Ryan Charles Leung Brewster

All Publications

• Managing Persistent Hypertension and Tachycardia Following Septic Shock, Limb Ischemia, and Amputation: The Role for beta-Blockade. Clinical pediatrics Brewster, R., Lee, J., Nguyen, E., Ward, V. 2021; 60 (4-5): 226–29

  View details for DOI 10.1177/00099228211006704

  View details for PubMedID 33853367

• Evaluation of Absolute Lymphocyte Count at Diagnosis and Mortality Among Patients With Localized Bone or Soft Tissue Sarcoma. JAMA network open Brewster, R., Purington, N., Henry, S., Wood, D., Ganjoo, K., Bui, N. 2021; 4 (3): e210845

  Abstract

  Importance: Host-related immune factors have been implicated in the development and progression of diverse malignant neoplasms. Identifying associations between immunologic laboratory parameters and overall survival may inform novel prognostic biomarkers and mechanisms of antitumor immunity in localized bone and soft tissue sarcoma.Objective: To assess whether lymphopenia at diagnosis is associated with overall survival among patients with localized bone and soft tissue sarcoma.Design, Setting, and Participants: This retrospective cohort study analyzed patients from the Stanford Cancer Institute with localized bone and soft tissue sarcoma between September 1, 1998, and November 1, 2018. Patients were included if laboratory values were available within 60 days of diagnosis and, if applicable, prior to the initiation of chemotherapy and/or radiotherapy. Statistical analysis was performed from January 1, 2019, to November 1, 2020.Exposures: Absolute lymphocyte count within 60 days of diagnosis and antimicrobial exposure, defined by the number of antimicrobial agent prescriptions and the cumulative duration of antimicrobial administration within 60 days of diagnosis.Main Outcomes and Measures: The association between minimum absolute lymphocyte count at diagnosis and 5-year overall survival probability was characterized with the Kaplan-Meier method and multivariate Cox proportional hazards regression models. Multivariable logistic regressions were fitted to evaluate whether patients with lymphopenia were at greater risk of increased antimicrobial exposure.Results: Among 634 patients, the median age at diagnosis was 53.7 years (interquartile range, 37.5-66.8 years), and 290 patients (45.7%) were women, with a 5-year survival probability of 67.9%. There was a significant inverse association between lymphopenia at diagnosis and overall survival (hazard ratio [HR], 1.82; 95% CI, 1.39-1.40), resulting in a 13.5% 5-year survival probability difference compared with patients who did not have lymphopenia at diagnosis (60.2% vs 73.7% for those who never had lymphopenia). In addition, poorer survival was observed with higher-grade lymphopenia (grades 3 and 4: HR, 2.44; 95% CI, 1.68-3.55; grades 1 and 2: HR, 1.60; 95% CI, 1.18-2.18). In an exploratory analysis, patients with increased antibiotic exposure were more likely to have lymphopenia (odds ratio, 1.96; 95% CI, 1.26-3.07 for total number of antimicrobial agents; odds ratio, 1.70; 95% CI, 1.10-2.57 for antimicrobial duration) than antimicrobial-naive patients.Conclusions and Relevance: This study suggests that an abnormally low absolute lymphocyte count at diagnosis is associated with higher mortality among patients with localized bone and soft tissue sarcoma; therefore, lymphopenia may serve as a reliable prognostic biomarker. Potential mechanisms associated with host immunity and overall survival include a suppressed antitumor response and increased infectious complications, which merit future investigation.

  View details for DOI 10.1001/jamanetworkopen.2021.0845

  View details for PubMedID 33666664

• Gut microbiome profiling of a rural and urban South African cohort reveals biomarkers of a population in lifestyle transition. BMC microbiology Oduaran, O. H., Tamburini, F. B., Sahibdeen, V., Brewster, R., Gomez-Olive, F. X., Kahn, K., Norris, S. A., Tollman, S. M., Twine, R., Wade, A. N., Wagner, R. G., Lombard, Z., Bhatt, A. S., Hazelhurst, S. 2020; 20 (1): 330

  Abstract

  BACKGROUND: Comparisons of traditional hunter-gatherers and pre-agricultural communities in Africa with urban and suburban Western North American and European cohorts have clearly shown that diet, lifestyle and environment are associated with gut microbiome composition. Yet, little is known about the gut microbiome composition of most communities in the very diverse African continent. South Africa comprises a richly diverse ethnolinguistic population that is experiencing an ongoing epidemiological transition and concurrent spike in the prevalence of obesity, largely attributed to a shift towards more Westernized diets and increasingly inactive lifestyle practices. To characterize the microbiome of African adults living in more mainstream lifestyle settings and investigate associations between the microbiome and obesity, we conducted a pilot study, designed collaboratively with community leaders, in two South African cohorts representative of urban and transitioning rural populations. As the rate of overweight and obesity is particularly high in women, we collected single time-point stool samples from 170 HIV-negative women (51 at Soweto; 119 at Bushbuckridge), performed 16S rRNA gene sequencing on these samples and compared the data to concurrently collected anthropometric data.RESULTS: We found the overall gut microbiome of our cohorts to be reflective of their ongoing epidemiological transition. Specifically, we find that geographical location was more important for sample clustering than lean/obese status and observed a relatively higher abundance of the Melainabacteria, Vampirovibrio, a predatory bacterium, in Bushbuckridge. Also, Prevotella, despite its generally high prevalence in the cohorts, showed an association with obesity. In comparisons with benchmarked datasets representative of non-Western populations, relatively higher abundance values were observed in our dataset for Barnesiella (log2fold change (FC)=4.5), Alistipes (log2FC=3.9), Bacteroides (log2FC=4.2), Parabacteroides (log2FC=3.1) and Treponema (log2FC=1.6), with the exception of Prevotella (log2FC=-4.7).CONCLUSIONS: Altogether, this work identifies putative microbial features associated with host health in a historically understudied community undergoing an epidemiological transition. Furthermore, we note the crucial role of community engagement to the success of a study in an African setting, the importance of more population-specific studies to inform targeted interventions as well as present a basic foundation for future research.

  View details for DOI 10.1186/s12866-020-02017-w

  View details for PubMedID 33129264

• The Effect of Socioeconomic Status on Age at Diagnosis and Overall Survival in Patients with Intracranial Meningioma. The International journal of neuroscience Brewster, R., Deb, S., Pendharkar, A. V., Ratliff, J., Li, G., Desai, A. 2020: 1–12

  Abstract

  Background: Intracranial meningiomas are the most common primary tumors of the central nervous system. How socioeconomic status (SES) impacts treatment access and outcomes for brain tumor subtypes is an emerging area of research. Few studies have examined the relationship between SES and meningioma survival and management with reference to relevant clinical factors, including age at diagnosis. We studied the independent effects of SES on receiving surgery and survival probability in patients with intracranial meningiomaMethods: 54,282 patients diagnosed with intracranial meningioma between 2003-2012 from the Surveillance, Epidemiology, and End Results (SEER) Program at the National Cancer Institute database were included. Patient SES was divided into tertiles. Patient age groups included "older" (>65, the median patient age) and "younger". Multivariable linear regression and Cox proportional hazards model were used with SAS v9.4. Results were adjusted for race, sex, and tumor grade. Kaplan Meier survival curves were constructed according to SES tertiles and age groups.Results: Meningioma prevalence increased with higher SES tertile. Higher SES tertile was also associated with younger age at diagnosis (OR= 0.890, p <0.05), an increased likelihood of undergoing gross total resection (GTR) (OR =1.112, p<0.05), and a trend towards greater 5-year survival probability (HR =1.773, p=0.0531). Survival probability correlated with younger age at diagnosis (HR =2.597, p<0.001), but not with GTR receipt.Conclusion: The findings from this national longitudinal study on patients with meningioma suggest that SES affects age at diagnosis and treatment access for intracranial meningiomas patients. Further studies are required to understand and address the mechanisms underlying these disparities.

  View details for DOI 10.1080/00207454.2020.1818742

  View details for PubMedID 32878534

• Using Telemedicine and Infographics for Physician-Guided Home Drain Removal. OTO open Go, B. C., Brewster, R., Patel, R., Rajasekaran, K. 2020; 4 (2): 2473974X20933566

  Abstract

  Objective: Measures to decrease hospital length of stay and outpatient visits are crucial during the coronavirus disease 2019 (COVID-19) pandemic. Physician-guided home drain removal presents a potential opportunity for mitigating viral spread and transmission.Methods: A prospective case series on patients undergoing major head and neck surgery with Jackson-Pratt drain placement was conducted. Patients were shown an infographic detailing drain care and removal at preoperative assessment and prior to discharge. At a 1-week follow-up telemedicine visit, patients were instructed to remove the drain under physician guidance. Patients were assessed 7 days after to determine complication rate and satisfaction.Results: Twenty-five patients were enrolled with 100% patients undergoing successful drain removal at home with caregiver support. There were no complications reported at the 7-day postdrain removal time point, and overall patient satisfaction was high.Discussion: Infographics and telemedicine are 2 synergistic strategies to guide safe and effective home drain removal.Implications for Practice: This study demonstrates how telemedicine and an infographic can be effectively used in physician-guided home drain removal. During a time like the COVID-19 pandemic, innovative measures are necessary to curb transmission and infection rates. We propose a unique and replicable yet safe solution to limit unnecessary exposure and encourage other surgical providers to adopt a similar strategy.

  View details for DOI 10.1177/2473974X20933566

  View details for PubMedID 32548544

• Justice is the Best Medicine. And, Yes, You Can Call Us by Our Pronouns. AMA journal of ethics Brewster, R. 2020; 22 (3): E253–254

  Abstract

  One recent essay suggests that emphasis on social justice in medical education is done at the expense of clinicians' technical competency. This response to that stance is a digitally illustrated series that contextualizes patient health as both physiological and determined by social, economic, and cultural conditions.

  View details for DOI 10.1001/amajethics.2020.253

  View details for PubMedID 32220273

• Optimizing telemedicine encounters for oral and maxillofacial surgeons during the COVID-19 pandemic. Oral surgery, oral medicine, oral pathology and oral radiology Moon, H. S., Wang, T. T., Rajasekaran, K. n., Brewster, R. n., Shanti, R. M., Panchal, N. n. 2020

  Abstract

  The coronavirus disease 2019 (COVID-19) pandemic has changed conventional patterns of medical practice across all health disciplines, including oral and maxillofacial surgery. The use of telemedicine has rapidly expanded to uphold safety strategies of physical distancing and disease transmission reduction while maintaining uninterrupted care of patients. To date, there are no specific guidelines to optimize telemedicine encounters in oral and maxillofacial surgery. The goal of this article is to provide best practices for both oral and maxillofacial surgeons and their patients to effectively use telemedicine for the duration of the COVID-19 pandemic and beyond.

  View details for DOI 10.1016/j.oooo.2020.08.015

  View details for PubMedID 32981876

• Optimizing your telemedicine visit during the COVID-19 pandemic: Practice guidelines for patients with head and neck cancer. Head & neck Prasad, A. n., Brewster, R. n., Newman, J. G., Rajasekaran, K. n. 2020

  Abstract

  The COVID-19 epidemic has resulted in many hospitals and practices to cancel in-person outpatient clinic visits, where head and neck patients receive their critical longitudinal care. Out of necessity, most practices have been encouraged to use telemedicine as a method to maintain a continuum of care with their patients. As a result, the prevalence of telemedicine has grown rapidly during this pandemic, without allowing the physicians and patients to be adequately educated on how best to utilize the services. There is a steep learning curve as we have learned, and our goal is to provide guidelines for both patients and physicians, as well as a valuable patient handout in preparation for their visit.

  View details for DOI 10.1002/hed.26197

  View details for PubMedID 32343458

• How to perform a nasopharyngeal swab - an otolaryngology perspective. The American journal of medicine Kaufman, A. C., Brewster, R. n., Rajasekaran, K. n. 2020

  View details for DOI 10.1016/j.amjmed.2020.05.004

  View details for PubMedID 32492374

  View details for PubMedCentralID PMC7261357

• Preparing for Telemedicine Visits: Guidelines and Setup. Frontiers in medicine Prasad, A. n., Brewster, R. n., Rajasekaran, D. n., Rajasekaran, K. n. 2020; 7: 600794

  View details for DOI 10.3389/fmed.2020.600794

  View details for PubMedID 33324665

  View details for PubMedCentralID PMC7724018

• Microbiota modification in hematology: still at the bench or ready for the bedside? Severyn, C. J., Brewster, R., Andermann, T. M. AMER SOC HEMATOLOGY. 2019: 303–14

  View details for Web of Science ID 000538564000044

• Cutaneous Patches to Monitor Myoelectric Activity of the Gastrointestinal Tract in Postoperative Pediatric Patients PEDIATRIC GASTROENTEROLOGY HEPATOLOGY & NUTRITION Taylor, J. S., de Ruijter, V., Brewster, R., Navalgund, A., Axelrod, L., Axelrod, S., Dunn, J. Y., Wall, J. K. 2019; 22 (6): 518–26

  View details for DOI 10.5223/pghn.2019.22.6.518

  View details for Web of Science ID 000496920200003

• Socioeconomic Predictors of Surgical Resection and Survival for Patients With Osseous Spinal Neoplasms CLINICAL SPINE SURGERY Deb, S., Brewster, R., Pendharkar, A., Veeravagu, A., Ratliff, J., Desai, A. 2019; 32 (3): 125–31

  View details for DOI 10.1097/BSD.0000000000000738

  View details for Web of Science ID 000464982800008

• Frameless Robot-Assisted Deep Brain Stimulation Surgery: An Initial Experience. Operative neurosurgery (Hagerstown, Md.) Ho, A. L., Pendharkar, A. V., Brewster, R., Martinez, D. L., Jaffe, R. A., Xu, L. W., Miller, K. J., Halpern, C. H. 2019

  Abstract

  BACKGROUND: Modern robotic-assist surgical systems have revolutionized stereotaxy for a variety of procedures by increasing operative efficiency while preserving and even improving accuracy and safety. However, experience with robotic systems in deep brain stimulation (DBS) surgery is scarce.OBJECTIVE: To present an initial series of DBS surgery performed utilizing a frameless robotic solution for image-guided stereotaxy, and report on operative efficiency, stereotactic accuracy, and complications.METHODS: This study included the initial 20 consecutive patients undergoing bilateral robot-assisted DBS. The prior 20 nonrobotic, frameless cohort of DBS cases was sampled as a baseline historic control. For both cohorts, patient demographic and clinical data were collected including postoperative complications. Intraoperative duration and number of Microelectrode recording (MER) and final lead passes were recorded. For the robot-assisted cohort, 2D radial errors were calculated.RESULTS: Mean case times (total operating room, anesthesia, and operative times) were all significantly decreased in the robot-assisted cohort (all P-values<.02) compared to frameless DBS. When looking at trends in case times, operative efficiency improved over time in the robot-assisted cohort across all time assessment points. Mean radial error in the robot-assisted cohort was 1.40±0.11mm, and mean depth error was 1.05±0.18mm. There was a significant decrease in the average number of MER passes in the robot-assisted cohort (1.05) compared to the nonrobotic cohort (1.45, P<.001).CONCLUSION: This is the first report of application of frameless robotic-assistance with the Mazor Renaissance platform (Mazor Robotics Ltd, Caesarea, Israel) for DBS surgery, and our findings reveal that an initial experience is safe and can have a positive impact on operative efficiency, accuracy, and safety.

  View details for PubMedID 30629245

• Surveying Gut Microbiome Research in Africans: Toward Improved Diversity and Representation. Trends in microbiology Brewster, R. n., Tamburini, F. B., Asiimwe, E. n., Oduaran, O. n., Hazelhurst, S. n., Bhatt, A. S. 2019

  Abstract

  Descriptive and translational investigations into the human gut microbiome (GM) are rapidly expanding; however, studies are largely restricted to industrialized populations in the USA and Europe. Little is known about microbial variability and its implications for health and disease in other parts of the world. Populations in Africa are particularly underrepresented. What limited research has been performed has focused on a few subject domains, including the impact of long-term lifestyle and dietary factors on GM ecology, its maturation during infancy, and the interrelationships between the microbiome, infectious disease, and undernutrition. Recently, international consortia have laid the groundwork for large-scale genomics and microbiome studies on the continent, with a particular interest in the epidemiologic transition to noncommunicable disease. Here, we survey the current landscape of GM scholarship in Africa and propose actionable recommendations to improve research capacity and output.

  View details for DOI 10.1016/j.tim.2019.05.006

  View details for PubMedID 31178123

• Microbiota modification in hematology: still at the bench or ready for the bedside? Hematology. American Society of Hematology. Education Program Severyn, C. J., Brewster, R. n., Andermann, T. M. 2019; 2019 (1): 303–14

  Abstract

  Growing evidence suggests that human microbiota likely influence diverse processes including hematopoiesis, chemotherapy metabolism, and efficacy, as well as overall survival in patients with hematologic malignancies and other cancers. Both host genetic susceptibility and host-microbiota interactions may impact cancer risk and response to treatment; however, microbiota have the potential to be uniquely modifiable and accessible targets for treatment. Here, we focus on strategies to modify microbiota composition and function in patients with cancer. First, we evaluate the use of fecal microbiota transplant to restore microbial equilibrium following perturbation by antibiotics and chemotherapy, and as a treatment of complications of hematopoietic stem cell transplantation (HSCT), such as graft-versus-host disease and colonization with multidrug-resistant organisms. We then address the potential use of both probiotics and dietary prebiotic compounds in targeted modulation of the microbiota intended to improve outcomes in hematologic diseases. With each type of therapy, we highlight the role that abnormal, or dysbiotic, microbiota play in disease, treatment efficacy, and toxicity and evaluate their potential promise as emerging strategies for microbiota manipulation in patients with hematologic malignancies and in those undergoing HSCT.

  View details for DOI 10.1182/hematology.2019000365

  View details for PubMedID 31808861

• Microbiota modification in hematology: still at the bench or ready for the bedside? Blood advances Severyn, C. J., Brewster, R. n., Andermann, T. M. 2019; 3 (21): 3461–72

  Abstract

  Growing evidence suggests that human microbiota likely influence diverse processes including hematopoiesis, chemotherapy metabolism, and efficacy, as well as overall survival in patients with hematologic malignancies and other cancers. Both host genetic susceptibility and host-microbiota interactions may impact cancer risk and response to treatment; however, microbiota have the potential to be uniquely modifiable and accessible targets for treatment. Here, we focus on strategies to modify microbiota composition and function in patients with cancer. First, we evaluate the use of fecal microbiota transplant to restore microbial equilibrium following perturbation by antibiotics and chemotherapy, and as a treatment of complications of hematopoietic stem cell transplantation (HSCT), such as graft-versus-host disease and colonization with multidrug-resistant organisms. We then address the potential use of both probiotics and dietary prebiotic compounds in targeted modulation of the microbiota intended to improve outcomes in hematologic diseases. With each type of therapy, we highlight the role that abnormal, or dysbiotic, microbiota play in disease, treatment efficacy, and toxicity and evaluate their potential promise as emerging strategies for microbiota manipulation in patients with hematologic malignancies and in those undergoing HSCT.

  View details for DOI 10.1182/bloodadvances.2019000365

  View details for PubMedID 31714965

• Meningioma transcription factors link cell lineage with systemic metabolic cues. Neuro-oncology Du, Z., Brewster, R., Merrill, P. H., Chmielecki, J., Francis, J., Aizer, A., Abedalthagafi, M., Sholl, L. M., Geffers, L., Alexander, B., Santagata, S. 2018; 20 (10): 1331-1343

  Abstract

  Tumor cells recapitulate cell-lineage transcriptional programs that are characteristic of normal tissues from which they arise. It is unclear why such lineage programs are fatefully maintained in tumors and if they contribute to cell proliferation and viability.Here, we used the most common brain tumor, meningioma, which is strongly associated with female sex and high body mass index (BMI), as a model system to address these questions. We screened expression profiling data to identify the transcription factor (TF) genes which are highly enriched in meningioma, and characterized the expression pattern of those TFs and downstream genes in clinical meningioma samples as well as normal brain tissues. Meningioma patient-derived cell lines (PDCLs) were used for further validation and characterization.We identified 8 TFs highly enriched in meningioma. Expression of these TFs, which included sine oculis homeobox 1 (SIX1), readily distinguished meningiomas from other primary brain tumors and was maintained in PDCLs and even in pulmonary meningothelial nodules. In meningioma PDCLs, SIX1 and its coactivator eyes absent 2 (EYA2) supported the expression of the leptin receptor (LEPR), the cell-surface receptor for leptin (LEP), the adipose-specific hormone that is high in women and in individuals with high BMI. Notably, these transcriptional regulatory factors, LEPR and LEP, both contributed to support meningioma PDCLs proliferation and survival, elucidating a survival dependency on both a core transcriptional program and a metabolic cell-surface receptor.These findings provide one rationale for why lineage TF expression is maintained in meningioma and for the epidemiological association of female sex and obesity with meningioma risk.

  View details for DOI 10.1093/neuonc/noy057

  View details for PubMedID 29660031

  View details for PubMedCentralID PMC6120365

• The Search for Meaning ACADEMIC MEDICINE Brewster, R., Vyas, D. 2018; 93 (6): 823

  View details for DOI 10.1097/ACM.0000000000002185

  View details for Web of Science ID 000435369500016

• Endoscope-assisted repair of CSF otorrhea and temporal lobe encephaloceles via keyhole craniotomy. Journal of neurosurgery Roehm, P. C., Tint, D., Chan, N., Brewster, R., Sukul, V., Erkmen, K. 2018; 128 (6): 1880-1884

  Abstract

  OBJECTIVE Temporal lobe encephaloceles and cerebrospinal fluid otorrhea from temporal bone defects that involve the tegmen tympani and mastoideum are generally repaired using middle fossa craniotomy, mastoidectomy, or combined approaches. Standard middle fossa craniotomy exposes patients to dural retraction, which can lead to postoperative neurological complications. Endoscopic and minimally invasive techniques have been used in other surgeries to minimize brain retraction, and so these methods were applied to repair the lateral skull base. The goal of this study was to determine if the use of endoscopic visualization through a middle fossa keyhole craniotomy could effectively repair tegmen defects. METHODS The authors conducted a retrospective review of 6 cases of endoscope-assisted middle fossa repairs of tegmen dehiscences at a tertiary care medical center within an 18-month period. RESULTS All cases were successfully treated using a keyhole craniotomy with endoscopic visualization and minimal retraction. Surgical times did not increase. There were no major postoperative complications, recurrences of encephaloceles, or cerebrospinal fluid otorrhea in these patients. CONCLUSIONS Endoscopic visualization allows for smaller incisions and craniotomies and less risk of brain retraction injury without compromising repair integrity during temporal encephalocele and tegmen repairs.

  View details for DOI 10.3171/2017.1.JNS161947

  View details for PubMedID 28799867

• Superior semicircular canal dehiscence syndrome. Journal of neurosurgery Bi, W. L., Brewster, R., Poe, D., Vernick, D., Lee, D. J., Eduardo Corrales, C., Dunn, I. F. 2017; 127 (6): 1268-1276

  Abstract

  Superior semicircular canal dehiscence (SSCD) syndrome is an increasingly recognized cause of vestibular and/or auditory symptoms in both adults and children. These symptoms are believed to result from the presence of a pathological mobile "third window" into the labyrinth due to deficiency in the osseous shell, leading to inadvertent hydroacoustic transmissions through the cochlea and labyrinth. The most common bony defect of the superior canal is found over the arcuate eminence, with rare cases involving the posteromedial limb of the superior canal associated with the superior petrosal sinus. Operative intervention is indicated for intractable or debilitating symptoms that persist despite conservative management and vestibular sedation. Surgical repair can be accomplished by reconstruction or plugging of the bony defect or reinforcement of the round window through a variety of operative approaches. The authors review the etiology, pathophysiology, presentation, diagnosis, surgical options, and outcomes in the treatment of this entity, with a focus on potential pitfalls that may be encountered during clinical management.

  View details for DOI 10.3171/2016.9.JNS16503

  View details for PubMedID 28084916

• Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas. Neuro-oncology Shankar, G. M., Abedalthagafi, M., Vaubel, R. A., Merrill, P. H., Nayyar, N., Gill, C. M., Brewster, R., Bi, W. L., Agarwalla, P. K., Thorner, A. R., Reardon, D. A., Al-Mefty, O., Wen, P. Y., Alexander, B. M., van Hummelen, P., Batchelor, T. T., Ligon, K. L., Ligon, A. H., Meyerson, M., Dunn, I. F., Beroukhim, R., Louis, D. N., Perry, A., Carter, S. L., Giannini, C., Curry, W. T., Cahill, D. P., Barker, F. G., Brastianos, P. K., Santagata, S. 2017; 19 (4): 535-545

  Abstract

  Patients with meningiomas have widely divergent clinical courses. Some entirely recover following surgery alone, while others have relentless tumor recurrences. This clinical conundrum is exemplified by rhabdoid meningiomas, which are designated in the World Health Organization Classification of Tumours as high grade, despite only a subset following an aggressive clinical course. Patient management decisions are further exacerbated by high rates of interobserver variability, biased against missing possibly aggressive tumors. Objective molecular determinants are needed to guide classification and clinical decision making.To define genomic aberrations of rhabdoid meningiomas, we performed sequencing of cancer-related genes in 27 meningiomas from 18 patients with rhabdoid features and evaluated breast cancer [BRCA]1-associated protein 1 (BAP1) expression by immunohistochemistry in 336 meningiomas. We assessed outcomes, germline status, and family history in patients with BAP1-negative rhabdoid meningiomas.The tumor suppressor gene BAP1, a ubiquitin carboxy-terminal hydrolase, is inactivated in a subset of high-grade rhabdoid meningiomas. Patients with BAP1-negative rhabdoid meningiomas had reduced time to recurrence compared with patients with BAP1-retained rhabdoid meningiomas (Kaplan-Meier analysis, 26 mo vs 116 mo, P < .001; hazard ratio 12.89). A subset of patients with BAP1-deficient rhabdoid meningiomas harbored germline BAP1 mutations, indicating that rhabdoid meningiomas can be a harbinger of the BAP1 cancer predisposition syndrome.We define a subset of aggressive rhabdoid meningiomas that can be recognized using routine laboratory tests. We implicate ubiquitin deregulation in the pathogenesis of these high-grade malignancies. In addition, we show that familial and sporadic BAP1-mutated rhabdoid meningiomas are clinically aggressive, requiring intensive clinical management.

  View details for DOI 10.1093/neuonc/now235

  View details for PubMedID 28170043

  View details for PubMedCentralID PMC5464371

• Genomic landscape of intracranial meningiomas. Journal of neurosurgery Bi, W. L., Abedalthagafi, M., Horowitz, P., Agarwalla, P. K., Mei, Y., Aizer, A. A., Brewster, R., Dunn, G. P., Al-Mefty, O., Alexander, B. M., Santagata, S., Beroukhim, R., Dunn, I. F. 2016; 125 (3): 525-35

  Abstract

  Meningiomas are the most common primary intracranial neoplasms in adults. Current histopathological grading schemes do not consistently predict their natural history. Classic cytogenetic studies have disclosed a progressive course of chromosomal aberrations, especially in high-grade meningiomas. Furthermore, the recent application of unbiased next-generation sequencing approaches has implicated several novel genes whose mutations underlie a substantial percentage of meningiomas. These insights may serve to craft a molecular taxonomy for meningiomas and highlight putative therapeutic targets in a new era of rational biology-informed precision medicine.

  View details for DOI 10.3171/2015.6.JNS15591

  View details for PubMedID 26771848

• Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma. Neuro-oncology Abedalthagafi, M., Bi, W. L., Aizer, A. A., Merrill, P. H., Brewster, R., Agarwalla, P. K., Listewnik, M. L., Dias-Santagata, D., Thorner, A. R., Van Hummelen, P., Brastianos, P. K., Reardon, D. A., Wen, P. Y., Al-Mefty, O., Ramkissoon, S. H., Folkerth, R. D., Ligon, K. L., Ligon, A. H., Alexander, B. M., Dunn, I. F., Beroukhim, R., Santagata, S. 2016; 18 (5): 649-55

  Abstract

  Meningiomas are the most common primary intracranial tumor in adults. Identification of SMO and AKT1 mutations in meningiomas has raised the possibility of targeted therapies for some patients. The frequency of such mutations in clinical cohorts and the presence of other actionable mutations in meningiomas are important to define.We used high-resolution array-comparative genomic hybridization to prospectively characterize copy-number changes in 150 meningiomas and then characterized these samples for mutations in AKT1, KLF4, NF2, PIK3CA, SMO, and TRAF7.Similar to prior reports, we identified AKT1 and SMO mutations in a subset of non-NF2-mutant meningiomas (ie, ∼9% and ∼6%, respectively). Notably, we detected oncogenic mutations in PIK3CA in ∼7% of non-NF2-mutant meningiomas. AKT1, SMO, and PIK3CA mutations were mutually exclusive. AKT1, KLF4, and PIK3CA mutations often co-occurred with mutations in TRAF7. PIK3CA-mutant meningiomas showed limited chromosomal instability and were enriched in the skull base.This work identifies PI3K signaling as an important target for precision medicine trials in meningioma patients.

  View details for DOI 10.1093/neuonc/nov316

  View details for PubMedID 26826201

  View details for PubMedCentralID PMC4827048

• How a Lumbar Diskectomy Influenced Medical Malpractice and the Landscape of Health Care. World neurosurgery Yang, B. W., Bi, W. L., Smith, T. R., Brewster, R., Gormley, W. B., Dunn, I. F., Laws, E. R. 2016; 86: 88-92

  Abstract

  Jeff Chandler was one of Hollywood's top leading men in the 1950s and 1960s. In 1961, at the peak of his career, Chandler died of complications following an aortic-iliac injury during a routine lumbar diskectomy. The subsequent public outcry and malpractice suit resulted in an unprecedented settlement award.Chandler's lawsuit marked a pivotal time in the evolution of medical malpractice and monetary awards. Before 1960, malpractice legal claims were rare, with little impact on the practice of medicine. Chandler's award, however, dwarfed the average malpractice verdict for its time and would influence the relationship between medicine and the legal world. This case helped issue a radical increase in total expenditure on medical liability insurance, frequency of successful claims, average numbers of neurosurgical malpractice suits, and financial award sizes. The trend ensuing from this time has continued to the contemporary era. To link Chandler's case to the current malpractice climate, we highlight the relationship of the case with 3 factors comprising the legal argument for the perpetuation of medical malpractice: 1) contingency fees, 2) citizen juries, and 3) the nature of tort law.This case illustrates an inflection point in American medical malpractice expenditure increases beginning in the 1960s to a current estimated $55.6 billion. As we investigate ways to provide value in health care, it is important to consider the historical factors that have influenced the status quo when seeking strategies to reform the malpractice system on both sides of the value equation: quality and cost.

  View details for DOI 10.1016/j.wneu.2015.09.039

  View details for PubMedID 26409087

• Evita's lobotomy. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Young, G. J., Bi, W. L., Smith, T. R., Brewster, R., Gormley, W. B., Dunn, I. F., Laws, E. R., Nijensohn, D. E. 2015; 22 (12): 1883-8

  Abstract

  For 60 years, the details about Eva Perón's illness and lobotomy at the end of her life have been obscured from the public. Here, we examine the sociopolitical factors that may have contributed to this secrecy. The first involves Eva Perón's political status and the personality cult surrounding her image, including partisan efforts to present her as a patron saint of Peronism. The second involves the social perceptions, which are often stigmatizing, regarding disease in political or public figures. Notably, neuropsychiatric illness and associated indications for treatment were viewed as oligarchic by the Perón regime, and admission to a lobotomy may have been perceived as anti-Peronist. A third factor involves the growing ignominy of prefrontal lobotomy as a surgical modality, which may have precluded operative exposés. A final factor may be that Eva Perón's lobotomy was in fact performed for behavior and personality modification, and not just for pain control. A brief history of lobotomy is presented, highlighting its adoption as a procedural panacea for psychiatric illnesses, relief of intractable pain from cancer, and management of belligerent behavior, and its subsequent fall from clinical favor. Although a shroud of secrecy still surrounds Eva Perón's prefrontal lobotomy, these factors provide a potential rationale for the circumstances, as well as foster a discussion of cultural elements that may still play a role in the public perception of psychosurgery today.

  View details for DOI 10.1016/j.jocn.2015.07.005

  View details for PubMedID 26463273

• The Assassination of Abraham Lincoln and the Evolution of Neuro-Trauma Care: Would the 16th President Have Survived in the Modern Era? World neurosurgery Yan, S. C., Smith, T. R., Bi, W. L., Brewster, R., Gormley, W. B., Dunn, I. F., Laws, E. R. 2015; 84 (5): 1453-7

  Abstract

  Abraham Lincoln was the 16(th) President of the United States of America. On April 14, 1865, shortly after his re-election and the conclusion of the Civil War, Lincoln was shot and killed by John Wilkes Booth. Although numerous physicians tended to the President shortly after his injury, he passed away the next morning. Today, we recognize Lincoln as one of the greatest Presidents in American history. His assassination profoundly influenced the future of the United States, especially as the country was coming back together again following the Civil War. Testaments to his lasting legacy can be seen in many places, from the stone carving of him on Mount Rushmore to his image gracing the $5 bill. What if the President had survived his injury? Would he have had a different outcome utilizing current critical care treatment? Neurotrauma care in 1865 was not yet developed, and head wounds such as the one Lincoln sustained were almost always fatal. The medical attention he received is considered by historians and physicians today to be excellent for that time. We look at the evolution of neurotrauma care during the last 150 years in the US. Particular focus is paid to the advancement of care for penetrating brain injuries in modern trauma centers.

  View details for DOI 10.1016/j.wneu.2015.06.011

  View details for PubMedID 26092530

• The neurosurgeon as baseball fan and inventor: Walter Dandy and the batter's helmet. Neurosurgical focus Brewster, R., Bi, W. L., Smith, T. R., Gormley, W. B., Dunn, I. F., Laws, E. R. 2015; 39 (1): E9

  Abstract

  Baseball maintains one of the highest impact injury rates in all athletics. A principal causative factor is the "beanball," referring to a pitch thrown directly at a batter's head. Frequent morbidities elicited demand for the development of protective gear development in the 20th century. In this setting, Dr. Walter Dandy was commissioned to design a "protective cap" in 1941. His invention became widely adopted by professional baseball and inspired subsequent generations of batting helmets. As a baseball aficionado since his youth, Walter Dandy identified a natural partnership between baseball and medical practice for the reduction of beaning-related brain injuries. This history further supports the unique position of neurosurgeons to leverage clinical insights, inform innovation, and expand service to society.

  View details for DOI 10.3171/2015.3.FOCUS1552

  View details for PubMedID 26126408