Minimized combinatorial CRISPR screens identify genetic interactions in autophagy.

Combinatorial CRISPR-Cas screens have advanced the mapping of genetic interactions, but their experimental scale limits the number of targetable gene combinations. Here, we describe 3Cs multiplexing, a rapid and scalable method to generate highly diverse and uniformly distributed combinatorial CRISPR libraries. We demonstrate that the library distribution skew is the critical determinant of its required screening coverage. By circumventing iterative cloning of PCR-amplified oligonucleotides, 3Cs multiplexing facilitates the generation of combinatorial CRISPR libraries with low distribution skews. We show that combinatorial 3Cs libraries can be screened with minimal coverages, reducing associated efforts and costs at least 10-fold. We apply a 3Cs multiplexing library targeting 12,736 autophagy gene combinations with 247,032 paired gRNAs in viability and reporter-based enrichment screens. In the viability screen, we identify, among others, the synthetic lethal WDR45B-PIK3R4 and the proliferation-enhancing ATG7-KEAP1 genetic interactions. In the reporter-based screen, we identify over 1,570 essential genetic interactions for autophagy flux, including interactions among paralogous genes, namely ATG2A-ATG2B, GABARAP-MAP1LC3B and GABARAP-GABARAPL2. However, we only observe few genetic interactions within paralogous gene families of more than two members, indicating functional compensation between them. This work establishes 3Cs multiplexing as a platform for genetic interaction screens at scale.

A 316MP, 120FPS, High Dynamic Range CMOS Image Sensor for Next Generation Immersive Displays.

We present a 2D-stitched, 316MP, 120FPS, high dynamic range CMOS image sensor with 92 CML output ports operating at a cumulative date rate of 515 Gbit/s. The total die size is 9.92 cm × 8.31 cm and the chip is fabricated in a 65 nm, 4 metal BSI process with an overall power consumption of 23 W. A 4.3 µm dual-gain pixel has a high and low conversion gain full well of 6600e- and 41,000e-, respectively, with a total high gain temporal noise of 1.8e- achieving a composite dynamic range of 87 dB.

Anatomic feasibility of endoscopic endonasal intracranial aneurysm clipping: a systematic review of anatomical studies.

Clinical studies have suggested the endoscopic endonasal approach (EEA) for aneurysm clipping as a feasible way to treat select intracranial aneurysms. Among neurosurgery, there is not a consensus on the utility of EEA aneurysm clipping. This review aims to define the anatomic feasibility of EEA for aneurysm clipping. Two databases (PubMed, Cochrane) were searched for anatomical studies assessing EEA for intracranial aneurysm clipping. Literature review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quantitative anatomical studies were included. Eleven studies met inclusion criteria. Vascular exposure and clip placement on vessels of interest were possible, although only one study assessed these parameters with physical aneurysm models. Anterior circulation vessels, although accessible in over 90% of specimens, had low successful clipping rates in a small and large aneurysm models. Small and large model posterior circulation aneurysms were more readily clipped. Proximal and distal controls were readily attainable in posterior circulation aneurysms, but not anterior. This current literature review highlights the relevance of anatomical studies in assessing the feasibility of the EEA for clipping intracranial aneurysms. As such, anterior circulation aneurysms are poor candidates for EEA given difficulties in clip placement and obtaining proximal control and distal control in small and large aneurysms. While our results suggest that clipping of posterior circulation aneurysms is feasible from a technical stand of view, further clinical experience is required to assess its feasibility in terms of safety and efficacy, balancing the indications with endovascular treatment options.

Ultrasound's Impact on Preclinical Medical Student Neurology Unit Grades: Findings After 2 Years.

OBJECTIVES: Ultrasound is a valuable tool for anatomy education, but limited evidence exists for using ultrasound to teach neuroanatomy and neurophysiology. Previous work demonstrated a potential increase in medical knowledge in preclinical medical students participating in a neurology ultrasound workshop, however, without comparison to a control group. After 2 years, we assessed how a neurology ultrasound workshop affected the medical knowledge of participating preclinical medical students compared to a traditional curriculum control group. METHODS: This quasiexperimental study compared academic performance of ultrasound workshop participants to nonparticipant classmates. The primary outcome was the overall neurologic disorders unit total score. An analysis of covariance was conducted to test for statistically significant differences while controlling for the average quiz score. RESULTS: A total of 360 medical students were included in the study. The intervention group (n = 57) showed no significant difference in the total unit score (F = 3.206; P = .074), with averages for the control and experimental groups being 87.3% ± 5.0% and 88.4% ± 4.8%, respectively. Additionally, anatomy practical scores and written final examination scores were not significantly different between groups (F = 1.035; P = .310; F = 2.035; P = .155). CONCLUSIONS: Participation in a neurologic disorders ultrasound workshop did not appear to be correlated with improved curricular performance in our cohort. Further research should continue to assess ultrasound workshops in other organ systems to elucidate the relationship between learning ultrasound and the impact on medical school academic performance.

Comparison of Perioperative Outcomes and Parental Satisfaction Outcomes of Strip Craniectomy with Postoperative Helmet versus Spring-Mediated Remodeling in Sagittal Craniosynostosis.

INTRODUCTION: We sought to compare outcomes and parental satisfaction between 2 approaches for sagittal craniosynostosis: strip craniectomy with spring-mediated skull remodeling (SMSR) and strip craniectomy with postoperative helmet (SCH). METHODS: Perioperative and outcome data for SMSR or SCH patients between September 2010 and July 2019 were retrospectively reviewed. A telephone survey was administered to parents of children who underwent both procedures. RESULTS: A total of 62 children were treated for sagittal craniosynostosis by either SMSR (n = 45) or SCH (n = 17). The SCH group had a lower estimated blood loss (27 vs. 47.06 mL, p = 0.021) and age at surgery (13.0 vs. 19.8 weeks) than the SMSR group. Three patients underwent early springs removal due to trauma or dislodgement, all of whom converted to helmeting. Of the 62 children initially identified, 59 were determined to have an adequate follow-up time to assess long-term outcomes. The mean follow-up time was 30.1 months (n = 16) in the SCH group and 32.0 months in the SMSR group (n = 43, p = 0.39). Two patients in the SCH group and one in the SMSR group converted to open cranial vault reconstruction. Thirty parents agreed to respond to the satisfaction survey (8 SCH, 22 SMSR) based on a Likert scale of responses (0 being most dissatisfied possible, 4 most satisfied possible). Average satisfaction was 3.86/4.0 in the SCH group and 3.45/4.0 in the SMSR group. No parents in the SCH group would change to SMSR, while 3 of the 22 SMSR survey responders would have changed to SCH. CONCLUSIONS: Perioperative outcomes and average parental satisfaction were similar in both groups. Importance of helmet wear compliance and risk of spring dislodgement should be discussed with parents.

CRL7SMU1 E3 ligase complex-driven H2B ubiquitylation functions in sister chromatid cohesion by regulating SMC1 expression.

Cullin-RING-type E3 ligases (CRLs) control a broad range of biological processes by ubiquitylating numerous cellular substrates. However, the role of CRL E3 ligases in chromatid cohesion is unknown. In this study, we identified a new CRL-type E3 ligase (designated as CRL7SMU1 complex) that has an essential role in the maintenance of chromatid cohesion. We demonstrate that SMU1, DDB1, CUL7 and RNF40 are integral components of this complex. SMU1, by acting as a substrate recognition module, binds to H2B and mediates monoubiquitylation at the lysine (K) residue K120 through CRL7SMU1 E3 ligase complex. Depletion of CRL7SMU1 leads to loss of H2B ubiquitylation at the SMC1a locus and, thus, subsequently compromised SMC1a expression in cells. Knockdown of CRL7SMU1 components or loss of H2B ubiquitylation leads to defective sister chromatid cohesion, which is rescued by restoration of SMC1a expression. Together, our results unveil an important role of CRL7SMU1 E3 ligase in promoting H2B ubiquitylation for maintenance of sister chromatid cohesion during mitosis.This article has an associated First Person interview with the first author of the paper.

The utility of pulmonary function testing in the preoperative risk stratification of patients undergoing transcatheter aortic valve replacement.

BACKGROUND: The role of pulmonary function testing (PFT) as a predictor of clinically relevant endpoints in transcatheter aortic valve replacement (TAVR) is unclear. OBJECTIVE: To determine the utility of PFT in the preoperative risk stratification of patients undergoing TAVR. METHODS: An evaluation of PFT (i.e., FEV1), arterial blood gases (i.e., PO2), the diagnosis of chronic obstructive lung disease (COPD) by the Global Initiative for COPD (GOLD), and the diagnosis of chronic lung disease (CLD) by the Society of Thoracic Surgeons (STS) was performed to determine whether a relationship exists among these parameters and clinically relevant outcomes, including all-cause 30-day and 1-year mortality. RESULTS: A total of 513 patients underwent TAVR between March 2013 and December 2016. Per STS criteria, 269/513 (52%) had CLD with a mean FEV1 of 55.4 ± 12%. Per GOLD criteria, 158/513 (30%) of patients had COPD with a mean FEV1/forced vital capacity of 61.8 ± 8.2%. The severity of CLD was affected by changes in ejection fraction, albumin, creatinine, and B-type natriuretic peptide levels (p = .009, p < .001, p < .001, and p < .001, respectively), whereas the severity of COPD was not affected by these same variables, (p = .302, .079, .137, and .102, respectively). An increased A-a gradient (p = .035), increased PCO2 (p = .016), and decreased PO2 (p = <.001) demonstrated increased risk of 30-day mortality. Neither classification (COPD or CLD), nor PFT changes, showed association with 30-day and 1-year mortality (p = NS). CONCLUSION: This study suggests that isolated abnormalities in spirometry are a poor indicator of clinically relevant outcomes in TAVR. When classified correctly, COPD does not predict clinically relevant postoperative outcomes.

Probing the role of proline -135 on the structure, stability, and cell proliferation activity of human acidic fibroblast growth factor.

Human acidic fibroblast growth factor 1 (hFGF1) is a protein intricately involved in cell growth and tissue repair. In this study, we investigate the effect(s) of understanding the role of a conserved proline (P135), located in the heparin binding pocket, on the structure, stability, heparin binding affinity, and cell proliferation activity of hFGF1. Substitution of proline-135 with a positively charged lysine (P135K) resulted in partial destabilization of the protein; however, the overall structural integrity of the protein was maintained upon substitution of proline-135 with either a negative charge (P135E) or a polar amino acid (P135Q). Interestingly, upon heparin binding, an increase in thermal stability equivalent to that of wt-hFGF1 was observed when P135 was replaced with a positive (P135K) or a negative charge (P135E), or with a polar amino acid (P135Q). Surprisingly, introduction of negative charge in the heparin-binding pocket at position 135 (P135E) increased hFGF1's affinity for heparin by 3-fold, while the P135K mutation, did not alter the heparin-binding affinity. However, the enhanced heparin-binding affinity of mutant P135E did not translate to an increase in cell proliferation activity. Interestingly, the P135K and P135E double mutations, P135K/R136E and P135/R136E, reduced the heparin binding affinity by ∼3-fold. Furthermore, the cell proliferation activity was increased when the charge reversal mutation R136E was paired with both P135E (P135E/R136E) and P135K (P135K/R136E). Overall, the results of this study suggest that while heparin is useful for stabilizing hFGF1 on the cell surface, this interaction is not mandatory for activation of the FGF receptor.

A Human Tyrosine Phosphatase Interactome Mapped by Proteomic Profiling.

Tyrosine phosphatases play a critical role in many cellular processes and pathogenesis, yet comprehensive analysis of their functional interacting proteins in the cell is limited. By utilizing a proteomic approach, here we present an interaction network of 81 human tyrosine phosphatases built on 1884 high-confidence interactions of which 85% are unreported. Our analysis has linked several phosphatases with new cellular processes and unveiled protein interactions genetically linked to various human diseases including cancer. We validated the functional importance of an identified interaction network by characterizing a distinct novel interaction between PTPN5 and Mob1a. PTPN5 dephosphorylates Mob1a at Y26 residue. Further, we identify that PTPN5 is required for proper midbody abscission during cytokinesis through regulation of Mob1a dephosphorylation. In conclusion, our study provides a valuable resource of tyrosine phosphatase interactions, which can be further utilized to dissect novel cellular functions of these enzymes.

Folding of Fibroblast Growth Factor 1 Is Critical for Its Nonclassical Release.

Fibroblast growth factor 1 (FGF1), a ubiquitously expressed pro-angiogenic protein that is involved in tissue repair, carcinogenesis, and maintenance of vasculature stability, is released from the cells via a stress-dependent nonclassical secretory pathway. FGF1 secretion is a result of transmembrane translocation of this protein. It correlates with the ability of FGF1 to permeabilize membranes composed of acidic phospholipids. Like several other nonclassically exported proteins, FGF1 exhibits ß-barrel folding. To assess the role of folding of FGF1 in its secretion, we applied targeted mutagenesis in combination with a complex of biophysical methods and molecular dynamics studies, followed by artificial membrane permeabilization and stress-induced release experiments. It has been demonstrated that a mutation of proline 135 located in the C-terminus of FGF1 results in (i) partial unfolding of FGF1, (ii) a decrease in FGF1's ability to permeabilize bilayers composed of phosphatidylserine, and (iii) drastic inhibition of stress-induced FGF1 export. Thus, folding of FGF1 is critical for its nonclassical secretion.

Identification of heat shock factor binding protein in Plasmodium falciparum.

BACKGROUND: Heat shock factor binding protein (HSBP) was originally discovered in a yeast two-hybrid screen as an interacting partner of heat shock factor (HSF). It appears to be conserved in all eukaryotes studied so far, with yeast being the only exception. Cell biological analysis of HSBP in mammals suggests its role as a negative regulator of heat shock response as it appears to interact with HSF only during the recovery phase following exposure to heat stress. While the identification of HSF in the malaria parasite is still eluding biologists, this study for the first time, reports the presence of a homologue of HSBP in Plasmodium falciparum. METHODS: PfHSBP was cloned and purified as his-tag fusion protein. CD (Circular dichroism) spectroscopy was performed to predict the secondary structure. Immunoblots and immunofluorescence approaches were used to study expression and localization of HSBP in P. falciparum. Cellular fractionation was performed to examine subcellular distribution of PfHSBP. Immunoprecipitation was carried out to identify HSBP interacting partner in P. falciparum. RESULTS: PfHSBP is a conserved protein with a high helical content and has a propensity to form homo-oligomers. PfHSBP was cloned, expressed and purified. The in vivo protein expression profile shows maximal expression in trophozoites. The protein was found to exist in oligomeric form as trimer and hexamer. PfHSBP is predominantly localized in the parasite cytosol, however, upon heat shock, it translocates to the nucleus. This study also reports the interaction of PfHSBP with PfHSP70-1 in the cytoplasm of the parasite. CONCLUSIONS: This study emphasizes the structural and biochemical conservation of PfHSBP with its mammalian counterpart and highlights its potential role in regulation of heat shock response in the malaria parasite. Analysis of HSBP may be an important step towards identification of the transcription factor regulating the heat shock response in P. falciparum.

Preoperative prescription opioid use as an independent predictor of 90-day mortality and adverse events in craniotomy and craniectomy patients.

OBJECTIVE: A growing body of literature suggests that preoperative opioid exposure is an independent predictor of poor outcomes in surgical patients. No outcomes data exist on preoperative opioid use and craniotomies/craniectomies. The objective of this study was to determine the impact of preoperative opioid use on 90-day adverse events after craniotomy or craniectomy. METHODS: A single-center retrospective cohort study of 2445 patients undergoing a craniotomy/craniectomy between January 1, 2013, and October 1, 2018, was conducted. Baseline demographics, pre- and postoperative opioid use (morphine milligram equivalents [MMEs]), and surgical metrics were recorded. Patients were categorized based on whether they took prescription opioids preoperatively, defined as within 1 month of surgery, or were opioid naive. The outcomes were mortality and adverse events 90 days after craniotomy/craniectomy. RESULTS: Overall, 26.6% of patients composed the preoperative opioid group. The median daily MME intake among this group was 34.6 (IQR 14.1-90) MMEs. Lower employment rates (p < 0.001), uninsured status (p = 0.016), and intravenous drug use (p = 0.006) were associated with preoperative opioid use. Preoperative opioid use was associated with increased venous thromboembolism (p = 0.001), acute kidney injury (p = 0.002), acute respiratory failure (p < 0.001), myocardial infarction (p = 0.002), delirium (p < 0.001), and infection (p < 0.001). Preoperative opioid use was an independent predictor of overall 90-day adverse events (OR 1.643, 95% CI 1.289-2.095; p < 0.001) and 90-day mortality (OR 1.690, 95% CI 1.254-2.277; p < 0.001). CONCLUSIONS: Preoperative opioid use was independently associated with 90-day postoperative adverse events and mortality. Opioid use increases vulnerability in craniotomy/craniectomy patients and necessitates close monitoring to improve outcomes.

Taxonomic Profiling and Metagenome Analysis of a Microbial Community from a Habitat Contaminated with Industrial Discharges.

Industrial units, manufacturing dyes, chemicals, solvents, and xenobiotic compounds, produce liquid and solid wastes, which upon conventional treatment are released in the nearby environment and thus are the major cause of pollution. Soil collected from contaminated Kharicut Canal bank (N 22°57.878'; E 072°38.478'), Ahmedabad, Gujarat, India was used for metagenomic DNA preparation to study the capabilities of intrinsic microbial community in dealing with xenobiotics. Sequencing of metagenomic DNA on the Genome Sequencer FLX System using titanium chemistry resulted in 409,782 reads accounting for 133,529,997 bases of sequence information. Taxonomic analyses and gene annotations were carried out using the bioinformatics platform Sequence Analysis and Management System for Metagenomic Datasets. Taxonomic profiling was carried out by three different complementary approaches: (a) 16S rDNA, (b) environmental gene tags, and (c) lowest common ancestor. The most abundant phylum and genus were found to be "Proteobacteria" and "Pseudomonas," respectively. Metagenome reads were mapped on sequenced microbial genomes and the highest numbers of reads were allocated to Pseudomonas stutzeri A1501. Assignment of obtained metagenome reads to Gene Ontology terms, Clusters of Orthologous Groups of protein categories, protein family numbers, and Kyoto Encyclopedia of Genes and Genomes hits revealed genomic potential of indigenous microbial community. In total, 157,024 reads corresponded to 37,028 different KEGG hits, and amongst them, 11,574 reads corresponded to 131 different enzymes potentially involved in xenobiotic biodegradation. These enzymes were mapped on biodegradation pathways of xenobiotics to elucidate their roles in possible catalytic reactions. Consequently, information obtained from the present study will act as a baseline which, subsequently along with other "-omic" studies, will help in designing future bioremediation strategies in effluent treatment plants and environmental clean-up projects.

Taxonomic profiling and metagenome analysis of a microbial community from a habitat contaminated with industrial discharges.

Industrial units, manufacturing dyes, chemicals,solvents, and xenobiotic compounds, produce liquid and solid wastes, which upon conventional treatment are released in the nearby environment and thus are the major cause of pollution. Soil collected from contaminated Kharicut Canalbank (N 22°57.878'; E 072°38.478'), Ahmeda bad, Gujarat,India was used for metagenomic DNA preparation to study the capabilities of intrinsic microbial community in dealing with xenobiotics. Sequencing of metagenomic DNA on the Genome Sequencer FLX System using titanium chemistry resulted in 409,782 reads accounting for 133,529,997 bases of sequence information. Taxonomic analyses and gene annotations were carried out using the bioinformatics platform Sequence Analysis and Management System for Metagenomic Datasets. Taxonomic profiling was carried out by three different complementary approaches: (a) 16S rDNA, (b) environmental gene tags, and (c) lowest common ancestor. The most abundant phylum and genus were found to be "Proteobacteria"and "Pseudomonas," respectively. Metagenome reads were mapped on sequenced microbial genomes and the highest numbers of reads were allocated to Pseudomonas stutzeri A1501. Assignment of obtained metagenome reads to Gene Ontology terms, Clusters of Orthologous Groups of protein categories, protein family numbers, and Kyoto Encyclopedia of Genes and Genomes hits revealed genomic potential of indigenous microbial community. In total, 157,024 reads corresponded to 37,028 different KEGG hits, and amongst them, 11,574 reads corresponded to 131 different enzymes potentially involved in xenobiotic biodegradation. These enzymes were mapped on biodegradation pathways of xenobiotics to elucidate their roles in possible catalytic reactions. Consequently, information obtained from the present study will act as a baseline which, subsequently along with other"-omic" studies, will help in designing future bioremediation strategies in effluent treatment plants and environmental cleanup projects.

Pretreatment findings on magnetic resonance imaging in primary central nervous system lymphoma may predict overall survival duration.

BACKGROUND: and purpose: Primary central nervous system lymphoma (PCNSL) lesions often show avid contrast enhancement on T1-weighted contrast-enhanced MRI sequences. However, several case reports and a clinical study have described PCNSL in patients with no contrast enhancement on MRI. We assessed whether overall survival (OS) time was related to any tumor characteristics (lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; and edema) on MRI in patients with PCNSL. MATERIALS AND METHODS: We retrospectively reviewed records (MRI features, pathology, and survival data) of all patients at our institution with PCNSL who had been seen from, 2007 through 2017, and had undergone pretreatment MRI. RESULTS: We identified 79 patients (42 men, 37 women) with a mean age at diagnosis of 61.7 ± 10.4 years. The mean OS duration was 44.6 ± 41.7 months. The most common pathological diagnosis (74 patients) was diffuse large B-cell lymphoma. No associations were found between OS time and lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; or edema. However, a sole patient with non-enhancing PCNSL on MRI was found to have low-grade disease, with prolonged survival (>83 months). Several other patients with leptomeningeal disease had a mean OS time of 80 months. Patients with hemorrhagic lesions had a mean OS of 25.5 months. CONCLUSIONS: The survival time for patients with PCNSL may be longer than previously thought, especially for patients with leptomeningeal seeding and lesions with hemorrhagic components Also, non-enhancing tumors may be less aggressive than enhancing tumors.

Impact of anemia on acute ischemic stroke outcomes: A systematic review of the literature.

INTRODUCTION: Anemia has been reported in nearly 40% of acute ischemic stroke (AIS) patients and is linked to significant morbidity and disability. The presence of anemia is associated with worse outcomes in AIS, specifically in the presence of large vessel occlusion (LVO). An optimal hemoglobin (Hb) target specific to this pathology has not yet been established. The goal of this review is to systematically review literature that observes the association that exists between AIS outcomes and hemoglobin (Hb) levels. METHODS: A systematic review was performed in accordance with guidelines for the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to identify studies from 2008-2022. The following inclusion and exclusion criteria were used: studies of adult patients with AIS; must describe outcomes with regard to Hb levels in AIS (not limited to LVO); must be written in English. The clinical variables extracted included Length of Stay (LOS), modified rankin score (mRS), Hb levels, and mortality. RESULTS: A total of 1,154 studies were gathered, with 116 undergoing full text review. 31 studies were included in this review. The age of patients ranged from 61.4 to 77.8. The presence of anemia in AIS increased LOS by 1.7 days on average and these patients also have a 15.2% higher rate of mortality at one year, on average. DISCUSSION: This data suggests that the contemporary thresholds for treating anemia in AIS patients may be inadequate because anemia is strongly associated with poor outcomes (e.g., mRS>2 or mortality) and increased LOS in AIS patients. The current generalized Hb threshold for transfusion (7 g/dL) is also used in AIS patients, however, a more aggressive transfusion parameter should be further explored based on these findings. Further studies are required to confirm these findings and to determine if a more liberal RBCT threshold will result in clinical benefits.

Localization matters in targeted protein degradation.

Many factors influence the efficiency of targeted protein degradation induced by proteolysis targeting chimeras (PROTACs). In this issue of Cell Chemical Biology,Simpson et al. (2022) highlight the impact of subcellular localization. Their study elucidates that the protein of interest exhibits different amenability to PROTAC-mediated degradation at different cellular compartments.

Effect of rapid EEG on anti-seizure medication usage

Objective: To study how early diagnoses from rapid EEG (rEEG) during the initial evaluation of patients with suspected non-convulsive seizures correlates with changes in anti-seizure medication (ASM) use. Methods: We performed a retrospective chart review of 100 consecutive adult patients at an academic medical center who underwent rEEG monitoring for suspected non-convulsive seizures. We collected information on the timing of ASM administration and categorized EEG diagnoses as seizures (SZ), highly epileptiform patterns (HEP), or normal or slow activity (NL/SL). We used a χ² test to determine whether the use of ASMs was significantly different between SZ/HEP and NL/SL cases. Results: Of 100 patients, SZ were found in 5%, HEP in 14%, and no epileptiform/ictal activity in 81%. Forty-six percent of patients had received ASM(s) before rEEG. While 84% of HEP/SZ cases were started or continued on ASMs, only 51% of NL/SL cases were started or continued on ASMs after rEEG (χ² [1, n=100] = 7.09, p=0.008). Thirty-seven patients had received sedation (i.e., propofol or dexmedetomidine) prior to rEEG. In 15 patients (13/30 NL/SL, 2/7 HEP/SZ), sedation was discontinued following rEEG. Significance: Our study demonstrates that seizures were rapidly ruled out with rEEG in 81% of patients while 19% of patients were rapidly identified as having seizures or being at higher risk for seizures. The rapid evaluation of patients correlated with a significant reduction in ASM treatment in NL/SL cases compared to HEP/SZ cases. Thus, early access to EEG information may lead to more informed and targeted management of patients suspected to have nonconvulsive seizures.

Complications after 1002 endoscopic endonasal approach procedures at a single center: lessons learned, 2010-2018.

OBJECTIVE: The endoscopic endonasal approach (EEA) has evolved into a mainstay of skull base surgery over the last two decades, but publications examining the intraoperative and perioperative complications of this technique remain scarce. A prior landmark series of 800 patients reported complications during the first era of EEA (1998-2007), parallel to the development of many now-routine techniques and technologies. The authors examined a single-institution series of more than 1000 consecutive EEA neurosurgical procedures performed since 2010, to elucidate the safety and risk factors associated with surgical and postoperative complications in this modern era. METHODS: After obtaining institutional review board approval, the authors retrospectively reviewed intraoperative and postoperative complications and their outcomes in patients who underwent EEA between July 2010 and June 2018 at a single institution. RESULTS: The authors identified 1002 EEA operations that met the inclusion criteria. Pituitary adenoma was the most common pathology (n = 392 [39%]), followed by meningioma (n = 109 [11%]). No patients died intraoperatively. Two (0.2%) patients had an intraoperative carotid artery injury: 1 had no neurological sequelae, and 1 had permanent hemiplegia. Sixty-one (6.1%) cases of postoperative cerebrospinal fluid leak occurred, of which 45 occurred during the original surgical hospitalization. Transient postoperative sodium dysregulation was noted after 87 (8.7%) operations. Six (0.6%) patients were treated for meningitis, and 1 (0.1%) patient died of a fungal skull base infection. Three (0.3%) patients died of medical complications, thereby yielding a perioperative 90-day mortality rate of 0.4% (4 deaths). High-grade (Clavien-Dindo grade III-V) complications were identified after 103 (10%) EEA procedures, and multivariate analysis was performed to determine the associations between factors and these more serious complications. Extradural EEA was significantly associated with decreased rates of these high-grade complications (OR [95% CI] 0.323 [0.153-0.698], p = 0.0039), whereas meningioma pathology (OR [95% CI] 2.39 [1.30-4.40], p = 0.0053), expanded-approach intradural surgery (OR [95% CI] 2.54 [1.46-4.42], p = 0.0009), and chordoma pathology (OR [95% CI] 9.31 [3.87-22.4], p < 0.0001) were independently associated with significantly increased rates of high-grade complications. CONCLUSIONS: The authors have reported a large 1002-operation cohort of EEA procedures and associated complications. Modern EEA surgery for skull base pathologies has an acceptable safety profile with low morbidity and mortality rates. Nevertheless, significant intraoperative and postoperative complications were correlated with complex intradural procedures and meningioma and chordoma pathologies.

Utility of the novel guide catheter in mechanical thrombectomy for emergent large vessel occlusion stroke.

BACKGROUND: A number of large bore guide catheters are currently available for use in neuroendovascular surgery. This study represents a multi-institutional retrospective series of patients undergoing mechanical thrombectomy with the use of a TracStar Large Distal Platform (LDP) guide catheter and assessed its performance in vivo in 107 patients. OBJECTIVE: To review a multi-institutional initial experience with the TracStar LDP guide catheter during mechanical thrombectomy for emergent large vessel occlusion (ELVO). METHODS: A retrospective review was performed at two level one stroke centres to include all patients who underwent mechanical thrombectomy and had the TracStar LDP guide catheter used during the intervention. RESULTS: The TracStar LDP guide catheter was successfully used in 107 mechanical thrombectomies. In anterior circulation ELVO, the guide catheter advanced into the cavernous segment of the internal carotid artery in 62.6% (62/99) of cases. In posterior circulation cases, the guide catheter advanced to the basilar artery in 87.5% (7/8) of cases. A thrombolysis in cerebral infarction 2b or greater reperfusion was obtained in 90.7% (97/107). No complications occurred related to the TracStar LDP guide catheter. Three complications occurred with aspiration catheters including a small dissection that did not require further intervention and fracturing of the AXS Catalyst 6 catheter tip in two cases. No thromboembolic events occurred. CONCLUSIONS: The TracStar LDP large bore guide catheter is safe and effective at navigating the tortuous vascular anatomy often encountered during mechanical thrombectomy for stroke. The flexible distal and stiffer proximal components provide a good combination of navigability and support for use in neuroendovascular interventions.