Sepsis can be life-threatening, which highlights the need to understand the condition's diverse phenotypes to enhance treatment effectiveness. Sepsis phenotypes are derived from 12-hour vital sign trajectories of children (N=12,824) with multiple organ dysfunction syndrome from 13 U.S. hospitals. Survival analysis of the two subgroups produced by hierarchical clustering (HAC) on pairwise trajectory similarity matrix from dynamic time warping (DTW) showed a hazards ratio of 4.7 for 30-day mortality, which was better than the stratification of subgroups from group-based trajectory modeling. The higher mortality subgroup from HAC on DTW displayed higher blood pressure and pulse but lower temperature, in addition to acidosis. This comprehensive analysis of phenotypes can greatly aid in early risk evaluation, tailored treatment approaches, and improved outcomes for pediatric sepsis patients.

OBJECTIVE: Bacterial infections (BIs) are common, costly, and potentially life-threatening in critically ill patients. Patients with suspected BIs may require empiric multidrug antibiotic regimens and therefore potentially be exposed to prolonged and unnecessary antibiotics. We previously developed a BI risk model to augment practices and help shorten the duration of unnecessary antibiotics to improve patient outcomes. Here, we have performed a transportability assessment of this BI risk model in 2 tertiary intensive care unit (ICU) settings and a community ICU setting. We additionally explored how simple multisite learning techniques impacted model transportability. METHODS: Patients suspected of having a community-acquired BI were identified in 3 datasets: Medical Information Mart for Intensive Care III (MIMIC), Northwestern Medicine Tertiary (NM-T) ICUs, and NM "community-based" ICUs. ICU encounters from MIMIC and NM-T datasets were split into 70/30 train and test sets. Models developed on training data were evaluated against the NM-T and MIMIC test sets, as well as NM community validation data. RESULTS: During internal validations, models achieved AUROCs of 0.78 (MIMIC) and 0.81 (NM-T) and were well calibrated. In the external community ICU validation, the NM-T model had robust transportability (AUROC 0.81) while the MIMIC model transported less favorably (AUROC 0.74), likely due to case-mix differences. Multisite learning provided no significant discrimination benefit in internal validation studies but offered more stability during transport across all evaluation datasets. DISCUSSION: These results suggest that our BI risk models maintain predictive utility when transported to external cohorts. CONCLUSION: Our findings highlight the importance of performing external model validation on myriad clinically relevant populations prior to implementation.

MOTIVATION: Sepsis is a leading cause of death and disability in children globally, accounting for ∼3 million childhood deaths per year. In pediatric sepsis patients, the multiple organ dysfunction syndrome (MODS) is considered a significant risk factor for adverse clinical outcomes characterized by high mortality and morbidity in the pediatric intensive care unit. The recent rapidly growing availability of electronic health records (EHRs) has allowed researchers to vastly develop data-driven approaches like machine learning in healthcare and achieved great successes. However, effective machine learning models which could make the accurate early prediction of the recovery in pediatric sepsis patients from MODS to a mild state and thus assist the clinicians in the decision-making process is still lacking. RESULTS: This study develops a machine learning-based approach to predict the recovery from MODS to zero or single organ dysfunction by 1 week in advance in the Swiss Pediatric Sepsis Study cohort of children with blood-culture confirmed bacteremia. Our model achieves internal validation performance on the SPSS cohort with an area under the receiver operating characteristic (AUROC) of 79.1% and area under the precision-recall curve (AUPRC) of 73.6%, and it was also externally validated on another pediatric sepsis patients cohort collected in the USA, yielding an AUROC of 76.4% and AUPRC of 72.4%. These results indicate that our model has the potential to be included into the EHRs system and contribute to patient assessment and triage in pediatric sepsis patient care. AVAILABILITY AND IMPLEMENTATION: Code available at https://github.com/BorgwardtLab/MODS-recovery. The data underlying this article is not publicly available for the privacy of individuals that participated in the study. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Multiple organ dysfunction syndrome (MODS) is one of the most common causes of death in critically ill children. However, despite decades of clinical trials, there are no comprehensive approaches to the management of MODS or effective targeted therapies that have consistently improved outcomes. Better understanding the heterogeneity of MODS and characterizing subgroups of MODS patients could improve our understanding of the syndrome and help us develop new management strategies. We analyzed a cohort of 5,297 children with MODS from two children's hospitals and used subgraph-augmented non-negative matrix factorization (SANMF) to identify unique temporal patterns in organ dysfunction across four novel subgroups. We demonstrate that these subgroups are composed of patients with distinct clinical characteristics and are independently predictive of clinical outcomes. Our work suggests that these subgroups represent four relevant phenotypes of pediatric MODS that could be used to identify novel management strategies.

Elevated serum chloride levels (hyperchloremia) and the administration of intravenous (IV) fluids with high chloride content have both been associated with increased morbidity and mortality in certain subgroups of critically ill patients, such as those with sepsis. Here, we demonstrate this association in a general intensive care unit (ICU) population using data from the Medical Information Mart for Intensive Care III (MIMIC-III) database and propose the use of supervised learning to predict hyperchloremia in critically ill patients. Clinical variables from records of the first 24h of adult ICU stays were represented as features for four predictive supervised learning classifiers. The best performing model was able to predict second-day hyperchloremia with an AUC of 0.80 and a ratio of 5 false alerts for every true alert, which is a clinically-actionable rate. Our results suggest that clinicians can be effectively alerted to patients at risk of developing hyperchloremia, providing an opportunity to mitigate this risk and potentially improve outcomes.