Faculty Bibliography

BACKGROUND/UNASSIGNED:Ulcerative colitis is monitored through clinical, laboratory, endoscopic, and histologic measures. Persistence of histologic inflammation despite clinical and endoscopic remission is associated with disease flare. METHODS/UNASSIGNED:We compared the identification of clinically significant histologic inflammation by general and IBD-specialized gastroenterologists (GI) using a simplified binary scoring system and looked at associations with disease relapse. RESULTS/UNASSIGNED:Both general and IBD-specialized GIs identified significant inflammation associated with relapse, though IBD-specialized GIs scoring had stronger correlations with relapse. CONCLUSIONS/UNASSIGNED:Our findings suggest simple histologic assessment can inform risk stratification, and further work is needed to optimize monitoring patients with histologic inflammation despite endoscopic remission.

BACKGROUND:Perioperative immune-checkpoint inhibition improves outcomes in muscle-invasive bladder cancer (MIBC). The phase III, randomized CA017-078 (ENERGIZE) trial evaluated perioperative nivolumab plus neoadjuvant gemcitabine-cisplatin (GC) versus neoadjuvant GC alone for previously untreated, resectable MIBC. PATIENTS AND METHODS/METHODS:Adults with previously untreated cT2-T4aN0M0 MIBC eligible for radical cystectomy (RC) and cisplatin were randomized to neoadjuvant nivolumab plus GC followed by RC and adjuvant nivolumab (nivolumab plus GC arm), or neoadjuvant GC followed by RC alone (GC arm). Co-primary endpoints were pathological complete response (pCR; defined as ypT0N0) and event-free survival (EFS). Overall survival (OS) was a secondary endpoint within the prespecified hierarchical testing strategy, and formal testing was contingent on a statistically significant EFS result. RESULTS:At this final analysis with 54.5 months of median follow-up, 325 patients were randomized to the nivolumab plus GC arm, 328 to the GC arm. pCR rates were 39.1% and 29.6%, respectively (adjusted difference 9.5%, 99.91% CI -2.6-21.6). EFS was not improved in the nivolumab plus GC versus GC arm (104 events in each arm; HR 0.94, 95.74% CI 0.71-1.25; P=0.6697). OS was summarized descriptively because EFS did not meet the testing criterion (HR 0.88, 95% CI 0.64-1.21). Grade 3-4 treatment-related adverse events occurred in 50.0% versus 49.5%; one treatment-related death occurred with nivolumab plus GC. Pretreatment ctDNA was positive in 229/416 tested patients (55%) overall, 108/211 (51%) in the GC arm, and 121/205 (59%) in the nivolumab plus GC arm. Clearance by cycle 4 day 1 (C4D1) occurred in 153/199 patients (76.9%) overall, 87/107 (81.3%) with nivolumab plus GC, and 66/92 (71.7%) with GC. ctDNA detection at baseline and at C4D1 was associated with shorter EFS and OS. CONCLUSIONS:The addition of perioperative nivolumab to neoadjuvant GC did not improve outcomes and was associated with predictable toxicity. Exploratory analysis showed ctDNA was strongly prognostic.

UNLABELLED:Student feedback is essential to curriculum evaluation. While methods for analyzing quantitative feedback data are readily available and easy to implement, methods for analyzing text-based, qualitative feedback data are less widely available, requiring more time, effort, and expertise. And yet, students' responses to open-ended questions hold great value for curriculum refinement because narrative comments can identify un-anticipated areas of concern that closed-ended rating scales might miss and often provide specific suggestions for improvement. In this paper, we describe efforts to analyze the feasibility and accuracy of using a Large Language Model (ChatGPT 4o) to analyze medical student comments in response to a question asking them to identify basic science topics they found challenging. ChatGPT 4o was used to categorize and summarize students' identification of and explanations for these challenging topics. We describe the specific prompts used to generate and refine results and then conducted a series of experiments to explore consistency, accuracy, and meaningfulness: (1) reviewing the consistency of 10 replications of the ChatGPT 4o request; (2) comparing "expert" human ratings of topic categories with ChatGPT's categorization; and (3) comparing "expert" human analyses of the explanations for a challenging topic with those generated by ChatGPT. Overall, we found the LLM output to be useful, fairly closely aligned with human experts, and easy to implement. However, results were not perfectly replicated across multiple trials and we found some differences between human and LLM analyses. Our use case is well suited to the current capabilities of genAI models in that summaries can be rapidly and easily generated with sufficient (but not perfect) consistency and accuracy to support continuous quality improvement of basic science curriculum. SUPPLEMENTARY INFORMATION/UNASSIGNED:The online version contains supplementary material available at 10.1007/s40670-025-02615-1.

Neoadjuvant therapy (NAT) is increasingly being used for pancreatic ductal adenocarcinoma (PDAC). This study investigates how NAT differentially impacts PDAC's carcinoma cells and the tumor microenvironment (TME). Spatial transcriptomics was used to compare gene expression profiles in carcinoma cells and the TME of 23 NAT-treated versus 13 NAT-naïve PDACs. Findings were validated by single-nucleus RNA sequencing (snRNA-seq) analysis. NAT induces apoptosis and inhibits proliferation of carcinoma cells and coordinately upregulates multiple complement genes (C1R, C1S, C3, C4B and C7) within the TME. Higher TME complement expression following NAT is associated with increased immunomodulatory and neurotrophic cancer-associated fibroblasts (CAFs); more CD4⁺ T cells; reduced immune exhaustion gene expression, and improved overall survival. snRNA-seq analysis demonstrates C3 complement is mainly upregulated in CAFs. These findings suggest that local complement dynamics could serve as a novel biomarker for prognosis, evaluating treatment response, and guiding therapeutic strategies in NAT-treated PDAC patients.

Spirochete colonization of the gastrointestinal tract is a poorly understood phenomenon presenting with varying signs and symptoms. Due to the lack of a unified approach and its varying presentations, the management decision for intestinal spirochetosis (IS) has always been challenging. While metronidazole is the commonly preferred antimicrobial treatment, it remains unclear if therapeutic intervention is indicated for everyone, especially asymptomatic patients. We present three patients, diagnosed with IS. They presented with varying demographics, clinical presentations, and past medical histories and underwent different clinical managements. Our decisions for treatment not only included presenting symptoms but also factors like history of pre-existing gastrointestinal diseases, age, and immune status.

BACKGROUND/UNASSIGNED:Neoadjuvant therapy (NAT) is increasingly being used for pancreatic ductal adenocarcinoma (PDAC) treatment. However, its specific effects on carcinoma cells and the tumor microenvironment (TME) are not fully understood. This study aims to investigate how NAT differentially impacts PDAC's carcinoma cells and TME. METHODS/UNASSIGNED:Spatial transcriptomics was used to compare gene expression profiles in carcinoma cells and the TME between 23 NAT-treated and 13 NAT-naïve PDAC patients, correlating with their clinicopathologic features. Analysis of an online single-nucleus RNA sequencing (snRNA-seq) dataset was performed for validation of the specific cell types responsible for NAT-induced gene expression alterations. RESULTS/UNASSIGNED:T cells, monocytes, and mast cells; and reduced immune exhaustion gene expression. snRNA-seq analysis demonstrates C3 complement was specifically upregulated in CAFs but not in other stroma cell types. CONCLUSIONS/UNASSIGNED:NAT can enhance complement production and signaling within the TME, which is associated with reduced immunosuppression in PDAC. These findings suggest that local complement dynamics could serve as a novel biomarker for prognosis, evaluating treatment response and resistance, and guiding therapeutic strategies in NAT-treated PDAC patients.

Although extraintestinal manifestations of inflammatory bowel disease (IBD) are common, pulmonary IBD is extremely rare. Owing to its nonspecific clinical, radiologic, and pathologic features, pulmonary IBD is difficult to diagnose and may mimic more concerning disease processes. We present a rare case of a patient with known Crohn's disease whose initial presentation was highly suspicious for malignancy before further investigation revealed pulmonary IBD.

BACKGROUND/UNASSIGNED:In ulcerative colitis (UC), endoscopic improvement, defined as a Mayo Endoscopic Score (MES) of 0 or 1, is a target of treatment. The aim of our study was to evaluate the risk of clinical relapse between patients with an MES of 0 or 1 and determine if histologic activity using the Robarts Histopathologic Index (RHI) was predictive of clinical relapse. METHODS/UNASSIGNED:UC patients with an MES score of 0 or 1, no prior colectomy, and at least 1 year of outpatient follow-up after colonoscopy were included. Demographic, clinical characteristics, and clinical relapse were retrospectively collected. Biopsy specimens were read by a gastrointestinal pathologist. Primary outcome was defined as a composite of relapse requiring change in medical therapy, new steroid use, UC-related hospitalization, and/or colectomy. RESULTS/UNASSIGNED: = .008). CONCLUSIONS/UNASSIGNED:UC patients with endoscopic improvement have a high rate of clinical relapse over time. Histologic activity is a predictor of clinical relapse.