Work done at Georgia Institute of Technology. Work done at Sutter Health.

The deployment of Large Language Models (LLMs) for structuring clinical data is critically hindered by their tendency to hallucinate facts and their inability to follow domain-specific rules. To address this, we introduce MedPAO, a novel agentic framework that ensures accuracy and verifiable reasoning by grounding its operation in established clinical protocols such as the ABCDEF protocol for CXR analysis. MedPAO decomposes the report structuring task into a transparent process managed by a Plan-Act-Observe (PAO) loop and specialized tools. This protocol-driven method provides a verifiable alternative to opaque, monolithic models. The efficacy of our approach is demonstrated through rigorous evaluation: MedPAO achieves an F1-score of 0.96 on the critical sub-task of concept categorization. Notably, expert radiologists and clinicians rated the final structured outputs with an average score of 4.52 out of 5, indicating a level of reliability that surpasses baseline approaches relying solely on LLM-based foundation models. The code is available at: https://github.com/MiRL-IITM/medpao-agent

Medical ontology graphs map external knowledge to medical codes in electronic health records via structured relationships. By leveraging domain-approved connections (e.g., parent-child), predictive models can generate richer medical concept representations by incorporating contextual information from related concepts. However, existing literature primarily focuses on incorporating domain knowledge from a single ontology system, or from multiple ontology systems (e.g., diseases, drugs, and procedures) in isolation, without integrating them into a unified learning structure. Consequently, concept representation learning often remains limited to intra-ontology relationships, overlooking cross-ontology connections. In this paper, we propose LINKO, a large language model (LLM)-augmented integrative ontology learning framework that leverages multiple ontology graphs simultaneously by enabling dual-axis knowledge propagation both within and across heterogeneous ontology systems to enhance medical concept representation learning. Specifically, LINKO first employs LLMs to provide a graph-retrieval-augmented initialization for ontology concept embedding, through an engineered prompt that includes concept descriptions, and is further augmented with ontology context. Second, our method jointly learns the medical concepts in diverse ontology graphs by performing knowledge propagation in two axes: (1) intra-ontology vertical propagation across hierarchical ontology levels and (2) inter-ontology horizontal propagation within every level in parallel. Last, through extensive experiments on two public datasets, we validate the superior performance of LINKO over state-of-the-art baselines. As a plug-in encoder compatible with existing EHR predictive models, LINKO further demonstrates enhanced robustness in scenarios involving limited data availability and rare disease prediction.

Despite significant advancements in adapting Large Language Models (LLMs) for radiology report generation (RRG), clinical adoption remains challenging due to difficulties in accurately mapping pathological and anatomical features to their corresponding text descriptions. Additionally, semantic agnostic feature extraction further hampers the generation of accurate diagnostic reports. To address these challenges, we introduce Medical Concept Aligned Radiology Report Generation (MCA-RG), a knowledge-driven framework that explicitly aligns visual features with distinct medical concepts to enhance the report generation process. MCA-RG utilizes two curated concept banks: a pathology bank containing lesion-related knowledge, and an anatomy bank with anatomical descriptions. The visual features are aligned with these medical concepts and undergo tailored enhancement. We further propose an anatomy-based contrastive learning procedure to improve the generalization of anatomical features, coupled with a matching loss for pathological features to prioritize clinically relevant regions. Additionally, a feature gating mechanism is employed to filter out low-quality concept features. Finally, the visual features are corresponding to individual medical concepts, and are leveraged to guide the report generation process. Experiments on two public benchmarks (MIMIC-CXR and CheXpert Plus) demonstrate that MCA-RG achieves superior performance, highlighting its effectiveness in radiology report generation.

Rare diseases affect an estimated 300-400 million people worldwide, yet individual conditions often remain poorly characterized and difficult to diagnose due to their low prevalence and limited clinician familiarity. While computational phenotyping algorithms show promise for automating rare disease detection, their development is hindered by the scarcity of labeled data and biases in existing label sources. Gold-standard labels from registries and expert chart reviews are highly accurate but constrained by selection bias and the cost of manual review. In contrast, labels derived from electronic health records (EHRs) cover a broader range of patients but can introduce substantial noise. To address these challenges, we propose a weakly supervised, transformer-based framework that combines a small set of gold-standard labels with a large volume of iteratively updated silver-standard labels derived from EHR data. This hybrid approach enables the training of a highly accurate and generalizable phenotyping model that scales rare disease detection beyond the scope of individual clinical expertise. Our method is initialized by learning embeddings of medical concepts based on their semantic meaning or co-occurrence patterns in EHRs, which are then refined and aggregated into patient-level representations via a multi-layer transformer architecture. Using two rare pulmonary diseases as a case study, we validate our model on EHR data from Boston Children's Hospital. Our framework demonstrates notable improvements in phenotype classification, identification of clinically meaningful subphenotypes through patient clustering, and prediction of disease progression compared to baseline methods. These results highlight the potential of our approach to enable scalable identification and stratification of rare disease patients for clinical care and research applications.

Automated chest radiographs interpretation requires both accurate disease classification and detailed radiology report generation, presenting a significant challenge in the clinical workflow. Current approaches either focus on classification accuracy at the expense of interpretability or generate detailed but potentially unreliable reports through image captioning techniques. In this study, we present RadAlign, a novel framework that combines the predictive accuracy of vision-language models (VLMs) with the reasoning capabilities of large language models (LLMs). Inspired by the radiologist's workflow, RadAlign first employs a specialized VLM to align visual features with key medical concepts, achieving superior disease classification with an average AUC of 0.885 across multiple diseases. These recognized medical conditions, represented as text-based concepts in the aligned visual-language space, are then used to prompt LLM-based report generation. Enhanced by a retrieval-augmented generation mechanism that grounds outputs in similar historical cases, RadAlign delivers superior report quality with a GREEN score of 0.678, outperforming state-of-the-art methods' 0.634. Our framework maintains strong clinical interpretability while reducing hallucinations, advancing automated medical imaging and report analysis through integrated predictive and generative AI. Code is available at https://github.com/difeigu/RadAlign.

Large language models (LLMs) have recently emerged as powerful tools, finding many medical applications. LLMs' ability to coalesce vast amounts of information from many sources to generate a response-a process similar to that of a human expert-has led many to see potential in deploying LLMs for clinical use. However, medicine is a setting where accurate reasoning is paramount. Many researchers are questioning the effectiveness of multiple choice question answering (MCQA) benchmarks, frequently used to test LLMs. Researchers and clinicians alike must have complete confidence in LLMs' abilities for them to be deployed in a medical setting. To address this need for understanding, we introduce a knowledge graph (KG)-based method to evaluate the biomedical reasoning abilities of LLMs. Essentially, we map how LLMs link medical concepts in order to better understand how they reason. We test GPT-4, Llama3-70b, and PalmyraMed-70b, a specialized medical model. We enlist a panel of medical students to review a total of 60 LLM-generated graphs and compare these graphs to BIOS, a large biomedical KG. We observe GPT-4 to perform best in our human review but worst in our ground truth comparison; vice-versa with PalmyraMed, the medical model. Our work provides a means of visualizing the medical reasoning pathways of LLMs so they can be implemented in clinical settings safely and effectively.

The adoption of digital systems in healthcare has resulted in the accumulation of vast electronic health records (EHRs), offering valuable data for machine learning methods to predict patient health outcomes. However, single-visit records of patients are often neglected in the training process due to the lack of annotations of next-visit information, thereby limiting the predictive and expressive power of machine learning models. In this paper, we present a novel framework MPLite that utilizes Multi-aspect Pretraining with Lab results through a light-weight neural network to enhance medical concept representation and predict future health outcomes of individuals. By incorporating both structured medical data and additional information from lab results, our approach fully leverages patient admission records. We design a pretraining module that predicts medical codes based on lab results, ensuring robust prediction by fusing multiple aspects of features. Our experimental evaluation using both MIMIC-III and MIMIC-IV datasets demonstrates improvements over existing models in diagnosis prediction and heart failure prediction tasks, achieving a higher weighted-F1 and recall with MPLite. This work reveals the potential of integrating diverse aspects of data to advance predictive modeling in healthcare.

Biomedical knowledge is uniquely complex and structured, requiring distinct reasoning strategies compared to other scientific disciplines like physics or chemistry. Biomedical scientists do not rely on a single approach to reasoning; instead, they use various strategies, including rule-based, prototype-based, and casebased reasoning. This diversity calls for flexible approaches that accommodate multiple reasoning strategies while leveraging in-domain knowledge. These triplets are then verified against a grounded KG to filter out erroneous information and ensure that only accurate, relevant data contribute to the final answer. Unlike RAG-based models, this multi-step process ensures robustness in reasoning while adapting to different models of medical reasoning. Medical reasoning involves making diagnostic and therapeutic decisions while also understanding the pathology of diseases (Patel et al., 2005). Unlike many other scientific domains, medical reasoning often relies on vertical reasoning, using analogy more heavily (Patel et al., 2005). For instance, in biomedical research, an organism such as Drosophila is used as an exemplar to model a disease mechanism, which is then applied by analogy to other organisms, including humans. In clinical practice, the patient serves as an exemplar, with generalizations drawn from many overlapping disease models and similar patient populations (Charles et al., 1997; Menche et al., 2015). In contrast, fields like physics and chemistry tend to be horizontally organized, where general principles are applied to specific cases (Blois, 1988). This distinction highlights the unique challenges that medical reasoning poses for question-answering (QA) models. While large language models (LLMs) (OpenAI, 2024; Dubey et al., 2024; Gao et al., 2024) have demonstrated strong general capabilities, their responses to medical questions often suffer from incorrect retrieval, missing key information, and misalignment with current scientific and medical knowledge.

Large language models (LLMs) have demonstrated significant potential in clinical decision support. Yet LLMs still suffer from hallucinations and lack fine-grained contextual medical knowledge, limiting their high-stake healthcare applications such as clinical diagnosis. Traditional retrieval-augmented generation (RAG) methods attempt to address these limitations but frequently retrieve sparse or irrelevant information, undermining prediction accuracy. We introduce KARE, a novel framework that integrates knowledge graph (KG) community-level retrieval with LLM reasoning to enhance healthcare predictions. KARE constructs a comprehensive multi-source KG by integrating biomedical databases, clinical literature, and LLM-generated insights, and organizes it using hierarchical graph community detection and summarization for precise and contextually relevant information retrieval. Our key innovations include: (1) a dense medical knowledge structuring approach enabling accurate retrieval of relevant information; (2) a dynamic knowledge retrieval mechanism that enriches patient contexts with focused, multi-faceted medical insights; and (3) a reasoning-enhanced prediction framework that leverages these enriched contexts to produce both accurate and interpretable clinical predictions. Extensive experiments demonstrate that KARE outperforms leading models by up to 10.8-15.0% on MIMIC-III and 12.6-12.7% on MIMIC-IV for mortality and readmission predictions. In addition to its impressive prediction accuracy, our framework leverages the reasoning capabilities of LLMs, enhancing the trustworthiness of clinical predictions.