The interplay mechanism between IDH mutation, MGMT-promoter methylation, and PRMT5 activity in the progression of grade 4 astrocytoma: unraveling the complex triad theory.

Background: The dysregulation of Isocitrate dehydrogenase (IDH) and the subsequent production of 2-Hydroxyglutrate (2HG) may alter the expression of epigenetic proteins in Grade 4 astrocytoma. The interplay mechanism between IDH, O-6-methylguanine-DNA methyltransferase (MGMT)-promoter methylation, and protein methyltransferase proteins-5 (PRMT5) activity, with tumor progression has never been described. Methods: A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors. Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis. Inter-cohort statistical significance was evaluated. Results: Both IDH-mutant WHO grade 4 astrocytomas (n = 22, 64.7%) and IDH-wildtype glioblastomas (n = 12, 35.3%) had upregulated PRMT5 gene expression except in one case. Out of the 22 IDH-mutant tumors, 10 (45.5%) tumors showed MGMT-promoter methylation and 12 (54.5%) tumors had unmethylated MGMT. All IDH-wildtype tumors had unmethylated MGMT. There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma (p-value = 0.006). Statistically significant differences in progression-free survival (PFS) were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide (TMZ) or TMZ plus other chemotherapies, regardless of their IDH or MGMT-methylation status (p-value=0.0014). Specifically, IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation, who received only TMZ, have exhibited longer PFS. Conclusions: The relationship between PRMT5, MGMT-promoter, and IDH is not tri-directional. However, accumulation of D2-hydroxyglutarate (2-HG), which partially activates 2-OG-dependent deoxygenase, may not affect their activities. In IDH-wildtype glioblastomas, the 2HG-2OG pathway is typically inactive, leading to PRMT5 upregulation. TMZ alone, compared to TMZ-plus, can increase PFS in upregulated PRMT5 tumors. Thus, using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.

Complications and visual outcomes following surgical resection of pediatric optic pathway/hypothalamic gliomas: a systematic review and meta-analysis.

Pediatric optic pathway/hypothalamic gliomas (OPHG) pose challenges in treatment due to their location and proximity to vital structures. Surgical resection plays a key role in the management of OPHG especially when the tumor exhibits mass effect and causes symptoms. However, data regarding outcomes and complications of surgical resection for OPHG remains heterogenous. The authors performed a systematic review on pediatric OPHG in four databases: PubMed, EMBASE, Cochrane Library, and Google Scholar. We included studies that reported on the visual outcomes and complications of OPHG resection. A meta-analysis was performed and reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 26 retrospective studies were included. Seven hundred ninety-seven pediatric patients with OPHG undergoing surgical resection were examined. A diagnosis of NF1 was confirmed in 9.7%. Gross total resection was achieved in 36.7%. Intraorbital optic pathway gliomas showed a significantly higher gross total resection rate compared to those located in the chiasmatic/hypothalamic region (75.8% vs. 9.6%). Postoperatively, visual acuity improved in 24.6%, remained unchanged in 68.2%, and worsened in 18.2%. Complications included hydrocephalus (35.4%), anterior pituitary dysfunction (19.6%), and transient diabetes insipidus (29%). Tumor progression post-resection occurred in 12.8%, through a mean follow-up of 53.5 months. Surgical resection remains an essential strategy for treating symptomatic and large pediatric OPHG and can result in favorable vision outcomes in most patients. Careful patient selection is critical. Patients should be monitored for hydrocephalus development postoperatively and followed up to assess for tumor progression and adjuvant treatment necessity.

Does exogenous hormonal therapy affect the risk of glioma among females: A systematic review and meta-analysis.

Background: The effect of exogenous hormone replacement therapy (HRT) and oral contraceptive pills (OCPs) on glioma risk in females is unclear despite numerous studies; hence, we conducted a meta-analysis to evaluate this relationship. Methods: Studies investigating the impact of exogenous female hormones on glioma risk were retrieved by searching 4 databases from inception until September 2022. Articles of any design, such as case-control and cohort studies, proving the relative risk (RR), odds ratio (OR), or hazard ratio were included. Summary OR values were calculated using a random effects model. Results: Both HRT and OCP use of any duration decreased the risk of developing glioma [HRT OR = 0.78, 95% CI 0.66-0.91, P = .00; OCP: OR = 0.80, 95% CI 0.67-0.96, P = .02]. When stratified by duration of use, HRT use >1 year significantly reduced glioma risk (<1 year: OR = 0.82, 95% CI 0.63-1.07, P = 0.15; 1-5 years: OR = 0.79, 95% CI 0.67-0.92, P = .00; 5-10 years: OR = 0.80, 95% CI 0.66-0.97, P = .02; >10 years: OR = 0.69, 95% CI 0.54-0.88, P = .00). In contrast, only OCP use for >10 years significantly reduced glioma risk (<1 year: OR = 0.72, 95% CI 0.49-1.05, P = .09; 1-5 years: OR = 0.88, 95% CI 0.72-1.02, P = .09; 5-10 years: OR = 0.85, 95% CI 0.65-1.1, P = 0.21; >10 years: OR = 0.58, 95% CI 0.45-0.74, P = .00). Conclusions: Our pooled results strongly suggest that sustained HRT and OCP use is associated with reduced risk of glioma development.

Intracranial Infantile Hemangioma: Highlighting a Rare Presentation With a Case Report and Literature Review.

Infantile hemangioma is a common benign vascular tumor in children, but it is very unusual to be found intracranially. Our literature review identified 44 reported cases. Presentation can vary from asymptomatic to a life-threatening presentation that necessitates urgent surgical removal. There is no general consensus on management of these rare lesions and until recently, treatment was limited to surgery or pharmacological management with steroids, propranolol or interferon. We present a case of a four-week-old male infant with history of vomiting and increase in head circumference since birth. MRI of the brain revealed a large complex cyst occupying the right frontoparietal region, with round soft tissue component that is isointense on T1 and hyperintense on T2 weighted images. Complete surgical resection with evacuation of the cyst was achieved. Histopathology of the mass showed infantile hemangioma with positive CD31 on immunohistochemistry. The patient achieved an excellent outcome following surgical resection.

Chiari type III malformation associated with Klippel-Feil syndrome, a case report with a narrative review of the literature.

BACKGROUND: Chiari malformation type III (CM III), a rare hindbrain anomaly, often presents with various concurrent anomalies. This paper reports a unique case of CM III associated with Klippel-Feil syndrome (KFS), a condition previously unreported in Saudi Arabia and documented in only one other case globally in Turkey. This study aims to share insights into the unusual association between CM III and KFS, considering their close embryological development and involvement in the craniocervical junction. METHODOLOGY: The study presents a case of a 2.5-year-old female diagnosed with CM III and KFS. Diagnostic tools such as ultrasound, CT scans, MRI, and physical examinations were used to confirm the patient's condition. Surgical interventions, including decompression and encephalocele repair, were performed. RESULTS: Successful surgical interventions, including encephalocele repair and duraplasty, were carried out. Follow-up visits indicated a stable condition, marked improvement in lower limb strength, and the patient's ability to walk with assistance. CT follow-up affirmed a satisfactory surgical outcome. CONCLUSION: This case study illustrates the potential for an optimistic prognosis in CM III, even when accompanied by complex conditions such as KFS, through early diagnosis and intervention. It underscores the significance of antenatal screening for effective care planning and calls for further research and publications due to the rarity of this association. These findings contribute to our understanding of CM III and its related conditions, emphasizing the need for open-minded consideration of potential embryological associations.

Application of Automated External Defibrillators Among the Public: A Cross-Sectional Study of Knowledge, Attitude, Practice, and Barriers of Use in Saudi Arabia.

Background: The likelihood of survival of an out-of-hospital cardiac arrest quadruples with the rapid application of basic life support (BLS). The public's ability to perform cardiopulmonary resuscitation (CPR) and use automated external defibrillators (AEDs) is extremely important. This study aimed to assess the public knowledge, attitudes, and practices (KAP) of utilizing AEDs and to understand barriers to AED application. Methods: We conducted a cross-sectional study from March 1-30, 2022. An electronic questionnaire was constructed and validated to measure the KAP for public AED utilization and its barriers. Results: Of the 406 participants, 244 (60.10%) were males. Male respondents had 17% less knowledge and poorer attitude towards using an AED as compared to female respondents. Knowledge and attitudes on using AEDs were low (70.7%) among Saudi nationals compared to those of foreign nationals. Those who were BLS/CPR trained had a 2.5 times greater understanding and willingness to use AEDs in public than those who were not. Barriers to AEDs in CPR/BLS-trained participants were: (1) accidentally hurting the victim (14.3%), (2) duty as a bystander to just call the ambulance and wait for help (12.1%), (3) never taught what to do (n = 41, 18.4%), (4) did not want to be scolded if performed wrong (3.1%), and (5) never witnessed such a situation (51.6%). Conclusion: There is a strong association between knowledge of and willingness to use AEDs in emergency situations among the public. Misconceptions about AEDs hinder their use. This calls for urgent training programs through accessible technology to reach the public.

Outcomes after laser interstitial thermal ablation for temporal lobe epilepsy: a systematic review and meta-analysis.

Epilepsy is a common condition that affects approximately 1% of the world's population, with about one-third being refractory epilepsy. Temporal lobe epilepsy is the most common type of drug-resistant epilepsy, and laser interstitial thermal therapy (LITT) is an innovative treatment. In this systematic review and meta-analysis, we aimed to summarize the current evidence on outcomes after LITT, including seizure freedom rate, complication rate, and neurocognitive outcome. PubMed and OVID Medline search engines were systematically searched for all indexed publications in the English language up to July15, 2023. The search was limited to human studies. Proportions and 95% confidence interval (CI) values were calculated for seizure, neurocognitive outcome, and complication rate. A total of 836 patients were included. Overall seizure outcomes, regardless of the pathology, included Engel I outcome in 56% (95% CI, 52.4-59.5%), Engel II outcome in 19.2% (95% CI, 15.4-23.6%), Engel III outcome in 17.3% (95% CI, 13.5-21.8%), and Engel IV outcome in 10.5% (95% CI 6.3-17%) of the patients. The overall decline in verbal and visual memory regardless of laterality was 24.2 (95% CI 8.6-52%) and 25.2% (8.3-55.8%). For naming, the decline was 13.4% (6.6-25.4%). The results of the pooled analysis in comparison with available data in the literature showed that seizure outcomes after LITT were slightly inferior to published data after temporal lobectomy. Data on cognitive outcomes after LITT are scarce and heterogeneous.

Major Histocompatibility Class-I (MHC-I) downregulation in glioblastoma is a poor prognostic factor but not a predictive indicator for treatment failure.

BACKGROUND: MHC-I expression is a crucial factor in cancer immunity, and its regulations can impact tumor progression and recurrence. The mechanism through which glioblastoma use MHC-I to avoid immunosurveillance has been rarely investigated. METHODS: A retrospective cohort of 35 patients with IDH-mutant WHO-Grade 4 astrocytoma and IDH-wildtype glioblastoma were examined for MHC-I using protein and gene expression assays. The association between IDH mutation, TP53 mutation, and MHC-I expression with recurrence-free interval were investigated. RESULTS: The average patients' age was 49.6 year. IDH was wildtype in 13 tumors. MHC-I protein expression was absent in 30 tumors, faint in 4 tumors, and membrane bound dense expression in single tumor. MHC-I expression was upregulated in 10 tumors and 25 tumors showed MHC-I downregulation. P53 was positively expressed in 19 cases and lost in 13 cases. A significant statistical difference was observed in the RFI between tumors with distinct MHC-I expression and IDH-mutation [p-value = 0.008]. IDH-wildtype tumors with upregulated MHC-I expression showed late tumor recurrence compared to IDH-wildtype tumors with downregulated MHC-I expression. There was insignificant statistical difference in RFI among patients with varying degree of MHC-I expression, who received TMZ or TMZ and other chemotherapies [P-value = 0.44] CONCLUSIONS: Glioblastoma with upregulated MHC-I showed a delayed tumor recurrence in comparison to those with downregulated MHC-I expression. However, downregulated MHC-I may not necessarily be an indicator of poor problems.

The synergistic effect of IDH mutation and NDRG-2 dysregulation in the progression of WHO-grade 4 astrocytomas.

BACKGROUND: NDRG2 is a tumour suppressor gene involved in tumor growth inhibition. Its effect on tumour recurrence remains controversial. The aim of this study is to explore the dual effect of IDH mutation and NDRG2 dysregulation in WHO-Grade 4 astrocytoma recurrence. METHODS: A group of 36 patients with WHO-Grade 4 astrocytoma were examined for NDRG2 expression using protein and gene expression assays. The relationship between IDH, NDRG2 protein and gene expressions, and recurrence-free interval [RFI] was explored. RESULTS: The mean patients age in this study was 45-years with 21 males and 15 females. IDH was mutant in 22 tumors. NDRG2 protein expression was low in 23 tumors, and high in 13 tumors. NDRG2 gene expression was upregulated in 4 tumors and 32 tumors showed NDRG2 gene downregulation. The consistency between two tasting methods of NDRG2 expression was 52.8%. There was a significant statistical difference in RFI among tumors with varying NDRG2 gene expression and IDH mutation [p-value= 0.021]. IDH-mutant tumours with downregulated NDRG2 expression showed late recurrence compared to IDH-wildtype glioblastoma. CONCLUSIONS: IDH-mutant WHO Grade-4 astrocytoma with downregulated NDRG2 gene are associated with late tumor recurrence. IDH mutations cause excessive accumulation of D-2-hydroxyglutarate, that may inhibit the activity of TET proteins, potentially leading to DNA hypermethylation and gene silencing.

Dynamic interplay between corticosteroid treatment and the role of SRC-1 gene dysregulation in the progression of WHO-Grade 4 Astrocytoma.

BACKGROUND: Corticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and cytotoxic T-cells has never been investigated. METHODS: A retrospective cohort of 36 patients with WHO-Grade 4 astrocytoma were examined for CD8 + T-cell and SRC-1 gene expressions through IHC and qRT-PCR. The impact of corticosteroid on CD8+T-cells infiltration, SRC-1 expression, and tumour recurrence was analyzed. RESULTS: The mean patients age was 47-years, with a male to female ratio 1.2. About 78% [n = 28] of the cases showed reduced or no CD8+T-cell expression while 22% [n = 8] of cases have showed medium to high CD8+T-cell expression. SRC-1 gene was upregulated in 5 cases [14%] and 31 cases [86%] showed SRC-1 downregulation. The average of total days and doses of administered corticosteroid from the preoperative period to the postoperative period was at range of 14-106 days and 41-5028 mg, respectively. There was no significant statistical difference in RFI among tumours expressing high or low CD8+T-cells when corticosteroid was administered in recommended or exceeded doses [p-value = 0.640]. There was a significant statistical difference in RFI between CD8+T-Cell expression and SRC-1 gene dysregulation [p-value = 002]. Tumours with high CD8+T T-cell expression and SRC-1 gene downregulation had late recurrence. CONCLUSIONS: Corticosteroid treatment can directly affect the SRC-1 gene regulation but does not directly influence cytotoxic T-cells infiltration or tumor progression. However, SRC-1 gene downregulation can facilitate late tumor recurrence.

Vasospasm following brain tumor resection in children: institutional experience and systematic review.

OBJECTIVE: Delayed cerebral ischemia (DCI) associated with vasospasm is well described in the setting of aneurysmal subarachnoid hemorrhage (SAH). In addition, DCI is very infrequently encountered in patients who have undergone resection of a brain tumor with unclear pathophysiology. The occurrence of DCI in the pediatric population is exceedingly rare, and outcomes in this population have, to the authors' knowledge, never been systematically reviewed. Therefore, the authors present what is to their knowledge the largest series of pediatric patients with this complication and systematically reviewed the literature for individual participant data. METHODS: The authors conducted a retrospective review of 172 sellar and suprasellar tumors in pediatric patients who underwent surgery at the Montreal Children's Hospital between 1999 and 2017 to identify cases of vasospasm occurring after tumor resection. Descriptive statistics, including patient characteristics, intraoperative and postoperative findings, and outcome status, were collected. A systematic review was also conducted using three databases (PubMed, Web of Science, Embase) to identify reported cases available in the literature of vasospasm after tumor resection in children and collect individual participant data on these patients for further analysis. RESULTS: Six patients treated at Montreal Children's Hospital were identified, with an average age of 9.5 years (range 6-15 years). The prevalence of vasospasm after tumor resection was 3.5% (6/172). Vasospasm in all 6 patients occurred after craniotomy was performed to treat a suprasellar tumor. The average interval from surgery to symptoms was 3.25 days (range 12 hours-10 days). The most common tumor etiology was craniopharyngioma, seen in 4 cases. Extensive tumor encasement of blood vessels requiring significant operative manipulation was described in all 6 patients. A rapid decrease in serum sodium (exceeding 12 mEq/L/24 hrs or below 135 mEq/L) was seen in 4 patients. On final follow-up, 3 patients were left with significant disability, and all patients had persistent deficits. A systematic review of the literature revealed a total of 10 other patients whose characteristics and treatment were compared with those of the 6 patients treated at Montreal Children's Hospital. CONCLUSIONS: Vasospasm after tumor resection in children and youth is likely a rare entity, with a prevalence of 3.5% in this case series. Suprasellar tumor location (particularly craniopharyngioma tumor etiology), significant encasement of blood vessels by the tumor, and postoperative hyponatremia may be predictive factors. Outcome is poor, with most patients having significant persistent neurological deficits.

Utilizing artificial intelligence and electroencephalography to assess expertise on a simulated neurosurgical task.

Virtual reality surgical simulators have facilitated surgical education by providing a safe training environment. Electroencephalography (EEG) has been employed to assess neuroelectric activity during surgical performance. Machine learning (ML) has been applied to analyze EEG data split into frequency bands. Although EEG is widely used in fields requiring expert performance, it has yet been used to classify surgical expertise. Thus, the goals of this study were to (a) develop an ML model to accurately differentiate skilled and less-skilled performance using EEG data recorded during a simulated surgery, (b) explore the relative importance of each EEG bandwidth to expertise, and (c) analyze differences in EEG band powers between skilled and less-skilled individuals. We hypothesized that EEG recordings during a virtual reality surgery task would accurately predict the expertise level of the participant. Twenty-one participants performed three simulated brain tumor resection procedures on the NeuroVR™ platform (CAE Healthcare, Montreal, Canada) while EEG data was recorded. Participants were divided into 2 groups. The skilled group was composed of five neurosurgeons and five senior neurosurgical residents (PGY4-6), and the less-skilled group was composed of six junior residents (PGY1-3) and five medical students. A total of 13 metrics from EEG frequency bands and ratios (e.g., alpha, theta/beta ratio) were generated. Seven ML model types were trained using EEG activity to differentiate between skilled and less-skilled groups. The artificial neural network achieved the highest testing accuracy of 100% (AUROC = 1.0). Model interpretation via Shapley analysis identified low alpha (8-10 Hz) as the most important metric for classifying expertise. Skilled surgeons displayed higher (p = 0.044) low-alpha than the less-skilled group. Furthermore, skilled surgeons displayed significantly lower TBR (p = 0.048) and significantly higher beta (13-30 Hz, p = 0.049), beta 1 (15-18 Hz, p = 0.014), and beta 2 (19-22 Hz, p = 0.015), thus establishing these metrics as important markers of expertise. ACGME CORE COMPETENCIES: Practice-Based Learning and Improvement.

Hemisensory Loss after Ventriculoperitoneal Shunt Insertion.

Idiopathic intracranial hypertension includes ventriculoperitoneal shunt (VPS) insertion, with a reported complication of shunt revision in 25% of the cases 1 year after insertion. We report a case of a 28-year-old female with pituitary adenoma who developed sensory loss after VPS placement that could be explained by disruption in thalamic pathways. A lesson learned from this case is that although VPS is a simple procedure, complications can occur. Modalities can be used to detect the complications, and further revisions might be needed.

A Newly Developed Interprofessional In-Situ Simulation-Based Training for Airway Management of COVID-19 Patients: Identification of Challenges and Safety Gaps, and Assessment of the Participants' Reaction.

Background: Healthcare providers performing aerosol-generating procedures like airway management are at the highest risk for contamination with coronavirus disease 2019 (COVID-19). We developed an in-situ simulation (ISS) airway management training in confirmed or suspected COVID-19 patients for emergency and anesthesiology staff, evaluated participants' reactions, and identified perceived challenges. Methods: We used a cross-sectional study design incorporating a quantitative questionnaire to describe participants' reaction to the ISS and a qualitative group interview using the plus-delta debriefing modality to explore participants' challenges in acquiring the knowledge and skills required for each learning objective. Data were analyzed using descriptive statistics and deductive content analysis. Results: Two hundred and ninety-nine healthcare providers participated in 62 ISS training sessions. Over 90% of our study participants agreed or strongly agreed that: they understood the learning objectives; the training material appropriately challenged them; the course content was relevant, easy to navigate, and essential; the facilitators' knowledge, teaching, and style were appropriate; the simulation facilities were suitable; and they had ample opportunities to practice the learned skills. The main challenges identified were anticipating difficult airways, preparing intubation equipment, minimizing the number of personnel inside the room, adhering to the proper doffing sequence, preparing needed equipment outside the intubation room, speaking up, and ensuring closed-loop communication. Conclusion: The newly developed ISS training was feasible for busy healthcare practitioners to safely perform airway management procedures for suspected or confirmed COVID-19 patients without affecting bedside care. Anticipation of difficult airways and speaking up were the most frequent challenges identified across all specialties in this study.

Mitigation strategies for heat-related illness during mass gatherings: Hajj experience.

Introduction: To mitigate morbidity, mortality, and impacts of heat-related illnesses (HRIs) on health, it was vital to implement a comprehensive framework for HRI prevention and control. A recognized tool from the field of trauma prevention known as the Haddon matrix was applied. The matrix states that any event is affected by three factors: host, agent, and environment. In addition, another recognized tool known as the combined model was used in this study. The combined model is a three-dimensional model that includes the idea for the three axes of Haddon's matrix with the methodology of the community risk reduction (CRR) model. Aim of the study: To identify the environmental and individual risk factors of HRIs based on the Haddon matrix and the recommended prevention strategies by the CRR tool by using the combined model. Methodology: An extensive literature review was conducted to assess all the risk factors associated with HRI, as well as preventive measures. Then the Haddon matrix was used to structure, separating human factors from technical and environmental details and timing. After that, the combined model was used to set all responses and mitigation measures for each element obtained from the Haddon matrix tool. Conclusion: Projected increases in heat stress over the globe require the formulation and implementation of evidence-based HRI mitigation and preventive measures. In this study, we implemented the combined model that was utilized as a systematic strategy for the more theoretical framework of Haddon's matrix. Using the Haddon matrix to determine the HRI risk factors and the combined model to mitigate its impact was practical and helpful in planning, preparedness, and mitigating the HRIs during Hajj, provided a broad approach equivalent to the Swiss cheese model, and would facilitate an informed decision.

Nondominant Hand Skills Spatial and Psychomotor Analysis During a Complex Virtual Reality Neurosurgical Task-A Case Series Study.

BACKGROUND: Virtual reality surgical simulators provide detailed psychomotor performance data, allowing qualitative and quantitative assessment of hand function. The nondominant hand plays an essential role in neurosurgery in exposing the operative area, assisting the dominant hand to optimize task execution, and hemostasis. Outlining expert-level nondominant hand skills may be critical to understand surgical expertise and aid learner training. OBJECTIVE: To (1) provide validity for the simulated bimanual subpial tumor resection task and (2) to use this simulation in qualitative and quantitative evaluation of nondominant hand skills for bipolar forceps utilization. METHODS: In this case series study, 45 right-handed participants performed a simulated subpial tumor resection using simulated bipolar forceps in the nondominant hand for assisting the surgery and hemostasis. A 10-item questionnaire was used to assess task validity. The nondominant hand skills across 4 expertise levels (neurosurgeons, senior trainees, junior trainees, and medical students) were analyzed by 2 visual models and performance metrics. RESULTS: Neurosurgeon median (range) overall satisfaction with the simulated scenario was 4.0/5.0 (2.0-5.0). The visual models demonstrated a decrease in high force application areas on pial surface with increased expertise level. Bipolar-pia mater interactions were more focused around the tumoral region for neurosurgeons and senior trainees. These groups spent more time using the bipolar while interacting with pia. All groups spent significantly higher time in the left upper pial quadrant than other quadrants. CONCLUSION: This work introduces new approaches for the evaluation of nondominant hand skills which may help surgical trainees by providing both qualitative and quantitative feedback.

Continuous monitoring of surgical bimanual expertise using deep neural networks in virtual reality simulation.

In procedural-based medicine, the technical ability can be a critical determinant of patient outcomes. Psychomotor performance occurs in real-time, hence a continuous assessment is necessary to provide action-oriented feedback and error avoidance guidance. We outline a deep learning application, the Intelligent Continuous Expertise Monitoring System (ICEMS), to assess surgical bimanual performance at 0.2-s intervals. A long-short term memory network was built using neurosurgeon and student performance in 156 virtually simulated tumor resection tasks. Algorithm predictive ability was tested separately on 144 procedures by scoring the performance of neurosurgical trainees who are at different training stages. The ICEMS successfully differentiated between neurosurgeons, senior trainees, junior trainees, and students. Trainee average performance score correlated with the year of training in neurosurgery. Furthermore, coaching and risk assessment for critical metrics were demonstrated. This work presents a comprehensive technical skill monitoring system with predictive validation throughout surgical residency training, with the ability to detect errors.

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.

Assessment of learning curves on a simulated neurosurgical task using metrics selected by artificial intelligence.

OBJECTIVE: Understanding the variation of learning curves of experts and trainees for a given surgical procedure is important in implementing formative learning paradigms to accelerate mastery. The study objectives were to use artificial intelligence (AI)-derived metrics to determine the learning curves of participants in 4 groups with different expertise levels who performed a series of identical virtual reality (VR) subpial resection tasks and to identify learning curve differences among the 4 groups. METHODS: A total of 50 individuals participated, 14 neurosurgeons, 4 neurosurgical fellows and 10 senior residents (seniors), 10 junior residents (juniors), and 12 medical students. All participants performed 5 repetitions of a subpial tumor resection on the NeuroVR (CAE Healthcare) platform, and 6 a priori-derived metrics selected using the K-nearest neighbors machine learning algorithm were used to assess participant learning curves. Group learning curves were plotted over the 5 trials for each metric. A mixed, repeated-measures ANOVA was performed between the first and fifth trial. For significant interactions (p < 0.05), post hoc Tukey's HSD analysis was conducted to determine the location of the significance. RESULTS: Overall, 5 of the 6 metrics assessed had a significant interaction (p < 0.05). The 4 groups, neurosurgeons, seniors, juniors, and medical students, showed an improvement between the first and fifth trial on at least one of the 6 metrics evaluated. CONCLUSIONS: Learning curves generated using AI-derived metrics provided novel insights into technical skill acquisition, based on expertise level, during repeated VR-simulated subpial tumor resections, which will allow educators to develop more focused formative educational paradigms for neurosurgical trainees.

Effect of Artificial Intelligence Tutoring vs Expert Instruction on Learning Simulated Surgical Skills Among Medical Students: A Randomized Clinical Trial.

Importance: To better understand the emerging role of artificial intelligence (AI) in surgical training, efficacy of AI tutoring systems, such as the Virtual Operative Assistant (VOA), must be tested and compared with conventional approaches. Objective: To determine how VOA and remote expert instruction compare in learners' skill acquisition, affective, and cognitive outcomes during surgical simulation training. Design, Setting, and Participants: This instructor-blinded randomized clinical trial included medical students (undergraduate years 0-2) from 4 institutions in Canada during a single simulation training at McGill Neurosurgical Simulation and Artificial Intelligence Learning Centre, Montreal, Canada. Cross-sectional data were collected from January to April 2021. Analysis was conducted based on intention-to-treat. Data were analyzed from April to June 2021. Interventions: The interventions included 5 feedback sessions, 5 minutes each, during a single 75-minute training, including 5 practice sessions followed by 1 realistic virtual reality brain tumor resection. The 3 intervention arms included 2 treatment groups, AI audiovisual metric-based feedback (VOA group) and synchronous verbal scripted debriefing and instruction from a remote expert (instructor group), and a control group that received no feedback. Main Outcomes and Measures: The coprimary outcomes were change in procedural performance, quantified as Expertise Score by a validated assessment algorithm (Intelligent Continuous Expertise Monitoring System [ICEMS]; range, -1.00 to 1.00) for each practice resection, and learning and retention, measured from performance in realistic resections by ICEMS and blinded Objective Structured Assessment of Technical Skills (OSATS; range 1-7). Secondary outcomes included strength of emotions before, during, and after the intervention and cognitive load after intervention, measured in self-reports. Results: A total of 70 medical students (41 [59%] women and 29 [41%] men; mean [SD] age, 21.8 [2.3] years) from 4 institutions were randomized, including 23 students in the VOA group, 24 students in the instructor group, and 23 students in the control group. All participants were included in the final analysis. ICEMS assessed 350 practice resections, and ICEMS and OSATS evaluated 70 realistic resections. VOA significantly improved practice Expertise Scores by 0.66 (95% CI, 0.55 to 0.77) points compared with the instructor group and by 0.65 (95% CI, 0.54 to 0.77) points compared with the control group (P < .001). Realistic Expertise Scores were significantly higher for the VOA group compared with instructor (mean difference, 0.53 [95% CI, 0.40 to 0.67] points; P < .001) and control (mean difference. 0.49 [95% CI, 0.34 to 0.61] points; P < .001) groups. Mean global OSATS ratings were not statistically significant among the VOA (4.63 [95% CI, 4.06 to 5.20] points), instructor (4.40 [95% CI, 3.88-4.91] points), and control (3.86 [95% CI, 3.44 to 4.27] points) groups. However, on the OSATS subscores, VOA significantly enhanced the mean OSATS overall subscore compared with the control group (mean difference, 1.04 [95% CI, 0.13 to 1.96] points; P = .02), whereas expert instruction significantly improved OSATS subscores for instrument handling vs control (mean difference, 1.18 [95% CI, 0.22 to 2.14]; P = .01). No significant differences in cognitive load, positive activating, and negative emotions were found. Conclusions and Relevance: In this randomized clinical trial, VOA feedback demonstrated superior performance outcome and skill transfer, with equivalent OSATS ratings and cognitive and emotional responses compared with remote expert instruction, indicating advantages for its use in simulation training. Trial Registration: ClinicalTrials.gov Identifier: NCT04700384.