Citations

The hospital setting can present physical, emotional, and spiritual challenges for individuals. It is important to recognize these challenges and empower individuals to manage them. The health care team is in a unique position to listen to the needs of hospitalized individuals. Three vignettes illustrate active listening, compassion, and access to resources. With these tools, health care clinicians can humanize the hospital experience and alleviate the emotional burden patients face in the hospital setting.

Abstract Objective Effective communication with humans and automated voice assistants (AVA) is essential for full participation in modern life. Because AVA relies on intelligible speech, individuals with speech impairments, such as those treated for oral cavity cancer (OCC), may face barriers when interacting with AVA. We assessed self‐reported communication difficulty in patients treated for OCC related to AVA and humans. Study Design Prospective cross‐sectional cohort study. Setting Out‐patient clinics in two tertiary care centers. Methods This study was conducted between July 2024 and March 2025 and included adults (≥18 years) diagnosed with and surgically treated for OCC (experimental group) and those without speech impairments (controls). Participants completed the Speech Communication Experience Survey (SCES), which assessed perceived intelligibility when communicating with familiar partners, strangers, and AVA; and, as reported elsewhere, the Speech Handicap Index (SHI). Results In total, 159 participants were included (69 OCC, 90 controls). OCC participants were more likely to report that familiar partners, strangers, and AVA “almost always” or “always” had difficulty understanding their speech ( P < .05). Free flap reconstruction and maxillectomy were associated with greater reported communication difficulty. AVA usage frequency and overall opinions toward AVA did not significantly differ between groups. Conclusion Patients treated for OCC report significantly greater difficulty being understood by both AVA and human listeners compared to controls. These perceptions may inform peri‐operative counseling and guide the development of more inclusive AVA technologies capable of accommodating diverse speakers. Level of Evidence : 3.

Objective: To evaluate the associations between surgeon-patient sex concordance, long-term clinical outcomes and healthcare costs. Background Data: Emerging data suggest surgeon-patient sex concordance may improve short-term outcomes, especially for female patients, yet its long-term effects remain unknown. Methods: We conducted a population-based retrospective cohort study of adults undergoing common surgeries in Ontario, Canada (2007-2019). Patients were followed for 90 and 365 days. Surgeon-patient sex concordance was categorized into four dyads. Multivariate generalized estimating equations clustered by procedure type evaluated composite and individual (complications, readmission, mortality) clinical outcomes and healthcare costs. Results: A total of 1,165,711 patients were included. Female patients treated by male surgeons, compared with female surgeons, were more likely to experience an adverse composite event (90 d: aOR 1.12, 95% CI 1.08–1.17, P <0.001; 365 d: aOR 1.09, 95% CI 1.05–1.14, P <0.001), with no association among male patients (90 d: aOR 1.00, 95% CI 0.94–1.05, P =0.89; 365 d: 0.99, 95% CI 0.92–1.07, P =0.87). Long-term total healthcare costs were greater for patients treated by male surgeons - an effect seen in both male patients (90 d: aRR 1.08, 95% CI 1.03-1.14, P =0.002 and 365 d: aRR 1.08, 95% CI 1.02-1.14, P =0.007) and female patients (90 d: aRR 1.10, 95% CI 1.05-1.14, P <0.001, 365 d: aRR 1.09, 95% CI 1.05-1.14, P <0.001). Conclusions: Surgeon-patient sex concordance was associated with improved long-term outcomes for female, but not male, patients, and female surgeons’ patients had lower healthcare costs. Given these benefits, further investigation into the mechanisms driving these outcomes is warranted.

Abstract Objective To examine the impact of immunosuppressive regimens on chronic rhinosinusitis (CRS) development in kidney and liver transplant recipients. Study Design Retrospective cohort study. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Patients who underwent kidney or liver transplantation between November 1, 2021, and November 1, 2022, were included. Patients with documented sinonasal complaints before transplantation were excluded. Diagnoses were based on ICD‐10 codes assigned by board‐certified otolaryngologists, with follow‐up extending through November 2024. Demographic data, relevant comorbidities, CRS diagnoses, and immunosuppressive regimens were collected. Results In total, 1459 transplant recipients (986 kidney, 473 liver) with a mean age of 55.1 years and M:F ratio of 1.5:1 were included. Kidney recipients who received anti‐thymocyte globulin (ATG, Thymoglobulin®) for immunosuppressive induction had a greater risk of CRS compared to those who did not (odds ratio [OR] = 3.0, 95% CI [1.3, 6.9], P = .005). Among liver recipients, patients on cyclosporine, mycophenolate mofetil (MMF), and corticosteroids had a greater risk of CRS compared to those on tacrolimus‐based regimens (OR = 6.0, 95% CI [1.5, 24.1], P = .027). Cyclosporine use was also associated with an increased rate of endoscopic sinus surgery (ESS) compared to tacrolimus (4.2% vs 0.3%, P = .015). Conclusion Tacrolimus‐based regimens are associated with significantly decreased rates of CRS compared to cyclosporine, suggesting that immunosuppressive choice is a modifiable risk factor for sinonasal morbidity in this population.

382 Background: Androgen receptor signaling drives prostate cancer (PC) progression, and genes involved in androgen production, uptake, and conversion (APUC) are key therapeutic targets. We previously defined a 6-APUC gene set ( HSD3B1, HSD3B2, CYP3A43, CYP11A1, CYP11B1, and CYP17A1 ), that identified metastatic PC with favorable prognosis and predict docetaxel benefit. However, the expression landscape and clinical relevance of APUC genes have not been interrogated in localized PC. Methods: We analyzed the expression of 21 APUC genes in 55,329 radical prostatectomy tumor samples that underwent Decipher prostate genomic classifier (GC) testing (Veracyte Inc) between 2016-2024. Baseline clinical/pathologic factors were retrieved from Decipher GRID database (NCT02609269). Associations between gene expression quartiles with PathoGenomic Risk Factors (PGRF) including Very High Decipher score >0.85 (VHD), Grade Group (GG) 4-5, LNI and SVI were examined. Associations with distant metastatic (DM) outcomes and metastasis free survival (MFS) were evaluated using logistic regression in Mayo545 and Cox regression in Meta855 RP cohorts, respectively. Results: High expression of SRD5A2 was associated with favorable PGRF (lower odds ratio (OR), p<0.0001), lower rate of development of DM (OR 0.36, p<0.05), and longer MFS (Hazard ratio (HR) 0.51, p<0.05). HSD17B6 showed similar results for PGRF (lower OR, p<0.0001), DM (OR 0.58, p<0.05) and longer MFS (HR 0.39, p<0.05) despite being associated with GG4-5 and SVI+ in samples with VHD. In contrast, high expression of SRD5A3 and HSD17B10 had high OR for PGRFs (p<0.0001). High expression of SLCO2B1 , an androgen uptake gene, had the strongest association with GG4-5 and SVI/LNI (p<0.001 for both). We noted that SRD5A2 lacked correlation with SRD5A1 and SRD5A3 , which instead correlated with each other. Compared to all APUC genes, SRD5A2 had limited correlations with almost all APUC genes, including ones that exhibited robust cross correlation with each other . Similar to our prior finding, most APUC genes demonstrated negative correlation with AR expression and AR activity signatures. Key outcomes were validated based on transcriptomic data from 492 samples from TCGA database. Conclusions: Comprehensive analysis of 21 APUC genes in over 55,000 PC identified distinct, context-dependent associations with metastatic outcomes and clinical and molecular risk factors. Notably, high SRD5A2 expression was associated with lower odds of high-risk features and metastatic outcomes, whereas SRD5A1 and SRD5A3 linked to adverse outcomes, suggesting critical yet divergent roles among 5-alpha-reductase family members. These findings underscoring androgen-metabolic heterogeneity and highlighting SRD5A2 as a potential biomarker of indolent biology in localized prostate cancer.

TPS276 Background: Metastatic castration-resistant prostate cancer (mCRPC) can evolve into a neuroendocrine-like subtype with aggressive behavior and poor outcomes (1). Nuclear Receptor-Binding SET Domain Protein 2 (NSD2) is overexpressed in prostate cancer and is a driver of both androgen-receptor (AR)-dependent signaling and of neuroendocrine differentiation, where cancer cells lose AR dependence and response to AR pathway inhibitors (ARPIs) (2,3,4). In studies of patient-derived neuroendocrine prostate cancer (NEPC) models, genetic depletion of NSD2 led to restoration of AR expression, reversal of adeno-to-neuroendocrine differentiation, and re-sensitization to ARPI (4). We hypothesize that NSD2 inhibition can reverse resistance to ARPIs in patients with progressive mCRPC, including with neuroendocrine differentiation. KTX-2001 is an oral, potent and selective small molecule inhibitor of NSD2. It is the sponsor’s second NSD2 inhibitor to enter the clinic. The sponsor’s first in class NSD2 inhibitor, KTX-1001, was shown to be tolerable and have preliminary efficacy in patients with relapsed/refractory multiple myeloma (5). Methods: STRIKE-001 (NCT07103018) is a multicenter, open-label phase 1 dose escalation trial of KTX-2001 monotherapy (Part A) and KTX-2001 + darolutamide (Part B). Key inclusion criteria are males age ≥18 years with mCRPC, progression after receiving ARPI, Eastern Cooperative Oncology Group performance score of 0-1, willingness to undergo biopsy if safe and feasible, and life expectancy of ≥6 months. Participants take KTX-2001 by mouth once daily alone (Part A) or with darolutamide 600 mg twice daily (Part B). Dose escalation of KTX-2001 in Parts A and B will follow a 3+3 design and occur in parallel at multiple planned dose levels. Primary objectives are to assess the safety and tolerability, determine MTD, and determine RP2D(s) for further study of KTX-2001 alone and in combination with darolutamide. Secondary objectives include characterization of efficacy and PK parameters for both KTX-2001 monotherapy and in combination with darolutamide. Exploratory objectives include study of pharmacodynamic effects, circulating tumor cells, and cell-free DNA. 1. Conteduca V, Eur J Cancer 2019. 2. Parolia A, Nat Genet 2024. 3. Aytes A, Nat Commun 2018 4. Li J, bioRxiv 2023.07.18.549585 5. Bories P, Blood Vol 144, Suppl 1,2024. Clinical trial information: NCT07103018 .

Background: To compare oncologic and postoperative outcomes in patients with scalp squamous cell carcinoma with periosteal, but not gross calvarial, involvement, treated with margin-clearing excision including either calvarial burring or periosteal excision alone. Study Design: Retrospective cohort study. Setting: Single tertiary academic referral center. Methods: We retrospectively reviewed surgical cases from January 2001 to January 2025. Inclusion criteria: patients ≥18 years with biopsy-proven scalp squamous cell carcinoma involving the periosteum without cortical invasion on imaging. Management of the deep margin included either burring of the outer table or periosteal excision alone. Demographic, surgical, and oncologic outcomes were collected and analyzed descriptively. Results: Twenty patients met inclusion criteria. Median age was 70 (range 56-92), and 18 (86%) were male. Thirteen (65%) patients underwent calvarial burring, 7 (35%) underwent periosteal excision. Local recurrence occurred in 31% and 29% of the burring group and non-burring group. Disease-free survival at 2 years was 46% and 57% in the burring and non-burring group, respectively. Overall survival at 2 years was 77% and 86% in the burring and non-burring group. Three patients in the burring group had local recurrences with intracranial extension, 1 died of disease, 1 died with disease and concurrent meningitis, 1 is alive with disease recurrence currently on palliative treatment. There were 7 disease-related deaths. Conclusion: Burring did not confer a significant oncologic advantage compared to periosteal excision alone when there was no gross cortical invasion. Local recurrence in patients undergoing calvarial burring was associated with intracranial extension of disease.