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Academic neurosurgeons with international medical training play a large role in the U.S. neurosurgical workforce. We aimed to compare U.S.-trained neurosurgeons with internationally trained neurosurgeons to reveal differences in subspecialty preferences and training opportunities abroad.We identified 1671 neurosurgeons from 115 Accreditation Council for Graduate Medical Education (ACGME)-accredited neurosurgical residency programs. Data on demographics, institution characteristics, and chosen subspecialty were collected, and faculty were divided based on location of training. Univariate analysis and multivariable logistic regression compared faculty characteristics between training locations.Compared with the U.S. medical school + U.S. residency group, the international medical graduate + U.S. residency group was more likely to subspecialize in oncology/skull base and vascular neurosurgery and complete a fellowship in the United States or internationally (P0.05). The international medical graduate + international residency group was more likely to subspecialize in oncology/skull base neurosurgery, more likely to complete an international fellowship, and less likely to practice general neurosurgery (P0.05). Neurosurgeons in pediatrics, radiosurgery, and vascular subspecialties were more likely to receive fellowship training in any location (P 0.05). Additionally, functional neurosurgeons were more likely to complete fellowships internationally, spinal neurosurgeons were less likely to pursue international fellowships, and peripheral nerve neurosurgeons were more likely to have dual fellowship training in both the United States and abroad (P0.05).International medical training affected subspecialty choice and fellowship training. Internationally trained neurosurgeons more often specialized in oncology and vascular neurosurgery. Functional neurosurgeons were more likely to complete international fellowships, spine neurosurgeons were less likely to complete international fellowships, and peripheral nerve neurosurgeons more often had both U.S. and international fellowships.

Sex as a variable of survival

One-way ANOVA analysis comparing expression of cytokines between Avelumab treated and Avelumab combined with Bevacizumab

Purpose:The treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy.Patient and Methods:Patients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells.Results:A total of 12 patients (median age 64; range, 37–73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4–16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5–4.5 months). The decrease in MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival.Conclusions:Avelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease.Significance:Our phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI.

The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM).To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012.PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived.From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided.Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis.https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-of-progressive-glioblastoma.

Target populationThese recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM).Question (Q1):In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy?Recommendation:Level III: Adult patients with pGBM might derive benefit in treatment with TMZ especially those who progress after more than 5 months of TMZ-treatment free interval. Level III: Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohypothermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy.There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits.Question (Q2):In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy?Recommendation:Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a suggestion about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen.Question (Q3):In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy?Recommendation:Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM.Level III: Other cytotoxic therapies like perillyl acohol and ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy.Question (Q4):In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy?Recommendation:Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM.There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM.Question (Q5):In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy?Recommendation:Level III: Oncolytic virotherapy is not suggested in patients with pGBM.

OBJECTIVE Neurosurgery is a highly competitive residency field with a match rate lower than that of other specialties. The aim of this study was to analyze trends associated with the residency match process from the applicants’ and program directors’ perspectives. METHODS Between 2010 and 2020, the National Residency Matching Program (NRMP) Applicant and Program Director Surveys, the NRMP Charting Outcomes reports, and the Accreditation Council for Graduate Medical Education (ACGME) Data Resource Books were analyzed to identify the number of applicants interviewed and ranked in US programs, the applicants’ ranking preferences, the program directors’ preferential factors in offering interviews, and rank list order. Applicants were divided between US senior medical students and independent applicants. Each cohort was dichotomized for matched and unmatched applicants. RESULTS Over the study period, 2935 applicants applied to neurosurgery residency, including 2135 US senior medical students and 800 independent applicants, with an overall match rate of 65%. Overall, matched applicants had a significantly higher number of publications (p < 0.05). Among US senior medical student applicants, the application-to-interview ratio more than doubled over the study period, yet the number of interview invitations received, interviews accepted, and programs ranked remained unchanged. In the US senior medical student cohort, the number of submitted applications, interview invitations, accepted interviews, and programs ranked did not significantly differ between matched and unmatched applicants. In both cohorts, applicants shifted ranking factors from a more academic focus in early years to more well-being in later years. Letters of recommendation and board scores were key factors for program directors while screening applicants for interviews and ranking. CONCLUSIONS Neurosurgery residency continues to be a highly competitive field in medicine, with match rates of 65%. Recently, applicants have placed greater importance on ranking programs that value residents’ well-being, as opposed to strictly academic factors. A data-driven understanding of factors important to applicants and program directors during the match process has the potential to improve resident candidate recruitment and overall resident-program fit, thereby improving well-being during residency, reducing the attrition rate, and overall enhancing the diversity of the neurosurgery resident workforce.

The following questions and recommendations are pertinent to the following: TARGET POPULATION: These recommendations apply to adults with progressive GBM who have undergone standard primary treatment with surgery and/or chemoradiation. QUESTION 1: In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION Level III: Treatment with bevacizumab is suggested in the treatment of progressive GBM, as it provides improved disease control compared to historical controls as measured by best imaging response and progression free survival at 6 months, while not providing evidence for improvement in overall survival. QUESTION 2: In adults with progressive glioblastoma is the use of bevacizumab as combination therapy with cytotoxic agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION Level III: There is insufficient evidence to show benefit or harm of bevacizumab in combination with cytotoxic therapies in progressive glioblastoma due to a lack of evidence supporting a clearly defined benefit without significant toxicity. QUESTION 3: In adults with progressive glioblastoma is the use of bevacizumab as a combination therapy with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION There is insufficient evidence to support a recommendation regarding this question. QUESTION 4: In adults with progressive glioblastoma is the use of targeted agents as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION There is insufficient evidence to support a recommendation regarding this question. QUESTION 5: In adults with progressive glioblastoma is the use of targeted agents in combination with cytotoxic therapies superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION There is insufficient evidence to support a recommendation regarding this question. QUESTION 6: In adults with progressive glioblastoma is the use of immunotherapy monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION There is insufficient evidence to support a recommendation regarding this question. QUESTION 7: In adults with progressive glioblastoma is the use of immunotherapy in combination with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION There is insufficient evidence to support a recommendation regarding this question. QUESTION 8: In adults with progressive glioblastoma is the use of immunotherapy in combination with bevacizumab superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION There is insufficient evidence to support a recommendation regarding this question.

OBJECTIVE Despite recently heightened advocacy efforts relating to pregnancy and family leave policies in multiple surgical specialties, no studies to date have described female neurosurgeons’ experiences with childbearing. The AANS/CNS Section of Women in Neurosurgery created the Women and Pregnancy Task Force to ascertain female neurosurgeons’ experiences with and attitudes toward pregnancy and the role of family leave policies. METHODS A voluntary online 28-question survey examined the pregnancy experiences of female neurosurgeons and perceived barriers to childbearing. The survey was developed and electronically distributed to all members of the American Association of Neurological Surgeons and Congress of Neurological Surgeons who self-identified as female in February 2016. Responses from female resident physicians, fellows, and current or retired practicing neurosurgeons were analyzed. RESULTS A total of 126 women (20.3%) responded to the survey; 57 participants (49%) already had children, and 39 (33%) planned to do so. Participants overwhelmingly had or planned to have children during the early practice and senior residency years. The most frequent obstacles experienced or anticipated included insufficient time to care for newborns (47% of women with children, 92% of women planning to have children), discrimination by coworkers (31% and 77%, respectively), and inadequate time for completion of board requirements (18% and 51%, respectively). There was substantial variability in family leave policies, and a minority of participants (35%) endorsed the presence of any formal policy at their institution. Respondents described myriad unique challenges associated with pregnancy and family leave. CONCLUSIONS Pregnancy and family leave pose significant challenges to the recruitment, retention, and advancement of women in neurosurgery. It is thus imperative to promote clear family leave policies for trainees and practitioners, address discrimination surrounding these topics, and encourage forethought and flexibility to tackle obstacles inherent in pregnancy and the early stages of child rearing.

Background Aneurysm clipping requires the proficiency of several skills, yet the traditional way of practicing them has been recently challenged, especially by the growth of endovascular techniques. The use of simulators could be an alternative educational tool, but some of them are cumbersome, expensive to implement, or lacking in realism. The aim of this study is to evaluate a reusable low-cost 3-dimensional printed training model we developed for aneurysm clipping. Methods The simulator was designed to replicate the bone structure, arteries, and targeted aneurysms. Thirty-two neurosurgery residents performed a craniotomy and aneurysm clipping using the model and then filled out a survey. They were divided into Junior and Senior groups. Descriptive, exploratory, and confirmatory factor analysis was performed using IBM SPSS statistical software. Results The overall residents' response was positive, with high scores to face validity and content validity questions. There was no significant statistical difference between the Junior and Senior groups. The confirmatory factor and internal consistency analysis confirmed that the evaluation was highly reliable. Globally, 97% of the residents found the model was useful and would repeat the simulator experience. The financial cost is $2500 USD for implementation and only $180 USD if further training sessions are required. Conclusions The main strengths of our training model are its highlighted realism, adaptability to trainees of different levels of expertise, sustainability, and low cost. Our data support the concept that it can be incorporated as a new training opportunity during professional specialty meetings and/or within residency academic programs.

These recommendations apply to adults with newly diagnosed or suspected glioblastoma. What is the effect of extent of surgical resection on patient outcome in the initial management of adult patients with suspected newly diagnosed glioblastoma? Level II: Maximal cytoreductive surgery is recommended in adult patients with suspected newly diagnosed supratentorial glioblastoma with gross total resection defined as removal of contrast enhancing tumor. Level III: Biopsy, subtotal resection, or gross total resection is suggested depending on medical comorbidities, functional status, and location of tumor if maximal resection may cause significant neurologic deficit. What is the role of cytoreductive surgery in adults with newly diagnosed bi-frontal “butterfly” glioblastoma? Level III: Resection of newly diagnosed bi-frontal “butterfly” glioblastoma is suggested to improve overall survival over biopsy alone. What is the goal of cytoreductive surgery in elderly adult patients with newly diagnosed glioblastoma? Level III: Elderly patients (> 65 years) show survival benefit with gross total resection and it is suggested they undergo cytoreductive surgery. What is the role of advanced intraoperative guidance techniques in cytoreductive surgery in adults with newly diagnosed glioblastoma? Level III: The use of intraoperative guidance adjuncts such as intraoperative MRI (iMRI) or 5-aminolevulinic acid (5-ALA) are suggested to maximize extent of resection in newly diagnosed glioblastoma. There is insufficient evidence to make a suggestion on the use of fluorescein, indocyanine green, or intraoperative ultrasound.

In the past 2 decades, a deeper understanding of the cancer molecular signature has resulted in longer longevity of cancer patients, hence a greater population, who potentially can develop metastatic disease. Spine metastases (SM) occur in up to 70% of cancer patients. Familiarizing ourselves with the key aspects of initial symptom-directed management is important to provide SM patients with the best patient-specific options. We will review key components of initial symptoms assessment such as pain, neurological symptoms, and spine stability. Radiographic evaluation of SM and its role in management will be reviewed. Nonsurgical treatment options are also presented and discussed, including percutaneous procedures, radiation, radiosurgery, and spine stereotactic body radiotherapy. The efforts of a multidisciplinary team will continue to ensure the best patient care as the landscape of cancer is constantly changing.

Biological subtypes have been strongly correlated with loco-regional recurrence after definitive treatment for localized breast cancer. Brain metastases (BM) occur in 15% of patient diagnosed with breast cancer (BC). Therefore, we sought to determine whether biologic subtype is predictive of local control (LC) in BC patients with BM treated with stereotactic radiosurgery (SRS). This is a single-center retrospective study conducted with Institutional Review Board approval for the period January 1, 2004–December 31, 2018. Eligibility criteria included (1) histopathologic proven BC with documented biologic subtype, (2) presence of BM treated with SRS (single fraction), (3) follow-up MRIs, and (4) clinical follow-up. Patients were subdivided into three biologic subtypes: ER+/HER2- (“luminal”), HER2+, and ER-/PR-/HER2 (TN). All patients were treated with LINAC-based SRS with dose according to published guidelines. Cox proportional hazard model and Kaplan-Meier were used for statistical analysis of LC and overall survival (OS). With a median follow-up of 11.1 months, 17 BC BM in 50 consecutive patients were included in this study. The median disease-specific GPA was 2.0, and all patients received systemic chemotherapy and/or hormonal therapy. The 12-month LC rates for the entire cohort were 85%, 87%, and 49% for luminal, HER2+, and TN, respectively, with a significantly shorter time to local failure for the TN subtype (p = 0.014). The 12-month OS rates were 83%, 88%, and 80% for luminal, HER2+, and TN, respectively, with a trend toward shorter OS in the TN group. This study shows that in BC patients with BM treated with SRS, biologic subtype affects LC. Consideration of radiation treatment intensification or altered fractionation to improve LC may be indicated for the TN subtype. Further multicenter studies are necessary to corroborate our results.

Globally, the discipline of neurosurgery has evolved remarkably fast. Despite being one of the latest medical specialties, which appeared only around hundred years ago, it has witnessed innovations in the aspects of diagnostics methods, macro and micro surgical techniques, and treatment modalities. Unfortunately, this development is not evenly distributed between developed and developing countries. The same is the case with neurosurgical education and training, which developed from only traditional apprentice programs in the past to more structured, competence-based programs with various teaching methods being utilized, in recent times. A similar gap can be observed between developed and developing counties when it comes to neurosurgical education. Fortunately, most of the scholars working in this field do understand the coherent relationship between neurosurgical education and neurosurgical practice. In context to this understanding, a symposium was organized during the World Federation of Neurological Surgeons (WFNS) Special World Congress Beijing 2019. This symposium was the brain child of Prof. Yoko Kato—one of the eminent leaders in neurosurgery and an inspiration for female neurosurgeons. Invited speakers from different continents presented the stages of development of neurosurgical education in their respective countries. This paper summarizes the outcome of these presentations, with particular emphasis on and the challenges faced by developing countries in terms of neurosurgical education and strategies to cope with these challenges.

OBJECTIVE In 2015, the Association of American Medical Colleges report titled "Altering the Course: Black Males in Medicine" showed a decline in the number of Black men matriculating into medical school. To alter this trend, the authors’ hypothesis was that formally exposing Black men to the clinical neurosciences during high school would enhance their chances of entering the physician workforce. For this reason, in 2007, the Doctors Reaching Minority Men Exploring Neuroscience (DR. MMEN) program was established at the Icahn School of Medicine at Mount Sinai. The program aimed to provide early exposure, mentorship, and inspiration to high school–age Black and Latinx men. The aim of this study was to evaluate the impact of the DR. MMEN program in the context of the recent race and ethnicity trends among medical school matriculants (MSMs). METHODS Association of American Medical Colleges data on MSMs stratified by race and ethnicity were reviewed for the period between 2015 and 2020. Data pertinent to the academic achievements of DR. MMEN participants, such as matriculation to college and/or medical school, were prospectively tracked and incorporated with mixed-methods exit assessment data. Qualitative responses were coded and analyzed using a thematic concept analysis method. RESULTS Over the study period, the increase of MSMs in the US was 1.0% and 1.7% for Black and Latinx individuals, respectively. Changes for the male MSM cohort were negligible: 0.3% for Black and 0.7% for Latinx. With respect to DR. MMEN, 42% of participants from 2017 to 2019 earned college scholarships, and 25% of students from the 2017–2018 cohort matriculated to a combined college–medical program. Survey data showed that 100% of DR. MMEN participants found the program useful. Analysis of qualitative data revealed that participants considered pursuing a career in neurosurgery or in another medical field. Diligence and a passion for medicine were identified as the top two most important lessons in the program, and witnessing patient satisfaction and observing a neurosurgery operation were described as the most important experiences. Participants considered availability to give advice and feedback and a passion for teaching as the principal attributes of their mentors. CONCLUSIONS Over the past 6 years, the slight increase in Black and Latinx MSMs has not been significant enough to remedy ethnoracial disparities among MSMs. In particular, Black male matriculation to medical school has remained stagnant. The DR. MMEN program is a promising model to inspire young scholars and improve diversity within neuroscience and medicine at large.

BACKGROUND The treatment of glioblastoma (GBM) poses many challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by a low mutational burden and low infiltration by T cells. The combination of ICI with other treatment modalities may improve efficacy. METHODS Patients with recurrent GBM were treated with 800 mg avelumab, a human IgG1 antibody directed against PD-L1, either alone (in part A) or within a week after MRI-guided laser interstitial thermal therapy (LITT, in part B) and by-weekly thereafter (NCT03341806). To spare steroid use, bevacizumab was allowed to be combined with avelumab. The primary objective was to characterize the tolerability and safety of the regimen. The secondary objectives included overall survival, progression-free survival, and signature of plasma analytes. RESULTS A total of 12 patients (median age 64, range 37 - 73) enrolled from June 2018 to November 2019, 5 in part A and 7 in part B. Three serious adverse events (SAE) occurred in the same patient, not leading to death. There were 94 AEs reported, 5 grade 3, 28 grade 2, and 61 grade 1. The median PFS was 16.7 weeks (range 7.4-56.7) for patients in Part A and 30.9 weeks (range 8.5-77.7) for patients in Part B. The median survival for patients in part A was 11 months and 13.5 months for part B. The risk ratio of death by combining bevacizumab was 0.573 (p=0.258) with significantly decreased levels of peripheral blood plasma inflammatory markers such as EGF, CXCL5, VEGFA, LAP.TGβ1, ANGPT2 in women. CONCLUSIONS Avelumab was generally well-tolerated, and the combination with LITT had a manageable safety profile and increased survival in a subset of patients. The addition of bevacizumab may increase survival by lowering cytokine expression in a gender-dependent manner. These results warrant further investigation in the next phase study.

Promoting workplace diversity leads to a variety of benefits related to a broader range of perspectives and insights. Underrepresented in medicine (URiM), including African Americans, Latinx, and Natives (Americans/Alaskan/Hawaiians/Pacific Islanders), are currently accounting for approximately 40% of the US population.To establish a snapshot of current URiM representation within academic neurosurgery (NS) programs and trends within NS residency.All 115 NS residencies and academic programs accredited by the Accreditation Council for Graduate Medical Education in 2020 were included in this study. The National Residency Matching Program database was reviewed from 2011 to 2020 to analyze URiM representation trends over time within the NS resident workforce. The academic rank, academic and clinical title(s), subspecialty, sex, and race of URiM NS faculty (NSF) were obtained from publicly available data.The Black and Latinx NS resident workforce currently accounts for 4.8% and 5.8% of the total workforce, respectively. URiM NSF are present in 71% of the Accreditation Council for Graduate Medical Education-accredited NS programs and account for 8% (148 of 1776) of the workforce. Black and Latinx women comprise 10% of URiM NSF. Latinx NSFs are the majority within the URiM cohort for both men and women. URiM comprise 5% of all department chairs. All are men. Spine (26%), tumor (26%), and trauma (17%) were the top 3 subspecialties among URiM NSF.NS has evolved, expanded, and diversified in numerous directions, including race and gender representation. Our data show that ample opportunities remain to improve URiM representation within NS.

These recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM). QUESTION (Q1): In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy?Level III: Adult patients with pGBM might derive benefit in treatment with TMZ, especially those who progress after more than 5 months of TMZ-treatment free interval.Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohyperthermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy. There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits. QUESTION (Q2): In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy?Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a recommendation about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen. QUESTION (Q3): In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy?Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM.Other cytotoxic therapies like perillyl acohol or ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy. QUESTION (Q4): In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy?Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM. There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM. QUESTION (Q5): In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy?Level III: Oncolytic virotherapy is not suggested in patients with pGBM.

Aneurysm clipping requires the proficiency of several skills, yet the traditional way of practicing them has been recently challenged. The use of simulators could be an alternative educational tool. The aim of this data analysis is to provide further evaluation of a reusable low-cost 3D printed training model we developed for aneurysm clipping [1]. The simulator was designed to replicate the bone structure, arteries and targeted aneurysms. Thirty-two neurosurgery residents performed a craniotomy and aneurysm clipping using the model and then filled out a survey. The survey was designed in two parts: a 5-point Likert scale questionnaire and three questions requiring written responses [1]. Two dimensions of the model were evaluated by the questionnaire: the face validity, assessed by 5 questions about the realism of the model, and the content validity, assessed by 6 questions regarding the usefulness of the model during the different steps of the training procedure. The three questions requiring written responses referred to the strengths and weaknesses of the simulator and a global yes/no question as to whether or not they would repeat the experience. Demographic data, experience level and survey responses of the residents were grouped in a dataset [2]. A descriptive analysis was performed for each dimension. Then, the groups were compared according to their level of expertise (Junior and Senior groups) with an independent sample t-test. A Confirmatory Factor Analysis (CFA) was estimated, using a Weighted Least Squares Mean Variance adjusted (WLSMV) which works best for the ordinal data [3]. Fitness was calculated using chi-square (χ2) test, Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), and the Root Mean Square Error of Approximation (RMSEA). A non-significant χ2, CFI and TLI greater than 0.90 and RMSEA < 0.08 were considered an acceptable fit [4]. All data analysis was performed using IBM SPSS 23.0 statistical software. Data are reported as mean + standard deviation (SD). A probability p < 0.05 was considered significant. Exploratory Factor Analysis was done to explore the factorial structure of the 11-items scale in the sample, first we performed a principal components analysis. The Kaiser-Meyer-Olkin measure verified the sampling adequacy for the analysis (KMO = 0.784; Bartlett's Test of Sphericity χ2 (55) = 243.44, p < .001), indicating correlation is adequate for factor analysis. Considering Eigen values greater than 1, a two-factor solution explained 73.1% of the variance but left one item in factor 2 (Q 11). The results of this factor analysis are presented in Table 1. Confirmatory Factor Analysis, considering only the 10 items in the first factor (removing question 11 of our model), was performed. This model reached the following fit: χ2 (35) = 38.821, p > .05; CFI = 0.997; TLI = 0.996; RMSEA 0.058, without any error terms to exhibit covariance. Regarding the reliability of the questionnaire, the internal consistency was explored in the 10 items selected in the confirmatory factor analysis with an alpha coefficient (α = 0.941).

Neuroendocrine dysfunction includes suspected hyper- and hypofunction of the pituitary gland. Causative lesions may include primary masses of the pituitary such as pituitary microadenomas and macroadenomas, as well as extrinsic masses, typically centered in the suprasellar cistern. Clinical syndromes related to hormonal dysfunction can be caused by excessive hormonal secretion or by inhibited secretion due to mass effect upon elements of the hypothalamic-pituitary axis. Additionally, complications such as hemorrhage may be seen in the setting of an underlying mass and can result in hormonal dysfunction. MRI with high-resolution protocols is the best first-line test to evaluate the sella turcica and parasellar region. CT provides complementary information regarding bony anatomy, and may be appropriate as a first-line test in certain instances, but it provides less detail and lesion characterization when compared to MRI. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

This article presents guidelines for imaging utilization in patients presenting with hearing loss or vertigo, symptoms that sometimes occur concurrently due to proximity of receptors and neural pathways responsible for hearing and balance. These guidelines take into account the superiority of CT in providing bony details and better soft-tissue resolution offered by MRI. It should be noted that a dedicated temporal bone CT rather than a head CT best achieves delineation of disease in many of these patients. Similarly, optimal assessment often requires a dedicated high-resolution protocol designed to assess temporal bone and internal auditory canals even though such a study will be requested and billed as a brain MRI. Angiographic techniques are helpful in some patients, especially in the setting of vertigo. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

OBJECTIVE Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors’ knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA–induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity. METHODS This single-arm, multicenter, prospective study included adults aged 18–80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3–5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables. RESULTS Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume. CONCLUSIONS PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.

To provide the status of women neurosurgeons (WNS) in academic faculty and/or leadership positions in neurosurgery in the United States.Neurosurgery academic programs were defined as having an Accreditation Council for Graduate Medical Education (ACGME) neurosurgery residency program (NSRP). Using a Google search, gender, academic rank, postgraduate degrees, academic and clinical titles, and subspecialty were recorded for each neurosurgery faculty. Officer gender was recorded for the top 7 neurosurgery U.S. organizations, 7 subspecialty sections, and 50 state neurosurgical societies.WNS were faculty at 77% (89/115) of ACGME NSRPs and constituted 10% of the workforce (186/1773). WNS residents were in 92% of ACGME NSRPs and constituted 19% of the workforce (293/1515). Two NSRPs (8%) had neither WNS faculty nor WNS residents. Of NSRPs without WNS faculty, 52% (13/25) had a faculty size10. WNS accounted for 3% of NSRP chair positions. Academic rank of WNS faculty was lower than academic rank of men neurosurgeons faculty (P0.05). WNS faculty had a higher number of postgraduate degrees (P0.05). Pediatrics was the most common subspecialty (30%) among WNS. Over time, WNS held 1% of the leadership positions within the top 7 U.S. neurosurgery organizations and 7% within the 7 subspecialty sections. Over the past 20 years, 28% (14/50) of U.S. state neurosurgical societies had WNS serve as president.In 2020, the gender gap for U.S. WNS faculty and residents still exists. By providing informed benchmarks, our study might help neurosurgery organizations, medical school leadership, hiring committees, editors, and conference speakers to plan their next steps.

BACKGROUND: Detection of glioma recurrence remains a challenge in modern neuro-oncology. Noninvasive radiographic imaging is unable to definitively differentiate true recurrence versus pseudoprogression. Even in biopsied tissue, it can be challenging to differentiate recurrent tumor and treatment effect. We hypothesized that intraoperative stimulated Raman histology (SRH) and deep neural networks can be used to improve the intraoperative detection of glioma recurrence. METHODS: We used fiber laser–based SRH, a label-free, nonconsumptive, high-resolution microscopy method (

The American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Section on Tumors was formed in December of 1984 as the first professional organization devoted to the study and treatment of brain tumors. One year earlier, the Journal of Neuro-Oncology had been established and went on to be sponsored by the Joint Section on Tumors. To celebrate the 35th anniversary of the founding of the Section, we are thrilled to bring you this special issue of Journal of Neuro-Oncology in which current leaders of the Joint Section on Tumors highlight their work and the work of others that have led to significant recent advances in the management of tumors of the central nervous system.

OBJECTIVESub-Saharan Africa (SSA) represents 17% of the world’s land, 14% of the population, and 1% of the gross domestic product. Previous reports have indicated that 81/500 African neurosurgeons (16.2%) worked in SSA—i.e., 1 neurosurgeon per 6 million inhabitants. Over the past decades, efforts have been made to improve neurosurgery availability in SSA. In this study, the authors provide an update by means of the polling of neurosurgeons who trained in North Africa and went back to practice in SSA.METHODSNeurosurgeons who had full training at the World Federation of Neurosurgical Societies (WFNS) Rabat Training Center (RTC) over the past 16 years were polled with an 18-question survey focused on demographics, practice/case types, and operating room equipment availability.RESULTSData collected from all 21 (100%) WFNS RTC graduates showed that all neurosurgeons returned to work to SSA in 12 different countries, 90% working in low-income and 10% in lower-middle-income countries, defined by the World Bank as a Gross National Income per capita of ≤ US$995 and US$996–$3895, respectively. The cumulative population in the geographical areas in which they practice is 267 million, with a total of 102 neurosurgeons reported, resulting in 1 neurosurgeon per 2.62 million inhabitants. Upon return to SSA, WFNS RTC graduates were employed in public/private hospitals (62%), military hospitals (14.3%), academic centers (14.3%), and private practice (9.5%). The majority reported an even split between spine and cranial and between trauma and elective; 71% performed between 50 and more than 100 neurosurgical procedures/year. Equipment available varied across the cohort. A CT scanner was available to 86%, MRI to 38%, surgical microscope to 33%, endoscope to 19.1%, and neuronavigation to 0%. Three (14.3%) neurosurgeons had access to none of the above.CONCLUSIONSNeurosurgery availability in SSA has significantly improved over the past decade thanks to the dedication of senior African neurosurgeons, organizations, and volunteers who believed in forming the new neurosurgery generation in the same continent where they practice. Challenges include limited resources and the need to continue expanding efforts in local neurosurgery training and continuing medical education. Focus on affordable and low-maintenance technology is needed.

Apparent increases in the size of cerebral metastases after stereotactic radiosurgery (SRS) can be caused by pseudoprogression or true disease progression, which poses a diagnostic challenge at conventional MRI. The purpose of this study was to assess whether interval change in DWI and perfusion MRI parameters can differentiate pseudoprogression from progressive disease after treatment with SRS.Patients with apparent growth of cerebral metastases after SRS treatment who underwent pre- and post-SRS DWI, dynamic susceptibility contrast (DSC)-MRI, and perfusion dynamic contrast-enhanced (DCE)-MRI were retrospectively evaluated. Final assignment of pseudoprogression or progressive disease was determined at 6-month follow-up imaging using the Response Assessment in Neuro-Oncology Brain Metastases criteria. Mean values of apparent diffusion coefficient (ADC), DCE-MRI-derived volume transfer constant (KOf 102 cerebral metastases evaluated, 32 lesions in 29 patients met our inclusion criteria. The mean duration of follow-up was 7.2 months (range, 6-14 months). Twenty-two lesions were determined as pseudoprogression, and 10 lesions were determined as progressive disease using the Response Assessment in Neuro-Oncology Brain Metastases criteria at 6-month follow-up MRI. The interval change pattern of our imaging parameters matched the expected patterns of treatment response for ADC (23/32 lesions; 72%; p = 0.055; odds ratio, 5.1), KPseudoprogression can be distinguished from disease progression in cerebral metastases treated with SRS via an interval decrease in relative CBV and K

Background For the first time in Southeast Asia, a Fundamentals of Neurosurgery Boot Camp was held at the University of Medicine 1 in Yangon, Myanmar, February 24–26, 2017. The aim of this course was to teach and train fundamental skills to neurosurgery residents. Methods The Myanmar Neurosurgical Society, Foundation for International Education in Neurosurgery, Society for Neurological Surgeons, The University of Medicine 1 in Yangon, Myanmar, and the Henry Ford Department of Neurosurgery developed a 2-day resident training course. Day 1 activities consisted of lectures by faculty, small group case discussions, and industry-supported demonstrations of surgical techniques. Day 2 activities consisted of hands-on skill stations for common neurosurgical procedures with each station supervised by attending faculty. Written evaluations were distributed before the meeting, immediately after the meeting, and 6 months after the meeting. Results Boot camp attendees included 40 residents and 24 neurosurgical faculty from Myanmar, Cambodia, Nepal, Singapore, South Korea, Thailand, and Vietnam. There were 35 evaluations completed before the boot camp, 34 completed immediately after boot camp, and 20 completed 6 months after boot camp. Knowledge of participants improved from 62.75% before boot camp to 71.50% 6 months after boot camp (P = 0.046). Conclusions Boot camps provide fundamental didactic and technical exposure to trainees in developed and developing countries and help standardize training in basic neurosurgical competencies, while exposing local faculty to important teaching methods. This model provides a sustainable solution to educational needs and demonstrates to local neurosurgeons how they can take ownership of the educational process.

Differentiation of radiation necrosis (RN) from recurrent tumor (RT) in treated patients with glioblastoma remains a diagnostic challenge. The purpose of this study is to evaluate the diagnostic performance of multiparametric MRI in distinguishing RN from RT in patients with glioblastoma, with the use of a combination of MR perfusion and diffusion parameters.Patients with glioblastoma who had a new enhancing mass develop after completing standard treatment were retrospectively evaluated. Apparent diffusion coefficient (ADC), volume transfer constant (KOf a total of 70 patients evaluated, 46 (34 with RT and 12 with RN) met our inclusion criteria. Patients with RT had significantly higher mean rCBV (p0.001) and KIn patients with treated glioblastoma, rCBV outperforms ADC and K

Tinnitus is the perception of sound in the absence of an external source. It is a common symptom that can be related to hearing loss and other benign causes. However, tinnitus may be disabling and can be the only symptom in a patient with a central nervous system process disorder. History and physical examination are crucial first steps to determine the need for imaging. CT and MRI are useful in the setting of pulsatile tinnitus to evaluate for an underlying vascular anomaly or abnormality. If there is concomitant asymmetric hearing loss, neurologic deficit, or head trauma, imaging should be guided by those respective ACR Appropriateness Criteria® documents, rather than the presence of tinnitus. Imaging is not usually appropriate in the evaluation of subjective, nonpulsatile tinnitus that does not localize to one ear. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Background The neurosurgical boot camp has been fully incorporated into U.S. postgraduate education. This is the first implementation of the neurosurgical boot in a developing country. To advance neurosurgical education, we developed a similar boot camp program, in collaboration with Bolivian neurosurgeons, to determine its feasibility and effectiveness in an international setting. Methods In a collective effort, the Bolivian Society for Neurosurgery, Foundation for International Education in Neurological Surgery, Solidarity Bridge, and University of Massachusetts organized and executed the first South American neurosurgical boot camp in Bolivia in 2015. Both U.S. and Bolivian faculty led didactic lectures followed by a practicum day using mannequins and simulators. South American residents and faculty were surveyed after the course to determine levels of enthusiasm and their perceived improvement in fund of knowledge and course effectiveness. Results Twenty-four neurosurgery residents from 5 South American countries participated. Average survey scores ranged between 4.2 and 4.9 out of 5. Five Bolivian neurosurgeons completed the survey with average scores of 4.5–5. This event allowed for Bolivian leaders in the field to unify around education, resulting in the formation of an institute to continue similar initiatives. Total cost was estimated at $40 000 USD; however, significant faculty, industry, and donor support helped offset this amount. Conclusion The first South American neurosurgical boot camp had significant value and was well received in Bolivia. This humanitarian model provides a sustainable solution to education needs and should be expanded to other regions as a means for standardizing the core competencies in neurosurgery.

Communicating hydrocephalus (cHCP) after radiosurgery (RS) for vestibular schwannomas (VS) has been reported. Many hypothetical mechanisms for this pathology have been proposed without consensus. The aim of this study is to determine if the platform used to treat the disease, Gamma Knife (GK) versus linear accelerator (LINAC)-based RS, makes a difference in outcome. We conducted a meta-analysis of databases PubMed and Cochrane to identify all articles for the period January 2000–August 2018 with the following inclusion criteria: (1) VS treated with single fraction SRS (2) > 10 patients (3) original reports only (4) hydrocephalus reported as complication (5) human study. A total of 7039 and 988 VS patients reported in 35 and 10 papers were treated with GK or LINAC RS, respectively. Demographic baseline characteristics not reported in aggregate did not differ between the two groups. The incidence of cHCP was 3% [95% CI 2–4] and 2% [95% CI 1–3] for GK and LINAC RS patients, respectively. Surgical CSF diversion was performed in 88% and 68% of patients evaluated for cHPC in the GK and LINAC group, respectively. Follow-up range was 30–150 and 29–92 months for GK and LINAC, respectively. The incidence of cHCP following RS for VS is very low in both GK and LINAC treated patients, albeit not identical. The higher reported surgical intervention rate for VS patients treated with GK RS might be multi-factorial, including longer follow-up in the GK group.

Background Machine learning (ML) is an application of artificial intelligence (AI) that gives computer systems the ability to learn data, without being explicitly programmed. Currently, ML has been successfully used for optical character recognition, spam filtering, and face recognition. The aim of the present study was to review the current applications of ML in the field of neuro-oncology. Methods We conducted a systematic literature review using the PubMed and Cochrane databases using a keyword search for January 30, 2000 to March 31, 2018. The data were clustered for neuro-oncology scope of ML into 3 categories: patient outcome predictors, imaging analysis, and gene expression. Results Data from 5346 patients in 29 studies were used to develop ML-based algorithms (MLBAs) in neuro-oncology. MLBAs were used to predict the outcomes for 2483 patients, with a sensitivity range of 78%–98% and specificity range of 76%–95%. In all studies, the MLBAs had greater accuracy than the conventional ones. MLBAs for image analysis showed accuracy in diagnosing low-grade versus high-grade gliomas, ranging from 80% to 93% and 90% for diagnosing high-grade glioma versus lymphoma. Seven studies used MLBAs to analyze gene expression in neuro-oncology. Conclusions MLBAs in neuro-oncology have been shown to predict patients' outcomes more accurately than conventional parameters in a retrospective analysis. If their high diagnostic accuracy in imaging analysis and detection of somatic mutations are corroborated in prospective studies, the use of tissue diagnosis or liquid biopsy might be curtailed. Finally, MLBAs are promising to help guide targeted therapy, can lead to personalized medicine, and open areas of study in the cancer cellular signaling system, not otherwise known.

OBJECT Women compose a minority of neurosurgery residents, averaging just over 10% of matched applicants per year during this decade. A recent review by Lynch et al. raises the concern that women may be at a higher risk than men for attrition, based on analysis of a cohort matched between 1990 and 1999. This manuscript aims to characterize the trends in enrollment, attrition, and postattrition careers for women who matched in neurosurgery between 2000 and 2009. METHODS Databases from the American Association of Neurological Surgeons (AANS) and the American Board of Neurological Surgery (ABNS) were analyzed for all residents who matched into neurosurgery during the years 2000–2009. Residents were sorted by female gender, matched against graduation records, and if graduation was not reported from neurosurgery residency programs, an Internet search was used to determine the residents’ alternative path. The primary outcome was to determine the number of women residents who did not complete neurosurgery training programs during 2000–2009. Secondary outcomes included the total number of women who matched into neurosurgery per year, year in training in which attrition occurred, and alternative career paths that these women chose to pursue. RESULTS Women comprised 240 of 1992 (12%) matched neurosurgery residents during 2000–2009. Among female residents there was a 17% attrition rate, compared with a 5.3% male attrition rate, with an overall attrition rate of 6.7%. The majority who left the field did so within the first 3 years of neurosurgical training and stayed in medicine—pursuing anesthesia, neurology, and radiology. CONCLUSIONS Although the percentage of women entering neurosurgical residency has continued to increase, this number is still disproportionate to the overall number of women in medicine. The female attrition rate in neurosurgery in the 2000–2009 cohort is comparable to that of the other surgical specialties, but for neurosurgery, there is disparity between the male and female attrition rates. Women who left the field tended to stay within medicine and usually pursued a neuroscience-related career. Given the need for talented women to pursue neurosurgery and the increasing numbers of women matching annually, the recruitment and retention of women in neurosurgery should be benchmarked and assessed.