The glycerophosphocholine acyltransferase Gpc1 contributes to phosphatidylcholine biosynthesis, long-term viability, and embedded hyphal growth in Candida albicans.

Candida albicans is a commensal fungus, opportunistic pathogen, and the most common cause of fungal infection in humans. The biosynthesis of phosphatidylcholine (PC), a major eukaryotic glycerophospholipid, occurs through two primary pathways. In Saccharomyces cerevisiae and some plants, a third PC synthesis pathway, the PC deacylation/reacylation pathway (PC-DRP), has been characterized. PC-DRP begins with the acylation of the lipid turnover product, glycerophosphocholine (GPC), by the GPC acyltransferase, Gpc1, to form Lyso-PC. Lyso-PC is then acylated by lysolipid acyltransferase, Lpt1, to produce PC. Importantly, GPC, the substrate for Gpc1, is a ubiquitous metabolite available within the host. GPC is imported by C. albicans, and deletion of the major GPC transporter, Git3, leads to decreased virulence in a murine model. Here we report that GPC can be directly acylated in C. albicans by the protein product of orf19.988, a homolog of ScGpc1. Through lipidomic studies, we show loss of Gpc1 leads to a decrease in PC levels. This decrease occurs in the absence of exogenous GPC, indicating that the impact on PC levels may be greater in the human host where GPC is available. A gpc1Δ/Δ strain exhibits several sensitivities to antifungals that target lipid metabolism. Furthermore, loss of Gpc1 results in both a hyphal growth defect in embedded conditions and a decrease in long-term cell viability. These results demonstrate for the first time the importance of Gpc1 and this alternative PC biosynthesis route (PC-DRP) to the physiology of a pathogenic fungus.

Transradial versus transfemoral access for mechanical thrombectomy in acute ischemic stroke: A retrospective cohort study.

BACKGROUND: The objective of this study was to compare procedural and clinical outcomes in patients with acute ischemic stroke (AIS) treated via transradial access (TRA) mechanical thrombectomy (MT) versus conventional transfemoral access (TFA). METHODS: We performed a retrospective analysis of consecutive patients with AIS treated with TRA versus TFA MT at our tertiary comprehensive stroke center. Access choice was individualized based on occlusion site, aortic and arch anatomy. Outcomes were extracted from our institutional stroke registry and included procedural time, Thrombolysis in Cerebral Infarction (TICI) reperfusion score, NIHSS, 90-day mRS and 90-day mortality. Comparisons were performed using Student t-Test and Fischer's exact test as appropriate. RESULTS: 175 mechanical thrombectomies were performed during the study interval; 39 (22%) were performed via TRA and 136 (79%) TFA. Access to reperfusion time was 36.3 ± 24.5 minutes in the TRA group and 21.9 ± 17.6 in the TFA group (p<0.001). The proportion of patients with a TICI reperfusion score of 2b or 3 was similar in both groups (TRA: 34 (87%) vs. TFA: 121 (89%) p=0.559. The median 90-day mRS was similar between both groups (p=0.170), as was the 90-day mortality (p = 0.509). CONCLUSIONS: While TFA is faster in our cohort, TFA and TRA are both safe and effective for MT in acute ischemic stroke. While TFA remains mainstay, TRA can be valuable in variant anatomy despite its technical limitations. Individualizing access based on advanced imaging and patient factors may improve practice; however, updates in catheter and access technology are necessary to optimize outcomes with TRA.

Diagnosis and endovascular management of vasospasm after aneurysmal subarachnoid hemorrhage - survey of real-life practices.

BACKGROUND: Vasospasm and delayed cerebral ischemia (DCI) are the leading causes of morbidity and mortality after intracranial aneurysmal subarachnoid hemorrhage (aSAH). Vasospasm detection, prevention and management, especially endovascular management varies from center to center and lacks standardization. We aimed to evaluate this variability via an international survey of how neurointerventionalists approach vasospasm diagnosis and endovascular management. METHODS: We designed an anonymous online survey with 100 questions to evaluate practice patterns between December 2021 and September 2022. We contacted endovascular neurosurgeons, neuroradiologists and neurologists via email and via two professional societies - the Society of NeuroInterventional Surgery (SNIS) and the European Society of Minimally Invasive Neurological Therapy (ESMINT). We recorded the physicians' responses to the survey questions. RESULTS: A total of 201 physicians (25% [50/201] USA and 75% non-USA) completed the survey over 10 months, 42% had >7 years of experience, 92% were male, median age was 40 (IQR 35-46). Both high-volume and low-volume centers were represented. Daily transcranial Doppler was the most common screening method (75%) for vasospasm. In cases of symptomatic vasospasm despite optimal medical management, endovascular treatment was directly considered by 58% of physicians. The most common reason to initiate endovascular treatment was clinical deficits associated with proven vasospasm/DCI in 89%. The choice of endovascular treatment and its efficacy was highly variable. Nimodipine was the most common first-line intra-arterial therapy (40%). Mechanical angioplasty was considered the most effective endovascular treatment by 65% of neurointerventionalists. CONCLUSION: Our study highlights the considerable heterogeneity among the neurointerventional community regarding vasospasm diagnosis and endovascular management. Randomized trials and guidelines are needed to improve standard of care, determine optimal management approaches and track outcomes.

Push and Fluff technique for optimization of clot integration with stent-retriever: An in vitro model.

BACKGROUND: For stent-retriever (SR) thrombectomy, technical developments such as the Push and Fluff technique (PFT) appear to have a significant impact on procedural success. This study aimed to (1) quantify the enhancement in clot traction when using PFT as compared to the standard unsheathing technique (SUT) and (2) to evaluate the performance of PFT in new versus established users of the technique. METHODS: Operators were divided between established PFT and SUT users. Each experiment was labeled according to the SR size, utilized technique, and operator experience. A three-dimensional-printed chamber with a clot simulant was used. After each retriever deployment, the SR wire was connected to a force gauge. Tension was applied by pulling the gauge until clot disengagement. The maximal force was recorded. RESULTS: A total of 167 experiments were performed. The median overall force to disengage the clot was 1.11 pounds for PFT and 0.70 pounds for SUT (an overall 59.1% increment with PFT; p < 0.001). The PFT effect was consistent across different retriever sizes (69% enhancement with the 3 × 32mm device, 52% with the 4 × 28mm, 65% with the 4 × 41mm, 47% with the 6 × 37mm). The ratio of tension required for clot disengagement with PFT versus SUT was comparable between physicians who were PFT versus SUT operators (1.595 [0.844] vs. 1.448 [1.021]; p: 0.424). The PFT/SUT traction ratio remained consistent from passes 1 to 4 of each technique in SUT users. CONCLUSION: PFT led to reproduceable improvement in clot engagement with an average ∼60% increase in clot traction in this model and was found not to have a significant learning curve.

Immune Thrombocytopenic Purpura Presenting with Pituitary Apoplexy: A Case Report and Literature Review.

Background Pituitary apoplexy is a rare condition that usually occurs in the setting of a pituitary adenoma. It can present with symptoms of visual disturbances, vertigo, headache, and neurological impairments. Computed tomography (CT) scans can aid in identifying pituitary apoplexy and ruling out other diseases. We present a unique case of pituitary apoplexy in the setting of immune thrombocytopenic purpura (ITP). Case Description A 61-year-old man with a past medical history significant for myocardial infarction presented to the emergency department with symptoms of diplopia and headache 36 hours after onset. The patient was found to have severe thrombocytopenia with a platelet count below 20,000. A CT of the head revealed a possible pituitary adenoma with compression of the optic chiasm. The patient's platelet count continued to decrease throughout his admission and dropped below 7,000 on day 2 of admission. The patient was given platelet transfusion along with intravenous immunoglobulins. The patient underwent endoscopic transsphenoidal resection of the pituitary mass. Pathology of the mass revealed immature platelets characteristic of immune ITP in the setting of pituitary apoplexy. Conclusion While ITP in the setting of pituitary apoplexy is a rare entity, we believe that clinicians should have pituitary apoplexy on their differential diagnosis in patients with ITP.

The Carbon Footprint and Cost of Virtual Residency Interviews.

Background: The shift from in-person to virtual residency interviews may impact greenhouse gas emissions (GHGE) and costs but the direction and amount of this change is not yet clear. Objective: To estimate GHGE and financial impacts of virtual interviews among applicants and programs. Methods: In 2020-2021 we sent a postinterview survey to 1429 applicants from 7 residency programs and 1 clinical psychology program at 1 institution. The survey collected origin of travel and transit type if in-person interviews had been held and excluded responses if the applicant would not have participated in an in-person interview, or if travel type or original city was missing. We used the International Civil Aviation Organization calculator to estimate flight-related GHGE in metric tons of carbon dioxide equivalent (MTCO2e) and Google Maps to estimate ground travel, with a standard CO2e per mile. Flight, hotel, and airport taxi costs were estimated using Expedia.com, Hotels.com, Uber, and Lyft. We aggregated these data and calculated median and interquartile ranges (IQRs) for applicant GHGE and cost savings, and assumed no cost or GHGE from virtual interviews. We used Wilcoxon signed rank sum tests to compare in-person 2019-2020 and virtual 2020-2021 GME program interview budgets. Results: The survey response rate was 565, or 40% of applicants; 543 remained after the exclusion criteria were applied. Reduction in applicant travel due to virtual interviews led to median estimated GHGE savings of 0.47 (IQR 0.30-0.61) MTCO2e and $490 (IQR $392-$544) per applicant, per interview. Programs savings ranged from $7,615 to $33,670 for the interview season. Conclusions: Virtual interviews in 8 GME programs were associated with lower estimated GHGE and costs, for applicants and programs, compared with in-person interviews.

Augmenting Career Longevity: An Analysis of Ergonomics Training Among 134 Neurological Surgeons.

BACKGROUND: Work-related pain among neurosurgeons remains understudied, yet can have long-term consequences which affect operative efficiency and efficacy, career longevity, and life outside of work. OBJECTIVE: This study provides insight into the extent of pain experienced by neurosurgeons and the effect of ergonomics training on pain. METHODS: An online survey pertaining to ergonomics and pain was sent to all neurosurgeons on the Council of State Neurosurgical Societies (CSNS) email distribution list. Statistical comparisons of age groups against pain levels and ergonomics training against pain levels, as well as multivariate linear regression of demographics, training, and operating factors against pain levels were performed. RESULTS: One hundred and thirty-four neurosurgeons responded to the survey. The mean average severity of pain across respondents was 3.3/10 and the mean peak severity of pain was 5.1/10. Among the reported peak pain severity scores, neurosurgeons with 21-30 years of operating experience had significantly higher pain scores than those with 11-20 years of experience (mean 6.2 vs. 4.2; P < 0.05), while neurosurgeons with more than 30 years of experience had significantly less pain than those with 21-30 years of experience (mean 4.4 vs. 6.2, P = 0.005). Training in ergonomics did not significantly improve respondents' reported peak or mean pain severities (17.9% reported having ergonomics training). CONCLUSIONS: Ergonomics training did not appear to make a difference in neurosurgeons' pain severities. This may signify a need to optimize ergonomics pedagogy to achieve observable benefits.

Safety and efficacy of the surpass streamline for intracranial aneurysms (SESSIA): A multi-center US experience pooled analysis.

BACKGROUND AND PURPOSE: Flow diversion has established as standard treatment for intracranial aneurysms, the Surpass Streamline is the only FDA-approved braided cobalt/chromium alloy implant with 72-96 wires. We aimed to determine the safety and efficacy of the Surpass in a post-marketing large United States cohort. MATERIALS AND METHODS: This is a retrospective multicenter study of consecutive patients treated with the Surpass for intracranial aneurysms between 2018 and 2021. Baseline demographics, comorbidities, and aneurysm characteristics were collected. Efficacy endpoint included aneurysm occlusion on radiographic follow-up. Safety endpoints were major ipsilateral ischemic stroke or treatment-related death. RESULTS: A total of 277 patients with 314 aneurysms were included. Median age was 60 years, 202 (73%) patients were females. Hypertension was the most common comorbidity in 156 (56%) patients. The most common location of the aneurysms was the anterior circulation in 89% (279/314). Mean aneurysm dome width was 5.77 ± 4.75 mm, neck width was 4.22 ± 3.83 mm, and dome/neck ratio was 1.63 ± 1.26. Small-sized aneurysms were 185 (59%). Single device was used in 94% of the patients, mean number of devices per patient was 1.06. At final follow-up, complete obliteration rate was 81% (194/239). Major stroke and death were encountered in 7 (3%) and 6 (2%) cases, respectively. CONCLUSION: This is the largest cohort study using a 72-96 wire flow diverter. The Surpass Streamline demonstrated a favorable safety and efficacy profile, making it a valuable option for treating not only large but also wide-necked small and medium-sized intracranial aneurysms.

Effectiveness of Virtual Residency Interviews: Interviewer Perspectives.

BACKGROUND AND OBJECTIVES: Virtual residency interviews were widely utilized during the COVID-19 pandemic. Little is known about the effectiveness, advantages, barriers, and acceptability of virtual interviews, casting uncertainty about how interviews should be conducted after the pandemic. We conducted a survey of interviewers to inform future decisions. METHODS: We developed and implemented an online postinterview survey of interviewers representing seven residency programs and two clinical psychology programs at one midsized academic medical center. We analyzed results using descriptive statistics. RESULTS: Of 312 interviewers, 136 completed the survey (44% response rate). A majority rated virtual interviews as very or extremely effective in creating a comfortable setting (79%), answering interviewee questions (86%), establishing a sense of connection (59%), evaluating interviewee strengths (64%), and communicating program culture (51%). About half felt virtual interviews were not effective at all or only slightly effective for evaluating interviewee strengths via informal interactions (51%). A similar portion agreed or strongly agreed that virtual tours (44%) and social environment (50%) information were adequate. The most frequent advantages were time efficiency (81%), reduced carbon footprint (61%) and cost savings (56%). Frequent disadvantages included technological issues (21%) and caregiving duties (18%). Most interviewers (91%) thought some form of virtual interviews should be incorporated postpandemic. CONCLUSIONS: Interviewers found virtual interviews to be effective in most aspects, and identified more advantages than barriers. The vast majority preferred incorporation of virtual interviews in the future. Virtual tours and social activities were areas for improvement.

Virtual Residency Interviews: Applicant Perceptions Regarding Virtual Interview Effectiveness, Advantages, and Barriers.

Background: Studies of the virtual interview format are needed to inform medical residency program leaders as they plan for future virtual interview seasons. Objective: In the current study, completed in 2021, we sought to assess applicant perspectives of virtual interview effectiveness, advantages, and barriers, including factors that might impact equity and inclusion. Methods: Interviewees applying to 7 residency programs and 2 clinical psychology programs at an academic medical center in the Pacific Northwest completed a post-interview survey. Results: A total of 565 of 1429 interviewees (40%) completed the survey. A vast majority (83%-96%) agreed virtual interviews were effective in each measured domain, except for learning institutional culture (352 of 565, 62%). Many also found information regarding social/living environments inadequate. Participants selected advantages to virtual interviews more frequently than disadvantages. Commonly selected advantages included cost savings, time efficiency, reduced burden of travel, and reduced carbon footprint. Disadvantages included time zone differences, access to an appropriate interview setting, and reliable access to internet. The majority of interviewees (84%, 456 of 542) desired to keep a component of virtual interviews in the future. There were no significant disparities in results based on gender, rural/suburban/urban location, race, or underrepresented minority status. Conclusions: Virtual interviews were perceived as effective, more advantageous than burdensome, and widely acceptable, with no disparities in these findings by included demographic characteristics.

Thoracic spinal arteriovenous malformation in a 16-year-old presenting with headache.

Spinal arteriovenous malformations (sAVM) are abnormally developed spinal blood vessels with an increased risk of hemorrhage. Current literature regarding sAVMs is sparse and describes classic presentations in very young children or adults. We report a unique case of a sAVM in an adolescent patient. A 16-year-old female patient presented to the emergency department with a 3-day history of headaches. Initial CT showed no abnormalities. Worsening headaches led the patient to a neurology clinic and a fundoscopy revealed papilledema. The patient was transferred to a pediatric emergency department where repeat head CT showed a possible subarachnoid hemorrhage, and a cranial MRI/MRV showed what appeared to be a non-occlusive sinus venous thrombosis. CT angiography of the head and neck showed no evidence of thrombosis, but it did reveal possible upper thoracic vascular abnormalities. Thoracic MRI revealed an intradural sAVM at T3-T5. The sAVM was successfully resected with thoracic laminectomy with reconstructive laminoplasty. The patient experienced complications with development of right lower extremity motor and sensory deficits intra-op, but is showing continued improvement. This unique case encourages emergency medicine clinicians to expand the differential diagnoses for pediatric patients presenting with a headache and intracranial hypertension without a clear intracranial cause.

Radial Access Intervention.

Leveraging from the interventional cardiology experience, the transradial access (TRA) for neurointervention has also started to become more used for both diagnostic and therapeutic procedures. A growing body of evidence is showing a superiority of the TRA compared with the conventional transfemoral access (TFA) in terms of access site complications (ACSs), patient satisfaction and preference, hospital length of stay, and cost. Outcomes via the transradial are noninferior, and at times superior, in select neuroendovascular procedures. Future advancements in technology with radial-specific catheters and further operator experience will aid in the full adoption of the TRA for endovascular procedures.

The Rist radial access system: a multicenter study of 152 patients.

BACKGROUND: Transradial access (TRA) for neurointervention is becoming increasingly popular as experience with the technique grows. Despite reasonable efficacy using femoral catheters off-label, conversion to femoral access occurs in approximately 8.6-10.3% of TRA cases, due to an inability of the catheter to track into the vessel of interest, lack of support, or radial artery spasm. METHODS: This is a multicenter, retrospective case series of patients undergoing neurointerventions using the Rist Radial Access System. We also present our institutional protocol for using the system. RESULTS: 152 patients were included in the cohort. The most common procedure was flow diversion (28.3%). The smallest radial diameter utilized was 1.9 mm, and 44.1% were performed without an intermediate catheter. A majority of cases (96.1%) were completed successfully; 3 (1.9%) required conversion to a different radial catheter, 2 (1.3%) required conversion to femoral access, and 1 (0.7%) was aborted. There was 1 (0.7%) minor access site complication and 4 (2.6%) neurological complications. CONCLUSIONS: The Rist catheter is a safe and effective tool for a wide range of complex neurointerventions, with lower conversion rates than classically reported.

Trevo 6 × 25mm vs. 4 × 30mm in Mechanical Thrombectomy of M1 LVO.

Objectives: Our primary objective was to determine the successful rate of recanalization of M1 large vessel occlusion using either the Trevo 4 × 30 mm or 6 × 25 mm stent during mechanical thrombectomy. Our secondary objectives were to determine differences between the use of these two stent retrievers regarding first-pass effect, periprocedural complications, and mortality in the first 90 days. Methods: This is a retrospective cohort study. Data regarding the stent used, recanalization, number of passes, periprocedural complications, and mortality were determined via our mechanical thrombectomy database along with chart review. Conclusion: When comparing Trevo 4 × 30 mm to 6 × 25 mm stent retrievers used in mechanical thrombectomy for middle cerebral artery large-vessel occlusion causing stroke, there is no statistically significant difference in successful recanalization rates, first-pass effect, perioperative complications, or mortality at 90 days. Studies like this will hopefully lead to further prospective, randomized controlled trials that will help show experts in the field an additional way to perform this procedure effectively and safely.

Neurosurgery perception of Enhanced Recovery After Surgery (ERAS) protocols.

Enhanced Recovery After Surgery (ERAS) protocols are widespread in several fields, particularly general surgery, and attempt to deliver surgical care at a lower cost while also improving patient outcomes. However, few institutions have implemented ERAS protocols in neurosurgery. As such, a survey of neurosurgeons on the current state of ERAS in neurosurgery was conducted to provide insight on scaling the practice nationally. A 15-question survey was designed to assess the implementation of andsatisfaction with ERAS protocols at individual institutions. A total of 39 responses were collected from 38 unique institutions. 58.9%(N = 23) reported implementation of neurosurgical ERAS protocols. 52.1% (N = 12) of the responses were neurosurgeons at academic institutions withneurosurgical residency programs. Most neurosurgeons used ERAS protocolsfor spine cases (N = 23), with only 17.3% (N = 4) employing ERAS protocolsfor cranial cases. 69.5% (N = 16) of survey participants reported that thedesign and implementation of ERAS was a multidisciplinary effort acrossmany departments, including neurosurgery, anesthesia, and pharmacy.Decreased costs and intensive care unit (ICU) admission were reported tobe unanticipated benefits of ERAS implementation. Unanticipated challenges to implementation of new protocols included difficulties withelectronic medical record (EMR) integration, agreement of protocoldetails amongst stakeholders, uniform implementation of protocols by allneurosurgeons, and lack of adaptability by multidisciplinary staff. Meandepartment satisfaction with ERAS protocol implementation was 4.00 +/- 0.81 (N = 22) on a 5-point Likert scale.