In the spring of 2021, reports of rare and unusual venous thrombosis in association with the ChAdOx1 and Ad26.COV2.S adenovirus-based coronavirus vaccines led to a brief suspension of their use by several countries. Thromboses in the cerebral and splanchnic veins among patients vaccinated in the preceding 4 weeks were described in 17 patients out of 7.98 million recipients of the Ad26.COV2.S vaccine (with 3 fatalities related to cerebral vein thrombosis) and 169 cases of cerebral vein thrombosis among 35 million ChAdOx1 recipients. Events were associated with thrombocytopenia and anti-PF4 (antibodies directed against platelet factor 4), leading to the designation vaccine-induced immune thrombotic thrombocytopenia. Unlike the related heparin-induced thrombotic thrombocytopenia, with an estimated incidence of <1:1000 patients treated with heparin, and a mortality rate of 25%, vaccine-induced immune thrombotic thrombocytopenia has been reported in 1:150 000 ChAdOx1 recipients and 1:470 000 Ad26.COV.2 recipients, with a reported mortality rate of 20% to 30%. Early recognition of this complication should prompt testing for anti-PF4 antibodies and acute treatment targeting the autoimmune and prothrombotic processes. Intravenous immunoglobulin (1 g/kg for 2 days), consideration of plasma exchange, and nonheparin anticoagulation (argatroban, fondaparinux) are recommended. In cases of cerebral vein thrombosis, one should monitor for and treat the known complications of venous congestion as they would in patients without vaccine-induced immune thrombotic thrombocytopenia. Now that the Ad26.COV2.S has been reapproved for use in several countries, it remains a critical component of our pharmacological armamentarium in stopping the spread of the human coronavirus and should be strongly recommended to patients. At this time, the patient and community-level benefits of these two adenoviral vaccines vastly outweigh the rare but serious risks of vaccination. Due to the relatively low risk of severe coronavirus disease 2019 (COVID-19) in young women (<50 years), it is reasonable to recommend an alternative vaccine if one is available. Ongoing postmarketing observational studies are important for tracking new vaccine-induced immune thrombotic thrombocytopenia cases and other rare side effects of these emergent interventions.

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Background We report the interim results of a process improvement initiative at a comprehensive stroke center in which all tPA (tissue‐type plasminogen activator)–eligible patients were given tenecteplase for acute ischemic stroke. Methods We retrospectively analyzed a prospectively maintained single‐center registry of consecutive patients with acute ischemic stroke treated at our comprehensive stroke center emergency department or transferred for further care. Patients treated with alteplase (tPA) before the process improvement initiative (October 2019–April 2020) were compared with those treated with tenecteplase (May 2020–July 2021). The primary efficacy outcome was the Target: Stroke Phase II recommendation of door‐to‐needle (DTN) time ≤45 minutes. Backward stepwise logistic regression was used to estimate an independent effect of tenecteplase against DTN time ≤45 minutes. Two contemporaneous, negative controls (time to first emergency department antibiotic for patients who presented with infectious symptoms and door‐to‐groin puncture for thrombectomy) were evaluated to confirm DTN time was unrelated to emergency department and other stroke treatment throughput. Results Of the 113 included patients, 53 (47%) received tenecteplase. DTN time was significantly faster in patients treated with tenecteplase (median, 41 [interquartile range, 34–62] minutes versus 58 [interquartile range, 45–70] minutes; P <0.01), with no significant difference in symptomatic intracranial hemorrhage (2% versus 7%; P =0.37). Despite the higher proportion of tPA patients being transferred for care (with slower DTN time), tenecteplase remained independently predictive of DTN time ≤45 minutes (adjusted odds ratio, 3.96; 95% CI, 1.58–9.91). There was no difference in time to first emergency department antibiotic ( P >0.05) or door‐to‐puncture ( P >0.05) when similar periods were compared. Conclusions Tenecteplase was associated with faster DTN time when compared with tPA in those with acute ischemic stroke. This can likely be attributed to the ease of single bolus administration of tenecteplase.

Background and ObjectivesCurrent guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO.MethodsWe analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6–24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days).ResultsOf 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72–87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13–22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78–8.79 and OR 3.10, 95% CI 1.20–7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97–6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86–0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75–0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR.DiscussionIn patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management.Classification of EvidenceThis investigation's results provide Class III evidence that in patients with preexisting disability presenting 6–24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function.

Mild traumatic brain injury (mTBI) presents a significant health concern with potential persisting deficits that can last decades. Although a growing body of literature improves our understanding of the brain network response and corresponding underlying cellular alterations after injury, the effects of cellular disruptions on local circuitry after mTBI are poorly understood. Our group recently reported how mTBI in neuronal networks affects the functional wiring of neural circuits and how neuronal inactivation influences the synchrony of coupled microcircuits. Here, we utilized a computational neural network model to investigate the circuit-level effects of N-methyl D-aspartate receptor dysfunction. The initial increase in activity in injured neurons spreads to downstream neurons, but this increase was partially reduced by restructuring the network with spike-timing-dependent plasticity. As a model of network-based learning, we also investigated how injury alters pattern acquisition, recall, and maintenance of a conditioned response to stimulus. Although pattern acquisition and maintenance were impaired in injured networks, the greatest deficits arose in recall of previously trained patterns. These results demonstrate how one specific mechanism of cellular-level damage in mTBI affects the overall function of a neural network and point to the importance of reversing cellular-level changes to recover important properties of learning and memory in a microcircuit.