Pediatric Sepsis Research Articles

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.

Younger Age and Female Gender Are Associated With Delayed Antibiotics in Pediatric Sepsis.

Sepsis is a leading cause of pediatric mortality and timely antibiotic administration has been shown to improve outcomes. In this retrospective review of a single center sepsis dataset, we identified younger age and female sex as more likely to have delays in antibiotics.

Delays to Antibiotics in the Emergency Department and Risk of Mortality in Children With Sepsis

Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes. To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis. This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour of emergency department arrival, from January 1, 2017, through December 31, 2021. Piecewise regression was used to identify the inflection point for sepsis-attributable 3-day mortality, and logistic regression was used to evaluate odds of sepsis-attributable mortality after adjustment for potential confounders. Data analysis was performed from March 2022 to February 2024. The number of minutes from emergency department arrival to antibiotic administration. The primary outcome was sepsis-attributable 3-day mortality. Sepsis-attributable 30-day mortality was a secondary outcome. A total of 19 515 cases (median [IQR] age, 6 [2-12] years) were included. The median (IQR) time to antibiotic administration was 69 (47-116) minutes. The estimated time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes. Patients who received an antibiotic in less than 330 minutes (19 164 patients) had sepsis-attributable 3-day mortality of 0.5% (93 patients) and 30-day mortality of 0.9% (163 patients). Patients who received antibiotics at 330 minutes or later (351 patients) had 3-day sepsis-attributable mortality of 1.2% (4 patients), 30-day mortality of 2.0% (7 patients), and increased adjusted odds of mortality at both 3 days (odds ratio, 3.44; 95% CI, 1.20-9.93; P = .02) and 30 days (odds ratio, 3.63; 95% CI, 1.59-8.30; P = .002) compared with those who received antibiotics within 330 minutes. In this cohort of pediatric patients with sepsis, 3-day and 30-day sepsis-attributable mortality increased with delays in antibiotic administration 330 minutes or longer from emergency department arrival. These findings are consistent with the literature demonstrating increased pediatric sepsis mortality associated with antibiotic administration delay. To guide the balance of appropriate resource allocation with time for adequate diagnostic evaluation, further research is needed into whether there are subpopulations, such as those with shock or bacteremia, that may benefit from earlier antibiotics.

Social Determinants of Health and Health-Related Quality of Life Following Pediatric Septic Shock: Secondary Analysis of the Life After Pediatric Sepsis Evaluation Dataset, 2014-2017.

Social determinants of health (SDOH) are associated with disparities in disease severity and in-hospital outcomes among critically ill children. It is unknown whether SDOH are associated with later outcomes. We evaluated associations between SDOH measures and mortality, new functional morbidity, and health-related quality of life (HRQL) decline among children surviving septic shock. Secondary analysis of the Life After Pediatric Sepsis Evaluation (LAPSE) prospective cohort study was conducted between 2014 and 2017. Twelve academic U.S. PICUs were involved in the study. Children younger than 18 years with community-acquired septic shock were involved in the study. None. We assessed associations between race, ethnicity, income, education, marital status, insurance, language, and home U.S. postal code with day 28 mortality, new functional morbidity at discharge per day 28, and HRQL decline using logistic regression. Of 389 patients, 32% ( n = 98) of families had household income less than $50,000 per year. Median Pediatric Risk of Mortality (PRISM) score was 11 (interquartile range 6, 17). We found that English language and Area Deprivation Index less than 50th percentile were associated with higher PRISM scores. Mortality was 6.7% ( n = 26), new functional morbidity occurred in 21.8% ( n = 78) of patients, and HRQL decline by greater than 10% occurred in 31.0% of patients ( n = 63). We failed to identify any association between SDOH measures and mortality, new functional morbidity, or HRQL decline. We are unable to exclude the possibility that annual household income greater than or equal to $50,000 was associated with up to 81% lesser odds of mortality and, in survivors, more than three-fold greater odds of HRQL decline by greater than 10%. In this secondary analysis of the 2014-2017 LAPSE dataset, we failed to identify any association between SDOH measures and in-hospital or postdischarge outcomes following pediatric septic shock. This finding may be reflective of the high illness severity and single disease (sepsis) of the cohort, with contribution of clinical factors to functional and HRQL outcomes predominating over prehospital and posthospital SDOH factors.

Evaluation of performance of Indonesian Sepsis National Guidelines (PNPK) 2021 in diagnosing pediatric bacterial sepsis

Background Sepsis remains one of the causes of child morbidity and mortality worldwide. The reference standard diagnosis of sepsis is blood culture, but its false negative is relatively high. Therefore, a validated triage tool is needed for rapid diagnosis. In Indonesia, diagnosis and management of pediatric sepsis are based on Indonesian Sepsis National Guidelines 2021. Objective To evaluate the performance of Indonesian Sepsis National Guidelines 2021 in diagnosing pediatric bacterial sepsis in PICU. Methods This cross-sectional study was conducted in the PICU unit of Dr. Sardjito Hospital, Yogyakarta, using subject’s the medical records. All patients with suspected bacterial infection who were admitted to the PICU, had complete evaluation of PELOD-2 score, and the blood culture results were included in this study. Sepsis was assessed with Indonesian Sepsis National Guidelines 2021. Performance analysis of the guidelines was conducted with SPSS version 25, by assessing sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and likelihood ratio. Results Two hundred subjects were enrolled in this study, of whom 52.5% were males. Most subjects aged under one year (40.5%), and the most common infection was respiratory system (49%). A total of 63.5% were referral cases, with the length of stay in the previous hospital more than 48 hours (69.7%). There were 77% of subjects had antibiotics treatment at the previous hospital. As for outcomes, 63.5% survived and 36.5% died. The positivity rate of blood culture in this study was 19%. Performance evaluation of Sepsis Indonesian Sepsis National Guidelines 2021 revealed sensitivity 28.95%, specificity 87.65%, accuracy 76.5%, positive predictive value 35.48%, negative predictive value 84.02%, positive likelihood ratio 2.34 (95%CI 1.28 to 4.32) and negative likelihood ratio 0.81 (95%CI 0.7 to 0.94). Conclusion Indonesian Sepsis National Guidelines 2021 (PNPK Sepsis 2021) has low sensitivity and high specificity in diagnosing bacterial sepsis.

Potential biomarkers used for risk estimation of pediatric sepsis-associated organ dysfunction and immune dysregulation.

Pediatric sepsis is a serious issue globally and is a significant cause of illness and death among infants and children. Refractory septic shock and multiple organ dysfunction syndrome are the primary causes of mortality in children with sepsis. However, there is incomplete understanding of mechanistic insight of sepsis associated organ dysfunction. Biomarkers present during the body's response to infection-related inflammation can be used for screening, diagnosis, risk stratification/prognostication, and/or guidance in treatment decision-making. Research on biomarkers in children with sepsis can provide information about the risk of poor outcomes and sepsis-related organ dysfunction. This review focuses on clinically used biomarkers associated with immune dysregulation and organ dysfunction in pediatric sepsis, which could be useful for developing precision medicine strategies in pediatric sepsis management in the future. IMPACT: Sepsis is a complex syndrome with diverse clinical presentations, where organ dysfunction is a key factor in morbidity and mortality. Early detection of organ complications is vital in sepsis management, and potential biomarkers offer promise for precision medicine in pediatric cases. Well-designed studies are needed to identify phase-specific biomarkers and improve outcomes through more precise management.

Potential risk factors of pediatric acute respiratory distress syndrome in sepsis

Background Sepsis in children is characterized by a dysregulated host response to infection and life-threatening organ dysfunction. Pediatric acute respiratory distress syndrome (PARDS) is a severe complication of sepsis. Several known risk factors of PARDS are immunodeficiency, obesity, source of infection, and genetic factors. Objective To describe the potential risk factors of PARDS in septic children at Haji Adam Malik General Hospital, Medan, North Sumatera. Methods This descriptive study using eligible medical record data from sepsis patients aged 1 month – 18 years was conducted at Haji Adam Malik General Hospital in 2020–2022. A total sampling method was used for subject selection. Patients’ demographic and clinical characteristics, mechanical ventilation modes and parameters, laboratory results, and outcomes were collected from medical records. Patients were classified as having sepsis with PARDS if Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria of ARDS was met. Results Of 112 pediatric sepsis patients, 33.9% developed PARDS. The mortality rates for PARDS was 73.7%. Of the patients with PARDS, 57.9% had immunodeficiency, 60.5% patients had an intrapulmonary infection, 39.5% had an extrapulmonary infection, and 23.7% of patients had a suspected genetic disorder. In addition, 39.5% had good nutritional status, followed by 21.1% with obese. Conclusion The majority of patients with PARDS have intrapulmonary infection and immunodeficiency. Some of patients with PARDS have suspected genetic disorders and well nourished.

Screening and Identification of Neutrophil Extracellular Trap-related Diagnostic Biomarkers for Pediatric Sepsis by Machine Learning.

Neutrophil extracellular trap (NET) is released by neutrophils to trap invading pathogens and can lead to dysregulation of immune responses and disease pathogenesis. However, systematic evaluation of NET-related genes (NETRGs) for the diagnosis of pediatric sepsis is still lacking. Three datasets were taken from the Gene Expression Omnibus (GEO) database: GSE13904, GSE26378, and GSE26440. After NETRGs and differentially expressed genes (DEGs) were identified in the GSE26378 dataset, crucial genes were identified by using LASSO regression analysis and random forest analysis on the genes that overlapped in both DEGs and NETRGs. These crucial genes were then employed to build a diagnostic model. The diagnostic model's effectiveness in identifying pediatric sepsis across the three datasets was confirmed through receiver operating characteristic curve (ROC) analysis. In addition, clinical pediatric sepsis samples were collected to measure the expression levels of important genes and evaluate the diagnostic model's performance using qRT-PCR in identifying pediatric sepsis in actual clinical samples. Next, using the CIBERSORT database, the relationship between invading immune cells and diagnostic markers was investigated in more detail. Lastly, to evaluate NET formation, we measured myeloperoxidase (MPO)-DNA complex levels using ELISA. A group of five important genes (MME, BST1, S100A12, FCAR, and ALPL) were found among the 13 DEGs associated with NET formation and used to create a diagnostic model for pediatric sepsis. Across all three cohorts, the sepsis group had consistently elevated expression levels of these five critical genes as compared to the normal group. Area under the curve (AUC) values of 1, 0.932, and 0.966 indicate that the diagnostic model performed exceptionally well in terms of diagnosis. Notably, when applied to the clinical samples, the diagnostic model also showed good diagnostic capacity with an AUC of 0.898, outperforming the effectiveness of traditional inflammatory markers such as PCT, CRP, WBC, and NEU%. Lastly, we discovered that children with high ratings for sepsis also had higher MPO-DNA complex levels. In conclusion, the creation and verification of a five-NETRGs diagnostic model for pediatric sepsis performs better than established markers of inflammation.

Diagnostic value of procalcitonin and hemocyte parameters in neonates with bloodstream infection: Role of activated hemocyte‐related genes

AbstractThis study aimed to evaluate the diagnostic potential of hemocyte parameters and procalcitonin (PCT) in detecting bloodstream infections (BSI) in neonates and explore the contribution of hemocyte activation‐related genes to pediatric sepsis through bioinformatics analysis. A cohort of 419 neonates, categorized as BSI (positive blood culture) and control, underwent comparative analysis of PCT and hemocyte parameters. A predictive model for neonatal BSI was established, demonstrating an impressive area under the receiver ROC curve of 0.968 with remarkable sensitivity (92%) and specificity (87.3%). Hemocyte parameters, including lymphocyte and neutrophil percentages, platelet distribution width (PDW), platelet to lymphocyte ratio (PLR), and PCT, emerged as independent predictors of neonatal BSI. Furthermore, bioinformatics analysis utilizing Gene Expression Omnibus (GEO) datasets yielded significant insights. Differential gene expression (DEGs), gene ontology (GO), pathway enrichment, gene set enrichment analysis (GSEA), and protein–protein interaction (PPI) networks were explored. The differentially expressed genes and hub genes were notably enriched in the activation of neutrophils, lymphocytes, and platelets. Notably, elevated expression levels of SPI1, TYROBP, and FCER1G were observed in pediatric sepsis or septic shock, with positive correlations between SPI1, FCER1G, and TYROBP. In summary, the combination of lymphocyte, PDW, PLR, and PCT effectively diagnosed neonatal BSI. Bioinformatics analysis underscored the pivotal role of activated hemocytes in diagnosing pediatric sepsis, with SPI1, TYROBP, and FCER1G co‐expression influencing the disease's pathophysiology by modulating neutrophil and platelet activity.

Lactate dynamics in paediatric patients with severe sepsis: insights from a prospective cohort study

BackgroundSepsis is an infection-related systemic inflammatory response that often leads to elevated lactate levels. Monitoring lactate levels during severe sepsis is vital for influencing clinical outcomes. The aim of this study was to assess the association between plasma lactate levels and mortality in children with severe sepsis or septic shock.MethodsThe current prospective study was conducted in the PICU of University Children’s Hospital. The International Paediatric Sepsis Consensus Conference criteria for Definitions of Sepsis and Organ Failure in 2005 were used to diagnose patients with sepsis. We measured plasma lactate levels upon admission (Lac H0) and 6 h later (Lac H6). The static indices included the absolute lactate values (Lac H0 and Lac H6), while the dynamic indices included the delta-lactate level (ΔLac) and the 6-hour lactate clearance. The 6-hour lactate clearance was calculated using the following formula: [(Lac H0–Lac H6)100/Lac H0]. ΔLac was calculated as the difference between the Lac H0 and Lac H6 levels. Patient survival or death after a PICU stay was the primary outcome.ResultsA total of 46 patients were included in this study: 25 had septic shock, and 21 had severe sepsis. The mortality rate was 54.3%. The Lac H0 did not significantly differ between survivors and nonsurvivors. In contrast, the survivors had significantly lower Lac H6 levels, higher ΔLac levels, and higher 6-hour lactate clearance rates than nonsurvivors. Lactate clearance rates below 10%, 20%, and 30% were significantly associated with mortality. The best cut-off values for the lactate clearance rate and Lac H6 for the prediction of mortality in the PICU were < 10% and ≥ 4 mmol/L, respectively. Patients with higher Lac H6 levels and lower lactate clearance rates had significantly higher PICU mortality based on Kaplan–Meier survival curve analysis.ConclusionsThis study highlights the significance of lactate level trends over time for the prediction of mortality in the PICU in patients with severe sepsis or septic shock. Elevated lactate levels and decreased lactate clearance six hours after hospitalisation are associated with a higher mortality rate.

Survey of Thai Physicians' Practice in Pediatric Septic Shock.

(1) Background: Sepsis management in children is crucial, especially in emergency services. This study aims to evaluate Thai physicians' knowledge gaps in the emergency management of sepsis in children and to evaluate their adherence to the current sepsis clinical practice guidelines. (2) Methods: This is a cross-sectional survey of Thai physicians' management of septic shock in children. The survey was conducted through online questionnaires from March 2019-April 2019. (3) Results: Of the 366 responders, 362 (98.9%) were completed. Most of the responders were general practitioners (89.2%) and pediatricians (10.8%). The time from positive sepsis screening to being evaluated by physicians within 15 min was reported by 83.9%. The most common choice of fluid resuscitation was normal saline solution (77.3%). The practice of a fluid loading dose (20 mL/kg) consistent with the guidelines was 56.3%. The selection of the first vasoactive agent in warm shock (norepinephrine) and cold shock (epinephrine) according to recommendations in the guidelines was 74.3% and 36.2%, respectively. There was a significant difference between general practitioners and pediatricians in terms of knowledge about initial fluid resuscitation and the optimal vasoactive agent in cold shock (p-value < 0.001). In the multivariate model, factors associated with the guideline-based decision-making of vasoactive agent choice for cold shock were specialist training (pediatrician) and the completion of sepsis management training certification, with adjusted odds ratios (AORs) of 7.81 and 2.96, but working experience greater than ten years was inconsistent with the guideline-based decision-making (AOR 0.14). (4) Conclusions: Thai clinicians were unfamiliar with pediatric sepsis therapy standards, specifically the quantity of early fluid resuscitation and the appropriate vasoactive medications for cold shock. To encourage adherence to the guidelines, we propose a regularly required training course on pediatric sepsis management.

Characteristics and Risk Factors for Pediatric Sepsis.

Sepsis is considered a major cause of health loss in children and had high mortality and morbidity. Currently, there is no reliable model for predicting the prognosis of pediatric patients with sepsis. This study aimed to analyze the clinical characteristics of sepsis in children and assess the risk factors associated with poor prognosis in pediatric sepsis patients to identify timely interventions and improve their outcomes. This study analyzed the clinical indicators and laboratory results of septic patients hospitalized in the Pediatric Intensive Care Unit of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, from January 1, 2019, to December 31, 2021. Risk factors for sepsis were identified by logistic regression analyses. A total of 355 children with sepsis were enrolled, with 333 children (93.8%) in the good prognosis group, and 22 children (6.2%) in the poor prognosis group. Among them, there were 255 patients (71.8%) in the sepsis group, and 100 patients (28.2%) in the severe sepsis group. The length of hospital stay in the poor prognosis group was longer than that in the good prognosis group (P<0.01). The levels of interleukin 1β (IL-1β) in the poor prognosis group were higher than those in the good prognosis group (P>0.05), and the platelet (PLT), albumin (ALB), and hemoglobin (Hb) levels were lower in the poor prognosis group (P<0.01). The IL-8 levels in the severe sepsis group were higher than those in the sepsis group (P<0.05). Multiple logistic regression analysis suggested that lower Hb levels, ALB levels, peak PLT counts, and higher IL-1β levels were independent risk factors for poor prognosis in children with sepsis. Lower Hb, ALB, and PLT counts and elevated IL-1β are independent risk factors for poor prognosis in children with sepsis.

Diagnostic Identification of Acute Brain Dysfunction in Pediatric Sepsis and Septic Shock in the Electronic Health Record: A Comparison of Four Definitions in a Reference Dataset.

Acute brain dysfunction (ABD) in pediatric sepsis has a prevalence of 20%, but can be difficult to identify. Our previously validated ABD computational phenotype (CP ABD ) used variables obtained from the electronic health record indicative of clinician concern for acute neurologic or behavioral change. We tested whether the CP ABD has better diagnostic performance to identify confirmed ABD than other definitions using the Glasgow Coma Scale or delirium scores. Diagnostic testing in a curated cohort of pediatric sepsis/septic shock patients. Quaternary freestanding children's hospital. The test dataset comprised 527 children with sepsis/septic shock managed between 2011 and 2021 with a prevalence (pretest probability) of confirmed ABD of 30% (159/527). CP ABD was based on use of neuroimaging, electroencephalogram, and/or administration of new antipsychotic medication. We compared the performance of the CP ABD with three GCS/delirium-based definitions of ABD-Proulx et al, International Pediatric Sepsis Consensus Conference, and Pediatric Organ Dysfunction Information Update Mandate. The posttest probability of identifying ABD was highest in CP ABD (0.84) compared with other definitions. CP ABD also had the highest sensitivity (83%; 95% CI, 76-89%) and specificity (93%; 95% CI, 90-96%). The false discovery rate was lowest in CP ABD (1-in-6) as was the false omission rate (1-in-14). Finally, the prevalence threshold for the definitions varied, with the CP ABD being the definition closest to 20%. In our curated dataset of pediatric sepsis/septic shock, CP ABD had favorable characteristics to identify confirmed ABD compared with GCS/delirium-based definitions. The CP ABD can be used to further study the impact of ABD in studies using large electronic health datasets.

Role of growth arrest-specific protein 6 in diagnosis and prognosis of sepsis in infants and children

Background Sepsis is a main cause of mortality in the pediatrics and neonates. Early goal-directed therapy is the cornerstone in sepsis management that is focuses on keeping organ perfusion and function normally. Diagnosis of pediatric sepsis in the emergency department is considered a significant challenge for clinicians for many reasons. These include a lack of fast and accurate diagnostic tools, an absence of simple and specific diagnostic criteria, and unclear symptoms during the early phase of illness. The best predictive tool in the future will likely be a combination of multiple biomarkers and physiomarkers. Growth arrest-specific protein 6 (Gas6) is an anti-apoptotic vitamin-K-dependent protein. It is secreted by endothelial cells and is important for the activation of endothelium during inflammation. Several studies hypothesize the use of Gas6 as a biomarker in the pathophysiology of sepsis, an early predictor of mortality, and were able to identify some life-threatening sepsis complications. Aim Evaluation of the diagnostic and prognostic values of plasma Gas6 in patients with sepsis, septic shock, and multiple organ dysfunction syndrome in infants and children. Patients and methods Case-control study was carried out from April 2019 to April 2020. 90 children were included and divided into two equal groups (cases and controls). The patients aged from 1 month to 18 years were diagnosed with sepsis, septic shock, or multiple organ dysfunction syndrome in the pediatric intensive care unit of Mansoura University Children’s Hospital. The level of plasma Gas6 was measured in both cases and controls and evaluated as regards its relation to diagnosis and outcome of the cases. Results The two groups were age and sex matched. The outcome of the cases group was: 16 cases are discharged, and 29 died. A significant elevation of plasma Gas6 level in the cases more than the controls (sensitivity= 84.4% and specificity= 66.7%). However, no statistically significant difference as regard the relation between plasma Gas6 level and the outcome of the cases (sensitivity= 55.2% and specificity= 62.7%). Conclusion Gas6 show statistically significant elevation in cases of sepsis, septic shock and multiorgan failure. Gas6 plasma level has high accuracy in prediction of sepsis and can be considered as a good negative marker of sepsis but not a reliable prognostic marker in septic patients.

Utility of Red Blood Cell Distribution Width to Albumin Ratio and Hemoglobin to Red Blood Cell Distribution Width Ratio as Biomarkers in Pediatric Sepsis

Objectives − The objective was to compare these parameters in children with severe and non-severe sepsis and to evaluate their utility in predicting mortality. Material and Methods − A cross-sectional study conducted in the Pediatric Intensive Care of a dis- trict hospital in India. The hematological parameters of 54 children with severe sepsis and 55 with non-severe sepsis were analysed.Results − The children with severe sepsis had significantly lower HRR (Hemoglobin-RDW ratio) with higher RDW, plateletcrit and RAR as compared to those with non-severe sepsis. There were no significant differences between the groups with respect to the differential and total white blood cell counts or their ratios and other platelet indices. As compared to the survivors, non-survivors had significantly lower HRR with higher RDW and RAR. At a cut-off value of 3.845, RAR was 79.2% sensitive and 59% specific and at a cut-off value of 0.712 HRR was 77.8% sensitive and 60% specific in prediction of mortality.Conclusions − Children with severe sepsis had higher RAR and lower HRR when compared with children with non-severe sepsis. Significantly higher RAR and lower HRR were also noted among non-survivors as compared to survivors. The biomarkers RAR and HRR are readily available and useful in predicting mortality in children with sepsis.

Adaptive platform trials rather than randomised controlled trials for paediatric sepsis.

Adaptive platform trials (APTs) offer a promising alternative to traditional randomised controlled trials for evaluating treatments for paediatric sepsis. Randomised controlled trials, despite being the gold standard for establishing causality between interventions and outcomes, make many assumptions about disease prevalence, severity and intervention effects, which are often incorrect. As a result, the evidence for most treatments for paediatric sepsis are based on low-quality evidence. APTs use accrued data rather than assumptions to power trial adaptations. They can assess multiple treatments simultaneously with shared research infrastructure. As such, APTs offer a more efficient, flexible and more effective way to identify optimal treatments. The proposed Paediatric Adaptive Sepsis Platform Trial, leveraging the Paediatric Research in Emergency Departments International Collaborative network's infrastructure, will evaluate resuscitation fluids, vasoactive medications, corticosteroids and antimicrobials. This trial has the potential to substantially impact clinical practice and reduce global sepsis mortality in children.

Predictive Value of a Diagnostic Five-Gene Biomarker for Pediatric Sepsis.

Pediatric sepsis has a very high morbidity and mortality rate. The purpose of this study was to evaluate diagnostic biomarkers and immune cell infiltration in pediatric sepsis. Three datasets (GSE13904, GSE26378, and GSE26440) were downloaded from the gene expression omnibus (GEO) database. After identifying overlapping genes in differentially expressed genes (DEGs) and modular sepsis genes selected via a weighted gene co-expression network (WGCNA) in the GSE26378 dataset, pivotal genes were further identified by using LASSO regression and random forest analysis to construct a diagnostic model. Receiver operating characteristic curve (ROC) analysis was used to validate the efficacy of the diagnostic model for pediatric sepsis. Furthermore, we used qRT-PCR to detect the expression levels of pivotal genes and validate the diagnostic model's ability to diagnose pediatric sepsis in 65 actual clinical samples. Among 294 overlapping genes of DEGs and modular sepsis genes, five pivotal genes (STOM, MS4A4A, CD177, MMP8, and MCEMP1) were screened to construct a diagnostic model of pediatric sepsis. The expression of the five pivotal genes was higher in the sepsis group than in the normal group. The diagnostic model showed good diagnostic ability with AUCs of 1, 0.986, and 0.968. More importantly, the diagnostic model showed good diagnostic ability with AUCs of 0.937 in the 65 clinical samples and showed better efficacy compared to conventional inflammatory indicators such as procalcitonin (PCT), white blood cell (WBC) count, C-reactive protein (CRP), and neutrophil percentage (NEU%). We developed and tested a five-gene diagnostic model that can reliably identify pediatric sepsis and also suggest prospective candidate genes for peripheral blood diagnostic testing in pediatric sepsis patients.

NOVEL ECHOCARDIOGRAM ANALYSIS OF CARDIAC DYSFUNCTION IS ASSOCIATED WITH MORTALITY IN PEDIATRIC SEPSIS.

Objectives: The objective of our study was to semiautomatically generate echocardiogram indices in pediatric sepsis using novel algorithms and determine which indices were associated with mortality. We hypothesized that strain and diastolic indices would be most associated with mortality. Design: Retrospective cohort study of children with sepsis from 2017 to 2022. Survivors and nonsurvivors were compared for echocardiogram indices. Multivariate Cox proportional hazard models were constructed for our primary outcome of in-hospital mortality. Linear regression was performed for secondary outcomes, which included multiple composite 28-day outcomes. Results: Of the 54 patients in the study, 9 (17%) died. Multiple echocardiogram indices of both right (RV) and left ventricles (LV) were associated with in-hospital mortality [RV GLS adjusted hazard ratio (aHR): 1.16 (1.03-1.29), P = 0.011; RV global longitudinal early diastolic strain rate (GLSre) aHR: 0.24 (0.07 to 0.75), P = 0.014; LV GLSre aHR: 0.33 (0.11-0.97), P = 0.044]. Impairment in GLS was associated with fewer ventilator-free days [RV GLS β-coefficient: -0.47 (-0.84 to -0.10), P = 0.013; LV GLS β-coefficient -0.62 (-1.07 to -0.17), P = 0.008], organ-support free days [RV GLS β-coefficient: -0.49 (-0.87 to -0.11), P = 0.013; LV GLS β-coefficient: -0.64 (-1.10 to -0.17), P = 0.008], and days free from ICU [RV GLS β-coefficient: -0.42 (-0.79 to -0.05), P = 0.026; LV GLS β-coefficient: -0.58 (-1.03 to -0.13), P = 0.012]. Systolic indices were not associated with mortality in this cohort. Conclusion: Our study demonstrates the feasibility of obtaining echocardiogram indices in a semiautomatic method using our algorithms. We showed that abnormal strain is associated with worse outcomes in a cohort of children with sepsis.

Retracted: Identification of a Four-Gene Signature for Diagnosing Paediatric Sepsis.

[This retracts the article DOI: 10.1155/2022/5217885.].

Clinical value of TAT, PIC and t-PAIC as predictive markers for severe sepsis in pediatric patients.

Sepsis in pediatric patients can progress to severe sepsis, and identifying biomarkers of this progression may permit timely intervention to prevent it. This study aimed to investigate the ability of thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC) and tissue-type plasminogen activator-inhibitor complex (t-PAIC) to predict severe sepsis in pediatrics early. 148 eligible pediatric sepsis patients were enrolled in this study, and were then divided into those who progressed to severe sepsis (n = 50) or not (n = 98). Serum levels of TAT, PIC, and t-PAIC were analysed, and simplified pediatric critical illness score (PCIS) and DIC score were calculated on the day of pediatric sepsis diagnosis. Compared with sepsis patients, severe sepsis patients had higher levels of TAT, PIC and t-PAIC. Correlation analysis revealed that TAT, PIC and t-PAIC were significantly correlated with simplified PCIS and DIC score. ROC curve analysis suggested that TAT, PIC and t-PAIC could serve as biomarkers for predicting severe sepsis with the AUC up to 0.862, 0.759 and 0.851, respectively. Stratified analysis demonstrated that the patients with increased levels of TAT, PIC and t-PAIC had worse illness severity and clinical outcome. Univariate logistic regression analysis revealed that TAT, PIC and t-PAIC were all risk factors for severe sepsis, yet only TAT and t-PAIC were independent risk factors in multivariate model. TAT, PIC and t-PAIC could serve as biomarkers for predicting severe sepsis, and correlated with illness severity in pediatrics, what's more, serum levels of TAT and t-PAIC may be independent risk factors for pediatric severe sepsis.