Quantitative noninvasive measurement of cerebrospinal fluid flow in shunted hydrocephalus.

OBJECTIVE: Standard MRI protocols lack a quantitative sequence that can be used to evaluate shunt-treated patients with a history of hydrocephalus. The objective of this study was to investigate the use of phase-contrast MRI (PC-MRI), a quantitative MR sequence, to measure CSF flow through the shunt and demonstrate PC-MRI as a useful adjunct in the clinical monitoring of shunt-treated patients. METHODS: The rapid (96 seconds) PC-MRI sequence was calibrated using a flow phantom with known flow rates ranging from 0 to 24 mL/hr. Following phantom calibration, 21 patients were scanned with the PC-MRI sequence. Multiple, successive proximal and distal measurements were gathered in 5 patients to test for measurement error in different portions of the shunt system and to determine intrapatient CSF flow variability. The study also includes the first in vivo validations of PC-MRI for CSF shunt flow by comparing phase-contrast-measured flow rate with CSF accumulation in a collection burette obtained in patients with externalized distal shunts. RESULTS: The PC-MRI sequence successfully measured CSF flow rates ranging from 6 to 54 mL/hr in 21 consecutive pediatric patients. Comparison of PC-MRI flow measurement and CSF volume collected in a bedside burette showed good agreement in a patient with an externalized distal shunt. Notably, the distal portion of the shunt demonstrated lower measurement error when compared with PC-MRI measurements acquired in the proximal catheter. CONCLUSIONS: The PC-MRI sequence provided accurate and reliable clinical measurements of CSF flow in shunt-treated patients. This work provides the necessary framework to include PC-MRI as an immediate addition to the clinical setting in the noninvasive evaluation of shunt function and in future clinical investigations of CSF physiology.

Gender Differences in the Pediatric Neurosurgical Workforce: Professional Practice, Work-Life Balance, and Beyond.

BACKGROUND AND OBJECTIVES: Evidence suggests that female neurosurgeons experience unique challenges in the workplace including lack of academic advancement, challenges with work-life balance, harassment, and discrimination. How these factors influence the gender gap in neurosurgery remains unclear. This analysis investigated gender differences in pediatric neurosurgeons in professional and nonprofessional activities and responsibilities. METHODS: A survey examining professional activities, work-life balance, family dynamics, career satisfaction, and workplace discrimination and harassment was administered to 495 pediatric neurosurgeons. Response rate was 49% (n = 241). RESULTS: One-third of the pediatric neurosurgical workforce is female. There were no gender differences in race/ethnicity, American Board of Neurological Surgery/American Board of Pediatric Neurological Surgery certification rates, or pediatric neurosurgery fellowship completion. No gender differences were found in operative caseload, weekly hours worked, or working after 8 pm or weekends. Women took call more frequently than men ( P = .044). Men were more likely to work in academia ( P = .004) and have salary subsidization from external sources ( P = .026). Women were more likely to anticipate retirement by age 65 years ( P = .044), were less happy with call commitments ( P = .012), and worked more hours at home while off ( P = .050). Women more frequently reported witnessing and experiencing racial discrimination ( P = .008; P < .001), sexual harassment ( P = .002, P < .001), and feeling less safe at work ( P < .001). Men were more likely married ( P = .042) with 1 ( P = .004) or more children ( P = .034). Women reported significantly greater responsibility for child and domestic care ( P < .001). There were no gender differences in work-life balance, feeling supported at work, or having enough time to do things outside of work. CONCLUSION: Despite little difference in workload and professional responsibilities, women held more domestic responsibilities and experienced and witnessed more racial and sexual discrimination in the workplace. Surprisingly, there were no reported differences in work-life balance or feeling supported at work between genders. These findings suggest that factors unique to female neurosurgeons may contribute to continued gender disparity in the field.

Should the existing science of teams be applied to fluid teams? An exploration of fluid team effectiveness within the context of healthcare simulation.

Introduction: Fluid teams have become increasingly prevalent and necessary for modern-day issues, yet they differ from more traditional teams, on which much of the current teams literature is based. For example, fluid teams are often comprised of members from different disciplines or organizational divisions who do not have a shared history or future, as they come together to perform a critical, time-sensitive task, and then disband. For these reasons, the mechanisms through which they function and perform may differ from those of more traditional teams, and research is needed to better understand these differences. Methods: To this end, this study utilized critical incident techniques and thematic analysis to examine fluid teams within healthcare, one of the primary contexts in which they are prevalent. Interdisciplinary faculty and students in the medical field who encounter fluid teams within simulation-based education were prompted to reflect on key factors that facilitate or hinder fluid team effectiveness. Results: Primary themes extracted pertained to the conditions fluid teams operate within (e.g., high-stress), the behaviors and emergent states that contribute to their success (e.g., communication), and the KSAO's of value for members of fluid teams to possess (e.g., readiness). These themes were then compared to existing literature, yielding the identification of some similarities but also many important differences between fluid and traditional teams. Discussion: A series of practical recommendations for how to promote fluid team effectiveness is then presented.

Surgical management of pediatric spinal aneurysmal bone cysts: patient series.

BACKGROUND: Aneurysmal bone cysts (ABCs) are rare, highly vascular osteolytic bone lesions that predominantly affect pediatric populations. This report evaluates the clinicopathological data of pediatric patients with spinal ABCs. The medical records for all patients at Children's Hospital Los Angeles with biopsy-proven ABCs of the spine between 1998 and 2018 were evaluated. OBSERVATIONS: Seventeen patients, 6 males and 11 females, were identified. The mean age at surgery was 10.4 years (range, 3.5-20 years). The most common presenting complaint was pain at the lesion site 16/17 (94%), followed by lower-extremity weakness 8/17 (47%). Resection and intralesional curettage were performed in all patients. Three (18%) of 17 patients underwent selective arterial embolization prior to resection. Spinal stability was compromised in 15 of 17 patients (88%), requiring instrumented fusion. Five (29%) of the 17 patients received additional therapy including radiation, calcitonin-methylprednisolone, or phenol. Four (23.5%) of 17 patients experienced a recurrence, and the mean time to recurrence was 15 months. The postoperative follow-up ranged from 6 to 108 months (median, 28 months). Reoperation occurred after an average of 35 months. At the recent follow-up, patients were free of disease. LESSONS: Gross-total resection by intralesional curettage with case-dependent instrumented spinal fusion for instability remains an effective strategy for managing pediatric spinal ABCs. Long-term follow-up is necessary to detect tumor recurrence.

Ex Vivo Drug Screening Assay with Artificial Membranes: Characterizing Cholesterol Desorbing Competencies of Beta-Cyclodextrins.

Despite advancements in contemporary therapies, cardiovascular disease from atherosclerosis remains a leading cause of mortality worldwide. Supported lipid bilayers (SLBs) are membrane interfaces that can be constructed with varying lipid compositions. Herein, we use a solvent-assisted lipid bilayer (SALB) construction method to build SLB membranes with varying cholesterol compositions to create a lipid-sterol interface atop a piezoelectric sensor. These cholesterol-laden SLBs were utilized to investigate the mechanisms of various cholesterol-lowering drug molecules. Within a flow-cell, membranes with varying cholesterol content were exposed to cyclodextrins 2-hydroxypropyl-beta-cyclodextrin (HPßCD) and methyl-beta-cyclodextrin (MßCD). Quartz-crystal microgravimetry with dissipation monitoring (QCM-D) enabled the collection of in vitro, real-time changes in relative areal mass and dissipation. We define the cholesterol desorbing competency of a cyclodextrin species via measures of the rate of cholesterol removal, the rate of the transfer of membrane-bound cholesterol to drug-complexed cholesterol, and the binding strength of the drug to the cholesterol-ladened membrane. Desorption data revealed distinct cholesterol removal kinetics for each cyclodextrin while also supporting a model for the lipid-cholesterol-drug interface. We report that MßCD removes a quantity of cholesterol 1.61 times greater, with a speed 2.12 times greater, binding affinity to DOPC lipid interfaces 1.97 times greater, and rate of internal cholesterol transfer 3.41 times greater than HPßCD.

Development of an ultrafast brain MR neuronavigation protocol for ventricular shunt placement.

OBJECTIVE: Advancements in MRI technology have provided improved ways to acquire imaging data and to more seamlessly incorporate MRI into modern pediatric surgical practice. One such situation is image-guided navigation for pediatric neurosurgical procedures, including intracranial catheter placement. Image-guided surgery (IGS) requires acquisition of CT or MR images, but the former carries the risk of ionizing radiation and the latter is associated with long scan times and often requires pediatric patients to be sedated. The objective of this project was to circumvent the use of CT and standard-sequence MRI in ventricular neuronavigation by investigating the use of fast MR sequences on the basis of 3 criteria: scan duration comparable to that of CT acquisition, visualization of ventricular morphology, and image registration with surface renderings comparable to standard of care. The aim of this work was to report image development, implementation, and results of registration accuracy testing in healthy subjects. METHODS: The authors formulated 11 candidate MR sequences on the basis of the standard IGS protocol, and various scan parameters were modified, such as k-space readout direction, partial k-space acquisition, sparse sampling of k-space (i.e., compressed sensing), in-plane spatial resolution, and slice thickness. To evaluate registration accuracy, the authors calculated target registration error (TRE). A candidate sequence was selected for further evaluation in 10 healthy subjects. RESULTS: The authors identified a candidate imaging protocol, termed presurgical imaging with compressed sensing for time optimization (PICO). Acquisition of the PICO protocol takes 25 seconds. The authors demonstrated noninferior TRE for PICO (3.00 ± 0.19 mm) in comparison with the default MRI neuronavigation protocol (3.35 ± 0.20 mm, p = 0.20). CONCLUSIONS: The developed and tested sequence of this work allowed accurate intraoperative image registration and provided sufficient parenchymal contrast for visualization of ventricular anatomy. Further investigations will evaluate use of the PICO protocol as a substitute for CT and conventional MRI protocols in ventricular neuronavigation.

Adolescent subdural empyema in setting of COVID-19 infection: illustrative case.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing viral pandemic that has affected modern medical practice and can complicate known pathology. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes symptoms that may mimic a viral pneumonia, with potential for serious sequelae, including acute respiratory distress syndrome, coagulopathy, multiorgan dysfunction, systemic vascular abnormalities, and secondary infection. OBSERVATIONS: The authors describe a case of a 15-year-old boy who presented with a right subdural empyema and sinusitis while having active COVID-19 infection. The patient initially presented with left-sided weakness, frontal sinusitis, and subdural empyema. Emergent surgery was performed for evacuation of empyema and sinus debridement. Samples of purulent material within the subdural space were tested for SARS-CoV-2 by reverse transcriptase polymerase chain reaction. The patient had a successful recovery and regained the use of his right side after combined treatment. To our knowledge, this is the first reported case of a bacterial subdural empyema associated with frontal sinusitis in a coinfected patient with COVID-19 without evidence of COVID-19 intracranial infection. LESSONS: A subdural empyema, which is a surgical emergency, was likely a superinfection caused by COVID-19. This, along with the coagulopathy caused by the virus, introduced unique challenges to the treatment of a known pathology.

The crystal structure and insight into the substrate specificity of the α-L rhamnosidase RHA-P from Novosphingobium sp. PP1Y.

Flavonoid natural products are well known for their beneficial antimicrobial, antitumor, and anti-inflammatory properties, however, some of these natural products often are rhamnosylated, which severely limits their bioavailability. The lack of endogenous rhamnosidases in the human GI tract not only prevents many of these glycosylated compounds from being of value in functional foods but also limits the modification of natural product libraries being tested for drug discovery. RHA-P is a catalytically efficient, thermostable α-l-rhamnosidase from the marine bacterium Novosphingobium sp. PP1Y that selectively hydrolyzes α-1,6 and α-1,2 glycosidic linkages between a terminal rhamnose and a flavonoid moiety. This work reports the 2.2 Šresolution crystal structure of RHA-P, which is an essential step forward in the characterization of RHA-P as a potential catalyst to increase the bioavailability of rhamnosylated natural compounds. The structure shows highly conserved rhamnose- and calcium-binding residues in a shallow active site that is housed in the (ß/α)8 domain. In comparison to BT0986 (pdbID: 5MQN), the only known structure of an RHA-P homolog, the morphology, electrostatic potentials and amino acid composition of the substrate binding pocket are significantly different, offering insight into the substrate preference of RHA-P for glycosylated aryl compounds such as hesperidin, naringin, rutin, and quercitrin, over polysaccharides, which are preferred by BT0986. These preferences were further explored by using in silico docking, the results of which are consistent with the known kinetic data for RHA-P acting on different rhamnosylated flavonoids. Due to its promiscuity, relative thermostability compared to other known rhamnosidases, and catalytic efficiency even in significant concentrations of organic solvents, RHA-P continues to show potential for biocatalytic applications.