Citations

ABSTRACT Background This study aimed to explore the effect of family history (FH) and polygenic risk scores (PRS) for multiple psychiatric disorders on lithium response in bipolar disorder (BD). Method The sample included patients from the Mayo Clinic BD Biobank. FH in first‐degree relatives was obtained via the patient questionnaire. Linear regression models tested the association of FH and PRS for BD, major depressive disorder (MDD), schizophrenia (SCZ), alcohol use disorder (AUD), anxiety disorder (ANX), and attention‐deficit/hyperactivity disorder (ADHD) with lithium response measured by the Alda A score adjusted for the Alda B sum score. Post hoc models additionally adjusted for clinical covariates (age at onset, rapid cycling, and BD subtype). Results 716 patients had Alda scores for lithium response (61.9% females, mean age = 43.4 years). FH‐BD ( β = −0.57, p = 0.015), AUD ( β = −0.44, p = 0.045), and ANX ( β = −0.61, p = 0.050) were associated with worse lithium response. After adjusting for clinical covariates, associations for FH‐BD and FH‐ANX were no longer significant. PRS‐BD was associated with better response ( β = 0.22, p = 0.041), while PRS‐MDD ( β = −0.28, p = 0.01) and PRS‐ADHD ( β = −0.24, p = 0.028) were associated with worse response, with effects largely unchanged after adjusting for clinical covariates. In the combined model considering all FHs simultaneously, only FH‐BD remained significantly associated with worse lithium response ( β = −0.71, p = 0.039). In the combined model for PRS, only PRS‐BD ( β = 0.31, p = 0.008; better response) and PRS‐MDD ( β = −0.29, p = 0.020; worse response) showed significant associations. Conclusions In this exploratory study, FH‐BD, AUD, and ANX were associated with poor response, though only FH‐AUD remained significant after adjusting for clinical factors. PRS‐BD predicted better response, while PRS‐MDD was associated with worse response. These findings suggest independent and potentially complementary roles of FH and PRS. Integrating both familial and genetic risk measures may improve personalized treatment strategies and outcomes for BD patients.

Abstract A low-cost, easy-to-adopt noninvasive imaging modality for differentiating bacterial infection from inflammation is desirable to accurately diagnose bacterial infections. Herein, a bacteria-specific PET probe, [68Ga]Ga-BP, was developed and evaluated in rat models of foreign body-associated osteomyelitis induced by methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae and was directly compared with sterile inflammation and uninstrumented uninfected controls. [68Ga]Ga-BP-based imaging of MRSA-infected tibiae was also compared to [68Ga]Ga-citrate and [18F]FDG. After iron depletion, dynamic PET/CT imaging was performed at 15–120 min postinjection of radiotracers, followed by assessment of ex vivo biodistribution. [68Ga]Ga-BP successfully detected tibial infection and demonstrated >6-fold higher uptake in infected tibiae with all three bacterial species versus contralateral tibiae via PET imaging. [68Ga]Ga-BP outperformed [68Ga]Ga-citrate and [18F]FDG in identifying MRSA infection. [68Ga]Ga-BP represents a promising, noninvasive PET imaging agent for direct bacterial detection and bacterial infection treatment monitoring.

Reasonable accommodations in higher education are being more frequently requested by graduate occupational and physical therapy students within didactic and clinical contexts. Researchers aimed to describe the experiences of clinical educators in occupational and physical therapy mentoring graduate students with a disclosed accommodation during terminal clinical education, employing a qualitative design. Semi-structured interviews and one-time electronic survey were completed. Reflexive thematic analysis was conducted following the approach described by Braun and Clarke. Twelve occupational or physical therapy clinical educators participated in semi-structured interviews, each having mentored 1–2 students with a disclosed disability accommodation during a terminal clinical education experience. Four major thematic categories regarding accommodation use in terminal clinical emerged: 1) accommodation process, 2) team approach to accommodating, 3) fostering accommodations, and 4) ambiguity in facilitating accommodations. Clinical educators emphasized the importance of being informed about accommodations well in advance, adapting teaching methods, and maintaining regular communication between academic institutions, clinical sites, and students. Training for clinical educators on the disclosure process, legal obligations, and strategies for effective mentorship to ensure alignment of accommodation, academic requirements, and site expectations is essential.

Prehabilitation with Impella 5.5 offers hemodynamic support while allowing early mobilization, yet its overall effect on post-transplant recovery remains unclear. The aim was to assess recovery during Impella 5.5–supported prehabilitation and determine its association with early post-heart transplant outcomes, including a potential dose–response relationship with ambulatory activity. We conducted a single-center retrospective cohort study of adults bridged to transplant with Impella 5.5 between April 1, 2022 and September 30, 2024. Daily walking distance, recorded by nursing staff, served as the intervention. Primary outcome was postoperative hospital length of stay (LOS); the secondary outcome was time to extubation. Fine–Gray competing-risk models, adjusted for age, Sequential Organ Failure Assessment (SOFA) score, New York Heart Association (NYHA) class, and days of Impella support, assessed associations. Longitudinal recovery trajectories were analyzed with linear mixed-effects models incorporating restricted cubic splines. Among 82 eligible patients, 65 met the inclusion criteria. Patients who walked farther during Impella 5.5 support in the intensive care unit (ICU) had shorter hospital stays and were taken off the ventilator sooner after transplantation. The overall recovery peaked during the first 2–3 weeks of support, with smaller recovery thereafter, indicating that most functional recovery occurred early during prehabilitation.

BACKGROUND: Cardiac computed tomography (CT) acquired during the acute stroke imaging protocol is an emerging modality to detect cardiac thrombi. We determined its yield in patients with acute ischemic stroke. METHODS: We performed a 1-stage individual patient data meta-analysis of 4 prospective observational cohorts (AIS of HEARTS [Acute Ischemic Stroke of Heart-Related Embolic Sources Detected on Acute Cardiac CT Scans]), including patients with acute ischemic stroke who underwent ECG-gated or non–ECG-gated cardiac CT between May 2018 and June 2024. We excluded patients with transient ischemic attack or stroke mimics. The primary outcome was the proportion of patients with a thrombus on cardiac CT. Secondary outcomes were additional scan time, radiation dose, comparison with echocardiography, and 90-day outcomes. We performed logistic regression analyses to compare 90-day outcomes between patients with and without thrombus, adjusting for age, sex, history of atrial fibrillation, ischemic heart disease, chronic heart failure, stroke or transient ischemic attack, anticoagulant use, prestroke modified Rankin Scale score, National Institutes of Health Stroke Scale score, large vessel occlusions, and intravenous thrombolysis, as appropriate for each outcome. RESULTS: We included 3919 patients (median age, 74 [interquartile range (IQR), 63–82], 58% male, median National Institutes of Health Stroke Scale score 6 [IQR, 3–12]). Cardiac CT detected a thrombus in 243 (6.2%) patients. Among 1323 patients that underwent both cardiac CT and transthoracic echocardiography, cardiac CT had a higher yield than transthoracic echocardiography (odds ratio, 7.4 [95% CI, 4.0–15.1]; P <0.001). Median additional scan time was 6 minutes (IQR, 5–7) for ECG-gated and 13 seconds (IQR, 12–61) for non–ECG-gated cardiac CT. Median additional radiation dose was 2.9 mSv (IQR, 1.6–4.1). Patients with thrombi had higher 90-day mortality (33% versus 15%, adjusted odds ratio, 1.6 [95% CI, 1.1–2.3]) and worse modified Rankin Scale scores (median modified Rankin Scale score 3 versus 2, adjusted odds ratio, 1.6 [95% CI, 1.2–2.0]), but similar recurrent stroke rates (5% versus 4%, adjusted odds ratio, 1.4 [95% CI, 0.7–2.5]). CONCLUSIONS: Implementing cardiac CT into the acute stroke imaging protocol is feasible, detects thrombi in ≈6% of patients, and has a higher yield than transthoracic echocardiography. Cardiac thrombi were associated with higher mortality, but not higher stroke recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT07165093.

Background/Objectives: Speech perception is measured in quiet and in the presence of background noise, such as multi-talker babble (MTB), to establish cochlear implant (CI) candidacy and measure post-operative outcomes. Testing protocols often use interrupted noise that begins just before and ends shortly after the target sentence, providing insufficient time for the noise-reduction algorithms to activate in the hearing device and provide an improved signal-to-noise ratio (SNR). Furthermore, interrupted noise does not allow the hearing-impaired user to acclimatize to the abrupt onset of noise or to focus on the target sentence, a challenge related to auditory stream segregation. The present study compares speech perception in bimodal CI users across interrupted and continuous MTB noise conditions to highlight performance differences between these two distinct listening environments. Methods: Speech perception was evaluated for two different bimodal CI groups. Group 1: This group evaluated an automatic hearing aid program across three environments: quiet, continuous MTB, and interrupted MTB. Group 2: This group evaluated two manual hearing aid programs across the same three environments (quiet, continuous, and interrupted MTB). Results: For Group 1, scores in quiet reached 88%, significantly declined in interrupted MTB (38%), but improved in continuous MTB (67%). For Group 2, no significant mean differences were found between interrupted and continuous noise across the two manual programs, though individual variations persisted. Conclusions: Based on the findings of this study, continuous noise rather than interrupted noise should be utilized for establishing CI candidacy and evaluating post-implantation speech perception.

Donation after circulatory death (DCD) livers increasingly use machine perfusion (MP). This study evaluates MP’s impact on older DCD livers based on data from the United Network for Data Sharing, covering all first adult DCD liver transplants (2016–2025). The cohort, divided into pre-MP and MP eras (separated by the FDA approval of the first normothermic MP platform in 2021), showed accelerated growth in DCD liver transplants during the MP era. Donors ≥60 rose 7.8-fold, including donors ≥70 (a USA first). By 2025, DCD livers accounted for 43.2%, with 61.35% from donors ≥50. Normothermic regional perfusion (NRP) (3.0%–21.7%), NMP (2.3%–35.6%), and sequential NRP-NMP (0.1%–19.2%) increased significantly (p &lt; 0.001). The MP era was associated with a decrease in median waitlist time from 112 to 62 days (p &lt; 0.001). Early graft survival was similar across ages. For ages 50–59, 1- and 3-year survivals were 87.9%/78.4% pre-MP and 90.1%/78.8% in the MP era. For 60–69, survival was 85.0%/80.6% pre-MP and 90.0%/71.3% in the MP era. DCD LTs for ≥70 were limited to the MP era with 87.8% 1-year survival. Multivariable Cox regression showed that static cold storage (HR = 1.19), donor age 50–69 versus 18–49, and recipient age (HR = 1.04) increased the risk of graft loss after adjustment. MP is associated with an increased number of older DCD liver transplants and acceptable early graft survival.

8519 Background: Non-classical mutations (NCM) of epidermal growth factor receptor (EGFR) represent a broad group of oncogenic mutations in non-small cell lung cancer (NSCLC), often associated with resistance to osimertinib (e.g., P-loop and αC-helix compressing [PACC] mutations). Patients (pts) with NCM have inferior clinical outcomes with a high incidence of CNS metastases (CNSm). Silevertinib (BDTX-1535) is a fourth-generation, covalent EGFR TKI with high CNS penetrance targeting both EGFR classical mutations and NCM. The antitumor activity and safety of silevertinib in pts with advanced NSCLC were evaluated in a Phase 2 trial (NCT05256290). Methods: Pts with advanced EGFR NCM NSCLC who received no prior systemic therapy were enrolled (Cohort 3) based on a local molecular test. Silevertinib 200 mg was administered orally once daily. The primary endpoint of objective response rate (ORR) was assessed using RECIST v1.1. CNS ORR was assessed using Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) in pts with no prior CNS therapy. Secondary endpoints include progression-free survival (PFS), duration of response (DOR), disease control rate (DCR), and safety. Results: From February 2024 to July 2025, 43 pts with 35 unique NCMs (including 25 pts with PACC mutations) were enrolled in Cohort 3: median age 70.0 years, 72% female, 74% white, and 42% never smoked cigarettes. As of November 3, 2025, median follow-up was 7.2 months. ORR by RECIST v1.1 is shown in the table. Sixteen pts (37%) had CNSm, including 7 pts (16%) with measurable CNS disease. RANO-BM CNS response was 86% (n=6/7). Complete clearance of EGFR VAF ctDNA was observed in 21/26 (81%) evaluable pts. Serious treatment-related adverse events (TRAEs) were reported in 5 pts (12%), and 4 pts (9%) discontinued treatment due to TRAEs. The most common TRAEs included rash (19%, grade 3), diarrhea (19%, grade 3), stomatitis (9%, grade 3), and paronychia (5%, grade 3). While 77% of pts had a dose reduction, 19/22 (86%) patients with a radiographic response maintained or deepened their response after dose reduction, including all patients with CNS response. Conclusions: Silevertinib demonstrated robust antitumor activity in treatment-naïve pts with a broad spectrum of NCM EGFR driver mutations with high intracranial activity in pts with brain metastases. The safety profile was consistent with the known AEs of the EGFR TKI class. Clinical trial information: NCT05256290 . Data as of November 3, 2025 N ORR n (%) 95% CI DCR n (%) 95% CI ITT Population * 43 26 (60) (44.4, 75.0) 39 (91) (77.9, 97.4) PACC mutations 25 14 (56) (34.9, 75.6) 22 (88) (68.8, 97.5) Compound mutations † 16 11 (69) (41.3, 89.0) 15 (94) (69.8, 99.8) *No pts with classical (E746_A750del or L858R) mutations were enrolled. † Presence of ≥ 2 NCMs. As of December 27, 2025, the 6-month PFS rate was 86% overall and 80% in pts with CNSm; available PFS and DOR data will be presented.