# Clinically Interpretable Sepsis Early Warning via LLM-Guided Simulation of Temporal Physiological Dynamics

arXiv: https://arxiv.org/abs/2604.20924 · HTML: https://mlsanity.com/paper/2604.20924/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 11 of its 58 references that are in the map.
- First posted on arXiv 22 Apr 2026.

## Builds on (most cited first, 11 of 11)

- [RoBERTa: A Robustly Optimized BERT Pretraining Approach](https://mlsanity.com/paper/1907.11692/) (2019)
- [Explaining and Harnessing Adversarial Examples](https://mlsanity.com/paper/1412.6572/) (2014)
- [Publicly Available Clinical BERT Embeddings](https://mlsanity.com/paper/1904.03323/) (2019)
- [Time-LLM: Time Series Forecasting by Reprogramming Large Language Models](https://mlsanity.com/paper/2310.01728/) (2023)
- [BioGPT: Generative Pre-trained Transformer for Biomedical Text Generation and Mining](https://mlsanity.com/paper/2210.10341/) (2022)
- [When Scaling Meets LLM Finetuning: The Effect of Data, Model and Finetuning Method](https://mlsanity.com/paper/2402.17193/) (2024)
- [Resnet in Resnet: Generalizing Residual Architectures](https://mlsanity.com/paper/1603.08029/) (2016)
- [Automatic Text Summarization of COVID-19 Medical Research Articles using BERT and GPT-2](https://mlsanity.com/paper/2006.01997/) (2020)
- [Early detection of sepsis utilizing deep learning on electronic health record event sequences](https://mlsanity.com/paper/1906.02956/) (2019)
- [MGP-AttTCN: An Interpretable Machine Learning Model for the Prediction of Sepsis](https://mlsanity.com/paper/1909.12637/) (2019)
- [Admissible Time Series Motif Discovery with Missing Data](https://mlsanity.com/paper/1802.05472/) (2018)

## Abstract (arXiv)

Timely and interpretable early warning of sepsis remains a major clinical challenge due to the complex temporal dynamics of physiological deterioration. Traditional data-driven models often provide accurate yet opaque predictions, limiting physicians' confidence and clinical applicability. To address this limitation, we propose a Large Language Model (LLM)-guided temporal simulation framework that explicitly models physiological trajectories prior to disease onset for clinically interpretable prediction. The framework consists of a spatiotemporal feature extraction module that captures dynamic dependencies among multivariate vital signs, a Medical Prompt-as-Prefix module that embeds clinical reasoning cues into LLMs, and an agent-based post-processing component that constrains predictions within physiologically plausible ranges. By first simulating the evolution of key physiological indicators and then classifying sepsis onset, our model offers transparent prediction mechanisms that align with clinical judgment. Evaluated on the MIMIC-IV and eICU databases, the proposed method achieves superior AUC scores (0.861-0.903) across 24-4-hour pre-onset prediction tasks, outperforming conventional deep learning and rule-based approaches. More importantly, it provides interpretable trajectories and risk trends that can assist clinicians in early intervention and personalized decision-making in intensive care environments.