Rare diseases, including Inborn Errors of Metabolism (IEM), pose significant diagnostic challenges. Case reports serve as key but computationally underutilized resources to inform diagnosis. Clinical dense information extraction refers to organizing medical information into structured predefined categories. Large Language Models (LLMs) may enable scalable information extraction from case reports but are rarely evaluated for this task. We introduce CaseReportBench, an expert-annotated dataset for dense information extraction of case reports, focusing on IEMs. Using this dataset, we assess various models and prompting strategies, introducing novel approaches such as category-specific prompting and subheading-filtered data integration. Zero-shot chain-of-thought prompting offers little advantage over standard zero-shot prompting. Category-specific prompting improves alignment with the benchmark. The open-source model Qwen2.5-7B outperforms GPT-4o for this task. Our clinician evaluations show that LLMs can extract clinically relevant details from case reports, supporting rare disease diagnosis and management. We also highlight areas for improvement, such as LLMs' limitations in recogni
Clinical case reports and discharge summaries may be the most complete and accurate summarization of patient encounters, yet they are finalized, i.e., timestamped after the encounter. Complementary structured data streams become available sooner but suffer from incompleteness. To train models and algorithms on more complete and temporally fine-grained data, we construct a pipeline to phenotype, extract, and annotate time-localized findings within case reports using large language models. We apply our pipeline to generate an open-access textual time series corpus for Sepsis-3 comprising 2,139 case reports from the PubMed-Open Access (PMOA) Subset. To validate our system, we apply it to PMOA and timeline annotations from i2b2/MIMIC-IV and compare the results to physician-expert annotations. We show high recovery rates of clinical findings (event match rates: GPT-5--0.93, Llama 3.3 70B Instruct--0.76) and strong temporal ordering (concordance: GPT-5--0.965, Llama 3.3 70B Instruct--0.908). Our work characterizes the ability of LLMs to time-localize clinical findings in text, illustrating the limitations of LLM use for temporal reconstruction and providing several potential avenues of i
Doctors and patients alike increasingly use Large Language Models (LLMs) to diagnose clinical cases. However, unlike domains such as math or coding, where correctness can be objectively defined by the final answer, medical diagnosis requires both the outcome and the reasoning process to be accurate. Currently, widely used medical benchmarks like MedQA and MMLU assess only accuracy in the final answer, overlooking the quality and faithfulness of the clinical reasoning process. To address this limitation, we introduce MedCaseReasoning, the first open-access dataset for evaluating LLMs on their ability to align with clinician-authored diagnostic reasoning. The dataset includes 14,489 diagnostic question-and-answer cases, each paired with detailed reasoning statements derived from open-access medical case reports. We evaluate state-of-the-art reasoning LLMs on MedCaseReasoning and find significant shortcomings in their diagnoses and reasoning: for instance, the top-performing open-source model, DeepSeek-R1, achieves only 48% 10-shot diagnostic accuracy and mentions only 64% of the clinician reasoning statements (recall). However, we demonstrate that fine-tuning LLMs on the reasoning tr
We present a new dataset for machine comprehension in the medical domain. Our dataset uses clinical case reports with around 100,000 gap-filling queries about these cases. We apply several baselines and state-of-the-art neural readers to the dataset, and observe a considerable gap in performance (20% F1) between the best human and machine readers. We analyze the skills required for successful answering and show how reader performance varies depending on the applicable skills. We find that inferences using domain knowledge and object tracking are the most frequently required skills, and that recognizing omitted information and spatio-temporal reasoning are the most difficult for the machines.
We introduce M-CARE (Model Clinical Assessment and Reporting for Evaluation), a clinical case report framework for AI model behavioral disorders adapted from human medicine. M-CARE provides a 13-section report format, a 4-axis diagnostic assessment system, and a nosological classification of AI behavioral conditions. We present 20 cases from three source categories: field observations of deployed agents (8), controlled experiments across three platforms (8), and published sources (4). Cases are organized into five categories: RLHF Performance Artifacts, Shell-Core Override Pathology, Context & Memory Conditions, Core Identity & Plasticity, and Stress, Methodology, & Boundary Conditions. As a featured case, we present Shell-Induced Behavioral Override (SIBO) -- a controlled experiment showing that Shell instructions categorically override a model's default cooperative behavior. SIBO was validated across five game domains (Trust Game, Poker, Avalon, Codenames, Chess), revealing a domain-dependent spectrum (SIBO Index: 0.75 to 0.10) that varies with action space complexity, Core domain expertise, and temporal directness. M-CARE is extensible: new cases and categories integ
Purpose: We investigated the utilization of privacy-preserving, locally-deployed, open-source Large Language Models (LLMs) to extract diagnostic information from free-text cardiovascular magnetic resonance (CMR) reports. Materials and Methods: We evaluated nine open-source LLMs on their ability to identify diagnoses and classify patients into various cardiac diagnostic categories based on descriptive findings in 109 clinical CMR reports. Performance was quantified using standard classification metrics including accuracy, precision, recall, and F1 score. We also employed confusion matrices to examine patterns of misclassification across models. Results: Most open-source LLMs demonstrated exceptional performance in classifying reports into different diagnostic categories. Google's Gemma2 model achieved the highest average F1 score of 0.98, followed by Qwen2.5:32B and DeepseekR1-32B with F1 scores of 0.96 and 0.95, respectively. All other evaluated models attained average scores above 0.93, with Mistral and DeepseekR1-7B being the only exceptions. The top four LLMs outperformed our board-certified cardiologist (F1 score of 0.94) across all evaluation metrics in analyzing CMR reports.
Breast cancer is a major global health concern, and mammography screening plays a central role in early detection. The large volume of screening examinations creates a substantial workload for radiologists, making accurate and consistent report generation a critical clinical challenge. Existing automated mammography report generation methods primarily focus on direct visual-to-text mapping, while overlooking the structured clinical reasoning process followed by radiologists in real-world practice. To address this limitation, we propose MammoRG, a mammography report generation framework that explicitly simulates the clinical reporting workflow by following the BI-RADS guideline and incorporating prior clinical knowledge to produce diagnostic reports. Specifically, MammoRG adopts a two-stage training framework. In the first stage, the model learns to integrate clinically relevant prior knowledge from a patient's four-view mammograms through classification-based supervision. In the second stage, a terminology-aware supervised fine-tuning strategy is introduced to model mammography-specific clinical terms as atomic semantic units, enabling the generation of high-quality reports with im
Clinical decision-making relies on the integrated analysis of medical images and the associated clinical reports. While Vision-Language Models (VLMs) can offer a unified framework for such tasks, they can exhibit strong biases toward one modality, frequently overlooking critical visual cues in favor of textual information. In this work, we introduce Selective Modality Shifting (SMS), a perturbation-based approach to quantify a model's reliance on each modality in binary classification tasks. By systematically swapping images or text between samples with opposing labels, we expose modality-specific biases. We assess six open-source VLMs-four generalist models and two fine-tuned for medical data-on two medical imaging datasets with distinct modalities: MIMIC-CXR (chest X-ray) and FairVLMed (scanning laser ophthalmoscopy). By assessing model performance and the calibration of every model in both unperturbed and perturbed settings, we reveal a marked dependency on text input, which persists despite the presence of complementary visual information. We also perform a qualitative attention-based analysis which further confirms that image content is often overshadowed by text details. Our
The competency of any intelligent agent is bounded by its formal account of the world in which it operates. Clinical AI lacks such an account. Existing frameworks address evaluation, regulation, or system design in isolation, without a shared model of the clinical world to connect them. We introduce the Clinical World Model, a framework that formalizes care as a tripartite interaction among Patient, Provider, and Ecosystem. To formalize how any agent, whether human or artificial, transforms information into clinical action, we develop parallel decision-making architectures for providers, patients, and AI agents, grounded in validated principles of clinical cognition. The Clinical AI Skill-Mix operationalizes competency through eight dimensions. Five define the clinical competency space (condition, phase, care setting, provider role, and task) and three specify how AI engages human reasoning (assigned authority, agent facing, and anchoring layer). The combinatorial product of these dimensions yields a space of billions of distinct competency coordinates. A central structural implication is that validation within one coordinate provides minimal evidence for performance in another, re
Case Report Forms (CRFs) are largely used in medical research as they ensure accuracy, reliability, and validity of results in clinical studies. However, publicly available, wellannotated CRF datasets are scarce, limiting the development of CRF slot filling systems able to fill in a CRF from clinical notes. To mitigate the scarcity of CRF datasets, we propose to take advantage of available datasets annotated for information extraction tasks and to convert them into structured CRFs. We present a semi-automatic conversion methodology, which has been applied to the E3C dataset in two languages (English and Italian), resulting in a new, high-quality dataset for CRF slot filling. Through several experiments on the created dataset, we report that slot filling achieves 59.7% for Italian and 67.3% for English on a closed Large Language Models (zero-shot) and worse performances on three families of open-source models, showing that filling CRFs is challenging even for recent state-of-the-art LLMs. We release the datest at https://huggingface.co/collections/NLP-FBK/e3c-to-crf-67b9844065460cbe42f80166
The increasing availability of unstructured clinical narratives in electronic health records (EHRs) has created new opportunities for automated disease characterization, cohort identification, and clinical decision support. However, modeling long, domain-specific clinical text remains challenging due to limited labeled data, severe class imbalance, and the high computational cost of adapting large pretrained language models. This study presents a GPT-based architecture for clinical text classification that adapts a pretrained decoder-only Transformer using a selective fine-tuning strategy. Rather than updating all model parameters, the majority of the GPT-2 backbone is frozen, and training is restricted to the final Transformer block, the final layer normalization, and a lightweight classification head. This approach substantially reduces the number of trainable parameters while preserving the representational capacity required to model complex clinical language. The proposed method is evaluated on radiology reports from the MIMIC-IV-Note dataset using uncertainty-aware CheXpert-style labels derived directly from report text. Experiments cover multiple problem formulations, includi
Medical report generation aims to automatically produce radiology-style reports from medical images, supporting efficient and accurate clinical decision-making.However, existing approaches predominately rely on token-level likelihood training, which favors local lexical matching and leaves clinical correctness under-specified in the training objective. This behavior can be attributed to token-level likelihood optimization, which rewards surface-form agreement and therefore fails to directly encode constraints on medically accurate findings. To address this objective mismatch, we introduce a semantic-driven reinforcement learning (SRL) framework for medical report generation, named MRG-R1, which directly optimizes report-level clinical correctness rather than token-level likelihood. The key module is a clinically grounded report-level reward function, which reinforces semantic agreement in clinically relevant findings between generated and reference reports, thereby enabling learning signals that explicitly constrain medical correctness beyond surface linguistic alignment. Our evaluations show that the proposed framework improves the accuracy and coverage of clinically relevant find
We introduce Clinical ModernBERT, a transformer based encoder pretrained on large scale biomedical literature, clinical notes, and medical ontologies, incorporating PubMed abstracts, MIMIC IV clinical data, and medical codes with their textual descriptions. Building on ModernBERT the current state of the art natural language text encoder featuring architectural upgrades such as rotary positional embeddings (RoPE), Flash Attention, and extended context length up to 8,192 tokens our model adapts these innovations specifically for biomedical and clinical domains. Clinical ModernBERT excels at producing semantically rich representations tailored for long context tasks. We validate this both by analyzing its pretrained weights and through empirical evaluation on a comprehensive suite of clinical NLP benchmarks.
The paper presents an approach for the recognition of toxic habits named entities in Spanish clinical texts. The approach was developed for the ToxHabits Shared Task. Our team participated in subtask 1, which aims to detect substance use and abuse mentions in clinical case reports and classify them in four categories (Tobacco, Alcohol, Cannabis, and Drug). We explored various methods of utilizing LLMs for the task, including zero-shot, few-shot, and prompt optimization, and found that GPT-4.1's few-shot prompting performed the best in our experiments. Our method achieved an F1 score of 0.65 on the test set, demonstrating a promising result for recognizing named entities in languages other than English.
Empiric antibiotic prescribing in high-risk clinical contexts often requires decision making under conditions of incomplete information, where inappropriate coverage or unjustified escalation may compromise safety and antimicrobial stewardship. While clinical decision-support systems have been proposed to assist in this process, many approaches lack explicit governance and evaluation mechanisms defining scope, abstention conditions, recommendation permissibility, and expected system behavior. This work specifies a governance and evaluation framework for deterministic clinical decision-support systems operating under explicitly constrained scope. Deterministic behavior is adopted to ensure that identical inputs yield identical outputs, supporting transparency, auditability, and conservative decision support in high-risk prescribing contexts. The framework treats governance as a first-class design component, separating clinical decision logic from rule-based mechanisms that determine whether a recommendation may be issued. Explicit abstention, deterministic stewardship constraints, and exclusion rules are formalized as core constructs. The framework defines an evaluation methodology
Introduction: Semantic search, which retrieves documents based on conceptual similarity rather than keyword matching, offers substantial advantages for retrieval of clinical information. However, deploying semantic search across entire health systems, comprising hundreds of millions of clinical notes, presents formidable engineering, cost, and governance challenges that have prevented adoption. Methods: We deployed a semantic search system at a large children's hospital indexing 166 million clinical notes (484 million vectors) from 1.68 million patients. The system uses instruction-tuned qwen3-embedding-0.6B embeddings, stores vectors in a managed database with storage-optimized indexing, maintains full-text metadata in a low-latency key-value store, and operates within a HIPAA-compliant governance framework. We evaluated the system through three experiments: optimization of embedding model and chunking strategy using a physician-authored benchmark dataset, characterization of full-scale performance (cost, latency, retrieval quality), and clinical utility assessment via comparison of chart abstraction efficiency across three tasks. Results: The system delivers sub-second query late
We introduce SoftTiger, a clinical large language model (CLaM) designed as a foundation model for healthcare workflows. The narrative and unstructured nature of clinical notes is a major obstacle for healthcare intelligentization. We address a critical problem of structuring clinical notes into clinical data, according to international interoperability standards. We collect and annotate data for three subtasks, namely, international patient summary, clinical impression and medical encounter. We then supervised fine-tuned a state-of-the-art LLM using public and credentialed clinical data. The training is orchestrated in a way that the target model can first support basic clinical tasks such as abbreviation expansion and temporal information extraction, and then learn to perform more complex downstream clinical tasks. Moreover, we address several modeling challenges in the healthcare context, e.g., extra long context window. Our blind pairwise evaluation shows that SoftTiger outperforms other popular open-source models and GPT-3.5, comparable to Gemini-pro, with a mild gap from GPT-4. We believe that LLMs may become a step-stone towards healthcare digitalization and democratization.
Developing AI models that are useful in clinical practice, requires efficient collaboration between clinicians and AI developers. This poses 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. Coding agents may help close this gap. They can write and refine code on their own, and they carry working knowledge of both medicine and AI to understand commands formulated by both medical experts and developers. We present a prototype that lets clinicians drive AI development directly. A clinician describes the task in plain language, and the system turns the description into a working pipeline, refines it through repeated experiments together with the clinician, and returns a model that meets the stated clinical objective. Across five clinical tasks, the system reliably produces models that matched the clinician's request and reached competitive performance. Most notably, on chest rad
Digital Twins hold great potential to personalize clinical patient care, provided the concept is translated to meet specific requirements emerging from established clinical workflows. We present a general and unspecialized Digital Twin design combining knowledge graphs and ensemble learning to reflect the entire patient's clinical journey and assist clinicians in their decision-making. Such a design is predictive, modular, evolving, informed, interpretable and explainable, thus opening broad clinical applications.
We evaluate the impact of large language model-based clinical decision support in live care. In partnership with Penda Health, a network of primary care clinics in Nairobi, Kenya, we studied AI Consult, a tool that serves as a safety net for clinicians by identifying potential documentation and clinical decision-making errors. AI Consult integrates into clinician workflows, activating only when needed and preserving clinician autonomy. We conducted a quality improvement study, comparing outcomes for 39,849 patient visits performed by clinicians with or without access to AI Consult across 15 clinics. Visits were rated by independent physicians to identify clinical errors. Clinicians with access to AI Consult made relatively fewer errors: 16% fewer diagnostic errors and 13% fewer treatment errors. In absolute terms, the introduction of AI Consult would avert diagnostic errors in 22,000 visits and treatment errors in 29,000 visits annually at Penda alone. In a survey of clinicians with AI Consult, all clinicians said that AI Consult improved the quality of care they delivered, with 75% saying the effect was "substantial". These results required a clinical workflow-aligned AI Consult i