Exploring chemical space in non-targeted analysis: a proposed ChemSpace tool.

Non-targeted analysis (NTA) using high-resolution mass spectrometry allows scientists to detect and identify a broad range of compounds in diverse matrices for monitoring exposure and toxicological evaluation without a priori chemical knowledge. NTA methods present an opportunity to describe the constituents of a sample across a multidimensional swath of chemical properties, referred to as "chemical space." Understanding and communicating which region of chemical space is extractable and detectable by an NTA workflow, however, remains challenging and non-standardized. For example, many sample processing and data analysis steps influence the types of chemicals that can be detected and identified. Accordingly, it is challenging to assess whether analyte non-detection in an NTA study indicates true absence in a sample (above a detection limit) or is a false negative driven by workflow limitations. Here, we describe the need for accessible approaches that enable chemical space mapping in NTA studies, propose a tool to address this need, and highlight the different ways in which it could be implemented in NTA workflows. We identify a suite of existing predictive and analytical tools that can be used in combination to generate scores that describe the likelihood a compound will be detected and identified by a given NTA workflow based on the predicted chemical space of that workflow. Higher scores correspond to a higher likelihood of compound detection and identification in a given workflow (based on sample extraction, data acquisition, and data analysis parameters). Lower scores indicate a lower probability of detection, even if the compound is truly present in the samples of interest. Understanding the constraints of NTA workflows can be useful for stakeholders when results from NTA studies are used in real-world applications and for NTA researchers working to improve their workflow performance. The hypothetical ChemSpaceTool suggested herein could be used in both a prospective and retrospective sense. Prospectively, the tool can be used to further curate screening libraries and set identification thresholds. Retrospectively, false detections can be filtered by the plausibility of the compound identification by the selected NTA method, increasing the confidence of unknown identifications. Lastly, this work highlights the chemometric needs to make such a tool robust and usable across a wide range of NTA disciplines and invites others who are working on various models to participate in the development of the ChemSpaceTool. Ultimately, the development of a chemical space mapping tool strives to enable further standardization of NTA by improving method transparency and communication around false detection rates, thus allowing for more direct method comparisons between studies and improved reproducibility. This, in turn, is expected to promote further widespread applications of NTA beyond research-oriented settings.

Interventional compared with medical management of symptomatic carotid web: A systematic review.

BACKGROUND: Carotid web (CaW) is non-atheromatous, shelf-like intraluminal projection, generally affecting the posterolateral wall of the proximal internal carotid artery, and associated with embolic stroke, particularly in younger patients without traditional stroke risk factors. Treatment options for symptomatic CaWs include interventional therapy with carotid endarterectomy or carotid stenting versus medical therapy with antiplatelet or anticoagulants. As safety and efficacy of these approaches have been incompletely delineated in small-to-moderate case series, we performed a systematic review of outcomes with interventional and medical management. METHODS: Systematic literature search was conducted and data analyzed per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) from January 2000 to October 2021 using the search strategy: "Carotid web" OR "Carotid shelf" OR "Web vessels" OR "Intraluminal web". Patient-level demographics, stroke risk factors, technical procedure details, medical and interventional management strategies were abstracted across 15 series. All data were analyzed using descriptive statistics. RESULTS: Among a total of symptomatic 282 CaW patients across 14 series, age was 49.5 (44-55.7) years, 61.7% were women, and 76.6% were black. Traditional stroke risk factors were less frequent than the other stroke causes, including hypertension in 28.6%, hyperlipidemia 14.6%, DM 7.0%, and smoking 19.8%. Thrombus adherent to CaW was detected on initial imaging in 16.2%. Among 289 symptomatic CaWs across 15 series, interventional management was pursued in 151 (52.2%), carotid artery stenting in 87, and carotid endarterectomy in 64; medical management was pursued in 138 (47.8%), including antiplatelet therapy in 80.4% and anticoagulants in 11.6%. Interventional and medical patients were similar in baseline characteristics. The reported time from index stroke to carotid revascularization was median 14 days (IQR 9.5-44). In the interventional group, no periprocedural mortality was noted, major periprocedural complications occurred in 1/151 (0.5%), and no recurrent ischemic events were observed over follow-up range of 3-60 months. In the medical group, over a follow-up of 2-55 months, the recurrence cerebral ischemia rate was 26.8%. CONCLUSION: Cumulative evidence from multiple series suggests that carotid revascularization is a safe and effective option for preventing recurrent ischemic events in patients with symptomatic carotid webs.

An Introduction to the Benchmarking and Publications for Non-Targeted Analysis Working Group.

Non-targeted analysis (NTA) encompasses a rapidly evolving set of mass spectrometry techniques aimed at characterizing the chemical composition of complex samples, identifying unknown compounds, and/or classifying samples, without prior knowledge regarding the chemical content of the samples. Recent advances in NTA are the result of improved and more accessible instrumentation for data generation and analysis tools for data evaluation and interpretation. As researchers continue to develop NTA approaches in various scientific fields, there is a growing need to identify, disseminate, and adopt community-wide method reporting guidelines. In 2018, NTA researchers formed the Benchmarking and Publications for Non-Targeted Analysis Working Group (BP4NTA) to address this need. Consisting of participants from around the world and representing fields ranging from environmental science and food chemistry to 'omics and toxicology, BP4NTA provides resources addressing a variety of challenges associated with NTA. Thus far, BP4NTA group members have aimed to establish a consensus on NTA-related terms and concepts and to create consistency in reporting practices by providing resources on a public Web site, including consensus definitions, reference content, and lists of available tools. Moving forward, BP4NTA will provide a setting for NTA researchers to continue discussing emerging challenges and contribute to additional harmonization efforts.

Conventional versus stereotactic image guided pedicle screw placement during spinal deformity correction: a retrospective propensity score-matched study of a national longitudinal database.

PURPOSE/AIM: To compare complications, readmissions, revisions, and payments between navigated and conventional pedicle screw fixation for treatment of spine deformity. METHODS: The Thomson Reuters MarketScan national longitudinal database was used to identify patients undergoing osteotomy, posterior instrumentation, and fusion for treatment of spinal deformity with or without image-guided navigation between 2007-2016. Conventional and navigated groups were propensity-matched (1:1) to normalize differences between demographics, comorbidities, and surgical characteristics. Clinical outcomes and charges were compared between matched groups using bivariate analyses. RESULTS: A total of 4,604 patients were identified as having undergone deformity correction, of which 286 (6.2%) were navigated. Propensity-matching resulted in a total of 572 well-matched patients for subsequent analyses, of which half were navigated. Rate of mechanical instrumentation-related complications was found to be significantly lower for navigated procedures (p = 0.0371). Navigation was also associated with lower rates of 90-day unplanned readmissions (p = 0.0295), as well as 30- and 90-day postoperative revisions (30-day: p = 0.0304, 90-day: p = 0.0059). Hospital, physician, and total payments favored the conventional group for initial admission (p = 0.0481, 0.0001, 0.0019, respectively); however, when taking into account costs of readmissions, hospital payments became insignificantly different between the two groups. CONCLUSIONS: Procedures involving image-guided navigation resulted in decreased instrumentation-related complications, unplanned readmissions, and postoperative revisions, highlighting its potential utility for the treatment of spine deformity. Future advances in navigation technologies and methodologies can continue to improve clinical outcomes, decrease costs, and facilitate widespread adoption of navigation for deformity correction.

Postoperative outcomes following pediatric intracranial electrode monitoring: A case for stereoelectroencephalography (SEEG).

BACKGROUND: For patients with medically refractory epilepsy, intracranial electrode monitoring can help identify epileptogenic foci. Despite the increasing utilization of stereoelectroencephalography (SEEG), the relative risks or benefits associated with the technique when compared with the traditional subdural electrode monitoring (SDE) remain unclear, especially in the pediatric population. Our aim was to compare the outcomes of pediatric patients who received intracranial monitoring with SEEG or SDE (grids and strips). METHODS: We retrospectively studied 38 consecutive pediatric intracranial electrode monitoring cases performed at our institution from 2014 to 2017. Medical/surgical history and operative/postoperative records were reviewed. We also compared direct inpatient hospital costs associated with the two procedures. RESULTS: Stereoelectroencephalography and SDE cohorts both showed high likelihood of identifying epileptogenic zones (SEEG: 90.9%, SDE: 87.5%). Compared with SDE, SEEG patients had a significantly shorter operative time (118.7 versus 233.4 min, P < .001) and length of stay (6.2 versus 12.3 days, P < .001), including days spent in the intensive care unit (ICU; 1.4 versus 5.4 days, P < .001). Stereoelectroencephalography patients tended to report lower pain scores and used significantly less narcotic pain medications (54.2 versus 197.3 mg morphine equivalents, P = .005). No complications were observed. Stereoelectroencephalography and SDE cohorts had comparable inpatient hospital costs (P = .47). CONCLUSION: In comparison with subdural electrode placement, SEEG results in a similarly favorable clinical outcome, but with reduced operative time, decreased narcotic usage, and superior pain control without requiring significantly higher costs. The potential for an improved postoperative intracranial electrode monitoring experience makes SEEG especially suitable for pediatric patients.

Utilization of Novel High-Resolution, MRI-Based Vascular Imaging Modality for Preoperative Stereoelectroencephalography Planning in Children: A Technical Note.

INTRODUCTION: Stereoelectroencephalography (SEEG) is a powerful intracranial diagnostic tool that requires accurate imaging for proper electrode trajectory planning to ensure efficacy and maximize patient safety. Computed tomography (CT) angiography and digital subtraction angiography are commonly used, but recent developments in magnetic resonance angiography allow for high-resolution vascular visualization without added risks of radiation. We report on the accuracy of electrode placement under robotic assistance planning utilizing a novel high-resolution magnetic resonance imaging (MRI)-based imaging modality. METHODS: Sixteen pediatric patients between February 2014 and October 2017 underwent SEEG exploration for epileptogenic zone localization. A gadolinium-enhanced 3D T1-weighted spoiled gradient recalled echo sequence with minimum echo time and repetition time was applied for background parenchymal suppression and vascular enhancement. Electrode placement accuracy was determined by analyzing postoperative CT scans laid over preoperative virtual electrode trajectory paths. Entry point, target point, and closest vessel intersection were measured. RESULTS: For any intersection along the trajectory path, 57 intersected vessels were measured. The mean diameter of an intersected vessel was 1.0343 ± 0.1721 mm, and 21.05% of intersections involved superficial vessels. There were 157 overall intersection + near-miss events. The mean diameter for an involved vessel was 1.0236 ± 0.0928 mm, and superficial vessels were involved in 20.13%. Looking only at final electrode target, 3 intersection events were observed. The mean diameter of an intersected vessel was 1.0125 ± 0.2227 mm. For intersection + near-miss events, 24 were measured. An involved vessel's mean diameter was 1.1028 ± 0.2634 mm. For non-entry point intersections, 45 intersected vessels were measured. The mean diameter for intersected vessels was 0.9526 ± 0.0689 mm. For non-entry point intersections + near misses, 126 events were observed. The mean diameter for involved vessels was 0.9826 ± 0.1008 mm. CONCLUSION: We believe this novel sequence allows better identification of superficial and deeper subcortical vessels compared to conventional T1-weighted gadolinium-enhanced MRI.

Cytotoxicity, cellular uptake and apoptotic responses in human coronary artery endothelial cells exposed to ultrasmall superparamagnetic iron oxide nanoparticles.

Ultrasmall superparamagnetic iron oxide nanoparticles (USPION) possess reactive surfaces, are metabolized and exhibit unique magnetic properties. These properties are desirable for designing novel theranostic biomedical products; however, toxicity mechanisms of USPION are not completely elucidated. The goal of this study was to investigate cell interactions (uptake and cytotoxicity) of USPION using human coronary artery endothelial cells as a vascular cell model. Polyvinylpirrolidone-coated USPION were characterized: average diameter 17 nm (transmission electron microscopy [TEM]), average hydrodynamic diameter 44 nm (dynamic light scattering) and zeta potential -38.75 mV. Cells were exposed to 0 (control), 25, 50, 100 or 200 µg/mL USPION. Concentration- and time-dependent cytotoxicity were observed after 3-6 hours through 24 hours of exposure using Alamar Blue and Real-Time Cell Electronic Sensing assays. Cell uptake was evaluated by imaging using live-dead confocal microscopy, actin and nuclear fluorescent staining, and TEM. Phase-contrast, confocal microscopy, and TEM imaging showed significant USPION internalization as early as 3 hours after exposure to 25 µg/mL. TEM imaging demonstrated particle internalization in secondary lysosomes with perinuclear localization. Three orthogonal assays were conducted to assess apoptosis. TUNEL staining demonstrated a marked increase in fragmented DNA, a response pathognomonic of apoptosis, after a 4-hour exposure. Cells subjected to agarose gel electrophoresis exhibited degraded DNA 3 hours after exposure. Caspase-3/7 activity increased after a 3-hour exposure. USPION uptake resulted in cytotoxicity involving apoptosis and these results contribute to further mechanistic understanding of the USPION toxicity in vitro in cardiovascular endothelial cells.

Topical vancomycin for surgical prophylaxis in non-instrumented pediatric spinal surgeries.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine if topical vancomycin irrigation reduces the incidence of post-operative surgical site infections following pediatric spinal procedures. Surgical site infections (SSIs) following spinal procedures performed in pediatric patients represent a serious complication. Prophylactic use of topical vancomycin prior to closure has been shown to be effective in reducing incidence of SSIs in adult spinal procedures. Non-instrumented cases make up the majority of spinal procedures in pediatric patients, and the efficacy of prophylactic topical vancomycin in these procedures has not previously been reported. METHODS: This retrospective study reviewed all non-instrumented spinal procedures performed over a period from 05/2014-12/2016 for topical vancomycin use, surgical site infections, and clinical variables associated with SSI. Topical vancomycin was utilized as infection prophylaxis, and applied as a liquid solution within the wound prior to closure. RESULTS: Ninety-five consecutive, non-instrumented, pediatric spinal surgeries were completed between 01/2015 and 12/2016, of which the last 68 utilized topical vancomycin. There was a 11.1% SSI rate in the non-topical vancomycin cohort versus 0% in the topical vancomycin cohort (P = 0.005). The number needed to treat was 9. There were no significant differences in risk factors for SSI between cohorts. There were no complications associated topical vancomycin use. CONCLUSIONS: Routine topical vancomycin administration during closure of non-instrumented spinal procedures can be a safe and effective tool for reducing SSIs in the pediatric neurosurgical population.

Topical Vancomycin for Surgical Prophylaxis in Pediatric Craniofacial Surgeries.

Topical vancomycin has been demonstrated to be safe and effective for reducing surgical site infections (SSIs) following spine surgery in both adults and children, however, there are no studies of its efficacy in reducing SSIs in craniofacial surgery. The SSIs are one of the most common complications following craniofacial surgery. The complexity of craniofacial procedures, use of grafts and implants, long operative durations and larger surgical wounds all contribute to the heightened risk of SSIs in pediatric craniofacial cases. A retrospective review of all open and endoscopic pediatric craniofacial procedures performed between May 2014 and December 2017 at a single children's hospital was conducted to examine SSI rates between patients receiving topical vancomycin and a historical control group. The treatment group received topical vancomycin irrigation before wound closure. An ad-hoc cost analysis was performed to determine the cost-savings associated with topical vancomycin use. A total of 132 craniofacial procedures were performed during the study period, with 50 cases in the control group and 82 cases in the vancomycin group. Overall, SSI rate was 3.03%. Use of topical vancomycin irrigation led to a significant reduction in SSIs (4/50 SSI or 8.0% in control group vs 0/82 or 0% in vancomycin group, P = 0.04). No adverse events were observed with topical vancomycin use. The potential cost-savings associated with the use of topical vancomycin as SSI prophylaxis in this study was $102,152. Addition of topical vancomycin irrigation as routine surgical infection prophylaxis can be an effective and low-cost method for reducing SSI in pediatric craniofacial surgery.

Deep Brain Stimulation for Chronic Cluster Headache: A Review.

OBJECTIVES: Cluster headaches are a set of episodic and chronic pain syndromes that are sources of significant morbidity for patients. The standard of care for cluster headaches remains medication therapy, however a minority of patients will remain refractory to treatment despite changes to dosage and therapeutic combinations. In these patients, functional neuromodulation using Deep Brain Stimulation (DBS) presents the opportunity to alleviate the significant pain that is experienced by targeting the neurophysiological substrates that mediate pain. MATERIAL AND METHODS: We review the literature on chronic cluster headache, including the growing number of DBS case reports and series that describe the alleviation of pain in a majority of patients through conventional or endoventricular targeting of the posterior hypothalamus and ventral tegmental area, with a minimal side effect profile. RESULTS: In this review, the history and outcomes of DBS use for medication-refractory cluster headaches are examined, with discussion on future directions for improving this novel treatment modality and providing efficacious, longer-lasting pain relief in headache patients. CONCLUSION: In patients with chronic cluster headache, functional neuromodulation using DBS presents the opportunity to alleviate the significant pain that is experienced by targeting the neurophysiological substrates that mediate pain.

Intracranial Hemorrhage in Deep Vein Thrombosis/Pulmonary Embolus Patients Without Atrial Fibrillation.

Background and Purpose- Deep vein thrombosis (DVTs) is a common disease with high morbidity if it progresses to pulmonary embolus (PE). Anticoagulation is the treatment of choice; warfarin has long been the standard of care. Early experience with direct oral anticoagulants (DOACs) suggests that these agents may be may be a safer and equally effective alternative in the treatment of DVT/PE. Nontraumatic intracranial hemorrhage (ICH) is one of the most devastating potential complications of anticoagulation therapy. We sought to compare the rates of ICH in patients treated with DOACs versus those treated with warfarin for DVT/PE. Methods- The MarketScan Commercial Claims and Medicare Supplemental databases were used. Adult DVT/PE patients without known atrial fibrillation and with prescriptions for either a DOAC or warfarin were followed for the occurrence of inpatient admission for ICH. Coarsened exact matching was used to balance the treatment cohorts. Cox proportional-hazards regressions and Kaplan-Meier survival curves were used to estimate the association between DOACs and the risk of ICH compared with warfarin. Results- The combined cohort of 218 620 patients had a median follow-up of 3.0 months, mean age of 55.4 years, and was 52.1% women. The DOAC cohort had 26 980 patients and 8 ICH events (1.0 cases per 1000 person-years), and the warfarin cohort had 191 640 patients and 324 ICH events (3.3 cases per 1000 person-years; P<0.0001). The DOAC cohort had a lower hazard ratio for ICH compared with warfarin in both the unmatched (hazard ratio=0.26; P=0.0002) and matched (hazard ratio=0.20; P=0.0001) Cox proportional-hazards regressions. Conclusions- DOACs show superior safety to warfarin in terms of risk of ICH in patients with DVT/PE.

Nurse Telephonic Triage Service for After-hour Patient Calls in Neurosurgery.

OBJECTIVE: The aim of this study was to report the utilization and experience of the nurse telephonic triage service for after-hour patient calls in Neurosurgery. BACKGROUND: It is challenging for patients to reach their clinicians after-hours in a timely manner. This may result in worse health outcomes for the patients, or inappropriate utilization of emergency rooms and urgent care facilities. Physicians continue to remain overwhelmed with frequent after-hours calls in addition to other clinical responsibilities while on-call. METHODS: In August 2015, our institution launched the Clinical Advice Service (CAS) to provide a patient-centric, nurse-run telephone triage service for after-hour calls from Neurosurgery patients. Clinical protocols were created for use by CAS staff by Neurosurgery clinicians. RESULTS: Between July 2016 and June 2017, CAS has accepted 1021 after-hours calls from Neurosurgery patients. A total of 71.4% of these calls were clinical, and the remaining nonclinical (directions, appointments, general information). CAS escalated 37.3% of the calls to the on-call Neurosurgery physician; 4.8% Neurosurgery patients were triaged to the emergency room by CAS. CONCLUSION: CAS has been able to provide well-coordinated care to Neurosurgery patients while reducing physician workload.

The nucleus accumbens and alcoholism: a target for deep brain stimulation.

Alcohol use disorder (AUD) is a difficult to treat condition with a significant global public health and cost burden. The nucleus accumbens (NAc) has been implicated in AUD and identified as an ideal target for deep brain stimulation (DBS). There are promising preclinical animal studies of DBS for alcohol consumption as well as some initial human clinical studies that have shown some promise at reducing alcohol-related cravings and, in some instances, achieving long-term abstinence. In this review, the authors discuss the evidence and concepts supporting the role of the NAc in AUD, summarize the findings from published NAc DBS studies in animal models and humans, and consider the challenges and propose future directions for neuromodulation of the NAc for the treatment of AUD.

Outpatient spine surgery: defining the outcomes, value, and barriers to implementation.

Spine surgery is a key target for cost reduction within the United States health care system. One possible strategy involves the transition of inpatient surgeries to the ambulatory setting. Lumbar laminectomy with or without discectomy, lumbar fusion, anterior cervical discectomy and fusion, and cervical disc arthroplasty all represent promising candidates for outpatient surgeries in select populations. In this focused review, the authors clarify the different definitions used in studies describing outpatient spine surgery. They also discuss the body of evidence supporting each of these procedures and summarize the proposed cost savings. Finally, they examine several patient- and surgeon-specific considerations to highlight the barriers in translating outpatient spine surgery into actual practice.

Propensity-matched comparison of outcomes and cost after macroscopic and microscopic lumbar discectomy using a national longitudinal database.

OBJECTIVE There has been considerable debate about the utility of the operating microscope in lumbar discectomy and its effect on outcomes and cost. METHODS A commercially available longitudinal database was used to identify patients undergoing discectomy with or without use of a microscope between 2007 and 2015. Propensity matching was performed to normalize differences between demographics and comorbidities in the 2 cohorts. Outcomes, complications, and cost were subsequently analyzed using bivariate analysis. RESULTS A total of 42,025 patients were identified for the "macroscopic" group, while 11,172 patients were identified for the "microscopic" group. For the propensity-matched analysis, the 11,172 patients in the microscopic discectomy group were compared with a group of 22,340 matched patients who underwent macroscopic discectomy. There were no significant differences in postoperative complications between the groups other than a higher proportion of deep vein thrombosis (DVT) in the macroscopic discectomy cohort versus the microscopic discectomy group (0.4% vs 0.2%, matched OR 0.48 [95% CI 0.26-0.82], p = 0.0045). Length of stay was significantly longer in the macroscopic group compared to the microscopic group (mean 2.13 vs 1.83 days, p < 0.0001). Macroscopic discectomy patients had a higher rate of revision surgery when compared to microscopic discectomy patients (OR 0.92 [95% CI 0.84-1.00], p = 0.0366). Hospital charges were higher in the macroscopic discectomy group (mean $19,490 vs $14,921, p < 0.0001). CONCLUSIONS The present study suggests that the use of the operating microscope in lumbar discectomy is associated with decreased length of stay, lower DVT rate, lower reoperation rate, and decreased overall hospital costs.

Stereoelectroencephalography in children: a review.

Stereoelectroencephalography (SEEG) is an intracranial diagnostic measure that has grown in popularity in the United States as outcomes data have demonstrated its benefits and safety. The main uses of SEEG include 1) exploration of deep cortical/sulcal structures; 2) bilateral recordings; and 3) 3D mapping of epileptogenic zones. While SEEG has gradually been accepted for treatment in adults, there is less consensus on its utility in children. In this literature review, the authors seek to describe the current state of SEEG with a focus on the more recent technology-enabled surgical techniques and demonstrate its efficacy in the pediatric epilepsy population.

Image-guided stereotactic radiosurgery for treatment of spinal hemangioblastoma.

OBJECTIVE Stereotactic radiosurgery (SRS) has been an attractive treatment option for hemangioblastomas, especially for lesions that are surgically inaccessible and in patients with von Hippel-Lindau (VHL) disease and multiple lesions. Although there has been a multitude of studies examining the utility of SRS in intracranial hemangioblastomas, SRS has only recently been used for spinal hemangioblastomas due to technical limitations. The purpose of this study is to provide a long-term evaluation of the effectiveness of image-guided radiosurgery in halting tumor progression and providing symptomatic relief for spinal hemangioblastomas. METHODS Between 2001 and 2011, 46 spinal hemangioblastomas in 28 patients were treated using the CyberKnife image-guided radiosurgery system at the authors' institution. Fourteen of these patients also had VHL disease. The median age at treatment was 43.5 years (range 19-85 years). The mean prescription radiation dose to the tumor periphery was 21.6 Gy (range 15-35 Gy). The median tumor volume was 0.264 cm3 (range 0.025-70.9 cm3). Tumor response was evaluated on serial, contrast-enhanced CT and MR images. Clinical response was evaluated by clinical and imaging evaluation. RESULTS The mean follow-up for the cohort was 54.3 months. Radiographic follow-up was available for 19 patients with 34 tumors; 32 (94.1%) tumors were radiographically stable or displayed signs of regression. Actuarial control rates at 1, 3, and 5 years were 96.1%, 92.3%, and 92.3%, respectively. Clinical evaluation on follow-up was available for 13 patients with 16 tumors; 13 (81.2%) tumors in 10 patients had symptomatic improvement. No patient developed any complications related to radiosurgery. CONCLUSIONS Image-guided SRS is safe and effective for the primary treatment of spinal hemangioblastomas and is an attractive alternative to resection, especially for those with VHL disease.

Clinical evaluation of concussion: the evolving role of oculomotor assessments.

Sports-related concussion is a change in brain function following a direct or an indirect force to the head, identified in awake individuals and accounting for a considerable proportion of mild traumatic brain injury. Although the neurological signs and symptoms of concussion can be subtle and transient, there can be persistent sequelae, such as impaired attention and balance, that make affected patients particularly vulnerable to further injury. Currently, there is no accepted definition or diagnostic criteria for concussion, and there is no single assessment that is accepted as capable of identifying all patients with concussion. In this paper, the authors review the available screening tools for concussion, with particular emphasis on the role of visual function testing. In particular, they discuss the oculomotor assessment tools that are being investigated in the setting of concussion screening.

Optogenetic modulation in stroke recovery.

Stroke is one of the leading contributors to morbidity, mortality, and health care costs in the United States. Although several preclinical strategies have shown promise in the laboratory, few have succeeded in the clinical setting. Optogenetics represents a promising molecular tool, which enables highly specific circuit-level neuromodulation. Here, the conceptual background and preclinical body of evidence for optogenetics are reviewed, and translational considerations in stroke recovery are discussed.

Different cytotoxicity responses to antimicrobial nanosilver coatings when comparing extract-based and direct-contact assays.

This study was performed to understand how the choice of cytotoxicity assay format affects the observed biocompatibility of nanosilver (nAg). nAg coatings are physical coatings containing silver (Ag) that have feature sizes of 100 nm or less, often in the form of nanoparticles or grains. They are used on medical devices to prevent infection, but in spite of this intended benefit, observations of potential cytotoxicity from nAg have been reported in numerous published studies. For medical device regulation, cytotoxicity testing is part of a biocompatibility evaluation, in which specific test methods are chosen based on the technological characteristics and intended use of a device. For this study, nAg-coated tissue culture polystyrene surfaces were prepared using magnetron sputter coating, resulting in nAg films of 0.2 to 311 µg cm(-2) Ag. These coatings exhibited nanometer-scale morphologies and demonstrated a > 4log10 reduction in Escherichia coli viability. It was observed that extracts of nAg caused no cytotoxicity to L929 mouse fibroblasts, but cells cultured directly on nAg coatings (direct-contact assay format) showed a dose-dependent reduction in viability by up to 100% (P < 0.001). Results using inductively coupled plasma mass spectrometry to measure Ag release suggested that extracts of nAg are not toxic because the dissolved Ag in those samples becomes less cytotoxic over time, probably owing to the reaction with cell culture media and serum (six-fold cytotoxicity reductions observed over a 24-h period). These findings highlight the potential value of direct-contact cytotoxicity testing for nAg in predicting biological interactions with cells or tissue in vivo.