The Impact of Dual Antiplatelet Therapy Duration on Unruptured Aneurysm Occlusion After Flow Diversion: A Multicenter Study.

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

Early Brain Injury and Soluble ST2 After Nontraumatic Subarachnoid Hemorrhage.

[Figure: see text].

Outcome Following Hemorrhage From Cranial Dural Arteriovenous Fistulae: Analysis of the Multicenter International CONDOR Registry.

Background and Purpose: Dural arteriovenous fistulae can present with hemorrhage, but there remains a paucity of data regarding subsequent outcomes. We sought to use the CONDOR (Consortium for Dural Arteriovenous Fistula Outcomes Research), a multi-institutional registry, to characterize the morbidity and mortality of dural arteriovenous fistula­related hemorrhage. Methods: A retrospective review of patients in CONDOR who presented with dural arteriovenous fistula­related hemorrhage was performed. Patient characteristics, clinical follow-up, and radiographic details were analyzed for associations with poor outcome (defined as modified Rankin Scale score ≥3). Results: The CONDOR dataset yielded 262 patients with incident hemorrhage, with median follow-up of 1.4 years. Poor outcome was observed in 17.0% (95% CI, 12.3%­21.7%) at follow-up, including a 3.6% (95% CI, 1.3%­6.0%) mortality. Age and anticoagulant use were associated with poor outcome on multivariable analysis (odds ratio, 1.04, odds ratio, 5.1 respectively). Subtype of hemorrhage and venous shunting pattern of the lesion did not affect outcome significantly. Conclusions: Within the CONDOR registry, dural arteriovenous fistula­related hemorrhage was associated with a relatively lower morbidity and mortality than published outcomes from other arterialized cerebrovascular lesions but still at clinically consequential rates.

Impact of growth media and pressure on the diversity and antimicrobial activity of isolates from two species of hexactinellid sponge.

Access to deep-sea sponges brings with it the potential to discover novel antimicrobial candidates, as well as novel cold- and pressure-adapted bacteria with further potential clinical or industrial applications. In this study, we implemented a combination of different growth media, increased pressure and high-throughput techniques to optimize recovery of isolates from two deep-sea hexactinellid sponges, Pheronema carpenteri and Hertwigia sp., in the first culture-based microbial analysis of these two sponges. Using 16S rRNA gene sequencing for isolate identification, we found a similar number of cultivable taxa from each sponge species, as well as improved recovery of morphotypes from P. carpenteri at 22-25 °C compared to other temperatures, which allows a greater potential for screening for novel antimicrobial compounds. Bacteria recovered under conditions of increased pressure were from the phyla Proteobacteria, Actinobacteria and Firmicutes, except at 4 %O2/5 bar, when the phylum Firmicutes was not observed. Cultured isolates from both sponge species displayed antimicrobial activity against Micrococcus luteus, Staphylococcus aureus and Escherichia coli.

Electroencephalography, Hospital Complications, and Longitudinal Outcomes After Subarachnoid Hemorrhage.

BACKGROUND: Following non-traumatic subarachnoid hemorrhage (SAH), in-hospital delayed cerebral ischemia is predicted by two chief events on continuous EEG (cEEG): new or worsening epileptiform abnormalities (EAs) and deterioration of cEEG background frequencies. We evaluated the association between longitudinal outcomes and these cEEG biomarkers. We additionally evaluated the association between longitudinal outcomes and other in-hospital complications. METHODS: Patients with nontraumatic SAH undergoing ≥ 3 days of cEEG monitoring were enrolled in a prospective study evaluating longitudinal outcomes. Modified Rankin Scale (mRS) was assessed at discharge, and at 3- and 6-month follow-up time points. Adjusting for baseline severity in a cumulative proportional odds model, we modeled the mRS ordinally and measured the association between mRS and two forms of in-hospital cEEG deterioration: (1) cEEG evidence of new or worsening epileptiform abnormalities and (2) cEEG evidence of new background deterioration. We compared the magnitude of these associations at each time point with the association between mRS and other in-hospital complications: (1) delayed cerebral ischemia (DCI), (2) hospital-acquired infections (HAI), and (3) hydrocephalus. In a secondary analysis, we employed a linear mixed effects model to examine the association of mRS over time (dichotomized as 0-3 vs. 4-6) with both biomarkers of cEEG deterioration and with other in-hospital complications. RESULTS: In total, 175 mRS assessments were performed in 59 patients. New or worsening EAs developed in 23 (39%) patients, and new background deterioration developed in 24 (41%). Among cEEG biomarkers, new or worsening EAs were independently associated with mRS at discharge, 3, and 6 months, respectively (adjusted cumulative proportional odds 4.99, 95% CI 1.60-15.6; 3.28, 95% CI 1.14-9.5; and 2.71, 95% CI 0.95-7.76), but cEEG background deterioration lacked an association. Among hospital complications, DCI was associated with discharge, 3-, and 6-month outcomes (adjusted cumulative proportional odds 4.75, 95% CI 1.64-13.8; 3.4; 95% CI 1.24-9.01; and 2.45, 95% CI 0.94-6.6), but HAI and hydrocephalus lacked an association. The mixed effects model demonstrated that these associations were sustained over longitudinal assessments without an interaction with time. CONCLUSION: Although new or worsening EAs and cEEG background deterioration have both been shown to predict DCI, only new or worsening EAs are associated with a sustained impairment in functional outcome. This novel finding raises the potential for identifying therapeutic targets that may also influence outcomes.

Treatment Approaches and Outcomes for Acute Anterior Circulation Stroke Patients with Tandem Lesions.

OBJECTIVES: Endovascular thrombectomy (EVT) has revolutionized stroke care for large vessel occlusions (LVOs). However, over half treated remain functionally disabled or die. Patients with tandem lesions, or severe stenosis/occlusion of the cervical internal carotid artery (ICA) with intracranial LVO, may have technical EVT challenges and worse outcomes. We sought to compare treatments and outcomes for patients with anterior circulation tandem lesions versus isolated LVOs. MATERIALS AND METHODS: Consecutive tandem lesion and isolated intracranial LVO patients were identified at a single center. Demographics, medical history, presentations, treatments, and outcomes were collected and analyzed. RESULTS: From 381 EVT patients, 62 had tandem lesions related to atherosclerosis (74%) or dissection (26%). Compared to isolated intracranial LVOs, they were younger (63 vs 70, p = 0.003), had less atrial fibrillation (13% vs 40%, p < 0.0001), less adequate reperfusion (TICI 2b-3, 58% vs 82%, p < 0.0001), more intracranial hemorrhage (ICH, 13% vs 5%, p = 0.037), but similar 90-day functional independence (mRS 0-2, 34% vs 43%, p = 0.181). The cervical ICA was treated before intracranial EVT (57%), after (13%), not acutely (22%), or was inaccessible (8%). Acute cervical ICA treatments were stenting (57%) or angioplasty alone (13%). Neither acute stenting nor order of treatment was associated with outcomes (TICI 2b-3, ICH, or 90-day mRS 0-2). Among acutely stented, neither alteplase nor antiplatelets were associated with outcomes or stent patency. CONCLUSIONS: Tandem lesions were associated with less reperfusion, more ICH, but similar 90-day functional independence. No treatment approach was associated with outcomes. These data illustrate the technical challenges of tandem lesion treatment and underscore the importance of developing new approaches.

Soluble ST2 links inflammation to outcome after subarachnoid hemorrhage.

OBJECTIVE: To investigate whether soluble growth stimulation expressed gene 2 (sST2), a prognostic marker in cardiovascular and inflammatory disorders, is associated with neurological injury after aneurysmal subarachnoid hemorrhage (SAH). METHODS: We studied SAH patients from 2 independent cohorts. Outcome assessments included functional status at 90 days using the modified Rankin Scale (mRS), mortality, and delayed cerebral ischemia (DCI). The relationships between sST2 plasma level and outcome measures were assessed in both cross-sectional and longitudinal analysis. Primary blood mononuclear cells from SAH patients and elective aneurysm controls were analyzed by multiparameter flow cytometry. RESULTS: In the discovery cohort, sST2 predicted 90-day mRS 3-6 (C index = 0.724, p < 0.001) and mortality in Kaplan-Meier analysis (p < 0.001). The association with functional status was independent of age, sex, World Federation of Neurosurgical Societies score, modified Fisher score, treatment modality, and cardiac comorbidities (adjusted odds ratio = 2.28, 95% confidence interval = 1.04-5.00, p = 0.039). Higher sST2 concentration was observed in those patients with DCI (90.8 vs 53.7ng/ml, p = 0.003). These associations were confirmed in a replication cohort. In patients with high sST2, flow cytometry identified decreased expression of CD14 (4.27 × 105 ± 2,950 arbitrary unit (AU) vs 5.64 × 105 ± 1,290 AU, p < 0.001), and increased expression of CD16 (39,960 ± 272 AU vs 34,869 ± 183 AU, p < 0.001). INTERPRETATION: Plasma sST2 predicts DCI, functional outcome, and mortality after SAH, independent of clinical and radiographic markers. Elevated sST2 is also associated with changes in CD14+ CD16+ monocytes. ANN NEUROL 2019;86:384-394.

Dynamic Changes in Arteriovenous Malformations (AVMs): Spontaneous Growth and Resolution of AVM-Associated Aneurysms in Two Pediatric Patients.

Arteriovenous malformations (AVMs) of the central nervous system are dynamic lesions that can change with time. One of the most clinically important concerns is the development and potential rupture of AVM-associated aneurysms. In this report, we review pediatric cases of de novo development of AVM-associated aneurysms in 2 children and present the relevant clinical and radiographic records. These 2 cases, coupled with a review of the current literature, offer insight into the risks of AVMs in children and underline the importance of timely treatment of appropriate cases.

Left Thalamus Arteriovenous Malformation Secondary to Radiation Therapy of Original Vermian Arteriovenous Malformation: Case Report.

A 70-year-old gentleman with history of hypothyroidism, hyperlipidemia, hypertension, and right superior cerebellar aneurysm presented to the neurosurgery service in 2008 with vertigo. Diagnostic cerebral angiography performed that year demonstrated a vermian arteriovenous malformations (AVM). The patient underwent stereotactic proton beam radiosurgery, which resulted in a decrease in flow and size of the lesion, and the patient was lost to follow-up. Now at the age of 80, the patient presented with acute gait instability. Cerebral angiogram demonstrated his stable vermian AVM and a new 1.1 cm AVM nidus in the region of the left posterior thalamus. Although AVMs are often described as congenital lesions, there is a growing body of literature suggesting that AVMs can grow, spontaneously regress, and even arise de novo in response to some insult. Understanding what leads to the growth, remodeling, regression, and hemorrhage of AVMs is crucial in order to better direct therapeutic endeavors. We would argue that this patient's AVM is secondary to endothelial cell damage from radiation therapy. Radiation can cause endothelial cell injury and upregulation of factors, such as vascular endothelial growth factor and transforming growth factor beta expression, which are implicated in AVM development pathways. We believe that this patient's new AVM is secondary to entrance radiation dosing affecting the thalamus during radiation therapy for the original vermian AVM.

Blood Flow Diversion as a Primary Treatment Method for Ruptured Brain Aneurysms-Concerns, Controversy, and Future Directions.

Flow diversion is a novel treatment for brain aneurysms that works by redirecting blood flow away from the aneurysm. Immediately after placement of the stent, blood flow stagnates within the aneurysm dome and it undergoes thrombosis. Over time, a new endothelium develops across the neck, thereby reconstructing the parent vessel and curing the aneurysm. The use of this treatment method for ruptured aneurysms has two specific concerns: 1) risk of hemorrhage from the aneurysm after treatment because of potential delayed aneurysm occlusion; and 2) hemorrhagic complications from antiplatelet use, which is required to prevent thromboembolic complications from the device. In this review, we explore these two concerns based on the emerging published literature. Optimal peri-procedural management of these issues in the neurocritical care setting is vital to improving outcomes. We also identify ongoing clinical trials of flow diversion for the treatment of ruptured aneurysms. Flow diversion is an alternative to clipping or coiling for many ruptured aneurysms and may be potentially more efficacious in certain aneurysm subtypes.

Diffuse patterns of nonaneurysmal subarachnoid hemorrhage originating from the Basal cisterns have predictable vasospasm rates similar to aneurysmal subarachnoid hemorrhage.

BACKGROUND: Nonaneurysmal subarachnoid hemorrhage (SAH) has been historically associated with a benign clinical course. However, recent studies have suggested that nonaneurysmal SAH can present with different hemorrhage patterns that may be associated with differential rates of morbidity. Herein, we analyze a retrospective consecutive cohort of patients with nonaneurysmal SAH to determine outcomes. We also seek to evaluate a validated radiographic grading scale to determine its utility in predicting vasospasm in the setting of different hemorrhage patterns. METHODS: After institutional review board approval, the records of 563 consecutive patients admitted with spontaneous SAH between January 2007 and 2014 were retrospectively reviewed. A total of 138 of these patients had no identifiable source of hemorrhage and were further divided into 2 groups depending on their pattern of hemorrhage: perimesencephalic or diffuse. Clinical characteristics and outcomes were assessed. RESULTS: In nonaneurysmal SAH, 70 patients (50.7%) had a perimesencephalic pattern of hemorrhage, whereas 68 (49.3%) experienced diffuse SAH. Radiographic vasospasm developed in 6 patients (8.6%) with perimesencephalic SAH and in 14 patients (20.6%) with a diffuse SAH pattern. When comparing historical rates of vasospasm based on the Barrow Neurological Institute (BNI) scale and rates in the nonaneurysmal diffuse pattern in this series, there was no significant difference in distribution (chi-square; P = .149), compared with a difference seen with the perimesencephalic group (P < .00001). CONCLUSIONS: Nonaneurysmal SAH is associated with the potential for vasospasm, with higher rates in the diffuse versus perimesencephalic SAH patterns. The BNI grading scale for aneurysmal SAH can be used to predict the risk of vasospasm in diffuse, nonaneurysmal SAH.

The Impact of Preprocedural Platelet Function Testing on Periprocedural Complication Rates Associated With Pipeline Flow Diversion: An International Multicenter Study.

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

Whole genomes of deep-sea sponge-associated bacteria exhibit high novel natural product potential.

Global antimicrobial resistance is a health crisis that can change the face of modern medicine. Exploring diverse natural habitats for bacterially-derived novel antimicrobial compounds has historically been a successful strategy. The deep-sea presents an exciting opportunity for the cultivation of taxonomically novel organisms and exploring potentially chemically novel spaces. In this study, the draft genomes of 12 bacteria previously isolated from the deep-sea sponges Phenomena carpenteri and Hertwigia sp. are investigated for the diversity of specialized secondary metabolites. In addition, early data support the production of antibacterial inhibitory substances produced from a number of these strains, including activity against clinically relevant pathogens Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Draft whole-genomes are presented of 12 deep-sea isolates, which include four potentially novel strains: Psychrobacter sp. PP-21, Streptomyces sp. DK15, Dietzia sp. PP-33, and Micrococcus sp. M4NT. Across the 12 draft genomes, 138 biosynthetic gene clusters were detected, of which over half displayed less than 50% similarity to known BGCs, suggesting that these genomes present an exciting opportunity to elucidate novel secondary metabolites. Exploring bacterial isolates belonging to the phylum Actinomycetota, Pseudomonadota, and Bacillota from understudied deep-sea sponges provided opportunities to search for new chemical diversity of interest to those working in antibiotic discovery.

Focused selection of open cerebrovascular cases for residents interested in cerebrovascular neurosurgery.

INTRODUCTION: National and international trends continue to show greater emphasis on endovascular techniques for the treatment of cerebrovascular disease. The cerebrovascular neurosurgeon however must be adequately equipped to treat these patients via both open and endovascular techniques. METHODS: The decline in open cerebrovascular cases for aneurysm clipping has forced many trainees to pursue open cerebrovascular fellowships to increase case volume. An alternative strategy has been employed at our institution, which is early identification of subspecialty focus with resident driven self-selection of open cerebrovascular cases. RESULTS: This has allowed recent graduates to obtain enfolded endovascular training and a significant number of open cerebrovascular cases in order to obtain competence and exposure. DISCUSSION: We advocate for further self-selection paradigms supplemented with simulation training in order to obviate the need for extended post-residency fellowships.

Intracranial-Intracranial Bypass for Aneurysms: Quantitative Intraoperative Assessment of Flow Preservation.

BACKGROUND: Intraoperative flow measurement has proven utility in extracranial-intracranial bypass, particularly in assessing the adequacy of donors by measurement of cut flow. The nature of intracranial-intracranial (IC-IC) bypass precludes cut flow measurement, but quantitative intraoperative flow measurements may evaluate augment assessment of the bypass. OBJECTIVE: To retrospectively evaluate flow measurements performed in IC-IC bypass to determine the adequacy of the constructs in preserving flow. METHODS: With institutional review board approval, we performed a retrospective review of our bypass database from 2001 to 2021 for aneurysms treated with IC-IC bypass and with intraoperative flow measurements. Patients' preoperative characteristics, bypass indications, prebypass and postbypass intraoperative flow measurements, and patient outcomes were recorded. RESULTS: Of 346 bypasses, 21 cases using 22 IC-IC bypasses were included. The median age was 55 years; 13 of 21 cases were ruptured aneurysms. Aneurysms involved posterior inferior cerebellar artery (n = 7), middle cerebral artery (n = 6), distal anterior cerebral artery (n = 5), and anterior communicating artery (n = 3). Six bypasses were end-to-side (ETS), 10 were side-to-side (STS), and 6 were excisional with reanastomosis (end-to-end, ETE). Intraoperatively, 21 of the bypasses were patent; the postbypass/prebypass flow index averaged 1.15 (±0.32): ETE (n = 6) 1.22 ± 0.34 and ETS/STS bypasses (n = 15) 1.11 ± 0.32. All intraoperatively patent bypasses were patent on postoperative angiography. One occluded on delayed angiography without clinical sequelae. CONCLUSION: Despite advances in endovascular therapy, IC-IC bypass remains essential to the treatment of large and fusiform aneurysms. We demonstrate quantitatively that IC-IC donors provide adequate direct (ETE) and redistributed (STS ETS) flow to the recipient territory. Flow measurement provides valuable information regarding the patency and adequacy of IC-IC bypass for flow preservation.

Angiographic Pulse Wave Coherence in the Human Brain.

A stroke volume of arterial blood that arrives to the brain housed in the rigid cranium must be matched over the cardiac cycle by an equivalent volume of ejected venous blood. We hypothesize that the brain maintains this equilibrium by organizing coherent arterial and venous pulse waves. To test this hypothesis, we applied wavelet computational methods to diagnostic cerebral angiograms in four human patients, permitting the capture and analysis of cardiac frequency phenomena from fluoroscopic images acquired at faster than cardiac rate. We found that the cardiac frequency reciprocal phase of a small region of interest (ROI) in a named artery predicts venous anatomy pixel-wise and that the predicted pixels reconstitute venous bolus passage timing. Likewise, a small ROI in a named vein predicts arterial anatomy and arterial bolus passage timing. The predicted arterial and venous pixel groups maintain phase complementarity across the bolus travel. We thus establish a novel computational method to analyze vascular pulse waves from minimally invasive cerebral angiograms and provide the first direct evidence of arteriovenous coupling in the intact human brain. This phenomenon of arteriovenous coupling may be a physiologic mechanism for how the brain precisely maintains mechanical equilibrium against volume displacement and kinetic energy transfer resulting from cyclical deformations with each heartbeat. The study also paves the way to study deranged arteriovenous coupling as an underappreciated pathophysiologic disturbance in a myriad of neurological pathologies linked by mechanical disequilibrium.

Prediction of bleb formation in intracranial aneurysms using machine learning models based on aneurysm hemodynamics, geometry, location, and patient population.

BACKGROUND: Bleb presence in intracranial aneurysms (IAs) is a known indication of instability and vulnerability. OBJECTIVE: To develop and evaluate predictive models of bleb development in IAs based on hemodynamics, geometry, anatomical location, and patient population. METHODS: Cross-sectional data (one time point) of 2395 IAs were used for training bleb formation models using machine learning (random forest, support vector machine, logistic regression, k-nearest neighbor, and bagging). Aneurysm hemodynamics and geometry were characterized using image-based computational fluid dynamics. A separate dataset with 266 aneurysms was used for model evaluation. Model performance was quantified by the area under the receiving operating characteristic curve (AUC), true positive rate (TPR), false positive rate (FPR), precision, and balanced accuracy. RESULTS: The final model retained 18 variables, including hemodynamic, geometrical, location, multiplicity, and morphology parameters, and patient population. Generally, strong and concentrated inflow jets, high speed, complex and unstable flow patterns, and concentrated, oscillatory, and heterogeneous wall shear stress patterns together with larger, more elongated, and more distorted shapes were associated with bleb formation. The best performance on the validation set was achieved by the random forest model (AUC=0.82, TPR=91%, FPR=36%, misclassification error=27%). CONCLUSIONS: Based on the premise that aneurysm characteristics prior to bleb formation resemble those derived from vascular reconstructions with their blebs virtually removed, machine learning models can identify aneurysms prone to bleb development with good accuracy. Pending further validation with longitudinal data, these models may prove valuable for assessing the propensity of IAs to progress to vulnerable states and potentially rupturing.

Determinants of intracranial aneurysm retreatment following embolization with a single flow-diverting stent.

PURPOSE: Flow diverting stents have revolutionized the treatment of intracranial aneurysms through endoluminal reconstruction of the parent vessel. Despite this, certain aneurysms require retreatment. The purpose of this study was to identify clinical and radiologic determinants of aneurysm retreatment following flow diversion. METHODS: A multicenter flow diversion database was evaluated to identify patients presenting with an unruptured, previously untreated aneurysm with a minimum of 12 months' clinical and angiographic follow-up. Univariate and multivariate logistic regression modeling was performed to identify determinants of retreatment. RESULTS: We identified 189 aneurysms treated in 189 patients with a single flow-diverting stent. Mean age was 54 years, and 89% were female. Complete occlusion was achieved in 70.3% and 83.6% of patients at six and 12 months, respectively. Aneurysm retreatment with additional flow-diverting stents occurred in 5.8% of cases. Univariate analysis revealed that dome diameter ≥10 mm (p = 0.012), pre-clinoid internal carotid artery location (p = 0.012), distal > proximal parent vessel diameter (p = 0.042), and later dual antiplatelet therapy (DAPT) discontinuation (p < 0.001) were predictive of retreatment. Multivariate analysis identified discontinuation of DAPT >12 months (p = 0.003) as a strong determinant of retreatment with dome diameter ≥10 mm trending toward statistical significance (p = 0.064). Large aneurysm neck diameter, presence of aneurysm branch vessels, patient age, smoking history, and hypertension were not determinant of retreatment on multivariate analysis. CONCLUSIONS: Prolonged DAPT is the most important determinant of aneurysm retreatment following single-device flow diversion. Abbreviating DAPT duration to only six months should be a consideration in this population, especially for patients with a large aneurysm dome diameter.

Small molecule probes of the receptor binding site in the Vibrio cholerae CAI-1 quorum sensing circuit.

Based on modification of separate structural features of the Vibrio cholerae quorum sensing signal, (S)-3-hydroxytridecan-4-one (CAI-1), three focused compound libraries have been synthesized and evaluated for biological activity. Modifications to the acyl tail and α-hydroxy ketone typically provided agonists with activities correlated to tail length and conservative changes to the hydroxy ketone. Among the molecules identified within this collection of agonists is Am-CAI-1 (B11), which is among the most potent agonists reported to date with an EC(50) of 0.21 µM. Modifications to the ethyl side chain delivered molecules with both agonist and antagonist activity, including m-OH-Ph-CAI-1 (C13) which is the most potent antagonist reported to date with an IC(50) of 36 µM. The molecules described in this manuscript are anticipated to serve as valuable tools in the study of quorum sensing in Vibrio cholerae and provide new leads in the development of an antivirulence therapy against this human pathogen.

Long-term follow-up results of the SMART coil in the endovascular treatment of intracranial aneurysms.

BACKGROUND: The Penumbra SMART coil is a novel device that becomes progressively softer from its distal to proximal end to maximize coil packing and prevent microcatheter prolapse or coil migration. Here, we report a large series of patients detailing the long-term experience of a single institution using the SMART coil among patients with intracranial aneurysms (IAs). METHODS: Prospective data of 105 consecutive patients with 106 IAs treated using SMART coils was collected between March 2015 and July 2018. Clinical and angiographic data were analyzed. RESULTS: Forty-nine patients (46.7%) presented with subarachnoid hemorrhage and 16 (14.2%) had recurrent aneurysms. Two patients had minor intraprocedural ruptures and remained neurologically stable. One patient had a thromboembolic complication with progressive neurologic decline. There was only one case microcatheter prolapse related to placement of a stent before coiling. An initial post-treatment modified Raymond-Roy Occlusion Classification (mRROC) I or II closure was achieved in 56 (52.8%) aneurysms. The average time to last follow-up was 8.4 months at which 70 (81.4%) aneurysms had mRROC I or II occlusion and a major recurrence was seen in 5 (5.8%) patients. Thirteen (12.3%) aneurysms required re-treatment of which one aneurysm was clipped. CONCLUSIONS: The Penumbra SMART coil is safe and effective for the endovascular treatment of appropriately selected IAs. Additional studies at multiple centers comparing safety and efficacy profile over long-term periods to other mainstream coils are necessary.