Characteristics and Outcomes of Mycoplasma Pneumoniae Pneumonia Associated with Pulmonary Embolism and Necrotizing Pneumonia in Children.

Purpose: To explore the clinical characteristics, treatment, and long-term prognosis of mycoplasma pneumoniae pneumonia (MPP) combined with pulmonary embolism (PE) in children. Patients and Methods: The medical records of 16 children who were diagnosed with MPP associated with PE between January 2016 and January 2023 at Children's Hospital, Zhejiang University School of Medicine were retrospectively reviewed. Results: The average age patients were 8.24 ± 1.99 years. All cases were diagnosed with refractory mycoplasma pneumoniae pneumonia (RMPP) and presented complications in the form of necrotizing pneumonia (NP). The main symptoms observed were cough and fever (n = 16, 100%), chest pain (n = 8, 50%), dyspnea (n = 8, 50%), and hemoptysis (n = 4, 25%). In these cases, 12 patients had involvement of the pulmonary artery, 3 patients experienced issues with the pulmonary vein, and 1 patient had simultaneous involvement of both the pulmonary artery and pulmonary vein. Among the 12 pulmonary artery embolism cases, 6 involved the right pulmonary artery, 4 involved the left pulmonary artery, and 2 involved both the right and left pulmonary arteries. The mean D-dimer level was 8.50 ± 4.76 mg/L. All patients received anticoagulant therapy, and after treatment, there was a significant improvement in their symptoms and lung lesions. Conclusion: Children with RMPP, chest pain, hemoptysis, and elevated D-dimer levels should be closely monitored for the potential development of PE. The co-occurrence of MPP and PE often involves the presence of NP. In cases of confirmed PE, anticoagulation therapy may be a suitable consideration. PE and NP resulting from MPP generally had a favorable overall prognosis.

An unusual presentation of necrotizing pneumonia caused by foreign body retention in a 20-month-old child: A case report and literature review.

Necrotizing pneumonia (NP) is a rare but serious complication that occurs after foreign body retention. We report a case of severe NP in an infant caused by foreign body retention in the airway with no choking history. After a timely tracheoscopy and effective antibiotic treatment, her initial clinical symptoms were alleviated. However, she subsequently exhibited pulmonary manifestations of necrotizing pneumonia. To reduce the risk of NP from foreign body aspiration, for patients with airway obstruction and asymmetrical opacity of both lungs, timely diagnostic bronchoscopic evaluation is essential.

Necrotizing Pneumonia in Children: Early Recognition and Management.

Necrotizing pneumonia (NP) is an uncommon complicated pneumonia with an increasing incidence. Early recognition and timely management can bring excellent outcomes. The diagnosis of NP depends on chest computed tomography, which has radiation damage and may miss the optimal treatment time. The present review aimed to elaborate on the reported predictors for NP. The possible pathogenesis of Streptococcus pneumoniae, Staphylococcus aureus, Mycoplasma pneumoniae and coinfection, clinical manifestations and management were also discussed. Although there is still a long way for these predictors to be used in clinical, it is necessary to investigate early predictors for NP in children.

Case report: Primary alveolar soft-part sarcoma of the lung in a child.

Alveolar soft-part sarcoma involving the lung is mostly metastatic in nature, while primary alveolar soft-part sarcoma involving the lung occurs more rarely. Herein, we report a rare case of a patient with primary alveolar soft-part sarcoma of the lung, which may represent the earliest onset of this condition reported thus far. In this patient, surgery was performed to excise the lesion to the greatest extent possible, and the combination of surgery with chemoradiotherapy and an antiangiogenic agent may provide an important reference for the development of standard or first-line treatment for such pediatric patients.

Investigation of Allergic Sensitizations in Children With Allergic Rhinitis and/or Asthma.

Objective: Allergic rhinitis (AR) and asthma are becoming one of the most prevalent diseases in children. Identifying sensitization to aeroallergens is seemed to be valuable for diagnosing allergic disease and guiding its treatment. This study aimed to analyze the profiles of sensitization to aeroallergen in children with AR and/or asthma by skin prick test (SPT) and explore the differences of sensitization between different kinds of allergic diseases, different sexes, and different ages. Methods: A total of 230 children with AR and/or asthma who were hospitalized in our hospital from June 2017 to September 2019 were eligible in this retrospective study. All patients completed standardized questionnaires and SPT. Based on the sex, age, or classification of allergic disease, the sensitizations to 13 aeroallergens were compared. Results: Of the 230 patients, 67.4% of enrolled were positive for SPT; the top 5 allergens were Dermatophagoides pteronyssinus (Der.p) (59.3%), Dermatophagoides farina (Der.f ) (58.7%), Blomia tropicalis (Blot.) (40.3%), dog hair (36.1%), and Blattella germanica (20.4%). More than 90% of patients were sensitized to two or more allergens. As to the effect of age on aeroallergens, we found that the sensitizations of Blot., dog fur, and multiple sensitizations (≥5 allergens) were more common in adolescence (P < 0.01, P < 0.05). Regarding sex, we found that the positive rate of SPT and the percentages of double-allergen sensitizations in boys were much higher than girls (P < 0.01, P < 0.01), and the positive rate to Der.p, Der.f , and ragweed were also significantly higher in boys (P < 0.01, P < 0.05, and P < 0.05, respectively). Furthermore, we found that asthma-rhinitis multimorbidity increased the incidences of sensitizations; patients with AR and asthma had significantly higher positive rates to Der.p and Der.f when compared with the AR or asthma group (P < 0.05, P < 0.05). Conclusion: Allergic sensitizations were common in children with AR and/or asthma; sex, age, and asthma-rhinitis multimorbidity might affect the prevalence of sensitizations to aeroallergens.

Mild Encephalitis/Encephalopathy with Reversible Splenial Lesion Associated with Scrub Typhus in a Child: A Case Report.

Background: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a rare clinicoradiological syndrome characterized by transient mild encephalopathy and magnetic resonance imaging (MRI) findings of a reversible lesion in the splenium of the corpus callosum (SCC). Multiple causes have been proposed for the pathogenesis of MERS, with infection as the most pre-eminent. Case Presentation: We report the case of a 10-year-old girl with MERS due to scrub typhus. Her clinical manifestations of headache and drowsiness, together with lesions involving the SCC, as shown by MRI, and their complete resolution upon follow-up fulfilled the diagnosis of MERS. At the same time, the characteristic eschar of the skin and the positive Weil-Felix test result confirmed the existence of scrub typhus infection. Conclusions: To the best of our knowledge, we described the first pediatric case of MERS associated with scrub typhus. The case indicated that an MERS patient with fever should be considered as possibly having a scrub typhus infection. The characteristic black eschar of scrub typhus generally occurs after bite of mite that is important and useful to the doctor for making proper diagnosis.

[The Association between the Level of Plasma D-dimer and Disease Severity and Prognosis of Mycoplasma pneumoniae Pneumonia in Children].

OBJECTIVE: To explore the association between the levels of plasma D-dimer and the disease severity and prognosis of Mycoplasma pneumoniae pneumonia (MPP) in children. METHODS: We retrospectively analyzed the clinical data of pediatric MPP patients who were admitted in our hospital between January 1, 2016 and December 31, 2018. According to the peak value of D-dimer, patients were divided into the normal group (D-dimer<0.55 mg/L) and the elevated group (D-dimer≥0.55 mg/L). Information regarding the demographics, clinical manifestations, auxiliary examinations and treatments of patients in the two groups was compared. RESULTS: Of the 231 MPP patients included in the study, 70 were in the normal group and 161 were in the elevated group. The age of patients in the D-dimer elevated group was significantly higher than that of the normal group ( P<0.01). Compared with the normal group, the elevated group had longer lengths of fever, hospital stay and antibiotic therapy, and more severe radiographic manifestations (all P<0.01). In addition, the incidence of extrapulmonary complications, refractory MPP and severe MPP in the elevated group were significantly higher than those in the normal group ( P<0.01). As for the laboratory data, we found that neutrophils, C-reactive protein, lactate dehydrogenase, interleukin-6, interleukin-10 and interferon-γ were significantly higher in the elevated group than those in the normal group ( P<0.05). After treatments, all patients showed improvement and were discharged, but the proportions of patients requiring glucocorticoids, bronchoscopy, thoracentesis were significantly higher in the elevated group than those in the normal group ( P<0.05). Follow-up findings showed that the absorption rate of lung lesions 4 weeks after admission was significantly higher, the time needed for lung lesions absorption was significantly shorter, and the incidence of pulmonary sequelae was significantly lower in the normal group than those in the elevated group (all P<0.05). Correlation analysis showed that D-dimer level was positively correlated with the severity of pneumonia ( r=0.272, P=0.000) and the incidence of pulmonary sequelae ( r=0.235, P=0.000). CONCLUSION: Pediatric patients of MPP who had elevated plasma D-dimer had clinical manifestations that were more severe, required longer duration of treatment and longer recovery time for lung lesions, and were more likely to have pulmonary sequelae.

Congenital Brucellosis: A Case Report.

Background: Brucellosis is the most common zoonotic infection worldwide, and is caused by bacterial genus Brucella. The disease is rarely transmitted through human-to-human transmission. Few cases have been reported about vertical transmission of human brucellosis. Herein, we reported a case of congenital brucellosis, with clear evidence of pathogen detected in mother's placental specimen. Case Presentation: A 34-day-old girl was admitted to the department of pulmonology with fever for 8 days. Three blood samples and one sample of cerebrospinal fluid were positive for Brucella melitensis. The diagnosis of brucellosis and B. melitensis meningitis were established, along with hyperbilirubinemia and liver dysfunction. Treatment of rifampicin (for 6 weeks) and meropenem (for 2 weeks) was administered. However, the disease relapsed within 18 days. Thereafter, a combination therapy of rifampicin and sulfamethoxazole/trimethiprim (SMZ/TMP) was administered for 8 weeks. The disease relapsed again in 42 days. For chronic brucellosis, three courses of combination therapy of rifampicin and SMZ/TMP was administered. The mother had fatigue and arthralgia for 2 weeks, fever and membrane rupture 1 day before the baby was born. B. melitensis DNA was detected in the mother's placental specimen by next-generation sequencing and bacterial identification under microscope proved chorioamnionitis. Conclusions: We reported a confirmed case of congenital brucellosis. This disease should be closely monitored even in nonepidemic areas. The treatment of brucellosis in infancy faces challenges of drug choice and disease relapse.

Serum CXCL10/IP-10 may be a potential biomarker for severe Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: How to early distinguish the severity of Mycoplasma pneumoniae pneumonia (MPP) is a worldwide concern in clinical practice. We therefore conducted this study to assess the relationship between levels of serum inflammatory chemokines and the severity of MPP. METHODS: In this prospective study, we enrolled 39 children with MPP, whose clinical information was collected, blood samples were assayed for cytokines and chemokines by ELISA. RESULTS: The levels of serum CXCL10 in children with severe MPP were significantly higher than those in children with mild MPP (2500.0 [1580.9-2500.0] vs. 675.7 [394.7-1134.9], P < 0.001). Measurement of CXCL10 levels in serum enabled the differentiation of children with severe MPP with an area under the curve (AUC) of 0.885 (95 % CI 0.779-0.991, P < 0.001), with a sensitivity of 81.0 % and a specificity of 83.3 %. CONCLUSIONS: Serum CXCL10 level may be a potential biomarker for severe MPP in children.

The Level of D-Dimer Is Positively Correlated With the Severity of Mycoplasma pneumoniae Pneumonia in Children.

Objective: Mycoplasma pneumoniae pneumonia (MPP) is an important disease in children. Studies have demonstrated that the levels of D-dimer are elevated in some children with MPP, especially those with thrombotic complications. However, the potential association between MPP and D-dimer remains unclear. In our study, we sought to explore the relationship between the levels of plasma D-dimer and clinical characteristics of MPP patients. Methods: Retrospective analysis was conducted on 356 patients who were hospitalized in our hospital for MPP between January 1, 2017, and December 31, 2019. According to the peak value of D-dimer, patients were divided into three groups: the normal group (D-dimer<0.55 mg/L), the mild-moderately elevated group (D-dimer 0.55-5.5 mg/L) and the severely elevated group (D-dimer >5.5 mg/L). The demographic and clinical information, radiological findings, laboratory data, and treatments of patients were compared among different groups. Results: 106 patients were in the normal group, 204 patients were in the mild-moderately elevated group, and 46 patients were in the severely elevated group. More severe clinical and radiographic manifestations, longer length of fever, hospital stay and antibiotic therapy duration, higher incidences of extra-pulmonary complications, refractory MPP (RMPP), severe MPP (SMPP) were found in the elevated group, when compared with the normal group (P<0.01). Meanwhile, we found that the percentage of neutrophil (N%) and CD8+ lymphocyte (CD8+%), C-reactive protein (CRP), lactate dehydrogenase (LDH), interleukin (IL)-6, IL-10, and interferon-gamma (IFN-γ) trended higher with increasing D-dimer, whereas the percentage of lymphocyte (L%) and prealbumin (PAB) trended lower (P<0.01). In addition, the proportions of patients requiring oxygen therapy, glucocorticoid, bronchoscopy, immunoglobulin use, thoracentesis, or ICU admission were significantly higher in the severely elevated group than those in the other two groups (P<0.01). Correlation analysis showed that N%, L%, CRP, LDH, IL-10, length of fever, length of stay, and length of antibiotic therapy had strong correlations with the level of D-dimer. Conclusions: MPP patients with higher levels of D-dimer had more severe clinical manifestations and needed longer duration of treatment, which might be closely related to the severity of lung inflammation after MP infection.

A multi-center study on Molecular Epidemiology of Human Respiratory Syncytial Virus from Children with Acute Lower Respiratory Tract Infections in the Mainland of China between 2015 and 2019.

Human respiratory syncytial virus (RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015-2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A (RSV-A) was the predominant subgroup during this research period except in 2016. Totally, 535 sequences of the second hypervariable region (HVR-2) of the G gene were obtained. Combined with 182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1 (512), NA1 (6) and GA5 (3), respectively; while 196 RSV-B sequences fell in BA9 (193) and SAB4 (3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258Q and H266L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than 10%, while the sequences with T290I and T312I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites (296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015-2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.

Molecular Characteristics of Human Adenovirus Type 3 Circulating in Parts of China During 2014-2018.

Human adenoviruses (HAdVs) are important pathogens causing respiratory infections; 3.5-11% of childhood community-acquired pneumonia is associated with HAdV infection. Human adenovirus type 3 (HAdV-3), leading to severe morbidity and mortality, is one of the most prevalent genotype among adenoviruses responsible for acute respiratory infections (ARIs) in children in China. To identify the genetic variation of HAdV-3 in children with ARIs in China, a molecular epidemiological study was conducted. A total of 54 HAdV-3 isolated strains were obtained from children with ARIs in Beijing, Wenzhou, Shanghai, Shijiazhuang, Hangzhou, Guangzhou, and Changchun from 2014 to 2018. Thirty-two strains of which were selected for whole-genome sequencing, while the hexon, penton base, and fiber genes were sequenced for remaining strains. Bioinformatics analysis was performed on the obtained sequences. The phylogenetic analyses based on whole-genome sequences, major capsid protein genes (hexon, penton base, and fiber), and early genes (E1, E2, E3, and E4) showed that the HAdV-3 strains obtained in this study always clustered together with the reference strains from Chinese mainland, while the HAdV-3 prototype strain formed a cluster independently. Compared with the prototype strain, all strains possessed nine amino acid (AA) substitutions at neutralization antigenic epitopes of hexon. The homology models of the hexon protein of the HAdV-3 prototype and strain BJ20160214 showed that there was no evident structural change at the AA mutation sites. Two AA substitutions were found at the Arg-Gly-Asp (RGD) loop and hypervariable region 1 (HVR1) region of the penton base. A distinct AA insertion (20P) in the highly conserved PPPSY motif of the penton base that had never been reported before was observed. Recombination analysis indicated that partial regions of protein IIIa precursor, penton base, and protein VII precursor genes among all HAdV-3 strains in this study were from HAdV-7. This study showed that the genomes of the HAdV-3 strains in China were highly homologous. Some AA mutations were found at antigenic sites; however, the significance needs further study. Our data demonstrated the molecular characteristics of HAdV-3 circulating in China and was highly beneficial for further epidemiological exploration and the development of vaccines and drugs against HAdV-3.

Recurrent Wheezing and Asthma After Respiratory Syncytial Virus Bronchiolitis.

Background: Respiratory syncytial virus (RSV) is the most common pathogen of acute bronchiolitis in children, which sometimes triggers the development of recurrent wheezing and increases the risk of childhood asthma. Methods: We enrolled 425 children who were diagnosed with RSV-infected bronchiolitis at the department of pulmonology, Children's Hospital Zhejiang University School of Medicine in 2011. Long-term follow-up was performed to explore the consequence of bronchiolitis on subsequent recurrent wheezing and asthma. Results: Of 425 patients, 266 cases completed the entire follow-up, the mean age of onset was 4.9 (3.3) months, and the male-to-female ratio was 2.5. The mean birth weight of all patients was 3.22 (0.63) kg, and the number of patients who had a history of cesarean section was 148. According to the outcome of follow-up, 36 were in the recurrent wheezing (RW) group, 65 were in the asthma (AS) group, and the remaining 165 were in the completely recovered (CR) group. The age of onset was older and the birth weights were higher in the AS group than those in the CR group (P < 0.05). And the higher proportion of cesarean sections was higher in the RW group than that in the CR group (P < 0.05). Furthermore, we found a remarkable increasing of serum IgE in the AS groups than that in the CR group (P < 0.01). Multiple logistic regression analysis showed that the cesarean section was the risk factor for the development of recurrent wheezing and the higher birth weight was the risk factor for the development of asthma. Conclusion: RSV bronchiolitis might increase the incidence of recurrent wheezing and asthma. Allergic constitution was an important prerequisite for the occurrence of asthma, and related risk factor such as cesarean section can only increase recurrent wheezing to a certain extent within a certain period of time. And we also find higher birth weight and older onset age for those who develop asthma, which should be verified in the future.

Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages.

A systematic and flexible immunoregulatory network is required to ensure the proper outcome of antiviral immune signaling and maintain homeostasis during viral infection. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been extensively studied in inflammatory response, apoptosis, and cancer. However, the function of TIPE2 in antiviral innate immunity is poorly clarified. In this study, we reported that the expression of TIPE2 declined at the early period and then climbed up in macrophages under RNA virus stimulation. Knockout of TIPE2 in the macrophages enhanced the antiviral capacity and facilitated type I interferon (IFN) signaling after RNA viral infection both in vitro and in vivo. Consistently, overexpression of TIPE2 inhibited the production of type I IFNs and pro-inflammatory cytokines, and thus promoted the viral infection. Moreover, TIPE2 restrained the activation of TBK1 and IRF3 in the retinoic acid inducible gene-I (RIG-I)-like receptors (RLR) signaling pathway by directly interacting with retinoic acid inducible gene-I (RIG-I). Taken together, our results suggested that TIPE2 suppresses the type I IFN response induced by RNA virus by targeting RIG-I and blocking the activation of downstream signaling. These findings will provide new insights to reveal the immunological function of TIPE2 and may help to develop new strategies for the clinical treatment of RNA viral infections.

Mitochondrial DNA insert into CD40 ligand gene-associated X-linked hyper-IgM syndrome.

BACKGROUND: X-linked hyper-IgM (X-HIGM), which results from mutations in the CD40LG gene located on chromosome Xq26.3, is the most common form of HIGM. To date, more than 130 variants of the CD40L gene have been reported. We described a patient with novel de novo nuclear mitochondrial DNA sequences (NUMTs) in the CD40LG gene that have resulted in X-HIGM. METHODS: Whole-exome sequencing (WES) analysis was used to screen for causal variants in the genome, and the candidate breakpoint was confirmed by Sanger sequencing. RESULTS: A new mutation of CD40LG, which deletes A at position 17 followed by a 147-nucleotide from mitochondrial DNA copies insertion in exon 1, was detected in a 20-month-old boy harbouring an X-HIGM combined with immunodeficiency syndrome. CONCLUSION: This is one of the few cases of a human genetic disease caused by nuclear mitochondrial DNA sequences (NUMTs). The presented data serve to demonstrate that de novo NUMT transfer of nucleic acid is a novel mechanism of X-HIGM.

Early prediction of necrotizing pneumonia from mycoplasma pneumoniae pneumonia with large pulmonary lesions in children.

To compare the different features of necrotizing pneumonia (NP) and non-NP (NNP) caused by Mycoplasma pneumoniae pneumonia (MPP) with large pulmonary lesions, and explore the predictor for NP to differentiate from MPP. A retrospective study of MPP patients with large pulmonary lesions hospitalized from January 2008 to December 2019 was enrolled, and clinical manifestations, laboratory findings, radiological findings were analyzed. Of 135 MPP patients with large pulmonary lesions, 56 were in the NP group, 79 were in the NNP group. We found the median length of fever days were much longer in NP group than those in NNP group. Higher levels of WBC, CRP, LDH, IL-6 in NP group were observed. Furthermore, the incidence of pulmonary consolidation was much higher in NP patients than that in NNP patients, while the CT value of large pulmonary lesion was much lower in NP patients. In ROC curve analysis, the cut-off values for the CT value and IFN-γ were 36.43 and 7.25 pg/ml, respectively. NP caused by MPP might be easier to suffer from prolonged clinical course, severe laboratory and radiological findings. CT value of large pulmonary lesions and IFN-γ could be used as biomarkers to predict NP from MPP with large pulmonary lesions in children.

Gastrodin Inhibits Virus Infection by Promoting the Production of Type I Interferon.

Type I interferon (IFN-I) plays a critical role in the antiviral immune response. However, viruses have developed different strategies to suppress the production of IFN-I for its own escape and amplification. Therefore, promoting the production of IFN-I is an effective strategy against virus infection. Gastrodin (GTD), a phenolic glucoside extracted from Gastrodia elata Blume, has been reported to play a protective role in some central nervous system -related diseases and is beneficial for the recovery of diseases by inhibiting inflammation. However, the effect of GTD on virus infection is largely unknown. Here we found GTD treatment increased the survival rate of mice infected with vesicular stomatitis virus (VSV) or herpes simplex virus-1 (HSV-1). The production of IFN-I was increased in GTD-treated mice or macrophages compared to the control group, during virus infection. Furthermore, the activation of interferon regulatory factor 3 (IRF3) was promoted by GTD in macrophages upon VSV and HSV-1 infection. Our results demonstrated that GTD could inhibit the VSV and HSV-1 infection by promoting the production of IFN-I in macrophages and might provide an effective strategy against virus infection.