All Publications

  • The CCR6-CCL20 axis promotes regulatory T cell glycolysis and immunosuppression in tumors. Cancer immunology research Pant, A., Jain, A., Chen, Y., Patel, K., Saleh, L., Tzeng, S., Nitta, R. T., Zhao, L., Wu, C. Y., Bederson, M., Wang, W. L., Bergsneider, B. H., Choi, J., Medikonda, R., Verma, R., Cho, K. B., Kim, L. H., Kim, J. E., Yazigi, E., Lee, S. Y., Rajendran, S., Rajappa, P., Mackall, C. L., Li, G., Tyler, B., Brem, H., Pardoll, D. M., Lim, M., Jackson, C. M. 2024

    Abstract

    Regulatory T cells (Tregs) are important players in the tumor microenvironment. However, the mechanisms behind their immunosuppressive effects are poorly understood. We found that CCR6-CCL20 activity in tumor-infiltrating Tregs is associated with greater glycolytic activity and ablation of Ccr6 reduced glycolysis and lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive activity towards CD8+ T cells was abrogated in Ccr6-/- Tregs due to reduction in activation-induced glycolysis. Furthermore, Ccr6-/- mice exhibited improved survival across multiple tumor models compared to wildtype mice, and Treg and CD8+ T-cell depletion abrogated the improvement. In addition, Ccr6 ablation further promoted the efficacy of anti-PD-1 therapy in a preclinical glioma model. Follow-up knockdown of Ccl20 with siRNA also demonstrated improvement in antitumor efficacy. Our results unveil CCR6 as a marker and regulator of Treg-induced immunosuppression and identify approaches to target the metabolic determinants of Treg immunosuppressive activity.

    View details for DOI 10.1158/2326-6066.CIR-24-0230

    View details for PubMedID 39133127

  • Diversity, Equity, and Inclusion Statements and Initiatives on US Residency Program Websites: A Cross-Sectional Study NEUROSURGERY PRACTICE Bederson, M., Bennett, N., Herrick, D., Harris, O. 2025; 6 (2)

    View details for DOI 10.1227/neuprac.0000000000000129

    View details for Web of Science ID 001441312800001

  • Celebrating advocacy: a pioneer and role model. Journal of neurosurgery Bederson, M. M., Haid, R. W. 2025; 142 (5): 1484-1489

    Abstract

    Continued advancement of the neurological surgery specialty depends on health policy engagement aimed at advocating for and protecting neurosurgeons and their patients. Dr. Ann R. Stroink, born in Seattle, Washington, and former president of the American Association of Neurological Surgeons (2022-2023), is an exemplar pioneer and role model in neurosurgery and advocacy. She has held numerous significant leadership positions in grassroots and national efforts to improve neurosurgical care and compensation, including serving as chair of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Washington Committee, the Neurosurgery Delegation to the American Medical Association, and the Council of State Neurosurgical Societies. This brief historical vignette highlights the qualities of a pioneer advocate in neurosurgery who rose to be a successful leader while overcoming the challenges of practicing in a rural setting and within a historically male-dominated profession. Dr. Stroink's legacy serves as a beacon of inspiration, reminding us that through perseverance and advocacy we can pave the way for a brighter future in neurosurgery and beyond.

    View details for DOI 10.3171/2024.9.JNS241229

    View details for PubMedID 39889287

  • Applications of mixed reality with medical imaging for training and clinical practice. Journal of medical imaging (Bellingham, Wash.) Lauinger, A. R., McNicholas, M., Bramlet, M., Bederson, M., Sutton, B. P., Cao, C. G., Ahmad, I. S., Brown, C., Jamison, S., Adve, S., Vozenilek, J., Rehg, J., Cohen, M. S. 2024; 11 (6): 062608

    Abstract

    This review summarizes the current use of extended reality (XR) including virtual reality (VR), mixed reality, and augmented reality (AR) in the medical field, ranging from medical imaging to training to preoperative planning. It covers the integration of these technologies into clinical practice and within medical training while discussing the challenges and future opportunities in this sphere. This will hopefully encourage more physicians to collaborate on integrating medicine and technology.The review was written by experts in the field based on their knowledge and on recent publications exploring the topic of extended realities in medicine.Based on our findings, XR including VR, mixed reality, and AR are increasingly utilized within surgery both for preoperative planning and intraoperative procedures. These technologies are also promising means for improved education at every level of physician training. However, there are still barriers to the widespread adoption of VR, mixed reality, and AR, including human factors, technological challenges, and regulatory issues.Based on the current use of VR, mixed reality, and AR, it is likely that the use of these technologies will continue to grow over the next decade. To support the development and integration of XR into medicine, it is important for academic groups to collaborate with industrial groups and regulatory agencies in these endeavors. These joint projects will help address the current limitations and mutually benefit both fields.

    View details for DOI 10.1117/1.JMI.11.6.062608

    View details for PubMedID 39734608

    View details for PubMedCentralID PMC11669596

  • Diagnostic predictive values for sport-related concussions: a systematic review and diagnostic meta-analysis. Journal of neurosurgery Dharnipragada, R., Naik, A., Denduluri, L. S., Bederson, M., Akkad, A., Cramer, S. W., Koester, S. W., Catapano, J. S., Zuckerman, S. L., Snyder, L., Arnold, P. M. 2024; 140 (2): 560-569

    Abstract

    Sport-related concussions (SRCs) can cause significant neurological symptoms, and approximately 10%-15% of athletes with SRC experience a prolonged recovery. Given the lack of visible injury on brain imaging and their varied presentations, concussions can be difficult to diagnose. A variety of tests and examination methods have been used to elicit a concussion diagnosis; however, the sensitivity and specificity of these tests are variable. The authors performed a systematic review and meta-analysis to evaluate the sensitivity and specificity of standardized tests and visible signs like balance and vision changes in the diagnosis of SRC.A PRISMA-adherent systematic review of concussion diagnostic examinations was performed using the PubMed, MEDLINE, Scopus, Cochrane, Web of Science, and Google Scholar databases on December 1, 2022. Search terms included "concussion," "traumatic brain injury," "diagnosis," "sensitivity," and "specificity." Each method of examination was categorized into larger group-based symptomatologic presentations or standardized tools. The primary outcome was the diagnosis of concussion. Pooled specificity and sensitivity for each method were calculated using a meta-analysis of proportion and were hierarchically ranked using P-scores calculated from a diagnostic frequentist network meta-analysis.Thirty full-length articles were identified for inclusion, 13 of which evaluated grouped symptomology examinations (balance and overall clinical presentation) and 17 of which evaluated established formalized tools (ImPACT, King-Devick [K-D] Test, Sport Concussion Assessment Tool [SCAT]). The pooled specificity of the examination methods differed minimally (0.8-0.85), whereas the sensitivity varied to a larger degree (0.5-0.88). In a random effects model, the SCAT had the greatest diagnostic yield (diagnostic OR 31.65, 95% CI 11.06-90.57). Additionally, P-score hierarchical ranking revealed SCAT as having the greatest diagnostic utility (p = 0.9733), followed sequentially by ImPACT, clinical presentation, K-D, and balance.In deciphering which concussion symptom-focused examinations and standardized tools are most accurate in making a concussion diagnosis, the authors found that the SCAT examination has the greatest diagnostic yield, followed by ImPACT, clinical presentation, and K-D, which have comparable value for diagnosis. Given the indirect nature of this analysis, however, further comparative studies are needed to validate the findings.

    View details for DOI 10.3171/2023.6.JNS23279

    View details for PubMedID 37877969

  • Factors influencing geographic gender disparity in neurosurgery: a nationwide geospatial clustering analysis. Journal of neurosurgery Naik, A., Peterman, N., Furey, C., Paisan, G., Catapano, J., Bhardwaj, D., Iyer, A., Bederson, M., Pappu, S., Snyder, L., Stroink, A., Lawton, M. T., Arnold, P. M. 2024; 140 (1): 282-290

    Abstract

    Women neurosurgeons (WNs) continue to remain a minority in the specialty despite significant initiatives to increase their representation. One domain less explored is the regional distribution of WNs, facilitated by the hiring practices of neurosurgical departments across the US. In this analysis, the authors coupled the stated practice location of WNs with regional geospatial data to identify hot spots and cold spots of prevalence and examined regional predictors of increases and decreases in WNs over time.The authors examined the National Provider Identifier (NPI) numbers of all neurosurgeons obtained via the National Plan and Provider Enumeration System (NPPES), identifying the percentage of WNs in each county for which data were appended with data from the US Census Bureau. Change in WN rates was identified by calculating a regression slope for all years included (2015-2022). Hot spots and cold spots of WNs were identified through Moran's clustering analysis. Population and surgeon features were compared for hot spots and cold spots.WNs constituted 10.73% of all currently active neurosurgical NPIs, which has increased from 2015 (8.81%). Three hot spots were found-including the Middle Atlantic and Pacific divisions-that contrasted with scattered cold spots throughout the East Central regions that included Memphis as a major city. Although relatively rapidly growing, hot spots had significant gender inequality, with a median WN percentage of 11.38% and a median of 0.61 WNs added to each respective county per year.The authors analyzed the prevalence of WNs by using aggregated data from the NPPES and US Census Bureau. The authors also show regional hot spots of WNs and that the establishment of WNs in a region is a predictor of additional WNs entering the region. These data suggest that female neurosurgical mentorship and representation may be a major driver of acceptance and further gender diversity in a given region.

    View details for DOI 10.3171/2023.5.JNS23203

    View details for PubMedID 37439489

  • Traumatic Brain Injury Mortality and Correlates in Low- and Middle-Income Countries: A Meta-Epidemiological Study. Neurosurgery Naik, A., Bederson, M. M., Detchou, D., Dharnipragada, R., Hassaneen, W., Arnold, P. M., Germano, I. M. 2023; 93 (4): 736-744

    Abstract

    It is estimated that up to 69 million people per year experience traumatic brain injury (TBI) with the highest prevalence found in low- and middle-income countries (LMICs). A paucity of data suggests that the mortality rate after severe TBI is twice as high in LMICs than in high-income countries.To analyze TBI mortality in LMICs and to evaluate what country-based socioeconomic and demographic parameters influence TBI outcomes.Four databases were searched for the period January 1, 2002, to January 1, 2022, for studies describing TBI outcomes in LMICs. Multivariable analysis was performed using multivariable linear regression, with the outcome as the pooled mortality by country and the covariates as the adjusted parameters.Our search yielded 14 376 records of which 101 were included in the final analysis, totaling 59 197 patients and representing 31 LMICs. The pooled TBI-related mortality was 16.7% (95% CI: 13.7%-20.3%) without significant differences comparing pediatrics vs adults. Pooled severe TBI-related mortality was significantly higher than mild. Multivariable analysis showed a significant association between TBI-related mortality and median income ( P = .04), population percentage below poverty line ( P = .02), primary school enrollment ( P = .01), and poverty head ratio ( P = .04).TBI-related mortality in LMICs is 3-fold to 4-fold higher than that reported in high-income countries. Within LMICs, parameters associated with poorer outcomes after TBI include factors recognized as social determinants of health. Addressing social determinants of health in LMICs might expedite the quest to close the care delivery gap after TBI.

    View details for DOI 10.1227/neu.0000000000002479

    View details for PubMedID 37010323

  • Efficacy of deep brain stimulation for the treatment of anorexia nervosa: a systematic review and network meta-analysis of patient-level data. Neurosurgical focus Shaffer, A., Naik, A., Bederson, M., Arnold, P. M., Hassaneen, W. 2023; 54 (2): E5

    Abstract

    Deep brain stimulation (DBS) has been approved as a therapy for movement disorders and obsessive-compulsive disorder. Recently, DBS has been studied in patients with anorexia nervosa (AN), which is a debilitating and life-threatening psychiatric disorder. Several stimulation locations have been tested without a clear indication of the best region. In this systematic review and network meta-analysis, the authors used patient-level data to identify stimulation targets with the greatest evidence for efficacy in increasing body mass index (BMI).A systematic search was performed on or before August 4, 2022, using PubMed/MEDLINE, Ovid, and Scopus. Articles were included if patient-level data were presented, patients were diagnosed with AN and treated with DBS, and 6 months or more of postoperative follow-up data were reported. Quality and risk of bias were assessed with the NIH assessment tools. Patient data were collected and stratified by stimulation location. A network meta-analysis was performed. This review was written in accordance with PRISMA guidelines for systematic reviews.Eleven studies consisting of 36 patients were included. The mean age and BMI at the time of surgery were 38.07 (SD 11.64) years and 12.58 (SD 1.4) kg/m2, respectively. After 6 months of DBS, a significant difference in percentage change in BMI was found between the nucleus accumbens and subcallosal cingulate cortex (SCC) (SMD 0.78; 95% CI 0.10, 1.45) and between the SCC and ventral anterior limb of the internal capsule (SMD -1.51; 95% CI -2.39, -0.62). Similarly, at 9-12 months, a significant difference in percentage change in BMI was found between the SCC and ventral anterior limb of the internal capsule (SMD -1.18; 95% CI -2.21, -0.15). With hierarchical ranking, this study identified SCC as the most supported stimulation location for BMI change at 6 and 9-12 months (P-scores 0.9449 and 0.9771, respectively).Several DBS targets have been tested for AN, and this study identified the SCC as the most supported region for BMI change. However, further studies with blinded on/off periods are necessary to confirm this finding.

    View details for DOI 10.3171/2022.11.FOCUS22616

    View details for PubMedID 36724522