Citations

Introduction: Frontotemporal lobar degeneration (FTLD) is a devastating disease that commonly results in early onset dementia, yet its rarity and heterogeneity limit large-scale research and clinical trials. Remote monitoring via low-burden digital health tools may overcome these barriers. We evaluated clinical utility of passive smartphone monitoring in FTLD using a multi-domain mobile assessment platform. Methods: Participants were 567 adults (53% clinically normal, 21% prodromal FTLD, 26% symptomatic FTLD) who completed an in-person study visit and downloaded the ALLFTD Mobile App on their personal smartphones. The app delivered unsupervised cognitive tests and passively collected continuous data on battery percentage (proxy for smartphone use) and step count. Longitudinal follow-up included smartphone monitoring and annual in-person study visits. Primary analyses examined associations between passive smartphone features and markers of disease severity at baseline and longitudinally, and tested whether passive features added incremental value beyond app-based cognitive testing. Results: Passive smartphone features were feasible to collect and showed excellent reliability with <2 weeks of monitoring (ICCs>0.9). Features capturing smartphone use and movement demonstrated sensitivity to gold-standard clinical measures of disease severity both at baseline and longitudinally. A classification model combining passive features, the app-based cognitive composite score, and demographics detected longitudinal functional decline (AUC=0.89); passive features alone (AUC=0.84) performed comparably to a cognitive screener (AUC=0.85). Discussion: Passive smartphone monitoring is a valid, zero-burden measure of disease severity and progression in FTLD that adds modest incremental value beyond app-based cognitive testing. Findings support its use as a scalable digital endpoint in longitudinal FTLD research.

Abstract Introduction Remote cognitive assessments offer an accessible, scalable way to support clinical characterization and longitudinal monitoring of cognition. This study evaluates the feasibility of implementing Mayo Test Drive (MTD), a remote, self-administered digital cognitive assessment, within a specialized clinic focused on eligibility assessments for anti-amyloid therapies for Alzheimer’s disease (AD). Method Two-hundred and nine ( N =209) patients (M age =71.2, 53% female) were evaluated through the Mayo Clinic Rochester Alzheimer’s Disease Treatment Clinic (ADTC) and had the opportunity to complete MTD, either as a remote, patient-initiated session through a patient-facing healthcare portal or during an in-clinic neuropsychological evaluation. Results Clinical diagnoses included 55.2% mild cognitive impairment (MCI), 31.0% mild dementia, and 11.6% moderate dementia, in addition to 2.2% cognitively unimpaired (CU), as determined by neurology consensus at a multidisciplinary case conference. Among those who initiated MTD ( n =197/209), 97.5% completed a session (70.6% remotely, 26.9% in clinic). Completion rates were high across diagnostic groups and did not significantly differ by clinical severity ( p =.12): CU (100%), MCI (99.1%), mild dementia (97.0%), and moderate dementia (89.5%). Remote completion rates overall were high (97.9%). Among completers, administration setting (remote vs. in-clinic) did not significantly differ by clinical stage, χ²(3)=2.37, p =.49. Reasons for non-initiation included not receiving or opening portal messages and other/unknown factors. Discussion Remote digital cognitive assessment is feasible within the context of clinic eligibility evaluations for AD therapies. The high completion rates of MTD across clinical impairment levels in this setting support development of paths for broader use in cognitive characterization in AD care.

Outcomes of kidney-alone transplantation (KAT) in former simultaneous liver-kidney (SLK) transplant candidates after liver waitlist delisting are not well defined. Using Scientific Registry of Transplant Recipients (SRTR) data, we identified adult recipients who underwent KAT between 2005 and 2025 after prior SLK listing (RLD-KAT), which was matched 1:5 to primary KAT recipients without liver disease by age, transplant year, and diabetes status. Patient and graft survival were evaluated using the Kaplan-Meier method and multivariable Cox proportional hazards models. We identified 163 RLD-KAT recipients matched to 815 controls. Unadjusted Kaplan-Meier analyses demonstrated lower patient survival in RLD-KAT (p = 0.020), whereas death-censored and overall graft survival were similar (p &gt; 0.05). In multivariable models, death-censored graft survival (HR 0.89; 95% CI 0.51–1.53), overall graft survival (HR 1.00; 95% CI 0.73–1.36), and patient survival (HR 1.07; 95% CI 0.76–1.5) did not differ significantly. Six RLD-KAT recipients (3.7%) subsequently underwent liver transplantation. Kidney-alone transplantation in prior SLK candidates was associated with acceptable patient and graft outcomes and a low incidence of subsequent liver transplantation.

Abstract Background Optimal treatment following first-line immunotherapy for advanced hepatocellular carcinoma (HCC) remains uncertain. This study evaluated futibatinib, a pan-FGFR inhibitor, combined with pembrolizumab in previously treated patients with FGF19-expressing HCC. Methods Eligible patients were ≥18 years old with advanced HCC, prior systemic therapy, Child-Pugh A-B7 liver function, ECOG 0–2, and FGF19 overexpression. Patients received futibatinib 20 mg orally daily plus pembrolizumab 200 mg intravenously every 3 weeks. The primary endpoint was progression-free survival at 6 months (PFS6). Secondary endpoints included overall survival (OS), objective response rate (ORR), quality of life, and safety. Results Between August 2021 and March 2024, 14 patients enrolled and 13 were evaluable. Median age was 72 years (range, 60–87), 53.8% were male, 92.3% had Child-Pugh A liver function, and all had received prior immunotherapy. Median progression-free survival was 15 weeks (95% CI, 9.0–NE), with a PFS6 rate of 23.1% (95% CI, 8.6–62.3%). ORR was 0% (95% CI, 0–24.7%), while stable disease was observed in 53.9% of patients. Median OS was 55.7 weeks (95% CI, 47.3–NE). Grade ≥3 adverse events occurred in 69.2% of patients, and grade ≥4 adverse events in 15.4%. One grade 5 event (acute-on-chronic kidney injury) was deemed unrelated to treatment. Common adverse events included hyperphosphatemia, fatigue, diarrhea, elevated transaminases, dry eye, nail changes, rash, and oral mucositis. Conclusions Futibatinib plus pembrolizumab demonstrated an acceptable safety profile but did not meet efficacy thresholds supporting further study in FGF19-expressing HCC. Effective post-immunotherapy treatment strategies remain an unmet need.

Background: Several breast cancer (BC) risk prediction models have been developed to provide personal risk assessments. Though individually validated, their performance has not been systematically evaluated across a wide range of populations or ages. Methods: We harmonized individual-level baseline questionnaire data and incident BC diagnoses from 21 cohorts from North America, Europe, and Australia participating in the Breast Cancer Risk Prediction Project. Five-year absolute risk of invasive BC was estimated for five established risk prediction models using classical risk factors only. Discrimination was evaluated by area under the curve (AUC). Calibration was assessed using average and risk-decile specific expected to observed (E/O) ratios. Performance metrics were meta-analyzed across cohorts and models. Metaregression tested associations between cohort characteristics and performance metrics. Results: This analysis included 1,595,977 women aged 20-75 years, enrolled in studies between 1976-2015, with 19,062 (1.2%) invasive BC cases ascertained within 5 years from exposure assessment. Age-adjusted AUCs were similar across models and cohorts (pooled AUCs by model: 0.57-0.58), while E/O ratios varied substantially (pooled E/O ratios by model: 0.83-1.25). Overestimation was common among predicted high-risk individuals (>3%). No appreciable differences in model performance by cohort age, birth year, race, and variable missingness emerged. Calibration improved after assigning race-specific incidence rates. Conclusion: Existing BC risk prediction models provided similar risk discrimination across multiple cohorts, although there was overestimation of risk for high-risk individuals. Performance variation across cohorts was not driven by specific characteristics, which supports development of a unified risk model for diverse populations that leverages appropriate incidence rates.

Introduction Out‐of‐hospital community births account for 1.6% to 2% of births in the United States and are associated with fewer obstetric interventions but increased neonatal risk. Little is known about how maternity care providers’ characteristics, values, and prior exposure to community birth influence attitudes toward community birth. Methods We conducted an observational cross‐sectional survey using a 40 to 43 item Research Electronic Data Capture questionnaire distributed October 2 to 30, 2024. Eligible participants (“providers”) included in‐hospital physicians, midwives, community birth providers, and registered nurses. The survey assessed demographics, practice characteristics, provider values, prior community birth experience, and attitudes toward community birth. Descriptive statistics were used to summarize characteristics. Group comparisons between in‐hospital and community birth providers were conducted using analysis of variance and χ 2 or Fisher exact tests. Associations between attitudes and provider values were evaluated using linear models with Bonferroni correction. Results Sixty‐seven providers completed the survey (51 in hospital, 16 community based). Most respondents were female (89.6%) and White (77.6%), with a median of 7 years in practice (IQR, 3‐14.5). Attitudes significantly differed by role ( P = .007) and credentials ( P = .002). In‐hospital providers reported safety concerns about community birth and perceived antenatal counseling to be inadequate. Perceived patient distrust during transfer was common among both in‐hospital and community‐based providers (69% and 81%, respectively). After adjustment for provider role and multiple comparisons, no significant differences in personal values were noted by attitude group; however, providers with positive attitudes toward community birth were more likely to believe that patients value compassion (β = 2.3, P = .004). Discussion Provider attitudes toward community birth appear to be shaped more by professional role and clinical experience than by differences in underlying value systems. High levels of perceived patient distrust during transfer highlight the need for interventions that strengthen compassion across maternity care settings.