Syllable processing is organized in discrete subregions of the human superior temporal gyrus.

Modular organization at approximately 1 mm scale could be fundamental to cortical processing, but its presence in human association cortex is unknown. Using custom-built, high-density electrode arrays placed on the cortical surface of 7 patients undergoing awake craniotomy for tumor excision, we investigated receptive speech processing in the left (dominant) human posterior superior temporal gyrus. Responses to consonant-vowel syllables and noise-vocoded controls recorded with 1,024 channel micro-grids at 200 µm pitch demonstrated roughly circular domains approximately 1.7 mm in diameter, with sharp boundaries observed in 128 channel linear arrays at 50 µm pitch, possibly consistent with a columnar organization. Peak latencies to syllables in different modules were bimodally distributed centered at 252 and 386 ms. Adjacent modules were sharply delineated from each other by their distinct time courses and stimulus selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

Effects of 24-hour versus night-float call schedules on the clinical and operative experiences of postgraduate year 2 and 3 neurosurgical residents.

OBJECTIVE: To comply with the removal of the 88-hour week exemption and to support additional operative experience during junior residency, Oregon Health & Science University (OHSU) switched from a night-float call schedule to a modified 24-hour call schedule on July 1, 2019. This study compared the volumes of clinical, procedural, and operative cases experienced by postgraduate year 2 (PGY-2) and PGY-3 residents under these systems. METHODS: The authors retrospectively studied billing and related clinical records, call schedules, and Accreditation Council for Graduate Medical Education case logs for PGY-2 and PGY-3 residents at OHSU, a tertiary academic health center, for the first 4 months of the academic years from 2017 to 2020. The authors analyzed the volumes of new patient consultations, bedside procedures, and operative procedures performed by each PGY-2 and PGY-3 resident during these years, comparing the volumes experienced under each call system. RESULTS: Changing from a PGY-2 resident-focused night-float call system to a 24-hour call system that was more evenly distributed between PGY-2 and PGY-3 residents resulted in decreased volume of new patient consultations, increased volume of operative procedures, and no change in volume of bedside procedures for PGY-2 residents. PGY-3 residents experienced a decrease in operative procedure volume under the 24-hour call system. CONCLUSIONS: Transition from a night-float system to a 24-hour call system altered the distribution of clinical and procedural experiences between PGY-2 and PGY-3 residents. Further research is necessary to understand the impact of these changes on educational outcomes, quality and safety of patient care, and resident satisfaction.

Compassion, communication, and the perception of control: a mixed methods study to investigate patients' perspectives on clinical practices for alleviating distress and promoting empowerment during awake craniotomies.

PURPOSE: To inquire into clinical practices perceived to mitigate patients' intraoperative distress during awake craniotomies. METHODS: This mixed-methods study involved administration of Amsterdam Preoperative Anxiety and Information Scale and PTSD Checklist prior to the awake craniotomy to evaluate anxiety and information-seeking related to the procedure and symptoms of PTSD. Generalized Anxiety Disorder Scale and Depression Module of the Patient Health Questionnaire were administered before and after the procedure to evaluate generalized anxiety and depression. Patient interviews were conducted 2-weeks postprocedure and included a novel set of patient experience scales to assess patients' recollection of intraoperative pain, overall distress, anxiety, distress due to noise, perception of empowerment, perception of being well-prepared, overall satisfaction with anaesthesia management, and overall satisfaction with the procedure. Qualitative data were analysed using conventional content analysis. RESULTS: Participants (n = 14) had undergone an awake craniotomy for tissue resection due to primary brain tumours or medically-refractory focal epilepsy. Validated self-report questionnaires demonstrated reduced levels of generalized anxiety (pre mean = 8.66; SD = 6.41; post mean= 4.36; SD = 4.24) following the awake craniotomy. Postprocedure interviews revealed very high satisfaction with the awake craniotomy and anaesthesia management and minimal levels of intraoperative pain, anxiety, and distress. The most stressful aspects of the procedure included global recognition of medical diagnosis, anxiety provoked by unfamiliar sights, sounds, and sensations, a perception of a lack of information or misinformation, and long periods of immobility. Important factors in alleviating intraoperative distress included the medical team's ability to promote patient perceptions of control, establish compassionate relationships, address unfamiliar intraoperative sensations, and deliver effective anaesthesia management. CONCLUSION: Compassion, communication, and patient perception of control were critical in mitigating intraoperative distress. Clinical practice recommendations with implications for all clinicians involved in patient care during awake craniotomies are provided. Use of these interventions and strategies to reduce distress are important to holistic patient care and patient experiences of care and may improve the likelihood of optimal brain mapping procedures to improve clinical outcomes during awake craniotomies.

Molecular features and clinical outcomes in surgically treated low-grade diffuse gliomas in patients over the age of 60.

PURPOSE: WHO grade II gliomas are uncommon in patients over the age of 60, and there is a lack in consensus regarding their management. We present molecular tumor characteristics as well as clinical outcomes in patients over the age of 60 undergoing surgical resection of a WHO grade II glioma. METHODS: After receiving IRB approval, patients were identified through the UCSF Brain Tumor Center. Pathologic diagnosis was completed using WHO 2016 grading criteria. RESULTS: Twenty-six patients with a mean age of 66 years met inclusion criteria with a median follow-up of 5.2 years. Diagnoses included diffuse astrocytoma IDH-mutant (19.2%), diffuse astrocytoma IDH-wildtype (26.9%), Oligodendroglioma IDH-mutant and 1p/19q-codeleted (50%), and a rare case of mixed oligoastrocytoma (3.9%). 66% of astrocytoma IDH-wildtype tumors possessed TERT mutation. Median extent of resection was 75.4%. Progression-free (PFS) and overall survival (OS) were 23.5 and 62.6 months, respectively. Shorter PFS was associated with the astrocytoma IDH-wildtype subtype despite similar extent of resection and adjuvant treatment rates compared to the other subtypes. OS did not differ between subtypes. Malignant transformation and death were associated with larger preoperative and residual tumor volume. CONCLUSIONS: Older patients with diffuse gliomas may safely undergo aggressive treatment with surgical resection and adjuvant therapy. Elderly patients with low grade gliomas have worse clinical outcomes compared to their younger counterparts. This may be due to an increased frequency of diffuse astrocytoma IDH-wildtype tumors in this age group.

Early tumor growth between initial resection and radiotherapy of glioblastoma: incidence and impact on clinical outcomes.

Early tumor growth, or increased contrast-enhancing tumor not related to evolving post-surgical injury, in the interval between surgical resection and initiation of radiotherapy has implications for treatment planning and clinical outcomes. In this study we evaluated the incidence of early tumor growth, correlated tumor growth with survival outcome measures, and assessed predictors of early tumor growth in glioblastoma. We reviewed the records of patients with newly-diagnosed glioblastoma who underwent surgical resection and chemoradiotherapy at our institution. Patients with preoperative, immediate postoperative, and preradiotherapy MRI were included. Conventional MRI and DWI features were assessed. The correlation between early tumor growth and extent of resection with survival was assessed with Kaplan-Meier analysis. Logistic regression was carried out to evaluate predictors of early tumor growth. Of 140 included patients, sixty-seven cases (48%) had new or increased contrast enhancement attributed to early tumor growth. Median progression free survival (PFS) and overall survival (OS) were shorter in patients with early tumor growth compared to those without early tumor growth (p < 0.001 for both). Additionally, PFS and OS were longer in patients who underwent gross total resection of enhancing tumor (p = 0.016 and <0.001, respectively). Of the evaluated predictors of early growth, subtotal resection was most likely to result in early growth (p < 0.001). Imaging evidence of early tumor growth is often observed at preradiotherapy MRI and is associated with shorter survival. Gross total resection of contrast enhancing tumor decreases likelihood of early tumor growth.

Familial melanoma-astrocytoma syndrome: synchronous diffuse astrocytoma and pleomorphic xanthoastrocytoma in a patient with germline CDKN2A/B deletion and a significant family history.

Familial melanoma-astrocytoma syndrome is a tumor predisposition syndrome caused by inactivating germline alteration of the CDKN2A tumor suppressor gene on chromosome 9p21. While some families with germline CDKN2A mutations are prone to development of just melanomas, other families develop both melanomas, astrocytomas, and occasionally other nervous-system neoplasms including peripheral nerve sheath tumors and meningiomas. The histologic spectrum of the astrocytomas that arise as part of this syndrome is not well described, nor are the additional genetic alterations that drive these astrocytomas apart from the germline CDKN2A inactivation. Herein, we report the case of a young man with synchronous development of a pleomorphic xanthoastrocytoma, diffuse astrocytoma, and paraspinal mass radiographically consistent with a peripheral nerve sheath tumor. His paternal family history is significant for melanoma, glioblastoma, and oral squamous cell carcinoma. Genomic profiling revealed that he harbors a heterozygous deletion in the germline of chromosome 9p21.3 encompassing the CDKN2A and CDKN2B tumor suppressor genes. Both the pleomorphic xanthoastrocytoma and diffuse astrocytoma were found to have homozygous deletion of CDKN2A/B due to somatic loss of the other copy of chromosome 9p containing the remaining intact alleles. Additional somatic alterations included BRAF p.V600E mutation in the pleomorphic xanthoastrocytoma and PTPN11, ATRX, and NF1 mutations in the diffuse astrocytoma. The presence of germline CDKN2A/B inactivation together with the presence of multiple anatomically, histologically, and genetically distinct astrocytic neoplasms, both with accompanying somatic loss of heterozygosity for the CDKN2A/B deletion, led to a diagnosis of familial melanoma-astrocytoma syndrome. This remarkable case illustrates the histologic and genetic diversity that astrocytomas arising as part of this rare glioma predisposition syndrome can demonstrate.
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The transsylvian approach for resection of insular gliomas: technical nuances of splitting the Sylvian fissure.

Insular gliomas represent a unique surgical challenge due to the complex anatomy and nearby vascular elements associated within the Sylvian fissure. For certain tumors, the transsylvian approach provides an effective technique for achieving maximal safe resection. The goal of this manuscript and video are to present and discuss the surgical nuances and appropriate application of splitting the Sylvian fissure. Our hope is that this video highlights the safety and efficacy of the transsylvian approach for appropriately selected insular gliomas.

Expression and prognostic impact of immune modulatory molecule PD-L1 in meningioma.

While immunotherapy may offer promising new approaches for high grade meningiomas, little is currently known of the immune landscape in meningiomas. We sought to characterize the immune microenvironment and a potentially targetable antigen mesothelin across WHO grade I-III cases of meningiomas, and how infiltrating immune populations relate to patient outcomes. Immunohistochemistry was performed on tissue microarrays constructed from 96 meningioma cases. The cohort included 16 WHO grade I, 62 WHO grade II, and 18 WHO grade III tumors. Immunohistochemistry was performed using antibodies against CD3, CD8, CD20, CD68, PD-L1, and mesothelin. Dual staining using anti-PD-L1 and anti-CD68 antibodies was performed, and automated cell detection and positive staining detection algorithms were utilized. Greater degree of PD-L1 expression was found in higher grade tumors. More specifically, higher grade tumors contained increased numbers of intratumoral CD68-, PD-L1+ cells (p = 0.022), but did not contain higher numbers of infiltrating CD68+, PD-L1+ cells (p = 0.30). Higher PD-L1+/CD68- expression was independently predictive of worse overall survival in our cohort when accounting for grade, performance status, extent of resection, and recurrence history (p = 0.014). Higher expression of PD-L1+/CD68- was also present in tumors that had undergone prior radiotherapy (p = 0.024). Approximately quarter of meningiomas overexpressed mesothelin to levels equivalent to those found in pancreatic carcinomas and malignant mesotheliomas. The association with poor survival outcomes in our study suggests that PD-L1 may play a significant biologic role in the aggressive phenotype of higher grade meningiomas. Thus, immunotherapeutic strategies such as checkpoint inhibition may have clinical utility in PD-L1 overexpressing meningiomas.

Nationwide shift from microscopic to endoscopic transsphenoidal pituitary surgery.

PURPOSE: Transsphenoidal pituitary surgery can be carried out with either an operating microscope or with an endoscope, but the relative frequency of both techniques is unknown. METHODS: All microscopic and endoscopic transsphenoidal pituitary surgeries were extracted from the Centers for Medicare and Medicaid Services Part B data files between the years 2003 and 2013. National and state-level trends were compared over time. RESULTS: Endoscopic surgery significantly increased and microscopic surgery significantly decreased over the years 2003-2013. Thirty-eight of 48 states increased their use of endoscopic surgery, while 38 of 48 states decreased their use of microscopic surgery. CONCLUSIONS: Nationwide data show a clear trend for an increasing use of endoscopic transsphenoidal surgery at the expense of microscopic surgery. The underlying causes of these trends are unknown, but clearly deserve further investigation.

Rathke's cleft cysts: review of natural history and surgical outcomes.

Rathke's cleft cysts (RCCs), also known as pars intermedia cysts, represent benign lesions formed from remnants of the embryologic Rathke's pouch. Commonly asymptomatic, they are identified in nearly 1 in 6 healthy volunteers undergoing brain imaging. When symptomatic, they can cause headaches, endocrine dysfunction, and, rarely, visual disturbances. A systematic review of the published English literature was performed focusing on large modern case series of RCCs to describe their natural history, clinicopathologic features, radiographic features, and surgical outcomes, including rates of recurrence. The natural history of asymptomatic RCCs is one of slow growth, suggesting that observation through serial magnetic resonance imaging is appropriate for smaller asymptomatic RCCs. Symptomatic RCCs can be treated by surgical resection with low morbidity, usually through an endonasal transsphenoidal corridor using either a microscope or an endoscope. Surgical treatment frequently provides symptomatic relief of headaches and visual disturbances, and sometimes even improves endocrine dysfunction. Rates of recurrence after surgical treatment range from 16 to 18 % in large series, and higher rates of recurrence are associated with suprasellar location, inflammation and reactive squamous metaplasia in the cyst wall, superinfection of the cyst, and use of a fat graft into the cyst cavity.

Rapid Passive Gamma Mapping as an Adjunct to Electrical Stimulation Mapping for Functional Localization in Resection of Primary Brain Neoplasms.

OBJECTIVE: We examined the utility of passive high gamma mapping (HGM) as an adjunct to conventional awake brain mapping during glioma resection. We compared functional and survival outcomes before and after implementing intraoperative HGM. METHODS: This was a retrospective cohort study of 75 patients who underwent a first-time, awake craniotomy for glioma resection. Patients were stratified by whether their operation occurred before or after the implementation of a U.S. Food and Drug Administration-approved high-gamma mapping tool in July 2017. RESULTS: The preimplementation and postimplementation cohorts included 28 and 47 patients, respectively. Median intraoperative time (261 vs. 261 minutes, P = 0.250) and extent of resection (97.14% vs. 98.19%, P = 0.481) were comparable between cohorts. Median Karnofsky performance status at initial follow-up was similar between cohorts (P = 0.650). Multivariable Cox regression models demonstrated an adjusted hazard ratio for overall survival of 0.10 (95% confidence interval: 0.02-0.43, P = 0.002) for the postimplementation cohort relative to the preimplementation cohort. Progression-free survival adjusted for insular involvement showed an adjusted hazard ratio of 1.00 (95% confidence interval: 0.49-2.06, P = 0.999) following HGM implementation. Falling short of statistical significance, prevalence of intraoperative seizures and/or afterdischarges decreased after HGM implementation as well (12.7% vs. 25%, P = 0.150). CONCLUSIONS: Our results tentatively indicate that passive HGM is a safe and potentially useful adjunct to electrical stimulation mapping for awake cortical mapping, conferring at least comparable functional and survival outcomes with a nonsignificant lower rate of intraoperative epileptiform events. Considering the limitations of our study design and patient cohort, further investigation is needed to better identify optimal use cases for HGM.

On-Call Workload Differences in Neurosurgery: Resident Call "Weather" and a Departure from Colored Cloud Labels.

BACKGROUND AND OBJECTIVES: Labeling residents as "black" or "white" clouds based on perceived or presumed workloads is a timeworn custom across medical training and practice. Previous studies examining whether such perceptions align with objective workload patterns have offered conflicting results. We assessed whether such peer-assigned labels were associated with between-resident differences in objective, on-call workload metrics in three classes of neurosurgery junior residents. In doing so, we introduce more inclusive terminology for perceived differences in workload metrics. METHODS: Residents were instructed to complete surveys to identify "sunny", "neutral", and "stormy" residents, reflecting least to greatest perceived workloads, of their respective classes. We retrospectively reviewed department and electronic medical records to record volume of on-call work over the first 4 months of each resident's 2nd postgraduate academic year. Inter-rater agreement of survey responses was measured using Fleiss' kappa. All statistical analyses were performed with a significance threshold of P < .05. RESULTS: Across all classes, there was strong inter-rater agreement in the identification of stormy and sunny residents (Kappa = 1.000, P = .003). While differences in on-call workload measures existed within each class, "weather" designations did not consistently reflect these differences. There were significant intraclass differences in per shift consult volume in two classes ( P = .035 and P = .009); however, consult volume corresponded to a resident's weather designations in only one class. Stormy residents generally saw more emergencies and, in 2 classes, performed more bedside procedures than their peers. CONCLUSION: Significant differences in objective on-call experience exist between junior neurosurgery residents. Self- and peer-assigned weather labels did not consistently align with a pattern of these differences, suggesting that other factors contribute to such labels.

Obesity and meningioma: a US population-based study paired with analysis of a multi-institutional cohort.

OBJECTIVE: Whether obesity is associated with meningioma and the impact of obesity by gender has been debated. The primary objective of this study was to investigate differences in BMI between male and female patients undergoing craniotomy for meningioma and compare those with patients undergoing craniotomy for other intracranial tumors. The secondary objective was to compare meningioma location and progression-free survival (PFS) between obese and nonobese patients in a multi-institutional cohort. METHODS: National data were obtained from the National Surgical Quality Improvement Program (NSQIP) database. Male and female patients were analyzed separately. Patients undergoing craniotomies for meningioma were compared with patients of the same sex undergoing craniotomies for other intracranial tumors. Institutional data from two academic centers were collected for all male and an equivalent number of female meningioma patients undergoing meningioma resection. Multivariate regression controlling for age was used to determine differences in meningioma location. Kaplan-Meier curves and log-rank tests were computed to investigate differences in PFS. RESULTS: From NSQIP, 4163 male meningioma patients were compared with 24,266 controls, and 9372 female meningioma patients were compared with 21,538 controls. Male and female patients undergoing meningioma resection were more likely to be overweight or obese compared with patients undergoing craniotomy for other tumors, with the odds ratio increasing with increasing weight class (all p < 0.0001). In the multi-institutional cohort, meningiomas were more common along the skull base in male patients (p = 0.0123), but not in female patients (p = 0.1246). There was no difference in PFS between obese and nonobese male (p = 0.4104) or female (p = 0.5504) patients. Obesity was associated with increased risk of pulmonary embolism in both male and female patients undergoing meningioma resection (p = 0.0043). CONCLUSIONS: Male and female patients undergoing meningioma resection are more likely to be obese than patients undergoing craniotomy for other intracranial tumors. Obese males are more likely to have meningiomas in the skull base compared with other locations, but this association was not found in females. There was no significant difference in PFS among obese patients. The mechanism by which obesity increases meningioma incidence remains to be determined.

Intraoperative application and early experience with novel high-resolution, high-channel-count thin-film electrodes for human microelectrocorticography.

OBJECTIVE: The study objective was to evaluate intraoperative experience with newly developed high-spatial-resolution microelectrode grids composed of poly(3,4-ethylenedioxythiophene) with polystyrene sulfonate (PEDOT:PSS), and those composed of platinum nanorods (PtNRs). METHODS: A cohort of patients who underwent craniotomy for pathological tissue resection and who had high-spatial-resolution microelectrode grids placed intraoperatively were evaluated. Patient demographic and baseline clinical variables as well as relevant microelectrode grid characteristic data were collected. The primary and secondary outcome measures of interest were successful microelectrode grid utilization with usable resting-state or task-related data, and grid-related adverse intraoperative events and/or grid dysfunction. RESULTS: Included in the analysis were 89 cases of patients who underwent a craniotomy for resection of neoplasms (n = 58) or epileptogenic tissue (n = 31). These cases accounted for 94 grids: 58 PEDOT:PSS and 36 PtNR grids. Of these 94 grids, 86 were functional and used successfully to obtain cortical recordings from 82 patients. The mean cortical grid recording duration was 15.3 ± 1.15 minutes. Most recordings in patients were obtained during experimental tasks (n = 52, 58.4%), involving language and sensorimotor testing paradigms, or were obtained passively during resting state (n = 32, 36.0%). There were no intraoperative adverse events related to grid placement. However, there were instances of PtNR grid dysfunction (n = 8) related to damage incurred by suboptimal preoperative sterilization (n = 7) and improper handling (n = 1); intraoperative recordings were not performed. Vaporized peroxide sterilization was the most optimal sterilization method for PtNR grids, providing a significantly greater number of usable channels poststerilization than did steam-based sterilization techniques (median 905.0 [IQR 650.8-935.5] vs 356.0 [IQR 18.0-597.8], p = 0.0031). CONCLUSIONS: High-spatial-resolution microelectrode grids can be readily incorporated into appropriately selected craniotomy cases for clinical and research purposes. Grids are reliable when preoperative handling and sterilization considerations are accounted for. Future investigations should compare the diagnostic utility of these high-resolution grids to commercially available counterparts and assess whether diagnostic discrepancies relate to clinical outcomes.

Functional prediction of response to therapy prior to therapeutic intervention is associated with improved survival in patients with high-grade glioma.

Patients with high-grade glioma (HGG) have an extremely poor prognosis compounded by a lack of advancement in clinical care over the past few decades. Regardless of classification, most newly diagnosed patients receive the same treatment, radiation and temozolomide (RT/TMZ). We developed a functional precision oncology test that prospectively identifies individual patient's response to this treatment regimen. Tumor tissues isolated from patients with newly diagnosed HGG enrolled in 3D PREDICT REGISTRY were evaluated for response to chemotherapeutic agents using the 3D Predict™ Glioma test. Patients receiving RT/TMZ were followed for 2 years. Clinical outcomes including imaging, assessments, and biomarker measurements were compared to patient matched test-predicted therapy response. Median survival between test-predicted temozolomide responders and test-predicted temozolomide non-responders revealed a statistically significant increase in progression-free survival when using the test to predict response across multiple subgroups including HGG (5.8 months), glioblastoma (4.7 months), and MGMT unmethylated glioblastoma (4.7 months). Overall survival was also positively separated across the subgroups at 7.6, 5.1, and 6.3 months respectively. The strong correlation of 3D Predict Glioma test results with clinical outcomes demonstrates that this functional test is prognostic in patients treated with RT/TMZ and supports aligning clinical treatment to test-predicted response across varying HGG subgroups.

Modular Phoneme Processing in Human Superior Temporal Gyrus.

Modular organization is fundamental to cortical processing, but its presence is human association cortex is unknown. We characterized phoneme processing with 128-1024 channel micro-arrays at 50-200µm pitch on superior temporal gyrus of 7 patients. High gamma responses were highly correlated within ~1.7mm diameter modules, sharply delineated from adjacent modules with distinct time-courses and phoneme-selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

Response to Preoperative Dexamethasone Predicts Postoperative Neurological Improvement of Focal Neurological Deficits in Patients With Brain Metastases.

BACKGROUND: Steroids are used ubiquitously in the preoperative management of patients with brain tumor. The rate of improvement in focal deficits with steroids and the prognostic value of such a response are not known. OBJECTIVE: To determine the rate at which focal neurological deficits respond to preoperative corticosteroids in patients with brain metastases and whether such an improvement could predict long-term recovery of neurological function after surgery. METHODS: Patients with brain metastases and related deficits in language, visual field, or motor domains who received corticosteroids before surgery were identified. Characteristics between steroid responders and nonresponders were compared. RESULTS: Ninety six patients demonstrated a visual field (13 patients), language (19), or motor (64) deficit and received dexamethasone in the week before surgery (average cumulative dose 43 mg; average duration 2.7 days). 38.5% of patients' deficits improved with steroids before surgery, while 82.3% of patients improved by follow-up. Motor deficits were more likely to improve both preoperatively ( P = .014) and postoperatively ( P = .010). All 37 responders remained improved at follow-up whereas 42 of 59 (71%) of nonresponders ultimately improved ( P < .001). All other clinical characteristics, including dose and duration, were similar between groups. CONCLUSION: A response to steroids before surgery is highly predictive of long-term improvement postoperatively in brain metastasis patients with focal neurological deficits. Lack of a response portends a somewhat less favorable prognosis. Duration and intensity of therapy do not seem to affect the likelihood of response.

Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial.

BACKGROUND: MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with poor clinical outcomes. METHODS: MDNA55-05 is an open-label, single-arm phase IIb study of MDNA55 in recurrent GBM (rGBM) patients with an aggressive form of GBM (de novo GBM, IDH wild-type, and nonresectable at recurrence) on their 1st or 2nd recurrence. MDNA55 was administered intratumorally as a single dose treatment (dose range of 18 to 240 ug) using convection-enhanced delivery (CED) with up to 4 stereo-tactically placed catheters. It was co-infused with a contrast agent (Gd-DTPA, Magnevist®) to assess distribution in and around the tumor margins. The flow rate of each catheter did not exceed 10µL/min to ensure that the infusion duration did not exceed 48 h. The primary endpoint was mOS, with secondary endpoints determining the effects of IL4R status on mOS and PFS. RESULTS: MDNA55 showed an acceptable safety profile at doses up to 240 µg. In all evaluable patients (n = 44) mOS was 11.64 months (80% one-sided CI 8.62, 15.02) and OS-12 was 46%. A subgroup (n = 32) consisting of IL4R High and IL4R Low patients treated with high-dose MDNA55 (>180 ug) showed the best benefit with mOS of 15 months, OS-12 of 55%. Based on mRANO criteria, tumor control was observed in 81% (26/32), including those patients who exhibited pseudo-progression (15/26). CONCLUSIONS: MDNA55 demonstrated tumor control and promising survival and may benefit rGBM patients when treated at high-dose irrespective of IL4R expression level.Trial Registration: Clinicaltrials.gov NCT02858895.

Multi-class glioma segmentation on real-world data with missing MRI sequences: comparison of three deep learning algorithms.

This study tests the generalisability of three Brain Tumor Segmentation (BraTS) challenge models using a multi-center dataset of varying image quality and incomplete MRI datasets. In this retrospective study, DeepMedic, no-new-Unet (nn-Unet), and NVIDIA-net (nv-Net) were trained and tested using manual segmentations from preoperative MRI of glioblastoma (GBM) and low-grade gliomas (LGG) from the BraTS 2021 dataset (1251 in total), in addition to 275 GBM and 205 LGG acquired clinically across 12 hospitals worldwide. Data was split into 80% training, 5% validation, and 15% internal test data. An additional external test-set of 158 GBM and 69 LGG was used to assess generalisability to other hospitals' data. All models' median Dice similarity coefficient (DSC) for both test sets were within, or higher than, previously reported human inter-rater agreement (range of 0.74-0.85). For both test sets, nn-Unet achieved the highest DSC (internal = 0.86, external = 0.93) and the lowest Hausdorff distances (10.07, 13.87 mm, respectively) for all tumor classes (p < 0.001). By applying Sparsified training, missing MRI sequences did not statistically affect the performance. nn-Unet achieves accurate segmentations in clinical settings even in the presence of incomplete MRI datasets. This facilitates future clinical adoption of automated glioma segmentation, which could help inform treatment planning and glioma monitoring.

Creating a culture of safety within operative neurosurgery: the design and implementation of a perioperative safety video.

OBJECT: Surgical and medical errors result from failures in communication and handoffs as well as lack of standardization in clinical protocols and safety practices. Checklists, simulation training, and teamwork training have been shown to decrease adverse patient events and increase the safety culture of surgical teams. The goal of this project was to simplify and standardize perioperative patient safety practices and team communication processes within operative neurosurgery through the creation of an educational safety video targeted at a neurosurgical provider audience. METHODS: A multidisciplinary group consisting of neurosurgeons, anesthesiologists, nurses, neuromonitoring specialists, quality champions, and a professional video production company met over several months in an iterative process to 1) determine the overall objectives of the video, 2) decide on the content and format of the video, 3) modify the proposed content and format based on stakeholder feedback, and 4) record the video and complete final revisions during postproduction. RESULTS: The video was launched within the authors' institution in July 2012 in conjunction with ongoing research projects to study the effects of the video on 1) multidisciplinary providers' knowledge of perioperative safety practices, 2) provider safety attitudes and safety culture in the operating room, and 3) provider behavior in performing predetermined elements of the preoperative timeout and postoperative debrief. CONCLUSIONS: The neurosurgical perioperative safety video can serve as a national model for how quality champions can drive changes in safety culture and provider behavior among multidisciplinary perioperative patient care teams. Ongoing research is being performed to assess the impact of the video on provider knowledge, behavior, and safety attitudes and culture.