A reactive species reactions module for integration into genome-scale metabolic models for improved insights: Application to cancer.

Reactive species (RS) play significant roles in many disease contexts. Despite their crucial roles in diseases including cancer, the RS are not adequately modeled in the genome-scale metabolic (GSM) models, which are used to understand cell metabolism in disease contexts. We have developed a scalable RS reactions module that can be integrated with any Recon 3D-derived human metabolic model, or after fine-tuning, with any metabolic model. With RS-integration, the GSM models of three cancers (basal-like triple negative breast cancer (TNBC), high grade serous ovarian carcinoma (HGSOC) and colorectal cancer (CRC)) built from Recon 3D, precisely highlighted the increases/decreases in fluxes (dysregulation) occurring in important pathways of these cancers. These dysregulations were not prominent in the standard cancer models without the RS module. Further, the results from these RS-integrated cancer GSM models suggest the following decreasing order in the ease of ferroptosis-targeting to treat the cancers: TNBC > HGSOC > CRC.

Carotid Web Phenotype Is Uncommonly Associated With Classic Fibromuscular Dysplasia: A Retrospective Observational Study.

BACKGROUND AND PURPOSE: Carotid web (CaW) is an intimal form of fibromuscular dysplasia (FMD) involving the carotid bulb which has been increasingly recognized as a potential cause of recurrent ischemic strokes. It is overlooked as a separate entity and often dismissed if no coexistent signs of classic FMD changes are observed. We aim to evaluate the frequency of classic FMD in high-yield vascular territories in patients with symptomatic CaW. METHODS: This was a retrospective analysis of a symptomatic CaW database of 2 comprehensive stroke centers (spanning September 2014-October 2020). The diagnosis of a CaW during a stroke workup was defined as the presence of a shelf-like linear filling defect in the posterior aspect of the carotid bulb on computed tomography angiography in patients with acute ischemic stroke or transient ischemic attack of undetermined cause after a thorough evaluation. Neck computed tomography angiography and renal conventional angiography images were independently evaluated by two readers blinded to the laterality and clinical details to inspect the presence of underlying classic FMD. RESULTS: Sixty-six patients with CaW were identified. Median age was 51 years (interquartile range, 42-57), and 74% were women. All patients had neck computed tomography angiography (allowing for bilateral vertebral and carotid evaluation), whereas 47 patients had additional digital subtraction angiography (which evaluated 47 carotids ipsilateral to the stroke and 10 contralateral carotids). Internal carotid artery classic FMD changes were noted in only 6 out of 66 (9%) in the ipsilateral carotids. No contralateral carotid or vertebral artery classic FMD changes were observed. Renal artery catheter-based angiography was obtained in 16 patients/32 arteries and only 1 patient/2 renal arteries demonstrated classic FMD changes. CONCLUSIONS: CaW phenotype is uncommonly associated with classic FMD changes. Coexistent classic FMD does not constitute a useful marker to corroborate or exclude CaW diagnosis.

No Racial Disparity in Outcome Measures After Endovascular Treatment for Stroke in the Elderly.

BACKGROUND AND PURPOSE: Despite the lower rates of good outcomes and higher mortality in elderly patients, age does not modify the treatment effect of mechanical thrombectomy for large vessel occlusion strokes. We aimed to study whether racial background influences the outcome after mechanical thrombectomy in the elderly population. METHODS: We reviewed a prospectively maintained database of patients with acute ischemic stroke treated with mechanical thrombectomy from October 2010 through June 2020 to identify all consecutive patients with age ≥80 years and anterior circulation large vessel occlusion strokes. The patients were categorized according to their race as Black and White. Univariable and multivariable analyses were performed to define the predictors of 90-day modified Rankin Scale and mortality in the overall population and in each race separately. RESULTS: Among 2241 mechanical thrombectomy, a total of 344 patients (median [interquartile range]; age 85 [82-88] years, baseline National Institutes of Health Stroke Scale score of 19 [15-23], Alberta Stroke Program Early CT Score 9 [7-9], 69.5% females) were eligible for the analysis. White patients (n=251; 73%) had significantly lower median body mass index (25.37 versus 26.89, P=0.04) and less frequent hypertension (78.9% versus 90.3%, P=0.01) but more atrial fibrillation (64.5% versus 44.1%, P=0.001) compared with African Americans (n=93; 27%). Other clinical, imaging, and procedural characteristics were comparable between groups. The rates of symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score of 0 to 2, and mortality were comparable among both groups. On multivariable analysis, race was neither a predictor of 90-day modified Rankin Scale score of 0 to 2 (White race: odds ratio, 0.899 [95% CI, 0.409-1.974], P=0.79) nor 90-day mortality (White race: odds ratio, 1.368; [95% CI, 0.715-2.618], P=0.34). CONCLUSIONS: In elderly patients undergoing mechanical thrombectomy for acute ischemic stroke, there was no racial difference in terms of outcome.

Direct to Angiosuite Versus Conventional Imaging in Suspected Large Vessel Occlusion: A Systemic Review and Meta-Analysis.

BACKGROUND: There is growing evidence to suggest that the direct transfer to angiography suite (DTAS) approach for patients with suspected large vessel occlusion stroke potentially requiring mechanical thrombectomy shortens treatment times and improves outcomes compared with the direct transfer to conventional imaging (DTCI) model. Therefore, we conducted this meta-analysis to compare both approaches to build more concrete evidence to support this innovative treatment concept. METHODS: All potentially relevant studies published in 4 electronic databases/search engines (PubMed, Web of Science, Cochrane Library, and Scopus) from inception to November 2021 were reviewed. Eligible studies were included if they enrolled ≥10 patients in both groups, were published in English, and reported baseline and procedural characteristics and outcomes. Relevant data were then extracted and analyzed. RESULTS: Among 4514 searched studies, 7 qualified for the analysis with 1971 patients (DTAS=675, DTCI=1296). Times from door to puncture (mean difference, -30.76 minutes [95% CI, -43.70 to -17.82]; P<0.001) as well as door-to-reperfusion (mean difference=-33.24 minutes [95% CI, -51.82 to -14.66]; P<0.001) were significantly shorter and the rates of functional independence (modified Rankin Scale score, 0-2: risk ratio [RR], 1.25 [95% CI, 1.02-1.53]; P=0.03) at 90 days were higher in the DTAS versus the DTCI approach. There was no difference across the DTAS and DTCI groups in terms of the rates of successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2B-3: RR, 1.03 [95% CI, 0.95-1.12]; P=0.42), near-complete/full reperfusion (modified Thrombolysis in Cerebral Infarction 2C-3: RR, 0.89 [95% CI, 0.74-1.08]; P=0.23), symptomatic intracranial hemorrhage (RR, 0.81 [95% CI, 0.56-1.17]; P=0.26), or fair outcomes (modified Rankin Scale score, 0-3: RR, 1.14 [95% CI, 0.88-1.47]; P=0.32) or mortality (RR, 0.98 [95% CI, 0.67-1.44]; P=0.93) at 90 days. Subgroup analysis showed no significant difference in 90-day functional independence across approaches in transfer patients (RR, 1.20 [95% CI, 0.96-1.51]; P=0.11). CONCLUSIONS: Our meta-analysis showed that the DTAS approach seems to be associated with improved time metrics and functional outcomes with comparable safety to the DTCI approach. Ongoing multicenter randomized clinical trials will hopefully provide more definite data about this promising approach.

Automated Large Artery Occlusion Detection in Stroke: A Single-Center Validation Study of an Artificial Intelligence Algorithm.

INTRODUCTION: Expediting notification of lesions in acute ischemic stroke (AIS) is critical. Limited availability of experts to assess such lesions and delays in large vessel occlusion (LVO) recognition can negatively affect outcomes. Artificial intelligence (AI) may aid LVO recognition and treatment. This study aims to evaluate the performance of an AI-based algorithm for LVO detection in AIS. METHODS: Retrospective analysis of a database of AIS patients admitted in a single center between 2014 and 2019. Vascular neurologists graded computed tomography angiographies (CTAs) for presence and site of LVO. Studies were analyzed by the Viz-LVO Algorithm® version 1.4 - neural network programmed to detect occlusions from the internal carotid artery terminus (ICA-T) to the Sylvian fissure. Comparisons between human versus AI-based readings were done by test characteristic analysis and Cohen's kappa. Primary analysis included ICA-T and/or middle cerebral artery (MCA)-M1 LVOs versus non-LVOs/more distal occlusions. Secondary analysis included MCA-M2 occlusions. RESULTS: 610 CTAs were analyzed. The AI algorithm rejected 2.5% of the CTAs due to poor quality, which were excluded from the analysis. Viz-LVO identified ICA-T and MCA-M1 LVOs with a sensitivity of 87.6%, specificity of 88.5%, and accuracy of 87.9% (AUC 0.88, 95% CI: 0.85-0.92, p < 0.001). Cohen's kappa was 0.74. In the secondary analysis, the algorithm yielded a sensitivity of 80.3%, specificity of 88.5%, and accuracy of 82.7%. The mean run time of the algorithm was 2.78 ± 0.5 min. CONCLUSION: Automated AI reading allows for fast and accurate identification of LVO strokes with timely notification to emergency teams, enabling quick decision-making for reperfusion therapies or transfer to specialized centers if needed.

Lack of Reperfusion Rather Than Number of Passes Defines Futility in Stroke Thrombectomy: A Matched Case-Control Study.

Background and Purpose: There is a robust relationship between the duration of ischemia and functional outcomes after mechanical thrombectomy. Higher number of mechanical thrombectomy passes strongly correlate with lower chances of favorable outcomes. Indeed, previous studies have suggested that after multiple passes the procedure may be futile. However, using uncontrolled thresholds to define thrombectomy futility might be misleading. We aim to compare the outcome of successful reperfusion after 4 to 5 passes and ≥6 passes with those of failed reperfusion. Methods: A prospectively acquired mechanical thrombectomy database from January 2012 to October 2019 was reviewed. Patients were included if they had intracranial internal carotid artery or middle cerebral artery-M1/M2 occlusions and either achieved successful reperfusion after ≥4 passes or failed reperfusion. Reperfused patients (mTICI2b-3) were divided into 2 subgroups; (1) 4 to 5 passes and (2) ≥6 passes. Each subgroup was compared with a matched group of mechanical thrombectomy failure (mTICI0-2a). The primary outcome was the shift in the degree of disability at 90-day as measured by the modified Rankin Scale. Results: A total of 273 patients were included. As compared with matched failed reperfusion patients (n=62), those reperfused after 4 to 5 passes (n=62) had a favorable shift in the overall modified Rankin Scale score distribution (adjusted odds ratio, 3.992 [95% CI, 1.807­8.512], P=0.001] and higher rates of functional independence (31% versus 8.9%, P=0.004, adjusted odds ratio; 9.860 [95% CI, 2.323­41.845], P=0.002) at 90 days. Similarly, when compared with a matched group of failed reperfusion (n=42), patients reperfused after ≥6 passes (n=42) demonstrated a favorable shift in the overall modified Rankin Scale score distribution (adjusted odds ratio, 2.640 [95% CI, 1.073­6.686], P=0.037) and had higher rates of functional independence (36.8% vs 11.1%, P=0.004, adjusted odds ratio, 5.392 [95% CI, 1.185­24.530], P=0.029) at 90 day. Rates of parenchymal hematoma type-2 and 90-day mortality were comparable in the reperfused and nonreperfused groups. Conclusions: Achieving reperfusion despite multiple passes leads to improved outcomes compared with failed procedures. Arbitrary uncontrolled thresholds for a maximum number of passes to predict futile recanalization may lead to inappropriate early termination of procedures.

Reliability of Field Assessment Stroke Triage for Emergency Destination Scale Use by Paramedics: Mobile Stroke Unit First-Year Experience.

Background and Purpose: Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale is a helpful tool to triage patients with stroke in the field. However, data on its reliability in the prehospital setting are lacking. We aim to test the reliability of FAST-ED scale when used by paramedics in a mobile stroke unit covering a metropolitan area. Methods: As part of standard operating mobile stroke unit procedures, paramedics initially evaluated patients. If the event characterized a stroke alert, the FAST-ED score was determined by the paramedic upon patient contact (in-person) and then independently by a vascular neurologist (VN) immediately after paramedic evaluation (remotely/telemedicine). This allowed testing of the interrater agreement of the FAST-ED scoring performance between on-site prehospital providers and remotely located VN. Results: Of a total of 238 patients transported in the first 15 months of the mobile stroke unit's activity, 173 were included in this study. Median age was 63 (interquartile range, 55.5­75) years and 52.6% were females. A final diagnosis of ischemic stroke was made in 71 (41%), transient ischemic attack in 26 (15%), intracranial hemorrhage in 15 (9%), whereas 61 (35%) patients were stroke mimics. The FAST-ED scores matched perfectly among paramedics and VN in 97 (56%) instances, while there was 0 to 1-point difference in 158 (91.3%), 0 to 2-point difference in 171 (98.8%), and 3 or more point difference in 2 (1.1%) patients. The intraclass correlation between VN and paramedic FAST-ED scores showed excellent reliability, intraclass correlation coefficient 0.94 (95% CI, 0.92­0.96; P<0.001). When VN recorded FAST-ED score ≥3, paramedics also scored FAST-ED≥3 in majority of instances (63/71 patients; 87.5%). A large vessel occlusion was identified in 16 (9.2%) patients; 13 occlusions were identified with a FAST-ED≥3 while 3 were missed. All of the latter patients had National Institutes of Health Stroke Scale score ≤5. Conclusions: We demonstrate excellent reliability of FAST-ED scale performed by paramedics when compared with VN, indicating that it can be accurately performed by paramedics in the prehospital setting.

Thermodynamically consistent estimation of Gibbs free energy from data: data reconciliation approach.

MOTIVATION: Thermodynamic analysis of biological reaction networks requires the availability of accurate and consistent values of Gibbs free energies of reaction and formation. These Gibbs energies can be measured directly via the careful design of experiments or can be computed from the curated Gibbs free energy databases. However, the computed Gibbs free energies of reactions and formations do not satisfy the thermodynamic constraints due to the compounding effect of measurement errors in the experimental data. The propagation of these errors can lead to a false prediction of pathway feasibility and uncertainty in the estimation of thermodynamic parameters. RESULTS: This work proposes a data reconciliation framework for thermodynamically consistent estimation of Gibbs free energies of reaction, formation and group contributions from experimental data. In this framework, we formulate constrained optimization problems that reduce measurement errors and their effects on the estimation of Gibbs energies such that the thermodynamic constraints are satisfied. When a subset of Gibbs free energies of formations is unavailable, it is shown that the accuracy of their resulting estimates is better than that of existing empirical prediction methods. Moreover, we also show that the estimation of group contributions can be improved using this approach. Further, we provide guidelines based on this approach for performing systematic experiments to estimate unknown Gibbs formation energies. AVAILABILITY AND IMPLEMENTATION: The MATLAB code for the executing the proposed algorithm is available for free on the GitHub repository: https://github.com/samansalike/DR-thermo. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Safety of Ticagrelor in Moderate and Severe Acute Ischemic Stroke: A Single-Center Retrospective Review.

OBJECTIVES: Ticagrelor may be superior to aspirin after minor ischemic stroke or TIA, particularly in patients with symptomatic atherosclerotic disease. However, there may be an increased risk of intracerebral hemorrhage in patients with moderate to severe ischemic stroke, and ticagrelor has not been studied in this patient population. Therefore, we sought to evaluate the safety of ticagrelor after moderate or severe ischemic stroke. MATERIALS AND METHODS: Retrospective chart review of all patients admitted with acute ischemic stroke and NIHSS 6 or greater who were discharged on ticagrelor between January 2016 and December 2019. Patients who underwent angioplasty, stenting or carotid revascularization during the hospitalization were excluded. RESULTS: Of 183 patients discharged on ticagrelor, 61 patients were included. Median age was 61 (IQR 52-68); 33 (54%) patients were men. Median NIHSS was 11 (IQR 8-15). Fourteen (23%) patients received IV alteplase and 35 (57%) patients received mechanical thrombectomy. Stroke mechanism was large artery atherosclerosis in 53 (87%) of patients, of which 40 (71%) were deemed intracranial atherosclerosis. Final infarct volume was greater than 10 mL in 32 (52%) patients. Follow-up information was available for 53 (87%) patients; median length of follow-up was 3 (IQR 2-6) months. Six (10%) patients experienced recurrent ischemic stroke. No patients experienced symptomatic intracerebral hemorrhage after initiation of ticagrelor. One (2%) patient experienced major bleeding. CONCLUSIONS: This study provides preliminary evidence supporting the potential safety of ticagrelor following moderate or severe acute ischemic stroke. These findings support the need for future prospective studies.

Patterns and Outcomes of Endovascular Therapy in Mild Stroke.

Background and Purpose- We aimed to evaluate the current practice patterns, safety and outcomes of patients who receive endovascular therapy (EVT) having mild neurological symptoms. Methods- From Jan 2010 to Jan 2018, 127,794 ischemic stroke patients were enrolled in the Florida-Puerto Rico Stroke Registry. Patients presenting within 24 hours of symptoms who received EVT were classified into mild (National Institutes of Health Stroke Scale [NIHSS] ≤5) or moderate/severe (NIHSS>5) categories. Differences in clinical characteristics and outcomes were evaluated using multivariable logistic regression. Results- Among 4110 EVT patients (median age, 73 [interquartile range=20] years; 50% women), 446 (11%) had NIHSS ≤5. Compared with NIHSS >5, those with NIHSS ≤5 arrived later to the hospital (median, 138 versus 101 minutes), were less likely to receive intravenous alteplase (30% versus 43%), had a longer door-to-puncture time (median, 167 versus 115 minutes) and more likely treated in South Florida (64% versus 53%). In multivariable analysis younger age, private insurance (versus Medicare), history of hypertension, prior independent ambulation and hospital size were independent characteristics associated with NIHSS ≤5. Among EVT patients with NIHSS ≤5, 76% were discharged home/rehabilitation and 64% were able to ambulate independently at discharge as compared with 53% and 32% of patients with NIHSS >5. Symptomatic intracerebral hemorrhage occurred in 4% of mild stroke EVT patients and 6.4% in those with NIHSS >5. Conclusions- Despite lack of evidence-based recommendations, 11% of patients receiving EVT in clinical practice have mild neurological presentations. Individual, hospital and geographic disparities are observed among endovascularly treated patients based on the severity of clinical symptoms. Our data suggest safety and overall favorable outcomes for EVT patients with mild stroke.

A Data-Centric Approach to improve performance of deep learning models.

The Artificial Intelligence has evolved and is now associated with Deep Learning, driven by availability of vast amount of data and computing power. Traditionally, researchers have adopted a Model-Centric Approach, focusing on developing new algorithms and models to enhance performance without altering the underlying data. However, Andrew Ng, a prominent figure in the AI community, has recently emphasized on better (quality) data rather than better models, which has given birth to Data Centric Approach, also known as Data Oriented technique. The transition from model oriented to data oriented approach has rapidly gained momentum within the realm of deep learning. Despite its promise, the Data-Centric Approach faces several challenges, including (a) generating high-quality data, (b) ensuring data privacy, and (c) addressing biases to achieve fairness in datasets. Currently, there has been limited effort in preparing quality data. Our work aims to address this gap by focusing on the generation of high-quality data through methods such as data augmentation, multi-stage hashing to eliminate duplicate instances, to detect and correct noisy labels, using confident learning. The experiments on popular datasets, namely MNIST, Fashion MNIST, and CIFAR-10 were performed by utilizing ResNet-18 as the common framework followed by both Model Centric and Data Centric Approach. Comparative performance analysis revealed that the Data Centric Approach consistently outperformed the Model Centric Approach by a relative margin of at least 3%. This finding highlights the potential for further exploration and adoption of the Data-Centric Approach in various domains such as healthcare, finance, education, and entertainment, where the quality of data could significantly enhance the performance.

Acquisition of Prehospital Stroke Severity Scale is associated with shorter door-to-puncture times in patients with prehospital notifications transported directly to a thrombectomy center.

BACKGROUND: We sought to identify systemic factors influencing door-to-puncture times (DTP) among patients with pre-arrival notifications presenting directly to a comprehensive stroke center (CSC) and undergoing emergent mechanical thrombectomy (MT). METHODS: In this retrospective analysis of a prospectively maintained registry of acute ischemic stroke (AIS) patients undergoing MT at two CSCs between January 2021 and October 2023, we included consecutive AIS patients presenting directly to the CSC with pre-arrival notifications via emergency medical services (EMS) and who underwent emergent MT. We excluded patients with known confounders to DTP and divided this cohort into two groups: DTP ≤75 min and >75 min. We used variables with P value <0.2 in the univariate analysis to build a binary logistic regression model to identify their association with DTP >75 min, adjusting for door-to-CT time. RESULTS: Of 900 patients, 605 were inter-facility transfers, 89 were excluded due to known confounders/missing prehospital notifications, leaving 206 qualifying patients. On multivariable analysis, not meeting American Heart Association (AHA) level 1 criteria (adjusted OR (aOR) 3.04, 95% CI 1.62 to 5.82, P<0.001), lack of Prehospital Stroke Severity Scale (PSSS) acquisition (aOR 2.2, 95% CI 1.19 to 4.11, P=0.01), and presentation after-hours (aOR 2.27, 95% CI 1.23 to 4.28, P=0.01) were associated with >75 min DTP times. Most patients (62.3%) had no clearly documented reasons for delay in MT, whereas 25.8% of delays were attributed to prolonged medical decision-making. CONCLUSION: Arrival outside business hours, not meeting AHA level 1 criteria, and lack of PSSS acquisition by EMS were associated with prolonged DTP. Impacting modifiable factors such as prehospital assessment of stroke severity is an optimal target for quality improvement.

Multiplane reconstruction modifies the diagnostic performance of CT angiography in carotid webs.

INTRODUCTION: Carotid Web (CaW) represents an overlooked stroke etiology and has been associated with high recurrence rates and to be amenable to stenting. We evaluated the diagnostic performance of different computed tomography angiography (CTA) projections in CaW. METHODS: Consecutive patients <65 years-old with symptomatic CaW (n=31), carotid atherosclerosis (n=27), or normal carotids (n=49) diagnosed with a thin-cut CTA were included. Deidentified CTAs were independently reviewed by three readers, who recorded the diagnosis and level of certainty after evaluating the axial plane alone, after adding sagittal/coronal maximum intensity projection (MIP), then after oblique MPR reformats. RESULTS: There were 93 total CaW, 81 atherosclerosis, and 147 normal carotid reads. With CTA axial projection alone, less CaW cases (44.1 %) were appropriately diagnosed as compared to atherosclerosis (87.7 %; p<0.001) and normal carotid (83 %; p<0.001) cases. Sagittal/coronal MIPS increased the rate of accurate CaW diagnosis (44.1-76.3 %; p<0.001). Inter-rater agreement in CaW detection increased from k= 0.46 (0.35-0.57) using axial to k= 0.80 (0.69-0.91) with sagittal/coronal planes. The axial projection alone had lower sensitivity (44 % vs. 76 %) but similar specificity (95 % vs. 96 %) in CaW detection compared to axial+ sagittal/coronal MIPS. The accuracy in detecting atherosclerosis or normal carotids did not increase after adding sagittal/coronal MIPS and oblique MPRs. The certainty level for CaW diagnosis was lower when compared to atherosclerosis and normal carotids using axial alone (3.0 [3.0-4.0] vs. 4.0 [3.0-5.0]; p<0.001 and 4.0 [3.0-5.0]; p<0.001) as well as after adding sagittal/coronal MIPS (4.0 [3.0-5.0] vs. 5.0[4.0-5.0]; p=0.01 and 4.0 [4.0-5.0]; p<0.001). CONCLUSION: CTA axial plane alone was insufficient for CaW detection. CTA sagittal/coronal MIP reconstructions as well as oblique MPR reformats enhanced the accuracy and confidence related to CaW diagnosis.

Distal Medium Vessel Occlusion Strokes: Understanding the Present and Paving the Way for a Better Future.

Distal medium vessel occlusions (DMVOs) are thought to cause as many as 25% to 40% of all acute ischemic strokes and may result in substantial disability amongst survivors. Although intravenous thrombolysis (IVT) is more effective for distal than proximal vessel occlusions, the overall efficacy of IVT remains limited in DMVO with less than 50% of patients achieving reperfusion and about 1/3 to 1/4 of the patients failing to achieve functional independence. Data regarding mechanical thrombectomy (MT) among these patients remains limited. The smaller, thinner, and more tortuous vessels involved in DMVO are presumably associated with higher procedural risks whereas a lower benefit might be expected given the smaller amount of tissue territory at risk. Recent advances in technology have shown promising results in endovascular treatment of DMVOs with room for future improvement. In this review, we discuss some of the key technical and clinical considerations in DMVO treatment including the anatomical and clinical terminology, diagnostic modalities, the role of IVT and MT, existing technology, and technical challenges as well as the contemporary evidence and future treatment directions.

Intraoperative neuromonitoring as real-time diagnostic for cerebral ischemia in endovascular treatment of ruptured brain aneurysms.

OBJECTIVE: To evaluate the diagnostic accuracy of intraoperative neurophysiological monitoring (IONM) during endovascular treatment (EVT) of ruptured intracranial aneurysms (rIA). METHODS: IONM and clinical data from 323 patients who underwent EVT for rIA from 2014-2019 were retrospectively reviewed. Significant IONM changes and outcomes were evaluated based on visual review of data and clinical documentation. RESULTS: Of the 323 patients undergoing EVT, significant IONM changes were noted in 30 patients (9.29%) and 46 (14.24%) experienced postprocedural neurological deficits (PPND). 22 out of 30 (73.33%) patients who had significant IONM changes experienced PPND. Univariable analysis showed changes in somatosensory evoked potential (SSEP) and electroencephalogram (EEG) were associated with PPND (p-values: <0.001 and <0.001, retrospectively). Multivariable analysis showed that IONM changes were significantly associated with PPND (Odd ratio (OR) 20.18 (95%CI:7.40-55.03, p-value: <0.001)). Simultaneous changes in both IONM modalities had specificity of 98.9% (95% CI: 97.1%-99.7%). While sensitivity when either modality had a change was 47.8% (95% CI: 33.9%-62.0%) to predict PPND. CONCLUSIONS: Significant IONM changes during EVT for rIA are associated with an increased risk of PPND. SIGNIFICANCE: IONM can be used confidently as a real time neurophysiological diagnostic guide for impending neurological deficits during EVT treatment of rIA.

Optical Coherence Tomography in the Evaluation of Suspected Carotid Webs.

BACKGROUND: Carotid web (CaW) is a subtype of fibromuscular dysplasia that predominantly involves the intimal layer of the arterial wall and is commonly overlooked as a separate causative entity for recurrent strokes. CaW is defined as a shelf-like lesion at the carotid bulb, although different morphological features have been reported. Optical coherence tomography (OCT) has been described in the literature as a useful microscopic and cross-sectional tomographic imaging tool. This study aimed to evaluate the potential utility of OCT in characterizing the wall structure features of patients with suspected CaW. METHODS: Retrospective analysis of patients with suspected CaW who underwent digital subtraction angiography (DSA) coupled with OCT of the carotid bulb from 2018 to 2021 in a single comprehensive stroke center. RESULTS: Sixteen patients were included. The median age was 56 years (IQR 46-61) and 50% were women. OCT corroborated the diagnosis of CaW in 12/16 (75%) cases and ruled it out in 4/16 (25%) patients in whom atherosclerotic disease was demonstrated. Five of the 12 lesions demonstrated a thick fibrotic ridge consistent with CaW but also showed atherosclerotic changes in the vicinity of the carotid bulb (labeled as "CaW+"). In 4/16 (25%) patients, microthrombi adhered to the vessel wall were noted on OCT (inside the CaW pocket or just distal to the web), none of which were observed on CT angiography or DSA. CONCLUSIONS: OCT may have value as a complementary imaging tool in the investigation of patients with suspected CaW and atypical morphological features. Further studies are warranted.

Intracranial stenting versus aggressive medical therapy for symptomatic intracranial stenosis: A meta-analysis of multicenter randomized controlled trials and an expert assessment of the current data.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is associated with high risk of recurrent strokes despite best medical management (MM). We aimed to synthesize the evidence from randomized studies comparing intracranial stenting plus MM versus MM alone. METHODS: Comprehensive search of MEDLINE database was performed until May 2023. The data were extracted and pooled as risk ratio (RR) with 95% confidence interval (95% CI). RESULTS: We included three multicenter RCTs totaling 919 patients. As compared to MM alone, intracranial stenting was associated with statistically significant higher risks of any stroke or death (RR = 2.93, 95%CI [1.80-4.78], p < 0.0001), stroke in the same territory of qualifying artery (RR = 3.56, 95%CI [1.97-6.44], p < 0.0001), any ischemic stroke (RR = 2.22, 95%CI [1.27-3.87], p = 0.005), hemorrhagic stroke (RR = 13.49, 95%CI [2.59-70.15], p = 0.0002), and death (RR = 5.43, 95%CI [1.21-24.40], p = 0.003) within 30 days of randomization. There was a persistent lack of benefit and signals of harm at the last follow up within 1-3 years: any stroke or death (RR = 1.57, 95%CI [0.92-2.67], p = 0.1), stroke in the same territory of qualifying artery (RR = 1.84, 95%CI [0.97-3.50], p = 0.06), any ischemic stroke (RR = 1.56, 95%CI [1.11-2.20], p = 0.01), death (RR = 1.61, 95%CI [0.77-3.38], p = 0.2). The cumulative rate of stroke in the same territory of qualified artery with MM alone within the 1-3-year follow up was lower than expected, with only 47 out of the 450 (10.4%) MM alone patients suffering such events. CONCLUSION: The findings from this meta-analysis do not recommend stenting as a routine care option for the broader symptomatic ICAS patient population. The rates of recurrent strokes in ICAS patients managed with aggressive MM do not seem to be as high as anticipated. Additional multicenter RCTs including safer devices, larger sample sizes, and patients at higher risk of recurrent events are warranted.

From therapeutic nihilism to armamentarium: A meta-analysis of randomized clinical trials assessing safety and efficacy of endovascular therapy for acute large ischemic strokes.

BACKGROUND: Three recent randomized clinical trials (RCTs) investigated the potential benefit of endovascular therapy (EVT) in acute ischemic stroke patients presenting with large infarcts. We aimed to confirm the safety and efficacy of EVT in patients presenting with large infarcts and provide more precise estimations of the treatment effects using study-level meta-analysis. METHODS: Comprehensive search of MEDLINE database through PubMed till February 2023 was performed including RCTs only. The data were then extracted from the selected studies and pooled as risk ratio (RR) with 95% confidence interval (95% CI). RESULTS: There were a total of 1005 patients across the three qualifying RCTs. Regarding the functional outcomes assessed by modified Rankin Scale (mRS) score, the analyzed data demonstrated statistically significant differences in favor of thrombectomy for both independent ambulatory status (mRS 0-3: RR = 1.78, 95% CI [1.28, 2.48], p = 0.0006) and functional independence (mRS 0-2: RR = 2.54, 95% CI [1.85, 3.48], p < 0.001). The analyzed data did not demonstrate any statistically significant differences between EVT and medical management alone in terms of 90-day mortality (RR = 0.95, 95% CI [0.78, 1.16], p = 0.61), symptomatic intracranial hemorrhage (RR = 1.83, 95% CI [0.95, 3.55], p = 0.07), and need for hemicraniectomy (RR = 1.22, 95% CI [0.43, 3.41], p = 0.71). CONCLUSION: This study confirms the benefit of EVT on functional outcomes of patients presenting with large ischemic infarcts without significant differences in the rates of symptomatic intracranial hemorrhage, hemicraniectomy, or 90-day mortality.

Optimization of collateral grading on computer tomography angiography.

BACKGROUND: As compared to single-phase CTA (sCTA), multi-phase CTA (mCTA) has been shown to more accurately estimate collateral flow in acute ischemic stroke (AIS). We sought to determine the characterization of poor collaterals across the three different phases of the mCTA. We also attempted to establish the optimal arterio-venous contrast timing parameters on sCTA that would prevent false positive reads of poor collateral status. METHODS: We retrospectively screened consecutive patients admitted for possible thrombectomy from February 2018 to June 2019. Only cases with intracranial internal carotid artery (ICA) or main trunk of the middle cerebral artery (MCA) occlusion and both baseline mCTA and CT Perfusion available were included. Mean Hounsfield units (HU) of torcula and torcula/patent ICA ratio were used for the arterio-venous timing analysis. RESULTS: Of the 105 patients included, 35 (34%) received IV-tPA treatment and 65 (61.9%) underwent mechanical thrombectomy. A total of 20 patients (19%) had poor collaterals on the third-phase CTA (ground-truth). The first-phase CTA often underestimated collateral score (37/105 [35%], p < 0.01), however there were no significant differences across the second- and third-phases (5/105[5%], p = 0.06. Venous opacification Youden's J point for identifying suboptimal sCTAs was found to be 207.9HU in the torcula (65% sensitivity,65% specificity) and 66.74% for torcula/patent ICA ratio (51% sensitivity,73% specificity). CONCLUSION: A dual-phase CTA is significantly similar to a mCTA assessment of collateral score and may be applied at community-based centers. Absolute or relative thresholds for torcula opacification may be used to identify poor bolus-scan timing thus preventing erroneous assumptions of poor collaterals on sCTA.

Characterizing Fast and Slow Progressors in Anterior Circulation Large Vessel Occlusion Strokes.

BACKGROUND AND PURPOSE: Infarct growth rate (IGR) in acute ischemic stroke is highly variable. We sought to evaluate impact of symptom-reperfusion time on outcomes in patients undergoing mechanical thrombectomy (MT). METHODS: A prospectively maintained database from January,2012-August,2020 was reviewed. All patients with isolated MCA-M1 occlusion who achieved complete reperfusion(mTICI2C-3), had a witnessed symptom onset and follow-up MRI were included. IGR was calculated as final infarct volume (FIV)(ml)/symptom onset to reperfusion time(hours) and was dichotomized according to the median value into slow-(SP) versus fast-progressors (FP). The primary analysis aimed to evaluate the impact of symptom-reperfusion time on 90-day mRS in SP and FP. Secondary analysis was performed to identify predictors of IGR. RESULTS: A total of 137 patients were eligible for analysis. Mean age was 63 ± 15.4 years and median IGR was 5.13ml/hour. SP(n = 69) had higher median ASPECTS, lower median rCBF<30% lesion volume, higher proportion of favorable collaterals and hypoperfusion intensity ratio (HIR)<0.4, higher minimal mean arterial blood pressure before reperfusion, and lower rates of general anesthesia compared to FP(n = 68). Symptom-reperfusion time was comparable between both groups. SP had higher rates of 90-day mRS0-2(71.9%vs.38.9%,aOR;7.226,95%CI[2.431-21.482],p < 0.001) and lower median FIV. Symptom-reperfusion time was associated with 90-day mRS0-2 in FP (aOR;0.541,95%CI[0.309-0.946],p = 0.03) but not in SP (aOR;0.874,95%CI[0.742-1.056],p = 0.16). On multivariable analysis, high ASPECTS and favorable collaterals in the NCCT/CTA model, and low rCBF<30% and HIR<0.4 in the CTP model were independent predictors of SP. CONCLUSIONS: The impact of symptom-reperfusion time on outcomes significantly varies across slow-versus fast-progressors. ASPECTS, collateral score, rCBF<30%, and HIR define stroke progression profile.