Global Landscape and Dynamics of Parkin and USP30-Dependent Ubiquitylomes in iNeurons during Mitophagic Signaling.

The ubiquitin ligase Parkin, protein kinase PINK1, USP30 deubiquitylase, and p97 segregase function together to regulate turnover of damaged mitochondria via mitophagy, but our mechanistic understanding in neurons is limited. Here, we combine induced neurons (iNeurons) derived from embryonic stem cells with quantitative proteomics to reveal the dynamics and specificity of Parkin-dependent ubiquitylation under endogenous expression conditions. Targets showing elevated ubiquitylation in USP30-/- iNeurons are concentrated in components of the mitochondrial translocon, and the ubiquitylation kinetics of the vast majority of Parkin targets are unaffected, correlating with a modest kinetic acceleration in accumulation of pS65-Ub and mitophagic flux upon mitochondrial depolarization without USP30. Basally, ubiquitylated translocon import substrates accumulate, suggesting a quality control function for USP30. p97 was dispensable for Parkin ligase activity in iNeurons. This work provides an unprecedented quantitative landscape of the Parkin-modified ubiquitylome in iNeurons and reveals the underlying specificity of central regulatory elements in the pathway.

Loss of BRD4 induces cell senescence in HSC/HPCs by deregulating histone H3 clipping.

Bromodomain-containing protein 4 (BRD4) is overexpressed and functionally implicated in various myeloid malignancies. However, the role of BRD4 in normal hematopoiesis remains largely unknown. Here, utilizing an inducible Brd4 knockout mouse model, we find that deletion of Brd4 (Brd4Δ/Δ ) in the hematopoietic system impairs hematopoietic stem cell (HSC) self-renewal and differentiation, which associates with cell cycle arrest and senescence. ATAC-seq analysis shows increased chromatin accessibility in Brd4Δ/Δ hematopoietic stem/progenitor cells (HSC/HPCs). Genome-wide mapping with cleavage under target and release using nuclease (CUT&RUN) assays demonstrate that increased global enrichment of H3K122ac and H3K4me3 in Brd4Δ/Δ HSC/HPCs is associated with the upregulation of senescence-specific genes. Interestingly, Brd4 deletion increases clipped H3 (cH3) which correlates with the upregulation of senescence-specific genes and results in a higher frequency of senescent HSC/HPCs. Re-expression of BRD4 reduces cH3 levels and rescues the senescence rate in Brd4Δ/Δ HSC/HPCs. This study unveils an important role of BRD4 in HSC/HPC function by preventing H3 clipping and suppressing senescence gene expression.

Enhanced Near-infrared Phosphorescent Emission Modulated by Clipping of Metallotweezers in Aqueous Media.

Near-infrared phosphorescent materials have received significant attention due to their potential applications in bioimaging and diagnostics. Although, many types of organic phosphors with near-infrared emission have been developed, the low phosphorescence efficiency in aqueous solution hampers their practical applications in biological systems. Hence, there is an urgent need to develop near-infrared phosphorescent materials with high emission efficiency in aqueous media. Metallotweezers, based on d8 transition metal complexes, emerge as the potential candidates for realizing this objective. Specifically, metallotweezers, featuring two positively charged platinum(II) terpyridine and neutral gold(III) diphenylpyridine pincers on diphenylpyridine spacer, have been designed and synthesized, respectively. The pre-organization effect, rendered by the rigid spacer, enables the resulting metallotweezers to complex with each other, resulting in the formation of clipping complex. The synergistic rigidifying and shielding effects of clipping structure results in enhanced phosphorescent emission intensity. Concurrently, due to phase segregation between the clipping units and the polyethylene glycol tail, the clipping complex undergoes self-assembly in aqueous solution, resulting in phosphorescent emission in the near-infrared region. Overall, non-covalent clipping of metallotweezers illustrated in this study presents a new and effective approach toward near-infrared phosphorescent materials.

Endoscopic closure of large gastric defects with a novel through-the-scope closing device in a porcine model (with videos).

BACKGROUND AND AIM: After endoscopic full-thickness resection (EFTR), defects require a reliable and sustained closure. We present a novel, through-the-scope "bow-tie" (TTS-BT) closing device enabling direct defect closure without scope withdrawal. This preclinical study aimed to evaluate the feasibility and safety of this device for large defect closure after EFTR in a porcine model. METHODS: Exposed EFTR was performed for virtual lesions > 2 cm in the stomach of twelve pigs. Subsequently, TTS-BT closing devices were used for defect closure. Conventional metal clips were used to close any remaining defects. Gastroscopy was performed for 8 weeks to examine the wound sites and the pigs were subsequently sacrificed. After sacrificing the pigs, the wound healing was histologically verified by hematoxylin-eosin (HE) staining. The primary outcome was a successful closure rate, while the secondary outcomes were complete healing rate, closure time, and incidence of adverse events. RESULTS: The median long and short diameters of perforations were 4.0 (3.0-6.0) cm and 3.0 (2.0-4.0) cm, respectively. Defect closure using novel TTS-BT closure devices and conventional metal clips was successfully performed in all pigs. Complete healing was achieved in the defects of 12 pigs. The median closure time was 13 (9-38) minutes. No serious adverse events occurred during the 8-week follow-up. CONCLUSIONS: The novel TTS-BT closure device is feasible and safe for closing large gastric perforations and could be a promising tool for clinical practice.

QTc prolongation after aneurysmal subarachnoid hemorrhage might be associated with worse neurologic outcome in patients receiving microsurgical clipping or embolization of the intracranial aneurysms: a retrospective observational study.

PURPOSE: QT interval prolongation is one of the most common electrocardiographic (ECG) abnormalities in patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether corrected QT interval (QTc) prolongation is associated with perioperative cardiac events and dismal neurological outcome in mid to long-term follow-up in patients after aSAH is insufficiently studied and remains controversial. METHODS: We retrospectively studied the adult (≥ 18 years) patients admitted to our institution between Jan 2018 and Dec 2020 for aSAH who underwent intracranial aneurysm clipping or embolization. The patients were divided into 2 groups (normal and QTc prolongation groups) according to their QTc. To minimize the confounding bias, a propensity score matching (PSM) analysis was performed to compare the neurologic outcomes between patients with normal QTc and QTc prolongation. RESULTS: After screening, 908 patients were finally included. The patients were divided into 2 groups: normal QTc groups (n = 714) and long QTc group (n = 194). Female sex, hypokalemia, posterior circulation aneurysm, and higher Hunt-Hess grade were associated with QTc prolongation. In multiple regression analysis, older age, higher hemoglobin level, posterior circulation aneurysm, and higher Hunt-Hess grade were identified to be associated with worse outcome during 1-year follow-up. Before PSM, patients with QTc prolongation had higher rate of perioperative cardiac arrest or ventricular arrhythmias. After PSM, there was no statistical difference between normal and QTc prolongation groups in perioperative cardiac events. However, patients in the QTc prolongation group still had worse neurologic outcome during 1-year follow-up. CONCLUSIONS: QTc prolongation is associated with worse outcome in patients following SAH, which is independent of perioperative cardiac events.

Clinical, onychoscopic, nail clipping, and histopathological findings of malignant onychopapilloma.

This report describes the clinical, onychoscopic, nail clipping, and histopathologic features of a malignant onychopapilloma. A 71-year-old male presented to our outpatient clinic for a stable, asymptomatic lesion on his left middle finger that had been present for 2 years. Prior nail clipping histopathology showed nail plate thinning with subungual abnormal onychocytes. Clinical examination revealed a 2-mm-wide streak of longitudinal xanthonychia extending to the proximal nail fold, with distal hyperkeratosis and onycholysis. Onychoscopy showed irregular longitudinal nail plate ridging with scattered punctate hemorrhagic foci. An excisional nail unit biopsy demonstrated cellular atypia of the nail bed epithelium, matrix metaplasia, longitudinal abnormal onychocytes, increased Ki-67 staining, and negative HPV immunoperoxidase staining, confirming the diagnosis of malignant onychopapilloma.

Endoscopic Eyebrow Approach for Aneurysms.

INTRODUCTION: Considerable effort has been made to reduce surgical invasiveness, since Axel Perneczky introduced the supraorbital eyebrow approach as a core part of his keyhole concept in neurosurgery. But a limited approach does not facilitate an already serious and demanding task as aneurysm surgery. In this regard, the enhancement of the visual field before, during, and after microsurgical aneurysm occlusion is a safe and effective method to increase the quality of treatment. Indications/Contraindications: Based on the individual anatomical findings, the supraorbital keyhole approach provides access to most aneurysms of the anterior circulation. The approach is not recommended in large complex aneurysms, giant aneurysms, BA aneurysms located beneath the dorsum sellae, as well as cases of severe subarachnoid hemorrhage (SAH) and expected brain edema. COMPLICATIONS: Experience with endoscopic procedures in aneurysm surgery is limited to several clinical retrospective articles, and no major complications in conjunction with the endoscope were observed. Outcome and Prognosis: The supraorbital eyebrow approach has a low rate of complications and provides highly favorable cosmetic results. Endoscopic inspection prior to clipping might reduce overexposure and mobilization of the aneurysm. It was found that the rate of intraoperative rupture was decreased. The endoscopic post-clipping control helped significantly to reduce aneurysm remnants and unattended parent, branch, or perforator occlusion. CONCLUSION: The supraorbital eyebrow approach is a safe, effective and elegant approach in the treatment of most aneurysms of the anterior circulation. The additional enhancement of the visual field provided by the endoscope before, during, and after microsurgical aneurysm clipping might decrease the rate of intraoperative aneurysm ruptures and unexpected findings concerning aneurysm remnant occlusion and compromise of involved parent, branching, and perforating vessels.

Microsurgical clipping of large MCA aneurysm in a 2-month-old child.

BACKGROUND: Cerebral aneurysms in children have a low incidence and accounts for less than 4% of all cerebral aneurysms. These aneurysms have been linked to various factors. Severe headache, seizures, and motor-sensory deficits are common presentations. CASE REPORT: We describe the case of a 2-month-old male patient who presented with generalized tonic-clonic seizures for 4 days. At the hospital, he was stabilized with ventilatory support, sedation, and antiepileptic drugs. A NCCT (Head) showed intraparenchymal hemorrhage in the left fronto-parieto-temporal lobe and subarachnoid hemorrhage. Subsequently a CT angiogram revealed an aneurysm of the left M3 segment of MCA. Successfully, the patient underwent microsurgical clipping of aneurysm and evacuation of hematoma. CONCLUSIONS: Pediatric cerebral aneurysms differ from their adult counterparts, mainly in their etiology and evolution. As per literature, aneurysmal clipping and neurological endovascular therapy have shown similar results.

Treatment of pediatric intracranial aneurysms: institutional case series and systematic literature review.

INTRODUCTION: Pediatric intracranial aneurysms (IAs) are rare and have distinct clinical profiles compared to adult IAs. They differ in location, size, morphology, presentation, and treatment strategies. We present our experience with pediatric IAs over an 18-year period using surgical and endovascular treatments and review the literature to identify commonalities in epidemiology, treatment, and outcomes. METHODS: We identified all patients < 20 years old who underwent treatment for IAs at our institution between 2005 and 2020. Medical records and imaging were examined for demographic, clinical, and operative data. A systematic review was performed to identify studies reporting primary outcomes of surgical and endovascular treatment of pediatric IAs. Demographic information, aneurysm characteristics, treatment strategies, and outcomes were collected. RESULTS: Thirty-three patients underwent treatment for 37 aneurysms over 18 years. The mean age was 11.4 years, ranging from one month to 19 years. There were 21 males (63.6%) and 12 females (36.4%), yielding a male: female ratio of 1.75:1. Twenty-six (70.3%) aneurysms arose from the anterior circulation and 11 (29.7%) arose from the posterior circulation. Aneurysmal rupture occurred in 19 (57.5%) patients, of which 8 (24.2%) were categorized as Hunt-Hess grades IV or V. Aneurysm recurrence or rerupture occurred in five (15.2%) patients, and 5 patients (15.2%) died due to sequelae of their aneurysms. Twenty-one patients (63.6%) had a good outcome (modified Rankin Scale score 0-2) on last follow up. The systematic literature review yielded 48 studies which included 1,482 total aneurysms (611 with endovascular treatment; 656 treated surgically; 215 treated conservatively). Mean aneurysm recurrence rates in the literature were 12.7% and 3.9% for endovascular and surgical treatment, respectively. CONCLUSIONS: Our study provides data on the natural history and longitudinal outcomes for children treated for IAs at a single institution, in addition to our treatment strategies for various aneurysmal morphologies. Despite the high proportion of patients presenting with rupture, good functional outcomes can be achieved for most patients.

Neuropsychological outcomes in patients with ruptured anterior communicating artery aneurysms treated by clipping versus coiling: a systematic review and meta-analysis.

Ruptured anterior communicating artery (ACoA) aneurysms are frequently associated with neuropsychological deficits. This review aims to compare neuropsychological outcomes between surgical and endovascular approaches to ACoA. We systematically searched PubMed, Embase, and Web of Science for studies comparing the endovascular and surgical approaches to ruptured ACoA aneurysms. Outcomes of interest were the cognitive function, covered by memory, attention, intelligence, executive, and language domains, as well as motor and visual functions. Nine studies, comprising 524 patients were included. Endovascularly-treated patients showed better memory than those treated surgically (Standardized Mean Difference (SMD) = -2; 95% CI: -3.40 to -0.61; p < 0.01). Surgically clipped patients had poorer motor ability than those with coiling embolization (p = 0.01). Executive function (SMD = -0.20; 95% CI: -0.47 to 0.88; p = 0.55), language (SMD = -0.33; 95% CI: -0.95 to 0.30; p = 0.30), visuospatial function (SMD = -1.12; 95% CI: -2.79 to 0.56; p = 0.19), attention (SMD = -0.94; 95% CI: -2.79to 0.91; p = 0.32), intelligence (SMD = -0.25; 95% CI: -0.73 to 0.22; p = 0.30), and self-reported cognitive status (SMD = -0.51; 95% CI: -1.38 to 0.35; p = 0.25) revealed parity between groups. Patients with ACoA treated endovascularly had superior memory and motor abilities. Other cognitive domains, including executive function, language, visuospatial function, attention, intelligence and self-reported cognitive status revealed no statistically significant differences between the two approaches. Trial Registration PROSPERO (International Prospective Register of Systematic Reviews) CRD42023461283; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=461283.

Endovascular coiling versus neurosurgical clipping in the management of aneurysmal subarachnoid haemorrhage in the elderly: a multicenter cohort study.

The comparability of endovascular coiling over neurosurgical clipping has not been firmly established in elderly patients with aneurysmal subarachnoid haemorrhage (aSAH). Data were obtained from all patients with aSAH aged ≥60 across three tertiary hospitals in Singapore from 2014 to 2019. Outcome measures included modified Rankin Scale (mRS) score at 3 and at 6 months, and in-hospital mortality. Of the 134 patients analyzed, 84 (62.7%) underwent coiling and 50 (37.3%) underwent clipping. The endovascular group showed a higher incidence of good mRS score 0-2 at 3 months (OR = 2.45 [95%CI:1.16-5.20];p = 0.018), and a lower incidence of in-hospital mortality (OR = 0.31 [95%CI:0.10-0.91];p = 0.026). There were no significant difference between the two treatment groups in terms of good mRS score at 6 months (OR = 1.98 [95%CI:0.97-4.04];p = 0.060). There were no significant differences in the incidence of complications, such as aneurysm rebleed, delayed hydrocephalus, delayed ischemic neurological deficit and venous thromboembolism between the two treatment groups. However, fewer patients in the coiling group developed large infarcts requiring decompressive craniectomy (OR = 0.32 [95%CI:0.12-0.90];p = 0.025). Age, admission WFNS score I-III, and coiling were independent predictors of good functional outcomes at 3 months. Only age and admission WFNS score I-III remained significant predictors of good functional outcomes at 6 months. Endovascular coiling, compared with neurosurgical clipping, is associated with significantly better short term outcomes in carefully selected elderly patients with aSAH. Maximal intervention is recommended for aSAH in the young elderly age group and those with favorable WFNS scores.

Efficacy and safety of adenosine, rapid ventricular pacing and hypothermia in cerebral aneurysms clipping: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Cerebral aneurysms in complex anatomical locations and intraoperative rupture can be challenging. Many methods to reduce blood flow can facilitate its exclusion from the circulation. This study evaluated the safety and efficacy of using adenosine, rapid ventricular pacing, and hypothermia in cerebral aneurysm clipping. METHODS: Databases (PubMed, Embase, and Web of Science) were systematically searched for studies documenting the use of adenosine, rapid ventricular pacing, and hypothermia in cerebral aneurysm clipping and were included in this single-arm meta-analysis. The primary outcome was 30-day mortality. Secondary outcomes included neurological outcomes by mRs and GOS, and cardiac outcomes. We evaluated the risk of bias using ROBIN-I, a tool developed by the Cochrane Collaboration. OpenMetaAnalyst version 2.0 was used for statistical analysis and I2 measured data heterogeneity. Heterogeneity was defined as an I2 > 50%. RESULTS: Our systematic search yielded 10,100 results. After the removal of duplicates and exclusion by title and abstract, 64 studies were considered for full review, of which 29 were included. The overall risk of bias was moderate. The pooled proportions of the adenosine analysis for the different outcomes were: For the primary outcome: 11,9%; for perioperative arrhythmia: 0,19%; for postoperative arrhythmia: 0,56%; for myocardial infarction incidence: 0,01%; for follow-up good recovery (mRs 0-2): 88%; and for neurological deficit:14.1%. In the rapid ventricular pacing analysis, incidences were as follows: peri operative arrhythmia: 0,64%; postoperative arrhythmia: 0,3%; myocardial infarction: 0%. In the hypothermia analysis, the pooled proportion of 30-day mortality was 11,6%. The incidence of post-op neurological deficits was 35,4% and good recovery under neurological analysis by GOS was present in 69.2%. CONCLUSION: The use of the three methods is safe and the related complications were very low. Further studies are necessary, especially with comparative analysis, for extended knowledge.

Minimally invasive keyhole craniotomies for microsurgical clipping of cerebral aneurysms: comparative meta-analysis of the mini-pterional and supraorbital keyhole approaches.

OBJECTIVE: Axel Perneczky is responsible for conceptualizing the "keyhole" philosophy as a new paradigm of minimal invasiveness within cranial neurosurgery. Keyhole neurosurgery aims to limit approach-related traumatization and minimize brain retraction while still enabling the neurosurgeon to achieve operative goals. The supraorbital keyhole craniotomy (SOKC) and minipterional (pterional keyhole, PKC) approaches have become mainstays for clipping intracranial aneurysms. While studies have compared these approaches to the traditional pterional craniotomy for clipping cerebral aneurysms, head-to-head comparisons of these workhorse keyhole approaches remain limited. METHODS: The authors queried three databases per PRISMA guidelines to identify all studies comparing the SOKC to the PKC for microsurgical clipping of cerebral aneurysms. Of 148 unique studies returned on initial query, a total of 5 studies published between 2013 and 2019 met inclusion criteria. Where applicable, quantitative meta-analysis was performed via the Mantel-Haenszel method using Review Manager v5.4 (Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark). Risk of bias (ROB) was assessed using the Cochrane ROBINS-I tool, and all studies were assigned a Level of Evidence (I-V). RESULTS: Across all five studies, the mean age ranged from 53.0 to 57.5 years old, and the cohort consisted of more females (n = 403, 60.6%) than males. The proportion of patients presenting with ruptured aneurysmal SAH was comparable between the SOKC and PKC cohorts (p = 0.43). Clipping rate [defined as the rate of successful aneurysm clip deployment with successful intraoperative occlusion] (OR 1.52 [0.49, 4.71], I2 = 0%, p = 0.47), final occlusion rates (OR 1.27 [0.37, 4.32], p = 0.70), and operative durations (SMD 0.33 [-0.83. 1.49], I2 = 97%, p = 0.58) were comparable regardless of approach used. Furthermore, rates of intraoperative rupture (OR 1.51 [0.64, 3.55], I2 = 0, p = 0.34), postoperative hemorrhage (OR 1.49 [0.74, 3.01], I2 = 0, p = 0.26), postoperative vasospasm (OR 0.94 [0.49, 1.80], I2 = 63, p = 0.86), and postoperative infection (OR 0.70 [0.16, 2.99], I2 = 0%, p = 0.63) were equivocal across SOKC and PKC cohorts. CONCLUSION: The PKC and SOKC approaches appear to afford comparable outcomes when used for open microsurgical clipping of cerebral aneurysms in select patients with both ruptured and unruptured aneurysms. Both are associated with excellent clipping and occlusion rates, minimal perioperative complication profiles, and favorable postoperative neurologic outcomes. Further investigations are merited so clinicians can further parse out the indications and contraindications for each keyhole approach.

Neurosurgical clipping versus endovascular coiling for patients with ruptured anterior circulation aneurysms: A systematic review and meta-analysis.

To compare the safety and efficacy of clipping and coiling in patients with ruptured anterior circulation aneurysms. A systematic search of four databases (PubMed, Web of Science, Cochrane Library, and Embase) was conducted to identify comparative articles on endovascular coiling and surgical clipping in patients with ruptured anterior circulation aneurysms. Meta-analyses were conducted using random-effects models. Nineteen studies, including 1983 patients, were included. The meta-analysis showed that neurosurgical clipping was associated with a lower incidence of retreatment (OR:0.28, 95% CI (0.11, 0.70), P = 0.006) than endovascular coiling, which seemed to be a result of incomplete occlusion (OR:0.22, 95% CI (0.11, 0.45), P < 0.001). Neurosurgical clipping was associated with lower mortality (OR:0.45, 95% CI (0.25, 0.82), P = 0.009) at short-term follow-up than endovascular coiling. However, neurosurgical clipping showed a higher incidence of ischemic infarction (OR:2.28, 95% CI (1.44, 3.63), P < 0.001) and a longer length of stay (LOS) (WMD:6.12, 95% CI (4.19, 8.04), P < 0.001) after surgery than endovascular coiling. Furthermore, the pooled results showed no statistically significant differences between the two groups regarding poor outcome, long-term mortality, rebleeding, vasospasm, and hydrocephalus. Evidence from this systematic review illustrates that neurosurgical clipping may be superior to endovascular coiling for ruptured anterior circulation aneurysms. Large-scale RCTs should be conducted to verify these outcomes and provide results according to patient status.

Optimizing surgical approaches for anterior communicating artery aneurysms: Development and internal validation of a novel surgical scoring system.

BACKGROUND: The objective was to provide comprehensive preoperative information on both the aneurysm orientation and the side and method of surgical approach for optimal preoperative information and safe clipping using 3D imaging modalities. This was achieved by making an objective risk assessment on the surgical side/method and evaluating its effectiveness with internal validation. MATERIALS AND METHODS: Radiologic data of 61 ACoA aneurysm patients between 2012 and 2020 were retrospectively analyzed. A scoring system based on five criteria; ACoA aneurysm dome orientation, A1 symmetry/control, perforating artery control, A2 trace orientation, and A2 fork symmetry was developed. The system is designed to align with the most common surgical approaches in ACoA aneurysm surgery. The patients were categorized into three groups based on the scoring results to determine the most appropriate surgical method. Group I was recommended, Group II was less recommended, and Group III was least recommended. Internal validation was performed to assess the system's effectiveness. Outcomes and complication rates were statistically evaluated. RESULTS: When the scoring system was utilized, the mean score difference between the first group and the other groups was 2.71 and 4.62, respectively. There was a homogeneous distribution among the groups in terms of age, sex, WFNS, and Fisher scores. Complication occurred in three patients in Group I and nine patients each in Group II and Group III. The further the deviation from the first option, the higher the complication rate (p = 0.016), and a significant cause-effect relationship was identified (p = 0.021). The ROC curve established a cut-off value of 12.5 points for complications and outcomes. CONCLUSION: Our study introduces a new scoring system for ACoA aneurysms, enhancing the use of 3D CTA in daily practice and providing internal validation for the proposed approach. By evaluating objective criteria, this scoring system helps predict surgical risks, prevent complications, and supports personalized evaluation and selection of the surgical approach based on objective criteria.

Microsurgical clipping versus endovascular therapy for treating patients with middle cerebral artery aneurysms presenting with neurological ischemic symptoms.

Studies comparing different treatment methods in patients with middle cerebral artery (MCA) aneurysms in different subgroups of onset symptoms are lacking. It is necessary to explore the safety and efficacy of open surgical treatment and endovascular therapy in patients with MCA aneurysms in a specific population. This study aimed to compare microsurgical clipping versus endovascular therapy regarding complication rates and outcomes in patients with MCA aneurysms presenting with neurological ischemic symptoms. This was a retrospective cohort study in which 9656 patients with intracranial aneurysms were screened between January 2014 and July 2022. Further, 130 eligible patients were enrolled. The primary outcome was the incidence of serious adverse events (SAEs) within 30 days of treatment, whereas secondary outcomes included postprocedural target vessel-related stroke, disabling stroke or death, mortality, and aneurysm occlusion rate. Among the 130 included patients, 45 were treated with endovascular therapy and 85 with microsurgical clipping. The primary outcome of the incidence of SAEs within 30 days of treatment was significantly higher in the clipping group [clipping: 23.5%(20/85) vs endovascular: 8.9%(4/45), adjusted OR:4.05, 95% CI:1.20-13.70; P = 0.024]. The incidence of any neurological complications related to the treatment was significantly higher in the clipping group [clipping:32.9%(28/85) vs endovascular:15.6%(7/45); adjusted OR:3.49, 95%CI:1.18-10.26; P = 0.023]. Postprocedural target vessel-related stroke, disabling stroke or death, mortality rate, and complete occlusion rate did not differ significantly between the two groups. Endovascular therapy seemed to be safer in treating patients with MCA aneurysms presenting with neurological ischemic symptoms compared with microsurgical clipping, with a significantly lower incidence of SAEs within 30 days of treatment and any neurological complications related to the treatment during follow-up.

An evaluation of physical and augmented patient-specific intracranial aneurysm simulators on microsurgical clipping performance and skills: a randomized controlled study.

OBJECTIVE: In the era of flow diversion, there is an increasing demand to train neurosurgeons outside the operating room in safely performing clipping of unruptured intracranial aneurysms. This study introduces a clip training simulation platform for residents and aspiring cerebrovascular neurosurgeons, with the aim to visualize peri-aneurysm anatomy and train virtual clipping applications on the matching physical aneurysm cases. METHODS: Novel, cost-efficient techniques allow the fabrication of realistic aneurysm phantom models and the additional integration of holographic augmented reality (AR) simulations. Specialists preselected suitable and unsuitable clips for each of the 5 patient-specific models, which were then used in a standardized protocol involving 9 resident participants. Participants underwent four sessions of clip applications on the models, receiving no interim training (control), a video review session (video), or a video review session and holographic clip simulation training (video + AR) between sessions 2 and 3. The study evaluated objective microsurgical skills, which included clip selection, number of clip applications, active simulation time, wrist tremor analysis during simulations, and occlusion efficacy. Aneurysm occlusions of the reference sessions were assessed by indocyanine green videoangiography, as well as conventional and photon-counting CT scans. RESULTS: A total of 180 clipping procedures were performed without technical complications. The measurements of the active simulation times showed a 39% improvement for all participants. A median of 2 clip application attempts per case was required during the final session, with significant improvement observed in experienced residents (postgraduate year 5 or 6). Wrist tremor improved by 29% overall. The objectively assessed aneurysm occlusion rate (Raymond-Roy class 1) improved from 76% to 80% overall, even reaching 93% in the extensively trained cohort (video + AR) (p = 0.046). CONCLUSIONS: The authors introduce a newly developed simulator training platform combining physical and holographic aneurysm clipping simulators. The development of exchangeable, aneurysm-comprising housings allows objective radio-anatomical evaluation through conventional and photon-counting CT scans. Measurable performance metrics serve to objectively document improvements in microsurgical skills and surgical confidence. Moreover, the different training levels enable a training program tailored to the cerebrovascular trainees' levels of experience and needs.

Complex intracranial aneurysms: a DELPHI study to define associated characteristics.

PURPOSE: Intracranial aneurysms present significant health risks, as their rupture leads to subarachnoid haemorrhage, which in turn has high morbidity and mortality rates. There are several elements affecting the complexity of an intracranial aneurysm. However, criteria for defining a complex intracranial aneurysm (CIA) in open surgery and endovascular treatment could differ, and actually there is no consensus on the definition of a "complex" aneurysm. This DELPHI study aims to assess consensus on variables defining a CIA. METHODS: An international panel of 50 members, representing various specialties, was recruited to define CIAs through a three-round Delphi process. The panelists participated in surveys with Likert scale responses and open-ended questions. Consensus criteria were established to determine CIA variables, and statistical analysis evaluated consensus and stability. RESULTS: In open surgery, CIAs were defined by fusiform or blister-like shape, dissecting aetiology, giant size (≥ 25 mm), broad neck encasing parent arteries, extensive neck surface, wall calcification, intraluminal thrombus, collateral branch from the sac, location (AICA, SCA, basilar), vasospasm context, and planned bypass (EC-IC or IC-IC). For endovascular treatment, CIAs included giant size, very wide neck (dome/neck ratio ≤ 1:1), and collateral branch from the sac. CONCLUSIONS: The definition of aneurysm complexity varies by treatment modality. Since elements related to complexity differ between open surgery and endovascular treatment, these consensus criteria of CIAs could even guide in selecting the best treatment approach.

Open surgical treatment of basilar artery aneurysms in the interventional therapy era.

PURPOSE: The purpose of this study was to describe the effectiveness and evaluation of open surgical treatment of basilar artery aneurysms in the context of interventional therapy era, including surgical clipping and blood reconstruction, by retrospectively analyzing the clinical data of basilar artery aneurysms in our center. METHODS: Patients with basilar artery aneurysms who were treated at our center were retrospectively included according to the inclusion and exclusion criteria. The basic clinical data, surgical approach, clinical follow-up and prognosis of the enrolled patients were analyzed in detail. In this study, the mRS score was applied to assess the neurological prognosis of the patients, and the relevant data were statistically analyzed using SPSS. RESULTS: A total of 104 eligible patients treated at our center from January 2010 to August 2023 were included in this study, of which 67 were treated by open surgery and 37 by bypass. For the 67 patients with open surgical clipping, the mean age was 60.0 (52.0, 65.0) years. The maximum diameter of the aneurysms ranged from 2.0 mm to 54.0 mm, with a mean of 13.9 (10.0, 19.0) mm. The mean follow-up time was 38 (20, 58) months. At the last follow-up, 61 (91.0%) completely obliterated aneurysms and 6 (9.0%) incompletely obliterated aneurysms were found. The prognosis was good in 59 (88.1%) patients and poor in 8 (11.9%). After surgical clipping, the difference between complete and incomplete postoperative aneurysm elimination was statistically significant between the favorable and poor prognosis groups (P < 0.001). For the 37 bypass group patients, the mean age was 52.0 (45.5, 59.0) years. The maximum diameter of the aneurysm ranged from 10.5 mm to 55.0 mm, with a mean of 28.55 ± 12.08 mm. Bypass combined with proximal occlusion was performed in 18 (48.6%) patients, and bypass only was performed in 19 (51.4%) patients. Clinical follow-up was 19.0 (10.5, 43.0) months. There were 19 (51.4%) patients with complete elimination of the aneurysm, 13 (35.1%) with incomplete elimination of the aneurysm, and 5 (13.5%) with aneurysm stabilization. The prognosis was good in 32 (86.5%) patients and poor in 5 (13.5%) patients. CONCLUSION: Treatment of basilar artery aneurysms is challenging. In the context of the rapidly evolving interventional therapy era, open surgery including surgical clipping and bypass is an ideal option for complex basilar artery aneurysms not amenable to intervention.

Changes in treatment of intracranial aneurysms during the last decade in a large European neurovascular center.

OBJECTIVE: Treatment modality for ruptured and unruptured intracranial aneurysms has shifted during the last two decades from microsurgical treatment towards endovascular treatment. We present how this transition happened in a large European neurovascular center. METHODS: We conducted a retrospective observational study consecutive patients treated for an unruptured or ruptured intracranial aneurysm at Helsinki University Hospital during 2012-2022. We used Poisson regression analysis to report age-adjusted treatment trends by aneurysm location and rupture status. RESULTS: A total of 2491 patients with intracranial aneurysms were treated (44% ruptured, 56% unruptured): 1421 (57%) surgically and 1070 (43%) endovascularly. A general trend towards fewer treated aneurysms was noted. The proportion of patients treated surgically decreased from 90% in 2012 to 20% in 2022. The age-adjusted decrease of surgical versus endovascular treatment was 6.9%/year for all aneurysms, 6.8% for ruptured aneurysms, and 6.8% for unruptured aneurysms. The decrease of surgical treatment was most evident in unruptured vertebrobasilar aneurysms (10.8%/year), unruptured communicating artery aneurysms (10.1%/year), ruptured communicating artery aneurysms (10.0%/year), and ruptured internal carotid aneurysms (9.0%/year). There was no change in treatment modality for middle cerebral artery aneurysms, of which 85% were still surgically treated in 2022. A trend towards an increasing size for treated ruptured aneurysms was found (p = 0.033). CONCLUSION: A significant shift of the treatment modality from surgical to endovascular treatment occurred for all aneurysm locations except for middle cerebral artery aneurysms. Whether this shift has affected long-term safety and patient outcomes should be assessed in the future.