Applied deep learning in neurosurgery: identifying cerebrospinal fluid (CSF) shunt systems in hydrocephalus patients.

BACKGROUND: Over the recent decades, the number of different manufacturers and models of cerebrospinal fluid shunt valves constantly increased. Proper identification of shunt valves on X-ray images is crucial to neurosurgeons and radiologists to derive further details of a specific shunt valve, such as opening pressure settings and MR scanning conditions. The main aim of this study is to evaluate the feasibility of an AI-assisted shunt valve detection system. METHODS: The dataset used contains 2070 anonymized images of ten different, commonly used shunt valve types. All images were acquired from skull X-rays or scout CT-images. The images were randomly split into a 80% training and 20% validation set. An implementation in Python with the FastAi library was used to train a convolutional neural network (CNN) using a transfer learning method on a pre-trained model. RESULTS: Overall, our model achieved an F1-score of 99% to predict the correct shunt valve model. F1-scores for individual shunt valves ranged from 92% for the Sophysa Sophy Mini SM8 to 100% for several other models. CONCLUSION: This technology has the potential to automatically detect different shunt valve models in a fast and precise way and may facilitate the identification of an unknown shunt valve on X-ray or CT scout images. The deep learning model we developed could be integrated into PACS systems or standalone mobile applications to enhance clinical workflows.

Training Performance Assessment for Intracranial Aneurysm Clipping Surgery Using a Patient-Specific Mixed-Reality Simulator: A Learning Curve Study.

BACKGROUND AND OBJECTIVES: The value of simulation-based training in medicine and surgery has been widely demonstrated. This study investigates the introduction and use of a new mixed-reality neurosurgical simulator in aneurysm clipping surgery, focusing on the learning curve and performance improvement. METHODS: Five true-scale craniotomy head models replicating patient-specific neuroanatomy, along with a mixed-reality simulator, a neurosurgical microscope, and a set of microsurgical instruments and clips, were used in the operation theater to simulate aneurysm microsurgery. Six neurosurgical residents participated in five video-recorded simulation sessions over 4 months. Complementary learning modalities were implemented between sessions. Thereafter, three blinded analysts reported on residents' use of the microscope, quality of manipulation, aneurysm occlusion, clipping techniques, and aneurysm rupture. Data were also captured regarding training time and clipping attempts. RESULTS: Over the course of training, clipping time and number of clipping attempts decreased significantly (P = .018, P = .032) and the microscopic skills improved (P = .027). Quality of manipulation and aneurysm occlusion scoring improved initially although the trend was interrupted because the spacing between sessions increased. Significant differences in clipping time and attempts were observed between the most and least challenging patient models (P = .005, P = .0125). The least challenging models presented higher rates of occlusion based on indocyanine green angiography evaluation from the simulator. CONCLUSION: The intracranial aneurysm clipping learning curve can be improved by implementing a new mixed-reality simulator in dedicated training programs. The simulator and the models enable comprehensive training under the guidance of a mentor.

Dynamic Mixed-Reality Patient-Specific Aneurysm Clipping Simulation for Two Cases-A Feasibility Study.

BACKGROUND AND OBJECTIVE: Intracranial aneurysm (IA) clipping is a complex neurosurgical procedure which demands advanced technology to minimize risks and maximize patient outcomes. This study aims to evaluate the feasibility of training patient-specific microsurgical clipping procedures using a mixed-reality physical neurosurgical simulator for unruptured IA. METHODS: Two board-certified neurosurgeons were asked to simulate surgery in 2 patient-specific left-side unruptured middle cerebral artery-bifurcation IA models. The study was conducted in the operation theater under realistic conditions using a mixed-reality physical neurosurgical simulator. Time, procedural, and outcome-related information was collected. The participating neurosurgeons were encouraged to attempt all possible clipping strategies, even those deemed suboptimal, reporting the outcome of each strategy. Finally, to evaluate the feasibility and added value of integrating indocyanine green fluorescence angiography (ICG-FA) with the simulator, the ICG-FA videos for each clipping strategy were analyzed and compared with the reported clipping outcomes. RESULTS: Between 4 and 8, different clipping strategies were applied per aneurysm model; the number of strategies was higher in Patient Model 1 (6.5 ± 1.5) (more complex aneurysm) than in Patient Model 2 (5.0 ± 1.0). The clipping strategies differed between surgeons. At most, 53.5 minutes were necessary to complete each training session, but more than double the time was spent on the more complex aneurysm. Up to 53.8% (Patient Model 1) and 50% (Patient Model 2) of the attempted strategies were discarded by the neurosurgeons during the simulation. Evaluation of aneurysm occlusion through ICG-FA was specific, although sensitivity was poor. CONCLUSION: The present mixed-reality patient-specific simulator allows testing, anticipating, and discarding different aneurysm microsurgical clipping strategies regardless of the pathology complexity. Specific limitations should be considered regarding ICG-FA aneurysm inspection after clipping.

Overcoming chemotherapy resistance in low-grade gliomas: A computational approach.

Low-grade gliomas are primary brain tumors that arise from glial cells and are usually treated with temozolomide (TMZ) as a chemotherapeutic option. They are often incurable, but patients have a prolonged survival. One of the shortcomings of the treatment is that patients eventually develop drug resistance. Recent findings show that persisters, cells that enter a dormancy state to resist treatment, play an important role in the development of resistance to TMZ. In this study we constructed a mathematical model of low-grade glioma response to TMZ incorporating a persister population. The model was able to describe the volumetric longitudinal dynamics, observed in routine FLAIR 3D sequences, of low-grade glioma patients acquiring TMZ resistance. We used the model to explore different TMZ administration protocols, first on virtual clones of real patients and afterwards on virtual patients preserving the relationships between parameters of real patients. In silico clinical trials showed that resistance development was deferred by protocols in which individual doses are administered after rest periods, rather than the 28-days cycle standard protocol. This led to median survival gains in virtual patients of more than 15 months when using resting periods between two and three weeks and agreed with recent experimental observations in animal models. Additionally, we tested adaptive variations of these new protocols, what showed a potential reduction in toxicity, but no survival gain. Our computational results highlight the need of further clinical trials that could obtain better results from treatment with TMZ in low grade gliomas.

Intraoperative Laser Speckle Contrast Imaging to Assess Vessel Flow in Neurosurgery: A Pilot Study.

BACKGROUND AND OBJECTIVES: Laser speckle contrast imaging (LSCI) has emerged as a promising tool for assessment of vessel flow during neurosurgery. We aimed to investigate the feasibility of visualizing vessel flow in the macrocirculation with a new fully microscope-integrated LSCI system and assess the validity and objectivity of findings compared with fluorescence angiography (FA). METHODS: This is a single-center prospective observational study enrolling adult patients requiring microsurgical treatment for brain vascular pathologies or brain tumors. Three independent raters, blinded toward findings of FA, reviewed regions of interest (ROIs) placed in exposed vessels and target structures. The primary end point was the validity of LSCI for assessment of vessel flow as measured by the agreement with FA. The secondary end point was objectivity, measured as the inter-rater agreement of LSCI findings. RESULTS: During 18 surgical procedures, 23 observations using FA and LSCI were captured simultaneously. Using LSCI, vessel flow was assessable in 62 (86.1%) and not assessable in 10 (13.9%) ROIs. The agreement between LSCI and FA was 86.1%, with an agreement coefficient of 0.85 (95% CI: 0.75-0.94). Disagreement between LSCI and FA was observed in the 10 ROIs that were not assessable. The agreement between ROIs that were assessable using LSCI and FA was 100%. The inter-rater agreement of LSCI findings was 87.9%, with an agreement coefficient of 0.86 (95% CI: 0.79-0.94). CONCLUSION: Fully microscope-integrated LSCI is feasible and has a high potential for clinical utility. Because of its characteristics, LSCI can be viewed as a full-field visual micro-Doppler that can be used as a complementary method to FA for assessing vessel flow during neurosurgery. Despite technical limitations related to the early development phase of the fully microscope-integrated system, we demonstrated reasonable validity and objectivity of findings compared with FA. Further research and refinement of the system may enhance its value in neurosurgical applications.

Robustness of the wide-field imaging Mueller polarimetry for brain tissue differentiation and white matter fiber tract identification in a surgery-like environment: an ex vivo study.

During neurooncological surgery, the visual differentiation of healthy and diseased tissue is often challenging. Wide-field imaging Muller polarimetry (IMP) is a promising technique for tissue discrimination and in-plane brain fiber tracking in an interventional setup. However, the intraoperative implementation of IMP requires realizing imaging in the presence of remanent blood, and complex surface topography resulting from the use of an ultrasonic cavitation device. We report on the impact of both factors on the quality of polarimetric images of the surgical resection cavities reproduced in fresh animal cadaveric brains. The robustness of IMP is observed under adverse experimental conditions, suggesting a feasible translation of IMP for in vivo neurosurgical applications.

Exploring Novel Innovation Strategies to Close a Technology Gap in Neurosurgery: HORAO Crowdsourcing Campaign.

BACKGROUND: Scientific research is typically performed by expert individuals or groups who investigate potential solutions in a sequential manner. Given the current worldwide exponential increase in technical innovations, potential solutions for any new problem might already exist, even though they were developed to solve a different problem. Therefore, in crowdsourcing ideation, a research question is explained to a much larger group of individuals beyond the specialist community to obtain a multitude of diverse, outside-the-box solutions. These are then assessed in parallel by a group of experts for their capacity to solve the new problem. The 2 key problems in brain tumor surgery are the difficulty of discerning the exact border between a tumor and the surrounding brain, and the difficulty of identifying the function of a specific area of the brain. Both problems could be solved by a method that visualizes the highly organized fiber tracts within the brain; the absence of fibers would reveal the tumor, whereas the spatial orientation of the tracts would reveal the area's function. To raise awareness about our challenge of developing a means of intraoperative, real-time, noninvasive identification of fiber tracts and tumor borders to improve neurosurgical oncology, we turned to the crowd with a crowdsourcing ideation challenge. OBJECTIVE: Our objective was to evaluate the feasibility of a crowdsourcing ideation campaign for finding novel solutions to challenges in neuroscience. The purpose of this paper is to introduce our chosen crowdsourcing method and discuss it in the context of the current literature. METHODS: We ran a prize-based crowdsourcing ideation competition called HORAO on the commercial platform HeroX. Prize money previously collected through a crowdfunding campaign was offered as an incentive. Using a multistage approach, an expert jury first selected promising technical solutions based on broad, predefined criteria, coached the respective solvers in the second stage, and finally selected the winners in a conference setting. We performed a postchallenge web-based survey among the solvers crowd to find out about their backgrounds and demographics. RESULTS: Our web-based campaign reached more than 20,000 people (views). We received 45 proposals from 32 individuals and 7 teams, working in 26 countries on 4 continents. The postchallenge survey revealed that most of the submissions came from single solvers or teams working in engineering or the natural sciences, with additional submissions from other nonmedical fields. We engaged in further exchanges with 3 out of the 5 finalists and finally initiated a successful scientific collaboration with the winner of the challenge. CONCLUSIONS: This open innovation competition is the first of its kind in medical technology research. A prize-based crowdsourcing ideation campaign is a promising strategy for raising awareness about a specific problem, finding innovative solutions, and establishing new scientific collaborations beyond strictly disciplinary domains.

Space-expanding flap in decompressive hemicraniectomy for stroke.

OBJECTIVE: Decompressive hemicraniectomy (DCE) is the standard of care for space-occupying malignant infarction of the medial cerebral artery in suitable patients. After DCE, the brain is susceptible to trauma and at risk for the syndrome of the trephined. This study aimed to assess the feasibility of using temporary space-expanding flaps, implanted during DCE, to shield the brain from these risks while permitting the injured brain to expand. METHODS: The authors performed a prospective feasibility study to analyze the safety of space-expanding flaps in 10 patients undergoing DCE and evaluated clinical and radiological outcomes. RESULTS: The relatives of 1 patient withdrew consent, leaving 9 patients in the final analysis. No patients required removal of the space-expanding flap because of uncontrolled increase of intracranial pressure or infection. One patient required additional external ventricular drainage and 1 received mannitol. The mean (range) midline shift decreased from 6.67 (3-12) mm to 1.26 (0-2.6) mm after DCE with the space-expanding flap. The authors observed no cases of sinking skin flap syndrome, other complications, or deaths. One patient underwent further treatment due to infection of the reimplanted autologous bone flap. Two patients later refused cranioplasty, preferring to keep the space-expanding flap and thus avoid the potential risks of cranioplasty. CONCLUSIONS: This feasibility study showed that the concurrent use of space-expanding flaps appeared to be safe in patients who underwent DCE for malignant infarction of the medial cerebral artery. Moreover, space-expanding flaps may permit patients to avoid a second surgery for reimplantation of the autologous bone flap and the risks inherent to this procedure.

Quantitative Analysis of the MGMT Methylation Status of Glioblastomas in Light of the 2021 WHO Classification.

Background: Glioblastomas with methylation of the promoter region of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene exhibit increased sensitivity to alkylating chemotherapy. Quantitative assessment of the MGMT promoter methylation status might provide additional prognostic information. The aim of our study was to determine a quantitative methylation threshold for better survival among patients with glioblastomas. Methods: We included consecutive patients ≥18 years treated at our department between 11/2010 and 08/2018 for a glioblastoma, IDH wildtype, undergoing quantitative MGMT promoter methylation analysis. The primary endpoint was overall survival. Results: A total of 321 patients were included. Median overall survival was 12.6 months. Kaplan−Meier and adjusted Cox regression analysis showed better survival for the groups with 16−30%, 31−60%, and 61−100% methylation. In contrast, survival in the group with 1−15% methylation was similar to those with unmethylated promoter regions. A secondary analysis confirmed this threshold. Conclusions: Better survival is observed in patients with glioblastomas with ≥16% methylation of the MGMT promoter region than with <16% methylation. Survival with tumors with 1−15% methylation is similar to with unmethylated tumors. Above 16% methylation, we found no additional benefit with increasing methylation.

Management of postoperative internal carotid artery intimal flap after carotid endarterectomy: a cohort study and systematic review.

OBJECTIVE: Postoperative internal carotid artery (ICA) intimal flap (IF) is a potential complication after carotid endarterectomy (CEA) for carotid artery stenosis. There are no clear recommendations in the current literature on the management of this condition due to sparse evidence. Some authors advocate carotid stent placement or reoperation, while others suggest watchful waiting. The aim of this study was to analyze incidence and management strategies of postoperative ICA-IF, and moreover, to put these findings into context with a systematic literature review. METHODS: The authors retrospectively reviewed all consecutive CEA cases performed at the University Hospital of Bern over a decade (January 2008 to December 2018). The incidence of postoperative ICA-IF, risk factors, management strategies, and outcomes were analyzed. These results were put into context with a systematic review following the PRISMA guidelines. RESULTS: A total of 725 CEAs were performed between January 2008 and December 2018. Postoperative ICA-IF was detected by routine duplex neurovascular ultrasound (NVUS) in 13 patients, corresponding to an incidence rate of 1.8% (95% CI 1.0%-3.1%). There were no associated intraluminal thrombi on the detected IF. Intraoperative shunt placement was used in 5.6% and one or more intima tack sutures were performed in 42.5% of the 725 cases. There was no significant association between intraoperative shunt placement and the occurrence of an IF (p > 0.99). Two patients (15.4%) with IF experienced a transient postoperative neurological deficit (transient ischemic attack). In these cases, the symptoms resolved spontaneously without any interventions or change in the antiplatelet regimen. All other cases (84.6%) with IF were asymptomatic. In 1 patient (7.7%) with IF, the antiplatelet treatment was switched from a mono- to a dual-antiaggregating regimen because the IF led to a stenosis > 70%; this patient remained asymptomatic. All cases of IFs were managed conservatively with close radiological follow-up evaluations, without reoperation or stenting of the ICA. All 13 IFs vanished spontaneously after a mean duration of 6.9 months (median 1.5 months, range 0.5-48 months). A systematic literature review revealed a postoperative ICA-IF incidence of 3.0% (95% CI 2.1%-4.1%) with relatively heterogenous management strategies. CONCLUSIONS: Postoperative ICA-IF is a rare finding after CEA. Conservative therapy with close NVUS follow-up evaluations appears to be an acceptable and safe management strategy for asymptomatic IFs without associated intraluminal thrombi.

Optimal Combinations of Chemotherapy and Radiotherapy in Low-Grade Gliomas: A Mathematical Approach.

Low-grade gliomas (LGGs) are brain tumors characterized by their slow growth and infiltrative nature. Treatment options for these tumors are surgery, radiation therapy and chemotherapy. The optimal use of radiation therapy and chemotherapy is still under study. In this paper, we construct a mathematical model of LGG response to combinations of chemotherapy, specifically to the alkylating agent temozolomide and radiation therapy. Patient-specific parameters were obtained from longitudinal imaging data of the response of real LGG patients. Computer simulations showed that concurrent cycles of radiation therapy and temozolomide could provide the best therapeutic efficacy in-silico for the patients included in the study. The patient cohort was extended computationally to a set of 3000 virtual patients. This virtual cohort was subject to an in-silico trial in which matching the doses of radiotherapy to those of temozolomide in the first five days of each cycle improved overall survival over concomitant radio-chemotherapy according to RTOG 0424. Thus, the proposed treatment schedule could be investigated in a clinical setting to improve combination treatments in LGGs with substantial survival benefits.

Universal scaling laws rule explosive growth in human cancers.

Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.

Exploring Novel Funding Strategies for Innovative Medical Research: The HORAO Crowdfunding Campaign.

BACKGROUND: The rise of the internet and social media has boosted online crowdfunding as a novel strategy to raise funds for kick-starting projects, but it is rarely used in science. OBJECTIVE: We report on an online crowdfunding campaign launched in the context of the neuroscience project HORAO. The aim of HORAO was to develop a noninvasive real-time method to visualize neuronal fiber tracts during brain surgery in order to better delineate tumors and to identify crucial cerebral landmarks. The revenue from the crowdfunding campaign was to be used to sponsor a crowdsourcing campaign for the HORAO project. METHODS: We ran a 7-week reward-based crowdfunding campaign on a national crowdfunding platform, offering optional material and experiential rewards in return for a contribution toward raising our target of Swiss francs (CHF) 50,000 in financial support (roughly equivalent to US $50,000 at the time of the campaign). We used various owned media (websites and social media), as well as earned media (press releases and news articles) to raise awareness about our project. RESULTS: The production of an explanatory video took 60 hours, and 31 posts were published on social media (Facebook, Instagram, and Twitter). The campaign raised a total of CHF 69,109. Approximately half of all donations came from donors who forwent a reward (CHF 28,786, 48.74%); the other half came from donors who chose experiential and material rewards in similar proportions (CHF 14,958, 25.33% and CHF 15,315.69, 25.93%, respectively). Of those with an identifiable relationship to the crowdfunding team, patients and their relatives contributed the largest sum (CHF 17,820, 30.17%), followed by friends and family (CHF 9288, 15.73%) and work colleagues (CHF 6028, 10.21%), while 43.89% of funds came from donors who were either anonymous or had an unknown relationship to the crowdfunding team. Patients and their relatives made the largest donations, with a median value of CHF 200 (IQR 90). CONCLUSIONS: Crowdfunding proved to be a successful strategy to fund a neuroscience project and to raise awareness of a specific clinical problem. Focusing on potential donors with a personal interest in the issue, such as patients and their relatives in our project, is likely to increase funding success. Compared with traditional grant applications, new skills are needed to explain medical challenges to the crowd through video messages and social media.

Visualization of White Matter Fiber Tracts of Brain Tissue Sections With Wide-Field Imaging Mueller Polarimetry.

Identification of white matter fiber tracts of the brain is crucial for delineating the tumor border during neurosurgery. A custom-built Mueller polarimeter was used in reflection configuration for the wide-field imaging of thick sections of fixed human brain and fresh calf brain. The maps of the azimuth of the fast optical axis of linear birefringent medium reconstructed from the experimental Mueller matrix images of the specimen by applying a non-linear data compression algorithm showed a strong correlation with the silver-stained sample histology image, which is the gold standard for ex-vivo brain fiber tract visualization. The polarimetric maps of fresh calf brain tissue demonstrated the same trends in the depolarization, the scalar retardance and the azimuth of the fast optical axis as seen in fixed human brain tissue. Thus, label-free imaging Mueller polarimetry shows promise as an efficient intra-operative modality for the visualization of healthy brain white matter fiber tracts, which could improve the accuracy of tumor border detection and, ultimately, patient outcomes.

Subdural versus subgaleal drainage for chronic subdural hematomas: a post hoc analysis of the TOSCAN trial.

OBJECTIVE: The use of subdural drains after surgical evacuation of chronic subdural hematoma (CSH) decreases the risk of recurrence and has become the standard of care. Halfway through the controlled, randomized TOSCAN (Randomized Trial of Follow-up CT after Evacuation of Chronic Subdural Hematoma) trial, the authors' institutional guidelines changed to recommend subgaleal instead of subdural drainage. The authors report a post hoc analysis on the influence of drain location in patients participating in the TOSCAN trial. METHODS: The study involved 361 patients enrolled in the TOSCAN trial. The patients were stratified according to whether they received surgery before (cohort A) or after (cohort B) the change in institutional protocol. An intention-to-treat analysis was performed with surgery for recurrence as the primary endpoint. Secondary endpoints were outcome-based on modified Rankin Scale scores, seizures, infections, parenchymal brain injuries, and hematoma diameter. RESULTS: Of the 361 patients included in the analysis, 214 were stratified into cohort A (subdural drainage recommended), while 147 were stratified into cohort B (subgaleal drainage recommended). There was a 31.78% rate of crossover from the subdural to the subgaleal drainage insertion site due to technical or anatomical difficulties. No differences in the rates of reoperation (21.5% [cohort A] vs 25.17% [cohort B], OR 0.81, 95% CI 0.50-1.34, p = 0.415), infections (0.47% [cohort A] vs 2.04% [cohort B], OR 0.23, 95% CI 0.02-2.19, p = 0.199), seizures (3.27% [cohort A] vs 2.72% [cohort B], OR 1.21, 95% CI 0.35-4.21, p = 0.765), or favorable outcomes (modified Rankin Scale score 0-3) at 1 and 6 months (91.26% [cohort A] vs 96.43% [cohort B], OR 0.39, 95% CI 0.14-1.07, p = 0.067; 89.90% [cohort A] vs 91.55% [cohort B], OR 0.82, 95% CI 0.39-1.73, p = 0.605) were noted between the two cohorts. Postoperatively, patients in cohort A had more frequent parenchymal brain tissue injuries (2.8% vs 0%, p = 0.041). Postoperative absolute and relative hematoma reduction was similar irrespective of the location of the drain. CONCLUSIONS: Subgaleal rather than subdural placement of the drain did not increase the risk for reoperation for recurrence of CSHs, nor did it have a negative impact on clinical or radiological outcome. The intention to place a subdural drain was associated with a higher rate of parenchymal injuries.

Computational design of improved standardized chemotherapy protocols for grade II oligodendrogliomas.

Here we put forward a mathematical model describing the response of low-grade (WHO grade II) oligodendrogliomas (LGO) to temozolomide (TMZ). The model describes the longitudinal volumetric dynamics of tumor response to TMZ of a cohort of 11 LGO patients treated with TMZ. After finding patient-specific parameters, different therapeutic strategies were tried computationally on the 'in-silico twins' of those patients. Chemotherapy schedules with larger-than-standard rest periods between consecutive cycles had either the same or better long-term efficacy than the standard 28-day cycles. The results were confirmed in a large trial of 2000 virtual patients. These long-cycle schemes would also have reduced toxicity and defer the appearance of resistances. On the basis of those results, a combination scheme consisting of five induction TMZ cycles given monthly plus 12 maintenance cycles given every three months was found to provide substantial survival benefits for the in-silico twins of the 11 LGO patients (median 5.69 years, range: 0.67 to 68.45 years) and in a large virtual trial including 2000 patients. We used 220 sets of experiments in-silico to show that a clinical trial incorporating 100 patients per arm (standard intensive treatment versus 5 + 12 scheme) could demonstrate the superiority of the novel scheme after a follow-up period of 10 years. Thus, the proposed treatment plan could be the basis for a standardized TMZ treatment for LGO patients with survival benefits.

Assisted Education for Specialized Medicine: A Sustainable Development Plan for Neurosurgery in Myanmar.

BACKGROUND: With only 4 active certified neurosurgeons for a population of 50 million, neurosurgical care was seriously underdeveloped in Myanmar in 2012. Together with the local neurosurgical community, Swiss Neurosurgeons International started a program of assisted education with the aim of increasing the neurosurgical capacity to 60 active neurosurgeons by 2023. METHODS: Our program included a fully sponsored fellowship at an academic hospital in Switzerland for every Myanmar neurosurgeon in training to observe contemporary neurosurgery and the organization of regular workshops, lectures, and educational surgeries in Myanmar. Halfway through the program, we performed a survey to assess its benefits and shortcomings. RESULTS: In 2019, the number of active neurosurgeons in Myanmar had increased to 20, with 50 more in training. Intracranial pressure monitoring, cervical spine surgery, transsphenoidal surgery, and intraoperative electrophysiology have become established procedures. Our survey showed an increased interest by the residents in tumor and vascular surgery and a new interest in spinal surgery. The overall rating of the fellowship was "very good," with language barriers, cultural differences, and coping with inclement weather reported as the greatest difficulties. CONCLUSIONS: Since the start of our project in 2013, a series of contemporary neurosurgical technologies and procedures have been introduced to Myanmar with the help of Swiss Neurosurgeons International. Our survey results have shown the strong points of the ongoing educational program and the weaknesses to be addressed. Midway through our 10-year project, with an expanded and improved education program, our goal of 60 active neurosurgeons in Myanmar by 2023 seems well within reach.

Frequent Diagnostic Under-Grading in Isocitrate Dehydrogenase Wild-Type Gliomas due to Small Pathological Tissue Samples.

BACKGROUND: In contrast to isocitrate dehydrogenase (IDH) mutation analysis, which is homogenous within a given tumor, diagnostic errors in histological analysis following the 2016 World Health Organization (WHO) classification could be due to small samples because of histological heterogeneity. OBJECTIVE: To assess whether the sample size sent to histopathology influences the tumor grading in IDH wild-type gliomas. METHODS: Histologically diagnosed WHO grade, sample volume, and preoperative tumor volume data of 111 patients aged who received resection of IDHwt gliomas between January 2007 and December 2015 at our hospital were evaluated. The differences between absolute and relative pathological sample sizes stratified by WHO grade were conducted using One-Way-Permutation-Test. RESULTS: With a mean sample size of 10.9 cc, 83.8% of patients were histologically diagnosed as WHO grade IV, while 16.2% of patients with a mean sample size of 2.62 cc were diagnosed as WHO grade II/III. One-Way-Permutation-Test showed a significant difference between absolute tissue samples stratified by WHO grade (P = .0374). The distribution of preoperative tumor volumes with WHO grade IV vs WHO grade II/III showed no significant difference (P = .8587). Of all tumors with a sample size >10 cc 100% were pathologically diagnosed as WHO grade IV and those with sample size >5 cc 93.5% were diagnosed as WHO grade IV. CONCLUSION: Small sample sizes are associated with a higher risk of under-estimating malignancy in histological grading in IDHwt gliomas. This study suggests a standard minimum sample size (>5cc) in every resection. Modalities of adjuvant treatment for IDHwt, WHO grade II/III gliomas need to reflect a prognosis that is only marginally better than of a glioblastoma.

ACE-inhibitors: a preventive measure for bone flap resorption after autologous cranioplasty?

OBJECTIVEDecompressive craniectomy (DC) is an established treatment for refractory intracranial hypertension. It is usually followed by autologous cranioplasty (AC), the reinsertion of a patient's explanted bone flap. A frequent long-term complication of AC is bone flap resorption (BFR), which results in disfigurement as well as loss of the protective covering of the brain. This study investigates risk factors for BFR after AC, including medical conditions and antihypertensive drug therapies, with a focus on angiotensin-converting enzyme inhibitors (ACEIs), which have been associated with a beneficial effect on bone healing and bone preservation in orthopedic, osteoporosis, and endocrinology research.METHODSIn this single-center, retrospective study 183 consecutive cases were evaluated for bone flap resorption after AC. Information on patient demographics, medical conditions, antihypertensive therapy, and BFR-defined as an indication for revision surgery established by a neurosurgeon based on clinical or radiographic assessments-was collected. A Kaplan-Meier analysis of time from AC to diagnosis of BFR was performed, and factors associated with BFR were investigated using the log-rank test and Cox regression.RESULTSA total of 158 patients were considered eligible for inclusion in the data analysis. The median follow-up time for this group was 2.2 years (95% CI 1.9-2.5 years). BFR occurred in 47 patients (29.7%), with a median time to event of 3.7 years (95% CI 3.3-4.1 years). An ACEI prescription was recorded in 57 cases (36.1%). Univariate Kaplan-Meier analysis and the log-rank test revealed that ACEI therapy (2-year event free probability [EFP] 83.8% ± 6.1% standard error vs 63.9% ± 5.6%, p = 0.02) and ventriculoperitoneal (VP) shunt treatment (2-year EFP 86.9% ± 7.1% vs 66% ± 5.0%, p = 0.024) were associated with a lower probability of BFR. Multiple Cox regression analysis showed ACEI therapy (HR 0.29, p = 0.012), VP shunt treatment (HR 0.278, p = 0.009), and male sex (HR 0.500, p = 0.040) to be associated with a lower risk for BFR, whereas bone fragmentation (HR 1.92, p = 0.031) was associated with a higher risk for BFR.CONCLUSIONSHypertensive patients treated with ACEIs demonstrate a lower rate of BFR than patients treated with other hypertensive medications and nonhypertensive patients. Our results are in line with previous reports on the positive influence of ACEIs on bone healing and preservation. Further analysis of the association between ACEI treatment and BFR development is needed and will be evaluated in a multicenter prospective trial.

A mathematical model describes the malignant transformation of low grade gliomas: Prognostic implications.

Gliomas are the most frequent type of primary brain tumours. Low grade gliomas (LGGs, WHO grade II gliomas) may grow very slowly for the long periods of time, however they inevitably cause death due to the phenomenon known as the malignant transformation. This refers to the transition of LGGs to more aggressive forms of high grade gliomas (HGGs, WHO grade III and IV gliomas). In this paper we propose a mathematical model describing the spatio-temporal transition of LGGs into HGGs. Our modelling approach is based on two cellular populations with transitions between them being driven by the tumour microenvironment transformation occurring when the tumour cell density grows beyond a critical level. We show that the proposed model describes real patient data well. We discuss the relationship between patient prognosis and model parameters. We approximate tumour radius and velocity before malignant transformation as well as estimate the onset of this process.