Thrombectomy With the pRESET vs Solitaire Stent Retrievers as First-Line Large Vessel Occlusion Stroke Treatment: A Randomized Clinical Trial.

Importance: Stent retriever-based thrombectomy is highly beneficial in large vessel occlusion (LVO) strokes. Many stent retriever designs are currently available, but comparison of these technologies in well-conducted studies is lacking. Objective: To determine whether thrombectomy for LVO stroke with the pRESET stent retriever is noninferior to treatment with the Solitaire stent retriever. Design, Setting, and Participants: This study was a multicenter, prospective, randomized, controlled, open-label, adaptive, noninferiority trial with blinded primary end point evaluation. Between October 2019 and February 2022, multicenter participation occurred across 19 research hospitals and/or universities in the US and 5 in Germany. Patients with LVO stroke were enrolled and included up to 8 hours after symptom onset. Interventions: Patients underwent 1:1 randomization to thrombectomy with the pRESET or Solitaire stent retriever. Main Outcomes and Measures: The primary outcome was the difference in the rate of 90-day functional independence across the 2 devices, using a -12.5% noninferiority margin for the lower bound of the 1-sided 95% CI of the difference between pRESET and Solitaire retrievers. Results: Of 340 randomized patients, 170 (50.0%) were female, and the median (IQR) age was 73.0 (64.0-82.0) years. The study procedure was completed in 322 of the 340 randomized patients. The primary end point of 90-day functional independence was achieved by 95 patients (54.9%; 95% CI, 48.7-61.1) in the pRESET group and in 96 (57.5%; 95% CI, 51.2-63.8) in the Solitaire group (absolute difference, -2.57%; 95% CI, -11.42 to 6.28). As the lower bound of the 95% CI was greater than -12.5%, the pRESET retriever was deemed noninferior to the Solitaire retriever. The noninferiority of pRESET over Solitaire was also observed in the secondary clinical end point (90-day shift in modified Rankin Scale score) and in both angiographic end points (Expanded Treatment in Cerebral Infarction [eTICI] score of 2b50 or greater within 3 passes: 146 of 173 [84.4%] vs 149 of 167 [89.2%]; absolute difference, -4.83%; 95% CI, -10.84 to 1.19; eTICI of 2c or greater following the first pass: 76 of 173 [43.7%] vs 74 of 167 [44.3%]; absolute difference, -0.63%; 95% CI, -9.48 to 8.21). Symptomatic intracranial hemorrhage occurred in 0 patients in the pRESET group and 2 (1.2%) in the Solitaire group. Mortality occurred in 25 (14.5%) in the pRESET group and in 24 (14.4%) in the Solitaire group at 90 days. Findings of the per-protocol and as-treated analyses were in concordance with findings of the intention-to-treat analysis. Conclusions and Relevance: In this study, among patients with LVO stroke, thrombectomy with the pRESET stent retriever was noninferior to thrombectomy with the Solitaire stent retriever. Findings suggest that pRESET offers a safe and effective option for flow restoration and disability reduction in patients with LVO stroke.

International controlled study of revascularization and outcomes following COVID-positive mechanical thrombectomy.

BACKGROUND AND PURPOSE: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates.

Characteristics of a COVID-19 Cohort With Large Vessel Occlusion: A Multicenter International Study.

BACKGROUND: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke. OBJECTIVE: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort. METHODS: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020. RESULTS: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates.

Use of flow-diverting stents as salvage treatment following failed stent-assisted embolization of intracranial aneurysms.

Flow-diverting stents, including the Pipeline embolization device (PED) and Silk, have been beneficial in the treatment of aneurysms previously unable to be approached via endovascular techniques. Recurrent aneurysms for which stent-assisted embolization has failed are a therapeutic challenge, given the existing intraluminal construct with continued blood flow into the aneurysm. We report our experience using flow-diverting stents in the repair of 25 aneurysms for which stent-assisted embolization had failed. Nineteen (76%) of these aneurysms at the 12-month follow-up showed improved Raymond class occlusion, with 38% being completely occluded, and all aneurysms demonstrated decreased filling. One patient developed a moderate permanent neurologic deficit. Appropriate stent sizing, proximal and distal construct coverage, and preventing flow diverter deployment between the previously deployed stent struts are important considerations to ensure wall apposition and prevention of endoleak. Flow diverters are shown to be a reasonable option for treating previously stented recurrent cerebral aneurysms.

Feasibility and safety of pipeline embolization device in patients with ruptured carotid blister aneurysms.

BACKGROUND: Treatment of internal carotid ruptured blister aneurysms (IC-RBA) presents many challenges to neurosurgeons because of the high propensity for rebleeding during intervention. The role of a Pipeline Embolization Device (PED) in the treatment of this challenging aneurysm subtype remains undefined despite theoretical advantages. OBJECTIVE: To present a series of 11 patients treated with a PED and to discuss the management and results of this novel application of flow diverters. METHODS: Medical records of patients who presented with IC-RBA from May 2011 to March 2013 were retrospectively reviewed at 6 institutions in the United States. All relevant data were independently compiled. RESULTS: A total of 12 IC-RBAs in 11 patients were treated during the study period. Nine (75%) were treated with a single PED; 1 was treated with 2 PEDs; 1 was treated with coils and 1 PED; and 1 was treated with coils and 2 PEDs. Three (27%) had major perioperative complications: middle cerebral artery territory infarction, vision loss, and death. Seven patients demonstrated complete obliteration of the aneurysm in postoperative imaging. Early clinical outcomes were favorable (modified Rankin Scale score, 0-2) in all 10 survivors. CONCLUSION: This study demonstrates the feasibility and safety of using the PED to treat IC-RBA with fair initial results. The proper introduction and management of antiplatelet regimen are key for successful results. Bleeding complications related to dual antiplatelet therapy were similar to those in previous studies of stent-assisted coiling for the same population. Larger cohort analysis is needed to define the precise role of flow diverters in the treatment of IC-RBA.

Solitaire Flow Restoration thrombectomy for acute ischemic stroke: retrospective multicenter analysis of early postmarket experience after FDA approval.

BACKGROUND: The promising results of the Solitaire Flow Restoration (FR) With the Intention for Thrombectomy (SWIFT) trial recently led to Food and Drug Administration (FDA) approval of the Solitaire FR stent retriever device for recanalization of cerebral vessels in patients with acute ischemic stroke. OBJECTIVE: To report the early postmarket experience with this device since its FDA approval in the United States, which has not been previously described. METHODS: We conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between March 2012 and July 2012 at 10 United States centers where the Solitaire FR was used as a single device or in conjunction with other intraarterial endovascular approaches. RESULTS: A total of 101 patients were identified (mean age, 64.7 years; mean admission National Institutes of Health Stroke Scale [NIHSS] score, 17.6). Intravenous thrombolysis was administered in 39% of cases; other endovascular techniques were utilized in conjunction with the Solitaire FR in 52%. Successful recanalization (Thrombolysis in Myocardial Infarction 2/3) was achieved in 88%. The rate of symptomatic intracranial hemorrhage within the first 24 hours was 15%. In-hospital mortality was 26%. At 30 days, 38% of patients had favorable functional outcome (modified Rankin scale score ≤2). Severity of NIHSS score on admission was a strong predictor of poor outcome. CONCLUSION: Our study shows that a variety of other endovascular approaches are used in conjunction with Solitaire FR in actual practice in the United States. Early postmarket results suggest that Solitaire FR is an effective tool for endovascular treatment of acute ischemic stroke.

CFTR: a cysteine at position 338 in TM6 senses a positive electrostatic potential in the pore.

We investigated the accessibility to protons and thiol-directed reagents of a cysteine substituted at position 338 in transmembrane segment 6 (TM6) of CFTR to test the hypothesis that T338 resides in the pore. Xenopus oocytes expressing T338C CFTR exhibited pH-dependent changes in gCl and I-V shape that were specific to the substituted cysteine. The apparent pKa of T338C CFTR was more acidic than that expected for a cysteine or similar simple thiols in aqueous solution. The pKa was shifted toward alkaline values when a nearby positive charge (R334) was substituted with neutral or negatively charged residues, consistent with the predicted influence of the positive charge of R334, and perhaps other residues, on the titration of a cysteine at 338. The relative rates of chemical modification of T338C CFTR by MTSET+ and MTSES- were also altered by the charge at 334. These observations support a model for CFTR that places T338 within the anion conduction path. The apparent pKa of a cysteine substituted at 338 and the relative rates of reaction of charged thiol-directed reagents provide a crude measure of a positive electrostatic potential that may be due to R334 and other residues near this position in the pore.