Citations

BACKGROUND: The EARLY TAVR trial (Evaluation of TAVR Compared to Surveillance for Patients with Asymptomatic Severe Aortic Stenosis) demonstrated that early transcatheter aortic valve replacement (TAVR) was superior to clinical surveillance (CS) in asymptomatic severe aortic stenosis. The relative impact of early TAVR versus CS strategy by age is unknown. METHODS: The study population of the EARLY TAVR trial was stratified into 4 age groups: 65 to 69 years (n=141), 70 to 74 years (n=263), 75 to 79 years (n=250), and ≥80 years (n=247). Associations between age and the trial primary end point of death, stroke, or unplanned cardiovascular hospitalization; the composite end point of death, stroke, or heart failure hospitalization; and its individual components were examined. Interaction tests evaluated whether the treatment effect of early TAVR versus CS differed by age. RESULTS: No interaction was detected between age and the treatment effect of early TAVR versus CS for the composites or individual outcomes. We observed lower stroke rates with early TAVR compared with CS in the youngest (65–69 years, absolute risk reduction, 13%; P =0.008) and oldest (≥80 years; absolute risk reduction, 12.3%; P =0.029) age groups. The absolute difference in heart failure hospitalization rates between the early TAVR and CS arms at 2 years was greatest in the oldest patients (≥80 years, 9.1%; 75–79 years, 5.9%; 70–74 years, 5.1%; 65–69 years, 4.4%). In the CS group, time to conversion to AVR was similar across all age groups (median, 11 months; P =0.73). Approximately one-third of younger patients (65–69 years) in the CS arm presented with acute valve syndrome at the time of conversion, the frequency of which tended to increase with age ( P =0.06). CONCLUSIONS: In the EARLY TAVR trial, the relative benefit of early TAVR over CS was consistent among all age groups. The greatest absolute reduction in stroke rate with early TAVR compared with CS appeared in the youngest and oldest groups, whereas reduction in heart failure hospitalization was most pronounced in the oldest patients. These data suggest that early TAVR should be considered in all age groups above 65 years. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03042104.

BACKGROUND Laser interstitial thermal therapy is a minimally invasive surgical technique commonly used for treating epileptogenic foci in patients with drug-resistant epilepsy. Densely calcified lesions pose a challenge because they prevent the placement of a laser cannula within them and act as a heat shield. A 22-year-old male presented with intractable epilepsy with imaging demonstrating a densely calcified lesion in the right medial occipitotemporal gyrus radiographically consistent with a polymorphous low-grade neuroepithelial tumor of the young. OBSERVATIONS Two laser cannulas were stereotactically positioned to flank the centrally calcified portion of the lesion at its anterior and posterior aspects. Intraoperative MR thermography during each ablation showed that the dense calcification shielded ablative heating from spreading to the other side of the lesion. The sum of the thermal ablation zones covered the entirety of the lesion. Postprocedure MRI demonstrated overlapping peripherally enhancing ablation zones, which subsumed the entirety of the calcified mass. The patient tolerated the procedure well and remained seizure free at the 14-month follow-up. LESSONS Using multiple stereotactically placed laser filaments to flank epileptogenic lesions that are densely calcified is a strategy to effectively encompass the entirety of the lesion within the combined ablation zones. https://thejns.org/doi/10.3171/CASE26184

This cross-sectional study evaluates the performance of the US Food and Drug Administration–cleared phosphorylated tau 217 (p-tau217) to β-amyloid 42 ratio cut points used to detect amyloid pathology associated with Alzheimer disease.

Introduction Women residing in rural areas or belonging to lower socioeconomic status (SES) strata experience disproportionately low rates of breast cancer screening, contributing to delayed diagnoses and poorer prognoses. In addition, their participation in clinical trials remains markedly limited, reducing opportunities to access preventive and screening interventions. Promoting research preparedness among women before disease onset may empower them to make informed decisions regarding their health and willingness to participate in clinical research with fewer emotional and logistical barriers. Methods and analysis This project applies a community-based participatory research approach to develop and refine the WeCARE (Women’s Engagement for Cancer Awareness, Resources and Education) intervention for women aged 50–74 years who have either never undergone breast cancer screening or have not received screening in the past 5 years and who reside in rural areas or belong to low SES groups. The intervention consists of two components. Component 1 is a single-day, in-person community forum that includes (a) an educational seminar led by an oncologist to address breast cancer risk and screening guidelines, (b) survivor storytelling to enhance emotional engagement and cultural resonance and (c) facilitated navigation to breast cancer screening and future research participation. Component 2 involves structured post-forum follow-up through multiple touchpoints (phone calls and mailed boosters) to reinforce knowledge, address barriers and support screening completion and research enrolment. Quantitative data (eg, screening completion, satisfaction and follow-up engagement) will be summarised using descriptive statistics to assess feasibility and reach on 50 participants. Qualitative feedback from participants will undergo thematic analysis to identify barriers, facilitators and perceived cultural relevance. Integrated mixed-method interpretation will inform iterative refinement of the WeCARE intervention and guide design of subsequent larger trials. Ethics and dissemination Approved by the Mayo Clinic Institutional Review Board (IRB #25–008934). All participants will provide informed consent. Procedures ensure confidentiality, cultural sensitivity and participant safety. Data will be stored in REDCap and disseminated through publications, conferences, local town halls and community reports.

PURPOSE In immunoglobulin light chain (AL) amyloidosis, amyloid fibrils cause organ dysfunction. Anselamimab, a monoclonal antibody, selectively binds to amyloid fibrils, accelerating their clearance. METHODS Newly diagnosed patients with European modification of Mayo 2004 stage IIIa or IIIb AL amyloidosis were randomly assigned to receive anselamimab or placebo with cyclophosphamide, bortezomib, and dexamethasone (with or without daratumumab). The primary end point was a hierarchical composite of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalizations (CVHs), analyzed using the Finkelstein-Schoenfeld test and win ratio estimation. RESULTS Among 406 randomly assigned patients, the primary end point win ratio for anselamimab versus placebo was 1.11 (95% CI, 0.83, 1.50; P = .332) and the hazard ratio (HR) for ACM was 0.80 (95% CI, 0.57, 1.13; P = .290). CVH rates in the anselamimab and placebo groups were 0.59 (95% CI, 0.42, 0.83) and 0.89 (95% CI, 0.55, 1.43), respectively ( P = .145). Among patients with kappa isotype (n = 72), the win ratio was 2.06 (95% CI, 0.98, 4.31; P = .100) and anselamimab reduced ACM by 62% versus placebo (HR, 0.38; 95% CI, 0.17 to 0.86; nominal P = .012), and CVH by 71% (IRR, 0.29; 95% CI, 0.10 to 0.87; nominal P = .028) with improvements in Kansas City Cardiomyopathy Questionnaire-Overall Score. There was no clinical benefit observed in the lambda population. Anselamimab was generally well-tolerated; safety data were comparable between treatment arms overall. CONCLUSION Treatment with anselamimab, an antifibril antibody used alongside antiplasma cell dyscrasia therapy, while not meeting the primary end point in the overall population, significantly improved ACM and CVH in patients with kappa AL, potentially offering a new therapeutic option for this isotype.

Abstract Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

TPS10628 Background: Despite advances in cancer treatment, a lack of established population-level cancer screening strategies for early detection across cancer types contributes to cancer-related mortality. Emerging MCED liquid biopsy tests represent a screening approach with potential to enable detection of multiple malignancies at earlier stages in the disease process. We previously showed that an initial classifier based on a genome-wide methylome enrichment platform detected 12 cancer types, including early-stage, low-shedding tumors (Park et al. AACR 2023. Abs 1030). However, clinical performance of the platform has not been evaluated prospectively. Thus, the CAMPERR study (NCT05366881) was designed to train and validate a cell-free methylated DNA immunoprecipitation and high throughput sequencing (cfMeDIP-seq)-based test for detection and differentiation of 20 pre-selected cancer types, representing 93% of annual cancer incidence and 88% of annual cancer deaths. Longitudinal follow-up for a subset of participants with lung cancer will enable training and validation for MRD-based recurrence prognostication. Methods: This case-control study is enrolling participants with 20 different pre-specified cancer types (n=2400) and those without known cancer (n=3900). Eligible participants are ≥40 years of age and not receiving treatment for cancer at the time of enrollment or taking any demethylating/hypomethylating agents. Cases include individuals with newly diagnosed (≤120 days), untreated cancer or recurrence of a cancer originally diagnosed >5 years ago. Cancers of interest are stage I-IV bladder, brain, breast, cervical, colorectal, endometrial, esophageal, gastric, head and neck, hepatobiliary, leukemia, lung, lymphoma, multiple myeloma, ovarian, pancreatic, prostate, renal, sarcoma, and thyroid. Participants with stage I-III lung cancer will have clinical follow-up and blood draws after completion of first-line treatment, every 3 mo for the first year thereafter, and every 6 mo for an additional 2 years. Eligible control participants have not been diagnosed with invasive cancer in the last 5 years and will have clinical follow-up ≥12 mo from enrollment to evaluate cancer status. Liquid biopsy results will not be returned to clinicians or participants. The primary objective is cancer detection. Secondary objectives include detection of specific cancer types, identification of the tissue of origin, and prognostication of clinical outcomes (eg, recurrence-free survival, overall survival). CAMPERR is currently enrolling at 15 sites. As of December 3, 2025, 2108 of 2400 cancer cases have been enrolled, including prostate (n=225), lung (n=216), colorectal (n=211), breast (n=193), and pancreatic (n=192); controls are fully enrolled. Clinical trial information: NCT05366881 .

Abstract Objectives Carbapenem resistance is a growing public health crisis with regional variability in incidence. We characterized the susceptibility of carbapenem-resistant Gram-negative rods (CR-GNRs) from the Pacific Northwest to five reserve beta-lactam agents including cefiderocol and aztreonam-avibactam. Methods A panel of 162 CR-GNRs from unique patients were tested against cefiderocol, aztreonam-avibactam, ceftazidime-avibactam, meropenem-vaborbactam and ceftolozane-tazobactam, with a subset of isolates derived from patients with bacteraemia (n = 55). Whole-genome sequencing (WGS) was performed on representative Stenotrophomonas maltophilia isolates displaying a range of cefiderocol MICs (n = 9). Results Among all isolates, the MIC50 and MIC90 to cefiderocol was 0.25 and 4 mg/L, respectively, compared with 4 and >64 mg/L for aztreonam-avibactam. Overall, 98.3% of S. maltophilia (n = 60), 91.2% of Enterobacterales (n = 34) and 88.5% of Pseudomonas aeruginosa (n = 26) isolates were susceptible to cefiderocol, while 78.6% of other non-fermenters had MICs ≤4 mg/L. Aztreonam-avibactam and cefiderocol exhibited similar activity against Enterobacterales and S. maltophilia, but aztreonam-avibactam was less active against other organisms. WGS of S. maltophilia isolates with elevated cefiderocol MICs identified disruptive mutations in PBP-encoding genes (mrcB/PBP1b and pbpC/PBP1c) that were not observed in highly susceptible isolates. The bacteraemia cohort had many comorbidities and a 29% 30 day all-cause mortality. In this cohort, cefiderocol demonstrated the highest in vitro activity as extrapolated from MICs, followed by ceftazidime-avibactam, aztreonam-avibactam, meropenem-vaborbactam and ceftolozane-tazobactam, respectively. Conclusions Cefiderocol exhibited the greatest in vitro activity against various CR-GNRs species in a Pacific Northwest population enriched for severely ill patients. Susceptibility to other agents was more variable among tested organisms.

7501 Background: AL amyloidosis is a plasma cell dyscrasia (PCD) characterized by κ or λ Ig light chain amyloid fibrils that deposit in vital organs. Anselamimab is an investigational mAb designed to complement anti-PCD therapy through accelerated removal of amyloid fibrils. Cardiac Amyloid Reaching for Extended Survival (CARES) studies (NCT04512235 and NCT04504825) investigated the efficacy and safety of anselamimab compared with placebo, in addition to anti-PCD therapy. Methods: Alongside anti-PCD therapy with CyBorD (daratumumab was permitted) newly diagnosed patients with European modification of Mayo stage IIIa or IIIb AL amyloidosis were randomized 2:1 to receive anselamimab (1000 mg/m 2 ) or placebo (normal saline) IV every 7 days for 4 weeks followed by every 14 days for the remainder of the blinded study (18 months after the last participant enrolled). The primary endpoint was a hierarchical combination of time to all-cause mortality (ACM) and frequency of adjudicated cardiovascular hospitalizations (CVH) using the Finkelstein-Schoenfeld test and win-ratio in the combined study population. Subgroup analysis by involved κ or λ free light chain (iFLC) was prespecified. Results: 271 patients were randomized to receive anselamimab and 135 placebo. Baseline characteristics were similar between treatment arms. The median duration of treatment was 21.4 months and 21.1 in the anselamimab and placebo arms, respectively. Daratumumab was used in 79.3% and 83.7% of the anselamimab and placebo arms, respectively. Results of the primary efficacy analyses are shown in the table. Anselamimab-treated patients with κ iFLC had a 62% reduction in ACM (HR = 0.38; 95% CI, 0.17, 0.86; nominal P = 0.012) and a 71% reduction in risk for CVH (estimated CVH rate ratio = 0.29; 95% CI, 0.10, 0.87; nominal P = 0.028). Patients with λ iFLC had a 10% reduction in risk for CVH; none in ACM. Safety data were comparable between both treatment arms. In anselamimab-treated patients, safety findings were similar between κ subgroup and full population. Conclusions: Anselamimab, a κ light chain–directed anti-fibril monoclonal antibody used alongside standard of care chemotherapy, offers a first-in-class, new therapeutic option for patients with newly diagnosed κ AL amyloidosis. Clinical trial information: NCT04512235 and NCT04504825 . Summary of primary efficacy endpoints. Endpoint Overall κ Isotype λ Isotype Anselamimab (N=271) Placebo (N=135) P -value Anselamimab (N=48) Placebo (N=24) P -value Anselamimab (N=219) Placebo (N=109) P -value ACM and CVH win ratio (95% CI) 1.1 (0.8, 1.5) 0.332 2.06 (0.98, 4.31) 0.100 0.9 (0.6, 1.3) 0.848 ACM n (%) 90 (33.2) 52 (38.5) 15 (31.3) 14 (58.3) 73 (33.3) 37 (33.9) HR (95% CI) 0.8 (0.6, 1.1) 0.290 0.38 (0.2, 0.9) 0.012 1.0 (0.7, 1.5) 0.647 CVH Frequency/year (95% CI) 0.6 (0.4, 0.8) 0.9 (0.6, 1.4) 0.145 0.41 (0.2, 0.8) 1.4 (0.6, 3.4) 0.028 0.7 (0.4, 1.0) 0.8 (0.4, 1.3) 0.664 Incidence risk ratio (95% CI) 0.7 (0.4, 1.2) 0.29 (0.1, 0.9) 0.9 (0.5, 1.7)