Clinical application of metagenomics sequencing in children with acute bacterial meningitis / 中华实用儿科临床杂志

Objective:To explore the application value of metagenomics sequencing in the etiological diagnosis of bacterial meningitis(BM) in children and improve the diagnosis and treatment effect of BM in children.Methods:All BM cases were collected from Jiangxi Provincial Children′s Hospital from February 1, 2018 to January 31, 2020.Meanwhile, such biological samples as blood and cerebrospinal fluid were collected for traditional etiological testing and metagenomics sequencing.The results of traditional etiological testing were regarded as the gold standard, and the specificity and sensitivity of metagenomics sequencing in the diagnosis of BM in children were confirmed.Results:A total of 45 cases were collected in this study, including 31 males and 14 females, with the age between (74.74 ± 58.67) months.Twenty-six cases were identified by metagenomics sequencing, with the positive rate being 57.78%.Among them, there were 8 cases of Streptococcus pneumoniae, 2 cases of Escherichia coli, 2 cases of Neisseria meningitidis, 2 cases of Staphylococcus, 2 cases of Salmonella, 2 cases of Mycobacterium multiplex, 1 case of Streptococcus intermedius, 1 case of Streptococcus pyogenes, 1 case of Streptococcus paris, 1 case of Streptococcus salivarius, 1 case of Haemophilus influenzae, 1 case of Pseudomonas aeruginosa, 1 case of Acinetobacter baumannii, and 1 case of Aspergillus.The traditional etiological positive rate was 17.78%, and the metagenomic next-generation sequencing (mNGS) positive rate was 57.78% ( P=0.014, kappa=0.273). As per the comparison results, the sensitivity, specificity, positive predictive value, negative predictive value, Youden index and misdiagnosis rate were 100.00%, 51.35%, 30.76%, 100.00%, 51.36%, 48.64% and 0, respectively. Conclusions:Metagenomics examination had high sensitivity, which can improve the etiological diagnosis rate of acute BM in children, especially in case of high clinical suspicion of infection.Therefore, metagenomics examination should be selected as early as possible when the etiology cannot be determined by traditional approaches.

Immunological mechanism of prednisone in the treatment of infantile spasm / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the immunological mechanism of prednisone in the treatment of infantile spasm (IS) by evaluating the immune function of IS children before and after treatment.</p><p><b>METHODS</b>Thirty children with IS were enrolled as IS group. Thirty healthy infants who underwent physical examination were enrolled as healthy control group. Fasting venous blood was collected for both groups before and after prednisone treatment. Chemiluminescence was used to measure serum levels of interleukin-1B (IL-1B), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Immunoturbidimetric assay was used to measure serum levels of immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG). Flow cytometry was used to measure the percentages of T lymphocyte subsets (CD3, CD4, and CD8). The clinical outcome and electroencephalographic findings were evaluated for all IS children after prednisone treatment.</p><p><b>RESULTS</b>The IS group had significantly higher serum levels of IL-2R, IL-8, and TNF-α than the healthy control group before treatment (P<0.05). The mean number of daily ictal clusters was positively correlated with the levels of IL-2R, IL-8, and TNF-α in IS children, the mean number of total daily seizures was positively correlated with IL-8 level, and any two indices out of IL-2R, IL-8, and TNF-α were positively correlated with each other (P<0.05). Among the 30 IS children treated with prednisone, 19 achieved seizure control; electroencephalography showed that 18 children achieved complete remission of hyperarrhythmia. After treatment, the IS group had significant reductions in the numbers of daily ictal clusters and total daily seizures, significant improvement in developmental quotient (P<0.05), and significant reductions in serum levels of IL-2R, L-8, and TNF-α, the percentage of CD4T lymphocytes, and CD4/CD8ratio (P<0.05), as well as a significant increase in the percentage of CD8T lymphocytes (P<0.05).</p><p><b>CONCLUSIONS</b>IS children have immune dysfunction. Prednisone can control seizures in IS children, possibly by regulating and improving immune dysfunction.</p>

The efficacy of prednisone in the treatment of infantile spasm and HPA axis mechanism analysis / 国际儿科学杂志

Objective By studying the changes of the seizures of infantile spasm(IS)、EEG and HPA axis function before and after the treatment of prednisone,to explore the efficacy of prednisone in treating infan-tile spasm,the role of HPA axis in the pathogenesis of IS,and elucidate the HPA axis mechanism of prednisone in controling seizure.Methods A total of 30 patients with IS (IS group) and 30 cases of healthy infants and young children (control group) were recruited.Number of seizures、EEG、HPA axis function was detected be-fore and after the treatment of prednisone in patients with infantile spasm.Serum cortisol,ACTH were deter-mined by the chemiluminescence analysis,serum CRH was measured by enzyme-linked immunosorbent assay. Results serum CRH levels of IS group was significantly higher than normal control group(P<0.05).Serum cortisol,ACTH in IS group were no evidently different compared with control group (P>0.05).The average number of daily ictal clusters and the average daily total seizure number positively correlated with CRH respec-tively.After the application of the prednisolone,seizure of 19 cases of the IS were controlled,11 cases were not controlled,18 cases of hyperarrhythmia were completely remited and 12 cases of hyperarrhythmia were not com-pletely remited.The average number of daily ictal clusters and The average daily total seizure number after treat-ment were significantly lower than before treatment(P<0.05);DQ after treatment was higher than DQ before treatment(P<0.05);The pathogenesis was the main influencing factor of the prednisone treatment effect,the length of the disease,the worse the treatment(P<0.05).CRH、cortisol、ACTH after treatment were significantly lower than before treatment(P<0.05).Conclusion Prednisone can effectively control the onset of infantile spasms,and early treatment is better.IS patient has HPA axis dysfunction,and prednisone can regulate HPA axis dysfunction to control spasm.

Influencing factors of infantile spasms relapse after remission / 中华实用儿科临床杂志

Objective To analyze the potential risk factors of infantile spasms (IS) relapse through following up the respondents with IS after different treatment protocols.Methods Sixty-nine cases were collected in the Department of Pediatric Neurology,Jiangxi Children's Hospital from May 2011 to September 2013,who had complete cessation of spasms for at least 28 days or more after the different treatment protocols.The follow-up was performed on these patients until spasms seizure relapse or at least 1 year for those without recurrence.According to the literature review,8 possible risk factors of IS recurrence (gender,age of onset,course of diseases,etiology,high irregular types of electroencephalogram,development quotient,onset time,treatment protocols) were selected,and then Logistic multiple regression was used to analyze the relationship of various potential risk factors with the relapse of spasms.Results (1) The recurrence rate at 6 months and 12 months were 40.6％ (28/69 cases)and 43.5 ％ (30/69 cases),respectively.(2) Among the various potential factors,the age at onset and the time to response were closely related to the IS recurrence.Namely,the non-classic onset(early-onset and late-onset) of IS were more likely to relapse than the classic onset[66.7％ (14/21 cases) vs 33.3％ (16/48 cases),x2 =6.605,P =0.010];the responders beyond 1 week were more likely to relapse than those within 1 week[63.6％ (14/22 cases) vs 34.0％ (16/47 cases),x2 =5.341,P =0.021].There were significant differences between the 2 groups (all P ＜ 0.05).(3) Logistic multiple regression analysis demonstrated that age at onset (Wald =3.603) was most closely related to the relapse of spasms.Conclusions (1) The relapse rate of IS in children was high,and the majority of them relapsed within 6 months.So a long-term,rational and effective clinical management solution should be explored.(2) The age at onset and the time to response are very important risk factors of the IS recurrence,and the former was more significant.So,early diagnosis and early treatment are more likely to improve the efficacy of IS,and reduce the risks of recurrence and improve the prognosis.

Efficacy and safety of different doses of prednisone combined with topiramate for the children with infantile spasms / 中华实用儿科临床杂志

Objective To evaluate the clinical efficacy and safety of different doses of prednisone combined with topiramate(TPM) in the treatment of infantile spasms(IS),in order to provide a new choice of the therapy of IS.Methods Fifty-six cases were collected in the Department of Neurology of Jiangxi Children's Hospital from May.2011 to Dec.2012.They were randomly divided into 2 groups:control group and trial group.The patients in control group took prednisone tablet of 1 mg/kg,2 times a day for 2 weeks;and the patients in trial group took prednisone tablet of 10 mg/ d,4 times a day for 2 weeks.In addition,TPM was used in both groups by initial dose 1 mg/(kg · d) or 2 times a day,and then was gradually increased to 3-5 mg/(kg · d) within 2 weeks.For those children in whom the spasms seizure completely ceased after 2 weeks,prednisone was then reduced by degrees to be discontinued for a 7-weeks course(extending to 4 weeks with the initial doses if spasms continued after 2 weeks).All patients underwent the assessment of spasms seizure and a 3-12 h video-electroencephalogram monitoring including wake and sleep states,which were performed before treatment,after 2 weeks and the end of the courses (7 or 9 weeks after treatment),respectively.Meanwhile,the side effects of the drugs during the treatment were recorded.The developmental quotient (DQ) tests of children with complete cessation of spasms more than 6 months were performed before treatment and after 6 months.All patients had been followed up for 2-18 months.Results 1.After 2 weeks of the therapy,the rate of cessation of spasms were 75.00％ (21/28 cases) and 28.57％ (8/28 cases) in the trial group and the control group,respectively,there was significant difference (x2 =12.087,P =0.001).And in the same term,the rate of complete resolution of hypsrrhythmia were 60.71％ (17/28 cases) and 21.43 ％ (6/28 cases),respectively,there was significant difference (x2 =8.928,P =0.003).At the end of treatment,the rate of cessation of spasms were 67.86％ (19/28 cases) and 35.71％ (10/28 cases) in the trial group and control group,respectively,there was significant difference (x2 =5.793,P =0.016).And in the mean time,the rate of complete resolution of hypsrrhythmia were 57.14％ (16/28 cases) and 14.29％ (4/28 cases),respectively,there was significant difference (x2 =11.200,P =0.001).2.Weight gain and increased appetite were the most frequent side effects.The incidence of side effects were 82.14％ (23/28 cases) and 67.86％ (19/28 cases) in the trial group and control group,respectively,there was no significant difference between the 2 groups (x2 =1.524,P =0.217).No death occurred in this clinical trail and no one discontinued the treatment protocol as result of the adverse events.3.The recurrence rate in the trial group and the control group were 31.82％ and 72.73％,respectively.And there was significant difference between the 2 groups (x2 =4.950,P =0.026).In the trial group,there were 9 cases with cessation of spasms more than 6 months,whose average business development values had no significant difference before and after treatment (t =2.271,P =0.053).Conclusion The efficacy of large-dose prednisone combined with TPM for IS was significantly better than that of conventional dose prednisone combined with TPM.