related to implementation of evidence-based recommendations for patient care. This study used the TDF to characterize barriers and facilitators to faculty engagement with EPAs.

Methods
A survey instrument constructed using the TDF was administered to faculty that were actively engaged in the supervision and teaching of general surgery residents at three general surgery residency programs. Results from the faculty survey were used to identify the most common barriers and facilitators to faculty engagement with EPAs.

Results
Barriers and facilitators to engagement with EPAs varied by institution and individual faculty characteristics. Barriers to Capability, Opportunity and Motivation were all identified as factors that negatively impacted the behavior of EPA completion. Common Opportunity barriers to EPA completion were environmental context and environmental resources. Common Capability barriers to EPA completion were knowledge, memory and attention, and behavioral regulation. Common Motivation barriers to EPA completion were beliefs about consequences, professional role, optimism, and intentions.

Conclusions
The survey results provided insightful data on the barriers and facilitators impacting the completion of EPA assessments among faculty across the three institutions. There was a significant amount of similarity across institutions in multiple domains, though context-specific factors had high variability.
Analyzing the findings by domain, "Capability," particularly in terms of knowledge and skill scored highly, indicating a strong sense of competence among faculty. "Opportunity" emerged as a significant area of concern, particularly in the dimensions of context and resources. This suggests a perceived lack of supportive conditions and materials necessary for effective EPA completion. “Motivation”-related factors, including beliefs about consequences and reinforcement, showed moderate scores, highlighting inconsistency in how faculty members view the benefits of completing EPAs and their motivation to engage in this process. Future directions may include application of these findings toward designing targeted interventions that facilitate EPA uptake in general surgery education.

Competition Category: Education

Mentor: Rebecca Williams-Karnesky, MD PhD MEdPsych

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Saad Hussain, MBChB

Fellow (Clinical or Postdoctoral Researcher)

Frailty and decompensated cirrhosis are associated with significantly higher mortality independent of race and ethnicity
Introduction
Mortality is very high in patients with cirrhosis. We examine if mortality varies across different racial and ethnic groups.

Methods
A retrospective cohort study was performed using CAPriCORN, a large EHR data repository across 7 health care systems in a large US metropolitan area from 2016-2021. Demographics and clinical covariates examined incl. age, sex, race/ethnicity; (White, Black, Hispanic), urban/rural, etiology, insurance, Area Deprivation Index (ADI) [Q1: high resourced, Q5: low resourced), MELD 3.0, CCI, decompensated status, frailty (HFRS); [Low: HFRS <5, severe: HFRS >15]. Primary outcome was mortality rates reported per 100 patient-years (PY). Univariate and multivariate analyses were performed. Significance = P<0.05.

Results
18,718 patients with cirrhosis were included. Mean age was 59.8, 43.1% were women, 45% were White, 19% Black, 21% Hispanic, and 97% lived in urban areas. Most common etiologies were MASLD (28.6%), MetALD (23.1%), ALD (12.8%). 29.5% had Medicare, 27.8% Private, 22.3% Medicaid, 14.3% other insurance, 6.2% uninsured. ADI (Q1: 5.7%, Q2: 30.8%, Q3: 36.4%, Q4: 23.6%, Q5: 2.4%). Mean MELD was 16.3, CCI 6.79 and 29.7% were decompensated at inclusion. 54.1% patients had low frailty, 28.1% intermediate and 15.7% severe frailty. Mortality per 100 PY was 13.26 (White: 16.13, Black: 9.08, Hispanic: 8.86 per 100PY). Severe vs low frailty was associated with increased mortality (25.48 vs 10.22 per 100PY) and was consistently associated with 3x higher mortality across races/ethnicity (White: 306%, Black: 367%, Hispanic: 289% increase, respectively). Decompensated vs compensated cirrhosis was associated with increased mortality (21.35 vs 10.35 per 100PY) and decompensation was consistently associated with 2x higher mortality across races/ethnicity (White: 233%, Black: 251%, Hispanic: 183% increase, respectively).

Conclusions
Frailty and decompensated cirrhosis were associated with 3-fold and 2-fold increased mortality and was race/ethnicity agnostic.

Competition Category: Health Services Outcomes or Clinical

Mentor: Daniela Ladner, MD, MPH

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Ryan Jacobs, MD MS

Senior Resident (Clinical PGY3-5)

Association of lymph node sampling criteria on pathologic nodal upstaging, short-term recurrence-free survival, and overall survival in patients with non-small cell lung cancer
Introduction
General and lobe-specific lymph node sampling criteria have been proposed for intraoperative lymph node assessment during lung cancer resections to guide the need for adjuvant systemic therapy. Oncologic outcomes across lymph node sampling criteria have not been compared. This study evaluates the association of lymph node sampling criteria on pathologic nodal upstaging, recurrence-free survival, and overall survival for patients with non-small cell lung cancer (NSCLC).

Methods
We conducted a retrospective cohort analysis using institutional data for patients with Stage I-III NSCLC undergoing resection from 2018-2023. Patients were categorized into those meeting general sampling criteria per ACS Commission on Cancer (ACS CoC) guidelines, those meeting lobe-specific sampling criteria per European Society for Thoracic Surgeons (ESTS) guidelines, or meeting neither criteria. We performed multivariable logistic regression for evaluating pathologic nodal upstaging, multivariable Fine and Gray modeling for recurrence-free survival, and multivariable Cox modeling for overall survival across sampling criteria.

Results
Of 968 patients, 416 (43.0%) met general sampling criteria (ACS CoC), 125 (12.9%) met lobe-specific sampling criteria (ESTS), and 427 (44.1%) met neither sampling criteria. Clinical T1N0 NSCLC comprised 265 (63.7%) patients meeting ACS CoC criteria, 71 (56.8%) meeting ESTS criteria, and 315 (73.8%) meeting neither sampling criteria (p=0.002). Risk-adjusted rates of pathologic nodal upstaging for patients meeting ACS CoC criteria were 12.3% (95% CI 8.2-16.4%) , 10.0% (95% CI 5.2-14.9%) meeting ESTS criteria, and 6.8% (95% CI 4.6-8.9%) meeting neither criteria. Compared to patients meeting ACS CoC criteria, patients meeting ESTS criteria had no difference in adjusted odds of identifying pathologic nodal upstaging (aOR 0.77 95% CI [0.35-1.69]), but patients meeting neither sampling criteria had lower adjusted odds of identifying pathologic nodal upstaging (aOR 0.47 95% CI [0.23-0.99]). Compared to patients meeting ACS CoC criteria, no significant differences were observed between patients meeting ESTS criteria or neither criteria in recurrence-free survival (aSHR 0.48 95% CI [0.17-1.37], aSHR 0.79 [0.34-1.83]) or overall survival (aHR 0.62 95% CI [0.31-1.27], aHR 0.63 95% CI [0.36-1.11]).

Conclusions
Lobe-specific sampling criteria offers no difference in identifying pathologic nodal upstaging compared to a general lymph node sampling criteria, though both sampling criteria are associated with higher rates of identifying pathologic nodal upstaging compared to meeting no criteria. No differences in recurrence-free or overall survival were observed across sampling criteria. When considering dissemination of lymph node sampling guidelines, a general lymph node sampling strategy may be sufficient when considering optimizing

Competition Category: Health Services Outcomes or Clinical

Mentor: David Odell, MD, MMSc

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Shareni Jeyamogan, PhD

Fellow (Clinical or Postdoctoral Researcher)

PIRCHE, DRTC and CTLp are Directly Correlated with HLA Mismatch and may be Predictive of Rejection in Kidney Transplant Patients
Introduction
The relationships among HLA mismatch, cellular immune responses and transplant outcomes are not fully understood. Therefore, we investigated the combined predictive power of donor-reactive T cell (DRTC) frequency and PIRCHE (Predicted Indirectly ReCognizable HLA Epitopes) analyses for acute rejection in transplant recipients as well as the correlation between HLA mismatch and cytotoxic T lymphocyte (CTL) precursor frequencies.

Methods
DRTC were identified by pretransplant anti-donor mixed lymphocyte reaction (MLR) assay, followed by flow sorting of CFSE-diluting CD4+ and CD8+ responder T cells and TCR β-chain sequencing. PIRCHE analysis was performed using recipient and donor HLA typing. CTL-precursor frequencies were estimated using classic limiting dilution analysis.

Results
Increasing pretransplant DRTC and PIRCHE scores were observed in kidney transplant patients with increasing HLA mismatches (n=54). Elevated PIRCHE and CD8+ DRTC were associated with abnormal posttransplant biopsies. In addition, increased posttransplant CD8+ DRTC in peripheral blood and urine strongly suggested systemic cellular immune response in rejection in patients who received mainly Simulect induction (n=18). When teased out further in normals, CTLs even at the precursor levels demonstrated direct correlation with increasing HLA mismatches.

Conclusions
Taken together these results showed the direct relationship with HLA mismatches and CTL immune responses and consequent deleterious effects in the posttransplant period thus highlighting the need for careful pretransplant immune evaluations of the recipients against the donor.

Competition Category: Basic Science or Translational

Mentor: James Mathew, PhD

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Kevin Jin, BS

Student

Reperfusion lung injury after pulmonary thromboendarterectomy: Risk factors and outcomes
Reperfusion lung injury after pulmonary thromboendarterectomy: Risk factors and outcomes

Introduction
Reperfusion lung injury (RPLI) is one of the most common post-operative complications of pulmonary endarterectomy (PTE), the guideline-recommended treatment for Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Risk factors and long-term outcomes for RPLI following PTE are not well understood. Previous research has linked severe pulmonary hypertension (PH) before PTE and residual PH after PTE with RPLI. This study aims to identify patient factors predicting higher risk for RPLI.

Methods
A retrospective chart review was conducted on patients who underwent PTE at Northwestern Memorial Hospital from 2016-2024. RPLI was defined as radiographic infiltrates in the region of endarterectomized tissue and new oxygen requirement (saturation <88%) within 48-72 hours following PTE without alternative explanation. Significant risk factors and outcomes associated with RPLI were identified with multivariable linear and logistic regression comparing PTE patients with and without post-operative RPLI.

Results
Among 155 PTE patients, 19(12.2%) developed RPLI. Higher pre-operative pulmonary vascular resistance (PVR) (OR 1.17, p=0.004), right atrial pressure (RAP) (OR 1.11, p=0.016), and mean pulmonary arterial pressure (mPAP) (OR 1.08, p=0.001) were associated with increased odds of RPLI while higher cardiac output (CO) (OR 0.61, p=0.031) was associated with reduced odds. Patients with severe tricuspid regurgitation (TR) had increased odds (OR 4.85, p=0.012) for developing RPLI after PTE than patients with mild, moderate, or no TR. Procedural differences associated with RPLI included longer cross-clamp time (OR 1.02, p=0.023), total circulatory arrest time (OR 1.04, p=0.025), and right-side circulatory arrest time (OR 1.05, p=0.043). Perioperative outcomes associated with RPLI included unplanned reoperation within 30 days (OR 7.22, p=0.002) and hospital/ventilator-associated pneumonia (OR 5.38, p=0.003). The RPLI group had longer ICU stays (+8.5 days, p=0.001), longer mechanical ventilatory support duration (8.7 days, p<0.001), and higher POD1 mPAP (+8.5 mmHg, p=0.001) relative to the non-RPLI group. Survival at 1 and 3 years was 95% in the RPLI group compared to 97% and 95% in the non-RPLI group, respectively. At 3-month follow-up, patients with RPLI had higher PVR (+2.4 WU, p<0.001) and mPAP (+8.9 mmHg, p=0.002) compared to those without RPLI.

Conclusions
CTEPH patients with high PVR, high mPAP, low CO, and severe TR seem to be at increased risk of RPLI following PTE. Following RPLI, patients experience increased rates of unplanned reoperation, pneumonia, increased ICU stays, and a lower rate of hemodynamic improvement after 3 months. However, survival rates were not significantly different.

Competition Category: Health Services Outcomes or Clinical

Mentor: Stephen Chiu, MD

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Michael Kemp, MD

Fellow (Clinical or Postdoctoral Researcher)

Transfemoral technique for thoracoabdominal multibranch endoprosthesis placement
Introduction
The thoracoabdominal multibranch endoprosthesis (TAMBE) is the first FDA-approved off-the-shelf option for thoracoabdominal endovascular aortic repair. While upper extremity access is mandatory per the instructions for use, a total transfemoral approach is feasible in cases of unfavorable arch anatomy or hostile upper extremity access. This case highlights our transfemoral technique using co-axial steerable sheaths.

Case study
A 68-year-old male smoker with hypertension and a known 4.0 cm ascending aortic aneurysm underwent surveillance imaging that revealed a 7.4 cm extent II thoracoabdominal aortic aneurysm. The patient was not an open surgery candidate due to his age and comorbid conditions. He was asymptomatic and was offered a staged endovascular repair. The first stage included a thoracic branch endoprosthesis (TBE) and TEVAR (Zones 2-5) to manage the distal arch and pre-condition the lumbar arteries to reduce spinal cord ischemia risk. The second stage utilized the GORE TAMBE device to complete the repair into the abdominal aorta (Zones 5-9). Due to a Type III aortic arch, and his TBE in place, bilateral femoral access was favored over upper extremity access. The 37 mm TAMBE endograft was fully deployed and molded proximally with a trilobe balloon. An 8.5-Fr steerable sheath was advanced through the large bore sheath above the branch vessel portals, retroflexed, and stabilized with a through-and-through 0.018” wire that was snared and exteriorized ipsilaterally to maintain directional control for bridging stent placement. The target arteries were sequentially cannulated and VBX stents were placed. Lastly the repair was extended distally to the aortic bifurcation. The procedure was completed in approximately 4 hours without complications. The patient was discharged on postoperative day 1. At three-month follow-up, he remains asymptomatic, with successful aneurysm exclusion, patent visceral and renal branches, and stable maximum aortic diameter.

Conclusion
Total transfemoral access using steerable sheaths enables branch vessel cannulation and is a feasible alternative to upper extremity access for TAMBE deployment.

Competition Category: Health Services Outcomes or Clinical

Mentor: Neel Mansukhani, MD

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Daniel Liesman, MD

Fellow (Clinical or Postdoctoral Researcher)

Novel maternal plasma micro-RNA signal diagnoses and risk stratifies congenital diaphragmatic hernia

Introduction
Congenital Diaphragmatic Hernia (CDH) is characterized by a wide range of severity. Although imaging studies are used for CDH risk stratification and prenatal therapy, these modalities remain limited in their prediction of the severity of the disease postnatally. miRNA has been useful in other prenatally diagnosed conditions including Twin-Twin Transfusion Syndrome for risk stratification. Furthermore, it has been shown to be differentially expressed in amniotic fluid in pregnancies with severe CDH suggesting their utility in risk stratification. We hypothesized that patients carrying fetuses with CDH would display a unique miRNA profile detectable within maternal plasma that can be used to diagnose and risk stratify the disease

Methods
Patients carrying fetuses with CDH (n = 20) and heathy singleton pregnancies (n = 8) were consented for peripheral blood collection. Twin gestation and those with significant cardiac or genetic anomalies were excluded. Whole genome miRNA-seq was performed. Subgroup analysis included clinical factors associated with disease severity (e.g., liver up versus down, pulmonary hypertension, type of repair, death, etc.) to determine if miRNA were correlated with disease severity.

Results
There were 628 miRNAs that remained after quality control with 17 differentially expressed including miR-210-3p, miR-30d-5p, and miR-92a-3p, all previously implicated in CDH or pulmonary hypertension. Subgroup analysis revealed further dysregulation in high-risk CDH patients with distinct clustering of severe and mild patients on a PCA plot. There were 10 miRNAs dysregulated across three or more markers of clinical severity including let-7c, miR-30d, and miR-98, miRNA that have previously been associated with disease pathogenesis of pulmonary hypertension severity in either animal models or other human samples. Gene target prediction identified interactions with VEGF and other genes relevant to CDH pathogenesis. Pathway analysis revealed distinct biological pathways contributing to CDH severity.

Conclusions
These results are the first to find that maternal plasma miRNA can differentiate pregnancies with CDH from those carrying healthy fetuses. Furthermore, our findings indicate that maternal plasma miRNA can potentially predict severity of disease prenatally. This suggests that maternal plasma miRNA during pregnancy may be used to diagnose and risk stratify CDH. A larger sample size and validation cohort is now prudent.


Competition Category: Basic Science or Translational

Mentor: Amir Alhajjat, MD

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Marjorie Liggett, MD

Senior Resident (Clinical PGY3-5)

Prolonged Partial Aortic Occlusion Worsens Neurologic Outcomes Without Affecting Brain Lesion Size in a Swine Model of TBI and Hemorrhage
Introduction
Traumatic brain injury (TBI) and hemorrhagic shock are the leading causes of death in trauma. The partially occluding resuscitative endovascular balloon occlusion of the aorta device (p-REBOA) has emerged as a tool for hemorrhage control with reduced ischemic consequences, allowing for prolonged use. Prior studies in swine show no increase in brain lesion size with prolonged p-REBOA use, but long-term neurologic outcomes remain unknown. We hypothesized that prolonged p-REBOA deployment would worsen neurological outcomes.

Methods
Female Yorkshire swine (n=5/group; 37-42 kg) were subjected to a controlled cortical impact plus right common iliac artery injury and randomized to either: 1) p-REBOA for two hours (p-REBOA group) followed by vascular repair, or 2) immediate vascular repair with no p-REBOA for 2-hours (control). Daily neurologic severity scores [NSS; 0 (normal)-32 (comatose)]), and brain lesion size on day 3 were compared.

Results
Blood loss, resuscitation, and physiologic parameters were similar between both the groups. While the brain lesion size did not differ between the two groups (p= 0.55), NSS were significantly worse in the p-REBOA group compared to controls (*, p=0.048 at 48 hours and **, p=0.006 at 72 hours, respectively).

Conclusion
This is the first study to show that prolonged p-REBOA is associated with worse neurologic outcomes, independent of the brain lesion size.

Competition Category: Basic Science or Translational

Mentor: Hasan Alam, MD

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Lara Lopes, MD, MS

Senior Resident (Clinical PGY3-5)

The impact of frailty on enhanced recovery pathway compliance and postoperative outcomes after infrainguinal arterial bypass
Introduction
Enhanced recovery pathways (ERP) protocols in vascular surgery remain scarce, partly due to the high frailty and multiple comorbidities of vascular surgery patients, which require tailored perioperative care that may not align with standardized ERP elements. The aim of this study was to evaluate the impact of frailty on the adherence to ERP and ERP's association with adverse postoperative outcomes in frail patients undergoing infra-inguinal arterial bypass (IB).

Methods
We performed a retrospective study of all patients undergoing IB between 2021 and 2024 at a single institution. Patients were categorized in 3 groups based on their level of frailty (F1 = 0-1 risk factor; F2 = 2 risk factors; F3 = 3-5 risk factors) using the NSQIP 5-item frailty index and the association between frailty and compliance with ERP was analyzed. The association of frailty with adverse postoperative outcomes with and without ERP was analyzed. Chi-square and Fisher's exact tests were used for categorical variables while continuous variables were analyzed by Kruskal-Wallis test.

Results
A total of 257 patients were identified, of which 89 (34.6%) were F1, 88 (34.2%) were F2 and 80 (31.1%) were F3. The F1 patients (p50=66.0 years) were significantly younger than F2 (p50=70.8 years; p=0.0014) and F3 patients (p50=71.3 years; p=0.0002) and less likely to present with tissue loss (F1=31.5%; F2=47.7%; F3=62.5%; p=0.000). ERP compliance was not associated with frailty group (F1=60.3%; F2=51.8%; F3=62.1%; p=0.476). Within the F3 cohort, ERP was associated with significantly lower in-hospital reintervention rate (ERP= 14.6% vs. Non-ERP=33.3%; p=0.044); lower postoperative length of stay (ERP=7.9 days vs. Non-ERP=9.7 days, p=0.0592); and 30-day mortality (ERP=2.4% vs. Non-ERP=7.7%;p=0.289).

Conclusions
In our study, high frailty was not a barrier to the implementation of ERP and ERP was associated with improved postoperative outcomes in highly frail patients.

Competition Category: Health Services Outcomes or Clinical

Mentor: Ashley Vavra, MD MS

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Krishnaraju Madavaraju, PhD

Fellow (Clinical or Postdoctoral Researcher)

Preventing Connexin 43 Loss in Endothelial Gap Junctions During Ischemia-Reperfusion: A Translational Strategy for Allograft Survival
Introduction
Cardiac transplantation remains the primary therapy for end-stage heart failure patients. However, ischemia-reperfusion injury (IRI) during organ transplantation primes the donor heart immunologically, leading to potential alloimmune rejection and eventual graft failure. Endothelial cells (ECs) lining the blood vessels of donor organs are particularly vulnerable to IRI, with compromised EC barriers triggering alloimmune responses. Connexin 43 (Cx43), a gap junction (GJ) protein, plays a crucial role in regulating EC barrier function, but its specific role in IRI within the context of heart transplantation remains incompletely understood. Hypothesis: This study aimed to investigate whether incorporating the aCT1 peptide during cold storage enhances Cx43 gap junction expression and improves endothelial cell barrier integrity in donor hearts.

Results
Our findings indicate that Mouse Cardiac Endothelial Cells (MCECs) when subjected to ischemic cold storage (CS) with University of Wisconsin (UW) preservation solution exhibit reduced Cx43 gap junction (GJ) expression. Under CS with re-warming (WR) conditions, Cx43 GJ expression is compromised, potentially due to altered Cx43 trafficking to the cell membrane. MCECs exposed to CS-WR conditions demonstrate decreased GJ activity and compromised EC barrier function. However, our experiments demonstrate that pre-treatment of MCECs with the aCT1 peptide during CS improves Cx43 GJ expression, preserves EC barrier integrity, and enhances overall EC health. Moreover, preconditioning murine donor cardiac allografts with aCT1 peptide during CS significantly improves microvascular permeability and mitigates IRI post-heart transplantation (HTx).

Conclusions
In summary, cold storage during cardiac transplantation reduces Cx43 gap junction expression in MCECs. However, the addition of the aCT1 peptide during cold storage effectively enhances Cx43 gap junction expression and preserves endothelial cell barrier integrity. These findings underscore the potential of aCT1 peptide as a therapeutic strategy to mitigate ischemia-reperfusion injury and improve outcomes in heart transplantation.

Competition Category: Basic Science or Translational

Mentor: Satish Nadig, MD PhD FACS

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Natalia Matiuto, BS

Student

Mitochondrial transplantation to attenuate endothelial dysfunction in diabetes mellitus
Introduction
Endothelial dysfunction is a hallmark of diabetes mellitus, driven by mitochondrial dysfunction and leading to vascular complications, such as impaired wound healing. Mitochondrial transplantation emerges as a promising strategy to address the underlying mitochondrial deficits, laying at the foundation. In this study, we aim to investigate the efficacy of mitochondrial transplantation in restoring the function of endothelial cells isolated from diabetic patients and in mouse wound model, providing insights into novel therapeutic interventions for diabetic vasculopathy.

Methods
Mesenchymal stem cells (MSCs) were differentiated from induced pluripotent stem cells and transduced with Mitochondria Cyto-Tracer (Mito-GFP) to serve as mitochondria donors. GFP+ MSCs were selected and subsequently co-cultured with pre-seeded diabetic human arterial endothelial cells (DHAECs) at varying ratios (0:1, 1:1, 2:1, 4:1, and 9:1) for 72 hours and imaged with fluorescence microscopy. Additionally, DHAECs were treated with freshly isolated Mito-GFP-labeled mitochondria at concentrations of 1µg of mitochondrial protein in a storage buffer per 5000 cells for 24 hours, after which the media was changed, and cells were further visualized using fluorescence microscopy. Flow cytometry was used to quantify mitochondrial transfer efficiency. Functional assessment of DHAECs post-transplantation was assessed with Seahorse assay and JC-1 staining for mitochondrial respiratory function and membrane potential. All measurements were taken in triplicates and treatment groups were compared to controls with two-sample t-test (significance p<0.05). For in vivo proof-of-concept study, two 6mm full thickness wounds were created on male C57BL/6 mice. Mitochondria were delivered in MMP-degradable PEG gel; ‘empty' gel was used as vehicle control. Wound healing and mitochondria distribution at 1-3-7 days were assessed.

Results
Fluorescent microscopy of cocultured cells revealed colocalization of CD31+ DHAECs containing GFP+ mitochondria, indicating successful mitochondrial transfer. Flow cytometry demonstrated mitochondrial transfer efficiency up to 30.03% which increased with increasing ratio of MSCs to DHAECs. In an isolated-mitochondria-treated group, exogenous mitochondria were observed in recipient DHAECs up to 4 days post-media change. Mitochondria treatment for 24 hours led to an increased respiration (p<0.05) and mitochondria membrane potential measured at three days post-removal, indicating improved mitochondria health. Animal studies are pending assessment.

Conclusions
Our study demonstrates the feasibility of mitochondrial transfer from MSCs to diabetic endothelial cells, highlighting the potential of this approach as a therapeutic strategy for mitigating endothelial dysfunction in diabetes. Further research will assess mitochondria delivery for promoting angiogenesis in a diabetic wound healing model.

Competition Category: Basic Science or Translational

Mentor: Bin Jiang, PhD

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Ben Mazurek, BS

Student

Residual pulmonary hypertension after pulmonary thromboendarterectomy and its effects on functional status
Introduction
Pulmonary thromboendarterectomy (PTE) is the gold standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH). While PTEs are associated with improved long-term survival, residual pulmonary hypertension (PH) can negate that effect. Little is known about residual PH and its effects on functional status.

Methods
From 2016-2024, patients with CTEPH were entered into an institutional database. Demographics, hemodynamics, echocardiography, and six-minute walk distance (6MWD) results were tracked preoperatively and postoperatively at 1 month, 3 months, and 1 year. Statistical analysis was performed using R (ANOVA, Kruskal-Wallis, and pairwise Wilcoxon tests).

Results
During the study period, 152 patients underwent PTE. 131 patients with complete hemodynamic data were divided into four quartiles based on residual mPAP at 3 months after PTE: < 20 mmHg, 20-26 mmHg, 26-38 mmHg, and > 38 mmHg. The four quartiles differed in age, weight, BMI, and preoperative mPAP (p = 0.01, 0.04, 0.04, < 0.001). Higher residual mPAP and PVR were associated with higher preoperative mPAP and PVR. The change in mPAP from baseline was highest in the bottom two quartiles at -19, -20, -10, and -2 mmHg, respectively. Preoperatively and postoperatively at 1 month, 3 months, and 1 year (p = 0.008, 0.03, 0.03, 0.12), the quartiles with higher residual mPAP had worse 6MWD; however, the change from baseline 6MWD between the four quartiles at all time points was similar (p = 0.59, 0.41, 0.16). Additionally, there were no significant differences in the proportion of patients with NYHA class III/IV symptoms across the four quartiles either preoperatively (p = 0.56) or postoperatively (p = 0.28). The median change of all four quartiles was a decrease in one NYHA class. There were no significant differences in PH medication use between quartiles either preoperatively (p = 0.15) or at 1 year (p = 0.20).

Conclusions
All patients across levels of residual PH experienced symptomatic benefit in comparison to baseline after PTE, however those with the highest degree of residual PH had worse functional status in terms of 6MWD than those without residual PH. Despite differences in residual mPAP, there were no significant differences in NYHA class distribution postoperatively, suggesting that symptomatic recovery may not correlate linearly with follow-up pulmonary pressures.

Competition Category: Health Services Outcomes or Clinical

Mentor: Stephen Chiu, MD

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Bradley Melnick, BS

Student

The role of nasal aesthetics in visual attention and facial attractiveness: an eye-tracking investigation
Introduction
Facial attractiveness significantly influences social perception. While prior studies identify the eyes and mouth as primary focal points of attention, the role of nasal aesthetics in overall facial attractiveness remains unclear. This study examines the relationship between nose shape, perceived attractiveness, and visual attention using eye-tracking technology.

Methods
Thirty-four models (mean age 38) and 31 observers (mean age 33) participated. Models underwent standardized 2D/3D imaging, and 17 anthropometric facial measurements were recorded. Observers viewed these images on an eye-tracker, recording fixation durations and revisit counts for the eyes, nose, and mouth. Observers also rated facial and nasal attractiveness using a 10-point visual analog scale. Gaze metrics were analyzed in relation to attractiveness ratings and anthropometric measurements.

Results
Models with unattractive noses received significantly more visual attention on the nose and mouth (total fixation duration (TFD): nose 0.81±0.14s vs. 0.72±0.12s, P=0.03; mouth 0.65±0.13s vs. 0.54±0.07s, P=0.03). Conversely, attractive noses permitted more visual attention on the eyes (TFD: 1.92±0.15s vs. 1.69±0.27s, P=0.02). Nasal tip deviation (P=0.01) and longer upper lips (P=0.05) correlated with lower attractiveness ratings, while traditional neoclassical canons and nasal width had limited impact (P>0.05).

Conclusions
Attractive noses enhance facial harmony by reducing visual attention on themselves, allowing gaze to focus on dominant features like the eyes. These findings highlight the importance of holistic facial assessments over isolated nasal evaluations during rhinoplasty consults. Future research should incorporate dynamic facial stimuli and diverse observer populations to further refine our understanding of nasal aesthetic perceptions.

Competition Category: Health Services Outcomes or Clinical

Mentor: Robert Galiano, MD FACS

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Bilal Khan Mohammed, MBBS,MD

Fellow (Clinical or Postdoctoral Researcher)

Multiple monocyte subtypes contribute to thrombus resolution and vein wall fibrosis in a murine model of deep vein thrombosis
Introduction
Deep vein thrombosis (DVT) and pulmonary embolism (PE) are life-threatening with the potential for significant long-term morbidity and mortality, including the development of chronic thromboembolic pulmonary hypertension (CTEPH). The nuclear receptor NR4A1 is a transcription factor required for the development of non-classical monocytes. CCR2 is a chemokine receptor necessary for the mobilization of classical monocytes into the bloodstream from their reservoirs. Here, we seek to understand the relative contributions of each monocyte subtype, classical and non-classical, to the formation of thrombus and its resolution.

Methods
We employed a partial inferior vena cava (IVC) ligation model in C57BL/6 (B6), CCR2 knockout (CCR2-KO), and NR4A1 knockout (NR4A1-KO) mice. Thrombus weights (including the vein wall) were measured at Days 1, 2, 7, and 14 post-ligation. Masson's Trichrome staining was used to quantify fibrosis in the specimen.

Results
Both CCR2-KO and NR4A1-KO mice showed accelerated robust thrombus formation at day 1 post-ligation in comparison to B6 controls. At subsequent time points, compared to B6 controls, both CCR2-KO and NR4A1-KO mice demonstrated impaired thrombus resolution, with elevated thrombus weights persisting through Day 14. B6 mice showed a ~60% decrease in thrombus weight between Days 2 and 14, while NR4A1-KO and CCR2-KO mice exhibited only ~47% and 33% reductions, respectively (p<0.05). NR4A1-KO mice showed progressive collagen accumulation, with a 1.8-fold increase in fibrosis compared to B6 at Day 14 (p<0.001).

Conclusions
Both non-classical and classical monocyte subtypes appear to play dynamic roles in the formation and resolution of acute thrombus. Genetic deletion of NR4A1 appears to aggravate the fibrotic response to thrombus, implying that nonclassical monocytes may play an anti-fibrotic role in the pathogenesis of post-thrombotic vein wall thrombosis and CTEPH.

Competition Category: Basic Science or Translational

Mentor: Stephen F Chiu, MD

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Bilal Naved, PhD

Fellow (Clinical or Postdoctoral Researcher)

Revealing gait as a murine biomarker of injury, disease, and age with multivariate statistics and machine learning
Introduction
According to a PubMed search, hundreds of rodent gait studies have been published over the past two decades. Treadmill gait data, for example from the DigiGait system, generates over 30+ spatial and temporal measures. Despite this multi-dimensional data, all but a handful of the published literature on rodent gait has conducted univariate analysis that reveals limited information on the relationships that are characteristic of different gait states. This study conducted rigorous multivariate analysis in the form of sequential feature selection and factor analysis on gait data from a variety of gait deviations (due to injury i.e. peripheral nerve transection and transplantation, disease i.e. IUGR and hyperoxia, and age-related changes) and used machine learning to train a classifier to distinguish between and score different gait states.

Methods
Treadmill gait data (DigiGait) of three different types of gait deviations was collected. Data was collected from B6 mice using the DigiGait system, with gait measurements taken at standardized treadmill speeds of 10, 17, and 24 cm/s over a period of 3-4 seconds per observation. Each mouse underwent at least two trials at each speed. Data was collected on B6 mice that were healthy and had various types of gait deficit due to: (a) a peripheral nerve injury model with increasing degrees damage to the neuromusculoskeletal sequence of gait i.e. nerve transection, total hind limb transplantation, (b) a central nerve injury model of increasing degrees of damage to the motor regions responsible for gait i.e. IUGR, IUGR + hyperoxia, and (c) gait changes due to increasing age. Multivariate factor analysis (using MATLAB's factoran) and forward feature selection (with ten-fold cross-validation) was conducted to identify those features and factors most descriptive of each gait state for comparison. Various machine learning classifier models were trained with ten-fold cross-validation and evaluated (e.g. random forest, regression, discriminant analysis, support vector machine, and ensemble) in a 70-30 training-testing split for their accuracy, precision, recall, and F-score. The highest performing model was used to score each type of gait for direct comparison on a scale of -0.5 to 0.5. The score distributions were plotted on a histogram for direct comparisons of score populations between various gait states.

Results
Multivariate feature selection revealed that not all 30+ features were relevant to describing the gait states. Plotting misclassification error (MCE) as a function of number of features included revealed that there was a critical number of features (~16) that minimized MCE (0.17 via univariate feature selection vs. 0.12 via multivariate feature selection). Incorporating more than 16 features led MCE to increase linearly indicating overfitting. Relationships between the identified features were understood via factor analysis. The factor analysis results were consistent with the biological differences between the groups (e.g. total hind limb transplantation was distinguishable via features descriptive of the positioning of the paw in relation to the body while nerve transection injury alone was distinguishable via features descriptive of changes to fine motor movements). Across all gait states, there was significant conservation of features and factors. This suggests certain relationships may be fundamental to rodent gait analysis regardless of the gait pathology in question. The highest performing machine learning classifier model (ensemble) was able to distinguish between gait deficits with high performance (F-score, recall, precision, and accuracy all >0.90). This included the ability to distinguish between peripheral vs. central gait deficit, between individual types of peripheral deficit, between individual types of central deficit, and between younger vs. older animals. Using the classifier to score individual animals and plot the scores by group revealed score distributions that were consistent with biological phenomena. For example, the multivariate gait score trends as a result of increasing central nerve injury were consistent with the trends of white matter volume loss in relevant motor regions of the brain as measured via MRI. Finally, the degrees of separation between multivariate gait scores were consistent with the degree of biological difference between gaits (e.g. central injury had greater separation from healthy vs. peripheral injury; older and younger animals had more moderate, yet still statistically significant, separation in scores vs. any of the injury / disease states did with each other).

Conclusion
In conclusion, this study establishes a new methodology to quantify and evaluate gait deviations across a variety of different models. Its novelty is in using multivariate statistics to describe the features and factors that characterize gait states due to injury, disease, and age for use in machine learning model training. This includes statistically describing the differences in gait between diseases with vastly different etiologies of gait deficits (peripheral vs. central). In doing so the methodology's novelty includes accounting for relationships between groupings of features in model training; something that traditional univariate analysis is unable to. It used multivariate statistics and machine learning to reveal gait as a quantifiable, preclinical biomarker of injury, disease, and age. It collapsed a multi-dimensional biological phenomena (gait) into a single score by encoding revealed biological relationships allowing for direct, quantifiable comparisons of function as it pertains to ambulation. It revealed how these multivariate gait scores can visualize biologically consistent separation and combined effects. Finally, we demonstrate the application of this methodology to already published univariate study that is representative of the hundreds of univariate treadmill gait analysis published over the last two decades. Thereby, opening the door to a new class of multivariate gait analyses that provides greater insight and value than the current state-of-the art.

Competition Category: Basic Science or Translational

Mentor: Zheng Zhang, MD

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Joy Obayemi, MD MS

Senior Resident (Clinical PGY3-5)

Examining the patient experience of a novel African American transplant access program: a qualitative study
Introduction
Black Americans are almost four times more likely to develop end-stage kidney disease (ESKD) than White Americans. However, they remain underrepresented on the kidney transplant waiting list due to well-documented structural barriers. To address this need, an African American Transplant Access Program (AATAP) was created at a large metropolitan transplant center. However, details about the patient experience of this novel program have not yet been described. Thus, we aimed to understand the experiences and perceptions of AATAP from the patient perspective.

Methods
From July-December 2024, we conducted one-on-one semi-structured interviews with patients currently and previously enrolled in AATAP to explore their experiences with the program. Random purposive sampling was used to recruit patients who were in evaluation, waitlisted, and transplanted. Inductive coding was performed using two independent coders (JO,AF). Data analysis using interpretive description is ongoing and includes coding, thematic reports, and iterative discussions of meanings. The socio-ecological framework was used to organize emergent themes.

Results
We interviewed 45 African American patients. 55.6% were male (n=25) and most developed ESKD from diabetes (n=18, 40.0%) and/or hypertension (n=20, 44.4%). Seven prominent themes have emerged within three socio-ecological domains: the individual, interpersonal, and community-level impact of the AATAP program. On the 1) individual level, patients expressed that AATAP (1a) increased activation and motivation towards transplantation, (1b) increased knowledge about dialysis, healthy living, and the transplant process and (1c) gave patients hope. Regarding 2) interpersonal interactions, patients felt that (2a) the racial concordance of the AATAP team was important and (2b) interactions with the team increased their comfort with the transplant process. On a 3) community-level, patients felt that AATAP 3a) addressed an important community need, stating that other providers sometimes lacked insight into the cultural norms and sensitivities of many in the Black community. However, patients felt that the program still had some (3b) unrealized potential for impact. Patients commented that they wished others in their social network and dialysis center communities were more aware that a culturally specific program like AATAP exists.

Conclusions
A novel African American Transplant Access Program has multi-level impact on the experiences and views of the transplant process for African American patients. These findings underscore the importance of such programs for African Americans and may inform future efforts to achieve equitable access to transplantation.

Competition Category: Health Services Outcomes or Clinical

Mentor: Dinee Simpson, MD

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Nicole Ontiveros, MD MS

Senior Resident (Clinical PGY3-5)

Sharpening the transition: A single-institution qualitative study on first-year faculty needs in academic surgery
Introduction
High attrition rates persist among early-career faculty in academic medicine despite exceptional achievement prior to appointment. A 2008 report by the Association of American Medical Colleges revealed that nearly half of clinical faculty left their positions within ten years of initial appointment. More recently, a 2023 study by Myers et al. documented an annual attrition rate of 11.5% among faculty at the University of New Mexico School of Medicine, with assistant professors reaching 50% attrition at just 4.6 years. This issue is particularly pronounced in academic surgery. While national surgical organizations have prioritized faculty development, there is a paucity of research examining the specific challenges faced by first-year academic surgeons. This study aims to identify first-year faculty needs and compare them with division chiefs' perspectives on faculty onboarding and development.

Methods
This ongoing qualitative study employs semi-structured interviews with first-year faculty and division chiefs in the Department of Surgery at Northwestern Memorial Hospital. Interviews explore experiences with onboarding, clinical integration, mentorship, and career development. Structural coding, guided by Schlossberg's Transition theory, provides a framework for assessing faculty adaptation and support needs. Two independent researchers conduct thematic analysis with member checking to ensure accuracy, and data collection will proceed until thematic saturation is achieved.

Results
Three themes have emerged from first-year faculty interviews (n=3): challenges with time management, the need for clinical support and structured mentorship, and struggles with research productivity. Division chief interviews (n=3) have revealed three distinct themes: importance of cultural fit, varied philosophies on mentorship implementation, and methods for monitoring early faculty success. Our analysis suggests a shared emphasis on the importance of mentorship but highlights divergence between faculty and leadership perspectives on how mentorship should be structured and what constitutes essential components of an effective faculty integration program.

Conclusion
Disparities exist between first-year faculty needs and division chiefs' perceptions of those needs in academic surgery. To bridge this gap, comprehensive faculty integration programs should include structured mentorship with clear expectations, time-management training, and research development workshops tailored to early-career surgeons. Periodic assessments of program effectiveness can optimize faculty support systems, ultimately improving retention rates and fostering long-term success in academic surgery careers. Findings from this study will improve the structured faculty integration initiative at our institution, with potential for broader application

Competition Category: Education

Mentor: Amy Halverson, MD

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Olisemeka Oputa, BA

Student

Disparities regarding surgical resection of small cell lung cancer
Introduction
Small cell lung cancer (SCLC) is a rare but aggressive malignancy with surgery traditionally playing a limited role in management. Recent advancements have led to increased recognition of surgery as an essential component of treatment for patients with early-stage SCLC. However, disparities in access to surgical care are especially prominent in the Black population and may limit these benefits. This study aimed to examine socioeconomic disparities in the utilization of oncologic resection and their impact on outcomes in patients with early-stage SCLC.

Methods
The National Cancer Database (NCDB) SCLC participant use file was used to identify patients with T1/T2, N0, M0 (clinical stage I-IIA) SCLC diagnosed between 2004 and 2017. Multivariable logistic regression identified predictors of receiving oncologic resection, defined as lobectomy or greater. Covariates included demographic, clinical, and facility-level factors. A multivariable Cox proportional hazards model assessed factors associated with overall survival (OS), adjusting for the same covariates along with the receipt of oncologic resection.

Results
Of 12,946 patients included, 960 (7.4%) were Black and 11,986 (92.6%) non-Black. Among them, 142 (14.8%) Black and 2,371 (19.8%) non-Black patients underwent oncologic resection. Of the 741 Black patients who did not receive surgery, 650 (87.7%) did not have surgery as part of the planned treatment, and 59 (8.0%) had contraindications due to risk factors. Black race (aOR 0.7, 95% CI 0.6-0.9), treatment at community cancer programs (aOR 0.6, 95% CI 0.5-0.7), comprehensive community cancer programs (aOR 0.66, 95% CI 0.59-0.74), and integrated network cancer programs (aOR 0.7, 95% CI 0.6-0.8) were associated with lower odds of oncologic resection. Private insurance (aOR 2.0, 95% CI 1.3-3.1), Medicare/Medicaid insurance (aOR 1.9, 95% CI 1.3-2.9), and higher income quartile (aOR 1.4, 95% CI 1.2-1.6) were associated with higher odds of oncologic resection. Survival analysis demonstrated that patients selected for oncologic resection had significantly improved OS (median 62.3 vs. 20.5 months, p<0.001). Oncologic resection (aHR 0.49, 95% CI 0.46-0.52) and higher incomes ($46,277 - $57,856: aHR 0.92, 95% CI 0.86-0.97; $57,857 - $74,062: aHR 0.87, 95% CI 0.82-0.93; $74,063+: aHR 0.83, 95% CI 0.78-0.88) were independently associated with improved OS.

Conclusions
Despite national guidelines, this study suggests oncologic resection remains underutilized among Black patients and those from marginalized socioeconomic backgrounds. Future studies are needed to understand reasons behind the underutilization of surgery and identify opportunities for improving guideline-concordant care in these populations.

Competition Category: Health Services Outcomes or Clinical

Mentor: David Bentrem, MD, MS

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Mallory Perez, MD

Fellow (Clinical or Postdoctoral Researcher)

Understanding variation in pediatric regional anesthesia: A National Surgical Quality Improvement Program-Pediatric (NSQIP-P) analysis
Introduction
Regional anesthesia provides targeted analgesia and promotes enhanced recovery in pediatric surgical patients. Despite these benefits, the prevalence and variation in regional anesthesia use for pediatric surgery have not been fully explored. This study aimed to examine factors associated with variation in regional anesthesia use and evaluate its relationship with discharge opioid prescribing practices in children undergoing surgery.

Methods
This prospective cohort study leveraged electronic health record data from the National Surgical Quality Improvement Program-Pediatric (NSQIP-Pediatric), supplemented with additional pain management-specific variables. Children (5-18 years) undergoing any procedure in NSQIP-Pediatric at four Illinois (IL) hospitals from 2021-2023 were eligible. Procedures were identified by CPT code and selected for procedure-level analysis based on overall volume and regional anesthesia use. Regional anesthesia included cryoablation, epidural/spinal, caudal, transversus abdominis plane (TAP), and other nerve blocks. Regional anesthesia use was first assessed across hospitals and surgical specialties using Fisher's exact tests. A multivariable logistic regression was then conducted to identify factors associated with regional anesthesia use. At the procedure level, discharge opioid exposure (opioid prescription at discharge) and dose intensity (total morphine milligram equivalents [MME]) were compared between patients with and without regional anesthesia, using chi-square and Wilcoxon rank sum tests. Statistical significance was defined as p<0.05.

Results
Of 1,666 pediatric surgical patients, 347(21%) received regional anesthesia, primarily nerve (N=116, 33%) or epidural/spinal (N=100, 29%) blocks. Regional anesthesia use varied by hospital (0.35-42%) and surgical specialty (3.7-38%) (p<0.001). For the regression, open surgery (OR=4.56; 95%CI [2.9,7.3]; p<0.001), elective cases (OR=2.52; 95%CI [1.5,4.1]; p<0.001), and use of preoperative non-opioid analgesia (OR=18.9; 95%CI [11.3,31.6]; p<0.001) were associated with higher odds of regional anesthesia use, while Black race was associated with lower odds (OR=0.33; 95%CI [0.18, 0.62]; p<0.001). Among children who underwent spine surgery (N=147), regional anesthesia was associated with higher odds of discharge opioid exposure (OR=13.5; 95%CI [3.81,47.9], p<0.001) and greater dose intensity (p<0.001). For abdominal surgery via laparotomy (N=82), regional anesthesia was also associated with higher odds of discharge opioid exposure (OR=2.49; 95%CI [1.01,6.13], p=0.04) but not with dose intensity (p=0.32).

Conclusions
Regional anesthesia for pediatric surgical patients was used in less than a quarter of NSQIP-Pediatric procedures and varied widely by hospital and surgical specialty. Further, for some procedures, regional anesthesia was not associated with reduced discharge opioid exposure or dose intensity.

Competition Category: Health Services Outcomes or Clinical

Mentor: Mehul Raval, MD, MS

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Megan Perez, MD

Senior Resident (Clinical PGY3-5)

Mesh suture closure for contaminated midline incisional hernia repair
Introduction
Contaminated and clean-contaminated midline hernia repairs are clinically challenging due to high recurrence and infection risks. While planar mesh reduces recurrence, its use in contaminated fields remains controversial. Mesh suture is a novel closure technique designed to combine the simplicity of suture with the reinforcement of mesh through a large-pore, braided construct that diffuses tension across the suture-tissue interface. Planar mesh implantation often requires extensive dissection and specialized expertise, potentially limiting its accessibility across general surgical settings. This study reports the early outcomes following mesh suture closure in this high-risk population.

Methods
A retrospective cohort study was conducted of 51 patients undergoing contaminated or clean-contaminated midline hernia repair with mesh suture between January 2023 and July 2024 across an integrated academic health system. Cases involving planar mesh were excluded. Outcomes included surgical site infections (SSI), surgical site events (SSE), reoperation, readmission, and hernia recurrence. Recurrence-free survival was analyzed using Kaplan-Meier methods, truncated at 18 months.

Results
Most patients (62.7%) had clean-contaminated wounds; 25.5% required anterior component separation. The 1-year SSI rate was 15.6%, with five patients requiring procedural intervention. SSE occurred in 17.6% of cases, with one enterocutaneous fistula. Readmission and reoperation rates within 1 year were 27.4% and 9.8%, respectively. Four hernia recurrences were observed (8.2%), yielding a 12-month recurrence-free survival of 91% and mean recurrence-free survival of 17.3 months (95% CI: 16.5-18.1). Presence of a stoma at time of closure was significantly associated with major complications (p = 0.041). There were no chronic mesh-related infections or draining sinuses. Repairs were performed by 22 surgeons across seven specialties.

Conclusions
In this early multi-surgeon, multi-specialty experience, mesh suture closure for contaminated midline incisional hernia repair was technically feasible and associated with acceptable short-term outcomes. Although the observed 1-year recurrence rate of 8.2% compares favorably to national benchmarks of 23-40% in contaminated fields, these findings should be interpreted cautiously given the small sample size and limited follow-up. The construct's low foreign body mass and rapid fibrovascular incorporation may contribute to its performance in high-risk settings. These preliminary results support further prospective investigation in larger cohorts with extended follow-up to better define the long-term safety and efficacy of mesh suture as an alternative to planar mesh.

Competition Category: Health Services Outcomes or Clinical

Mentor: Michael Shapiro, MD

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Bianka Progri, MS

Fellow (Clinical or Postdoctoral Researcher)

Evaluating the Safety of Transdermal Deferoxamine Patch In Oncological Settings
Introduction
The transdermal deferoxamine (DFO) patch (TauTona Group) has a potential to mitigate radiation-induced skin damage in breast cancer patients undergoing radiotherapy. However, its safety profile in oncological settings remains unexplored. This study investigates the effects of DFO on cancer cell biology using a xenograft murine breast cancer model.

Methods
Human breast cancer cells (MCF7-Luc2) and an estrogen pellet were implanted in the mammary glands of 8-week-old immunodeficient female mice (NSG). In vivo tumor growth was evaluated weekly by bioluminescence imaging after luciferin injection. Once tumors reached desired growth, DFO patches were applied daily for 30 days. The non-DFO-treated mice serves as controls. Body weight changes were monitored weekly. At study endpoint skin and tumor samples were preserved for downstream analyses. The success of DFO delivery was verified by evaluating HIF-1α protein level by Western blot. Immunofluorescence staining of Ki-67 and CD31 was performed to assess cell proliferation and vascularization, respectively.

Results
Our data indicated an increase in HIF-1α in DFO-treated skin, confirming successful DFO treatment. We have not observed significant differences in tumor growth (FC=0.8, p=0.392), cell proliferation (FC=0.8, p=0.131), and vascularization (FC=0.7, p=0.132) in tumors extracted from DFO-treated mice compared to control. Notably, the DFO-treated mice exhibited 10% greater body weight loss than control (p=0.011).

Conclusions
This study underlines the necessity of assessing the oncological safety of radioprotective interventions. DFO appears to primarily affect superficial tissues without significantly impacting tumor growth, proliferation, or vascularization. Further research is needed to evaluate DFO's influence on radiation therapy efficacy.

Competition Category: Basic Science or Translational

Mentor: Arun Gosain, MD

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Parul Rai, BS

Fellow (Clinical or Postdoctoral Researcher)

Profiling breast implant rupture: a systematic review and meta-analysis of patient, surgical, and device characteristics
Introduction
While individual studies have explored specific risk factors, clinicians lack a clear and synthesized overview of how various patient, surgical, and implant characteristics contribute to rupture. This systematic review and meta-analysis aims to address the need for a comprehensive understanding of the factors that contribute to breast implant rupture. By synthesizing the available evidence on patient demographics, surgical techniques, and implant characteristics, this study seeks to provide clinicians with a clearer and more complete picture of the risks associated with this complication, ultimately informing clinical decision-making and improving patient outcomes in breast implant surgery.

Methods
PubMed, CINHAL, Scopus, and Cochrane Library databases were searched for relevant articles on October 26, 2024. This systematic review includes observational studies involving adult females who experienced implant rupture following breast augmentation or reconstruction. Results were synthesized using random-effects models to generate pooled risk ratios (RRs) with 95% confidence intervals.

Results
This meta-analysis of 20 studies (15,811 implants) found that round implants were associated with a significantly higher rupture risk compared to anatomical implants (RR = 2.27 [1.04-4.94], p = 0.0387). Similarly, implants placed in the subpectoral plane had higher risk of rupture compared to those in the prepectoral plane (RR = 1.63 [1.22-218], p = 0.0007). No significant differences in rupture risk were found between saline and silicone implants, smooth and textured implants, or aesthetic and reconstructive patients.

Conclusions
Implant shape and plane may affect the risk of breast implant rupture, with round implants and subpectoral placement being associated with higher rupture rates. These findings can inform clinical decision-making and surgical planning to minimize the risk of this complication. The increased risk observed with subpectoral implants is consistent with the understanding that compressive forces from the pectoralis muscle may contribute to implant shell damage and rupture. While the association between round implant shape and higher rupture rates aligns with existing literature, the underlying mechanisms and physical forces contributing to this phenomenon remain poorly understood and warrant further investigation. By identifying modifiable risk factors, this systematic review can empower clinicians to make more informed decisions, leading to better patient outcomes, reduced complications, and improved patient satisfaction. The information can also facilitate shared decision-making between clinicians and patients, allowing for more informed discussions about different implant types and surgical approaches as they reconcile the risk of implant rupture with other complications.

Competition Category: Health Services Outcomes or Clinical

Mentor: Arun Gosain, MD

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Saieesh Rao, MD

Senior Resident (Clinical PGY3-5)

Inpatient rehabilitation after spinal cord injury is associated with reduced 90-day acute care hospital costs compared to skilled nursing facility care
Introduction
Inpatient rehabilitation after spinal cord injury (SCI) is often not covered by insurers due to up-front cost, resulting in inappropriate triage of patients to skilled nursing facilities (SNFs). It is unknown whether this practice increases post-injury health care costs for SCI patients due to morbidity otherwise avoidable with appropriate rehabilitation, and whether costs averted by rehabilitation would justify up-front admission to inpatient rehabilitation facilities (IRFs). We compared 90-day hospital costs for SCI patients receiving post-acute care at IRFs and SNFs to estimate hospital costs averted with IRF care.

Methods
Using a difference-in-differences (DID) study design, we analyzed retrospective cohort data from the Healthcare Cost and Utilization Project State Inpatient and Emergency Department Databases. Patients with SCI in six states (AR, FL, MA, MD, NY, WI) between years 2016-2021 were included if they were at least 18 years old, discharged to either IRF or SNF following SCI, and were injured after the first quarter of the year but discharged before the fourth quarter of the year to ensure 90-day pre- and post-periods for DID. Encounter costs were calculated from total hospital charges using hospital-specific cost-to-charge ratios. Subgroup analyses were performed by spinal injury level - cervical, thoracic, and lumbosacral - and insurance type to determine which patients had the greatest cost benefit. We repeated the DID analysis conditional on patient covariates (age, sex, race, state, injury severity scores, Elixhauser comorbidity score, ZIP income quartile, and presence of traumatic brain injury) using the method of Callaway & Sant'Anna to address baseline covariate difference between SNF and IRF cohorts.

Results
A total of 4266 patients were identified, of whom 1722 went to SNF and 2544 went to IRF. Patients receiving rehabilitation in an IRF averted $3253 in mean 90-day hospital costs compared to patients receiving rehabilitation in a SNF before adjustment for covariates (p<0.001). This difference persisted after adjusting for covariates though the absolute difference was smaller ($2737, p<0.001). Subgroup analysis by injury level showed greatest costs averted for cervical SCI patients ($3807, p<0.001). Considering insurance type, publicly insured patients had greater savings associated with IRF than the overall cohort ($4030, p<0.001).

Conclusions
Inpatient rehabilitation after SCI is associated with significantly reduced 90-day hospital costs compared with SNF care. These cost-savings are magnified for patients with cervical SCI and public insurance. Payors begin to recoup investments in IRF care within a 90-day window; future work will examine this finding over a longer time horizon.

Competition Category: Health Policy

Mentor: Anne Stey, MD, MSc

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Margaret Reilly, MD, MS

Senior Resident (Clinical PGY3-5)

What's in a Name? A Mixed Methods Study of Patient Knowledge, Understanding, and Experience with Peripheral Artery Disease Education
Introduction
Peripheral artery disease (PAD) is a chronic disease that leads to increased risk of cardiovascular death, walking impairment, and leg amputation. However, knowledge of PAD in the general public is low when compared to knowledge of other cardiovascular diseases. We aimed to quantify awareness and knowledge of PAD and to understand the patient experience of PAD education using mixed methods.

Methods

In this single-center, convergent parallel mixed methods study, participants with an established PAD diagnosis were recruited from a vascular surgery practice. Participants completed an 87-item survey assessing demographics, awareness of PAD diagnosis, and PAD knowledge. Functional health literacy (FHL) was measured using the short Test of Functional Health Literacy Assessment. Multivariable linear regression was used to identify factors associated with PAD knowledge. Semi-structed interviews were conducted in a subset of participants to assess PAD experience and understanding. Interview transcripts were analyzed with inductive and deductive coding, and a constant comparative approach was used to identify themes. Qualitative and quantitative data were integrated to develop overarching themes.

Results
There were 91 participants (77.2% response rate, 49.5% female, 29.7% Black, mean age 68.6 years). Most participants (51.7%) had chronic limb-threatening ischemia and 17.6% had undergone a major leg amputation. While 21.3% had poor FHL and 24.4% were unaware of their PAD diagnosis, the average knowledge score was 79.1%. Multivariable linear regression revealed that poor FHL and a lack of awareness of PAD diagnosis were significantly correlated with lower PAD knowledge. Qualitative analysis of semi-structured interviews of twenty participants revealed four themes that participants: (1) were not aware of their diagnosis of PAD; (2) did not understand the terms “peripheral,” “artery,” or “peripheral artery disease;” (3) had deficits in basic understanding of PAD; and (4) believed that a lack of patient and provider knowledge about PAD led to delays in diagnosis and treatment. Data integration and triangulation yielded three overarching themes: (1) Not understanding the name of the disease led to further knowledge deficits; (2) the knowledge test was not a sensitive assessment of patient understanding of PAD; (3) physician trust led to engagement with treatment regardless of disease knowledge.

Conclusions
While PAD knowledge correlates directly with functional health literacy, the PAD knowledge test is not a sensitive assessment of PAD understanding. Future research will focus on identifying strategies to appropriately gauge patient understanding of PAD and to examine how this affects patient behavior.

Competition Category: Health Services Outcomes or Clinical

Mentor: Karen Ho, MD

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John Rode, MD

Senior Resident (Clinical PGY3-5)

Cost-effectiveness of metabolic and bariatric surgery in adolescents: a 10-year analysis
Introduction
Obesity affects approximately one in five children in the United States, with an estimated annual medical cost of $1.3 billion. While metabolic and bariatric surgery provides substantial weight loss and improvement in weight-related comorbidities in adolescents with severe obesity, there are limited data regarding its long-term cost-effectiveness.

Methods
A patient-level, state-transition model was developed to assess the cost-effectiveness of three strategies: Roux-en-Y gastric bypass (RYGB), vertical sleeve gastrectomy (VSG), and no surgery over 10 years. Demographic, pre-operative, and postsurgical outcomes for the model's hypothetical cohort were based on the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. A non-surgical comparator group was modeled from a separate cohort study of adolescents with obesity who did not undergo bariatric surgery. Costs of surgery, complications, micronutrient deficiency management, and total direct health care were incorporated. Quality of life was dependent on surgical complications, type 2 diabetes status, and BMI reduction. Endpoints included quality-adjusted life years (QALYs), total costs, and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay (WTP) threshold of $100,000 per QALY gained was used to
determine cost-effectiveness. To assess the impact of model uncertainty on cost-effectiveness results, one-way and probabilistic sensitivity analyses were performed.

Results
Over 10 years, no surgery, VSG, and RYGB were estimated to cost $40,882, $72,048, and $79,626, respectively. RYGB was associated with the most QALYs at a value of 6.888 compared to no surgery and VSG at 6.117 and 6.875, respectively. The ICER of VSG versus no surgery was $41,164 per QALY gained, which was below our WTP threshold of $100,000 per QALY gained. Therefore, VSG was cost-effective over 10 years. When compared with VSG, RYGB had an ICER of $557,751 per QALY gained and was not cost-effective. However, when RYGB was compared with no surgery in a scenario where VSG was unavailable, it was cost-effective with an ICER of $50,271 per QALY gained.

Conclusion
Our model demonstrates that VSG and RYGB are cost-effective when compared to no surgery alone. However, when all three strategies were simultaneously compared, VSG was the cost-effective option.

Competition Category: Health Services Outcomes or Clinical

Mentor: Thomas Inge, MD PhD

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Gabrielle Rodriguez, MD

Fellow (Clinical or Postdoctoral Researcher)

The Benefits of Antifibrinolytic Administration in Minimally Invasive Craniosynostosis Repair
Introduction
The use of antifibrinolytics in minimally invasive craniosynostosis repair is a topic without a clear consensus. This study aimed to assess the impact of antifibrinolytics on intraoperative blood loss, blood transfusion frequency and volume, complication rates, and length of hospital stay in children undergoing minimally invasive craniosynostosis repair.

Methods
A single institution retrospective chart review was conducted on children who underwent minimally invasive craniosynostosis repair from 2007 to 2023. Patients were divided into two groups based on their AF administration status. Calculated blood loss (CBL) was derived from estimated blood volume (EBV) and hematocrit values to determine estimated red cell mass (ERCM) at various points. Intraoperative transfusion management was also evaluated, considering transfusion volumes appropriate within 15% of preoperative ERCM.

Results
85 patients were included, with 40 receiving antifibrinolytic (AF) therapy and 45 not. No significant differences were found in demographics, operative time, complications, or transfusion volume. However, the mean weight-adjusted CBL (38.93 mL/kg vs. 62.89 mL/kg, p = 0.001), length of hospital stay (1.5 days vs. 2.2 days, p < 0.0001) and percentage of patients requiring transfusions were all significantly lower in the AF group (42.5% vs. 95.6%, p < 0.0001). Surprisingly, patients in the AF group were under-transfused at discharge at significantly higher rates (62.5% vs 26.7%, p = 0.0009).

Conclusions
The findings support the safety and efficacy of antifibrinolytics in minimally invasive craniosynostosis repair. Antifibrinolytic administration reduced blood loss and length of stay, suggesting these agents should be standard practice in minimally invasive craniosynostosis repair, and one should strive for transfusion to match blood volume loss irrespective of whether antifibrinolytic agents are utilized.

Competition Category: Health Services Outcomes or Clinical

Mentor: Arun Gosain, MD

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Joseph Sanchez, MD MS

Senior Resident (Clinical PGY3-5)

Association of Patient-reported Social Needs with Area Deprivation Index in Assessing Social Drivers of Health
Introduction
Patient-reported, health-related social needs data collection has been mandated by Centers for Medicare & Medicaid Services. It is unclear if patient-reported health-related social needs are associated with census-level indices, such as the Area Deprivation Index (ADI).

Methods
This was a retrospective cohort study of patients undergoing urgent or emergent surgery between 2022-2024 within a single healthcare system including nine hospitals. Patients with unmet, health-related social needs reported either limited primary care access, medication payment insecurity, transportation needs, food insecurity, unsafe housing/recent housing emergency, or mental health needs. Patients' zip codes linked to ADI state percentile rankings from least to most deprived. Mixed effects multivariable logistic regression modeled having unmet social needs to estimate the association with ADI state rankings. This controlled for race/ethnicity, gender, language, operation year, insurance type, ASA class, procedure service, and discharge disposition.

Results
Of 25,924 patients, 4,314 (16.6%) reported unmet social needs. 15,893 (61%) were female and a greater proportion of patients underwent procedures by General Surgery (27.1%), Obstetric/Gynecology (21.2%) and Orthopedics (15.8%). Of 4,727 patients residing in the least deprived area, 685 (14.5%) had unmet social needs. Of 245 patients residing in the most deprived area, 60 (24.5%) had unmet social needs. After controlling for confounders, increasing degrees of area deprivation was not associated with patient-reported, unmet social needs (OR 1.04, 95% Confidence Interval [0.98-1.10]).

Conclusions
Patient-reported health related social needs are not associated with increased ADI percentile rankings, suggesting that census-level socioeconomic indices may not fully capture individual-level social determinants of health. These findings highlight the importance of direct patient-reported data collection to identify unmet social needs that may otherwise be overlooked. Hospitals and healthcare systems should consider integrating patient-reported social needs into routine assessments as a complementary measure of socioeconomic status to better inform resource allocation and targeted interventions.

Competition Category: Health Services Outcomes or Clinical

Mentor: Anne Stey, MD, MS

Kirtana Sandepudi, MS

Student

Psychometric validation of a modified Female Sexual Function Index in transgender and gender-diverse patients after gender-affirming bottom surgery
Introduction
Sexual function is an important aspect of quality of life that can be linked bidirectionally to gender dysphoria for some transgender and gender-diverse (TGD) individuals. For those who undergo genital gender-affirming surgery (GGAS or bottom surgery), sexual function sees significant changes. Still there are no validated patient reported outcome measures (PROM) for assessing sexual function in TGD patients after bottom surgery. The Inclusive Sexual Function Index (ISFI, previously known as Sexual Function Index-Gender Spectrum) is a PROM adapted for transgender and gender-diverse (TGD) patients from the Female Sexual Function Index (FSFI). The purpose of this study is to psychometrically validate ISFI for the TGD GGAS population via cognitive debriefing interviews and convergent validity.

Methods
Twenty-two participants were recruited and consented from a database of GGAS patients (including vulvoplasty, vaginoplasty, and phalloplasty) at our institution. Semi-structured cognitive debriefing interviews were conducted, following a pre-established interview guide eliciting feedback on item meaning (“What does this question mean to you?”), comprehension and completeness (“Is there anything confusing or missing.”), and overall applicability of SFI-GS (“How well did it apply to you?”). Interview transcripts were cleaned and analyzed by 6 coders utilizing a rapid qualitative approach to assess consistency in item interpretation, explore content validity in the context of GGAS, and inform suggested modifications to survey elements. Convergent validity was assessed against the Gender Congruence and Life Satisfaction (GCLS) scale, which is well-validated in TGD patients. Cronbach's alpha was calculated to assess internal consistency.

Results
Participants felt ISFI addressed many potential effects of GGAS on their sexual functioning. However, 9/19 questions were interpreted inconsistently (>2 participants interpreted question differently from others), with two questions warranting deletion or complete replacement. ISFI also failed to capture some sexual experiences unique to GGAS, including the role of gender dysphoria, comfort in their body during sexual activity, and learning how to use their new anatomy. Asexual participants felt the survey framed questions in a way that pathologized or excluded their identity. Quantitatively, ISFI had high internal consistency (alpha = 0.96) and demonstrated modest correlation with the GCLS emotional and physical intimacy subscale (r-squared = 0.4791**).

Conclusions
ISFI is an internally consistent scale that assesses important aspects of sexual function. Still, our study identified gaps in content and applicability of ISFI in TGD GGAS patients. Modifying the survey according to this feedback is crucial to prevent utilization of an incomplete or potentially misleading PROM in this patient population.

Competition Category: Quality Improvement

Mentor: Sumanas Jordan, MD, PhD

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Rashi Singh, MD

Fellow (Clinical or Postdoctoral Researcher)

No FOMO for TOMO: ADH ppstage in the era of breast tomosynthesis
Introduction
In recent years, there has been an overall trend towards active surveillance for benign, high-risk lesions due to the low upstaging rate after excisional biopsy. However, surgical excision is still recommended for atypical ductal hyperplasia (ADH) because of the upstaging to DCIS or invasive breast cancer (IBC) in 15-30% of cases as reported in the literature. With recent advancements in breast imaging such as digital breast tomosynthesis (DBT) and vacuum-assisted core needle biopsy (CNB) techniques, we hypothesized that the overall upstage rate for ADH would be lower than previously reported using digital 2D mammography and conventional CNB techniques, and that we could potentially identify a subset of women who could avoid excisional biopsy.

Methods
We queried our institutional EnterpriseData Warehouse(EDW) to extract electronic health record data for this retrospective review. Women > 18 years old who had a screening DBT between 2016-24 with ADH diagnosed by stereotactic or ultrasound-guided CNB followed by surgical excision were included in the cohort. Those who underwent MRI-guided imaging for detection or tissue sampling, and women with a prior/concurrent history of breast cancer or with a known pathogenic mutation were excluded.

Results
684 women (mean age = 53 years) were identified from the EDW. Sixty percent were postmenopausal and 61% reported a family history of breast cancer. Over 70% of women had mammographically dense breast tissue. A total of 712 distinct cases of biopsy-proven ADH that underwent surgical excision were identified. Our upstage rate was 12.1%. This included 16 IBC (2.2%) and 67 cases of DCIS (9.4%), with 54% of those with DCIS having grade 1 disease. All upstaged cases were ER+. Imaging factors associated with upstage included fine/pleomorphic calcifications, asymmetry, multiple imaging findings, ADH bordering on DCIS on biopsy, and a larger lesion size. Moreover, 135 cases (19%) had benign pathology upon surgical excision. Having “focal” ADH on biopsy was significantly associated with downstage.

Conclusions
The overall upstage rate for biopsy-proven ADH detected by DBT and diagnosed with vacuum-assisted biopsy at our institution was lower than what has been previously reported in the literature. Most cases upstaged to low-grade DCIS, and of the cases that upstaged to invasive disease, two-thirds were T1mic or T1a. Future directions include analysis of our entire cohort (including patients with high-risk lesions after surgical excision) and modeling of patient, imaging, and biopsy characteristics to predict patients who are at highest and lowest risk of upstaging.

Competition Category: Health Services Outcomes or Clinical

Mentor: Swati Kulkarni, MD

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Krishay Sridalla, BA

Student

Circulating tumor DNA as assessed by NGS is a prognostic biomarker in patients with localized pancreatic cancer
Introduction
Circulating tumor DNA (ctDNA) has emerged as a promising blood-based biomarker with prognostic relevance in various cancers. However, the role of ctDNA in localized pancreatic ductal adenocarcinoma (PDAC) is not yet well established. This study aimed to use next-generation sequencing (NGS) to determine the impact of ctDNA detection and dynamics on overall survival (OS).

Methods
Patients with localized PDAC were enrolled in a prospective study at Northwestern Medicine between October 2020 and November 2024. Peripheral blood samples were collected at diagnosis, after neoadjuvant chemotherapy (NAC), and after local therapy. Samples were then sent for commercial, tumor-agnostic NGS using a panel of over 75 genes. KRAS-specific and overall NGS detection rates were assessed. The detection and dynamics of ctDNA throughout treatment were assessed for association with CA 19-9 levels and OS. CA 19-9 levels across timepoints and their comparisons based on NGS detection status were analyzed using the Mann-Whitney U test. Log-rank tests and a Cox proportional hazards model assessed factors associated with OS.

Results
119 patients were included in the analysis. Mutant KRAS ctDNA was detected in 17 (14.3%) patients at diagnosis, 4 (3.4%) patients after NAC, and 4 (3.4%) patients after surgical resection. 6 (5.0%) patients cleared mutational ctDNA over treatment. KRAS detection rates significantly decreased following NAC (17.7% vs 5.3%; p=0.018). CA 19-9 levels decreased significantly after NAC (164.0 U/mL vs 45.0 U/mL; p<0.001) and after resection (45.0 U/mL vs 21.0 U/mL; p=0.003). The presence of overall ctDNA after NAC was associated with a higher median CA 19-9 level (54.0 U/mL vs 33.0 U/mL; p=0.046). Overall NGS detection at diagnosis was associated with shorter OS (median 16.5 vs 27.8 months; p<0.001), as was KRAS detection at diagnosis (median 11.2 vs 27.2 months; p<0.001). On multivariable analysis, KRAS detection at diagnosis was predictive of reduced OS (aHR 6.1, 95% CI 2.5-14.8). Clearance or lack of detection of KRAS after NAC was not associated with improved OS.

Conclusions
This study showed that absence of ctDNA detection at diagnosis as assessed by NGS is predictive of favorable prognosis in patients with localized pancreatic cancer. NGS-based KRAS ctDNA detection after NAC also served as a biomarker of treatment response. Additionally, KRAS ctDNA detection at diagnosis independently predicted worse OS in patients receiving NAC. These findings suggest that NGS-based ctDNA analysis may inform adaptive treatment trials aimed at optimizing management for patients with ctDNA during NAC.

Methods: Patients with localized PDAC were enrolled in a prospective study at Northwestern Medicine between October 2020 and November 2024. Peripheral blood samples were collected at diagnosis, after neoadjuvant chemotherapy (NAC), and after local therapy. Samples were then sent for commercial, tumor-agnostic NGS using a panel of over 75 genes. KRAS-specific and overall NGS detection rates were assessed. The detection and dynamics of ctDNA throughout treatment were assessed for association with CA 19-9 levels and OS. CA 19-9 levels across timepoints and their comparisons based on NGS detection status were analyzed using the Mann-Whitney U test. Log-rank tests and a Cox proportional hazards model assessed factors associated with OS.

Results: 119 patients were included in the analysis. Mutant KRAS ctDNA was detected in 17 (14.3%) patients at diagnosis, 4 (3.4%) patients after NAC, and 4 (3.4%) patients after surgical resection. 6 (5.0%) patients cleared mutational ctDNA over treatment. KRAS detection rates significantly decreased following NAC (17.7% vs 5.3%; p=0.018). CA 19-9 levels decreased significantly after NAC (164.0 U/mL vs 45.0 U/mL; p<0.001) and after resection (45.0 U/mL vs 21.0 U/mL; p=0.003). The presence of overall ctDNA after NAC was associated with a higher median CA 19-9 level (54.0 U/mL vs 33.0 U/mL; p=0.046). Overall NGS detection at diagnosis was associated with shorter OS (median 16.5 vs 27.8 months; p<0.001), as was KRAS detection at diagnosis (median 11.2 vs 27.2 months; p<0.001). On multivariable analysis, KRAS detection at diagnosis was predictive of reduced OS (aHR 6.1, 95% CI 2.5-14.8). Clearance or lack of detection of KRAS after NAC was not associated with improved OS.

Conclusions: This study showed that absence of ctDNA detection at diagnosis as assessed by NGS is predictive of favorable prognosis in patients with localized pancreatic cancer. NGS-based KRAS ctDNA detection after NAC also served as a biomarker of treatment response. Additionally, KRAS ctDNA detection at diagnosis independently predicted worse OS in patients receiving NAC. These findings suggest that NGS-based ctDNA analysis may inform adaptive treatment trials aimed at optimizing management for patients with ctDNA during NAC.

Competition Category: Basic Science or Translational

Mentor: Akhil Chawla, MD

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Fang Tang, PhD

Fellow (Clinical or Postdoctoral Researcher)

Design and characterization of controlled mitochondrial eluting vascular stents
Introduction
Mitochondrial dysfunction and the associated reactive oxygen species (ROS) levels are significant contributors to cardiovascular diseases. Mitochondrial transplantation offers a promising strategy to restore cellular homeostasis, thereby enhancing bioenergetics and vascular repair [1]. However, achieving targeted and controlled mitochondrial delivery to affected regions remains challenging. Here, we propose the development of mitochondria-eluting endovascular stents, wherein engineered mitochondria are coated onto the stent via ROS-sensitive bonds. These bonds are designed to cleave in response to high ROS levels at the injury site[2], enabling localized mitochondrial release and subsequent endocytosis to restore mitochondrial function.

Methods
In the current preliminary experiments, we utilized nitinol wires composed of the same material as nitinol stents to serve as a proof of concept. Chemical modifications on the surface of nitinol stents via ROS-responsive phenylboronic acid linkages enable the loading of engineered mitochondria. Mitochondria (approximately 100-400 nm in size) were isolated from mesenchymal stem cells and loaded onto the surface of the chemically modified nitinol wires through incubation. The materials were characterized with X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), while the controlled release and subsequent uptake of mitochondria were assessed with fluorescent microscopy in the presence of H2O2.

Results
ROS-responsive linkages were successfully introduced onto the surface of nitinol wire, which is the same material used in nitinol stents, through a multi-step chemical modification, as confirmed by XPS. Fluorescence imaging confirmed successful mitochondria (MitoTracker Red labeled) loading on the surface of nitinol wire. SEM imaging further revealed surface morphology changes, showing a transition to a roughened texture upon mitochondrial loading. The uptake of released mitochondria by endothelial cells in culture was evaluated after exposure to H2O2. Fluorescence microscopy showed the presence of red-fluorescent mitochondria within the endothelial cells, suggesting that ROS facilitated mitochondrial release and their subsequent cellular uptake. The next step of the study focuses on the evaluation of mitochondria and cellular function after mitochondria are released from the endovascular stents.

Conclusions
This study demonstrates effective modification of ROS-responsive linkage on the surface of the vascular stent for targeted and controlled delivery of mitochondria in a ROS-stimulated environment.

Competition Category: Basic Science or Translational

Mentor: Bin Jiang, PhD

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Veronica Villanueva, PhD

Fellow (Clinical or Postdoctoral Researcher)

Microglia depletion attenuates immune cell chemotaxis after traumatic brain injury in aged mice
Introduction
Traumatic brain injury (TBI) afflicts over 3 million Americans every year. Patients over 65 years of age experience increased mortality and greater long-term neurocognitive morbidity compared to young adults. Aged microglia produce chemoattractants leading to a selective recruitment of T-cells into the aged brain. Our previously published data shows an age-specific influx of CD8+ effector T-cells into aged brains after TBI correlating to worse neurocognitive outcomes. Therefore, we hypothesized that depletion of microglia would attenuate accumulation of T-cells in the injured brain after TBI in aged mice.

Methods
Young adult (14-weeks) and aged (80-weeks) C57BL/6 male mice (N=40) underwent microglia depletion via PLX5622, a colony stimulating factor 1 receptor (CSFR1) inhibitor, formulated into standard rodent chow at 1200 ppm vs. sham depletion with a control diet. Microglia depletion was confirmed via flow cytometry. After depletion, mice underwent TBI via controlled cortical impact vs sham injury. Brains were harvested at either 8 hours or 2 months post TBI. Flow cytometry was used to assess the immune cell infiltrate and cytokine levels were assessed with a Luminex-based assay. Data was analyzed using two-way ANOVA and Tukey's multiple comparison test.

Results
Microglia depletion led to significant reduction of IL-2 at 8 hours post-TBI as compared to sham depletion (4.4pg/mL ± 0.3 vs. 2.5pg/mL ± 0.7, p<0.002). This correlated to a 90% reduction of CD8+ effector T cell infiltration as compared to mice receiving the control diet (p<0.0001). IL2 stimulates growth, proliferation, and subsequent differentiation of T cells. In addition, microglia depletion also led to significant reduction in the proinflammatory cytokines CXCL10, CCL3, CCL7, CCL2, CXCL2, and CCL4 at 8 hours post-injury. Each of these cytokines/chemokines have been associated with recruitment of inflammatory leukocytes after TBI. This suggests that T cell recruitment into the injured brain is an acute, age-specific, response.

Conclusions
We hypothesized that depletion of microglia would attenuate accumulation of T-cells in the injured brain after TBI in aged mice. Our data shows a marked reduction in several chemoattractant cytokines in microglia depleted TBI mice correlating to a significant reduction in effector T-cells with the aged, injured, brain. In particular, IL2 and CXCL10 expression are known to be associated with T-cell responses. This gives novel insight into a potential mechanism for T-cell recruitment in aged TBI. Further understanding of microglia and T-cell interactions/mechanisms has therapeutic potential in reducing the long-term morbidity and inflammation in aged subjects post-TBI.

Competition Category: Basic Science or Translational

Mentor: Steven Schwulst, MD

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Maxime Visa, BA

Student

Association of postoperative complications and lymph node sampling criteria in lung cancer resection
Introduction
The American College of Surgeons Commission on Cancer (ACS CoC) recommends lymph node sampling from 3 mediastinal stations and 1 hilar station, while the European Society of Thoracic Surgeons (ESTS) recommends a lobe-specific lymph node station sampling strategy for lung cancer resection. While both of these guidelines seek to maximize pathological upstaging while minimizing the adverse effects associated with nodal resection, comparative postoperative complications associated with these two strategies are unknown. The objective of this study is to evaluate the association of lymph node sampling strategy on postoperative outcomes for lung cancer patients.

Methods
We conducted a retrospective cohort analysis of elective lung cancer resections from 2018-2023 in a large, single-center, urban academic health system. We performed multivariable Poisson regression with robust variance to evaluate the association of any 30-day postoperative complications and 30-day postoperative complications across ACS CoC and ESTS nodal sampling criteria.

Results
Of 961 total patients, 406 (42.2%) met ACS CoC, 118 (12.3%) met ACS CoC+ESTS, and 437 (45.5%) met neither criteria. Risk-adjusted rates of 30-day postoperative complications were not significantly different between ACS CoC (29.6%), ACS CoC+ESTS (26.4%), and those who met neither criteria (35.4%). However, risk-adjusted rates for major 30-day postoperative complications were similar between ACS CoC (18.5%) and neither criteria (17.9%), but was lower for patients meeting ACS CoC+ESTS criteria (13.2%, aRR 0.71 [95% CI: 0.59-0.87]).

Conclusions
We found no risk-adjusted differences in 30-day postoperative complications between lymph node sampling criteria, and statistical but not clinical significance between major 30-day postoperative complications. These findings suggest that postoperative morbidity associated with lymph node sampling criteria may be less important than considering oncologic outcomes for the optimization of lymph node evaluation.

Competition Category: Health Services Outcomes or Clinical

Mentor: David Odell, MD, MMSc

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Dominic Vitello, MD MS

Senior Resident (Clinical PGY3-5)

The assay matters: ctDNA detection by NGS vs ddPCR lead to distinct outcomes in localized pancreatic cancer
Introduction
We have previously identified that KRAS circulating tumor DNA (ctDNA) is prognostic in patients undergoing neoadjuvant chemotherapy (NAC). We sought to understand the significance of increasing sensitivity to mutant KRAS ctDNA detection with digital droplet PCR (ddPCR) by 1) comparing the sensitivity of mutant KRAS ctDNA detection by NGS and ddPCR and 2) understanding the prognostic implication of enhanced sensitivity for KRAS ctDNA detection throughout treatment with NAC.

Methods
Patients with newly diagnosed, localized PDAC were enrolled in a prospective cohort study and treated under the standard of care. Peripheral blood samples were collected at diagnosis, after NAC, and after local therapy. Samples were analyzed using NGS and ddPCR probing for KRAS G12D, G12V, G12R mutations. Kaplan-Meier with log-rank tests were performed.

Results
99 patients were enrolled. The median (IQR) follow-up time was 27.1 (15.8-68.9) months. At diagnosis, mutant KRAS ctDNA detection by ddPCR was seen in 37 of 48 patients (77.1%) and in only 15 of 75 (20.0%) by NGS, all of whom were detectable by ddPCR. Detection of mutant KRAS ctDNA by ddPCR or NGS at diagnosis were both associated with worse OS, yet with prognostically distinct outcomes (ddPCR ctDNA+ 24.3 months vs. not reached, p<0.05; NGS ctDNA+ 11.2 vs. 27.2 months, p<0.001, Figure 1). Over the course of NAC and local therapy, 10 of 53 patients (18.9%) gained ctDNA KRAS mutations as assessed by ddPCR compared to 3 of 75 patients (3.9%) for NGS. 15 patients cleared a ctDNA KRAS mutation as assessed by ddPCR, compared to only 6 as assessed by NGS. Patients who cleared a mutation by ddPCR had longer OS compared to those that did not (NR vs. 18.0 months, p=0.034). NGS was unable to provide similar predictive discrimination (p=0.13).

Conclusions
In localized pancreatic cancer, ddPCR is far more sensitive in the detection of mutant KRAS ctDNA than NGS and has greater prognostic value as a dynamic biomarker throughout treatment. Patients with KRAS ctDNA detected by NGS have far worse outcomes than those detected by ddPCR, likely due to high ctDNA load required for detection by NGS.

Competition Category: Basic Science or Translational

Mentor: Akhil Chawla, MD

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Samantha Watson, BS

Student

Understanding preoperative patient education in vascular surgery: A systematic review and meta-analysis
Introduction
Preoperative patient education is associated with improved disease knowledge, increased procedural understanding during the informed consent process, enhanced shared decision making, and decreased patient anxiety and postoperative complications. Poor disease and procedural knowledge have been reported among patients with peripheral artery disease (PAD) and abdominal aortic aneurysm (AAA). The objectives of this systematic review and meta-analysis were to summarize the preoperative patient education interventions used in vascular surgery and determine their impact on patient understanding of their surgical procedures.

Methods
Embase, PubMed, and Ovid (MEDLINE) were searched in accordance with PRISMA guidelines. Included studies addressed a vascular specialty-specific procedure with an educational intervention and included patient knowledge as a key outcome variable. Using pre- and post-educational intervention mean knowledge scores for experimental and control groups, a forest plot with standardized mean difference (SMD) was generated. Sub group analyses were performed for patients undergoing AAA repair and for interventions using decision aids.

Results
A total of 6 studies were identified (5 randomized controlled trials and 1 prospective cohort study). A total of 654 patients were studied (mean age 66±9.9 years; 68% male) with procedures including open and endovascular AAA repair, femoral-popliteal bypass, carotid surgery, and endovenous thermal ablation. Educational interventions included verbal and written informed consent discussions, online and written decision aid tools, 3D and virtual reality (VR) displays, and a multimedia interactive digital health education tool. Given the small sample size, prospective power analysis for the fixed-effects mean effect was performed and yielded a Z-score of 5.38 (p<0.01), suggesting that the power of this study is approximately 100% to detect significant mean effect. Across the six included studies, the SMD was 0.64 (95% CI, 0.48-0.79), suggesting a significant, moderately positive effect of educational interventions on patient knowledge. For AAA repair and decision aid subgroups, 4 papers were included in each analysis. Both analyses yielded significant results with a SMD of 0.58 (95% CI, 0.42-0.75) and 0.62 (95% CI, 0.45-0.79), respectively.

Conclusions
Online, written, and multimedia patient education tools including decision aids, 3D and VR displays, and videos have been utilized to improve patient knowledge in vascular surgery. Preoperative patient education, especially decision aids, can enhance understanding of operative interventions. The limited number of studies on this topic in vascular surgery underscores the importance of further investigation. Continuing to develop and implement procedure-specific and patient-oriented education interventions is essential to address knowledge gaps among patients undergoing surgery for vascular diseases.

Competition Category: Health Services Outcomes or Clinical

Mentor: Karen Ho, MD

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Zhaoyu Xing, MD

Fellow (Clinical or Postdoctoral Researcher)

Macrophage-specific XBP-1 deletion alleviate renal fibrosis and improves graft survival in murine kidney transplantation
Introduction
Chronic kidney disease (CKD) affects approximately 10% of global population and remains the crucial cause of chronic allograft dysfunction with interstitial fibrosis and tubular atrophy (IF/TA) as a late feature of the renal allograft. Macrophage-driven inflammation and endoplasmic reticulum (ER) stress have emerged as potential regulators of fibrotic remodeling. Activated by toll-like receptor (TLR), the transcription factor X-box binding protein 1 (XBP-1) plays a central role in macrophage immune responses via enhancing pro-inflammatory cytokine production, activating NF-κB signaling, and facilitating M1-type macrophage polarization. However, the roles of macrophage ER stress pathways, particularly the XBP-1 signaling, in kidney fibrosis and transplant survival remain unknown.

Methods
To investigate the roles of XBP-1 pathways in macrophage-specific ER-stress induced kidney fibrosis, we use unilateral ureteral obstruction (UUO) model to establish the kidney fibrosis with macrophage XBP-1 conditional knockout (XBP-1^mK.O.) B6 mice and wild-type (W.T.) controls. The supernatant form cultured bone marrow-derived macrophages (BMDMs) of XBP-1^mK.O. or W.T. mice were co-cultured with W.T. tubular epithelial cells (TECs) which was treated with TGF-β to model fibrosis in vitro. Additionally, on post-operation day 7, UUO mice served as recipients after removing bilateral kidneys, for allogeneic kidney transplantation (Balb/c mice as donor), with overall survival (OS) evaluated in KO and W.T. groups.

Results
XBP-1^mK.O. mice with 14d UUO model exhibited more alleviated hydronephrosis in gross observation as well as relieved renal fibrosis characterized by massive collagen deposition in Masson staining, which was further confirmed by the significantly decrease fibrotic markers, fibronectin and α-SMA expression at transcriptional level compared to W.T. mice. Besides, splenomegaly observed in WT but not XBP-1^mK.O. mice was consistent with suppressed systemic immune activation in the knockout group. Together, these findings suggest that myeloid XBP-1 deletion mitigates fibrotic progression and dampens innate immune responses. To further assess the translational relevance, we used UUO mice as recipients in an allogeneic kidney transplant model. Notably, XBP-1^mK.O. mice with 7d UUO, which transplanted a donor kidney, displayed prolonged survival (>3 weeks) post-transplantation versus W.T. (about 5 days), with improved graft renal function exhibited as decreased BUN, Creatinine levels and elevated glomerular filtration rate (GFR) value. In vitro, the supernatant from XBP-1^mK.O. BMDMs suppressed TGF-β-induced fibrotic gene expression in TECs, indicating an anti-fibrotic effect of XBP-1^mK.O. BMDMs on TECs.

Conclusions
These findings highlight macrophage XBP-1 as a novel therapeutic target for mitigating renal fibrosis and improving graft survival. However, the underlying mechanisms warranting further investigation.

Competition Category: Basic Science or Translational

Mentor: Zheng Zhang, MD

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Andrew Yoon, BA

Student

Using Implementation Science to increase resident engagement in Entrustable Professional Activities
Introduction
Implementing new assessment practices, such as Entrustable Professional Activities (EPAs), requires not only resident behavior change, but also an understanding of the facilitators and barriers present in the unique educational environments of surgical training. Implementation Science is the scientific study of the methods and strategies that facilitate the uptake of evidence-based practice and research into regular use. To encourage or reinforce new behavior, it is important to identify intrinsic and extrinsic influences on Capability, Opportunity, and Motivation (COM-B model). The Theoretical Domains Framework (TDF) has been used to identify influences on health professional behavior related to implementation of evidence-based practices. This study used the TDF and COM-B models to characterize barriers and facilitators to general surgery resident engagement with EPAs.

Methods
An online survey instrument constructed using the TDF was administered via QualtricsXM to general surgery residents in a single academic program. Survey results were analyzed in the context of the COM-B model and TDF to identify barriers and facilitators to resident engagement with EPAs.

Results
Data collection is ongoing, but preliminary analysis identified that barriers to EPA completion included memory and attention (e.g., remembering to request EPAs), environmental context, social influences (e.g., faculty engagement), and concrete goal setting. Facilitators of engagement included resident knowledge about EPAs, optimism, positive beliefs about EPAs, and the intentions of increasing EPA use.

Conclusions
Barriers to EPA engagement were most frequently identified in the domains related to Opportunity, followed by Motivation and Capability. Potential avenues for facilitating EPA completion among general surgery residents include interventions that focus on increasing opportunities for EPA completion, such as environmental restructuring (e.g., automation of EPA completion reminders), enablement (e.g., structuring EPA assessment into daily tasks), modeling (e.g., faculty engagement), and persuasion (e.g., support from departmental leaders).

Competition Category: Education

Mentor: Rebecca Williams-Karnesky, MD, PhD, MEdPsych

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Will Yuen, BA

Student

Xbp1 knockdown produces a protective effect against IRI in mice and human TECs
Introduction
Renal ischemia-reperfusion injury (IRI) is the major cause of acute kidney injury (AKI) in the transplant setting. Tubular epithelial cells (TECs) are the primary target of IRI and the source of the resulting stress response. Activation of the endoplasm reticulum (ER) stress has been implicated in the possible aggravation of this injury. We thus sought to determine how Xbp1, a vital transcription factor in the ER stress pathway, affected kidney IRI using both TEC culture system and kidney transplantation in mice.

Methods
We developed an in vitro IRI model of TEC culture, in which primary mouse TECs (mTECs) or human TECs (hTECs) were subjected to cold ischemia time (CIT, 4℃) for 6hr followed by replacement with fresh media (37℃) for 2 or 24hr. mRNA-sequencing was performed using the normal mTECs and 2hr IRI mTECs to explore the predominantly regulated pathways. The in vitro IRI model was used in combination with Xbp1-siRNA transfection or 4μ8C, an IRE1α/Xbp1 inhibitor, to investigate the effects or co-cultured with bone marrow-derived macrophages (BMDMs). In the kidney transplant model, donor kidneys were kept in cold storage for 3hr, then transplanted into allogeneic recipients and analyzed at 3 or 24hr post-transplant.

Results
In vitro IRI significantly increased expression of TEC injury markers (Kim-1, NGAL, TNF), and cell death, similar to observations in the kidney transplants. The transcriptome landscape revealed distinct changes in mTECs that underwent IRI. Specifically, the unfolded protein response, ER stress, and regulation of epithelial cell apoptosis were the predominantly upregulated processes. DEG analysis identified upregulated Xbp1 as a key mediator, which was further confirmed in kidney grafts in vivo. Additionally, there was also a significant increase in cell death and inflammatory cytokine production (IL-6, TNFα) during 24h IRI for mTECs. Suppression of Xbp1 expression significantly downregulated the expression of injury markers, production of inflammatory cytokines, and protected mTECs from death. Interestingly, BMDMs adopted an inflammatory M1 phenotype when co-cultured with injured mTECs, however, si-Xbp1 treatment significantly decreased M1 polarization. Lastly, using the same in vitro IRI model, hTECs exhibited a similar increase in ER stress response, inflammatory cytokines secretion, and apoptosis. However, attenuation of ER stress with 4μ8C provided a protective effect for injured hTECs.

Conclusion
These findings indicate that IRI-induced activation of TEC intrinsic ER stress pathways drives pro-inflammatory response and cell death. The inhibition of the Xbp1-dependent ER stress pathway presents as a promising approach to mitigating IRI.

Competition Category: Basic Science or Translational

Mentor: Zheng Zhang, MD, MS

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Norah Zaza, MD

Senior Resident (Clinical PGY3-5)

Risk of Financial Catastrophe for Breast Cancer Patients in Nigeria: A Retrospective Analysis
Introduction
Cancer imposes significant financial burden on patients in low and middle-income countries like Nigeria, where breast cancer (BC) is the most common cancer and has the highest mortality. This study aims to investigate the financial burden of BC care at Lakeshore Cancer Center (LCC) in Nigeria and identify risk factors for financial catastrophe (FC).

Methods
LCC was queried for uninsured patients diagnosed with breast cancers between 2013-2023, linked to cost data through chart abstraction of billing data and adjusted to 2023 USD. All costs were out-of-pocket costs (OOP) as all patients were uninsured. Risk for financial catastrophe was defined as OOP exceeding 20% of Nigeria's 2023 per capita GDP ($467). Total OOP and risk for financial catastrophe were measured with descriptive statistics and stratified by clinical characteristics.

Results
352 BC patients (99% female, median age 47, 41% stage 4, 28% stage 3) were included. 260 (74%) patients risked financial catastrophe, despite only 30% completing treatment. Patients with HER2+/HR+ disease exhibited the highest treatment costs. Among patients that underwent multiple treatment modalities (n =130), the average OOP was $17992 with 100% risking financial catastrophe. The highest contributors to the cohort's total costs were chemotherapy (29%), immunotherapy (18%), and other drugs (12%). Surgery contributed 7%.

Discussion
Less than one-third of BC patients completed treatment, and the majority faced financial catastrophe, especially those with HER2+/HR+ disease and patients who underwent multiple treatment modalities or immunotherapy. Targeted efforts are essential to ensure equitable access to quality cancer care while minimizing risk of financial catastrophe.

Competition Category: Health Policy

Mentor: Juliet Lumati, MD

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Kaijie Zhang, MD

Fellow (Clinical or Postdoctoral Researcher)

NAD⁺ Depletion in Vein Grafts Contributes to Intimal Hyperplasia and Failure: A Potential Therapeutic Target
Introduction
Autologous vein grafts (VG) are the most commonly used conduits in bypass surgery but exhibit up to 50% failure within 10 years, largely due to intimal hyperplasia (IH) driven by endothelial cell (EC) dysfunction. Suboptimal pre-bypass storage conditions can impair ECs. Nicotinamide adenine dinucleotide (NAD⁺), essential for metabolism and redox signaling, has been linked to EC dysfunction in various diseases. However, its role in VG failure remains unexplored.

Methods
Using Seurat v5.0 and SingleR, we re-analyzed single-nucleus RNA sequencing (snRNA-seq, GSE263280) and spatial transcriptomics data (GSE263281) to assess the expression of NAD⁺-related and EC dysfunction-associated genes. In vivo, a rat VG bypass model was developed by storing jugular veins in different solutions before grafting them onto carotid arteries using intima-intima anastomosis.

Results
Transcriptomic re-analysis revealed significant changes in EC gene expression linked to dysfunction and decreased NAD⁺ biosynthesis. VG storage conditions led to NAD⁺ depletion, while ex vivo NAD⁺ supplementation preserved EC function and significantly improved post-bypass VG patency.

Conclusion
NAD⁺ dysregulation contributes to EC dysfunction and IH, playing a critical role in VG failure. NAD⁺ replenishment represents a potential therapeutic strategy to enhance VG outcomes after bypass surgery.

Competition Category: Basic Science or Translational

Mentor: Bowen Wang, PhD

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