SMARCB1 Loss in Poorly Differentiated Chordomas Drives Tumor Progression.

Poorly differentiated (PD) chordoma, a rare, aggressive tumor originating from notochordal tissue, shows loss of SMARCB1 expression, a core component of the Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes. To determine the impact of SMARCB1 re-expression on cell growth and gene expression, two SMARCB1-negative PD chordoma cell lines with an inducible SMARCB1 expression system were generated. After 72 hours of induction of SMARCB1, both SMARCB1-negative PD chordoma cell lines continued to proliferate. This result contrasted with those observed with SMARCB1-negative rhabdoid cell lines in which SMARCB1 re-expression caused the rapid inhibition of growth. We found that the lack of growth inhibition may arise from the loss of CDKN2A (p16INK4A) expression in PD chordoma cell lines. RNA-sequencing of cell lines after SMARCB1 re-expression showed a down-regulation for rRNA and RNA processing as well as metabolic processing and increased expression of genes involved in cell adhesion, cell migration, and development. Taken together, these data establish that SMARCB1 re-expression in PD chordomas alters the repertoire of SWI/SNF complexes, perhaps restoring those associated with cellular differentiation. These novel findings support a model in which SMARCB1 inactivation blocks the conversion of growth-promoting SWI/SNF complexes to differentiation-inducing ones, and they implicate SMARCB1 loss as a late event in tumorigenic progression. Importantly, the absence of growth inhibition after SMARCB1 restoration creates a unique opportunity to identify therapeutic vulnerabilities.

Genetic analysis of sinonasal undifferentiated carcinoma discovers recurrent SWI/SNF alterations and a novel PGAP3-SRPK1 fusion gene.

BACKGROUND: Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown. METHODS: We evaluated survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We performed exome sequencing to characterize a series of SNUC tumors (n = 5) and cell line (MDA8788-6) to identify high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA were utilized for validation of a novel PGAP3-SRPK1 gene fusion. RESULTS: Overall survival analysis revealed no significant difference in outcomes between patients treated with surgery +/- CRT and CRT alone. Tobacco use was the only significant predictor of survival. We also confirmed previously published findings on IDH and SMARC family mutations and identified novel recurrent aberrations in the JAK/STAT and PI3K pathways. We also validated a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling. CONCLUSION: Collectively, these data demonstrate recurrent alterations in the SWI/SNF family as well as IDH, JAK/STAT, and PI3K pathways and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.

Catastrophic Allergic Fungal Sinusitis: A Report of Two Cases.

BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a common condition in which sinusitis develops as an IgE-mediated response to common sinonasal fungal organisms. If that response leads to blockage of sinus ostia, bone expansion and erosion by expansive cysts containing dense inspissated debris may occur with the potential for critical neurovascular compression including damage to the anterior visual pathway. METHODS: Review of clinical and imaging features of 2 patients who sustained catastrophic clinical outcomes. RESULTS: The first patient had pansinusitis with massive mucocele-like cysts expanding the sphenoid sinus and cranial base and causing compression of the anterior visual pathway that led to persistent severe vision loss despite extensive sinus surgery. The second patient developed sphenoethmoidal expansion with a marked inflammatory response and presumed conversion to invasive fungal sinusitis that caused anterior visual pathway vision loss, bilateral ocular motor palsies from extension into the cavernous sinuses, and death from a large middle cerebral artery stroke. CONCLUSIONS: Although AFRS is most often benign and treatable, it may rarely produce catastrophic outcomes, especially if the sphenoid sinus is involved. Irreversible vision loss may occur from compression, and ocular motor palsies and death from conversion to invasive fungal disease. Close ophthalmologic and imaging monitoring is necessary in patients with expanded sinuses, and prophylactic sinus surgery may be indicated in certain cases.

A machine learning approach to predict early outcomes after pituitary adenoma surgery.

OBJECTIVEPituitary adenomas occur in a heterogeneous patient population with diverse perioperative risk factors, endocrinopathies, and other tumor-related comorbidities. This heterogeneity makes predicting postoperative outcomes challenging when using traditional scoring systems. Modern machine learning algorithms can automatically identify the most predictive risk factors and learn complex risk-factor interactions using training data to build a robust predictive model that can generalize to new patient cohorts. The authors sought to build a predictive model using supervised machine learning to accurately predict early outcomes of pituitary adenoma surgery.METHODSA retrospective cohort of 400 consecutive pituitary adenoma patients was used. Patient variables/predictive features were limited to common patient characteristics to improve model implementation. Univariate and multivariate odds ratio analysis was performed to identify individual risk factors for common postoperative complications and to compare risk factors with model predictors. The study population was split into 300 training/validation patients and 100 testing patients to train and evaluate four machine learning models using binary classification accuracy for predicting early outcomes.RESULTSThe study included a total of 400 patients. The mean ± SD patient age was 53.9 ± 16.3 years, 59.8% of patients had nonfunctioning adenomas and 84.7% had macroadenomas, and the mean body mass index (BMI) was 32.6 ± 7.8 (58.0% obesity rate). Multivariate odds ratio analysis demonstrated that age < 40 years was associated with a 2.86 greater odds of postoperative diabetes insipidus and that nonobese patients (BMI < 30) were 2.2 times more likely to develop postoperative hyponatremia. Using broad criteria for a poor early postoperative outcome-major medical and early surgical complications, extended length of stay, emergency department admission, inpatient readmission, and death-31.0% of patients met criteria for a poor early outcome. After model training, a logistic regression model with elastic net (LR-EN) regularization best predicted early postoperative outcomes of pituitary adenoma surgery on the 100-patient testing set-sensitivity 68.0%, specificity 93.3%, overall accuracy 87.0%. The receiver operating characteristic and precision-recall curves for the LR-EN model had areas under the curve of 82.7 and 69.5, respectively. The most important predictive variables were lowest perioperative sodium, age, BMI, highest perioperative sodium, and Cushing's disease.CONCLUSIONSEarly postoperative outcomes of pituitary adenoma surgery can be predicted with 87% accuracy using a machine learning approach. These results provide insight into how predictive modeling using machine learning can be used to improve the perioperative management of pituitary adenoma patients.

Esthesioneuroblastoma: updating histologic grading as it relates to prognosis.

OBJECTIVE: The Hyams grading system has been extensively used to predict prognosis in patients with esthesioneuroblastoma (ENB). However, most studies showing prognostic correlation group grading into I/II versus III/IV, essentially comparing low versus high grade. In addition, these studies include patients with variable treatment regimens, including some that were treated with chemoradiation alone. We aimed to determine whether additional histologic variables correlate with outcome with regard to disease free and overall survival in a series of patients universally treated with anterior skull base resection and +/- adjuvant chemoradiation. STUDY DESIGN: A retrospective review of 27 patients with ENB was performed. METHODS: The sections of tumor from these 27 patients were studied and reviewed with attention to percentage lobularity, degree of pleomorphism, degree of neurofibrillary matrix, and degree of apoptosis. In addition, the presence or absence of rosettes, necrosis, calcification, spindle cells, gland hyperplasia, and bone invasion were noted. Finally, the number of mitoses per high power field and the nature of chromatin (fine vs coarse) were recorded. The histopathologic features of these 27 ENBs were reviewed and correlated with clinical outcome. RESULTS: There were 11 patients with recurrence (40.7% recurrence). There were 5 deaths (81.5% survival). The study cohort's mean overall survival was 158 months and the mean disease-free survival was 70.6 months. In terms of overall survival, necrosis and mitosis (#/10hpf) were significant but not when multivariate analysis was performed, these were not individually significant. In terms of disease-free survival, mitosis (#/10hpf) was significant but not on multivariate analysis. Gland hyperplasia was found to be a positive prognostic variable, associated with longer overall and disease-free survival, but only in combination with no spindle features and without necrosis. CONCLUSIONS: An updated histologic grading system may provide more valuable prognostic information in patients with esthesioneuroblastoma treated with a standardized treatment paradigm.

Survey of Skull Base Surgeons' Approach to Carcinomas Involving the Cavernous Sinus.

Objectives Carcinomas involving the cavernous sinus are challenging to resect without compromising important neurovascular structures. Given the morbidity and mortality of these operations, radiotherapy, chemotherapy, and immunotherapy are more often utilized. Although limited to case reports and small series, radical resection of the cavernous sinus has been proposed. We aimed to study surgeons' willingness to perform cavernous sinus exenteration (CSE) under different clinical scenarios. Design, Setting, Participants, Main Outcome Measures We conducted an online survey from April to July 2021 among members of the Skull Base Congress and the North American Skull Base Society. Descriptive statistics were used to analyze the main outcome measure of willingness to perform CSE . Results The analytic sample ( n = 112) included 54% otolaryngologists and 43% neurosurgeons. Eighty-six percent practiced in an academic setting. Surgeons' willingness to perform CSE was low (6-16% under different clinical scenarios), citing a belief that they could not obtain oncologic margins and the procedure's morbidity. Forty-five percent had at least one patient undergo CSE with 72% of patients surviving no more than 2 years. Complications included chronic intractable pain, cerebrospinal fluid leak, cerebrovascular accident, and/or intraoperative/postoperative death within 30 days. Sixty percent agreed that the availability of immunotherapy and genomic sequencing has affected their willingness to offer CSE. Conclusion Overall, most of the surgeons surveyed were unwilling to offer CSE for carcinomatous cavernous sinus invasion, whether for primary disease or recurrence. Given the rarity of these tumors and the limited data on CSE, these results may provide more information for clinicians and patients for these treatment decisions.

A comparison of particulate and Onyx embolization in preoperative devascularization of carotid body tumors.

INTRODUCTION: Preoperative embolization of a carotid body tumor (CBT) is a useful adjunct prior to surgical excision because it decreases operative blood loss and improves surgical outcomes. Traditionally, this is performed by transarterial particulate embolization (TAPE). More recently, direct percutaneous embolization (DPE) with Onyx is recognized as a promising technique for preoperative embolization. We compared these two techniques in patients treated for CBTs at our institution. METHODS: We retrospectively reviewed cases of preoperative devascularization of CBT from 1 January 1995 through 1 September 2012. Patient cases were placed into two groups: TAPE and DPE. Operative blood loss, operative length, angiographic devascularization, embolization procedure complications, operative transfusion requirements, postoperative hospital stay, intensive care unit (ICU) stay, and procedure-related mortalities were compared. RESULTS: A total of 17 patients underwent preoperative devascularization of their CBT with TAPE technique and ten patients using the DPE technique with Onyx. Average operative blood loss was significantly higher in the TAPE group (Mann-Whitney U test, p = 0.04). Operative time was also higher, although this difference was not significant. Two patients required intraoperative blood transfusions in the TAPE group while none required transfusions in the DPE group. There was no significant difference in ICU stay or length of hospitalization. One serious embolization procedure complication occurred in the TAPE group and none in the DPE group. CONCLUSION: Operative blood loss in the DPE group was significantly less than the TAPE group. Blood transfusion requirement, operative time, and complications were less in the DPE group, although they did not reach statistical significance.

A comparison of particulate and onyx embolization in preoperative devascularization of juvenile nasopharyngeal angiofibromas.

INTRODUCTION: Juvenile nasopharyngeal angiofibromas (JNAs) are hypervascular tumors that may benefit from preoperative devascularization to reduce intraoperative blood loss (IBL). The purpose of this study was to compare transarterial particulate embolization (TAPE) with the direct percutaneous embolization (DPE) technique using ethylene vinyl alcohol (Onyx, ev3, Irvine, CA) for the preoperative devascularization of a JNA. METHODS: We retrospectively reviewed 50 consecutive JNA resections since 1995 for which preoperative embolization was either transarterial with particulate material (n = 39) or DPE (n = 11) using only Onyx. The IBL, transfusion requirements, operative time, and length of hospital admission were compared between the two groups. RESULTS: The mean IBL was 1,348.7 ± 932.2 mL particulate group, 569.1 ± 700.7 mL Onyx group (one-tailed Student's t test p = 0.003). The mean unit of packed red blood cells was 1.56 ± 2.01 units particulate group, 0.45 ± 1.04 units Onyx group (p = 0.009). The relationship between embolization type and IBL remained significant or strongly correlated when accounting for the Fisch stage of the tumor (p = 0.010 and p = 0.056, respectively, by a multivariate least squares fit; alternately p = 0.0003 and p = 0.023, respectively, in the subset of patients with Fisch stage III tumors only). We also found that the proportion of resections for which an endoscopic approach could be used was significantly higher in the Onyx group than the particulate group (81.8 and 18.2 %; Pearson p = 0.0002), and this was also significant both in our multivariate nominal logistic fit (p < 0.001) and in the subset of patients with Fisch stage III tumors (p = 0.018). CONCLUSION: Pre-operative DPE with Onyx of a JNA when compared to TAPE significantly decreased IBL and RBC transfusion requirement during surgical resection. The proportion of surgical resections performed from an endoscopic approach was higher in the DPE Onyx group, which may have affected the results.

Repeat endoscopic transsphenoidal surgery for acromegaly: remission and complications.

Reported biochemical remission rates following surgical intervention for acromegaly range from 38 to 83%. In patients not achieving surgical remission, few options remain, mostly limited to medical management and radiation therapy. There is debate over whether or not to offer reoperation to patients in whom surgical remission is not achieved with initial resection. Retrospective chart review was undertaken to determine all patients having acromegaly with persistently elevated GH and/or IGF-1 levels after initial pituitary adenoma resection, and who underwent reoperation using endoscopic endonasal approach at a single institution. Biochemical remission was defined as a postoperative GH level <1 ng/mL and a normal postoperative IGF-1 level in the absence of any medical therapy. In total, 14 patients underwent repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach. Of the 14 patients, 8 (57%) achieved biochemical remission following repeat surgical intervention. Lower preoperative GH levels were associated with greater chance of biochemical remission (P = 0.048). New endocrinopathies were seen in 2 patients (14%), and both were transient diabetes insipidus. Meningitis occurred in 2 patients (14%); both were aseptic meningitis with no sequelae. No mortality was encountered. Repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach appears safe and effective. With no mortality and minimal morbidity, repeat surgical intervention via endoscopic transsphenoidal approach appears a reasonable option for these hard-to-treat patients and should be considered for patients in whom surgical remission is not achieved with initial surgery.

Sinonasal Neuroendocrine Carcinoma: 15 Years of Experience at a Single Institution.

Objectives Sinonasal neuroendocrine carcinomas (SNECs) are among the rarest paranasal sinus cancers. Consensus guidelines for therapy are difficult to develop due to limited data regarding the natural history and successful treatment of these tumors. This study presents 15 years of experience treating SNEC at a single institution and a review of the literature. Design Retrospective review. Setting Academic medical center in the United States. Participants Patients diagnosed with primary SNEC. Main Outcome Measures Overall survival. Results Thirteen patients were identified and included. Overall estimated survival was 74.6% at 5 years. Ten of 13 (76.9%) patients were diagnosed with high-grade neuroendocrine carcinoma and three (23.1%) with intermediate or low grade. All three patients with low- or intermediate-grade cancer survived more than 10 years from their initial diagnosis (median survival: 11.6 years) and are currently alive. The four patients who died had high-grade carcinoma, and estimated overall 5-year survival for all patients with high-grade carcinomas was 65.6%. Five patients, all with high-grade carcinoma, of seven who completed primary chemoradiation therapy (CRT) required salvage resection, and 60% are alive without disease. Conclusion This cohort has a higher overall rate of survival than many recent case series and reviews. There is consensus that multimodal therapy is preferred over monotherapy, but approaches to treatment vary widely. Our approach of surgical resection as primary therapy for low-grade tumors and primary CRT for high-grade SNEC has been successful, and could indicate hope for improved survival among these patients.

Survey of student mistreatment experienced during the core clinical clerkships.

BACKGROUND: The goal of this study was to learn more about the potential impact of medical student mistreatment on patient safety and care. METHODS: A web-based survey was sent to members of the class of 2021 and 2022 who have completed their core clerkships at a single academic institution. Descriptive statistics were performed to understand how prior and future mistreatment impacted communication among students and team members. RESULTS: We received 290 of 376 responses (77.1%). 26% of respondents indicated that past mistreatment negatively impacted their communication with other team members. 30% of respondents reported that fear of future mistreatment negatively impacted their communication with other team members. CONCLUSION: Mistreatment of medical students has many sources and occurs throughout the clinical curriculum. Past and fear of future student mistreatment can negatively impact intrateam communication and therefore negatively impact patient care, with the potential of causing poor patient outcomes.

Assessing Quality of Life among Radiation-Induced Hypopituitary Patients.

Introduction Radiation-induced hypopituitarism (RIH) has long been recognized as one of the deleterious side effects of skull base radiation. This study aims to assess the quality of life (QoL) among patients with RIH compared with radiated patients who did not develop hypopituitarism using the validated Anterior Skull Base Questionnaire (ASBQ). Methods This was a single-institution retrospective cohort study. Included patients had a history of anterior skull base tumor, underwent at least one round of radiation to the skull base, and had filled out at least one ASBQ survey after their radiation treatment. Three statistical models were used to determine the effect of hypopituitarism and treatment on QoL scores. Results A total of 145 patients met inclusion criteria, and 330 ASBQ surveys were analyzed. Thirty-five percent (51/145) had evidence of RIH at some point after their radiation treatment. Those with hypopituitarism had significantly lower overall ASBQ scores across all three models even after adjusting for potential confounders and intraperson correlation (average decrease of 0.24-0.45 on a 5-point Likert scale; p -values ranging from 0.0004 to 0.018). The increase in QoL with hormonal replacement was modulated by time out from radiation, with long-term survivors (5+ years out from radiation) gaining the most benefit from treatment (increase of 0.89 on a 5-point Likert scale, p 0.0412), especially in the vitality domain. Conclusion This data demonstrates that hypopituitarism is an independent predictor of lower QoL. Early detection and appropriate treatment are essential to avoid the negative impact of hypopituitarism on QoL.

Central Skull Base Osteomyelitis: A Case Series from a Tertiary Care Center Over 5 Years.

OBJECTIVE: Skull base osteomyelitis may rarely present in the sphenoid bone or clivus without an otologic source. This is referred to as central skull base osteomyelitis (CSBO). Knowledge regarding CSBO is limited to case reports and small case series. Here we present a case series to further describe typical patient characteristics, clinical presentation, and clinical course associated with this rare infection. METHODS: All patients treated at a single academic tertiary care institution for CSBO from 2016 through 2020 were identified. Inclusion criteria included culture proven CSBO without an otologic or iatrogenic source. Data were extracted via patient chart review and qualitatively analyzed. RESULTS: Seven patients were identified with CSBO, 5 male and 2 female. Age ranged from 63 to 87 (average 76). Risk factors included advanced age, diabetes, and history of radiation. The most common presenting symptom was headache (6), followed by otalgia (4). Two patients presented with cranial neuropathies. Diagnosis was facilitated by history and exam (including flexible laryngoscope exam), imaging (MRI), and labs (ESR). All patients received endoscopic biopsy and culture (most commonly polymicrobial, with diverse species). Treatment involved IV antibiotics, with a limited role for surgery. All patients survived and achieved resolution of infection. CONCLUSIONS: CSBO remains a diagnostic challenge due to its rarity and vague presenting symptoms that overlap with presentation of sinonasal malignancies. A high index of suspicion is required by the evaluating provider to ensure a timely diagnosis with early treatment in order to limit the significant morbidity which can be associated with this infection. LEVEL OF EVIDENCE: 4.

Developing an Integrated Multidisciplinary Pituitary Management Team.

Interdisciplinary teams have many potential and proven benefits, including decreased burnout, decreased medical errors, increased quality, and leveraging of competing values and skills. Pituitary Tumor Centers of Excellence must have adequate volumes and high-functioning teams in order to provide exceptional, high-value care. Organizational logistics, attentive operations management, facilitated collaboration, and clear communication are key teamwork tools in delivering that care.

Surgical Management of Rhabdomyosarcoma of the Nasal Cavity and Paranasal Sinuses: Analysis of Operative Indications, Settings, and Outcomes.

Objectives The role of surgery in management of sinonasal rhabdomyosarcoma (SNRMS) has traditionally been limited, owing to anatomic and technological challenges and the established role of systemic therapy. Herein, we report our institutional experience with surgical management of SNRMS, with a particular focus on operative approaches, extent and outcomes. Design This study is a retrospective cohort study. Setting This study was conducted at a single-institution, academic center. Participants Patients of any age with histologically confirmed RMS of the nasal cavity, maxillary, ethmoid, frontal, or sphenoid sinus, nasolacrimal duct, or nasopharynx presenting between 1994 and 2020 were included in this study. Main Outcome Measures Demographics, tumor characteristics, operative settings, complications and recurrence, and survival outcomes were the primary outcomes of this study. Results Our study cohort comprised of 29 patients (mean [range] age: 27.0 [3.1-65.7], n = 12 [41%] female). Tumors of the nasal cavity ( n = 10, 35%) and ethmoid sinuses ( n = 10, 35%) and those with alveolar histology ( n = 21, 72%) predominated. Patients who had surgery as part of their treatment ( n = 13, 45%) had improved distant metastasis-free survival (DMFS) overall (hazard ratio [HR]: 0.32, 95% CI: 0.11, 0.98, p = 0 .05 ) as compared with those who did not have surgery. Surgical approaches included open ( n = 7), endoscopic ( n = 4), and combined ( n = 2). Eight of these 13 patients (62%) had an R0 resection. Additionally, surgical salvage of recurrent disease was employed in five patients (17%). Conclusion SNRMS is an aggressive malignancy with a high rate of recurrence and spread requiring a multidisciplinary approach for optimal outcomes. Our data supports an expanding role for surgery for SNRMS given its feasibility, tolerability, and potential to improve outcomes.

Treatment and Prognosis of Inflammatory Pseudotumor of the Skull Base.

Background Inflammatory pseudotumor (IPT) of the skull base is a rare, locally destructive lesion managed with a variety of treatments. We explore the impact of treatment on outcome and assess the prognosis of IPT. Methods This is a retrospective review of IPT of the skull base at a tertiary academic medical center. The primary outcome was radiographic progression after treatment. Outcome versus tumor location was also examined and a prognostic model was developed using a logistic regression. Results The demographics of 21 patients with IPT are reported. Treatment consisted of corticosteroids (in 80.1% of patients), disease modifying antirheumatic drugs (DMARDs; 33.3%), surgical resection (28.6%), radiation (23.8%), antibiotics (14.3%), chemotherapy (rituximab; 9.5%), and antivirals (4.8%). At 50.7 months, 50.8% had radiographic progression. Local therapy trended toward having a better response than systemic therapy ( p = 0.60). IPT of the orbit required 2.4 treatment modalities, compared with 2.0 for pharyngeal IPT, and 1.3 for posterior skull base masses ( p = 0.14). A total of 75% orbital IPT underwent radiographic progression, compared with 71% of pharyngeal IPT and 50% of posterior skull base masses ( p = 0.62). Sixteen patients were used to create the logistic model of radiographic progression. The Cox-Snell R 2 was 0.71 ( p = 0.03). No individual variables were statistically significant. Conclusion To our knowledge, this is among the largest sample of cases describing the presentation, treatment, and prognosis of IPT of the skull base. Our data suggest that there may be an improved response with local therapy over systemic therapy and better prognosis among posterolateral skull base masses.

Gender Microaggressions During Virtual Residency Interviews and Impact on Ranking of Programs During the Residency Match.

Background: Microaggressions are one form of gender bias contributing to gender disparities and mistreatment, but their prevalence during virtual residency interviews has not been explored. Objective: To explore applicants' recall of experiencing gender microaggressions during virtual residency interviews and whether these experiences affected programs' rank position on applicants' rank lists. Methods: Fourth-year medical students at a single institution who participated in the 2021 Match were surveyed after submitting their rank lists. Students were surveyed categorically on (1) their recall of the frequency they experienced 17 gender microaggressions during interviews, and (2) how these affected reported ranking of programs on their rank lists. Results: Sixty-one percent (103 of 170) of eligible students responded to the survey. Seventy-two percent (36 of 50) of women experienced at least one microaggression compared to 30% (9 of 30) of men. The largest difference was in the experience of environmental microaggressions, which are demeaning cues communicated individually or institutionally, delivered visually, or that refer to climate (P<.001). Women experienced more microaggressions than men in nonsurgical (P=.003) and surgical specialties excluding obstetrics and gynecology (P=.009). When microaggressions were experienced at 1 to 2 programs, 36% of applicants (26 of 73) reported significantly lowering program ranking, compared to 5% (1 of 19) when microaggressions occurred at more than 5 programs (P=.038). Conclusions: Women applicants experience more microaggressions than men do during nonsurgical and male-dominated surgical specialty residency interviews. Respondents who recalled experiencing microaggressions at fewer programs were more likely to report significantly lowering the rank of those programs compared to those who experienced them at more programs.

Antibiotic Use in Lateral Skull Base Surgery: A Survey of the North American Skull Base Society.

Objectives Antibiotic use in lateral skull base surgery (LSBS) has not been thoroughly investigated in the literature. There is wide variability in antibiotic use and insufficient data to guide management. This study aims to describe the factors and patterns influencing antibiotic use in LSBS among the membership of the North American Skull Base Society (NASBS). Design An online-based survey was designed and distributed to the membership of the NASBS. Data was analyzed using bivariate analysis and logistic regression modeling. Setting Online-based questionnaire. Participants NASBS membership. Main Outcome Measures Use of intraoperative antibiotics and use of postoperative antibiotics. Results The survey response rate was 26% (208 respondents). Of the 208 total respondents, 143 (69%) respondents performed LSBS. Most respondents are neurosurgeons (69%) with the remaining being otolaryngologists (31%). The majority of respondents (79%) are fellowship-trained in skull base surgery. Academic or government physicians make up 69% of respondents and 31% are in private practice with or without academic affiliations. Bivariate analysis showed that practice setting significantly influenced intraoperative antibiotic use ( p = 0.01). Geographic location significantly affected postoperative antibiotic use ( p = 0.01). Postoperative antibiotic duration was significantly affected by presence of chronic otitis media, cerebrospinal fluid leak, and surgeon training ( p = 0.02, p = 0.01, and p = 0.006, respectively). Logistic regression modeling showed that the motivation to reduce infection significantly impacted postoperative antibiotic use ( p = 0.03). Conclusion This study demonstrates significant variations in intraoperative and postoperative antibiotic use in LSBS among the NASBS membership. Appropriate guidelines for optimal perioperative antibiotic use patterns should be determined with randomized studies in the future.

Advancement of PI3 Kinase Inhibitor Combination Therapies for PI3K-Aberrant Chordoma.

Objectives Targeted inhibitors of the PI3 kinase (PI3K) pathway have shown promising but incomplete antitumor activity in preclinical chordoma models. The aim of this study is to advance methodology for a high-throughput drug screen using chordoma models to identify new combination therapies for chordoma. Study Design Present work is an in vitro study. Setting The study conducted at an academic research laboratory. Materials and Methods An in vitro study on automated high-throughput screening of chordoma cells was performed using a library of 1,406 drugs as both mono- and combination therapies with PI3K inhibitors. Combination indices were determined for dual therapies and synergistic outliers were identified as potential therapeutic agents. T (brachyury) siRNA knockdown in combination with PI3K pathway inhibition was also assessed. Results Fifty-nine combination therapies were identified as having potential therapeutic efficacy. Effective combinations included PI3K inhibitors with GSK1838705A (ALK/IGF-1R inhibitor), LY2874455 (VEGFR/FGFR inhibitor), El1 (selective Ezh2 inhibitor), and (-)-p-bromotetramisole oxalate (alkaline phosphatase inhibitor). The top ranking targets identified included ALK, PDGFR, VEGFR, aurora kinase, and BCL-2. T (brachyury) inhibition produced significant reduction in cell viability and growth; however PI3K inhibition in combination with T (brachyury) knockdown did not result in further reduction in growth and viability in vitro. Conclusion High throughput with in vitro combination screening is feasible with chordoma cells and allows for rapid identification of synergistic dual-therapies. Potential combination therapies and targetable pathways were identified. T (brachyury) knockdown produced significant reduction in cell viability, but did not show additional benefit with PI3K pathway inhibition in this model. Further in vitro and in vivo validation of these therapeutic combinations is warranted.

Phosphaturic Mesenchymal Tumors of the Sinonasal Area and Skull Base: Experience at a Single Institution.

OBJECTIVES: Phosphaturic mesenchymal tumor (PMT) is a rare, polymorphous neoplasm with a highly variable presentation and natural history and unpredictable clinical course. The primary objective was to describe our clinical experience with and management of 4 markedly different cases of sinonasal and skull base PMT. METHODS: A retrospective case series with chart review, and relevant literature review, was performed at a tertiary academic medical center between 1998 and 2020. Adult patients treated for PMTs of the sinonasal area and skull base were included. Our main outcome measures included postoperative laboratory findings and radiological evidence of disease remission. RESULTS: Four patients (2 Males, 2 Females; Mean Age: 63.5 years) with PMTs of the skull base have been managed at our institution since 1998. Patient presentations varied, ranging from severe phosphorus wasting and osteoporosis to symptoms secondary to mass effect, including nasal obstruction and rhinorrhea. All 4 patients were eventually found to have elevated levels of fibroblast growth factor 23. Tumors were located in the sinonasal area (right frontal sinus, right ethmoid sinus, and right nasal cavity, respectively) in 3 patients and in the lateral skull base (right jugular foramen) in 1 patient. All 4 patients underwent complete surgical resection of their tumors. PMT tissue pathology was confirmed in all cases. Gross total resection was achieved in all patients. There was no chemical or radiological evidence of disease recurrence in any patients at follow-up. CONCLUSIONS: The presentation of skull base PMT is variable, and it may mimic other mass pathologies of the head and neck. Complete surgical resection with negative margins is potentially curative.