Citations

Abstract INTRODUCTION The tau positron emission tomography (PET) overlap index (OI) has shown promise in maximizing signal‐to‐noise for longitudinal tau PET imaging, particularly for early tau pathology, but requires validation against neuropathology. METHODS Fifty‐seven participants who underwent serial tau PET imaging (flortaucipir) and subsequent autopsy were included. Tau PET OI and standardized uptake value ratios (SUVRs) were compared across neuropathological diagnoses. RESULTS Tau PET OI showed greater concordance with neurofibrillary tangle (NFT) severity in the entorhinal cortex (a key region for Alzheimer's disease [AD] tauopathy) than SUVR, particularly in early Braak tangle stages (positivity: 52.2% for OI vs. 13.0% for SUVR). OI detected overlapping tau voxels that exhibited spatial correspondence with immunohistochemical and autoradiography measures of tau deposition across both AD and non‐AD tauopathies. DISCUSSION These findings demonstrate the enhanced capacity of OI in serial tau PET to robustly detect early and spatially localized tau pathology, supporting its application as a sensitive imaging metric in AD and select non‐AD tauopathies.

LBA629 Background: Whether BCG strain influences clinical efficacy is unclear. BCG shortages and a reliance on a single strain may impact disease outcomes. Evidence also suggests that priming with intradermal (ID) BCG vaccination prior to intravesical (IVe) BCG enhances anti-tumor immunity and cancer clearance. Co-primary objectives address these issues. Methods: The trial design calls for 924 eligible patients with BCG naïve non-muscle invasive bladder cancer (NMIBC) (HG Ta/T1 +/- CIS or CIS alone) with negative purified protein derivative (PPD) to be randomized in a 1:1:1 ratio, to IVe TICE (Arm 1), IVe Tokyo-172 (Arm 2), or ID + IVe Tokyo-172 (Arm 3) BCG, stratifying on age group and clinical stage. IVe BCG included 6 weekly instillations (induction) and three weekly instillations (maintenance) at 3 and 6 months (mo), then every 6 mo for 3 years. Objective 1 tests whether Tokyo-172 BCG is non-inferior (NI) to TICE BCG, specifying a NI hazard ratio=1.34 (84% power). Objective 2 tests whether priming with ID prior to IVe Tokyo-172 is superior to IVe Tokyo-172 (HR=0.71, 83% power). The primary endpoint is high-grade recurrence-free survival (HG-RFS) censored at last cystoscopy, using a one-sided α=0.021 for each test. A Cox model adjusting for the stratification factors is used. Secondary endpoints include adverse events, 6-mo biopsy-proven complete response (CR) in patients with CIS +/- Ta, T1, duration of CR, PPD conversion and HG-RFS, progression-free survival (PFS) and quality of life. Max follow-up is 5 years. Results: 1000 (984 eligible) patients were enrolled from 2/17-12/20. Median (IQR) follow up is 4.6 (3.6, 5.0) yrs. Median age (range) is 70 yrs (26, 99), 17% are female, 9% are non-white, and 34% had CIS at entry. HG-RFS, CR, duration of CR at 4 yrs, and PFS were similar among arms (Table). PPD conversion occurred in 29% and was not correlated with HG-RFS. Gr 1-2 AE rate was similar (67%, 71%, and 67%) and Gr 3-4 (no Gr 5s) rate was 6%, 11%, and 14% for Arms 1,2, and 3, respectively. Conclusions: Tokyo-172 is non-inferior to TICE BCG in terms of HG RFS and CIS CR and is similar for PFS. Gr 3-4 AE rate is higher with Tokyo-172. Priming with Tokyo-172 BCG does not improve HG RFS. PPD conversion is not prognostic. Clinical trial information: NCT #03091660 . CIS Component N (eligible) 5-yr HG RFS HG RFSHR (95.8% CI) @ 5-yrPFS PFS HR(95% CI) @ CR %(95% CI) 4 yr CR duration Tice Ive 333 (330) 58% 79% 62%; 71/114(53%, 71%) 80% Tokyo Ive 332 (327) 64% *0.82(0.63, 1.08) 79% *0.99(0.70, 1.39) 60%; 66/110(50%, 69%) 83% Tokyo ID + Ive 335 (327) 63% **1.00(0.76, 1.33) 77% **1.07(0.76, 1.51) 63%; 69/109(54%, 72%) 80% 3 mo. PPD + conversionY vs. N 782 evaluable225 (29%)557 (71%) 69%67% ^HR=0.91(0.68, 1.22) * Tokyo-172 vs. Tice, ** Tokyo Priming vs. Tokyo no priming. ^conversion to PPD + vs. – @ adjusted for 2 strat factors (and arms for PPD model). PFS event = MIBC, metastasis, or death.

696 Background: EVP is the preferred 1st-line therapy for patients (pts) with aUC. Upfront EV dose reductions may be utilized to enhance tolerance and minimize treatment-related toxicities when intolerance is anticipated. Prior studies of EV monotherapy suggest that starting dose 1.25 mg/kg resulted in exposure that maximized chance of response. We hypothesize that upfront EV dose reductions would not compromise EVP efficacy. Methods: Pts with aUC treated with EVP in the multi-site UNITE database were analyzed. Upfront dose reduction was defined as starting dose < 1.25 mg/kg. Correlation between clinical features and EV dose reduction were assessed using Fisher’s Exact test. Endpoints include progression-free survival (PFS) and overall survival (OS) from EVP initiation, assessed by Kaplan-Meier analysis and Cox models. Multivariable Cox analysis (MVA) included age (< 75 vs ≥ 75), ECOG performance status (PS) (0-1 vs 2-3), hemoglobin level (< 10 vs ≥ 10), and liver metastases (present vs absent), chosen in accordance with Bellmunt criteria. Correlation with investigator-assessed observed response rate (ORR) was determined using logistic regressions. All tests were 2-sided with p < 0.05 considered significant. Results: A total of 456 pts across 17 sites were included (median age 72; 77% Caucasian; 75% male; 26% upper tract primary; 66% pure UC; 77% ECOG PS 0-1; 17% with liver metastasis; 89% 1 st line EVP). Upfront dose reduction occurred in 96 pts (21%); 76 pts (79%) started at 1.0 mg/kg and 20 pts (21%) at 0.75 mg/kg. Upfront dose reduction was significantly associated with age ≥ 75 (p = 0.002), ECOG PS 2/3 (p = 0.04), and hemoglobin < 10 (p = 0.01) but not with liver metastasis (p = 0.9). Lower starting EV dose correlated with shorter median PFS (5 vs 6 months) and OS (9 vs 10 months), and lower ORR (28% vs. 60%) when compared to full dose (Table). In MVA adjusting for prognostic factors for PFS and OS, these associations were no longer statistically significant. Conclusions: In this real-world analysis, upfront EV dose reductions were most frequently used in pts with factors associated with frailty and poor prognosis, e.g. older age and ECOG PS 2/3, and were associated with lower ORR. When adjusted for these factors, upfront EV dose reductions were not associated with shorter PFS/OS though a trend towards inferior outcomes persisted. These differences in outcomes may reflect baseline risk factors rather than dose intensity; however, prospective investigation is required to validate our hypothesis-generating results. Association of upfront EV dose reduction with outcomes. Outcome (Upfront dose reduction vs no upfront dose reduction) Univariable analysis Multivariable analysis PFS: HR (95% CI), p 1.50 (1.11 – 2.02), 0.008 1.33 (0.95-1.86), 0.09 OS: HR (95% CI), p 1.56 (1.11-2.20), 0.01 1.41 (0.96-2.06), 0.08 ORR: OR (95% CI), p 0.35 (0.21-0.60), 0.0001 0.38 (0.21-0.67), 0.0009

Background Cardiovascular disease is linked to mental health conditions. Patients with cardiovascular disease and comorbid psychiatric illnesses such as major depressive disorder or generalized anxiety disorder often experience greater physical limitations and decreased overall health. Objective To determine if proactive psychiatric interventions improve staff satisfaction and patient outcomes, such as reducing length of stay and decreasing the 30-day readmission rate, for patients hospitalized on cardiac units with psychiatric comorbidities. Methods The implementation of a proactive psychiatric consultation-liaison service, which included proactive screening of psychiatric needs among patients hospitalized on cardiac units, targeted support for cardiovascular staff, and supportive interactions for patients. Results Comparison between preintervention and postintervention periods indicated a 21% reduction in the 30-day readmission rate for patients hospitalized on cardiac inpatient units with psychiatric comorbidities without adversely affecting hospital length of stay. Staff satisfaction significantly increased with the availability of psychiatric resources. Conclusion The implementation of a multi-disciplinary proactive psychiatric consultation-liaison service on inpatient cardiac units was associated with an increase in cardiovascular staff satisfaction with psychiatric services and a decrease in the 30-day readmission rate of patients with psychiatric comorbidities who were hospitalized for cardiovascular services without significantly affecting length of stay.

Introduction Burnout among healthcare professionals remains a critical public health issue linked to impaired cognition, emotional exhaustion and diminished clinical performance. Structured breathing practices have demonstrated promise in improving autonomic regulation and cerebral oxygenation, yet their feasibility, acceptability and implementation in real-world healthcare settings remain underexplored. Objectives This single-arm pilot feasibility trial aims to evaluate the feasibility, acceptability and implementation appropriateness of a structured breathing-based intervention for healthcare professionals across community-based Mayo Clinic Health System (MCHS) sites. Secondary objectives include assessing usability and engagement with the mobile breathing platform, while exploratory analyses will describe magnitude of variability and feasibility of collecting psychological and cerebral haemodynamic measures. This study will commence in November 2025 and is expected to be completed by June 2026. Methods and analysis A total of 40 clinicians (MD/DO/MBBS/PA) and nurses reporting moderate or greater burnout will be enrolled across four MCHS sites. Participants will complete a 4-month structured breathing programme delivered primarily online, supported by a mobile application for practice tracking. Assessments will occur at baseline, 2 months and 4 months, with functional near-infrared spectroscopy (fNIRS) measures of cerebral oxygenation collected at baseline and 4 months in a population subset. Primary outcomes include (1) recruitment yield, retention and adherence rates; (2) acceptability and participant satisfaction (survey and qualitative feedback); and (3) implementation appropriateness measured by the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM). Secondary outcomes include digital engagement and usability through mobile analytics and the System Usability Scale. Exploratory outcomes are psychological indicators (burnout, depression, anxiety, perceived stress, sleep, fatigue, professional fulfilment and resilience) and physiological endpoints (fNIRS). Analyses will be descriptive, summarising feasibility metrics with 95% CIs. Progression criteria (recruitment≥75%, retention≥80%, adherence≥70%, AIM/IAM/FIM≥4.0) will determine readiness for a definitive hybrid effectiveness–implementation trial. Ethics and dissemination The study is approved by the Mayo Clinic Institutional Review Board (IRB # 25-009320). All participants will provide informed consent. Study procedures ensure confidentiality, cultural sensitivity and participant safety. Data will be securely stored in REDCap and disseminated through peer-reviewed publications and scientific conference Trial registration number NCT07218458 .

Abstract Background: Amyloidosis is a complex disease with a multitude of sequalae, particularly with the variants that cause cardiac amyloidosis. There is minimal literature on the types of procedures these patients undergo and the associated postprocedural outcomes. This gap of knowledge makes it difficult for anesthesia providers to risk stratify amyloidosis patients. Methods: This is a single-center, retrospective chart review study performed at a tertiary care medical center that serves as a referral center for patients with amyloidosis. Patients with a known diagnosis of transthyretin (ATTR) or light chain (AL) amyloidosis who underwent procedures requiring anesthesia between January 1, 2018 and October 24, 2024 were included in the study. The primary outcome was 30-day all-cause mortality. Secondary outcomes included other postoperative complications and analysis of types of procedures requiring anesthesia. Results: During the study period, 160 patients underwent a total of 466 procedures requiring anesthesia. Overall, 30-day mortality rate for all encounters was 1.7% (2.7% AL vs 0.5% ATTR, OR 5.71). Endoscopy was the most common procedure, accounting for 26.6% of all procedures. At the patient level, several procedures were more common in ATTR patients including TEE/Cardioversions (21.7% vs 6.6%, p=0.008), electrophysiology (36.2% vs 9.9%, p<0.001), and neurosurgery (13.0% vs 3.3%, p=0.031). Conclusions: In conclusion, patients with amyloid variants that cause cardiac amyloidosis carry substantial postoperative risk when undergoing procedures, with a trend toward increased mortality in patients with AL compared to ATTR. Patients with ATTR are more likely to require neurosurgery and treatment of arrythmias than patients with AL. Additional studies are needed to determine specific diagnostic parameters to help optimize these patients in the future. Trial Registration : Not applicable. Not a clinical trial

Background: Stroke is a leading cause of mortality and long-term disability, and aphasia is among its most common and debilitating sequelae. Diffusion tensor imaging (DTI) and advanced diffusion imaging techniques enable the assessment of white matter integrity and provide clinically relevant measures in post-stroke aphasia. Methods: We conducted a comprehensive review of studies applying DTI or advanced diffusion imaging to investigate structural connectivity in adults with post-stroke aphasia (PSA). PubMed, CENTRAL, Ovid MEDLINE, and Embase were searched, and eligible studies were synthesized according to their diagnostic, prognostic, or therapeutic focus. Results: Ninety-five studies were included. Of these, 59 were classified as diagnostic, 17 as prognostic, and 19 as therapeutic. Most studies employed conventional DTI (n = 77), while a growing body of research utilized advanced diffusion models, including CSD, DSI, and DKI (n = 18). Conclusions: This comprehensive synthesis demonstrates the evolution of diffusion imaging in PSA research. While conventional DTI has provided foundational insights, advanced diffusion methods offer superior characterization of complex fiber architecture and improved clinical–anatomical correlation. Diffusion-derived markers of dorsal and ventral language pathways were consistently associated with language performance, while connectome-level analyses highlighted the importance of preserved global network architecture for recovery. Continued efforts are needed to translate diffusion imaging findings into clinical applicable biomarkers to guide personalized aphasia rehabilitation, with greater use of advanced methods.

Intramedullary screw fixation (ISF) of metacarpal fractures is a well-established technique. Prior techniques either involve placement of the intramedullary screw in a retrograde fashion or placement of the guidewire in a retrograde fashion before placing the screw in an antegrade fashion. While effective, previously described techniques have risks of extensor tendon irritation, articular cartilage disruption, and limited access to multiple metacarpals from a single incision. We present a novel antegrade intramedullary screw placement and antegrade guidewire technique for ISF that avoids disruption of the metacarpal head and allows for access to multiple metacarpals through a single incision. Cadaveric evaluation confirmed consistent sparing of the distal carpal row and demonstrated the feasibility of this technique across the index through small finger metacarpals. Compared with previously described methods, this technique offers improved soft tissue preservation, reduced risk of tendon scarring, and enhanced surgical efficiency. Level of Evidence: Level IV—case report; cadaveric study.