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Article: Immunotherapy Resistance in Glioblastoma.

Wang, Elaina J / Chen, Jia-Shu / Jain, Saket / Morshed, Ramin A / Haddad, Alexander F / Gill, Sabraj / Beniwal, Angad S / Aghi, Manish K

Frontiers in genetics

2021 Volume 12, Page(s) 750675

Abstract: Glioblastoma is the most common malignant primary brain tumor in adults. Despite treatment consisting of surgical resection followed by radiotherapy and adjuvant chemotherapy, survival remains poor at a rate of 26.5% at 2 years. Recent successes in using ...

Abstract	Glioblastoma is the most common malignant primary brain tumor in adults. Despite treatment consisting of surgical resection followed by radiotherapy and adjuvant chemotherapy, survival remains poor at a rate of 26.5% at 2 years. Recent successes in using immunotherapies to treat a number of solid and hematologic cancers have led to a growing interest in harnessing the immune system to target glioblastoma. Several studies have examined the efficacy of various immunotherapies, including checkpoint inhibitors, vaccines, adoptive transfer of lymphocytes, and oncolytic virotherapy in both pre-clinical and clinical settings. However, these therapies have yielded mixed results at best when applied to glioblastoma. While the initial failures of immunotherapy were thought to reflect the immunoprivileged environment of the brain, more recent studies have revealed immune escape mechanisms created by the tumor itself and adaptive resistance acquired in response to therapy. Several of these resistance mechanisms hijack key signaling pathways within the immune system to create a protumoral microenvironment. In this review, we discuss immunotherapies that have been trialed in glioblastoma, mechanisms of tumor resistance, and strategies to sensitize these tumors to immunotherapies. Insights gained from the studies summarized here may help pave the way for novel therapies to overcome barriers that have thus far limited the success of immunotherapy in glioblastoma.
Language	English
Publishing date	2021-12-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.750675
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Article: Glioblastoma induces the recruitment and differentiation of hybrid neutrophils from skull bone marrow.

Lad, By Meeki / Beniwal, Angad S / Jain, Saket / Shukla, Poojan / Jung, Jangham / Shah, Sumedh S / Yagnik, Garima / Babikir, Husam / Nguyen, Alan T / Gill, Sabraj / Young, Jacob S / Lui, Austin / Salha, Diana / Diaz, Aaron / Aghi, Manish K

bioRxiv : the preprint server for biology

2023

Abstract: Tumor-associated neutrophil (TAN) effects on glioblastoma biology remain under-characterized. We show here that 'hybrid' neutrophils with dendritic features - including morphological complexity, expression of antigen presentation genes, and the ability ... ...

Abstract	Tumor-associated neutrophil (TAN) effects on glioblastoma biology remain under-characterized. We show here that 'hybrid' neutrophils with dendritic features - including morphological complexity, expression of antigen presentation genes, and the ability to process exogenous peptide and stimulate MHCII-dependent T cell activation - accumulate intratumorally and suppress tumor growth
Language	English
Publishing date	2023-03-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.24.534105
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Article ; Online: Identifying risk factors for postoperative diabetes insipidus in more than 2500 patients undergoing transsphenoidal surgery: a single-institution experience.

Joshi, Rushikesh S / Pereira, Matheus P / Osorio, Robert C / Oh, Taemin / Haddad, Alexander F / Pereira, Kaitlyn M / Donohue, Kevin C / Peeran, Zain / Sudhir, Sweta / Jain, Saket / Beniwal, Angad / Chandra, Ankush / Han, Seunggu J / Rolston, John D / Theodosopoulos, Philip V / Kunwar, Sandeep / Blevins, Lewis S / Aghi, Manish K

Journal of neurosurgery

2022 , Page(s) 1–11

Abstract: Objective: Diabetes insipidus (DI) following transsphenoidal surgery can adversely impact quality of life and be difficult to manage. This study sought to characterize pre- and perioperative risk factors that may predispose patients to DI after ... ...

Abstract	Objective: Diabetes insipidus (DI) following transsphenoidal surgery can adversely impact quality of life and be difficult to manage. This study sought to characterize pre- and perioperative risk factors that may predispose patients to DI after pituitary surgery. Methods: A retrospective review of patients treated at a single institution from 2007 to 2019 was conducted. DI was defined as postoperative sodium > 145 mEq/L and urine output > 300 ml/hr and/or postoperative desmopressin (ddAVP) use. DI was further characterized as transient or permanent. Uni- and multivariate analyses were performed to determine variables associated with postoperative DI. Results: The authors identified 2529 patients who underwent transsphenoidal surgery at their institution. Overall, DI was observed in 270 (10.7%) of the 2529 patients, with 114 (4.5%) having permanent DI and 156 (6.2%) with transient symptoms. By pathology type, DI occurred in 31 (46.3%) of 67 craniopharyngiomas, 10 (14.3%) of 70 apoplexies, 46 (14.3%) of 322 Rathke's cleft cysts, 77 (7.7%) of 1004 nonfunctioning pituitary adenomas (NFPAs), and 62 (7.6%) of 811 functioning pituitary adenomas (FPAs). Final lesion pathology significantly affected DI rates (p < 0.001). Multivariate analysis across pathologies showed that younger age (odds ratio [OR] 0.97, p < 0.001), intraoperative CSF encounter (OR 2.74, p < 0.001), craniopharyngioma diagnosis (OR 8.22, p = 0.007), and postoperative hyponatremia (OR 1.50, p = 0.049) increased the risk of DI. Because surgery for each pathology created specific risk factors for DI, the analysis was then limited to the 1815 pituitary adenomas (PAs) in the series, comprising 1004 NFPAs and 811 FPAs. For PAs, younger age (PA: OR 0.97, p < 0.001; NFPA: OR 0.97, p < 0.001; FPA: OR 0.97, p = 0.028) and intraoperative CSF encounter (PA: OR 2.99, p < 0.001; NFPA: OR 2.93, p < 0.001; FPA: OR 3.06, p < 0.001) increased DI rates in multivariate analysis. Among all PAs, patients with DI experienced peak sodium levels later than those without DI (postoperative day 11 vs 2). Increasing tumor diameter increased the risk of DI in FPAs (OR 1.52, p = 0.008), but not in NFPAs (p = 0.564). Conclusions: In more than 2500 patients treated at a single institution, intraoperative CSF encounter, craniopharyngioma diagnosis, and young age all increased the risk of postoperative DI. Patients with postoperative hyponatremia exhibited higher rates of DI, suggesting possible bi- or triphasic patterns to DI. Greater vigilance should be maintained in patients meeting these criteria following transsphenoidal surgery to ensure early recognition and treatment of DI.
Language	English
Publishing date	2022-01-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	3089-2
ISSN	1933-0693 ; 0022-3085
ISSN (online)	1933-0693
ISSN	0022-3085
DOI	10.3171/2021.11.JNS211260
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Article ; Online: CD97 is associated with mitogenic pathway activation, metabolic reprogramming, and immune microenvironment changes in glioblastoma.

Safaee, Michael M / Wang, Elaina J / Jain, Saket / Chen, Jia-Shu / Gill, Sabraj / Zheng, Allison C / Garcia, Joseph H / Beniwal, Angad S / Tran, Y / Nguyen, Alan T / Trieu, Melissa / Leung, Kevin / Wells, Jim / Maclean, James M / Wycoff, Keith / Aghi, Manish K

Scientific reports

2022 Volume 12, Issue 1, Page(s) 1464

Abstract: Glioblastoma (GBM) is the most common primary brain tumor with a median survival under two years. Using in silico and in vitro techniques, we demonstrate heterogeneous expression of CD97, a leukocyte adhesion marker, in human GBM. Beyond its previous ... ...

Abstract	Glioblastoma (GBM) is the most common primary brain tumor with a median survival under two years. Using in silico and in vitro techniques, we demonstrate heterogeneous expression of CD97, a leukocyte adhesion marker, in human GBM. Beyond its previous demonstrated role in tumor invasion, we show that CD97 is also associated with upregulation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways in GBM. While CD97 knockout decreased Akt activation, CD97 targeting did not alter MAPK/Erk activation, did not slow GBM cell proliferation in culture, and increased levels of glycolytic and oxidative phosphorylation metabolites. Treatment with a soluble CD97 inhibitor did not alter activation of the MAPK/Erk and PI3K/Akt pathways. Tumors with high CD97 expression were associated with immune microenvironment changes including increased naïve macrophages, regulatory T cells, and resting natural killer (NK) cells. These data suggest that, while CD97 expression is associated with conflicting effects on tumor cell proliferative and metabolic pathways that overall do not affect tumor cell proliferation, CD97 exerts pro-tumoral effects on the tumor immune microenvironment, which along with the pro-invasive effects of CD97 we previously demonstrated, provides impetus to continue exploring CD97 as a therapeutic target in GBM.
MeSH term(s)	Activation, Metabolic/immunology ; Antigens, CD/genetics ; Antigens, CD/metabolism ; Brain Neoplasms/genetics ; Brain Neoplasms/immunology ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/immunology ; Gene Knockdown Techniques ; Gene Knockout Techniques ; Glioblastoma/genetics ; Glioblastoma/immunology ; Glioblastoma/pathology ; Humans ; MAP Kinase Signaling System/drug effects ; MAP Kinase Signaling System/immunology ; Metabolomics ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, G-Protein-Coupled/antagonists & inhibitors ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology
Chemical Substances	ADGRE5 protein, human ; Antigens, CD ; Receptors, G-Protein-Coupled ; AKT1 protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2022-01-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-05259-y
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Article ; Online: Pediatric moyamoya MRI score: an imaging-based scale to predict outcomes in surgically treated pediatric patients with moyamoya.

Garcia, Joseph H / Morshed, Ramin A / Winkler, Ethan A / Li, Yi / Fox, Christine K / Fullerton, Heather J / Rutledge, Caleb / Beniwal, Angad S / Lawton, Michael T / Abla, Adib A / Gupta, Nalin / Hetts, Steven W

Neurosurgical focus

2021 Volume 51, Issue 3, Page(s) E8

Abstract: Objective: Moyamoya is a progressive arteriopathy that predisposes patients to stroke due to stenosis of the intracranial internal carotid arteries and their proximal branches. Despite the morbidity caused by this condition, the ability to accurately ... ...

Abstract	Objective: Moyamoya is a progressive arteriopathy that predisposes patients to stroke due to stenosis of the intracranial internal carotid arteries and their proximal branches. Despite the morbidity caused by this condition, the ability to accurately predict prognosis for individual patients remains challenging. The goal of this study was to develop a systematic scoring method based on parenchymal findings on preoperative brain MRI to predict long-term outcomes for surgically treated pediatric patients with moyamoya. Methods: A retrospective surgical cohort of pediatric patients (≤ 18 years of age at the time of the initial surgery) with moyamoya from a single center were studied. Radiological variables with existing correlations between outcomes in moyamoya or other vascular diseases were chosen to score preoperative MRI based on easily defined parenchymal findings that could be rapidly assessed and used to make a numeric score. Calculated scores were correlated with clinical outcome measures using the Pearson correlation coefficient and area under the receiver operating characteristic curve (AUROC). Results: A total of 35 children with moyamoya disease or moyamoya syndrome were included in the study, with a median follow-up time of 2.6 years from the time of surgery. The pediatric moyamoya MRI score (PMMS) consists of ischemic changes (0-2; 0 = none, 1 = focal, 2 = diffuse), encephalomalacia (0-2; 0 = none, 1 = focal, 2 = diffuse), and hemorrhage (0-1; 0 = not present, 1 = present). PMMSs were highly correlated with pediatric modified Rankin Scale scores at the last follow-up (r = 0.7, 95% CI 0.44-0.84; p < 0.001) as a six-point scale, and when dichotomized (AUROC = 0.85). Conclusions: The PMMS was found to be a simple tool based on preoperative MRI data that could be quickly and easily calculated and correlated with disability. This scoring method may aid future development of predictive models of outcomes for children with moyamoya disease and moyamoya syndrome.
MeSH term(s)	Cerebral Revascularization ; Child ; Humans ; Magnetic Resonance Imaging ; Moyamoya Disease/diagnostic imaging ; Moyamoya Disease/surgery ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2021-08-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2026589-X
ISSN	1092-0684 ; 1092-0684
ISSN (online)	1092-0684
ISSN	1092-0684
DOI	10.3171/2021.6.FOCUS21283
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Article ; Online: Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects.

The Journal of clinical investigation

2023 Volume 133, Issue 5

Abstract: Cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of glioblastoma specimens yielded cells with CAF morphology and single-cell transcriptomic profiles based on their lack ... ...

Abstract	Cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of glioblastoma specimens yielded cells with CAF morphology and single-cell transcriptomic profiles based on their lack of copy number variations (CNVs) and elevated individual cell CAF probability scores derived from the expression of 9 CAF markers and absence of 5 markers from non-CAF stromal cells sharing features with CAFs. Cells without CNVs and with high CAF probability scores were identified in single-cell RNA-Seq of 12 patient glioblastomas. Pseudotime reconstruction revealed that immature CAFs evolved into subtypes, with mature CAFs expressing actin alpha 2, smooth muscle (ACTA2). Spatial transcriptomics from 16 patient glioblastomas confirmed CAF proximity to mesenchymal glioblastoma stem cells (GSCs), endothelial cells, and M2 macrophages. CAFs were chemotactically attracted to GSCs, and CAFs enriched GSCs. We created a resource of inferred crosstalk by mapping expression of receptors to their cognate ligands, identifying PDGF and TGF-β as mediators of GSC effects on CAFs and osteopontin and HGF as mediators of CAF-induced GSC enrichment. CAFs induced M2 macrophage polarization by producing the extra domain A (EDA) fibronectin variant that binds macrophage TLR4. Supplementing GSC-derived xenografts with CAFs enhanced in vivo tumor growth. These findings are among the first to identify glioblastoma CAFs and their GSC interactions, making them an intriguing target.
MeSH term(s)	Humans ; Glioblastoma/genetics ; Cancer-Associated Fibroblasts ; Transcriptome ; DNA Copy Number Variations ; Endothelial Cells ; Sequence Analysis, RNA
Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI147087
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Article ; Online: Plurihormonal PIT-1-Positive Pituitary Adenomas: A Systematic Review and Single-Center Series.

Andrews, John P / Joshi, Rushikesh S / Pereira, Matheus P / Oh, Taemin / Haddad, Alexander F / Pereira, Kaitlyn M / Osorio, Robert C / Donohue, Kevin C / Peeran, Zain / Sudhir, Sweta / Jain, Saket / Beniwal, Angad / Chopra, Ashley S / Sandhu, Narpal S / Tihan, Tarik / Blevins, Lewis / Aghi, Manish K

World neurosurgery

2021 Volume 151, Page(s) e185–e191

Abstract: Objective: The 2017 World Health Organization classification of pituitary adenomas identified the plurihormonal PIT-1-positive (PP1) adenoma as a distinct subtype. The reported data suggest that PP1 adenomas encompass the former class of silent subtype ... ...

Abstract	Objective: The 2017 World Health Organization classification of pituitary adenomas identified the plurihormonal PIT-1-positive (PP1) adenoma as a distinct subtype. The reported data suggest that PP1 adenomas encompass the former class of silent subtype 3 (SS3) adenomas and might have an aggressive phenotype. In the present study, we summarized the current clinical data on PP1 and SS3 adenomas and compared the reported data with the data from a single institutional cohort. Methods: Medline and Google Scholar were searched from 1990 to 2020 for clinical series of PP1 and SS3 adenomas in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Studies were included if they had reported pituitary pathology as PP1 or SS3 adenomas and had reported the clinical outcomes after surgical intervention. To better define the PP1 phenotype compared with non-PP1 adenomas, we also reviewed the adenomas treated surgically at our institution from 2012 to 2019. Results: Of all the tumors reported in the studies as PP1 or SS3, 99% were macroadenomas and 18% were giant adenomas (>4 cm). Of the reported patients, 31.8% had received radiotherapy, and 22.9% had undergone multiple surgeries for their pituitary tumor. In our single-center experience, 20 patients had an adenoma that met the criteria for a PP1 adenoma. Compared with the 1146 non-PP1 tumors, the PP1 tumors did not show statistically significant differences in the extent of resection, size, number of previous surgeries, future reoperations, rate of radiotherapy, p53 staining, or MIB-1 labeling index. Conclusions: The findings from the present large, single-center study comparing PP1 and non-PP1 adenomas do not suggest that PP1 tumors are more aggressive. Further work is warranted to identify the pathologic subtypes of pituitary adenomas that are consistently more clinically aggressive.
MeSH term(s)	Adenoma/pathology ; Adenoma/surgery ; Adult ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Pituitary Neoplasms/pathology ; Pituitary Neoplasms/surgery
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2021.04.003
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Article ; Online: Correlation between tumor volume and serum prolactin and its effect on surgical outcomes in a cohort of 219 prolactinoma patients.

Journal of neurosurgery

2022 , Page(s) 1–11

Abstract: Objective: Prolactinoma is the most common pituitary adenoma and can be managed medically or surgically. The authors assessed the correlation between tumor volume and prolactin level and its effect on surgical outcomes.: Methods: The authors reviewed ...

Abstract	Objective: Prolactinoma is the most common pituitary adenoma and can be managed medically or surgically. The authors assessed the correlation between tumor volume and prolactin level and its effect on surgical outcomes. Methods: The authors reviewed 219 patients who underwent transsphenoidal prolactinoma resection at a single institution from 2012 to 2019. Outcomes were compared between patients with and without biochemical remission. Tumor volumes were quantified with BrainLab Smartbrush. Correlation analysis and linear regression were used to examine the association between tumor volume and serum prolactin level. Volume-adjusted prolactin level was defined as serum prolactin level divided by tumor volume. The authors utilized receiver operating characteristic (ROC) curve analysis to determine the thresholds for predicting biochemical remission status. Results: The mean tumor volume was 5.66 cm3, and the mean preoperative prolactin level was 752.3 µg/L. Men had larger prolactinomas than women (mean volume 11.32 vs 2.54 cm3; p < 0.001), and women had a greater volume-adjusted prolactin level (mean 412.5 vs 175.9 µg/L/cm3, p < 0.001). In total, 66.7% of surgical patients achieved biochemical remission 6 weeks after surgery, whereas a similar cohort of medically treated patients during the same time frame demonstrated a 69.4% remission rate. Pearson correlation and linear regression analysis revealed a strong association between preoperative tumor volume and prolactin levels, with an increase in serum prolactin level of 101.31 µg/L per 1-cm3 increase in tumor volume (p < 0.001). This held true for men (R = 0.601, p < 0.001) and women (R = 0.935, p < 0.001), with women demonstrating a greater increase in prolactin level per 1-cm3 increase in volume (185.70 vs 79.77 µg/L, p < 0.001). Patients who achieved remission exhibited a 66.08-µg/L increase in preoperative prolactin level per 1 cm3 of preoperative tumor volume (p < 0.001), which was less than the 111.46-µg/L increase per 1 cm3 in patients without remission (p < 0.001). Patients who failed to achieve remission had residual tumors with a 77.77-µg/L increase in prolactin per 1 cm3 of remaining tumor volume after resection (p < 0.001). ROC curve analysis revealed significant thresholds that optimally predicted lack of postoperative remission on the basis of preoperative prolactin and tumor volume. These thresholds were rendered nonsignificant in patients with documented Knosp grade ≥ 3. Conclusions: Although the authors found a correlation between prolactinoma volume and serum prolactin level, patients without remission had a greater increase in serum prolactin level per increase in preoperative tumor volume than those who achieved remission, suggesting unique tumor composition. The authors also identified prolactin and tumor volume thresholds that optimally predicted biochemical remission status. The authors hope that their results can be used to identify prolactinomas for which surgery could achieve remission as an alternative to medical management.
Language	English
Publishing date	2022-10-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	3089-2
ISSN	1933-0693 ; 0022-3085
ISSN (online)	1933-0693
ISSN	0022-3085
DOI	10.3171/2022.8.JNS221890
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Article ; Online: The neurosurgery applicant's "arms race": analysis of medical student publication in the Neurosurgery Residency Match.

Wadhwa, Harsh / Shah, Sumedh S / Shan, Judy / Cheng, Justin / Beniwal, Angad S / Chen, Jia-Shu / Gill, Sabraj A / Mummaneni, Nikhil / McDermott, Michael W / Berger, Mitchel S / Aghi, Manish K

Journal of neurosurgery

2019 Volume 133, Issue 6, Page(s) 1913–1921

Abstract: Objective: Neurosurgery is consistently one of the most competitive specialties for resident applicants. The emphasis on research in neurosurgery has led to an increasing number of publications by applicants seeking a successful residency match. The ... ...

Abstract	Objective: Neurosurgery is consistently one of the most competitive specialties for resident applicants. The emphasis on research in neurosurgery has led to an increasing number of publications by applicants seeking a successful residency match. The authors sought to produce a comprehensive analysis of research produced by neurosurgical applicants and to establish baseline data of neurosurgery applicant research productivity given the increased emphasis on research output for successful residency match. Methods: A retrospective review of publication volume for all neurosurgery interns in 2009, 2011, 2014, 2016, and 2018 was performed using PubMed and Google Scholar. Missing data rates were 11% (2009), 9% (2011), and < 5% (all others). The National Resident Matching Program report "Charting Outcomes in the Match" (ChOM) was interrogated for total research products (i.e., abstracts, presentations, and publications). The publication rates of interns at top 40 programs, students from top 20 medical schools, MD/PhD applicants, and applicants based on location of residency program and medical school were compared statistically against all others. Results: Total publications per neurosurgery intern (mean ± SD) based on PubMed and Google Scholar were 5.5 ± 0.6 in 2018 (1.7 ± 0.3, 2009; 2.1 ± 0.3, 2011; 2.6 ± 0.4, 2014; 3.8 ± 0.4, 2016), compared to 18.3 research products based on ChOM. In 2018, the mean numbers of publications were as follows: neurosurgery-specific publications per intern, 4.3 ± 0.6; first/last author publications, 2.1 ± 0.3; neurosurgical first/last author publications, 1.6 ± 0.2; basic science publications, 1.5 ± 0.2; and clinical research publications, 4.0 ± 0.5. Mean publication numbers among interns at top 40 programs were significantly higher than those of all other programs in every category (p < 0.001). Except for mean number of basic science publications (p = 0.1), the mean number of publications was higher for interns who attended a top 20 medical school than for those who did not (p < 0.05). Applicants with PhD degrees produced statistically more research in all categories (p < 0.05) except neurosurgery-specific (p = 0.07) and clinical research (p = 0.3). While there was no statistical difference in publication volume based on the geographical location of the residency program, students from medical schools in the Western US produced more research than all other regions (p < 0.01). Finally, research productivity did not correlate with likelihood of medical students staying at their home institution for residency. Conclusions: The authors found that the temporal trend toward increased total research products over time in neurosurgery applicants was driven mostly by increased nonindexed research (abstracts, presentations, chapters) rather than by increased peer-reviewed publications. While we also identified applicant-specific factors (MD/PhDs and applicants from the Western US) and an outcome (matching at research-focused institutions) associated with increased applicant publications, further work will be needed to determine the emphasis that programs and applicants will need to place on these publications.
Language	English
Publishing date	2019-11-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3089-2
ISSN	1933-0693 ; 0022-3085
ISSN (online)	1933-0693
ISSN	0022-3085
DOI	10.3171/2019.8.JNS191256
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Article ; Conference proceedings: Effects of Preoperative Serum Prolactin and Tumor Volume on Postoperative Remission in a Cohort of 219 Prolactinoma Resections

Journal of Neurological Surgery Part B: Skull Base

2023 Volume 84, Issue S 01

Event/congress	32nd Annual Meeting North American Skull Base Society, JW Marriott Tampa Water Street, Tampa, Florida, United States, 2023-02-17
Language	English
Publishing date	2023-02-01
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	2654269-9
ISSN	2193-634X ; 2193-6331
ISSN (online)	2193-634X
ISSN	2193-6331
DOI	10.1055/s-0043-1762042
Database	Thieme publisher's database

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