Development and Validation of a Model for Endotracheal Intubation and Mechanical Ventilation Prediction in PICU Patients.

OBJECTIVES: To develop and externally validate an intubation prediction model for children admitted to a PICU using objective and routinely available data from the electronic medical records (EMRs). DESIGN: Retrospective observational cohort study. SETTING: Two PICUs within the same healthcare system: an academic, quaternary care center (36 beds) and a community, tertiary care center (56 beds). PATIENTS: Children younger than 18 years old admitted to a PICU between 2010 and 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical data was extracted from the EMR. PICU stays with at least one mechanical ventilation event (≥ 24 hr) occurring within a window of 1-7 days after hospital admission were included in the study. Of 13,208 PICU stays in the derivation PICU cohort, 1,175 (8.90%) had an intubation event. In the validation cohort, there were 1,165 of 17,841 stays (6.53%) with an intubation event. We trained a Categorical Boosting (CatBoost) model using vital signs, laboratory tests, demographic data, medications, organ dysfunction scores, and other patient characteristics to predict the need of intubation and mechanical ventilation using a 24-hour window of data within their hospital stay. We compared the CatBoost model to an extreme gradient boost, random forest, and a logistic regression model. The area under the receiving operating characteristic curve for the derivation cohort and the validation cohort was 0.88 (95% CI, 0.88-0.89) and 0.92 (95% CI, 0.91-0.92), respectively. CONCLUSIONS: We developed and externally validated an interpretable machine learning prediction model that improves on conventional clinical criteria to predict the need for intubation in children hospitalized in a PICU using information readily available in the EMR. Implementation of our model may help clinicians optimize the timing of endotracheal intubation and better allocate respiratory and nursing staff to care for mechanically ventilated children.

The 2024 Pediatric Sepsis Challenge: Predicting In-Hospital Mortality in Children With Suspected Sepsis in Uganda.

The aim of this "Technical Note" is to inform the pediatric critical care data research community about the "2024 Pediatric Sepsis Data Challenge." This competition aims to facilitate the development of open-source algorithms to predict in-hospital mortality in Ugandan children with sepsis. The challenge is to first develop an algorithm using a synthetic training dataset, which will then be scored according to standard diagnostic testing criteria, and then be evaluated against a nonsynthetic test dataset. The datasets originate from admissions to six hospitals in Uganda (2017-2020) and include 3837 children, 6 to 60 months old, who were confirmed or suspected to have a diagnosis of sepsis. The synthetic dataset was created from a random subset of the original data. The test validation dataset closely resembles the synthetic dataset. The challenge should generate an optimal model for predicting in-hospital mortality. Following external validation, this model could be used to improve the outcomes for children with proven or suspected sepsis in low- and middle-income settings.

The Pediatric Data Science and Analytics Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network: Use of Supervised Machine Learning Applications in Pediatric Critical Care Medicine Research.

OBJECTIVE: Perform a scoping review of supervised machine learning in pediatric critical care to identify published applications, methodologies, and implementation frequency to inform best practices for the development, validation, and reporting of predictive models in pediatric critical care. DESIGN: Scoping review and expert opinion. SETTING: We queried CINAHL Plus with Full Text (EBSCO), Cochrane Library (Wiley), Embase (Elsevier), Ovid Medline, and PubMed for articles published between 2000 and 2022 related to machine learning concepts and pediatric critical illness. Articles were excluded if the majority of patients were adults or neonates, if unsupervised machine learning was the primary methodology, or if information related to the development, validation, and/or implementation of the model was not reported. Article selection and data extraction were performed using dual review in the Covidence tool, with discrepancies resolved by consensus. SUBJECTS: Articles reporting on the development, validation, or implementation of supervised machine learning models in the field of pediatric critical care medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 5075 identified studies, 141 articles were included. Studies were primarily (57%) performed at a single site. The majority took place in the United States (70%). Most were retrospective observational cohort studies. More than three-quarters of the articles were published between 2018 and 2022. The most common algorithms included logistic regression and random forest. Predicted events were most commonly death, transfer to ICU, and sepsis. Only 14% of articles reported external validation, and only a single model was implemented at publication. Reporting of validation methods, performance assessments, and implementation varied widely. Follow-up with authors suggests that implementation remains uncommon after model publication. CONCLUSIONS: Publication of supervised machine learning models to address clinical challenges in pediatric critical care medicine has increased dramatically in the last 5 years. While these approaches have the potential to benefit children with critical illness, the literature demonstrates incomplete reporting, absence of external validation, and infrequent clinical implementation.

Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing.

BACKGROUND: Preschool children with recurrent wheezing are heterogeneous, with differing responses to respiratory viral infections. Although neutrophils are crucial for host defense, their function has not been studied in this population. OBJECTIVE: We performed functional immunophenotyping on isolated blood neutrophils from 52 preschool children with recurrent wheezing (aeroallergen sensitization, n = 16; no sensitization, n = 36). METHODS: Blood neutrophils were purified and cultured overnight with polyinosinic:polycytidylic acid [poly(I:C)] as a viral analog stimulus. Neutrophils underwent next-generation sequencing with Reactome pathway analysis and were analyzed for cytokine secretion, apoptosis, myeloperoxidase, and extracellular DNA release. CD14+ monocytes were also exposed to neutrophil culture supernatant and analyzed for markers of M1 and M2 activation. RESULTS: A total of 495 genes, related largely to the innate immune system and neutrophil degranulation, were differently expressed in children with versus without aeroallergen sensitization. Functional experiments identified more neutrophil degranulation and extracellular trap formation (ie, more myeloperoxidase and extracellular DNA) and less neutrophil proinflammatory cytokine secretion in children with aeroallergen sensitization. Neutrophils also shifted CD14+ monocytes to a more anti-inflammatory (ie, M2) phenotype in sensitized children and a more proinflammatory (ie, M1) phenotype in nonsensitized children. Although both groups experienced viral exacerbations, annualized exacerbation rates prompting unscheduled health care were also higher in children without aeroallergen sensitization after enrollment. CONCLUSIONS: Systemic neutrophil responses to viral infection differ by allergic phenotype and may be less effective in preschool children without allergic inflammation. Further studies of neutrophil function are needed in this population, which often has less favorable therapeutic responses to inhaled corticosteroids and other therapies directed at type 2-high inflammation.

Exacerbation-prone pediatric asthma is associated with arginine, lysine, and methionine pathway alterations.

BACKGROUND: The asthma of some children remains poorly controlled, with recurrent exacerbations despite treatment with inhaled corticosteroids. Aside from prior exacerbations, there are currently no reliable predictors of exacerbation-prone asthma in these children and only a limited understanding of the potential underlying mechanisms. OBJECTIVE: We sought to quantify small molecules in the plasma of children with exacerbation-prone asthma through mass spectrometry-based metabolomics. We hypothesized that the plasma metabolome of these children would differ from that of children with non-exacerbation-prone asthma. METHODS: Plasma metabolites were extracted from 4 pediatric asthma cohorts (215 total subjects, with 41 having exacerbation-prone asthma) and detected with a mass spectrometer. High-confidence annotations were retained for univariate analysis and were confirmed by a sensitivity analysis in subjects receiving high-dose inhaled corticosteroids. Metabolites that varied by cohort were excluded. MetaboAnalyst software was used to identify pathways of interest. Concentrations were calculated by reference standardization. RESULTS: We identified 32 unique, cohort-independent metabolites that differed in children with exacerbation-prone asthma compared to children with non-exacerbation-prone asthma. Comparison of metabolite concentrations to literature-reported values for healthy children revealed that most metabolites were decreased in both asthma groups, but more so in exacerbation-prone asthma. Pathway analysis identified arginine, lysine, and methionine pathways as most impacted. CONCLUSIONS: Several plasma metabolites are perturbed in children with exacerbation-prone asthma and are largely related to arginine, lysine, and methionine pathways. While validation is needed, plasma metabolites may be potential biomarkers for exacerbation-prone asthma in children.

Integrating structured and unstructured data for timely prediction of bloodstream infection among children.

BACKGROUND: Hospitalized children with central venous lines (CVLs) are at higher risk of hospital-acquired infections. Information in electronic health records (EHRs) can be employed in training deep learning models to predict the onset of these infections. We incorporated clinical notes in addition to structured EHR data to predict serious bloodstream infections, defined as positive blood culture followed by at least 4 days of new antimicrobial agent administration, among hospitalized children with CVLs. METHODS: Structured EHR information and clinical notes were extracted for a retrospective cohort including all hospitalized patients with CVLs at a single tertiary care pediatric health system from 2013 to 2018. Deep learning models were trained to determine the added benefit of incorporating the information embedded in clinical notes in predicting serious bloodstream infection. RESULTS: A total of 24,351 patient encounters met inclusion criteria. The best-performing model restricted to structured EHR data had a specificity of 0.951 and positive predictive value (PPV) of 0.056 when the sensitivity was set to 0.85. The addition of contextualized word embeddings improved the specificity to 0.981 and PPV to 0.113. CONCLUSIONS: Integrating clinical notes with structured EHR data improved the prediction of serious bloodstream infections among pediatric patients with CVLs. IMPACT: Developed an advanced infection prediction model in pediatrics that integrates the structured and unstructured EHRs. Extracted information from clinical notes to do timely prediction in a clinical setting. Developed a deep learning model framework that can be employed in predicting rare events in a complex and dynamic environment.

Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model.

BACKGROUND: Identifying patterns within ICU medication regimens may help artificial intelligence algorithms to better predict patient outcomes; however, machine learning methods incorporating medications require further development, including standardized terminology. The Common Data Model for Intensive Care Unit (ICU) Medications (CDM-ICURx) may provide important infrastructure to clinicians and researchers to support artificial intelligence analysis of medication-related outcomes and healthcare costs. Using an unsupervised cluster analysis approach in combination with this common data model, the objective of this evaluation was to identify novel patterns of medication clusters (termed 'pharmacophenotypes') correlated with ICU adverse events (e.g., fluid overload) and patient-centered outcomes (e.g., mortality). METHODS: This was a retrospective, observational cohort study of 991 critically ill adults. To identify pharmacophenotypes, unsupervised machine learning analysis with automated feature learning using restricted Boltzmann machine and hierarchical clustering was performed on the medication administration records of each patient during the first 24 h of their ICU stay. Hierarchical agglomerative clustering was applied to identify unique patient clusters. Distributions of medications across pharmacophenotypes were described, and differences among patient clusters were compared using signed rank tests and Fisher's exact tests, as appropriate. RESULTS: A total of 30,550 medication orders for the 991 patients were analyzed; five unique patient clusters and six unique pharmacophenotypes were identified. For patient outcomes, compared to patients in Clusters 1 and 3, patients in Cluster 5 had a significantly shorter duration of mechanical ventilation and ICU length of stay (p < 0.05); for medications, Cluster 5 had a higher distribution of Pharmacophenotype 1 and a smaller distribution of Pharmacophenotype 2, compared to Clusters 1 and 3. For outcomes, patients in Cluster 2, despite having the highest severity of illness and greatest medication regimen complexity, had the lowest overall mortality; for medications, Cluster 2 also had a comparably higher distribution of Pharmacophenotype 6. CONCLUSION: The results of this evaluation suggest that patterns among patient clusters and medication regimens may be observed using empiric methods of unsupervised machine learning in combination with a common data model. These results have potential because while phenotyping approaches have been used to classify heterogenous syndromes in critical illness to better define treatment response, the entire medication administration record has not been incorporated in those analyses. Applying knowledge of these patterns at the bedside requires further algorithm development and clinical application but may have the future potential to be leveraged in guiding medication-related decision making to improve treatment outcomes.

Untargeted, High-Resolution Metabolomics in Pediatric Eosinophilic Esophagitis.

BACKGROUND/OBJECTIVES: Eosinophilic esophagitis (EoE) is an inflammatory disease of unclear etiology. The aim of this study was to use untargeted plasma metabolomics to identify metabolic pathway alterations associated with EoE to better understand the pathophysiology. METHODS: This prospective, case-control study included 72 children, aged 1-17 years, undergoing clinically indicated upper endoscopy (14 diagnosed with EoE and 58 controls). Fasting plasma samples were analyzed for metabolomics by high-resolution dual-chromatography mass spectrometry. Analysis was performed on sex-matched groups at a 2:1 ratio. Significant differences among the plasma metabolite features between children with and without EoE were determined using multivariate regression analysis and were annotated with a network-based algorithm. Subsequent pathway enrichment analysis was performed. RESULTS: Patients with EoE had a higher proportion of atopic disease (85.7% vs 50%, P = 0.019) and any allergies (100% vs 57.1%, P = 0.0005). Analysis of the dual chromatography features resulted in a total of 918 metabolites that differentiated EoE and controls. Glycerophospholipid metabolism was significantly enriched with the greatest number of differentiating metabolites and overall pathway enrichment ( P < 0.01). Multiple amino and fatty acid pathways including linoleic acid were also enriched, as well as pyridoxine metabolism ( P < 0.01). CONCLUSIONS: In this pilot study, we found differences in metabolites involved in glycerophospholipid and inflammation pathways in pediatric patients with EoE using untargeted metabolomics, as well as overlap with amino acid metabolome alterations found in atopic disease.

ClotCatcher: a novel natural language model to accurately adjudicate venous thromboembolism from radiology reports.

INTRODUCTION: Accurate identification of venous thromboembolism (VTE) is critical to develop replicable epidemiological studies and rigorous predictions models. Traditionally, VTE studies have relied on international classification of diseases (ICD) codes which are inaccurate - leading to misclassification bias. Here, we developed ClotCatcher, a novel deep learning model that uses natural language processing to detect VTE from radiology reports. METHODS: Radiology reports to detect VTE were obtained from patients admitted to Emory University Hospital (EUH) and Grady Memorial Hospital (GMH). Data augmentation was performed using the Google PEGASUS paraphraser. This data was then used to fine-tune ClotCatcher, a novel deep learning model. ClotCatcher was validated on both the EUH dataset alone and GMH dataset alone. RESULTS: The dataset contained 1358 studies from EUH and 915 studies from GMH (n = 2273). The dataset contained 1506 ultrasound studies with 528 (35.1%) studies positive for VTE, and 767 CT studies with 91 (11.9%) positive for VTE. When validated on the EUH dataset, ClotCatcher performed best (AUC = 0.980) when trained on both EUH and GMH dataset without paraphrasing. When validated on the GMH dataset, ClotCatcher performed best (AUC = 0.995) when trained on both EUH and GMH dataset with paraphrasing. CONCLUSION: ClotCatcher, a novel deep learning model with data augmentation rapidly and accurately adjudicated the presence of VTE from radiology reports. Applying ClotCatcher to large databases would allow for rapid and accurate adjudication of incident VTE. This would reduce misclassification bias and form the foundation for future studies to estimate individual risk for patient to develop incident VTE.

Coronavirus Disease 2019 Temperature Trajectories Correlate With Hyperinflammatory and Hypercoagulable Subphenotypes.

OBJECTIVES: Body temperature trajectories of infected patients are associated with specific immune profiles and survival. We determined the association between temperature trajectories and distinct manifestations of coronavirus disease 2019. DESIGN: Retrospective observational study. SETTING: Four hospitals within an academic healthcare system from March 2020 to February 2021. PATIENTS: All adult patients hospitalized with coronavirus disease 2019. INTERVENTIONS: Using a validated group-based trajectory model, we classified patients into four previously defined temperature trajectory subphenotypes using oral temperature measurements from the first 72 hours of hospitalization. Clinical characteristics, biomarkers, and outcomes were compared between subphenotypes. MEASUREMENTS AND MAIN RESULTS: The 5,903 hospitalized coronavirus disease 2019 patients were classified into four subphenotypes: hyperthermic slow resolvers (n = 1,452, 25%), hyperthermic fast resolvers (1,469, 25%), normothermics (2,126, 36%), and hypothermics (856, 15%). Hypothermics had abnormal coagulation markers, with the highest d-dimer and fibrin monomers (p < 0.001) and the highest prevalence of cerebrovascular accidents (10%, p = 0.001). The prevalence of venous thromboembolism was significantly different between subphenotypes (p = 0.005), with the highest rate in hypothermics (8.5%) and lowest in hyperthermic slow resolvers (5.1%). Hyperthermic slow resolvers had abnormal inflammatory markers, with the highest C-reactive protein, ferritin, and interleukin-6 (p < 0.001). Hyperthermic slow resolvers had increased odds of mechanical ventilation, vasopressors, and 30-day inpatient mortality (odds ratio, 1.58; 95% CI, 1.13-2.19) compared with hyperthermic fast resolvers. Over the course of the pandemic, we observed a drastic decrease in the prevalence of hyperthermic slow resolvers, from representing 53% of admissions in March 2020 to less than 15% by 2021. We found that dexamethasone use was associated with significant reduction in probability of hyperthermic slow resolvers membership (27% reduction; 95% CI, 23-31%; p < 0.001). CONCLUSIONS: Hypothermics had abnormal coagulation markers, suggesting a hypercoagulable subphenotype. Hyperthermic slow resolvers had elevated inflammatory markers and the highest odds of mortality, suggesting a hyperinflammatory subphenotype. Future work should investigate whether temperature subphenotypes benefit from targeted antithrombotic and anti-inflammatory strategies.

Neurocritical Care Performance Measures Derived from Electronic Health Record Data are Feasible and Reveal Site-Specific Variation: A CHoRUS Pilot Project.

BACKGROUND: We evaluated the feasibility and discriminability of recently proposed Clinical Performance Measures for Neurocritical Care (Neurocritical Care Society) and Quality Indicators for Traumatic Brain Injury (Collaborative European NeuroTrauma Effectiveness Research in TBI; CENTER-TBI) extracted from electronic health record (EHR) flowsheet data. METHODS: At three centers within the Collaborative Hospital Repository Uniting Standards (CHoRUS) for Equitable AI consortium, we examined consecutive neurocritical care admissions exceeding 24 h (03/2015-02/2020) and evaluated the feasibility, discriminability, and site-specific variation of five clinical performance measures and quality indicators: (1) intracranial pressure (ICP) monitoring (ICPM) within 24 h when indicated, (2) ICPM latency when initiated within 24 h, (3) frequency of nurse-documented neurologic assessments, (4) intermittent pneumatic compression device (IPCd) initiation within 24 h, and (5) latency to IPCd application. We additionally explored associations between delayed IPCd initiation and codes for venous thromboembolism documented using the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) system. Median (interquartile range) statistics are reported. Kruskal-Wallis tests were measured for differences across centers, and Dunn statistics were reported for between-center differences. RESULTS: A total of 14,985 admissions met inclusion criteria. ICPM was documented in 1514 (10.1%), neurologic assessments in 14,635 (91.1%), and IPCd application in 14,175 (88.5%). ICPM began within 24 h for 1267 (83.7%), with site-specific latency differences among sites 1-3, respectively, (0.54 h [2.82], 0.58 h [1.68], and 2.36 h [4.60]; p < 0.001). The frequency of nurse-documented neurologic assessments also varied by site (17.4 per day [5.97], 8.4 per day [3.12], and 15.3 per day [8.34]; p < 0.001) and diurnally (6.90 per day during daytime hours vs. 5.67 per day at night, p < 0.001). IPCds were applied within 24 h for 12,863 (90.7%) patients meeting clinical eligibility (excluding those with EHR documentation of limiting injuries, actively documented as ambulating, or refusing prophylaxis). In-hospital venous thromboembolism varied by site (1.23%, 1.55%, and 5.18%; p < 0.001) and was associated with increased IPCd latency (overall, 1.02 h [10.4] vs. 0.97 h [5.98], p = 0.479; site 1, 2.25 h [10.27] vs. 1.82 h [7.39], p = 0.713; site 2, 1.38 h [5.90] vs. 0.80 h [0.53], p = 0.216; site 3, 0.40 h [16.3] vs. 0.35 h [11.5], p = 0.036). CONCLUSIONS: Electronic health record-derived reporting of neurocritical care performance measures is feasible and demonstrates site-specific variation. Future efforts should examine whether performance or documentation drives these measures, what outcomes are associated with performance, and whether EHR-derived measures of performance measures and quality indicators are modifiable.

A Wearable Multimodal Sensing System for Tracking Changes in Pulmonary Fluid Status, Lung Sounds, and Respiratory Markers.

Heart failure (HF) exacerbations, characterized by pulmonary congestion and breathlessness, require frequent hospitalizations, often resulting in poor outcomes. Current methods for tracking lung fluid and respiratory distress are unable to produce continuous, holistic measures of cardiopulmonary health. We present a multimodal sensing system that captures bioimpedance spectroscopy (BIS), multi-channel lung sounds from four contact microphones, multi-frequency impedance pneumography (IP), temperature, and kinematics to track changes in cardiopulmonary status. We first validated the system on healthy subjects (n = 10) and then conducted a feasibility study on patients (n = 14) with HF in clinical settings. Three measurements were taken throughout the course of hospitalization, and parameters relevant to lung fluid status-the ratio of the resistances at 5 kHz to those at 150 kHz (K)-and respiratory timings (e.g., respiratory rate) were extracted. We found a statistically significant increase in K (p < 0.05) from admission to discharge and observed respiratory timings in physiologically plausible ranges. The IP-derived respiratory signals and lung sounds were sensitive enough to detect abnormal respiratory patterns (Cheyne-Stokes) and inspiratory crackles from patient recordings, respectively. We demonstrated that the proposed system is suitable for detecting changes in pulmonary fluid status and capturing high-quality respiratory signals and lung sounds in a clinical setting.

Using Machine Learning to Predict Early Onset Acute Organ Failure in Critically Ill Intensive Care Unit Patients With Sickle Cell Disease: Retrospective Study.

BACKGROUND: Sickle cell disease (SCD) is a genetic disorder of the red blood cells, resulting in multiple acute and chronic complications, including pain episodes, stroke, and kidney disease. Patients with SCD develop chronic organ dysfunction, which may progress to organ failure during disease exacerbations. Early detection of acute physiological deterioration leading to organ failure is not always attainable. Machine learning techniques that allow for prediction of organ failure may enable early identification and treatment and potentially reduce mortality. OBJECTIVE: The aim of this study was to test the hypothesis that machine learning physiomarkers can predict the development of organ dysfunction in a sample of adult patients with SCD admitted to intensive care units (ICUs). METHODS: We applied diverse machine learning methods, statistical methods, and data visualization techniques to develop classification models to distinguish SCD from controls. RESULTS: We studied 63 sequential SCD patients admitted to ICUs with 163 patient encounters (mean age 30.7 years, SD 9.8 years). A subset of these patient encounters, 22.7% (37/163), met the sequential organ failure assessment criteria. The other 126 SCD patient encounters served as controls. A set of signal processing features (such as fast Fourier transform, energy, and continuous wavelet transform) derived from heart rate, blood pressure, and respiratory rate was identified to distinguish patients with SCD who developed acute physiological deterioration leading to organ failure from patients with SCD who did not meet the criteria. A multilayer perceptron model accurately predicted organ failure up to 6 hours before onset, with an average sensitivity and specificity of 96% and 98%, respectively. CONCLUSIONS: This retrospective study demonstrated the viability of using machine learning to predict acute organ failure among hospitalized adults with SCD. The discovery of salient physiomarkers through machine learning techniques has the potential to further accelerate the development and implementation of innovative care delivery protocols and strategies for medically vulnerable patients.

Applying Artificial Intelligence to Identify Physiomarkers Predicting Severe Sepsis in the PICU.

OBJECTIVES: We used artificial intelligence to develop a novel algorithm using physiomarkers to predict the onset of severe sepsis in critically ill children. DESIGN: Observational cohort study. SETTING: PICU. PATIENTS: Children age between 6 and 18 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Continuous minute-by-minute physiologic data were available for a total of 493 critically ill children admitted to a tertiary care PICU over an 8-month period, 20 of whom developed severe sepsis. Using an alert time stamp generated by an electronic screening algorithm as a reference point, we studied up to 24 prior hours of continuous physiologic data. We identified physiomarkers, including SD of heart rate, systolic and diastolic blood pressure, and symbolic transitions probabilities of those variables that discriminated severe sepsis patients from controls (all other patients admitted to the PICU who did not meet severe sepsis criteria). We used logistic regression, random forests, and deep Convolutional Neural Network methods to derive our models. Analysis was performed using data generated in two windows prior to the firing of the electronic screening algorithm, namely, 2-8 and 8-24 hours. When analyzing the physiomarkers present in the 2-8 hours analysis window, logistic regression performed with specificity of 87.4% and sensitivity of 55.0%, random forest performed with 79.6% specificity and 80.0% sensitivity, and the Convolutional Neural Network performed with 83.0% specificity and 75.0% sensitivity. When analyzing physiomarkers from the 8-24 hours window, logistic regression resulted in 77.1% specificity and 39.3% sensitivity, random forest performed with 82.3% specificity and 61.1% sensitivity, whereas the Convolutional Neural Network method achieved 81% specificity and 76% sensitivity. CONCLUSIONS: Artificial intelligence can be used to predict the onset of severe sepsis using physiomarkers in critically ill children. Further, it may detect severe sepsis as early as 8 hours prior to a real-time electronic severe sepsis screening algorithm.

Lung segment anything model (LuSAM): a decoupled prompt-integrated framework for automated lung segmentation on chest X-Ray images.

Accurate lung segmentation in chest X-ray images plays a pivotal role in early disease detection and clinical decision-making. In this study, we introduce an innovative approach to enhance the precision of lung segmentation using the Segment Anything Model (SAM). Despite its versatility, SAM faces the challenge of prompt decoupling, often resulting in misclassifications, especially with intricate structures like the clavicle. Our research focuses on the integration of spatial at- tention mechanisms within SAM. This approach enables the model to concentrate specifically on the lung region, fostering adaptability to image variations and reducing the likelihood of false positives. This work has the potential to significantly advance lung segmentation, improving the identification and quantification of lung anomalies across diverse clinical contexts.

Improving mixed-integer temporal modeling by generating synthetic data using conditional generative adversarial networks: A case study of fluid overload prediction in the intensive care unit.

OBJECTIVE: The challenge of mixed-integer temporal data, which is particularly prominent for medication use in the critically ill, limits the performance of predictive models. The purpose of this evaluation was to pilot test integrating synthetic data within an existing dataset of complex medication data to improve machine learning model prediction of fluid overload. MATERIALS AND METHODS: This retrospective cohort study evaluated patients admitted to an ICU ≥ 72 h. Four machine learning algorithms to predict fluid overload after 48-72 h of ICU admission were developed using the original dataset. Then, two distinct synthetic data generation methodologies (synthetic minority over-sampling technique (SMOTE) and conditional tabular generative adversarial network (CTGAN)) were used to create synthetic data. Finally, a stacking ensemble technique designed to train a meta-learner was established. Models underwent training in three scenarios of varying qualities and quantities of datasets. RESULTS: Training machine learning algorithms on the combined synthetic and original dataset overall increased the performance of the predictive models compared to training on the original dataset. The highest performing model was the meta-model trained on the combined dataset with 0.83 AUROC while it managed to significantly enhance the sensitivity across different training scenarios. DISCUSSION: The integration of synthetically generated data is the first time such methods have been applied to ICU medication data and offers a promising solution to enhance the performance of machine learning models for fluid overload, which may be translated to other ICU outcomes. A meta-learner was able to make a trade-off between different performance metrics and improve the ability to identify the minority class.

Dysfunctional neutrophil type 1 interferon responses in preschool children with recurrent wheezing and IL-4-mediated aeroallergen sensitization.

Background: The innate mechanisms associated with viral exacerbations in preschool children with recurrent wheezing are not understood. Objective: We sought to assess differential gene expression in blood neutrophils from preschool children with recurrent wheezing, stratified by aeroallergen sensitization, at baseline and after exposure to polyinosinic:polycytidylic acid (poly(I:C)) and also to examine whether poly(I:C)-stimulated blood neutrophils influenced airway epithelial gene expression. Methods: Blood neutrophils were purified and cultured overnight with poly(I:C) and underwent next-generation sequencing with Reactome pathway analysis. Primary human small airway epithelial cells were treated with poly(I:C)-treated neutrophil culture supernatants and were analyzed for type 1 interferon gene expression with a targeted array. Symptoms and exacerbations were assessed in participants over 12 months. Results: A total of 436 genes were differently expressed in neutrophils from children with versus without aeroallergen sensitization at baseline, with significant downregulation of type 1 interferons. These type 1 interferons were significantly upregulated in sensitized children after poly(I:C) stimulation. Confirmatory experiments demonstrated similar upregulation of type 1 interferons in IL-4-treated neutrophils stimulated with poly(I:C). Poly(I:C)-treated neutrophil supernatants from children with aeroallergen sensitization also induced a type 1 interferon response in epithelial cells. Children with aeroallergen sensitization also had higher symptom scores during exacerbations, and these symptom differences persisted for 3 days after prednisolone treatment. Conclusions: Type 1 interferon responses are dysregulated in preschool children with aeroallergen sensitization, which is in turn associated with exacerbation severity. Given the importance of type 1 interferon signaling in viral resolution, additional studies of neutrophil type 1 interferon responses are needed in this population.