Research On The Early Diagnosis Of Severe Infections In Children

Part One Clinical application of metagenomic next-generation sequencing in pediatric patients with central nervous system infectionsObjective: Etiological diagnosis is crucial for central nervous system infection(CNS)infection.Metagenomic next-generation sequencing(m NGS)is an emerging and powerful diagnostic method for identifying a wide range of pathogens.Its diagnostic value in CNS infection remains to be investigated,especially in pediatric patients with suspected CNS infections that were treated with empirical antibiotics.The purpose of this study was to evaluate the role of cerebrospinal fluid m NGS in clinical diagnosis and therapeutic adjustment in children with CNS infections.Methods: We collected clinical data of children with suspected CNS infections who were hospitalized in the Department of Neurology,Hebei Children’s Hospital from April 2019 to December 2020.Cerebrospinal fluid m NGS of all children were detected.The laboratory results of the patients,including routine cerebrospinal fluid analysis,biochemistry,culture,PCR,m NGS report,and autoantibodies,were collected.The results of m NGS were compared with conventional methods(including culture,smear,etc.),and the sensitivity,specificity,positive percentage agreement and negative percentage agreement was calculated.After the m NGS results were reported,clinicians further evaluated whether the results were in agreement with the clinical outcome based on their clinical manifestations.In case of agreement,the treatment plan was adjusted based on the results,and the impact of m NGS on clinical treatment was evaluated accordingly.Results: In total,57 pediatric patients receiving empirical treatment were enrolled in this study,including 43 children diagnosed with CNS infections(31 were positive for cerebrospinal fluid m NGS).The sensitivity and specificity of cerebrospinal fluid m NGS in the diagnosis of CNS infections were 72.09%(31/43)and 85.71%(12/14)respectively,and the positive and negative percentage agreement was 72.09%(95% CI:0.49-1.02)and 85.71%(95% CI: 0.44-1.49)respectively.Of 57 patients,28(49.12%)had the original treatment plan adjusted according to the results of cerebrospinal fluid m NGS,leading to significantly improved clinical symptoms.Conclusions: Cerebrospinal fluid m NGS is superior to conventional microbiological examinations concerning microorganism detection.It is conducive to the diagnosis of nervous system infections and the identification of pathogens,which is also helpful in further development of more effective and targeted treatment plans in clinical practice.Part Two Predictive value of a dynamic increase in red blood cell distribution width in severe bacterial infection in preterm infantsObjective: Severe bacterial infection(SBI)is responsible for high morbidity and mortality in preterm infants.The objective of this study was to evaluate the predictive value of a dynamic increase in red cell distribution width(RDW)in the diagnosis of neonatal SBI.Methods: Based on the hospitalization information of more than 8000 neonates from June 2001 to October 2012 in the Medical Information Mart for Intensive Care(MIMIC-III version 1.4)database,infants with birth weight less than 1500 g were screened for a retrospective analysis.Birth weight,sex,diagnosis,initial RDW,and the maximum values of RDW during hospitalization were retrieved from the MIMIC-III database.Infants were divided into four groups based on baseline RDW values and ΔRDW(ΔRDW= maximum RDW-baseline RDW).Univariate and multivariate logistic regression analyses were used to assess the risk of SBI in each group.The area under receiver operating characteristic(ROC)curve(AUC)was applied to evaluate and compare the value of baseline RDW,ΔRDW and a combination of the two in predicting SBI,respectively.Results: A total of 334 preterm infants were included in the study.The subjects were divided into four groups based on median baseline RDW(17%)and median ΔRDW(2%).Infants with increased RDW at baseline(>17%),and ΔRDW >2%(group 4)exhibited the highest risks of developing SBI,whereas those with normal RDW level at baseline(≤ 17%)and ΔRDW ≤2%(group 1,the reference group)had the lowest risk.The risk of developing SBI was 10.96 times higher in group 4 than in group 1.The AUC of the combination of baseline RDW and ΔRDW for predicting SBI was 0.81(95%CI,0.76-0.87),with a sensitivity of 78.16% and a specificity of 72.47%.Conclusions: The combination of elevated baseline RDW and a persistent and dynamic increase inΔRDW during hospitalization can be used to predict SBI.Therefore,this combination may be a potential independent diagnostic indicator of neonatal SBI.Part Three RDW to predict sepsis in very-low-birth-weight infants: a case-control studyObjective: To explore the potential clinical value of RDW in the diagnosis of sepsis in very-low-birth-weight(VLBW)infants.Methods: A retrospective case-control study was performed on VLBW infants admitted to the NICU within 24 h of birth following delivery in Department of Obstetrics,the Central Hospital of Cangzhou City from January2020 to June 2021.The patients were divided into the sepsis group and the control group.Demographic characteristics and laboratory findings including RDW were compared between the two groups.ROC curve of RDW,C-reactive protein(CRP),and procalcitonin(PCT)was plotted,and univariate logistic regression analysis was performed to evaluate the performance of RDW in predicting sepsis.In the meantime,the sepsis group was divided into Gram-negative sepsis group and Gram-positive sepsis group according to the type of pathogenic bacteria for comparative analysis with the control group.Indicators of infection were also compared between the early-onset and late-onset sepsis groups and the control group.Finally,changes in indicators of infection before and after treatment in the sepsis group were also analyzed.Results: A total of 60 VLBW infants were enrolled in this study,including 25 in the sepsis group and 35 in the control group.RDW was significantly higher in the sepsis group than in the control group(17.75±0.85 vs.16.37±1.52,P<0.001).The AUC of ROC curve for RDW,CRP,and PCT in predicting neonatal sepsis was 0.781,0.721,and 0.686,respectively.At RDW cut-off values >17.29%,the sensitivity and specificity for predicting neonatal sepsis was 76.00% and 77.14% respectively.Univariate logistics regression analysis showed a positive correlation between RDW and neonatal sepsis(OR=2.85).There was no correlation between RDW and either CRP or PCT(P>0.05).No statistical difference was found between the Gram-positive sepsis group and the control group with respect to RDW(P=0.473),while Gram-negative sepsis group had significantly higher RDW,as compared with the control group(P=0.013).RDW was higher in both the early-onset and late-onset sepsis groups than in the control group.RDW was decreased significantly in the sepsis group after treatment compared to those before treatment [15.28(15.17,16.21)vs.17.52(17.38,18.37)P<0.001].Conclusions: RDW was significantly elevated in VLBW infants infected with sepsis.Therefore,RDW may be a useful indicator of infection for the diagnosis of sepsis in clinical practice.