David F Kallmes’s research while affiliated with Mayo Clinic - Rochester and other places

The purpose of this study is to pool the evidence on the safety and efficacy of mechanical thrombectomy (MT) in patients who develop acute ischemic stroke (AIS) due to large vessel occlusion (LVO) following recent cardiac interventions. PubMed, Embase and Scopus were searched from inception up to February 2024 using a combination of “cardiac interventions” and “mechanical thrombectomy” as keywords. Studies that evaluated AIS within 30 days of a recent cardiac intervention who underwent MT were included. The proportion of mortality, favorable functional outcome (modified Rankin Scale (mRS) 0–2), successful reperfusion (TICI ≥ 2b or TIMI ≥ 2) and symptomatic intracranial hemorrhage (sICH) were pooled using generalized linear mixed model. Thirty-one case reports/series and 11 observational studies including 195 MT procedures were included. The patients’ mean age was 72 years. The most common cardiac intervention associated with AIS was transcatheter aortic valve replacement/implantation in 96/192 cases (50%). The median onset of stoke was 0 (IQR 0–3) days after cardiac intervention. Rate of successful reperfusion was 79.4% [95%confidence interval (CI) 66.7–88.1%], rate of mRS 0–2 after 90 days was 42.7% [95%CI 32.5–53.6%], and rate of mortality at 90 days was 30.3% [95%CI 21.7–40.6%]. The rate of sICH was 11.6% [95%CI 5.9–21.5%]. MT to treat AIS due to LVO after cardiac interventions may result in good rates of functional recovery, though mortality and sICH may be higher. Regular and repeated neurological examinations should be performed following cardiac interventions, with special attention to stroke. If stroke is detected, MT should be considered as a viable option.

Introduction: In recent years, artificial intelligence (AI) has emerged as a transformative tool for enhancing stroke diagnosis, aiding treatment decision making, and improving overall patient care. Leading AI-driven platforms such as RapidAI, Brainomix®, and Viz.ai have been developed to assist healthcare professionals in the swift and accurate assessment of stroke patients. Methods: Following the PRISMA guidelines, a comprehensive systematic review was conducted using PubMed, Embase, Web of Science, and Scopus. Characteristic descriptive measures were gathered as appropriate from all included studies, including the sensitivity, specificity, accuracy, and comparison of the available tools. Results: A total of 31 studies were included, of which 29 studies focused on detecting acute ischemic stroke (AIS) or large vessel occlusions (LVOs), and 2 studies focused on hemorrhagic strokes. The four main tools used were Viz.ai, RapidAI, Brainomix®, and deep learning modules. Conclusions: AI tools in the treatment of stroke have demonstrated usefulness for diagnosing different stroke types, providing high levels of accuracy and helping to make quicker and more precise clinical judgments.

Bevacizumab (BCZ), commercially known as Avastin, is a monoclonal antibody that targets vascular endothelial growth factor (VEGF). Initially recognized as a breakthrough in oncology, it has since gained FDA approval for various ocular conditions and more recently, for the treatment of glioblastoma multiforme (GBM). Bevacizumab's ability to inhibit excessive neovascularization suggests it may have a potential role in treating chronic subdural hematomas (cSDH). Recent studies have shown that the pathophysiology of cSDH is more complex than previously understood, with VEGF concentrations in subdural fluid significantly exceeding those in serum, contributing to the high recurrence rates. Intra-arterial administration of bevacizumab has shown promising results in recent case series against chronic subdural hematoma, and may be a viable alternative to middle meningeal artery embolization. If successful, this treatment could significantly decrease the rate of recurrence and result in lower rates of severe neurological complications such as visual loss. This literature review explores the connection between bevacizumab and cSDH, focusing on the pharmacological, safety, and delivery aspects of this approach while summarizing the current evidence supporting its use.

BACKGROUND The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots. METHODS EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee. RESULTS After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (<25%) and RBC-rich (>75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P <0.001), pointing to a potential preprocedure indicator of challenging clot. CONCLUSIONS The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03685578.

Background Aneurysm treatments are crucial to minimize the rupture risk. The underlying molecular processes mediating cellular remodeling, endothelialization, and aneurysm healing following endovascular treatment are poorly understood. The current study aims to explore circulating miRNA as a treatment and outcome-associated biomarkers in patients undergoing endovascular treatment. Methods Patients undergoing endovascular interventions for unruptured intracranial aneurysms, using either flow diverter placement or coil embolization, were enrolled. Blood samples were collected before the intervention and during a follow-up period between 6 and 18 months. Total mRNA/miRNA was isolated from plasma, followed by RNA-seq analysis. Gene Ontology analysis was used to identify pathways linked to altered miRNA expression. Results Twenty-three patients participated, with 13 (56.5%) undergoing flow diversion and 10 (43.5%) coil embolization. The median follow-up sample collection time was 10.70 months (SEM ± 1.32). No significant differences in angiographic occlusion were noted between intervention groups. Differentially expressed miRNAs were not identified between groups at baseline. However, at follow-up, 39 miRNAs were upregulated and 41 were downregulated, independent of intervention. Notably, three miRNAs (miR-4746-5p, miR-4685-3p, and miR-490-3p) were downregulated in the flow diversion group compared to the coil embolization group. Bioinformatics analysis revealed associations with upregulated fluid shear stress, p53, adherens junction pathways, along with downregulated apoptosis pathways. Conclusions This study suggests that fluid shear stress and apoptosis may influence aneurysm healing or thromboembolic events in flow diverter-treated patients. Further research is warranted to elucidate the functional significance of these findings in treatment outcomes, providing valuable insights for improved patient care in intracranial aneurysm management.

Introduction: Intracranial aneurysms are associated with local degradation of the vessel wall resulting in the formation of a blood-filled sac. Approximately 6 million people are estimated to have intercranial saccular aneurysms in the US alone. Most aneurysms remain undetected until rupture, resulting in hemorrhage which carries a high mortality rate (>50%). Flow diverters are placed across the aneurysm neck to divert blood flow away from the sac, preventing rupture once occluded. However, flow diverters carry significant risk for thromboembolism, which is a major cause of morbidity. The elevated risk of thromboembolism is likely due to endothelial injury of the parent artery at the neck of the aneurysm. We hypothesize that the bionanomatrix can promote faster endothelialization and aneurysm occlusion thereby reducing the risk of thromboembolism after flow diverter treatment. Methods: The bionanomatrix is composed of peptide amphiphiles containing endothelial cell adhesive ligand (YIGSR) and a nitric oxide (NO) donor (KKKKK), both components critical for recruiting and retaining endothelial cells on the device. The NO releasing bionanomatrix was coated onto the flow diverters using ultrasonic spray coating, and the NO effects on endothelial cell (EC) and smooth muscle cell (SMC) proliferation on the coated devices was assessed, in vitro, using calcien-AM staining. For the in vivo study, an elastase-induced rabbit aneurysm model was created. The bionanomatrix coated and uncoated flow diverters were implanted into the rabbit aneurysm model for 4 weeks. The coated and uncoated flow diverters were then analyzed for endothelialization, smooth muscle cell proliferation, and aneurysm occlusion by angiography, gross image, and immunohistochemistry analyses. Results: In vitro , the bionanomatrix coated flow diverters significantly enhanced endothelial cell proliferation as well as reduced smooth muscle cell proliferation on the flow diverters compared to the uncoated device. In vivo, after 4 weeks, the bionanomatrix coated flow diverters demonstrated enhanced neck coverage, more complete endothelialization, and reduced smooth muscle thickness on the coated flow diverters compared to the uncoated devices as seen by gross image analysis and histology. Conclusions: The bionanomatrix coated flow diverters can successfully promote faster endothelialization and brain aneurysm occlusion which is critical for reducing the risk of thromboembolism after neurointervention.

Introduction While incidentally discovered covert cerebrovascular diseases (id-CCD) are associated with future stroke, it is not known if patients with id-CCD are prescribed statins. Methods Patients age ≥50 with id-CCD on neuroimaging from 2009 to 2019 with no prior ischaemic stroke, transient ischaemic attack or dementia were identified using natural language processing in a large real-world cohort. Robust Poisson multivariable regression was used to assess statin prescription among patients without prior statins. Results Among 2 41 050 patients, 74 975 patients (31.1%; 4.7% with covert brain infarcts (CBI); 29.0% with white matter disease (WMD)) had id-CCD. 53.5% (95% CI 53.2 to 53.9%) were not on statins within 6 months prior to the scan. Of those, 12.0% (95% CI 11.7 to 12.3%) were prescribed statins in the next 6 months compared with 9.3% (95% CI 9.1 to 9.4%) in those without CCD, a 2.7% (95% CI 2.4 to 3.1%) absolute increase in statin prescription for those with id-CCD. In adjusted analyses, the presence of id-CCD was only associated with minor increases in statin prescription (CBI or WMD (risk ratio (RR) 1.09, 95% CI 1.05 to 1.13), CBI alone (RR 1.34, 95% CI 1.21 to 1.47), WMD alone (RR 1.05, 95% CI 1.01 to 1.09), and CBI and WMD (RR 1.23, 95% CI 1.12 to 1.35)). Discussion Identification of id-CCD is not associated with substantial changes in statin prescription in routine clinical practice.

Background Acute ischemic stroke (AIS) imposes a major healthcare burden. It is hypothesized that bacterial infection could influence atherosclerosis and thrombus formation, potentially contributing to AIS. Objectives We aim to systematically review all studies that have investigated the presence of bacterial signatures within thrombi retrieved following mechanical thrombectomy (MT) procedures in patients with AIS. Design This systematic review is designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist. Data sources and methods A comprehensive search was conducted in the Web of Sciences, PubMed, Scopus, and Embase databases to identify relevant studies. Results The literature search and screening included 11 studies involving 674 patients, with 414 (61.4%) being male and 260 (38.6%) females. Among all the patients, 393 (58.3%) were positive for bacterial presence in their retrieved thrombi. The most utilized technique for bacterial signature detection was bacterial DNA extraction followed by polymerase chain reaction amplification of the 16S rRNA gene sequence. Staphylococcus aureus was the most studied bacteria among the studies analyzed. Conclusion Bacterial infections and the presence of bacteria within thrombi may significantly contribute to AIS by initiating or exacerbating atherosclerosis or thrombosis. Understanding the mechanisms by which bacteria affect vascular health is crucial for developing effective preventive and therapeutic strategies for stroke patients.