{'fraction_non_alphanumeric': 0.056055646481178396, 'fraction_numerical': 0.03927986906710311, 'mean_word_length': 5.554959785522788, 'pattern_counts': {'":': 0, '<': 4, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 1, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Derivation of four computable 24-hour pediatric sepsis phenotypes to facilitate personalized enrollment in early precise anti-inflammatory clinical trials

ABSTRACT Objective: Thrombotic microangiopathy induced Thrombocytopenia Associated Multiple Organ Failure and hyperinflammatory Macrophage Activation Syndrome are important causes of late pediatric sepsis mortality that are often missed or have delayed diagnosis. Our objective is to derive computable 24-hour sepsis phenotypes to facilitate enrollment in early precise anti-inflammatory trials targeting mortality from these conditions. Design: Machine learning analysis using consensus k-means clustering. Setting: Nine pediatric intensive care units. Patients: 404 children with severe sepsis. Interventions: 24-hour computable phenotypes derived using 25 bedside variables including C-reactive protein and ferritin. Measurements and Main Results: Four computable phenotypes (PedSep-A, B, C, and D) are derived. Compared to the overall population mean, PedSep-A has the least inflammation (median C-reactive protein 7.3 mg/dL, ferritin 125 ng/mL), younger age, less chronic illness, and respiratory failure (n = 135; 2% mortality); PedSep-B (median C-reactive protein 13.2 mg/dL, ferritin 225 ng/ mL) has multiple organ failure with intubated respiratory failure, shock, and Glasgow Coma Scale score < 7 (n = 102, 12% mortality); PedSep-C has elevated ferritin (median C-reactive protein 15.2 mg/dL, ferritin 405 ng/mL), lymphopenia, shock, and relative absence of intubation (n = 110; mortality 10%); and, PedSep D has hyperferritinemic (median C-reactive protein 13.1 mg/dL ferritin 610 ng/mL), thrombocytopenic multiple organ failure with more cardiovascular, hepatic, renal, hematologic, and central nervous system failures (n = 56, 34% mortality). PedSep-D has highest likelihood of Thrombocytopenia Associated Multiple Organ Failure (Adj OR 47.51 95% CI [18.83-136.83], p < 0.0001) and Macrophage Activation Syndrome (Adj OR 38.63 95% CI [13.26-137.75], p <0.0001), and shows a survival interaction with combined methylprednisolone and intravenous immunoglobulin therapy (p < 0.05). CONCLUSIONS AND RELEVANCE: Four machine learning computable phenotypes are identified (www.pedsepsis.pitt.edu). Membership in PedSep-D appears optimal for enrollment in early anti-inflammatory trials targeting Thrombocytopenia Associated Multiple Organ Failure and Macrophage Activation Syndrome.