The role of LDH and ferritin levels as biomarkers for corticosteroid dosage in children with refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: This study explored the relationship between inflammatory markers and glucocorticoid dosage upon admission. METHODS: We conducted a retrospective analysis of 206 patients with refractory Mycoplasma pneumoniae pneumonia (RMPP) admitted to a Children's Hospital from November 2017 to January 2022. Patients were categorized into three groups based on their methylprednisolone dosage: low-dose (≤ 2 mg/kg/d), medium-dose (2-10 mg/kg/d), and high-dose (≥ 10 mg/kg/d). We compared demographic data, clinical manifestations, laboratory findings, and radiological outcomes. Spearman's rank correlation coefficient was used to assess relationships between variables. RESULTS: The median age was highest in the low-dose group at 7 years, compared to 5.5 years in the medium-dose group and 6 years in the high-dose group (P < 0.001). The body mass index (BMI) was also highest in the low-dose group at 16.12, followed by 14.86 in the medium-dose group and 14.58 in the high-dose group (P < 0.001). More severe radiographic findings, longer hospital stays, and greater incidence of hypoxia were noted in the high-dose group (P < 0.05). Additionally, significant increases in white blood cells, C-reactive protein, procalcitonin, lactate dehydrogenase (LDH), alanine transaminase, aspartate transaminase, ferritin, erythrocyte sedimentation rate, and D-dimer levels were observed in the high-dose group (P < 0.05). Specifically, LDH and ferritin were markedly higher in the high-dose group, with levels at 660.5 U/L and 475.05 ng/mL, respectively, compared to 450 U/L and 151.4 ng/mL in the medium-dose group, and 316.5 U/L and 120.5 ng/mL in the low-dose group. Correlation analysis indicated that LDH and ferritin levels were significantly and positively correlated with glucocorticoid dose (Spearman ρ = 0.672 and ρ = 0.654, respectively; P < 0.001). CONCLUSIONS: Serum LDH and ferritin levels may be useful biomarkers for determining the appropriate corticosteroid dosage in treating children with RMPP.

Development and validation of a nomogram for predicting severe respiratory syncytial virus-associated bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and is related to the severity of the disease. This study aimed to develop and validate a nomogram for predicting severe bronchiolitis in infants and young children with RSV infection. METHODS: A total of 325 children with RSV-associated bronchiolitis were enrolled, including 125 severe cases and 200 mild cases. A prediction model was built on 227 cases and validated on 98 cases, which were divided by random sampling in R software. Relevant clinical, laboratory and imaging data were collected. Multivariate logistic regression models were used to determine optimal predictors and to construct nomograms. The performance of the nomogram was evaluated by the area under the characteristic curve (AUC), calibration ability and decision curve analysis (DCA). RESULTS: There were 137 (60.4%) mild and 90 (39.6%) severe RSV-associated bronchiolitis cases in the training group (n = 227) and 63 (64.3%) mild and 35 (35.7%) severe cases in the validation group (n = 98). Multivariate logistic regression analysis identified 5 variables as significant predictive factors to construct the nomogram for predicting severe RSV-associated bronchiolitis, including preterm birth (OR = 3.80; 95% CI, 1.39-10.39; P = 0.009), weight at admission (OR = 0.76; 95% CI, 0.63-0.91; P = 0.003), breathing rate (OR = 1.11; 95% CI, 1.05-1.18; P = 0.001), lymphocyte percentage (OR = 0.97; 95% CI, 0.95-0.99; P = 0.001) and outpatient use of glucocorticoids (OR = 2.27; 95% CI, 1.05-4.9; P = 0.038). The AUC value of the nomogram was 0.784 (95% CI, 0.722-0.846) in the training set and 0.832 (95% CI, 0.741-0.923) in the validation set, which showed a good fit. The calibration plot and Hosmer‒Lemeshow test indicated that the predicted probability had good consistency with the actual probability both in the training group (P = 0.817) and validation group (P = 0.290). The DCA curve shows that the nomogram has good clinical value. CONCLUSION: A nomogram for predicting severe RSV-associated bronchiolitis in the early clinical stage was established and validated, which can help physicians identify severe RSV-associated bronchiolitis and then choose reasonable treatment.

Development and validation of a nomogram to predict plastic bronchitis in children with refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: Early identification of plastic bronchitis (PB) is of great importance and may aid in delivering appropriate treatment. This study aimed to develop and validate a nomogram for predicting PB in patients with refractory Mycoplasma pneumoniae pneumonia (RMPP). METHODS: A total of 547 consecutive children with RMPP who underwent fiberoptic bronchoscopy (FOB) intervention from January 2016 to June 2021 were enrolled in this study. Subsequently, 374 RMPP children (PB: 137, without PB: 237) from January 2016 to December 2019 were assigned to the development dataset to construct the nomogram to predict PB and 173 RMPP children from January 2020 to June 2021 were assigned to the validation dataset. The clinical, laboratory and radiological findings were screened using Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression was applied to construct a nomogram. The performance of the nomogram was evaluated by discrimination, calibration and clinical utility. Comparsion of ROC analysis and decision curve analysis (DCA) between nomogram and other models was performed to evaluate the discrimination ability and clinical utility. RESULTS: The development dataset included 374 patients with a mean age of 6.6 years and 185(49.5%) were men. The validation dataset included 173 patients and the mean age of the dataset was 6.7 years and 86 (49.7%) were men. From 26 potential predictors, LASSO regression identified 6 variables as significant predictive factors to construct the nomogram for predicting PB, including peak body temperature, neutrophil ratio (N%), platelet counts (PLT), interleukin-6 (IL-6), actic dehydrogenase (LDH) and pulmonary atelectasis. The nomogram showed good discrimination, calibration and clinical value. The mean AUC of the nomogram was 0.813 (95% CI 0.769-0.856) in the development dataset and 0.895 (95% CI 0.847-0.943) in the validation dataset. Through calibration plot and Hosmer-Lemeshow test, the predicted probability had a good consistency with actual probability both in the development dataset (P = 0.217) and validation dataset (P = 0.183), and DCA showed good clinical utility. ROC analysis indicated that the nomogram showed better discrimination ability compared with model of peak body temperature + pulmonary atelactsis and another model of N% + PLT + IL-6 + LDH, both in development dataset (AUC 0.813 vs 0.757 vs 0.754) and validation dataset (AUC 0.895 vs 0.789 vs 0.842). CONCLUSIONS: In this study, a nomogram for predicting PB among RMPP patients was developed and validated. It performs well on discrimination ability, calibration ability and clinical value and may have the potential for the early identification of PB that will help physicians take timely intervention and appropriate management.

A systematic review and meta-analysis of children with coronavirus disease 2019 (COVID-19).

To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings, and imaging features of coronavirus disease 2019 (COVID-19) in pediatric patients. A meta-analysis was carried out to identify studies on COVID-19 from 25 December 2019 to 30 April 2020. A total of 48 studies with 5829 pediatric patients were included. Children of all ages were at risk for COVID-19. The main illness classification ranged as: 20% (95% confidence interval [CI]: 14%-26%; I2 = 91.4%) asymptomatic, 33% (95% CI: 23%-43%; I2 = 95.6%) mild and 51% (95% CI: 42%-61%; I2 = 93.4%) moderate. The typical clinical manifestations were fever 51% (95% CI: 45%-57%; I2 = 78.9%) and cough 41% (95% CI: 35%-47%, I2 = 81.0%). The common laboratory findings were normal white blood cell 69% (95% CI: 64%-75%; I2 = 58.5%), lymphopenia 16% (95% CI: 11%-21%; I2 = 76.9%) and elevated creatine-kinase MB 37% (95% CI: 25%-48%; I2 = 59.0%). The frequent imaging features were normal images 41% (95% CI: 30%-52%; I2 = 93.4%) and ground-glass opacity 36% (95% CI: 25%-47%; I2 = 92.9%). Among children under 1 year old, critical cases account for 14% (95% CI: 13%-34%; I2 = 37.3%) that should be of concern. In addition, vomiting occurred in 33% (95% CI: 18%-67%; I2 = 0.0%) cases that may also need attention. Pediatric patients with COVID-19 may experience milder illness with atypical clinical manifestations and rare lymphopenia. High incidence of critical illness and vomiting symptoms reward attention in children under 1 year old.

Clinical characteristics of refractory mycoplasma pneumoniae pneumonia in children treated with glucocorticoid pulse therapy.

BACKGROUND: To observe the effect of corticosteroids in the treatment of children with refractory Mycoplasma pneumoniae pneumonia (RMPP) under different doses, to summarize the clinical features of children treated with glucocorticoid pulse therapy. METHODS: The clinical data of 125 children with RMPP hospitalized in Tianjin Children's Hospital from September 2018 to October 2019 were retrospectively analyzed. They were divided into two groups according to the dose of hormone. Compare the clinical features, laboratory findings, and imaging between the two groups, and use meaningful related indicators as ROC curves to find reference indicators for pulse therapy. RESULTS: (1) The median age of the group II was older than that of the group I(P < 0.05). (2) We found more severe presentations, higher incidence of extra-pulmonary complications and more serious radiological findings in group II, which needed oxygen more often, higher the hormone, higher usage rate of gamma globulin, higher usage rate of bronchoscopy, and higher incidence of plastic bronchitis(P < 0.05). (3) WBC, CRP, LDH, FER, D-D dimer, APTT, TT, PCT, IL-6 and the percentage of neutrophils in peripheral blood in Group II were higher than those in Group I(P < 0.05). (4) In ROC curve analysis, CRP, LDH, FER, and neutrophils of leukocyte classification were independent related factors that could be used as valuable predictors of methylprednisolone pulse therapy for RMPP in children. The cut-off values were CRP44.45 mg/L, LDH590IU/L, FER411ng/L, and neutrophils in leukocyte classification were 73.75%, respectively. CONCLUSION: CRP ≥ 44.45 mg/L, LDH ≥ 590 IU/L, FER ≥ 411 ng/L, neutrophil≥73.75%, lung consolidation, and pleural effusion may be predictors that guide the treatment of RMPP with pulse dose of GC.

Evaluation of Xpert MTB/RIF Ultra Assay for Diagnosis of Childhood Tuberculosis: a Multicenter Accuracy Study.

A multicenter study was performed to evaluate the value of testing gastric aspirate (GA) with Xpert MTB/RIF Ultra assay (Ultra) for childhood tuberculosis (TB) detection in China. In total, 129 children with active TB and 173 children without TB were enrolled. The sensitivity of Ultra in bacteriologically confirmed TB and probable TB cases was 87.5% (42/48) and 44.4% (36/81), respectively. The specificity of Ultra was high (99.4%, 172/173). When Ultra, culture, and acid-fast bacilli outcomes were integrated as a composite reference standard, the percentage of children with definite TB increased from 37.2% (48/129) to 67.4% (87/129). The sensitivity of Ultra is 80.0% (40/50) in children aged <4 years, which is significantly higher than that in older children (48.1%, 38/79) (P < 0.001). Ultra conducted using GA samples can provide faster results, allowing an early and accurate TB diagnosis, especially in younger children with difficulty producing sputum.

Detectable SARS-CoV-2 viral RNA in feces of three children during recovery period of COVID-19 pneumonia.

Coronavirus Disease 2019 (COVID-19) is a newly emerging infectious disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After its first occurrence in Wuhan of China from December 2019, COVID-19 rapidly spread around the world. According to the World Health Organization statement on 13 March 2020, there had been over 132 500 confirmed cases globally. Nevertheless, the case reports of children are rare, which results in the lack of evidence for preventing and controlling of children's infection. Here, we report three cases of SARS-CoV-2 infected children diagnosed from 3 February to 17 February 2020 in Tianjin, China. All of these three cases experienced mild illness and recovered soon after the treatment, with the nucleic acid of throat swab turning negative within 14, 11, and 7 days after diagnosis, respectively. However, after been discharged, all three cases were tested SARS-CoV-2 positive in the stool samples within 10 days, in spite of their remained negative nucleic acid in throat swab specimens. Therefore, it is necessary to be aware of the possibility of fecal-oral transmission of SARS-CoV-2 infection, especially for children cases.

Children with coronavirus disease 2019: A review of demographic, clinical, laboratory, and imaging features in pediatric patients.

There is a current outbreak of coronavirus disease 2019 (COVID-19), with a global spread. With the rapid increase in the number of infections, an increase is observed in the number of children with COVID-19. Most research findings are regarding adult cases, which are not always transferrable to children. Evidence-based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we included 2597 pediatric patients that reported recently and evaluated the demographic, clinical, laboratory, and imaging features of children with COVID-19. We found that even lymphopenia was the most common lab finding in adults; it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to occur in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children and to develop strategies to control the disease transmission.

Identify clinical factors related to Mycoplasma pneumoniae pneumonia with hypoxia in children.

BACKGROUND: To analyze the clinical characteristics of Mycoplasma pneumoniae pneumonia with hypoxia in children, and identify the associated risk factors of hypoxia in MPP. METHODS: A retrospective case-control study was performed on 345 children with Mycoplasma pneumoniae pneumonia (MPP) admitted to our hospital wards from January 2017 to June 2019. They were divided into three groups, namely MPP with hypoxia, refractory Mycoplasma pneumoniae pneumonia (RMPP), and general Mycoplasma pneumoniae pneumonia (GMPP). The clinical features, laboratory findings, imaging, and management were collected and compared in the three groups. RESULTS: The MPP with hypoxia patients (n = 69) had longer disease duration, a higher extra-pulmonary complications rate, and more severe radiological abnormalities (P < 0.05). They also needed more complicated treatments (P < 0.05). Meanwhile, the levels of white blood cell count (WBC), C-reactive protein (CRP), lactic dehydrogenase (LDH), interleukin (IL)-6, ferritin, D-dimer, fibrinogen (FG), alanine aminotransferase (ALT) and the percentage of neutrophils in the MPP with hypoxia group were significantly higher than those in the RMPP group and the GMPP group (P < 0.05). In ROC curve analysis, the percentage of neutrophils, WBC, CRP, LDH, IL-6, ferritin, D-dimer, and ALT were contributed to identify the MPP with hypoxia patients. Multivariate logistic regression analysis revealed that ferritin> 174.15 ng/mL, IL-6 > 25.475 pg/ml, and pleural effusion were significantly associated with the incidence of hypoxia in MPP (P < 0.01). CONCLUSION: MPP with hypoxia patients presented more serious clinical manifestations. Ferritin> 174.15 ng/mL, IL-6 > 25.475 pg/ml and pleural effusion were related risk factors for hypoxia in MPP.

[Molecular epidemiology of norovirus in children with acute gastroenteritis in Tianjin, China].

OBJECTIVE: To investigate the molecular epidemiological characteristics of norovirus (NoV) among children with acute gastroenteritis in Tianjin in 2017. METHODS: A total of 758 stool specimens were collected from the children with acute gastroenteritis possibly caused by viral infection in Tianjin Children's Hospital between January and December, 2017. Quantitative real-time RT-PCR was used for primary screening of NoV, and conventional RT-PCR was used for gene amplification, sequencing and genotype identification of the VP1 region of capsid protein in positive specimens. RESULTS: Among the 758 specimens, 241 (31.8%) were found to have GII NoV. Sequencing of the VP1 region of capsid protein in positive specimens showed that among the 241 specimens with GII NoV, 69 (28.6%) had GII.4 subtype, 51 (21.2%) had GII.3 subtype, 24 (10.0%) had GII.2 subtype, and 18 (7.5%) had other subtypes. There was a significant difference in NoV detection rate between different age groups (P=0.018), and the 1- <4 years group had the highest NoV detection rate (37.3%). There was also a significant difference in NoV detection rate across seasons (P<0.001), and there was a highest NoV detection rate in winter (48.1%). Twenty-seven children (3.6%) had co-infections with NoV and rotavirus. CONCLUSIONS: NoV is one of the major pathogens of the children with acute gastroenteritis from Tianjin in 2017. GII genotype, especially GII.4 subtype, is the prevalent strain. NoV infection is commonly seen in children less than 4 years and reaches the peak in winter. Some children are found to have co-infections with rotavirus.

Distinct clinical characteristics of bocavirus and Mycoplasma pneumoniae infection in children plastic bronchitis.

BACKGROUND: This study investigated clinical and laboratory characteristics of human bocavirus type 1 (HBoV1)-plastic bronchiolitis (PB), Mycoplasma pneumoniae (MP)-associated plastic bronchitis (PB) and MP-NPB in children, highlighting inflammation, coagulation, and bronchoscopic needs. METHODS: Data on preschool children with PB during HBoV1 or MP infection were collected, comparing MP-PB to severe Mycoplasma pneumoniae pneumonia. RESULT: Compared with the MP-PB group, the HBoV1-PB group, with younger children, had significantly milder clinical symptoms but higher WBC counts (p = .028). The MP-PB group exhibited notably elevated Fibrinogen (p = .045) and d-dimer levels (p < .001). When contrasting the MP-PB with the MP-NPB group, children in MP-PB group still had higher levels of d-dimer and increased inflammatory indicators such as C-reactive protein, procalcitonin, lactate dehydrogenase, and interleukin-6, which were significantly elevated compared with the MP-NPB group. MP-PB showed a higher prevalence of plastic bronchial casts in lower lobes (p = .016) and a dominance of neutrophils in BALF cytology. Additionally, children in the MP-PB group tended to undergo a greater number of bronchoscopies. CONCLUSION: This study identifies key differences in plastic bronchitis in children due to HBoV1 and MP, highlighting HBoV1's milder inflammation in younger kids and MP's link to severe inflammatory and coagulation responses, guiding clinical diagnosis and treatment.

Establishment of a Mouse Model of Mycoplasma pneumoniae-Induced Plastic Bronchitis.

Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to Mycoplasma pneumoniae (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15-20 min) and intratracheal administration (6-50 µL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 108 CFU/50 µL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP.

Clinical Evaluation of Metagenomic Next-Generation Sequencing for the detection of pathogens in BALF in severe community acquired pneumonia.

BACKGROUND: Rapid and accurate identification of pathogens is very important for the treatment of Severe community-acquired pneumonia (SCAP) in children. Metagenomic Next-generation sequencing (mNGS) has been applied in the detection of pathogenic bacteria in recent years, while the overall evaluation the application of SCAP in children is lacking. METHODS: In our study, 84 cases of SCAP were enrolled. Bronchoalveolar lavage fluid (BALF) samples were analysed using mNGS; and sputum, blood, and BALF samples were analysed using conventional technology (CT). RESULTS: Among the 84 children, 41 were boys, and 43 were girls, with an average age ranging from 2 months to 14 years. The pathogen detection rate of mNGS was higher than that of CT (83.3% [70/84] vs. 63.1% [53/84], P = 0.003). The mNGS was much greater than that of the CT in detecting Streptococcus pneumoniae (89.2% [25/29] vs. 44.8% [13/29], P = 0.001) and Haemophilus influenzae (91.7% [11/12] vs. 33.3% [4/12], P < 0.005). The mNGS also showed superior fungal detection performance compared with that of the CT (81.8% [9/11] vs. 18.2% [2/11], P = 0.004). The mNGS test can detect viruses, such as bocavirus, rhinovirus, and human metapneumovirus, which are not frequently recognised using CT. However, the mNGS detection rate was lower than that of the CT (52.4% [11/21] vs. 95.2% [20/21], P = 0.004) for Mycoplasma pneumoniae (MP). The detection rate of mNGS for mixed infection was greater than that of the CT, although statistical significance was not observed (26.3% [20/39] vs. 21.1% [16/39], P > 0.005). Treatment for 26 (31.0%) children was changed based on mNGS results, and their symptoms were reduced; nine patients had their antibiotic modified, five had antibiotics added, nine had their antifungal medication, and seven had their antiviral medication. CONCLUSION: mNGS has unique advantages in the detection of SCAP pathogens in children, especially S. pneumoniae, H. influenzae, and fungi. However, the detection rate of MP using mNGS was lower than that of the CT. Additionally, mNGS can detect pathogens that are not generally covered by CT, which is extremely important for the modification of the treatment strategy.

Efficacy and safety of CO2 cryotherapy in the treatment of infants with tracheobronchial tuberculosis.

Objective: This study aimed to investigate the efficacy and safety of CO2 cryotherapy for lymph node fistula tracheobronchial tuberculosis (TBTB) in infants. Patients and methods: A retrospective analysis was undertaken on seven patients with lymph node fistula tracheobronchial tuberculosis who underwent fiberoptic bronchoscopy (FB) interventional therapy in the respiratory department of Tianjin Children's Hospital from July 2012 to July 2020. The efficacy, safety, and prognosis of CO2 cryotherapy intervention for the treatment of lymph node fistula TBTB in infants were summarized and analyzed. Results: Seven patients with lymph node fistula TBTB were included in this study. Their ages ranged from 6-13 months. The course of the disease from onset to TBTB ranged from 20 to 70 days. The pathological diagnoses of seven cases by FB combined with tissue biopsy were lymph node fistula TBTB, of which 28.57% (two cases) were in the early stage of rupture and 71.43% (five cases) were in the rupture stage. All patients were treated with CO2 cryotherapy combined with foreign body forceps and local injection drugs based on systemic antituberculosis chemotherapy. Two patients were treated once with CO2 cryotherapy, and five were treated three times. According to the comparison of the clinical symptoms, imaging results, and endoscopic presentations before and after the intervention, six patients achieved clinical cure, and one achieved clinical improvement. No severe intraoperative or postoperative complications were observed. The clinical symptoms, endoscopic findings, radiological manifestations, and quality of life of all patients showed marked improvement. No recurrence occurred after 3-6 months of follow-up with FB. Conclusion: CO2 cryotherapy can improve the treatment effect of lymph node fistula in infants with TBTB and reduce the incidence of complications. This treatment is safe and reliable in infants.

Development and Validation of a Novel Gene Signature for Predicting the Prognosis of Idiopathic Pulmonary Fibrosis Based on Three Epithelial-Mesenchymal Transition and Immune-Related Genes.

Background: Increasing evidence has revealed that epithelial-mesenchymal transition (EMT) and immunity play key roles in idiopathic pulmonary fibrosis (IPF). However, correlation between EMT and immune response and the prognostic significance of EMT in IPF remains unclear. Methods: Two microarray expression profiling datasets (GSE70866 and GSE28221) were downloaded from the Gene Expression Omnibus (GEO) database. EMT- and immune-related genes were identified by gene set variation analysis (GSVA) and the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the functions of these EMT- and immune-related genes. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to screen prognostic genes and establish a gene signature. Gene Set Enrichment Analysis (GSEA) and Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) were used to investigate the function of the EMT- and immune-related signatures and correlation between the EMT- and immune-related signatures and immune cell infiltration. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to investigate the mRNA expression of genes in the EMT- and immune-related signatures. Results: Functional enrichment analysis suggested that these genes were mainly involved in immune response. Moreover, the EMT- and immune-related signatures were constructed based on three EMT- and immune-related genes (IL1R2, S100A12, and CCL8), and the K-M and ROC curves presented that the signature could affect the prognosis of IPF patients and could predict the 1-, 2-, and 3-year survival well. Furthermore, a nomogram was developed based on the expression of IL1R2, S100A12, and CCL8, and the calibration curve showed that the nomogram could visually and accurately predict the 1-, 2-, 3-year survival of IPF patients. Finally, we further found that immune-related pathways were activated in the high-risk group of patients, and the EMT- and immune-related signatures were associated with NK cells activated, macrophages M0, dendritic cells resting, mast cells resting, and mast cells activated. qRT-PCR suggested that the mRNA expression of IL1R2, S100A12, and CCL8 was upregulated in whole blood of IPF patients compared with normal samples. Conclusion: IL1R2, S100A12, and CCL8 might play key roles in IPF by regulating immune response and could be used as prognostic biomarkers of IPF.

Clinical evaluation of metagenomic next-generation sequencing for detecting pathogens in bronchoalveolar lavage fluid collected from children with community-acquired pneumonia.

This study is to evaluate the usefulness of pathogen detection using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) specimens from children with community-acquired pneumonia (CAP). We retrospectively collected BALF specimens from 121 children with CAP at Tianjin Children's Hospital from February 2021 to December 2021. The diagnostic performances of mNGS and conventional tests (CT) (culture and targeted polymerase chain reaction tests) were compared, using composite diagnosis as the reference standard. The results of mNGS and CT were compared based on pathogenic and non-pathogenic organisms. Pathogen profiles and co-infections between the mild CAP and severe CAP groups were also analyzed. The overall positive coincidence rate was 86.78% (105/121) for mNGS and 66.94% (81/121) for CT. The proportion of patients diagnosed using mNGS plus CT increased to 99.18%. Among the patients, 17.36% were confirmed only by mNGS; Streptococcus pneumoniae accounted for 52.38% and 23.8% of the patients were co-infected. Moreover, Bordetella pertussis and Human bocavirus (HBoV) were detected only using mNGS. Mycoplasma pneumoniae, which was identified in 89 (73.55%) of 121 children with CAP, was the most frequent pathogen detected using mNGS. The infection rate of M. pneumoniae in the severe CAP group was significantly higher than that in the mild CAP group (P = 0.007). The symptoms of single bacterial infections (except for mycoplasma) were milder than those of mycoplasma infections. mNGS identified more bacterial infections when compared to the CT methods and was able to identify co-infections which were initially missed on CT. Additionally, it was able to identify pathogens that were beyond the scope of the CT methods. The mNGS method is a powerful supplement to clinical diagnostic tools in respiratory infections, as it can increase the precision of diagnosis and guide the use of antibiotics.

Development of a Nomogram for Predicting Refractory Mycoplasma pneumoniae Pneumonia in Children.

Background: In children, refractory Mycoplasma pneumoniae pneumonia (RMPP) may result in severe complications and high medical costs. There is research on a simple and easy-to-use nomogram for early prediction and timely treatment of RMPP. Methods: From December 2018 to June 2021, we retrospectively reviewed medical records of 299 children with Mycoplasma pneumoniae pneumonia (MPP) hospitalized in Tianjin Children's Hospital. According to their clinical manifestations, patients were divided into the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group. The clinical manifestations, laboratory indicators, and radiological data of the two groups were obtained. Stepwise regression was employed for variable selection of RMPP. The predictive factors selected were used to construct a prediction model which presented with a nomogram. The performance of the prediction model was evaluated by C statistics, calibration curve, and receiver operating characteristic (ROC) curve. Results: The RMPP group significantly showed a higher proportion of females, longer fever duration, and longer hospital stay than the GMPP group (P < 0.05). Additionally, the RMPP group revealed severe clinical characteristics, including higher incidences of extrapulmonary complications, decreased breath sounds, unilateral pulmonary consolidation >2/3, and plastic bronchitis than the GMPP group (P < 0.05). The RMPP group had higher neutrophil ratio (N%), C-reactive protein (CRP), interleukin-6 (IL-6), lactic dehydrogenase (LDH), and D-dimer than the GMPP group (P < 0.05). Stepwise regression demonstrated that CRP [OR = 1.075 (95% CI: 1.020-1.133), P < 0.001], LDH [OR = 1.015 (95% CI: 1.010-1.020), P < 0.001], and D-dimer [OR = 70.94 (95% CI: 23.861-210.904), P < 0.001] were predictive factors for RMPP, and developed a prediction model of RMPP, which can be visualized and accurately quantified using a nomogram. The nomogram showed good discrimination and calibration. The area under the ROC curve of the nomogram was 0.881, 95% CI (0.843, 0.918) in training cohorts and 0.777, 95% CI (0.661, 0.893) in validation cohorts, respectively. Conclusion: C-reactive protein, LDH, and D-dimer were predictive factors for RMPP. The simple and easy-to-use nomogram assisted us in quantifying the risk for predicting RMPP, and more accurately and conveniently guiding clinicians to recognize RMPP, and contribute to a rational therapeutic choice.

Analysis of the risk factors and clinical features of Mycoplasma pneumoniae pneumonia with embolism in children: a retrospective study.

BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) is a prevalent disease in community-acquired pneumonia among children. However, in addition to respiratory manifestations, it may also develop extra-pulmonary complications. Embolism is one of the uncommon extra-respiratory manifestations prone to severe sequelae and even death. This study aims to analyze the clinical features of MPP with embolism in children, and explore the associated risk factors of embolism in MPP patients. METHODS: A retrospective case-control analysis was performed on 48 children with MPP admitted to our hospital wards between January 2010 and December 2021. Embolism group comprised children with embolism by CTA or MRA results, whereas the non-embolism group comprised children with clinical suspicion of embolism but negative diagnostic imaging support. The clinical features, laboratory findings and imaging were analyzed to explore the risk factors for embolism in children with MPP. RESULTS: A total of 48 children with MPP were enrolled in the study (16 cases and 32 controls). In the embolism group, 10 patients (62.5%) had pulmonary embolism, 3 patients (18.75%) presented ventricle embolism, 2 patients (12.5%) presented cerebral and carotid artery embolism, one patient (6.25%) had a cerebral embolism, limb, and spleen, respectively. The univariate analysis revealed the maximum body temperature (Tmax), CRP, D-dimer (closest to CTA/MRA), the percentage of neutrophils (N%), pulmonary consolidation (⩾ 2/3 lobe), pleural effusion and atelectasis have significant differences between the embolism group and non-embolism group (P < 0.05). Multivariate logistic regression analysis showed that D-dimer (closest to CTA/MRA) > 3.55 mg/L [OR = 1.255 (95% CI: 1.025-1.537), P < 0.05], pulmonary consolidation (⩾ 2/3 lobe) [OR = 8.050 (95% CI: 1.341-48.327), P < 0.05], and pleural effusion [OR = 25.321 (95% CI: 2.738-234.205), P < 0.01] were independent risk factors for embolism in children with MPP. CONCLUSION: In conclusion, MPP with embolism patients have more D-dimer values and severe radiologic manifestations.

Case Report: Cardiac Multiple Thrombus and Pulmonary Embolism Associated With Mycoplasma Pneumonia Infection in a Child.

Mycoplasma pneumoniae (MP) is a common pathogen of lower respiratory tract infection in children and adolescents. Some patients with MP infection are self-limiting, while with the increase of severe or refractory Mycoplasma pneumoniae pneumonia (MPP) in recent years, there is a great increase in reports of thromboembolism in multiple organs, including lung, brain, spleen, and peripheral arteries. Cardiac multiple thrombi and pulmonary embolism associated with MP infection have not been reported. The most effective treatment option for cardiac thrombus was surgical resection for fear of thrombus detachment and causing new thromboembolism. Herein, we present a patient with cardiac multiple thrombi and pulmonary embolism in MPP for the first time. In our case, the child recovered after conservative medical treatment, which provides a therapeutic option for children with cardiac multiple thrombi.

Successful treatment of pleural empyema and necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus infection following influenza A virus infection: A case report and literature review.

With the rapid increase in the number of infections, children with Staphylococcus aureus (S. aureus) infection secondary to Influenza A virus (IAV), appear to have a great possibility of causing severe complications and illness. Despite some cases and research findings regarding the death of children with IAV and S. aureus, coinfection included, there were few details about successful treatment of pleural empyema and necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) infection following IAV. In this case report, we describe the clinical symptoms and treatment of a teenager with pleural empyema and necrotizing pneumonia related to S. aureus secondary infection who was initially infected by IAV. This case highlights the importance of early recognition and application of thoracoscopy for this potentially fatal pleural empyema caused by MRSA and IAV coinfection. We conclude that this is a significant case that contributes to raising awareness regarding rarely occurring severe respiratory infections by MRSA in a child with normal immune function after IAV. In addition, further studies are needed to explore risk factors for IAV coinfection with S. aureus.