Jennifer Juhl Majersik

BACKGROUND: Ninety percent of left atrial thrombi in nonvalvular atrial fibrillation arise in the left atrial appendage, which can be occluded percutaneously (left atrial appendage closure [LAAC]). Two 2026 trials (CHAMPION-AF [Watchman Flx Versus Non-Vitamin K Antagonist Oral Anticoagulant for Embolic Protection in the Management of Patients With Non-Valvular Atrial Fibrillation] and CLOSURE-AF [Left Atrial Appendage Closure in Patients With Atrial Fibrillation Compared to Medical Therapy]) more than doubled the available randomized evidence comparing LAAC with oral anticoagulation. We evaluated pooled effects of LAAC on stroke, bleeding, and mortality by bleeding risk, anticoagulation eligibility, and comparator. METHODS: In this systematic review and meta-analysis, we searched PubMed, Scopus, and Embase from inception to April 15, 2026, for randomized controlled trials comparing percutaneous LAAC with oral anticoagulation in nonvalvular atrial fibrillation. Risk of bias was assessed with the Cochrane Risk of Bias 2 tool. Cumulative-incidence outcomes were pooled as odds ratios using random-effects models, with prediction intervals, prespecified subgroups, and trial sequential analysis. RESULTS: Six randomized controlled trials (2014–2026; 358 sites in North America, Europe, and Asia; 7028 patients) compared LAAC with warfarin (2 trials) or a direct oral anticoagulant (4 trials); populations were predominantly anticoagulation-eligible with low prior-stroke prevalence, plus 2 high-bleeding-risk and 1 postablation trial. Overall stroke rates were similar between arms (odds ratio, 1.10 [95% CI, 0.78–1.56]). Ischemic stroke was more frequent with LAAC (odds ratio, 1.41 [95% CI, 1.07–1.86]) but did not reach the required information size. Nonprocedural bleeding was lower with LAAC (odds ratio, 0.58 [95% CI, 0.35–0.96]), the only outcome reaching a sufficient information size, in standard-risk and postablation but not high-bleeding-risk patients. CONCLUSIONS: LAAC is best positioned to reduce nonprocedural bleeding in anticoagulation-eligible patients at standard-to-moderate bleeding risk, rather than as a stroke-equivalent substitute for oral anticoagulation. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD420261370546.

Background and objectives: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common monogenic cerebral small vessel disease. Though neuropsychiatric symptoms (NPS) of CADASIL profoundly impact function and quality of life, these symptoms remain understudied. This analysis characterizes the prevalence, severity, and profile of NPS among individuals with CADASIL-causing NOTCH3 variants and non-carrier biological family controls in the United States CADASIL Consortium (USCC). Methods: This cross-sectional analysis used multimodal baseline data from 12 enrollment sites across the country. Statistical analyses used nonparametric tests and regression models to compare clinical and neuropsychiatric outcomes across CADASIL risk tiers and controls, adjusting for age, sex, race, and education where appropriate. The primary outcome measure was the Neuropsychiatric Inventory Questionnaire (NPI-Q), an informant-reported measure which assesses 12 categories of NPS. NPI-Q item severity and distress were evaluated for individuals with confirmed cysteine-altering pathogenic NOTCH3 variants and compared with controls. Results: Four hundred fifty-nine USCC participants were included in the analytic cohort: 343 cases [256 high-risk (HR); 63 medium-risk (MR); 24 low-risk (LR)]; and 116 controls. Among participants with available NPI-Q data, at least one neuropsychiatric symptom was reported by 72.6% (n = 228/314) of cases compared with 53.2% (n = 58/109) of controls. Reported symptoms were more common among CADASIL cases than controls, occurring in 75.0%, 71.2%, and 72.7% of participants in the LR, MR, and HR groups, respectively, compared with 53.2% of controls. Compared with controls, participants in the MR group and HR group had higher NPI-Q severity scores. HR participants also had higher NPI-Q distress scores than controls. Discussion: Our findings support the notion that NPS are an important clinical manifestation of CADASIL. Beyond previously reported symptoms, additional neuropsychiatric manifestations were identified. Given the higher burden and variability in the neuropsychiatric presentation of CADASIL, the relationships among neuropsychiatric, neurological, and patient-reported outcomes merit further investigation. The NPS profile may enhance the evaluation of the safety and efficacy of different treatments to target these symptoms for CADASIL patients. Trial Registration Information: The study is registered at ClinicalTrials.gov ( NCT05677880 , 12/12/2022).

Background and Objectives: Vascular contributions to cognitive impairment and dementia (VCID) represent the second leading cause of dementia and a common comorbidity for reduced functional capacity in many individuals, but clinical management and clinical trial readiness are severely hindered by extreme phenotypic and mechanistic heterogeneity. This study establishes the baseline clinical, functional, and multimodal biomarker characteristics of the first United States (US) cohort of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), serving as a single-cause, monogenic small vessel disease model for sporadic VCID. Methods: Cross-sectional analysis of baseline data collected from October 2022 through January 2025 from a longitudinal cohort at 12 US enrollment sites. Adults from families with a documented NOTCH3 variant were recruited through clinical referrals, medical record review, advocacy organizations, and community outreach. Exclusion criteria included other conditions that prevented interpretation of findings and modified Rankin Scale (mRS) scores greater than 3. Central genetic characterization assigned persons with a pathogenic or likely pathogenic NOTCH3 variant to low-, medium-, or high-risk tiers based on epidermal growth factor-like repeat domains. Standardized assessments included clinical histories, exams, objective cognitive and physical assessments, self-reported, companion-reported, and clinician-rated measures, MRI, genetics, and proteomics acquired under harmonized protocols. Group comparisons used Fishers exact and Kruskal–Wallis tests. Multivariable regression used adjustment for age, sex, race, and education. Results: Of 560 participants completing baseline visits, 46 had variants of unknown significance, and 55 had pending genetic analyses. The analytic cohort included 343 persons with a CADASIL-causing NOTCH3 variant and 116 non-carrier family controls. Median age was 47.9 years (IQR 38.7–59.1), median education was 16 years (IQR 14– 17), 62.5% were female, and 91.4% were White. Carriers were classified in CADASIL risk tiers: low (7.0%), medium (18.4%), or high (74.6%). Compared with controls, adjusted odds of classification into a more impaired CDR category were higher in all tiers (OR 2.55-5.08, 95% CI 1.22–11.34). Discussion: The US CADASIL Consortium has established a large, genetics-confirmed cohort spanning presymptomatic to moderate disease stages, providing a robust, harmonized platform to define early biomarker signatures and endpoints for targeted VCID therapies.

ObjectivesNational trends in hospital charges and Medicare reimbursement for inpatient neurologic care are poorly characterized. We evaluated longitudinal changes in utilization, charges, and reimb...

There is a large burden of stroke in the United States, and extensive systems of care have been established to address it. The resources devoted to stroke centers are analogous to those of trauma centers, both sharing many strict requirements for certification, clinical preparedness, quality improvement, data management, and reporting. However, trauma programs partly defray these costs through a trauma activation billing code, a billable fee that is charged for activation of the trauma team under strict criteria. There are potential benefits to establishing an analogous national stroke code activation fee. Although a billable stroke code activation fee may increase financial burden on patients, this may be counterbalanced by the significant potential for individual and societal benefits. Providing additional financial support for stroke systems of care may improve acute stroke treatment, reduce stroke burden and poststroke disability, and reduce inequality by broadening the reach of stroke systems of care to disadvantaged communities. Further evaluation of the costs and benefits of implementing a stroke code activation fee based on that currently used by trauma centers is needed.

Previous research demonstrated that the numerical Cincinnati Prehospital Stroke Scale (CPSS) identifies large vessel occlusion (LVO) at similar rates compared to dedicated LVO screening tools. We aimed to compare numerical CPSS to additional stroke scales using a national Emergency Medical Services (EMS) database. Using the ESO Data Collaborative, the largest EMS database with linked hospital data, we retrospectively analyzed prehospital patient records from 2022. Each EMS record was linked to corresponding emergency department (ED) and inpatient records through a data exchange platform. Prehospital CPSS was compared to the Cincinnati Stroke Triage Assessment Tool (C-STAT), the Field Assessment Stroke Triage for Emergency Destination (FAST-ED), and the Balance Eyes Face Arm Speech Time (BE-FAST). The optimal prediction cut points for LVO screening were determined by intersecting the sensitivity and specificity curves for each scale. To compare the discriminative abilities of each scale among those diagnosed with LVO, we used the area under the receiver operating curve (AUROC). We identified 17,442 prehospital records from 754 EMS agencies with ≥ 1 documented stroke scale of interest: 30.3% (n = 5,278) had a hospital diagnosis of stroke, of which 71.6% (n = 3,781) were ischemic; of those, 21.6% (n = 817) were diagnosed with LVO. CPSS score ≥ 2 was found to be predictive of LVO with 76.9% sensitivity, 68.0% specificity, and AUROC 0.787 (95% CI 0.722-0.801). All other tools had similar predictive abilities, with sensitivity/specificity/AUROC of: C-STAT 62.5%/76.5%/0.727 (0.555-0.899); FAST-ED 61.4%/76.1%/0.780 (0.725-0.836); BE-FAST 70.4%/67.1%/0.739 (0.697-0.788). The less complex CPSS exhibited comparable performance to three frequently employed LVO detection tools. The EMS leadership, medical directors, and stroke system directors should weigh the complexity of stroke severity instruments and the challenges of ensuring consistent and accurate use when choosing which tool to implement. The straightforward and widely adopted CPSS may improve compliance while maintaining accuracy in LVO detection.

Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT. Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status. We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA. Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.

Background Previous research demonstrated that the numerical Cincinnati Prehospital Stroke Scale (CPSS) identifies large vessel occlusion (LVO) at similar rates compared to a limited number of stroke severity screening tools. We aimed to compare numerical CPSS to additional stroke scales using a national EMS database. Methods Using the ESO Data Collaborative, the largest EMS database with hospital linked data, we retrospectively analyzed prehospital patient records for the year 2022. Stroke and LVO diagnoses were determined by ICD-10 codes from linked hospital discharge and emergency department records. Prehospital CPSS was compared to the Cincinnati Stroke Triage Assessment Tool (C-STAT), the Field Assessment Stroke Triage for Emergency Destination (FAST-ED), and the Balance Eyes Face Arm Speech Time (BE-FAST). The optimal prediction cut-points for LVO screening were determined by intersecting the sensitivity and specificity curves for each scale. To compare the discriminative abilities of each scale among those diagnosed with LVO, we used the area under the receiver operating curve (AUROC). Results We identified 17,442 prehospital records from 754 EMS agencies with ≥ 1 documented stroke scale of interest: 30.3% (n=5,278) had a hospital diagnosis of stroke, of which 71.6% (n=3,781) were ischemic; of those, 21.6% (n=817) were diagnosed with LVO. CPSS score ≥ 2 was found to be predictive of LVO with 76.9% sensitivity, 68.0% specificity, and AUROC 0.787 (95% CI 0.722-0.801). All other tools had similar predictive abilities, with sensitivity / specificity / AUROC of: C-STAT 62.5% / 76.5% / 0.727 (0.555-0.899); FAST-ED 61.4% / 76.1%/ 0.780 (0.725-0.836); BE-FAST 70.4% / 67.1% / 0.739 (0.697-0.788). Conclusion The less complex CPSS exhibited comparable performance to three frequently employed LVO detection tools. EMS agency leadership, medical directors, stroke system directors, and other stroke leaders may consider the complexity of stroke severity instruments and challenges with ensuring accurate recall and consistent application when selecting which instrument to implement. Use of the simpler CPSS may enhance compliance with the utilization of LVO screening instruments while maintaining the accuracy of prehospital LVO determination.