Most Promising Approaches to Improve Stroke Outcomes: The Stroke Treatment Academic Industry Roundtable XII Workshop.

The Stroke Treatment Academic Industry Roundtable XII included a workshop to discuss the most promising approaches to improve outcome from acute stroke. The workshop brought together representatives from academia, industry, and government representatives. The discussion examined approaches in 4 epochs: pre-reperfusion, reperfusion, post-reperfusion, and access to acute stroke interventions. The participants identified areas of priority for developing new and existing treatments and approaches to improve stroke outcomes. Although many advances in acute stroke therapy have been achieved, more work is necessary for reperfusion therapies to benefit the most possible patients. Prioritization of promising approaches should help guide the use of resources and investigator efforts.

A review of biocompatible polymer-functionalized two-dimensional materials: Emerging contenders for biosensors and bioelectronics applications.

Bioelectronics, a field pivotal in monitoring and stimulating biological processes, demands innovative nanomaterials as detection platforms. Two-dimensional (2D) materials, with their thin structures and exceptional physicochemical properties, have emerged as critical substances in this research. However, these materials face challenges in biomedical applications due to issues related to their biological compatibility, adaptability, functionality, and nano-bio surface characteristics. This review examines surface modifications using covalent and non-covalent-based polymer-functionalization strategies to overcome these limitations by enhancing the biological compatibility, adaptability, and functionality of 2D nanomaterials. These surface modifications aim to create stable and long-lasting therapeutic effects, significantly paving the way for the practical application of polymer-functionalized 2D materials in biosensors and bioelectronics. The review paper critically summarizes the surface functionalization of 2D nanomaterials with biocompatible polymers, including g-C3N4, graphene family, MXene, BP, MOF, and TMDCs, highlighting their current state, physicochemical structures, synthesis methods, material characteristics, and applications in biosensors and bioelectronics. The paper concludes with a discussion of prospects, challenges, and numerous opportunities in the evolving field of bioelectronics.

Endovascular Embolization of Traumatic Vessel Injury Using N-butyl Cyanoacrylate: A Case Series.

There is limited evidence of N-butyl cyanoacrylate (n-BCA) use in endovascular embolization of traumatic face and neck vessel injuries. We investigated the safety and effectiveness of n-BCA for this purpose. We retrospectively analyzed consecutive patients presenting to a Level 1 trauma center between April 2021 and July 2022. We included patients aged ≥ 18 years old with any vessel injury in the face and neck circulation requiring n-BCA embolization. The primary endpoint was n-BCA effectiveness defined as immediate control of active bleeding post-embolization. In total, 13 patients met the inclusion criteria. The median decade of life was 3 (IQR 3 - 5) with a male predominance (n = 11, 84.6%). Median Glasgow Coma Scale score on presentation was 15 (IQR 3-15). Eleven patients suffered gunshot wound injuries; two patients suffered blunt injuries. Injured vessels included facial artery (n = 6, 46.2%), buccal branch artery (n = 3, 23.1%), internal maxillary (n = 5, 38.5%), cervical internal carotid artery (n = 1, 7.7%), and vertebral artery (n = 1, 7.7%). All patients were treated with 1:2 n-BCA to ethiodol mixture with immediate extravasation control. No bleeding recurrence or need for retreatment occurred. One patient died in-hospital (7.7%). Patients were discharged to home (n = 8, 61.5%), day rehabilitation (n = 1, 7.7%), or acute rehabilitation (n = 3, 23.1%). One patient developed a right posterior cerebral artery infarct with hemorrhagic transformation. To our knowledge, this is the first study demonstrating the safety and effectiveness of n-BCA liquid embolism in traumatic vessel injuries, especially penetrating gunshot wounds.

What is a Challenging Clot? : A DELPHI Consensus Statement from the CLOTS 7.0 Summit.

BACKGROUND: Predicting a challenging clot when performing mechanical thrombectomy in acute stroke can be difficult. One reason for this difficulty is a lack of agreement on how to precisely define these clots. We explored the opinions of stroke thrombectomy and clot research experts regarding challenging clots, defined as difficult to recanalize clots by endovascular approaches, and clot/patient features that may be indicative of such clots. METHODS: A modified DELPHI technique was used before and during the CLOTS 7.0 Summit, which included experts in thrombectomy and clot research from different specialties. The first round included open-ended questions and the second and final rounds each consisted of 30 closed-ended questions, 29 on various clinical and clot features, and 1 on number of passes before switching techniques. Consensus was defined as agreement ≥ 50%. Features with consensus and rated ≥ 3 out of 4 on the certainty scale were included in the definition of a challenging clot. RESULTS: Three DELPHI rounds were performed. Panelists achieved consensus on 16/30 questions, of which 8 were rated 3 or 4 on the certainty scale, namely white-colored clots (mean certainty score 3.1), calcified clots under histology (3.7) and imaging (3.7), stiff clots (3.0), sticky/adherent clots (3.1), hard clots (3.1), difficult to pass clots (3.1) and clots that are resistant to pulling (3.0). Most panelists considered switching endovascular treatment (EVT) techniques after 2-3 unsuccessful attempts. CONCLUSION: This DELPHI consensus identified 8 distinct features of a challenging clot. The varying degree of certainty amongst the panelists emphasizes the need for more pragmatic studies to enable accurate a priori identification of such occlusions prior to EVT.

A Review of the Advancements in the in-vitro Modelling of Acute Ischemic Stroke and Its Treatment.

In-vitro neurovascular models of large vessel occlusions (LVOs) causing acute ischemic stroke (AIS) are used extensively for pre-clinical testing of new treatment devices. They enable physicians and engineers to examine device performance and the response of the occlusion to further advance design solutions for current unmet clinical needs. These models also enable physicians to train on basic skills, to try out new devices and new procedural approaches, and for the stroke team to practice workflows together in the comfort of a controlled environment in a non-clinical setting. Removal of the occlusive clot in its entirety is the primary goal of the endovascular treatment of LVOs via mechanical thrombectomy (MT) and the medical treatment via thrombolysis. In MT, recanalization after just one pass is associated with better clinical outcomes than procedures that take multiple passes to achieve the same level of recanalization, commonly known as first pass effect (FPE). To achieve this, physicians and engineers are continually investigating new devices and treatment approaches. To distinguish between treatment devices in the pre-clinical setting, test models must also be optimized and expanded become more nuanced and to represent challenging patient cohorts that could be improved through new technology or better techniques. The aim of this paper is to provide a perspective review of the recent advancements in the in-vitro modeling of stroke and to outline how these models need to advance further in future. This review provides an overview of the various in-vitro models used for the modeling of AIS and compares the advantages and limitations of each. In-vitro models remain an extremely useful tool in the evaluation and design of treatment devices, and great strides have been made to improve replication of physiological conditions. However, further advancement is still required to represent the expanding indications for thrombectomy and thrombolysis, and the generation of new thrombectomy devices, to ensure that smaller treatment effects are captured.

Systematic Review on Endovascular Access to Intracranial Arteries for Mechanical Thrombectomy in Acute Ischemic Stroke.

PURPOSE: In acute ischemic stroke for large vessel occlusions, delayed or failed access to intracranial occlusions has a negative impact on procedural and clinical outcomes. The aim of this review is to identify and quantify access failures and challenges in mechanical thrombectomy. METHODS: A systematic literature review of PubMed and Scopus databases from January 2014 to October 2020 was performed. Articles reporting consecutive patients were used to calculate a crude failure rate of femoral and alternative accesses. RESULTS: A total of 50 articles met the inclusion criteria, totalling 12,838 interventions. Failure to access the occlusion through transfemoral access occurred in 4.4% of patients, most commonly due to challenging supra-aortic vessel anatomy, decreasing to 3.6% when all alternative access routes were attempted. Failed access from alternative routes (direct carotid, radial and brachial approaches) attempted first-line or after failed femoral attempt were reported in 7.3% of patients. The occurrence rate of potentially challenging features (anatomical, diseases or others) ranged from 4.7% to 47.4%, primarily impacting the access time, procedure time, recanalization and clinical outcomes. CONCLUSION: Failure to access the occlusion is a significant contributor to failed recanalization, regardless of access routes. Challenging, but eventually successful access is also a relevant factor in procedural and clinical outcomes; however challenging access requires a universal definition to enable quantification, so that methods for procedural optimization can be critically assessed.

Aspects of ischemic stroke biomechanics derived using ex-vivo and in-vitro methods relating to mechanical thrombectomy.

Establishing the underlying biomechanics of acute ischemic stroke (AIS) and its treatment is fundamental to developing more effective clinical treatments for one of society's most impactful diseases. Recent changes in AIS management, driven by clinical evidence of improved treatments, has already led to a rapid rate of innovation, which is likely to be sustained for many years to come. These unprecedented AIS triage and treatment innovations provide a great opportunity to better understand the disease. In this article we provide a perspective on the recreation of AIS in the laboratory to inform contemporary device design and procedural techniques in mechanical thrombectomy. Presentation of these findings, which have been used to solve the applied problem of designing mechanical thrombectomy devices, is intended to help inform the development of basic biomechanics solutions for AIS.

DyxMnFe2-xO4 nanoparticles decorated over mesoporous silica for environmental remediation applications.

An efficient, environment-friendly and economical catalyst to control contaminants of environment is an enduring interest in recent years. In this study, a new composite, DyxMnFe2-xO4nanoparticles decorated over mesoporous silica was synthesized and utilized for removal of organic pollutant. Highly crystalline nature of DyxMnFe2-xO4 nanoparticles and amorphous nature of material was confirmed by XRD (X-ray diffraction) technique. Infrared spectra of fabricated material before and after adsorption of dye molecules evidenced the successful adsorption of dye molecules by fabricated adsorbent. From field emission scanning electron microscopic (FESEM) images of Dy3+ substituted MnFe2O4 composite with mesoporous silica, it was clearly observed that ferrite particles of size 20-30 nm were decorated on the surface of mesoporous silica particles and distributed well over spherical silica balls homogeneously. Its magnificent mesoporous nature was revealed from BET (nitrogen adsorption-desorption measurements) analysis. Surface area, pore volume and average pore size was found 387.95 m2/g, 0.390 cm3/g and 4.02 nm respectively. Tri-modal pore size distribution showed its effective utilization in adsorption. The abundant (SiOH) hydroxyl groups of mesoporous silica, the broad diffraction hump of silica depicted its superior loading capacity of target molecular specie inside its porous network. From band gap analysis, a red shift of 2.43 eV exhibited semiconductor photocatalysis of DyxMnFe2-xO4 nanoparticles. Degradation efficiency of bare MnFe2O4, DyxMnFe2-xO4 and mesoporous silica-based composite was tested using crystal violet dye. Its explored adsorption-photocatalysis synergy, degradation mechanism, kinetic investigation, easily recovery and remarkable recycling ability suggested that the new fabricated composite is best for environmental remediation.

A radiofrequency transseptal needle: initial animal studies.

OBJECTIVES: The objective of this study was to demonstrate the safety and efficacy of a new transseptal needle design with a radiofrequency (RF) tip combined with the ease of use of the needle configuration. BACKGROUND: RF transseptal puncture to enter the left heart, with a RF wire-catheter system is a successful technique in patients with complex access using a standard transseptal needle. METHODS: The RF transseptal needle (NRG™ Transseptal Needle; Baylis Medical, Montreal, Canada) was designed for RF percutaneous transseptal access to the left heart. Eight pigs underwent transvenous cardiac catheterization with baseline intracardiac electrograms and right atrial pressure waveforms. Transseptal RF puncture was performed followed by left atrial pressure waveform monitoring. RESULTS: An intracardiac electrogram was recorded in each animal while dragging the needle tip from the superior caval vein across the atrial septum and into the inferior caval vein. Contrast staining of the atrial septum was accomplished in all animals, with subsequent RF septal puncture. After 0.1 sec, impedance increased from 300 to 1,200 Ohms with the creation of a vapor layer, and voltage increased steadily to a threshold of 230 volts over the first 0.4 sec. This dielectric breakdown results in tissue vaporization and tissue perforation. The needle's location within the left atrium was confirmed by the pressure waveform and contrast injection. Repeated RF punctures with the NRG™ was compatible with various manufactures transseptal sheaths. CONCLUSION: RF puncture of the interatrial septum using the NRG™ Transseptal Needle facilitates an alternative effective technique to enter the left atrium. © 2010 Wiley-Liss, Inc.

Clot friction variation with fibrin content; implications for resistance to thrombectomy.

BACKGROUND: Despite significant advancements in the procedural efficacy of mechanical thrombectomy in patients with ischemic stroke in recent years, there still remains a portion of the population that does not achieve good recanalization. The reasons for this may be varied. We hypothesized that static friction between the clot and the vessel, or catheter wall might contribute to the difficulty in removing the clot. OBJECTIVE: To determine if there is a relationship between clot composition and the resistance to sliding (friction) which might contribute to resistance to clot removal. METHODS: As clot composition can vary significantly, we investigated five different types of clot in order to measure their respective frictional properties. To do this, a custom-made testing apparatus was created, consisting of various replaceable low-friction surfaces on which the clots could be placed. The surface was then gradually tilted until the clots began to slide; the angle at which this occurred is related to the coefficient of friction of the clots. The experiment was repeated on a bovine aortic surface in order to confirm the results. RESULTS: We found that fibrin-rich clots (<20% red blood cell content) have a significantly higher coefficient of friction than clots with a red blood cell content >20%. This result was confirmed by repeating the experiment on a bovine aortic surface as a representation of the interaction between clots and the arterial wall. CONCLUSIONS: The friction properties of clots were found to be related to the content ratio of fibrin to red blood cells. Future imaging techniques that could show fibrin and red blood cell content might help us to predict the 'stickiness' of a clot.

Differentiation of Clot Composition Using Conventional and Dual-Energy Computed Tomography.

BACKGROUND AND PURPOSE: In unenhanced computed tomography (CT) of acute ischemic stroke, the density of occluding clots is associated with the content of red blood cells and successful recanalization with stent thrombectomy. However, no CT marker for fibrin content is established. In order to improve clot diagnostics, we conducted an in vitro study to investigate thrombus composition of histologically defined ovine blood clots with unenhanced and contrast-enhanced CT using spectral detector CT (SDCT). METHODS: Ovine blood clot types containing defined amounts of red blood cells (RBC; pure fibrin clots: RBC 0% ± 0, fibrin 100% ± 0), mixed clots (RBC 35.1% ± 4.11, fibrin 79.2% ± 5.6) and red clots (RBC 99.05% ± 1.14, fibrin 0.95% ± 1.14) were scanned in a SDCT (IQon®, Philips, Amsterdam, The Netherlands) (a) in a tube containing saline, (b) 5 min and (c) 3 days after exposure to a 1:50 dilution of iohexol (Accupaque-350®, GE-Healthcare, Boston, MA, USA). The attenuation of the clots was measured in Hounsfield units (HU) in conventional CT datasets as well as virtual noncontrast reconstructions (VNC) of nonenhanced and contrast-enhanced SDCT in a blinded and randomized fashion. Statistical analysis was conducted with ANOVA, Spearman's correlation, linear and multivariable regression models. RESULTS: In unenhanced scans, clots differed in density with linear interrelation (fibrin 23.6 ± 1.1, mixed 34.9 ± 1.6, red 46.7 ± 1.6, mean HU ± SD). The blood clots did not show any overlap of density in the native scans and VNC at different time points (p < 0.0001 for each setting and clot type). However, they could not be differentiated after initial contrast exposure (fibrin 108.5 ± 7.8, mixed 105.3 ± 3.5, red 104.8 ± 3.8, mean HU ± SD). After prolonged exposure, the fibrin rich clots showed a significant increase of density due to further uptake of contrast medium (fibrin 163.6 ± 3.6, mixed 138.3 ± 4.1, red 109.6 ± 5.4, mean HU ± SD). In multivariable models, native CT density and contrast enhancement were independent variables associated with thrombus type (p < 0.01 each). CONCLUSION: The fibrin content in blood clots is strongly associated with contrast uptake. As previously shown, the density of the clot formations in native CT scans is dependent on the RBC. Our data show that CT density and relative enhancement of clots are independent determinants of clot composition. Using both variables in the CT workup of acute ischemic stroke has the potential to have a decisive impact on patient stratification for treatment.

Is bridging therapy still required in stroke due to carotid artery terminus occlusions?

INTRODUCTION: Studies comparing endovascular stroke treatment using mechanical thrombectomy (MT) with or without prior IV tissue plasminogen activator (tPa) have included only 30% of internal carotid artery terminus occlusions (ICA-O), a known predictor of recanalization failure with IV tPa. OBJECTIVE: To carry out a retrospective multicenter analysis of prospectively collected data of consecutive patients to investigate the impact of intravenous thrombolysis on ICA-O by comparing patients treated with MT alone or bridging therapy (BT). MATERIAL AND METHODS: Patients with ICA-O treated with MT alone or BT were retrospectively examined and compared. Demographic data, vascular risk factors, treatment modalities, complications, technical and clinical outcomes were recorded. A propensity score (PS) analysis was used to compare modified Rankin Scale (mRS) score at 3 months and intracerebral hemorrhage (ICH) between groups. RESULTS: 141 consecutive patients (60% BT/40% MT) were included between January 2014 and June 2016. Baseline characteristics did not differ between the groups. There was no significant difference in the rate of Thrombolysis in Cerebral Infarction 2b/3, distal emboli, and median number of passes between the groups. There was a significant difference between BT and MT groups in the median time between imaging and groin puncture (median 97 min vs 75, p=0.007), the rate of ICH (44% vs 27%, p=0.05), but not for symptomatic ICH (18% vs 13%, p=0.49). With PS, there was a trend towards a higher rate of ICH (OR=2.3, 95% CI 0.9 to 5.9, p=0.09) in the BT group compared with the MT alone group, with no difference in mRS score ≤2 at 3 months (OR=1.6, 95% CI 0.7 to 3.7, p=0.29). CONCLUSION: There was no significant difference in clinical outcomes between patients receiving bridging therapy versus direct thrombectomy. Bridging therapy delayed time to groin puncture and increased ICH rate.

MRI Interscanner Agreement of the Association between the Susceptibility Vessel Sign and Histologic Composition of Thrombi.

BACKGROUND AND PURPOSE: The susceptibility vessel sign (SVS) on magnetic resonance imaging (MRI) is related to thrombus location, composition, and size in acute stroke. No previous study has determined its inter-MRI scanner variability. We aimed to compare the diagnostic accuracy in-vitro of four different MRI scanners for the characterization of histologic thrombus composition. METHODS: Thirty-five manufactured thrombi analogs of different composition that were histologically categorized as fibrin-dominant, mixed, or red blood cell (RBC)-dominant were scanned on four different MRI units with T2* sequence. Nine radiologists, blinded to thrombus composition and MRI scanner model, classified twice, in a 2-week interval, the SVS of each thrombus as absent, questionable, or present. We calculated the weighted kappa with 95% confidence interval (CI), sensitivity, specificity and accuracy of the SVS on each MRI scanner to detect RBC-dominant thrombi. RESULTS: The SVS was present in 42%, absent in 33%, and questionable in 25% of thrombi. The interscanner agreement was moderate to good, ranging from .45 (CI: .37-.52) to .67 (CI: .61-.74). The correlation between the SVS and the thrombus composition was moderate (κ: .50 [CI: .44-.55]) to good κ: .76 ([CI: .72-.80]). Sensitivity, specificity, and accuracy to identify RBC-dominant clots were significantly different between MRI scanners (P < .001). CONCLUSION: The diagnostic accuracy of SVS to determine thrombus composition varies significantly among MRI scanners. Normalization of T2*sequences between scanners may be needed to better predict thrombus composition in multicenter studies.