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Background and Objectives: Although previous trials have established the efficacy and safety of endovascular thrombectomy (EVT) in large ischemic core strokes, most of them excluded patients with extracranial internal carotid artery (e-ICA) occlusion. We aimed to compare outcomes in patients with e-ICA occlusion and large ischemic core infarcts treated with EVT vs medical management (MM)., Methods: This was a secondary analysis of the SELECT2 trial, a randomized controlled trial conducted at 31 international sites. Adult patients with proximal intracranial anterior circulation large ischemic strokes, defined as Alberta Stroke Program Early CT Score (ASPECTS) 3-5 on noncontrast CT or ischemic core ≥50 mL on CT-perfusion/magnetic resonance-diffusion imaging, and concomitant e-ICA occlusion were selected. The primary outcomes were the distribution of modified Rankin Scale (mRS) score at 90-day follow-up and symptomatic intracranial hemorrhage (sICH)., Results: Among 352 enrolled patients, 62 (17.6%) with e-ICA occlusions were included. Of those 62 patients, 37 received EVT (median [interquartile range (IQR)] age, 65 [58-71] years; 15 women [38.5%]) and 25 received MM (median [IQR] age, 66 [61-71] years; 7 women [28%]). ASPECTS (EVT: 5 [3-5] vs MM: 5 [4-5]) and ischemic core volume (EVT: 100 [69-134] mL vs MM: 103 [78-135] mL) were similar between groups. The successful reperfusion rate with EVT was 64.9%. Patients receiving EVT demonstrated significantly better functional outcomes (adjusted generalized odds ratio 2.51; 95% CI 1.43-4.39; p = 0.001) and a higher proportion of patients achieving 90-day independent ambulation (EVT: 37.8% vs MM: 8%; adjusted relative ratio [aRR] 4.58; 95% CI 1.18-17.79; p = 0.037) and functional independence (EVT: 21.6% vs MM: 8%; aRR 2.16; 95% CI 0.53-8.83; p = 0.285). Furthermore, no heterogeneity of EVT benefit was observed by the presence or absence of e-ICA occlusion ( p -interaction = 0.248). There were no sICH or parenchymal hemorrhage type 2 events in either group, and mortality was similar in the 2 groups (aRR 0.75; 95% CI 0.39-1.45; p = 0.388)., Discussion: Among patients with e-ICA occlusions and large ischemic core stroke, EVT was associated with better functional outcomes without significant safety concerns when compared with MM. Our findings suggest that EVT in these patients is beneficial, while the optimal treatment of the extracranial carotid occlusion remains unclear., Trial Registration Information: Name of the trial: SELECT2 trial. Registration number: ClinicalTrials.gov Identifier: NCT03876457. Date of registration submission: August 3, 2019. Date of first patient enrollment: November 10, 2019., Classification of Evidence: This study provides Class II evidence that for patients with large core acute ischemic stroke and concomitant e-ICA occlusion, EVT is associated with better functional outcome at 90 days compared with MM alone.

Background: Cerebral venous thrombosis (CVT) is a rare condition that presents with significant treatment challenges and has traditionally been managed with anticoagulation. However, for patients who fail anticoagulation or present with severe symptoms, endovascular thrombectomy (EVT) has emerged as a favorable treatment modality. This study examines the outcomes, complications, and comorbidities associated with EVT in patients with CVT., Methods: A query of the 2015-2019 National (Nationwide) Inpatient Sample was performed for patients admitted to hospitals with ICD-10 diagnosis codes for CVT and ICD-10 procedure codes for usage of EVT. Demographic information, baseline comorbidities, complications, and discharge dispositions were compared between patients who underwent EVT and those who were managed medically., Results: A total of 36,005 patients diagnosed with CVT were identified from 2015(Q4) to 2019. Of these patients, 325 (0.9%) received EVT. Patients who underwent EVT were older (<0.001), more likely to be female (p = 0.016), and had higher rates of diabetes mellitus (p = 0.012), hypertension (p < 0.001), and obesity (p < 0.001). These patients also presented with more severe neurological symptoms, including higher National Institutes of Health Stroke Scale scores (p < 0.001), coma (p < 0.001), and cerebral edema (p < 0.001). Patients undergoing EVT had a higher incidence of in-hospital mortality (p = 0.007) and were less likely to be discharged routinely (p < 0.001)., Conclusions: This study found that patients with CVT who underwent EVT were older, more likely to be female, and presented with more severe neurological conditions. After controlling for severity, EVT in patients with CVT was associated with significant risks, including higher rates of complications and inpatient mortality. Although EVT is associated with significant risks, the findings of this study suggest that its outcomes may reflect the severity of the underlying condition rather than the procedure itself. Careful patient selection and individualized management strategies are essential for optimizing outcomes in this high-risk population., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chronic subdural hematoma (cSDH) is increasingly prevalent in the elderly and traditionally treated with surgical interventions. Middle meningeal artery embolization (MMAE) has emerged as an adjunctive therapy to reduce recurrence rates. Transfemoral access (TFA) is the conventional route for neuroendovascular procedures, but transradial access (TRA) offers potential advantages, including reduced access-site complications, earlier ambulation, and shorter hospital stays., Objective: The aim of this systematic review and meta-analysis was to compare the safety and efficacy of TRA versus TFA for MMAE in cSDH patients., Methods: This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and involved a comprehensive search of four databases to identify studies comparing TRA and TFA in MMAE. Outcomes included hematoma recurrence, hospital length of stay, procedural duration, access-site complications, and overall complications., Results: Four studies met the inclusion criteria. There were no significant differences between TRA and TFA in hematoma recurrence (Relative Risk (RR) 0.65, 95 % Confidence Interval [CI] 0.09-4.85), hospital length of stay (Mean Difference [MD] 0.10 days, 95 % CI -0.11-0.31), procedural duration (MD 0.04 h, 95 % CI -0.49-0.56), access-site complications (RR 0.24, 95 % CI 0.04-1.40), or overall complications (RR 0.76, 95 % CI 0.33-1.75)., Conclusion: TRA demonstrates comparable safety and efficacy to TFA for MMAE in cSDH patients. Although current evidence is limited to observational studies, these findings support the feasibility of TRA as an access route. Future large-scale studies are necessary to validate these results and optimize procedural strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Data about the safety and the efficacy of flow diversion for distal anterior cerebral artery (DACA) aneurysms are limited. We present the largest multicenter analysis evaluating the outcomes of flow diversion in unruptured DACA aneurysm treatment., Methods: Databases from 39 centers were retrospectively reviewed for unruptured DACA aneurysms treated with flow-diverting stents. Demographics, clinical presentation, radiographic characteristics, procedural complications, and outcomes were assessed., Results: A total of 168 patients with 168 unruptured DACA aneurysms were treated between January 2018 and December 2022. One hundred and twenty-five were women (74.4%) and the median age was 61 (IQR 52-67) years. The most common morphology was saccular (91.7%), with branch involvement in 61.9% of cases. Median parent vessel diameter was 1.9 mm (IQR 1.7-2.2) and stents were successfully deployed in 99.4% of cases. In 96.4% a single stent was implanted, while 3.6% of cases required two stents. Median imaging follow-up was 16.5 (IQR 7-24) months. At last follow-up the rate of occlusion (O'Kelly-Marotta scale C or D) was 82.1%. Symptomatic thromboembolic or hemorrhagic complications occurred in 5.3% of patients and the mortality rate was 0.6%. The rate of retreatment was 1.2%., Conclusions: Flow-diverting stents are a reasonably safe and effective treatment option for unruptured DACA aneurysms., Competing Interests: Competing interests: TM: Outside the submitted work, received lecturer’s fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Pfizer, Tsumura and UCB; manuscript fee from Pfizer; advisory board for GlaxoSmithKline, Novartis and Teijin. FS: Outside the submitted work received lecturer’s fee from Idorsia Pharmaceuticals for the past 36 months. OG: Outside the submitted work, MicroVention proctor for the WEB device, Stryker consultant, Route 92 consultant.ML: Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, AIDoc and Arsenal Medical; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. AMA: educational grants from Medtronic, Stryker, Balt and Microvention/Terumo unrelated to the current study. AP: educational grants from Medtronic, Stryker, Balt and Microvention/Terumo unrelated to the current study. AEH: Consultant/Speaker: Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care, Galaxy Therapeutics, Route 92, Perfuze, CorTech, Shockwave, Toro and Xcath. Principal Investigator: COMPLETE study – Penumbra, LVO SYNCHRONISE – Viz.ai, MARRS - Perfuze, RESCUE - ICAD - Medtronic. Steering Committee/Publication committee member: SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR, ENVI, DELPHI, DISTALS. DSMB - COMAND trial. ML Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, AIDoc and Arsenal Medical; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. FC reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work. CC consultant for Medtronic, Microvention, Cerenovus, Stryker, Anaconda, unrelated to the current study., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite the widespread use of heparin during and following endovascular procedures in the management of aneurysmal subarachnoid hemorrhage (SAH) patients, limited research has explored the incidence and impact of heparin-induced thrombocytopenia (HIT) on SAH., Methods: Descriptive statistics, multivariate regressions, and propensity score-matching were employed to compare clinical characteristics, comorbidities, interventions, complications, and outcomes of HIT in SAH patients identified within the US National Inpatient Sample database from 2010 to 2019., Results: Among 76 387 SAH patients from 2010 to 2019, 166 (0.22%) developed HIT. HIT was identified as a significant predictor of prolonged length of stay (OR 6.799, 95% CI 3.985 to 11.6, P<0.01) and poor functional outcomes (OR 2.541, 95% CI 1.628 to 3.966, P<0.01) after adjusting for relevant factors. HIT incidence was higher in patients with elevated SAH severity scores (1.42 vs 1.06, P<0.01), younger patients (58.04 vs 61.39 years, P=0.01), overweight individuals (0.4% vs 0.2%, P<0.01), those on long-term anticoagulants (10.84% vs 5.72%, P<0.01), or with a cerebrospinal fluid drainage device (external ventricular drain, ventriculoperitoneal shunt; P<0.01). HIT patients showed increased rates of endovascular coiling, ventricular drain placement, shunt placement, deep vein thrombosis, urinary tract infection, acute kidney injury, pulmonary embolism, venous sinus thrombosis, pneumonia, and cerebral vasospasm (all P<0.01)., Conclusion: SAH patients with HIT exhibited various comorbidities and increased rates of complications, which may contribute to extended hospital stays. This nationwide study aids clinical suspicion and highlights HIT's impact on SAH patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Owing to the relative rarity of unruptured intracranial aneurysms (UIAs) in the pediatric population, evidence regarding treatment modalities and clinical outcomes remains limited., Objective: To characterize the use and clinical outcomes of endovascular therapy (EVT) and microsurgical clipping (MSC) for pediatric UIAs over a two-decade interval using a large national registry., Methods: Pediatric (<18 years of age) UIA hospitalizations were identified in the National Inpatient Sample from 2002 to 2019. Temporal use and clinical outcomes were compared for treatment with EVT and MSC., Results: Among 734 UIAs identified, 64.9% (n=476) were treated with EVT. Use of EVT significantly increased during the study period from 54.3% (2002-2004) to 78.6% (2017-2019) (P=0.002 by Cochrane-Armitage test). In comparison with those treated with MSC, pediatric patients treated with EVT demonstrated higher rates of favorable outcomes (discharge to home without services) (96.0% vs 91.1%, P=0.006), shorter durations of hospital stay (4.6 vs 10.0 days, P<0.001), and lower rates of ischemic or hemorrhagic procedural-related complications (1% vs 4%, P=0.010). Conservative management also increased significantly over the study period (P<0.001 by Cochrane-Armitage test)., Conclusion: A retrospective evaluation of nearly 20 years of population-level data from the United States demonstrates increasing use of EVT for the treatment of pediatric UIAs, with high rates of favorable outcomes and shorter hospital stays in comparison with those treated with microsurgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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 (P interaction =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., Competing Interests: Competing interests: MC has received consulting fees from Medtronic and Microvention. AH has received grants from RESCUE - ICAD – Medtronic. He has also reported consulting fees from Medtronic, Microvention, Stryker, and Cerenovus. SO-G has received grants from Stryker Neurovascular and Microvention. He has also received modest consulting fees from Medtronic, Stryker Neurovascular, and Microvention. JB is a member of the speakers’ bureau for Stryker Neurovascular and Microvention, and holds leadership roles in Inspire S and A registries (Medtronics). TNN is a DSMB member for the SELECT2 trial and has received grants from Medtronic. SD is a DSMB member for the SELECT2 trial and on the advisory board for Medtronic. JF and LW are DSMB members for the SELECT2 trial. GA reports compensation from iSchemaView for consultant services; and stock holdings in iSchemaView. AS has received grant support from Stryker Neurovascular for the SELECT2 trial. He is also a member of the speaker’s bureau and advisory board for Stryker Neurovascular. The other authors have no competing interest relevant to this study., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objective: Among patients with large vessel occlusion (LVO) and large ischemic cores, critical decisions often need to be made about decompressive hemicraniectomy (DHC) or early withdrawal of life-sustaining therapy (WLST). In this study, we aimed to evaluate utilization of DHC and early WLST and factors associated with them in patients with large strokes from the SELECT2 trial., Methods: We analyzed the entire SELECT2 trial population, which randomized 352 patients with stroke due to LVO and large ischemic cores to endovascular thrombectomy (EVT) or medical management. We used the as-treated principle to compare the use of DHC and early WLST within 7 days after randomization. We further assessed functional outcomes (modified Rankin Score) after these decisions., Results: Of 352 patients enrolled in this study, 55 received DHC and 81 transitioned to early WLST. Patients treated with EVT were as likely to undergo DHC (16% vs 15%, adjusted relative risk [aRR] = 1.19, 95% CI:0.75-1.88, p = 0.46) or WLST (22% vs 24%, aRR = 0.94, 95% CI: 0.66-1.34, p = 0.72) as those given medical management. DHC was used more frequently in younger patients and WLST more in older patients. EVT efficacy was maintained after adjusting for DHC (adjusted generalized odds ratio [aGenOR] = 1.68, 95% CI: 1.24-2.11, p < 0.001), with no interaction between DHC and treatment (p-interaction = 0.93). At 1 year, 21% of DHC-treated patients were ambulatory; the outcomes were universally poor after early WLST., Interpretation: In the SELECT2 trial of patients with large ischemic core, DHC was performed in ~1 of 6 patients and early WLST in ~1 of 5 patients, without differences based on treatment with EVT or medical management, nor successful reperfusion. DHC or WLST did not detract from thrombectomy treatment benefit. Additionally, ~20% of patients achieved independent ambulation despite receiving DHC by the 1-year follow-up. The similar distribution of these critical care decisions provides reassurance that the overall trial outcomes were not biased by open-label treatment allocation. ANN NEUROL 2024., (© 2024 American Neurological Association.)

Background/objectives: Recent studies reveal an "obesity paradox", suggesting better clinical outcomes after intracranial hemorrhage for obese patients compared to patients with a healthy BMI. While this paradox indicates improved survival rates for obese individuals in stroke cases, it is unknown whether this trend remains true across all forms of intracranial hemorrhage. Therefore, the objective of our study was to investigate the incidence, characteristics, and outcomes of hospitalized obese patients with intracranial hemorrhage., Methods: The National Inpatient Sample (NIS) database was queried for data from 2015 to 2019 to identify adult patients aged 18 years and older with a primary diagnosis of non-traumatic intracranial hemorrhage. Using International Classification of Disease 10th Edition codes, patients were stratified by BMI categories: healthy weight, overweight, class I-II obesity, and class III obesity. The cohorts were examined for demographic characteristics, comorbidities, stroke severity, inpatient complications, interventions, and clinical outcomes, including length of stay (LOS), discharge disposition, and inpatient mortality., Results: Of 41,960 intracranial hemorrhage patients identified, 13,380 (33.0%) also had an obese BMI. Class I-II obese intracranial hemorrhage patients were more likely to be of white race (OR: 1.101, 95% CI: 1.052, 1.152, p < 0.001), less likely to be female (OR: 0.773, 95% CI: 0.740, 0.808, p < 0.001), and more likely to have diabetes mellitus (OR: 1.545, 95% CI: 1.477, 1.616, p < 0.001) and hypertension (OR: 1.828, 95% CI: 1.721, 1.943, p < 0.001) in comparison to healthy-weight patients. In a matched cohort analysis adjusting for demographics and severity, intracranial hemorrhage patients with class I-II obesity had a shorter length of stay (LOS) (OR 0.402, 95% CI: 0.118, 0.705, p < 0.001), reduced inpatient mortality (OR 0.847, 95% CI: 0.798, 0.898, p < 0.001), and more favorable discharge disposition (OR 1.395, 95% CI: 1.321, 1.474, p < 0.001) compared to their healthy-weight counterparts. Furthermore, these patients were less likely to require decompressive hemicraniectomy (OR 0.697, 95% CI: 0.593, 0.820, p < 0.001). Following an analysis of individual ICH subtypes, obese subarachnoid hemorrhage (SAH) patients demonstrated reduced mortality (OR: 0.692, 95% CI: 0.577-0.831, p < 0.001) and LOS (OR: 0.070, 95% CI: 0.466-0.660, p = 0.039), with no differences in discharge disposition. Similarly, intracerebral hemorrhage patients demonstrated reduced mortality (OR: 0.891, 95% CI: 0.827-0.959, p = 0.002) and LOS (OR: 0.480, 95% CI: 0.216-0.743, p < 0.001). Other ICH subtypes showed improved discharge outcomes (OR: 1.504, 95% CI: 1.368-1.654, p < 0.001), along with decreased mortality (OR: 0.805, 95% CI: 0.715-0.907, p < 0.001) and LOS (OR: -10.313, 95% CI: -3.599 to -2.449, p < 0.001)., Conclusions: Intracranial hemorrhage patients with class I-II obesity exhibited more favorable clinical outcomes than those who were of a healthy weight or overweight. Despite its association with risk factors contributing to intracranial hemorrhage, class I-II obesity was associated with improved outcomes, lending support to the existence of the obesity paradox in stroke.

Endovascular thrombectomy (EVT) was shown to be safe and efficacious in patients with large core stroke in multiple randomized controlled trials. However, the impact of reperfusion and other procedural metrics on EVT outcomes in this population has not been well-characterized., Methods: From the SELECT2 trial, we evaluated the association between reperfusion status, first-pass effect (near-complete or complete reperfusion [extended thrombolysis in cerebral infarction (eTICI) 2c-3] in 1 pass), procedure time and primary technique (aspiration vs stent-retriever) with functional outcomes in patients receiving EVT across ASPECTS (3 vs 4 vs 5) and core estimate strata (<70 vs ≥70ml, <100 vs ≥100ml, and <150 vs ≥150ml)., Results: Of 180 patients who received thrombectomy, 144 (80%) achieved successful reperfusion (eTICI 2b-3) and demonstrated better clinical outcomes (adjusted generalized odds ratios [aGenOR]: 1.48, 95% confidence interval [CI]: 1.01-2.15), compared with unsuccessful reperfusion. Results were consistent across ASPECTS and core estimate strata. Additionally, complete or near-complete reperfusion (eTICI 2c-3) was associated with better functional outcome (aGenOR: 1.99, 95% CI: 1.33-2.97) in patients achieving successful reperfusion. Functional outcome point estimates favored those with first-pass-effect (42 of 167 (25%), aGenOR: 1.46, 95% CI: 0.96-2.24). Longer procedure time was associated with worse modified Rankin scale (mRS) distribution (aGenOR: 0.92, 95% CI: 0.87-0.96, p-value = 0.001 for 10 minutes increment). Aspiration-first technique was used in 43 of 154 (25%) patients and was not associated with higher reperfusion (88% vs 78%, p = 0.18) or better functional outcome (aGenOR: 0.74, 95% CI: 0.50-1.10) as compared with stent-retriever first., Interpretation: Successful reperfusion resulted in improved clinical outcomes in large core patients across baseline ischemic core strata. Near complete or complete reperfusion was further associated with better outcomes, whereas prolonged procedures were associated with worse outcomes. Results were consistent regardless of the technique used. ANN NEUROL 2024., (© 2024 American Neurological Association.)

Glioblastoma (GBM) is categorized by the World Health Organization (WHO) as a grade 4 glioma and is a uniformly fatal tumor of the central nervous system. With the discovery of specific gene anomalies, GBM classification has been modified several times to provide better diagnostic and prognostic accuracy. Survival outcomes remain dismal despite the current therapeutic modalities, which include a combination of surgical resection, adjuvant chemotherapy, and radiotherapies, providing brief control of tumor progression. GBM remains aggressive and reoccurs primarily due to the presence of a unique population of untreatable glioblastoma stem cells (GSC). The presence of high mutation rates and a dysregulated transcriptional landscape increase GSC resistance to conventional chemotherapy and radiation therapy, contributing to poor outcomes seen in GBM patients. Accordingly, GSCs have emerged as targets of interest in new GBM treatment paradigms. Consequently, it is important to understand their distinct properties, such as GSC interactions with the hypoxic microenvironment, enhancing their growth. The epigenomic regulators and fundamental molecular components of the signaling pathways represent potential targets for GBM therapies. In this review, we aimed to describe the evolution of GBM classification and highlight the current therapeutic modalities, including gene and immunotherapies, and mammalian target of rapamycin (mTOR) inhibitors to target GBM. Furthermore, we explored the molecular pathway of GSCs and the ongoing investigation of circulating tumor cells (CTC), along with precision therapeutics, which aim to provide novel discoveries and effective treatments for GBM with improved survival., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Dural venous sinus stenting is an emerging and exciting area in otolaryngology in collaboration with neurosurgeons and neuroradiologists. The first cases were reported 20 years ago. It is now considered part of the routine treatment of increased intracranial pressure due to transverse sinus stenosis. ENT doctors are the first to see these patients in their clinics, as sinus headaches, pulsating tinnitus, and dizziness are the most common symptoms. Previously, with limited success, high-dose diuretics and intracranial shunts had been the only options for treating these patients. Other methods, such as covering the sigmoid sinuses with graft material, appear to cause a sudden increase in intracranial pressure that can lead to blindness and even death. This overview summarizes the clinical and imaging characteristics of patients who will benefit from endovascular sinus stenting for elevated intracranial pressure., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2024 American Neurological Association.)

Background: Migraine prevalence has been estimated to be as high as 25% during reproductive years. Despite this, and the known significantly lower odds of acute stroke being correctly diagnosed among women versus men, little is known about the migraine-stroke connection in this vulnerable population. Our study seeks to provide a consolidated examination of cerebrovascular and obstetric complications of migraines in pregnant women and to evaluate the role of concurrent comorbidities. Methods: We utilized the 2016-2020 Healthcare Cost and Utilization Project's National Inpatient Sample with the International Classification of Diseases, 10th Revision diagnostic codes to compare pregnant patients with migraines with those without migraines. Multivariable logistic regression was used to examine the incidence of subtypes of stroke while controlling for confounding variables. Results: Overall, 19,825,525 pregnant patients were evaluated; 219,175 (1.1%) had a concomitant diagnosis of migraine. Pregnant patients with migraines were more likely to suffer ischemic (0.1% versus 0.0%) or hemorrhagic stroke (0.3% versus 0.1%). On multivariate analysis, acute ischemic stroke was most strongly associated with migraine with aura (odds ratio [OR], 23.26; 95% confidence interval [CI], 18.46-29.31), followed by migraine without aura (OR, 8.15; 95% CI, 4.79-13.88). Conclusions: Pregnant women with migraine are at a significantly increased risk for both ischemic and hemorrhagic stroke. Pregnant women with migraines should be cautioned that they may be at an increased risk of stroke, particularly if they are experiencing an aura, and encouraged to contact their medical providers to rule out neurological complications.

Catheter-based angiography is an essential procedure for the diagnosis and treatment of vascular complications in patients. Since cerebral and coronary angiography are similar techniques that utilize the same access sites and general principles, the associated risks overlap and should be identified to help direct patient care. The purpose of this study was to determine complication rates in a combined cohort of cerebral and coronary angiography patients, as well as conduct a comparative analysis of coronary and cerebral angiography complications. The National Inpatient Sample was queried from 2008 to 2014 to identify patients who underwent coronary or cerebral angiography. After assessment of baseline characteristics, complication rates, and disposition in the combined cohort, propensity matching was utilized to create sub-cohorts of coronary and cerebral angiography patients based on demographics and comorbidities. Comparative analysis of procedural complications and disposition was then performed. A total of 3,763,651 hospitalizations were included in our study cohort (3,505,715 coronary angiographies and 257,936 cerebral angiographies). The median age was 62.9 years, with females being 46.42%. The most prevalent comorbidities in the overall cohort were hypertension (69.92%), coronary artery disease (69.48%), smoking (35.64%), and diabetes mellitus (35.13%). Propensity matching demonstrated that the cerebral angiography cohort had lower rates of acute and unspecified renal failure (5.4% vs 9.2%, OR 0.57, 95% CI, 0.53-0.61, P < 0.001), hemorrhage/hematoma formation (0.8% vs 1.3%, OR 0.63, 95% CI, 0.54-0.73, P < 0.001), and equivalent rates of retroperitoneum hematoma formation (0.03% vs 0.04%, OR 1.49, 95% CI, 0.76-2.90, P = 0.247) and arterial embolism/thrombus formation (0.3% vs 0.3%, OR 1.01, 95% CI, 0.81-1.27, P = 0.900). Our study showed both cerebral and coronary angiography have generally low rates of procedural complications. Matched cohort analysis demonstrated that cerebral angiography patients are at no greater risk for complications than coronary angiography patients., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The conducting polymer polyaniline (PANI) has shown significant interest for the development of electrified membranes (EMs) with superior antifouling characteristics. However, the blending and doping of PANI with other polymers and nanomaterials highly influence the properties of the membrane surface. PANI exists in two forms: oxidized, known as emeraldine salt (ES), and unoxidized, referred to as emeraldine base (EB). Therefore, understanding the different forms of PANI and the variations between the oxidized and unoxidized forms along the length of the polymer chain is intriguing. In this paper, we present the design of a novel copolymer consisting of EB and ES monomers with varying charge densities and different segmental arrangements. We present various intra- and intermolecular structural properties of the PANI chains using all-atom molecular dynamics (MD) simulations. Herein, we present a detailed conformational free energy analysis to understand the conformational transitions of the PANI chains. Our results show increased radius of gyration ( R g ) values with increased charge density. Furthermore, we also present the H-bonding, free energy analysis, reduced density gradient (RDG), and solvent-accessible surface area (SASA) values for the observed conformational transitions of PANI. Therefore, these observations are crucial in understanding the complex behavior of chains for designing target-specific polymeric materials.

Background: Glioblastoma multiforme (GBM), a high-grade primary brain tumor, presents a formidable challenge in neuro-oncology because of its aggressive nature, infiltrative growth, and limited response to treatment. The septum pellucidum represents an uncommon and unexpected location for GBM, adding complexity to the diagnosis and management of this rare intracranial malignancy., Observations: A 69-year-old male with a previous history of prostate carcinoma presented to an outside hospital with a 2-week history of a "trance-like state" and cognitive decline. Initial head computed tomography showed prominent ventricles without distinct mass lesions. Upon admission, magnetic resonance imaging demonstrated a mass within the inferior septum pellucidum extending to the third and both lateral ventricles. Biopsy findings indicated a GBM, World Health Organization central nervous system tumor grade 4, with immunopositivity for glial fibrillary acidic protein and a Ki-67 labeling index of 60%-70%., Lessons: Identifying only 5 cases in more than 60 years of literature, this systematic review illustrates the diverse clinical presentations, diagnostic advancements, and management approaches for septum pellucidum GBM. https://thejns.org/doi/10.3171/CASE23770.

Background The proportion of women surgeons is increasing, but studies show that women in surgical residency are granted less autonomy than men. Objective We utilized the Surgical Autonomy Program (SAP), an educational framework, to evaluate gender differences in self-reported autonomy, attending-reported autonomy, and operative feedback among US neurosurgical residents. Methods The SAP tracks resident progression and guides teaching in neurosurgery. Surgeries are divided into zones of proximal development (opening, exposure, critical portion, and closure). Postoperatively, resident autonomy is rated on a 4-point scale by the resident and the attending for each part of the case, or zone. We utilized data from July 2017 to February 2024 from 8 institutions. Ordinal regression was used to evaluate the odds of self- and attending-evaluated autonomy, accounting for gender, training year, case difficulty, and institution. Differences between attending assessment and self-assessment were calculated across time. Chi-square analyses were used to measure any differences in feedback given to men and women. Results From 128 residents (32 women, 25%), 11894 cases were included. Women were granted less autonomy (OR 0.81; 95% CI 0.74-0.89; P <.001) and self-evaluated as having less autonomy (OR 0.73; 95% CI 0.67-0.80; P <.001). The odds of women operating at higher autonomy were similar to the odds of operating on a hard case compared to average difficulty (OR 0.77; 95% CI 0.71-0.84; P <.001). Men's and women's self-assessment became closer to attending assessment over time, with women improving more quickly for the critical portions of surgeries. Women residents received meaningful postoperative feedback on fewer cases (women: 74.2%, men: 80.5%; X 2 =31.929; P <.001). Conclusions Women operated with lower autonomy by both attending and self-assessment, but the assessment gap between genders decreased over time. Women also received less feedback from their attendings.

Background and Objectives: Although ventriculoperitoneal (VP) shunts are a common treatment for hydrocephalus, there are complication risks including infections. Late complications such as ventriculitis from ascending abdominal infections can have severe consequences. However, the incidence of central nervous system (CNS) infections in VP shunt patients with abdominal infections is not well understood. We aimed to determine the incidence of CNS infections in VP shunt patients admitted with abdominal infections., Methods: Using the National Inpatient Sample, we studied patients from 2016 to 2019 to determine the incidence of CNS infections in VP shunt patients admitted with abdominal infections. Results were compared with VP shunt patients admitted for primary pneumonia., Results: Among 725 VP shunt patients presenting with abdominal infections, 20 (2.8%) had CNS infections. Chronic obstructive pulmonary disease, hypertension, older age, and a smoking history were more common in patients with CNS infections and primary abdominal infection (P < .05). Patients who developed CNS infection had a significantly higher likelihood of both blood transfusion and coma but a lower likelihood of seizures. VP shunt patients with CNS infections were more likely to undergo shunt removal (odds ratio [OR] = 23.167, P < .001). 4.1% of VP shunt patients with primary abdominal infections died during admission. In a population of primary abdominal infection and pneumonia patients with VP shunts, a multivariate logistic regression analysis controlling for age, sex, and comorbidities identified abdominal infection as an independent risk factor for both CNS infection (OR = 51.208, P < .001) and inpatient death (OR = 3.417, P < .001). Among 6620 VP shunt patients admitted with primary pneumonia, only 5 (0.1%) had CNS infection compared with 20 (2.8%) in those with a primary abdominal infection (OR = 37.532, P < .001), and mortality was 1.6% vs 4.1% for those with a primary abdominal infection (P < .05)., Conclusion: CNS infections in VP-shunted patients with abdominal infections are relatively rare but may lead to increased risks of death and other serious adverse outcomes., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Purpose: Cerebral venous thrombosis (CVT) is associated with a high degree of morbidity and mortality. Our objective is to elucidate characteristics, treatments, and outcomes of patients with cancer and CVT (CA-CVT)., Methods: The 2016-2019 National Inpatient Sample (NIS) database was queried for patients with a primary diagnosis of CVT. Patients with a currently active diagnosis of malignancy (CA-CVT) were then identified. Demographics and comorbidities were compared between CA-CVT and CVT patients. Subgroup analyses explored patients with hematopoietic cancer and non-hematopoietic cancers. Stroke severity and treatment were explored. Inpatient outcomes studied were discharge disposition, length of stay, and mortality., Results: Between 2016 and 2019, 6,140 patients had a primary diagnosis code of CVT, and 370 (6.0%) patients had a coexisting malignancy. The most common malignancy was hematopoietic (n=195, 52.7%), followed by central nervous system (n=40, 10.8%), respiratory (n=40, 10.8%), and breast (n=40, 10.8%). These patients tended to be older than non-CA-CVT and were more likely to have coexisting comorbidities. CA-CVT patients had higher severity scores on the International Study of Cerebral Vein and Dural Sinus Thrombosis Risk Score (ISCVT-RS) and increased complications. In a propensity-score matched cohort, there were no differences in inpatient outcomes., Conclusion: Malignancy occurs in 6% of patients presenting with CVT and should be considered a potential comorbidity in instances where clear causes of hypercoagulabilty have not been identified. Malignancy was linked to higher mortality rates. Nonetheless, after adjusting for the severity of CVT, the outcomes for inpatients with cancer-associated CVT were comparable to those without cancer, indicating that the increased mortality associated with malignancy is probably due to more severe CVT conditions.

Objectives: Subarachnoid hemorrhage (SAH) from spontaneous aneurysm rupture is a debilitating condition with high morbidity and mortality. Patients with SAH remain understudied, particularly concerning the evaluation of incidence and consequences of subsequent acute kidney injury (AKI). In this study, we aim to explore the risk factors and outcomes of AKI in SAH patients., Materials and Methods: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were used to query the National Inpatient Sample (NIS) for patients with a diagnosis of SAH between 2010-2019. Subgroup analysis was stratified by AKI diagnosis during the same hospitalization. AKI and non-AKI groups were assessed for baseline clinical characteristics, interventions, complications, and outcomes. Descriptive statistics, multivariate regressions, and propensity score-matching were performed using IBM SPSS 28., Results: Of 76,553 patients diagnosed with nontraumatic SAH between 2010-2019, 10,634 (13.89 %) had a comorbid diagnosis of AKI. SAH patients with AKI were older (p < 0.01) and more often obese (p < 0.01) compared to the non-AKI group. A multivariate regression found the diagnosis of AKI to be independently correlated with poor functional outcome (p < 0.001), above average length of stay (p < 0.001), and in-hospital mortality (p < 0.001) when controlling for age, SAH severity, and other comorbidities., Conclusions: This study showed significant association between AKI and adverse outcomes in SAH patients, and a correlation between AKI and heightened complication rates, poor functional outcome, extended hospital stays, and elevated mortality rates. Early detection of AKI in SAH patients is vital to improve their chances of recovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Traumatic spinal injury (TSI) can lead to severe morbidity and significant health care resource utilization. Intraoperative navigation (ION) systems have been shown to improve outcomes in some populations. However, controversy about the benefit of ION remains. To our knowledge, there is no large database analysis studying the outcomes of ION on TSI patients. Here we hope to compare complications and outcomes in patients with TSI undergoing spinal fusion of 3 or more levels with or without the use of ION., Methods: The 2015-2019 National Surgical Quality Improvement Program (NSQIP) database was queried for cases of posterior spinal instrumentation of 3 or more levels. This population was then selected for postoperative diagnosis consistent with TSI. The effect of prolonged operative time was analyzed for all patients. Propensity score matching analysis was performed to create ION case and non-ION control groups. Baseline demographic characteristics, complications, and outcome data were collected and compared between ION and non-ION groups., Results: A total of 1,034 patients were included in the propensity matched analysis. Among comorbidities, only obesity was significantly more likely in the non-ION group. There was no difference in case complexity between the two groups. ION was associated with higher incidence of prolonged operative time but was a negative independent predictor for sepsis. Prolonged operative time was a significant independent predictor for pulmonary embolism and requirement of transfusion in all patients. Discharge to home, readmission, and reoperation rates did not differ between TSI patients with or without ION., Conclusions: Use of ION during posterior spinal fusion of 3 or more levels in TSI patients is not associated with worse outcomes. Prolonged operative time, rather than ION, appears to have a higher influence on the rate of complications in this population. Evaluation of ION in the context of specific populations and pathology is warranted to optimize its use.

Introduction: Renal cell carcinoma (RCC) has been associated with an increased risk for acute ischemic stroke (AIS). As individuals with cancer who experience AIS tend to face higher mortality rates compared to AIS patients without cancer, recognizing the implications of RCC in AIS is crucial for identifying high-risk patients for major complications and directing management strategies., Objective: To examine risk factors, interventions, and outcomes for patients with AIS stratified by their RCC diagnosis., Methods: The National Inpatient Sample (NIS) database was queried for the period 2010-2019 using International Classification of Disease 10th Edition (ICD-10) codes for acute ischemic stroke and renal malignancies. We assessed demographic information, comorbidities, and clinical interventions between patients presenting with AIS, with and without renal malignancies. A logistic regression model was employed to further examine mortality outcomes., Results: Among 1,609,817 patients identified with AIS, 2,068 (0.12%) had a concomitant diagnosis of RCC. AIS patients with RCC were older (72.09 yrs. vs. 70.9 yrs., p < 0.01), more often white (72.05% vs. 68.16%, p < 0.01), and had similar stroke severity scores. RCC patients received less tissue plasminogen activator (tPA; 4.98% vs. 6.2%, p = 0.02) but underwent endovascular mechanical thrombectomy (MT) at similar rates. RCC patients had more complications (p < 0.01) as well as longer hospital stays (8.19 days vs. 5.98 days, p < 0.01), and higher rates of mortality (11.27% vs. 5.63%, p < 0.01), when compared to their non-RCC counterparts. Propensity score-adjusted analysis largely confirmed these findings, with RCC being positively associated with in-hospital mortality (OR: 1.373, p < 0.01) and longer stays (OR: 2.591, p < 0.01)., Conclusion: In addition to describing the demographics and clinical course of AIS patients diagnosed with RCC, our study underscores the substantial impact of RCC on AIS outcomes. Despite experiencing strokes of similar severity, AIS patients diagnosed with RCC are at a heightened risk of complications, including thromboembolic events and infections, leading to elevated in-hospital mortality rates and prolonged hospital stays., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Intracranial abscess (IA) causes significant morbidity and mortality. The impact of baseline frailty status on post-operative outcomes of IA patients remains largely unknown. The present study evaluated if frailty status can be used to prognosticate outcomes in IA patients., Methods: We retrospectively reviewed all IA patients undergoing craniotomy at our institution from 2011 to 2018 (N.=18). These IA patients were age and gender matched with patients undergoing craniotomy for intracranial tumor (IT), an internal control for comparison. Demographic and clinical data were collected to measure frailty, using the modified frailty index-11 (mFI-11) and pre-operative American Society of Anesthesiologists Physical Status Classification System (ASA). Post-operative complications were measured by the Clavien-Dindo Grade (CDG)., Results: No significant difference in mFI-11 or ASA score was observed between the IA and IT groups (P=0.058 and P=0.131, respectively). IA patients had significantly higher CDG as compared with the control IT patients (P<0.001). There was a trend towards increasing LOS in the IA group as compared to the IT group (P=0.053). Increasing mFI and ASA were significant predictors of LOS by multiple linear regression in the IA group (P=0.006 and P=0.001, respectively), but not in the control IT group. Neither mFI-11 nor ASA were found to be predictors for CDG in either group. Within this case-control group of patients, we found an increase for odds of having IA with increasing mFI (OR=1.838, 95% CI: 1.016-3.362, P=0.044)., Conclusions: Frail IA patients tend to have more severe postoperative complications. The mFI-11 seems to predict increased resource utilization in the form of LOS. This study provides the initial retrospective data of another neurosurgical pathology where frailty leads to significantly worse outcomes. We also found that mFI may serve as a potential risk factor for severe disease.

Background and Objectives: Dual antiplatelet therapy (DAPT) is necessary to minimize the risk of periprocedural thromboembolic complications associated with aneurysm embolization using pipeline embolization device (PED). We aimed to assess the impact of platelet function testing (PFT) on reducing periprocedural thromboembolic complications associated with PED flow diversion in patients receiving aspirin and clopidogrel., Methods: Patients with unruptured intracranial aneurysms requiring PED flow diversion were identified from 13 centers for retrospective evaluation. Clinical variables including the results of PFT before treatment, periprocedural DAPT regimen, and intracranial complications occurring within 72 h of embolization were identified. Complication rates were compared between PFT and non-PFT groups. Differences between groups were tested for statistical significance using the Wilcoxon rank sum, Fisher exact, or χ 2 tests. A P -value <.05 was statistically significant., Results: 580 patients underwent PED embolization with 262 patients dichotomized to the PFT group and 318 patients to the non-PFT group. 13.7% of PFT group patients were clopidogrel nonresponders requiring changes in their pre-embolization DAPT regimen. Five percentage of PFT group [2.8%, 8.5%] patients experienced thromboembolic complications vs 1.6% of patients in the non-PFT group [0.6%, 3.8%] ( P = .019). Two (15.4%) PFT group patients with thromboembolic complications experienced permanent neurological disability vs 4 (80%) non-PFT group patients. 3.7% of PFT group patients [1.5%, 8.2%] and 3.5% [1.8%, 6.3%] of non-PFT group patients experienced hemorrhagic intracranial complications ( P > .9)., Conclusion: Preprocedural PFT before PED treatment of intracranial aneurysms in patients premedicated with an aspirin and clopidogrel DAPT regimen may not be necessary to significantly reduce the risk of procedure-related intracranial complications., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Delayed cerebral ischemia (DCI) represents a devastating complication of aneurysmal subarachnoid hemorrhage (aSAH) and is a significant predictor of morbidity and mortality. Recent studies have implicated inflammatory processes in the pathogenesis of DCI., Methods: aSAH patient data were retrospectively obtained from the eICU Collaborative Research Database (eICU CRD). Multivariable logistic regression models and receiver operating characteristic (ROC) curve analyses were employed to assess the association between low serum albumin (<3.4 g/dL) and clinical endpoints: DCI and in-hospital mortality., Results: Among 276 aSAH patients included in the analysis, 35.5% (N.=98) presented with low serum albumin levels and demonstrated a higher incidence of DCI (18.4% vs. 8.4%, OR=2.45, 95% CI=1.17, 5.10; P=0.017) and in-hospital mortality (27.6% vs. 16.3%, OR=1.95, 95% CI=1.08, 3.54; P=0.027) compared to patients with normal admission albumin values. In a multivariable model controlling for age and World Federation of Neurosurgical Societies grade, low serum albumin remained significantly associated with DCI (OR=2.52, 95% CI=1.18, 5.36; P=0.017), but not with in-hospital mortality. A combined model for prediction of DCI, encompassing known risk factors in addition to low serum albumin, achieved an area under the curve of 0.65 (sensitivity = 0.55, specificity = 0.75)., Conclusions: Serum albumin, a routine and inexpensive laboratory measurement, may potentially aid in the identification of patients with aSAH at risk for the development of DCI.

Background: Recent studies indicate endovascular thrombectomy (EVT) as a safe, effective treatment for acute ischemic stroke (AIS) with large ischemic regions. Our study updates an ongoing living systematic review and meta-analysis of randomized controlled trials (RCTs) comparing outcomes of EVT to medical management only., Methods: We searched MEDLINE, EMBASE, and the Cochrane Library for RCTs comparing EVT to medical management in AIS patients with large ischemic areas. Using fixed-effect models, we conducted a meta-analysis to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH) between EVT and standard medical management. We evaluated bias risk with the Cochrane tool and graded the certainty of evidence using the GRADE approach., Results: Of 1363 new citations, we included six RCTs with a total of 1876 patients. We found low-certainty evidence of improved functional independence (risk difference [RD] 29.9%, 95% CI 17.2% to 46.9%), increase in sICH (RD 2.6%, 95% CI 0.3% to 6.4%), and a non-significant decrease in mortality (RD -1.8%, 95% CI -3.9% to 0.6%) for AIS patients with large infarcts who underwent EVT compared to medical management only., Conclusion: Our revised meta-analysis suggests low-certainty evidence that there is improved functional independence, a non-significant decrease in mortality, and an increase in sICH among AIS patients with large infarcts who undergo EVT compared to those receiving medical management alone., Systematic Review Protocol Registration: PROSPERO (CRD42023398742)., Competing Interests: Declaration of competing interest All authors reported no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Intracerebral hemorrhage (ICH) is the second most common type of stroke, accounting for approximately 10-20% of all strokes, and is linked to severe neurological disability and death. Since the most accurate predictor of outcome in patients with ICH is hematoma volume, there is a great need for pharmacologic therapy that can reduce hematoma expansion and resultant mass effect and edema. This is especially critical within the ultra-early window of 3-4 hours after the presentation. Hemostatic therapies are exceptionally important for those patients taking antiplatelet or anticoagulant medications to reverse the effects of these medications and therefore prevent hematoma expansion. Furthermore, the recent publication of the 2023 Guideline for the Management of Patients with Aneurysmal Subarachnoid Hemorrhage by the American Heart Association/American Stroke Association, the first update to the guidelines since 2012, underscores the importance of optimizing anticoagulation reversal for this population. The purpose of this selective, nonsystematic review is to examine current literature regarding the use of hemostatic therapies in ICH, with particular attention paid to antiplatelet, anticoagulation, and antifibrinolytic therapies., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite renewed interest and recently demonstrated efficacy for endovascular thrombectomy (EVT) for treatment of acute ischemic stroke (AIS) of the posterior circulation, to date, no randomized clinical trials have been conducted to evaluate EVT for isolated occlusions of the posterior cerebral artery (IPCA)., Methods: Hospitalizations for adult patients with primary admission diagnoses of IPCA occlusion were identified in the National Inpatient Sample registry during the period of 2016-2020. The study exposure was treatment with EVT, and primary clinical endpoints included favorable functional outcome (defined as discharge disposition to home without services, previously shown to have high concordance with modified Rankin scale scores 0-2), in-hospital mortality, and any intracranial hemorrhage (ICH). Inverse probability of treatment weighting (IPTW) was performed to balance baseline clinical characteristics between those receiving EVT or medical management (MM)., Results: This analysis identified 34,880 IPCA occlusion hospitalizations, 730 (2.1%) of which documented treatment with EVT. Following IPTW adjustment, EVT was associated with favorable outcome in IPCA patients presenting with mild deficits (M-D) (NIHSS < 6) [adjusted odds ratio (aOR) 2.36, 95% confidence interval (CI) 2.27, 2.45; p < 0.001] and in those presenting with moderate-to-severe deficits (M-S-D) (NIHSS 6-42) (aOR 2.00, 95% CI 1.86, 2.15; p < 0.001). Mortality rates did not differ among those with M-S-D [EVT 4.8% vs. MM 4.7%, p = 0.742], while ICH rates were lower., Conclusion: Retrospective analysis of a large administrative registry in the Unites States demonstrates an association of EVT with favorable outcomes following IPCA occlusion, without concomitant risk of hemorrhagic transformation or mortality., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

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.

The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions via its discrete binding partners to form two multiprotein complexes, mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin-sensitive mTORC1, which regulates protein synthesis and cell growth, is tightly controlled by PI3K/Akt and is nutrient-/growth factor-sensitive. In the brain, mTORC1 is also sensitive to neurotransmitter signaling. mTORC2, which is modulated by growth factor signaling, is associated with ribosomes and is insensitive to rapamycin. mTOR regulates stem cell and cancer stem cell characteristics. Aberrant Akt/mTOR activation is involved in multistep tumorigenesis in a variety of cancers, thereby suggesting that the inhibition of mTOR may have therapeutic potential. Rapamycin and its analogues, known as rapalogues, suppress mTOR activity through an allosteric mechanism that only suppresses mTORC1, albeit incompletely. ATP-catalytic binding site inhibitors are designed to inhibit both complexes. This review describes the regulation of mTOR and the targeting of its complexes in the treatment of cancers, such as glioblastoma, and their stem cells.

Background and Objective: Although high-grade (Hunt and Hess 4 and 5) aneurysmal subarachnoid hemorrhage (aSAH) typically portends a poor prognosis, early and aggressive treatment has previously been demonstrated to confer a significant survival advantage. This study aims to evaluate geographic, demographic, and socioeconomic determinants of high-grade aSAH treatment in the United States., Methods: The National Inpatient Sample (NIS) was queried to identify adult high-grade aSAH hospitalizations during the period of 2015 to 2019 using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD) codes. The primary clinical endpoint of this analysis was aneurysm treatment by surgical or endovascular intervention (SEI), while the exposure of interest was geographic region by census division. Favorable functional outcome (assessed by the dichotomous NIS-SAH Outcome Measure, or NIS-SOM) and in-hospital mortality were evaluated as secondary endpoints in treated and conservatively managed groups., Results: Among 99 460 aSAH patients identified, 36 795 (37.0%) were high-grade, and 9210 (25.0%) of these were treated by SEI. Following multivariable logistic regression analysis, determinants of treatment by SEI included female sex (adjusted OR (aOR) 1.42, 95% CI 1.35 to 1.51), transfer admission (aOR 1.18, 95% CI 1.12 to 1.25), private insurance (ref: government-sponsored insurance) (aOR 1.21, 95% CI 1.14 to 1.28), and government hospital ownership (ref: private ownership) (aOR 1.17, 95% CI 1.09 to 1.25), while increasing age (by decade) (aOR 0.93, 95% CI 0.91 to 0.95), increasing mortality risk (aOR 0.60, 95% CI 0.57 to 0.63), urban non-teaching hospital status (aOR 0.66, 95% CI 0.59 to 0.73), rural hospital location (aOR 0.13, 95% CI 0.7 to 0.25), small hospital bedsize (aOR 0.68, 95% CI 0.60 to 0.76), and geographic region (South Atlantic (aOR 0.72, 95% CI 0.63 to 0.83), East South Central (aOR 0.75, 95% CI 0.64 to 0.88), and Mountain (aOR 0.72, 95% CI 0.61 to 0.85)) were associated with a lower likelihood of treatment. High-grade aSAH patients treated by SEI experienced significantly greater rates of favorable functional outcomes (20.1% vs 17.3%; OR 1.20, 95% CI 1.13 to 1.28, P<0.001) and lower rates of mortality (25.8% vs 49.1%; OR 0.36, 95% CI 0.34 to 0.38, P<0.001) in comparison to those conservatively managed., Conclusion: A complex interplay of demographic, socioeconomic, and geographic factors influence treatment patterns of high-grade aSAH in the United States., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT)., Objective: To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes., Design, Setting, and Participants: This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024., Interventions: EVT vs MM., Main Outcomes and Measures: Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication., Results: A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80)., Conclusions and Relevance: Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport., Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Background/aim: Brain metastasis (BM) is a complex multi-step process involving various immune checkpoint proteins. Mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), and signal transducer and activator of transcription 3 (STAT3) are implicated in tumorigenesis and are critical upstream regulators of Programmed Death Ligand 1 (PD-L1), an immunotherapy target. Tumor suppressor p53, dysregulated in cancers, regulates STAT3 and ERK1/2 signaling. This study examined the roles of STAT3, MAPK and p53 status in BM initiation and maintenance., Materials and Methods: Twenty-six BM, with various primary malignancies, were used (IRB-approved) to determine mutant p53 (p53 mt ), pSTAT3 Tyr705 , pERK1/2 Thr202/Tyr204 , and PD-L1 expression using immunohistochemistry. cDNA microarray was used for gene expression analysis. Brain-metastatic breast cancer cells (MDA-MB-231) were treated with STAT3 (NSC74859) or MAPK/ERK1/2 (U0126) inhibitors in regular or astrocytic media. ERK1/2 pathway was assessed using western blotting, and cell proliferation and migration were determined using MTT and scratch-wound assays, respectively., Results: pSTAT3 Tyr705 and pERK1/2 Thr202/Tyr204 were expressed at tumor margins, whereas p53 mt and PD-L1 were uniformly expressed, with significant overlap between expression of these proteins. Gene expression analysis identified alterations in 18 p53- and 32 STAT3- or MAPK-associated genes contributing to dysregulated immune responses and cell cycle regulation. U0126 and NSC74859 reduced pERK1/2 Thr202/Tyr204 expression. Cell proliferation decreased following each treatment (p≤0.01). Migration stagnated following U0126 treatment in astrocytic media (p≤0.01)., Conclusion: Activation of STAT3 and ERK1/2 promotes BM and provides compelling evidence for use of STAT3, ERK1/2 and p53 status as potential immunotherapeutic targets in BM., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Respiratory failure following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a known complication, and requirement of tracheostomy is associated with worse outcomes. Our objective is to evaluate characteristics associated with tracheostomy timing in AIS patients treated with MT., Methods: The National Inpatient Sample was queried for adult patients treated with MT for AIS from 2016 to 2019. Baseline demographic characteristics, comorbidities, and inpatient outcomes were analyzed for associations in patients who received tracheostomy. Timing of early tracheostomy (ETR) was defined as placement before day 8 of hospital stay., Results: Of 3505 AIS-MT patients who received tracheostomy, 915 (26.1%) underwent ETR. Patients who underwent ETR had shorter length of stay (LOS) (25.39 days vs 32.43 days, p < 0.001) and lower total hospital charges ($483,472.07 vs $612,362.86, p < 0.001). ETR did not confer a mortality benefit but was associated with less acute kidney injury (OR, 0.697; p = 0.013), pneumonia (OR, 0.449; p < 0.001), and sepsis (OR, 0.536; p = 0.002)., Conclusion: An expected increase in complications and healthcare resource utilization is seen in AIS-MT patients receiving tracheostomy, likely reflecting the severity of patients' post-stroke neurologic injury. Among these high-risk patients, ETR was predictive of shorter LOS and fewer complications., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interests to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Acute ischemic stroke is a leading cause of morbidity and mortality in the United States. Treatment goals remain focused on restoring blood flow to compromised areas. However, a major concern arises after reperfusion occurs. Cerebral ischemic reperfusion injury is defined as damage to otherwise salvageable brain tissue occurring with the reestablishment of the vascular supply to that region. The pool of eligible patients for revascularization continues to grow, especially with the recently expanded endovascular therapeutic window. Neurointensivists should understand and manage complications of successful recanalization. In this review, we examine the pathophysiology, diagnosis, and potential management strategies in cerebral ischemic reperfusion injury., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Few studies have evaluated frailty in the setting of aneurysmal subarachnoid hemorrhage (aSAH) using large-scale data. The risk analysis index (RAI) may be implemented at the bedside or assessed retrospectively, differentiating it from other indices used in administrative registry-based research., Methods: Adult aSAH hospitalizations were identified in the National Inpatient Sample (NIS) from 2015 to 2019. Complex samples statistical methods were performed to evaluate the comparative effect size and discriminative ability of the RAI, the modified frailty index (mFI), and the Hospital Frailty Risk Score (HFRS). Poor functional outcome was determined by the NIS-SAH Outcome Measure (NIS-SOM), shown to have high concordance with modified Rankin Scale scores > 2., Results: 42,300 aSAH hospitalizations were identified in the NIS during the study period. By both ordinal [adjusted odds ratio (aOR) 3.20, 95% confidence interval (CI) 3.05, 3.36, p < 0.001] and categorical stratification [frail aOR 3.59, 95% CI 3.39, 3.80, p < 0.001; severely frail aOR 6.67, 95% CI 5.78, 7.69, p < 0.001], the RAI achieved the largest effect sizes for NIS-SOM in comparison with the mFI and HFRS. Discrimination of the RAI for NIS-SOM in high-grade aSAH was significantly greater than that of the HFRS (c-statistic 0.651 vs. 0.615). The mFI demonstrated the lowest discrimination in both high-grade and normal-grade patients. A combined Hunt and Hess-RAI model (c-statistic 0.837, 95% CI 0.828, 0.845) for NIS-SOM achieved significantly greater discrimination than both the combined models for mFI and HFRS (p < 0.001)., Conclusion: The RAI was robustly associated with poor functional outcomes in aSAH independent of established risk factors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective/aim: To investigate the effect of cerebral microbleeds (CMBs) on the functional and safety outcomes of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO)., Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for systematic review and meta-analysis. We included observational studies that recruited AIS-LVO patients, used susceptibility-sensitive magnetic resonance imaging (MRI) to detect CMBs, and examined the association between them and predefined outcome events. The extracted data included study and population characteristics, risk of bias domains, and outcome measures. The outcomes of interest included functional independence, revascularization success, procedural and hemorrhagic adverse events. We conducted a meta-analysis using the Mantel-Haenszel method and calculated the risk ratios., Results: Four studies with a total of 1,514 patients were included. A significant reduction in the likelihood of achieving a favorable functional outcome was observed in patients with CMBs (Risk ratio (RR) 0.69, 95% confidence interval (CI): 0.52 to 0.91, P=0.01). No significant differences were observed between the CMBs and no CMBs groups in terms of successful revascularization, mortality, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and parenchymal hematoma., Conclusions: The presence of CMBs significantly reduced the likelihood of achieving functional independence post-EVT in AIS-LVO patients. However, CMBs did not impact the rates of successful revascularization, mortality, or the occurrence of various hemorrhagic events. Future research should explore the mechanisms of this association and strategies to mitigate its impact., Competing Interests: Declaration of Competing Interest The Authors declare that they did not receive any financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Patients with developmental disabilities (DD) are frequently excluded from acute ischemic stroke (AIS) randomized control trials. We sought to evaluate the impact of having DD on this patient cohort., Methods: The National Inpatient Sample was analyzed to explore the impact of AIS and treatment on discharge dispositions in patients with DD. Clinical characteristics, treatments, and outcomes were compared to fully-abled patients with AIS., Results: 1,605,723 patients with AIS were identified from 2010-2019, of whom 4094 (0.30%) had a DD. AIS patients with DD were younger (60.31 vs 70.93 years, p < 0.01), less likely to be Caucasian (66.37%vs 68.09%, p = 0.01), and had higher AIS severity (0.63 vs 0.58, p < 0.01). Tissue plasminogen activator (tPA) was administered in 99,739 (6.2%) fully-abled patients and 196 (4.79%) of patients with DD (p < 0.01). Endovascular thrombectomy (EVT) was performed in 21,066 (1.31%) of fully-abled patients and 35 (0.85%) of patients with DD (p < 0.01). The presence of developmental disabilities were predictive of lower rates of tPA (OR:0.71,CI:0.56-0.87,p < 0.01) and EVT (OR:0.24,CI:0.16-0.36,p < 0.01). In a propensity score-matched cohort of all AIS patients who underwent EVT, there was no difference in functional outcome (p = 0.41), in-hospital mortality (0.10), and LOS (p = 0.79)., Conclusion: AIS patients with DD were less likely to receive tPA and EVT compared to fully-abled patients. Individuals with DD had higher mortality and worse discharge disposition. There was no significant difference in post-EVT outcomes between fully-abled patients and patients with developmental disabilities. In the absence of prospective clinical trials, population based cross-sectional analyses such as the present study provide valuable clinical insight., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The objective of this study was to investigate the prognostic significance of chronic antiplatelet therapy (APT) usage in acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). Long-term APT may enhance recanalization but may also predispose patients to an increased risk of hemorrhagic transformation., Methods: Weighted hospitalizations for anterior-circulation AIS treated with EVT were identified in a large United States claims-based registry. Baseline clinical characteristics and outcomes were compared between patients with and without chronic APT usage prior to admission. Multivariable logistic regression analysis was performed to assess adjusted associations between APT and study endpoints., Results: This analysis identified 36,560 patients, of whom 8170 (22.3%) were on a chronic APT regimen prior to admission. These patients were older and demonstrated a higher burden of comorbid disease, but had similar stroke severity on presentation in comparison with those not on APT. On unadjusted analysis, patients with prior APT demonstrated higher rates of favorable outcomes (24.3% vs 21.5%, p < 0.001), lower rates of mortality (7.0% vs 10.1%, p < 0.001), and lower rates of any intracranial hemorrhage (ICH; 20.3% vs 24.2%, p < 0.001), but no difference in rates of symptomatic ICH (sICH). Following multivariable adjustment for baseline clinical characteristics including age, acute stroke severity, and comorbidity burden, prior APT was associated with favorable outcome (adjusted odds ratio [aOR] 1.21, 95% CI 1.17-1.24, p < 0.001) and a lower likelihood of mortality (aOR 0.73, 95% CI 0.70-0.77, p < 0.001), without an increased likelihood of ICH (any ICH aOR 0.84, 95% CI 0.81-0.87, p < 0.001; sICH aOR 0.92, 95% CI 0.82-1.03, p = 0.131)., Conclusions: Retrospective evaluation of patients with AIS treated with EVT using registry-based data demonstrated an association of prior APT usage with favorable outcomes, without an increased risk of hemorrhagic transformation.

Background: Intracerebral hemorrhage (ICH) carries significant morbidity and mortality. Previous single-center retrospective analysis suggests that end-stage renal disease (ESRD) is a risk factor for severe ICH and worse outcomes. This investigation aims to examine the impact of ESRD on ICH severity, complications, and outcomes using a multicenter national database., Methods: The International Classification of Disease, Ninth and Tenth Revision Clinical Modification codes were used to query the National Inpatient Sample for patients with ICH and ESRD between 2010 and 2019. Primary endpoints were the functional outcome, length of stay (LOS), and in-hospital mortality. Multivariate variable regression models and a propensity-score matched analysis were established to analyze patient outcomes associated with baseline patient characteristics., Results: We identified 211,266 patients with ICH, and among them, 7,864 (3.77%) patients had a concurrent diagnosis of ESRD. Patients with ESRD were younger (60.85 vs. 67.64, P < 0.01) and demonstrated increased ICH severity (0.78 vs. 0.77, P < 0.01). ESRD patients experienced higher rates of sepsis (15.9% vs. 6.15%, P < 0.01), acute myocardial infarction (8.05% vs. 3.65%, P < 0.01), and cardiac arrest (5.94% vs. 2.4%, P < 0.01). In addition, ESRD predicted poor discharge disposition (odds ratio [OR]: 2.385, 95% confidence interval [CI]: 2.227-2.555, P < 0.01), longer hospital LOS (OR: 1.629, 95% CI: 1.553-1.709, P < 0.01), and in-hospital mortality (OR: 2.786, 95% CI: 2.647-2.932, P < 0.01)., Conclusions: This study utilizes a multicenter database to analyze the effect of ESRD on ICH outcomes. ESRD is a significant predictor of poor functional outcomes, in-hospital mortality, and prolonged stay in the ICH population., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Brain Circulation.)

Development of antifouling membranes for water treatment using conducting polymers and their composites is a fundamental strategy to mitigate the fouling. This manuscript presents an all-atom molecular dynamics simulations of a conducting polymer, polyaniline (PANI), immersed in an ionic liquids (ILs)-water mixtures. We have considered the ionic liquid 1-ethyl-3-methyl imidazolium bistriflimide, [EMIM] + [BIS] - . The two forms of polyaniline, emeraldine base (EB) and emeraldine salt (ES), were considered. Various intra- and intermolecular structural properties of PANI were analyzed, such as polymer chain radius of gyration R g , radial distribution functions, and torsional angle distributions. The R g of EB shows an increase, while the R g of ES shows a decrease with an increase in the IL concentration. The backbone torsional angle probability distributions show a significant trans state for EB, while a combination of trans and gauche states was observed for ES. Similar supportive distributions were seen in the backbone angular distributions. Radial distribution functions between the carbon atoms at ortho and meta positions of the benzene ring on both ES and EB, as well as the amine group attached between two benzene rings, show an enhanced interaction with the ionic liquid compared to water. Anions have a dominant interaction with the polymer chain when compared to cations. The solvent accessible surface area (SASA) calculations were in accordance with the EB and ES structural properties. The SASA values are more favorable for ES than for EB. H-bond analysis shows a decrease in the number of H-bonds with water as the IL concentration increases.

Objective: Endoluminal flow diversion reduces blood flow into intracranial aneurysms, promoting thrombosis. Postprocedural dual antiplatelet therapy (DAPT) is necessary for the prevention of thromboembolic complications. The purpose of this study is to therefore assess the impact that the type and duration of DAPT has on aneurysm occlusion rates and iatrogenic complications after flow diversion., Methods: A retrospective review of a multicenter aneurysm database was performed from 2012 to 2020 to identify unruptured intracranial aneurysms treated with single device flow diversion and ≥12-month follow-up. Clinical and radiologic data were analyzed with aneurysm occlusion as a function of DAPT duration serving as a primary outcome measure., Results: Two hundred five patients underwent flow diversion with a single pipeline embolization device with 12.7% of treated aneurysms remaining nonoccluded during the study period. There were no significant differences in aneurysm morphology or type of DAPT used between occluded and nonoccluded groups. Nonoccluded aneurysms received a longer mean duration of DAPT (9.4 vs 7.1 months, P = 0.016) with a significant effect of DAPT duration on the observed aneurysm occlusion rate (F(2, 202) = 4.2, P = 0.016). There was no significant difference in the rate of complications, including delayed ischemic strokes, observed between patients receiving short (≤6 months) and prolonged duration (>6 months) DAPT (7.9% vs 9.3%, P = 0.76)., Conclusions: After flow diversion, an abbreviated duration of DAPT lasting 6 months may be most appropriate before transitioning to low-dose aspirin monotherapy to promote timely aneurysm occlusion while minimizing thromboembolic complications., Competing Interests: J.R.M. has received consulting compensation for Stryker and Penumbra. A.B.P. has received consulting, proctoring, and lecturing compensation from Medtronic, Microvention, and Penumbra. J.S. has received consulting compensation from Medtronic. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Infective Endocarditis (IE) patients are known to have a variety of complications with one of the rarest, but serious being cerebral mycotic aneurysm, which can result in subarachnoid hemorrhage (SAH). Using the National In-Patient Sample database, we sought to determine the rate of acute ischemic stroke (AIS) and outcomes in IE- patients with and without SAH. In total, we identified 82,844 IE-patients from 2010 to 2016, of which 641 had a concurrent diagnosis of SAH. IE patients with SAH had a more complicated course, higher mortality rate (OR 4.65 CI 95% 3.9-5.5, P < 0.001), and worse outcomes. This patient population also had a significantly higher rate of AIS (OR 6.3 CI 95% 5.4-7.4, P < 0.001). Overall, 41.5% of IE-patients with SAH had AIS during their hospitalization as compared to 10.1% of IE only patients. IE-patients with SAH were more likely to undergo endovascular treatment (3.6%) with 0.8% of the IE patients with AIS undergoing mechanical thrombectomy. While IE-patients are at risk for various complications, our study suggests a significant increase in the mortality and risk of AIS in those with SAH., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Heparin induced thrombocytopenia Type II (HIT-II) is a dangerous thromboembolic complication of heparin therapy. The current literature on incidence and outcomes of HIT-II in aneurysmal subarachnoid hemorrhage (aSAH) patients remains sparse., Objective: We report our institution's incidence and outcomes of HIT-II in aSAH patients., Methods: We performed a retrospective cohort study at an academic medical center between June 2014 and July 2018. All patients had aSAH confirmed by digital subtraction angiography. Diagnosis of HIT-II was determined by positive results on both heparin PF4-platelet antibody ELISA (anti-PF4) and serotonin release assay (SRA)., Results: 204 patients met inclusion criteria. Seven patients (7/204, 3.5%) underwent laboratory testing, three of whom met clinical criteria. HIT-II incidence was confirmed in two of these seven patients (2/204, 0.98%), who had high BMI and T4 scores., Conclusion: Our institution's report of HIT-II incidence in aSAH patients is lower than previously reported in this population and more closely parallels HIT-II incidence in the general and surgical ICU setting. Widely-accepted American College of Chest Physicians (ACCP) clinical diagnostic criteria in conjunction with anti-PF4 and SRA testing is the gold standard of clinical diagnosis of HIT-II in aSAH patients.

Competing Interests: Competing interests: None declared.