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Doxorubicin is an effective chemotherapeutic agent, but its long-term cardiotoxicity contributes substantially to morbidity and mortality, with ~9% of patients developing cardiomyopathy in the years following treatment. Prior studies show that intermittent fasting exacerbates doxorubicin-induced cardiotoxicity by promoting nuclear translocation of transcription factor EB (TFEB), which drives cardiac muscle atrophy and fibrosis. Because high-fat diets (HFD) have been shown to suppress TFEB activity, we hypothesized that HFD could mitigate doxorubicin-induced cardiotoxicity. Male C57BL/6N mice were fed standard chow until 8 weeks of age, were subsequently randomized to standard chow or HFD, and then treated with doxorubicin (5mg/kg intraperitoneally) or saline (n=5/group). On echocardiogram and stress testing, compared with chow-fed mice, HFD-fed mice preserved lean mass, exercise capacity, and cardiac function, with reduced fibrosis and improved ejection fraction, left ventricular mass, and fractional shortening. Mechanistically, doxorubicin increased mRNA abundance of the main lysosomal hydrolytic enzyme, lysosomal acid lipase (LAL), a key regulator of lipophagy. LAL knockout mice showed increased mortality, cardiac atrophy, fibrosis, and enhanced TFEB nuclear translocation. These findings suggest that lipid availability sustains LAL activity, suppresses TFEB, and protects against excess cardiac catabolism. Conclusively, HFD preserved cardiac structure and function during doxorubicin therapy, highlighting a potential translational dietary strategy to reduce cardiotoxicity in human cancer patients.

AMA Research Challenge 2025 

Exploiting Lysosomal Lipolysis to Prevent Doxorubicin Cardiotoxicity

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Background 
Inguinal hernias account for nearly 800,000 surgical repairs annually. While generally associated with good outcomes, elective inguinal hernia repair (IHR) has postoperative complications in over 10% of cases. Identifying modifiable risk factors remains important. As an important risk factor, obesity has previously been shown to have a negative impact on surgical outcomes. However, limited research has analyzed the effects of obesity specifically on robot-assisted IHRs. This study aims to determine whether Body Mass Index (BMI) is associated with a combined outcome of postoperative complications within 30 days of robotic IHR.
Methods
This retrospective cohort study analyzed 290 patients who underwent robotic IHR at a single center. BMI was primary independent variable, and the outcome was any complication within 30 days of surgery, comprising wound-related complications (surgical site infection, hematoma, or seroma) and other adverse events (urinary retention, severe pain, reoperation). Univariate analysis was used to evaluate associations between covariates and the primary outcome. A multivariable logistic regression model was constructed with the statistically significant covariates in the univariate analysis. 
Results
Of the 290 patients analyzed, 23 (7.9%) experienced a postoperative complication within 30 days according to the criteria. Based on the multivariate logistic regression, higher BMI was independently associated with increased odds of complication (OR 1.10, 95% CI 1.01-1.20, p = 0.0214). Use of anticoagulants (OR 7.15, 95% CI 1.30-32.70, p = 0.0135) and ASA class ≥3 (OR 2.68, 95% CI 1.02-6.76, p = 0.0386) were also significantly associated with postoperative complication. The model demonstrated acceptable discrimination (AUC 0.723) and good fit (Hosmer-Lemeshow p = 0.47). Additional univariate analyses were performed for surgical site occurrences (SSOs) and emergency department (ED) visits. For SSOs, ASA class ≥3 was significantly associated with increased odds (OR 7.60, 95% CI 1.81-38.0, p = 0.0066). For ED visits, male sex was associated with decreased odds compared to female sex (OR 0.21, 95% CI 0.05-1.12, p = 0.048), and concomitant procedures were associated with increased odds (OR 5.53, 95% CI 1.19-28.8, p = 0.028).
Conclusion
Higher BMI, ASA Class (≤2 vs. ≥3), and use of anticoagulants were each independently associated with an increased odds for postoperative complication within 30 days of robotic IHR. This suggests that patient-specific risk factors should be considered during perioperative planning, and selected patients may benefit from preoperative weight-loss prehabilitation programs. Future work should focus on refining risk stratification and assessing potential interventions for at risk populations.

BMI and 30-Day Complications After Robotic Inguinal Hernia Repair: A Multivariate Analysis

Abstract Title
Comparative Analysis of PRDX Expression in Bladder Urothelial Carcinoma and Decoding Its Prognostic Value

Background
Bladder urothelial carcinoma (BLCA) is one of the most common types of urologic malignancies that disproportionately affects older males and is projected to double by 2040. Oxidative stress is a common hallmark of cancer, resulting from an imbalance between the overproduction of reactive oxygen species (ROS) and dysfunctional antioxidant defenses. Peroxiredoxin (PRDX1-6) are a family of antioxidant enzymes with each possessing unique biological roles. However, their contributions in cancer progression, immune modulation, and prognostic qualities in patients with BLCA remain unclear. This study investigates the association between PRDXs expression and their impact on genomic instability, tumor immune microenvironment, and tumor characteristics in BLCA.

Methods
Clinical information and RNA sequencing data of the PRDX genes were acquired from The Cancer Genome Atlas (TCGA). Samples were grouped by PRDX expression levels using their z-score relative to all samples (n = 411). An analysis was conducted to assess the relationship between PRDXs expression levels to genomic instability metrics (aneuploidy score, mutation score, TMB, MSI), tumor immune microenvironment (immune score, stromal score, estimate score), and expression of innate immune and checkpoint genes. Kaplan–Meier survival analysis and ROC curves were also generated to evaluate their prognostic relevance. 

Results
Overexpression of PRDX1, PRDX4, and PRDX5 were significantly associated with genomic instability. While the overexpression of PRDX2, PRDX4, and PRDX6 were significantly associated with tumor immune microenvironment. The heatmap analysis for innate immune genes showed that PRDX4 and PRDX6 exhibited a hot immune phenotype with high expression of immune checkpoint genes (PDCD1LG2), whereas PRDX2 and PRDX3 exhibited colder immune profiles with downregulation of immune checkpoints. Notably, the overexpression of PRDX6 was associated with poor prognosis and more advanced tumor characteristics. In contrast, the overexpression of PRDX1 was also linked to reduced overall survival and a colder immune phenotype, suggesting potential immune evasion. 

Conclusion
PRDX6 was linked to poor prognosis as evidenced by its reduced survival outcome and hot immune phenotype, suggesting a role in driving tumor progression. PRDX4 emerged as a gene of interest due to its impact on genomic instability and tumor immune microenvironment. In contrast, PRDX2 overexpression were associated with more advanced tumor stage and size, but not a significant impact on overall survival suggesting a role in tumor growth dynamics rather survival. Our findings may have important clinical implications for utilizing PRDXs as a potential prognostic biomarker to stratify BLCA patients and as a target to enhance immunotherapy response in BLCA. Future studies should validate findings and explore the role of PRDXs as useful biomarkers when combined with other biomarkers to improve BLCA prognosis. 




Comparative Analysis of PRDX Expression in Bladder Urothelial Carcinoma and Decoding its Prognostic Value

The COVID-19 pandemic has revealed significant secondary complications affecting musculoskeletal (MSK) health, especially in patients with pre-existing conditions. This review synthesizes data from clinical and experimental studies on key MSK biomarkers, including cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), osteocalcin, alkaline phosphatase (ALP), procollagen type I N-terminal peptide (PINP), osteopontin (OPN), matrix metalloproteinases (MMP-3 and MMP-9), myostatin, IGF-1, follistatin, and creatine kinase. COVID-19 is associated with decreased COMP and osteocalcin levels, indicating cartilage degradation and impaired bone formation, alongside elevated HA, ALP, PINP, OPN, and MMPs, reflecting increased joint inflammation, bone remodeling, and tissue breakdown. Changes in myostatin, IGF-1, follistatin, and creatine kinase levels have been showen to be linked with COVID-19 related sarcopenia. These biomarker alterations provide insight into the underlying mechanisms of MSK damage in COVID-19 patients and highlight the potential for using these markers in early diagnosis and management of post-COVID musculoskeletal disorders. Further longitudinal research is essential to develop targeted therapies aimed at mitigating long-term MSK complications in affected individuals.

Understanding Musculoskeletal Complications in COVID-19 Through Biomarkers

•In 2025, it is estimated that there will be 84,870 new cases of bladder
cancer and an estimated 17,420 people will die of this disease.
•Bladder cancer is associated with significant renal-related mortality.
•Patients with muscle invasive bladder cancer (MIBC) scheduled for radical
cystectomy (RC) have reported baseline CKD prevalence rates of
approximately 37%. Studies have shown higher CKD stages post-RC
increases all cause mortality.
•This can be attributed to chemotherapy-associated nephrotoxicity, acute
kidney injury (AKI), chronic kidney disease (CKD) with possible dialysis
dependence.
•Older adults are particularly vulnerable due to age-related declines in renal
function, comorbidities, and higher prevalence rates.
•In our study we plan to evaluate the burden and trends of renal function
decline in bladder cancer patients using national database.
•Using the CDC WONDER Database, this study aimed to evaluate renal-
related events as a cause of death in bladder cancer patients, with a focus
on demographic trends and the preferred place of death (PPOD) in the
United States.

The Impact of Declining Renal Function on Bladder Cancer in the U.S. (1999-2023): A Regression Analysis Using the CDC WONDER Database

Introduction: The diagnostic yield of endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA) can approach 72-95% in mediastinal and hilar lymph nodes. However, these percentages refer to the final diagnosis made by the pathologist after the procedure is completed. Rapid On-Site Evaluation (ROSE) is used during the procedure to obtain a preliminary pathology report. When performed on FNA samples, ROSE is frequently non-diagnostic, compelling the bronchoscopist to sample additional lymph nodes or switch modalities to navigational bronchoscopy for direct sampling of the lesion. Here, we investigate the utility of performing intranodal forceps biopsies under EBUS guidance to improve the diagnostic accuracy of ROSE. 



Methods: 58 adult patients with mediastinal or hilar lymphadenopathy were included in this single-center retrospective study with procedure dates between February 2021 and January 2023. A single bronchoscopist performed all procedures. After identification of the pathologic lymph node(s), EBUS-FNA sampling was performed, with samples being evaluated by ROSE. If these specimens were non-diagnostic, then intranodal forceps biopsy was attempted. When successful, forceps biopsies underwent ROSE as well. The diagnostic sensitivity for biopsy ROSE was calculated using the final pathology reports as the “gold standard” for diagnosis. 



Results: In our 58 patients, 65 lymph nodes and nodules underwent forceps biopsy. 83% (54/65) of the lymph nodes sampled had ROSE performed on both FNA and the biopsy, the majority of which were performed due to non-diagnostic ROSE. Of these, 18 (38%) had a positive biopsy ROSE. In one patient, there was a false positive with ROSE of the biopsy being read as “lesional cells”, but the final pathology had a diagnosis of “reactive cells.” When used as an add-on procedure for negative FNA ROSE, intranodal forceps biopsies had a sensitivity of 61.5%, specificity of 87.5%, positive predictive value of 94.1%, and negative predictive value of 41.2%. No complications were attributed to the intranodal forceps biopsies. 



Conclusion: While EBUS-FNA is an excellent diagnostic tool, false-negative preliminary results on ROSE frequently occur. Our study shows that intra-nodal forceps biopsy can be performed safely and effectively on a wide array of mediastinal lymph node stations, and that it can improve the immediate diagnostic yield of ROSE. In our experience, the use of intranodal forceps biopsy as an add-on procedure for negative FNA ROSE reduced the need for additional procedures in over one-third of cases. Further studies are recommended to generalize these findings as well as investigate the overall meaningful clinical benefits of intranodal forceps biopsy.

Using Endobronchial Ultrasound-Guided Forceps Biopsy to Improve Yield of Rapid On-Site Examination During Bronchoscopy

Abstract Title
The Impact of Anesthesia-Induced Intraoperative Hypotension on Hemostasis during Holmium Laser Enucleation of the Prostate

Background
Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in men. Holmium laser enucleation of the prostate (HoLEP) has emerged as a superior option for patients with hemostatic concerns. Intraoperative hypotension (IOH) during general anesthesia is a phenomenon whereby general anesthetics reduce a patient’s blood pressure (BP) and is commonly defined as a >20% reduction from baseline. Existing literature on the relationship between IOH and postoperative blood loss is sparse in urology but has been proposed in plastic surgery literature. This study aims to address this critical knowledge gap by investigating the effect of IOH during HoLEP on post-operative hematuria.

Methods
A retrospective analysis was conducted of all patients who underwent HoLEP by a single surgeon from 1/1/2024 to 12/31/2024. The primary comparison group was the incidence of clinically significant hematuria (CSH). Groups with and without CSH were matched by preoperative prostate volume as determined by preoperative imaging using coarsened exact matching. Mean baseline systolic BP (SBP) within 1 year before HoLEP, highest SBP during the first half of the procedure (the “enucleation phase”), and highest SBP during the second half (the “hemostasis and morcellation phase”) were recorded. Patients were considered to have IOH if highest SBP was at least 20% below the mean baseline. Perioperative characteristics were compared using the Wilcoxon Rank Sum test for continuous variables and either the Chi-squared or Fisher’s exact test for categorical variables.

Results
Out of 182 HoLEPs in the study period there were 26 included in each group after matching. Baseline characteristics were similar. The CSH cohort had a greater incidence of IOH during the hemostasis and morcellation phase (21 vs 0%, p=0.022). The CSH cohort also demonstrated greater length of stay and incidence of ED visits and readmissions.

Conclusion
Patients with IOH throughout the hemostasis and morcellation phase of HoLEP appeared more likely to progress to CSH. Considering IOH role when identifying bleeding vessels and obtaining hemostasis is critical to improving patient safety. Thus, it may be prudent to optimize blood pressure during the hemostasis and morcellation phase of the procedure in order to minimize risk of CSH.

Intraoperative Hypotension and Postoperative Risk of Bleeding in Hemostasis during Holmium Laser Enucleation of the Prostate 

This case report describes myeloperoxidase-anti-neutrophil cytoplasmic antibody
associated vasculitis with kidney involvement in a patient with relapsing
polychondritis, which was successfully treated with Avacopan. Although
relapsing polychondritis has been associated with anti-neutrophil cytoplasmic
antibody-associated vasculitis, overlap can result in severe organ involvement,
particularly renal damage progressing to end-stage kidney disease. This case
presents a unique opportunity to evaluate the potential role of Avacopan as an
alternative therapeutic option in managing myeloperoxidase-anti-neutrophil
cytoplasmic antibody-associated vasculitis in the context of relapsing polychondritis highlighting a positive renal response despite treatment challenges.

Avacopan in the Treatment of Relapsing Polychondritis with p-ANCA Associated Vasculitis


A Novel Method for Curriculum Evaluation: A Cognitive Diagnostic Modeling Approach 

Background 

Integrating basic science education with clinical application in the pre-clerkship years has been shown to strengthen knowledge retention and improve clinical performance later on. In 2017, the University of Toledo College of Medicine and Life Sciences launched a new competency-based curriculum called “Rocket Medicine.” This redesign emphasized early clinical exposure and a more seamless connection between foundational sciences and clinical skills. The transition created an opportunity to compare student mastery of these areas using the DINA model under both the traditional Legacy curriculum and Rocket Medicine. To assess this, we examined retention of foundational science knowledge and student proficiency across key domains, including Diagnosis, Management, Prevention, and Foundation. 

Methods 

The Deterministic Input, Noisy “And” Gate (DINA) model, a type of Cognitive Diagnostic Assessment (CDA), was used to evaluate students’ content mastery based on their performance on NBME subject exams. We applied the DINA model to calculate percentage content mastery across four core skills: Diagnosis, Management, Prevention, and Foundation. Data were collected from all required core clerkships for students in both the Legacy curriculum and the redesigned Rocket Medicine curriculum between academic years 2017 and 2024. To perform the analysis, we built a question-by-content Q-matrix using NBME item analysis reports. Differences in performance between the two curricula were tested using one-way ANOVA and two-sample t-tests, with significance set at P < 0.05. Each medical school cohort included approximately 175 students. 

Results 

Overall, students in the Rocket Medicine curriculum demonstrated higher content mastery across the four core skills (Diagnosis, Management, Prevention, and Foundation) compared to those in the Legacy curriculum. This trend was seen in most clerkships, including significant gains in Diagnosis for internal medicine (95% vs. 81%, p < 0.05), Management for pediatrics, and all four skills in OBGYN. 

Prevention consistently emerged as the lowest mastered skill across both curricula and clerkships. Within Rocket Medicine students, Prevention was significantly lower than Diagnosis in internal medicine (75% vs. 95%, p < 0.05) and lower than other skills in pediatrics, neurology, psychiatry, and surgery (all p < 0.05). 

An exception to these trends was noted in emergency medicine, where Legacy students showed higher overall mastery, likely due to small cohort sizes before becoming a required clerkship. No significant differences were observed between curricula in family medicine. 

Conclusion 

The DINA model revealed higher overall content mastery with Rocket Medicine. However, Prevention remained a consistent gap, highlighting a key area for curriculum refinement and targeted improvement.

A Novel Method for Curriculum Evaluation: A Cognitive Diagnostic Modeling Approach

Background/Objective: 
In fast-paced clinical settings like labor and delivery, quick access to accurate, evidence-based guidance is critical. Traditional methods of sharing protocols can be inefficient, especially for trainees managing complex scenarios. Advances in artificial intelligence (AI) and large language models (LLMs) offer the potential to transform how critical clinical decision-making tools are disseminated, making them more accessible, responsive, and integrated into real-time learning. Our objective was to develop our own chatbot to facilitate quick retrieval and enhanced learning. 

Methods: 
The AI chatbot was developed by IUSM researchers using Microsoft Copilot Studio and made accessible via Microsoft Teams. The AI chatbot was built on a retrieval-augmented generation (RAG) framework, leveraging a fine-tuned LLM. The base LLM was augmented with domain-specific documents, including IUSM protocols – developed by the Maternal-Fetal Medicine division - which incorporate evidence-based practices and provide a consistent management strategy for OB conditions. The RAG architecture was configured to retrieve contextually relevant documents from the collection of protocols in response to user queries.

Results:
The chatbot retrieves information from the protocols based on a user’s query and generates a relevant answer with reference to the sources. Upon testing the chatbot, we learned that the chatbot was unable to retrieve information from figures, flowcharts, and diagrams. Therefore, figures were manually annotated and narrated, enabling the model to process and retrieve relevant visual information during inference. With other adjustments, the chatbot is able to read all aspects of the protocols and synthesize accurate answers to clinical questions.

Conclusion and Potential Impact: 
We optimized an RAG model AI chatbot for clinical education, demonstrating that existing educational material can be used to activate a chatbot to serve clinical needs with sufficient oversight to ensure clinical accuracy. Future directions include evaluating its impact on clinical decision making and student perception of the learning environment once the chatbot is more uniformly adopted. 


Optimization of a RAG Model Chatbot for Obstetric Medical Education

Introduction: Adequate sleep during childhood is important for learning, memory formation, and physical and mental well-being. In 2019, around 79,000 individuals passed away due to drug use. Insufficient sleep has been found to decrease positive emotions. Many drugs that are commonly abused - opioids, cocaine, or nicotine - flood the reward pathway with dopamine, reproducing positive emotions.

Research Questions: Is there an association between childhood sleep inadequacy and deaths from substance use in early adulthood? Are there differences in the types of drugs that are more likely to be used? 

Methods: This project was a correlational study using secondary data across all 50 states and the District of Columbia. Correlational testing was performed at a 95% Confidence Interval, and p-values < 0.05 were considered significant. The correlations between sleep inadequacy and 5 outcomes were explored: total substance abuse, alcohol use, amphetamine use, opioid use, and cocaine use. Data analyses were conducted using SAS Software 9.4, and maps were generated using Tableau. 

Results: West Virginia had the highest prevalence of substance use deaths for total substance use, cocaine use, amphetamine use, and opioid use. New Mexico had the highest prevalence of deaths from alcohol use. Mississippi had the lowest percentage of children meeting sleep guidelines, and Utah had the highest percentage of children meeting sleep guidelines. Total substance use, amphetamine use, opioid use, and cocaine use were positively correlated with less sleep during childhood, and Alcohol use was negatively correlated. Deaths from opioid use in early adulthood were significantly correlated with less sleep during childhood (p = 0.0132). 

Conclusions: Chronic sleep deprivation may dysregulate neurobiological pathways in the brain, potentially increasing susceptibility to opioid misuse later in life. Prevention and treatment services for sleep disorders and substance abuse are not equitable and accessible across all states and the District of Columbia.

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BMI and 30-Day Complications After Robotic Inguinal Hernia Repair: A Multivariate Analysis

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