Pediatric Sepsis Research Articles

Sepsis-Associated Acute Kidney Injury in Critically Ill Children: Incidence and Outcomes

Background: Acute kidney injury (AKI) is a major concern in pediatric critical care, often occurring in conjunction with sepsis. This study aimed to identify the incidence, outcomes, and risk factors for AKI in the context of pediatric sepsis. Methods: This was a bicentric retrospective cohort study conducted at two university hospitals in Saudi Arabia. All patients aged 1 month to 14 years admitted to pediatric intensive care units (PICUs) with evidence of sepsis between January 2021 and December 2022 were included. AKI was defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Demographic, clinical, and laboratory data were collected from electronic medical records. Results: 309 patients were included, 38 (12.3%) developed stage 1 AKI, 64 (20.7%) developed stage 2 AKI, and 183 (59.2%) developed stage 3 AKI. Patients with sepsis-associated AKI had significantly longer PICU stays and higher mortality rates than those without AKI (p < 0.01). Inflammatory markers and certain medications were associated with increased AKI risk. Factors independently associated with stage 3 AKI include younger age, positive blood culture, gentamycin use, and higher SOFA score. Conclusions: Sepsis-associated AKI is a common and serious complication in critically ill children, contributing to increased morbidity and mortality. Identification of specific risk factors may facilitate early recognition and targeted interventions to mitigate the impact of AKI in this vulnerable population.

Relationship between lactate levels and 28-day mortality in pediatric sepsis: results from the pediatric intensive care database

ObjectiveThis study aimed to investigate the relationship between serum lactate levels at admission to the intensive care unit (ICU) and the clinical outcomes of children with sepsis.MethodsWe used the Pediatric Intensive Care (PIC) database to identify 288 pediatric patients with sepsis. We analyzed the relationship between lactate levels and hospital and ICU mortality in sepsis by establishing a segmented multivariable Cox regression model. We also conducted subgroup analysis as well as analyzed the restricted cubic spline curves.ResultsAfter adjusting for all potential confounding factors, an increase of 1 mmol/L in lactate levels was found to be associated with an 17% rise in the 28-day hospital mortality risk among sepsis patients (HR: 1.17, 95% CI: 1.08–1.27, P = 0.0002). When considering lactate as a categorical variable, the mortality risk of patients with lactate levels ≥ 2.2 mmol/L was significantly increased (HR: 3.61, 95% CI: 1.24–10.54, P = 0.0189). The restricted cubic spline curve analysis revealed a nonlinear correlation between lactate and 28-day mortality, with an inflection point at 2.2 mmol/L. Similar findings were also observed in the assessment of secondary outcomes.ConclusionsOur study demonstrates a non-linear correlation between lactate levels and 28-day mortality in pediatric sepsis, with a critical threshold of 2.2mmol/l for lactate levels in septic patients. Early assessment of lactate levels is recommended for children with sepsis to facilitate prompt intervention and mitigate the risk of fatality.

Assessment of Facility Readiness for Pediatric Emergency and Critical Care Utilizing a 2-Phase Survey Conducted in Six Hospitals in Uganda and Cameroon: A Quality Improvement Study.

Each year, 5.3 million children under 5 years of age die in low-resource settings, often due to delayed recognition of disease severity, inadequate treatment, or a lack of supplies. We describe the use of a comprehensive digital facility-readiness survey tool, recently developed by the Pediatric Sepsis Data CoLaboratory, which aims to identify target areas for quality improvement related to pediatric emergency and critical care. Facility-readiness surveys were conducted at six sub-Saharan African hospitals providing pediatric emergency and critical care in Uganda (n = 4) and Cameroon (n = 2). The tool is a 2-phase survey to assess readiness to provide pediatric essential emergency and critical care: (1) an "environmental scan," focusing on infrastructure, availability, and functionality of resources, and (2) an "observational scan" assessing the quality and safety of care through direct observation of patients receiving treatment for common diseases. Data were captured in a mobile application and the findings analyzed descriptively. Varying levels of facility readiness to provide pediatric emergency care were observed. Only 1 of 6 facilities had a qualified staff member to assess children for danger signs upon arrival, and only 2 of 6 had staff with skills to manage emergency conditions. Only 21% of essential medicines required for pediatric emergency and critical care were available at all six facilities. Most facilities had clean running water and soap or disinfectants, but most also experienced interruptions to their electricity supply. Less than half of patients received an appropriate discharge note and fewer received counseling on postdischarge care; follow-up was arranged in less than a quarter of cases. These pilot findings indicate that facilities are partially equipped and ready to provide pediatric emergency and critical care. This facility-readiness tool can be utilized in low-resource settings to assist hospital administrators and policymakers to determine priority areas to improve quality of care for the critically ill child.

Phoenix criteria for sepsis: are these enough to guide a clinician?

In conclusion, Phoenix criteria are a step in the right direction to define life-threatening organ dysfunction in sepsis, but clinicians need to be mindful that diagnosis/treatment of less severe sepsis should not be delayed if these criteria are not met. Therefore, local early detection and management tools for sepsis should be followed. • There has always been a quest for a definition for pediatric sepsis. There are limitations to the previous pediatric sepsis criteria which were published in 2005 by the International Pediatric Sepsis Consensus Conference (IPSCC). IPSCC defines sepsis as a suspected or confirmed infection in the presence of systemic inflammatory response syndrome (SIRS). These new Phoenix Pediatric Sepsis (PPS) criteria for sepsis and septic shock are intended to identify children with life-threatening organ dysfunction due to infection, and the score was developed based on a very large pediatric dataset. • Though the intention of Phoenix criteria is to help identify children with life threatening organ dysfunction, unfortunately the crietria will miss signs of early sepis. In this manuscript, we point out some of the drawbacks of these criteria which need to be borne in mind while applying these criteria.

OP060 Topic: AS14–Infections: Sepsis and Septic Shock/Antimicrobial Stewardship/Tropical and Parasite Infections/Other: CHARACTERISATION OF PAEDIATRIC SEPSIS MORTALITY IN QUEENSLAND 2004-2021: THE QUEENSLAND PAEDIATRIC SEPSIS MORTALITY STUDY.

OP060 Topic: AS14–Infections: Sepsis and Septic Shock/Antimicrobial Stewardship/Tropical and Parasite Infections/Other: CHARACTERISATION OF PAEDIATRIC SEPSIS MORTALITY IN QUEENSLAND 2004-2021: THE QUEENSLAND PAEDIATRIC SEPSIS MORTALITY STUDY.

A novel digital health approach to improving global pediatric sepsis care in Bangladesh using wearable technology and machine learning.

Sepsis is the leading cause of child death globally with low- and middle-income countries (LMICs) bearing a disproportionate burden of pediatric sepsis deaths. Limited diagnostic and critical care capacity and health worker shortages contribute to delayed recognition of advanced sepsis (severe sepsis, septic shock, and/or multiple organ dysfunction) in LMICs. The aims of this study were to 1) assess the feasibility of a wearable device for physiologic monitoring of septic children in a LMIC setting and 2) develop machine learning models that utilize readily available wearable and clinical data to predict advanced sepsis in children. This was a prospective observational study of children with sepsis admitted to an intensive care unit in Dhaka, Bangladesh. A wireless, wearable device linked to a smartphone was used to collect continuous recordings of physiologic data for the duration of each patient's admission. The correlation between wearable device-collected vital signs (heart rate [HR], respiratory rate [RR], temperature [T]) and manually collected vital signs was assessed using Pearson's correlation coefficients and agreement was assessed using Bland-Altman plots. Clinical and laboratory data were used to calculate twice daily pediatric Sequential Organ Failure Assessment (pSOFA) scores. Ridge regression was used to develop three candidate models for advanced sepsis (pSOFA > 8) using combinations of clinical and wearable device data. In addition, the lead time between the models' detection of advanced sepsis and physicians' documentation was compared. 100 children were enrolled of whom 41% were female with a mean age of 15.4 (SD 29.6) months. In-hospital mortality rate was 24%. Patients were monitored for an average of 2.2 days, with > 99% data capture from the wearable device during this period. Pearson's r was 0.93 and 0.94 for HR and RR, respectively) with r = 0.72 for core T). Mean difference (limits of agreement) was 0.04 (-14.26, 14.34) for HR, 0.29 (-5.91, 6.48) for RR, and -0.0004 (-1.48, 1.47) for core T. Model B, which included two manually measured variables (mean arterial pressure and SpO2:FiO2) and wearable device data had excellent discrimination, with an area under the Receiver-Operating Curve (AUC) of 0.86. Model C, which consisted of only wearable device features, also performed well, with an AUC of 0.78. Model B was able to predict the development of advanced sepsis more than 2.5 hours earlier compared to clinical documentation. A wireless, wearable device was feasible for continuous, remote physiologic monitoring among children with sepsis in a LMIC setting. Additionally, machine-learning models using wearable device data could discriminate cases of advanced sepsis without any laboratory tests and minimal or no clinician inputs. Future research will develop this technology into a smartphone-based system which can serve as both a low-cost telemetry monitor and an early warning clinical alert system, providing the potential for high-quality critical care capacity for pediatric sepsis in resource-limited settings.

Investigating the effect of synbiotic supplementation on inflammatory indices in critically ill septic children: a protocol study for randomized control trial

BackgroundSepsis, a severe inflammatory response to infection, is a global health priority due to its high mortality and long-term disability rates. Its pathophysiology involves both inflammation and immune suppression. Managing sepsis requires significant healthcare resources and expenditure, with sepsis being a leading cause of hospital costs. Gut microbiotas play a crucial role in sepsis, and probiotics show promise in managing it by restoring microbial balance. Despite advances, targeted therapies for sepsis remain elusive, necessitating innovative approaches such as probiotic therapy.MethodFifty-four eligible patients with sepsis will be randomly assigned to either the synbiotic or placebo group. The synbiotic supplement, KidiLact, comprises ten probiotic strains and prebiotic fructooligosaccharides. Participants will receive two sachets daily for 7 days, mixed with sterile water and administered orally or via gavage. Inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) will be evaluated. Anthropometric measurements, nutritional assessment, biochemical analysis, and clinical evaluation will be conducted to assess treatment outcomes. Statistical analysis will be performed to compare results between the two groups, employing SPSS version 19 with a significance level of P < .05.ConclusionThis randomized clinical trial aims to evaluate synbiotic supplementation effects on inflammatory markers and clinical outcomes in pediatric sepsis patients in the pediatric intensive care unit (PICU). Probiotics have shown promise in reducing proinflammatory cytokines like IL-6, TNF-α, and CRP, which are vital in the inflammatory response. Synbiotics can enhance gut integrity, preventing pathogen translocation and reducing inflammation. If our expectations regarding the effects of probiotics are correct, we can use them as a cost-effective supplement to improve the condition of pediatric sepsis in hospitals.Trial registrationIRCT,IRCT20230523058266N1 Registered 30 October 2023, https://irct.behdasht.gov.ir/trial/71397.

FedDSS: A data-similarity approach for client selection in horizontal federated learning

Background and objectiveFederated learning (FL) is an emerging distributed learning framework allowing multiple clients (hospitals, institutions, smart devices, etc.) to collaboratively train a centralized machine learning model without disclosing personal data. It has the potential to address several healthcare challenges, including a lack of training data, data privacy, and security concerns. However, model learning under FL is affected by non-i.i.d. data, leading to severe model divergence and reduced performance due to the varying client's data distributions. To address this problem, we propose FedDSS, Federated Data Similarity Selection, a framework that uses a data-similarity approach to select clients, without compromising client data privacy. MethodsFedDSS comprises a statistical-based data similarity metric, a N-similar-neighbor network, and a network-based selection strategy. We assessed FedDSS' performance against FedAvg's in i.i.d. and non-i.i.d. settings with two public pediatric sepsis datasets (PICD and MIMICIII). Selection fairness was measured using entropy. Simulations were repeated five times to evaluate average loss, true positive rate (TPR), and entropy. ResultsIn i.i.d setting on PICD, FedDSS achieved a higher TPR starting from the 9th round and surpassing 0.6 three rounds earlier than FedAvg. On MIMICIII, FedDSS's loss decreases significantly from the 13th round, with TPR > 0.8 by the 2nd round, two rounds ahead of FedAvg (at the 4th round). In the non-i.i.d. setting, FedDSS achieved TPR > 0.7 by the 4th and > 0.8 by the 7th round, earlier than FedAvg (at the 5th and 11th rounds). In both settings, FedDSS showed reasonable fairness (entropy of 2.2 and 2.1). ConclusionWe demonstrated that FedDSS contributes to improved learning in FL by achieving faster convergence, reaching the desired TPR with fewer communication rounds, and potentially enhancing sepsis prediction (TPR) over FedAvg.

Development of a Prognosis Prediction Model for Pediatric Sepsis Based on the NLPR.

Identifying high-risk children with poor prognoses during the early stages of sepsis and providing timely and appropriate interventions are imperative. The objective of this study was to develop a prognostic prediction model for pediatric sepsis utilizing the neutrophil to lymphocyte and platelet ratio (NLPR). A multivariable logistic regression analysis was conducted to investigate the association between the NLPR and in-hospital mortality among septic children upon admission. To minimize the potential confounding factors that could introduce bias, a propensity score matching analysis was employed. Subsequently, a nomogram prediction model was developed to assess the risk of in-hospital mortality in septic children, incorporating the NLPR as a key factor. The performance of this prediction model was then evaluated. A total of 230 septic children were enrolled in the study. Multivariate logistic regression analysis revealed that the NLPR was an independent risk factor for in-hospital mortality, with an odds ratio of 8.31 (95% CI 3.69-18.68). The finding remained consistent after propensity score matching analysis. A nomogram prediction model was developed that incorporates the NLPR, arterial blood lactate level, and Pediatric Critical Illness Score (PCIS). Among the various models, this nomogram exhibited the highest area under the curve (AUC) value of 0.831. The calibration curve demonstrated good agreement between the predicted and observed outcomes. Decision curve analysis indicated that the prediction model outperformed the PCIS. Internal validation of the model yielded an AUC value of 0.824 and a kappa value of 0.420, indicating its reliability and accuracy. The NLPR serves as an independent risk factor for in-hospital mortality among septic children. The nomogram prognostic prediction model could effectively guide clinicians in accurately predicting the prognosis of septic children, thus enabling timely and effective treatment interventions.

Role of CD64 and myeloperoxidase as biomarkers for early diagnosis of sepsis in pediatric intensive care unit

Globally, sepsis is the primary cause of death for children. While research conducted on adults has a significant impact on the diagnosis and treatment of sepsis in newborns and young children, there are significant factors that are pertinent to pediatrics as well. This prospective case-control study was conducted during the period from August 2020 to October 2022 after approval by the institutional ethical committee. The study included 48 critically ill children admitted at the Pediatric intensive care unit and 30 apparently healthy children as a control group. Laboratory investigations including complete blood picture, C-reactive protein (CRP), blood culture and sensitivity and plasma level of cluster of differentiation 64 (CD64) and myeloperoxidase (MPO) were investigated for all participants. A daily follow up for the signs of systemic inflammatory response syndrome (SIRS) or sepsis was done, and the patients were divided into SIRS and non-SIRS subgroups then patients were divided into two groups according to the presence of severe sepsis. A follow up CD64 and MPO sample were withdrawn from them to assess their prognostic value. SIRS was reported in 39.58 % of patients while severe sepsis was reported in 20.8%. CD64 and MPO were significantly higher in cases than controls (p= 0.003, p&lt;0.001, respectively) and, in patients with SIRs and severe sepsis CD64 was 1559.00± 367.09 pg/ml and 1547.9 4± 436.14 pg/ml, respectively. Also, MPO was significantly higher in patients with SIRS (113.58± 25.19 mU/ml) and severe sepsis (111.70± 26.50 mU/ml). CD64 and MPO significantly increased after development of sepsis in admitted patients. ROC was significantly higher for CD64 and MPO at admission than that for CRP at admission (p=0.123, p=0.014, respectively). In conclusion, plasma level of CD64 and MPO in peripheral blood can be considered an early sensitive marker for the detection and follow up of pediatric sepsis.

Transfer learning-enabled outcome prediction for guiding CRRT treatment of the pediatric patients with sepsis

Continuous renal replacement therapy (CRRT) is a life-saving procedure for sepsis but the benefit of CRRT varies and prediction of clinical outcomes is valuable in efficient treatment planning. This study aimed to use machine learning (ML) models trained using MIMIC III data for identifying sepsis patients who would benefit from CRRT. We first selected patients with sepsis and CRRT in the ICU setting and their gender, and an array of routine lab results were included as features to train machine learning models using 30-day mortality as the primary outcome. A total of 4161 patients were included for analysis, among whom there were 1342 deaths within 30 days. Without data augmentation, extreme gradient boosting (XGBoost) showed an accuracy of 64.2% with AUC-ROC of 0.61. Data augmentation using a conditional generative adversarial neural network (c-GAN) resulted in a significantly improved accuracy (82%) and ROC-AUC (0.78%). To enable prediction on pediatric patients, we adopted transfer learning approaches, where the weights of all but the last hidden layer were fixed, followed by fine-tuning of the weights of the last hidden layer using pediatric data of 200 patients as the inputs. A significant improvement was observed using the transfer learning approach (AUCROC = 0.76) compared to direct training on the pediatric cohort (AUCROC = 0.62). Through this transfer-learning-facilitated patient outcome prediction, our study showed that ML can aid in clinical decision-making by predicting patient responses to CRRT for managing pediatric sepsis.

Proteomic Signatures of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Narrative Review.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious complication of COVID-19. MIS-C has overlapping features with other pediatric inflammatory disorders including Kawasaki Disease (KD), Macrophage Activation Syndrome (MAS), Toxic Shock Syndrome and sepsis. The exact mechanisms responsible for the clinical overlap between MIS-C and these conditions remain unclear, and biomarkers that could distinguish MIS-C from its clinical mimics are lacking. This study aimed to provide an overview of how proteomic methods, like Mass Spectrometry (MS) and affinity-based proteomics, can offer a detailed understanding of pathophysiology and aid in the diagnosis and prognosis of MIS-C. A narrative review of relevant studies published up to July 2024 was conducted. We identified 15 studies and summarized their key proteomic findings. These studies investigated the serum or plasma proteome of MIS-C patients using MS, Proximity Extension, or Aptamer-based assays. The studies associated the proteomic profile of MIS-C with laboratory and clinical parameters and/or compared it with that of other diseases including acute COVID-19, KD, MAS, pediatric rheumatic diseases, sepsis and myocarditis or pericarditis following COVID-19 mRNA immunization. Depending on the method and the control group, different proteins were increased or decreased in the MIS-C group. The limitations and challenges in MIS-C proteomic research are also discussed, and future research recommendations are provided. Although proteomics appear to be a promising approach for understanding the pathogenesis and uncovering candidate biomarkers in MIS-C, proteomic studies are still needed to recognize and validate biomarkers that could accurately discriminate MIS-C from its clinical mimics.

Corticosteroids for Managing Pediatric Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock. Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched. Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate. Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials. Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50-0.85), shorter length of hospital stay (MD: -3.76 days, 95% CI: -6.66 to -0.86), and shorter pediatric intensive care unit length of stay (MD -2.34 days, 95% CI: -3.14 to -1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence. While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.

A Critical Assessment of Time-to-Antibiotics Recommendations in Pediatric Sepsis

Abstract The Pediatric Surviving Sepsis Campaign Guidelines recommend delivery of antibiotics within 1 hour for children with septic shock and, for those without shock but with sepsis-related organ dysfunction, as soon as feasible within 3 hours. In this review, we summarize the available adult and pediatric literature supporting these recommendations. We also explore the implications of implementing time-to-antibiotic goals at the point of antibiotic initiation in clinical practice, as well as the potential downstream impacts of these goals on antibiotic de-escalation.

Emergency clinicians' use of adult and paediatric sepsis pathways: An implementation redesign using the behaviour change wheel

AbstractAimsTo identify facilitators and barriers and tailor implementation strategies to optimize emergency clinician's use of adult and paediatric sepsis pathways.DesignA qualitative descriptive study using focus group methodology.MethodsTwenty‐two emergency nurses and ten emergency medical officers from four Australian EDs participated in eight virtual focus groups. Participants were asked about their experiences using the New South Wales Clinical Excellence Commission adult and paediatric sepsis pathways using a semi‐structured interview template. Facilitators and barriers to use of the sepsis pathways were categorized using the Theoretical Domains Framework. Tailored interventions were selected to address facilitators and barriers, and a re‐implementation plan was devised guided by the Behaviour Change Wheel.ResultsThirty‐two facilitators and 58 barriers were identified corresponding to 11 Theoretical Domains Framework domains. Tailored strategies were selected to optimize emergency clinicians' use of the sepsis pathways including refinement of existing education and training programmes, modifications to the electronic medical record system, introduction of an audit and feedback system, staffing strategies and additional resources.ConclusionThe implementation of sepsis pathways in the Emergency Department setting is complex, impacted by a multitude of factors requiring tailored strategies to address facilitators and barriers and optimize uptake.Implications for Patient CareThis study presents a theory‐informed systematic approach to successfully implement and embed adult and paediatric sepsis pathways into clinical practice in the Emergency Department.ImpactOptimizing uptake of sepsis pathways has the potential to improve sepsis recognition and management, subsequently improving the outcome of patients with sepsis.Reporting MethodThe Consolidated Criteria for REporting Qualitative research guided the preparation of this report.Patient or Public ContributionNil.

Frequency of and Risk Factors for Increased Healthcare Utilization After Pediatric Sepsis Hospitalization.

To determine the frequency of and risk factors for increased post-sepsis healthcare utilization compared with pre-sepsis healthcare utilization. Retrospective observational cohort study. Years 2016-2019 MarketScan Commercial and Medicaid Database. Children (0-18 yr) with sepsis treated in a U.S. hospital. None. We measured the frequency of and risk factors for increased healthcare utilization in the 90 days post- vs. pre-sepsis hospitalization. We defined increased healthcare utilization as an increase of at least 3 days in the 90 days post-hospitalization compared with the 90 days pre-hospitalization based on outpatient, emergency department, and inpatient hospitalization. We identified 2801 patients hospitalized for sepsis, of whom 865 (30.9%) had increased healthcare utilization post-sepsis, with a median (interquartile range [IQR]) of 3 days (1-6 d) total in the 90 days pre-sepsis and 10 days (IQR, 6-21 d) total in the 90 days post-sepsis ( p < 0.001). In multivariable models, the odds of increased healthcare use were higher for children with longer lengths of hospitalization (> 30 d adjusted odds ratio [aOR], 4.35; 95% CI, 2.99-6.32) and children with preexisting complex chronic conditions, specifically renal (aOR, 1.47; 95% CI, 1.02-2.12), hematologic/immunologic (aOR, 1.34; 95% CI, 1.03-1.74), metabolic (aOR, 1.39; 95% CI, 1.08-1.79), and malignancy (aOR, 1.89; 95% CI, 1.38-2.59). In this nationally representative cohort of children who survived sepsis hospitalization in the United States, nearly one in three had increased healthcare utilization in the 90 days after discharge. Children with hospitalizations longer than 30 days and complex chronic conditions were more likely to experience increased healthcare utilization.

Elevated total bile acid levels as an independent predictor of mortality in pediatric sepsis.

The close relationship between bile acid (BA) metabolism and sepsis has been investigated in recent years, as knowledge of the role of the gut microbiome and metabolomics in sepsis has grown and become more comprehensive. Patients with sepsis who were admitted to the PICU of the Children's Hospital, Zhejiang University School of Medicine from January 2016 to December 2021 were enrolled in this study. Preoperative non-infectious pediatric patients undergoing elective surgeries in our hospital's department of surgery were recruited as controls during the same period. Clinical data were collected and analyzed. 702 children were enrolled, comprising 538 sepsis survivors, 164 sepsis fatalities, and 269 non-infected controls. Statistical analysis revealed that total BA (TBA) increased in both the early and severe stages of pediatric sepsis. In the severe stage, TBA (OR = 2.898, 95% CI 1.946-4.315, p < 0.05) was identified as a risk factor for sepsis. A clinical model identified TBA (the cut-off value is >17.95 µmol/L) as an independent predictor of sepsis mortality with an AUC of 0.842 (95% CI 0.800-0.883), sensitivity of 54.9%, specificity of 96.6%, and HR = 7.658 (95% CI 5.575-10.520). The study showed that elevated TBA was associated with a heightened risk of mortality in pediatric sepsis. Many clinical indicators show differences between children with sepsis and the control group, among which the difference in serum total bile acid levels is the most significant. During the hospitalization of the patients, the overall bile acid levels in the sepsis death group were higher and exhibited greater fluctuations compared to the survival group, with significant differences. Serum total bile acid levels can serve as effective biomarker for predicting the prognosis of children with sepsis.

IMPACT OF ABCC8 AND TRPM4 GENETIC VARIATION IN CENTRAL NERVOUS SYSTEM DYSFUNCTION ASSOCIATED WITH PEDIATRIC SEPSIS.

Background: Sepsis-associated brain injury is associated with deterioration of mental status, persistent cognitive impairment, and morbidity. The SUR1/TRPM4 channel is a nonselective cation channel that is transcriptionally upregulated in the central nervous system with injury, allowing sodium influx, depolarization, cellular swelling, and secondary injury. We hypothesized that genetic variation in ABCC8 (SUR1 gene) and TRPM4 would associate with central nervous system dysfunction in severe pediatric sepsis. Methods: 326 children with severe sepsis underwent whole exome sequencing in an observational cohort. We compared children with and without central nervous system dysfunction (Glasgow Coma Scale <12) to assess for associations with clinical characteristics and pooled rare variants in ABCC8 and TRPM4. Sites of variation were mapped onto protein structure and assessed for phenotypic impact. Results: Pooled rare variants in either ABCC8 or TRPM4 associated with decreased odds of central nervous system dysfunction in severe pediatric sepsis (OR 0.14, 95% CI 0.003-0.87), P = 0.025). This association persisted following adjustment for race, organ failure, viral infection, and continuous renal replacement therapy (aOR 0.11, 95% CI 0.01-0.59, P = 0.038). Structural mapping showed that rare variants concentrated in the nucleotide-binding domains of ABCC8 and N-terminal melastatin homology region of TRPM4 . Conclusion : This study suggests a role for the ABCC8/TRPM4 channel in central nervous system dysfunction in severe pediatric sepsis. Although exploratory, the lack of therapies to prevent or mitigate central nervous system dysfunction in pediatric sepsis warrants further studies to clarify the mechanism and confirm the potential protective effect of these rare ABCC8/TRPM4 variants.

Med-MGF: multi-level graph-based framework for handling medical data imbalance and representation

BackgroundModeling patient data, particularly electronic health records (EHR), is one of the major focuses of machine learning studies in healthcare, as these records provide clinicians with valuable information that can potentially assist them in disease diagnosis and decision-making.MethodsIn this study, we present a multi-level graph-based framework called MedMGF, which models both patient medical profiles extracted from EHR data and their relationship network of health profiles in a single architecture. The medical profiles consist of several layers of data embedding derived from interval records obtained during hospitalization, and the patient-patient network is created by measuring the similarities between these profiles. We also propose a modification to the Focal Loss (FL) function to improve classification performance in imbalanced datasets without the need to imputate the data. MedMGF’s performance was evaluated against several Graphical Convolutional Network (GCN) baseline models implemented with Binary Cross Entropy (BCE), FL, class balancing parameter α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha$$\\end{document}, and Synthetic Minority Oversampling Technique (SMOTE).ResultsOur proposed framework achieved high classification performance (AUC: 0.8098, ACC: 0.7503, SEN: 0.8750, SPE: 0.7445, NPV: 0.9923, PPV: 0.1367) on an extreme imbalanced pediatric sepsis dataset (n=3,014, imbalance ratio of 0.047). It yielded a classification improvement of 3.81% for AUC, 15% for SEN compared to the baseline GCN+α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha$$\\end{document}FL (AUC: 0.7717, ACC: 0.8144, SEN: 0.7250, SPE: 0.8185, PPV: 0.1559, NPV: 0.9847), and an improvement of 5.88% in AUC and 22.5% compared to GCN+FL+SMOTE (AUC: 0.7510, ACC: 0.8431, SEN: 0.6500, SPE: 0.8520, PPV: 0.1688, NPV: 0.9814). It also showed a classification improvement of 3.86% for AUC, 15% for SEN compared to the baseline GCN+α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha$$\\end{document}BCE (AUC: 0.7712, ACC: 0.8133, SEN: 0.7250, SPE: 0.8173, PPV: 0.1551, NPV: 0.9847), and an improvement of 14.33% in AUC and 27.5% in comparison to GCN+BCE+SMOTE (AUC: 0.6665, ACC: 0.7271, SEN: 0.6000, SPE: 0.7329, PPV: 0.0941, NPV: 0.9754).ConclusionWhen compared to all baseline models, MedMGF achieved the highest SEN and AUC results, demonstrating the potential for several healthcare applications.

Postmortem CT and MRI for detecting bowel obstruction in cases of pediatric sepsis deaths.

This article describes the utility of postmortem CT and MRI in diagnosing pediatric bowel obstruction (BO) as the cause of septic shock-induced death. Six pediatric cases with confirmed septic shock were retrospectively analyzed. Postmortem CT scans revealed clear signs of BO in all cases, with volvulus, intussusception, diaphragmatic hernia, or Meckel's diverticulum identified. MRI scans, performed in three cases, did not provide additional diagnostic information. The presented case series highlights the potential of postmortem CT for diagnosing BO in children, potentially aiding in understanding the cause and manner of death. While MRI offered limited additional benefits, its role in conjunction with CT and autopsy warrants further exploration. Combining these modalities could enhance diagnostic accuracy and provide a more complete picture of the cause of death in children.