Prospective Observational Cohort Study of Tenecteplase Versus Alteplase in Routine Clinical Practice.

BACKGROUND: A 10-hospital regional network transitioned to tenecteplase as the standard of care stroke thrombolytic in September 2019 because of potential workflow advantages and reported noninferior clinical outcomes relative to alteplase in meta-analyses of randomized trials. We assessed whether tenecteplase use in routine clinical practice reduced thrombolytic workflow times with noninferior clinical outcomes. METHODS: We designed a prospective registry-based observational, sequential cohort comparison of tenecteplase- (n=234) to alteplase-treated (n=354) stroke patients. We hypothesized: (1) an increase in the proportion of patients meeting target times for target door-to-needle time and transfer door-in-door-out time, and (2) noninferior favorable (discharge to home with independent ambulation) and unfavorable (symptomatic intracranial hemorrhage, in-hospital mortality or discharge to hospice) in the tenecteplase group. Total hospital cost associated with each treatment was also compared. RESULTS: Target door-to-needle time within 45 minutes for all patients was superior for tenecteplase, 41% versus 29%; adjusted odds ratio, 1.85 (95% CI, 1.27-2.71); P=0.001; 58% versus 41% by Get With The Guidelines criteria. Target door-in-door-out time within 90 minutes was superior for tenecteplase 37% (15/43) versus 14% (9/65); adjusted odds ratio, 3.62 (95% CI, 1.30-10.74); P=0.02. Favorable outcome for tenecteplase fell within the 6.5% noninferiority margin; adjusted odds ratio, 1.26 (95% CI, 0.89-1.80). Unfavorable outcome was less for tenecteplase, 7.3% versus 11.9%, adjusted odds ratio, 0.77 (95% CI, 0.42-1.37) but did not fall within the prespecified 1% noninferior boundary. Net benefit (%favorable-%unfavorable) was greater for the tenecteplase sample: 37% versus 27%. P=0.02. Median cost per hospital encounter was less for tenecteplase cases ($13 382 versus $15 841; P<0.001). CONCLUSIONS: Switching to tenecteplase in routine clinical practice in a 10-hospital network was associated with shorter door-to-needle time and door-in-door-out times, noninferior favorable clinical outcomes at discharge, and reduced hospital costs. Evaluation in larger, multicenter cohorts is recommended to determine if these observations generalize.

Post-stroke Dysphagia: Recent Insights and Unanswered Questions.

PURPOSE OF REVIEW: We explored themes in recent post-stroke dysphagia literature, focusing on the following questions: (1) What does post-stroke dysphagia look like?; (2) Who gets post-stroke dysphagia?; (3) What are the consequences of post-stroke dysphagia?; and (4) How can we improve treatment of post-stroke dysphagia? RECENT FINDINGS: There have been several improvements in quantitative descriptions of swallowing physiology using standard and new evaluation techniques. These descriptions have been correlated with lesion locations, and several factors can predict development of post-stroke dysphagia and its sequelae. Novel treatment paradigms have leveraged post-stroke neuroplastic improvements using neurostimulation and biofeedback techniques. Despite recent findings, the field is limited by lack of standardization and unanswered questions on rehabilitation variables. Our improved understanding of post-stroke dysphagia will enhance our ability to prevent, identify, and treat it. Future work should be grounded in swallowing physiology and continue refining treatments, particularly in the acute stage.

Cortical excitation and inhibition following focal traumatic brain injury.

Cortical compression can be a significant problem in many types of brain injuries, such as brain trauma, localized brain edema, hematoma, focal cerebral ischemia, or brain tumors. Mechanical and cellular alterations can result in global changes in excitation and inhibition on the neuronal network level even in the absence of histologically significant cell injury, often manifesting clinically as seizures. Despite the importance and prevalence of this problem, however, the precise electrophysiological effects of brain injury have not been well characterized. In this study, the changes in electrophysiology were characterized following sustained cortical compression using large-scale, multielectrode measurement of multiunit activity in primary somatosensory cortex in a sensory-evoked, in vivo animal model. Immediately following the initiation of injury at a distal site, there was a period of suppression of the evoked response in the rat somatosensory cortex, followed by hyper-excitability that was accompanied by an increase in the spatial extent of cortical activation. Paired-pulse tactile stimulation revealed a dramatic shift in the excitatory/inhibitory dynamics, suggesting a longer term hyperexcitability of the cortical circuit following the initial suppression that could be linked to the disruption of one or more inhibitory mechanisms of the thalamocortical circuit. Together, our results showed that the use of a sensory-evoked response provided a robust and repeatable functional marker of the evolution of the consequences of mild injury, serving as an important step toward in vivo quantification of alterations in excitation and inhibition in the cortex in the setting of traumatic brain injury.

Early restitution of electrocorticogram predicts subsequent behavioral recovery from cardiac arrest.

Previous studies have shown that parameters of EEG restitution reflect the severity of global hypoxic-ischemic brain injury. Here, the hypothesis is tested that patterns of EEG restitution during the first 4 hours predict later behavioral recovery. Time course and correlations between behavior, electrocorticogram (EcoG), and neuronal injury were investigated in a rodent model of asphyctic cardiac arrest. Forty Wistar rats were subjected to 5 minutes of asphyxia and cardiopulmonary resuscitation. Behavior was assessed by repeated scoring of neurodeficits and open field activity until euthanasia at 48 hours. Electrocorticographic bursting occurred at 13.2 +/- 4 minutes after resuscitation. Bursts increased in frequency and duration until the EcoG reverted to a continuous signal. The resuscitation-continuous EcoG interval correlated with the first appearance of spontaneous movements (r = 0.80, P < 0.05). Larger intervals were associated with hyperactivity in the open field at 24 hours (r = 0.61, P < 0.05), indicating a more severe behavioral deficit. Larger intervals were also associated with worse 48-hour neurodeficit scores (P < 0.05). Neuronal damage in the hippocampus correlated with the degree of open field hyperactivity at 14 hours (P < 0.05). These findings demonstrate a close temporal and prognostic relationship between electrical and behavioral recovery after hypoxic-ischemic brain injury.