Gillian Fell

All Publications

• BA-ECM Score: Automated Quantification of Liver Fibrosis Architecture in Biliary Atresia with Potential for Prognostic Value - A Pilot Study. Annals of surgery Liang, N. E., Guo, J. L., Griffin, M. F., Bauer-Rowe, K. E., Narang, A., Januszyk, M., Fell, G. L., Dunn, J. C., Chao, S. D., Tan, S. Y., Longaker, M. T., Hyun, J. S. 2025

  Abstract

  To quantify liver fibrosis in infants with biliary atresia (BA) through automated analysis of collagen extracellular matrix (ECM) ultrastructure in index liver biopsies and use a composite fibrosis architecture score to predict native liver survival.Despite early management with Kasai portoenterostomy , BA remains the leading indication for pediatric liver transplantation. There is no established method for quantitatively assessing liver fibrosis in patients with BA, and no factors to accurately predict which patients will ultimately require transplantation early versus late.Index liver biopsies from 12 BA patients were retrieved from our pathology archives Masson's Trichrome-stained biopsies were scanned, tiled, binarized, and quantified for 147 ECM features. These features were reduced by Uniform Manifold Approximation and Projection. Pseudotime analysis was applied to summarize global variations in architecture and assign BA-ECM scores to all biopsy images. Retrospective chart review was performed to correlate clinical characteristics with BA-ECM score.BA-ECM score, a multi-dimensional fibrosis architecture score, was significantly higher for biopsies from listed patients compared to non-listed patients (35.9 vs. 22.9, *P<0.0001). High BA-ECM score was characterized by thick, patchy, irregular ECM, while low BA-ECM score was associated with large-volume thin, porous collagen fibers. Survival analysis stratified by the third quartile BA-ECM score of all data points demonstrated a significant difference in native liver survival (*P=0.02).We present the application of an automated ECM ultrastructure analysis tool designed to capture and quantify 147 aspects of fibrotic tissue heterogeneity. These manifold features are summarized using a multi-dimensional BA-ECM score that could be used to prognosticate disease course for BA patients.

  View details for DOI 10.1097/SLA.0000000000006698

  View details for PubMedID 40109267

• Dipeptidylpeptidase 4 Is Overexpressed in the Extracellular Matrix of Biliary Atresia-Associated Liver Fibrosis Liang, N., Griffin, M., Parker, J. L., Guo, J. L., Bauer-Rowe, K. E., Fell, G. L., Dunn, J. Y., Tan, S. S., Hyun, J. S., Longaker, M. T. LIPPINCOTT WILLIAMS & WILKINS. 2024: S347-S348

  View details for Web of Science ID 001348680702168

• Pediatric metabolic and bariatric surgery: indications and preoperative multidisciplinary evaluation. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery Mangarelli, C., Fell, G., Hobbs, E., Lowry, K. W., Williams, E., Pratt, J. S. 2024

  Abstract

  The standard of care for pediatric patients with severe obesity considering metabolic and bariatric surgery is a preoperative multidisciplinary evaluation. A multidisciplinary team allows for the efficient use of variable personnel expertise to evaluate, manage, and support a pediatric patient and family through metabolic and bariatric surgery. This review discusses the purpose, recommended team members, patient selection, content, and benefits of the multidisciplinary preoperative evaluation. This evaluation should reduce barriers to care and optimize patient safety and outcomes while taking into consideration the unique developmental needs of this age group.

  View details for DOI 10.1016/j.soard.2024.08.025

  View details for PubMedID 39304458

• beta-Endorphin mediates radiation therapy fatigue SCIENCE ADVANCES Hermann, A. L., Fell, G. L., Kemeny, L., Fung, C. Y., Held, K. D., Biggs, P. J., Rivera, P. D., Bilbo, S. D., Igras, V., Willers, H., Kung, J., Gheorghiu, L., Hideghety, K., Mao, J., Woolf, C. J., Fisher, D. E. 2022; 8 (50): eabn6025

  Abstract

  Fatigue is a common adverse effect of external beam radiation therapy in cancer patients. Mechanisms causing radiation fatigue remain unclear, although linkage to skin irradiation has been suggested. β-Endorphin, an endogenous opioid, is synthesized in skin following genotoxic ultraviolet irradiation and acts systemically, producing addiction. Exogenous opiates with the same receptor activity as β-endorphin can cause fatigue. Using rodent models of radiation therapy, exposing tails and sparing vital organs, we tested whether skin-derived β-endorphin contributes to radiation-induced fatigue. Over a 6-week radiation regimen, plasma β-endorphin increased in rats, paralleled by opiate phenotypes (elevated pain thresholds, Straub tail) and fatigue-like behavior, which was reversed in animals treated by the opiate antagonist naloxone. Mechanistically, all these phenotypes were blocked by opiate antagonist treatment and were undetected in either β-endorphin knockout mice or mice lacking keratinocyte p53 expression. These findings implicate skin-derived β-endorphin in systemic effects of radiation therapy. Opioid antagonism may warrant testing in humans as treatment or prevention of radiation-induced fatigue.

  View details for DOI 10.1126/sciadv.abn6025

  View details for Web of Science ID 000917907400012

  View details for PubMedID 36525492

  View details for PubMedCentralID PMC9757747