Artificial intelligence holds great promise for expanding access to expert medical knowledge and reasoning. However, most evaluations of language models rely on static vignettes and multiple-choice questions that fail to reflect the complexity and nuance of evidence-based medicine in real-world settings. In clinical practice, physicians iteratively formulate and revise diagnostic hypotheses, adapting each subsequent question and test to what they've just learned, and weigh the evolving evidence before committing to a final diagnosis. To emulate this iterative process, we introduce the Sequential Diagnosis Benchmark, which transforms 304 diagnostically challenging New England Journal of Medicine clinicopathological conference (NEJM-CPC) cases into stepwise diagnostic encounters. A physician or AI begins with a short case abstract and must iteratively request additional details from a gatekeeper model that reveals findings only when explicitly queried. Performance is assessed not just by diagnostic accuracy but also by the cost of physician visits and tests performed. We also present the MAI Diagnostic Orchestrator (MAI-DxO), a model-agnostic orchestrator that simulates a panel of physicians, proposes likely differential diagnoses and strategically selects high-value, cost-effective tests. When paired with OpenAI's o3 model, MAI-DxO achieves 80% diagnostic accuracy--four times higher than the 20% average of generalist physicians. MAI-DxO also reduces diagnostic costs by 20% compared to physicians, and 70% compared to off-the-shelf o3. When configured for maximum accuracy, MAI-DxO achieves 85.5% accuracy. These performance gains with MAI-DxO generalize across models from the OpenAI, Gemini, Claude, Grok, DeepSeek, and Llama families. We highlight how AI systems, when guided to think iteratively and act judiciously, can advance diagnostic precision and cost-effectiveness in clinical care.

--We introduce PRISM (Predictive Reasoning in Sequential Medicine), a transformer-based architecture designed to model the sequential progression of clinical decision-making processes. Unlike traditional approaches that rely on isolated diagnostic classification, PRISM frames clinical trajectories as tokenized sequences of events -- including diagnostic tests, laboratory results, and diagnoses -- and learns to predict the most probable next steps in the patient diagnostic journey. Leveraging a large custom clinical vocabulary and an autoregressive training objective, PRISM demonstrates the ability to capture complex dependencies across longitudinal patient timelines. Experimental results show substantial improvements over random baselines in next-token prediction tasks, with generated sequences reflecting realistic diagnostic pathways, laboratory result progressions, and clinician ordering behaviors. These findings highlight the feasibility of applying generative language modeling techniques to structured medical event data, enabling applications in clinical decision support, simulation, and education. PRISM establishes a foundation for future advancements in sequence-based healthcare modeling, bridging the gap between machine learning architectures and real-world diagnostic reasoning. Accurate and timely clinical decision-making is fundamental to high-quality patient care.

Identifying the optimal diagnostic test and hardware system instance to infer reliability characteristics using field data is challenging, especially when constrained by fixed budgets and minimal maintenance cycles. Active Learning (AL) has shown promise for parameter inference with limited data and budget constraints in machine learning/deep learning tasks. However, AL for reliability model parameter inference remains underexplored for repairable hardware systems. It requires specialized AL Acquisition Functions (AFs) that consider hardware aging and the fact that a hardware system consists of multiple sub-systems, which may undergo only partial testing during a given diagnostic test. To address these challenges, we propose a relaxed Mixed Integer Semidefinite Program (MISDP) AL AF that incorporates Diagnostic Coverage (DC), Fisher Information Matrices (FIMs), and diagnostic testing budgets. Furthermore, we design empirical-based simulation experiments focusing on two diagnostic testing scenarios: (1) partial tests of a hardware system with overlapping subsystem coverage, and (2) partial tests where one diagnostic test fully subsumes the subsystem coverage of another. We evaluate our proposed approach against the most widely used AL AF in the literature (entropy), as well as several intuitive AL AFs tailored for reliability model parameter inference. Our proposed AF ranked best on average among the alternative AFs across 6,000 experimental configurations, with respect to Area Under the Curve (AUC) of the Absolute Total Expected Event Error (ATEER) and Mean Squared Error (MSE) curves, with statistical significance calculated at a 0.05 alpha level using a Friedman hypothesis test.

We present HiRMed (Hierarchical RAG-enhanced Medical Test Recommendation), a novel tree-structured recommendation system that leverages Retrieval-Augmented Generation (RAG) for intelligent medical test recommendations. Unlike traditional vector similarity-based approaches, our system performs medical reasoning at each tree node through a specialized RAG process. Starting from the root node with initial symptoms, the system conducts step-wise medical analysis to identify potential underlying conditions and their corresponding diagnostic requirements. At each level, instead of simple matching, our RAG-enhanced nodes analyze retrieved medical knowledge to understand symptom-disease relationships and determine the most appropriate diagnostic path. The system dynamically adjusts its recommendation strategy based on medical reasoning results, considering factors such as urgency levels and diagnostic uncertainty. Experimental results demonstrate that our approach achieves superior performance in terms of coverage rate, accuracy, and miss rate compared to conventional retrieval-based methods. This work represents a significant advance in medical test recommendation by introducing medical reasoning capabilities into the traditional tree-based retrieval structure.

Performance of large language models (LLMs) on medical tasks has traditionally been evaluated using multiple choice question benchmarks. However, such benchmarks are highly constrained, saturated with repeated impressive performance by LLMs, and have an unclear relationship to performance in real clinical scenarios. Clinical reasoning, the process by which physicians employ critical thinking to gather and synthesize clinical data to diagnose and manage medical problems, remains an attractive benchmark for model performance. Prior LLMs have shown promise in outperforming clinicians in routine and complex diagnostic scenarios. We sought to evaluate OpenAI's o1-preview model, a model developed to increase run-time via chain of thought processes prior to generating a response. We characterize the performance of o1-preview with five experiments including differential diagnosis generation, display of diagnostic reasoning, triage differential diagnosis, probabilistic reasoning, and management reasoning, adjudicated by physician experts with validated psychometrics. Our primary outcome was comparison of the o1-preview output to identical prior experiments that have historical human controls and benchmarks of previous LLMs. Significant improvements were observed with differential diagnosis generation and quality of diagnostic and management reasoning. No improvements were observed with probabilistic reasoning or triage differential diagnosis. This study highlights o1-preview's ability to perform strongly on tasks that require complex critical thinking such as diagnosis and management while its performance on probabilistic reasoning tasks was similar to past models. New robust benchmarks and scalable evaluation of LLM capabilities compared to human physicians are needed along with trials evaluating AI in real clinical settings.

Background: Artificial intelligence language models have shown promise in various applications, including assisting with clinical decision-making as demonstrated by strong performance of large language models on medical licensure exams. However, their ability to solve complex, open-ended cases, which may be representative of clinical practice, remains unexplored. Methods: In this study, the accuracy of large language AI models GPT4 and GPT3.5 in diagnosing complex clinical cases was investigated using published Case Records of the Massachusetts General Hospital. A total of 50 cases requiring a diagnosis and diagnostic test published from January 1, 2022 to April 16, 2022 were identified. For each case, models were given a prompt requesting the top three specific diagnoses and associated diagnostic tests, followed by case text, labs, and figure legends. Model outputs were assessed in comparison to the final clinical diagnosis and whether the model-predicted test would result in a correct diagnosis. Results: GPT4 and GPT3.5 accurately provided the correct diagnosis in 26% and 22% of cases in one attempt, and 46% and 42% within three attempts, respectively. GPT4 and GPT3.5 provided a correct essential diagnostic test in 28% and 24% of cases in one attempt, and 44% and 50% within three attempts, respectively. No significant differences were found between the two models, and multiple trials with identical prompts using the GPT3.5 model provided similar results. Conclusions: In summary, these models demonstrate potential usefulness in generating differential diagnoses but remain limited in their ability to provide a single unifying diagnosis in complex, open-ended cases. Future research should focus on evaluating model performance in larger datasets of open-ended clinical challenges and exploring potential human-AI collaboration strategies to enhance clinical decision-making.

The application of natural language processing (NLP) to cancer pathology reports has been focused on detecting cancer cases, largely ignoring precancerous cases. Improving the characterization of precancerous adenomas assists in developing diagnostic tests for early cancer detection and prevention, especially for colorectal cancer (CRC). Here we developed transformer-based deep neural network NLP models to perform the CRC phenotyping, with the goal of extracting precancerous lesion attributes and distinguishing cancer and precancerous cases. We achieved 0.914 macro-F1 scores for classifying patients into negative, non-advanced adenoma, advanced adenoma and CRC. We further improved the performance to 0.923 using an ensemble of classifiers for cancer status classification and lesion size named entity recognition (NER).

Fox News Flash top headlines are here. Check out what's clicking on Foxnews.com. The United States Food and Drug Administration (FDA) wants the public to be aware of counterfeit at-home over-the-counter (OTC) COVID-19 diagnostic tests circulating in the United States, according to a recent press release. "Counterfeit COVID-19 tests are tests that are not authorized, cleared, or approved by the FDA for distribution or use in the United States, but are made to look like authorized tests so the users will think they are the real, FDA-authorized test," the administration said. "The performance of these counterfeit tests has not been adequately established and the FDA is concerned about the risk of false results when people use these unauthorized tests." The at home diagnostic kits are primarily antigen tests.

Background Machine learning (ML) has captured the attention of many clinicians who may not have formal training in this area but are otherwise increasingly exposed to ML literature that may be relevant to their clinical specialties. ML papers that follow an outcomes-based research format can be assessed using clinical research appraisal frameworks such as PICO (Population, Intervention, Comparison, Outcome). However, the PICO frameworks strain when applied to ML papers that create new ML models, which are akin to diagnostic tests. There is a need for a new framework to help assess such papers. Objective We propose a new framework to help clinicians systematically read and evaluate medical ML papers whose aim is to create a new ML model: ML-PICO (Machine Learning, Population, Identification, Crosscheck, Outcomes).

A new COVID-19 diagnostic low-cost test now allows users to self-test for variants at home using a sample of their saliva. According to experts, the test could cost as low as $2. Scientists from Wyss Institute for Biologically Inspired Engineering at Harvard University and the Massachusetts Institute of Technology (MIT), and several Boston-area hospitals recently created the Minimally Instrumented SHERLOCK (miSHERLOCK) diagnostic test that gives users their results within 55 minutes. The CRISPR-based diagnostic test was designed to be able to distinguish between three different COVID-19 variants, including the highly contagious Delta strain. The test will only need a sample of the user's saliva. The results will then be sent to an accompanying smartphone app within an hour.