The effects of delayed appropriate antimicrobial therapy on children with Staphylococcus aureus blood infection.

Early appropriate antimicrobial therapy plays a critical role for patients with Staphylococcus aureus bloodstream infection (SAB). We aim to determine the optimal time-window for appropriate antimicrobial therapy and evaluate the effects of delayed therapy on adverse clinical outcomes (in-hospital mortality, sepsis, and septic shock) in children with SAB by propensity score matching (PSM) analysis. Receiver-operating characteristic was used to determine the cut-off point of the time to appropriate therapy (TTAT), the patients were divided into timely and delayed appropriate antimicrobial therapy (delayed therapy) groups accordingly. The PSM was used to balance the characteristics between the two groups, controlling the effects of potential confounders. Kaplan-Meier methods and Cox proportional hazards regression were applied to the matched groups to analyze the association between delayed therapy and clinical outcomes. Inverse probability of treatment weighting and propensity score covariate adjustment were also performed to investigate the sensitivity of the results under different propensity score-based approaches. In total, 247 patients were included in this study. The optimal cut-off point of TTAT was identified as 6.4 h, with 85.0% sensitivity and 69.2% specificity (AUC 0.803, 95% confidence interval 0.702-0.904). Eighty-seven (35.22%) of the 247 patients who received delayed therapy (TTAT ≥ 6.4 h) had higher in-hospital mortality (19.54% vs 1.88%, p < 0.001), higher incidences of sepsis (44.83% vs 15.00%, p < 0.001) and septic shock (32.18% vs 6.25%, p < 0.001) when compared to timely therapy (TTAT < 6.4 h) patients. After PSM analysis, a total of 134 episodes (67 in each of the two matched groups) were further analyzed. No statistically significant difference was observed in in-hospital mortality between delayed and timely -therapy groups (log-rank test, P = 0.157). Patients with delayed therapy had a higher incidence of sepsis or septic shock than those with timely therapy (log-rank test, P = 0.009; P = 0.018, respectively). Compared to the timely-therapy group, the hazard ratio and 95% confidence interval in delayed-therapy group were 2.512 (1.227-5.144, P = 0.012) for sepsis, 3.109 (1.166-8.290, P = 0.023) for septic shock.    Conclusion: Appropriate therapy delayed 6.4 h may increase the incidence of sepsis and septic shock, with similar in-hospital mortality in patients with SAB. What is Known: • Staphylococcus aureus (S. aureus) is a major cause of bloodstream infections in children. Undoubtedly, early antimicrobial application plays a critical role in the treatment of children with Staphylococcus aureus bloodstream infections (SAB). • However, rapid, and aggressive administration of antimicrobials may lead to the overuse of these drugs and the emergence of multidrug-resistant microorganisms. Therefore, it is crucial to determine the optimal time-window for appropriate antimicrobial administration in children with SAB. Unfortunately, the optimal time-window for appropriate antimicrobial administration in children with SAB remains unclear. What is New: • Determining the optimal time-window for appropriate antimicrobial administration in patients with matched data variables is particularly important. The Propensity score matching (PSM) analysis effectively controls for confounding factors to a considerable extent when assessing the impact of treatment, thereby approximating the effects observed in randomized controlled trials. • To our knowledge, this is the first study using PSM method to assess the effects of delayed appropriate antimicrobial therapy on adverse outcomes in children with SAB. In low-risk populations with SAB, a delay of 6.4 h in appropriate therapy might increase the occurrence rate for sepsis and septic shock; however, no correlation has been found between this delay and an increased risk for hospital mortality.

Impact of the introduction of high-speed rail on the income gap between urban and rural residents.

The unprecedented expansion and development of high-speed rail (HSR) in China provides a unique opportunity and a new way of thinking for addressing the problem of urban-rural wealth disparities. In this paper, I examine the impact of the introduction of HSRs on the income disparity between urban and rural residents in China. Using panel data from 285 prefecture-level cities from 2004 to 2018, in this paper I employ the double-difference method to assess the impact of HSR on the income gap between urban and rural populations and the mechanism of its action; furthermore, I explore the influence of HSR on urban residents' per capita disposable income and rural residents' per capita net income, as well as the impact of HSR on the flow of elements such as labor and capital. My research findings reveal that the introduction of HSR has greatly widened the income gap between urban and rural residents; however, there is heterogeneity between different East, Central, and West regions, as well as between different levels of cities. A further mechanism study finds that HSR lowers farmers' per capita net income, raises urban residents' per capita disposable income, and widens the urban/rural income gap via mechanisms such as facilitating the interregional mobility of labor and capital factors. Therefore, it is necessary to comprehensively assess the economic effects brought about by HSR, strengthen the construction of urban-rural transport networks, and improve support for rural areas, so as to promote the coordinated development of inter-regional and urban-rural areas.

Effects of multi-gradient equilibration during vitrification on oocyte survival and embryo development in mice.

Vitrification has been widely used for oocyte cryopreservation, but there is still a need for optimization to improve clinical outcomes. In this study, we compared the routine droplet merge protocol with modified multi-gradient equilibration vitrification for cryopreservation of mouse oocytes at metaphase II. Subsequently, the oocytes were thawed and subjected to intracytoplasmic sperm injection (ICSI). Oocyte survival and spindle status were evaluated by morphology and immunofluorescence staining. Moreover, the fertilization rates and blastocyst development were examined in vitro. The results showed that multi-gradient equilibration vitrification outperformed droplet merge vitrification in terms of oocyte survival, spindle morphology, blastocyst formation, and embryo quality. In contrast, droplet merge vitrification exhibited decreasing survival rates, a reduced proportion of oocytes with normal spindle morphology, and lower blastocyst rates as the number of loaded oocytes increased. Notably, when more than six oocytes were loaded, reduced oocyte survival rates, abnormal oocyte spindle morphology, and poor embryo quality were observed. These findings highlight that the vitrification of mouse metaphase II oocytes by the modified multi-gradient equilibration vitrification has the advantage of maintaining oocyte survival, spindle morphology, and subsequent embryonic development.

The association between PM2.5 concentration and the severity of acute asthmatic exacerbation in hospitalized children: A retrospective study in Chongqing, China.

BACKGROUND: Ambient PM2.5 is associated with asthma exacerbation. The association between the concentration of PM2.5 and the severity of asthma exacerbation has yet to be thoroughly clarified. The study aims to explore the association between the piror 30 days average concentration of PM2.5 and the severity of acute asthma exacerbation in hospitalized children. METHODS: A total of 269 children with acute exacerbation of asthma were enrolled and divided into three groups according to the PM2.5 exposure concentrations: group 1 (PM2.5: <37.5 µg/m3 ), group 2 (PM2.5: 37.5-75 µg/m3 ), group 3 (PM2.5: ≥75 µg/m3 ), respectively. The ordered logistic regression modeling was conducted to explore the influence of daily PM2.5 concentration on the clinical severity of children's asthma exacerbation. Multiple linear regression was conducted to explore the association between the concentration of PM2.5 and the length of stay in the hospital (LOS). We also conducted a receiver operating characteristic (ROC) curve analysis to explore the cutoff value of PM2.5 to predict the children's asthma exacerbation. RESULTS: There was no statistical difference among the three groups of children in gender, age, body mass index, ethnicity, the first diagnosis of asthma, allergic history, passive smoke exposure, or family history of asthma. There was a statistically significant difference in many hospitalization characteristics (p < 0.05) among the three groups of children. Significant differences were found in terms of accessory muscles of respiration (p = 0.005), respiratory failure (p = 0.012), low respiratory tract infectious (p = 0.020), and the severity of asthma exacerbation (p < 0.001) among the three groups. PM2.5 concentration was primarily positively correlated to neutrophile inflammation. The ordered multivariate logistic regression model showed that higher PM2.5 concentrations were significantly associated with greater odds of more severe asthma exacerbation in one and two-pollutant models. The adjusted odds ratio of severe asthma exacerbation was 1.029 (1.009, 1.049) in the one-pollutant model. The most significant odds ratio of severe asthma exacerbation was 1.050 (1.027, 1.073) when controlling NO2 in the two-pollutant models. Multiple linear regression showed that PM2.5 concentration was significantly associated with longer LOS in both one-pollutant and two-pollutant models. By performing ROC analysis, the average daily concentration of 44.5 µg/m3 of PM2.5 (AUC = 0.622, p = 0.002) provided the best performance to predict severe asthma of children exacerbation with a sensitivity of 59.2% and a specificity of 63.8%. CONCLUSION: The increased prior 30 days average concentration of PM2.5 was associated with greater asthma exacerbation severity and longer length of stay in the hospital of children with asthma exacerbation.

[Clinical characteristics of plastic bronchitis and risk factors for recurrence in children]. / å„¿ç«¥å¡‘åž‹æ€§æ”¯æ°”ç®¡ç‚Žä¸´åºŠç‰¹å¾åŠå¤å‘å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB. METHODS: This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed. RESULTS: A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05). CONCLUSIONS: Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.

The role of small airway function parameters in preschool asthmatic children.

BACKGROUND: Small airways are the major sites of inflammation and airway remodeling in all severities of asthma patients. However, whether small airway function parameters could reflect the airway dysfunction feature in preschool asthmatic children remain unclear. We aim to investigate the role of small airway function parameters in evaluating airway dysfunction, airflow limitation and airway hyperresponsiveness (AHR). METHODS: Eight hundred and fifty-one preschool children diagnosed with asthma were enrolled retrospectively to investigate the characteristics of small airway function parameters. Curve estimation analysis was applied to clarify the correlation between small and large airway dysfunction. Spearman's correlation and receiver-operating characteristic (ROC) curves were employed to evaluate the relationship between small airway dysfunction (SAD) and AHR. RESULTS: The prevalence of SAD was 19.5% (166 of 851) in this cross-sectional cohort study. Small airway function parameters (FEF25-75%, FEF50%, FEF75%) showed strong correlations with FEV1% (r = 0.670, 0.658, 0.609, p<0.001, respectively), FEV1/FVC% (r = 0.812, 0.751, 0.871, p<0.001, respectively) and PEF% (r = 0.626, 0.635, 0.530, p<0.01, respectively). Moreover, small airway function parameters and large airway function parameters (FEV1%, FEV1/FVC%, PEF%) were curve-associated rather than linear-related (p<0.001). FEF25-75%, FEF50%, FEF75% and FEV1% demonstrated a positive correlation with PC20 (r = 0.282, 0.291, 0.251, 0.224, p<0.001, respectively). Interestingly, FEF25-75% and FEF50% exhibited a higher correlation coefficient with PC20 than FEV1% (0.282 vs. 0.224, p = 0.031 and 0.291 vs. 0.224, p = 0.014, respectively). ROC curve analysis for predicting moderate to severe AHR showed that the area under the curve (AUC) was 0.796, 0.783, 0.738, and 0.802 for FEF25-75%, FEF50%, FEF75%, and the combination of FEF25-75% and FEF75%, respectively. When Compared to children with normal lung function, patients with SAD were slightly older, more likely to have a family history of asthma and airflow obstruction with lower FEV1% and FEV1/FVC%, lower PEF% and more severe AHR with lower PC20 ( all p<0.05). CONCLUSION: Small airway dysfunction is highly correlated with large airway function impairment, severe airflow obstruction and AHR in preschool asthmatic children. Small airway function parameters should be utilized in the management of preschool asthma.

Dysregulation of iron homeostasis in airways associated with persistent preschool wheezing.

BACKGROUND: Currently, there are no reliable clinical tools available to identify persistent asthma symptoms among preschool children with recurrent wheezing. We investigated iron homeostasis in the airways of preschoolers with recurrent wheezing and assessed whether iron homeostasis-related indices may reliably predict persistent wheezing. METHODS: Iron levels and mRNA expression levels of iron homeostasis molecules were examined in bronchoalveolar lavage samples from 89 preschoolers with recurrent wheezing and 56 controls, with a 12-month follow-up conducted. Risk factors for persistent wheezing were identified using least absolute shrinkage and selection operator and multivariate logistic regression. The addition of predictive values of iron indices to the modified Asthma Predictive Index (mAPI) or clinical predictors was determined using area under receiver operating characteristic curves (AUC). RESULTS: Preschoolers with recurrent wheezing had reduced iron levels in their airways, associated with significantly decreased expression of iron export molecule SLC40A1 and increased expression of iron intake factor TFR1 and iron storage factors FTH and FTL. Risk factors for persistent wheezing included mAPI positivity, iron predictors (lower expression of SLC40A1 and higher expression of FTL), and clinical predictors (aeroallergen sensitivity, shorter breastfeeding duration, and earlier age of first wheezing episode). The addition of information on iron predictors significantly enhanced the power of clinical predictors (AUC: 84%, increase of 12%) and mAPI (AUC: 81%, increase of 14%). CONCLUSIONS: Iron homeostasis is altered in the airways of preschoolers with recurrent wheezing. Adding information on iron-related indices to clinical information significantly improves accurate prediction of persistent wheezing in preschool-aged children.

Vancomycin efficiency and safety of a dosage of 40-60 mg/kg/d and corresponding trough concentrations in children with Gram-positive bacterial sepsis.

Background: Optimal vancomycin trough concentrations and dosages remain controversial in sepsis children. We aim to investigate vancomycin treatment outcomes with a dosage of 40-60 mg/kg/d and corresponding trough concentrations in children with Gram-positive bacterial sepsis from a clinical perspective. Methods: Children diagnosed with Gram-positive bacterial sepsis and received intravenous vancomycin therapy between January 2017 and June 2020 were enrolled retrospectively. Patients were categorized as success and failure groups according to treatment outcomes. Laboratory, microbiological, and clinical data were collected. The risk factors for treatment failure were analyzed by logistic regression. Results: In total, 186 children were included, of whom 167 (89.8%) were enrolled in the success group and 19 (10.2%) in the failure group. The initial and mean vancomycin daily doses in failure group were significantly higher than those in success group [56.9 (IQR =42.1-60.0) vs. 40.5 (IQR =40.0-57.1), P=0.016; 57.0 (IQR =45.8-60.0) vs. 50.0 (IQR =40.0-57.6) mg/kg/d, P=0.012, respectively] and median vancomycin trough concentrations were similar between two groups [6.9 (4.0-12.1) vs.7.3 (4.5-10.6) mg/L, P=0.568)]. Moreover, there was no significant differences in treatment success rate between vancomycin trough concentrations ≤15 mg/L and >15 mg/L (91.2% vs. 75.0%, P=0.064). No vancomycin-related nephrotoxicity adverse effects occurred among all enrolled patients. Multivariate analysis revealed that a PRISM III score ≥10 (OR =15.011; 95% CI: 3.937-57.230; P<0.001) was the only independent clinical factor associated with increased incidence of treatment failure. Conclusions: Vancomycin dosages of 40-60 mg/kg/d are effective and have no vancomycin-related nephrotoxicity adverse effects in children with Gram-positive bacterial sepsis. Vancomycin trough concentrations >15 mg/L are not an essential target for these Gram-positive bacterial sepsis patients. PRISM III scores ≥10 may serve as an independent risk factor for vancomycin treatment failure in these patients.

[Clinical and bronchoscopy features of tracheobronchial tuberculosis in children]. / å„¿ç«¥æ°”ç®¡æ”¯æ°”ç®¡ç»“æ ¸çš„ä¸´åºŠåŠæ”¯æ°”ç®¡é•œä¸‹ç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical and bronchoscopic characteristics of tracheobronchial tuberculosis (TBTB) in children and to identify factors influencing residual airway obstruction or stenosis. METHODS: The clinical data of children with TBTB were retrospectively collected. The children were divided into two groups based on the last bronchoscopic result within one year of follow-up: a group with residual airway obstruction or stenosis (n=34) and a group without residual airway obstruction or stenosis (n=58). A multivariate logistic regression analysis was used to identify the factors influencing residual airway obstruction or stenosis in children with TBTB. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the factors influencing residual airway obstruction or stenosis in children with TBTB. RESULTS: A total of 92 children with TBTB were included, and the main symptoms were cough (90%) and fever (68%). In children under 1 year old, the incidence rates of dyspnea and wheezing were significantly higher than in other age groups (P<0.008). Chest CT findings included mediastinal or hilar lymph node enlargement (90%) and tracheobronchial stenosis or obstruction (61%). The lymphatic fistula type was the main type of TBTB observed bronchoscopically (77%). All children received interventional treatment, and the effective rate was 84%. During one year of follow-up, 34 children had residual airway obstruction or stenosis. The TBTB diagnostic time and the initiation of interventional treatment were significantly delayed in the group with residual airway obstruction or stenosis compared with the group without residual airway obstruction or stenosis (P<0.05). The multivariate logistic regression analysis showed that the TBTB diagnostic time was closely related to residual airway obstruction or stenosis in children (P<0.05). ROC curve analysis showed that at the cut-off value of 92 days of TBTB diagnostic time, the area under the curve for predicting residual airway obstruction or stenosis in children with TBTB was 0.707, with a sensitivity of 58.8% and a specificity of 75.9%. CONCLUSIONS: The clinical manifestations of TBTB are nonspecific, and symptoms are more severe in children under 1 year old. TBTB should be suspected in children with tuberculosis and chest imaging indicating airway involvement. Delayed diagnosis of TBTB is associated with the development of residual airway obstruction or stenosis.

The pregnancy outcomes of day-5 poor-quality and day-6 high-quality blastocysts in single blastocyst transfer cycles.

OBJECTIVE: This study compared the outcomes of single blastocyst transfer cycles, using day- 5 poor-quality blastocysts and day-6 high-quality blastocysts. METHODS: We analyzed 462 frozen-thawed embryo transfer (FET) cycles performed at our center from January 2014 to December 2019. The cycles were divided into two groups: a day-5 poor-quality blastocyst transfer group (group A) and a day-6 high-quality blastocyst transfer group (group B). The clinical outcomes were tested. RESULTS: In groups A and B, respectively, the clinical pregnancy rate (CPR; 61.65% vs. 67.17%, p=0.258), implantation rate (IR; 61.65% vs. 67.17%, p=0.258), and live birth rate (LBR; 69.51% vs. 77.83%, p=0.134) showed no significant differences. Moreover, when day-3 embryo quality was considered, the CPR, IR, and LBR were also similar in group A and group B (p>0.05). CONCLUSION: The clinical outcomes of day-5 poor-quality blastocysts and day-6 high-quality blastocysts were similar, suggesting that the developmental speed of the embryo might be more important than embryo quality for the clinical outcomes of single blastocyst transfer in FET cycles.

Network analyses of upper and lower airway transcriptomes identify shared mechanisms among children with recurrent wheezing and school-age asthma.

Background: Predicting which preschool children with recurrent wheezing (RW) will develop school-age asthma (SA) is difficult, highlighting the critical need to clarify the pathogenesis of RW and the mechanistic relationship between RW and SA. Despite shared environmental exposures and genetic determinants, RW and SA are usually studied in isolation. Based on network analysis of nasal and tracheal transcriptomes, we aimed to identify convergent transcriptomic mechanisms in RW and SA. Methods: RNA-sequencing data from nasal and tracheal brushing samples were acquired from the Gene Expression Omnibus. Combined with single-cell transcriptome data, cell deconvolution was used to infer the composition of 18 cellular components within the airway. Consensus weighted gene co-expression network analysis was performed to identify consensus modules closely related to both RW and SA. Shared pathways underlying consensus modules between RW and SA were explored by enrichment analysis. Hub genes between RW and SA were identified using machine learning strategies and validated using external datasets and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the potential value of hub genes in defining RW subsets was determined using nasal and tracheal transcriptome data. Results: Co-expression network analysis revealed similarities in the transcriptional networks of RW and SA in the upper and lower airways. Cell deconvolution analysis revealed an increase in mast cell fraction but decrease in club cell fraction in both RW and SA airways compared to controls. Consensus network analysis identified two consensus modules highly associated with both RW and SA. Enrichment analysis of the two consensus modules indicated that fatty acid metabolism-related pathways were shared key signals between RW and SA. Furthermore, machine learning strategies identified five hub genes, i.e., CST1, CST2, CST4, POSTN, and NRTK2, with the up-regulated hub genes in RW and SA validated using three independent external datasets and qRT-PCR. The gene signatures of the five hub genes could potentially be used to determine type 2 (T2)-high and T2-low subsets in preschoolers with RW. Conclusions: These findings improve our understanding of the molecular pathogenesis of RW and provide a rationale for future exploration of the mechanistic relationship between RW and SA.

Development and validation of a prediction model to predict school-age asthma in preschool children.

OBJECTIVE: To develop and validate a clinical prediction model to identify school-age asthma in preschool asthmatic children. STUDY DESIGN: In this retrospective prognosis cohort study, asthmatic children aged 3-5 years were enrolled with at least 2 years of follow-up, and their potential variables at baseline and the prognosis of school-age asthma were collected from medical records. A clinical prediction model was developed using Logistic regression. The performance of prediction model was assessed and quantified by discrimination of the area under the receiver operating characteristic curve (AUC) and calibration of Brier score. The model was validated by the temporal-validation method. RESULTS: In the development dataset, 2748 preschool asthmatic children were included for model development, and 883 (32.13%) children were translated to school-age asthma. The independent prognostic variables with an increased risk for school-age asthma were used to develop the prediction model, including: age, parental asthma, early frequent wheezing, allergic rhinitis, eczema, allergic conjunctivitis, obesity, and aeroallergen of dust mite. While assessing model performance, the discrimination power of AUC was moderate [0.788 (0.770-0.805)] with sensitivity (81.5%) and specificity (60.9%), and the calibration of Brier score was 0.169, supporting the calibration ability. In the temporal-validation dataset of 583 preschool asthmatic children, our model showed satisfactory discrimination (AUC 0.818) and calibration (Brier score 0.150). The prediction model was presented by the web-based calculator (https://casthma.shinyapps.io/dynnomapp/) and a nomogram for clinical application. CONCLUSION: In preschool asthmatic children, our prediction model could be used to predict the risk of school-age asthma.

Inappropriate empirical antibiotic therapy was an independent risk factor of pediatric persistent S. aureus bloodstream infection.

Persistent S. aureus bloodstream infection (PSBSI) increased the incidence of metastatic infection and mortality. We aimed to clarify its risk factors and correlation with metastatic infection and septic shock in children. This retrospective and observational study enrolled children with S. aureus bloodstream infection who admitted to Children's Hospital of Chongqing Medical University between January 2016 and December 2021. The logistic regression model was used for multivariable analyses to determine independent factors associated with PSBSI and clarify the effect of persistent S. aureus bloodstream infection and other factors on metastatic infection and septic shock. One hundred and twenty-seven children were included in this study retrospectively. There were thirty-two cases in the persistent S. aureus bloodstream infection group and ninety-five children in the non-persistent infection group. Multivariate logistic regression analysis indicated that inappropriate empirical antibiotic therapy (OR, 7.26; 95%CI, 2.48-21.30; P<0.01) was an independent risk factor of persistent S. aureus bloodstream infection. Persistent S. aureus bloodstream infection (OR, 6.40; 95%CI, 2.08-19.70; P<0.01) and community-acquired S. aureus bloodstream infection (OR, 4.75; 95%CI, 1.34-16.89; P=0.02) were independent predictors of metastatic infection. Pittsburgh bacteremia scores ≥ 2 (OR, 28.81; 95%CI, 5.26-157.99; P<0.01), hypoalbuminemia (OR, 13.34; 95%CI, 2.43-73.28; P<0.01) and persistent S. aureus bloodstream infection (OR, 5.48; 95%CI, 1.13-26.54; P=0.04) were independent risk factors of septic shock. CONCLUSION: Inappropriate empirical antibiotic therapy was an independent risk factor of pediatric persistent S. aureus bloodstream infection. Pediatric persistent S. aureus bloodstream infection was associated with metastatic infection and septic shock. WHAT IS KNOWN: • Pathogenic features such as Methicillin-resistant S. aureus and sources of infection such as central venous catheter related infection were risk factors of PSBSI in adults. • PSBSI increased the incidence of metastatic infection and mortality in adults. WHAT IS NEW: • Inappropriate empirical antibiotic therapy was an independent risk factor of pediatric persistent S. aureus bloodstream infection. • Pediatric persistent S. aureus bloodstream infection was associated with metastatic infection and septic shock.

Short-Course vs Long-Course Antibiotic Therapy for Children With Nonsevere Community-Acquired Pneumonia: A Systematic Review and Meta-analysis.

Importance: Short-course antibiotic therapy could enhance adherence and reduce adverse drug effects and costs. However, based on sparse evidence, most guidelines recommend a longer course of antibiotics for nonsevere childhood community-acquired pneumonia (CAP). Objective: To determine whether a shorter course of antibiotics was noninferior to a longer course for childhood nonsevere CAP. Data Sources: MEDLINE, Embase, Web of Science, the Cochrane Library, and 3 Chinese databases from inception to March 31, 2022, as well as clinical trial registries and Google.com. Study Selection: Randomized clinical trials comparing a shorter- vs longer-course therapy using the same oral antibiotic for children with nonsevere CAP were included. Data Extraction and Synthesis: Random-effects models were used to pool the data, which were analyzed from April 15, 2022, to May 15, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence. Main Outcomes and Measures: Treatment failure, defined by persistence of pneumonia or the new appearance of any general danger signs of CAP (eg, lethargy, unconsciousness, seizures, or inability to drink), elevated temperature (>38 °C) after completion of treatment, change of antibiotic, hospitalization, death, missing more than 3 study drug doses, loss to follow-up, or withdrawal of informed consent. Results: Nine randomized clinical trials including 11 143 participants were included in this meta-analysis. A total of 98% of the participants were aged 2 to 59 months, and 58% were male. Eight studies with 10 662 patients reported treatment failure. Treatment failure occurred in 12.8% vs 12.6% of participants randomized to a shorter vs a longer course of antibiotics. High-quality evidence showed that a shorter course of oral antibiotic was noninferior to a longer course with respect to treatment failure for children with nonsevere CAP (risk ratio, 1.01; 95% CI, 0.92-1.11; risk difference, 0.00; 95% CI, -0.01 to 0.01; I2 = 0%). A 3-day course of antibiotic treatment was noninferior to a 5-day course for the outcome of treatment failure (risk ratio, 1.01; 95% CI, 0.91-1.12; I2 = 0%), and a 5-day course was noninferior to a 10-day course (risk ratio, 0.87; 95% CI, 0.50-1.53; I2 = 0%). A shorter course of antibiotics was associated with fewer reports of gastroenteritis (risk ratio, 0.79; 95% CI, 0.66-0.95) and lower caregiver absenteeism (incident rate ratio, 0.74; 95% CI, 0.65-0.84). Conclusions and Relevance: Results of this meta-analysis suggest that a shorter course of antibiotics was noninferior to a longer course in children aged 2 to 59 months with nonsevere CAP. Clinicians should consider prescribing a shorter course of antibiotics for the management of pediatric nonsevere CAP.

Long-term effects of vitamin D on exacerbation rate, health care utilization and lung function in children with asthma.

Background: Asthma exacerbations lead to unplanned health care utilization and reduced lung function in children. Sufficient vitamin D level has been found to have a short-term protective effect against asthma exacerbation in children. However, it is unclear whether this effect remains in the long term. We evaluated the long-term effects of vitamin D levels on the occurrence of asthma exacerbations, emergency department visits or hospitalizations, and lung function among children with asthma, and further investigated the temporal trends of the effects. Methods: In this retrospective cohort study, children with asthma who were admitted to the Children's Hospital of Chongqing Medical University from 2017 to 2021 were enrolled. Negative binomial, Poisson, or logistic regression model was used for the multivariable analysis, adjusting for age, sex, body mass index z-score, and severity of asthma exacerbation. Results: Of the 370 children with asthma, 87.8% had vitamin D level less than or equal to 30 ng/mL. After adjustment for confounding factors, higher baseline vitamin D levels in asthma children were significantly associated with reduced occurrence of asthma exacerbations during the first [odds ratio 0.842, 95% confidence interval (CI): 0.805-0.881; P<0.001], second (odds ratio 0.848, 95% CI: 0.793-0.907; P<0.001) and third years (odds ratio 0.865, 95% CI: 0.811-0.922; P<0.001) of follow-up. Higher vitamin D levels in asthmatic children were also strongly associated with a reduced number of emergency department visits or hospitalizations during the first (odds ratio 0.880, 95% CI: 0.842-0.920; P<0.001), second (odds ratio 0.885, 95% CI: 0.832-0.941; P<0.001), and third years (odds ratio 0.922, 95% CI: 0.851-0.998; P=0.044) of follow-up. In addition, the vitamin D levels in asthmatic children were found to be negatively associated with the odds of large airway dysfunction (odds ratio 0.865, 95% CI: 0.771-0.970; P=0.013) and small airway dysfunction (odds ratio 0.922, 95% CI: 0.855-0.996; P=0.038) during the first year of follow-up. Conclusions: Sufficient vitamin D level is associated with lower risk of asthma exacerbations and health care utilization over a 3-year period, and improved lung function over 1 year. The protective effects of vitamin D on asthmatic children decreased over time.

Time to appropriate antimicrobial therapy serves an independent prognostic indicator in children with nosocomial Klebsiella pneumoniae bloodstream infection.

We tend to investigate the connection between time to appropriate therapy (TTAT) and prognosis in pediatric patients with nosocomial Klebsiella pneumoniae (K. pneumoniae) bloodstream infection, and find the optimal cutoff point for the empirical administration of antimicrobials. This retrospective study was conducted in Children's Hospital of Chongqing Medical University, and inpatients with nosocomial K. pneumoniae bloodstream infection were finally enrolled. We applied the Classification and Regression Tree (CART) analysis to find the TTAT cutoff point and the Logistic Regression analysis to evaluate prognostic indicators. The incidence of septic shock and mortality was 17.91% (12/67) and 13.43% (9/67), respectively. The CART-derived TTAT cutoff point was 10.7 h. The multivariate logistic regression analysis indicated delayed therapy (TTAT ≥ 10.7 h), pediatric risk of mortality (PRISM) III scores ≥ 10, time to positivity (TTP) ≤ 13 h, and requiring for invasive mechanical ventilation were independently associated with the incidence of septic shock (Odds ratio [OR] 9.87, 95% Confidence interval [CI] 1.46-66.59, P = 0.019; OR 9.69, 95% CI 1.15-81.39, P = 0.036; OR 8.28, 95% CI 1.37-50.10, P = 0.021; OR 6.52, 95% CI 1.08-39.51, P = 0.042; respectively) and in-hospital mortality (OR 22.19, 95% CI 1.25-393.94, P = 0.035; OR 40.06, 95% CI 2.32-691.35, P = 0.011; OR 22.60, 95% CI 1.78-287.27, P = 0.016; OR 12.21, 95% CI 1.06-140.67, P = 0.045; respectively).Conclusions: TTAT is an independent predictor of poor outcomes in children with nosocomial K. pneumoniae bloodstream infection. Initial appropriate antimicrobial therapy should be administrated timely and within 10.7 h from the onset of bloodstream infection is recommended.

Vitamin D Supplementation and Allergic Diseases during Childhood: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis to investigate the effects of vitamin D (VitD) supplementation on children with allergic diseases. MEDLINE, Embase, Web of Science, the Cochrane library, and three Chinese databases were searched up to 15 August 2022. Randomized controlled trials (RCTs) comparing a VitD supplementation versus a placebo for children with allergic diseases were included. Thirty-two RCTs with 2347 participants were included. VitD supplementation did not reduce the risk of asthma exacerbations in children compared with placebo overall (risk ratio (RR) = 0.84, 95% confidence interval (CI): 0.65 to 1.08, p = 0.18), but reduced the risk of asthma exacerbation in children with baseline serum 25(OH)D of <10 ng/mL compared with placebo (RR = 0.48, 95% CI: 0.28 to 0.83, p = 0.009). VitD supplementation significantly reduced Scoring Atopic Dermatitis or the Eczema Area and Severity Index scores in children with atopic dermatitis compared with placebo (standard mean difference = −0.5, 95% CI: −0.87 to −0.12, p = 0.009). VitD supplementation also reduced the symptom-medication score in children with allergic rhinitis compared with placebo (mean (standard deviation): 43.7 (3.3) vs. 57.8 (4.4), p = 0.001). In conclusion, VitD supplementation did not reduce asthma exacerbation risk in children overall but may reduce asthma exacerbation risk in children with serum 25(OH)D concentration < 10 ng/mL. VitD supplementation reduces the severity of atopic dermatitis and symptoms of allergic rhinitis in children.

Neonatal Streptococcus pneumoniae infection induces long-lasting dysbiosis of the gut microbiota in a mouse model.

Early life is a "critical window" for gut microbiota development, antibiotic use during this period exerts a profound effect on gut microbial dysbiosis and asthma. In clinical practice, antibiotics are usually used in patients with bacterial infections, we previously showed that neonatal S. pneumoniae pneumonia promoted adult-onset asthma in mice model, while it remains unclear whether neonatal S. pneumoniae infection have long-term effects on gut microbiota. Neonatal BALB/c mice were inoculated with 5*106 CFU D39 to establish non-lethal S. pneumoniae pneumonia model. At 2, 3, 8 weeks of age, feces in the cecum were prepared for 16S rRNA sequencing, lungs were collected for histopathologic and lung function analysis. S. pneumoniae-infected neonatal mice exhibited histopathologic lesions in their lungs and increased airway hyperresponsiveness, obvious alterations in alpha and beta diversities in the entire gut microbiota, and changes of the community structure during the breastfeeding period, infancy, and adulthood. Furthermore, gut microbial composition was modified after neonatal S. pneumoniae infection, with a decreased relative abundance of Lactobacillus in the breastfeeding period and infancy; in adulthood, the relative abundance of Allobaculum diminished while that of Proteobacteria was augmented. Neonatal S. pneumoniae infection induced a long-term alteration in microbial community composition.

Mettl3 downregulation in germinal vesicle oocytes inhibits mRNA decay and the first polar body extrusion during maturation†.

In oocytes, mRNA decay is essential for maturation and subsequent events, such as maternal-zygotic transition, zygotic genomic activation, and embryo development. Reversible N6-methyladenosine RNA methylation directly regulates transcription, pre-mRNA splicing, mRNA export, mRNA stability, and translation. Here, we identified that downregulation of N6-methyladenosine modification by microinjecting a methyltransferase-like 3 (Mettl3)-specific small interfering RNA into mouse germinal vesicle oocytes led to defects in meiotic spindles and the first polar body extrusion during maturation in vitro. By further quantitative real-time polymerase chain reaction and Poly(A)-tail assay analysis, we found that N6-methyladenosine methylation mainly acts by reducing deadenylation of mRNAs mediated by the carbon catabolite repression 4-negative on TATA less system, thereby causing mRNA accumulation in oocytes. Meanwhile, transcriptome analysis of germinal vesicle oocytes revealed the downregulation of transcripts of several genes encoding ribosomal subunits proteins in the Mettl3 small interfering RNA-treated group, suggesting that N6-methyladenosine modification might affect translation. Together, our results indicate that RNA methylation accelerates mRNA decay, confirming the critical role of RNA clearance in oocyte maturation.

[The Effect of Interventional Treatment with Bronchoscopy in 10 Children with Acquired Subglottic Stenosis].

OBJECTIVE: To explore the effects of interventional therapy with bronchoscopy in children with acquired subglottic stenosis (SGS). METHODS: The clinical data of ten pediatric inpatients with acquired SGS who were admitted to Children's Hospital of Chongqing Medical University, as well as their follow-up information obtained 1 week, 1 month, 3 months and 6 months after the procedure was done.were retrospectively analyzed to examine the effect of interventional bronchoscopic therapies, including balloon dilatation, holmium laser, and cryotherapy, in pediatric patients with acquired SGS. RESULTS: Among the 10 patients with acquired SGS, there were 5 boys and 5 girls aged between 1 month and 6 years and 5 months, with a median age of 11 months and 1 day. Among the 5 patients with acute acquired SGS, two were treated with balloon dilatation only, with one cured and one showing clinical improvement, while three received comprehensive interventional therapy combining balloon dilatation, holmium laser, and cryotherapy, with two cured and one showing improvement. Among the 5 patients with chronic acquired SGS, four cases were cured with comprehensive interventional therapy, while one case suffered from aggravated upper airway obstruction 4 + hours after balloon dilatation. The patient was subsequently put on invasive mechanical ventilation for 4 days, but was unable to be extubated. The parents signed do-not-resuscitate order and the patient died afterwards. Bronchoscopy performed 1 week, 1 month and 3 months after the procedure was done showed that the SGS was improved to varying degrees. CONCLUSION: Bronchoscopy intervention is an effective therapy for acquired SGS in children.