Publications by authors named "Lola B Chambless"

89 Publications

An Examination of Standardized Letters of Recommendation Rating Scales Among Neurosurgical Residency Candidates During the 2020-2021 Application Cycle.

Neurosurgery 2021 Nov;89(6):1005-1011

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Background: Letters of recommendation (LORs) are historically an important, though subjective, component of the neurosurgery residency application process. Standardized LORs (SLORs) were introduced during the 2020 to 2021 application cycle. The intent of SLORs is to allow objective comparison of applicants and to reduce bias.

Objective: To examine the utility of SLORs during this application cycle. We hypothesized that "grade inflation" and poor inter-rater reliability, as described by other specialties using SLORs, would limit the utility of SLORs in their current form.

Methods: This cross-sectional study analyzed all SLORs submitted to a single neurosurgery residency program over the 2020 to 2021 cycle. Data from 7 competency domains and the overall rating were recorded and stratified by academic category of letter writer. Inter-rater reliability was evaluated using Krippendorff's alpha.

Results: One or more SLORs was submitted as part of 298 of 393 applications (76%). Approximately 58.3% of letters written by neurosurgery chairpersons rated a given applicant as being within the top 5% across all competencies. Approximately 44.4% of program director letters similarly rated applicants as amongst the top 5%, while 73.2% and 81.4% of letters by other neurosurgeons and general surgery evaluators, respectively, rated applicants in the top 5%. Inter-rater reliability was poor (<0.33) in all rating categories, including overall (α = 0.18).

Conclusion: The utility of the first iteration of SLORs in neurosurgery applications is undermined by significant "grade inflation" and poor inter-rater reliability. Improvements are necessary for SLORs if they are to provide meaningful information in future application cycles.
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http://dx.doi.org/10.1093/neuros/nyab346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600167PMC
November 2021

Team Sport Participation Protects Against Burnout During Neurosurgery Training: Cross-Sectional Survey Study.

World Neurosurg 2021 Dec 7;156:e104-e110. Epub 2021 Sep 7.

Department of Neurological Surgery, Vanderbilt University Medical Center, Medical Center North, Nashville, Tennessee, USA.

Objective: Burnout is experienced by up to two thirds of neurosurgery residents. Team sport participation as an adolescent protects against adverse mental health outcomes in adulthood. The objective of this study was to determine whether high school or collegiate team sport participation is associated with improved psychological well-being during neurosurgery residency.

Methods: A cross-sectional survey study of U.S. neurosurgery residents was conducted between June 2020 and February 2021. Outcomes included self-ratings of sadness, anxiety, stress, burnout, optimism, and fulfillment, on 100-point scales, which were averaged into a "Burnout Composite Score" (BCS). Respondents were grouped and compared according to their prior self-reported participation in team sports (participants vs. nonparticipants). A 3-way analysis of variance tested the effects of resident level, exercise days, and team sport participation on BCS.

Results: Of 229 submitted responses, 228 (99.5%) provided complete data and 185 (81.1%) residents participated in team sports. Days/week of exercise was similar across groups (2.5 ± 1.8 vs. 2.1 ± 1.8, P = 0.20). The team sport group reported lower mean BCS (37.1 vs. 43.6 P = 0.030, Cohen d = 0.369). There was a significant interaction between prior team sport participation and exercise regimen on BCS (F [3, 211] = 3.39, P = 0.019, n = 0.046), such that more exercise days per week was associated with decreased BCS for prior team sport athletes (F [3, 211] = 11.10, P < 0.0005), but not for nonparticipants (F [3, 211] = 0.476, P = 0.699). The positive impact of prior team sport participation was more pronounced for senior residents (-11.5 points, P = 0.016) than junior residents (-4.3 points, P = 0.29).

Conclusions: Prior team sport participation was associated with lower BCS among neurosurgery residents, an effect more pronounced during senior residency. Lessons imparted during early team sport experience may have profound impacts on reducing burnout throughout a 7-year neurosurgery residency.
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http://dx.doi.org/10.1016/j.wneu.2021.08.146DOI Listing
December 2021

Data-Driven Residency Training: A Scoping Review of Educational Interventions for Neurosurgery Residency Programs.

Neurosurgery 2021 Oct;89(5):750-759

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Background: Neurosurgery residency programs are tasked with imparting large volumes of both clinical knowledge and technical skill to trainees in limited time. Many investigators have described local practices, which may offer evidence-based interventions in neurosurgical residency education, but this literature has not been systematically reviewed.

Objective: To perform a scoping review of educational practices in neurosurgery, which are supported by quantitative, peer-reviewed research.

Methods: A scoping review of the literature was performed. PubMed, Embase, and Web of Science databases were queried for articles describing educational interventions for neurosurgery residents, which included a quantitative assessment of the effect on resident performance.

Results: From an initial set of 1785 unique articles, 29 studies were ultimately screened and included. Studies were into the following 6 topics: (1) didactics and curricula (n = 13), (2) nontechnical skills (n = 6), (3) wellness and burnout (n = 4), (4) assessment and feedback (n = 2), (5) mentorship and career development (n = 2), and (6) research (n = 2). Individual study results were described.

Conclusion: Several educational interventions in neurosurgical training are supported by quantitative evidence. Methodological shortcomings are prevalent among studies of education, particularly in the selection of meaningful outcome measures. A summary of evidence-based considerations is provided for current and future program directors.
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http://dx.doi.org/10.1093/neuros/nyab322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510850PMC
October 2021

Subgroup and subtype-specific outcomes in adult medulloblastoma.

Acta Neuropathol 2021 11 18;142(5):859-871. Epub 2021 Aug 18.

Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Chonnam, South Korea.

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p < 0.0001). Five-year progression-free survival (PFS) for WNT, SHH, Group 3, and Group 4 tumours was 64.4 (48.0-86.5), 61.9% (51.6-74.2), 80.0% (95% CI 51.6-100.0), and 44.9% (95% CI 28.6-70.7), respectively (p = 0.06). None of the clinical variables (age, sex, metastatic status, extent of resection, chemotherapy, radiotherapy) were associated with subgroup-specific PFS. Survival among patients with SHH tumours was significantly worse for cases with chromosome 3p loss (HR 2.9, 95% CI 1.1-7.6; p = 0.02), chromosome 10q loss (HR 4.6, 95% CI 2.3-9.4; p < 0.0001), chromosome 17p loss (HR 2.3, 95% CI 1.1-4.8; p = 0.02), and PTCH1 mutations (HR 2.6, 95% CI 1.1-6.2; p = 0.04). The prognostic significance of 3p loss and 10q loss persisted in multivariable regression models. For Group 4 tumours, chromosome 8 loss was strongly associated with improved survival, which was validated in a non-overlapping cohort (combined cohort HR 0.2, 95% CI 0.1-0.7; p = 0.007). Unlike in pediatric medulloblastoma, whole chromosome 11 loss in Group 4 and chromosome 14q loss in SHH was not associated with improved survival, where MYCN, GLI2 and MYC amplification were rare. In sum, we report unique subgroup-specific cytogenetic features of adult medulloblastoma, which are distinct from those in younger patients, and correlate with survival disparities. Our findings suggest that clinical trials that incorporate new strategies tailored to high-risk adult medulloblastoma patients are urgently needed.
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http://dx.doi.org/10.1007/s00401-021-02358-4DOI Listing
November 2021

Perceptions of the Virtual Neurosurgery Application Cycle During the Coronavirus Disease 2019 (COVID-19) Pandemic: A Program Director Survey.

World Neurosurg 2021 10 4;154:e590-e604. Epub 2021 Aug 4.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address:

Objective: The novel coronavirus disease 2019 (COVID-19) pandemic has led to a shift to virtual residency interviews for the 2020-2021 neurosurgery match, with unknown implications for stakeholders. This study seeks to analyze the perceptions of residency program directors (PDs) and associate program directors (APDs) regarding the current virtual format used for residency selection and interviews.

Methods: An anonymous, 30-question survey was constructed and sent to 115 neurosurgery PDs and 26 APDs to assess respondent demographics, factors used to review applicants, perceptions of applicants and applicant engagement, perceptions of standardized letters and interview questions, the effect of the virtual interview format on various stakeholders, and the future outlook for the virtual residency interview format.

Results: A total of 38 PDs and APDs completed this survey, constituting a response rate of 27.0%. Survey respondents received significantly more Electronic Residency Application Service applications in the 2020-2021 cycle compared with the 2019-2020 cycle (P = 0.0029). Subinternship performance by home-rotators, (26.3%), letters of recommendation (23.7%), and Step 1 score (18.4%) were ranked as the most important factors for evaluating candidates during the current virtual application cycle.

Conclusions: Our study highlights that applicants applied to a greater number of residency programs compared with years prior, that the criteria used by PDs/APDs to evaluate applicants remained largely consistent compared to previous years, and that the virtual residency interview format may disproportionately disadvantage Doctor of Osteopathic medicine and international medical graduate applicants. Further exploring attitudes toward signaling mechanisms and standardized letters may serve to inform changes to future neurosurgery match cycles.
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http://dx.doi.org/10.1016/j.wneu.2021.07.078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461646PMC
October 2021

Outcomes of Transzygomatic Middle Cranial Fossa Approach for Skull Base Tumors-A Single Institutional Experience.

J Neurol Surg B Skull Base 2021 Jul 28;82(Suppl 3):e205-e210. Epub 2020 Mar 28.

Department of Otolaryngology, The Otology Group of Vanderbilt, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

 This study aimed to evaluate surgical outcomes after transzygomatic middle cranial fossa (MCF) (TZ-MCF) approach for tumor control in patients with large skull base lesions involving the MCF and adjacent sites.  This study was done at the tertiary skull base center.  This is a retrospective case series.  The main outcome measures were tumor control (recurrence), new-onset cranial neuropathies, facial nerve and audiometric outcomes, cerebrospinal fluid (CSF) leak, and wound complications.  Sixteen patients were identified with a median age of 45 years (range: 20-72). The mean maximum tumor dimension was 5.49 cm (standard deviation [SD]: 1.2, range: 3.1-7.3) and the mean tumor volume was 28.5 cm (SD: 18.8, range: 2.9-63.8). Ten (62.5%) tumors were left sided. The most common pathology encountered was meningioma (  = 7) followed by chondrosarcoma (  = 4). Mean follow-up was 36.3 (SD: 26.9) months. Gross total resection or near total resection was achieved in nine (56.2%) and planned subtotal resection was used in seven (43.7%). Postoperative additional new cranial nerve (CN) deficits included CN V (  = 1), CN III (  = 2), CN VI (  = 1), and CN X (  = 1). Major neurological morbidity (hemiplegia) was encountered in two patients with resolution. There were no cases of CSF leak, meningitis, hemorrhage, seizures, aphasia, or death. There was no recurrence or regrowth of residual tumor. Facial nerve function was preserved in all but one patient (House-Brackmann grade 2).  Various skull base tumors involving MCF with extension to adjacent sites can be successfully resected using the TZ-MCF approach in a multidisciplinary fashion. This approach yields optimal exposure and permits excellent tumor control with acceptable CN and neurological morbidity.
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http://dx.doi.org/10.1055/s-0040-1708881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289522PMC
July 2021

The Effect of Timing of Surgery in Pituitary Apoplexy on Continuously Valued Visual Acuity.

J Neurol Surg B Skull Base 2021 Jul 24;82(Suppl 3):e70-e78. Epub 2020 Jan 24.

Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

 Pituitary apoplexy is often treated urgently, but this is based on studies which assess vision categorically and dichotomizes the time interval between symptom onset and surgery which may introduce bias in measuring an association between the two.  This study was aimed to assess for a relationship between continuously valued surgery delay and visual acuity recovery after pituitary apoplexy.  In this retrospective study, all patients presenting with symptomatic pituitary apoplexy between 2004 and 2016 were identified from an institutional database. The primary endpoint was visual acuity improvement, measured as the difference in acuity from the pre- to postoperative period, and measured in Logarithm of the Minimal Angle of Resolution (LogMAR) units. Analysis was performed using continuous values of time delay and visual acuity to assess for an underlying association.  Thirty-two pituitary apoplexy patients were identified. Visual acuity deficits were reported in 81%. The median visual acuity was 0.35 LogMAR (Snellen's fraction 20/40) preoperatively, and 0.1 (20/25) postoperatively (  < 0.01). The time between symptom onset and surgery was not associated with improvement in visual acuity (  = 0.46). When the time delay and visual outcome were intentionally dichotomized, patients undergoing surgery within 2 days of symptom onset had 0.21 times the odds of a good visual outcome (95% confidence interval [CI]: 0.04-1.05).  When assessed as continuously valued measures, the time from symptom onset to surgical intervention and the improvement in visual acuity are not associated, although intentional dichotomization of data produced conflicting results.
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http://dx.doi.org/10.1055/s-0040-1701217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289513PMC
July 2021

Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma.

J Neurol Surg B Skull Base 2021 Jul 5;82(Suppl 3):e51-e58. Epub 2020 May 5.

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

 Hypofractionated stereotactic radiotherapy (HSRT) in two to five fractions may offer patients with large nonfunctioning pituitary adenomas (NFPAs) with chiasm involvement a safe and effective treatment over a single week. However, little has been reported regarding this novel approach.  We compared the feasibility, outcomes, and toxicity of single-fraction stereotactic radiosurgery and HSRT.  This study was conducted at a tertiary academic referral center.  After approval by the institutional review board, we performed a retrospective cohort study of patients treated at our institution with stereotactic radiosurgery (SRS) and HSRT for NFPA. Selection for SRS or HSRT was based on clinicopathologic factors including tumor size and cavernous sinus invasion at the discretion of the treating physician.  Local control, endocrinopathy, and radiation-associated toxicity were evaluated by binary logistic regression and Cox's proportional hazards regression.  A total of 45 patients with mean follow-up of 5 years were enrolled including 26 patients treated by HSRT with mean follow-up of 3 years and 19 patients treated by SRS with median follow-up of 6 years. Clinicopathologic characteristics were balanced between cohorts. Local failure at last follow-up was 5% in the SRS cohort and 8% in the HSRT cohort, and rates of post-SRS endocrinopathy were similar between each cohort. Late complications including radionecrosis, visual deficit, and secondary malignancy were minimal in either cohort.  HSRT is an appropriate treatment strategy for patients with NFPAs, particularly for optic pathway preservation in the setting of large tumors with chiasm involvement. Further studies are needed to optimize fractionated approaches and patient selection.
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http://dx.doi.org/10.1055/s-0040-1710518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289501PMC
July 2021

Progressive Vestibular Schwannoma following Subtotal or Near-Total Resection: Dose-Escalated versus Standard-Dose Salvage Stereotactic Radiosurgery.

J Neurol Surg B Skull Base 2021 Jul 26;82(Suppl 3):e9-e14. Epub 2020 May 26.

Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

 Local failure of incompletely resected vestibular schwannoma (VS) following salvage stereotactic radiosurgery (SRS) using standard doses of 12 to 13 Gy is common. We hypothesized that dose-escalated SRS, corrected for biologically effective dose, would have superior local control of high-grade VS progressing after subtotal or near-total resection compared with standard-dose SRS.  Retrospective cohort study.  Tertiary academic referral center.  Adult patients treated with linear accelerator-based SRS for progressive VS following subtotal or near-total resection.  Dose-escalated SRS was defined by a biologically effective dose exceeding a single-fraction 13-Gy regimen. Study outcomes were local control and neurologic sequelae of SRS. Binary logistic regression was used to evaluate predictors of study outcomes.  A total of 18 patients with progressive disease following subtotal (71%) and near-total (39%) resection of Koos grade IV disease (94%) were enrolled. Of the 18 patients, 7 were treated with dose-escalated SRS and 11 with standard-dose SRS. Over a median follow-up of 32 months after SRS, local control was 100% in the dose-escalated cohort and 91% in the standard-dose cohort (  = 0.95). Neurologic sequelae occurred in 28% of patients, including 60% of dose-escalated cohort and 40% of the standard-dose cohort (  = 0.12), although permanent neurologic sequelae were low at 6%.  Dose-escalated SRS has similar local control of recurrent VS following progression after subtotal or near-total resection and does not appear to have higher neurologic sequalae. Larger studies are needed.
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http://dx.doi.org/10.1055/s-0040-1712462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289534PMC
July 2021

In Reply: Neurosurgery Resident Interviews: The Prevalence and Impact of Inappropriate and Potentially Illegal Questions.

Neurosurgery 2021 08;89(3):E196-E197

Division of Neurosurgery University of Vermont Medical Center Burlington, Vermont, USA.

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http://dx.doi.org/10.1093/neuros/nyab219DOI Listing
August 2021

Mechatronic Design of a Two-Arm Concentric Tube Robot System for Rigid Neuroendoscopy.

IEEE ASME Trans Mechatron 2020 Jun 27;25(3):1432-1443. Epub 2020 Feb 27.

Department of Mechanical Engineering at Vanderbilt University, Nashville, TN 37235, USA.

Open surgical approaches are still often employed in neurosurgery, despite the availability of neuroendoscopic approaches that reduce invasiveness. The challenge of maneuvering instruments at the tip of the endoscope makes neuroendoscopy demanding for the physician. The only way to aim tools passed through endoscope ports is to tilt the entire endoscope; but, tilting compresses brain tissue through which the endoscope passes and can damage it. Concentric tube robots can provide necessary dexterity without endoscope tilting, while passing through existing ports in the endoscope and carrying surgical tools in their inner lumen. In this paper we describe the mechatronic design of a new concentric tube robot that can deploy two concentric tube manipulators through a standard neuroendoscope. The robot uses a compact differential drive and features embedded motor control electronics and redundant position sensors for safety. In addition to the mechatronic design of this system, this paper contributes experimental validation in the context of colloid cyst removal, comparing our new robotic system to standard manual endoscopy in a brain phantom. The robotic approach essentially eliminated endoscope tilt during the procedure (17.09° for the manual approach vs. 1.16° for the robotic system). The robotic system also enables a single surgeon to perform the procedure - typically in a manual approach one surgeon aims the endoscope and another operates the tools delivered through its ports.
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http://dx.doi.org/10.1109/tmech.2020.2976897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971161PMC
June 2020

Neurosurgery Resident Interviews: The Prevalence and Impact of Inappropriate and Potentially Illegal Questions.

Neurosurgery 2021 06;89(1):53-59

Division of Neurosurgery, University of Vermont Medical Center, Burlington, Vermont, USA.

Background: The impact of workplace discrimination has gained recognition. Nearly two-thirds of all medical residency applicants reported being asked inappropriate or potentially illegal interview questions. The use of such questions during neurosurgery residency interviews has not yet been studied.

Objective: To evaluate the prevalence of inappropriate or potentially illegal questions in residency interviews and the impact on applicants' rank lists.

Methods: All 2018 to 2019 United States neurosurgery resident applicants were anonymously surveyed. The survey included 46 questions focused on demographics; if they were asked questions regarding rank list, age, gender, marital status, family planning, religion, sexual orientation, or disability and whether such questions affected their rank list formation.

Results: Of 265 surveyed United States applicants, 133 (50%) responded. Most respondents were male (78%), 24% were married, and 10% had children. During the formal interview, 94% were asked at least 1 inappropriate or potentially illegal question. About 78% reported being asked about marital status, 29% were asked about intent to have children. About 46% reported being counseled on their personal life, 30% were asked about their ethnic background, and 15% were asked about their religion. A total of 2 candidates reported questions about mental illness/disability, and 2 candidates reported being asked about sexual orientation. About 45% of applicants that were asked at least 1 of these questions ranked those programs lower.

Conclusion: Nearly all (94%) neurosurgical residency applicants reported being asked at least 1 inappropriate or potentially illegal question during interviews. Our results indicate that inappropriate questions negatively affected program rankings.
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http://dx.doi.org/10.1093/neuros/nyab059DOI Listing
June 2021

Prognostic relevance of CSF and peri-tumoral edema volumes in glioblastoma.

J Clin Neurosci 2021 Feb 28;84:1-7. Epub 2020 Dec 28.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, United States. Electronic address:

Background: We conducted a segmental volumetric analysis of pre-operative brain magnetic resonance images (MRIs) of glioblastoma patients to identify brain- and tumor-related features that are prognostic of survival.

Methods: Using a dataset of 210 single-institutional adult glioblastoma patients, total volumes of the following tumor- and brain-related features were quantified on pre-operative MRIs using a fully automated segmentation tool: tumor enhancement, tumor non-enhancement, tumor necrosis, peri-tumoral edema, grey matter, white matter, and cerebrospinal fluid (CSF). Their association with survival using Cox regression models, adjusting for the well-known predictors of glioblastoma survival. The findings were verified in a second dataset consisting of 96 glioblastoma patients from The Cancer Imaging Archive and The Cancer Genome Atlas (TCIA/TCGA).

Results: CSF volume and edema were independently and consistently associated with overall survival of glioblastoma patients in both datasets. Greater edema was associated with increased hazard or decreased survival [adjusted hazard ratio (aHR) with 95% confidence interval (CI): 1.34 [1.08-1.67], p = 0.008 (institutional dataset); and, 1.44 [1.08-1.93], p = 0.013 (TCIA/TCGA dataset)]. Greater CSF volume also correlated with increased hazard or decreased survival [aHR 1.27 [1.02-1.59], p = 0.035 (institutional dataset), and 1.42 [1.03-1.95], p = 0.032 (TCIA/TCGA dataset)].

Conclusions: Higher brain CSF volume and higher edema levels at diagnosis are independently associated with decreased survival in glioblastoma patients. These results highlight the importance of a broader, quantitative brain-wide radiological analyses and invite investigations to understand tumor-related causes of increased edema and possibly increased CSF volume.
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http://dx.doi.org/10.1016/j.jocn.2020.12.014DOI Listing
February 2021

Predicting Discharge Disposition Following Meningioma Resection Using a Multi-Institutional Natural Language Processing Model.

Neurosurgery 2021 03;88(4):838-845

Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Machine learning (ML)-based predictive models are increasingly common in neurosurgery, but typically require large databases of discrete variables for training. Natural language processing (NLP) can extract meaningful data from unstructured text.

Objective: To present an NLP model that predicts nonhome discharge and a point-of-care implementation.

Methods: We retrospectively collected age, preoperative notes, and radiology reports from 595 adults who underwent meningioma resection in an academic center from 1995 to 2015. A total of 32 algorithms were trained with the data; the 3 best performing algorithms were combined to form an ensemble. Predictive ability, assessed by area under the receiver operating characteristic curve (AUC) and calibration, was compared to a previously published model utilizing 52 neurosurgeon-selected variables. We then built a multi-institutional model by incorporating notes from 693 patients at another center into algorithm training. Permutation importance was used to analyze the relative importance of each input to model performance. Word clouds and non-negative matrix factorization were used to analyze predictive features of text.

Results: The single-institution NLP model predicted nonhome discharge with AUC of 0.80 (95% CI = 0.74-0.86) on internal and 0.76 on holdout validation compared to AUC of 0.77 (95% CI = 0.73-0.81) and 0.74 for the 52-variable ensemble. The multi-institutional model performed similarly well with AUC = 0.78 (95% CI = 0.74-0.81) on internal and 0.76 on holdout validation. Preoperative notes most influenced predictions. The model is available at http://nlp-home.insds.org.

Conclusion: ML and NLP are underutilized in neurosurgery. Here, we construct a multi-institutional NLP model that predicts nonhome discharge.
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http://dx.doi.org/10.1093/neuros/nyaa585DOI Listing
March 2021

Virtual education in neurosurgery during the COVID-19 pandemic.

Neurosurg Focus 2020 12;49(6):E17

Departments of1Neurosurgery and.

Objective: Neurosurgical education in the US has changed significantly as a consequence of the novel coronavirus (COVID-19) pandemic. Institutional social distancing requirements have resulted in many neurosurgical programs utilizing video conferencing for educational activities. However, it is unclear how or if these practices should continue after the pandemic. The objective of this study was to characterize virtual education in neurosurgery and understand how it should be utilized after COVID-19.

Methods: A 24-question, 3-part online survey was administered anonymously to all 117 US neurosurgical residency programs from May 15, 2020, to June 15, 2020. Questions pertained to the current use of virtual conferencing, preferences over traditional conferences, and future inclinations. The Likert scale (1 = strongly disagree, 3 = neutral, 5 = strongly agree) was used. Comparisons were calculated using the Mann-Whitney U-test. Statistical significance was set at 0.05.

Results: One-hundred eight responses were recorded. Overall, 38 respondents (35.2%) were attendings and 70 (64.8%) were trainees. Forty-one respondents (38.0%) indicated attending 5-6 conferences per week and 70 (64.8%) attend national virtual conferences. When considering different conference types, there was no overall preference (scores < 3) for virtual conferences over traditional conferences. In regard to future use, respondents strongly agreed that they would continue the practice at some capacity after the pandemic (median score 5). Overall, respondents agreed that virtual conferences would partially replace traditional conferences (median score 4), whereas they strongly disagreed with the complete replacement of traditional conferences (median score 1). The most common choices for the partial replacement of tradition conferences were case conferences (59/108, 55%) and board preparation (64/108, 59%). Lastly, there was a significant difference in scores for continued use of virtual conferencing in those who attend nationally sponsored conferences (median score 5, n = 70) and those who do not (median score 4, n = 38; U = 1762.50, z = 2.97, r = 0.29, p = 0.003).

Conclusions: Virtual conferences will likely remain an integral part of neurosurgical education after the COVID-19 pandemic has abated. Across the country, residents and faculty report a preference for continued use of virtual conferencing, especially virtual case conferences and board preparation. Some traditional conferences may even be replaced with virtual conferences, in particular those that are more didactic. Furthermore, nationally sponsored virtual conferences have a positive effect on the preferences for continued use of virtual conferences.
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http://dx.doi.org/10.3171/2020.9.FOCUS20672DOI Listing
December 2020

Antiepileptic Drugs in the Management of Cerebral Metastases.

Neurosurg Clin N Am 2020 Oct;31(4):589-601

Department of Neurological Surgery, Vanderbilt University Medical Center, T-4224 Medical Center North, Nashville, TN 37232-2380, USA. Electronic address:

Seizures represent a common and debilitating complication of central nervous system metastases. The use of prophylactic antiepileptic drugs (AEDs) in the preoperative period remains controversial, but the preponderance of evidence suggests that it is not helpful in preventing seizure and instead poses a significant risk of adverse events. Studies of postoperative seizure prophylaxis have not shown substantial benefit, but this practice remains widespread. Careful analysis of the risk of seizure based on patient-specific factors, such as tumor location and primary tumor histology, should guide the physician's decision on the initiation and cessation of prophylactic AED therapy.
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http://dx.doi.org/10.1016/j.nec.2020.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054036PMC
October 2020

Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma.

Cell Rep Med 2020 Jun;1(3)

Departments of Pediatrics, Anatomy, and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA.

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.
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http://dx.doi.org/10.1016/j.xcrm.2020.100038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394286PMC
June 2020

International Medical Graduates Applying to Neurosurgical Residency in the United States Through the Lenses of an Applicant Versus a Program Director.

World Neurosurg 2020 10 16;142:299-300. Epub 2020 Jul 16.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

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http://dx.doi.org/10.1016/j.wneu.2020.07.046DOI Listing
October 2020

The neurosurgery residency interview: assessing applicant perspectives on question content, utility, and stress.

J Neurosurg 2020 07 17;134(6):1974-1982. Epub 2020 Jul 17.

2Division of Neurosurgery, University of Vermont Medical Center, Burlington, Vermont.

Objective: Residency interviews are integral to the recruitment process yet imperfect. Through surveys of neurosurgery residency applicants, the authors describe interview content and the perceived utility and stress of topics from the applicant's perspective.

Methods: All 2018-2019 neurosurgery resident applicants applying to three particular programs were surveyed. Across 10 interview topics, survey questions assessed topic frequency and the applicant's opinion of the utility and stress of each topic (Likert scale 1-5). Analyses included descriptive statistics, Spearman's rank correlation, and logistic regression.

Results: One hundred thirty-three of 265 surveyed US residency applicants (50%) responded. Extracurricular activities, research, future career, non-medicine interests, and small talk were discussed in all interviews. The least frequent topics included neurosurgical knowledge assessment (79%) and manual dexterity tests (45%). The most useful topics according to respondents were future career objectives (4.78 ± 0.49) and prior research (4.76 ± 0.50); the least useful were neurosurgical knowledge assessment (2.67 ± 1.09) and manual dexterity tests (2.95 ± 1.05). The most stressful topics were neurosurgical knowledge assessment (3.66 ± 1.23) and ethical/behavioral scenarios (2.94 ± 1.28). The utility and stress of manual dexterity tests and neurosurgical knowledge assessments were inversely correlated (r = -0.40, p < 0.01; r = -0.36, p < 0.01), whereas no such correlation existed for ethical/behavioral questions (r = -0.12, p = 0.18), indicating that ethical/behavioral questions may have been stressful but were potentially useful topics. Respondents who attended ≥ 15 interviews were more likely to be asked about the three most stressful topics (each p < 0.05). Respondents with children were less likely to be asked about ethical/behavioral scenarios (OR 0.13, 95% CI 0.03-0.52, p < 0.01).

Conclusions: Applicants found several of the most frequently discussed topics to be less useful, indicating a potential disconnect between applicant opinion and the faculty's preferred questions. Ethical/behavioral scenarios were rated as stressful but still useful, representing a potentially worthwhile type of question. These data provide several avenues for potential standardization and improvement of the interview process.
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http://dx.doi.org/10.3171/2020.4.JNS2046DOI Listing
July 2020

Unsupervised machine learning reveals risk stratifying glioblastoma tumor cells.

Elife 2020 06 23;9. Epub 2020 Jun 23.

Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States.

A goal of cancer research is to reveal cell subsets linked to continuous clinical outcomes to generate new therapeutic and biomarker hypotheses. We introduce a machine learning algorithm, Risk Assessment Population IDentification (RAPID), that is unsupervised and automated, identifies phenotypically distinct cell populations, and determines whether these populations stratify patient survival. With a pilot mass cytometry dataset of 2 million cells from 28 glioblastomas, RAPID identified tumor cells whose abundance independently and continuously stratified patient survival. Statistical validation within the workflow included repeated runs of stochastic steps and cell subsampling. Biological validation used an orthogonal platform, immunohistochemistry, and a larger cohort of 73 glioblastoma patients to confirm the findings from the pilot cohort. RAPID was also validated to find known risk stratifying cells and features using published data from blood cancer. Thus, RAPID provides an automated, unsupervised approach for finding statistically and biologically significant cells using cytometry data from patient samples.
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http://dx.doi.org/10.7554/eLife.56879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340505PMC
June 2020

Longitudinal Radiographic Outcomes of Vestibular Schwannoma in Single and Fractionated Stereotactic Radiosurgery: A Retrospective Cohort Study.

J Neurol Surg B Skull Base 2020 Jun 12;81(3):308-316. Epub 2019 Jun 12.

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

Management of vestibular schwannoma (VS) includes stereotactic radiosurgery (SRS) in single or fractionated treatments. There is a paucity of literature on the three-dimensional (3D) volumetric kinetics and radiological changes following SRS and no consensus on appropriate post-SRS surveillance imaging timeline. This is a retrospective cohort study with institutional review board approval. A total of 55 patients met study criteria. We collected volumetric kinetic data in VS treated with SRS over time using a target volume contouring software. We also tracked radiographic phenomena such as pseudoprogression and necrosis. A secondary objective was to describe our overall treatment success rate and any failures. For all treatments groups, pseudoprogression most typically occurred within 12 months post-SRS, after which tumor volumes on average normalized and then decreased from pretreatment size at the last follow-up. Only two patients required salvage therapy post-SRS and were considered SRS treatment failures. Both patients were in the five-fraction cohort but with a lower biologically equivalent dose. Our study is first to collect 3D volumetric kinetics of VS following single and fractionated SRS in contrast to extrapolations from single and two-dimensional measurements. Our longitudinal data also show initial increases in volume in the first 12 months post-SRS followed by later declines, setting up interesting questions regarding the utility of early posttreatment surveillance imaging in the asymptomatic patient. Finally, we show low rates of treatment failure (3.6%) and show in our cohort that SRS dose de-escalation posed a risk of treatment failure.
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http://dx.doi.org/10.1055/s-0039-1692642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253303PMC
June 2020

Secondary malignancy following stereotactic radiosurgery for benign neurologic disease: A cohort study and review of the literature.

J Radiosurg SBRT 2020 ;6(4):287-294

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.

Radiation-associated malignancy and malignant transformation are risks associated with stereotactic radiosurgery (SRS); however, incidence is uncertain. The purpose of our study is to present the rate of radiation-associated malignancy and malignant transformation at our institution. After IRB approval, we undertook a retrospective cohort study evaluating patients treated with Gamma Knife® or linac-based SRS between 1990 and 2014 for benign CNS pathology with at least 5 years of clinical follow-up. Risk of transformation was calculated using the Kaplan-Meier method. A total of 273 patients met selection criteria. Median clinical follow-up after SRS was 11 years (range 5-27). Over 3,216 patient-years following SRS, we found zero cases of radiation-associated malignancy and two cases of radiation-associated malignant transformation for a crude rate of 0.73% or case rate of 0.62 per 1,000 patient-years. The Kaplan-Meier risk of malignant transformation at 5, 10, and 15 years was 0.4% (95% CI 0.05% 2.6%). These data support the continued use of SRS for benign intracranial pathology without significant concern for secondary malignancy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065897PMC
January 2020

Body mass index and response to stereotactic radiosurgery in the treatment of refractory trigeminal neuralgia: A retrospective cohort study.

J Radiosurg SBRT 2020 ;6(4):253-261

Department of Radiation Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, PRB-B1003, Nashville, TN 37232, USA.

Stereotactic radiosurgery (SRS) is used as a noninvasive treatment option for patients with trigeminal neuralgia (TN), but the effect of obesity on pain relief post SRS, if any, is unknown. The primary goal of our study was to evaluate the association between obesity and response to SRS in patients with TN. We conducted an IRB-approved retrospective review of patients treated with SRS for TN between 2010 and 2017. Barrow Neurologic Institute (BNI) Score was assigned pre-and post-SRS to quantify pain level. Thirty-two patients (65% female) between the ages of 24 and 96 were studied with a median follow-up time of 11 months. Patients with BMI >25 were significantly less likely to have improvement in their symptoms with SRS (p = 0.005). Elevated BMI may be associated with worsened response to SRS in the treatment of TN.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065898PMC
January 2020

Current Volumetric Models Overestimate Vestibular Schwannoma Size Following Stereotactic Radiosurgery.

Otol Neurotol 2020 02;41(2):e262-e267

Department of Radiation Oncology.

Objective: Accurate volume assessment is essential for the management of vestibular schwannoma after stereotactic radiosurgery (SRS). A cuboidal approximation for volume is the standard surveillance method; however, this may overestimate tumor volume. We sought to evaluate several volumetric models and their suitability for post-SRS surveillance.

Study Design: Retrospective cohort study.

Setting: Tertiary referral center.

Patients: We evaluated 54 patients with vestibular schwannoma before and after SRS.

Intervention(s): Gold-standard volumes were obtained by a radiation oncologist using contouring software. Volume was also calculated by cuboidal, ellipsoidal, and spherical formulae using tumor diameters obtained by a neuroradiologist.

Main Outcome Measure(s): Percent error (PE) and absolute percent error (APE) were calculated. Paired t test evaluated bias, and the Bland-Altman method evaluated reproducibility. Linear regression evaluated predictors of model error.

Results: All models overestimated volume compared with the gold standard. The cuboidal model was not reproducible before SRS (p < 0.001), and no model was reproducible after SRS (cuboidal p < 0.001; ellipsoidal p = 0.02; spherical p = 0.02). Significant bias was present before SRS for the cuboidal model (p < 0.001), and post-SRS for all models [cuboidal (p < 0.001), ellipsoidal (p < 0.02), and spherical (p = 0.005)]. Model error was negatively associated with pretreatment volume for the cuboidal (PE p = 0.03; APE p = 0.03), ellipsoidal (PE p = 0.03; APE p = 0.04), and spherical (PE p = 0.02; APE p = 0.03) methods and lost linearity post-SRS.

Conclusions: The standard cuboidal practice for following vestibular schwannoma tumor volume after SRS overestimates size. Ellipsoidal and spherical estimations have improved performance but also overestimate volume and lack reliability post-SRS. The development of other volumetric models or application of contouring software should be investigated.
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http://dx.doi.org/10.1097/MAO.0000000000002488DOI Listing
February 2020

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

Nature 2019 10 9;574(7780):707-711. Epub 2019 Oct 9.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only <0.1% of 2,442 cancers, across 36 other tumour types. The mutations occur in 97% of adults (subtype SHHδ) and 25% of adolescents (subtype SHHα) with SHH medulloblastoma, but are largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5' splice-site binding region, and snRNA-mutant tumours have significantly disrupted RNA splicing and an excess of 5' cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivates tumour-suppressor genes (PTCH1) and activates oncogenes (GLI2 and CCND2), and represents a target for therapy. These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer.
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http://dx.doi.org/10.1038/s41586-019-1650-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141958PMC
October 2019

Scheduling Neurosurgery Residency Interviews: Avenues for Improvement.

World Neurosurg 2019 Oct;130:589-592

Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

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http://dx.doi.org/10.1016/j.wneu.2019.07.175DOI Listing
October 2019

Big Data Defined: A Practical Review for Neurosurgeons.

World Neurosurg 2020 Jan 25;133:e842-e849. Epub 2019 Sep 25.

Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA. Electronic address:

Background: Modern science and healthcare generate vast amounts of data, and, coupled with the increasingly inexpensive and accessible computing, a tremendous opportunity exists to use these data to improve care. A better understanding of data science and its relationship to neurosurgical practice will be increasingly important as we transition into this modern "big data" era.

Methods: A review of the literature was performed for key articles referencing big data for neurosurgical care or related topics.

Results: In the present report, we first defined the nature and scope of data science from a technical perspective. We then discussed its relationship to the modern neurosurgical practice, highlighting key references, which might form a useful introductory reading list.

Conclusions: Numerous challenges exist going forward; however, organized neurosurgery has an important role in fostering and facilitating these efforts to merge data science with neurosurgical practice.
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http://dx.doi.org/10.1016/j.wneu.2019.09.092DOI Listing
January 2020

Outcomes of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for refractory Cushing's disease.

Pituitary 2019 Dec;22(6):607-613

Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2220 Pierce Avenue, Preston Research Building, Rm B-1003, Nashville, TN, 37232-5671, USA.

Purpose: Hypofractionated stereotactic radiotherapy (HSRT) for refractory Cushing's disease may offer a condensed treatment schedule for patients with large tumors abutting the optic chiasm unsuitable for stereotactic radiosurgery (SRS). To-date only four patients have been treated by HSRT in the published literature. We investigated the feasibility, toxicity, and efficacy of HSRT compared to SRS.

Methods: After approval, we retrospectively evaluated patients treated at our institution for refractory Cushing's disease with SRS or HSRT. Study outcomes included biochemical control, time to biochemical control, local control, and late complications. Binary logistic regression and Cox proportional hazards regression evaluated predictors of outcomes.

Results: Patients treated with SRS (n = 9) and HSRT (n = 9) were enrolled with median follow-up of 3.4 years. Clinicopathologic details were balanced between the cohorts. Local control was 100% in both cohorts. Time to biochemical control was 6.6. and 9.5 months in the SRS and HSRT cohorts, respectively (p = 0.6258). Two patients in each cohort required salvage bilateral adrenalectomy. Late complications including secondary malignancy, radionecrosis, cranial nerve neuropathy, and optic pathway injury were minimal for either cohort.

Conclusions: HSRT is an appropriate treatment approach for refractory Cushing's disease, particularly for patients with large tumors abutting the optic apparatus. Prospective studies are needed to validate these findings and identify factors suggesting optimal fractionation approaches.
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http://dx.doi.org/10.1007/s11102-019-00992-6DOI Listing
December 2019
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