Multi-Large Language Model Orchestrated Severity Assessment of Clinical Records (MOSAIC)

Background: Disease severity is a multidimensional construct difficult to capture with rule-based approaches in Electronic Healthcare Records (EHR). Agentic large language model (LLM) systems could synthesise clinical evidence and reason over EHRs, but remain unevaluated for this task. Methods: MOSAIC is a two-phase agentic LLM framework for severity phenotyping, using type 2 diabetes (T2D) as a proof-of-concept. MOSAIC was evaluated on a synthetic cohort (SyntheticMass; open-weight N = 4,886; closed-weight N = 200) against three algorithmic ground truths (DCSI, DiSSCo, Cooper) and against all-cause mortality and incident complications. Open-weight (locally deployable) and proprietary pipelines were also compared. Results: The generated framework spanned domains absent from the comparators, including biomarker-based glycaemic staging, beta-cell function, and social determinants of health. Open-weight MOSAIC matched the proprietary pipeline (closed- vs open-weight weighted kappa = 0.773) and reached moderate agreement with Cooper (kappa = 0.597) and DCSI (kappa = 0.534) and fair agreement with DiSSCo (kappa = 0.320). Agent-based (Type 1) tiers showed significant separation of all-cause mortality (log-rank p < 0.001; crude hazard ratios 1.6-2.4 for non-Baseline tiers), with non-monotonic separation at the upper tiers, and an inverse gradient for incident complications (log-rank p < 0.001) consistent with depletion of susceptibles. Agentic classification also diverged from deterministic execution of the same rubric (MOSAIC Frozen; kappa = 0.428), indicating reasoning beyond fixed rules. Conclusion: MOSAIC shows agentic LLM systems can generate and apply clinically meaningful severity phenotypes from structured EHR data in T2D. Extending it to other diseases with similarly multidimensional severity warrants further research.

TopoAgent: An Agentic Framework for Automated Topology Learning in Medical Imaging

Topological data analysis (TDA), particularly persistent homology (PH), captures geometric structural properties in medical images (e.g., connected components, loops, shape characteristics), which conventional pixel-level deep learning approaches often neglect. While many topological descriptors are known for converting persistence diagrams (PDs) or raw images into topological feature vectors, existing methods mostly default to a single fixed descriptor (e.g., persistence images), leaving the diversity of topological representations largely unexplored. To the best of our knowledge, there is no known large language model (LLM)-based agentic framework that can automatically determine the most suitable topological descriptors for a given image dataset and produce the corresponding topological feature vectors for downstream tasks. To fill this gap, we propose \textbf{TopoAgent}, an LLM-based agentic framework that automates topology learning for medical image analysis.TopoAgent operates through a Perception--Reasoning--Action--Reflection loop supported by 21 domain-specific tools and dual memory that accumulates experience across runs. Its skill set is distilled from systematic evaluation of 15 topological descriptors across 26 datasets with six classifiers. TopoAgent analyzes input images and their topological characteristics, reasons about which topological descriptors best suit the input, and determines the optimal descriptor and its configuration, all without task-specific training.

Evo-RAD: Navigating Rare Retinal Disease Diagnosis via Self-Evolving Agentic Retrieval

Large-scale pretrained foundation models have revolutionized general medical screening, but often falter on rare diseases because such conditions are underrepresented in real-world clinical datasets. While retrieval-augmented diagnosis attempts to mitigate this, conventional static methods frequently succumb to the hubness problem, retrieving visually similar but semantically incorrect common diseases. To address this, we propose Evo-RAD, a self-evolving agentic framework that transforms evidence acquisition into a dynamic decision-making task. We formulate retrieval as a Markov Decision Process (MDP) where a graphbased agent observes the reference set state and executes actions to purge discordant evidence (DELETE), acquire pathologically consistent samples (INSERT), or conclude the evolution (TERMINATE). Optimized via Group Relative Policy Optimization (GRPO) with a homogeneityaware reward, the agent learns to maximize the diagnostic homogeneity of the support reference set. Experiments on retinal disease benchmarks show that Evo-RAD substantially improves rare-disease diagnosis, outperforming retinal foundation models by +21.04%, while also surpassing retrieval-based and parameter-efficient fine-tuning methods by +3.56%. Code is available at https://github.com/SDH-Lab/Evo-RAD.