Citations

Chimeric antigen receptor (CAR) T cell therapy faces many challenges against solid tumors including T cell exhaustion and poor CAR durability. Here, we show that engaging the CAR T cell endogenous T cell receptor (TCR) using an oncolytic virus enhances CAR T cell functionality, durability, and therapy. Upon combination therapy of solid tumors with CAR T cells and vesicular stomatitis virus (VSV), a subpopulation of antiviral, TCR-primed CAR T cells was generated with enhanced effector functions, altered activation states, and differential gene and protein expression when compared to non–TCR-primed CAR T cells. Single-cell RNA sequencing showed clonal expansion of anti-VSV CAR T cells and enhancement of effector-associated genes with VSV-mediated CAR T cell expansion. CD4 T cells played a pivotal role in the development of these TCR-primed CAR T cells. These results provide a strong rationale both for a novel use of systemic oncolytic virotherapy and for directly exploiting the CAR T cell TCR to fine tune the CAR T cell phenotype and function.

Thoracic aortic aneurysm (TAA) is a relatively common, under-recognised and lethal condition. Yet, current management remains anchored on absolute diameter for prophylactic repair, despite many dissections occurring below surgical thresholds—particularly in women. This review synthesises evidence showing that while rigorous standardisation of imaging is foundational, diameter alone is insufficient for accurate risk prediction. We appraise clinically available biomarkers beyond size: indexed metrics (Aortic Size Index, Aortic Height Index, Indexed Aortic Area) that adjust for body habitus—especially relevant in women; morphological descriptors (ascending length, arch tortuosity, aortic volume) that capture geometry; dynamic and biomechanical measures (growth rate, regional deformation, distensibility/stiffness) that reflect disease activity and advanced modalities (four-dimensional flow MRI, vascular deformation mapping) that quantify haemodynamics such as flow displacement and wall shear stress. Functional aortic markers—including central blood pressure, aortic stiffness, pulsatile arterial load and arterial age—independently predict expansion and improve risk stratification when combined with diameter. Furthermore, recognition of sex differences in TAA growth and outcomes supports sex-informed, precision aortic imaging and functional approaches to risk assessment. Future priorities include prospective multicentre validation, actionable sex-specific thresholds and multidisciplinary collaboration to translate these tools into personalised surveillance and timely intervention.

Purpose: Nasopharyngoscopy is an imaging method used to visualize the velopharyngeal mechanism. To quantify the movement of the mechanism during speech, an international working group recommended standardized rating guidelines. While these guidelines are widely cited in research, the extent to which cleft teams apply them in a clinical setting is unclear. Method: This cross-sectional study examined clinical nasopharyngoscopy reports from 11 cleft teams in North America. Descriptive statistics were used to summarize the proportion of reports that included ratings for the extent of velar movement, left and right lateral pharyngeal wall movement, gap size, and a surgical recommendation. Fisher's exact and chi-square tests were used to assess differences in reporting by cleft team and whether the inclusion of quantitative ratings was associated with a surgical recommendation being included. Results: A total of 188 nasopharyngoscopy reports were included. The extent of velar movement was reported in 68% ( n = 127) of reports, the left and right lateral pharyngeal wall movement was reported in 38% ( n = 71), and the size of the gap was reported in 70% ( n = 132). Only 34% ( n = 63) of reports included all three quantitative ratings. Inclusion of all three quantitative ratings varied significantly ( p < .001) across teams. Teams either never included all the ratings ( n = 4/11) or inconsistently included all ratings ( n = 7/11). Conclusions: Findings suggest that what is documented clinically in nasopharyngoscopy reports varies both within and across teams. To achieve more consistent reporting within individual teams, providers may consider implementing standardized clinical templates. To achieve consistency across teams, these findings suggest a need for renewed efforts at developing consensus on the nasopharyngoscopy elements important to clinicians.

Importance Decentralized clinical trials (DCTs) aim to increase trial access for underrepresented populations (URP) and ensure study outcomes, conclusions, and policy-related decisions are applicable to diverse populations. Objective To assess trends in the percentage of accrued participants from more than 120 miles from the research site upon DCT program implementation. Design, Setting, and Participants This descriptive quality improvement study was conducted from January 2024 to March 2025 at Mayo Clinic, a US multiregional, academic medical center (AMC) comprising 3 sites and an affiliated, community-based health care system. All individuals who consented and/or accrued to an institutional review board–approved clinical trial were included. Exposure DCTs are defined as trials with at least 1 decentralized capability beyond remote consent. DCT program development began July 2022. By January 2024, remote consent, video telehealth visits, remote phlebotomy, and device services were implemented across all sites and departments. Remote monitoring and oral medication delivery were available on a limited basis. Prospective automated program and DCT participant data collection and quarterly reporting began in January 2024. Main Outcomes and Measures Percentage of all DCT accrued participants with a residential zip code more than 120 miles from 1 of 3 AMC sites. Results There were 7469 participants (median [IQR] age, 62 [51-70] years; 3594 [48.1%] female; 241 [3.2%] Asian, 391 [5.2%] Black or African American, and 6347 [85.0%] White individuals) accrued to 765 DCTs. During the study period, the percentage of DCT participants residing more than 120 miles from an AMC site ranged from 18.9% in the first quarter (Q1) of 2024 (383 of 2032 participants) to 29.6% in Q1 of 2025 (346 of 1170 participants). Of those accrued, 1147 (15.4%) were of a racial or ethnic URP, ranging from 12.5% in Q1 of 2024 (253 participants) to 17.4% in Q1 of 2025 (204 participants). There were 1554 (20.8%) participants from a rural location, ranging from 16.6% in Q1 of 2024 (338 participants) to 24.9% in Q1 of 2025 (291 participants). Additionally, by geospatial distance from an AMC site, the male-to-female ratio was nearly 50:50, and the age distribution appeared similar. Conclusions and Relevance In this quality improvement study of a DCT program implementation, DCT accruals trended favorably among those residing more than 120 miles from an AMC site and those of rural or URP populations. While these findings cannot be directly attributed to program implementation, they are reassuring that this strategy may address some barriers to clinical trial access. Future studies should assess the sustained effectiveness and scalability of DCT models in improving equitable trial access.

Abstract Purpose The temporarily implanted nitinol device (TIND) is a minimally invasive surgical technique (MIST) for benign prostatic hyperplasia (BPH) that promises fewer unwanted side effects compared with traditional bladder outlet procedures for small glands with high-riding bladder necks, including transurethral incision of the prostate (TUIP). This study sought to compare the effect of TIND vs. TUIP on ejaculatory function in sexually active males using the Male Sexual Health Questionnaire Ejaculatory Function Short Form (MSHQ-EjD-SF). Methods A retrospective review of a prospectively maintained database of all patients who underwent TIND at our institution between 1/1/2022 and 10/1/2024. Patients were excluded if they reported no postoperative ejaculations. Patients who underwent TUIP during the same period were compared. Age, prostate volume, PSA, and urinary parameters were collected. MSHQ-EjD-SF scores were collected for all patients. Continuous variables were compared using Wilcoxon Rank sum test and categorical variables using Fisher’s exact test. Results A total of 27 patients underwent TIND, of which 17 reported postoperative ejaculations and were compared with 17 patients who underwent TUIP during the same period with similar baseline age, prostate volume, and urinary parameters. Median MSHQ-EjD-SF score was higher after TIND compared with TUIP (15.0 (14.0, 15.0) vs. 13.0 (11.0, 13.0), p < 0.01), while bother score was lower (0.0 (0.0, 0.0) vs. 1.0 (0.0, 2.0), p = 0.02). Conclusions Patients experienced negligible effect on ejaculatory function after TIND compared with TUIP. This may be an effective bladder outlet procedure for patients who prioritize their postoperative ejaculatory function.

Abstract The objective of the study was to assess the frequency of interictal epileptiform discharges (IEDs) in calcified neurocysticercosis (NCC) and its relationship with calcification burden. Forty‐nine patients with calcified NCC (low‐burden, 1–2 calcifications, n = 24; high‐burden, ≥15 calcifications, n = 25) and seizure history underwent prolonged (8‐h) electroencephalography (EEG), interpreted by epileptologists who were blinded to patient history and calcification category. Clinical seizure outcomes were also assessed. We found that IEDs occurred in 7 of 49 participants (14.3%), with no difference between low‐burden (12.5%) and high‐burden (16.0%) groups ( p = 1.000). All IEDs (spikes and/or sharp waves) in the high‐burden group ( n = 4) were high‐voltage (100–150 μV), whereas those in the low‐burden group ( n = 3) were low or medium voltage (20–70 μV). Among the participants who had IEDs, 5 (71.4%) had seizures in the last year, compared with 14 (33.3%) in the group without IEDs detected ( p = 0.093). Among 19 participants with seizures in the last year, 5 were identified as having drug‐resistant epilepsy (DRE). All five cases of DRE occurred in individuals with 15 or more calcifications (5/25, 20%, vs 0/24, p = 0.023). We conclude that IEDs occur frequently in individuals with calcified NCC. Although calcification burden itself was not associated with the presence of IEDs, drug‐resistant cases and high‐voltage IEDs were concentrated in the high‐burden group, supporting the role of calcified parasites as epileptogenic foci.