[Correlation of nutritional status with clinical characteristics and lung function in children with cystic fibrosis]. / å›Šæ€§çº¤ç»´åŒ–å„¿ç«¥è¥å »çŠ¶å†µä¸Žä¸´åºŠç‰¹å¾å’Œè‚ºåŠŸèƒ½çš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To investigate the nutritional status of children with cystic fibrosis (CF) and understand the correlation between malnutrition and clinical characteristics as well as lung function. METHODS: A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023. Clinical characteristics of CF children with different nutritional statuses were compared, and the correlation between malnutrition and lung function was analyzed. RESULTS: A total of 52 CF children were included, comprising 25 boys (48%) and 27 girls (52%), aged between 7 months and 17 years. Respiratory symptoms were the predominant clinical manifestations (96%, 50/52). The prevalence of malnutrition was 65% (34/52), with moderate/severe malnutrition being the most common (65%, 22/34). The malnutrition group had a longer duration of illness, higher proportion of digestive system symptoms, and lower levels of serum albumin (P<0.05). Pulmonary function parameters, including forced expiratory volume in one second as a percentage of the predicted value, ratio of forced expiratory volume in one second to forced vital capacity, forced expiratory flow at 25% of forced vital capacity exhaled, forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled, and maximum mid-expiratory flow as a percentage of the predicted value, were lower in the malnutrition group compared to the normal nutrition group (P<0.05). Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters (P<0.05). CONCLUSIONS: The prevalence of malnutrition is high in CF children and is associated with decreased lung function. CF children with higher body mass index have better lung function. Therefore, screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.

Genetic spectrum of Chinese children with cystic fibrosis: comprehensive data analysis from the main referral centre in China.

BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF) is a heterogeneous disease with a diverse genetic spectrum among populations. Few patients with CF of Chinese origin have been reported worldwide. The objective of this study is to characterise the genotypic features of CF in Chinese children. METHODS: We recruited and characterised the genetic manifestations of 103 Chinese children with CF in Beijing Children's Hospital from 2010 to 2022. Whole-exome sequencing were performed to define the genotypes. Meanwhile, other 99 genetically confirmed patients with Chinese origin described in 45 references were also summarised. RESULTS: 158 different variants including 23 novel observations were identified after sequencing. The majority of CFTR variants (82.3%) in Chinese have been observed only once or twice. 43.7% of the variants were only identified in patients of Chinese origin. The c.2909G>A(p.Gly970Asp), c.1766+5G>T and c.1657C>T(p.Arg553X) were the most frequent variants among Chinese patients, with allele frequency of 12.1%, 5.4% and 3.6%, respectively. The first two variants both showed significant Chinese ethnic tendency, while the latter one most likely came from Europeans for historical reasons. They also demonstrated significant differences in geographical distribution. c.1521_1523delCTT(p.F508del) was rarely observed in patients of pure Chinese origin, with an allele frequency of 1.8%. Two de novo variants (c.960dupA[p.Ser321IlefsX43] and c.2491-2A>G) and two deep-intronic variants (c.3718-2477C>T and c.3874-4522A>G) were identified, which were also quite rare among Chinese. CONCLUSIONS: The genetic spectrum of CF in Chinese is unique and quite different from that observed in Caucasians. The geographical distributions of the most frequent variants were reported for the first time.

Clinical and genetic analysis of two patients with primary ciliary dyskinesia caused by a novel variant of DNAAF2.

BACKGROUND: The study describes the clinical manifestations and variant screening of two Chinese siblings with primary ciliary dyskinesia (PCD). They carry the same DNAAF2 genotype, which is an extremely rare PCD genotype in the Chinese population. In addition, the study illustrated an overview of published variants on DNAAF2 to date. METHODS: A two-child family was recruited for the study. Clinical manifestations, laboratory tests, bronchoscopic and otoscopic images, and radiographic data were collected. Whole blood was collected from siblings and their parents for whole-exome sequencing (WES) and Sanger sequencing to screen variants. RESULTS: The two siblings exhibited typical clinical manifestations of PCD. Two compound heterozygous variants in DNAAF2 were detected in both by WES. Nonsense variant c.156 C>A and frameshift variant c.177_178insA, which was a novel variant. CONCLUSION: The study identified a novel variant of DNAAF2 in Chinese children with a typical phenotype of PCD, which may enrich our knowledge of the clinical, diagnostic and genetic information of DNAAF2-induced PCD in children.

Methodology and experiences of rapid advice guideline development for children with COVID-19: responding to the COVID-19 outbreak quickly and efficiently.

BACKGROUND: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.

Guidelines for the prevention and management of children and adolescents with COVID-19.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Childhood-onset Takayasu arteritis presenting as pyoderma gangrenosum-like vasculitic ulceration: Three case reports and a literature review.

We report a small case series of childhood-onset Takayasu arteritis (c-TA) presenting as pyoderma gangrenosum (PG)-like vasculitic ulceration. The cutaneous vasculitic ulcers in systemic vasculitis are rare and severe, sometimes leading to delayed diagnosis and treatment. We summarised the clinical features and highlighted the warning signs of c-TA associated with PG-like vasculitic ulceration.

Perceived parental support and college students' depressive symptoms during the COVID-19 pandemic: The mediating roles of emotion regulation strategies and resilience.

The current study examined the mediating roles of emotion regulation strategies (i.e., cognitive reappraisal and expressive suppression) and resilience in the relationship between perceived parental support and depressive symptoms among college students during the first wave of the COVID-19 pandemic in China. A large sample of Chinese college students (N = 2, 423) participated in this investigation. Results indicated that perceived parental support was negatively related to depressive symptoms. The two emotion regulation strategies and resilience partially and serially mediated the relation between perceived parental support and depressive symptoms. Theoretical and practical implications of these results are discussed.

The potential roles of m6A modification in regulating the inflammatory response in microglia.

BACKGROUND: Microglia are key regulators of the inflammatory response in the brain. Adenosine in RNAs can be converted to m6A (N6-methyladenosine), which regulates RNA metabolism and functions as a key epitranscriptomic modification. The m6A modification pattern and m6A-related signatures under pro-inflammatory and anti-inflammatory conditions of microglia remain unclear. METHODS: Primary rat microglia were differentiated into pro-inflammatory M1-like (M1-L), anti-inflammatory M2-like (M2-L), and resting, unstimulated (M0-L) phenotypes. m6A mRNA and lncRNA epitranscriptomic microarray analyses were performed, and pathway analysis was conducted to understand the functional implications of m6A methylation in mRNAs and lncRNAs. The m6A methylation level and gene expression of mRNAs and lncRNAs were subsequently verified by m6A Me-RIP and qRT-PCR. RESULTS: A total of 1588 mRNAs and 340 lncRNAs, 315 mRNAs and 38 lncRNAs, and 521 mRNAs and 244 lncRNAs were differentially m6A methylated between M1-L and M0-L (M1-L/M0-L), M2-L and M0-L (M2-L/M0-L), M2-L and M1-L (M2-L/M1-L), respectively. Furthermore, 4902 mRNAs, 4676 mRNAs, and 5095 mRNAs were identified distinctively expressed in M1-L/M0-L, M2-L/M0-L, and M2-L/M1-L, respectively. Pathway analysis of differentially m6A methylated mRNAs and lncRNAs in M1-L/M0-L identified immune system, signal transduction, and protein degradation processes. In contrast, the distinct m6A methylated mRNAs in M2-L/M0-L were involved in genetic information processing, metabolism, cellular processes, and neurodegenerative disease-related pathways. We validated m6A methylation and the expression levels of five mRNAs and five lncRNAs, which were involved in upregulated pathways in M1-L/M0-L, and five mRNAs involved in upregulated pathways in M2-L/M0-L. CONCLUSIONS: These findings identify a distinct m6A epitranscriptome in microglia, and which may serve as novel and useful regulator during pro-inflammatory and anti-inflammatory response of microglia.

Salidroside Inhibits Reactive Astrogliosis and Glial Scar Formation in Late Cerebral Ischemia via the Akt/GSK-3ß Pathway.

Cerebral ischemia leads to reactive astrogliosis and glial scar formation. Glial scarring can impede functional restoration during the recovery phase of stroke. Salidroside has been shown to have neuroprotective effects after ischemic stroke, but its impact on long-term neurological recovery, especially whether it regulates reactive astrogliosis and glial scar formation, is unclear. In this study, male adult C57/BL6 mice were subjected to transient cerebral ischemia injury followed by intravenous salidroside treatment. Primary astrocytes were treated with lipopolysaccharide (LPS) or conditioned medium from cultured primary neurons subjected to oxygen-glucose deprivation (CM-OGD). Salidroside significantly improved long-term functional outcomes following ischemic stroke in the rotarod and corner tests. It also reduced brain glial scar volume and decreased expression of the glial scar marker, glial fibrillary acidic protein (GFAP) and inhibited astrocyte proliferation. In primary astrocyte cultures, salidroside protected astrocytes from CM-OGD injury-induced reactive astroglial proliferation, increasing the percentage of cells in G0/G1 phase and reducing the S populations. The inhibitory effect of salidroside on the cell cycle was related to downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA expression and increased p27Kip1 mRNA expression. Similar results were found in the LPS-stimulated injury model in astroglial cultures. Western blot analysis demonstrated that salidroside attenuated the CM-OGD-induced upregulation of phosphorylated Akt and glycogen synthase kinase 3ß (GSK-3ß). Taken together, these results suggested that salidroside can inhibit reactive astrocyte proliferation, ameliorate glial scar formation and improve long-term recovery, probably through its effects on the Akt/GSK-3ß pathway.

Prognosis and treatment of 46 Chinese pediatric cystic fibrosis patients.

BACKGROUND: Since public awareness of cystic fibrosis (CF) has increased, more children have been diagnosed with CF in China. This study aimed to investigate medical and other challenges faced by pediatric CF patients in China. METHOD: Treatments and treatment outcomes were retrospectively analyzed for 46 pediatric CF patients diagnosed from August 2009 to June 2019. Pre- and post-treatment results were compared using independent samples t-test. RESULTS: Of 46 pediatric CF study patients, four died and five were lost to follow-up. Thirty-seven patients were monitored for 0.03 to 9.21 years; patients exhibited fewer attacks of respiratory tract infections after diagnosis (4.49 ± 2.13 episodes/year before diagnosis vs 1.97 ± 1.87 times/year after 1-year treatment, p < 0.05), significantly reduced sputum production and experienced 1.62 ± 1.71 exacerbations/year. Patient mean body mass index was 16.87 ± 3.53 and pancreatic malfunction persisted in 15 patients. For 17 children, no significant differences in lung function were found at follow-up as compared to lung function at diagnosis (FEV1: 82.45% ± 16.56% vs 75.26% ± 22.34%, FVC: 87.18% ± 13.64% vs 86.99% ± 19.95%, FEF75%: 46.51% ± 28.78% vs 36.63% ± 24.30%, P = 0.27, 0.97, 0.20, respectively). Pseudomonas aeruginosa (17/27) and bronchiectasis (22/22) were found during follow-up evaluation. Twenty-four patients (64.8%) maintained good adherence to therapies. Overall, azithromycin and tobramycin treatments were administered for 0.5-62 months and 0.5-48 months, respectively, and triggered no obvious adverse reactions. CONCLUSION: No obvious declines in clinical presentation or lung function were found in Chinese pediatric CF patients after receiving standard therapeutic and active treatments, although malnutrition and low compliance were persistent challenges.

[Case Report: Three Pediatric Pulmonary Cryptococcosis Patients with Prominent Manifestation of Mediastinal Lymphadenopathy].

In this study, we report on three immunocompetent children with pulmonary cryptococcosis presenting mediastinal lymphadenopathy as the prominent manifestation. All three children were otherwise healthy previously. Two children had a history of exposure to pigeons and poultry. All three presented persistent fever accompanied by mild cough. There were no obvious positive signs in the lungs. One patient had enlarged cervical lymph nodes. All three had elevated levels of white blood cells, neutrophil count, and C-reactive protein (CRP). The levels of IgG, IgM, IgA, IgE and T cell subsets were normal in all cases, and they were all tested negative for HIV antibody. Two children were tested positive for serum cryptococcal antigen (sCRAG). The chest X-ray and pulmonary CT findings of the three patients all demonstrated marked enlargement of mediastinal lymph nodes, and one patient had nodules in the parenchyma. Surgical biopsies of mediastinal lymph nodes were performed in two children and large numbers of capsule spores were found in the histological examination. In the three cases, definitive diagnosis of pulmonary cryptococcosis were made in two patients, and clinical diagnosis was made in the third patient. Two patients were treated with fluconazole alone. The other patient whose condition was complicated with spleen infection was treated with fluconazole combined with amphotericin B for the first month, and was then given fluconazole for maintenance treatment. The overall treatment course lasted 5-9 months and all three were cured eventually. In conclusion, immunocompetent children with pulmonary cryptococcosis may present mediastinal lymphadenopathy as a prominent or isolated manifestation, which should be considered in differential diagnosis. Treatment with fluconazole alone or in combination with amphotericin B when it was necessary showed good therapeutic outcomes.

Efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children: a real-world study. / æ§æžé»„é¢—ç²’è¾ åŠ©æ²»ç–—å„¿ç«¥æ”¯æ°”ç®¡å“®å–˜ç–—æ•ˆçš„çœŸå®žä¸–ç•Œç ”ç©¶.

OBJECTIVES: To study the efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children. METHODS: A multicenter, prospective, and registered real-world study was performed for the children, aged 2-5 years, who had a confirmed diagnosis of bronchial asthma in the outpatient service of 21 hospitals in China. Among these children, the children treated with medications for long-term asthma control (inhaled corticosteroid and/or leukotriene receptor antagonist) without Huaiqihuang granules were enrolled as the control treatment group, and those treated with medications for long-term asthma control combined with Huaiqihuang granules were enrolled as the combined treatment group. The medical data of all children were collected. Outpatient or telephone follow-up was performed at weeks 4, 8, 12, 20, 28, and 36 after treatment, including asthma attacks and rhinitis symptoms. A statistical analysis was performed for the changes in these indices. RESULTS: There was no significant difference in the frequency of asthma attacks or rhinitis attacks between the two groups before treatment (P>0.05). After treatment, the combined treatment group had significantly lower frequencies of asthma attacks, severe asthma attacks, and rhinitis attacks compared with the control treatment group (P<0.05). There was no signification difference in the incidence rate of adverse reactions between the two groups (P=0.667). CONCLUSIONS: Huaiqihuang granules in addition to medications for long-term asthma control can alleviate the symptoms of bronchial asthma and rhinitis and improve the level of asthma control in children with bronchial asthma, with good safety and little adverse effect. Citation.

STING-Associated Vasculopathy with Onset in Infancy in Three Children with New Clinical Aspect and Unsatisfactory Therapeutic Responses to Tofacitinib.

PURPOSE: STING-associated vasculopathy with onset in infancy (SAVI) is a new rare auto-inflammatory disease. The purpose of this study is to report new cases and summarize the manifestations and outcome of SAVI. METHODS: We made a retrospective analysis of three pediatric patients diagnosed with SAVI between March 2016 and July 2018 in Beijing Children's Hospital. RESULTS: Three patients comprised one boy and two girls. The median age of onset was 4 months. All patients had the same de novo heterozygous mutation (c.463G>A, p. V155M) of TMEM173. All patients presented with interstitial lung disease and one coexisted with diffuse alveolar hemorrhage. Rashes were presented in two patients. Other clinical manifestations include febrile attacks, failure to thrive, arthritis, myositis, cerebrovascular involvement, ureteral calculus, gastroesophageal reflux, and malnutrition. Ground-glass opacities were the most common features of chest computed tomography, followed with cysts and reticular opacities. Transbronchial lung biopsy was performed in one patient revealing pulmonary vasculitis. Skin biopsy was performed in one patient with changes of vasculitis. All patients were treated with corticosteroids and two patients received combined treatment of tofacitinib. The therapeutic effects of tofacitinib were limited on interstitial lung disease in both patients and were poor on rashes in one patient. One patient under the treatment of tofacitinib died. CONCLUSIONS: New clinical aspect of diffuse alveolar hemorrhage is first reported to be associated with SAVI. Unsatisfactory therapeutic effects of tofacitinib are observed in this study and further evaluations are needed.

Airway microbiome, host immune response and recurrent wheezing in infants with severe respiratory syncytial virus bronchiolitis.

BACKGROUND: Early interactions between respiratory viruses and microbiota might modulate host immune responses and subsequently contribute to later development of recurrent wheezing and asthma in childhood. We aimed to study the possible association between respiratory microbiome, host immune response, and the development of recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis. METHODS: Seventy-four infants who were hospitalized at Beijing Children's Hospital during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included and followed up until the age of 3 years. Sputum samples were collected, and their microbiota profiles, LPS, and cytokines were analyzed by 16S rRNA-based sequencing, ELISA, and multiplex immunoassay, respectively. RESULTS: Twenty-six (35.1%) infants developed recurrent wheezing by the age of 3 years, and 48 (64.9%) did not. The relative abundance of Haemophilus, Moraxella, and Klebsiella was higher in infants who later developed recurrent wheezing than in those who did not (LDA score >3.5). Airway levels of LPS (P = .003), CXCL8 (P = .004), CCL5 (P = .029), IL-6 (P = .004), and IL-13 (P < .001) were significantly higher in infants who later developed recurrent wheezing than in those who did not. Moreover, high airway abundance of Haemophilus was associated with CXCL8 (r = 0.246, P = .037) level, and that of Moraxella was associated with IL-6 level (r = 0.236, P = .046) and IL-10 level (r = 0.266, P = .024). CONCLUSION: Our study suggests that higher abundance of Haemophilus and Moraxella in airway microbiome might modulate airway inflammation during severe RSV bronchiolitis in infancy, potentially contributing to the development of subsequent recurrent wheezing in later childhood.

Mycoplasma pneumoniae pneumonia associated thrombosis at Beijing Children's hospital.

BACKGROUND: With the increase of awareness of mycoplasma pneumoniae pneumonia (MPP), we found thrombosis in severe MPP (SMPP) was not rare. The aim of the study was to investigate the clinical characteristics, treatment, and long-term prognosis of MPP-associated thrombosis. METHODS: We retrospectively reviewed the medical records of 43 children with MPP-associated thrombosis between January 2013 and June 2019 at Beijing Children's Hospital. The results of blood coagulation studies, autoimmune antibody, thrombophilia screening, contrast-enhanced lung computed tomography, echocardiography, and blood vessel ultrasonography were analyzed, as were treatment outcomes. RESULTS: Forty-two patients were diagnosed with SMPP. D-dimer was higher than 5.0 mg/L in 58.1% (25/43) of patients. The mean D-dimer level was 11.1 ± 12.4 mg/L. Anticardiolipin-IgM was positive in 60.0% of patients, ß2-glycoprotein-IgM in 64.0%, and lupus anticoagulant in 42.1%. Chest imaging revealed pulmonary consolidation with lobe distribution in all patients (2/3-1 lobe in 10 patients, > 1 lobe in 29 patients). In our experience, thrombosis can occur in a vessel of any part of the body, and it can be initially detected as late as 31 days after disease onset. Thrombosis in the brain and abdomen can occur early, at 5 days after disease onset. Pulmonary vessels were the most commonly involved sites in the current study, and accordingly chest pain was the most common symptom (32.6%), followed by neurological symptoms (14.0%) and abdominal pain (9.3%). Thirty-five percent of patients were asymptomatic with regard to thrombosis. All patients underwent anticoagulant therapy, and thrombus absorption took > 3 months in most patients. All patients were followed until October 2019, at which time 41 were asymptomatic and 2 had mild recurrent cough. CONCLUSIONS: SMPP with pulmonary consolidation (> 2/3 lobe) was the most strongly associated risk factor for thrombosis. Thrombosis-associated symptoms may be subtle, even absent. Elevated D-dimer, specifically > 11.1 mg/L (even > 5.0 mg/L), would assist in the early diagnosis of thrombosis. The long-term prognosis of thrombosis was good after timely administration of anticoagulant therapy.

High Mycoplasma pneumoniae loads and persistent long-term Mycoplasma pneumoniae DNA in lower airway associated with severity of pediatric Mycoplasma pneumoniae pneumonia.

BACKGROUND: An increased number of refractory mycoplasma pneumoniae (MP) pneumonia (MPP) cases have been reported. However the duration of MP infection in lower airway and the course of anti-MP treatment remains unclear. METHODS: We retrospectively reviewed the medical records of 94 MPP children. Patients were classified into two groups. The long-term group (Group LT) was defined as bronchoalveolar lavage fluid (BALF) remained MP-positive by PCR after 30 days of the disease course. The non-long-term group (Group NLT) was defined as BALF became MP-negative by PCR within 30 days of disease and patients who only needed one bronchoscopy lavage therapy. MP loads, clinical outcomes were analyzed along with other clinical measurements. RESULTS: The average levels of inflammatory markers such as C reactive protein and lactate dehydrogenase in Group LT were significantly higher than those in Group NLT. Airway and lung damage in Group LT were more severe than Group NLT. 28 patients developed necrotizing pneumonia and 8 patients developed pulmonary embolism in Group LT. Mean maximum MP loads in BALF were 107.46 ± 0.93 and 104.86 ± 0.93 in Groups LT and NLT, respectively. There was persistent MP DNA in Group LT, even lasted for 120 days. One severe MPP patient in Group LT had MP-associated bloodstream infection. After 3 months of follow-up, chest imaging revealed incomplete absorption of pulmonary consolidation in 33 patients of Group LT [including 13 airway obliterans (AO) patients] and in 7 patients of Group NLT (including 2 AO patients). CONCLUSION: MP loads of BALF were associated with the subsequent duration of MP DNA in lower airway. High MP loads and persistent long-term MP DNA in lower airway were associated with severity of pediatric MPP.

Computed tomography-based predictive nomogram for differentiating primary progressive pulmonary tuberculosis from community-acquired pneumonia in children.

BACKGROUND: To investigate the value of predictive nomogram in optimizing computed tomography (CT)-based differential diagnosis of primary progressive pulmonary tuberculosis (TB) from community-acquired pneumonia (CAP) in children. METHODS: This retrospective study included 53 patients with clinically confirmed pulmonary TB and 62 patients with CAP. Patients were grouped at random according to a 3:1 ratio (primary cohort n = 86, validation cohort n = 29). A total of 970 radiomic features were extracted from CT images and key features were screened out to build radiomic signatures using the least absolute shrinkage and selection operator algorithm. A predictive nomogram was developed based on the signatures and clinical factors, and its performance was assessed by the receiver operating characteristic curve, calibration curve, and decision curve analysis. RESULTS: Initially, 5 and 6 key features were selected to establish a radiomic signature from the pulmonary consolidation region (RS1) and a signature from lymph node region (RS2), respectively. A predictive nomogram was built combining RS1, RS2, and a clinical factor (duration of fever). Its classification performance (AUC = 0.971, 95% confidence interval [CI]: 0.912-1) was better than the senior radiologist's clinical judgment (AUC = 0.791, 95% CI: 0.636-0.946), the clinical factor (AUC = 0.832, 95% CI: 0.677-0.987), and the combination of RS1 and RS2 (AUC = 0.957, 95% CI: 0.889-1). The calibration curves indicated a good consistency of the nomogram. Decision curve analysis demonstrated that the nomogram was useful in clinical settings. CONCLUSIONS: A CT-based predictive nomogram was proposed and could be conveniently used to differentiate pulmonary TB from CAP in children.

Hypersensitive Pneumonitis: an Initial Presentation of Chronic Granulomatous Disease in a Child.

Hypersensitive pneumonitis (HP) is a rare initial presentation of chronic granulomatous disease (CGD), especially in children. CGD presenting as HP may result from exposure to inhaled environmental antigens and be induced by excessive production of inflammatory cytokines due to loss of reactive oxygen species production. We herein describe a 2-year-old boy with CGD caused by a mutation in CYBB gene, who initially presented with HP. The patient developed dry cough, progressive dyspnea, and fever after playing in dusty air in a factory that produced plastic materials containing isocyanates. The patient's symptoms and radiological abnormalities did not improve after antigen avoidance, but disappeared after corticosteroid therapy. Because HP is uncommon in children, we should consider the possibility of CGD in children who present with HP. A prompt diagnosis of CGD is essential to enable initiation of prophylactic antibacterial and antifungal therapies.

Mediastinal teratoma presenting with hemoptysis and pleuritis misdiagnosed as tuberculosis (empyema).

BACKGROUND: Mediastinal teratoma is uncommon in children. It can be very difficult to diagnose especially in early stage. Rarely, teratoma may rupture into adjacent structures and lead to lung lesions or pleuritis. The main rarity of our reported cases was the dynamic imaging findings very similar to the developmental process of tuberculosis in patients 1 and 2, the pachypleuritis in patients 2 and 3, the extremely elevated inflammatory markers very similar to empyema in patient 3, and the extremely atypical tumor shape in all patients. CASE PRESENTATION: We present three pediatric patients presenting predominantly with recurrent hemoptysis and/or chest pain who were ultimately diagnosed with mediastinal teratoma containing pancreatic tissue. All three patients were initially suspected to have tuberculosis or empyema, and underwent relevant treatment, but without improvement. Patient 1 had left hilar enlargement, and subsequently an enlarging calcified cavity within high-density consolidation was identified. Patient 2 initially presented with right-sided pulmonary consolidation and pleuritis, and subsequently developed right lower lobe calcification, pleural thickening, and irregular soft tissue in the right inferior mediastinum. Patient 3 was initially found to have right lobe consolidation accompanied by a massive right-sided pleural effusion with extremely elevated inflammatory markers in serum and pleural effusion. The effusion later acquired heterogeneous density and appeared to become encapsulated. In patients 2 and 3, pleural biopsy identified fibrous tissue (with and without granuloma). Thoracotomy/thoracoscopy revealed mediastinal teratoma in each case, all of which were completely excised and the patients made uneventful recoveries. Histopathologic analysis revealed mature cystic-solid teratoma containing pancreatic tissue in all patients, and calcification in patients 1 and 2. CONCLUSIONS: Clinicians should be mindful that mediastinal teratoma is a potential cause of hemoptysis, lung lesions and pleuritis. Calcification and pachypleuritis on chest imaging especially in patients without fever should be highly suspected of mediastinal teratoma. Pleural biopsy sometimes fails to assist in making a definitive diagnosis.

Clinical characteristics of disseminated cryptococcosis in previously healthy children in China.

BACKGROUND: Disseminated cryptococcosis is a rare and fatal disease, and limited data exist regarding it in children. This study aimed to investigate the clinical characteristics of disseminated cryptococcosis in previously healthy children in China. METHODS: Hospitalized patients with disseminated cryptococcosis were enrolled during January 1996 to December 2015 in Beijing Children's Hospital, Capital Medical University, China. Data on clinical manifestations, laboratory tests, treatment, and prognosis were evaluated. RESULTS: A total of 52 pediatric patients with no underlying disease were enrolled, including 38 boys and 14 girls. Only 10 cases had a history of exposure to pigeon droppings. Fever, cough, and hepatomegaly were 3 main manifestations of disseminated cryptococcosis. However, headache was more common in patients with central nervous system (CNS) invasion than in patients with non-CNS invasion (P < 0.05). Lung (96.2%, 50/52) was the most commonly invaded organ, but only 9.6% (5/52) of patients had respiratory signs. The most common findings on chest imaging were hilar or mediastinal lymphadenopathy (46.8%, 22/47), and nodules (44.7%, 21/47), including small nodules in a scattered distribution (57.1%, 12/21) or miliary distribution (42.9%, 9/25), especially localized in subpleural area. Subsequent invasion occurred in the CNS, abdomen lymph nodes, liver, spleen, peripheral lymph nodes, and skin. In all patients, 42.3% (22/52) and 51.9% (27/52) had elevated eosinophils or IgE, respectively. The positive rate of serum cryptococcal antigen was higher, especially in patients with CNS invasion (approximately 83.3%), than with other primary methods used for pathogen detection, including cerebrospinal fluid (CSF) cryptococcal antigen, cultures of blood, bone marrow, or CSF, and CSF ink staining. The overall mortality rate of pediatric patients in our study was 11.5% (6/52). Some cases had long-term sequela, including hydrocephalus, cirrhosis, or blindness. CONCLUSIONS: Disseminated cryptococcosis can occur in previously healthy or immunocompetent children in China. Lung and CNS were most commonly invaded by this disease. Furthermore, most cases usually showed no obvious or specific symptoms or signs, and therefore pediatricians should pay more careful attention to identify this disease.