Thomas A. Buckley

Peter G. Brodeur, Thomas A. Buckley, Zahir Kanjee et al.

A seminal paper published by Ledley and Lusted in 1959 introduced complex clinical diagnostic reasoning cases as the gold standard for the evaluation of expert medical computing systems, a standard that has held ever since. Here, we report the results of a physician evaluation of a large language model (LLM) on challenging clinical cases against a baseline of hundreds of physicians. We conduct five experiments to measure clinical reasoning across differential diagnosis generation, display of diagnostic reasoning, triage differential diagnosis, probabilistic reasoning, and management reasoning, all adjudicated by physician experts with validated psychometrics. We then report a real-world study comparing human expert and AI second opinions in randomly-selected patients in the emergency room of a major tertiary academic medical center in Boston, MA. We compared LLMs and board-certified physicians at three predefined diagnostic touchpoints: triage in the emergency room, initial evaluation by a physician, and admission to the hospital or intensive care unit. In all experiments--both vignettes and emergency room second opinions--the LLM displayed superhuman diagnostic and reasoning abilities, as well as continued improvement from prior generations of AI clinical decision support. Our study suggests that LLMs have achieved superhuman performance on general medical diagnostic and management reasoning, fulfilling the vision put forth by Ledley and Lusted, and motivating the urgent need for prospective trials.

Thomas A. Buckley, Kian R. Weihrauch, Katherine Latham et al.

Despite being widely used to support clinical care, general-purpose large multimodal models (LMMs) have generally shown poor or inconclusive performance in medical image interpretation, particularly in pathology, where gigapixel images are used. However, prior studies have used either low-resolution thumbnails or random patches, which likely underestimated model performance. Here, we ask whether LMMs can be adapted to reason coherently and accurately in the evaluation of such images. In this study, we introduce Gigapixel Image Agent for Navigating Tissue (GIANT), the first framework that allows LMMs to iteratively navigate whole-slide images (WSIs) like a pathologist. Accompanying GIANT, we release MultiPathQA, a new benchmark, which comprises 934 WSI-level questions, encompassing five clinically-relevant tasks ranging from cancer diagnosis to open-ended reasoning. MultiPathQA also includes 128 questions, authored by two professional pathologists, requiring direct slide interpretation. Using MultiPathQA, we show that our simple agentic system substantially outperforms conventional patch- and thumbnail-based baselines, approaching or surpassing the performance of specialized models trained on millions of images. For example, on pathologist-authored questions, GPT-5 with GIANT achieves 62.5% accuracy, outperforming specialist pathology models such as TITAN (43.8%) and SlideChat (37.5%). Our findings reveal the strengths and limitations of current foundation models and ground future development of LMMs for expert reasoning in pathology.

Thomas A. Buckley, Riccardo Conci, Peter G. Brodeur et al.

BACKGROUND: For over a century, the New England Journal of Medicine Clinicopathological Conferences (CPCs) have tested the reasoning of expert physicians and, recently, artificial intelligence (AI). However, prior AI evaluations have focused on final diagnoses without addressing the multifaceted reasoning and presentation skills required of expert discussants. METHODS: Using 7102 CPCs (1923-2025) and 1021 Image Challenges (2006-2025), we conducted extensive physician annotation and automated processing to create CPC-Bench, a physician-validated benchmark spanning 10 text-based and multimodal tasks, against which we evaluated leading large language models (LLMs). Then, we developed "Dr. CaBot," an AI discussant designed to produce written and slide-based video presentations using only the case presentation, modeling the role of the human expert in these cases. RESULTS: When challenged with 377 contemporary CPCs, o3 (OpenAI) ranked the final diagnosis first in 60% of cases and within the top ten in 84% of cases, outperforming a 20-physician baseline; next-test selection accuracy reached 98%. Event-level physician annotations quantified AI diagnostic accuracy per unit of information. Performance was lower on literature search and image tasks; o3 and Gemini 2.5 Pro (Google) achieved 67% accuracy on image challenges. In blinded comparisons of CaBot vs. human expert-generated text, physicians misclassified the source of the differential in 46 of 62 (74%) of trials, and scored CaBot more favorably across quality dimensions. To promote research, we are releasing CaBot and CPC-Bench. CONCLUSIONS: LLMs exceed physician performance on complex text-based differential diagnosis and convincingly emulate expert medical presentations, but image interpretation and literature retrieval remain weaker. CPC-Bench and CaBot may enable transparent and continued tracking of progress in medical AI.