Citations

Background Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown. Methods This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. Only patients with occlusion of the distal branches (M2 and M3) of the middle cerebral artery territory were included. Unsuccessful MT was defined as a modified Thrombolysis in Cerebral Infarction score of 0–2a. Propensity score matching was used to control for confounders. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0–2 at 90 days after treatment. Multivariable regression analysis was used to assess factors associated with the primary outcome. Results Of 2903 patients screened for eligibility, 532 patients were analyzed (266 per group) after propensity score matching. The MM group had superior functional outcomes, with 32% achieving mRS 0–1 at 90 days compared with 21% in the MT group (P=0.011). Patients in the MM group also had significantly lower rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 16%, P<0.001) and any hemorrhage (18% vs 48%, P<0.001). On multivariable regression, unsuccessful MT was associated with reduced odds of functional independence (OR 0.50, 95% CI 0.29 to 0.85, P=0.011) and increased odds of sICH (OR 4.32, 95% CI 1.84 to 10.10, P<0.001). Mortality rates were similar between groups (27% in MM vs 29% in MT, P=0.73). Conclusion Unsuccessful MT for MeVO was linked to worse outcomes than best MM. These findings highlight the risks of prolonged attempts and emphasize the importance of efficient procedural decision-making to reduce complications and improve patient outcomes.

Introduction/Purpose The multicenter, prospective, single‐arm, controlled, non‐randomized SCENT trial on flow diverter (FD) treatment for intracranial aneurysms (IA) was analyzed for patients’ age and IA characteristics impacting stroke and occlusion rates over 5 years. Materials and Methods Impact on major ipsilateral stroke and IA occlusion was studied by stratifying age as </= 65 years versus >65 years. Twice as many subjects treated were </= 65 years old (n=119/180). Product‐limit (Kaplan‐Meier) estimates of time to both endpoints, stratified by age group, were created. Univariate predictors of time to stroke were identified by including candidate variables in univariable proportional hazards regression models. Those variables found to be significant (p<0.10) at the univariate level were entered into a multivariable survival model to identify independent predictors. The stepwise selection produced a final reduced model with a significance level to both enter and stay set at 0.05. Results When parent artery stenosis and IA size were entered into a multiple‐stepwise survival model, only stenosis remained as an independently significant predictor of time to stroke. At 3‐year follow‐up, there were a total of 23 strokes (12.8%), with 11 (47.8%) occurring in subjects </= 65 years; there was a greater risk for seniors (HR1.96, 95% CI 0.83‐4.78, p=.122). Four patients (4/180; 2.2%) experienced aneurysm ruptured within the first week post‐treatment, with 3 being </= 65 and the fourth aged 66 years. No new strokes were reported between 3 and 5 years. Complete IA occlusion rates for seniors were 60.0% (33/55), 67.6% (25/37), and 85.7% (18/21) at 12, 36, and 60 months, respectively, as compared to 79.1% (87/110), 82.5% (66/80), and 91.8% (56/61) for younger subjects. The time to complete IA occlusion was shorter in younger patients (HR1.53, 95% CI 1.07‐2.19, p=.020). Five subjects (2.8%) underwent retreatment, 2 in 60‐year‐old patients, and one each aged 64, 70, and 75. Conclusion Stroke, early rupture risk, and aneurysm occlusion in patients treated with FD are related to age and pre‐existing parent artery stenosis, IA size, and location. With demographic shifts, future treatments need to focus on expedited and improved healing.

OBJECTIVE Cervical spondylotic myelopathy (CSM) shows varying levels of improvement after surgical treatment. While some patients improve soon after surgery, others may take months to years to show any signs of improvement. The goal of this study was to evaluate postoperative improvement, patient-reported outcomes, and patient satisfaction up to 2 years after surgical treatment for CSM, which will help optimize the current treatment strategies and effectively manage patient expectations. METHODS This was a retrospective study of prospectively collected data using the Quality Outcomes Database. The primary outcomes of interest were achievement of the minimal clinically important difference (MCID) for the numeric rating scale for neck and arm pain, modified Japanese Orthopaedic Association, Neck Disability Index, and EQ-5D scores and postoperative satisfaction (North American Spine Society scale). Early and sustained improvement was defined as MCID achievement in at least one patient-reported outcome measure (PROM) at the 3-, 12-, and 24-month follow-ups. Transient improvement was defined as MCID achievement only at the 3-month and/or 12-month follow-up but not at the 24-month follow-up. Late improvement was defined as MCID achievement in at least one PROM only at the 24-month follow-up. RESULTS There were 630 patients included in the comparative analysis. A total of 463 (73.5%) patients achieved early and sustained improvement, 105 (16.7%) patients experienced transient improvement with subsequent decline, 25 (4.0%) patients reported late improvement, and 37 (5.9%) patients did not report any clinically meaningful improvement after surgery. Patients with an anterior approach were more likely to be in the early and sustained improvement group. African American patients (OR 2.98, 95% CI 1.14–7.76; p = 0.03) were more likely to report late improvement when compared with White patients. The overall satisfaction rate at the 24-month follow-up was 87.8%. CONCLUSIONS These findings indicate that 73.5% of patients achieve early and sustained improvement, and 87.8% of patients are satisfied with surgery 24 months postoperatively.

Summary Integrins are heterodimeric receptors important for cell adhesion and signaling. Integrin α5β1 is a key mediator of angiogenesis and its dysregulation is associated with tumor progression and metastasis. Despite numerous efforts, α5β1-targeting therapeutics have been unsuccessful due to poor efficacy and off-target effects. A contributing factor is our limited understanding of how integrin conformation influences interactions with therapeutics. Using cell-based functional assays, patient-derived xenografts, biophysics, and electron microscopy, we shed light on these relationships by characterizing two anti-α5β1 antibodies, BIIG2 and MINT1526A. We show that both antibodies bind α5β1 with nanomolar affinity, reduce tube formation in vitro , and bind overlapping epitopes that block fibronectin binding. However, using electron microscopy, we reveal that while BIIG2 binding does not substantially alter the conformational states, MINT1526A preferentially recognizes the bent conformation and restricts the conformational ensemble. These insights can guide which aspects to prioritize to improve the design of future integrin-targeted therapeutics.

AbstractBackgroundNeuron‐derived extracellular vesicles (NDEVs) are a valuable resource for understanding brain conditions and discovering neurodegenerative diseases biomarkers, notably Alzheimer’s disease (AD). Recent interest focuses on capturing neuron‐specific EVs from patient‐derived samples, characterizing their contents as a pathological reflection of the central nervous system (CNS). Our recent study identified ATPase Na+/K+ Transporting Subunit Alpha 3 (ATP1A3) as a prevalent neuron‐specific EV marker specifically expressed in brains. This study systematically analyzes neuronal EVs to assess the specificity of ATP1A3 to NDEVs and its potential as a target for NDEV pulldown from accessible biofluids for disease monitoring. Additionally, ATP1A3 is compared with other proposed NDEV markers.MethodWe applied immunoelectron microscopy to detect ATP1A3, L1 cell adhesion molecule (L1CAM) and neural cell adhesion molecule 1 (NCAM1) in EVs isolated from iPSC‐derived excitatory neurons, brain tissue, cerebrospinal fluid (CSF) and plasma. Neuronal EV enrichment was achieved through immunoaffinity isolation, utilizing anti‐ATP1A3, L1CAM and NCAM1 antibodies separately. Evaluation involved quantitative mass‐spectrometry, immunoblotting and ELISA. To compare the enrichment of neuronal markers, EVs isolated from CSF and plasma samples were analyzed using ExoView and Nanoimager. Additionally, we investigated the potential of ATP1A3+ plasma EVs as AD biomarker by comparing the value of amyloid‐beta peptide (Aβ) in ATP1A3+ plasma EVs measured by Nanoimager and other plasma AD biomarkers as determined by SIMOA.ResultATP1A3, identified as a neuron‐specific protein, exhibits substantial enrichment in NDEVs isolated from induced human neurons, brain tissue, CSF, and plasma samples, surpassing NCAM1 or L1CAM. Both single‐ and bulk‐EV analysis consistently demonstrate a higher enrichment of ATP1A3 associated EVs in human samples. Immunoprecipitation of ATP1A3+ EVs from human brain tissues reveals superior neuronal cell‐type specificity over NCAM1+ and L1CAM+ EVs by label‐free mass spectrometry. Increased Aβ levels are observed in ATP1A3+ EVs derived from CSF and plasma of AD cases by SIMOA. Moreover, Aβ+ populations in ATP1A3+ EVs from plasma can distinguish AD from mild cognitive impairment and control cases via Nanoimager compared to the conventional quantification of AD markers.ConclusionOur findings demonstrate that ATP1A3 as a promising target for isolating NDEVs from biofluids, offering potential diagnostic advancements in neurological research.

Abstract Cholecystectomy (CCY) is the standard treatment for acute cholecystitis. For non-surgical patients, percutaneous cholecystostomy tube (PT-GBD) is recommended but is associated with high readmission rates and poor quality of life. Endoscopic gallbladder decompression techniques, including endoscopic transpapillary gallbladder drainage (ET-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD), are alternatives. Studies comparing ET-GBD and EUS-GBD have shown EUS-GBD to have superior outcomes. However, these studies assessed ET-GBD mostly via single transcystic stent placement (SSET-GBD). This study aimed to compare outcomes of dual transcystic stents (DSET-GBD) and EUS-GBD in non-surgical candidates with acute cholecystitis. A multicenter analysis was conducted on patients who underwent ET-GBD or EUS-GBD between January 2019 and January 2023. Data were extracted from electronic medical records and outcomes including technical success, success, adverse events (AEs), and recurrence rates of cholecystitis were measured. Of 129 procedures (56 EUS-GBD; 73 ET-GBD), technical success was achieved in 87.5% of EUS-GBD and 86.3% of ET-GBD attempts. Immediate clinical success was achieved in 98.1% for EUS-GBD and 100% for DSET-GBD. AE rates were similar between the groups. Recurrent cholecystitis rates were 5.3% for EUS-GBD and 8.2% for DSET-GBD (P = 0.692). This study demonstrates that DSET-GBD has similarly low rates of recurrent acute cholecystitis compared with EUS-GBD. DSET-GBD should be considered as an alternative management strategy for management of acute cholecystitis in patients who are unable to undergo CCY.

Background: This study aimed to explore the potential associations between voice metrics of patients with PD and their motor symptoms. Methods: Motor and vocal data including the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III), Harmonic–Noise Ratio (HNR), jitter, shimmer, and smoothed cepstral peak prominence (CPPS) were analyzed through exploratory correlations followed by univariate linear regression analyses. We employed these four voice metrics as independent variables and the total and sub-scores of the UPDRS-III as dependent variables. Results: Thirteen subjects were included, 76% males and 24% females, with a mean age of 62.9 ± 10.1 years, and a median Hoehn and Yahr stage of 2.3 ± 0.7. The regression analysis showed that CPPS is associated with posture (UPDRS-III posture scores: β = −0.196; F = 10.0; p = 0.01; R2 = 0.50) and UPDRS-III postural stability scores (β = −0.130; F = 5.57; p = 0.04; R2 = 0.35). Additionally, the associations between CPPS and rapid alternating movement (β = −0.297; p = 0.07), rigidity (β= −0.36; p = 0.11), and body bradykinesia (β = −0.16; p = 0.13) showed a trend towards significance. Conclusion: These findings highlight the potential role of CPPS as a predictor of postural impairments secondary to PD, emphasizing the need for further investigation.

ImportanceFenestrated and branched endovascular aortic repairs (F/BEVAR) have been adopted by many centers. However, national trends of F/BEVAR use remain unclear, particularly at sites who perform them without an US Food and Drug Adminstration (FDA)–approved investigational device exemption (IDE).ObjectiveTo quantify the use of F/BEVAR in the US and to determine if mortality was different at IDE vs non-IDE sites.Design, Setting, and ParticipantsThis retrospective cohort study examined 100% fee-for-service Medicare claims data from 2016 to 2023. Participants were patients who underwent endovascular treatment of the visceral aorta incorporating 2 or more visceral artery endoprostheses. Hospitals with vs without an IDE were identified using hospitals’ Employer Identification Number as a time varying exposure.ExposureF/BEVAR.Main Outcomes and MeasuresTrends in the center-level F/BEVAR case volume stratified by IDE status were assessed using cumulative incidence curves. Mortality outcomes at 30 days and 3 years were compared using Kaplan-Meier methods and Cox proportional hazards models with adjustment for baseline patient characteristics.ResultsFrom 2016 to 2023, 8017 patients were treated with F/BEVAR at 549 hospitals. The median (IQR) age was 75.8 (71.3-80.8) years; 5795 patients (72.3%) were male and 2222 (27.7%) female. A total of 2226 F/BEVAR (27.8%) were performed at 22 hospitals with an IDE. The number of patients treated with F/BEVAR increased from 771 in 2016 to 1251 in 2023. The median (IQR) annual case volume per hospital was significantly higher at IDE sites (22.3 [11.0-30.4] vs 1.2 [1.0-2.0] cases/y; P &amp;lt; .001); 18 IDE sites (90.0%) and 20 non-IDE sites (3.7%) completed 9 or more cases per year. The 30-day mortality (3.0% vs 4.9%) but not 3-year mortality (26.0% vs 27.1%) was lower for patients treated at hospitals with vs without an IDE. After risk adjustment, both 30-day (odds ratio, 0.47; 95% CI, 0.32-0.69) and midterm mortality (hazard ratio, 0.81; 95% CI, 0.69-0.95) were lower for patients treated at IDE sites.Conclusions and RelevanceThe use of F/BEVAR is increasing across the United States, with the majority of cases being performed outside of IDE studies and at low-volume centers. F/BEVAR performed at non-IDE centers are associated with higher adjusted 30-day and midterm mortality. Transparent outcome reporting and identification of process measures from IDE sites may help achieve more equity in patient outcomes.

Abstract Introduction COVID-19 infection is associated with an increased risk of complications, prolonged hospitalization, and mortality despite vaccination in patients with cancer. Evusheld (tixagevimab-cilgavimab) was granted emergency use approval in December 2021 for pre-exposure prophylaxis based on preliminary results from the PROVENT trial. However, studies evaluating the impact of Evusheld in cancer patients in the real-world are limited. In this study, we assessed the impact of Evusheld on the incidence and severity of COVID-19 infection in cancer patients at our institution. Methods and Materials We conducted a retrospective descriptive study at our institution on patients with current and prior history of cancer diagnosis regardless of treatment history who received Evusheld between December 2021 and March 2022. The primary outcome was incidence of COVID-19 during a 6 month follow up period. Secondary outcomes included rate of hospitalization related to COVID-19 and associated mortality. Results A total of 228 patients were included, 43% of which received 2 doses of Evusheld during the study period. Twenty-nine patients (12.7%, 95% CI 9.4% – 18.7%) developed COVID-19, with an average time to diagnosis of 2.5 months (SD 1.6) from receiving Evusheld. Most had hematologic malignancies (68.4%) and were receiving active chemotherapy (71.5%) at the time of diagnosis. Five (17.2%) patients were hospitalized for COVID-19, of whom 4 had hematological malignancy. One patient with hematological malignancy required mechanical ventilation and died. Conclusion Overall, the incidence of COVID-19 following Evusheld was higher than in the PROVENT trial. Infections appeared to be more common and severe in patients with hematologic malignancies.