Mapping patient education encounters in elective surgery: a cohort study and cross-sectional survey.

OBJECTIVE: Develop a process map of when patients learn about their proposed surgery and what resources patients use to educate themselves. DESIGN: A mixed methods design, combining semistructured stakeholder interviews, quantitative validation using electronic healthcare records (EHR) in a retrospective cohort and a cross-sectional patient survey. SETTING: A single surgical centre in the UK. PARTICIPANTS: Fourteen members of the spinal multidisciplinary team were interviewed to develop the process map.This process map was validated using the EHR of 50 patients undergoing elective spine surgery between January and June 2022. Postprocedure, feedback was gathered from 25 patient surveys to identify which resources they used to learn about their spinal procedure. Patients below the age of 18 or who received emergency surgery were excluded. INTERVENTIONS: Elective spine surgery and patient questionnaires given postoperatively either on the ward or in follow-up clinic. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the percentage of the study cohort that was present at encounters on the process map. Key timepoints were defined if >80% of patients were present. The secondary outcome was the percentage of the study cohort that used educational resources listed in the patient questionnaire. RESULTS: There were 342 encounters which occurred across the cohort, with 16 discrete event categories identified. The initial surgical clinic (88%), anaesthetic preoperative assessment (96%) and admission for surgery (100%) were identified as key timepoints. Surveys identified that patients most used verbal information from their surgeon (100%) followed by written information from their surgeon (52%) and the internet (40%) to learn about their surgery. CONCLUSIONS: Process mapping is an effective method of illustrating the patient pathway. The initial surgical clinic, anaesthetic preoperative assessment and surgical admission are key timepoints where patients receive information. This has future implications for guiding patient education interventions to focus at key timepoints.

Early evaluation of a natural language processing tool to improve access to educational resources for surgical patients.

PURPOSE: Accessible patient information sources are vital in educating patients about the benefits and risks of spinal surgery, which is crucial for obtaining informed consent. We aim to assess the effectiveness of a natural language processing (NLP) pipeline in recognizing surgical procedures from clinic letters and linking this with educational resources. METHODS: Retrospective examination of letters from patients seeking surgery for degenerative spinal disease at a single neurosurgical center. We utilized MedCAT, a named entity recognition and linking NLP, integrated into the electronic health record (EHR), which extracts concepts and links them to systematized nomenclature of medicine-clinical terms (SNOMED-CT). Investigators reviewed clinic letters, identifying words or phrases that described or identified operations and recording the SNOMED-CT terms as ground truth. This was compared to SNOMED-CT terms identified by the model, untrained on our dataset. A pipeline linking clinic letters to patient-specific educational resources was established, and precision, recall, and F1 scores were calculated. RESULTS: Across 199 letters the model identified 582 surgical procedures, and the overall pipeline after adding rules a total of 784 procedures (precision = 0.94, recall = 0.86, F1 = 0.91). Across 187 letters with identified SNOMED-CT terms the integrated pipeline linking education resources directly to the EHR was successful in 157 (78%) patients (precision = 0.99, recall = 0.87, F1 = 0.92). CONCLUSIONS: NLP accurately identifies surgical procedures in pre-operative clinic letters within an untrained subspecialty. Performance varies among letter authors and depends on the language used by clinicians. The identified procedures can be linked to patient education resources, potentially improving patients' understanding of surgical procedures.

Distribution of case volumes in surgery: an analysis of the British Spine Registry.

Objectives: To characterize the distribution of case volumes within a surgical field. Design: An analysis of British Spine Registry. Setting: 295 centers in England that conducted at least one spinal operation either within the NHS or private settings between 1 May 2016 and 27 February 2021. Participants: 644 surgeons. Main outcome measures: Mathematical descriptions of distributions of cases among surgeons and the extent of workforce-level case-volume concentration as a surrogate marker. Results: There were wide variations in monthly caseloads between surgeons, ranging from 0 to average monthly high of 81.8 cases. The curves showed that 37.7% of surgeons were required to perform 80% of all spinal operations, which is substantially less than in fields outside of healthcare.With the COVID-19 pandemic, the case volumes of surgeons with the highest volumes dropped dramatically, whereas those with the lowest case numbers remained nearly unchanged. This, along with the relatively low level of case-volume concentration within spinal surgery, may indicate an inevitability of at least some level of surgical care being provided by the relatively lower volume surgeons. Conclusions: While there is a reasonable degree of workforce-level case volume concentration within spinal surgery, with high volume spinal surgeons providing a large proportion of care, it is not clear whether a further concentration of case volumes into those few hands is possible or desirable.

A Sensorised Surgical Glove to Analyze Forces During Neurosurgery.

BACKGROUND: Measuring intraoperative forces in real time can provide feedback mechanisms to improve patient safety and surgical training. Previous force monitoring has been achieved through the development of specialized and adapted instruments or use designs that are incompatible with neurosurgical workflow. OBJECTIVE: To design a universal sensorised surgical glove to detect intraoperative forces, applicable to any surgical procedure, and any surgical instrument in either hand. METHODS: We created a sensorised surgical glove that was calibrated across 0 to 10 N. A laboratory experiment demonstrated that the sensorised glove was able to determine instrument-tissue forces. Six expert and 6 novice neurosurgeons completed a validated grape dissection task 20 times consecutively wearing the sensorised glove. The primary outcome was median and maximum force (N). RESULTS: The sensorised glove was able to determine instrument-tissue forces reliably. The average force applied by experts (2.14 N) was significantly lower than the average force exerted by novices (7.15 N) ( P = .002). The maximum force applied by experts (6.32 N) was also significantly lower than the maximum force exerted by novices (9.80 N) ( P = .004). The sensorised surgical glove's introduction to operative workflow was feasible and did not impede on task performance. CONCLUSION: We demonstrate a novel and scalable technique to detect forces during neurosurgery. Force analysis can provide real-time data to optimize intraoperative tissue forces, reduce the risk of tissue injury, and provide objective metrics for training and assessment.

Intraoperative Applications of Artificial Intelligence in Robotic Surgery: A Scoping Review of Current Development Stages and Levels of Autonomy.

OBJECTIVE: A scoping review of the literature was conducted to identify intraoperative artificial intelligence (AI) applications for robotic surgery under development and categorize them by (1) purpose of the applications, (2) level of autonomy, (3) stage of development, and (4) type of measured outcome. BACKGROUND: In robotic surgery, AI-based applications have the potential to disrupt a field so far based on a master-slave paradigm. However, there is no available overview about this technology's current stage of development and level of autonomy. METHODS: MEDLINE and EMBASE were searched between January 1, 2010 and May 21, 2022. Abstract screening, full-text review, and data extraction were performed independently by 2 reviewers. The level of autonomy was defined according to the Yang and colleagues' classification and stage of development according to the Idea, Development, Evaluation, Assessment, and Long-term follow-up framework. RESULTS: One hundred twenty-nine studies were included in the review. Ninety-seven studies (75%) described applications providing Robot Assistance (autonomy level 1), 30 studies (23%) application enabling Task Autonomy (autonomy level 2), and 2 studies (2%) application achieving Conditional autonomy (autonomy level 3). All studies were at Idea, Development, Evaluation, Assessment, and Long-term follow-up stage 0 and no clinical investigations on humans were found. One hundred sixteen (90%) conducted in silico or ex vivo experiments on inorganic material, 9 (7%) ex vivo experiments on organic material, and 4 (3%) performed in vivo experiments in porcine models. CONCLUSIONS: Clinical evaluation of intraoperative AI applications for robotic surgery is still in its infancy and most applications have a low level of autonomy. With increasing levels of autonomy, the evaluation focus seems to shift from AI-specific metrics to process outcomes, although common standards are needed to allow comparison between systems.

Quality in Clinical Consultations: A Cross-Sectional Study.

The coronavirus disease 2019 pandemic may have affected the quality of clinical consultations. The objective was to use 10 proposed quality indicator questions to assess outpatient consultation quality; to assess whether the recent shift to telemedicine during the pandemic has affected consultation quality; and to determine whether consultation quality is associated with satisfaction and consultation outcome. A cross-sectional study was used to survey clinicians and patients after outpatient consultations (1 February to 31 March 2021). The consultation quality score (CQS) was the sum of 'yes' responses to the survey questions. In total, 78% (538/690) of consultations conducted were assessed by a patient, clinician, or both. Patient survey response rate was 60% (415/690) and clinician 42% (291/690). Face-to-face consultations had a greater CQS than telephone (patients and clinicians < 0.001). A greater CQS was associated with higher overall satisfaction (clinicians log-odds: 0.77 ± 0.52, p = 0.004; patients log-odds: 1.35 ± 0.57, p < 0.001) and with definitive consultation outcomes (clinician log-odds: 0.44 ± 0.36, p = 0.03). In conclusion, consultation quality is assessable; the shift to telemedicine has negatively impacted consultation quality; and high-quality consultations are associated with greater satisfaction and definitive consultation outcome decisions.

Comparative Learning Curves of Microscope Versus Exoscope: A Preclinical Randomized Crossover Noninferiority Study.

Background: An exoscope heralds a new era of optics in surgery. However, there is limited quantitative evidence describing and comparing the learning curve. Objectives: This study aimed to investigate the learning curve, plateau, and rate of novice surgeons using an Olympus ORBEYE exoscope compared to an operating microscope (Carl Zeiss OPMI PENTERO or KINEVO 900). Methods: A preclinical, randomized, crossover, noninferiority trial assessed the performance of seventeen novice and seven expert surgeons completing the microsurgical grape dissection task "Star's the limit." A standardized star was drawn on a grape using a stencil with a 5 mm edge length. Participants cut the star and peeled the star-shaped skin off the grape with microscissors and forceps while minimizing damage to the grape flesh. Participants repeated the task 20 times consecutively for each optical device. Learning was assessed using model functions such as the Weibull function, and the cognitive workload was assessed with the NASA Task Load Index (NASA-TLX). Results: Seventeen novice (male:female 12:5; median years of training 0.4 [0-2.8 years]) and six expert (male:female 4:2; median years of training 10 [8.9-24 years]) surgeons were recruited. "Star's the limit" was validated using a performance score that gave a threshold of expert performance of 70 (0-100). The learning rate (ORBEYE -0.94 ± 0.37; microscope -1.30 ± 0.46) and learning plateau (ORBEYE 64.89 ± 8.81; microscope 65.93 ± 9.44) of the ORBEYE were significantly noninferior compared to those of the microscope group (p = 0.009; p = 0.027, respectively). The cognitive workload on NASA-TLX was higher for the ORBEYE. Novices preferred the freedom of movement and ergonomics of the ORBEYE but preferred the visualization of the microscope. Conclusions: This is the first study to quantify the ORBEYE learning curve and the first randomized controlled trial to compare the ORBEYE learning curve to that of the microscope. The plateau performance and learning rate of the ORBEYE are significantly noninferior to those of the microscope in a preclinical grape dissection task. This study also supports the ergonomics of the ORBEYE as reported in preliminary observational studies and highlights visualization as a focus for further development.

The clinical outcomes of imaging modalities for surgical management Cushing's disease - A systematic review and meta-analysis.

Introduction: Cushing's disease presents major diagnostic and management challenges. Although numerous preoperative and intraoperative imaging modalities have been deployed, it is unclear whether these investigations have improved surgical outcomes. Our objective was to investigate whether advances in imaging improved outcomes for Cushing's disease. Methods: Searches of PubMed and EMBASE were conducted. Studies reporting on imaging modalities and clinical outcomes after surgical management of Cushing's disease were included. Multilevel multivariable meta-regressions identified predictors of outcomes, adjusting for confounders and heterogeneity prior to investigating the effects of imaging. Results: 166 non-controlled single-arm studies were included, comprising 13181 patients over 44 years.The overall remission rate was 77.0% [CI: 74.9%-79.0%]. Cavernous sinus invasion (OR: 0.21 [CI: 0.07-0.66]; p=0.010), radiologically undetectable lesions (OR: 0.50 [CI: 0.37-0.69]; p<0.0001), previous surgery (OR=0.48 [CI: 0.28-0.81]; p=0.008), and lesions ≥10mm (OR: 0.63 [CI: 0.35-1.14]; p=0.12) were associated with lower remission. Less stringent thresholds for remission was associated with higher reported remission (OR: 1.37 [CI: 1.1-1.72]; p=0.007). After adjusting for this heterogeneity, no imaging modality showed significant differences in remission compared to standard preoperative MRI.The overall recurrence rate was 14.5% [CI: 12.1%-17.1%]. Lesion ≥10mm was associated with greater recurrence (OR: 1.83 [CI: 1.13-2.96]; p=0.015), as was greater duration of follow-up (OR: 1.53 (CI: 1.17-2.01); p=0.002). No imaging modality was associated with significant differences in recurrence.Despite significant improvements in detection rates over four decades, there were no significant changes in the reported remission or recurrence rates. Conclusion: A lack of controlled comparative studies makes it difficult to draw definitive conclusions. Within this limitation, the results suggest that despite improvements in radiological detection rates of Cushing's disease over the last four decades, there were no changes in clinical outcomes. Advances in imaging alone may be insufficient to improve surgical outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020187751.

Automated operative workflow analysis of endoscopic pituitary surgery using machine learning: development and preclinical evaluation (IDEAL stage 0).

OBJECTIVE: Surgical workflow analysis involves systematically breaking down operations into key phases and steps. Automatic analysis of this workflow has potential uses for surgical training, preoperative planning, and outcome prediction. Recent advances in machine learning (ML) and computer vision have allowed accurate automated workflow analysis of operative videos. In this Idea, Development, Exploration, Assessment, Long-term study (IDEAL) stage 0 study, the authors sought to use Touch Surgery for the development and validation of an ML-powered analysis of phases and steps in the endoscopic transsphenoidal approach (eTSA) for pituitary adenoma resection, a first for neurosurgery. METHODS: The surgical phases and steps of 50 anonymized eTSA operative videos were labeled by expert surgeons. Forty videos were used to train a combined convolutional and recurrent neural network model by Touch Surgery. Ten videos were used for model evaluation (accuracy, F1 score), comparing the phase and step recognition of surgeons to the automatic detection of the ML model. RESULTS: The longest phase was the sellar phase (median 28 minutes), followed by the nasal phase (median 22 minutes) and the closure phase (median 14 minutes). The longest steps were step 5 (tumor identification and excision, median 17 minutes); step 3 (posterior septectomy and removal of sphenoid septations, median 14 minutes); and step 4 (anterior sellar wall removal, median 10 minutes). There were substantial variations within the recorded procedures in terms of video appearances, step duration, and step order, with only 50% of videos containing all 7 steps performed sequentially in numerical order. Despite this, the model was able to output accurate recognition of surgical phases (91% accuracy, 90% F1 score) and steps (76% accuracy, 75% F1 score). CONCLUSIONS: In this IDEAL stage 0 study, ML techniques have been developed to automatically analyze operative videos of eTSA pituitary surgery. This technology has previously been shown to be acceptable to neurosurgical teams and patients. ML-based surgical workflow analysis has numerous potential uses-such as education (e.g., automatic indexing of contemporary operative videos for teaching), improved operative efficiency (e.g., orchestrating the entire surgical team to a common workflow), and improved patient outcomes (e.g., comparison of surgical techniques or early detection of adverse events). Future directions include the real-time integration of Touch Surgery into the live operative environment as an IDEAL stage 1 (first-in-human) study, and further development of underpinning ML models using larger data sets.

Pituitary society expert Delphi consensus: operative workflow in endoscopic transsphenoidal pituitary adenoma resection.

PURPOSE: Surgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice. METHODS: A mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached. RESULTS: There was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured. CONCLUSIONS: Through an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed "core" steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The "optional" steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world.

Skull base repair following endonasal pituitary and skull base tumour resection: a systematic review.

PURPOSE: Postoperative cerebrospinal fluid rhinorrhoea (CSFR) remains a frequent complication of endonasal approaches to pituitary and skull base tumours. Watertight skull base reconstruction is important in preventing CSFR. We sought to systematically review the current literature of available skull base repair techniques. METHODS: Pubmed and Embase databases were searched for studies (2000-2020) that (a) reported on the endonasal resection of pituitary and skull base tumours, (b) focussed on skull base repair techniques and/or postoperative CSFR risk factors, and (c) included CSFR data. Roles, advantages and disadvantages of each repair method were detailed. Random-effects meta-analyses were performed where possible. RESULTS: 193 studies were included. Repair methods were categorised based on function and anatomical level. There was absolute heterogeneity in repair methods used, with no independent studies sharing the same repair protocol. Techniques most commonly used for low CSFR risk cases were fat grafts, fascia lata grafts and synthetic grafts. For cases with higher CSFR risk, multilayer regimes were utilized with vascularized flaps, gasket sealing and lumbar drains. Lumbar drain use for high CSFR risk cases was supported by a randomised study (Oxford CEBM: Grade B recommendation), but otherwise there was limited high-level evidence. Pooled CSFR incidence by approach was 3.7% (CI 3-4.5%) for transsphenoidal, 9% (CI 7.2-11.3%) for expanded endonasal, and 5.3% (CI 3.4-7%) for studies describing both. Further meaningful meta-analyses of repair methods were not performed due to significant repair protocol heterogeneity. CONCLUSIONS: Modern reconstructive protocols are heterogeneous and there is limited evidence to suggest the optimal repair technique after pituitary and skull base tumour resection. Further studies are needed to guide practice.

Attitudes of the Surgical Team Toward Artificial Intelligence in Neurosurgery: International 2-Stage Cross-Sectional Survey.

BACKGROUND: Artificial intelligence (AI) has the potential to disrupt how we diagnose and treat patients. Previous work by our group has demonstrated that the majority of patients and their relatives feel comfortable with the application of AI to augment surgical care. The aim of this study was to similarly evaluate the attitudes of surgeons and the wider surgical team toward the role of AI in neurosurgery. METHODS: In a 2-stage cross sectional survey, an initial open-question qualitative survey was created to determine the perspective of the surgical team on AI in neurosurgery including surgeons, anesthetists, nurses, and operating room practitioners. Thematic analysis was performed to develop a second-stage quantitative survey that was distributed via social media. We assessed the extent to which they agreed and were comfortable with real-world AI implementation using a 5-point Likert scale. RESULTS: In the first-stage survey, 33 participants responded. Six main themes were identified: imaging interpretation and preoperative diagnosis, coordination of the surgical team, operative planning, real-time alert of hazards and complications, autonomous surgery, and postoperative management and follow-up. In the second stage, 100 participants responded. Responders somewhat agreed or strongly agreed about AI being used for imaging interpretation (62%), operative planning (82%), coordination of the surgical team (70%), real-time alert of hazards and complications (85%), and autonomous surgery (66%). The role of AI within postoperative management and follow-up was less agreeable (49%). CONCLUSIONS: This survey highlights that the majority of surgeons and the wider surgical team both agree and are comfortable with the application of AI within neurosurgery.

Antipsychotic drug use and risk of stroke and myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: The effect of antipsychotic (AP) drugs on risk of stroke and myocardial infarction (MI) remains unclear due to methodological limitations of, and inconsistencies across, existing studies. We aimed to systematically review studies reporting on the associations between AP drug use and stroke or MI risk, and to investigate whether associations differed among different sub-populations. METHODS: We searched Medline, EMBASE, PsychINFO and Cochrane Library (from inception to May 28, 2017) for observational studies reporting on AP drug use and MI or stroke occurrence. We performed random-effects meta-analyses for each outcome, performing sub-groups analyses by study population - specifically general population (i.e. those not restricted to patients with a particular indication for AP drug use), people with dementia only and psychiatric illness only. Where feasible we performed subgroup analyses by AP drug class. RESULTS: From 7008 articles, we included 29 relevant observational studies, 19 on stroke and 10 on MI. Results of cohort studies that included a general population indicated a more than two-fold increased risk of stroke, albeit with substantial heterogeneity (pooled HR 2.31, 95% CI 1.13, 4.74, I2 = 83.2%). However, the risk among patients with dementia was much lower, with no heterogeneity (pooled HR 1.16, 95% CI 1.00, 1.33, I2 = 0%) and there was no clear association among studies of psychiatric populations (pooled HR 1.44, 95% CI 0.90, 2.30; substantial heterogeneity [I2 = 78.8])). Associations generally persisted when stratifying by AP class, but few studies reported on first generation AP drugs. We found no association between AP drug use and MI risk (pooled HR for cohort studies: 1.29, 95% CI 0.88, 1.90 and case-control studies: 1.07, 95% CI 0.94, 1.23), but substantial methodological and statistical heterogeneity among a relatively small number of studies limits firm conclusions. CONCLUSIONS: AP drug use may be associated with an increased risk of stroke, but there is no clear evidence that this risk is further elevated in patients with dementia. Further studies are need to clarify the effect of AP drug use on MI and stroke risk in different sub-populations and should control for confounding by indication and stratify by AP drug class.

Compressive Pressure Versus Time in Cauda Equina Syndrome: A Systematic Review and Meta-Analysis of Experimental Studies.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To examine the relationship between compressive pressure and its duration in cauda equina compression, and the effects of subsequent decompression, on neurophysiological function, and pathophysiology in animal studies. We further aim to investigate these relationships with systemic blood pressure to assess whether a vascular component in the underlying mechanism may contribute to the clinical heterogeneity of this disease. SUMMARY OF BACKGROUND DATA: The complex relationship between preoperative factors and outcomes in cauda equina syndrome (CES) suggests heterogeneity within CES which may inform better understanding of pathophysiological process, their effect on neurological function, and prognosis. METHODS: Systematic review identified 17 relevant studies including 422 animals and reporting electrophysiological measures (EP), histopathology, and blood flow. Modeling using meta-regression analyzed the relationship between compressive pressure, duration of compression, and electrophysiological function in both compression and decompression studies. RESULTS: Modeling suggested that electrophysiological dysfunction in acute cauda equina compression has a sigmoidal response, with particularly deterioration when mean arterial blood pressure is exceeded and, additionally, sustained for approximately 1 hour. Accounting for pressure and duration may help risk-stratify patients pre-decompression. Outcomes after decompression appeared to be related more to the degree of compression, where exceeding systolic blood pressure tended to result in an irreversible lesion, rather than duration of compression. Prognosis was most strongly associated with residual pre-decompression function. CONCLUSION: Compressive pressure influences effects and outcomes of cauda equina compression. We suggest the presence of two broad phenotypic groups within CES defined by the degree of ischaemia as a potential explanatory pathophysiological mechanism. LEVEL OF EVIDENCE: 1.

Cytotoxicity of ultraviolet-C radiation on a heterogeneous population of human glioblastoma multiforme cells: Meta-analysis.

INTRODUCTION: Current treatment strategies for glioblastoma multiforme are limited due to early recurrence and heterogeneity of the cell population that causes a varied response to treatment. Ultraviolet-C (UVC) radiation may be a potential adjuvant treatment that could theoretically be delivered locally by implantable micro-electromechanical systems that sense and kill early recurrence and/or minimally residual cancer. in vitro irradiation experiments are limited because they commonly use a single cell line. Therefore other methods are required to investigate cytotoxicity across a heterogeneous population of GBM. METHODS: A meta-analysis was conducted to assess the cytotoxic effects of UVC radiation on human GBM cell lines, with or without genetic modification, in monolayer to simulate a heterogeneous model. 16 publications were included using 14 different cell lines and 19 gene vectors. Effect sizes were calculated for cell survival, viability, apoptosis and proliferation. Univariate meta-regression was used to investigate the effects of radiant exposure (J/m2) and timing on cytotoxicity. RESULTS: UVC resulted in a 70.9% (CI: 63.6%-78.2%) reduction in survival, 16.6% (CI: 10.8%-22.4%) increase in apoptosis, 32.0% (CI: 9.95%-54.2%) reduction in viability, and 413.8% (CI: 95.7%-731.9%) reduction in proliferation of GBM cell lines compared to controls. Radiant exposure was significantly associated with survival (R2 = 0.486, p < 0.0001) but not with apoptosis or viability. CONCLUSIONS: This study provides more data on the therapeutic translational potential of UVC to a more clinically-realistic context. Overall, UVC is cytotoxic to GBM cell lines in aggregate and may be clinically useful when combined with genetic modification or other adjuvant treatments.

Chondroitinase ABC for neurological recovery after acute brain injury: systematic review and meta-analyses of preclinical studies.

OBJECTIVES: Damage to critical brain regions causes deficits in important neurological functions. Chondroitinase ABC (ChABC) has been shown to promote neuroplasticity and may ameliorate neurological deficits caused by disease or trauma. This systematic review identifies and evaluates preclinical studies of ChABC as a treatment for acute brain injury. METHODS: Four databases were searched for studies relating to ChABC and brain or brain injuries. Controlled studies in mammals with acute brain injuries treated with ChABC were included in meta-analyses of neurobehavioural outcomes. Means and standard deviations from the fifth day of treatment were extracted, and normalised mean differences were calculated. RESULTS: Of 775 identified records, 16 studies administered ChABC after acute brain injury, of which 9 reported neurobehavioural outcomes. The estimated treatment effect on neurological recovery over the duration of included studies was 49.4% (CI: 30.3-68.4% with Hartung-Knapp-Sidik-Jonkman adjustment, p = 0.0002). The mechanisms of action may involve decreasing astroglial scar formation, promoting neuronal sprouting, and selective synaptic strengthening of sprouting neurites and activated neural pathways. CONCLUSIONS: The summary of published evidence suggests that ChABC treatment is effective in improving neurological outcomes in preclinical models of acute brain injury. However, more studies are needed for better assessment of the specific translational potential of ChABC. ABBREVIATIONS: AVM - Arteriovenous Malformation; ChABC - Chondroitinase ABC; CI - Confidence Interval; CSPG - Chondroitin Sulphate Proteoglycans; HKSJ - Hartung-Knapp-Sidik-Jonkman; MCA - Middle Cerebral Artery; NMD - Normalised Mean Difference; NSPC - Neural Stem/Progenitor Cells; PI - Prediction Interval; SD - Standard Deviation; SMD - Standardised Mean Difference; TBI - Traumatic Brain Injury.

Effects of Ultraviolet Radiation on Glioma: Systematic Review.

Glioblastoma multiforme is the most aggressive primary brain tumor. Treatment is largely palliative, with current strategies unable to prevent inevitable tumor recurrence. Implantable micro-electromechanical systems are becoming more feasible for the management of several human diseases. These systems may have a role in detecting tumor recurrence and delivering localized therapies. One potential therapeutic tool is ultraviolet (UV) light. This systematic review assesses the effects of UV light on glioma cells. A total of 47 publications are included. The large majority were in vitro experiments conducted on human glioblastoma cell lines in monolayer. In these cells, UV light was shown to induce apoptosis and the expression of genes or activation of proteins that modulate cell death, repair, and proliferation. The nature and magnitude of cellular response varied by UV wavelength, dose, cell line, and time after irradiation. UVC (wavelength 100-280 nm) was most effective at inducing apoptosis, and this effect was dose dependent. The included studies had varied methodologies, complicating reconciliation of results. Further work will be required to determine the best regime of UV irradiation for therapeutic use. J. Cell. Biochem. 118: 4063-4071, 2017. © 2017 Wiley Periodicals, Inc.