Pederson, John M.

OBJECTIVE Cerebral revascularization surgery (CRS) has been used to prevent stroke in children with sickle cell disease (SCD) and cerebral vasculopathy (e.g., moyamoya syndrome). While results suggest that it may be an effective treatment, surgical indications have not been well defined. This study sought to determine indications for offering revascularization surgery in centers with established sickle cell programs in the US. METHODS Three sequential surveys utilizing the Delphi methodology were administered to neurosurgeons participating in the Stroke in Sickle Cell Revascularization Surgery study. Respondents were presented with clinical scenarios of patients with SCD and varying degrees of ischemic presentation and vasculopathy, and the group’s agreement to offer surgical revascularization was measured. Consensus was defined as ≥ 75% similar responses. RESULTS The response rate to all 3 surveys was 100%. Seventeen neurosurgeons from 16 different centers participated. The presence of moyamoya collaterals (MMCs) and arterial stenosis matching an ischemic distribution yielded the strongest recommendations to offer surgery. There was consensus to offer revascularization in the presence of MMCs and at least 50% arterial stenosis matching an ischemic distribution. In contrast, there was no consensus to offer revascularization with 50%–70% stenosis not matching an ischemic presentation in the absence of MMCs. The presence of the ivy sign in the distribution of the stenotic artery also contributed to the consensus to offer surgery in certain scenarios. CONCLUSIONS There were several clinical scenarios that attained consensus to offer surgery; the strongest was moderate to severe arterial stenosis that matched the distribution of ischemic presentation in the presence of MMCs. Radiological findings of decreased cerebral flow or perfusion also facilitated attaining consensus to offer surgery. The findings of this study reflect expert opinion about questions that deserve prospective clinical research. Determination of indications for CRS can guide clinical practice and aid the design of prospective studies.

Background Balloon guide catheters (BGCs) can be used adjunctively during mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Evaluating the potential economic impact associated with adjunctive BGC use is an important consideration for resource allocation. Methods Decision tree models were used to estimate the economic value of BGC use in MT through its impact on functional outcomes. Healthcare utilization cost estimates in the short- and long-term for patients with different 90-day mRS scores were analyzed for MT-only and MT + BGC scenarios. Deterministic (one-way) and probabilistic sensitivity analyses were performed to evaluate the robustness and uncertainty of model parameters. Results Per-patient index hospitalization cost was estimated at $65,260 for MT-only and $62,883 for MT + BGC scenarios. Per-patient one-year post-index hospitalization cost was estimated at $27,569 for MT-only and $24,830 for MT + BGC. MT + BGC had a total cost savings of $5117 compared with MT-only. Deterministic (one-way) sensitivity analysis demonstrated that cost saving per patient was most sensitive to the proportion of patients in the mRS 0–2 category in both MT + BGC and MT-only. In a probabilistic sensitivity analysis, mean per-patient costs for the index hospitalization were estimated at $63,737 for MT-only and $61,425 for MT + BGC. Mean per-patient cost estimates one-year post-index hospitalization was $27,445 for MT-only and $24,715 for MT + BGC. MT + BGC had a total cost savings of $5043 compared with MT-only. Conclusion Mechanical thrombectomy with adjunctive BGC use may reduce short-term and long-term patient costs due to improved functional outcomes when compared to MT treatment alone for AIS.

Aim: Stent-retriever (SR) thrombectomy has demonstrated superior outcomes in patients with acute ischemic stroke compared with medical management alone, but differences among SRs remain unexplored. We conducted a Systematic Review/Meta-Analysis to compare outcomes between three SRs: EmboTrap ® , Solitaire™, and Trevo ® . Methods: We conducted a PRISMA-compliant Systematic Review among English-language studies published after 2014 in PubMed/MEDLINE that reported SRs in ≥25 patients. Functional and safety outcomes included 90-day modified Rankin scale (mRS 0-2), mortality, symptomatic intracranial hemorrhage (sICH), and embolization to new territory (ENT). Recanalization outcomes included modified thrombolysis in cerebral infarction (mTICI) and first-pass recanalization (FPR). We used a random effects Meta-Analysis to compare outcomes; subgroup and outlier-influencer analysis were performed to explore heterogeneity. Results: Fifty-one articles comprising 9,804 patients were included. EmboTrap had statistically significantly higher rates of mRS 0-2 (57.4%) compared with Trevo (50.0%, p = 0.013) and Solitaire (45.3%, p < 0.001). Compared with Solitaire (20.4%), EmboTrap (11.2%, p < 0.001) and Trevo (14.5%, p = 0.018) had statistically significantly lower mortality. Compared with Solitaire (7.7%), EmboTrap (3.9%, p = 0.028) and Trevo (4.6%, p = 0.049) had statistically significantly lower rates of sICH. There were no significant differences in ENT rates across all three devices (6.0% for EmboTrap, 5.3% for Trevo, and 7.7% for Solitaire, p = 0.518). EmboTrap had numerically higher rates of recanalization; however, no statistically significant differences were found. Conclusion: The results of our Systematic Review/Meta-Analysis suggest that EmboTrap may be associated with significantly improved functional outcomes compared with Solitaire and Trevo. EmboTrap and Trevo may be associated with significantly lower rates of sICH and mortality compared with Solitaire. No significant differences in recanalization and ENT rates were found. These conclusions are tempered by limitations of the analysis including variations in thrombectomy techniques in the field, highlighting the need for multi-arm RCT studies comparing different SR devices to confirm our findings.

Background The benefit of mechanical thrombectomy (MT) and efficacy of different first-line MT techniques remain unclear for distal and medium vessel occlusions (DMVOs). In this systematic review, we aimed to compare the performance of three first-line MT techniques in DMVOs. Methods The PubMed database was searched for studies examining the utility of MT in DMVOs (middle cerebral artery M2-3-4, anterior cerebral artery, and posterior cerebral artery). Studies providing data for aspiration thrombectomy (ASP), stent retriever thrombectomy (SR), and combined SR+ASP technique were included. Non-comparative studies were excluded. Safety and efficacy data were collected for each technique. The Nested Knowledge AutoLit platform was utilized for literature search, screening, and data extraction. Pooled data were presented as descriptive statistics. Results 13 studies comprising 2422 MT procedures were identified. The overall successful recanalization rate was 77.0% (1513/1964) for DMVOs. SR+ASP had a successful recanalization rate of 83.7% (297/355), SR had a 75.6% rate (638/844), while ASP alone had a 74.2% rate (386/520). The overall functional independence rate was 51.3% (851/1659) among DMVOs. The ASP alone group had a functional independence rate of 46.9% (219/467), while functional independence rates of the SR and SR+ASP groups were 51.5% (372/723) and 61.7% (174/282), respectively. Finally, the subarachnoid hemorrhage rates were 1.8% (4/217) for the ASP group, 9.3% (26/281) for the SR group, and 11.9% (41/344) for the SR+ASP group. Conclusions Our systematic review supports the proposition that MT is a safe and effective treatment option for DMVOs. Additionally, while the SR+ASP group had consistently high rates of clot clearance and good neurological outcomes, the SR and SR+ASP groups also had higher rates of subarachnoid hemorrhage, highlighting the need for improved DMVO treatment devices.

Background Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke attributable to the anterior circulation large‐vessel occlusion. Randomized trials of patients with posterior circulation large‐vessel occlusion (PC‐LVO) have failed to show a benefit of EVT over medical therapy (MEDT). We performed a systematic review and meta‐analysis to understand better whether EVT is beneficial for PC‐LVO. Methods Using the Nested Knowledge AutoLit living review platform, we identified randomized control trials and prospective studies that reported functional outcomes in patients with PC‐LVO treated with EVT versus MEDT. The primary outcome variable was 90‐day modified Rankin scale score of 0 to 3, and secondary outcome variables included 90‐day modified Rankin scale score of 0 to 2, 90‐day mortality, and rate of symptomatic intracranial hemorrhage. A separate random effects model was fit for each outcome measure to calculate pooled odds ratios. Results Three studies with 1248 patients, 860 in the EVT arm and 388 in the MEDT arm, were included in the meta‐analysis. The favorable outcome rate (modified Rankin scale score of 0–3) in patients undergoing EVT was 39.9% (95% CI, 30.6%–50.1%) versus 24.5% in patients undergoing MEDT (95% CI, 9.6%–49.8%). Patients undergoing EVT had higher modified Rankin scale score of 0 to 2 rates (31.8% [95% CI, 25.7%–38.5%] versus 19.7% [95% CI, 7.4%–42.7%]) and lower mortality (42.1% [95% CI, 35.9%–48.6%] versus 52.8% [95% CI, 33.3%–71.5%]) compared with patients undergoing MEDT, but neither result was statistically significant. Patients undergoing EVT were more likely to develop symptomatic intracranial hemorrhage (odds ratio, 10.36; 95% CI, 3.92–27.40). Conclusions EVT treatment of PC‐LVO trended toward superior functional outcomes and reduced mortality compared with MEDT despite a trend toward increased symptomatic intracranial hemorrhage in patients undergoing EVT. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MEDT in patients with PC‐LVO.

Background and Purpose: Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke (AIS) due to large vessel occlusion of the anterior circulation (AC-LVO). Randomized trials of posterior circulation large vessel occlusion (PC-LVO) patients have failed to show a benefit of EVT over medical therapy (MEDT). We performed a systematic review and meta-analysis to understand better whether EVT is beneficial for PC-LVO. Methods: Using the Nested Knowledge AutoLit living review platform, we identified randomized control trials and prospective studies that reported functional outcomes in patients with PC-LVO treated with EVT versus MEDT. The primary outcome variable was 90-day modified Rankin Scale (mRS) 0-3, and secondary outcome variables included 90-day mRS 0-2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure to calculate pooled odds ratios. Results: Three studies with 1,248 patients, 860 in the EVT arm and 388 in the MEDT arm, were included in the meta-analysis. The favorable outcome rate (mRS 0-3) in EVT patients was 39.9% (95% CI: 30.6-50.1%) versus 24.5% in MEDT patients (95% CI: 9.6-49.8%). EVT patients had higher mRS 0-2 rates (31.8% [95% CI: 25.7-38.5%] versus 19.7% [95% CI: 7.4-42.7%]) and lower mortality (42.1% [95% CI: 35.9-48.6%] versus 52.8% [95% CI: 33.3-71.5%]) compared to MEDT patients, but neither result was statistically significant. EVT patients were more likely to develop sICH (OR=10.36; 95% CI: 3.92-27.40). Conclusions: EVT treatment of PC-LVO trended toward superior functional outcomes and reduced mortality compared to MEDT despite a trend toward increased sICH in EVT patients. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MEDT in PC-LVO patients.

Background and aim The use of endoluminal flow diversion in bifurcation aneurysms has been questioned due to the potential for complications and lower occlusion rates. In this study we assessed outcomes of endovascular treatment of intracranial sidewall and bifurcation aneurysms with flow diverters Methods In July 2020, a literature search for all studies utilizing endoluminal flow diverter treatment for sidewall or bifurcation aneurysms was performed. Data were collected from studies that met our inclusion/exclusion criteria by two independent reviewers and confirmed by a third reviewer. Using random-effects meta-analysis the target outcomes including overall complications (hematoma, ischemic events, minor ischemic stroke, aneurysm rupture, side vessel occlusion, stenosis, thrombosis, transient ischemic stroke, and other complications), perioperative complications, and follow-up (long-term) aneurysm occlusion were intestigated. Results Overall, we included 35 studies with 1084 patients with 1208 aneurysms. Of these aneurysms, 654 (54.14%) and 554 (45.86%) were classified as sidewall and bifurcation aneurysm, respectively, based on aneurysm location. Sidewall aneurysms had a similar total complication rate (R) of 27.12% (95% CI, 16.56%–41.09%), compared with bifurcation aneurysms (R, 20.40%, 95% CI, 13.24%–30.08%) (p = 0.3527). Follow-up angiographic outcome showed comparable complete occlusion rates for sidewall aneurysms (R 69.49%; 95%CI, 62.41%–75.75%) and bifurcation aneurysms (R 73.99%; 95% CI, 65.05%–81.31%; p = 0.4328). Conclusions This meta-analysis of sidewall and bifurcation aneurysms treated with endoluminal flow diverters demonstrated no significant differences in complications or occlusion rates. These data provide new information that can be used as a benchmark for comparison with emerging devices for the treatment of bifurcation aneurysms.

Abstract Background: Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19. Methods: We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection. Results: A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections. Conclusion: Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.

AbstractThe purpose of this systematic review and meta‐analysis was to examine clinical outcomes associated with convalescent plasma therapy in COVID‐19 patients. We performed a literature search on PubMed, medRxiv, Web of Science, and Scopus to identify studies published up to December 10th, 2020 that examined the efficacy of convalescent plasma treatment for COVID‐19. The primary endpoints were mortality, clinical improvement, and hospital length of stay. We screened 859 studies that met the search criteria, performed full‐text reviews of 56 articles, and identified 15 articles that fulfilled inclusion criteria for meta‐analysis. The odds of mortality were significantly lower in the convalescent plasma group compared to the control group (OR = 0.59 [95% CI = 0.44; 0.78], P < .001), although results from two key randomized controlled trials did not support the mortality benefit. The odds of clinical improvement were significantly higher in the convalescent plasma group compared to the control group (OR = 2.02 [95% CI = 1.54; 2.65], P < .001). There was no difference in hospital length of stay between the convalescent plasma group and the control group (MD = −0.49 days [95% CI = −3.11; 2.12], P = .713). In all, these data indicate that a mortality benefit with convalescent plasma is unclear, although there remain benefits with convalescent plasma therapy for COVID‐19.