Multimodal neuroimmune diagnostic profiling for pediatric lower urinary tract dysfunction associated with occult sacral nerve abnormalities
- 1Department of Pediatric Surgery, Guizhou Provincial People’s Hospital
- 2Department of Pediatric Urology, Shanghai Children’s Medical Center GuiZhou Hospital, Shanghai Jiao Tong University School of Medicine
- 3Department of Children’s Ultrasound, Shanghai Children’s Medical Center GuiZhou Hospital, Shanghai Jiao Tong University School of Medicine
Abstract
Background: Persistent pediatric lower urinary tract dysfunction (LUTD) may be associated with occult sacral neural impairment, a clinically challenging condition characterized by subtle sacral pathway dysfunction without overt spinal dysraphism.
Objective: To develop, internally validate, and externally validate a multimodal diagnostic model integrating ultrasound, urodynamics, neuroelectrophysiology, and urinary biomarkers.
Methods: The development dataset comprised 120 records (45 occult sacral neuropathy-related LUTD, 45 functional non-neurogenic LUTD, and 30 controls). The target-condition label followed a prespecified multidisciplinary composite reference standard based on clinical phenotype, neurological examination, spinal/pelvic MRI when available, conventional urodynamic interpretation, and longitudinal course; biomarker values and model probabilities were not components of that label. Preanalytical metadata included pre-catheterization collection, centrifugation at 3000 or 5000 x g for 10 minutes, 1.0- 1.5 mL aliquots, storage at -80 °C, limited freeze-thaw exposure, and creatinine normalization. We internally validated a six-predictor logistic model with 1,000 bootstrap repetitions. We assessed a separate 90-record, two-site dataset without refitting or threshold optimization.
Results: The locked model had an apparent AUC of 0.937 and Brier score of 0.099; optimism-corrected values were 0.920 and 0.116, respectively. The bootstrap mean calibration intercept was -0.065, and the slope was 1.032. In the external transportability analysis, the AUC was 0.928 (95% CI, 0.861-0.977), the Brier score was 0.098, the calibration intercept was -0.400, the calibration slope was 0.887, sensitivity was 80.0%, and specificity was 88.3%.
Conclusion: Multimodal neuroimmune profiling demonstrated strong discrimination and acceptable calibration after optimism correction and external validation in an independent two-site cohort. Prospective multicenter validation is required before clinical implementation.
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BibTeX
@article{wang2026multimodal,
title = {{Multimodal neuroimmune diagnostic profiling for pediatric lower urinary tract dysfunction associated with occult sacral nerve abnormalities}},
author = {Dan Wang and Jun Pei and Hongyong Liao and Yimeng Liu and Yuangui Yang and Min Deng and Nini An},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1947984},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1947984/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multimodal neuroimmune diagnostic profiling for pediatric lower urinary tract dysfunction associated with occult sacral nerve abnormalities
AU - Dan Wang
AU - Jun Pei
AU - Hongyong Liao
AU - Yimeng Liu
AU - Yuangui Yang
AU - Min Deng
AU - Nini An
PY - 2026
DA - 2026/10/06
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1947984
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1947984/full
AB - Background: Persistent pediatric lower urinary tract dysfunction (LUTD) may be associated with occult sacral neural impairment, a clinically challenging condition characterized by subtle sacral pathway dysfunction without overt spinal dysraphism. Objective: To develop, internally validate, and externally validate a multimodal diagnostic model integrating ultrasound, urodynamics, neuroelectrophysiology, and urinary biomarkers. Methods: The development dataset comprised 120 records (45 occult sacral neuropathy-related LUTD, 45 functional non-neurogenic LUTD, and 30 controls). The target-condition label followed a prespecified multidisciplinary composite reference standard based on clinical phenotype, neurological examination, spinal/pelvic MRI when available, conventional urodynamic interpretation, and longitudinal course; biomarker values and model probabilities were not components of that label. Preanalytical metadata included pre-catheterization collection, centrifugation at 3000 or 5000 x g for 10 minutes, 1.0- 1.5 mL aliquots, storage at -80 °C, limited freeze-thaw exposure, and creatinine normalization. We internally validated a six-predictor logistic model with 1,000 bootstrap repetitions. We assessed a separate 90-record, two-site dataset without refitting or threshold optimization. Results: The locked model had an apparent AUC of 0.937 and Brier score of 0.099; optimism-corrected values were 0.920 and 0.116, respectively. The bootstrap mean calibration intercept was -0.065, and the slope was 1.032. In the external transportability analysis, the AUC was 0.928 (95% CI, 0.861-0.977), the Brier score was 0.098, the calibration intercept was -0.400, the calibration slope was 0.887, sensitivity was 80.0%, and specificity was 88.3%. Conclusion: Multimodal neuroimmune profiling demonstrated strong discrimination and acceptable calibration after optimism correction and external validation in an independent two-site cohort. Prospective multicenter validation is required before clinical implementation.
SN - 1664-3224
ER -