Ella Adeline Nettnin

All Publications

• Role of health literacy in neurosurgical outcomes among pediatric and adult patients: a systematic review of international studies and call to action. Journal of neurosurgery. Pediatrics Barros Guinle, M. I., Nettnin, E. A., Prolo, L. M. 2025: 1-9

  Abstract

  Limited health literacy (HL) is associated with worse clinical outcomes across medical specialties. The association between limited HL and neurosurgical outcomes remains largely unknown. In this systematic review, the authors synthesized the existing literature on the association between limited patient and/or caregiver HL and neurosurgical outcomes.A systematic search was conducted in PubMed, Embase, CINAHL, and JBI EBP from inception to February 12, 2025, following PRISMA guidelines. Study quality was assessed using the Newcastle-Ottawa Scale. The study design, sample size, population of interest, neurosurgical diagnoses/procedures, HL assessment used, pertinent findings, and related demographic factors were collected.The search yielded 698 article titles and abstracts, of which 37 underwent full-text review and 6 met inclusion criteria for this systematic review. These 6 studies included 695 neurosurgical patients and/or caregivers and used various methods to assess HL. Neurosurgical outcomes were grouped into the following categories: 1) delivery and timing of neurosurgical care, 2) hospital admission and discharge, and 3) quality of life (QOL) and well-being. Study results were split evenly across these 3 categories, with 2 studies that explored the delivery and timing of neurosurgical care, 2 that examined hospital admission and discharge, and 2 that investigated QOL and well-being. Study designs included 2 prospective observational studies, 3 cross-sectional studies, and 1 qualitative study. Sample sizes ranged from 27 to 300 patients, including pediatric, adult, and mixed (pediatric and adult) populations, as well as caregivers of pediatric and adult patients. All 6 studies were conducted outside the United States. Limited HL was found to be associated with delays in neurosurgical care, increased rates of discharge against medical advice, decreased patient independence, and worse psychological well-being.This systematic review highlights the paucity of studies on neurosurgical outcomes among patients and/or caregivers with limited HL, while suggesting that limited HL is associated with worse neurosurgical outcomes. In addition, the lack of studies conducted in the US indicates a geographic gap in the literature. The authors provide a call to action and concrete steps to address the critical need for further research on HL to achieve more equitable neurosurgical care.

  View details for DOI 10.3171/2025.5.PEDS25172

  View details for PubMedID 41004858

• Circadian rhythms in pediatric high-grade gliomas may contribute to treatment efficacy. Scientific reports Nettnin, E. A., Garcia, C. A., Sayed, F. F., Schonfeld, E., Nguyen, T., Guinle, M. I., Petritsch, C. K., Gibson, E. M., Prolo, L. M. 2025; 15 (1): 32010

  Abstract

  Pediatric high-grade gliomas (pHGG) are highly invasive with poor survival outcomes. Timing of Temozolomide administration has been shown to affect survival of adult patients with glioblastoma. We investigated whether pHGGs express circadian genes rhythmically and whether underlying rhythms affect Temozolomide sensitivity. Circadian gene expression in pediatric gliomas was analyzed using PedcBioPortal. Immunoblotting was used to assess protein levels in patient-derived pHGG lines and in high- and low- grade (pLGG) glioma specimens. Rhythmic gene expression in pHGG lines was measured via qPCR, and Temozolomide efficacy was tested during peak versus trough Bmal1 expression. Patient data revealed significantly different mRNA expression in multiple circadian genes between pHGGs and pLGGs, including higher Bmal1 expression in pHGG specimens and lower Rev-Erbα expression. Significantly higher BMAL1 and CLOCK protein levels and lower REV-ERBα were present in pHGG versus pLGG tissue specimens. Our three pHGG lines displayed rhythmic Bmal1 and Rev-Erbα expression post-synchronization. We found significantly decreased proliferation when Temozolomide was applied during trough versus peak Bmal1 expression. The positive arm of the circadian clock appears upregulated in pHGGs compared to pLGGs. Pediatric HGGs rhythmically express circadian genes and exhibit differential Temozolomide sensitivity based on timing of administration.

  View details for DOI 10.1038/s41598-025-17461-9

  View details for PubMedID 40887493

  View details for PubMedCentralID 6395056

• Health care utilization among Medicare beneficiaries with newly diagnosed back pain. North American Spine Society journal Barros Guinle, M. I., Johnstone, T., Ruiz Colón, G. D., Weng, Y., Nettnin, E. A., Ratliff, J. K. 2024; 20: 100565

  Abstract

  Low back pain (LBP) is the most common medical cause of disability among adults 65 or older. No previous study has characterized health care costs and treatment patterns of LBP among Medicare beneficiaries.This retrospective cohort study quantifies health care utilization costs among Medicare beneficiaries with newly diagnosed LBP, compares costs between patients managed operatively and nonoperatively, identifies costs associated with treatment guideline nonadherence, and characterizes opioid prescribing patterns. Patients were queried via ICD codes from a 20% random sample of Medicare claims records. Patients with concomitant or previous "red flag" diagnoses, neurological deficits, or diagnoses that could cause nondegenerative LBP were excluded. Total costs of care in the year of diagnosis were calculated and stratified by operative versus nonoperative management. To assess for guideline adherence, utilization and costs of different services were tabulated. Opioid prescription patterns were characterized by quantity, cost, duration, and medication type.About 1,269,896 patients were identified; 23,919 (1.8%) underwent surgery. These accounted for 7% of the cohort's total cost ($514 million total, $21,496 per person). Patients treated nonoperatively accounted for over $7 billion in costs ($5,880 per person; p<.001). Within the nonoperative cohort, 626,896 (50.3%) patients were nonadherent to current guidelines for conservative management of LBP. Guideline nonadherence increased total annual costs by $4,012 per person ($7,873 for nonadherent vs. $3,861 for adherent patients, p<.001). About 460,867 opioid prescriptions were filled for 303,796 unique patients (23.9%) within 30 days of LBP diagnosis. Within the nonsurgical cohort, patients nonadherent to imaging guidelines were more likely to have an opioid prescription within this window than adherent patients (26.5% vs. 21.2%; p<.001).Nonoperative management of LBP is associated with significantly lower costs per patient. Early imaging and opioid prescription are significant drivers of excess cost. Adherence to proposed treatment guidelines can save over $2.8 billion in total health care costs.

  View details for DOI 10.1016/j.xnsj.2024.100565

  View details for PubMedID 39670143

  View details for PubMedCentralID PMC11636345

• PEDIATRIC GLIOMAS EXPRESS CIRCADIAN GENES AND DEMONSTRATE CIRCADIAN REGULATION OF TEMOZOLOMIDE SENSITIVITY Nettnin, E. A., Garcia, C. A., Schonfeld, E., Mehl, L. C., Guinle, M., Petritsch, C. K., Gibson, E. M., Prolo, L. M. OXFORD UNIV PRESS INC. 2024

  View details for DOI 10.1093/neuonc/noae165.0157

  View details for Web of Science ID 001362582300007

• THE ROLE OF MAP4K4 IN TUMOR CELL INVASION OBSERVED IN A 3D IN VITRO MODEL OF PEDIATRIC GLIOBLASTOMA Garcia, C., Nettnin, E., Arana, S., Nguyen, T., Guinle, M., Wilson, C., Petritsch, C. K., Bassik, M. C., Prolo, L. M. OXFORD UNIV PRESS INC. 2024

  View details for DOI 10.1093/neuonc/noae165.0226

  View details for Web of Science ID 001362572400036

• CDC42BPA::BRAF represents a novel fusion in desmoplastic infantile ganglioglioma/desmoplastic infantile astrocytoma. Neuro-oncology advances Barros Guinle, M. I., Nirschl, J. J., Xing, Y. L., Nettnin, E. A., Arana, S., Feng, Z. P., Nasajpour, E., Pronina, A., Garcia, C. A., Grant, G. A., Vogel, H., Yeom, K. W., Prolo, L. M., Petritsch, C. K. 2024; 6 (1): vdae050

  View details for DOI 10.1093/noajnl/vdae050

  View details for PubMedID 38741773

  View details for PubMedCentralID PMC11089409

• Review: therapeutic approaches for circadian modulation of the glioma microenvironment. Frontiers in oncology Nettnin, E. A., Nguyen, T., Arana, S., Barros Guinle, M. I., Garcia, C. A., Gibson, E. M., Prolo, L. M. 2023; 13: 1295030

  Abstract

  High-grade gliomas are malignant brain tumors that are characteristically hard to treat because of their nature; they grow quickly and invasively through the brain tissue and develop chemoradiation resistance in adults. There is also a distinct lack of targeted treatment options in the pediatric population for this tumor type to date. Several approaches to overcome therapeutic resistance have been explored, including targeted therapy to growth pathways (ie. EGFR and VEGF inhibitors), epigenetic modulators, and immunotherapies such as Chimeric Antigen Receptor T-cell and vaccine therapies. One new promising approach relies on the timing of chemotherapy administration based on intrinsic circadian rhythms. Recent work in glioblastoma has demonstrated temporal variations in chemosensitivity and, thus, improved survival based on treatment time of day. This may be due to intrinsic rhythms of the glioma cells, permeability of the blood brain barrier to chemotherapy agents, the tumor immune microenvironment, or another unknown mechanism. We review the literature to discuss chronotherapeutic approaches to high-grade glioma treatment, circadian regulation of the immune system and tumor microenvironment in gliomas. We further discuss how these two areas may be combined to temporally regulate and/or improve the effectiveness of immunotherapies.

  View details for DOI 10.3389/fonc.2023.1295030

  View details for PubMedID 38173841

  View details for PubMedCentralID PMC10762863

• CDC42BPA::BRAF REPRESENTS A NOVEL FUSION IN DESMOPLASTIC INFANTILE GLIOMA Guinle, M., Nettnin, E. A., Nasajpour, E., Nirschl, J., Garcia, C. A., Vogel, H., Yeom, K., Prolo, L., Petritsch, C. OXFORD UNIV PRESS INC. 2023

  View details for Web of Science ID 001115245400685