Citations

Background: High-grade intracranial atherosclerosis (ICAS) is associated with an elevated risk of recurrent ischemic stroke, particularly in patients with severe stenosis (70–99%). Identifying predictors of early recurrence can inform risk stratification and guide treatment strategies. Methods: The Biomarkers and Recurrence Risk in Symptomatic Intracranial Arterial Stenosis (BIORISK-ICAS) study is a multicenter, international, retrospective cohort analysis pooling data from 35 comprehensive stroke centers. We included hospitalized adult patients with symptomatic ICAS, defined as 50–99% stenosis of an intracranial artery (intracranial vertebral, basilar, distal ICA, or M1 MCA), confirmed by vascular imaging and associated with a qualifying ischemic event. Patients with only high-grade stenosis (70-99%) were included in this analysis. The primary outcome was to determine predictors of recurrent ischemic stroke in the territory of the symptomatic artery within 90 days of the index event. Baseline demographic, clinical, and imaging characteristics were recorded. Multivariable Cox proportional hazards regression with stepwise selection (p < 0.1) was used to identify independent predictors of recurrence; model discrimination was assessed using Harrell’s C-statistics. Results: Among 2,050 patients, 1,476 had high-grade (70-99%) symptomatic ICAS. The mean age was 67 ± 12.5 years, and 767 (55%) were male. Most patients were non-Hispanic (90.1%), taking dual antiplatelet therapy (77.8%), and statins (94.5%). Recurrent stroke occurred in 160 patients (10.8%) within 90 days. In multivariable Cox model, independent predictors of recurrence included atrial fibrillation (HR 2.05; 95% CI, 1.26–3.33; p = 0.004), hyperlipidemia (HR 1.57; 95% CI, 1.10–2.24; p = 0.014), diabetes mellitus (HR 1.36; 95% CI, 0.98–1.88; p = 0.064), and home use of dual antiplatelet therapy (HR 1.60; 95% CI, 1.01–2.54; p = 0.043)(Harrell’s C-statistic=0.62). In patients who underwent perfusion(n=402), mistmatch >10seconds were associated with increased recurrence (HR 1.80; 95% CI 0.95-3.38, p=0.07) and atrial fibrillation (HR 2.06: 95% CI 0.03-4.60, p=0.78) though did not reach statistical significance. Conclusion: In this population, diabetes, hyperlipidemia, atrial fibrillation, and prior use of dual antiplatelet therapy were associated with increased risk of 90-day recurrent ischemic stroke. Perfusion imaging may help identify high-risk patients who could benefit from intensified secondary prevention.

Introduction: Intracranial atherosclerosis (ICAS) is a leading cause of ischemic stroke (IS) worldwide and carries a high risk of recurrence. Current guidelines favor 90 days of dual antiplatelet therapy (DAPT) for severe symptomatic ICAS, but recurrence remain high. Limited data suggest possible benefit of single antiplatelet plus anticoagulation (SAPT+AC). We compared the effectiveness and safety of DAPT versus SAPT+AC. We hypothesized that DAPT would lower 90-day recurrent IS risk without significantly increasing bleeding. Methods: This substudy of the Biomarkers and Recurrence Risk in Symptomatic Intracranial Arterial Stenosis (BIORISK-ICAS) included patients from 35 centers (Jan 2019–Jun 2024) with symptomatic 50–99% ICAS in the intracranial internal carotid, vertebral, basilar, or M1 segment of the MCA, presenting ≤72 hours from last known well. The primary efficacy outcome was recurrent IS in the same vascular territory at 90 days; the primary safety outcome was severe bleeding (symptomatic intracranial hemorrhage or major extracranial bleeding). Categorical variables were compared using χ 2 and continuous variables with the Student's t test; multivariable Cox regression adjusted for key covariates. Results: Of 2050 BIORISK-ICAS patients, 1658 met criteria (DAPT n=1499; SAPT+AC n=159). Mean age was 67 vs. 73 years, and 44% were women. At 90 days, recurrent IS occurred in 121 DAPT patients (8.07%) vs. 13 SAPT+AC patients (8.17%); unadjusted HR 0.83 (95% CI, 0.50–1.36; p=0.46). After adjustment for age, diabetes, coronary heart disease, atrial fibrillation, active smoking, and borderzone infarct, the adjusted HR was 0.99 (95% CI, 0.52–1.86; p=0.97). Severe bleeding occurred in 34 DAPT patients (2.26%) and 5 SAPT+AC patients (3.14%); unadjusted HR 0.79 (95% CI, 0.28–1.85; p=0.50), adjusted HR 0.66 (95% CI, 0.21–2.09; p=0.47). Conclusions: In patients with symptomatic ICAS, DAPT and SAPT+AC were associated with similar risks of 90-day recurrent ischemic stroke and severe bleeding. Well-powered randomized trials are needed to determine the optimal antithrombotic regimen in this high-risk population.

BACKGROUND: Cervical artery dissection (CeAD) may result in dissecting aneurysm (DA) formation. We aimed to characterize risk factors and clinical outcomes associated with DA in a large, international CeAD cohort. METHODS: We performed a secondary analysis of STOP-CAD (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), an international, multicenter, retrospective cohort. Patients with spontaneous CeAD were assessed for DA at baseline and de novo DA formation. Significant covariates in univariable analysis were included in multivariable regression models aiming to identify factors associated with DA formation. Logistic regression and Cox proportional hazards models evaluated the association of DA with ischemic and hemorrhagic outcomes. RESULTS: Among 4008 patients with CeAD, 546 (13.6%) had a DA at baseline, and 221/2938 (7.5%) patients developed a de novo DA during follow-up, of which 172/221 (78.2%) were detected in the first 180 days. Patients with DA had a mean age of 47 years, and 383 (49.9%) were women. Baseline or de novo DA was associated with a history of connective tissue disorder (adjusted odds ratio [aOR], 2.02 [95% CI, 1.22–3.36]), fibromuscular dysplasia (aOR, 1.69 [95% CI, 1.28–2.25]), and multiple vessel dissection (aOR, 1.53 [95% CI, 1.19–1.98]). Lower odds of DA were seen in Hispanic ethnicity (aOR, 0.64 [95% CI, 0.43–0.97]) and ischemic stroke presentation (aOR, 0.41 [95% CI, 0.34–0.49]). Fibromuscular dysplasia was associated with de novo DA formation (aOR, 2.30 [95% CI, 1.52–3.49]). DA was not associated with ischemic stroke (hazard ratio, 0.71 [95% CI, 0.44–1.16]; P =0.173) or intracranial hemorrhage (HR, 1.09 [95% CI, 0.42–2.84]; P =0.86) by day 180. CONCLUSIONS: DAs are relatively common manifestations of CeAD, typically occurring within 6 months of CeAD diagnosis. DA was not associated with an increased risk of subsequent ischemic stroke or intracranial hemorrhage.

Abstract Background Diabetes mellitus is a prevalent global health issue, affecting approximately 14% of individuals as latest reported. Among its complications, diabetic peripheral polyneuropathy (DPN) is a major cause of morbidity, impacting up to half of patients with long-standing diabetes. Given the limitations of current diagnostic methods, there is an urgent need for reliable biomarkers for early detection and management of DPN. Neurofilament light chain (NFL), a structural neuronal protein, has been proposed as a potential biomarker due to its release into the blood and cerebrospinal fluid following axonal damage. This systematic review and meta-analysis aim to evaluate serum NFL levels in diabetic patients with and without polyneuropathy compared to healthy controls. Methods A systematic search was conducted in four databases: Web of Science, PubMed, Scopus, and Embase. Studies were included if they measured serum NFL levels in diabetic patients, with or without polyneuropathy, and compared these levels to healthy controls. The Newcastle-Ottawa Scale (NOS) and JBI Critical Appraisal tools were used for quality assessment. We performed a meta-analysis using Review Manager 5.4 version, and assessed heterogeneity through chi-square tests and I² statistics. Results Eight studies (n = 2980 participants, including 950 diabetic patients and 2030 healthy controls) met the inclusion criteria. Three studies specifically evaluated serum NFL levels in diabetic patients with polyneuropathy. Meta-analysis revealed significantly elevated serum NFL levels in diabetic patients compared to healthy controls. Similarly, diabetic patients with polyneuropathy exhibited higher NFL levels than healthy controls. However, due to the limited number of studies comparing diabetic patients with and without neuropathy, a definitive conclusion on NFL's specificity to DPN remains uncertain. Heterogeneity analysis showed a moderate to high variation among studies, with a slight reduction after sensitivity analysis. Conclusion This study highlights elevated serum NFL levels in diabetic patients, irrespective of polyneuropathy status, suggesting that diabetes itself may contribute to increased NFL release. However, due to limited studies assessing NFL in DPN, further research is required to clarify its role as a specific biomarker for DPN.

Abstract Chimeric antigen receptor (CAR) T-cell therapy enriched for a memory-like phenotype may persist and function longer than a nonenriched product, thereby improving duration of response (DOR). We conducted a phase I study with bb21217 (NCT03274219), an anti–B-cell maturation antigen CAR T-cell therapy manufactured in the presence of the phosphoinositide 3-kinase inhibitor bb007 to enrich for T cells with a memory-like phenotype, in patients with relapsed/refractory multiple myeloma (N = 72). No new safety concerns were raised with bb21217 therapy (three cases each of grade ≥3 cytokine release syndrome and grade ≥3 neurotoxicity were observed). The objective response rate was 69.4% and the median DOR was 23.8 (95% confidence interval, 16.8–34.8) months. Analysis of the drug product established an association between early memory phenotype and robust expansion and depth of response. Examination of baseline characteristics indicated that tumor burden and prior therapies influenced DOR. The data indicate that generation of CAR T cells early in a disease course when tumor burden is lower and source material exhibits a more naïve phenotype may maximize the clinical benefit potential of the drug product.

Abstract Objective To measure the relative levels of signal and noise in expert diagnosis of epilepsy. Methods Twenty multinational epileptologists independently reviewed 50 vignettes of adult and pediatric patients presenting with suspected seizure(s) on two separate occasions with a ≥30‐day washout period. Experts provided a diagnosis of epilepsy or non‐epilepsy based on clinical information and, if requested, routine EEG and neuroimaging data. Cases had an established clinical diagnosis of epilepsy or non‐epilepsy based on capture of habitual paroxysmal events on video‐EEG or long‐term clinical follow‐up. Experts' judgments were analyzed to decompose variability into different sources: signal (objective differences between cases), level noise (experts' bias toward over/under‐diagnosis), pattern noise (experts' idiosyncratic reactions to specific case features), and occasion noise (inconsistency across occasions). Results The probability of an expert making a different diagnosis for a given case on two different occasions was 16%. The probability of two different experts making a different diagnosis for the same case was 26%. Signal (case “difficulty”) accounted for 66–69% of total variation, with 31–34% attributable to noise. Level noise was the largest contributor in the absence of EEG/neuroimaging results (23%), while pattern noise dominated when test results were available (24%). Occasion noise contributed relatively little (1%) but was still sufficient to cause diagnostic reversals in 16–22% between occasions. Significance The degree of noise in expert diagnosis of epilepsy is substantial, stemming primarily from physicians' idiosyncratic interpretations of case features and variable dispositions toward over‐ or under‐diagnosis. Strategies to improve reliability are needed, including standardized data collection protocols and structured decision algorithms. For “difficult cases,” where expert reliability and accuracy are lowest, our findings support current clinical practice which favors early referral for video‐EEG monitoring over reliance on diagnostic anchoring. This diagnostic pathway may become more accessible with advances in EEG technology (e.g., wearable devices) and artificial intelligence.

ABSTRACT Background The COVID‐19 pandemic presented unprecedented challenges to hospital system and critical care resources, leading to significant changes to operations and patient care. There are limited national data on these changes and instances of unsanctioned deviations from patient care, yet understanding the COVID response is key to future preparedness efforts. We sought to understand how hospitals and states navigated scarcity during COVID‐19, particularly in the absence of a declaration of crisis standards of care. Methods Between February 2022 and September 2022 we conducted 34 interviews with 36 leaders of U.S. states' COVID‐19 planning and response efforts. Interviews were transcribed verbatim and verified. We analyzed interviews using iterative inductive thematic analysis for descriptions of resource scarcity and changes to policies and procedures to prevent rationing lifesaving care. Results Nearly all participants described equipment and personnel scarcity in their home institution or state during COVID‐19. Hospitals across regions and states developed formal and informal coordination processes for load and resource sharing in response to influxes of high‐acuity patients, avoiding formal rationing of lifesaving resources in many regions. Participants also described unsanctioned patient triage, early discharge, and patients counseled to accept less aggressive care (e.g., premature transition to hospice) in states that had not declared crisis standards of care. Conclusions Extending limited resources and inter‐institutional collaboration helped avoid formal rationing. Yet, patient care was unquestionably impacted due to scarcity, both real and perceived. Reports of using hospital triage protocols to deny patients lifesaving care outside of formally recognized crisis conditions and attempts to nudge patients to accept less‐resource‐intensive care are concerning. This may have had disproportionate effects on older adults, individuals with disabilities, and racial and ethnic minoritized groups. To avoid unsanctioned deviations from standard practice in future health emergencies, we recommend that transparent and equitable triage protocols are implemented with robust oversight.

Abstract Introduction Cervical arterial dissections (CeAD) can involve either single (sCeAD) or multiple (mCeAD) arteries. Whether the involvement of a single versus multiple arteries is associated with outcomes remains unclear. We aimed to study associations between the number of affected arteries and clinical, imaging and outcome parameters. Patients and methods Patients with CeAD from the STOP-CAD multicenter registry study were included. Clinical, imaging, treatment and outcome parameters were compared between patients with sCeAD and mCeAD. Regression analyses were performed to identify associations with multi-arteries involvement. Results Overall, 3858 STOP-CAD patients were included in this analysis and 443 (11.5%) had mCeAD. The presence of mCeAD was associated with age (adjusted odds ratio [aOR] 95% confidence intervals [95% CI] 0.99; (0.98–1.00)), female sex (aOR 1.5; 95% CI 1.17–1.91), recent upper respiratory infection (aOR 2.25; 95% CI 1.55–3.27), presence of connective tissue disease (aOR 3.11; 95% CI 2.32–4.17), severe arterial stenosis (aOR 1.95; 95% CI 1.95–2.58), intracranial extension (aOR 1.47; 95% CI 1.04–2.09), vertebral artery involvement (aOR 2.50; 95% CI 1.94–3.22) and presence of dissecting aneurysm (aOR 2.59; 95% CI 1.95–3.42). In adjusted analyses, mCeAD was not associated with clinical outcomes (ischemic stroke, mortality, and sICH; all p &gt; 0.05). Conclusions mCeAD does not appear to increase risk of subsequent stroke as compared to sCAD despite baseline risk factors suggestive of vasculopathy. mCeAD patients who did develop a stroke presented with milder strokes and less often had vessel occlusions compared to those with sCeAD. The presence of mCeAD did not impact outcomes.