EVT is standard care for acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but benefit with mild stroke (NIHSS ≤ 5) remains unclear. Patients from the INSPIRE‑S global registry with AIS treated with Medtronic Neurovascular devices on the first pass were grouped by mild stroke (NIHSS ≤ 5) and moderate-to-severe stroke (NIHSS > 5) at baseline. Clinical and safety outcomes were compared, with analysis for the subset treated with Solitaire™ on first pass with or without aspiration. From May 2020–December 2022, 801 patients (29 sites, 13 countries) met eligibility criteria and were enrolled into stent retriever, aspiration alone, or combination therapy cohorts. For this analysis, outcomes were compared by baseline NIHSS: mild stroke (n = 75) versus moderate-to-severe stroke (n = 713). Mild stroke patients had higher rates of 90-day mRS 0–2 (75.3
OBJECTIVES:Bacillus cereus sensu lato (s.l.) or B. cereus group increasingly causes severe infections in preterm neonates. However, species-level identification and virulence characterization remain limited. This study aimed to identify B. cereus group species responsible for invasive infections in preterm neonates and to correlate genomic virulence profiles with clinical outcomes. METHODS:We conducted a retrospective, multicentre study across 13 French hospitals (2010-2021), including 40 B. cereus group isolates from blood or cerebrospinal fluid of preterm neonates with invasive infections. Clinical data were extracted from patient records. Whole-genome sequencing (WGS) (Illumina and Oxford Nanopore) with hybrid assemblies enabled species identification using digital DNA-DNA hybridization and average nucleotide identity. Virulence genes were screened against a curated database of 65 virulence genes, and associations with clinical outcomes were analysed. RESULTS:Forty isolates were analysed, 42.5% (17 of 40) of patients developed septic shock, and 37.5% (15 of 40), died, usually after rapid clinical deterioration. WGS identified seven species, predominantly Bacillus paranthracis (47.5%, 19 of 40) and B. cereus sensu stricto (20%, 8 of 40). Virulence gene content varied by species. The presence of hblCDAB (60%, 9 of 15), nprB (46.5%, 7 of 15), asbABCDEF (80%, 12 of 15), and essC-cereus/esxA (66.7%, 10 of 15) genes correlated with mortality (p 0.00015, 0.002, 0.0027, and 0.02, respectively). B. cereus sensu stricto carried more virulence determinants and was associated with higher mortality than B. paranthracis and other species, at day 7 (p 0.05) and at day 28 (p 0.0065). The cesH gene (60%, 15 of 25) is significantly associated with survival (p 0.007), particularly with B. paranthacis, the predominant species in our cohort. CONCLUSIONS:Invasive B. cereus group infections in preterm neonates are associated with high mortality, particularly in cases due to B. cereus sensu stricto. WGS enables precise species identification and virulence profiling, which are essential insights for diagnostic refinement, outbreak control, and risk stratification in neonatal intensive care settings.
BACKGROUND:Glenzocimab is a humanized fragment of a monoclonal antibody directed against the human platelet glycoprotein VI, which has shown promising features, including thrombus growth inhibition and minimal bleeding risk. The first inpatient study suggested the benefit of glenzocimab with alteplase in subgroups of patients with acute ischemic stroke (AIS) receiving endovascular treatment (EVT), with increased reperfusion rates and decreased risk of symptomatic hemorrhagic transformation. The objective of the GREEN (Glenzocimab for REperfusion in the setting of Endovascular therapy for brain infarctioN) study is to evaluate the efficacy of glenzocimab with EVT compared with EVT plus placebo, with or without intravenous thrombolysis (IVT), on functional outcome. METHODS:GREEN is a multicenter, randomized, double blind, placebo controlled study. Participants presenting with AIS and a large vessel occlusion of the anterior circulation (intracranial internal carotid artery or middle cerebral artery, or both), with symptoms onset within 24 hours, will be randomized to one of two groups: intravenous glenzocimab 1000 mg with standard of care (SoC-EVT±IVT) or SoC (EVT±IVT) plus placebo. The main primary efficacy endpoint is functional outcome (assessed by the modified Rankin Scale score) at 90 days. CONCLUSION:This is the first randomized trial evaluating the efficacy of glenzocimab with EVT. This prospective trial aims to determine whether glenzocimab with EVT improves functional outcome. TRIAL REGISTRATION:ClinicalTrials.gov NCT05559398.
Background and ObjectivesDevelopmental and epileptic encephalopathies (DEEs) with early burst-suppression EEG (EIDEE-BS) are among the most severe neonatal epileptic syndromes, typically presenting in the first months of life with refractory seizures and profound neurodevelopmental impairment. Although variants in the KCNQ2, STXBP1, and SCN2A genes are recognized as major causes, the full genetic spectrum remains uncertain. We aimed to delineate the electroclinical characteristics, genetic etiologies, and long-term outcomes in a large MRI-negative EIDEE-BS cohort.MethodsWe retrospectively analyzed 110 patients with BS EEG enrolled from a database of 1,540 individuals with suspected genetic epilepsies (2008-2023). Clinical, EEG, and genetic data were systematically collected. Patients were stratified into 4 groups: KCNQ2, STXBP1, "other pathogenic variants," and "without a genetic diagnosis." EEG traces were reviewed independently, and outcomes were assessed through long-term follow-up.ResultsPathogenic or likely pathogenic variants were identified in 62.7% of patients and involved 23 genes, including 2 copy number variants. KCNQ2 (n = 24) and STXBP1 (n = 16) accounted for one-third of diagnoses, whereas SCN2A (n = 3) and KCNT1 (n = 2) were less frequent. In KCNQ2 cases, seizures and BS onset occurred earlier than in STXBP1 cases: mean 2 days vs 6 weeks for seizures and 3 days vs 2 months for BS, respectively. A typical BS pattern (bursts longer than suppressions) strongly correlated with KCNQ2 and STXBP1 variants. Novel associations were found with DPM1, GRIN2A, KCNT2, PIGO, PURA, WWOX, and candidate genes (KMT2E, SNAP25, and SYT1). Most variants were de novo heterozygous; however, recessive and X-linked inheritance patterns were also observed. Mortality was high (25%), primarily from status epilepticus and complications of severe disability. Most patients (72.5%) had persistent seizures at follow-up (a mean of 6.5 years), as well as profound intellectual disabilities, irrespective of genotype.DiscussionThis large series highlights the strong monogenic basis of EIDEE-BS. KCNQ2, STXBP1, and SCN2A were the most commonly affected genes. Early EEG features, particularly BS timing and morphology, can help anticipate the underlying genotype and guide precision therapy, including the early use of sodium channel blockers in selected cases. These findings support recent ILAE reclassification efforts and underscore the importance of comprehensive genomic testing for improved diagnosis and counseling.
INTRODUCTION:The Woven EndoBridge (WEB) Embolization System is the first intrasaccular device developed for the treatment of wide-necked bifurcation aneurysms (WNBAs). Here we report the 1-year outcomes for the unruptured aneurysm cohort of the WISE Study (WEB Implant Safety and long-term Effectiveness) database, a pooled analysis of subject-level data from seven prospective WEB trials. METHODS:Individual subject-level data from seven prospective, multicenter, core laboratory adjudicated, externally monitored studies evaluating the WEB device for the treatment of unruptured WNBAs were pooled. The included aneurysms had a mean dome width of 6.5 mm. All studies shared the same core laboratory, and five of the seven shared the same clinical events committee. Subject demographic and aneurysm characteristics, procedural data, and effectiveness and safety outcomes were combined and evaluated as a single population. Adequate occlusion was defined as complete occlusion or residual neck on core laboratory assessment. RESULTS:A total of 449 unruptured aneurysms were successfully treated within WISE. The 1-year rates of complete occlusion and adequate occlusion were 54.7% (223/408) and 82.8% (338/408), respectively. Aneurysm recurrence was 6.4% (19/298) and the retreatment rate was 2.5% (11/449). All-cause morbidity was 1.2% (5/416) and treatment-related morbidity (device- and/or procedure-related) was 0.5% (2/416) at 12 months. No ruptures were observed after WEB treatment through 1 year. Complete occlusion was less likely for anterior circulation aneurysms, larger aneurysm height and width, and wider neck. Complete occlusion was less likely for anterior circulation aneurysms and for aneurysms with larger height, width, and neck size (all p<0.05). Greater WEB lateral compression was associated with higher rates of complete occlusion (OR 1.289 for absolute difference and OR 7.042 for ratio, p≤0.0066), and with higher rates of adequate occlusion (OR 1.288 and 8.846, respectively). Retreatment was associated with larger aneurysm height and width, and smoking history. CONCLUSION:The WEB device is safe and effective for the treatment of unruptured intracranial aneurysms with high rates of adequate occlusion, low rates of recurrence and retreatment, and reliable protection from rupture.
