CalTwin: Towards Calibrated, Shift-Robust Medical World Models via Fisher-Information Regularisation

Medical world models offer a framework for extending medical artificial intelligence beyond static prediction by representing evolving patient states and modelling how they change over time and in response to clinical interventions. This Review defines the conceptual boundaries, technical foundations, application domains, and evidence requirements of the field through a structured narrative synthesis with reproducible evidence mapping. We screened 1,455 unique records and assembled a corpus of 98 sources, including 14 studies that met a strict empirical definition of a medical world model. The field is organised around four capabilities: patient state representation, temporal dynamics modelling, intervention-conditioned simulation, and clinician-supervised planning. Evidence spans medical imaging, longitudinal electronic health records, treatment response modelling, physiological and multimodal state modelling, ultrasound and surgical interaction, and population and health-system simulation; clinical digital twins are treated as a cross-cutting integration framework. Current studies provide early evidence of technical feasibility for trajectory forecasting and comparison of candidate interventions, but most remain retrospective, task-specific, or preclinical. The evidence base is further limited by incomplete longitudinal intervention data, inconsistent action semantics, limited causal identifiability, long-horizon error accumulation, inadequate uncertainty estimation, and limited external validation. Clinical translation will therefore depend on precise intervention representations, robust causal and mechanistic grounding, calibrated trajectory-level uncertainty, safety-constrained planning, and prospective multicentre validation against clinically meaningful endpoints.

The Segment Anything Model (SAM) exhibits strong zero-shot performance on natural images but suffers from domain shift and overconfidence when applied to medical volumes. We propose \textbf{CalSAM}, a lightweight adaptation framework that (i) reduces encoder sensitivity to domain shift via a \emph{Feature Fisher Information Penalty} (FIP) computed on 3D feature maps and (ii) penalizes overconfident voxel-wise errors through a \emph{Confidence Misalignment Penalty} (CMP). The combined loss, $\mathcal{L}_{\mathrm{CalSAM}}$ fine-tunes only the mask decoder while keeping SAM's encoders frozen. On cross-center and scanner-shift evaluations, CalSAM substantially improves accuracy and calibration: e.g., on the BraTS scanner split (Siemens$\to$GE) CalSAM shows a $+7.4\%$ relative improvement in $\mathrm{DSC}$ (80.1% vs.\ 74.6%), a $-26.9\%$ reduction in $\mathrm{HD95}$ (4.6 mm vs.\ 6.3 mm), and a $-39.5\%$ reduction in $\mathrm{ECE}$ (5.2% vs.\ 8.6%). On ATLAS-C (motion corruptions), CalSAM achieves a $+5.3\%$ relative improvement in $\mathrm{DSC}$ (75.9%) and a $-32.6\%$ reduction in $\mathrm{ECE}$ (5.8%). Ablations show FIP and CMP contribute complementary gains ($p<0.01$), and the Fisher penalty incurs a modest $\sim$15% training-time overhead. CalSAM therefore delivers improved domain generalization and better-calibrated uncertainty estimates for brain MRI segmentation, while retaining the computational benefits of freezing SAM's encoder.

Long-horizon clinical simulation -- predicting how a patient's physiology evolves over years under specified interventions -- is central to chronic-disease care, yet existing electronic health record (EHR) models are predominantly discriminative, and general-purpose large language models drift under repeated interventions. We propose the \textbf{ChronoMedicalWorld Model (CMWM)}, an action-conditioned latent world-model framework for learning patient trajectories from longitudinal care data. CMWM couples a joint-embedding state encoder with a wide action encoder that admits both structured intervention indicators and free-text communication embeddings, and trains a recurrent latent transition module under a six-term objective: next-observation supervision, next-latent prediction, SIGReg latent regularisation, and three physiology-aware shape priors (slope, continuity, large-jump penalty). A closed-loop rollout-prefix protocol matches training to deployment, so the model is optimised against the same multi-step error it exhibits at inference. As a concrete case study, we instantiate CMWM for annual estimated glomerular filtration rate (eGFR) trajectory forecasting in chronic kidney disease (CKD). On a 2{,}232-patient nephrology cohort, the CKD instantiation achieves a dynamic-50% history rollout test mean absolute error (MAE) of 7.384 and root-mean-square error (RMSE) of 10.256, against 7.964 and 11.069 for a tuned GPT-5.5 structured-prompting baseline ($-7.28\%$ MAE, $-7.35\%$ RMSE), with the gain dominated by the dialogue portion of patient--health-coach communication. The framework is not CKD-specific: its architecture, loss design, and training protocol apply to any chronic condition that can be cast as periodic clinical state interleaved with structured and conversational interventions.