Background：Pneumomediastinum （PM） secondary to foreign body aspiration （FBA） is rare in children.Although it is mainly benign,some cases may be fatal.Due to the rare nature of this clinical entity,proper assessme...Background：Pneumomediastinum （PM） secondary to foreign body aspiration （FBA） is rare in children.Although it is mainly benign,some cases may be fatal.Due to the rare nature of this clinical entity,proper assessment and management have been poorly studied so far.Here,we characterized the presentation and management of this clinical entity and provided an evaluation system for the management.Methods：We retrospectively reviewed children with PM secondary to FBA,who were treated in Beijing Children＇s Hospital from January 2010 to December 2015.All patients were stratified according to the degree of dyspnea on admission,and interventions were given accordingly.Bronchoscopic removals of airway foreign bodies （FBs） were performed on all patients.For patients in acute respiratory distress,emergent air evacuation and/or resuscitations were performed first.Admission data,interventions,and clinical outcomes were recorded.Results：A total of 39 patients were included in this study.The clinical severity was divided into three grades （Grades Ⅰ,Ⅱ,and Ⅲ） according to the degree of dyspnea.Thirty-one patients were in Grade Ⅰ dyspnea,and they simply underwent bronchoscopic FBs removals.PM resolved spontaneously and all patients recovered uneventfully.Six patients were in Grade Ⅱ dyspnea,and emergent drainage preceded rigid bronchoscopy.They all recovered uneventfully under close observation.Two exhausted patients were in Grade Ⅲ dyspnea.They died from large PM and bilateral pneumothorax,respectively,despite of aggressive interventions in our hospital.Conclusions：PM secondary to FBA could be life-threatening in some patients.The degree of dyspnea should be evaluated immediately,and patients in different dyspnea should be treated accordingly.For patients in Grade Ⅰ dyspnea,simple bronchoscopic FBs removals could promise a good outcome.For patients in Grade Ⅱ dyspnea,emergent air evacuation and/or resuscitation should precede a bronchoscopy before the children become exhausted.展开更多
Bardet-Biedl syndrome(BBS) is a genetically heterogeneous disorder characterized by retinal dystrophy, polydactyly, obesity,developmental delay, and renal defects. At least 21 candidate BBS-associated genes(BBS1-19, N...Bardet-Biedl syndrome(BBS) is a genetically heterogeneous disorder characterized by retinal dystrophy, polydactyly, obesity,developmental delay, and renal defects. At least 21 candidate BBS-associated genes(BBS1-19, NPHP1, and IFT172) have previously been identified, and all of them play important roles in ciliary function. Here, we collected a BBS pedigree with four members and performed whole-exome sequencing on the proband. The variants were analyzed and evaluated to confirm their pathogenicity. We found compound heterozygous variants(c.1192C>T, p.Q398* and c.1175C>T, p.T392M) in MKKS in both the siblings, and these were likely to be pathogenic variants. We also found a missense variant(c.2029G>C, p.E677Q) in NPHP1 and a missense variant(c.2470C>T, p.R824C) in BBS9 in the proband only, which are variants of uncertain significance. The compound heterozygous variants were probably responsible for the BBS phenotype in this Chinese pedigree and the missense mutations in NPHP1 and BBS9 might contribute to the mutation load.展开更多
To the Editor:Chronic granulomatous disease(CGD)is an inherited primary immunodeficiency disease characterized by recurrent life-threatening bacterial or fungal infection and tissue granuloma formation.^([1])Pulmonary...To the Editor:Chronic granulomatous disease(CGD)is an inherited primary immunodeficiency disease characterized by recurrent life-threatening bacterial or fungal infection and tissue granuloma formation.^([1])Pulmonary infection is the most frequent manifestation,affecting nearly 80%of patients,[2]and remains the major cause of morbidity and mortality in patients with CGD.Details of the pathogenic microorganisms responsible for first-episode pulmonary infection provide information on the spectrum of infection in patients with CGD,help guide the empirical choice of antibiotics or antifungal therapy,and contribute to the early identification and management of CGD.Aspergillus is the commonest causative agent of pulmonary infection,but the distribution of other pathogens varies among countries.^([2–5])Few studies have investigated the etiology of pulmonary infection in CGD in a large cohort in China.展开更多
Importance:Bacteremia tuberculosis(TB)is a severe form of extrapulmonary TB.Studies assessing bacteremia TB in children are limited,especially for HIV-negative children.Objective:To explore the detailed clinical featu...Importance:Bacteremia tuberculosis(TB)is a severe form of extrapulmonary TB.Studies assessing bacteremia TB in children are limited,especially for HIV-negative children.Objective:To explore the detailed clinical features of the bacteremia TB in children under 18 years of age.Methods:We reviewed the clinical records of the patients retrospectively and collected the strains isolated from their blood cultures.We used mycobacterial interspersed repetitive-unit-variable-number tandem-repeat(MIRU-VNTR)to characterize the bacterial genotypes and alamarBlue to determine their drug susceptibility profiles.Polymerase chain reactions and DNA sequencing were used to identify drug-resistant mutations.Results:There were 13 pediatric bacteremia TB patients,10 of whom were diagnosed with Bacillus Calmette–Guérin(BCG)bacteremia TB.Thirteen patients aged from 0.30 to 11.58 years were enrolled,of whom 76.92%were boys.All had fevers before hospitalization,and 76.92%had respiratory symptoms.All had received BCG vaccinations,and 46.15%had adverse post-vaccination reactions.Compared withMycobacterium tuberculosis,BCG bacteremia was more likely to appear in younger children.Patients with BCG bacteremia had primary immunodeficiency diseases,and lower CD4,IgA,and IgE levels.Interpretation:Bacteremia TB was rapidly fatal in a large proportion of the immunodeficient children.Because classic findings may not be diagnostically specific,a high level of clinical suspicion is required,especially for patients with certain types of immunosuppression.Studies are needed to develop rapid diagnostic tests and to determine the value of empirical therapy in childhood bacteremia TB.展开更多
Importance:First branchial cleft anomalies(FBCAs)are rare congenital malformations,accounting for<8%of all branchial cleft anomalies.However,little is currently known about the cause of FBCAs at the molecular level...Importance:First branchial cleft anomalies(FBCAs)are rare congenital malformations,accounting for<8%of all branchial cleft anomalies.However,little is currently known about the cause of FBCAs at the molecular level.Objective:To identify genomic alterations related to the genetic etiology of FBCAs in Chinese children.Methods:We performed whole-exome sequencing of samples from 10 pediatric patients with FBCAs.Data analysis was carried out using the Burrow-Wheeler Alignment software package,and the dbSNP database for comparisons.Rare variants were further validated by Sanger sequencing.Insertion/deletions(indels)were examined using the Genome Analysis Toolkit.Results:We identified 14 non-synonymous mutations in seven potential FBCA-susceptibility genes(TRAPPC12,NRP2,NPNT,SH3RF2,RHPN1,TENM4,and ARMCX4).We also detected 133 shared small indels in 125 genes.Gene Ontology analysis indicated that most of the identified genes played critical roles in development and differentiation pathways involved in regulating organ development.Interpretation:We characterized the mutational landscape in pathways involved in development and differentiation in Chinese children with FBCA.The results identified potential pathogenic genes and mutations related to FBCA,and provide molecular-level support for the branchial theory of FBCA pathogenesis.展开更多
文摘Background：Pneumomediastinum （PM） secondary to foreign body aspiration （FBA） is rare in children.Although it is mainly benign,some cases may be fatal.Due to the rare nature of this clinical entity,proper assessment and management have been poorly studied so far.Here,we characterized the presentation and management of this clinical entity and provided an evaluation system for the management.Methods：We retrospectively reviewed children with PM secondary to FBA,who were treated in Beijing Children＇s Hospital from January 2010 to December 2015.All patients were stratified according to the degree of dyspnea on admission,and interventions were given accordingly.Bronchoscopic removals of airway foreign bodies （FBs） were performed on all patients.For patients in acute respiratory distress,emergent air evacuation and/or resuscitations were performed first.Admission data,interventions,and clinical outcomes were recorded.Results：A total of 39 patients were included in this study.The clinical severity was divided into three grades （Grades Ⅰ,Ⅱ,and Ⅲ） according to the degree of dyspnea.Thirty-one patients were in Grade Ⅰ dyspnea,and they simply underwent bronchoscopic FBs removals.PM resolved spontaneously and all patients recovered uneventfully.Six patients were in Grade Ⅱ dyspnea,and emergent drainage preceded rigid bronchoscopy.They all recovered uneventfully under close observation.Two exhausted patients were in Grade Ⅲ dyspnea.They died from large PM and bilateral pneumothorax,respectively,despite of aggressive interventions in our hospital.Conclusions：PM secondary to FBA could be life-threatening in some patients.The degree of dyspnea should be evaluated immediately,and patients in different dyspnea should be treated accordingly.For patients in Grade Ⅰ dyspnea,simple bronchoscopic FBs removals could promise a good outcome.For patients in Grade Ⅱ dyspnea,emergent air evacuation and/or resuscitation should precede a bronchoscopy before the children become exhausted.
文摘Bardet-Biedl syndrome(BBS) is a genetically heterogeneous disorder characterized by retinal dystrophy, polydactyly, obesity,developmental delay, and renal defects. At least 21 candidate BBS-associated genes(BBS1-19, NPHP1, and IFT172) have previously been identified, and all of them play important roles in ciliary function. Here, we collected a BBS pedigree with four members and performed whole-exome sequencing on the proband. The variants were analyzed and evaluated to confirm their pathogenicity. We found compound heterozygous variants(c.1192C>T, p.Q398* and c.1175C>T, p.T392M) in MKKS in both the siblings, and these were likely to be pathogenic variants. We also found a missense variant(c.2029G>C, p.E677Q) in NPHP1 and a missense variant(c.2470C>T, p.R824C) in BBS9 in the proband only, which are variants of uncertain significance. The compound heterozygous variants were probably responsible for the BBS phenotype in this Chinese pedigree and the missense mutations in NPHP1 and BBS9 might contribute to the mutation load.
基金supported by a grant from the Respiratory Research Project of the National Clinical Research Center for Respiratory Diseases(No.HX2X-202103).
文摘To the Editor:Chronic granulomatous disease(CGD)is an inherited primary immunodeficiency disease characterized by recurrent life-threatening bacterial or fungal infection and tissue granuloma formation.^([1])Pulmonary infection is the most frequent manifestation,affecting nearly 80%of patients,[2]and remains the major cause of morbidity and mortality in patients with CGD.Details of the pathogenic microorganisms responsible for first-episode pulmonary infection provide information on the spectrum of infection in patients with CGD,help guide the empirical choice of antibiotics or antifungal therapy,and contribute to the early identification and management of CGD.Aspergillus is the commonest causative agent of pulmonary infection,but the distribution of other pathogens varies among countries.^([2–5])Few studies have investigated the etiology of pulmonary infection in CGD in a large cohort in China.
基金National Natural Science Foundation of China(Grant/Award Number:81401739)Beijing Talent Training Funded Project(Grant/Award Number:2018000021469G277)。
文摘Importance:Bacteremia tuberculosis(TB)is a severe form of extrapulmonary TB.Studies assessing bacteremia TB in children are limited,especially for HIV-negative children.Objective:To explore the detailed clinical features of the bacteremia TB in children under 18 years of age.Methods:We reviewed the clinical records of the patients retrospectively and collected the strains isolated from their blood cultures.We used mycobacterial interspersed repetitive-unit-variable-number tandem-repeat(MIRU-VNTR)to characterize the bacterial genotypes and alamarBlue to determine their drug susceptibility profiles.Polymerase chain reactions and DNA sequencing were used to identify drug-resistant mutations.Results:There were 13 pediatric bacteremia TB patients,10 of whom were diagnosed with Bacillus Calmette–Guérin(BCG)bacteremia TB.Thirteen patients aged from 0.30 to 11.58 years were enrolled,of whom 76.92%were boys.All had fevers before hospitalization,and 76.92%had respiratory symptoms.All had received BCG vaccinations,and 46.15%had adverse post-vaccination reactions.Compared withMycobacterium tuberculosis,BCG bacteremia was more likely to appear in younger children.Patients with BCG bacteremia had primary immunodeficiency diseases,and lower CD4,IgA,and IgE levels.Interpretation:Bacteremia TB was rapidly fatal in a large proportion of the immunodeficient children.Because classic findings may not be diagnostically specific,a high level of clinical suspicion is required,especially for patients with certain types of immunosuppression.Studies are needed to develop rapid diagnostic tests and to determine the value of empirical therapy in childhood bacteremia TB.
基金Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education(KZ201810025034)Fund of Beijing Excellent Talent Training(2017000021469G252)+1 种基金Special Fund of The Pediatric Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals(XTCX201806)Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University & Capital Medical University, Beijing(BHME- 201804)
文摘Importance:First branchial cleft anomalies(FBCAs)are rare congenital malformations,accounting for<8%of all branchial cleft anomalies.However,little is currently known about the cause of FBCAs at the molecular level.Objective:To identify genomic alterations related to the genetic etiology of FBCAs in Chinese children.Methods:We performed whole-exome sequencing of samples from 10 pediatric patients with FBCAs.Data analysis was carried out using the Burrow-Wheeler Alignment software package,and the dbSNP database for comparisons.Rare variants were further validated by Sanger sequencing.Insertion/deletions(indels)were examined using the Genome Analysis Toolkit.Results:We identified 14 non-synonymous mutations in seven potential FBCA-susceptibility genes(TRAPPC12,NRP2,NPNT,SH3RF2,RHPN1,TENM4,and ARMCX4).We also detected 133 shared small indels in 125 genes.Gene Ontology analysis indicated that most of the identified genes played critical roles in development and differentiation pathways involved in regulating organ development.Interpretation:We characterized the mutational landscape in pathways involved in development and differentiation in Chinese children with FBCA.The results identified potential pathogenic genes and mutations related to FBCA,and provide molecular-level support for the branchial theory of FBCA pathogenesis.
