AI Morbidity and Mortality: A Framework for Clinical AI Failure Review

Clinical artificial intelligence is increasingly embedded in real-world care, yet existing safety mechanisms are poorly suited to reconstructing and learning from individual AI-related errors and near-misses. Aggregate model monitoring can identify performance changes, and traditional patient safety reporting can capture adverse events, but neither is designed to explain how risk emerges across the interaction among AI systems, clinicians, workflows, and institutional controls. We propose AI Morbidity and Mortality (AI M&M), a structured, blameless framework for case-based review of clinical AI failures. The framework combines standardized case intake, evidence preservation and investigator-level reconstruction, tool-in-loop attribution, and corrective-action tracking. Each event is classified across four linked dimensions: Trigger - Mechanism - Clinical Pathway - Corrective Action, separating the condition that exposed a vulnerability from the process that produced risk, its consequence for care, and the remediation assigned. We demonstrate the framework using five illustrative outpatient medication and clinical decision-support cases; two clinician reviewers independently applied all four classification axes and reached agreement across all 20 axis-level classifications. AI M&M is intended to complement, rather than replace, model monitoring, patient safety reporting, and regulatory oversight by converting individual AI-in-workflow failures into actionable institutional learning. Prospective evaluation across institutions, AI systems, and clinical settings is needed.

When Patients Cut In: Extending Clinical Conversational AI Safety to Interruptions

Clinical voice agents are now deployed in routine care, where real patients do not wait their turn: they interrupt. These systems typically use a cascaded architecture (speech-to-text -> LLM -> text-to-speech), so when a patient cuts the agent off mid-utterance, clinically required content can be lost even when the model handles cooperative transcripts well. Yet clinical conversational-AI benchmarks almost universally assume patients wait for the agent to finish, missing interruption-induced loss of required content. We present a transcript-based evaluation of interruption recovery, adapting conversation-analytic overlap categories into three operational types (recognitional, competitive, transitional sub-unit) and testing four deployment-oriented, non-reasoning LLM configurations across four cells spanning history-taking (information gathering) and FAQ (information provision), scored on whether the agent preserves the clinically required content. In the gathering cells, target-question failure varied across models; in the provision cells, where arms are directly comparable, failure rose for every model. Rankings differ across cells, and competitive FAQ interruption produced 30/30 provision-coverage failures for all four models (Wilson 95% CI: 88.6-100.0%; baseline 0/30 for three, 4/30 for Llama). A brief apology marker ("sorry to interrupt") shifts recovery by tens of percentage points, inconsistently across models, and for one it reduces recovery. Interruption robustness therefore cannot be a single score: evaluation must be content-grounded, reported per cell, and matched to the deployment's interruption profile.

Volumetric Radiology AI in the Era of Multimodal Large Language Models

Advances in multimodal large language models (MLLMs) are extending radiological artificial intelligence (AI) beyond task-specific image analysis toward multimodal understanding and reasoning. Volumetric radiology, however, presents a fundamental representational mismatch: clinical interpretation often requires full-volume spatial context and acquisition-dependent quantitative information, whereas current MLLMs are commonly conditioned on selected two-dimensional (2D) images, compressed visual representations, or report-derived text. Reliable volumetric radiology AI therefore requires representations that preserve task-relevant three-dimensional (3D) information and systems that can access, verify, and integrate this information across clinical workflows. In this Review, we examine more than 200 publications through July 2026. We organize the literature around volumetric representation and multimodal understanding at the model level, agentic orchestration at the system level, and their links to clinical applications and evaluation. We review volumetric foundation models, language alignment and compression strategies, and agentic systems that extend MLLMs through planning, tools, memory, and workflow interaction. We distinguish settings in which selected 2D views or report-mediated reasoning may suffice from those that warrant native volumetric modeling. We also introduce a Claim-Design-Validation framework to assess whether technical, workflow, and clinical claims are matched by appropriate design and validation. Across the literature, native volumetric modeling and agentic capabilities depend on the spatial, quantitative, contextual, and workflow requirements of the intended task. Clinical credibility requires faithful volumetric representation, traceable system behavior, claim-aligned validation, and clearly defined human oversight in realistic workflows.

Towards Expert-level Medical AI for Real-time Video Consultations

Audio-visual interaction is the standard for patient-physician consultations, enabling natural communication and effective assessment of illness through non-verbal cues. While text-based AI has shown promise, it discards essential perceptual dimensions and limits patients who cannot articulate symptoms in writing. Early efforts to extend medical AI to audio-visual interaction have demonstrated feasibility but not reached clinician-level performance. Here, we provide the first demonstration of expert-level AI in real-time clinical video consultations using AMIE (Articulate Medical Intelligence Explorer) in a video configuration. AMIE (Video) is a Gemini-based multi-agent system integrating low-latency dialogue, clinical reasoning, and real-time audio-visual perception. To guide development, we established a taxonomy and automated evaluations for clinical audio-visual cues in telehealth settings. In a randomized Objective Structured Clinical Examination (OSCE) study with 30 primary care physicians (PCPs), 15 patient actors and 100 clinical scenarios, we compared AMIE (Video), its text-only counterpart AMIE (Text), and PCPs consulting via video. Clinical evaluators rated AMIE (Video) on par or better than PCPs in history-taking, diagnosis, management, and physical observation and examination. Patient actors preferred AMIE's approach to assessing and explaining conditions, while PCPs were preferred for rapport and partnership building. In modality ablation, patient actors preferred AMIE (Video)'s interface over text chat for communicative effectiveness, convenience, and feeling understood. Limitations remain in fine anatomical precision, subtle affective nuances, and high-frequency movements. While further research is needed before real-world translation, these results mark an important milestone toward AI systems capable of augmenting care across the sensory complexity of clinical practice.

Tracing the Heart: An Evidence-Linked Pipeline for Heart-Failure Feature Engineering

Electronic health record (EHR) feature engineering is a major bottleneck in clinical research and AI, accounting for 39-45% of data scientists' workload. This is especially pronounced in heart failure, which affects an estimated 6.7 million U.S. adults and requires integrating fragmented EHR data with disease-specific, guideline-based clinical reasoning. Existing rule-based and large language model (LLM)-based approaches offer only partial automation with limited maintainability and evidence traceability. We developed the Nimblemind Multi-Agent System (nMAS), an evidence-linked, rubric-grounded pipeline for automated heart-failure feature engineering, and evaluated it on 500 dummy patient records from nine EHR source tables. nMAS generated 132 structured and 70 rubric-scored aggregated features, verified for structural integrity, rubric compliance, and provenance, and audited by a restricted LLM. Adding the aggregated features improved held-out AUROC from 0.895 to 0.963 for HFrEF and 0.870 to 0.910 for HFpEF phenotyping, and an independent LLM-based rubric assessment of evidence support and methodological soundness scored the features at 81.5% of maximum points. These results demonstrate the feasibility of automated, auditable feature engineering for complex cardiovascular EHR data, though evaluation was limited to a single-institution cohort and external validation is needed.

Rethinking Artificial Intelligence in Medical Imaging: Assumptions, Reality, and Reframing

Medical imaging has served as primary proving ground for clinical artificial intelligence (AI), yet a decade of intense research has not translated into proportionate bedside impact. We argue that this gap is not primarily a product of insufficient algorithmic performance, inadequate regulation, or limited explainability. Rather, it reflects a structural misalignment, between how AI systems are designed and evaluated, and how clinical decisions are made. This Perspective identifies six interconnected dimensions of this misalignment: the dominance of pixel-only models in a multimodal clinical world; the erosion of physician trust through opaque and inflexible systems; the unfulfilled promise of foundation models in data-sparse medical domains; the persistent bottleneck of non-shareable, under-curated datasets; the gap between validated algorithms and deployable clinical platforms; and the failure of prediction-centric AI to generate actionable clinical guidance. For each dimension, we reframe the problem and propose a path forward, culminating in a vision of agentic, physician-aligned AI that extends, rather than replaces, clinical judgment.

MamaBench: Benchmarking LLM Robustness in Maternal and Child Health Diagnosis through Counterfactual Clinical Perturbation

Large language models achieve strong scores on medical benchmarks, yet these benchmarks evaluate each question in isolation, providing no measure of whether a system can distinguish clinically similar presentations requiring different interventions. We introduce MamaBench, the first counterfactual benchmark for maternal and paediatric AI: 434 expert-authored clinical narratives in 217 pairs across 371 pathologies, evaluated via the Bias Trap Rate (BTR), the conditional probability that a model fails the counterfactual given success on the base case. We propose Evidence-Anchored RAG (EA-RAG), a three-stage retrieval method that replaces aggregate similarity with an evidence coverage objective through clinical parameter extraction, coverage auditing, and contrastive sub-queries. Across eight configurations of four frontier LLMs, base accuracy overstates robust accuracy by 16-28 percentage points in every model. EA-RAG achieves 20.3% BTR and 65.0% robust accuracy on Claude Sonnet 4.6, a 5.5 percentage point BTR reduction without degrading base accuracy. The residual 20% BTR confirms that counterfactual robustness in clinical AI remains an open challenge. Keywords: counterfactual evaluation, clinical AI, maternal healthcare, retrieval-augmented generation, diagnostic robustness

Evidence-Grounded AI for Musculoskeletal Care

Musculoskeletal diseases are among the leading causes of disability worldwide and create the greatest global need for rehabilitation. Because recovery, remodelling and degeneration often unfold over months to years, musculoskeletal care requires longitudinal management that repeatedly integrates evolving patient evidence, external medical knowledge and stage-specific functional goals. In routine practice, this evidence is fragmented across visits, departments and hospital systems, limiting individualized, evidence-based care. Here we report OrthoPilot, a clinical artificial intelligence system powered by a large language model that integrates hospital data streams with authoritative external knowledge for continuous musculoskeletal management. OrthoPilot autonomously retrieves real-time imaging, laboratory, pathology and order data and converts evolving patient states into evidence-based decisions from admission diagnosis to rehabilitation planning. We established a specialist-validated benchmark from real-world electronic health records spanning 1,000 disease codes. In a reader study across the complete care pathway, OrthoPilot was compared with 81 orthopaedic physicians and surpassed experts with 25 years of experience in diagnostic reasoning, clinical decision-making and management planning. It also outperformed all evaluated intelligent systems across 60 external clinical centres. In a prospective study of 1,870 complex cases, OrthoPilot increased full-chain management success by 10.6%. During an 8-month randomised deployment involving 8,240 inpatients, it increased cumulative cases per bed by 9.7% and improved patient-reported access to health information. These results move clinical AI from predicting isolated events toward executing longitudinal management across complete musculoskeletal care pathways.

Retrieval, not hallucinations, will be the limiting factor for LLM-based clinical AI tools

Discussions around large language model (LLM) errors in clinical artificial intelligence (AI) generally center around precision errors like hallucinations. This perspective, targeting both clinicians and AI researchers, seeks to shift that discussion to recall errors, particularly in retrieval of patient-level data needed for many clinical AI tools. The perspective outlines types of errors and mitigation strategies, describes research directions in LLMs and retrieval, and provides an overview of retrieval evaluation.

Clinical Harness for Governable Medical AI Skill Ecosystems

Medical AI remains organized around isolated models, whereas clinical care requires accountable capabilities that persist across time. We propose clinical AI skills and the Clinical Harness: a runtime governance architecture for registering, orchestrating, guarding and monitoring AI-enabled clinical capabilities. Using osteoporosis as an exemplar, we show how knowledge-driven, data-driven and physics-enhanced skills can support lifecycle care under runtime governance.

Towards Dys-XAI: Influence-Based Explanations for Dysarthria Severity Assessment

Dysarthria severity assessment is essential for therapy planning and longitudinal monitoring, yet manual perceptual rating is time-consuming and variable across clinicians. Although deep learning models achieve strong performance, their black-box nature limits clinical adoption. Existing speech explainability methods typically provide acoustic feature importance scores that are difficult for end-users to interpret. We propose an influence-based, instance-level explainability framework that explains each decision through supportive and competing training samples. Using gradient-based influence approximations, we compute per-utterance influence scores to identify supportive and competing training samples for each prediction. Controlled deletion experiments from 5 to 20 percent validate the explanations, showing that removing highly influential samples systematically shifts predictions. This approach provides auditable explanations by linking decisions to perceptible reference cases.

GEN-Guard: Correcting Generalization Failures for Deployable Federated Surgical AI

Federated Learning (FL) in surgical video AI enables collaborative model training without sharing sensitive data. However, standard evaluation practices - selecting the "best" global model based only on validation data from participating hospitals - can lead to suboptimal deployment choices. We identify this critical failure mode as performance leakage, where the selected model overfits internal federation data and fails to generalize to unseen institutions. We propose GEN-Guard, a practical post-hoc framework to detect and correct generalization failures in federated surgical AI. It integrates Generalization Detection via Client-Blocked Evaluation (CBE), which validates performance on isolated client distributions to prevent performance leakage, and Generalization Correction through Disagreement-Aware Distillation (DAD), which learns adaptive feature-level corrections for cross-institutional robustness. Both components operate after standard FL convergence while providing robust support for zero-shot adaptation to unseen environments. We first quantify the severity of performance leakage, observing Model Selection Failures (MSFs) exceeding 80% under standard evaluation. GEN-Guard is evaluated on two multi-center clinical challenges: surgical phase recognition in laparoscopic cholecystectomy and polyp segmentation in colonoscopy. Across both datasets, GEN-Guard consistently corrects these failures, improving in-federation F1 scores by up to 2 points, unseen-institution performance by up to 3 points, and worst-case institutional performance by 3-9 points. Performance leakage represents a systematic and previously under-recognized risk in federated surgical AI. GEN-Guard provides a practical solution for detecting and correcting such failures. By improving cross-institutional robustness and zero-shot generalization, it strengthens the reliability of FL for real-world surgical deployment.

Compositional Reasoning Depth Predicts Clinical AI Failure: Empirical Evidence Consistent with Transformer Compositionality Limits in Electronic Health Record Question Answering

Aggregate accuracy benchmarks conceal a systematic structure in how large language models fail at electronic health record (EHR) question answering: questions requiring more inferential steps produce disproportionately more errors. Motivated by theoretical results on transformer compositionality limits, we introduce a pre-specified hop-count taxonomy -- the number of distinct reasoning steps required to answer a clinical question from an EHR -- as a principled predictor of model failure. We annotate 313 clinician-generated MedAlign EHR question-answer pairs across four hop levels and evaluate 301 questions in a within-model ablation (claude-sonnet-4-6, zero-shot vs. extended thinking) and cross-architecture replications (gpt-4o and gpt-5.4-2026-03-05, zero-shot). All three models, spanning two providers and two OpenAI generations (GPT-4 and GPT-5), show monotone accuracy decline with hop count: Claude Sonnet zero-shot falls from 30.6% (hop=1) to 17.6% (hop=4) (Cochran-Armitage z=-2.30, p=0.011; OR per hop 0.72, 95% CI [0.56,0.92], p=0.008); GPT-4o replicates this (37.8% to 14.7%; OR 0.58 [0.45,0.75], p<0.001); and gpt-5.4-2026-03-05 confirms it (37.8% to 23.5%; OR 0.80 [0.66,0.98], p=0.027). A pre-specified context-sufficiency audit shows higher-hop questions are not differentially disadvantaged by EHR truncation (answerability 93-95% at hops 2-4 vs. 79% at hop=1), so the decline reflects compositional reasoning difficulty. Extended thinking did not significantly flatten the accuracy-depth curve across three reasoning conditions, and thinking-token usage scaled with hop count (r=0.31, p<0.0001), consistent with the predicted O(k) computational requirement. Hop count is thus a theory-motivated, cross-architecture predictor of large-language-model error on EHR question answering, with direct implications for deployment risk stratification of clinical AI.

SepsisAI Orchestrator: A Containerized and Scalable Platform for Deploying AI Models and Real-Time Monitoring in Early Sepsis Detection

Despite strong predictive results in the clinical machine learning literature, the translation of these models into bedside use remains limited by systems-level barriers: heterogeneous data representations, the absence of standardized deployment workflows, and a mismatch between research prototypes and the concurrency and latency requirements of hospital environments. We present the SepsisAI-Orchestrator, an open-source modular platform that addresses this deployment gap for early sepsis detection. The platform integrates HL7 FHIR-inspired Clinical Document Architecture (CDA) preprocessing, NoSQL storage, a containerized LightGBM classifier served via REST APIs, and a Streamlit clinical dashboard, orchestrated with Docker and Kubernetes. A previously validated LightGBM model (F1 0.87-0.94 on PhysioNet 2019) is reused without modification; the contribution lies in the surrounding infrastructure and its empirical characterization under load. Using k6 with 50-1000 concurrent virtual users, we find that replica count must be matched to the physical CPU thread count of the host: scaling from 3 to 12 replicas on a 12-thread CPU reduces p95 latency from 3.3s to 1.41s (57.3% reduction) and eliminates all request failures, while over-provisioning to 24 or 48 replicas degrades performance due to scheduler contention. To our knowledge this U-shaped scaling behavior has not been quantified previously for clinical AI inference workloads. We do not claim prospective clinical validation. Source code and deployment manifests are available at https://github.com/nucleusai/sepsisai-orchestrator.

Learning from Disagreement: Clinician Overrides as Implicit Preference Signals for Clinical AI in Value-Based Care

We reframe clinician overrides of clinical AI recommendations as implicit preference data - the same signal structure exploited by reinforcement learning from human feedback (RLHF), but richer: the annotator is a domain expert, the alternatives carry real consequences, and downstream outcomes are observable. We present a formal framework extending standard preference learning with three contributions: a five-category override taxonomy mapping override types to distinct model update targets; a preference formulation conditioned on patient state s, organizational context c, and clinician capability kappa, where kappa decomposes into execution capability kappa-exec and alignment capability kappa-align; and a dual learning architecture that jointly trains a reward model and a capability model via alternating optimization, preventing a failure mode we term suppression bias-the systematic suppression of correct-but-difficult recommendations when clinician capability falls below the execution threshold. We argue that chronic disease management under outcome-based payment contracts produces override data with uniquely favorable properties-longitudinal density, concentrated decision space, outcome labels, and natural capability variation-and that training environments combining longitudinal outcome measurement with aligned financial incentives are a necessary condition for learning a reward model aligned with patient trajectory rather than with encounter economics. This framework emerged from operational work to improve clinician capability in a live value-based care deployment.

End-to-End Evaluation and Governance of an EHR-Embedded AI Agent for Clinicians

Clinical AI systems require not just point-in-time evaluation but continuous governance: the ongoing practice of monitoring, evaluating, iterating, and re-evaluating performance throughout deployment. We present an end-to-end framework of governance that integrates rubric validation, live deployment feedback, technical performance monitoring, and cost tracking, with controlled experimentation gating system changes before deployment. Applied to Hyperscribe, an EHR-embedded agent that converts ambient audio into structured chart updates, twenty clinicians authored 1,646 validated rubrics across 823 cases. Seven Hyperscribe versions were evaluated through controlled experiments, with median scores improving from 84% to 95%. Analysis of 107 live feedback entries over three months showed feedback composition shifting from 79% error reports and 14% positive observations to 30% errors and 45% positive observations as engineering interventions resolved failures. Median processing time per audio segment was 8.1 seconds with a 99.6% effective completion rate after retry mechanisms absorbed transient model errors. These results demonstrate that continuous, multi-channel governance of deployed clinical AI is both achievable and effective.

From Black-Box Confidence to Measurable Trust in Clinical AI: A Framework for Evidence, Supervision, and Staged Autonomy

Trust in clinical artificial intelligence (AI) cannot be reduced to model accuracy, fluency of generation, or overall positive user impression. In medicine, trust must be engineered as a measurable system property grounded in evidence, supervision, and operational boundaries of AI autonomy. This article proposes a practical framework for trustworthy clinical AI built around three principles: evidence, supervision, and staged autonomy. Rather than replacing deterministic clinical logic wholesale with end-to-end black-box models, the proposed approach combines a deterministic core, a patient-specific AI assistant for contextual validation, a multi-tier model escalation mechanism, and a human supervision layer for verification, escalation, and risk control. We demonstrate that trust also depends on selective verification of clinically critical findings, bounded clinical context, disciplined prompt architecture, and careful evaluation on realistic cases. Classifier-driven modular prompting is examined as an incremental path to scaling clinical depth without sacrificing prompt performance and without waiting for complete rule-based coverage. To operationalize trust, a set of trust metrics is proposed, built on metrological principles -- measurement uncertainty, calibration, traceability -- enabling quantitative rather than subjective assessment of each architectural layer. In this perspective, trustworthy clinical AI emerges not as a property of an individual model, but as an architectural outcome of a system into which evidence trails, human oversight, tiered escalation, and graduated action rights are embedded from the outset.