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An approximation of the fluid-structure interaction problem in the cylindrical coordinate system is studied. First, we solve the free boundary problem by means of Schauder's fixed point theorem. After that, we regularize the linear viscoelastic cylindrical Koiter shell equation that was considered in [12], by adding higher order terms in order to get the strong convergence of the second derivatives of a sequence of radial displacements. We need the strong convergence of the second derivatives in order to guarantee the strong convergence of corresponding divergence free test functions due to [8]. [ABSTRACT FROM AUTHOR]

Background: The Matsushima Grade has traditionally been used to evaluate vessel ingrowth from the STA after EDAS for MMD-patients. However, this grading is subjective and prone to measurement variability. Herein, we propose the orbital grading system quantifying leptomeningeal and burr hole-related vessel-ingrowth from the STA and/or MMA to the middle and anterior cerebral arteries post-EDAS in MMD patients., Methods: An anatomical classification was developed by reference to two parallel vertical lines from the bony landmarks of the orbit, categorized from Grade 0-3. Regression models were used to compare clinical and functional outcomes of our grading system with the Matsushima scale., Results: Forty MMD patients, with median age of 48 years, mostly females (72.5%), were included. Presentation included ischemic events (65.0%), hemorrhage (22.5%), and seizures (7.5%). Most patients were categorized as Suzuki ≥ IV (69.5%). Fifty EDAS (89.9%) had concurrent burr holes placed (parietal and frontal regions). At a median follow-up of 13.7 months, collateral growth was graded as follows: grade 0 (6;10.8%), grade 1 (12;21.4%), grade 2 (23;41.1%) and grade 3 (15;26.8%). Linear regression showed similarities in the distribution between the orbital grading system and Matsushima grading (r=0.86;p<0.01). Ischemic events were fewer in hemispheres categorized as grade 2-3 compared to grade 0-1 (p=0.047) as well as in Matsushima grading A or B compared to C (p=0.047)., Conclusion: The orbital grading system demonstrated agreement in identifying postoperative ischemic events as the Matsushima grade and provides a more practical and objective evaluation of collateral vessel ingrowth after EDAS with and without burr-holes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study aims to evaluate the length of stay (LOS) in patients who had adjunct middle meningeal artery embolization (MMAE) for chronic subdural hematoma after conventional surgery and determine the factors influencing the LOS in this population., Methods: A retrospective review of 107 cases with MMAE after conventional surgery between September 2018 and January 2024 was performed. Factors associated with prolonged LOS were identified through univariable and multivariable analyses., Results: The median LOS for MMAE after conventional surgery was 9 days (interquartile range = 6-17), with a 3-day interval between procedures (interquartile range = 2-5). Among 107 patients, 58 stayed ≤ 9 days, while 49 stayed longer. Univariable analysis showed the interval between procedures, type of surgery, MMAE sedation, and the number of complications associated with prolonged LOS. Multivariable analysis confirmed longer intervals between procedures (odds ratio [OR] = 1.52; P < 0.01), ≥2 medical complications (OR = 13.34; P = 0.01), and neurological complications (OR = 5.28; P = 0.05) were independent factors for lengthier hospitalizations. There was a trending association between general anesthesia during MMAE and prolonged LOS (P = 0.07). Subgroup analysis revealed diabetes (OR = 5.25; P = 0.01) and ≥2 medical complications (OR = 5.21; P = 0.03) correlated with a LOS over 20 days, the 75th percentile in our cohort., Conclusions: The interval between procedures and the number of medical and neurological complications were strongly associated with prolonged LOS in patients who had adjunct MMAE after open surgery. Reducing the interval between the procedures and potentially performing both under 1 anesthetic may decrease the burden on patients and shorten their hospitalizations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Primary pituitary lymphoma (PPL) is a rare finding in immunocompetent patients, with only 54 patients reported to date (including ours). It presents most often with headache and hypopituitarism, with MRI findings comparable to more common pituitary tumours, making the diagnosis challenging. There is no consensus on the ideal management for these lesions with the role of surgical resection not clearly established., Case Report: We present here a 49-year-old female who presented with acute vision loss and was found to have PPL of diffuse large B-cell lymphoma, non-germinal centre type. The radiologic findings were distinct from prior cases with haemorrhagic components and perilesional edoema in the bilobed sellar mass. Surgical resection was halted when a diagnosis of lymphoma was suspected. This decision was based on the guidelines for the treatment of primary CNS lymphoma (PCNSL) and the lack of evidence to support surgical resection of PPL specifically. Our patient lacked mutations commonly associated with a poor prognosis in DLBCL, such as TP53 and BCL6. She remains in remission with normal vision nearly two years after treatment with minimal resection, MR-CHOP, and consolidation radiotherapy., Conclusion: We highlight here the clinical and diagnostic features of PPL to guide clinicians to early recognition and diagnosis. Surgical resection should be limited to what is necessary to obtain a diagnosis and critical decompression; otherwise, these lesions respond excellently to steroids and typical chemoradiation regimens.

Objective: Thromboembolic (TE) events are among the most feared complications after flow diversion (FD) and have been reported to occur even with adequate dual antiplatelet therapy. Herein, the authors characterize thrombotic and embolic events that developed after FD, focusing on the morbidity of each of these events and the predisposing factors associated with their development., Methods: A retrospective analysis of aneurysms treated with FD at a single institution in the US between 2013 and 2023 was performed. The authors documented the emergence of intraprocedural and postoperative TE events. A survival analysis and a Cox regression model was conducted to identify predictors associated with these events., Results: The authors included 651 procedures performed in 591 patients to treat 746 aneurysms. TE events occurred in 38 of the procedures performed (5.8%), causing permanent deficit in 20 patients and death in 4 patients. Eleven cases presented with acute stent thrombosis, 11 with large-vessel occlusion, and 9 with perforator strokes. At a median follow-up of 9.5 months, 73.0% of patients with an ischemic event had a modified Rankin Scale score ≤ 2. Three of the deaths were secondary to occlusion at the basilar trunk and vertebral artery. In patients with TE events in the anterior circulation, 7 of 11 patients with middle cerebral artery occlusion and 9 of 12 patients with internal carotid artery occlusion achieved independence. Time-to-event Cox regression analysis demonstrated that TE events were more frequent in patients exhibiting aspirin resistance (hazard ratio 2.66; 95% CI 1.10-6.70)., Conclusions: TE events after FD result from multiple factors, including age, aneurysm characteristics, aneurysm location, antiplatelet resistance, and procedural factors. In our cohort, we found the highest morbidity for patients with TE events presenting with large-vessel occlusion at the middle cerebral artery, and vertebrobasilar system.

Background: Factors impacting the rate of aneurysm occlusion after flow diversion (FD) have been well described in the literature. In this article, we sought to evaluate those variables to develop and validate a scoring system predicting aneurysm incomplete occlusion after FD., Methods: Retrospective review of patients with intracranial aneurysms treated with FD at a single institution between March 2013 and March 2023. Multivariable logistic regression model was developed using factors associated with aneurysm incomplete occlusion. The ABC scoring system consisted of: Age (<60 years old: 0, 60-69 years: 1, 70-79: 2, and ≥80: 3), Branch coming out of the aneurysm dome/neck (yes: 2, no: 0), and Cigarette smoking history (never smoker: 1, current or past smoker: 0). The scoring system performance was evaluated with receiver operating characteristic curve and calculating the area under the curve., Results: A total of 449 patients with 563 aneurysms treated in 482 procedures were evaluated. Most cases were females (81.7%) with a median age of 59 years old. At a median follow-up of 13.2 months, 84.0% of aneurysms were completely or near-complete occluded. The scoring system had an area under the curve of 0.71. A value ≥ 2, reached a sensitivity of 74.4%, a specificity of 60.9%, a likelihood ratio+ of 1.90, and proved to be reliable in predicting the risk of incomplete occlusion (odds ratio = 4.53; 95% confidence interval: 2.73-7.54; P < 0.001)., Conclusions: The proposed ABC scoring system can be used to evaluate the risk of aneurysm incomplete occlusion after treatment with FD, identifying patients who would benefit from adjunctive coiling or alternative treatment modalities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: The pipeline embolization device (PED) Flex with Shield technology is a third-generation flow diverter used for intracranial aneurysm treatment designed to decrease thrombogenicity through a phosphorylcholine coating. Herein, we aim to compare the rate of thromboembolic events in PED with Shield technology and PED without it through propensity score matching., Methods: We conducted a retrospective analysis of aneurysms treated with PED first-generation/PED Flex and PED with Shield between 2013 and 2023 at a single academic institution. Patients were matched through propensity score by controlling for confounding factors including age, smoking history, diabetes, previous subarachnoid hemorrhage, modified Rankin Scale pretreatment, location, aneurysm size, previous treatment, and clopidogrel or aspirin resistance. After matching, we evaluated for periprocedural and postoperative thromboembolic events. Data analysis was performed using Stata 14., Results: A total of 543 patients with 707 aneurysms treated in 605 procedures were included in the analysis. From these, 156 aneurysms were treated with PED with Shield (22.07%) and 551 (77.93%) without Shield technology. Propensity score matching resulted in 84 matched pairs. The rate of thromboembolic events was 3.57% for PED Shield and 10.71% for PED first-generation/PED Flex ( P = .07), while retreatment rates were 2.38% for PED Shield and 8.32% for PED Flex ( P = .09). Complete occlusion at first ( P = .41) and last imaging follow-up ( P = .71), in-stent stenosis ( P = .95), hemorrhagic complications ( P = .31), and functional outcomes ( P = .66) were comparable for both groups., Conclusion: This is the first study in the literature performing a propensity scored-matched analysis comparing PED with PED with Shield technology. Our study suggests a trend toward lower thromboembolic events for PED Shield, even after controlling for aspirin and clopidogrel resistance, and a trend toward lower aneurysm retreatment rates with PED Shield, without reaching statistical significance., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: As endovascular neurosurgery techniques continue to evolve, medical students in the United States have widely varying exposures to the field, particularly with respect to opportunities for hands-on experiences. Current medical school curricula could benefit from a novel and adaptive course on vascular neurosurgery to increase student exposure earlier in their training., Methods: We launched a yearly hands-on vascular neurosurgery course for medical students and residents. The day-long course is a combination of lectures focused on neurovascular disease and management accompanied by hands-on sessions where students practiced fundamental microsurgery and angiography techniques using real microscopes and angiography simulators. We surveyed the students before and after each of the 2 courses. The survey following the second annual course included quiz questions the students had not previously seen., Results: Over 2 courses, we had 149 attendees, 71.8% of which were first and second-year medical students representing fifteen institutions. The average survey completion rate was 41.4% for the 4 surveys across the 2 courses. Attendees' interest in pursuing a surgical specialty (t = 1.815, P = 0.039) along with their comfort with neuroanatomy (t = 8.780, P ≤ 0.001) and neurosurgical disease (t = 6.133, P ≤ 0.001) was significantly elevated after the completion of the second course. Responses to the post-survey showed a good grasp of the fundamentals with 68% of attendees answering 70% of the quiz questions correctly., Conclusions: An interactive course on vascular neurosurgery may be an effective vehicle to provide medical students with exposure to the field and the opportunity to learn the fundamentals., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Endovascular options for the treatment of basilar apex aneurysms (BAAs) are heterogeneous, and evidence is limited to retrospective cohorts and case series. We seek to evaluate the efficacy and complications associated with various endovascular treatment methods of BAAs., Methods: Systematic review of PubMed, Embase, and Web of Science adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Retrospective and prospective studies evaluating endovascular treatment of BAAs between January 2010 and July 2024 were included. Relevant information including occlusion rates, aneurysm recurrence, retreatment rates, and complications were subjected to meta-analysis., Results: Fifteen studies with 1049 BAAs were included. The median aneurysm diameter was 8.5 mm (range, 4.6-19.75), with a median follow-up of 33.7 months (range, 6.0-117.6). Residual aneurysm filling occurred in 24% after primary coiling (95% CI = 0.16-0.32), 25% after single stent-assisted coiling (s-SAC; 95% CI = 0.04-0.46), 25% after Y-stents (95% CI = 0.12-0.37), and 23% after flow diverter stent (FDS; 95% CI = 0.11-0.35). Recurrence rates were high for primary coiling (27%, 95% CI = 0.18-0.36) and s-SAC (19%, 95% CI = 0.13-0.26), but significantly lower for Y-stents (9%, 95% CI = 0.03-0.15) and FDS (4%, 95% CI = -0.04-0.11). Retreatment rates were 19% for primary coiling (95% CI = 0.12-0.26), 17% for s-SAC (95% CI = 0.07-0.27), 5% for Y-stents (95% CI = -0.03-0.12), and 13% for FDS (95% CI = -0.01-0.27). Meta-regression indicated larger aneurysms had higher complication rates (P = 0.02). Thromboembolic events were most frequent with FDS and Y-stents(12%)., Conclusions: Occlusion rates were similar across treatments, but recurrence rates were significantly lower after Y-stents and FDS compared to primary coiling, although they carried a higher number of thromboembolic complications., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Craniotomies for tumor resection can at times result in wound complications which can be devastating in the treatment of neuro-oncological patients. A cranial stair-step technique was recently introduced as an approach to mitigate these complications, especially in this patient population who often exhibit additional risk factors including steroids, chemoradiation, and VEGF inhibitor treatments. This study evaluates our cranial stair-step approach by comparing its postoperative complications using propensity score matching with those of a standard craniotomy wound closure., Methods: A retrospective chart review was conducted on patients with intracranial neoplasms undergoing primary craniotomy at a single institution. Patients with prior craniotomies and less than three months of follow-up were excluded. Analyses were performed using R Studio., Results: 383 patients were included in the study, 139 of whom underwent the stair-step technique while the rest underwent traditional craniotomy closures. The stair-step cohort was older, had higher ASA classes, and had a higher prevalence of coronary artery disease. The stair-step patients were administered fewer steroids before (40.29% vs. 56.56%, p < 0.01) and after surgery (87.05% vs. 94.26%, p = 0.02), fewer immunotherapy (12.95% vs. 20.90%, p = 0.05), but they received more radiation preoperatively (15.11% vs. 8.61%, p = 0.05). They also underwent fewer operations for recurrences and residuals (0.72% vs. 10.66%, p = 0.01). On propensity score matching, we found 111 matched pairs with no differences except follow-up duration (p < 0.01). The stair-step group had fewer soft tissue infections (0% vs. 3.60%, p = 0.04), fewer total wound complications (0% vs. 4.50%, p = 0.02), was operated on less for these complications (0% vs. 3.60%, p = 0.04), and had a shorter length of stay (6 vs. 9 days, p < 0.01). Notably, the average time to wound complication in our cohort was 44 days, well within our exclusion criteria and follow-up duration., Conclusion: The cranial stair-step technique is safe and effective in reducing rates of wound complications and reoperation for neuro-oncologic patients requiring craniotomy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Advances in the use of flow diversion (FD) now extend to bifurcation aneurysms; herein, we compare thromboembolic events in patients with internal carotid artery (ICA) aneurysms treated with and without exclusion of the anterior cerebral artery (ACA)., Methods: Retrospective analysis of aneurysms in the terminal ICA treated with FD from 2013 to 2023 at a single-center study. Procedures were classified according to the coverage at the origin of the ACA and compared through bivariate-analysis. A review was also carried on PubMed, Web of Science, and EMBASE until April 2024, adhering to the PRISMA reporting guidelines., Results: Ninety-five patients harboring 113 aneurysms treated in 102 procedures were evaluated. Fifty-eight were treated covering the ACA origin. Dual antiplatelet regimens included aspirin-clopidogrel (50%), aspirin-ticagrelor (44.1%), and aspirin-prasugrel (4.9%). Thromboembolic events occurred in 6 patients (5.9%), all of which presented with large vessel occlusion of the ICA, but without reaching statistical difference in the 2 treated cohorts (P = 0.46). At a median clinical follow-up of 5.95 months, there were no differences in the functional outcomes in the 2 groups (P = 0.22). Contralateral angiographic runs post-treatment after covering the ACA origin demonstrated increase in the A1 (median: 0.45 mm; IQR = 0.4-1.2) and ICA diameter (median: 0.55 mm; IQR = 0.1-1.2). After pooling data from literature and our cohort, complete side branch occlusion after the coverage of ACA was seen in 25% of branches (95%CI = 0.16-0.36), and thromboembolic events were observed after 3% (95%CI = 0.01-0.04) of procedures., Conclusions: Thromboembolic events can occur in distal ICA aneurysms treated with FD, but no significant association was seen with covering the ACA origin., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Flow diversion for bifurcation aneurysms requires excluding one of the branches from the parent artery, raising concern for ischemic events. We evaluated thromboembolic events and their relationship with covering the origin of the posterior cerebral artery (PCA)., Methods: This retrospective analysis included patients with confirmed basilar and proximal PCA aneurysms treated with flow diversion between 2013 and 2023. Procedures were classified according to the coverage of the origin of the PCA. Thromboembolic events associated with the excluded PCA were evaluated., Results: Of the total 28 aneurysms included, 7 were at the basilar tip, 16 in the basilar trunk, and 5 in the first segment of the PCA; 15 were treated by excluding one of the PCAs. Dual antiplatelet therapy included aspirin and ticagrelor (57.1%), aspirin and clopidogrel (35.7%), or aspirin and prasugrel (3.57%). Complete and near-complete aneurysm occlusion was achieved in 80.8% of the aneurysms treated at a median follow-up of 12.31 months. Thromboembolic complications occurred in 3 patients (2 with basilar perforator stroke and 1 with basilar in-stent thrombosis). However, the difference in these events was not statistically significant between patients with PCA coverage and those without (P = 0.46). Diminished flow and a lack of flow was seen in 8 and 7 of the covered vessels, respectively. A modified Rankin scale score of ≤2 was reported for 89.3% of patients at a median clinical follow-up of 5.5 months., Conclusions: The incidence of thromboembolic events is high in distal basilar and proximal PCA aneurysms; however, PCA coverage was not associated with their occurrence. There was no difference in postprocedural disability between patients whose aneurysms were treated by excluding one of the PCAs and those who were not., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The long-term outcomes after stereotactic radiosurgery (SRS) for pediatric brain arteriovenous malformations (AVMs) remain poorly understood given the paucity of longitudinal studies. A systematic review was conducted to pool cumulative incidences for all outcomes., Methods: PubMed, Embase, and Web of Science were queried to systematically extract potential references. The articles relating to AVMs treated via SRS were required to be written in English, involve pediatric patients (<18 years of age), and include a mean follow-up period of >5 years. Individual patient data were obtained to construct a pooled Kaplan-Meier plot on obliteration rates over time., Results: Among the 6 studies involving 1315 pediatric patients averaging a follow-up period of 86.6 months (range, 6-276), AVM obliteration was observed in 66.1% with cumulative probabilities of 48.28% (95% confidence interval [CI], 41.89-54.68), 76.11% (95% CI, 67.50-84.72), 77.48% (95% CI, 66.37-88.59) over 3, 5, and 10 years, respectively. The cumulative incidence of post-SRS hemorrhage, tumors, cysts, and de novo seizures was 7.2%, 0.3%, 1.6%, and 1.5%, respectively. The cumulative incidence of radiation-induced necrosis, edema, radiologic radiation-induced changes (RICs), symptomatic RICs, and permanent RICs were 8.0%, 1.4%, 28.0%, 8.7%, and 4.9%, respectively., Conclusions: Studies assessing long-term outcomes after SRS are moderate in quality and retrospective. Thus, interpretation with caution is advised given the variable degree of loss to follow-up, which suggests that complication rates may be higher than the values stated in the literature. Future prospective studies are needed to validate these findings., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Concern about thromboembolic events after flow diversion (FD) warrants dual antiplatelet therapy for 3 to 6 months. Platelet function tests are routinely performed prior to the procedure to detect clopidogrel responsiveness, as resistance is associated with CYP2C19 gene polymorphisms. This study aimed to identify optimal cutoff values in light transmission aggregometry (LTA) for clopidogrel and aspirin as predictive indicators of thromboembolic complications., Methods: The authors conducted a retrospective analysis of aneurysms treated with FD between 2013 and 2023 at a single academic institution. Patients with LTA data for adenosine diphosphate (ADP) and arachidonic acid (ARA) were included, excluding those with aborted procedures. Receiver operating characteristic curves were plotted for ADP and ARA assays to determine optimal cutoff values., Results: A total of 442 patients harboring 552 aneurysms treated in 485 procedures were selected for this analysis. Complete and near-complete aneurysm occlusion on the last radiological follow-up was achieved in 81.8% of aneurysms in a median last imaging follow-up of 13.9 months. A good functional outcome (modified Rankin Scale score ≤ 2) was achieved in 96.3% of patients on the last follow-up. Thromboembolic complications occurred in 4.9% of procedures, and intracranial hemorrhagic complications in 1.9%. For the ADP assay, a value ≥ 40% reached a sensitivity of 82.1% and a specificity of 42.9% with a positive likelihood ratio (LR) of 1.50. For the ARA assay, a value ≥ 13.5% reached a sensitivity of 82.1% and a specificity of 45.6% with a positive LR of 1.51., Conclusions: This study analyzed the largest FD-treated cohort in which optimal LTA platelet function thresholds for clopidogrel were evaluated and is the first to assess LTA values for aspirin. The authors found that values ≥ 40% for clopidogrel and ≥ 13.5% for aspirin were optimal for predicting thromboembolic complications after FD in treating aneurysms.

Background: Recent data have identified that certain risk factors for rupture differ between small and larger intracranial aneurysms (IAs). Such differing risk factors make up 5 out of the 6 predictor variables used in the PHASES score, which raises the question on whether IA size has a significant effect on the score's performance., Methods: Patients who were diagnosed with an IA incidentally or due to a subarachnoid hemorrhage between 2015 and 2023 were selected for potential inclusion. The median IA size of the cohort was chosen as the cutoff point to categorize small and large (6 mm). The PHASES score was calculated for all patients, and a receiver operating characteristic curve analysis was performed to evaluate the classification accuracy of PHASES in predicting rupture for small and large IAs., Results: A total of 677 IAs were included. Among the IAs, 400 (58.9%) presented as UIAs and 279 (41.0%) as subarachnoid hemorrhage. The average PHASES score was 2.9 and 6.5 for small (n = 322) and large (n = 355) IAs, respectively. The PHASES score performed significantly lower for predicting rupture in smaller IAs (area under the curve: 0.634) compared with the larger (area under the curve: 0.741) (P = 0.00083)., Conclusions: PHASES was shown to underperform on small IAs. The decision to treat small unruptured IAs remains highly controversial, and the development of a new score to estimate the annual rupture rate while accounting for IA morphology is of great need. Our findings can help encourage future researchers to develop such a score., (Copyright © 2024. Published by Elsevier Inc.)

Background: The collar sign has been previously described as an angiographic indicator of incomplete occlusion after deployment of a pipeline embolization device (PED) for intracranial aneurysms. In the present study, we explore the predictors for a collar sign in aneurysms treated with the PED., Methods: Aneurysms with a collar sign at the initial follow-up angiogram were identified in a retrospective review of single-center data. The predictors of a collar sign were analyzed through univariate and multivariate analyses., Results: A total of 492 cases of cerebral aneurysm treated with the PED were identified. Among them, 53 were found to have a collar sign on the initial follow-up angiogram. Univariate analysis showed that previous treatment of the same aneurysm (odds ratio [OR], 2.46; P = 0.01), a branch vessel from the aneurysm neck or dome (OR, 6.2; P < 0.001), and a smaller aneurysm neck size (OR, 0.75; P = 0.01) were all predictors for the presence of a collar sign. A larger diameter (OR, 0.92; P = 0.06), increased dome/neck ratio (OR, 1.38; P = 0.1), increased aspect ratio (OR, 1.14; 0 P =.17), and previous treatment showed a trend toward an association with a collar sign. However, after multivariate analysis, a branch from the aneurysm neck or dome (OR, 6.23; P < 0.001), aneurysm diameter (OR, 0.75; P = 0.032), an increased dome/neck ratio (OR, 4.62; P = 0.006), and previous treatment were the strongest predictors for a collar sign., Conclusions: The presence of a branch vessel arising from the aneurysm neck or dome, an increased dome/neck ratio, aneurysm diameter, and previous treatment are the strongest predictive factors for a collar sign in the angiographic follow-up of PED-treated aneurysms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Invited for the cover of this issue are Marek Cigáň, Anna M. Grabarz and co-workers. The image depicts how a non-expert might imagine a "molecular photoswitch". Read the full text of the article at 10.1002/chem.202303509., (© 2024 Wiley-VCH GmbH.)

Background and Objectives: Studies have shown that use of statin can improve radiographic and clinical outcomes in patients receiving treatment for coronary artery or peripheral vascular stenosis. Statins are thought to be effective by reducing arterial wall inflammation. The same mechanism may have an influence on the efficacy of pipeline embolization device (PED) for intracranial aneurysm treatment. Although this question has been of interest, there is a lack of well-controlled data in the literature. The objective of this study is to analyze the effect of statins on outcomes of aneurysms treated with pipeline embolization through propensity score matching., Methods: Patients who underwent PED for unruptured intracranial aneurysms at our institution between 2013 and 2020 were identified. Patients on statin treatment vs those who were not were matched through propensity score by controlling for confounding factors including age, sex, current smoking status, diabetes, aneurysm morphology, volume, neck size, location of aneurysm, history of treatment for the same aneurysm, type of antiplatelet therapy, and elapsed time at last follow-up. Occlusion status at first follow up and last follow-up, and incidence of in-stent stenosis and ischemic complications during the follow-up period were extracted for comparison., Results: In total, 492 patients with PED were identified, of whom 146 were on statin therapy and 346 were not. After one-to-one nearest neighbor matching, 49 cases in each group were compared. At last follow-up, 79.6%, 10.2%, and 10.2% of cases in the statin therapy group and 67.4%, 16.3%, and 16.3% in the nonstatin group were noted to have Raymond-Roy 1, 2, and 3 occlusions, respectively ( P = .45). No significant difference was observed in immediate procedural thrombosis ( P > .99), long-term in-stent stenosis ( P > .99), ischemic stroke ( P = .62), or retreatment ( P = .49)., Conclusion: Statin use does not affect occlusion rate or clinical outcomes in patients treated with PED treatment for unruptured intracranial aneurysms., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Coumarins remain one of the most important groups of fluorescent bio-probes, thanks to their high quantum yields, moderate photostability, efficient cell permeation and low (cyto)toxicity. Herein, we introduce new 3-aminocoumarins as turn-on pH probes under strongly acidic conditions and for indicators capable of significantly improving yeast vacuolar lumen staining compared to the commercial CMAC derivatives. We present the details of the on-off switching mechanism revealed by the TD-DFT and ab initio calculations complemented by a Franck-Condon analysis of the probes' emission profiles.

Herein, we investigate the structure-property relationships in a new series of benzothiazole based unsymmetrical hexafluorocyclopentene dithienylethenes (DTEs) and compare the results with the known facts for symmetric diarylethenes (DAEs). We reveal high photocyclization efficiency resulting from a significant shift of ground state equilibrium to the antiparallel conformation and a barrierless excited state pathway to conical intersection, which remains unperturbed even in polar solvents for most of the prepared DTEs. Furthermore, we uncover that the rate of back thermal cycloreversion correlates clearly more with the central C-C bond-length in the transition state than with the central C-C bond-length in the ground state of the cyclic form. Finally, our detailed vibrational spectral analysis of studied DTEs points out significant changes in Raman and infrared spectra during photoswitching cycles which pave the way for a non-destructive readout of stored information.

Imine resveratrol analogs (IRAs) are promising new agents that can have higher positive effects and, simultaneously, lower negative properties than resveratrol. In this study, three imine hydroxy derivatives (2-((4-hydroxyphenylimino) methyl) phenol [IRA1], 3-((4-hydroxyphenylimino) methyl) phenol [IRA2], and 4-((4-hydroxyphenylimino) methyl) phenol [IRA3]) were prepared and tested in several biological assays. They performed superior to resveratrol in several antioxidant and biological assays, showing high antioxidant capacity and low genotoxicity. Ferric reducing antioxidant power assay (FRAP) and hydroxyl radicals scavenging assay revealed good Fe 3+ to Fe 2+ reduction and strong inhibition of hydroxyl radical formation, respectively. High dosage (1 mmol/dm 3 ) of IRA2 and IRA3 did not cause genotoxicity in human lymphocytes. Moreover, lymphocytes pretreated with all three IRAs accumulated only very few DNA breaks induced by H 2 O 2 than lymphocytes pretreated with resveratrol. Additionally, the number of detected DNA breaks appearing after removal of damaged DNA bases, 8-oxo-7,8-dihydroguanine (8-oxoG), did not dramatically increase in lymphocytes treated with IRA2. Thus, we concluded that IRAs, especially IRA2, are strong antioxidants with the ability to protect lymphocytes from oxidative damage., (© 2021 The Authors. Journal of Biochemical and Molecular Toxicology published by Wiley Periodicals LLC.)

Loss of genome stability leads to reduced fitness, fertility and a high mutation rate. Therefore, the genome is guarded by the pathways monitoring its integrity and neutralizing DNA lesions. To analyze the mechanism of DNA damage induction by cytidine analog zebularine, we performed a forward-directed suppressor genetic screen in the background of Arabidopsis thaliana zebularine-hypersensitive structural maintenance of chromosomes 6b (smc6b) mutant. We show that smc6b hypersensitivity was suppressed by the mutations in EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 3 (ENT3), DNA METHYLTRANSFERASE 1 (MET1) and DECREASE IN DNA METHYLATION 1 (DDM1). Superior resistance of ent3 plants to zebularine indicated that ENT3 is likely necessary for the import of the drug to the cells. Identification of MET1 and DDM1 suggested that zebularine induces DNA damage by interference with the maintenance of CG DNA methylation. The same holds for structurally similar compounds 5-azacytidine and 2-deoxy-5-azacytidine. Based on our genetic and biochemical data, we propose that zebularine induces enzymatic DNA-protein crosslinks (DPCs) of MET1 and zebularine-containing DNA in Arabidopsis, which was confirmed by native chromatin immunoprecipitation experiments. Moreover, zebularine-induced DPCs accumulate preferentially in 45S rDNA chromocenters in a DDM1-dependent manner. These findings open a new avenue for studying genome stability and DPC repair in plants., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Alterations in the balance between excitation and inhibition, especially in the brain's critical developmental periods, are considered an integral part of the pathophysiology of autism. However, the precise mechanisms have not yet been established. SH3 and multiple Ankyrin repeat domains 3 (Shank3) deficient mice represent a well-established transgenic model of a neurodevelopmental disorder with autistic symptomatology. In this study, we characterize the consequences of Shank3 deficiency according to (1) expression of specific markers of different neuronal populations in pups and adult mice and (2) social behaviour and anxiety in adult mice. Our research found enhanced expression of serotonin transporter and choline acetyltransferase in the hippocampus and hypothalamus in Shank3-deficient pups. We demonstrated marked brain region differences in expression of excitatory glutamatergic markers in pups and adult Shank3 deficient mice. We also observed reduced expression of inhibitory GABAergic markers and GABA receptor subunits in several brain areas in both pups and adult Shank3 deficient mice. Further analysis of dopaminergic brain areas (nucleus accumbens, ventral tegmental area) revealed lower expression levels of GABAergic markers in adult Shank3 deficient mice. Adult Shank3 - deficient mice exhibited excessive repetitive behaviour, a higher level of anxiety, and lower locomotor activity. Our data support the theory of an imbalance between excitatory and inhibitory neurotransmission in conditions of abnormal SHANK3 protein. We therefore suggest that autism-like conditions are accompanied by reduced expression of GABAergic markers in the brain during early development as well as in the adult age, which could be associated with long-lasting behavioural abnormalities., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diastereoselective double C-H heteroarylation of chiral ferrocenes provides valuable compounds with multiple functionalities using mild reaction conditions and simple reagents. Pd-Complexes with chiral mono-protected amino acids afforded corresponding heteroarylated ferrocenyl amines in good yields and high diastereomeric purities. In this way, a variety of indole, thiophene, pyrrole, or furan substituents were introduced to the ferrocene moiety. Furthermore, a range of relevant functional groups, for example ketone, ester, chloro, nitro, or silyl, are tolerated by this method. An alternative combination of amino acid and ferrocenyl amine configurations was leveraged to provide the complementary diastereomeric products. The products of C-H heteroarylation can be transformed into corresponding phosphines. Absolute configurations of CH-activation products were confirmed by the combination of X-ray crystallographic analysis and CD spectroscopy. 19 F NMR kinetic study and DFT calculations provided insights into the reaction mechanism and reasons governing stereoinduction., (© 2021 Wiley-VCH GmbH.)

The design of P-type photoswitches with thermal stability of the metastable form of hundreds of years that would efficiently transform using excitation wavelengths above 350 nm remains a challenge in the field of photochromism. In this regard, we designed and synthesized an extended set of 13 pyridine/quinoline hydrazones and systematically investigated the structure-property relationships, defining their kinetic and photoswitching parameters. We show that the operational wavelengths of the pyridine hydrazone structural motif can be effectively shifted toward the visible region without simultaneous loss of their high thermal stability. Furthermore, we characterized the ground-state and excited-state potential energy surfaces with quantum-chemical calculations and ultrafast transient absorption spectroscopy, which allowed us to rationalize both the thermal and photochemical reaction mechanisms of the designed hydrazones. Whereas introducing an electron-withdrawing pyridyl moiety in benzoylpyridine hydrazones leads to thermal stabilities exceeding 200 years, extended π-conjugation in naphthoylquinoline hydrazones pushes the absorption maxima toward the visible spectral region. In either case, the compounds retain highly efficient photoswitching characteristics. Our findings open a route to the rational design of a new family of hydrazone-based P-type photoswitches with high application potential in photonics or photopharmacology.

Photochromic hydrazones are attracting the attention in the field of photochromic systems especially due to their P-type character. To understand the structural features and their correlation with the spectroscopic data, UV-Vis, vibrational and ellipsometry spectroscopic techniques are employed with the support of density functional theory (DFT) calculations to three hydrazone derivatives based on benzoylpyridine. Interestingly, analysis of the structure shows the presence of two distinct rotamers around the pyridine ring with different energy and the well-defined conjugation path that changes due to E to Z isomerization especially in the hydrazone -C=N-NH part of the skeleton. IR and Raman spectra are analyzed, showing a higher selectivity in the Z form; moreover, the comparison with the normal modes proves the effect of the reaction on the backbone structure. The experimental results are in good agreement with the theoretical predictions, especially in the case of the Raman spectrum. The molecular polarization also changes from E to Z forms as predicted by DFT calculations. Spectroscopic ellipsometry on thin films of TOPAS doped with 10 %wt of the dimethylamino hydrazone derivative is used to prove such change at the molecular level. A modulation of the refractive index is observed, and it is correlated with the concentration of the active moiety and the calculated electronic polarizabilities., (© 2021 Wiley-VCH GmbH.)

Self-immolation (SI) is the key principle of ProTide nucleotide prodrugs such as remdesivir, which is currently used to treat COVID-19 patients. Developing novel tailor-made SI systems requires new analytical methods for the detection and monitoring of SI. We developed a robust method for SI analysis using novel phosphate-based SI linkers with NMR traceable cyclic intermediates to distinguish SI from alternative fragmentation pathways and to monitor cargo release in real time.

Photochromic systems with an ultrahigh rate of thermal relaxation are highly desirable for the development of new efficient photochromic oscillators. Based on DFT calculations, we designed a series of 5-phenylazopyrimidines with strong push-pull character in silico and observed very low energy barriers for the thermal (Z)-to-(E) isomerization. The structure of the (Z)-isomer of the slowest isomerizing derivative in the series was confirmed by NMR analysis with in situ irradiation at low temperature. The substituents can tune the lifetime of thermal back isomerization from hundreds of microseconds to several nanoseconds (8 orders of magnitude). The photoswitching parameters were extracted from transient absorption techniques and a dominant rotation mechanism of the (Z)-to-(E) thermal fading was proposed based on DFT calculations., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A range of chiral hydrogen-bond-donating organocatalysts was tested in the Ireland-Claisen rearrangement of silyl ketene acetals. None of these organocatalysts was able to impart any enantioselectivity on the rearrangements. Furthermore, these organocatalysts slowed down the Ireland-Claisen rearrangement in comparison to an uncatalyzed reaction. The catalyst-free reaction proceeded well in green solvents or without any solvent. DFT calculations showed that the activation barriers are higher for reactions involving hydrogen-donating organocatalysts and kinetic experiments suggest that the catalysts bind stronger to the starting silyl ketene acetals than to transition structures thus leading to inefficient rearrangement reactions., (Copyright © 2019, Krištofíková et al.; licensee Beilstein-Institut.)

The photoswitching properties of three readily accesible benzoylpyridine hydrazones were investigated. Interestingly, replacing classical stirring with ultrasound wave activation results in pure thermodynamically less stable E isomer crystallization at room temperature. The studied benzoylpyridine hydrazones exhibit both P- and T-photochromic behaviour, depending on the benzoyl substituent, and improved addressability compared to most of the previously published pyridyl based hydrazones and 2-pyridylcarboxaldehyde acylhydrazones. Low activation entropy and calculated transition state geometry favour the inversion mechanism of their thermal isomerization rather than tautomerization followed by rotation recently found for pyridyl-hydrazone ester or nitrile rotary switches. The association behaviour of the nitro derivative during its thermal E-to-Z isomerization in highly polar DMSO indicates an important role of intermolecular hydrogen bonding in the thermal kinetics of benzoylpyridine-based hydrazone photoswitches. Moreover, the addition of triethylamine significantly accelerates the rate of Z-isomer thermal isomerization from days to seconds and could thus pave the way to fast pyridyl hydrazone T-type photochromic compounds in polar solvents. This study could therefore contribute to general knowledge related to the photochromic behaviour of hydrazones as an important class of modern photoswitches.

The bromate-aniline oscillatory reaction was discovered 4 decades ago, but neither the detailed mechanism nor the key products or intermediates of the reaction were described. We report herein a detailed study of this reaction, which yielded new insights. We found that oscillatory oxidation of aniline by acidic bromate proceeds, to a significant extent, via a novel reaction pathway with the periodic release of carbon dioxide. Several products were isolated, and their structures, not described so far, were justified on the basis of MS and NMR. One of the main products of the reaction associated with the CO 2 release route can be assigned to 2,2-dibromo-5-(phenylimino)cyclopent-3-en-1-one. A number of known compounds produced in the studied reaction, including unexpected brominated 1-phenylpyrroles and 1-phenylmaleimides, were identified by comparison with standards. A mechanism is suggested to explain the appearance of the detected compounds, based on coupling of the anilino radical with the produced 1,4-benzoquinone. We assume that the radical adduct reacts with bromine to form a cyclopropanone intermediate that undergoes a Favorskii-type rearrangement. Further oxidation and bromination steps including decarboxylation lead to the found brominated phenyliminocyclopentenones. The detected derivatives of 1-phenylpyrrole could be produced by a one-electron oxidation of a proposed intermediate 2-phenylamino-5-bromocyclopenta-1,3-dien-1-ol followed by β-scission with the abstraction of carbon monoxide. Such a mechanism is known from the combustion chemistry of cyclopentadiene. The proposed mechanism of this reaction provides a framework for understanding the observed oscillatory kinetics.

Four novel isatin hydrazones containing bipyridyl fragments were synthesized as potential ON/OFF switches. Hydrazone Z -isomers exhibit high thermal stability. The characteristic photochemical reaction for all studied hydrazones is the Z - E isomerization in CHCl 3 . After irradiation of hydrazones 1 and 2 in dimethylformamide (DMF), the photoreaction products are tautomers. When using light with the appropriate wavelength, the photo-tautomerization reaction is reversible. In these conditions, studied hydrazones have ON/OFF switch properties. In the case of hydrazones 1 and 2 , by alternating heat and light stimulation it is possible to control the isomerization process reversibly. In the presence of fluoride ions, NH hydrogen from the studied hydrazones is cleaved, and the corresponding anions are formed. The resulting anions of Z -isomers are changed to the corresponding E -isomer at room temperature.

The emission properties of three 4-azafluorenone and five new α-carboline fluorophores in both solution and thin solid films were investigated. Fluorescence of the azafluorenone is clearly enhanced in thin solid films due to the presence of phenyl/biphenyl rotors, and these derivatives can be classified as green Aggregation-Induced Emission luminogens (AIEgens) with a non-emissive heteroaromatic core structure. Compared to azafluorenones, emission of α-carbolines is hypsochromically shifted to the blue region of the electromagnetic spectrum, and most of these derivatives exhibit strong violet-blue fluorescence in both solution and thin solid film layers. Further, the effective mobility and electroluminescence of new α-carbolines were investigated in prepared organic field-effect transistors and organic light-emitting diodes, respectively.

The photoswitching properties of two easily synthesized isatin 4-nitrophenylhydrazones were investigated. Although the parent isatin 4-nitrophenylhydrazones exhibit low addressability which hampers their photochromic applications, the addition of strongly basic anions to phenylhydrazone solutions creates a new Vis-Vis photochromic system with the unusual azo/azine-to-hydrazone photo-tautomerization process as the photoswitching mechanism. To the best of our knowledge, this is the first report related to the anion-assisted azo/azine-to-hydrazone photo-tautomerism., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: To analyze self-reported changes in physical function in older women with breast cancer receiving adjuvant chemotherapy., Design: Secondary analysis of the Cancer and Leukemia Group B (CALGB) 49907 prospective randomized clinical trial., Setting: CALGB institutions in the United States., Participants: Women aged 65 and older with Stage I to III breast cancer enrolled in CALGB 49907 who had physical function data from before and after receipt of adjuvant chemotherapy (N=256; mean age 71.5, range 65-85)., Measurements: Participants were administered the physical function subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire before chemotherapy, at the end of chemotherapy, and 12 months after chemotherapy initiation. Functional decline was defined as a more than 10-point decrease from baseline at each time point. Resilience was defined as return to within 10 points of baseline. Multivariable regression was used to examine pretreatment characteristics associated with physical function changes., Results: Of 42% of participants who had physical function decline from before to the end of chemotherapy, 47% recovered by 12 months (were resilient). Almost one-third experienced functional decline from before chemotherapy to 12 months later. Pretreatment fatigue was a risk factor for functional decline from before to the end of chemotherapy (P=.02). Risk factors for functional decline at 12 months included pretreatment dyspnea (P=.007) and being unmarried (P=.01)., Conclusion: Functional decline was common in older women receiving adjuvant chemotherapy for breast cancer in a clinical trial. Although half recovered their physical function, one-third had a clinically meaningful decline at 12 months. Strategies are needed to prevent functional decline in older adults receiving chemotherapy. J Am Geriatr Soc 67:920-927, 2019., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

A new hybrid photo-catalyst based on ZSM-5 zeolite suitable for reduction of carbon dioxide was synthesized. The photo-catalyst was prepared by oxidative polymerization of thiophene with FeCl₃ in the presence of ZSM-5 with participation of ultrasound. The synthesized photo-catalyst strongly absorbs light radiation up to approx. 650 nm, with the absorption edge in the NIR region. Reactive radicals were generated by VIS light irradiation in an aqueous suspension consisting of the photo-catalyst with CO₂. Formic acid and acetic acid were generated as the main products of the CO₂ reduction. EPR spin trapping technique was applied to identify the reactive radical intermediates. In this work, the mechanism of product formation is also discussed.