Sepsis In Pediatric Patients Research Articles

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.

Examining the relationship between alterations in plasma cholesterol, vascular endothelin-1 levels, and the severity of sepsis in children: An observational study.

Considering the significant impact of total cholesterol (TC) and vascular endothelin-1 (ET-1) on children sepsis outcomes, this research aimed to explore the association between the levels of plasma cholesterol and vascular endothelin-1 and the severity of sepsis and evaluated its clinical implications. In this study, we examined 250 pediatric patients diagnosed with sepsis between February 2019 and April 2021, collecting data on their plasma levels of TC and ET-1. Depending on the observed outcomes, the participants were divided into 2 categories: a group with a positive prognosis (control group, n = 100) and a group with a negative prognosis (n = 50). We assessed the significance of plasma TC and ET-1 levels in forecasting the outcomes for these pediatric patients. Patients in the group with a poor prognosis experienced notably longer hospital stays and higher treatment expenses than those in the control group (P < .05). Within the first 24 hours of admission and again on days 3 and 7, the levels of ET-1 were significantly higher in the poor prognosis group, whereas plasma TC levels were notably lower in comparison to the control group (P < .05). A Spearman correlation analysis identified a significant correlation between the levels of plasma TC and ET-1 and the severity of sepsis among the children (P < .05). The diagnostic performance for the severity of sepsis in children, as measured by the area under the curve (AUC), was 0.805 for plasma TC, 0.777 for ET-1 levels, and 0.938 when both were combined. This investigation underscores a meaningful relationship between the levels of plasma TC and ET-1 in pediatric sepsis patients, suggesting these biomarkers are highly valuable in predicting patient outcomes. High levels of ET-1 and low levels of TC in these patients signify a grave condition and a poor prognosis.

Comparative Analysis of C-reactive Protein and Procalcitonin as Biomarkers for Prognostic Assessment in Pediatric Sepsis.

Background Sepsis poses a critical medical challenge due to its profound systemic inflammatory response, which frequently results in organ dysfunction and high mortality rates, especially in pediatric patients. The condition requires prompt recognition and aggressive management to mitigate its severe outcomes. Methods This prospective study enrolled 248 pediatric patients admitted with sepsis to the pediatric intensive care unit (PICU) at our tertiary care center. Patients were randomly assigned to either the C-reactive protein (CRP) or procalcitonin (PCT) groups, with biomarker levels measured upon admission (hour zero) and again at 72 hours post-admission. Clinical parameters such as the need for ionotropic support, use of steroids, incidence of acute kidney injury (AKI), requirement for invasive ventilation, patient outcomes, and changes in antibiotic management were assessed based on these biomarker levels. Results Procalcitonin-positive sepsis cases demonstrated notable clinical severity compared to their C-reactive protein counterparts, showing significantly lower systolic blood pressure (p = 0.012), heightened need for ionotropic support (p < 0.0001), and more pronounced liver and renal dysfunction as indicated by elevated serum bilirubin (p = 0.001) and creatinine levels (p = 0.0058). The incidence of AKIwas also higher in procalcitonin-positive cases. Despite these severe clinical parameters, there were no significant differences in the length of the PICU stay or in patient outcomes concerning discharge and mortality rates. Procalcitonin levels effectively guided antibiotic management, resulting in therapy adjustments in a substantial proportion of cases, with 67 (54%) experiencing downgrades and 33 (27%) requiring upgrades based on procalcitonin levels measured 72 hours post-admission. Conclusion Procalcitonin proves to be a valuable biomarker in assessing the severity and management of sepsis in pediatric patients. It correlates significantly with clinical parameters such as blood pressure, the need for ionotropic support, and markers of organ dysfunction.

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.

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.

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.

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.

A tagging polymorphism in fat mass and obesity-associated (FTO) gene is associated with sepsis status in children.

Sepsis is one of the most common causes of death in patients admitted to intensive care units (ICUs). The development of sepsis is significantly influenced by genetic predisposition. In this study, we highlight a potential association between a variant of the fat mass and obesity-associated (FTO) gene and risk of sepsis in children and adolescents. We investigated a first-intron tagging FTO polymorphism (rs17817449) by comparing a severe condition (SC) group, comprising 598 paediatric patients (ages 0-19 years) admitted to an ICU with fever, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple organ dysfunction syndrome (MODS), with a control group consisting of 616 healthy young adults. We observed a lower prevalence (p < 0.01; OR = 0.59, 95% CI = 0.39-0.87) of the FTO TT genotype in febrile and SIRS patients compared to patients with severe illness. There was a borderline trend towards a lower prevalence of the FTO TT genotype in the control group compared to the SC group (p < 0.09, OR = 0.81, 95% CI = 0.62-1.06). Our findings suggest that rs17817449, a common FTO polymorphism, may be a predictor of sepsis in paediatric patients, and that higher body weight is protective against this clinical complication.

Pediatric sepsis inflammatory blood biomarkers that correlate with clinical variables and severity of illness scores

BackgroundSepsis is a dysregulated systemic inflammatory response triggered by infection, resulting in organ dysfunction. A major challenge in clinical pediatrics is to identify sepsis early and then quickly intervene to reduce morbidity and mortality. As blood biomarkers hold promise as early sepsis diagnostic tools, we aimed to measure a large number of blood inflammatory biomarkers from pediatric sepsis patients to determine their predictive ability, as well as their correlations with clinical variables and illness severity scores.MethodsPediatric patients that met sepsis criteria were enrolled, and clinical data and blood samples were collected. Fifty-eight inflammatory plasma biomarker concentrations were determined using immunoassays. The data were analyzed with both conventional statistics and machine learning.ResultsTwenty sepsis patients were enrolled (median age 13 years), with infectious pathogens identified in 75%. Vasopressors were administered to 85% of patients, while 55% received invasive ventilation and 20% were ventilated non-invasively. A total of 24 inflammatory biomarkers were significantly different between sepsis patients and age/sex-matched healthy controls. Nine biomarkers (IL-6, IL-8, MCP-1, M-CSF, IL-1RA, hyaluronan, HSP70, MMP3, and MMP10) yielded AUC parameters > 0.9 (95% CIs: 0.837-1.000; p < 0.001). Boruta feature reduction yielded 6 critical biomarkers with their relative importance: IL-8 (12.2%), MCP-1 (11.6%), HSP70 (11.6%), hyaluronan (11.5%), M-CSF (11.5%), and IL-6 (11.5%); combinations of 2 biomarkers yielded AUC values of 1.00 (95% CI: 1.00–1.00; p < 0.001). Specific biomarkers strongly correlated with illness severity scoring, as well as other clinical variables. IL-3 specifically distinguished bacterial versus viral infection (p < 0.005).ConclusionsSpecific inflammatory biomarkers were identified as markers of pediatric sepsis and strongly correlated to both clinical variables and sepsis severity.

The efficacy and acceptability of anti-inflammatory omega-3 polyunsaturated fatty acid supplements in sepsis management: a network meta-analysis of randomized controlled trials

Sepsis is a critical medical condition associated with high mortality for patients. Current pharmacological strategies for sepsis management or prevention had not achieved satisfactory results. The omega-3 fatty acids, with anti-inflammatory benefits, are considered to be promising agents for sepsis management/prevention. The aim of this network meta-analysis (NMA) is to compare the efficacy of various dosages and formulations of fish oil supplements for sepsis management and sepsis prevention. The current NMA consisted of two parts: (1) sepsis management and (2) sepsis prevention. The PubMed, ClinicalKey, Embase, ProQuest, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of February 22nd, 2024 for relevant randomized controlled trials (RCTs). RCTs were eligible for inclusion if they enrolled participants with a diagnosis of sepsis or who with high risk for sepsis. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed are (1) mortality rate in sepsis treatment or (2) incidence of sepsis in sepsis prevention. Our NMA, based on 28 RCTs and 1718 participants (mean age=51.6 years, mean female proportion=35.6 %), showed that (1) high dose parenteral fish oil supplement yield the lowest mortality rate in sepsis management in adult patients, and (2) high dose enteral fish oil supplement yield the lowest incidence of sepsis in pediatric patients. This study provides compelling evidence that high-dose fish oil supplements provide beneficial effects for both sepsis management and sepsis prevention. Our findings provide a preliminary rationale for future large-scale RCTs to investigate the role of fish oil supplementation in sepsis management or prevention.

Validating the performance of organ dysfunction scores in children with infection: A cohort study.

We aimed to validate the performance of six available scoring models for predicting hospital mortality in children with suspected or confirmed infections. This single-center retrospective cohort study included pediatric patients admitted to the PICU for infection. The primary outcome was hospital mortality. The six scores included the age-adapted pSOFA score, SIRS score, PELOD2 score, Sepsis-2 score, qSOFA score, and PMODS. Of the 5,356 children admitted to the PICU, 9.1% (488) died, and 25.1% (1,342) had basic disease with a mortality rate of 12.7% (171); 65.3% (3,499) of the patients were younger than 2 years, and 59.4% (3,183) were male. The discrimination abilities of the pSOFA and PELOD2 scores were superior to those of the other models. The calibration curves of the pSOFA and PELOD2 scores were consistent between the predictions and observations. Elevated lactate levels were a risk factor for mortality. The pSOFA and PELOD2 scores had superior predictive performance for mortality. Given the relative unavailability of items and clinical operability, the pSOFA score should be recommended as an optimal tool for acute organ dysfunction in pediatric sepsis patients. Elevated lactate levels are related to a greater risk of death from infection in children in the PICU.

Cortisol levels associated with mortality in children with critical illness: a systematic review

Background Critically ill patients, including those with sepsis, have increased cortisol levels due to activation of the hypothalamic-pituitary-adrenal (HPA) axis or critical illness-related corticosteroid insufficiency (CIRCI).&#x0D; Objective To evaluate for a possible association between cortisol levels and mortality from sepsis in pediatric patients by systematic review of the literature.&#x0D; Methods A systematic review was conducted on studies involving critically ill children, including those with sepsis. We included studies published between 2011-2020 analyzing data on cortisol levels (total serum cortisol, serum-free cortisol, salivary cortisol, real-time free cortisol, basal serum cortisol and post-adrenocorticotropin hormone (ACTH) stimulation test, or basal salivary cortisol and post-ACTH stimulation test), the predictive score for mortality (Pediatric Logistic Organ Dysfunction/PELOD), Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality (PIM), Vasotropic Inotropic Score (VIS), or Pediatric Critical Illness Score (PCIS)], mortality (non-survivor percentage), and CIRCI percentage as an outcome in patients with critical illness, sepsis, and septic shock.&#x0D; Results Twenty-one observational studies were included in our systematic review, with a total of 2,212 subjects, 916 of whom had sepsis. Nineteen studies indicated a positive association between elevated cortisol levels and mortality in critically ill children, but 2 studies stated that there was no association with the CIRCI percentage of 32.3 and 84.3% respectively. The mortality percentage of critically ill patients with elevated cortisol levels and sepsis were 25.81 (2.7-60)% and 35.31 (6-60)%, respectively. The percentages of CIRCI in critically ill and sepsis patients were 21.91 (0-84.3)% and 21.35 (0-84.3)%, respectively.&#x0D; Conclusion Cortisol levels may increase or decrease in critically ill children. Elevated cortisol levels are associated with mortality in septic children. The effect of CIRCI on mortality in critically ill children cannot be concluded.

Diagnostic Accuracy of Serum Presepsin as Biomarker of Bacterial Sepsis in Paediatric Patients

Diagnostic Accuracy of Serum Presepsin as Biomarker of Bacterial Sepsis in Paediatric Patients

Pediatric sepsis profile in a tertiary-care hospital in Indonesia: a 4-year retrospective study.

This study aimed to explore the factors contributing to mortality and its management among pediatric sepsis patients at a single center in Indonesia. We conducted a retrospective study of children admitted due to sepsis from January 2015 to December 2019 in an Indonesian tertiary hospital. The mortality rate of pediatric sepsis in our study was 76.1% among 176 records with outcome identified. Mortality was significantly associated with septic shock at triage, number of organ failure, intensive care unit admission, inotropic use, septic shock and severe sepsis during hospitalization. Timing of antibiotic use did not affect mortality. Death within the first 24 h occurred in 41.8% of subjects, mostly due to septic shock. This study illuminates the current state of pediatric sepsis management in our Indonesian hospital, revealing it as inadequate. Findings highlight the need for improved pre-hospital systems and sepsis recognition tools, and wider use of mechanical ventilators and advanced monitoring due to limited pediatric intensive care unit beds. Future research should focus on hospital-specific sepsis protocols to reduce pediatric sepsis mortality rates.

A study of Antibiotic Susceptibility Pattern of Bacteria Isolates in Blood Culture in septicemic Children in Tertiary Care Hospital

Introduction: Sepsis in children is a life-threatening condition triggered by an infection. Most commonly, the infection is caused by bacteria. Antibiotic susceptibility patterns of bacterial isolates in blood cultures play a crucial role in the management of septicemia in children. Aim of the study: The aim of this study was to assess the antibiotic susceptibility pattern of bacteria isolates in blood culture in septicemic children. Methods: This cross-sectional study was conducted in Department of Paediatric, Dr. Sirajul Islam Medical College, Dhaka, Bangladesh, during the period from October 2021 to February 2023. Total 849 children aged less than 18 years with septicemia were included in this study. Result: The study involved 849 participants where majority were in the age group of 5 years or younger and with a near-even gender distribution. In this study, 10.1% tested positive for bacterial growth in blood cultures, with Pseudomonas (33.7%) and Staphylococcus epidermidis (22.1%) being most prevalent. Other organisms were also detected in varying proportions. The distribution of these organisms varied according to age and sex. Antibiotic sensitivity and resistance patterns were observed. A range of antibiotics showed different effectiveness, with varying levels of sensitivity and resistance against the bacterial isolates. Notably, Pseudomonas displayed considerable sensitive to cephalosporins (24.4%) and carbapenems (11.6%). Conclusion: The current study found that pseudomonas, staphylococcus epidermidis, and staphylococcus aureus were the most prevalent. Notably, a significant percentage of these bacteria displayed varying levels of antibiotic resistance, underscoring the challenge of managing sepsis in pediatric patients. These findings highlight the need for continuous surveillance of bacterial isolates and their resistance patterns.

Causal Association of Physician-in-Triage with Improved Pediatric Sepsis Care: A Single-Center, Emergency Department Experience.

A multidisciplinary sepsis task force formed in the Spring of 2020 aimed to assess and improve pediatric sepsis care in the pediatric emergency department (ED). The electronic medical record identified pediatric sepsis patients from September 2015 to July 2021. Data for time to sepsis recognition and antibiotic delivery were analyzed using statistical process control charts (X̄-S charts). We identified special cause variation, and Bradford-Hill Criteria guided multidisciplinary discussions to identify the most probable cause. In the fall of 2018, the average time from ED arrival to blood culture orders decreased by 1.1 hours, and the time from arrival to antibiotic administration decreased by 1.5 hours. After qualitative review, the task force hypothesized that initiation of attending-level pediatric physician-in-triage (P-PIT) as a part of ED triage was temporally associated with the observed improved sepsis care. P-PIT reduced the average time to the first provider exam by 14 minutes and introduced a process for physician evaluation before ED room assignment. Timely assessment by an attending-level physician improves time to sepsis recognition and antibiotic delivery in children who present to the ED with sepsis. Implementing a P-PIT program with early attending-level physician evaluation is a potential strategy for other institutions.

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning.

Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children. It is associated with high rates of morbidity and mortality, and rapid detection and administration of antimicrobials have been emphasized. The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness. Three gene expression datasets were available from the Gene Expression Omnibus collection. First, the differentially expressed genes (DEGs) were found with the use of the R program, and then gene set enrichment analysis was carried out. Subsequently, the DEGs were combined with the major module genes chosen using the weighted gene co-expression network. The hub genes were identified by the use of three machine-learning algorithms: random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator. The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes. In addition, the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). The relationship between the diagnostic markers and infiltrating immune cells was further studied. Overall, after overlapping key module genes and DEGs, we detected 402 overlapping genes. As pediatric sepsis diagnostic indicators, CYSTM1 (AUC = 0.988), MMP8 (AUC = 0.973), and CD177 (AUC = 0.986) were investigated and demonstrated statistically significant differences (P < 0.05) and diagnostic efficacy in the validation set. As indicated by the immune cell infiltration analysis, multiple immune cells may be involved in the development of pediatric sepsis. Additionally, all diagnostic characteristics may correlate with immune cells to varying degrees. The candidate hub genes (CD177, CYSTM1, and MMP8) were identified, and the nomogram was constructed for pediatric sepsis diagnosis. Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.

Effect of Antibiotics and Gut Microbiota on the Development of Sepsis in Children with Hematopoietic Stem Cell Transplants

Abstract Objective To describe the association between antibiotic use, gut microbiota composition, and the development of sepsis in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) to treat acute lymphoblastic leukemia. Methods A cohort of pediatric patients was followed up between days −30 (pre-HSCT) and +30 (post-HSCT), and sequential stool samples were collected for analysis of the taxonomic composition of bacterial communities by comparing the sequences of the 16s ribosomal RNA gene. Clinically, patients were divided into those with or without sepsis according to their clinical and laboratory data. Gut microbiota was categorized as potentially pathogenic or commensal and was described according to antibiotic use in patients with and without sepsis. Results A cohort of eight patients provided 34 stool samples at different time points during their pre- and post-HSCT periods. There was a greater diversity in the microbial composition in patients who did not develop sepsis. In contrast, patients who developed sepsis had low microbiota diversity, a slight dominance of the genus Bacteroides and order Enterobacterales, and a low abundance of the genus Akkermansia. The use of antibiotics was associated with a low relative abundance of commensal bacteria, a high relative abundance of potentially pathogenic microbiota, and a risk of sepsis. Conclusion Our results suggest that gut microbiota sequencing in pediatric HSCT recipients could predict the clinical course and guide direct interventions to improve patient outcomes. Accordingly, short-spectrum, tailored antibiotic therapy could be provided to patients with fever pre- and post-HSCT to prevent dysbiosis and reduce the risk of sepsis.

Prognostic factors and models to predict pediatric sepsis mortality: A scoping review.

Several scoring systems are available to assess the severity of sepsis in pediatric patients in diverse settings worldwide. This study investigates the quality and applicability of predictive models for determining pediatric sepsis mortality, especially in acute care and limited-resource settings. Mortality prediction factors and models were searched in four databases using the following criteria: developed for pediatric health care, especially in acute settings, and with mortality as an outcome. Two or more reviewers performed the study selection to ensure no bias occurred. Any disagreements were solved by consensus or by the decision of a third reviewer. The authors extracted the results and mapped the selected studies qualitatively to describe the prognostic properties of the risk factors and models proposed in the study. The final analysis included 28 mortality prediction models. Their characteristics, analysis, and performance measures were summarized. Performance was described in terms of calibration and discrimination, including assessing for risk of bias and applicability. A modified version of the PRISM-III score based on physiologic criteria (PRISM-III-APS) increased its predictive value to 0.85-0.95. The vasoactive-inotropic score at 12 h had a strong independent association with death. Albumin had an excellent predictive value when combined with other variables. Lactate, a biomarker widely measured in patients with sepsis, was highly associated with mortality. The bioimpedance phase angle was not considered applicable in our setting. Measurement using more straightforward methods, such as mid-upper arm circumference, was feasible in numerous health care facilities. Leveraging prognostic models to predict mortality among pediatric patients with sepsis remains an important and well-recognized area of study. While much validation and development work remains to be done, available prognostic models could aid clinicians at the bedside of children with sepsis. Furthermore, mortality prediction models are essential and valuable tools for assessing the quality of care provided to critically ill pediatric patients.

Early Identification of Severe Sepsis in Pediatric Patients Using an Electronic Alert System.

Prompt sepsis recognition and the initiation of standardized treatment bundles lead to improved outcomes. We developed automated severe sepsis alerts through the electronic medical record and paging system to aid clinicians in rapidly identifying pediatric patients with severe sepsis in our emergency department and inpatient units. Our Specific, Measurable, Applicable, Realistic, Timely aim was to improve 1-hour severe sepsis treatment bundle compliance to 60% with these electronic interruptive alerts. We developed the alert's criteria based on the 2005 International Pediatric Sepsis Consensus definitions. We performed 2 interventions: requiring the bedside nurse to answer the already implemented nurse-targeted (NT) severe sepsis alert, and the implementation of the physician-targeted (PT) severe sepsis alert. When systemic inflammatory response syndrome criteria were met, the NT alert triggered, and when organ dysfunction was also identified, an interruptive PT alert triggered, and the respective clinician was paged to evaluate the patient. Our primary outcome measure was bundle compliance; our secondary measure was PT alert response compliance. Baseline severe sepsis treatment bundle compliance was 37%. After requiring nursing response to the NT alert in 2016 and implementing the PT alert in 2018, our bundle compliance rose to 69% in 2020, demonstrating statistically significant difference (P = .006). PT alert response compliance rose from 67% in 2018 to 91% in 2020. An interruptive severe sepsis screening alert sent directly to clinicians is a valuable tool to ensure prompt severe sepsis recognition and treatment. This biphasic alert system facilitated multidisciplinary collaboration in early sepsis diagnosis and management.