The clinical data of a case of Niemann-Pick disease type C diagnosed at Beijing Children′s Hospital, Capital Medical University on December 22, 2017 were retrospectively analyzed.The patient, male, 1 year and 28 days old, was admitted to the hospital primarily due to intermittent fever, cough and dyspnea for 8 months, and hepatosplenomegaly for 20 days.The patient initially presented with cough, expectoration, and wheezing, followed by hypotonia and delayed motor development.At the age of 1 year, the child developed hepatosplenomegaly and diffuse interstitial changes in both lungs.At the age of 3 years, the child had obvious vertical supranuclear gaze palsy and gelastic cataplexy, followed by dysarthria and dysphagia.The foam cells were found by bone marrow cytology, while sphingomyelinase and glucocerebrosidase were normal, so Niemann-Pick disease type A/B and Gaucher disease were excluded.Finally, genetic testing revealed two pathogenic mutations in the NPC1 gene, so Niemann-Pick disease type C was confirmed.Miglustat treatment began when the child was 3 years old, and vertical supranuclear gaze palsy and gelastic cataplexy improved for a while, but then the neurological symptoms worsened again, with dysphagia and dyspnea gradually increasing, and finally he died at the age of 4 years and 11 months.

Background:Antibiotics can reduce the efficacy of immunotherapy for melanoma,non-small cell lung cancer and renal cell carcinoma by altering the intestinal microbiome,but their effect in the treatment of gastrointestinal cancer is unclear.Aims:To investigate the prognostic effect of antibiotics on PD-1/PD-L1 inhibitors in the treatment of colorectal cancer(CRC)patients.Methods:The clinicopathological data of 95 patients diagnosed with CRC and treated with immune checkpoint inhibitors(ICIs)from December 2018 to May 2022 at Renmin Hospital of Wuhan University were retrospectively analyzed,and the patients were divided into antibiotic group and control group according to whether antibiotics were used.Risk factors of progression free survival(PFS)and overall survival(OS)were analyzed by univariate and multivariate analysis.Results:Among the 95 patients with CRC,64 were male and 31 were female.The mean age was(60.46±11.82)years.PFS(10.9 months vs.24.8 months,P=0.032)and OS(14.5 months vs.35.5 months,P=0.008)were significantly decreased in antibiotic group than in control group,and one-year survival rate was 56.5%and 78.7%,respectively.Multivariate analysis showed that tumor location and antibiotic use were independent risk factors of PFS(P<0.05),while tumor location,antibiotic use and no radical surgery were independent risk factors of OS(P<0.05).Univariate and multivariate analyses showed that antibiotic administration route,dose were not risk factors of PFS(P>0.05);univariate analysis showed that antibiotic administration route was correlated with OS(P=0.045),however,multivariate analysis showed that antibiotic administration route,infection location were not risk factors of OS(P>0.05).Conclusions:Tumors located in colon and antibiotics applied within 30 days before and after the first dose of ICIs can shorten PFS and OS in CRC patients,while radical surgery can prolong the OS of CRC patients.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

Objective:A case of cystic fibrosis admitted in the Respiratory Department of Beijing Children′s Hospital, Capital Medical University in June 2018 and underwent lung transplantation later was analyzed retrospectively.A 10-year-old girl had intermittent productive cough for more than 4 years with clubbed-finger.The lung high resolution CT (HRCT) showed bronchiectasis and mucus impaction, and the nasal sinus HRCT showed sinusitis.She had cystic fibrosis transmembrane conductance regulator ( CFTR) gene complex heterozygous mutation and positive sweat test.The immunoglobulin E (IgE) level and eosinophil count increased, and aspergillus fumigatus-specific IgE was positive.She was diagnosed as cystic fibrosis, allergic bronchopulmonary aspergillosis and sinusitis.Anti-infection, glucocorticoid and symptomatic treatment were given.During the following 21 months, the child had repeated respiratory difficulties and respiratory failure.Her lung function declined.Bilateral lung transplantation was performed in March 2020.She had a good recovery at more than 1 year and 3 months postoperatively.

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.

Objective:To explore the clinical features, follow-up characteristics and prognosis of rheumatic disease complicated with pulmonary arterial hypertension (PAH) in children, and to provide support for its clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the data of rheumatic 24 patients complicated with PAH hospitalized in the Department of Rheumatology and Immunology, Children′s Hospital Affiliated to the Capital Institute of Pediatrics, Department of Rheumatology and Immunology, Jiangxi Children′s Hospital, Department of Pediatrics Ⅰ, the First Affiliated Hospital of Zhengzhou University and Department of Pediatrics, the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to June 2022.The rheumatic patients complicated with PAH were followed up by telephone on June 30, 2022, and their clinical symptoms, treatment, follow-up, and prognosis data were collected.According to different treatment methods, the patients were divided into different clinical subgroups. The change of PAH was analyzed. The t-test was used for comparison between groups. P<0.05 was statistically significant. Results:A total of 24 cases were enrolled, with 7 males and 17 females.The average onset age of PAH was (10.97±3.79) years old.The median duration of PAH was 6.00 (32.20) months.The average pulmonary artery pressure was (51.71±17.66) mmHg(1 mmHg=0.133 kPa). There were 9 cases of systemic lupus erythematosus, 5 cases of Takayasu′s arteritis, 3 cases of juvenile dermatomyositis, 3 cases of undifferentiated connective tissue disease, 2 cases of systemic juvenile idiopathic arthritis, 1 case of Behcet′s disease, and 1 case of Kawasaki disease.Among 24 cases, the common symptoms were fever (14 cases), fatigue (10 cases) and dyspnea (7 cases). Of the 24 cases, 10 cases were complicated with hydropericardium, 9 cases with valve regurgitation, and 5 cases with decreased systolic and/or diastolic function.Lung changes were observed in 17 cases.Eleven cases were tested for B-type natriuretic peptide (BNP), and the BNP levels were all elevated in them (11 cases), with a median BNP of 3 073 (10 645) ng/L.After the first occurrence of PAH, 12 cases were treated with Methylprednisolone therapy, 10 cases received Cyclophosphamide therapy, and 2 cases who were both systemic lupus erythematosus, underwent blood purification.In the treatment of PAH, 11 cases were treated with pulmonary artery pressure reduction, and 7 of the 11 cases took PAH-targeted drugs.The mean decrease of the average pulmonary artery pressure in children receiving the targeted therapy[(44.80±24.08) mmHg] was significant higher than that in children not receiving the targeted therapy [(16.15±17.25) mmHg] ( t=2.661, P=0.016). Twenty children were reexamined and/or followed up, and the average course of PAH at the telephone follow-up was (36.29±26.67) months.The pulmonary arterial hypertension in 6 cases completely recovered, with median recovery time of 8.00 (13.47) months, but 2 of them died after the complete recovery.The pulmonary arterial hypertension improved in 11 children, 1 of whom died and the remaining children were in stable condition.The pulmonary arterial hypertension worsened in 2 children, 1 of them improved previously but aggravated recently, and the other child did not monitor pulmonary artery pressure and died during telephone follow-up. Conclusions:Rheumatic diseases complicated with PAH are rare and most often diagnosed in severe rheumatic children.It can lead to death, and is commonly accompanied by notably elevated BNP levels.The patients who have early PAH detection, intensive treatment of the primary disease, symptomatic and targeted pulmonary artery pressure reduction show a better prognosis.

Objective:To summarize the clinical features of children with autosomal dominant hyper-IgE syndrome (AD-HIES) and the differential diagnosis of hyper-IgE syndrome and allergic diseases as well.Methods:All clinical data, including general information, clinical features, and genetic changes, from 7 children with AD-HIES who were diagnosed in Beijing Children′s Hospital Affiliated to Capital Medical University from April 2016 to June 2020 were analyzed retrospectively.The diagnostic criteria are based on the National Institutes of Health′s (NIH)′s hyper-IgE syndrome score and combined with the results of gene detection, shown as follows: (1) NIH score over 40, with signal transducer and activator of transcription 3 gene ( STAT3) pathogenic mutation; (2) NIH score between 20 and 40, with reported STAT3 pathogenic mutation; (3) NIH score less than 20 points was excluded. Results:There were 3 males and 4 females.The onset age of 7 cases was within 2 months after birth, and the mean age at diagnosis was 3 years old.All seven cases had recurrent skin or lung infections, with 4 cases having skin and lung infections, 1 case of skin abscesses at the BCG vaccination site, and 2 cases without skin infection suffering from recurrent pneumonia.The mean onset age of skin abscess in 5 cases was 1.5 years, and pus culture of 3 cases were Staphylococcus aureus.Four cases developed bullae and 6 cases had lung infections.Four cases had otitis media, and oral thrush was seen in 4 cases.One case of skin and lung infection developed liver abscess and sepsis.Seven cases had eczema, which was disco-vered in the neonatal period for 6 cases.Four cases had the symptoms of eczema for the first visit.Two cases had food allergy, and 1 case had recurrent wheezing within 1 year old.The serum IgE level and blood eosinophil count in 7 children were elevated.All children had heterozygous pathogenic mutations in STAT3.Six patients had de novo mutations.There were 6 different mutation sites.The 4 mutation sites were reported: c.1145G>A, c.1144C>T, and c. 1699A>G were missense mutations, and c. 1139+ 5G>A was splicing mutation.Two mutation sites had not been reported: c.1031A>C was missense mutation, and c. 2050G>T was nonsense mutation.The pathogenic grade of them were likely pathogenic, and the NIH score of 2 cases were above 40 score, which was consistent with the clinical diagnosis of hyper-IgE syndrome. Conclusions:Eczema is a common and early clinical manifestation of hyper-IgE syndrome, along with elevated IgE levels and eosinophil counts that need to be differentiated from allergic diseases.On the contrary, it often had recurrent skin abscesses or pneumonia, which was prone to bullae.The clinical manifestations of young children were atypical, and genetic testing was helpful for early diagnosis.

Objective:To understand the clinical characteristics of empyema caused by Streptococcus pneumoniae in children. Methods:The clinical manifestations, imaging characteristics, treatment and prognosis of 49 children with pneumococcal empyema admitted to Beijing Children′s Hospital, Capital Medical University from March 2007 to February 2018 were retrospectively analyzed.Results:Among the 49 children, 26 were male and 23 were female, with a median age of 2.63 years old.All the cases had cough and fever, 46 cases of them had high fever, 2 cases had moderate fever and 1 case had ultrahyperpyrexia.The course of disease before admission was 2-90 days, with a median of 10 days.All cases had toxic symptoms and signs of pleural effusion; 26 patients had dyspnea; 23 patients had moist rales, while 8 cases of whom had wheezing sounds.Eleven cases had extrapulmonary complications, including purulent meningitis in 6 cases, purulent pericarditis 1 case, 2 cases of hemophagocytic syndrome and hemolytic uremic syndrome respectively.The medians of leukocytes in the whole blood, white blood cells in pleural effusion and multinuclear cell percentage were 26.97×10 9/L, 32×10 9/L and 0.85, respectively.The average C-reactive protein (CRP) was 177.79 mg/L.The drug sensitivity test of Streptococcus pneumoniae showed that 68.89% strains were insensitive to Penicillin and all strains were resistant against Erythromycin.Chest image showed bilateral consolidation in 32 cases and pneumothorax in 31 cases.Besides antimicrobial therapy, 34 patients were treated with chest drainage, and 7 cases underwent surgery.Ten of the 49 cases were treated with nasal continuous positive airway pressure, tracheal intubated was used in 6 cases, and 1 case was given cardiopulmonary resuscitation.Forty-five cases discharged with improvement, 3 cases were not cured and 1 case died. Conclusions:Pneumococcal empyema is more common in children under 5 years old.Children with pneumococcal empyema usually have poor mental status, high fever, cough accompanied by dyspnea, high peripheral white blood cells and CRP.Their radiographic findings are usually serious, and the insensitive rate to Penicillin is high.The main treatment is anti-infection therapy and closed thoracic drainage.The prognosis of most patients is good, but there are still dead cases.

Primary immunodeficiency diseases (PIDs) refer to immune function decrease and deficiency or immune regulation function imbalance resulted from immune cell or immunomolecular defects caused by single gene mutation.Children with PIDs are prone to develop infectious diseases.Because the immune mechanisms of hosts infected by different pathogens infecting vary, different types of PIDs are relatively susceptible to different pathogens.A number of studies have indicated that some PIDs children are more likely to develop Bacilles Calmétte-Guerin infection, severe tuberculosis and non- Tuberculous mycobacteria severe infection.In this review, several major primary immunodeficiency diseases closely related to the susceptibility of mycobacteria were summarized, including chronic granulomatous disease, severe combined immunodeficiency disease, mendelian susceptibility to mycobacterial disease, and high IgM syndrome, in order to provide a theoretical basis for early identification of such diseases.