Background and Objectives Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). Methods We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1–6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1–4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4–5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6–0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31–1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82–2.97], 5,656/195,539) of all stroke hospitalizations. Discussion There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. Trial Registration Information This study is registered under NCT04934020.

BACKGROUND: Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non–vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS: We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS: Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76–86]; 40% women; median hematoma volume, 11.5 [4.8–27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22–1.82]; P =0.40). There was a signal for interaction with onset-to-treatment time ( P _interaction =0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37–3.04]; P =0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37–9.50]; P =0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS: In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. REGISTRATION: URL: https://clinicaltrials.gov ; Unique identifier: NCT02866838.

Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.

Background: We assessed the efficacy and safety of mechanical thrombectomy (MT) in adult stroke patients with anterior circulation large vessel occlusion presenting in the late time window not fulfilling the DEFUSE-3 (Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging trial) and DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct trial) inclusion criteria. Methods: Cohort study of adults with anterior circulation large vessel occlusion admitted between 6 and 24 hours after last-seen-well at 5 participating Swiss stroke centers between 2014 and 2021. Mismatch was assessed by computer tomography or magnetic resonance imaging perfusion with automated software (RAPID or OLEA). We excluded patients meeting DEFUSE-3 and DAWN inclusion criteria and compared those who underwent MT with those receiving best medical treatment alone by inverse probability of treatment weighting using the propensity score. The primary efficacy end point was a favorable functional outcome at 90 days, defined as a modified Rankin Scale score shift toward lower categories. The primary safety end point was symptomatic intracranial hemorrhage within 7 days of stroke onset; the secondary was all-cause mortality within 90 days. Results: Among 278 patients with anterior circulation large vessel occlusion presenting in the late time window, 190 (68%) did not meet the DEFUSE-3 and DAWN inclusion criteria and thus were included in the analyses. Of those, 102 (54%) received MT. In the inverse probability of treatment weighting analysis, patients in the MT group had higher odds of favorable outcomes compared with the best medical treatment alone group (modified Rankin Scale shift: acOR, 1.46 [1.02–2.10]; P =0.04) and lower odds of all-cause mortality within 90 days (aOR, 0.59 [0.37–0.93]; P =0.02). There were no significant differences in symptomatic intracranial hemorrhage (MT versus best medical treatment alone: 5% versus 2%, P =0.63). Conclusions: Two out of 3 patients with anterior circulation large vessel occlusion presenting in the late time window did not meet the DEFUSE-3 and DAWN inclusion criteria. In these patients, MT was associated with higher odds of favorable functional outcomes without increased rates of symptomatic intracranial hemorrhage. These findings support the enrollment of patients into ongoing randomized trials on MT in the late window with more permissive inclusion criteria.

Contrast-associated acute kidney injury (CA-AKI) is a potentially preventable complication after exposure to iodinated contrast media. In patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke (AIS), the incidence and clinical impact are poorly characterized, and no validated prediction tool is currently available. The aim of this study was to assess the incidence and prognostic significance of CA-AKI in EVT-treated patients with AIS and to develop and validate a predictive score. A retrospective, multicenter cohort study was conducted involving EVT-treated patients across 73 centers in 16 countries (January-December 2023). Inclusion criteria were age ≥18 years, absence of dialysis, availability of preprocedural and 48-hour postprocedural creatinine levels, and available 90-day follow-up (modified Rankin Scale [mRS] score). The primary outcome was CA-AKI, defined by KDIGO (Kidney Disease: Improving Global Outcomes criteria;creatinine increase ≥0.3 mg/dL or ≥1.5 times baseline, within 48 hours). Secondary outcomes were (1) in-hospital mortality, (2) 90-day mRS score, and (3) 90-day severe disability or death (mRS score >3). Logistic models assessing associations with outcomes accounted for within-center clustering by applying robust standard errors. CA-AKI prediction models were developed across imputed data sets using univariable selection (p < 0.20), backward elimination (p < 0.05), and coefficient-based scoring after categorization of continuous predictors, with internal validation by bootstrap to obtain optimism-adjusted estimates. Among 6,638 patients (median age 74 years; 48.7% male), CA-AKI occurred in 326 (4.9%) and was independently associated with in-hospital mortality (adjusted odds ratio [aOR] 2.269; 95% CI 1.615-3.190), higher 90-day mRS scores (adjusted common odds ratio 1.584; 95% CI 1.110-2.258), and 90-day severe disability or death (aOR 1.530; 95% CI 1.057-2.216). A preprocedural risk model including 12 routine clinical variables-sex, ethnicity, arterial hypertension, dyslipidemia, chronic kidney disease, antiplatelet therapy, NIH Stroke Scale score at admission, serum glucose, estimated glomerular filtration rate, hemoglobin, mean arterial pressure, and IV thrombolysis-demonstrated acceptable discrimination (area under the receiver operating characteristic curve 0.710 [95% CI 0.682-0.738]; precision-recall area under the curve 0.13 [95% CI 0.10-0.16]), good calibration (slope 0.870 [95% CI 0.759-0.928]), good overall performance (Brier score 0.045 [95% CI 0.042-0.049]). A second model that included EVT-related variables (e.g., contrast volume) showed similar performances. In this large, international cohort, CA-AKI occurred in approximately 1 in 20 EVT-treated patients with AIS and was independently associated with poor outcomes. A simple preprocedural risk score enables early identification of high-risk individuals and may support preventive strategies.

Background and Objectives: Proximal humerus fractures (PHFs) are common in the elderly, but the treatment results are often poor. A clear understanding of fracture morphology and distribution of cortical bone loss is important for improved surgical decision making, operative considerations, and new implant designs. The aim of this study was to develop a 3D segmentation fracture mapping technique to create a statistical description of the spatial pattern and cortical bone loss of complex PHFs. Materials and Methods: Fifty clinical computed tomography (CT) scans of complex PHFs and their contralateral intact shoulders were collected. In-house software was developed for semi-automated segmentation and fracture line detection and was combined with manual fracture reduction to the contralateral template in a commercial software. A statistical mean model of these cases was built and used to describe probability maps of the fracture lines and cortical fragments. Results: The fracture lines predominantly passed through the surgical neck and between the tuberosities and tendon insertions. The superior aspects of the tuberosities were constant fragments where comminution was less likely. Some fracture lines passed through the bicipital sulcus, but predominantly at its edges and curving around the tuberosities proximally and distally. Conclusions: A comprehensive and systematic approach was developed for processing clinical CT images of complex fractures into fracture morphology and fragment probability maps and applied on PHFs. This information creates an important basis for better understanding of fracture morphology that could be utilized in future studies for surgical training and implant design.