Citations

Background: Sarcoidosis is a multisystem disorder characterized by non-caseating granulomas in various organs. While cardiac sarcoidosis (CS) is clinically rare, it has significant implications, including heart failure, ventricular arrhythmias, and sudden cardiac death. Speckle-tracking echocardiography has emerged as a promising tool for detecting subclinical myocardial dysfunction, which is cost-efficient and readily available. This meta-analysis aims to evaluate differences in functional echocardiographic parameters between patients with CS and extracardiac sarcoidosis (ECS) to improve early recognition and management. Methods: A comprehensive search of major bibliographic databases was conducted to identify studies up to December 2024. Mean differences (MDs) with 95% CIs were pooled using the inverse-variance random-effect model. Results: Seven studies with 478 patients with sarcoidosis (CS: 159 and ECS: 319) were included. Patients with CS had a significant reduction in left ventricular global longitudinal strain (MD: −2.73; 95% CI: −4.09, −1.38; p < 0.0001) and tricuspid annular plane systolic excursion (MD: −0.59; 95% CI: −1.12, −0.05; p = 0.03) compared to patients with ECS. No significant differences in the LV global circumferential strain, interventricular septum thickness, left ventricular ejection fraction, E/A ratio, E/E’ ratio, LV end-diastolic diameter, and LV end-systolic diameter were noted. Conclusions: LV GLS and TAPSE are promising parameters for the early detection of cardiac involvement in sarcoidosis, with significant prognostic implications. Although STE provides a cost-effective and accessible alternative to CMR and FDG-PET, further research is needed to standardize its use and validate diagnostic cut-offs.

745 Background: The combination of EV-P therapy has recently been approved as first-line (1L) therapy for patients with LA/mUC based on the results of the EV-302 trial. Herein, we report the updated results from a cohort of patients with LA/mUC who received EV-P in real world clinical setting. Methods: This retrospective study included patients with LA/mUC (07/2022-08/2024) at the Mayo Clinic who completed at least one cycle of EV-P. The best overall response (BOR) was evaluated using radiographic imaging and was adjudicated as complete response (CR), partial response (PR), stable disease (SD), mixed response (MR), or progressive disease (PD). The median progression-free survival (PFS), defined as the time from treatment initiation to disease progression or death, was estimated using the Kaplan-Meier method. Patients who had not experienced disease progression by their last follow-up were censored for the PFS analysis. Results: A total of 120 patients were included; 79 (65.8%) were males, 41 (34.1%) females, 109 (91%) White, and 119 (99%) were non-Hispanic/Latino. The median age was 72 years (IQR: 65-77). Of these, only 22 (18.3%) had locally advanced disease while the remaining had mUC; 62 (51.6%) had lower tract urothelial carcinoma (LUTC), 36 (30%) had upper tract urothelial carcinoma (UTUC). The median follow-up time was 7.1 months (IQR: 4.93-9.26). In terms of BOR, 56 patients (46.6%) experienced PR, 34 (28.3%) CR, 12 (10%) PD, 7 (5.8%) MR, and 8 (6.6%) experienced SD. 3 (2.5%) patients were not evaluable. The BOR across subgroups, LA and mUC, including LUTC and UTUC, is summarized in the table. Among the responders, the median number of treatment cycles to first response was 3 (IQR: 2.25–4). Within the follow-up, 28 patients (23.3%) experienced eventual radiographic disease progression; death was observed in 25 patients (20.8%). The median PFS was 12.7 months (95% CI: 9.8-NE), and OS was 25.1 months (16.3-NE). Conclusions: In real world setting, the combination of EV-P in LA/mUC demonstrated clinical efficacy compatible with the findings from the EV-302 trial. Our results showed comparable efficacy with EV-P in both UTUC and LUTC, highlighting it's broad therapeutic potential. However, clinical data at longer follow-up is required to fully evaluate overall survival and the durability of response. mUC LA Overall LUTC UTUC Total patients 98 62 36 22 BOR CR 23 (23.4%) 13 (20.9%) 10 (28.5%) 11 (50%) PR 49 (52.6%) 31 (50%) 18 (50%) 7 (31.8%) SD 6 (6.4%) 2 (3.2%) 4 (11.4%) 2 (9.0%) PD 10 (10.7%) 9 (15.5%) 1 (2.8%) 2 (9.0%) MR 7 (7.5%) 5 (8.6%) 2 (5.7%) 0 (0%)

134 Background: Prostate cancer patients with visceral metastases at diagnosis are often treated using one-size-fits-all approach. For example, CHAARTED criteria treats any visceral metastasis as high volume. Therefore, we aimed to assess overall survival (OS) by site of visceral involvement in patients with metastatic PCa. Methods: Surveillance, Epidemiology, and End Results (SEER) database (2010-2021) was queried to obtain case listing data on metastatic PCa patients from 17 registries. The patients were categorized into three groups based on visceral metastasis at diagnosis: lung metastasis, liver metastasis, and others. Kaplan-Meier survival analysis was performed to estimate median OS with 95% confidence interval (CI). Log-rank test was conducted to assess if survival was significantly different among the groups. Cox proportional hazard regression analysis was performed to assess the magnitude of difference among the groups. P-value <0.05 established statistical significance. Results: This analysis included 21,007 metastatic PCa patients (lung: n=319; liver: n=123; brain: 107; bone: 20538). Metastatic PCa population with lung metastasis exhibited a median OS of 60 months (95% CI: 48-72) compared to 24 months (95% CI: 12-36) in population with liver metastases and to 36 months (95% CI: 36-36) in population with other metastases. The difference in OS among the groups was statistically significant (p < 0.001). Compared to population with lung metastasis, those with liver (HR: 1.91; 95% CI: 1.41-2.57) but not those with other metastases (1.16; 0.97-1.39) had significantly worse OS adjusting for Gleason score, PSA and race (Table). Conclusions: In metastatic PCa, patients with lung-only metastasis have significantly better overall survival and should be considered differently in prognostication to liver metastases. Consideration of site of visceral metastasis is critical for treatment intensification decisions. Limitations of this analysis include lack of accounting for confounding relationships at individual patient level. Variable Hazard Ratio (95% CI) Metastases (Lung) REFERENCE Metastases (Liver) 1.91 (1.41-2.57) Metastases (Other) 1.16 (0.97-1.39) Gleason score≥8 REFERENCE Gleason score <8 0.68 (0.64 -0.72) PSA - ng/dL 1.01 (1.00 – 1.01) Race (White) REFERENCE Race (Black) 0.99 (0.94 – 1.05) Race (Asian or Pacific Islander) 0.70 (0.64 – 0.76)

866 Background: Emerging data suggests that Language Models (LLMs) provide an unprecedented opportunity to extract critical data from the unstructured pathology reports. However, the performance of state of art (SOTA) models on clinically meaningful tasks such as assessment of pathologic responses in patients receiving neoadjuvant chemotherapy (NAC) in muscle invasive bladder cancer(MIBC) is not well known. Methods: This retrospective cohort included patients with pathologically confirmed Muscle-Invasive Bladder Cancer from the year 2018 to 2024. Selected patients included those who underwent Neoadjuvant chemotherapy followed by definitive cystectomy at Mayo Clinic. Gold standard labels were manually curated by trained clinicians. The state of the art (SOTA) LLM – GPT4 – was utilized using a structured zero-shot prompt to extract relevant phenotypic variables such as tumor site, tumor histology and additional histological variants if any, presence of in-situ / invasive carcinoma, presence of lamina propria / muscularis propria / lympho-vascular / perineural invasion, and T-stage from unstructured pathology reports. Structured prompts were iteratively developed for each data variable and validated using ~5% of the total dataset. The extracted variables were manually compared and labelled as True positive / True negative / False positive / False negative. Final performance was assessed against a held-out expert annotated test dataset using evaluation metric (accuracy). Results: A total of 200 reports from 99 patients were extracted by the LLM. Of the 200 reports, 41 duplicate / other pathology reports (e.g. – autopsy, cholecystectomy, etc.) were removed during final assessment. Significant characteristics such as tumor site, histology, and additional histology variant had an accuracy of 89%, 87%, and 91% respectively. Notably, accuracy of detection of in-situ versus invasive carcinoma was 70% versus 91%. Specific variables such as lamina propria / muscularis propria invasion / T-stage / lympho-vascular invasion / perineural invasion were answered with the accuracy of 75%, 75%, 67%, 90%, and 94% respectively. Conclusions: LLMs have the potential to extract critical data from unstructured pathology reports and automate assessment of pathologic responses in MIBC patients receiving NAC. Iterative improvements in performance can be achieved by improving prompt design using expert clinical input. This process can be potentially scaled to automate cancer registries.

ABSTRACTObjective(s)We aim to identify the diversity of barriers to care for otolaryngology‐head and neck surgery patients in Harare, Zimbabwe.MethodsInterviews were conducted at four general otolaryngology clinics in Harare in October 2022.The patient population included children and adults presenting to either government or private clinics. Via interpreter, six standardized questions were discussed with each patient. Survey responses were used to categorize patients into one or more of three types of delays: (1) deciding to seek care, (2) reaching the appropriate healthcare facility, and (3) receiving adequate care after reaching that facility.ResultsForty‐six patients participated in this survey. The average time from problem presentation to treatment in this population was 16.3 months. Twenty‐six percent of patients experienced more than one type of delay. The most common type of delay was Type 3 (67%). Many of these patients reached appropriate facilities but could not receive timely treatment due to lengthy wait times. Type 1 delays affected 35% of patients. Notable causes were fear of doctors, preference for traditional healing, or ignorance to a treatable problem. Type 2 delays were also reported in 37%, commonly due to long distance and time to travel and insufficient finances for these journeys.ConclusionsENT patients in Zimbabwe experience a myriad of delays to receiving appropriate care. Systemic issues, including backlogged surgical lists, convoluted referral patterns, and poor transportation infrastructure, are significant contributors to patient delays. The 3‐delay model is useful for identifying barriers to care for future efforts to improve patient access to safe and affordable surgical care.Level of EvidenceLevel VI.

Abstract Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor of adults. Current therapeutic options yield dismal prognoses that have remained essentially unchanged over nearly two decades. Diffuse growth patterns, high intratumoral heterogeneity, and variable blood–brain barrier integrity limit treatment efficacy, creating challenges that rational small molecule design has not overcome. Antibody–drug conjugates have shown some promise, leading us to hypothesize that smaller folded DNA aptamers, developed in vivo via principles of natural selection, might eventually have advantages for drug delivery. Here, we document the first in vivo DNA aptamer selection involving an orthotopic patient-derived xenograft GBM mouse model to identify tumor-homing DNA aptamers. We demonstrate the preferential accumulation of these aptamers in the tumor relative to other tissues 4 h after intraperitoneal injection. The aptamers can be detected by quantitative polymerase chain reaction, fluorescent tumor staining, and stain GBM tumor section from untreated mice and the GBM tumor cells in culture. Two of three candidates are selective for the target cell line in vitro and do not bind other human tumor cells. In vivo selection of tumor-specific DNA aptamers demonstrates a novel approach for diagnostics or toxin delivery that might allow for the development of individualized therapies.

Background: Carotid stenosis has been associated with stroke and cognitive impairment. It remains unclear if hypometablism, a marker for neurodegeneration, may be in the mechanistic pathway in the association between carotid stenosis and cognitive decline. This study aims to investigate whether patients with carotid stenosis exhibit reduced cerebral glucose metabolism, using 18-FDG PET imaging as a sensitive measure of brain’s glucose metabolism. Methods: We have identified 138 patients from one health care system who underwent 18-FDG PET imaging and had extracranial carotid imaging (doppler ultrasound/CT angiography/MR angiography) within 1 year of PET scan. Severity of carotid stenosis was defined using NASCET criteria as <50% (mild), 50-69% (moderate), >70% (high-grade). Cerebral glucose metabolism was quantified by measuring standardized uptake value ratio (SUVR) after normalizing to pons in 12 different regions of interest (ROI). Hypometabolism was defined using the cutoff of SUVR <1.41. SUVR and hypometabolism measures were compared across severity of carotid stenosis. Results: Of 138 patients identified, 54 were excluded due to indeterminant ipsilateral hemisphere status. Mild, moderate and severe stenosis was present in 86.9%, 4.8%, 8.3%, respectively. The analysis revealed a numerically reduced cerebral glucose metabolism in patients with moderate to severe carotid stenosis compared to control subjects (Table 1). The most pronounced decrease in FDG uptake was observed in regions supplied by the affected carotid artery, particularly the ipsilateral cortical areas. There was a numerically increased risk of hypometabolism with increasing carotid stenosis: Adjusted odds of hypometabolism ipsilateral to the carotid stenosis were 2.90, 5.56 across patients with moderate and high-grade carotid stenosis in sensorimotor cortex (trend-P=0.095). These findings were consistent across different regions supplied by the stenotic carotid artery but attenuated in territories supplied by unaffected posterior arteries (Table 2). Conclusions: FDG-PET imaging demonstrates reduced glucose metabolism in patients with carotid stenosis, suggesting that cerebral hypoperfusion may contribute to the metabolic disturbances observed in these patients. These results underscore the importance of early detection and management of carotid stenosis to mitigate potential cerebral metabolic deficits and the associated risk of dementia and ischemic stroke.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression. Anti-inflammatory therapy, therefore, presents a unique dilemma for cancer survivors: while it may decrease cardiovascular risk, it might also promote cancer growth and metastasis by suppressing the immune response. Senescence presents a potentially targetable solution to this challenge; senescence increases the risk of both cancer therapy resistance and vascular disease. Exercise, notably, shows promise in delaying this premature senescence, potentially improving cancer outcomes and lowering vascular disease risk post-treatment. This review focuses on the long-term impact of cancer therapies on vascular health. We underscore the importance of modulating senescence to balance cancer treatment’s effectiveness and its vascular impact, and we emphasize investigating the role of exercise-mediated suppression of senescence in improving cancer survivorship.