Citations

Abstract STUDY QUESTION What is the fertility preservation (FP) utilization rate among transgender and gender diverse (TGD) patients at the Transgender and Intersex Specialty Care Clinic (TISCC) within the Mayo Clinic? SUMMARY ANSWER The rate of utilization of FP services by TGD patients at Mayo Clinic’s TISCC was determined to be 6.62%. WHAT IS KNOWN ALREADY TGD patients encounter several barriers when pursuing FP, which may contribute to a lower utilization rate of these services. These barriers include financial constraints and lack of insurance coverage, as well as societal and healthcare provider attitudes; TGD individuals face discrimination or lack of understanding, making it uncomfortable or difficult to discuss FP options. Additionally, there continues to be a lack of inclusive policies and support within healthcare systems that can further impede access to FP services for TGD individuals. STUDY DESIGN, SIZE, DURATION The study was executed in two phases. In the first phase, a retrospective cohort study was completed with TGD patients who provided electronic health record (EHR) research authorization from Mayo Clinic’s TISCC in Rochester, MN between 1 January 2015 and 30 July 2021. Search terms related to FP were used to determine the FP utilization rate among this patient population. In the second phase of the study, two sets of patients, (i) patients who were included in the cohort study in Phase 1, and (ii) members of JASMYN, a community organization specializing in care and wellness coordination for Lesbian, Gay, Bisexual, and Transgender (LGBT) teens and young adults in North Florida. Individuals were invited to participate in a qualitative interview exploring their cumulative healthcare experiences accessing gender-affirming care. Interviews were conducted from January 2023 to June 2023. Interviews examined participants’ perceptions of FP options, motivations for pursuing FP, and barriers to accessing both gender and fertility care. When applicable, participants also discussed their experiences pursuing FP and reflected on their satisfaction with their fertility and family planning decisions. PARTICIPANTS/MATERIALS, SETTING, METHODS In phase 1, a total of N = 1189 patients sought care from Mayo Clinic’s TISCC in Rochester, MN. Out of these patients, N = 589 patients provided research authorization and were included in the retrospective cohort study. The study team assessed whether FP terms were mentioned in each patient’s EHR, and whether patients scheduled and attended appointments with either the Department of Reproductive Endocrinology or the Department of Urology. FP search terms included sperm cryopreservation, sperm extraction, sperm aspiration, testicular tissue cryopreservation, oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation. In phase 2, N = 36 participants were interviewed, with N = 25 participants recruited from Mayo Clinic’s TISCC in Rochester, MN, and N = 11 participants recruited from JASMYN in Jacksonville, FL. Participants recruited from the Mayo Clinic participated in a video-call-based interview and those enrolled from JASMYN were interviewed in person. MAIN RESULTS AND THE ROLE OF CHANCE The study team observed a 6.62% utilization rate of FP services among N = 589 patients (median age: 28 years; age range: 8–78 years) included in the retrospective cohort study. N = 39 patients completed FP, with N = 14 receiving these services at other institutions before seeking care with the TISCC at Mayo Clinic. N = 25 patients pursued FP services within the Mayo Clinic. Patients with testes were more likely to complete FP via sperm cryopreservation when compared to the utilization of egg cryopreservation among patients with ovaries. Participants who completed an interview in Phase 2 (median age 27 years; age range: 22–80 years) reflected on their decision on whether to preserve their fertility and what factors influenced these decisions, and how their satisfaction with this decision has changed over their lifespan. The major themes reported here include the desire for biological children, planning gender care around fertility desires, conversations about FP options, physical and psychosocial barriers to pursuing FP, reflections on personal FP decisions, and reflections on having to make decisions about FP at a young age. LIMITATIONS, REASONS FOR CAUTION All participants who completed an interview have done so voluntarily; as such, there is a possibility of selection and recall bias. WIDER IMPLICATIONS OF THE FINDINGS Findings suggest that there is a need for more structured conversations around FP when TGD patients seek medical and surgical gender-affirming care. Accessibility, including financial barriers and limited insurance coverage, continues to limit the utilization of FP services among TGD patients. Increased affordability through insurance coverage may additionally improve FP utilization. STUDY FUNDING/COMPETING INTEREST(S) This project was funded by the Mayo Clinic Department of Obstetrics and Gynecology and the Mayo Clinic Center for Clinical and Translational Science (CCaTS), grant number UL1TR002377. This project was also supported by Clinical and Translational Science Award (CTSA) Grant Number TL1TR002380 from the National Center for Advancing Translational Sciences (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Felicity Enders reports grants from the National Institutes of Health and the Agency for Healthcare Research and Quality paid to her institution; speakers’ fees for lectures or presentations from Mount Sinai, University of Washington, University of Minnesota, University of Rochester, Cincinnati University, the National Institutes of Health, Duke University, Wake Forest University, the Patient Centered Outcomes Research Institute, Johns Hopkins University; travel support from the Association for Clinical and Translational Science and Cold Spring Harbor Laboratory; and an unpaid leadership role on the Board of Directors of the Association for Clinical and Translational Science. All other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal human malignancies due to its silent clinical onset, rapid progression, and limited responsiveness to current treatment options. These features underscore the urgent need for early detection strategies and for new molecular targets that can be exploited therapeutically. Epithelial Cell Transforming Sequence 2 (ECT2) is a Rho family guanine nucleotide exchange factor that was originally identified as an oncoprotein and later shown to regulate cytokinesis. In this study, we examined the clinical relevance of ECT2 expression in PDAC and determined its functional contribution to transformed growth and tumorigenicity. Our analyses revealed that ECT2 expression increases at the earliest stages of PDAC development, remains persistently elevated during disease progression, and associates with reduced overall patient survival. Furthermore, a substantial fraction of ECT2 is aberrantly localized to the cytoplasm of PDAC cells. Functional studies demonstrated that depletion of ECT2 suppresses three-dimensional growth, invasive behavior, and tumor formation in vivo, while having little impact on PDAC cell cytokinesis. Mechanistically, we found that ECT2 is required for activation of Rac1 and RhoA and downstream MEK/ERK and ROCK signaling, respectively. Consistent with these results, analyses of PDAC patient datasets revealed a strong positive association between ECT2 expression and Rho GTPase as well as MEK/ERK and ROCK pathway signatures. Together, our data identify ECT2 as an early driver of PDAC transformation and highlight it as a promising therapeutic target. Citation Format: Dania Al-Qasrawi, Nayya N. Murray, Ryan A. Argo, Alicia K. Fleming Martinez, Prita Pandya, Anaya Y. Clarke, Kayla C. Winter, Murli Krishna, Peter Storz, Nicole R. Murray, Verline Justilien, . The Rho-GEF ECT2 links Rho GTPases to MEK/ERK pathway activation in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5993.

Abstract Background NRG/RTOG 1010 evaluated trastuzumab added to trimodality therapy for HER2+ localized esophageal adenocarcinoma (EAC) management. Secondary PRO objectives assessed improvement in the FACT‐Esophageal Cancer Subscale (ECS), version 4, with trastuzumab, and if improved ECS correlated with pathologic complete response (pCR). Methods Patients were randomized to weekly paclitaxel/carboplatin/radiation (chemoradiation, CRT) followed by surgery ± trastuzumab (CRT + Tras). Disease‐free survival (DFS) was the primary end point. The projected PRO sample size of 158 patients, based on an 80% participation rate of the DFS primary endpoint sample size of 197 HER2+ patients, would provide ≥ 89% power to detect ≥25% increase in the proportion of CRT + Tras patients with ECS improvement from baseline to 6–8 weeks post‐CRT; one‐sided α = 0.05, using a χ 2 test. Improvement in ECS and its swallowing index (SI) and eating index (EI) was defined as 5‐, 2‐, and 2‐point increases, respectively, from baseline to 6–8 weeks post‐CRT. Univariate logistic regression was assessed if pCR was associated with improved ECS. Results From 2010 to 2015, 203 HER2+ patients were randomized and 194 were eligible. Of 171 PRO consenting patients, the ECS was completed by 162 (95%) at baseline, 108 (64%) 6–8 weeks, 82 (49%) 1 year, and 55 (33%) at 2 years. The proportion of patients with an improvement in 6–8 weeks ECS was higher on the CRT + Tras arm (46% vs. 38%), although not significantly different ( p = .39). There was no correlation between pCR and ECS scores at 1 year, with 39% and 37% of pCR and non‐pCR patients, respectively, having improved 1‐year ECS scores. Conclusions The addition of trastuzumab to CRT for localized HER2+ EAC did not improve PROs.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin lymphoma provide expert, multidisciplinary recommendations for the diagnosis and treatment of Hodgkin lymphoma. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Hodgkin Lymphoma focuses on the management of newly diagnosed and relapsed/refractory classic Hodgkin lymphoma in adults aged 18 to 60 years.

In this short report, we detail new data on the upper limits of human energy expenditure (9.6 times basal metabolic rate) and water turnover (10.5 L·12 h −1 ) during continuous single-day exercise in the cold. Our results indicated elevated energy use, and impressively, water turnover comparable to exercise in warmer conditions. These findings have implications for training and endurance performance of strenuous exercise in cold weather environments.

Abstract Background Computed tomography coronary angiography (CCTA) has emerged as a powerful non-invasive imaging modality for the evaluation of coronary artery disease (CAD), with a global trend towards a "CT-first" strategy in stable patients with suspected CAD. While overall beneficial, this approach requires a shift in resources, straining specific parts of healthcare systems. Pre-test probability (PTP) models stratify risks of obstructive CAD and are intended to result in better utilization of CCTA. However, these models show variability across subpopulations and have modest discriminatory power with low positive predictive values (PPV). Purpose This study aims to leverage explainable artificial intelligence (XAI) for optimization of PTP models. Methods Patients that underwent a CCTA for suspected CAD with a CAD-Reporting and Data System (CAD-RADS) classification and Coronary Artery Calcium Score (CACS) were included. Obstructive CAD was defined as stenosis >50% (CAD-RADS 3 or higher). Missing data was imputed. The Risk Factor Weighted Clinical Likelihood (RF-CL) model based on clinical risk factors (age, sex, type of symptoms, smoking, hypertension, dyslipidemia, diabetes and familial predisposition) was calculated. Two gradient descent-based decision tree models, "AI-ECG" and "AI-CAC" were developed. AI-ECG is built using clinical risk factors and electrocardiogram (ECG) classification. AI-CAC is built using the aforementioned features with addition of CACS. Sensitivity analysis was performed using a 15% threshold, aligning with the threshold for CCTA acquisition. Comparative analysis was performed using Python 3.10.2, with area under the curve (AUC) analysis using the DeLong test and feature importance calculation using shapely values. Preliminary results: We identified 6178 patients with a CCTA between 2022 and 2024 in the Cardiology Centers Netherlands (CCN) and included 2083 patients (mean age 57.4 ± 10.2; 48.1% male). Obstructive CAD was present in 413 (19.8%) patients. The RF-CL model was outperformed by the AI-ECG model (AUC: 0.69 vs 0.80, p<0.001) and the AI-CACS model (AUC: 0.69 vs 0.90, p<0.001). Although sensitivity increased in both the AI-ECG and AI-CACS models from 0.46 to 0.87 and 0.83 respectively, PPV increased only in the AI-CACS model (0.37 to 0.61). Most important features were CACS, age, sex, ECG classification and familial predisposition. Conclusion and Discussion Our study demonstrates that the incorporation of XAI with clinical risk factors, ECG classification and CACS improves the pre-test probability estimation of obstructive CAD. ECG classification appears to be a robust feature. Adopting these models can stratify patients at risk for obstructive CAD, enabling targeted use of CCTA, reducing unnecessary testing, and thus alleviate the burden on healthcare systems. However, further external validation is necessary to assess the model’s performance in prospective real-world settings.Sensitivity analysis feature importance

Abstract Background Coronary Computed Tomography Angiography (CCTA) is the first-line diagnostic tool for suspected stable Coronary Artery Disease (CAD) to rule out obstructive CAD and is recommended for risk stratification. Both obstructive CAD and total plaque burden on CCTA predict cardiovascular (CV) risk. Prior studies demonstrated that type 2 diabetes (T2D) patients exhibit greater plaque burden and higher CV event risk. Purpose This study evaluates whether T2D patients undergoing CCTA for stable CAD symptoms, when matched for traditional cardiovascular risk factors, have a higher prevalence of CAD and greater atherosclerotic plaque burden. Methods A total of 568 patients were included: 284 T2D patients were 1:1 propensity-matched to 284 non-T2D patients based on age, sex, and CV risk factors. All underwent diagnostic CCTA between January 2022 and November 2023. CCTA parameters included CAD-Reporting and Data System (RADS) classification, segment involvement score (SIS), coronary artery calcium (CAC) score, and plaque composition. SIS was defined as the number of segments with at least mild plaque. Coronary segmentation followed the 16-segment model (SCCT). Plaque burden was classified as P1 (mild), P2 (moderate), P3 (severe), and P4 (extensive) per CAD-RADS 2.0, based on SIS, CAC score, and the number and severity of affected vessels. Results The mean age was 60.8 ± 9.97 years (T2D) vs. 61.2 ± 9.80 years (non-T2D), with similar gender distribution (48.6% vs. 48.9% female). BMI was significantly higher in T2D patients (29.2 vs. 26.5, p < 0.05). Smoking was less frequent in T2D patients (56.0% vs. 60.9%, p = 0.03). Other CV risk factors were similar. T2D patients were more likely to use antiplatelet and lipid-lowering agents. CAD prevalence was higher in T2D patients (83.1% vs. 76.4%, p < 0.05), while obstructive CAD was not significantly higher in T2D (33.5% vs. 27.5%, p = 0.13). No significant differences were observed in 1-, 2-, or 3-vessel disease. The SIS was significantly higher in T2D patients (3.85 vs. 3.37, p = 0.03). CAC scores were higher in T2D patients (median 60 [6–369] vs. 31 [0–224]), though not statistically significant. For plaque burden classification, P2 (moderate plaque burden) was more common in non-T2D patients (23.6% vs. 15.5%, p = 0.02), while P4 (extensive plaque burden) was significantly higher in T2D patients (21.1% vs. 14.1%, p = 0.03). Conclusion When matched for cardiovascular risk factors, T2D patients more frequently exhibited CAD on CCTA, with higher SIS scores and a greater prevalence of extensive plaque burden (P4 classification). Despite greater use of preventive medication and a lower smoking prevalence in the T2D group, plaque burden remained higher in these patients. These findings emphasize the need for improved risk stratification and preventive strategies in individuals with T2D.

Abstract Background Coronary computed tomography angiography (CCTA) and myocardial perfusion imaging (MPI) are guideline-recommended to assist in clinical decision-making in patients with prior coronary artery bypass grafting (CABG). However, the value of combining CCTA and MPI for guiding revascularization decision-making in post-CABG patients with recurrent ischemic symptoms remains unexplored. In this study, we compared Heart Team strategies for revascularization based on CCTA and MPI as standalone and hybrid CCTA/MPI imaging, to strategies guided by invasive coronary angiography (ICA). Methods We included symptomatic patients with prior CABG who underwent CCTA and MPI (single-photon emission computed tomography, positron emission tomography or stress perfusion cardiac magnetic resonance imaging) preceding ICA. Simulated Heart Teams, blinded to other Heart teams and outcomes, performed revascularization decision-making based on conventional CCTA, MPI and a hybrid CCTA/MPI strategy (non-invasive Heart Team) or based on ICA (invasive Heart Team). The primary outcome was the Cohen’s kappa agreement (κ) between non-invasive and invasive Heart Teams. Results A total of 115 patients (mean age 73±7 years; 99 [86%] male) were included. Revascularization was recommended in 96 patients (83.5%) by CCTA, 92 patients (80.0%) by MPI, 80 patients (69.6%) by hybrid CCTA/MPI and 76 patients (66.1%) by ICA. The agreements were significant but low for CCTA (κ: 0.25 [95% confidence interval (CI): 0.07-0.42], P=0.003) and MPI (κ: 0.27 [95% CI: 0.09-0.48], P=0.002) compared to ICA, with only a modest increase when using the hybrid non-invasive imaging strategy (κ: 0.32 [95% CI: 0.14-0.51], P<0.001). Conclusions In patients with recurrent ischemic symptoms after CABG, Heart Team assessment of conventional CCTA and MPI yielded similarly poor agreements with revascularization strategies based on ICA, with only a modest improvement observed when using a hybrid CCTA/MPI approach. Overall, non-invasive imaging alone appears insufficient to accurately guide treatment strategies in patients with prior CABG, and their use as gatekeeping for ICA in these patients should be questioned.

Abstract Background Polycystic ovary syndrome (PCOS) affects 10% to 13% of individuals assigned female at birth (AFAB), although a greater prevalence is reported in transgender/gender diverse individuals (TGD) (23.8-38.8%). Testosterone therapy (TT) in TGD individuals is linked to worsening cardiovascular risk factors (CVRFs). Whether TT induces more adverse cardiometabolic changes in TGD with PCOS than TGD without PCOS remains uncertain. Objective To compare the effects of TT on CVRF in TGD with and without PCOS. Methods We retrospectively reviewed 373 records to identify 62 TGD with PCOS (withestablished guideline criteria) and 132 age-matched TGD without PCOS. Data included longitudinal anthropometric measurements, hormone and metabolic parameters, and CVRF before and after TT. Group comparison of PCOS vs without PCOS before and after TT was conducted via independent t-tests, Mann–Whitney-U, and Chi-square. Results At baseline, TGD with PCOS had significantly greater body mass index (BMI), obesity prevalence, and, after controlling for BMI, baseline metformin use. There were no significant differences between TGD with and without PCOS when comparing intra-participant changes after TT. Controlling for BMI, TGD with PCOS on TT exhibited significantly greater hyperlipidemia prevalence, alanine transaminase (ALT) levels, and bioavailable testosterone concentrations than TGD without PCOS on TT. Conclusion Greater baseline cardiometabolic risk was largely BMI-related in TGD with PCOS compared to TGD without PCOS. Only hyperlipidemia and elevated ALT were more prevalent during TT after adjusting for BMI. These findings support cardiometabolic monitoring during TT in all TGD individuals without significant increased risk with PCOS history.