The Time Has Come: The Case for Initiating Pilot Clinical Trials of Pig Kidney Xenotransplantation.

In vitro studies indicate that kidney transplantation from gene-edited pigs in which expression of all three of the known glycan xenoantigens has been deleted may be more challenging in nonhuman primates (NHPs) than it will be in human recipients. Furthermore, pig-to-human xenotransplantation offers several other advantages - (i) the patient can communicate with the surgical team; (ii) recipient microbiological monitoring and environment will be clinical-grade; and (iii) sophisticated graft monitoring and imaging techniques, (v) therapeutic interventions, e.g., dialysis, plasmapheresis, and (v) intensive care can be deployed that are not easily available in NHP laboratory models. We suggest, therefore, that progress to develop safe, informative human clinical trials will be accelerated if pilot clinical cases are initiated. The selection of patients for kidney xenotransplantation can include those who are at high risk of dying imminently, e.g., those experiencing increasing vascular access challenges with no realistic alternative therapy available, and those who have been accepted onto the waitlist for an allograft, but who are unlikely ever to receive one. Patients with an increased risk of dying include those with (i) age >60 years, (ii) blood groups O or B, and (iii) diabetic nephropathy. UNOS data indicate that an average of 25 patients on the kidney waitlist in the USA die or are removed from the list every day (i.e., >9,000 each year). Given the improved xenograft survival observed in preclinical studies, we suggest that it is time to plan a small pilot clinical trial for healthy dialysis patients who understand the risks and potential benefits of kidney xenotransplantation.

Long-term changes in wearable sensor data in people with and without Long Covid.

To better understand the impact of Long COVID on an individual, we explored changes in daily wearable data (step count, resting heart rate (RHR), and sleep quantity) for up to one year in individuals relative to their pre-infection baseline among 279 people with and 274 without long COVID. Participants with Long COVID, defined as symptoms lasting for 30 days or longer, following a SARS-CoV-2 infection had significantly different RHR and activity trajectories than those who did not report Long COVID and were also more likely to be women, younger, unvaccinated, and report more acute-phase (first 2 weeks) symptoms than those without Long COVID. Demographic, vaccine, and acute-phase sensor data differences could be used for early identification of individuals most likely to develop Long COVID complications and track objective evidence of the therapeutic efficacy of any interventions.Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT04336020 .

Ablation for Atrial Fibrillation in Patients With Rare Pathogenic Variants in Cardiomyopathy and Arrhythmia Genes.

BACKGROUND: Patients with rare, pathogenic cardiomyopathy (CM) and arrhythmia variants can present with atrial fibrillation (AF). The efficacy of AF ablation in these patients is unknown. OBJECTIVE: This study tested the hypotheses that: 1) patients with a pathogenic variant in any CM or arrhythmia gene have increased recurrence following AF ablation; and 2) patients with a pathogenic variant associated with a specific gene group (arrhythmogenic left ventricular CM [ALVC], arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, or a channelopathy) have increased recurrence. METHODS: We performed a prospective, observational, cohort study of patients who underwent AF catheter ablation and whole exome sequencing. The primary outcome measure was ≥30 seconds of any atrial tachyarrhythmia that occurred after a 90-day blanking period. RESULTS: Among 1,366 participants, 109 (8.0%) had a pathogenic or likely pathogenic (P/LP) variant in a CM or arrhythmia gene. In multivariable analysis, the presence of a P/LP variant in any gene was not significantly associated with recurrence (HR 1.15; 95% CI 0.84-1.60; P = 0.53). P/LP variants in the ALVC gene group, predominantly LMNA, were associated with increased recurrence (n = 10; HR 3.75; 95% CI 1.84-7.63; P < 0.001), compared with those in the arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, and channelopathy gene groups. Participants with P/LP TTN variants (n = 46) had no difference in recurrence compared with genotype-negative-controls (HR 0.93; 95% CI 0.54-1.59; P = 0.78). CONCLUSIONS: Our results support the use of AF ablation for most patients with rare pathogenic CM or arrhythmia variants, including TTN. However, patients with ALVC variants, such as LMNA, may be at a significantly higher risk for arrhythmia recurrence.

Evidence of longitudinal differences in spring migration strategies of an Arctic-nesting goose.

During spring, migratory birds are required to optimally balance energetic costs of migration across heterogeneous landscapes and weather conditions to survive and reproduce successfully. Therefore, an individual's migratory performance may influence reproductive outcomes. Given large-scale changes in land use, climate, and potential carry-over effects, understanding how individuals migrate in relation to breeding outcomes is critical to predicting how future scenarios may affect populations. We used GPS tracking devices on 56 Greater White-fronted Geese (Anser albifrons) during four spring migrations to examine whether migration characteristics influenced breeding propensity and breeding outcome. We found a strong longitudinal difference in arrival to the breeding areas (18 days earlier), pre-nesting duration (90.9% longer), and incubation initiation dates (9 days earlier) between western- and eastern-Arctic breeding regions, with contrasting effects on breeding outcomes, but no migration characteristic strongly influenced breeding outcome. We found that breeding region influenced whether an individual likely pursued a capital or income breeding strategy. Where individuals fell along the capital-income breeding continuum was influenced by longitude, revealing geographic effects of life-history strategy among conspecifics. Factors that govern breeding outcomes likely occur primarily upon arrival to breeding areas or are related to individual quality and previous breeding outcome, and may not be directly tied to migratory decision-making across broad scales.

Integrated Single-Cell Multiomic Profiling of Caudate Nucleus Suggests Key Mechanisms in Alcohol Use Disorder.

Alcohol use disorder (AUD) is likely associated with complex transcriptional alterations in addiction-relevant brain regions. We characterize AUD-associated differences in cell type-specific gene expression and chromatin accessibility in the caudate nucleus by conducting a single-nucleus RNA-seq assay and a single-nucleus RNA-seq + ATAC-seq (multiome) assay on caudate tissue from 143 human postmortem brains (74 with AUD). We identified 17 cell types. AUD was associated with a higher proportion of microglia in an activated state and more astrocytes in a reactive state. There was widespread evidence for differentially expressed genes across cell types with the most identified in oligodendrocytes and astrocytes, including genes involved in immune response and synaptic regulation, many of which appeared to be regulated in part by JUND and OLIG2. Microglia-astrocyte communication via interleukin-1 beta, and microglia-astrocyte-oligodendrocyte interaction via transforming growth factor beta 1 were increased in individuals with AUD. Expression quantitative trait loci analysis revealed potential driver genes of AUD, including ADAL, that may protect against AUD in medium spiny neurons and interneurons. This work provides a thorough profile of the effects of AUD in the human brain and identifies several promising genes for further study.

Creation of a predictive calculator to determine adequacy of occlusion of the woven endobridge (WEB) device in intracranial aneurysms-A retrospective analysis of the WorldWide WEB Consortium database.

BACKGROUND: Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond-Roy classification 1 or 2) remains challenging. OBJECTIVE: Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. METHODS: We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. RESULTS: A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535-0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024-0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer-Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/. CONCLUSION: The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.

Genomic Profiling of Small Intestine Cancers From a Real-World Data Set Identifies Subgroups With Actionable Alterations.

PURPOSE: Panel-based comprehensive genomic profiling (CGP) is used in clinical practice worldwide; however, large real-world data (RWD) of patients with advanced small intestine cancer have not been characterized. We investigated differences in the prevalence of clinically relevant alterations across molecularly defined or age-stratified subgroups. PATIENTS AND METHODS: This was a collaborative biomarker study of RWD from CGP testing (Foundation Medicine, Inc). Hybrid capture was conducted on at least 324 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. Overall, 1,364 patients with advanced small intestine cancer were available for analyses and were stratified by age (≥40 years/<40 years), microsatellite instability (MSI) status, tumor mutational burden (TMB) status (high ≥10/low <10 Muts/Mb), and select gene alterations. The frequency of alterations was analyzed using a chi-square test with Yate's correction. RESULTS: Genes with frequent alterations included TP53 (59.8%), KRAS (54.8%), APC (27.7%), and CDKN2A (22.4%). Frequent genes with amplifications were MYC (6.7%), MDM2 (5.9%), GATA6 (5.5%), and CCND1 (3.4%). Patients younger than 40 years had significantly lower frequency of APC mutations than those 40 years and older (10.4% v 28.7%; P = .0008). Druggable genomic alterations were detected in 22.3% of patients: BRAF V600E (1.2%), BRCA1 (1.8%), BRCA2 (3.2%), ERBB2 amplification (3.2%), KRAS G12C (3.3%), NTRK1/2/3 fusion (0.07%), MSI-high (7.0%), and TMB-high (12.2%), with no significant differences in the frequency according to age (<40 years v ≥40 years; 22.1% v 22.3%). TMB of 10-20 Mut/Mb was observed in 4.8% of patients, and TMB ≥20 Mut/Mb was seen in 7.3% of the cohort. CONCLUSION: RWD from clinical panel testing revealed the genomic landscape in small intestine cancer by subgroup. These findings provide insights for the future development of treatments in advanced small intestine cancer.

Effects of Breast Cancer Treatment on Neural Noise: a Longitudinal Design.

OBJECTIVE: Cognitive dysfunction has been observed consistently in a subset of breast cancer survivors. Yet the precise neurophysiological origins of cancer-related cognitive decline remain unknown. The current study assessed neural noise (1/f activity in electroencephalogram [EEG]) in breast cancer survivors as a potential contributor to observed cognitive dysfunction from pre- to post-treatment. METHODS: We measured EEG in a longitudinal design during performance of the paired-click task and the revised Attention Network Test (ANT-R) to investigate pre- versus post-treatment effects of neural noise in breast cancer patients (n = 20 in paired click; n = 19 in ANT-R) compared with healthy controls (n = 32 in paired click; n = 29 in ANT-R). RESULTS: In both paradigms, one sensory (paired click) and one cognitive (ANT-R), we found that neural noise was significantly elevated after treatment in patients, remaining constant from pretest to posttest in controls. In the ANT-R, patients responded more slowly than controls on invalid cuing trials. Increased neural noise was associated with poorer alerting and poorer inhibitory control of attention (as measured by behavioral network scores), particularly for patients after treatment. CONCLUSIONS: The current study is the first to show a deleterious effect of breast cancer and/or cancer treatment on neural noise, pointing to alterations in the relative balance of excitatory and inhibitory synaptic inputs, while also suggesting promising approaches for cognitive rehabilitation.

Solid Metal Chemical and Thermal Injury Management.

INTRODUCTION: Solid metals may create a variety of injuries. White phosphorous (WP) is a metal that causes both caustic and thermal injuries. Because of its broad use in munitions and smoke screens during conflicts and wars, all military clinicians should be competent at WP injury identification and acute therapy, as well as long-term consequence recognition. MATERIALS AND METHODS: English-language manuscripts addressing WP injuries were curated from PubMed and Medline from inception to January 31, 2024. Data regarding WP injury identification, management, and sequelae were abstracted to construct a Scale for the Assessment of Narrative Review Articles guideline-consistent narrative review. RESULTS: White phosphorous appears to be ubiquitous in military conflicts. White phosphorous creates a characteristic wound appearance accompanied by smoke, a garlic aroma, and spontaneous combustion on contact with air. Decontamination and burning prevention or cessation are key and may rely on aqueous irrigation and submersion or immersion in substances that prevent air contact. Topical cooling is a key aspect of preventing spontaneous ignition as well. Disposal of all contaminated clothing and gear is essential to prevent additional injury, especially to rescuers. Long-term sequelae relate to phosphorous absorption and may lead to death. Chronic or repeated exposure may induce jaw osteonecrosis. Tactical Combat Casualty Care recommendations do not currently address WP injury management. CONCLUSIONS: Education and management regarding WP acute injury and late sequelae is essential for acute battlefield and definitive facility care. Resource-replete and resource-limited settings may use related approaches for acute management and ignition prevention. Current burn wound management recommendations should incorporate specific WP management principles and actions for military clinicians at every level of skill and environment.

Poor Prognosis among Radiation-Associated Bladder Cancer Is Defined by Clinicogenomic Features.

Radiotherapy (RT) for prostate cancer has been associated with an increased risk for the development of bladder cancer. We aimed to integrate clinical and genomic data to better understand the development of RT-associated bladder cancer. A retrospective analysis was performed to identify control patients (CTRL; n = 41) and patients with RT-associated bladder cancer (n = 41). RT- and CTRL-specific features were then identified through integration and analysis of the genomic sequencing data and clinical variables. RT-associated bladder tumors were significantly enriched for alterations in KDM6A and ATM, whereas CTRL tumors were enriched for CDKN2A mutation. Globally, there were an increased number of variants within RT tumors, albeit at a lower variant allele frequency. Mutational signature analysis revealed three predominate motif patterns, with similarity to SBS2/13 (APOBEC3A), SBS5 (ERCC2/smoking), and SBS6/15 (MMR). Poor prognostic factors in the RT cohort include a short tumor latency, smoking status, the presence of the smoking and X-ray therapy mutational signatures, and CDKN2A copy number loss. Based on the clinical and genomic findings, we suggest at least two potential pathways leading to RT-associated bladder cancer: The first occurs in the setting of field cancerization related to smoking or preexisting genetic alterations and leads to the development of more aggressive bladder tumors, and the second involves RT initiating the oncogenic process in otherwise healthy urothelium, leading to a longer latency and less aggressive disease. SIGNIFICANCE: Clinicogenomic analysis of radiation-associated bladder cancer uncovered mutational signatures that, in addition to a short tumor latency, smoking, and CDKN2A loss, are associated with a poor outcome. These clinical and genomic features provide a potential method to identify patients with prostate cancer who are at an increased risk for the development of aggressive bladder cancer following prostate RT.

Direct piriform-to-auditory cortical projections shape auditory-olfactory integration.

In a real-world environment, the brain must integrate information from multiple sensory modalities, including the auditory and olfactory systems. However, little is known about the neuronal circuits governing how odors influence and modulate sound processing. Here, we investigated the mechanisms underlying auditory-olfactory integration using anatomical, electrophysiological, and optogenetic approaches, focusing on the auditory cortex as a key locus for cross-modal integration. First, retrograde and anterograde viral tracing strategies revealed a direct projection from the piriform cortex to the auditory cortex. Next, using in vivo electrophysiological recordings of neuronal activity in the auditory cortex of awake male or female mice, we found that odors modulate auditory cortical responses to sound. Finally, we used in vivo optogenetic manipulations during electrophysiology to demonstrate that olfactory modulation in auditory cortex, specifically, odor-driven enhancement of sound responses, depends on direct input from the piriform cortex. Together, our results identify a novel role of piriform-to-auditory cortical circuitry in shaping olfactory modulation in the auditory cortex, shedding new light on the neuronal mechanisms underlying auditory-olfactory integration.

Predictors of Aneurysm Obliteration in Patients Treated with the WEB Device: Results of a Multicenter Retrospective Study.

BACKGROUND AND PURPOSE: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment. MATERIALS AND METHODS: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up. RESULTS: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis was observed in 485/537 (90.3%) of nonoccluded aneurysms. At the final follow-up, complete occlusion was achieved in 497/763 (65.1%) patients, and retreatment was required for 56/763 (7.3%) patients. On multivariable analysis, history of smoking, maximal aneurysm diameter, and the presence of an aneurysm wall branch were negative predictors of complete occlusion (OR, 0.5, 0.8, and 0.4, respectively). Maximal aneurysm diameter, the presence of an aneurysm wall branch, posterior circulation location, and male sex increase the chances of retreatment (OR, 1.2, 3.8, 3.0, and 2.3 respectively). Intraprocedural occlusion resulted in a 3-fold increase in the long-term occlusion rate and a 5-fold decrease in the retreatment rate (P < .001), offering a specificity of 87% and a positive predictive value of 85% for long-term occlusion. CONCLUSIONS: Intraprocedural occlusion can be used to predict the chance of long-term aneurysm occlusion and the need for retreatment after embolization with a WEB device. Smoking, aneurysm size, and the presence of an aneurysm wall branch are associated with decreased chances of successful treatment.

Trained immunity inducers in cancer immunotherapy.

While most of the cancer immunotherapy strategies engage adaptive immunity, especially tumor-associated T cells, the small fraction of responding patients and types of cancers amenable, and the possibility of severe adverse effects limit its usage. More effective and general interventions are urgently needed. Recently, a de facto innate immune memory, termed 'trained immunity', has become a new research focal point, and promises to be a powerful tool for achieving long-term therapeutic benefits against cancers. Trained immunity-inducing agents such as BCG and fungal glucan have been shown to be able to avert the suppressive tumor microenvironment (TME), enhance T cell responses, and eventually lead to tumor regression. Here, we review the current understating of trained immunity induction and highlight the critical roles of emergency granulopoiesis, interferon γ and tissue-specific induction. Preclinical and clinical studies that have exploited trained immunity inducers for cancer immunotherapy are summarized, and repurposed trained immunity inducers from other fields are proposed. We also outline the challenges and opportunities for trained immunity in future cancer immunotherapies. We envisage that more effective cancer vaccines will combine the induction of trained immunity with T cell therapies.

Feasibility of wearable sensor signals and self-reported symptoms to prompt at-home testing for acute respiratory viruses in the USA (DETECT-AHEAD): a decentralised, randomised controlled trial.

BACKGROUND: Early identification of an acute respiratory infection is important for reducing transmission and enabling earlier therapeutic intervention. We aimed to prospectively evaluate the feasibility of home-based diagnostic self-testing of viral pathogens in individuals prompted to do so on the basis of self-reported symptoms or individual changes in physiological parameters detected via a wearable sensor. METHODS: DETECT-AHEAD was a prospective, decentralised, randomised controlled trial carried out in a subpopulation of an existing cohort (DETECT) of individuals enrolled in a digital-only observational study in the USA. Participants aged 18 years or older were randomly assigned (1:1:1) with a block randomisation scheme stratified by under-represented in biomedical research status. All participants were offered a wearable sensor (Fitbit Sense smartwatch). Participants in groups 1 and 2 received an at-home self-test kit (Alveo be.well) for two acute respiratory viral pathogens: SARS-CoV-2 and respiratory syncytial virus. Participants in group 1 could be alerted through the DETECT study app to take the at-home test on the basis of changes in their physiological data (as detected by our algorithm) or due to self-reported symptoms; those in group 2 were prompted via the app to self-test only due to symptoms. Group 3 served as the control group, without alerts or home testing capability. The primary endpoints, assessed on an intention-to-treat basis, were the number of acute respiratory infections presented (self-reported) and diagnosed (electronic health record), and the number of participants using at-home testing in groups 1 and 2. This trial is registered with ClinicalTrials.gov, NCT04336020. FINDINGS: Between Sept 28 and Dec 30, 2021, 450 participants were recruited and randomly assigned to group 1 (n=149), group 2 (n=151), or group 3 (n=150). 179 (40%) participants were male, 264 (59%) were female, and seven (2%) identified as other. 232 (52%) were from populations historically under-represented in biomedical research. 118 (39%) of the 300 participants in groups 1 and 2 were prompted to self-test, with 61 (52%) successfully completing self-testing. Participants were prompted to home-test more frequently due to symptoms (41 [28%] in group 1 and 51 [34%] in group 2) than due to detected physiological changes (26 [17%] in group 1). Significantly more participants in group 1 received alerts to test than did those in group 2 (67 [45%] vs 51 [34%]; p=0·047). Of the 61 individuals who were prompted to test and successfully did so, 19 (31%) tested positive for a viral pathogen-all for SARS-CoV-2. The individuals diagnosed as positive for SARS-CoV-2 in the electronic health record were eight (5%) in group 1, four (3%) in group 2, and two (1%) in group 3, but it was difficult to confirm if they were tied to symptomatic episodes documented in the trial. There were no adverse events. INTERPRETATION: In this direct-to-participant trial, we showed early feasibility of a decentralised programme to prompt individuals to use a viral pathogen diagnostic test based on symptoms tracked in the study app or physiological changes detected using a wearable sensor. Barriers to adequate participation and performance were also identified, which would need to be addressed before large-scale implementation. FUNDING: Janssen Pharmaceuticals.

Second-generation checkpoint inhibitors and Treg depletion synergize with a mouse cancer vaccine in accordance with tumor microenvironment characterization.

BACKGROUND: Despite advances in checkpoint inhibitor (CPI) therapy for cancer treatment, many cancers remain resistant. Tumors deemed "cold" based on lack of T cell infiltration show reduced potential for CPI therapy. Cancer vaccines may overcome the inadequacy of existing T cells by inducing the needed antitumor T cell response to synergize with CPIs and overcome resistance. METHODS: CT26 and TC1 tumor cells were injected subcutaneously into mice. Mice were treated with combinations of CPIs alone or a cancer vaccine specific to the tumor antigen E7 present in TC1 cells. CPIs for the TC1 model were selected because of immunophenotyping TC1 tumors. Antitumor and protumor immunity, tumor size and survival, sequence and timing of vaccine and CPI administration, and efficacy of treatment in young and aged mice were probed. RESULTS: While "hot" CT26 tumors are treatable with combinations of second-generation CPIs alone or with anti-TGFß, "cold" TC1 tumor reduction requires the synergy of a tumor-antigen-specific vaccine in combination with two CPIs, anti-TIGIT and anti-PD-L1, predicted by tumor microenvironment (TME) characterization. The synergistic triple combination delays tumor growth better than any pairwise combination and improves survival in a CD8+T cell-dependent manner. Depletion of CD4+T cells improved the treatment response, and depleting regulatory T cells (Treg) revealed Tregs to be inhibiting the response as also predicted from TME analysis. We found the sequence of CPI and vaccine administration dictates the success of the treatment, and the triple combination administered concurrently induces the highest E7-specific T cell response. Contrary to young mice, in aged mice, the cancer vaccine alone is ineffective, requiring the CPIs to delay tumor growth. CONCLUSIONS: These findings show how pre-existing or vaccine-mediated de novo T cell responses can both be amplified by and facilitate synergistic CPIs and Treg depletion that together lead to greater survival, and how analysis of the TME can help rationally design combination therapies and precision medicine to enhance clinical response to CPI and cancer vaccine therapy.

Adherence to buprenorphine-XR through hybrid telehealth contingency management procedures: a case series.

Background and objectives: Contingency management (CM) for substance use disorders (SUD) is effective in strengthening recovery behaviors, however can be quite burdensome. When health facilities experience staff shortages, adapting current CM protocols to be less staff and time intensive may be one way to address this challenge. Methods: Case series (N = 3). Results: Three veterans with opioid use disorder (OUD) received CM for treatment adherence through a Veteran Health Administration Outpatient Substance Disorder program. Due to the COVID-19 pandemic, traditional CM procedures resulted in limited accessibility and staff, delayed appointments, and decreased patient satisfaction. In response, the hybrid telehealth contingency management (HTCM) procedure was developed and implemented. Flexibility offered by HTCM allowed for consecutive completion of appointments and maintained adherence to BUP-XR treatment. Conclusions: This is a novel method of CM implementation. HTCM streamlined the process and was successful in increasing accessibility, reducing time-burden on patients and staff, while preserving fidelity to key components of the model. Considerations for future implementation and implications of HTCM are discussed.

Treatment of large intracranial aneurysms using the Woven EndoBridge (WEB): a propensity score-matched analysis.

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence of multiple aneurysms, bifurcation location, or prior treatment between the two groups. After PSM, 302 matched pairs showed significantly lower last follow-up adequate occlusion rates (81% vs 90%, p = 0.006) and higher retreatment rates (12% vs 3.6%, p < 0.001) in the large aneurysm group. These findings may inform treatment decisions and patient counseling. Future studies are needed to further explore this area.