Learning a Continuous Sepsis Severity Score Without Hour-by-Hour Supervision: A Two-Site Retrospective Study
Authors: Kevin Zhu, Ryan Zhang, Baraa Abed, Tilendra Choudhary, Malvern Madondo, Mehak Arora, Yixuan Yang, Alasdair Gent, Aditya Nagori, Omer T. Inan, Krista L. Haines, Patrick Georgoff, Suresh M. Agarwal, Vijay Krishnamoorthy, Tetsu Ohnuma, Mihai V. Podgoreanu, Michael R. Pinsky, Gilles Clermont, Craig M. Coopersmith, Craig S. Jabaley, Rishikesan Kamaleswaran
Organizations: Department of Biomedical Engineering, Duke University, Durham, NC. · Department of Surgery, Duke University School of Medicine, Durham, NC. · Department of Electrical and Computer Engineering, Duke University, Durham, NC. · Department of Anesthesiology, Duke University, Durham, NC. · School of Electrical and Computer Engineering, Georgia Institute of Technology, GA. · Department of Biomedical Engineering, Georgia Institute of Technology, GA. · Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA. · Department of Critical Care Medicine, University of Pittsburgh, PA. · School of Medicine, University of Pittsburgh, PA. · Emory Critical Care Center, Emory Healthcare, Atlanta, GA. · Department of Surgery, Emory University School of Medicine, Atlanta, GA. · Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA.
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 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.
Yikun Ou, Wei Li
School of Computer Science, University of Sydney Sydney, Australia
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.
POLITEHNICA Bucharest National University of Science and Technology, Bucharest, Romania · Carol Davila University of Medicine and Pharmacy, Faculty of Medicine, Bucharest, Romania · General Surgery Department, University Emergency Hospital of Bucharest, Bucharest, Romania +1
Verifying whether clinical care follows evidence-based protocols is a natural neuro-symbolic problem, yet the safety-critical setting defeats either paradigm alone. We present an expert-guided pipeline that constrains a large language model strictly to semantic normalization, mapping messy drug and microbiology strings onto a fixed clinical vocabulary, while a Sugeno fuzzy inference system reasons over the normalized events. The fuzzy layer encodes eight Surviving Sepsis Campaign bundle rules and replaces binary judgments with graded scores in [0,1]. Applied to 2,438 MIMIC-IV v3.1 sepsis episodes, it surfaces antibiotic timing as the most critical breakdown (mean 0.24, 13% within one hour), Hour-1 underperformance (mean 36.7%), a 51% elevated-lactate drop-off, and descriptive differences in ICU stay across compliance groups (3.8 versus 5.1 days).
Himanshu Tripathi, Kaushik Roy, Subash Neupane +1
Department of Computer Science, The University of Alabama