Kristin Huntoon - Academia.edu (original) (raw)

Papers by Kristin Huntoon

Research paper thumbnail of Fig. S11 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S11. Effects of lower NL-201 dose and later irradiation on EO771 tumor growth. a, Experiment... more Fig. S11. Effects of lower NL-201 dose and later irradiation on EO771 tumor growth. a, Experimental design for EO771 tumor model using C57BL/6J mice. b, Changes in mouse body weight over time. c, Tumor growth was monitored until 45 days after tumor inoculation, or when tumor volume exceeded 2000 mm 3. d, Spider plots of individual tumor growth curves in c. e, Survival curves for the mice in c. Mean ± s.e.m. (b,c). n=7 (PBS), n=10 (NL-201 alone, RT alone), n=8 (NL-201+RT). Two-sided logrank (Mantel-Cox) test (e), and one-way ANOVA with Tukey's multiple comparisons test (b,c). TF, tumor-free.

Research paper thumbnail of Fig. S21 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Research paper thumbnail of Fig. S12 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S12. NL-201+RT induces activation of STING-IRF signaling in bone marrow-derived macrophages ... more Fig. S12. NL-201+RT induces activation of STING-IRF signaling in bone marrow-derived macrophages (BMDMs). ad , EO771 cells were irradiated with 6 Gy and cultured for another 24 h. Normal or irradiated EO771 cells were collected and co-cultured with BMDMs from WT or STING-/-C57BL/6J mice and treated with NL-201 for 24 h. a,c, Representative confocal fluorescence microscopy images show nuclear translocation of activated IRF-3 (phospho-IRF-3) (a) or NF-κB (p65) (c). Scale bar=20 μm. b,d, Quantification of nuclear fluorescent-positive cells in a,c by randomly measuring 500 cells from three view fields in each group. e, Western blotting to verify the expression levels STING in different cells. Data are presented as mean ± s.d. with n=3; statistical significance was calculated by one-way ANOVA with Tukey's multiple comparisons test. All data are representative of three biological independent experiments.

Research paper thumbnail of Fig. S23 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Research paper thumbnail of Fig. S1 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

In vivo growth of EO771 breast tumors. a, Spider plots of individual tumor growth curves in wildt... more In vivo growth of EO771 breast tumors. a, Spider plots of individual tumor growth curves in wildtype (WT) mice (n=9) from Fig. 1c. Tumor growth was monitored until 45 days after tumor inoculation, or when tumor volume exceeded 2000 mm 3. PBS, phosphate-buffered saline; NL-201, engineered IL-2/IL-15 mimic; RT, radiation therapy; TF, tumor-free. b, Accumulation of IFN-γ in tumors determined by ELISA. Data are representative of three biologically independent experiments. Mean ± s.d., and n=3. One-way ANOVA with Tukey's multiple comparisons test. c,

Research paper thumbnail of Fig. S19 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S19. NL-201+RT+aPD1 enhances interferon-γ + cytotoxic CD8 + T cell infiltration in tumors. a... more Fig. S19. NL-201+RT+aPD1 enhances interferon-γ + cytotoxic CD8 + T cell infiltration in tumors. a-c, Mice treated as shown in (Fig. 6a) were killed at 18 days after tumor inoculation, and single-cell suspensions from tumor tissues were prepared for T cell analysis by flow cytometry. a, Flow cytometry gating strategy for experiments in b. b, Interferon-γ-expressing tumoral cytotoxic T cells were identified by gating IFN-γ + /CD8 + cells. c, Quantification of IFN-γ + /CD8 + T cells as gated in b. d, IFN-γ protein detected by immunostaining. Scale bar=50 μm. e, Quantification and comparison of fluorescence intensity from three random fields of view. f, Accumulation of IFN-α, IFN-β, and IFN-γ in serum from the above mice by ELISA. c,e,f, Data are representative of three biological independent experiments, and are shown as mean ± s.d. (n=3). One-way ANOVA with Tukey's multiple comparisons test.

Research paper thumbnail of Fig. S2 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Research paper thumbnail of Fig. S15 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S15. NL-201+RT with aPD1 prompts robust anti-tumor effects in 4T1 breast tumor model. a-c, B... more Fig. S15. NL-201+RT with aPD1 prompts robust anti-tumor effects in 4T1 breast tumor model. a-c, BALB/C mice were inoculated with luciferase-expressing 4T1 (Luc-4T1) tumors and treated as indicated (Fig. 6). a, Combination of the left and right portions of Fig. 6g. Mean ± s.e.m. One-way ANOVA with Tukey's multiple comparisons test. b, Spider plots of individual tumor growth curves in Fig. 6g. c, Combination of the left and right portions of Fig. 6h. TF, tumor-free.

Research paper thumbnail of Fig. S20 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S20. Immune checkpoints (PD1 and PDL1) are induced by NL-201+RT. a,b, Mice treated as shown ... more Fig. S20. Immune checkpoints (PD1 and PDL1) are induced by NL-201+RT. a,b, Mice treated as shown in (Fig. 6a) were killed at 18 days after tumor inoculation, and PD1 (a) and PDL1 (b) proteins were detected by immunostaining. Scale bar=50 μm. Right panels, quantification and comparison of fluorescence-positive cells as percentages of tumor area from three random fields of view. Data are representative of three biological independent experiments and are shown as mean ± s.d. (n=3). Oneway ANOVA with Tukey's multiple comparisons test.

Research paper thumbnail of Fig. S17 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Research paper thumbnail of Fig. S22 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S22. NL-201+RT+aPD1 enriches splenic memory T cells. a-f, Mice treated as shown in (Fig. 6a)... more Fig. S22. NL-201+RT+aPD1 enriches splenic memory T cells. a-f, Mice treated as shown in (Fig. 6a) were killed at 18 days after tumor inoculation and splenic memory CD8 + T cells (a-c) or CD4 + T cells (d-f) were assessed by flow cytometry to verify immune memory enhancement after treatment with NL-201, RT, and aPD1, alone and in combination. a,d, Flow cytometry gating strategy for experiments in b,e, respectively. b,e, NL-201+RT+aPD1 enhanced the shift from naïve T cells to memory T cells, with predominantly central memory (TCM) and effector memory (TEM) T cell phenotypes. c,f, Percentages of naïve T cell, TCM and TEM from flow cytometry in b,e. Data are representative of three biological independent experiments, and are shown as means ± s.d. (n=3), one-way ANOVA with Tukey's multiple comparisons test.

Research paper thumbnail of Differential time-to-promotion trajectories among female and male neurosurgeons contributes to gender disparities in academic rank achievement

World Neurosurgery, Nov 30, 2023

Research paper thumbnail of Malignant primary tumors of scalp with cranial extension: multidisciplinary surgical strategies and outcomes

Journal of Neurosurgery

OBJECTIVE Malignant cancers arising in the scalp may exhibit calvarial invasion, dural extension,... more OBJECTIVE Malignant cancers arising in the scalp may exhibit calvarial invasion, dural extension, and rarely cerebral involvement. Typically, such lesions require a multidisciplinary approach involving both neurosurgery and plastic surgery for optimal resection and reconstruction. The authors present a retrospective analysis of patients with scalp malignancies who underwent resection and reconstruction. METHODS Patients presenting with scalp malignancies (1993–2021, n = 84) who required neurosurgical assistance for tumor resection were prospectively entered into a database. These data were retrospectively reviewed for this case series. The extent of neurosurgical resection was classified into four levels of involvement: scalp (level I), calvarial (level II), dural (level III), or intraparenchymal (level IV). Complications and evidence of local, locoregional, or regional recurrence were documented. RESULTS Patients underwent level I (n = 2), level II (n = 61), level III (n = 13), and...

Research paper thumbnail of Guidelines for surveillance of patients with von Hippel‐Lindau disease: Consensus statement of the International VHL Surveillance Guidelines Consortium and VHL Alliance

Research paper thumbnail of Trends in Racial and Ethnic Representation Among Neurosurgery Applicants and Residents: A Comparative Analysis of Procedural Specialties

World Neurosurgery, Apr 1, 2022

BACKGROUND Diversity, equity, and inclusion within the healthcare workforce are conducive to prov... more BACKGROUND Diversity, equity, and inclusion within the healthcare workforce are conducive to providing culturally competent care. However, few existing studies assess the level of racial and ethnic diversity among resident physicians and residency applicants. OBJECTIVE To provide a comparative analysis of trends in racial and ethnic representation within different subspecialities in medicine. METHODS Using data from the American Association of Medical Colleges and the Journal of the American Medical Association, we evaluated the racial/ethnic identification of residency applicants and current residents in nine procedural-focused specialties from 2005 - 2019 and performed a descriptive analysis comparing different levels of racial/ethnic diversity in these specialties. RESULTS Among the specialties analyzed during the specified time period, neurosurgery had the greatest magnitude of difference between Black/African American residency applicants and current residents. The percentage of Black/African American applicants was 92% greater than the percentage of Black/African American residents (10% of applicants compared to 5.2% of residents). Conversely, the percentage of White neurosurgery residents was 17.6% greater than the percentage of White neurosurgery applicants (53.9% of applicants compared to 63.4% of residents). Similar trends were noted in all of the specialties evaluated, and obstetrics and gynecology demonstrated the least disparity between Black/African American applicants and residents (13.7% of applicants, 10.2% of residents, 35.4% difference). Hispanic and Asian representation varied widely between specialties. CONCLUSION Among the surveyed specialties, neurosurgery demonstrates the greatest disparity between the percentage of Black/African American residency applicants and current residents. To further drive progress in this domain, we advocate for a series of initiatives designed to increase underrepresented minority participation in neurosurgery practice and scholarship.

Research paper thumbnail of Nervous System Manifestations of von Hippel-Lindau Disease

von Hippel-Lindau (VHL) disease is a highly penetrant multiple organ heritable cancer syndrome wi... more von Hippel-Lindau (VHL) disease is a highly penetrant multiple organ heritable cancer syndrome with a spectrum of benign and malignant tumors. VHL is results from a germline mutation of the VHL tumor suppressor gene (short arm of chromosome 3). VHL affects 1 in 36,000 to 39,000 livebirths as an autosomal dominant trait. Individuals harboring a mutation in VHL can develop benign and malignant tumors, both of the central nervous system (CNS) and systemically. VHL-associated lesions of the CNS include retinal and craniospinal hemangioblastomas, as well as endolymphatic sac tumors (ELSTs). While CNS hemangioblastomas (most common tumor in VHL) and ELSTs are benign tumors, they are associated with significant neurologic morbidity and mortality based on their location and multiplicity. Because of the management complexities of this disease, multidisciplinary screening and treatment, as well as a deep understanding of the natural course of the disease are needed.

Research paper thumbnail of Effect of Dexmedetomidine on Perception of Paresthesia during Subthalamic Nucleus Deep Brain Stimulation Surgery for Parkinson's Disease

PubMed, May 6, 2023

Background: Deep brain stimulation (DBS) has become a well-established treatment for the manageme... more Background: Deep brain stimulation (DBS) has become a well-established treatment for the management of Parkinson's disease (PD). The most common method of lead targeting utilizes microelectrode recording (MER) and intraoperative macrostimulation to confirm accurate placement of the lead. This has been significantly aided by the use of dexmedetomidine (DEX) sedation during the procedure. Despite the frequent use of DEX, it has been theorized that DEX may have some effects on the MER during intraoperative testing. The effect on the perception of sensory thresholds during macrostimulation in the form of paresthesia is still unreported. Objectives: To investigate the effect of the sedative DEX on sensory perception thresholds observed in the intraoperative versus postoperative settings for patients undergoing subthalamic nucleus (STN) DBS surgery for PD. Materials and methods: Adult patients (n = 8) with a diagnosis of PD underwent placement of DBS leads (n = 14) in the STN. Patients were subjected to intraoperative macrostimulation for capsular and sensory thresholds prior to placement of each DBS lead. These were compared to sensory thresholds observed in the postoperative setting during outpatient programming at three depths on each lead (n = 42). Results: In most contacts (22/42) (P = 0.19), sensory thresholds for paresthesia perception were either perceived at a higher voltage or absent during intraoperative testing in comparison to those observed in the postoperative setting. Conclusions: DEX appears to have measurable (though not statistically significant) effect on the perception of paresthesia observed during intraoperative testing.

Research paper thumbnail of Neurosurgeons Relate Heterogeneous Practices Regarding Activity and Return to Work After Spine Surgery

World Neurosurgery, Jun 1, 2022

OBJECTIVE Given the paucity of relevant data, the Council of State Neurosurgical Societies (CSNS)... more OBJECTIVE Given the paucity of relevant data, the Council of State Neurosurgical Societies (CSNS) Workforce Committee launched a survey of neurosurgeons to assess patterns in activity restriction recommendations following spine surgery; the ultimate goal was to optimize and potentially standardize these recommendations. The aim of this initial study was to determine current practices in f activity restrictions and return to work guidelines following common spinal procedures. METHODS The survey included questions regarding general demographics and practice data, postoperative bracing/orthoses utilization, and guidelines for postoperative return to different levels of activity/types of work following specific spine surgery interventions. A spectrum of typical spine surgeries was assessed, including microdiscectomy, anterior cervical discectomy and fusion (ACDF), and lumbar fusion (open and minimal invasive surgery (MIS) approaches). RESULTS There was significant inter- and intra-procedure variation in neurosurgeon recommendations for postoperative activity and return to work recommendations after various spinal surgery procedures. Comparison between the different surgical procedures evaluated revealed significant differences in cervical collar usage (more often used following two level or greater ACDF than single level ACDF, p<0.001), return to both sedentary and light physical work (greater restriction with a two level or greater ACDF than single level ACDF, p<0.001), and return to a light exercise regimen (sooner following MIS vs. open lumbar fusion, p<0.001). CONCLUSIONS This survey demonstrated little consistency regarding return to work recommendations, general activity restrictions and orthosis utilization following common spinal surgical procedures. Addressing this issue also has significant implication for the societal and personal costs of spine surgery.

Research paper thumbnail of Efficacy and Safety of Endoscopic Transsphenoidal Resection for Prolactinoma: A Retrospective Multicenter Case-series

Archives of Medical Research, Nov 30, 2023

Background. Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine a... more Background. Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment. Aims. To report on outcomes of ETSS in a cohort of prolactinomas. Methods. Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 ± 13.7 years; 61.3% female, median follow-up 28.0 [15.0-55.5] months) operated between 2010-2019 with histopathological confirmation. Results. Median preoperative prolactin levels were 166 (98-837 μg/L; males 996 [159-2145 μg/L] vs. females 129 [84-223 μg/L], p &lt; 0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), p &lt; 0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (p &lt; 0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), p = 0.006. Long-term remission (i.e., DAfree prolactin level &lt; 1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], p = 0.002). Transient DI (n = 29, 21.2%) was the most frequent complication. Conclusions. Despite high proportions of macroprolactinoma and KNOSP 3-4, longterm remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.

Research paper thumbnail of Efficacy and Safety of Endoscopic Transsphenoidal Resection for Prolactinoma: A Retrospective Multicenter Case-series

Background. Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine a... more Background. Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment. Aims. To report on outcomes of ETSS in a cohort of prolactinomas. Methods. Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 ± 13.7 years; 61.3% female, median follow-up 28.0 [15.0-55.5] months) operated between 2010-2019 with histopathological confirmation. Results. Median preoperative prolactin levels were 166 (98-837 μg/L; males 996 [159-2145 μg/L] vs. females 129 [84-223 μg/L], p < 0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), p < 0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (p < 0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), p = 0.006. Long-term remission (i.e., DAfree prolactin level < 1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], p = 0.002). Transient DI (n = 29, 21.2%) was the most frequent complication. Conclusions. Despite high proportions of macroprolactinoma and KNOSP 3-4, longterm remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.

Research paper thumbnail of Fig. S11 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S11. Effects of lower NL-201 dose and later irradiation on EO771 tumor growth. a, Experiment... more Fig. S11. Effects of lower NL-201 dose and later irradiation on EO771 tumor growth. a, Experimental design for EO771 tumor model using C57BL/6J mice. b, Changes in mouse body weight over time. c, Tumor growth was monitored until 45 days after tumor inoculation, or when tumor volume exceeded 2000 mm 3. d, Spider plots of individual tumor growth curves in c. e, Survival curves for the mice in c. Mean ± s.e.m. (b,c). n=7 (PBS), n=10 (NL-201 alone, RT alone), n=8 (NL-201+RT). Two-sided logrank (Mantel-Cox) test (e), and one-way ANOVA with Tukey's multiple comparisons test (b,c). TF, tumor-free.

Research paper thumbnail of Fig. S21 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Research paper thumbnail of Fig. S12 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S12. NL-201+RT induces activation of STING-IRF signaling in bone marrow-derived macrophages ... more Fig. S12. NL-201+RT induces activation of STING-IRF signaling in bone marrow-derived macrophages (BMDMs). ad , EO771 cells were irradiated with 6 Gy and cultured for another 24 h. Normal or irradiated EO771 cells were collected and co-cultured with BMDMs from WT or STING-/-C57BL/6J mice and treated with NL-201 for 24 h. a,c, Representative confocal fluorescence microscopy images show nuclear translocation of activated IRF-3 (phospho-IRF-3) (a) or NF-κB (p65) (c). Scale bar=20 μm. b,d, Quantification of nuclear fluorescent-positive cells in a,c by randomly measuring 500 cells from three view fields in each group. e, Western blotting to verify the expression levels STING in different cells. Data are presented as mean ± s.d. with n=3; statistical significance was calculated by one-way ANOVA with Tukey's multiple comparisons test. All data are representative of three biological independent experiments.

Research paper thumbnail of Fig. S23 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Research paper thumbnail of Fig. S1 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

In vivo growth of EO771 breast tumors. a, Spider plots of individual tumor growth curves in wildt... more In vivo growth of EO771 breast tumors. a, Spider plots of individual tumor growth curves in wildtype (WT) mice (n=9) from Fig. 1c. Tumor growth was monitored until 45 days after tumor inoculation, or when tumor volume exceeded 2000 mm 3. PBS, phosphate-buffered saline; NL-201, engineered IL-2/IL-15 mimic; RT, radiation therapy; TF, tumor-free. b, Accumulation of IFN-γ in tumors determined by ELISA. Data are representative of three biologically independent experiments. Mean ± s.d., and n=3. One-way ANOVA with Tukey's multiple comparisons test. c,

Research paper thumbnail of Fig. S19 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S19. NL-201+RT+aPD1 enhances interferon-γ + cytotoxic CD8 + T cell infiltration in tumors. a... more Fig. S19. NL-201+RT+aPD1 enhances interferon-γ + cytotoxic CD8 + T cell infiltration in tumors. a-c, Mice treated as shown in (Fig. 6a) were killed at 18 days after tumor inoculation, and single-cell suspensions from tumor tissues were prepared for T cell analysis by flow cytometry. a, Flow cytometry gating strategy for experiments in b. b, Interferon-γ-expressing tumoral cytotoxic T cells were identified by gating IFN-γ + /CD8 + cells. c, Quantification of IFN-γ + /CD8 + T cells as gated in b. d, IFN-γ protein detected by immunostaining. Scale bar=50 μm. e, Quantification and comparison of fluorescence intensity from three random fields of view. f, Accumulation of IFN-α, IFN-β, and IFN-γ in serum from the above mice by ELISA. c,e,f, Data are representative of three biological independent experiments, and are shown as mean ± s.d. (n=3). One-way ANOVA with Tukey's multiple comparisons test.

Research paper thumbnail of Fig. S2 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Research paper thumbnail of Fig. S15 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S15. NL-201+RT with aPD1 prompts robust anti-tumor effects in 4T1 breast tumor model. a-c, B... more Fig. S15. NL-201+RT with aPD1 prompts robust anti-tumor effects in 4T1 breast tumor model. a-c, BALB/C mice were inoculated with luciferase-expressing 4T1 (Luc-4T1) tumors and treated as indicated (Fig. 6). a, Combination of the left and right portions of Fig. 6g. Mean ± s.e.m. One-way ANOVA with Tukey's multiple comparisons test. b, Spider plots of individual tumor growth curves in Fig. 6g. c, Combination of the left and right portions of Fig. 6h. TF, tumor-free.

Research paper thumbnail of Fig. S20 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S20. Immune checkpoints (PD1 and PDL1) are induced by NL-201+RT. a,b, Mice treated as shown ... more Fig. S20. Immune checkpoints (PD1 and PDL1) are induced by NL-201+RT. a,b, Mice treated as shown in (Fig. 6a) were killed at 18 days after tumor inoculation, and PD1 (a) and PDL1 (b) proteins were detected by immunostaining. Scale bar=50 μm. Right panels, quantification and comparison of fluorescence-positive cells as percentages of tumor area from three random fields of view. Data are representative of three biological independent experiments and are shown as mean ± s.d. (n=3). Oneway ANOVA with Tukey's multiple comparisons test.

Research paper thumbnail of Fig. S17 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Research paper thumbnail of Fig. S22 from Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity

Fig. S22. NL-201+RT+aPD1 enriches splenic memory T cells. a-f, Mice treated as shown in (Fig. 6a)... more Fig. S22. NL-201+RT+aPD1 enriches splenic memory T cells. a-f, Mice treated as shown in (Fig. 6a) were killed at 18 days after tumor inoculation and splenic memory CD8 + T cells (a-c) or CD4 + T cells (d-f) were assessed by flow cytometry to verify immune memory enhancement after treatment with NL-201, RT, and aPD1, alone and in combination. a,d, Flow cytometry gating strategy for experiments in b,e, respectively. b,e, NL-201+RT+aPD1 enhanced the shift from naïve T cells to memory T cells, with predominantly central memory (TCM) and effector memory (TEM) T cell phenotypes. c,f, Percentages of naïve T cell, TCM and TEM from flow cytometry in b,e. Data are representative of three biological independent experiments, and are shown as means ± s.d. (n=3), one-way ANOVA with Tukey's multiple comparisons test.

Research paper thumbnail of Differential time-to-promotion trajectories among female and male neurosurgeons contributes to gender disparities in academic rank achievement

World Neurosurgery, Nov 30, 2023

Research paper thumbnail of Malignant primary tumors of scalp with cranial extension: multidisciplinary surgical strategies and outcomes

Journal of Neurosurgery

OBJECTIVE Malignant cancers arising in the scalp may exhibit calvarial invasion, dural extension,... more OBJECTIVE Malignant cancers arising in the scalp may exhibit calvarial invasion, dural extension, and rarely cerebral involvement. Typically, such lesions require a multidisciplinary approach involving both neurosurgery and plastic surgery for optimal resection and reconstruction. The authors present a retrospective analysis of patients with scalp malignancies who underwent resection and reconstruction. METHODS Patients presenting with scalp malignancies (1993–2021, n = 84) who required neurosurgical assistance for tumor resection were prospectively entered into a database. These data were retrospectively reviewed for this case series. The extent of neurosurgical resection was classified into four levels of involvement: scalp (level I), calvarial (level II), dural (level III), or intraparenchymal (level IV). Complications and evidence of local, locoregional, or regional recurrence were documented. RESULTS Patients underwent level I (n = 2), level II (n = 61), level III (n = 13), and...

Research paper thumbnail of Guidelines for surveillance of patients with von Hippel‐Lindau disease: Consensus statement of the International VHL Surveillance Guidelines Consortium and VHL Alliance

Research paper thumbnail of Trends in Racial and Ethnic Representation Among Neurosurgery Applicants and Residents: A Comparative Analysis of Procedural Specialties

World Neurosurgery, Apr 1, 2022

BACKGROUND Diversity, equity, and inclusion within the healthcare workforce are conducive to prov... more BACKGROUND Diversity, equity, and inclusion within the healthcare workforce are conducive to providing culturally competent care. However, few existing studies assess the level of racial and ethnic diversity among resident physicians and residency applicants. OBJECTIVE To provide a comparative analysis of trends in racial and ethnic representation within different subspecialities in medicine. METHODS Using data from the American Association of Medical Colleges and the Journal of the American Medical Association, we evaluated the racial/ethnic identification of residency applicants and current residents in nine procedural-focused specialties from 2005 - 2019 and performed a descriptive analysis comparing different levels of racial/ethnic diversity in these specialties. RESULTS Among the specialties analyzed during the specified time period, neurosurgery had the greatest magnitude of difference between Black/African American residency applicants and current residents. The percentage of Black/African American applicants was 92% greater than the percentage of Black/African American residents (10% of applicants compared to 5.2% of residents). Conversely, the percentage of White neurosurgery residents was 17.6% greater than the percentage of White neurosurgery applicants (53.9% of applicants compared to 63.4% of residents). Similar trends were noted in all of the specialties evaluated, and obstetrics and gynecology demonstrated the least disparity between Black/African American applicants and residents (13.7% of applicants, 10.2% of residents, 35.4% difference). Hispanic and Asian representation varied widely between specialties. CONCLUSION Among the surveyed specialties, neurosurgery demonstrates the greatest disparity between the percentage of Black/African American residency applicants and current residents. To further drive progress in this domain, we advocate for a series of initiatives designed to increase underrepresented minority participation in neurosurgery practice and scholarship.

Research paper thumbnail of Nervous System Manifestations of von Hippel-Lindau Disease

von Hippel-Lindau (VHL) disease is a highly penetrant multiple organ heritable cancer syndrome wi... more von Hippel-Lindau (VHL) disease is a highly penetrant multiple organ heritable cancer syndrome with a spectrum of benign and malignant tumors. VHL is results from a germline mutation of the VHL tumor suppressor gene (short arm of chromosome 3). VHL affects 1 in 36,000 to 39,000 livebirths as an autosomal dominant trait. Individuals harboring a mutation in VHL can develop benign and malignant tumors, both of the central nervous system (CNS) and systemically. VHL-associated lesions of the CNS include retinal and craniospinal hemangioblastomas, as well as endolymphatic sac tumors (ELSTs). While CNS hemangioblastomas (most common tumor in VHL) and ELSTs are benign tumors, they are associated with significant neurologic morbidity and mortality based on their location and multiplicity. Because of the management complexities of this disease, multidisciplinary screening and treatment, as well as a deep understanding of the natural course of the disease are needed.

Research paper thumbnail of Effect of Dexmedetomidine on Perception of Paresthesia during Subthalamic Nucleus Deep Brain Stimulation Surgery for Parkinson's Disease

PubMed, May 6, 2023

Background: Deep brain stimulation (DBS) has become a well-established treatment for the manageme... more Background: Deep brain stimulation (DBS) has become a well-established treatment for the management of Parkinson's disease (PD). The most common method of lead targeting utilizes microelectrode recording (MER) and intraoperative macrostimulation to confirm accurate placement of the lead. This has been significantly aided by the use of dexmedetomidine (DEX) sedation during the procedure. Despite the frequent use of DEX, it has been theorized that DEX may have some effects on the MER during intraoperative testing. The effect on the perception of sensory thresholds during macrostimulation in the form of paresthesia is still unreported. Objectives: To investigate the effect of the sedative DEX on sensory perception thresholds observed in the intraoperative versus postoperative settings for patients undergoing subthalamic nucleus (STN) DBS surgery for PD. Materials and methods: Adult patients (n = 8) with a diagnosis of PD underwent placement of DBS leads (n = 14) in the STN. Patients were subjected to intraoperative macrostimulation for capsular and sensory thresholds prior to placement of each DBS lead. These were compared to sensory thresholds observed in the postoperative setting during outpatient programming at three depths on each lead (n = 42). Results: In most contacts (22/42) (P = 0.19), sensory thresholds for paresthesia perception were either perceived at a higher voltage or absent during intraoperative testing in comparison to those observed in the postoperative setting. Conclusions: DEX appears to have measurable (though not statistically significant) effect on the perception of paresthesia observed during intraoperative testing.

Research paper thumbnail of Neurosurgeons Relate Heterogeneous Practices Regarding Activity and Return to Work After Spine Surgery

World Neurosurgery, Jun 1, 2022

OBJECTIVE Given the paucity of relevant data, the Council of State Neurosurgical Societies (CSNS)... more OBJECTIVE Given the paucity of relevant data, the Council of State Neurosurgical Societies (CSNS) Workforce Committee launched a survey of neurosurgeons to assess patterns in activity restriction recommendations following spine surgery; the ultimate goal was to optimize and potentially standardize these recommendations. The aim of this initial study was to determine current practices in f activity restrictions and return to work guidelines following common spinal procedures. METHODS The survey included questions regarding general demographics and practice data, postoperative bracing/orthoses utilization, and guidelines for postoperative return to different levels of activity/types of work following specific spine surgery interventions. A spectrum of typical spine surgeries was assessed, including microdiscectomy, anterior cervical discectomy and fusion (ACDF), and lumbar fusion (open and minimal invasive surgery (MIS) approaches). RESULTS There was significant inter- and intra-procedure variation in neurosurgeon recommendations for postoperative activity and return to work recommendations after various spinal surgery procedures. Comparison between the different surgical procedures evaluated revealed significant differences in cervical collar usage (more often used following two level or greater ACDF than single level ACDF, p<0.001), return to both sedentary and light physical work (greater restriction with a two level or greater ACDF than single level ACDF, p<0.001), and return to a light exercise regimen (sooner following MIS vs. open lumbar fusion, p<0.001). CONCLUSIONS This survey demonstrated little consistency regarding return to work recommendations, general activity restrictions and orthosis utilization following common spinal surgical procedures. Addressing this issue also has significant implication for the societal and personal costs of spine surgery.

Research paper thumbnail of Efficacy and Safety of Endoscopic Transsphenoidal Resection for Prolactinoma: A Retrospective Multicenter Case-series

Archives of Medical Research, Nov 30, 2023

Background. Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine a... more Background. Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment. Aims. To report on outcomes of ETSS in a cohort of prolactinomas. Methods. Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 ± 13.7 years; 61.3% female, median follow-up 28.0 [15.0-55.5] months) operated between 2010-2019 with histopathological confirmation. Results. Median preoperative prolactin levels were 166 (98-837 μg/L; males 996 [159-2145 μg/L] vs. females 129 [84-223 μg/L], p &lt; 0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), p &lt; 0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (p &lt; 0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), p = 0.006. Long-term remission (i.e., DAfree prolactin level &lt; 1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], p = 0.002). Transient DI (n = 29, 21.2%) was the most frequent complication. Conclusions. Despite high proportions of macroprolactinoma and KNOSP 3-4, longterm remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.

Research paper thumbnail of Efficacy and Safety of Endoscopic Transsphenoidal Resection for Prolactinoma: A Retrospective Multicenter Case-series

Background. Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine a... more Background. Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment. Aims. To report on outcomes of ETSS in a cohort of prolactinomas. Methods. Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 ± 13.7 years; 61.3% female, median follow-up 28.0 [15.0-55.5] months) operated between 2010-2019 with histopathological confirmation. Results. Median preoperative prolactin levels were 166 (98-837 μg/L; males 996 [159-2145 μg/L] vs. females 129 [84-223 μg/L], p < 0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), p < 0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (p < 0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), p = 0.006. Long-term remission (i.e., DAfree prolactin level < 1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], p = 0.002). Transient DI (n = 29, 21.2%) was the most frequent complication. Conclusions. Despite high proportions of macroprolactinoma and KNOSP 3-4, longterm remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.