Probing the function of long noncoding RNAs in the nucleus.

The nucleus is a highly organized and dynamic environment where regulation and coordination of processes such as gene expression and DNA replication are paramount. In recent years, noncoding RNAs have emerged as key participants in the regulation of nuclear processes. There are a multitude of functional roles for long noncoding RNA (lncRNA), mediated through their ability to act as molecular scaffolds bridging interactions with proteins, chromatin, and other RNA molecules within the nuclear environment. In this review, we discuss the diversity of techniques that have been developed to probe the function of nuclear lncRNAs, along with the ways in which those techniques have revealed insights into their mechanisms of action. Foundational observations into lncRNA function have been gleaned from molecular cytology-based, single-cell approaches to illuminate both the localization and abundance of lncRNAs in addition to their potential binding partners. Biochemical, extraction-based approaches have revealed the molecular contacts between lncRNAs and other molecules within the nuclear environment and how those interactions may contribute to nuclear organization and regulation. Using examples of well-studied nuclear lncRNAs, we demonstrate that the emerging functions of individual lncRNAs have been most clearly deduced from combined cytology and biochemical approaches tailored to study specific lncRNAs. As more functional nuclear lncRNAs continue to emerge, the development of additional technologies to study their interactions and mechanisms of action promise to continually expand our understanding of nuclear organization, chromosome architecture, genome regulation, and disease states.

"Empty Cyst Sign" Appearance of CSF-Venous Fistula on Digital Spinal Myelography.

Cerebrospinal fluid venous fistulas (CSF-VFs) are an uncommon, yet increasingly recognized, cause of spontaneous intracranial hypotension.1-5 The workup involves magnetic resonance imaging (MRI) of the brain with and without contrast and MRI of the neuroaxis without contrast before dynamic myelography, either computed tomography or digital subtraction.6 The present case of an older woman with symptomatic intracranial hypotension is notable for the specific appearance of CSF-VFs on digital spinal myelography (Video 1). Among her numerous perineural cysts, it was the "disappearing" or "empty" cyst from which the fistula originated. The diagnosis was made using a second lateral fluoroscopy view, not typically used in digital spinal myelography, which demonstrated emptying of contrast from the T6 perineural cyst into the segmental vein at this level, or the "empty cyst sign." The patient then underwent transvenous onyx embolization with resolution of her orthostatic headaches and improvement of contrast-enhanced MRI of the brain with the Bern score decreasing from 7 to 0 at 3 months of follow-up.7 Because transvenous embolization of CSF-VFs is a relatively new procedure, the long-term outcomes of the procedure are not yet known.

Safety and efficacy comparison of embolic agents for middle meningeal artery embolization for chronic subdural hematoma.

OBJECTIVE: To perform a systematic review and meta-analysis evaluating the efficacy of middle meningeal artery embolization in terms of both clinical and radiographic outcomes, when performed with different embolic agents. METHODS: A systematic literature review and meta-analysis was performed to evaluate the impact of embolic agents on outcomes for middle meningeal artery (MMA) embolization. The use of polyvinyl alcohol (PVA) with or without (±) coils, N-butyl cyanoacrylate (n-BCA) ± coils, and Onyx alone were separately evaluated. Primary outcome measures were recurrence, the need for surgical rescue and in-hospital periprocedural complications. RESULTS: Thirty-one studies were identified with a total of 1,134 patients, with 786 receiving PVA, 167 receiving n-BCA, and 181 patients receiving Onyx. There was no difference in the recurrence rate (5.5% for PVA, 4.5% for n-BCA, and 6.5% for Onyx, with P=0.71) or need for surgical rescue (5.0% for PVA, 4.0% for n-BCA, and 6.9% for Onyx, with P=0.89) based on the embolic agent. Procedural complications also did not differ between embolic agents (1.8% for PVA, 3.6% for n-BCA, and 1.6% for Onyx, with P=0.48). CONCLUSIONS: Rates of recurrence, need for surgical rescue, and periprocedural complication following MMA embolization are not impacted by the type of embolic agent utilized. Ongoing clinical trials may be used to further investigate these findings.

Stroke emboli from patients with atrial fibrillation enriched with neutrophil extracellular traps.

Background: Recent literature has demonstrated remarkable heterogeneity in the composition of acute ischemic stroke (AIS) emboli, which may impact susceptibility to therapy. Objectives: In this study, we explored differences in proteomic composition of retrieved embolic material from patients with stroke with and without atrial fibrillation (AF) (AF+ and AF-, respectively). Methods: The full proteome of retrieved thromboembolic material from 24 patients with AIS was obtained by mass spectrometry. Known marker proteins were assigned groups representing broad classes of embolus components: red blood cells, platelets, neutrophils, eosinophils, histones, complement, and other clotting-associated proteins (eg, fibrinogen). Relative protein abundances were compared between AF+ and AF- samples. Functional implications of differences were explored with gene set enrichment analysis and Gene Ontology enrichment analysis and visualization tool. Results: One hundred sixty-six proteins were differentially expressed between AF+ and AF- specimens. Eight out of the 15 neutrophil proteins (P < .05; fold change, >2) and 4 of the 14 histone proteins were significantly enriched in AF+ emboli (P < .05; fold change, >2). Gene set enrichment analysis revealed a significant representation of proteins from published neutrophil extracellular trap (NET) proteomic gene sets. The most significantly represented functional Gene Ontology pathways in patients with AF involved neutrophil activation and degranulation (P < 1 × 10-7). Conclusion: The present analysis suggests enrichment of NETs in emboli of patients with stroke and AF. NETs are a significant though understudied structural component of thrombi. This work suggests not only unique stroke biology in AF but also potential therapeutic targets for AIS in this population.

Histone content, and thus DNA content, is associated with differential in vitro lysis of acute ischemic stroke clots.

BACKGROUND: Fibrin, von Willebrand factor, and extracellular DNA from neutrophil extracellular traps all contribute to acute ischemic stroke thrombus integrity. OBJECTIVES: In this study, we explored how the proteomic composition of retrieved thromboemboli relates to susceptibility to lysis with distinct thrombolytics. METHODS: Twenty-six retrieved stroke thromboemboli were portioned into 4 segments, with each subjected to 1 hour of in vitro lysis at 37 °C in 1 of 4 solutions: tissue plasminogen activator (tPA), tPA + von Willebrand factor-cleaving ADAMTS-13, tPA + DNA-cleaving deoxyribonuclease (DNase) I, and all 3 enzymes. Lysis, characterized by the percent change in prelysis and postlysis weight, was compared across the solutions and related to the corresponding abundance of proteins identified on mass spectrometry for each of the thromboemboli used in lysis. RESULTS: Solutions containing DNase resulted in approximately 3-fold greater thrombolysis than that with the standard-of-care tPA solution (post hoc Tukey, P < .01 for all). DNA content was directly related to lysis in solutions containing DNase (Spearman's ρ > 0.39 and P < .05 for all significant histones) and inversely related to lysis in solutions without DNase (Spearman's ρ < -0.40 and P < .05 for all significant histones). Functional analysis suggests distinct pathways associated with susceptibility to thrombolysis with tPA (platelet-mediated) or DNase (innate immune system-mediated). CONCLUSION: This study demonstrates synergy of DNase and tPA in thrombolysis of stroke emboli and points to DNase as a potential adjunct to our currently limited selection of thrombolytics in treating acute ischemic stroke.

Preoperative Embolization of Meningiomas Facilitates Reduced Surgical Complications and Improved Clinical Outcomes : A Meta-analysis of Matched Cohort Studies.

PURPOSE: The utility of preoperative embolization (PE) of intracranial meningiomas is unclear and controversial. The aim of this study was to investigate the effect of PE on meningioma surgical resection by completing a meta-analysis of matched cohort studies. METHODS: A systematic review and meta-analysis of matched cohort studies was completed to evaluate the effect of PE on meningioma resection and outcomes. Outcome measures included: intraoperative blood loss, major surgical complications, total surgical complications including minor ones, total major complications including major surgical and embolization complications, total overall complications, and postoperative functional independence defined as modified Rankin Score (mRS) of 0-2. Pooled odds ratios (OR) were determined via a fixed effects model. RESULTS: A total of 6 matched cohort studies were identified with 219 embolized and 215 non-embolized meningiomas. There was no significant difference in intraoperative blood loss between the two groups (P = 0.87); however, the embolization group had a significantly lower odds ratio of major surgically related complications (OR: 0.37, 95% confidence interval, CI: 0.21-0.67, P = 0.0009, I2 = 0%), but no difference in minor surgical complications (P = 0.86). While there was a significantly lower odds ratio of total overall surgical and PE-related complications in PE cases (OR: 0.64, CI: 0.41-1.0, P = 0.05, I2 = 66%), there was no difference in total combined major complications between the groups (OR: 0.57, CI: 0.27-1.18, P = 0.13, I2 = 33%). Lastly, PE was associated with a higher odds ratio of functional independence on postoperative follow-up (OR: 2.3, CI: 1.06-5.02, P = 0.04, I2 = 0%). CONCLUSION: For certain meningiomas, PE facilitates lower overall complications, lower major surgical complications, and improved functional independence. Further research is required to identify the particular subset of meningiomas that benefit from PE.

Carotid Intimal Sarcoma Presenting as Large Vessel Occlusion and Diagnosed by Embolus Histopathology: Case Report.

Objective: The objective of this study was to present the clinical, histopathologic, and radiographic findings of a unique case of intimal sarcoma (IS) embolus presenting as a large vessel occlusion causing an ischemic stroke without a detectable primary tumor site. Methods: Extensive examinations, multimodal imaging, laboratory testing, and histopathologic analysis were used in evaluation. Results: We report the case of a patient who presented with acute embolic ischemic stroke and was found to have IS based on a histopathologic evaluation of his embolectomy specimen. Subsequent comprehensive imaging studies failed to detect a primary tumor site. Multidisciplinary interventions including a course of radiotherapy were performed. The patient died of recurrent multifocal strokes 92 days after diagnosis. Discussion: Meticulous histopathologic analysis should be conducted on cerebral embolectomy specimens. Histopathology may be useful in diagnosing IS.

Symptomatic carotid artery intraluminal thrombus: risk of medical management failure and distal embolization.

BACKGROUND: Carotid artery intraluminal thrombus (ILT), or free-floating thrombus, is an uncommon cerebrovascular entity with considerable equipoise regarding its clinical management. Likewise, in patients treated with medical management (MM), distal embolization and/or intracranial hemorrhage (ICH) may still occur. METHODS: All patients with symptomatic ILT from 2016 to 2023 were identified from our tertiary care institution. Patients with MM failure (recurrent cerebral ischemia and/or symptomatic ICH) were compared with patients with MM non-failure. Differences in ILT volume and length were calculated. Receiver operator characteristic (ROC) curve analysis was used to identify the cut-off volume and length for risk of MM failure. RESULTS: In total, 45 patients with ILT were identified with 41 treated with frontline MM. Of these 41 patients treated with MM, seven (17%) had MM failure with six (14.6%) having new embolic stroke and one (2.3%) with symptomatic ICH. Patients with MM failure had a significantly higher mean thrombus volume than MM non-failure patients (257 mm3 vs 59.6 mm3, P=0.0006). Likewise, patients with MM failure had significantly longer thrombus on average (21 mm vs 6.6 mm, P=0.0009). ROC curve analysis showed that an ILT volume of 90 mm3 resulted in a sensitivity of 71.4% and specificity of 85.3% for MM failure (AUC 0.775; CI 0.55 to 1.0, P=0.023). CONCLUSIONS: Carotid ILTs that fail MM are significantly larger and longer. These findings suggest that a thrombus volume of 90 mm3 may serve as a guide for intervention with good sensitivity and specificity for risk of MM failure.

HER2 categorical changes after neoadjuvant chemotherapy: A study of 192 matched breast cancers with the inclusion of HER2-Low category.

Understanding the changes of HER2 expression after neoadjuvant chemotherapy (NAC) in breast cancer (BC) is more important than ever, since it may allow more patients to access the effective therapeutic drugs targeting HER2-low BC. 192 matched pre- and post-NAC BCs were analyzed. HER2 immunohistochemistry (IHC) was re-evaluated with consensus according to the current ASCO/CAP guidelines. Tumors were categorized into HER2-0 (IHC0+), HER2-low (IHC1+ or IHC2+/ISH-) and HER2-positive (IHC3+ or IHC2+/ISH+) subgroups. 55 (28.6 %) patients achieved pathologic complete response (pCR). HER2-low BC accounted for 75/192 (39.1 %) baseline tumors, and 48/133 (36.1 %) residual tumors. In the non-pCR cohort, 53 (39.9 %) patients had HER2 categorical change after NAC, most commonly converting from HER2-low to HER2-0 (20.3 %, n = 27). Among patients with residual tumor, 25.6 % (11/43) of patients with baseline HER2-0 expression experienced a categorical change to HER2-low after NAC, significantly higher (p < 0.05) in the hormone receptor (HR) positive (9/23, 39.1 %) compared to the HR negative tumors (10 %, 2/20). Exploratory analysis failed to reveal a statistically significant difference in disease free survival and overall survival in non-pCR patients with or without HER2 change. Our results suggest that a substantial number of patients may experience HER2 categorical change after NAC, supporting re-testing of HER2 status in post-NAC residual tumors. Retesting HER2 status may be particularly important for evaluating post-NAC HER2-low status, in order to better assess which patients will more likely benefit from therapeutic drugs targeting HER2-low BC.

Efficacy of transvenous embolization of CSF-venous fistula in spontaneous intracranial hypotension: Case-series.

BACKGROUND: Spontaneous intracranial hypotension is a debilitating neurological condition which can be caused by a cerebrospinal fluid-venous fistula. Transvenous embolization is a promising technique to provide minimally invasive yet durable treatment. METHODS: A retrospective single-center case series was performed on all patients who underwent transvenous embolization of a cerebrospinal fluid (CSF)-venous fistula. Clinical and radiographic parameters, including Bern score, were reported preoperatively and at 3-month follow-up. RESULTS: Six patients underwent embolization of a CSF-venous fistula. All fistulae were located in the thoracic spine and technical success was achieved in all cases. Three patients had symptom resolution, two had significant improvement, and one had stable symptoms on follow-up. The mean Bern score was 6.83 (SD = 1.47) preoperatively and 1.83 (SD = 1.64) postoperatively with a mean improvement in Bern score of 5.0 (SD = 1.9, p = 0.0013). CONCLUSIONS: CSF-venous fistulas are an increasingly recognized clinical entity which may be treated with transvenous embolization. This case series serves to further validate this technique and suggests it can be performed with similar outcomes in lower volume centers.

CT hyperdense cerebral artery sign reflects distinct proteomic composition in acute ischemic stroke thrombus.

BACKGROUND: Hyperdense cerebral artery sign (HCAS) is an imaging biomarker in acute ischemic stroke (AIS) that has been shown to be associated with various clinical outcomes and stroke etiology. While prior studies have correlated HCAS with histopathological composition of cerebral thrombus, it is unknown whether and to what extent HCAS is also associated with distinct clot protein composition. METHODS: Thromboembolic material from 24 patients with AIS were retrieved via mechanical thrombectomy and evaluated with mass spectrometry in order to characterize their proteomic composition. Presence (+) or absence (-) of HCAS on preintervention non-contrast head CT was then determined and correlated with thrombus protein signature with abundance of individual proteins calculated as a function HCAS status. RESULTS: 24 clots with 1797 distinct proteins in total were identified. 14 patients were HCAS(+) and 10 were HCAS(-). HCAS(+) were most significantly differentially abundant in actin cytoskeletal protein (P=0.002, Z=2.82), bleomycin hydrolase (P=0.007, Z=2.44), arachidonate 12-lipoxygenase (P=0.004, Z=2.60), and lysophospholipase D (P=0.007, Z=2.44), among other proteins; HCAS(-) clots were differentially enriched in soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (P=0.0009, Z=3.11), tyrosine-protein kinase Fyn (P=0.002, Z=2.84), and several complement proteins (P<0.05, Z>1.71 for all), among numerous other proteins. Additionally, HCAS(-) thrombi were enriched in biological processes involved with plasma lipoprotein and protein-lipid remodeling/assembling, and lipoprotein metabolic processes (P<0.001), as well as cellular components including mitochondria (P<0.001). CONCLUSIONS: HCAS is reflective of distinct proteomic composition in AIS thrombus. These findings suggest that imaging can be used to identify mechanisms of clot formation or maintenance at the protein level, and might inform future research on thrombus biology and imaging characterization.

Direct percutaneous puncture versus transarterial embolization for head and neck paragangliomas: A systematic review and meta-analysis.

INTRODUCTION: Embolization of head and neck paragangliomas (HNPs) is a well-established treatment strategy and adjunctive therapy. However, the optimal mode of intervention, whether by direct percutaneous puncture (DP) or via transarterial embolization (TAE), remains unclear. METHODS: The aim of this study was to complete a systematic literature review and meta-analysis to compare the safety and efficacy of DP versus TAE for HNP embolization. The Cochrane Library and MEDLINE databases were used to identify studies describing the clinical outcomes of either DP or TAE for HNP embolization. Outcome measures included: complete angiographic devascularization, major complications, and minor complications. Pooled rates were calculated for each variable which were then compared with meta-regression using a random effects model. RESULTS: Thirty-one retrospective studies met inclusion criteria, detailing 394 patients with 411 HNPs. Overall, DP was associated with a higher rate of complete devascularization (91.5%, 95% confidence interval [CI]: 85.6% to 97.4%; I2 = 0%) when compared to TAE technique (40.1%, CI: 27.2% to 58.9%; I2 = 93%). However, there was no difference regarding major complication rates between DP (6%, CI:1.3% to 10.8%; I2 = 0%) and TAE for HNP embolization (3.3%, CI: 1.4% to 5.3%; I2 = 0%) (p = 0.370), nor in minor complications between the techniques (p = 0.211). Subgroup analysis of TAE embolic agents revealed that particle embolics were associated with a significantly lower rate of major complications (2.5%; 0.4% to 4.6%; I2 = 0%) when compared to liquid embolics (10.6%, CI:4% to 17.3%; I2 = 48%; p = 0.022). CONCLUSIONS: A DP approach for HNP embolization results in a higher rate of complete devascularization and with a similar complication profile when compared to TAE. These findings also suggest that particle embolics are associated with fewer major complications compared to liquid embolics when TAE is utilized.

Impact of aspiration catheter size on clinical outcomes in aspiration thrombectomy.

BACKGROUND: Direct aspiration thrombectomy is a well-established method for mechanical thrombectomy in acute ischemic stroke. Yet, the influence of aspiration catheter internal diameter (ID) on aspiration thrombectomy efficacy is incompletely understood. METHODS: A systematic literature review and meta-regression analysis was completed to evaluate the impact of primary aspiration thrombectomy outcomes based on the ID of the aspiration catheter. Primary outcome measures were: final recanalization of modified Thrombolysis In Cerebral Ischemia (mTICI) 2b-3 with aspiration only and with rescue modalities, first pass effect (FPE), need for rescue modalities, intracranial hemorrhagic complication rates, and functional outcomes of 90-day modified Rankin Scale (mRS) of 0-2. RESULTS: 30 studies were identified with 3228 patients. Meta-regression analysis revealed a significant association between increasing aspiration catheter ID and FPE (p=0.032), between ID and final recanalization with aspiration only (p=0.05), and between ID size and recanalization including cases with rescue modalities (p=0.002). Further, subgroup analysis indicated that catheters with an ID ≥0.064 inch had a lower rate of need for rescue than smaller catheters (p=0.013). Additionally, catheters with an ID ≥0.068 inch had a higher rate of intracranial bleeding complications (p=0.025). Lastly, no significant association was found in functional outcomes overall. CONCLUSIONS: Larger aspiration catheters are associated with a higher rate of FPE, final recanalization with only an aspiration catheter, and in cases with rescue modalities, though with a higher rate of hemorrhagic complications. These findings confirm that aspiration catheter size functions as a variable in aspiration thrombectomy, which should be considered in future study and trial design.

Ischemic Stroke Thrombus Perviousness Is Associated with Distinguishable Proteomic Features and Susceptibility to ADAMTS13-Augmented Thrombolysis.

BACKGROUND AND PURPOSE: Perviousness is the differential attenuation on CT of an intracranial arterial occlusive thrombus before and after IV contrast administration. While perviousness/permeability has been shown to be related to various clinical outcomes and reflects histopathologic composition, it remains unclear whether perviousness is also associated with differences in proteomic composition. MATERIALS AND METHODS: Retrieved clots from 59 patients were evaluated with quantitative mass spectrometry. Proteomic differences between high-perviousness (≥11 HU) and low-perviousness (<11 HU) clots were investigated. Perviousness as a continuous variable was also correlated with protein abundance. Last, an ex vivo lysis assay was performed to investigate the differential susceptibility to tPA, deoxyribonuclease, and ADAMTS13 thrombolysis as a function of perviousness. RESULTS: In total, 2790 distinct proteins were identified. Thrombus perviousness was associated with distinct proteomic features, including depletion of the macrophage marker CD14 (P = .039, z = 1.176) and hemoglobin subunit ζ (P = .046, z = 1.68) in pervious clots. Additionally, proteins involved in platelet cytoskeleton remodeling (tropomyosin α-3-chain) and granule secretion/aggregation (synaptotagmin-like protein 4/FC region receptor II-a) were associated with increasing perviousness (P < .006), among numerous other proteins. Monocyte/macrophage-associated proteins (apoptosis-associated specklike protein containing a CARD/SAMHD1) were also depleted in pervious emboli (P < .002). Ex vivo lysis indicated that pervious clots were more susceptible to ADAMTS13-augmented tPA thrombolysis compared with impervious clots (P < .05), though without differences in deoxyribonuclease digestion. CONCLUSIONS: Thrombus perviousness is associated with complex proteomic features, including differential abundance of platelet-related proteins in highly permeable clots with monocyte/macrophage depletion. This association may help to explain why highly pervious thrombi were also found more susceptible to ADAMTS13-augmented thrombolysis.

Complications of transradial versus transfemoral access for neuroendovascular procedures: a meta-analysis.

BACKGROUND: Transradial access (TRA) has gained increased usage among neurointerventionalists. However, the overall safety profile of access site complications (ASCs) and non-access site complications (NASCs) of TRA versus transfemoral access (TFA) for neuroendovascular procedures remains unclear. METHODS: A systematic literature review and meta-analysis using a random effects model was conducted to investigate the pooled odds ratios (OR) of ASCs and NASCs. Randomized, case-control, and cohort studies comparing access-related complications were analyzed. An assessment of study heterogeneity and publication bias was also completed. RESULTS: Seventeen comparative studies met the inclusion criteria for final analysis. Overall, there was a composite ASC rate of 1.8% (49/2767) versus 3.2% (168/5222) for TRA and TFA, respectively (P<0.001). TRA was associated with a lower odds of ASC compared with TFA (OR 0.42; 95% CI 0.25 to 0.68, P<0.001, I2=31%). There was significantly lower odds of complications within the intervention and diagnostic subgroups. For NASC, TRA had a lower composite incidence of complications than TFA at 1.2% (31/2586) versus 4.2% (207/4909), P<0.001). However, on meta-analysis, we found no significant difference overall between TRA and TFA for NASCs (OR 0.79; 95% CI 0.51 to 1.22, P=0.28, I2=0%), which was also the case on subgroup analysis. CONCLUSION: On meta-analysis, the current literature indicates that TRA is associated with a lower incidence of ASCs compared with TFA, but is not associated with a lower rate of NASCs.

Observation versus intervention for Borden type I intracranial dural arteriovenous fistula: A pooled analysis of 469 patients.

BACKGROUND: While it is thought that Borden Type I intracranial dural arteriovenous fistula (dAVF) have a benign clinical course, their management remains controversial. METHODS: A comparative meta-analysis was completed to evaluate the outcomes of intervention verses observation of Borden Type I intracranial dAVF. Outcome measures included: grade progression, worsening symptoms, death due to dAVF, permanent complications other than death, functional independence (mRS 0-2), and rate of death combined with permanent complication, were evaluated. Risk differences (RD) were determined using a random effects model. RESULTS: Three comparative studies combined with the authors' institutional experience resulted in a total of 469 patients, with 279 patients who underwent intervention and 190 who were observed. There was no significant difference in dAVF grade progression between the intervention and observation arms, 1.8% vs. 0.7%, respectively (RD: 0.01, 95% CI: -0.02 to 0.04, P = 0.49), or in symptom progression occurring in 31/279 (11.1%) intervention patients and 11/190 (5.8%) observation patients (RD: 0.03, CI: -0.02 to 0.09, P = 0.28). There was also no significant difference in functional independence on follow up. However, there was a significantly higher risk of dAVF related death, permanent complication from either intervention or dAVF related ICH or stroke in the intervention group (11/279, 3.9%) compared to the observation group (0/190, 0%) (RD: 0.04, CI: 0.1 to 0.06, P = 0.007). CONCLUSION: Intervention of Borden Type I dAVF results in a higher risk of death or permanent complication, which should be strongly considered when deciding on management of these lesions.

Mobile Stroke Unit Operational Metrics: Institutional Experience, Systematic Review and Meta-Analysis.

Background: The available literature on mobile stroke units (MSU) has focused on clinical outcomes, rather than operational performance. Our objective was to establish normalized metrics and to conduct a meta-analysis of the current literature on MSU performance. Methods: Our MSU in upstate New York serves 741,000 people. We present prospectively collected, retrospectively analyzed data from the inception of our MSU in October of 2018, through March of 2021. Rates of transportation/dispatch and MSU utilization were reported. We also performed a meta-analysis using MEDLINE, SCOPUS, and Cochrane Library databases, calculating rates of tPA/dispatch, tPA-per-24-operational-hours ("per day"), mechanical thrombectomy (MT)/dispatch and MT/day. Results: Our MSU was dispatched 1,719 times in 606 days (8.5 dispatches/24-operational-hours) and transported 324 patients (18.8%) to the hospital. Intravenous tPA was administered in 64 patients (3.7% of dispatches) and the rate of tPA/day was 0.317 (95% CI 0.150-0.567). MT was performed in 24 patients (1.4% of dispatches) for a MT/day rate of 0.119 (95% CI 0.074-0.163). The MSU was in use for 38,742 minutes out of 290,760 total available minutes (13.3% utilization rate). Our meta-analysis included 14 articles. Eight studies were included in the analysis of tPA/dispatch (342/5,862) for a rate of 7.2% (95% CI 4.8-9.5%, I2 = 92%) and 11 were included in the analysis of tPA/day (1,858/4,961) for a rate of 0.358 (95% CI 0.215-0.502, I2 = 99%). Seven studies were included for MT/dispatch (102/5,335) for a rate of 2.0% (95% CI 1.2-2.8%, I2 = 67%) and MT/day (103/1,249) for a rate of 0.092 (95% CI 0.046-0.138, I2 = 91%). Conclusions: In this single institution retrospective study and meta-analysis, we outline the following operational metrics: tPA/dispatch, tPA/day, MT/dispatch, MT/day, and utilization rate. These metrics are useful for internal and external comparison for institutions with or considering developing mobile stroke programs.

Noncurative microsurgery for cerebral aneurysms: a systematic review and meta-analysis of wrapping, residual, and recurrence rates.

OBJECTIVE: Microsurgery for cerebral aneurysms is called definitive, yet some patients undergo a craniotomy that results in noncurative treatment. Furthermore, the overall rate of noncurative microsurgery for cerebral aneurysms is unclear. The objective of this study was to complete a systematic review and meta-analysis to quantify three scenarios of noncurative treatment: aneurysm wrapping, postclipping remnants, and late regrowth of completely obliterated aneurysms. METHODS: A PRISMA-guided systematic literature review of the MEDLINE and Cochrane Library databases and meta-analysis was completed. Studies were included that detailed rates of aneurysm wrapping, residua confirmed with imaging, and regrowth after confirmed total occlusion. Pooled rates were subsequently calculated using a random-effects model. An assessment of statistical heterogeneity and publication bias among the included studies was also completed for each analysis, with resultant I2 values and p values determined with Egger's test. RESULTS: Sixty-four studies met the inclusion criteria for final analysis. In 41 studies, 573/15,715 aneurysms were wrapped, for a rate of 3.5% (95% CI 2.7%-4.2%, I2 = 88%). In 43 studies, 906/13,902 aneurysms had residual neck or dome filling, for a rate of 6.4% (95% CI 5.2%-7.6%, I2 = 93%). In 15 studies, 71/2568 originally fully occluded aneurysms showed regrowth, for a rate of 2.1% (95% CI 1.2%-3.1%, I2 = 58%). Together, there was a total rate of noncurative surgery of 12.0% (95% CI 11.5%-12.5%). Egger's test suggested no significant publication bias among the studies. Meta-regression analysis revealed that the reported rate of aneurysm wrapping has significantly declined over time, whereas the rates of aneurysm residua and recurrence have not significantly changed. CONCLUSIONS: Open microsurgery for cerebral aneurysm results in noncurative treatment approximately 12% of the time. This metric may be used to counsel patients and as a benchmark for other treatment modalities. This investigation is limited by the high degree of heterogeneity among the included studies.