Citations

Abstract Background: African American men experience disproportionately high prostate cancer (PCa) mortality and are underrepresented in genomic studies. We evaluated real-world Decipher utilization and oncologic outcomes among African American men treated definitively for localized PCa. Methods: We retrospectively identified African American men with localized prostate cancer treated with radical prostatectomy (RP) or radiation therapy with or without androgen-deprivation therapy (RT±ADT) across 3 Mayo Clinic sites between 2010 and 2024. Baseline variables included age, prostate-specific antigen (PSA ng/mL), clinical T stage, treatment, Gleason score, and radiographic findings. Biochemical progression was defined as PSA ≥0.2 ng/mL after RP or ≥2 ng/mL above nadir after RT; metastases were determined by imaging. All time-to-event outcomes were measured from diagnosis. Kaplan–Meier methods estimated overall survival (OS), biochemical progression-free survival (bPFS), and metastasis-free survival (MFS) by Decipher status and clinical subgroups, with comparisons using log-rank tests. Multivariable Cox proportional-hazards models were fitted, and the proportional-hazards assumption was assessed using Schoenfeld residuals. Two-sided p<0.05 was considered statistically significant. Results: Among 191 identified patients, 69 underwent RP and 122 received RT±ADT; median follow-up was 62 months. Decipher testing was performed in 12 patients (6.3%), and germline testing in 51 (26.7%). Tested patients had lower-grade disease (Gleason <8 in 92% vs 58%; p=0.03). Four deaths occurred, including 1 among Decipher-tested patients and 3 among untested patients. There were 60 bPFS events (31%) and 34 MFS events (18%). In overall population, there was no statistically significant difference in patients who received decipher testing compared to those who did not in terms of OS (p=0.13), bPFS (p=0.14), or MFS (p=0.22). In exploratory multivariable models, PSA ≥20 ng/mL (aHR 11.4, 95% CI 4.8–27.3), Gleason score ≥8 (aHR 2.40, 95% CI 1.01–5.69), and clinical stage T3–T4 (aHR 2.58, 95% CI 1.15–5.81) was associated with worse MFS, whereas the addition of ADT to RT was associated with improved MFS compared to RT alone (aHR 0.15, 95% CI 0.04–0.50). Moreover, RT±ADT improved bPFS compared to RP (aHR 0.21, 95% CI 0.09–0.47) and patients with PSA ≥20 at baseline were associated with worsened bPFS compared to those who had PSA <20 (aHR 2.33, 95% CI 1.12–4.88). OS data was not mature. Conclusions: The utilization of decipher testing was limited in African American men with localized PCa, suggesting a potential gap in access to precision-oncology tools in this patient population. Testing status was not associated with outcomes, although analyses were limited by the small sample size. Exploratory analyses showed association of clinicopathological charatersitics with MFS and bPFS and can be considered for clinical decision making. Prospective, adequately powered studies are needed to evaluate equitable genomic-testing use and prognostic value in African American men. Citation Format: Kaneez Zahra R. Khakwani, Muhammad Ali Khan, Muhammad Umar Afzal, Ahmed A. Khan, Usama Mumtaz Cheema, Syed Arsalan Ahmed Naqvi, Chueh Hsuan Hsu, Ewan Cobran, Irbaz B. Riaz. Low utilization of the Decipher genomic classifier and oncologic outcomes in African American men with localized prostate cancer: A cancer-disparities analysis [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr A176.

Abstract Black men face a disproportionate burden of prostate cancer, yet screening uptake remains low, underscoring the need for targeted rather than one-size-fits-all screening messages. Grounded in dual-process theories of information processing and the Health Belief Model, this study tested whether narrative framing is more effective than reason-based framing in shaping screening attitudes and intentions among Black men who have never been screened. In a randomized experiment, 268 Black men aged ≥40 years (never screened by PSA or DRE) were assigned to read a reason-based brochure presenting scientific facts, anatomy, and statistics (e.g., 1 in 7 Black men diagnosed; twice the death rate) to urge screening (n = 91), a narrative brochure telling a first-person survivor's story of getting screened (n = 97), or a control brochure containing the same message resource, header, photo, and screening recommendation but no persuasive body text (n = 80). Post-brochure surveys measured affect toward screening and intention to discuss testing with a physician, alongside moderators including attitudes towards screening, perceived behavioral control, cultural orientation, fatalism, knowledge, and demographics; effects were tested using ANCOVA and regression, adjusting for demographics. Narrative framing did not outperform reason-based messaging on affect (F(2,245) = 1.62, p = .201) or intention (F(2,245) = 1.19, p = .305); however, the effect depended on the reader, with a significant condition-by-ethnicity interaction (F(2,245) = 5.22, p = .006) and, most notably, a condition-by-attitude interaction (F(2,242) = 8.11, p < .001). Among men with the least favorable baseline attitudes toward screening, the narrative significantly raised intention over control (+0.61, p < .001), while message style ceased to matter at average or high attitudes toward screening. Attitude was the strongest predictor of intention (b = 0.41, p < .001), followed by perceived behavioral control (b = 0.16, p = .041), cultural orientation (b = 0.15, p = .034), and fatalism (b = −0.16, p = .016), each independently predicting stronger screening intentions (fatalism negatively). The narrative brochure scored highest for reader engagement (F(2,244) = 3.38, p = .036). These findings indicate that there is no universal “best” message; narrative framing is most valuable for reaching the least-convinced men and for outreach engagement, and screening interventions should target the underlying beliefs—attitude, perceived control, and fatalism—that most strongly drive intention. Citation Format: Tingyu Zou, Quincy A. Wimberly, Chelsea C. Reeves, Gui R. Pradieu, Jade Thompson-Reeves, Michelle Fudge, Monica L. Albertie, Folakemi T. Odedina. Motivating Prostate Cancer Screening in Black Men: A Randomized Messaging Experiment [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr C178.

To compare the 1-year risk of biliary/pancreatic adverse events among patients with obesity and type 2 diabetes treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus dipeptidyl peptidase-4 inhibitors (DPP-4i), and to directly compare tirzepatide with semaglutide. Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Global Collaborative Network. Adults with obesity and type 2 diabetes without prior biliary or pancreatic disease were included. Two prespecified comparisons were performed: GLP-1RA (semaglutide or tirzepatide) versus DPP-4i, and tirzepatide versus semaglutide. The primary outcome was incident cholelithiasis at 1 year. Secondary outcomes included cholecystitis, cholangitis, acute pancreatitis, and cholecystectomy. Hazard ratios (HRs) were estimated using Cox proportional hazards models. Results: After matching, 281,283 patients were included in each GLP-1RA and DPP-4i cohort, and 242,876 patients in each tirzepatide and semaglutide cohort. Compared with DPP-4i, GLP-1RA therapy was associated with lower risks of cholelithiasis (1.02% vs. 1.16%; HR 0.92, 95%CI 0.87–0.96), cholecystitis (HR 0.88, 95%CI 0.79–0.98), cholangitis (HR 0.46, 95%CI 0.36–0.58), acute pancreatitis (HR 0.68, 95%CI 0.61–0.76), and cholecystectomy (HR 0.51, 95%CI 0.38–0.69). In the head-to-head comparison, semaglutide was associated with higher risks of cholelithiasis (HR 1.11, 95%CI 1.05–1.18) and cholecystitis (HR 1.22, 95%CI 1.10–1.37) compared with tirzepatide, while risks of pancreatitis, cholangitis, and cholecystectomy did not differ significantly. Conclusions: In this large real-world study, GLP-1RA therapy was associated with lower risks of biliary and pancreatic events compared with DPP-4i. Tirzepatide demonstrated a modestly more favorable biliary safety profile than semaglutide, supporting the overall hepatobiliary safety of contemporary GLP-1-based therapies.

Aims: The aims of this study were to evaluate the association between the red cell distribution width (RDW)–albumin ratio (RAR) and subclinical myocardial impairment, as assessed by left ventricular global longitudinal strain (LVGLS), and to examine the relationships between the RAR, heart failure (HF) hospitalization, and all-cause mortality. Methods: We conducted a retrospective cohort study on adults who underwent transthoracic echocardiography (TTE) with LVGLS assessment across three Mayo Clinic centers (2017–2024) and who had RDW and serum albumin measured on the same day or within seven days. The RAR was calculated as RDW/albumin and categorized into the following tertiles: <2.93, 2.93–3.48, and >3.48. Impaired LVGLS was defined as >−18%. Associations between the RAR and outcomes were assessed using multivariable logistic regression (LVGLS) and Cox models (HF and mortality), adjusting for demographics and comorbidities. Results: Among 5069 patients, 39.7% had impaired LVGLS, and its prevalence increased across RAR tertiles (26.8%, 41.9%, and 51.1%). Adjusted odds ratios for impaired LVGLS were 1.74 and 2.30 for tertiles 2 and 3, respectively. A higher RAR was associated with increased risk of HF hospitalization (aHR 2.54 and 4.48) and all-cause mortality (aHR 2.39 and 7.30). These associations persisted after adjusting for LVGLS. The effect of the RAR on mortality was stronger in patients with normal LVGLS compared to those with impaired LVGLS (p for interaction = 0.0004). Conclusions: A higher RAR was associated with abnormal LVGLS, HF hospitalization, and all-cause mortality after adjustment for clinical risk factors. However, the RAR did not provide discriminative value beyond its individual components.

Purpose To evaluate objective return‐to‐sport (RTS) outcomes and limb symmetry index (LSI) data after primary medial patellofemoral ligament reconstruction (MPFLR) in patients with patellar instability. Methods A systematic search of Scopus, PubMed, CINAHL, and Embase (2000‐2024) identified studies reporting RTS outcomes and LSI‐based performance testing in patients undergoing primary MPFLR. Clinical and observational studies reporting objective metrics such as isokinetic strength and hop testing were included. Results Six studies including 243 patients (64% women, mean age 19.4 years) undergoing primary MPFLR were included. Several studies included patients undergoing concomitant bone procedures (41%), such as tibial tubercle osteotomy or trochleoplasty. Objective RTS testing commonly included isokinetic strength (4 studies), hop testing (3 studies), and Y‐Balance testing (2 studies). Follow‐up testing ranged from 6 to 8 months postoperatively. Reported LSI values ranged from 83% to 94% for isokinetic flexion, 70% to 96% for isokinetic extension, 85% to 93% for single hop, and 90% to 97% for triple hop. Time to RTS ranged from 6.1 to 8.1 months across studies, with RTS rates from 85% to 100%. However, only 14% to 40% of patients met all study‐specific RTS criteria when reported. Testing protocols and thresholds varied across studies, contributing to heterogeneity in outcomes. Conclusions Few studies reporting RTS outcomes after MPFLR incorporate LSI measures as part of RTS assessment, and only a minority define explicit RTS criteria based on objective testing. Among studies that reported LSI, quadriceps strength frequently remained below 90% LSI at the time of RTS. Despite high reported RTS rates, substantial variability exists in RTS assessment after MPFLR. Level of Evidence Level IV, systematic review of Level III to IV studies.

Purpose: This study examined whether phoneme-level posterior probabilities generated by an articulatory-informed deep learning model (Phonet) can serve as interpretable and sensitive markers of articulatory impairment in motor speech disorders (MSDs). The goal was to determine whether these features distinguish individuals with and without MSDs and reflect varying severity levels of articulatory impairment. Method: A total of 676 participants (199 with MSDs, 477 without MSDs) completed a remotely captured word repetition task. Speech recordings were phonetically aligned, and posterior probabilities were extracted using a retrained version of the Phonet model, which estimates frame-level probabilities for 23 phonological classes. Segment-level posterior values were computed and compared across groups and severity levels using linear mixed-effects regression models. Results: Posterior probabilities were significantly reduced in the MSD group across all phoneme types. Within the MSD group, posterior probabilities decreased progressively with greater clinical severity, as measured by both perceptual sound distortion ratings and a cumulative articulation error score. Segment-specific analyses revealed systematic differences across phoneme classes, indicating that posterior probabilities capture distinct patterns of articulatory degradation associated with motor speech impairment. Conclusions: Phoneme-level posterior probabilities serve as interpretable, segment-specific indicators of articulatory impairment in MSDs. These features differentiate clinical status and reflect gradations of severity, making them promising tools for augmenting traditional perceptual speech assessments. Their linguistic transparency and scalability support future clinical applications in diagnosis, monitoring, and targeted intervention.

Background : Diabetic-foot osteomyelitis (DFO) is a severe complication of diabetic-foot ulcers associated with delayed healing, amputation, and increased mortality. Machine learning (ML) has increasingly been explored for diagnosis and clinical decision-making in diabetic-foot care; however, the current evidence specific to DFO has not been systematically synthesized. Methods : We performed systematic searches of MEDLINE, Embase, Scopus, and Web of Science for studies published between January 2000 and May 2026. Studies that developed or evaluated ML models for DFO diagnosis, prediction, or outcomes were included. Data extraction was performed using the CHARMS framework, reporting followed PRISMA 2020 and TRIPOD-SRMA recommendations, and methodological quality was evaluated using PROBAST + AI. Due to considerable heterogeneity, narrative synthesis was performed. Results : A total of 10 studies published from 2022 to 2026 met the inclusion criteria. Five studies developed or evaluated ML models with a direct DFO diagnostic endpoint, one additional study evaluated model explainability, and four evaluated complementary DFO-relevant diabetic-foot applications. Reported discrimination ranged from 0.879 to 0.998, but comparisons were limited by differences in clinical endpoints, reference standards, input modalities and validation strategies. Only one direct DFO model was externally validated, and no study developed a multimodal model combining clinical and imaging data. Conclusion : Current evidence is limited by heterogeneous methodologies, limited external validation, and inconsistent reporting despite promising discrimination reported by several models. Future studies should evaluate whether multimodal models integrating clinical and imaging data provide incremental value over unimodal approaches, with external validation, calibration, and clinical utility assessment before clinical implementation.

PURPOSE Patients with breast cancer requiring postmastectomy radiation therapy (PMRT) often desire breast reconstruction. Reconstructions can be adversely affected by PMRT, and fear of reconstruction complications has discouraged adoption of short-course radiation therapy used after lumpectomy. To fill the evidence gap, we conducted a noninferiority trial of hypofractionated versus conventional PMRT in patients undergoing breast reconstruction. The primary outcome was reconstruction complication rate, a composite of wound healing, readmission, capsular contracture, unplanned reoperation, and reconstruction failure. METHODS Women with unilateral invasive breast cancer with planned immediate or delayed reconstruction and PMRT were randomly assigned (1:1) to 50 Gy (25 fractions/5 weeks) or 42.56 Gy (16 fractions/3 weeks). This study was designed with a noninferiority margin of 10%, assuming a 2-year reconstruction complication rate of 25% with conventional PMRT. Randomization was stratified by immediate versus delayed and autologous versus implant-only reconstruction. RESULTS Between 2018 and 2021, 898 patients enrolled with a median follow-up of 3.9 years; 825 patients were evaluable for the primary end point. The 24-month reconstruction complication rates were 12.3% (52/422) with hypofractionated PMRT and 10.2% (41/403) with conventional PMRT, corresponding to an estimated difference of -2.1% (95% CI, -6.5 to 2.2). The complication rate was higher (regardless of arm) with implant-only versus autologous reconstruction (odds ratio = 1.65). There was no statistically significant difference in 36-month locoregional recurrence rates: 1.5% (95% CI, 0.7 to 3.2) with hypofractionated and 2.2% (95% CI, 1.1 to 4.3) with conventional PMRT. Acute and late toxicity rates were not statistically different. CONCLUSION A 16-fraction course of hypofractionated PMRT is safe and noninferior to conventional PMRT in women undergoing breast reconstruction after mastectomy.

BACKGROUND: Type 2 long-QT syndrome results from KCNH2 -encoded Kv11.1 loss-of-function, but whether secondary inward-current dysfunction amplifies dysfunction remains unclear. METHODS: We characterized sodium ( SCN5A , I Na ) and L-type calcium channel ( CACNA1C , I Ca ) function in KCNH2-G604S and variant-corrected isogenic control induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs). Whole-cell patch-clamp measured action potential duration at 90% repolarization (APD90), and potassium (I Kr ), sodium (I Na ), and calcium (I Ca, L ) currents. Fluo-4 imaging quantified calcium transients. A modified Kernik-Clancy iPSC-CM model incorporated experimentally measured persistent I Na,L and I Ca,L fractions and simulated isolated and combined current defects. RESULTS: KCNH2-G604S caused severe I Kr loss-of-function (72.5% reduction). APD90 was prolonged in G604S-iPSC-CMs (765±58 ms) compared with isogenic controls (368±37 ms; P <0.005), with early afterdepolarizations in 50% of G604S cells. Nifedipine, verapamil, and mexiletine successfully shortened APD90 and abolished early afterdepolarizations. Compared with isogenic control, I Na,L (0.60±0.1% versus 0.26±0.06%; P <0.01), persistent I Ca,L (2.88±0.55% versus 1.26±0.35%; P <0.05), and calcium transient decay times ( P <0.0001) were greater in G604S iPSC-CMs. Increased persistent I Ca,L was phenocopied by E-4031 in isogenic controls and reduced by nifedipine in G604S iPSC-CMs. In silico modeling revealed that the I Kr defect alone prolonged APD90 to only 620 ms. The addition of the observed I Na,L defect had a small additive effect (+20 ms); however, incorporating persistent I Ca,L synergistically extended APD90 to 758 ms, replicating the experimental phenotype. Flux dynamics analysis indicated that this persistent Ca 2+ entry suppresses the forward-mode sodium-calcium exchanger, forcing a compensatory reliance on sarcoplasmic-endoplasmic reticulum Ca-ATPase that primes for calcium instability. CONCLUSIONS: The KCNH2-G604S variant drives a severe multihit phenotype via primary I Kr loss-of-function and secondary state-dependent gain-of-function in persistent I Ca,L . These comprehensive validations demonstrate that the remodeled persistent I Ca,L acts as the essential amplifier driving extreme action potential duration prolongation and Ca 2+ mishandling.