Daily Papers

Objectives: While Large Language Models (LLMs) have been widely used to assist clinicians and support patients, no existing work has explored dialogue systems for standard diagnostic interviews and assessments. This study aims to bridge the gap in mental healthcare accessibility by developing an LLM-powered dialogue system that replicates clinician behavior. Materials and Methods: We introduce TRUST, a framework of cooperative LLM modules capable of conducting formal diagnostic interviews and assessments for Post-Traumatic Stress Disorder (PTSD). To guide the generation of appropriate clinical responses, we propose a Dialogue Acts schema specifically designed for clinical interviews. Additionally, we develop a patient simulation approach based on real-life interview transcripts to replace time-consuming and costly manual testing by clinicians. Results: A comprehensive set of evaluation metrics is designed to assess the dialogue system from both the agent and patient simulation perspectives. Expert evaluations by conversation and clinical specialists show that TRUST performs comparably to real-life clinical interviews. Discussion: Our system performs at the level of average clinicians, with room for future enhancements in communication styles and response appropriateness. Conclusions: Our TRUST framework shows its potential to facilitate mental healthcare availability.

Clinical machine learning research and AI driven clinical decision support models rely on clinically accurate labels. Manually extracting these labels with the help of clinical specialists is often time-consuming and expensive. This study tests the feasibility of automatic span- and document-level diagnosis extraction from unstructured Dutch echocardiogram reports. We included 115,692 unstructured echocardiogram reports from the UMCU a large university hospital in the Netherlands. A randomly selected subset was manually annotated for the occurrence and severity of eleven commonly described cardiac characteristics. We developed and tested several automatic labelling techniques at both span and document levels, using weighted and macro F1-score, precision, and recall for performance evaluation. We compared the performance of span labelling against document labelling methods, which included both direct document classifiers and indirect document classifiers that rely on span classification results. The SpanCategorizer and MedRoBERTa.nl models outperformed all other span and document classifiers, respectively. The weighted F1-score varied between characteristics, ranging from 0.60 to 0.93 in SpanCategorizer and 0.96 to 0.98 in MedRoBERTa.nl. Direct document classification was superior to indirect document classification using span classifiers. SetFit achieved competitive document classification performance using only 10\% of the training data. Utilizing a reduced label set yielded near-perfect document classification results. We recommend using our published SpanCategorizer and MedRoBERTa.nl models for span- and document-level diagnosis extraction from Dutch echocardiography reports. For settings with limited training data, SetFit may be a promising alternative for document classification.

Synthetic Data Generation (SDG) based on Artificial Intelligence (AI) can transform the way clinical medicine is delivered by overcoming privacy barriers that currently render clinical data sharing difficult. This is the key to accelerating the development of digital tools contributing to enhanced patient safety. Such tools include robust data-driven clinical decision support systems, and example-based digital training tools that will enable healthcare professionals to improve their diagnostic performance for enhanced patient safety. This study focuses on the clinical evaluation of medical SDG, with a proof-of-concept investigation on diagnosing Inflammatory Bowel Disease (IBD) using Wireless Capsule Endoscopy (WCE) images. Its scientific contributions include a) a novel protocol for the systematic Clinical Evaluation of Medical Image Synthesis (CEMIS); b) a novel variational autoencoder-based model for the generation of high-resolution synthetic WCE images; and c) a comprehensive evaluation of the synthetic images using the CEMIS protocol by 10 international WCE specialists, in terms of image quality, diversity, and realism, as well as their utility for clinical decision-making. The results show that TIDE-II generates clinically plausible, very realistic WCE images, of improved quality compared to relevant state-of-the-art generative models. Concludingly, CEMIS can serve as a reference for future research on medical image-generation techniques, while the adaptation/extension of the architecture of TIDE-II to other imaging domains can be promising.

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical diagnosis rates primarily due to a lack of experienced physicians and the complexity of differentiating among many rare diseases. In this context, recent news such as "ChatGPT correctly diagnosed a 4-year-old's rare disease after 17 doctors failed" underscore LLMs' potential, yet underexplored, role in clinically diagnosing rare diseases. To bridge this research gap, we introduce RareBench, a pioneering benchmark designed to systematically evaluate the capabilities of LLMs on 4 critical dimensions within the realm of rare diseases. Meanwhile, we have compiled the largest open-source dataset on rare disease patients, establishing a benchmark for future studies in this domain. To facilitate differential diagnosis of rare diseases, we develop a dynamic few-shot prompt methodology, leveraging a comprehensive rare disease knowledge graph synthesized from multiple knowledge bases, significantly enhancing LLMs' diagnostic performance. Moreover, we present an exhaustive comparative study of GPT-4's diagnostic capabilities against those of specialist physicians. Our experimental findings underscore the promising potential of integrating LLMs into the clinical diagnostic process for rare diseases. This paves the way for exciting possibilities in future advancements in this field.

The need for improved diagnostic methods in ophthalmology is acute, especially in the underdeveloped regions with limited access to specialists and advanced equipment. Therefore, we introduce VisionUnite, a novel vision-language foundation model for ophthalmology enhanced with clinical knowledge. VisionUnite has been pretrained on an extensive dataset comprising 1.24 million image-text pairs, and further refined using our proposed MMFundus dataset, which includes 296,379 high-quality fundus image-text pairs and 889,137 simulated doctor-patient dialogue instances. Our experiments indicate that VisionUnite outperforms existing generative foundation models such as GPT-4V and Gemini Pro. It also demonstrates diagnostic capabilities comparable to junior ophthalmologists. VisionUnite performs well in various clinical scenarios including open-ended multi-disease diagnosis, clinical explanation, and patient interaction, making it a highly versatile tool for initial ophthalmic disease screening. VisionUnite can also serve as an educational aid for junior ophthalmologists, accelerating their acquisition of knowledge regarding both common and underrepresented ophthalmic conditions. VisionUnite represents a significant advancement in ophthalmology, with broad implications for diagnostics, medical education, and understanding of disease mechanisms. The source code is at https://github.com/HUANGLIZI/VisionUnite.

Coronary artery disease (CAD) remains the leading cause of death globally and invasive coronary angiography (ICA) is considered the gold standard of anatomical imaging evaluation when CAD is suspected. However, risk evaluation based on ICA has several limitations, such as visual assessment of stenosis severity, which has significant interobserver variability. This motivates to development of a lesion classification system that can support specialists in their clinical procedures. Although deep learning classification methods are well-developed in other areas of medical imaging, ICA image classification is still at an early stage. One of the most important reasons is the lack of available and high-quality open-access datasets. In this paper, we reported a new annotated ICA images dataset, CADICA, to provide the research community with a comprehensive and rigorous dataset of coronary angiography consisting of a set of acquired patient videos and associated disease-related metadata. This dataset can be used by clinicians to train their skills in angiographic assessment of CAD severity and by computer scientists to create computer-aided diagnostic systems to help in such assessment. In addition, baseline classification methods are proposed and analyzed, validating the functionality of CADICA and giving the scientific community a starting point to improve CAD detection.

Medical Large Vision-Language Models (Med-LVLMs) have shown strong potential in multimodal diagnostic tasks. However, existing single-agent models struggle to generalize across diverse medical specialties, limiting their performance. Recent efforts introduce multi-agent collaboration frameworks inspired by clinical workflows, where general practitioners (GPs) and specialists interact in a fixed sequence. Despite improvements, these static pipelines lack flexibility and adaptability in reasoning. To address this, we propose MMedAgent-RL, a reinforcement learning (RL)-based multi-agent framework that enables dynamic, optimized collaboration among medical agents. Specifically, we train two GP agents based on Qwen2.5-VL via RL: the triage doctor learns to assign patients to appropriate specialties, while the attending physician integrates the judgments from multi-specialists and its own knowledge to make final decisions. To address the inconsistency in specialist outputs, we introduce a curriculum learning (CL)-guided RL strategy that progressively teaches the attending physician to balance between imitating specialists and correcting their mistakes. Experiments on five medical VQA benchmarks demonstrate that MMedAgent-RL not only outperforms both open-source and proprietary Med-LVLMs, but also exhibits human-like reasoning patterns. Notably, it achieves an average performance gain of 20.7% over supervised fine-tuning baselines.

Annotating medical data for training AI models is often costly and limited due to the shortage of specialists with relevant clinical expertise. This challenge is further compounded by privacy and ethical concerns associated with sensitive patient information. As a result, well-trained medical segmentation models on private datasets constitute valuable intellectual property requiring robust protection mechanisms. Existing model protection techniques primarily focus on classification and generative tasks, while segmentation models-crucial to medical image analysis-remain largely underexplored. In this paper, we propose a novel, stealthy, and harmless method, StealthMark, for verifying the ownership of medical segmentation models under black-box conditions. Our approach subtly modulates model uncertainty without altering the final segmentation outputs, thereby preserving the model's performance. To enable ownership verification, we incorporate model-agnostic explanation methods, e.g. LIME, to extract feature attributions from the model outputs. Under specific triggering conditions, these explanations reveal a distinct and verifiable watermark. We further design the watermark as a QR code to facilitate robust and recognizable ownership claims. We conducted extensive experiments across four medical imaging datasets and five mainstream segmentation models. The results demonstrate the effectiveness, stealthiness, and harmlessness of our method on the original model's segmentation performance. For example, when applied to the SAM model, StealthMark consistently achieved ASR above 95% across various datasets while maintaining less than a 1% drop in Dice and AUC scores, significantly outperforming backdoor-based watermarking methods and highlighting its strong potential for practical deployment. Our implementation code is made available at: https://github.com/Qinkaiyu/StealthMark.

Positron emission tomography/computed tomography (PET/CT) is essential in oncology, yet the rapid expansion of scanners has outpaced the availability of trained specialists, making automated PET/CT report generation (PETRG) increasingly important for reducing clinical workload. Compared with structural imaging (e.g., X-ray, CT, and MRI), functional PET poses distinct challenges: metabolic patterns vary with tracer physiology, and whole-body 3D contextual information is required rather than local-region interpretation. To advance PETRG, we propose PETRG-3D, an end-to-end 3D dual-branch framework that separately encodes PET and CT volumes and incorporates style-adaptive prompts to mitigate inter-hospital variability in reporting practices. We construct PETRG-Lym, a multi-center lymphoma dataset collected from four hospitals (824 reports w/ 245,509 paired PET/CT slices), and construct AutoPET-RG-Lym, a publicly accessible PETRG benchmark derived from open imaging data but equipped with new expert-written, clinically validated reports (135 cases). To assess clinical utility, we introduce PETRG-Score, a lymphoma-specific evaluation protocol that jointly measures metabolic and structural findings across curated anatomical regions. Experiments show that PETRG-3D substantially outperforms existing methods on both natural language metrics (e.g., +31.49\% ROUGE-L) and clinical efficacy metrics (e.g., +8.18\% PET-All), highlighting the benefits of volumetric dual-modality modeling and style-aware prompting. Overall, this work establishes a foundation for future PET/CT-specific models emphasizing disease-aware reasoning and clinically reliable evaluation. Codes, models, and AutoPET-RG-Lym will be released.

Specialized clinical AI assistants are rapidly entering medical practice, often framed as safer or more reliable than general-purpose large language models (LLMs). Yet, unlike frontier models, these clinical tools are rarely subjected to independent, quantitative evaluation, creating a critical evidence gap despite their growing influence on diagnosis, triage, and guideline interpretation. We assessed two widely deployed clinical AI systems (OpenEvidence and UpToDate Expert AI) against three state-of-the-art generalist LLMs (GPT-5, Gemini 3 Pro, and Claude Sonnet 4.5) using a 1,000-item mini-benchmark combining MedQA (medical knowledge) and HealthBench (clinician-alignment) tasks. Generalist models consistently outperformed clinical tools, with GPT-5 achieving the highest scores, while OpenEvidence and UpToDate demonstrated deficits in completeness, communication quality, context awareness, and systems-based safety reasoning. These findings reveal that tools marketed for clinical decision support may often lag behind frontier LLMs, underscoring the urgent need for transparent, independent evaluation before deployment in patient-facing workflows.

The increasing use of tools and solutions based on Large Language Models (LLMs) for various tasks in the medical domain has become a prominent trend. Their use in this highly critical and sensitive domain has thus raised important questions about their robustness, especially in response to variations in input, and the reliability of the generated outputs. This study addresses these questions by constructing a textual dataset based on the ICD-10-CM code descriptions, widely used in US hospitals and containing many clinical terms, and their easily reproducible rephrasing. We then benchmarked existing embedding models, either generalist or specialized in the clinical domain, in a semantic search task where the goal was to correctly match the rephrased text to the original description. Our results showed that generalist models performed better than clinical models, suggesting that existing clinical specialized models are more sensitive to small changes in input that confuse them. The highlighted problem of specialized models may be due to the fact that they have not been trained on sufficient data, and in particular on datasets that are not diverse enough to have a reliable global language understanding, which is still necessary for accurate handling of medical documents.

Across medical specialties, clinical practice is anchored in evidence-based guidelines that codify best studied diagnostic and treatment pathways. These pathways routinely fall short for the long tail of real-world care not covered by guidelines. Most medical large language models (LLMs), however, are trained to encode common, guideline-focused medical knowledge in their parameters. Current evaluations test models primarily on recalling and reasoning with this memorized content, often in multiple-choice settings. Given the fundamental importance of evidence-based reasoning in medicine, it is neither feasible nor reliable to depend on memorization in practice. To address this gap, we introduce OGCaReBench, a free-form retrieval-focused benchmark aimed at evaluating LLMs at answering clinical questions that require going beyond typical guidelines. Extracted from published medical case reports and validated by medical experts, OGCaReBench contains long-form clinical questions requiring free-text answers, providing a systematic framework for assessing open-ended medical reasoning in rare, case-based scenarios. Our experiments reveal that even the best-performing baseline (GPT-5.2) correctly answers only 56% of our benchmark with specialized models only reaching 42%. Augmenting models with retrieved medical articles improves this performance to up to 82% (using GPT-5.2) highlighting the importance of evidence-grounding for real-world medical reasoning tasks. This work thus establishes a foundation for benchmarking and advancing both general-purpose and medical LLMs to produce reliable answers in challenging clinical contexts.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

The development of clinical natural language processing (NLP) systems is severely hampered by the sensitive nature of medical records, which restricts data sharing under stringent privacy regulations, particularly in France and the broader European Union. To address this gap, we introduce PARHAF, a large open-source corpus of clinical documents in French. PARHAF comprises expert-authored clinical reports describing realistic yet entirely fictitious patient cases, making it anonymous and freely shareable by design. The corpus was developed using a structured protocol that combined clinician expertise with epidemiological guidance from the French National Health Data System (SNDS), ensuring broad clinical coverage. A total of 104 medical residents across 18 specialties authored and peer-reviewed the reports following predefined clinical scenarios and document templates. The corpus contains 7394 clinical reports covering 5009 patient cases across a wide range of medical and surgical specialties. It includes a general-purpose component designed to approximate real-world hospitalization distributions, and four specialized subsets that support information-extraction use cases in oncology, infectious diseases, and diagnostic coding. Documents are released under a CC-BY open license, with a portion temporarily embargoed to enable future benchmarking under controlled conditions. PARHAF provides a valuable resource for training and evaluating French clinical language models in a fully privacy-preserving setting, and establishes a replicable methodology for building shareable synthetic clinical corpora in other languages and health systems.

Medical question answering systems face deployment challenges including hallucinations, bias, computational demands, privacy concerns, and the need for specialized expertise across diverse domains. Here, we present SOLVE-Med, a multi-agent architecture combining domain-specialized small language models for complex medical queries. The system employs a Router Agent for dynamic specialist selection, ten specialized models (1B parameters each) fine-tuned on specific medical domains, and an Orchestrator Agent that synthesizes responses. Evaluated on Italian medical forum data across ten specialties, SOLVE-Med achieves superior performance with ROUGE-1 of 0.301 and BERTScore F1 of 0.697, outperforming standalone models up to 14B parameters while enabling local deployment. Our code is publicly available on GitHub: https://github.com/PRAISELab-PicusLab/SOLVE-Med.

Physicians now pose millions of clinical questions to AI tools each week, yet these tools are evaluated largely on hypothetical or exam-style questions, not those actually asked in practice. We report a blinded evaluation built on 620 Real-world Point-Of-Care Queries (Real-POCQi) submitted to the OpenEvidence (OE) platform by physicians spanning 30 specialties, as well as 187 questions from HealthBench. 149 practicing physicians across 36 states made head-to-head comparisons between answers from three frontier general-purpose models (Claude Opus 4.8, Gemini 3.1 Pro, and GPT-5.5) and a specialized clinical tool (OE), with graders matched to each question's specialty. When comparing answers along five dimensions relevant to clinical decision support -- accuracy, clinical utility, source quality, verifiability, & completeness -- physicians scored the specialized tool highest on all axes; in the primary analysis on Real-POCQi, win differences (margins between win and loss rates) ranged from 25 to 39 percentage points (p<0.001). Results remained consistent in sensitivity analyses stratifying by citation display, answer length, OE-user status, and Real-POCQi versus HealthBench. In parallel, LLM judges were found to systematically differ from expert judges, though both generally agreed on the best model. These findings underscore two conclusions: (i) AI tool evaluations should reflect real-world query distributions and use expert judges that mirror the specialization defining modern medicine and (ii) the consistent advantage of the specialized tool over general-purpose models does not necessarily mean that the latter cannot serve similar purposes, but that targeted engineering and customization can yield meaningful gains in performance for its users. We release Real-POCQi as a public benchmark, as well as the prespecified statistical analysis for reproducing results of this study.

Medical coding translates clinical documentation into standardized codes for billing, research, and public health, but manual coding is time-consuming and error-prone. Existing automation efforts rely on small datasets that poorly represent real-world patient heterogeneity. We trained a language model on 5.8 million electronic health records from 1.8 million patients across nearly all specialties in Eastern Denmark (2006--2016) to predict ICD-10 codes from clinical notes, medications, and laboratory results. Evaluated on 270,000 held-out patients, the model achieved a micro F1 of 71.8% and a top-10 recall of 95.5%. Performance varied by specialty (F1: 53--91%), with higher scores in specialties with well-defined diagnostic criteria. Codes appearing predominantly as secondary diagnoses had markedly lower F1 scores. For three such codes (suicide-related behaviors, weight disorders, and hypertension), the model identified thousands of uncoded cases, of which 76-86% were confirmed valid upon manual review, suggesting systematic under-coding rather than model error. These findings suggest under-coding of secondary diagnoses in Eastern Denmark during this period, with potential implications for epidemiological research, public health surveillance, and understanding of multimorbidity. Similar time constraints and reimbursement structures in other healthcare systems suggest this may not be isolated to this dataset. The model can automate coding for approximately 50% of cases and provide accurate suggestions for most others, and may offer a practical solution to help capture missed secondary conditions.

Transformers-based models, such as BERT, have dramatically improved the performance for various natural language processing tasks. The clinical knowledge enriched model, namely ClinicalBERT, also achieved state-of-the-art results when performed on clinical named entity recognition and natural language inference tasks. One of the core limitations of these transformers is the substantial memory consumption due to their full self-attention mechanism. To overcome this, long sequence transformer models, e.g. Longformer and BigBird, were proposed with the idea of sparse attention mechanism to reduce the memory usage from quadratic to the sequence length to a linear scale. These models extended the maximum input sequence length from 512 to 4096, which enhanced the ability of modeling long-term dependency and consequently achieved optimal results in a variety of tasks. Inspired by the success of these long sequence transformer models, we introduce two domain enriched language models, namely Clinical-Longformer and Clinical-BigBird, which are pre-trained from large-scale clinical corpora. We evaluate both pre-trained models using 10 baseline tasks including named entity recognition, question answering, and document classification tasks. The results demonstrate that Clinical-Longformer and Clinical-BigBird consistently and significantly outperform ClinicalBERT as well as other short-sequence transformers in all downstream tasks. We have made our source code available at [https://github.com/luoyuanlab/Clinical-Longformer] the pre-trained models available for public download at: [https://huggingface.co/yikuan8/Clinical-Longformer].

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.

Although recent advances in scaling large language models (LLMs) have resulted in improvements on many NLP tasks, it remains unclear whether these models trained primarily with general web text are the right tool in highly specialized, safety critical domains such as clinical text. Recent results have suggested that LLMs encode a surprising amount of medical knowledge. This raises an important question regarding the utility of smaller domain-specific language models. With the success of general-domain LLMs, is there still a need for specialized clinical models? To investigate this question, we conduct an extensive empirical analysis of 12 language models, ranging from 220M to 175B parameters, measuring their performance on 3 different clinical tasks that test their ability to parse and reason over electronic health records. As part of our experiments, we train T5-Base and T5-Large models from scratch on clinical notes from MIMIC III and IV to directly investigate the efficiency of clinical tokens. We show that relatively small specialized clinical models substantially outperform all in-context learning approaches, even when finetuned on limited annotated data. Further, we find that pretraining on clinical tokens allows for smaller, more parameter-efficient models that either match or outperform much larger language models trained on general text. We release the code and the models used under the PhysioNet Credentialed Health Data license and data use agreement.

Clinical AI development has traditionally followed a collaborative paradigm that depends on close interaction between clinicians and specialized AI teams. This paradigm imposes a practical challenge: clinicians must repeatedly communicate and refine their requirements with AI developers before those requirements can be translated into executable model development. This iterative process is time-consuming, and even after repeated discussion, misalignment may still exist because the two sides do not fully share each other's expertise. However, autonomous coding agents may change this paradigm, raising the possibility that clinicians could develop clinical AI models independently through natural-language interaction alone. In this study, we present such an autonomous prototype for clinician-driven clinical AI development. We evaluated the system on five clinical tasks spanning dermoscopic lesion classification, melanoma-versus-nevus triage, wrist-fracture detection (including a weakly supervised variant with only 5% bounding-box annotations), and debiased pneumothorax classification on chest radiographs. Across these settings, the system consistently developed models from clinician requests and achieved promising performance. Notably, in a debiased pneumothorax classification task on chest radiographs, where chest drains can act as a major confounder, the system successfully mitigated shortcut learning and nearly halved the model's reliance on chest drains. These findings provide proof of concept that autonomous coding agents may help shift clinical AI development toward a more clinician-driven paradigm, reducing the communication overhead and dependence on specialized AI developers. Although further validation and robustness assessment are needed, this study suggests a promising path toward making clinical AI development more accessible.

An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.

While large language models (LLMs) achieve near-perfect scores on medical licensing exams, these evaluations inadequately reflect the complexity and diversity of real-world clinical practice. We introduce MedHELM, an extensible evaluation framework for assessing LLM performance for medical tasks with three key contributions. First, a clinician-validated taxonomy spanning 5 categories, 22 subcategories, and 121 tasks developed with 29 clinicians. Second, a comprehensive benchmark suite comprising 35 benchmarks (17 existing, 18 newly formulated) providing complete coverage of all categories and subcategories in the taxonomy. Third, a systematic comparison of LLMs with improved evaluation methods (using an LLM-jury) and a cost-performance analysis. Evaluation of 9 frontier LLMs, using the 35 benchmarks, revealed significant performance variation. Advanced reasoning models (DeepSeek R1: 66% win-rate; o3-mini: 64% win-rate) demonstrated superior performance, though Claude 3.5 Sonnet achieved comparable results at 40% lower estimated computational cost. On a normalized accuracy scale (0-1), most models performed strongly in Clinical Note Generation (0.73-0.85) and Patient Communication & Education (0.78-0.83), moderately in Medical Research Assistance (0.65-0.75), and generally lower in Clinical Decision Support (0.56-0.72) and Administration & Workflow (0.53-0.63). Our LLM-jury evaluation method achieved good agreement with clinician ratings (ICC = 0.47), surpassing both average clinician-clinician agreement (ICC = 0.43) and automated baselines including ROUGE-L (0.36) and BERTScore-F1 (0.44). Claude 3.5 Sonnet achieved comparable performance to top models at lower estimated cost. These findings highlight the importance of real-world, task-specific evaluation for medical use of LLMs and provides an open source framework to enable this.

Developing clinical prediction models (e.g., mortality prediction) based on electronic health records (EHRs) typically relies on expert opinion for feature selection and adjusting observation window size. This burdens experts and creates a bottleneck in the development process. We propose Retrieval-Enhanced Medical prediction model (REMed) to address such challenges. REMed can essentially evaluate an unlimited number of clinical events, select the relevant ones, and make predictions. This approach effectively eliminates the need for manual feature selection and enables an unrestricted observation window. We verified these properties through experiments on 27 clinical tasks and two independent cohorts from publicly available EHR datasets, where REMed outperformed other contemporary architectures that aim to handle as many events as possible. Notably, we found that the preferences of REMed align closely with those of medical experts. We expect our approach to significantly expedite the development of EHR prediction models by minimizing clinicians' need for manual involvement.