Citations

Abstract Background Amyloid-β (Aβ) pathology in Alzheimer’s disease (AD) includes distinct types of plaques and cerebral amyloid angiopathy (CAA). Post-translational modifications (PTMs) may define Aβ deposit-specific signatures. Among them, nitration of tyrosine-10 (3′-nitrotyrosine, 3-NT) links oxidative stress to Aβ modification and microglial activation, but its spatial distribution across deposit types and impact on aggregation dynamics remain unclear. Methods Parietal cortex tissue from AD and CAA cases (n = 19) and controls (n = 9) was analyzed by multiplex immunofluorescence for Aβ species (Aβaa1-8, AβN3pE, pSer8-Aβ), 3-NT, thioflavin-S, and CD68. Distinct deposits, including diffuse plaques (n = 70) classic cored plaques (n = 70), coarse-grained plaques (n = 40), capillary CAA (capCAA; n = 80), larger vessel CAA (n = 80), and leptomeningeal CAA (n = 25) were annotated, together with gray matter regions from control tissue lacking Aβ pathology (n = 90). In vitro assays evaluated how 3-NT affects Aβ aggregation kinetics, microglial morphology, and neuronal viability. Results We observed Aβ deposit-specific PTM signatures. Classic cored and coarse-grained plaques contained increased pyroglutamylated (Aβ N3pE ) and phosphorylated (pSer8-Aβ) species compared to diffuse plaques. In contrast, 3-NT showed a distinct vascular predilection, with the highest relative burden in larger vessel and leptomeningeal CAA. 3-NT colocalized with β-sheet–rich thioflavin-S-positive fibrils and areas of CD68-positive microglia. In vitro, nitration slowed oligomer-to-fibril conversion but accelerated the growth of pre-formed fibrils and sustained microglial activation without increasing neuronal toxicity. Conclusions Distinct PTMs delineate the compartment-specific architectural signatures of Aβ deposits. Whereas AβN3pE and pSer8-Aβ broadly label parenchymal plaques, 3-NT shows a vascular predilection, particularly in leptomeningeal CAA. This compartmentalized pattern identifies nitration as a candidate marker of vascular Aβ pathology and a possible risk indicator for amyloid-related imaging abnormalities (ARIA) during anti-Aβ immunotherapy.

ABSTRACT Introduction Changes in peripheral eosinophils follow endoscopic sinus surgery (ESS) in chronic rhinosinusitis with nasal polyps (CRSwNP), with and without aspirin sensitivity. Cytometry by time‐of‐flight (CyTOF) identifies more immune cell subsets than conventional assays or clinical testing. We hypothesized that ESS‐associated changes in peripheral immune cell subsets differ between aspirin‐tolerant (AT)‐CRSwNP and aspirin‐exacerbated respiratory disease (AERD) as measured by CyTOF. Methods Pre‐ and post‐ESS peripheral blood from patients with CRSwNP ( n = 13) or with AERD ( n = 15) was analyzed for immune cell populations using a 37‐marker CyTOF panel. CITRUS analysis identified cell clusters most predictive of patient group or sample timepoint. Results In the combined cohort of 28 patients, circulating CD4 + naïve T cells and CD194 + neutrophils increased after ESS, while eosinophils decreased. When stratified by disease, CD4 + naïve T cells increased in both AERD and CRSwNP post‐ESS; however, eosinophils decreased after ESS only in CRSwNP. Neutrophil subsets showed a mixed response in both patient groups after ESS. Dendritic cells increased in CRSwNP but not in AERD after ESS. Individual timepoint analyses showed more CD141 + monocyte‐derived DCs (moDCs) in CRSwNP than in AERD pre‐ and post‐ESS. Pre‐ESS, both CD185 + and CD194 + neutrophils were higher in AERD compared to CRSwNP. Conclusion CD141 + moDCs were more prevalent in CRSwNP versus AERD, both before and after ESS. Naïve CD4 + T cells increased, and neutrophil subsets changed in all groups after ESS, but eosinophils decreased only in CRSwNP. Our study points to possible systemic immune effects of ESS and candidate immune signatures in CRSwNP and AERD.

Abstract Objective To characterize the prevalence, severity, and clinical correlates of subjective ictal-phase cognitive impairment across the migraine attack cycle in a large, specialty-center cohort. Background Cognitive dysfunction is a prevalent and disabling feature of migraine attacks, yet standardized tools for measuring migraine attack-related cognitive impairment are limited, and the clinical predictors of cognitive burden remain incompletely characterized. Prior work has largely focused on the ictal phase, although cognitive symptoms are reported across the prodromal, ictal, and postdromal phases of the migraine attack. Methods This is a cross-sectional analysis of data from the American Registry for Migraine Research (ARMR), a multicenter registry enrolling patients with migraine diagnosed by headache specialists using ICHD-3 criteria. Participants completed the Migraine-Specific Cognitive Impairment Scale (Mig-SCog; range 0–18, higher scores indicating greater impairment). Associations between cognitive impairment and clinical variables were evaluated using correlation analyses, group comparisons, and multivariable linear regression. Results Among 1,231 patients (87.2% women; mean age 46.0 ± 13.7 years; 71.5% chronic migraine), 1,175/1,231 (95.5%) endorsed cognitive symptoms, with a mean Mig-SCog total score of 8.2 ± 4.8. Executive dysfunction accounted for 71.1%±18.6% of total cognitive burden, but the proportional contribution of language impairment increased with migraine frequency category, from 22.4%±18.9% in low-frequency episodic migraine to 28.8%±19.5% in chronic migraine (p = 0.003). In multivariable regression, migraine frequency classification was not independently associated with cognitive impairment. The strongest independent predictors of cognitive impairment were anxiety symptom score (β = 0.15, p < 0.001) and depression symptom score (β = 0.13, p = 0.002), with standardized coefficients exceeding those of all migraine frequency classification categories. Women reported significantly greater cognitive impairment than men across all domains (8.4 ± 4.8 vs. 6.8 ± 4.7; p < 0.001, small effect). Word-finding difficulty demonstrated the largest ictal symptom-frequency association, with scores rising from 3.3 ± 2.6 among those never reporting word-finding difficulty to 13.6 ± 3.6 among those always reporting it (adjusted p < 0.001, large effect). In phase-based analyses, word-finding difficulty and impaired concentration were associated with 4.6- and 3.7-point higher cognitive impairment scores than in patients who did not report these symptoms during the prodrome and 5.1- and 4.0-point higher scores during the postdrome, respectively (all p < 0.001, large effects). Among patients with chronic migraine and available disease duration data (n = 661), cognitive burden was lower among those within the first 12 months of chronicity compared with those with longer-standing chronic migraine (7.7 ± 4.9 vs. 9.0 ± 4.6; p = 0.010, d = 0.27). Sound hypersensitivity (β = 0.25) and cutaneous allodynia (β = 0.20) were the strongest independent sensory predictors of cognitive impairment (both p < 0.001). Conclusion Migraine-related cognitive dysfunction was nearly universal in this specialty-center cohort and was not adequately captured by migraine frequency classification alone. Anxiety and depression symptom burden, language impairment, full-cycle cognitive symptoms spanning prodrome through postdrome, and sensory sensitization are clinically meaningful markers of cognitive burden that should be assessed alongside more traditional migraine characteristics when evaluating patients who have migraine.

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&lt;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 &lt;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 &lt;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 Background Obesity has been associated with complications after Achilles tendon surgery, but evidence specific to insertional Achilles tendinopathy is limited and conflicting. We evaluated the association between body mass index and 90-day complications after a standardized insertional Achilles operation. Methods This retrospective procedure-level cohort included all eligible primary operations at a single tertiary referral center from 2013 through 2025. The primary outcome was any adjudicated complication within 90 days. BMI was evaluated with an adjusted three-knot restricted cubic spline and summarized by an odds ratio per 5 kg/m². Logistic regression used patient-clustered robust standard errors and adjusted for age, diabetes, and smoking status at initial surgical evaluation. The BMI ≥ 35 kg/m² comparison was post hoc. Time to documented return to usual activity was analyzed with an adjusted Cox model. Results Among 217 procedures in 194 patients, 32 had a 90-day complication (14.7%). The adjusted spline demonstrated an association between BMI and complications (global p = 0.030) with evidence of nonlinearity (p = 0.023). Each 5-kg/m² increase in BMI was associated with higher average odds of a complication (adjusted OR 1.43, 95% CI 1.11–1.85; p = 0.006). In the post hoc analysis, complications occurred after 21 of 82 procedures with BMI ≥ 35 kg/m² (25.6%) and 11 of 135 with BMI < 35 kg/m² (8.1%; adjusted OR 3.89, 95% CI 1.71–8.85; p = 0.001). Seventeen wound complications occurred (7.8%). BMI was not associated with time to documented return to usual activity (adjusted HR 0.91 per 5 kg/m², 95% CI 0.74–1.11; p = 0.355). Conclusions Higher BMI was associated with greater 90-day complication risk after primary insertional Achilles surgery, with a nonlinear relationship across the observed range. BMI ≥ 35 kg/m² may be a pragmatic counseling reference, but it was selected post hoc and is not a validated threshold or stand-alone contraindication. Compared with prior insertional Achilles series, this study used a standardized 90-day endpoint, nonlinear BMI modeling, blinded complication adjudication, and methods accounting for repeated procedures.

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.

Purpose The purpose of this study was to identify risk factors and evaluate clinical outcomes associated with incidental left common iliac vein compression on CT imaging. Methods This is a retrospective study that reviewed venous-phase abdomen and pelvis CT scans to identify patients with incidental extrinsic compression of the left common iliac vein due to an overlying right common iliac artery. A total of 726 patients were included (364 females, 362 males; mean patient age: 61.9 ± 15.9 years). Board-certified radiologists reviewed all CT scans. Significant left iliac vein compression was defined as >50% luminal narrowing. Results Significant iliac vein compression was identified in 114 (15.7%) patients and was more common in females (19.5%) versus males (11.9%) ( p < 0.01). Patients with iliac vein compression >50% had significantly lower BMI than those without compression (24.8 ± 6.2 vs 28.7 ± 7.2 kg/m 2 , p < 0.01). Patients with incidental left iliac vein compression had a higher rate of prior left lower extremity DVT ( p = 0.02). Conclusion Incidental left common iliac vein compression was present in approximately 16% of patients and was more frequent among females. Compression was associated with lower BMI and more than twice the rate of ipsilateral DVT, despite no prior diagnosis of MTS. These findings suggest that incidental iliac vein compression could have more clinical significance than previously recognized.

Abstract Comprehensive genomic profiling has expanded the ability to identify potentially actionable molecular alterations across cancers, but identification of an actionable finding does not ensure that a patient will receive a genomically matched therapy. Studies of precision-oncology programs and molecular tumor boards consistently demonstrate substantial attrition between treatment recommendation and treatment initiation. The reasons extend beyond molecular interpretation and include the timing of genomic profiling, clinical deterioration, geographic availability of biomarker-selected trials, insurance and financial barriers, and disparities in access to specialty cancer care. Importantly, these barriers arise after a potentially useful molecular finding has already been identified, creating a distinction between molecular actionability and practical treatment access. This commentary argues that the next implementation challenge for precision oncology is to make clinically meaningful genomic findings realistically actionable. Comprehensive genomic profiling should occur early enough to inform treatment planning; molecular tumor board recommendations should be linked to realistic treatment and trial opportunities; financial and insurance barriers should be anticipated when recommendations are made; and equity should be evaluated beyond access to testing to include receipt of genomically informed treatment. As genomic profiling becomes increasingly integrated into routine cancer care, precision oncology should be judged not only by its ability to identify therapeutic opportunities but also by whether patients can reach those opportunities while they remain clinically relevant.