The Diagnostic Value of Pan-Trk Expression to Detect Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion in CNS Tumours: A Study Using Next-Generation Sequencing Platform.

Background: Neurotrophic tyrosine receptor kinase (NTRK) fusion has been detected in rare types of CNS tumours, which can promote tumorigenesis. The efficacy of Trk inhibitor became a significant therapeutic interest. Our aim was to investigate whether Pan-Trk immunohistochemistry (IHC) is a reliable and efficient marker for detecting NTRK-fusion in different brain tumours. Methods: This study included 23 patients diagnosed with different types of CNS tumours. Testing for Pan-Trk IHC with monoclonal Ab (EPR17341) has been performed on all FFPE tissues. Parallelly, NTRK-rearrangements were tested using both DNA and RNA-based next-generation sequencing (NGS) assay using TruSight Onco500 platform. Results: The cohort included eight pilocytic astrocytomas, one oligodendroglioma, six IDHwildtype glioblastomas, four IDHmutant grade four astrocytomas, and one sample of each (astroblastoma, central neurocytoma, medulloblastoma, and liponeurocytoma). The mean age was 35 years; seven cases were in the paediatric age group, and 16 were adult. Pan-Trk expression was detected in 11 (47.8%) tumours, and 12 (52.1%) tumours showed no Pan-Trk expression. Nine Cases (82%) with different Pan-Trk expressions did not reveal NTRK-rearrangement. The other two positively expressed cases (liponeurocytoma and glioblastoma) were found to have NTRK2-fusions (SLC O 5A1-NTRK2, AGBL4-NTRK2, BEND5-NTRK2). All the 12 cases (100%) with no Pan-Trk expression have shown no NTRK-fusions. There was no statistically significant association between Pan-Trk expression and NTRK-fusion (p = 0.217). The detection of NTRK- fusions using NGS had high specificity over NTRK-fusion detection by using Pan-Trk IHC. Conclusion: Pan-Trk IHC is not a suitable tissue-efficient biomarker to screen for NTRK-fusions in CNS tumours, however RNA-based NGS sequencing should be used as an alternative method.

Knowledge and attitude towards hydrocephalus among healthcare providers and the general population in Saudi Arabia.

BACKGROUND: Hydrocephalus is a worldwide disorder characterized by abnormal flow or rarely excessive production of cerebrospinal fluid, leading to the widening of the cerebral ventricles system due to the accumulation of the cerebrospinal fluid in the brain. Previous researches have shown that knowledge about the disorder is limited among healthcare providers and the population, affecting attitudes toward patients, as well as patient outcomes. AIM: To investigate healthcare providers and population's knowledge and attitudes towards hydrocephalus in Saudi Arabia. METHODOLOGY: A descriptive cross-sectional study was conducted through an electronic questionnaire. The survey was self-constructed in Arabic and English by the research team and inspired by other awareness questionnaires and validated before use by three experts. RESULTS: There were 444 participants in this study, aged between 17 and 73 years with a mean age of 32.60 ± 10.98. Most of the participants were from the general population (74.8%). More than half of the participants had a bachelor's degree (60.1%). 38.4% of healthcare providers had negative knowledge while 61.6% had positive knowledge. In addition, 82.5% of the general population had negative knowledge, although 17.5% had positive knowledge. Moreover, it was observed that 17.0% of the healthcare providers had a bad attitude while 83.0% had a good attitude. In addition, 60.2% of the general population had a bad attitude, whereas 39.8% had a good attitude. CONCLUSION: This study revealed that the level of knowledge and attitude towards hydrocephalus among healthcare providers was good on both aspects, while it was poor among the general population.

Is Virtual Reality Surgical Performance Influenced by Force Feedback Device Utilized?

OBJECTIVE: The study objectives were to assess if surgical performance and subjective assessment of a virtual reality simulator platform was influenced by changing force feedback devices. DESIGN: Participants used the NeuroVR (formerly NeuroTouch) simulator to perform 5 practice scenarios and a realistic scenario involving subpial resection of a virtual reality brain tumor with simulated bleeding. The influence of force feedback was assessed by utilizing the Omni and Entact haptic systems. Tier 1, tier 2, and tier 2 advanced metrics were used to compare results. Operator subjective assessment of the haptic systems tested utilized seven Likert criteria (score 1 to 5). SETTING: The study is carried out at the McGill Neurosurgical Simulation Research and Training Centre, Montreal Neurological Institute and Hospital, Montreal, Canada. PARTICIPANTS: Six expert operators in the utilization of the NeuroVR simulator platform. RESULTS: No significant differences in surgical performance were found between the two haptic devices. Participants significantly preferred the Entact system on all 7 Likert criteria of subjective assessment. CONCLUSIONS: Our results show no statistical differences in virtual reality surgical performance utilizing the two bimanual haptic devices tested. Subjective assessments demonstrated that participants preferred the Entact system. Our results suggest that to maximize realism of the training experience educators employing virtual reality simulators may find it useful to assess expert opinion before choosing a force feedback device.

Automaticity of Force Application During Simulated Brain Tumor Resection: Testing the Fitts and Posner Model.

OBJECTIVE: The Fitts and Posner model of motor learning hypothesized that with deliberate practice, learners progress through stages to an autonomous phase of motor ability. To test this model, we assessed the automaticity of neurosurgeons, senior residents, and junior residents when operating on 2 identical tumors using the NeuroVR virtual reality simulation platform. DESIGN: Participants resected 9 identical simulated tumors on 2 occasions (total = 18 resections). These resections were separated by the removal of a variable number of tumors with different visual and haptic complexities to mirror neurosurgical practice. Consistency of force application was used as a metric to assess automaticity and was defined as applying forces 1 standard deviation above or below a specific mean force application. Amount and specific location of force application during second identical tumor resection was compared to that used for the initial tumor. SETTING: This study was conducted at the McGill Neurosurgical Simulation Research and Training Center, Montreal Neurologic Institute and Hospital, Montreal, Canada. PARTICIPANTS: Nine neurosurgeons, 10 senior residents, and 8 junior residents. RESULTS: Neurosurgeons display statistically significant increased consistency of force application when compared to resident groups when results from all tumor resections were assessed. Assessing individual tumor types demonstrates significant differences between the neurosurgeon and resident groups when resecting hard stiffness similar-to-background (white) tumors and medium-stiffness tumors. No statistical difference in consistency of force application was found when junior and senior residents were compared. CONCLUSION: "Experts" display significantly more automaticity when operating on identical simulated tumors separated by a series of different tumors using the NeuroVR platform. These results support the Fitts and Posner model of motor learning and are consistent with the concept that automaticity improves after completing residency training. The potential educational application of our findings is outlined related to neurosurgical resident training.

Impact of acute stress on psychomotor bimanual performance during a simulated tumor resection task.

OBJECTIVE Severe bleeding during neurosurgical operations can result in acute stress affecting the bimanual psychomotor performance of the operator, leading to surgical error and an adverse patient outcome. Objective methods to assess the influence of acute stress on neurosurgical bimanual psychomotor performance have not been developed. Virtual reality simulators, such as NeuroTouch, allow the testing of acute stress on psychomotor performance in risk-free environments. Thus, the purpose of this study was to explore the impact of a simulated stressful virtual reality tumor resection scenario by utilizing NeuroTouch to answer 2 questions: 1) What is the impact of acute stress on bimanual psychomotor performance during the resection of simulated tumors? 2) Does acute stress influence bimanual psychomotor performance immediately following the stressful episode? METHODS Study participants included 6 neurosurgeons, 6 senior and 6 junior neurosurgical residents, and 6 medical students. Participants resected a total of 6 simulated tumors, 1 of which (Tumor 4) involved uncontrollable "intraoperative" bleeding resulting in simulated cardiac arrest and thus providing the acute stress scenario. Tier 1 metrics included extent of blood loss, percentage of tumor resected, and "normal" brain tissue volume removed. Tier 2 metrics included simulated suction device (sucker) and ultrasonic aspirator total tip path length, as well as the sum and maximum forces applied in using these instruments. Advanced Tier 2 metrics included efficiency index, coordination index, ultrasonic aspirator path length index, and ultrasonic aspirator bimanual forces ratio. All metrics were assessed before, during, and after the stressful scenario. RESULTS The stress scenario caused expected significant increases in blood loss in all participant groups. Extent of tumor resected and brain volume removed decreased in the junior resident and medical student groups. Sucker total tip path length increased in the neurosurgeon group, whereas sucker forces increased in the senior resident group. Psychomotor performance on advanced Tier 2 metrics was altered during the stress scenario in all participant groups. Performance on all advanced Tier 2 metrics returned to pre-stress levels in the post-stress scenario tumor resections. CONCLUSIONS Results demonstrated that acute stress initiated by simulated severe intraoperative bleeding significantly decreases bimanual psychomotor performance during the acute stressful episode. The simulated intraoperative bleeding event had no significant influence on the advanced Tier 2 metrics monitored during the immediate post-stress operative performance.

The force pyramid: a spatial analysis of force application during virtual reality brain tumor resection.

OBJECTIVE Virtual reality simulators allow development of novel methods to analyze neurosurgical performance. The concept of a force pyramid is introduced as a Tier 3 metric with the ability to provide visual and spatial analysis of 3D force application by any instrument used during simulated tumor resection. This study was designed to answer 3 questions: 1) Do study groups have distinct force pyramids? 2) Do handedness and ergonomics influence force pyramid structure? 3) Are force pyramids dependent on the visual and haptic characteristics of simulated tumors? METHODS Using a virtual reality simulator, NeuroVR (formerly NeuroTouch), ultrasonic aspirator force application was continually assessed during resection of simulated brain tumors by neurosurgeons, residents, and medical students. The participants performed simulated resections of 18 simulated brain tumors with different visual and haptic characteristics. The raw data, namely, coordinates of the instrument tip as well as contact force values, were collected by the simulator. To provide a visual and qualitative spatial analysis of forces, the authors created a graph, called a force pyramid, representing force sum along the z-coordinate for different xy coordinates of the tool tip. RESULTS Sixteen neurosurgeons, 15 residents, and 84 medical students participated in the study. Neurosurgeon, resident and medical student groups displayed easily distinguishable 3D "force pyramid fingerprints." Neurosurgeons had the lowest force pyramids, indicating application of the lowest forces, followed by resident and medical student groups. Handedness, ergonomics, and visual and haptic tumor characteristics resulted in distinct well-defined 3D force pyramid patterns. CONCLUSIONS Force pyramid fingerprints provide 3D spatial assessment displays of instrument force application during simulated tumor resection. Neurosurgeon force utilization and ergonomic data form a basis for understanding and modulating resident force application and improving patient safety during tumor resection.