Citations

OBJECTIVE Cognard type V dural arteriovenous fistulas (dAVFs), defined by spinal perimedullary venous drainage, represent a rare and aggressive neurovascular pathology. Comprehensive multicenter data remain scarce. The authors present the largest multicenter analysis to date, characterizing presentation, radiology, treatment, complications, and functional outcomes of Cognard type V dAVFs. METHODS The authors retrospectively analyzed patients with angiographically confirmed Cognard type V dAVFs from the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR), spanning 16 academic centers. Patient demographics, imaging features, treatment strategies, procedural complications, and modified Rankin Scale (mRS) scores were recorded. RESULTS Among 1077 patients with dAVFs, 37 (3%) had Cognard type V lesions. The mean patient age was 57 years, and 59.5% of patients were male. Most presented with nonhemorrhagic neurological deficits (68%), while 14% had hemorrhage. The most common location was the foramen magnum (32%). Embolization was the primary treatment in 67% of cases, complete obliteration was achieved in 71% of cases. Upfront microsurgery was performed in 22% of patients (obliteration rate 88%), and radiosurgery in 14% (success rate 40%). Salvage treatment further improved obliteration outcomes. Temporary complications occurred in 8% of patients (3/37): 2 with transient neurological deficits postembolization and 1 with transient hydrocephalus after surgery. Permanent complications were observed in 3% (1/37) due to treatment-related hemorrhage. At the last follow-up (mean 2.4 years), 69% (24/35) of patients maintained or improved to an mRS score ≤ 2. No deaths occurred. Functional improvement was seen in 29% (10/35), while mRS decline was in 40% of patients (14/35), all unrelated to the dAVF itself. CONCLUSIONS Cognard type V dAVFs carry a high risk of neurological morbidity. However, favorable functional outcomes are achievable with timely, multimodal intervention. Complication rates remain low, with most being transient. These data support aggressive but tailored management to prevent permanent disability in this high-risk population.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

Background Motor disturbances are common in neurologic and neurodegenerative syndromes. A standard motor speed and dexterity measure is the finger tapping test (FTT). The FTT has traditionally been administered in clinic using a mechanical FTT, limiting accessibility and early motor change quantification. This study assessed the validity of a smartphone app-based FTT, which may expand access and enable more frequent testing. Methods The cohort was diagnostically diverse, including participants with frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal syndrome, primary progressive aphasia, multiple sclerosis, and clinically unimpaired controls. Participants completed a 20-second ALLFTD Mobile App (mApp)-FTT with each hand. Tapping speed metrics were extracted. Participants completed the gold-standard mechanical FTT, a neurologist-administered finger tapping exam, the PSP Rating Scale (PSPRS) and the Unified Parkinson’s Disease Rating Scale (UPDRS). Correlations assessed mApp-FTT and mechanical FTT relationships; regressions evaluated associations with neurologist-rated finger tapping impairment, PSPRS and UPDRS, adjusting for age and sex. Results The mApp-FTT showed moderate-to-strong correlations with the mechanical FTT (dominant: r=0.63, p<0.001; non-dominant: r=0.55, p<0.001). Taps per second were associated with PSPRS motor severity (dominant hand: std. β=-0.59, 95% CI [-0.91, -0.27], p<0.001) and the UPDRS (dominant hand: std. β=-0.41, 95% CI [-0.82, 0.00], p=0.049). Flight time was modestly associated with neurologist-rated finger tapping impairment (dominant hand: std. β=0.15, 95% CI [0.00, 0.29], p=0.044). Conclusion These findings support mApp-FTT validity as a measure of motor function across neurodegenerative conditions. Validation in longitudinal and unsupervised remote settings is warranted to understand scalability and evaluate change over time.

Abstract Background Glioblastoma (GBM) is the most common malignant primary brain tumor and is associated with a poor prognosis. Repurposed posaconazole (PCZ) has demonstrated efficacy in vitro by targeting key metabolic pathways. The aim of this study was to determine the neuropharmacological profile of PCZ in patients with GBM through a Phase 0 first-in-human trial for this indication (NCT04825275). Methods We conducted an open-label, non-randomized, parallel-arm trial in participants with primary or recurrent GBM. Patients in the treatment arm received oral PCZ for 7-10 days presurgically to achieve steady-state concentrations. Microdialysis catheters were implanted to measure interstitial drug levels. Postoperative tissue and fluid samples were analyzed to evaluate PCZ pharmacokinetics (mass spectrometry) and pharmacodynamics, including vascular density, apoptosis, and metabolite concentrations (lactate and pyruvate) compared to controls. Results The trial was closed early due to slow accrual, enrolling 2 participants in the PCZ arm and three in the control arm. No drug-related safety issues were observed. Although PCZ was undetectable in microdialysate fluid, it accumulated in tumor tissue, with concentrations showing an association with CD31-measured endothelial content. PCZ-treated tumors exhibited trends toward lower BCL2 expression indicative of increased apoptosis, and significantly lower pyruvate levels in the tumor periphery compared to controls. Plasma lactate levels in treated patients normalized to control levels over 24 h. Conclusions Despite limited accrual, this trial provides the first clinical evidence that oral PCZ accumulates in human GBM tissue and shows preliminary signals of metabolic modulation. These findings provide biological rationale warranting further clinical investigation, potentially utilizing direct tissue sampling rather than microdialysis.

Brexucabtagene-autoleucel (brexu-cel) produces high rates of measurable residual disease-negative (MRD-) complete response (CR) in adults with Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia (ALL); however, subsequent relapses remain frequent. It is unclear whether maintenance with tyrosine kinase inhibitors (TKIs) can enhance remission durability. We evaluated outcomes among adults with relapsed/refractory Ph+ ALL who received commercial brexu-cel and achieved MRD- CR across 19 U.S. institutions. Considering TKI maintenance as a time-varying covariate, we analyzed outcomes based on receipt of subsequent TKI maintenance versus no maintenance. Patients receiving consolidative transplantation or non-TKI maintenance were excluded. Fifty-one patients were included: 20 received TKI maintenance and 31 received no maintenance. The use of TKI maintenance was associated with a significantly lower 1-year cumulative incidence of relapse (HR 0.12; 95% CI, 0.02-0.88; p=0.037) which translated into improved progression-free survival (PFS, HR 0.19; 95% CI, 0.04-0.85; p=0.029) and a trend towards improved overall survival (OS, HR 0.34; 95% CI, 0.07-1.62; p=0.18). There was no difference in non-relapse mortality (NRM, HR 0.83; 95% CI, 0.12-5.87; p=0.85). This real-world analysis supports the administration of TKI maintenance in Ph+ ALL following achievement of MRD- CR with brexu-cel as a strategy to improve PFS following chimeric antigen receptor T cell therapy.

Abstract Purpose: To explore the potential of the metaverse, a three-dimensional platform merging physical and virtual realities (VRs), in advancing the field of ophthalmology. This study examines its applications in areas such as VR-based surgical training, augmented reality (AR)-assisted surgeries, artificial intelligence (AI)-driven diagnostics, and teleophthalmology. This review builds upon previous literature by integrating recent evidence and technological advancements, offering a more comprehensive analysis of particular applications and barriers in ophthalmology. Methods: Academic literature published between 2019 and 2024 was identified through searches in the PubMed database and Google Scholar search engine using relevant keywords. This review focused on studies discussing the application of the metaverse in health care and ophthalmology, with particular attention to key trends, emerging uses, technological features, and associated challenges. Results: A total of 60 studies were deemed relevant for inclusion in this review. The infrastructure supporting the Metaverse comprises technologies such as the Internet of Things, digital twins, mirror worlds, nonfungible tokens, blockchain technology, and lifelogging. Together, these technologies create immersive environments that users can access through VR headsets, AR glasses, and handheld controllers. The metaverse presents promising opportunities in ophthalmology, particularly in enhancing clinical training through simulators such as the EyeSi™ surgical simulator, VRmagic EyeSi Slit Lamp, and the HelpMeSee™ VR simulator. In addition, it facilitates remote consultations and improves diagnostic and treatment options, exemplified by tools such as the Vivid Vision™ system for amblyopia, the Microsoft HoloLens™ for navigating complex anatomical structures, and AI-based platforms for the early detection of diseases such as glaucoma and diabetic retinopathy. Furthermore, the metaverse may enhance patient education by simulating the visual effects of ophthalmic conditions and visualizing postoperative outcomes. However, challenges, including financial limitations, data security concerns, and cultural acceptance, must be addressed. Conclusions: A gradual and context-specific integration of the metaverse is essential, particularly in underdeveloped regions. As the metaverse evolves, it holds significant potential to transform the field of ophthalmology by promoting global collaboration and innovation, complementing traditional practices, and ensuring equitable access to advanced healthcare solutions.

Abstract Rationale Impaired lung health may serve as a risk factor for, and a post-acute sequela of, SARS-CoV-2 infection. Yet most prior studies of lung health sequelae of COVID-19 lacked information on pre-infection lung health, a major antecedent confounder. To identify associations of COVID-19 with changes in lung health, we leveraged paired pre- and post-pandemic data on respiratory symptoms, lung function, and lung structure in a general population-based cohort. Methods We studied participants in the Multi-Ethnic Study of Atherosclerosis Lung Study with paired pre-pandemic (2016-2018) and post-pandemic (2022-2024) assessments of respiratory symptoms, spirometry, and lung CT. SARS-CoV-2 infection (2020-2023) was ascertained using a composite of questionnaires, serology, and medical record adjudication, and classified as severe (requiring hospitalization) or non-severe (not requiring hospitalization). Lung health was assessed by questionnaire (mMRC grade ≥2 dyspnea, chronic cough, chronic phlegm, chronic bronchitis), pre-bronchodilator spirometry (FEV1, FVC, FEV1:FVC), and lung density on non-contrast lung CT (% low attenuation areas, % high attenuation areas). Each post-pandemic lung health measure was regressed on infection history and the corresponding pre-pandemic lung health measure, adjusting for age at post-pandemic exam, sex, race/ethnicity, smoking status, and vaccination status at infection. Sensitivity analyses were included- (a) restriction to participants without pre-pandemic respiratory symptoms and (b) with additional adjustment for time since infection and variant wave. Results Among 2,015 participants (mean age 77.2±7.5 years; 55% female; 40% non-Hispanic White; 25% Black; 11% Asian; 23% Hispanic/Latino), 59 (3%) experienced severe and 506 (25%) non-severe SARS-CoV-2 infection. The prevalence of respiratory symptoms was similar or slightly higher at the post- vs. pre-pandemic exam (grade ≥2 dyspnea: 14% vs. 10%; chronic cough: 10% vs. 8%; chronic phlegm: 9% vs. 8%; chronic bronchitis: 4% vs. 4%; p-values &lt;0.0001). Compared with participants without infection, those with severe infection had higher odds of chronic cough (OR:2.9, 95%CI:1.3-6.3) and chronic bronchitis (OR:3.3, 95%CI:1.2-9.0) at the post-pandemic exam (Table). Associations were stronger among individuals infected &gt;90 days prior to the post-pandemic assessment and during pre-Omicron waves. Results were similar when restricted to participants without pre-pandemic symptoms. No significant associations were observed for non-severe infection (vs. no infection) or for any other lung health outcomes. Conclusions Controlling for pre-pandemic lung health, severe COVID-19 was associated with increased odds of chronic cough and chronic bronchitis but not with changes in lung function or structure in a general population-based sample. Non-severe COVID-19 was not associated with lung health outcomes. This abstract is funded by: OT2HL156812, R21HL165405, R01HL077612, 75N92025D00022, 75N92025D00026, 75N92020D00002, 75N92025D00024, 75N92025D00027, 75N92025D00025, 75N92025D00028

Background The wide reach and unique short audiovisual nature of TikTok make it a potential modality for disseminating information about orthopaedic surgery to both patients and medical professionals. However, only a few recent studies have assessed the purpose and creators of orthopaedic surgery content on TikTok. Methods The top 100 most-liked TikTok videos about orthopaedic surgery topics were included for analysis. Data reflecting video and creator account characteristics were collected. Video validity was determined by three reviewers according to the DISCERN criteria and Kruskal-Wallis H tests were performed to correlate validity to creator and video type. Results The majority of videos were created by orthopaedic surgeons (n=57/100) and for entertainment purposes (n=82/100). Orthopaedic surgeons had the highest DISCERN score (34.7) and greater video reliability compared to all other creator types (H = 59.0-67.1, all p<0.001). Videos made for educational and procedural purposes had the highest DISCERN scores (38.9 and 40.5, respectively) while entertainment videos had lower reliability (H=-56.7 to -113.5, all p<0.05). Conclusion The most popular orthopaedic surgery-related videos on the TikTok platform are primarily being created by orthopaedic surgeons for entertainment purposes. Less frequently were videos made to educate, describe procedures, and explain the lifestyle of an orthopaedic surgeon. Potential applications of utilizing the platform by orthopaedic surgeons include case or research discussions, educational videos on different pathologies, recruitment of prospective students to the field, and entertainment highlighting a day in the life of an orthopaedic surgeon.

Artificial intelligence (AI) is now applied across oncology, including imaging, pathology, therapy selection, toxicity assessment, and survival modeling, and large language models (LLMs) have been adopted particularly quickly. Reported physician use of AI roughly doubled between 2023 and 2026. The frameworks used to evaluate these tools have not advanced at the same rate. Many are available, but each was designed for a single stage of the AI lifecycle, and none directly answers the question most relevant to a treating clinician: whether a given tool is appropriate for the individual patient under care. We reviewed the frameworks in current use, including TRIPOD+AI, PROBAST+AI, CLAIM, SPIRIT-AI, CONSORT-AI, DECIDE-AI, MINIMAR, and CREMLS, together with the oncology-specific ESMO EBAI and the newer LLM-specific guidance (TRIPOD-LLM, MI-CLEAR-LLM, CHART, and ESMO ELCAP). Each addresses part of the evaluation problem, but none is sufficient on its own for oncology, where the standard of care changes rapidly, assays drift, biomarker-defined subgroups are small, and a model validated in one period may perform poorly in the next. LLMs introduce additional challenges, including sensitivity to prompting, undisclosed vendor updates, behavioral drift, and hallucination rates approaching 50% on clinical quality-assurance tasks. The predictive-model frameworks were not designed to capture these failure modes. The central argument of this review is that the frameworks the field requires already exist; what is missing is their mandatory adoption. We propose that journals and regulators move from recommending these frameworks to requiring their use, and we outline a cancer-aware evaluation pathway together with the specific responsibilities of authors, reviewers, journals, and regulators in implementing it.

Background Gastro-oesophageal reflux disease (GORD) occurs in most (∼75%) patients with systemic sclerosis (SSc) and significantly impacts quality of life. Current recommendations lack depth and therefore our aim was to produce practical, consensus-based recommendations for refractory SSc-related GORD. Methods An international, multidisciplinary steering board (SB) was assembled (n=19) consisting of clinicians (rheumatologists, gastroenterologists, gastrointestinal surgeons), an expert methodologist and patient representation. After reviewing the latest definitions of GORD and refractory GORD in the published literature, the SB collectively devised a practical definition of SSc refractory-GORD. Initial recommendations were drafted/agreed on by the SB based on review of the existing guidelines, published literature and expert opinion. Two online voting rounds were conducted to determine whether items should be accepted, with >75% and >60% SB agreement required for first and second rounds, respectively. Results There was a good response/completion rate for the initial (74%) and final (84%) voting rounds. The SB agreed on all 36 draft recommendations. The majority (n=34) were approved in the first round. Recommendations were organised according to the following categories: general approach to management (n=5), assessment (n=6), non-pharmacological (n=2) and pharmacological (n=10) management, endoscopic and surgical treatment (n=3), and special circumstances including refractory GORD and SSc-interstitial lung disease (n=3), myositis and SSc connective tissue disease-overlap (n=3) and perilung transplant (n=4). Conclusion The group of experts has drafted extended and practical recommendations for the management of SSc refractory-GORD. The necessity of a structured approach and a patient assessment is highlighted in order to provide a multidisciplinary approach to the tailored choice of the treatment. Our work also has also identified significant unmet needs and has provided a research agenda to advance the field.