Diagnostic prediction and clinical reasoning are critical tasks in healthcare applications. While Large Language Models (LLMs) have shown strong capabilities in commonsense reasoning, they still struggle with diagnostic reasoning due to limited domain knowledge. Existing approaches often rely on internal model knowledge or static knowledge bases, resulting in knowledge insufficiency and limited adaptability, which hinder their capacity to perform diagnostic reasoning. Moreover, these methods focus solely on the accuracy of final predictions, overlooking alignment with standard clinical reasoning trajectories. To this end, we propose MultiDx, a two-stage diagnostic reasoning framework that performs differential diagnosis by analyzing evidence collected from multiple knowledge sources. Specifically, it first generates suspected diagnoses and reasoning paths by leveraging knowledge from web search, SOAP-formatted case, and clinical case database. Then it integrates multi-perspective evidence through matching, voting, and differential diagnosis to generate the final prediction.~Extensive experiments on two public benchmarks demonstrate the effectiveness of our approach.
The application of large language models (LLMs) in clinical decision support faces significant challenges of "tunnel vision" and diagnostic hallucinations present in their processing unstructured electronic health records (EHRs). To address these challenges, we propose a novel chain-based clinical reasoning framework, called DxChain, which transforms the diagnostic workflow into an iterative process by mirroring a clinician's cognitive trajectory that consists of "Memory Anchoring", "Navigation" and "Verification" phases. DxChain introduces three key methodological innovations to elicit the potential of LLM: (i) a Profile-Then-Plan paradigm to mitigate cold-start hallucinations by establishing a panoramic patient baseline, (ii) a Medical Tree-of-Thoughts (Med-ToT) algorithm for strategic look ahead planning and resource aware navigation, and (iii) a Dialectical Diagnostic Verification procedure utilizing "Angel-Devil" adversarial debates to resolve complex evidence conflicts. Evaluated on two real world benchmarks, MIMIC-IV-Ext Cardiac Disease and MIMIC-IV-Ext CDM, DxChain achieves state-of-the-art performances in both diagnostic accuracy and logical consistency, offering a modular and reliable architecture for next-generation clinical AI. The code is at https://anonymous.4open.science/r/Dx-Chain.
Clinical diagnostic evaluation should not only assess whether models can provide correct diagnoses, but also reflect the realities of clinical practice, including progressive disclosure of multimodal information, dynamic updating of diagnostic hypotheses, and continuous refinement of clinical reasoning. However, existing evaluations of multimodal large language models (MLLMs) typically rely on single-turn or isolated tasks, making it difficult to fully capture the complexity of real-world clinical diagnosis. To bridge this gap, we developed ClinMM-Bench, the largest multi-turn multimodal clinical diagnostic evaluation benchmark to date. ClinMM-Bench contains 1,089 challenging real-world clinical cases and 3,760 medical images across eight specialties. We systematically evaluated 15 representative MLLMs using a two-level evaluation framework that assessed both diagnostic accuracy and diagnostic reasoning quality. Results showed that proprietary models achieved the highest overall diagnostic accuracy, but the proportion of completely correct diagnoses remained limited across all models. In terms of diagnostic reasoning quality, current models can identify plausible diagnostic directions but still have considerable limitations in generating reliable diagnostic reasoning. Error analysis further identified five representative failure modes: information synthesis failure, knowledge mapping error, perception error, premature closure, and visual hallucination.
Large language models (LLMs) are increasingly used for health-related decision support. Yet most evaluations treat diagnosis as a single-shot task with complete information provided upfront, often as a multiple-choice selection. This diverges from clinical practice, where diagnosis is interactive and open-ended, involving sequential hypothesis refinement through targeted questioning. We address this gap. We build MeDxBench, a large-scale benchmark of 4,421 clinical cases across 20 specialties. We further propose MeDxAgent, a multi-agent consultation system for interactive diagnosis, and systematically study its prompt-, flow- and agent-level design choices. MeDxAgent achieves a 10.3% accuracy gain over the baseline on MeDxBench, closing 52.3% of the gap to a full-information oracle. We find that specific design choices: collecting demographics first, passing summarized dialogue for diagnosis, and feeding candidate diagnoses for targeted questioning, improve accuracy, mirroring how physicians reason, though their effect emerges fully only in combination. Code and dataset will be released upon publication.