Scaffolding protein Gab2 is involved in postnatal development and lipopolysaccharide-induced activation of microglia in the mouse brain.

Grb2-associated-binding protein-2 (Gab2) is a member of the Gab/DOS family and functions as an adapter protein downstream of several growth factor signaling pathways. Gab2 is considered an Alzheimer's disease susceptibility gene. However, the role of Gab2 in the brain is still largely unknown. Herein, we report that Gab2 is involved in the postnatal development of microglia in mice. The Gab2 expression in the brain was detected at postnatal day 1 (P1) and increased until P14 but decreased thereafter. The tyrosine phosphorylation of Gab2 (pGab2) was also detected at P1 and increased until P14. Next, we focused on microglial development in Gab2 knockout and heterozygous mice. Although differences were not detected in the cytoplasmic area of Iba1-labeled microglia between Gab2(±) and Gab2(-/-) mice, the analysis of CD68 and cathepsin D (indicators of microglial lysosomal activation) immunolabeling within Iba1+ cells revealed significant underdevelopment of microglial lysosomes in Gab2(-/-) mice at P60. In addition to the developmental abnormality of microglia in Gab2(-/-) mice, lipopolysaccharide-induced lysosomal activation was selectively suppressed in Gab2(-/-) mice compared to that in Gab2(±) mice. Our findings suggest that Gab2 is involved not only in postnatal development but also in lysosomal activation of microglia, therefore Gab2 dysfunction in microglia might potentially contribute to the development of neurodegenerative diseases.

Thrombolysis in Large Diffusion-Weighted Imaging Lesions: Lower Chance but Still a Chance.

BACKGROUND: We sought to investigate whether early thrombolytic treatment can result in favorable functional outcome even in patients with large diffusion-weighted imaging (DWI) lesions. MATERIALS AND METHODS: We analyzed 566 patients who received intravenous alteplase within 4.5 hours from onset, initially underwent DWI and magnetic resonance angiography, and had acute infarction confined to anterior circulation. DWI lesion volumes were measured semiautomatically. The association between DWI lesion volume and 3-month outcome in patients who achieved early recanalization was assessed. The DWI lesion volume cutoff, which predicts unfavorable outcome despite recanalization, was determined. In patients with large DWI lesions, the distributions of modified Rankin Scale (mRS) score were compared according to the recanalization status. RESULTS: Four hundred thirty-six patients achieved early recanalization. Among these patients, 283 (65%) patients had a favorable functional outcome (mRS score 0-2). DWI lesion volume (odds ratio [OR], 1.38 per 10 mL; 95% confidence interval [CI], 1.22-1.56) was an independent variable associated with poor outcome, along with hypertension (OR, 1.87; 95% CI, 1.12-3.10), National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.13; 95% CI, 1.08-1.19), and onset-to-needle time (OR, 1.08 per 10 minutes; 95% CI, 1.03-1.13). The DWI lesion of 60 mL or higher highly predicted an unfavorable outcome with a positive predictive value of 95.3%. In patients with a DWI lesion of 60 mL or higher, recanalization had no benefit for an mRS score of 0-2 but was significantly associated with an mRS score of 0-3 (OR, 4.64; 95% CI, 1.08-19.97). CONCLUSIONS: Despite early recanalization, the probability of favorable outcome is low in patients with a DWI lesion of 60 mL or higher. Nevertheless, the benefit of recanalization still persists in large DWI lesions.

High residual platelet reactivity (HRPR) for adenosine diphosphate (ADP) stimuli is a determinant factor for long-term outcomes in acute ischemic stroke with anti-platelet agents: The meaning of HRPR after ADP might be more prominent in large atherosclerotic infarction than other subtypes of AIS.

High residual platelet activation (HRPA) after ADP stimuli has associated with recurrent vascular events in acute atherothrombosis with the use of antiplatelet agents (APAs). However, there has been little evidence supporting this association in acute ischemic stroke (AIS). In this study, we evaluated the influences of HRPR after ADP stimuli on the 1-year incidence of recurrent cardiovascular events and mortality in AIS with APAs. We conducted an observational, referral center cohort study on 968 AIS patients with APAs from January 2010 to December 2013 who were evaluated using optical platelet aggregometry (OPA). All patients received the dual APA combination of aspirin and clopidogrel or aspirin alone. We evaluated their platelet function 5 days after hospital admission using OPA. HRPR after ADP stimuli was defined as platelet aggregation of 70 % or greater according to OPA after 10 µM ADP stimuli. The primary endpoint was a composite of all causes of death, myocardial infarction, and stroke at the 1-year follow-up. The secondary endpoints were each component of the primary endpoint. The event rate of primary endpoint was 11.3 % (109/968). Its rate was significantly higher in the patients with HRPR (16.7 %) than in those without (9.7 %). HPRP was independently associated with the primary endpoint (OR = 1.97, CI 1.22-3.18, p < 0.01). According to the AIS subtype, the presence of HRPR was independently significant for the occurrence of the primary endpoint in the large artery atherosclerosis (LAA) subtype only (OR = 2.26, CI 1.15-4.45, p = 0.02). In this study, the presence of HRPR after ADP stimuli is associated with a poor long-term outcome after acute ischemic stroke. In particular, the influence of this factor might be more prominent in LAA compared with other types of AIS.

Impact of Prehospital Intervention on Delay Time to Thrombolytic Therapy in a Stroke Center with a Systemized Stroke Code Program.

BACKGROUND: The use of emergency medical services (EMS) and notification to hospitals by paramedics for patients with suspected stroke are crucial determinants in reducing delay time to acute stroke treatment. The aim of this study is to investigate whether EMS use and prehospital notification (PN) can shorten the time to thrombolytic therapy in a stroke center with a systemized stroke code program. METHODS: Beginning in January 2012, stroke experts in our stroke center received direct calls via mobile phone from paramedics prenotifying the transport of patients with suspected stroke. We compared baseline characteristics and prehospital/in-hospital delay time in stroke patients treated with intravenous recombinant tissue plasminogen activator for 44 months with and without EMS use and/or PN. RESULTS: Intravenous thrombolytic therapy was performed on 274 patients. Of those patients, 215 (78.5%) were transported to the hospital via EMS and 59 (21.5%) were admitted via private modes of transportation. The patients who used EMS had shorter median onset-to-arrival times (62 minutes versus 116 minutes, P < .001). There was no difference in in-hospital delay time between the 2 groups. In 28 cases (13%) of EMS transport, EMS personnel called the clinical staff to notify the incoming patient. Prenotification by EMS was associated with shorter median door-to-imaging time (9 minutes versus 12 minutes, P = .045) and door-to-needle time (20 minutes versus 29 minutes, P = .011). CONCLUSIONS: We found that EMS use reduces prehospital delay time. However, EMS use without prenotification does not shorten in-hospital processing time in a stroke center with a systemized stroke code program.

A systemized stroke code significantly reduced time intervals for using intravenous tissue plasminogen activator under magnetic resonance imaging screening.

BACKGROUND: A stroke code can shorten time intervals until intravenous tissue plasminogen activator (IV t-PA) treatment in acute ischemic stroke (AIS). Recently, several reports demonstrated that magnetic resonance imaging (MRI)-based thrombolysis had reduced complications and improved outcomes in AIS despite longer processing compared with computed tomography (CT)-based thrombolysis. METHODS: In January 2009, we implemented CODE RED, a computerized stroke code, at our hospital with the aim of achieving rapid stroke assessment and treatment. We included patients with thrombolysis from January 2007 to December 2008 (prestroke code period) and from January 2009 to May 2013 (poststroke code period). The IV t-PA time intervals and 90-day modified Rankin Scale (mRS) scores were collected. RESULTS: During the observation period, 252 patients used IV t-PA under the CODE RED (MRI based: 208; CT based: 44). The remaining 71 patients (MRI based: 53; CT based: 18) received it before the implementation of our stroke code. After implementation of CODE RED, door-to-image time, door-to-needle time, and the onset-to-needle time were significantly reduced by 11, 18, and 22 minutes in MRI-based thrombolysis. Particularly, the proportion of favorable outcome (mRS score 0-2) was significantly increased (from 41.5% to 60.1%, P = .02) in poststroke than in prestroke code period in MRI-based thrombolysis. However, in ordinal regression, the presence of stroke code showed just a trend for favorable outcome (odds ratio, .99-2.87; P = .059) at 90 days of using IV t-PA after correction of age, sex, and National Institutes of Health Stroke Scale. CONCLUSIONS: In this study, we demonstrated that a systemized stroke code shortened time intervals for using IV t-PA under MRI screening. Also, our results showed a possibility that a systemized stroke code might enhance the efficacy of MRI-based thrombolysis. In the future, we need to carry out a more detailed prospective study about this notion.

Outcomes after tissue plasminogen activator administration under the drip and ship paradigm may differ according to the regional stroke care system.

The drip and ship paradigm for stroke patients enhances the rate of using intravenous tissue plasminogen activator (IVT) in community hospitals. The safety and outcomes of patients treated with IVT for acute ischemic stroke (AIS) under the drip and ship paradigm were compared with patients directly treated at a comprehensive stroke center in the Busan metropolitan area of Korea. This was a retrospective study of patients with AIS treated with IVT between January 2009 and January 2012. Information on patients' baseline characteristics, neuroimaging, symptomatic intracerebral hemorrhage (sICH), and outcome 90 days after using IVT was obtained from our stroke registry. We surveyed stroke neurologists regarding their pattern of post-thrombolysis care. During the observation periods, we selected 317 patients using IVT. Among these, 239 patients received IVT at our stroke center, and 78 were treated at 21 community hospitals under the drip and ship paradigm. Initial neurologic deficits and the size of ischemic lesions on magnetic resonance imaging were much more severe in patients treated with IVT under the drip and ship paradigm compared with patients treated at our comprehensive stroke center. The prevalence of a poor outcome (modified Rankin Scale score 3-6) 90 days after IVT was much higher in patients treated with the drip and ship paradigm than in those treated at our comprehensive stroke center. Regarding the occurrence of sICH, there was no significant difference between the 2 groups. The clinical characteristics and outcomes after using IVT under the drip and ship paradigm may differ greatly among stroke care systems.

FX: an RNA-Seq analysis tool on the cloud.

UNLABELLED: FX is an RNA-Seq analysis tool, which runs in parallel on cloud computing infrastructure, for the estimation of gene expression levels and genomic variant calling. In the mapping of short RNA-Seq reads, FX uses a transcriptome-based reference primarily, generated from ~160 000 mRNA sequences from RefSeq, UCSC and Ensembl databases. This approach reduces the misalignment of reads originating from splicing junctions. Unmapped reads not aligned on known transcripts are then mapped on the human genome reference. FX allows analysis of RNA-Seq data on cloud computing infrastructures, supporting access through a user-friendly web interface. AVAILABILITY: FX is freely available on the web at (http://fx.gmi.ac.kr), and can be installed on local Hadoop clusters. Guidance for the installation and operation of FX can be found under the 'Documentation' menu on the website. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Dissemination and Symptoms of Monkeypox Virus Infection.

The monkeypox virus is endemic in Africa. However, the virus has spread worldwide since May 2022, and it has now been confirmed in 109 countries (as of September 22, 2022). Thus, an urgent investigation of the outbreak patterns of confirmed cases and evidence of viral infection is needed. This study investigated the spread of monkeypox in 109 countries, including 15 Asian-Pacific countries, by examining the number of cases, symptoms of infection, and the period between diagnosis and death.

A Python-based educational software tool for visualizing bioinformatics alignment algorithms.

Bioinformatics education can be defined as the teaching and learning of how to use software tools, along with mathematical and statistical analysis, to solve biological problems. Although many resources are available, most students still struggle to understand even the simplest sequence alignment algorithms. Applying visualizations to these topics benefits both lecturers and students. Unfortunately, educational software for visualizing step-bystep processes in the user experience of sequence alignment algorithms is rare. In this article, an educational visualization tool for biological sequence alignment is presented, and the source code is released in order to encourage the collaborative power of open-source software, with the expectation of further contributions from the community in the future. Two different modules are integrated to enable a student to investigate the characteristics of alignment algorithms.

Feasibility of Prompt Lumbar Drainage in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Numerous studies have shown that continuous lumbar drainage (LD) reduces spontaneous subarachnoid hemorrhage (SAH)-related complications, decreasing the incidence of cerebral vasospasm, delayed cerebral ischemia , and hydrocephalus in patients treated with coiling or clipping, but performing LD before securing the aneurysm is still controversial. Our hospital has been implementing prompt LD for several years, and we present the results in this paper. METHODS: Between January 2014 and December 2020, a total of 438 patients with SAH were included in this retrospective study. The indication for prompt LD was aneurysmal SAH of modified Fisher grade III or higher without dense intraventricular hemorrhage with obstructive hydrocephalus requiring extraventricular drainage or large intracranial hemorrhage requiring immediate decompression. Prompt LD was performed for 229 patients with SAH, and the control group included 209 patients. We compared in-hospital mortality and vasospasm or hydrocephalus occurrence and procedure-related complications between the two groups. RESULTS: The in-hospital mortality rate was 7.4% for patients with prompt LD and 14.4% for patients without LD, and the difference was significant (P = 0.019). Vasospasm occurred in 10% of patients with prompt LD and 16.7% of controls (P = 0.039). Hydrocephalus requiring extraventricular drainage occurred in 10.9% of the LD group and 28.7% of the control group (P < 0.001). Rebleeding occurrence was 3.1% in the prompt LD group and 5.7% in the non-LD group (P = 0.168). Cerebrospinal fluid infection occurred in 0.4% of the prompt LD group and 1.4% of controls(P = 0.272). CONCLUSIONS: Prompt LD is a feasible option for treating patients with selective aneurysmal SAH.

TcellInflamedDetector: an R package to distinguish T cell inflamed tumor types from non-T cell inflamed tumor types.

A major issue in the use of immune checkpoint inhibitors is their lack of efficacy in many patients. Previous studies have reported that the T cell inflamed signature can help predict the response to immunotherapy. Thus, many studies have investigated mechanisms of immunotherapy resistance by defining the tumor microenvironment based on T cell inflamed and non-T cell inflamed subsets. Although methods of calculating T cell inflamed subsets have been developed, valid screening tools for distinguishing T cell inflamed from non-T cell inflamed subsets using gene expression data are still needed, since general researchers who are unfamiliar with the details of the equations can experience difficulties using extant scoring formulas to conduct analyses. Thus, we introduce TcellInflamedDetector, an R package for distinguishing T cell inflamed from non-T cell inflamed samples using cancer gene expression data via bulk RNA sequencing.

Comparison of transorbital ultrasound measurements to predict intracranial pressure in brain-injured patients requiring external ventricular drainage.

OBJECTIVE: The optic nerve sheath diameter (ONSD) excluding the dura mater (ONSDE; i.e., the subarachnoid diameter) and the ONSD including the dura mater (ONSDI) have been used differently in studies, but the predictive ability of these two different measurements of the ONSD as measured by invasive intracranial pressure (ICP) monitoring has never been compared. Additionally, studies on the prediction of ICP using central retinal artery (CRA) Doppler ultrasonography are scarce. The authors aimed to determine how the two different ONSD measurements, the ONSD/eyeball transverse diameter (ETD) ratio, and transorbital Doppler ultrasonography parameters are associated with ICP via external ventricular drainage (EVD). METHODS: This prospective observational study included 50 patients with brain injury who underwent EVD between August 2019 and September 2020. The mean of three repeated measurements of the ONSDI and ONSDE was calculated to reduce artifact and off-axis measurements. ETD, an immutable value, was measured from the initial brain CT with a clear outline of the eyeball. Simultaneously, flow velocities in the CRA and posterior ciliary artery (PCA) were compared with the ICP. RESULTS: The ONSDE, ONSDI, and ONSD/ETD ratio were significantly associated with ICP (p = 0.005, p < 0.001, and p < 0.001, respectively). The ONSD/ETD ratio showed the highest predictive power of increased ICP (area under the curve [AUC] 0.897). The ONSDI was correlated more with the ICP than was the ONSDE (AUC 0.855 vs 0.783). None of the Doppler ultrasonography parameters in the CRA and PCA were associated with ICP. CONCLUSIONS: The ONSD/ETD ratio is a better predictor of increased ICP compared with the ONSDI or ONSDE in brain-injured patients with nonsevere ICP. The ONSDI may be more available for predicting the ICP than the ONSDE.

Analysis of the Rate of Confirmed COVID-19 Cases in Seoul and Factors Affecting It Using Big Data Analysis.

Coronavirus disease (COVID-19) is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and presents with mild to severe symptoms. Vaccines have been developed, but COVID-19 persists. Therefore, it is necessary to analyze big data at an early stage to establish an effective infection prevention strategy. To reduce SARS-CoV-2 infection, this study aimed to analyze the infection factors by region within Seoul, Korea and identify the major factors affecting the infection rate. For ease of data aggregation, the study was conducted after a data refinement operation that organized data in the same group into categories, and classified them in detail by specific keywords. Based on the results of this study, if preventive measures are established after identifying the representative infectious factors, periods, and routes of COVID-19 infection, the infection rate could be effectively reduced in the future.

Estimation of the journal distance of Genomics & Informatics from other bioinformatics-driven journals, 2003-2018.

This study explored the trends of Genomics & Informatics during the period of 2003-2018 in comparison with 11 other scholarly journals: BMC Bioinformatics, Algorithms for Molecular Biology: AMB, BMC Systems Biology, Journal of Computational Biology, Briefings in Bioinformatics, BMC Genomics, Nucleic Acids Research, American Journal of Human Genetics, Oncogenesis, Disease Markers, and Microarrays. In total, 22,423 research articles were reviewed. Content analysis was the main method employed in the current research. The results were interpreted using descriptive analysis, a clustering analysis, word embedding, and deep learning techniques. Trends are discussed for the 12 journals, both individually and collectively. This is an extension of our previous study (PMCID: PMC6808643).

Using the PubAnnotation ecosystem to perform agile text mining on Genomics & Informatics: a tutorial review.

The prototype version of the full-text corpus of Genomics & Informatics has recently been archived in a GitHub repository. The full-text publications of volumes 10 through 17 are also directly downloadable from PubMed Central (PMC) as XML files. During the Biomedical Linked Annotation Hackathon 6 (BLAH6), we experimented with converting, annotating, and updating 301 PMC full-text articles of Genomics & Informatics using PubAnnotation, a system that provides a convenient way to add PMC publications based on PMCID. Thus, this review aims to provide a tutorial overview of practicing the iterative task of named entity recognition with the PubAnnotation/PubDictionaries/TextAE ecosystem. We also describe developing a conversion tool between the Genia tagger output and the JSON format of PubAnnotation during the hackathon.

Impact of Neurointensivist Co-Management in a Semiclosed Neurocritical-Care Unit.

BACKGROUND AND PURPOSE: The importance of the specialized management of neurocritical patients is being increasingly recognized. We evaluated the impact of neurointensivist comanagement on the clinical outcomes (particularly the mortality rate) of neurocritical patients admitted to a semiclosed neurocritical-care unit (NCU). METHODS: We retrospectively included neurocritical patients admitted to the NCU between March 2015 and February 2018. We analyzed the clinical data and compared the outcomes between patients admitted before and after the initiation of neurointensivist co-management in March 2016. RESULTS: There were 1,785 patients admitted to the NCU during the study period. Patients younger than 18 years (n=28) or discharged within 48 hours (n=200) were excluded. The 1,557 remaining patients comprised 590 and 967 who were admitted to the NCU before and after the initiation of co-management, respectively. Patients admitted under neurointensivist co-management were older and had higher Acute Physiologic Assessment and Chronic Health Evaluation II scores. The 30-day mortality rate was significantly lower after neurointensivist co-management (p=0.042). A multivariate logistic regression analysis demonstrated that neurointensivist co-management significantly reduced mortality rates in the NCU and in the hospital overall [odds ratio=0.590 (p=0.002) and 0.585 (p=0.001), respectively]. CONCLUSIONS: Despite the higher severity of the condition during neurointensivist co-management, co-management significantly improved clinical outcomes (including the mortality rate) in neurocritical patients.

Organizing an in-class hackathon to correct PDF-to-text conversion errors of Genomics & Informatics 1.0.

This paper describes a community effort to improve earlier versions of the full-text corpus of Genomics & Informatics by semi-automatically detecting and correcting PDF-to-text conversion errors and optical character recognition errors during the first hackathon of Genomics & Informatics Annotation Hackathon (GIAH) event. Extracting text from multi-column biomedical documents such as Genomics & Informatics is known to be notoriously difficult. The hackathon was piloted as part of a coding competition of the ELTEC College of Engineering at Ewha Womans University in order to enable researchers and students to create or annotate their own versions of the Genomics & Informatics corpus, to gain and create knowledge about corpus linguistics, and simultaneously to acquire tangible and transferable skills. The proposed projects during the hackathon harness an internal database containing different versions of the corpus and annotations.

Trends in Genomics & Informatics: a statistical review of publications from 2003 to 2018 focusing on the most-studied genes and document clusters.

Genomics & Informatics (NLM title abbreviation: Genomics Inform) is the official journal of the Korea Genome Organization. Herein, we conduct a statistical analysis of the publications of Genomics & Informatics over the 16 years since its inception, with a particular focus on issues relating to article categories, word clouds, and the most-studied genes, drawing on recent reviews of the use of word frequencies in journal articles. Trends in the studies published in Genomics & Informatics are discussed both individually and collectively.

Safety and Efficacy of Minimally Invasive Stereotactic Aspiration with Multicatheter Insertion Compared with Conventional Craniotomy for Large Spontaneous Intracerebral Hemorrhage (≥50 mL).

BACKGROUND: Conventional craniotomy (CC) is generally favored for treating large intracerebral hemorrhage (ICH), but the feasibility of minimally invasive stereotactic aspiration for large ICH is controversial. We investigated the efficacy and safety of stereotactic aspiration with multicatheter insertion (SAMCI) for large ICH (≥50 mL). METHODS: In January 2014, we implemented SAMCI for large ICH. The inclusion criteria for SAMCI were as follows: 1) spontaneous supratentorial ICH, 2) ICH volume ≥50 mL, 3) Glasgow Coma Scale score ≥5, and 4) no bilateral fixed dilated pupils. Forty-seven patients who underwent SAMCI from January 2014 to July 2018 composed the SAMCI group, and 34 patients who underwent CC between January 2010 and December 2013 and retrospectively met the inclusion criteria for SAMCI composed the control group (CC group). RESULTS: The mean preoperative ICH volume in the SAMCI and CC groups was 73.1 ± 22.8 and 72.4 ± 21.5 mL, respectively. There were no significant differences between the groups in baseline characteristics except for ICH location. The deep portion of the ICH was higher in the SAMCI group than in the CC group. Postoperative mortality and rebleeding rates were significantly lower in the SAMCI group than in the CC group (4.3% vs. 26.5% and 0% vs. 14.7%, respectively; P < 0.05). Logistic regression analysis showed that SAMCI contributed to a decrease in the mortality rate (odds ratio, 0.04; P = 0.008). CONCLUSIONS: SAMCI is a feasible therapeutic option for large ICH and has low complication rates.

A new definition for wide-necked cerebral aneurysms.

BACKGROUND: Endovascular management of wide-necked aneurysms often requires assisted-techniques with adjunctive devices. Wide-necked aneurysm can be defined with a dome-to-neck ratio or aspect ratio; however, clinical definitions of wide-necked aneurysms vary. This study aimed to determine the most useful definition of wide-necked aneurysm to predict the need for an adjunctive device. METHODS: Among 552 cases of aneurysms, 343 (62.1%) and 209 (37.9%) cases of unruptured and ruptured aneurysms, respectively, were treated in a single institution. For each aneurysm, the (1) dome-to-neck ratio, (2) aspect ratio, and (3) K-ratio (defined as [dome height+maximum dome width]/[2×maximum neck width]) were measured. We statistically analyzed patient data to determine which of the three ratios was most predictive of the need for adjunctive devices. RESULTS: Among 552 cases of aneurysms, 277 (50.2%) and 275 (49.8%) cases were treated with and without adjunctive techniques, respectively. The mean dome-to-neck ratio, aspect ratio, and K-ratio were 1.17±0.39, 1.58±0.61, and 1.37±0.47, respectively. The K-ratio was the strongest predictor of the use of adjunctive devices (P<0.001), and 1.3 was the most appropriate K-ratio cut-off value (sensitivity, 72.9%; specificity, 63.6%). CONCLUSIONS: K-ratio was the most useful predictor of the need for adjunctive devices in the treatment of endovascular aneurysms. These results suggest that the K-ratio may be used to define wide-necked aneurysms requiring complicated management via adjunctive devices.