Anticoagulation Use and Endovascular Thrombectomy in Patients with Large Core Stroke: A Secondary Analysis of the SELECT2 Trial.

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.89 [0.53-1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3-6] vs MM 5 [4-6], adjusted generalized odds ratio 1.87 [1.45-2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024;96:887-894.

Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient-Level Analysis of EXTEND-IA Trials and SELECT Prospective Cohort.

OBJECTIVE: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. METHODS: In a pooled, patient-level analysis of the EXTEND-IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. RESULTS: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8-48.4), and median midline shift was 0mm (IQR = 0-2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89-4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (ß = -1.19, 95% confidence interval [CI] = -1.51 to -0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23-0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86-3.88, p < 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95-2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. INTERPRETATION: In this mediation analysis from a pooled, patient-level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793-804.

Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles.

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Clinical relevance of intracranial hemorrhage after thrombectomy versus medical management for large core infarct: a secondary analysis of the SELECT2 randomized trial.

BACKGROUND: The incidence of intracerebral hemorrhage (ICH) and its effect on the outcomes after endovascular thrombectomy (EVT) for patients with large core infarcts have not been well-characterized. METHODS: SELECT2 trial follow-up imaging was evaluated using the Heidelberg Bleeding Classification (HBC) to define hemorrhage grade. The association of ICH with clinical outcomes and treatment effect was examined. RESULTS: Of 351 included patients, 194 (55%) and 189 (54%) demonstrated intracranial and intracerebral hemorrhage, respectively, with a higher incidence in EVT (134 (75%) and 130 (73%)) versus medical management (MM) (60 (35%) and 59 (34%), both P<0.001). Hemorrhagic infarction type 1 (HBC=1a) and type 2 (HBC=1b) accounted for 93% of all hemorrhages. Parenchymal hematoma (PH) type 1 (HBC=1c) and type 2 (HBC=2) were observed in 1 (0.6%) EVT-treated and 4 (2.2%) MM patients. Symptomatic ICH (sICH) (SITS-MOST definition) was seen in 0.6% EVT patients and 1.2% MM patients. No trend for ICH with core volumes (P=0.10) or Alberta Stroke Program Early CT Score (ASPECTS) (P=0.74) was observed. Among EVT patients, the presence of any ICH did not worsen clinical outcome (modified Rankin Scale (mRS) at 90 days: 4 (3-6) vs 4 (3-6); adjusted generalized OR 1.00, 95% CI 0.68 to 1.47, P>0.99) or modify EVT treatment effect (Pinteraction=0.77). CONCLUSIONS: ICH was present in 75% of the EVT population, but PH or sICH were infrequent. The presence of any ICH did not worsen functional outcomes or modify EVT treatment effect at 90-day follow-up. The high rate of hemorrhages overall still represents an opportunity for adjunctive therapies in EVT patients with a large ischemic core.

Bypassing the intensive care unit for patients with acute ischemic stroke secondary to large-vessel occlusion.

OBJECTIVE: Endovascular mechanical thrombectomy is safe and effective for the treatment of acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). Still, despite high rates of procedural success, it is routine practice to uniformly admit postthrombectomy patients to an intensive care unit (ICU) for postoperative observation. Predictors of ICU criteria and care requirements in the postmechanical thrombectomy ischemic stroke patient population are lacking. The goal of the present study is to identify risk factors associated with requiring ICU-level intervention following mechanical thrombectomy. METHODS: The authors retrospectively analyzed data from 245 patients undergoing thrombectomy for AIS from anterior circulation LVO at a comprehensive stroke and tertiary care center from January 2015 to March 2020. Clinical variables that predicted the need for critical care intervention were identified and compared. The performance of a binary classification test constructed from these predictive variables was also evaluated using a validation cohort. RESULTS: Seventy-six patients (31%) required critical care interventions. A recanalization grade lower than modified Thrombolysis in Cerebral Infarction (mTICI) scale grade 2B (odds ratio [OR] 3.625, p = 0.001), Alberta Stroke Program Early Computed Tomography Score (ASPECTS) < 8 (OR 3.643, p < 0.001), and presence of hyperdensity on postprocedure cone-beam CT (OR 2.485, p = 0.005) were significantly associated with the need for postthrombectomy critical care intervention. When applied to a validation cohort, a clearance classification scheme using these three variables demonstrated high positive predictive value (0.88). CONCLUSIONS: A recanalization grade lower than mTICI 2B, ASPECTS < 8, and postprocedure hyperdensity on cone-beam CT were shown to be independent predictors of requiring ICU-level care. Routine admission to ICU-level care can be costly and confer increased risk for hospital-acquired conditions. Safely and reliably identifying low-risk patients has the potential for cost savings, value-based care, and decreasing hospital-acquired conditions.

Stroke in pregnancy.

Stroke in pregnancy is rare and has a wide range of etiologies and implications on stroke management that differ from nonpregnant individuals. The highest risk of stroke is during the third trimester and puerperium period, where hypertensive disorders of pregnancy occur; however, stroke can occur at any point during pregnancy. In this chapter, we will provide an overview of the epidemiology of stroke in pregnancy and then review the specific etiologies of ischemic and hemorrhagic stroke as they relate to pregnant women. Finally, we discuss the process of acute stroke evaluation in pregnancy and the management of women after stroke with regard to long-term risk factors, medications, and implications in future pregnancies. Throughout the chapter, we highlight relevant guidelines from the American Heart Association and American Stroke Association and key literature on stroke in pregnancy.

Predictors of Atrial Fibrillation During Long-Term Implantable Cardiac Monitoring Following Cryptogenic Stroke.

Background Following cryptogenic stroke, guidelines recommend cardiac monitoring for occult atrial fibrillation (AF). We aimed to evaluate predictors of AF during long-term implantable cardiac monitoring. Methods and Results We studied 293 consecutive patients who underwent implantable cardiac monitor implant (Medtronic LINQ) following hospitalization for cryptogenic stroke at the University of Rochester Medical Center from January 2013 to September 2018. Multivariable Cox proportional hazards regression modeling was used to identify predictors of AF during long-term monitoring. At 36 months of follow-up, the cumulative rate of implantable cardiac monitor-detected AF events was 32% in the total study population. Multivariable analysis identified age ≥70 years as the most powerful predictor of the development of AF events during follow-up (hazard ratio, 2.28 [95% CI, 1.39-3.76]; P=0.001). Replacing age with the CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex category) score resulted in a weaker association, for which each 1-point increment in the CHA2DS2-VASC score was associated with an 18% increased risk of developing AF (95% CI, 1.00-1.38; P=0.047). Consistent results were shown using Kaplan-Meier analysis by age and by the CHA2DS2VASc score. Conclusions Cryptogenic stroke patients continue to develop AF episodes during 36 months of implantable cardiac monitoring following the index event. Age is the most powerful predictor of occult AF in this population.

Variability in student perceptions of mistreatment.

BACKGROUND: As medical schools strive to improve the learning environment, it is important to understand medical students' perceptions of mistreatment. The purpose of this study was to explore student interpretations of previously reported mistreatment incidents to better understand how they conceptualise the interactions. METHODS: Medical students were presented with case scenarios of previously reported instances of mistreatment and asked to indicate their agreement as to whether the scenarios demonstrated mistreatment, using a five-point Likert scale (1, strongly disagree; 5, strongly agree). It is important to understand medical student's perceptions of mistreatment RESULTS: One hundred and twenty-seven third-year medical students gave feedback on 21 mistreatment cases. There was variability in the categorisation of the scenarios as mistreatment. The highest degree of consensus (96% agreement) was for a scenario in which a resident claimed a student made statements about a patient's status that the student did not make. There was also relative consensus on three additional scenarios: (1) a patient making disparaging remarks about a student's role in health care in relation to the student's ethnicity (88% agreement); (2) a resident asking a student to run personal errands (86% agreement); and (3) a nurse calling a student an expletive in front of others (77% agreement). For the majority of the cases, there was no consensus amongst students as to whether mistreatment had occurred. Students self-identifying as minorities and students who had previously reported mistreatment were more likely to perceive mistreatment in the scenarios. CONCLUSIONS: There is remarkable variability, and in many cases a lack of agreement, in medical student perceptions of mistreatment. This inconsistency needs to be considered in order to effectively address and mitigate the issue.