Sepsis Prediction

Preprocessing is an under-measured reliability risk in clinical prediction: a model can keep a similar AUROC and still change who receives an alert. Imputation quality is commonly evaluated using reconstruction error or aggregate discrimination, neither of which directly measures agreement on which patients are flagged. At a matched alert rate, pipelines with similar aggregate performance can produce different patient lists. This question is especially relevant under the frequent, structured missingness of real ICU records. We therefore introduce alert-list concordance, which asks whether two pipelines identify the same high-risk patients, measured by the Jaccard similarity of their top-k% alert sets with patient-level bootstrap confidence intervals. On PhysioNet/CinC 2019 (40,336 patients, 71.9% missingness), we compare nine imputation strategies and a native-missingness baseline using a fixed XGBoost configuration, fitted and Platt-calibrated separately for each strategy. After Bonferroni correction, 22 of the 28 reconstruction-method pairs showed no statistically significant difference in patient-level AUROC, yet their alert lists overlap at Jaccard 0.518 to 0.750. Similar aggregate discrimination can therefore accompany different patient selections. ForwardFill is a separate outlier, pairing higher discrimination with the lowest overlap in the matrix, 0.40 to 0.45. The broad pattern holds within each hospital system and under six patient-level aggregation rules. At the row level, eight of ten methods fall within an AUROC range of 0.011. In this row-level pipeline, deep imputers did not outperform mean imputation on discrimination, and the sequential implementations cost 5 to 12 times mean imputation in total pipeline wall-clock time on our hardware.

Early sepsis warning from ICU records can be cast as a structure-preserving prediction problem. A model needs to detect deterioration from irregular measurements while keeping each alert connected to the physiological signals that support it. Many temporal models fuse clinical variables into a patient-level representation, supporting scalar risk prediction but weakening the structure needed for clinical decomposition. We present SepsisLens, which preserves variable-indexed temporal states until risk composition. Observation-aware representations encode each variable's dynamics and measurement history, while a shared temporal encoder models each trajectory without collapsing the variable axis. The StructuredRiskHead composes multi-horizon risk from explicit variable-level and organ-level components. We evaluate SepsisLens on three public ICU cohorts and one private-hospital cohort under a common pre-onset protocol. SepsisLens achieves strong discrimination on all four cohorts and lower alert burden at matched event recall on MIMIC-IV. Structural ablations support the design, while input-side masking shows that the ranked components reflect variables with greater influence on prediction.

Continuous-time sensing and monitoring with timely and accurate decision-making are critical for many real-world applications. In healthcare monitoring systems, physiological signals are often available or sampled at irregular time intervals, hence requiring continuous-time processing to provide accurate prediction. Moreover, such systems often need to solve multiple detection/prediction tasks to provide a comprehensive patient review from different physiological aspects for more accurate decision-making. To solve this, continuous-time neural networks (CTNNs) can be employed. However, state-of-the-art works typically solve only one task at each network, thereby limiting their efficiency gains. To address this limitation, we propose MTLiquid, a novel methodology to enable efficient multi-task learning in continuous-time processing for healthcare monitoring systems through effective network design and training strategy. MTLiquid employs: (1) multiple input and output heads to accommodate different tasks, while sharing the same backbone network across tasks; as well as (2) an effective training strategy that leverages a loss-weighting technique to balance learning updates across different tasks and a proportional data presentation technique to address imbalanced dataset sizes. Experimental results for mortality prediction (P12) and sepsis early detection (P19) tasks for ICU patients show that, MTLiquid achieves strong performance (AUROC: 0.84 for P12 and 0.94 for P19) comparable to the state-of-the-art single-task learning in both continuous-time networks (AUROC: 0.84 for P12 and 0.95 for P19) and discrete-time networks (AUROC: 0.79-0.82 for P12 and 0.92-0.94 for P19), while incurring significantly smaller memory cost by 44%-94%. These results highlight the potential of our MTLiquid methodology to enable lightweight continuous-time healthcare monitoring systems for better decision-making.

Currently used sepsis severity indices rely on fixed variables and weights established decades ago, which are coarsely discretized and calibrated to a cohort that no longer reflects contemporary critical care. No alternative learned directly from patient trajectories is in routine use. We conducted a retrospective two-cohort study on a total of 29,116 and 7,691 adult patients meeting Sepsis-3 criteria from two hospital systems in Massachusetts and Georgie, respectively. We developed a sepsis index using 43 routinely charted variables over a 72-hour treatment window. Unlike previous studies, we use mortality as a treatment-level ranking signal rather than a per-state target, allowing credit to be redistributed non-uniformly across timesteps. Evaluation was done on a permanent 20% test holdout, using clinical vignettes and Spearman correlation. Uncertainty intervals were obtained by bootstrap resampling of whole patients. Under this ranking scheme, non-survivors scored 1.19-1.64 points higher than survivors on a 0-10 scale within all strata of baseline SOFA-2, with similar results stratifying within lactate, mean arterial pressure (MAP), and creatinine. Within-patient change in the index correlated with change in lactate (Spearman rho = 0.39; n = 1,854). Similar, weaker correlations were found for MAP and creatinine. On a cohort level, cross-institutional agreement measured by Spearman correlation between models trained on different sites, were 70-77% of same-site correlation. External within-patient correlations were 0.54 and 0.59 against ceilings of 0.92 and 0.90. Our index also correlated with established indices, while null controls stayed near zero. Our index demonstrated hourly prognostic information that meaningfully separates patient outcomes and is consistent with clinical expectation, indicating potential as a decision support tool complementing clinical judgement.

Early sepsis prediction from electronic health records is challenged by irregular sampling, high missingness, and class imbalance. We systematically compare four modeling paradigms -- self-supervised Joint Embedding Predictive Architecture (JEPA) via masked latent prediction, self-supervised VICReg (variance-invariance-covariance regularization) with two-view augmentation, semi-supervised fine-tuning of a VICReg-pretrained encoder, and supervised Temporal Convolutional Network (TCN) -- alongside raw-feature baselines. All models share a common preprocessing pipeline of hourly binning with forward-fill imputation applied to 7 biomarkers selected via sparsity analysis from the MIMIC-III dataset. Our best model (JEPA + XGBoost + mean pooling) achieves AUPRC 0.636 at the time of onset (H0), approaching the SupMix benchmark (0.667) while using 83% fewer biomarkers. The Tier 1 pipeline -- VICReg pretraining followed by semi-supervised fine-tuning and XGBoost -- achieves AUPRC 0.510 at H0, a 3.1$\times$ improvement over the raw-feature baseline (0.165) and a 7.6% improvement over the end-to-end supervised TCN (0.474). Crucially, the fine-tuned VICReg encoder exhibits the most temporally persistent representations, degrading only 16.8% from H0 to H10 compared to 47.5% for supervised TCN and 65.3% for JEPA, demonstrating that self-supervised pretraining with task-aware fine-tuning yields features that are both sharp near onset and robust across prediction horizons.

Privacy-sensitive and distributed characteristics of multi-center medical data bring severe obstacles to centralized modeling for accurate early prediction of sepsis. Federated learning (FL) has attracted growing attention as a promising framework for collaborative model development, as it allows multiple institutions to jointly train predictive models without directly sharing or centralizing raw data. Nevertheless, its practical performance, robustness, and privacy-preserving benefits remain insufficiently evaluated using real-world clinical datasets. To bridge this gap, this study systematically examines the application of federated learning to multi-center sepsis prediction. The experimental dataset consists of 648 clinically screened samples collected from three tertiary hospitals in China, with rigorous inclusion and exclusion criteria. We establish a centralized training paradigm as the performance baseline, and then implement a horizontal federated learning framework for distributed collaborative modeling. Extensive experimental results demonstrate that the federated learning-based model achieves highly comparable prediction accuracy to the centralized counterpart, while fundamentally avoiding privacy leakage. Further privacy security analysis verifies that malicious attackers cannot reconstruct the original patient data from the transmitted model parameters, indicating strong resistance against data reconstruction attacks. This work not only validates the practicality and security of federated learning in clinical sepsis prediction, but also provides a reliable and feasible solution for privacy-preserving multi-center medical collaboration.

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.

Timely and interpretable early warning of sepsis remains a major clinical challenge due to the complex temporal dynamics of physiological deterioration. Traditional data-driven models often provide accurate yet opaque predictions, limiting physicians' confidence and clinical applicability. To address this limitation, we propose a Large Language Model (LLM)-guided temporal simulation framework that explicitly models physiological trajectories prior to disease onset for clinically interpretable prediction. The framework consists of a spatiotemporal feature extraction module that captures dynamic dependencies among multivariate vital signs, a Medical Prompt-as-Prefix module that embeds clinical reasoning cues into LLMs, and an agent-based post-processing component that constrains predictions within physiologically plausible ranges. By first simulating the evolution of key physiological indicators and then classifying sepsis onset, our model offers transparent prediction mechanisms that align with clinical judgment. Evaluated on the MIMIC-IV and eICU databases, the proposed method achieves superior AUC scores (0.861-0.903) across 24-4-hour pre-onset prediction tasks, outperforming conventional deep learning and rule-based approaches. More importantly, it provides interpretable trajectories and risk trends that can assist clinicians in early intervention and personalized decision-making in intensive care environments.

Accurate prediction of future risk and disease progression in sepsis is clinically important for early warning and timely intervention in intensive care. However, short-window sepsis prediction remains challenging, because shorter observation windows provide limited historical evidence, whereas longer prediction horizons reduce the number of patient trajectories with valid future supervision. To address this problem, we propose CSRA, a Controlled Spectral Residual Augmentation framework for short-window multi-system ICU time series. CSRA first groups variables by clinical systems and extracts system-level and global representations. It then performs input-adaptive residual perturbation in the spectral domain to generate structured and clinically plausible trajectory variations. To improve augmentation stability and controllability, CSRA is trained end-to-end with the downstream predictor under a unified objective, together with anchor consistency loss and controller regularization. Experiments on a MIMIC-IV sepsis cohort across multiple downstream models show that CSRA is consistently competitive and often superior, reducing regression error by 10.2% in MSE and 3.7% in MAE over the non-augmentation baseline, while also yielding consistent gains on classification. CSRA further maintains more favorable performance under shorter observation windows, longer prediction horizons, and smaller training data scales, while also remaining effective on an external clinical dataset~(ZiGongICUinfection), indicating stronger robustness and generalizability in clinically constrained settings.

We develop and analyze explainable machine learning (ML) models for sepsis outcome prediction using a novel Electronic Health Record (EHR) dataset from 12,286 hospitalizations at a large emergency hospital in Romania. The dataset includes demographics, International Classification of Diseases (ICD-10) diagnostics, and 600 types of laboratory tests. This study aims to identify clinically strong predictors while achieving state-of-the-art results across three classification tasks: (1)deceased vs. discharged, (2)deceased vs. recovered, and (3)recovered vs. ameliorated. We trained five ML models to capture complex distributions while preserving clinical interpretability. Experiments explored the trade-off between feature richness and patient coverage, using subsets of the 10--50 most frequent laboratory tests. Model performance was evaluated using accuracy and area under the curve (AUC), and explainability was assessed using SHapley Additive exPlanations (SHAP). The highest performance was obtained for the deceased vs. recovered case study (AUC=0.983, accuracy=0.93). SHAP analysis identified several strong predictors such as cardiovascular comorbidities, urea levels, aspartate aminotransferase, platelet count, and eosinophil percentage. Eosinopenia emerged as a top predictor, highlighting its value as an underutilized marker that is not included in current assessment standards, while the high performance suggests the applicability of these models in clinical settings.

The early prediction of sepsis in intensive care unit (ICU) patients is crucial for improving survival rates. However, the development of accurate predictive models is hampered by data fragmentation across healthcare institutions and the complex, temporal nature of medical data, all under stringent privacy constraints. To address these challenges, we propose a novel framework that uniquely integrates federated learning (FL) with a medical knowledge graph and a temporal transformer model, enhanced by meta-learning capabilities. Our approach enables collaborative model training across multiple hospitals without sharing raw patient data, thereby preserving privacy. The model leverages a knowledge graph to incorporate structured medical relationships and employs a temporal transformer to capture long-range dependencies in clinical time-series data. A model-agnostic meta-learning (MAML) strategy is further incorporated to facilitate rapid adaptation of the global model to local data distributions. Evaluated on the MIMIC-IV and eICU datasets, our method achieves an area under the curve (AUC) of 0.956, which represents a 22.4% improvement over conventional centralized models and a 12.7% improvement over standard federated learning, demonstrating strong predictive capability for sepsis. This work presents a reliable and privacy-preserving solution for multi-center collaborative early warning of sepsis.