Fish oil fat emulsion alleviates traumatic brain injury in mice by regulation of microglia polarization.

Microglia activation, a hallmark of brain neuroinflammation, contributes to the secondary damage following traumatic brain injury (TBI). To explore the potential roles of different fat emulsions-long chain triglyceride (LCT) / medium chain triglyceride (MCT) and fish oil (FO) fat emulsion in neuroprotection and neuroinflammation in TBI, in this study, we first generated the controlled cortical impact (CCI) model of TBI mice. Then either LCT/MCT or FO fat emulsion treated mice were studied by Nissl staining to assess the lesion volume. Sham and TBI mice treated with 0.9% saline were used as controls. The fatty acid composition in different TBI mouse brains was further evaluated by gas chromatography. Immunofluorescent staining and quantitative RT-PCR both demonstrated the suppression of pro-inflammatory microglia and upregulated anti-inflammatory microglia in FO fat emulsion treated TBI brain or primary microglia induced by lipopolysaccharide (LPS) in vitro. Furthermore, motor and cognitive behavioral tests showed FO fat emulsion could partially improve the motor function in TBI mice. Together, our results indicate that FO fat emulsion significantly alleviates the TBI injury and neuroinflammation probably by regulating microglia polarization.

A fatal case of viral sepsis and encephalitis in a child caused by human adenovirus type 7 infection.

Adenoviruses are highly prevalent pathogens responsible for a wide range of clinical diseases, including respiratory tract infection, acute gastroenteritis, and conjunctivitis. However, adenovirus infection is rarely associated with central nervous system involvement. Here, we report a fatal viral sepsis and encephalitis in a child caused by a human adenovirus type 7 infection. We detected human adenovirus type 7 in the patient's nasopharyngeal swab, blood, and cerebrospinal fluid. Our findings indicate clinicians should be aware of the possible central nervous system involvement in adenovirus infection.

Comparison between hospital- and community-acquired septic shock in children: a single-center retrospective cohort study.

BACKGROUND: We explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factors between children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatric intensive care unit (PICU). METHODS: This retrospective study enrolled children with septic shock at the PICU of Beijing Children's Hospital from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into the HASS and CASS group. Logistic regression analysis was used to identify risk factors for mortality. RESULTS: A total of 298 children were enrolled. Among them, 65.9% (n = 91) of HASS patients had hematologic/oncologic diseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASS patients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratory or central nervous system. The 28-day mortality was 62.6% and 32.7% in the HASS and CASS groups, respectively (P < 0.001). Platelet [odds ratio (OR) = 0.996, 95% confidence interval (CI) = 0.992-1.000, P = 0.028], positive pathogen detection (OR = 3.557, 95% CI = 1.307-9.684, P = 0.013), and multiple organ dysfunction syndrome (OR = 10.953, 95% CI = 1.974-60.775, P = 0.006) were risk factors for 28-day mortality in HASS patients. Lactate (OR = 1.104, 95% CI = 1.022-1.192, P = 0.012) and mechanical ventilation (OR = 8.114, 95% CI = 1.806-36.465, P = 0.006) were risk factors for 28-day mortality in patients with CASS. CONCLUSIONS: The underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between the HASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patients with septic shock.

Cerebral blood vessels and perfusion in the pediatric brain death: five cases studied by neuroimaging.

PURPOSE: To detect the cerebral blood vessels and perfusion using neuroimaging modalities including computed tomography angiography (CTA), computed tomography perfusion (CTP), and arterial spin labeling (ASL) in children with brain death (BD). METHODS: According to the current children's BD criteria, 5 children (3 males, 2 females, mean age of 5.65 years) with BD were enrolled from January 2019 to December 2020. The imaging features of CTA, CTP, and ASL were evaluated to analyze the visualization of important intracranial blood vessels and the states of the cerebral blood flow (CBF) and cerebral blood volume (CBV) related to the region of interest (ROI) brain tissue during the two clinical assessments for BD. RESULTS: The "4-point scale" scoring system of CTA was applied to evaluate BD and no negative results were detected. The CTP results of the 5 children suggested the cessation of cerebral circulation with 100% positive results. The ranges of CBF and CBV were 0.00-9.52 ml/100 g/min (mean value 4.95 ± 1.69 ml/100 g/min) and 0.00-1.34 ml/100 g (mean value 0.36 ± 0.20 ml/100 g), respectively. One patient also underwent ASL examination, which demonstrated a significant reduction in whole brain perfusion, indicating the absence of cerebral circulation. The CBF values of the brainstem, basal ganglia, and prefrontal lobe were 11.61 ± 1.49 ml/100 g/min, 7.81 ± 2.42 ml/100 g/min, and 9.94 ± 2.01 ml/100 g/min, respectively. CONCLUSION: Neuroimaging examinations particularly CTA and CTP reveal well the hemodynamic and cerebral blood vessels changes of BD, which can be used as supplementary supportive evidence for the declaration of brain death in children.

Case Report : Li-Fraumeni Syndrome with Central Nervous System Tumors in Two Siblings.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome caused by germline TP53 gene mutations. It is characterized by high risk of early-onset cancer, and has been confirmed as associated with multiple tumors clinically. So pediatricians should be more alert to LFS in children with tumors. Choroid plexus carcinoma (CPC) is a rare, malignant tumor which account for less than 1% of all central nervous system (CNS) tumors. However, when such tumorigenesis occurs, it is important to be vigilant for the presence of LFS. CASE PRESENTATION: The first patient is a 32-month-old boy admitted for convulsions and then was found intracranial space-occupying lesion. Underwent operation, he was diagnosis as choroid plexus carcinoma (WHO Grade III). After 5 months, his elder sister, a 13-year-old girl, was brought to emergency department for confusion and intermittent convulsions. Surgery was performed immediately after head CT examination found the lesion. The pathology result indicated glioblastoma. Because the siblings of the same family have successively suffered from malignant tumors, we performed genetic testing on this family. TP53 gene mutation occurred in both children of these two cases from their father, and their other brother was not spared either. So the two siblings both met the diagnostic criteria of LFS. Then they all received systematic anti-tumor therapy, and follow-up hitherto. CONCLUSION: Here we reported a rare LFS case that two siblings were inherited the same TP53 germline mutations from their father. They suffered from choroid plexus carcinoma and glioblastoma and were finally diagnosed with LFS. In this LFS family, the primary tumors of the two children were both central nervous system tumors, which were not reported in the previous literature. It is suggested that clinicians should be alert to LFS related tumors, which is helpful for early diagnosis. Timely detection of TP53 gene is an important way for early diagnosis of LFS, especially in children with tumor. The incidence of secondary tumor in LFS patients is significantly higher, and other family members of the LFS patient also have an increased risk of suffering from the tumors. Therefore, early diagnosis and timely tumor surveillance can obtain better therapeutic effect and prognosis for both proband and their family.

Complete Genome Sequences of Two WU Polyomaviruses Detected in Pediatric Patients with Fatal Respiratory Infection.

Here, we report the complete genome sequences of two WU polyomavirus (WUPyV) strains, both obtained in 2020 from pediatric patients with fatal respiratory infection in Beijing, China. The double-stranded DNA (dsDNA) genome sequences of BCH2008-1 and BCH2020_1 are 5,229 bp and 5,228 bp long, respectively.

Diagnostic Yield of Bronchoalveolar Lavage in Immunocompromised Children.

Results from early studies in the diagnostic yield of bronchoalveolar lavage (BAL) in immunocompromised adults and children were variable. This prospective study aimed to determine the diagnostic yield of BALs in immunocompromised children over the first 18 months of service at a newly established children's hospital. Relationship between BAL results and changes in antimicrobial management was also studied. Twenty-one bronchoscopic BALs were performed on 18 children; 14 BALs (66.7%) yielded at least 1 pathogen and 7 (33.3%) yielded no pathogen. Two pathogens were found in 2 samples, and 1 pathogen was identified in 12 samples. Bacteria (n = 7 patients), viruses (n = 8 patients) and fungus (Pneumocycstis jirovecii in one patient) were yielded. Of the 21 BALs, 8 (38.1%) were associated with changes in antimicrobial management (Fisher's exact test, p = 0.018). No significant side effects such as pneumothorax or pulmonary hemorrhages were observed in this series. In conclusion, BAL in immunocompromised children is rewarding and has potential to impact on antimicrobial management.

WU Polyomavirus Infection in Children With Acute Lower Respiratory Tract Infections in China, 2017 to 2019: Case Reports and Multicentre Epidemiological Survey.

WU polyomavirus (WUPyV) is a novel member of the family Polyomaviridae recently detected in respiratory tract specimens. So far, it has not been proven whether WUPyV is a real causative agent for respiratory diseases. In this study, we described two patients with fatal infection who had WUPyV detected in their nasopharyngeal swabs. Furthermore, we conducted a multicentre study in six hospitals from different districts of China. WUPyV was detected by real-time polymerase chain reaction assays, and the clinical and molecular epidemiological characteristics of WUPyV strains among hospitalized children with acute lower respiratory tract infections all around China from 2017 to 2019 were analysed. Two complete WUPyV genome sequences were assembled from fatal patients' airway specimens. Phylogenetic tree analysis revealed that they were most closely related to strains derived from Fujian and Chongqing, China, in 2008 and 2013, respectively. In 2017-2019, a total of 1,812 samples from children with acute lower respiratory tract infections were detected for WUPyV, of which 11 (0.6%) were positive. Children aged ≤5 were more susceptible to WUPyV infection. A total of 81.8% of WUPyV-positive patients were coinfected with other viruses, of which rhinovirus enjoyed the highest frequency. The main clinical symptoms of infected patients include fever, coughing and sputum expectoration. Most patients were diagnosed with pneumonia, followed by bronchial surgery. Three patients manifested severe infection, and all patients improved and were discharged. Our results show that WUPyV persistently circulates in China. Further investigations on the clinical role and pathogenicity of WUPyV are necessary.

Treatment and outcomes of 1041 pediatric patients with neuroblastoma who received multidisciplinary care in China.

IMPORTANCE: Neuroblastoma is the most common extracranial malignant solid tumor in children. Multidisciplinary care is critical to improving the survival of pediatric patients with neuroblastoma. OBJECTIVE: To systematically summarize the clinical characteristics of children with neuroblastoma and evaluate their prognosis with multidisciplinary care provided in a single center. METHODS: This retrospective study analyzed the clinical data of 1041 patients with neuroblastoma who were diagnosed, treated, and followed-up in the Hematology-Oncology Center of Beijing Children's Hospital from 2007 to 2019. RESULTS: The median age at diagnosis was 34 months; 80.8% of the patients were younger than 5 years of age. Notably, 243 patients (23.3%) were classified as low-risk, 249 patients (23.9%) were classified as intermediate-risk, and 549 (52.7%) were classified as high-risk. Furthermore, 956 patients underwent surgical resections; 986 (94.7%) patients received chemotherapy; and 176 patients with high-risk neuroblastoma received hematopoietic stem cell transplantation. The 5-year event-free survival (EFS) rate was 91.3% and 5-year overall survival (OS) rate was 97.5% in low-risk group; in the intermediate-risk group, these rates were 85.1% and 96.7%, respectively, while they were 37.7% and 48.9% in the high-risk group (P < 0.001 for both). The 5-year EFS and OS rates were significantly higher in patients diagnosed between 2015 and 2019 than in patients diagnosed between 2007 and 2014 (P < 0.001). In total, 278 patients (26.7%) exhibited tumor relapse or progression; the median interval until relapse or progression was 14 months. Of the 233 patients who died, 83% died of relapse or progression of neuroblastoma and 4.3% died of therapy-related complications. INTERPRETATION: The 5-year OS rate was low in high-risk patients, compared with low-and intermediate-risk patients. Multidisciplinary care is critical for improvement of survival in pediatric patients with neuroblastoma. Additional treatment strategies should be sought to improve the prognosis of patients with high-risk neuroblastoma.

Chemokine (C-X-C Motif) Ligand 4 Is a Restrictor of Respiratory Syncytial Virus Infection and an Indicator of Clinical Severity.

Rationale: Respiratory syncytial virus (RSV) is the leading cause of childhood respiratory infections worldwide; however, no vaccine is available, and treatment options are limited. Identification of host factors pivotal to viral replication may inform the development of novel therapies, prophylaxes, or diagnoses.Objectives: To identify host factors involved in RSV replication and to evaluate their potential for disease management.Methods: A gain-of-function screening was performed on the basis of a genome-wide human complementary DNA library screen for host factors involved in RSV replication. The antiviral mechanism of CXCL4 (chemokine [C-X-C motif] ligand 4) was analyzed. Its clinical role was evaluated via nasopharyngeal aspirates and plasma samples from patients with RSV infection and different disease severities.Measurements and Main Results: Forty-nine host factors restricting RSV replication were identified by gain-of-function screening, with CXCL4 showing the strongest antiviral effect, which was secretion dependent. CXCL4 blocked viral attachment through binding to the RSV main receptor heparan sulfate, instead of through interacting with RSV surface proteins. Intranasal pretreatment with CXCL4 alleviated inflammation in RSV-infected mice, as shown by decreased concentrations of tumor necrosis factor and viral load in BAL fluid samples as well as by viral nucleocapsid protein histological staining in lungs. Compared with non-RSV infections, RSV infections induced elevated CXCL4 concentrations both in plasma and airway samples from mice and pediatric patients. The airway CXCL4 concentration was correlated with viral load and disease severity in patients (P < 0.001).Conclusions: Our results suggest that CXCL4 is an RSV restriction factor that can block viral entry and serve as an indicator of clinical severity in RSV infections.

Whole-exome sequencing identifies a novel compound heterozygous mutation of ANKS6 gene in a Chinese nephronophthisis patient.

BACKGROUND: Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that leads to renal failure in childhood or adolescence. NPHP and the related syndromes have been termed 'ciliopathies' because most NPHP gene products localize to the cilium or its associated structures. METHODS: Here, we report a 2-year and 11-month-old Chinese girl with end-stage renal disease (ESRD), severe anemia, thrombocytopenia and myocardial hypertrophy. We performed trio-whole-exome sequencing to identify the causative variant of this patient. RESULTS: We identified an unreported compound heterozygous mutation (c.2420dupT, p.Thr808Aspfs*2 and c.1973-1G > A) in ANKS6 in the proband. The frameshift mutation c.2420dupT of ANKS6 was inherited from the proband's unaffected father and the splicing mutation c.1973-1G > A of ANKS6 was inherited from the proband's unaffected mother. Homozygous mutation in ANKS6 leads to NPHP16 (OMIM#615382) and this is the first case with a compound heterozygous mutation in the NPHP16 gene. CONCLUSION: We have identified a patient with ANKS6 variants in the East-Asian population for the first time. This case report expands the clinical and genetic spectra of NPHP and emphasizes the usefulness of whole-exome sequencing for genetic diagnosis of kidney disease.

Clinical analysis of early death in children with pleuropulmonary blastoma in a single center in China.

OBJECTIVE: Pleuropulmonary blastoma (PPB) is a rare malignant tumor in childhood that is highly invasive and has poor prognosis. We retrospectively analyzed patients with PPB who died within 30 days in hopes of providing a basis for improving diagnosis and treatment. METHODS: We retrospectively reviewed six children with PPB who died within 30 days of admission at our hospital from January 2004 to March 2018, including their clinical features, pathological diagnosis, course of treatment, and major causes of death. RESULTS: Six patients (two female, four male; median age, 38 months) were included. All patients presented with respiratory symptoms. Chest imaging showed that all tumors had diameters greater than 10 cm, with varying degrees of serous effusion. Four patients underwent ultrasound-guided fine-needle aspiration (FNA), one patient underwent exploratory thoracotomy, and one underwent partial tumor resection. Five cases were type III, and another was type II. Four patients developed adverse events while waiting for pathological results after FNA, and four patients were treated with chemotherapy but their tumors failed to decrease in size one to two weeks later. The median hospitalization to death time was 17 days (range, 5-24 days). CONCLUSIONS: PPB often presents with respiratory symptoms that rapidly develop into respiratory distress. The rapid tumor enlargement contributes to the disease's progression. Chemoreduction in such tumors is not obviously effective, and the mortality rate is high. The main causes of death were respiratory failure and sepsis. Further clinical studies will be required to evaluate the role of initial biopsy compared with upfront total excision.

A fatal case associated with respiratory syncytial virus infection in a young child.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common viral cause of pediatric bronchiolitis and pneumonia worldwide. Risk factors for high mortality and prolonged morbidity after RSV infection include premature birth, bronchopulmonary dysplasia, congenital heart disease, and Down syndrome. However, some previously healthy, full-term children who are infected with RSV also require hospitalization and even experience severe sequelae or death. CASE PRESENTATION: In this report, we present the case of an RSV-associated death of a child who was born at full-term and developed normally up to the age of 2 years old. Cardiopulmonary arrest occurred within 3 days after the onset of symptoms, which included cough and high fever. Complete brain edema was prominent, and encephalopathy was developing. Viral antigen detection and microbiome analyses of oral swab and nasopharyngeal aspirate specimens verified an RSV infection, while bacterial culture of blood specimens yielded negative results. The RSV strain detected in this patient was subtyped as RSVB9, and no mutation was found in the six antigenic sites for targeted drugs or vaccines. CONCLUSIONS: The patient had a severe infection associated with RSV, which was very likely the cause of her central nervous system infection and acute neurological complications.

Pneumocystis pneumonia in non-HIV children: a 10-year retrospective study.

BACKGROUND: Pneumocytis pneumonia (PCP) is a life-threatening disease in non-HIV infected children. However, there have been few studies that have examined the clinical characteristics associated with PCP and outcomes for these pediatric patients. OBJECTIVES: A retrospective review was performed over a 10-year period to evaluate the clinical characteristics and outcome of non-HIV children diagnosed with PCP at Beijing Children's Hospital in China. RESULTS: A total of 60 non-HIV children diagnosed with PCP were included in the study. The overall mortality was 41.7% (25/60). Underlying diseases included connective tissue disease (n = 23; 38.3%), hematological disease (n = 14; 23.3%), nephrotic disease (n = 8; 13.3%) and immunodeficiency disease (n = 10; 16.7%). In all, 26/40 (65.0%) children developed PCP after receiving a follow-up large dose of glucocorticoid because of recurrent disease. Median time from beginning glucocorticoid medication to PCP diagnosis was 245.9 days (range: 14-2100 days). The area under the ROC curve of CD4/CD8 T cell levels for the diagnosis of PCP was 0.902 (95% confidence interval, 0.849-0.955). The analysis rendered an optimum cut-off value of 0.715 corresponding to 89.2% sensitivity and 80.4% specificity. Using a multivariate logistic regression model, three parameters were identified as significantly associated with mortality: LDH level, mechanical ventilation and co-infection. CONCLUSION: The outcome of PCP in non-HIV children remains poor. A critical stage for PCP development is administration of follow-up glucocorticoid without prophylaxis. CD4/CD8 ratio is a suitable biomarker for predicting PCP and diagnostic of PCP in non-HIV children. Poor prognostic factors include LDH level, need for mechanical ventilation and co-infection.

Adenovirus infection in children with acute lower respiratory tract infections in Beijing, China, 2007 to 2012.

BACKGROUND: Human adenoviruses (HAdV) play a significant role in pediatric respiratory tract infections. To date, over 60 types of HAdV have been identified. Here, HAdV types are characterized in children in the Beijing area with acute lower respiratory tract infections (ALRTIs) and the clinical features and laboratory findings of hospitalized HAdV-infected cases are described. METHODS: Respiratory specimens were collected from pediatric patients with ALRTIs in the emergency department or from those admitted to Beijing Children's Hospital between March 2007 and December 2012. Infections with common respiratory viruses were determined by PCR or RT-PCR. HAdV positive samples were further typed by PCR and sequencing. RESULTS: Among 3356 patients with ALRTIs, 194 (5.8 %) were found to have HAdV infection. HAdV infection was primarily confined to children (88.35 %) less than 5 years of age. A total of 11 different types of HAdV were detected throughout the study period, with HAdV-B7 (49.0 %) and HAdV-B3 (26.3 %) as the most prevalent types, followed by HAdV-C2 (7.7 %) and HAdVC1 (4.6 %). Newly emerging and re-emergent types or variants, HAdV-B55 (n = 5), HAdV-C57 (n = 3), and HAdV-B14p1 (n = 1), were identified. Results also included the reported first case of co-infection with HAdV-C2 and HAdV-C57. Clinical entities of patients with single HAdV infection (n = 49) were similar to those with mixed HAdV/respiratory syncytial virus (RSV) infections (n = 41). Patients with HAdV-B7 infection had longer duration of fever and higher serum levels of muscle enzymes than HAdV-B3-infected patients. CONCLUSIONS: During the study period, HAdV-B7 and HAdV-B3 were the predominant types identified in pediatric ALRTIs. HAdV-B7 infection tends to have more severe clinical consequences. The presence of newly emerging types or variants and co-infection with different types of HAdV highlights the need for constant and close surveillance of HAdV infection.

[Viral etiology of acute respiratory tract infection among pediatric inpatients and outpatients from 2010 to 2012 in Beijing, China].

OBJECTIVE: Acute respiratory tract infections (ARI) are the leading cause of pediatric morbidity and mortality worldwide, particularly in developing countries. Viruses are the main pathogens of ARI in children. The purpose of the present study was to determine the epidemiologic features of respiratory viruses, including novel viruses, in outpatient and hospitalized children with ARI. METHOD: From March 2010 to February 2012, 2066 children with ARI, including 1050 outpatients and 1016 inpatients, were involved in this study. One nasopharyngeal aspirate or throat swab specimen was collected from each patient. Reverse transcription (RT) PCRs were performed to detect common respiratory tract viruses including respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus (IFV), parainfluenza virus (PIV) type 1-4, adenovirus (ADV), enterovirus (EV), human coronavirus (HCOV), human metapneumonia virus (HMPV) and human bocavirus (HBOV). RESULT: At least one viral pathogen was identified in each of 1274 out of 2066 patients and the overall positive rate was 61.7%. The positive rate in inpatient (69.7%) was higher than that in outpatient (53.9%). The frequencies of detection of various viruses among in- and outpatients were different. RSV was the most prevalent virus detected among hospitalized children, followed by HRV and PIV, whereas IFV was the most frequently identified virus in the outpatient group, followed by ADV and PIV. Simultaneous detection of two or more viruses was found in 377 cases. Coinfection was more frequent in inpatients than in outpatients (30.1% vs. 6.8%, P < 0.001). CONCLUSION: Respiratory viruses play an important role in children with ARI, especially in young children. RSV was the most prevalent virus detected among hospitalized children, whereas IFV was the most frequently identified virus in the outpatient group. Viral coinfections are frequently identified, particularly in hospitalized patients. Further studies are required to better understand the impact of coinfections in children with ARI.

[Three years surveillance of viral etiology of acute lower respiratory tract infection in children from 2007 to 2010].

OBJECTIVE: Viruses are common pathogens of acute lower respiratory tract infection (ALRTI) in children. There are few studies on consecutive monitoring of viral pathogens of ALRTI in a larger cohort during the past several years. The aim of this study was to investigate the viral pathogens of ALRTI in children of different age groups and to outline the epidemic feature of different viruses. METHOD: (1) Totally 1914 (1281 male and 709 female) children with clinical diagnosis of ALRTI during the period of March 2007 to March 2010 were recruited into this study. These patients were hospitalized patients in department of internal medicine or outpatients in emergency department in Beijing Children's Hospital. The patients were divided into four groups, including 1072 patients < 1 year old, 326 patients 1- < 3 years old, 158 patients 3- < 6 years old, 358 patients ≥ 6 years old. One nasopharyngeal aspirate specimen was collected from each patient. Reverse transcription (RT) PCR methods were applied to detect common respiratory viruses including respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus type A, B and C (IFA, IFB, IFC), parainfluenza virus (PIV) type 1-4, adenovirus (ADV), enterovirus (EV), human coronavirus (HCOV), human metapneumovirus (HMPV) and human bocavirus (HBOV). RESULT: (1) The total positive rate of viruses was 70.3%. The positive rate was 83.0% (890/1072) in the group of < 1 year old, and 80.1% (261/326) in group of 1- < 3 years old, 60.8% (96/158) in group of 3- < 6 years old and 27.7% (99/358) in group of ≥ 6 years old, respectively. There was a significant difference in the positive rate among different age groups (χ² = 2213.5, P = 0.000). The top three viruses were RSV, HRV and PIV; and the positive rates were 50.9%, 36.2% and 12.0% respectively in group of < 1 year old. (2) The epidemic seasons of RSV and HRV were winter and spring, and PIV infection was epidemic in spring and summer. (3) The detection rates of 2 or more viruses were 38.2%, 36.4%, 30.2% and 15.2% in groups of < 1 year old, 1- < 3 years old, 3- < 6 years old and ≥ 6 years old, respectively. There was a significant difference in the mixed infection rate among different age groups (χ² = 1346.00, P = 0.000). CONCLUSION: RSV, HRV and PIV were the most predominant pathogens in younger children with ALRTI. Different viral infections had different seasonal features. Mixed infections with two or more viruses were detected in substantial proportion of patients with ALRTI, but further studies are needed to explore the clinical significance of mixed infection with viruses in patients with ALRTI.

[Diagnosis and treatment of invasive pulmonary aspergillosis in 21 children with non-hematologic diseases].

OBJECTIVE: To explore diagnosis and treatments of invasive pulmonary aspergillosis (IPA) in children with non-hematologic diseases. METHOD: Twenty one patients without hematological malignancy were diagnosed with proven or possible IPA from July 2002 to June 2008. The risk factors, clinical manifestations, chest radiographic findings, microbiological and histopathological evidence, diagnostic procedures, treatment and prognosis were retrospectively reviewed. RESULT: Five children had proven IPA, and 16 patients had possible IPA. Thirteen children were classified as having acute invasive pulmonary aspergillosis (AIPA), eight children as having chronic necrotizing pulmonary aspergillosis (CNPA). Definitive diagnosis of primary immunodeficiency (PID) was made in 6 children (4 with chronic granulomatous disease, 2 with cellular immunodeficiency); three children were suspected of having PID. Corticosteroids and multiple broad-spectrum antibiotics had been administered in 5 patients (3 of these 5 patients also had invasive mechanical ventilation). Two children had underlying pulmonary disease. Three patients had unknown risk factors. Among these three patients, two had history of environmental exposure. Fever and cough were present in all the children. Fine rales were found in nineteen children. Six children had hepatosplenomegaly. The common roentgenographic feature of AIPA in 13 patients was nodular or mass-like consolidation with multiple cavity. "air-crescent" was seen in 10 of patients with AIPA. Lobar consolidation with cavity and adjacent pleural thickening was found in all children with CNPA. The positive rate of sputum and/or BALF culture in AIPA and CNPA were 72.1% and 22.4%, respectively. A large number of septate hyphae on wet smear were found in all of the children whose sputum and/or BALF culture were positive. Lung biopsy was performed in 3 children with CNPA, and necrosis, granulomatous inflammation, as well as septate, branching hyphae were observed on histopathologic examination. Fifteen children were treated with anti-fungal therapy (amphotericin B, voriconazole, itraconazole and caspofungin used alone or in combination), symptoms and lung lesions resolved in 12 children. Three children died. Six children did not receive anti-fungal therapy and died. The side effects of amphotericin B include chill, fever, hypokalemia and transient increase in BUN, none of which needed discontinuation of the antifungal therapy. Children had a good tolerance to fluconazole and caspofungin, there were no apparent side effects. CONCLUSION: Most of the children without hematologic diseases who suffered from invasive pulmonary aspergillosis had risk factors or exposure history. Roentgenographic findings were relatively characteristic for invasive pulmonary aspergillosis. Risk factors and roentgenographic findings were clues to consider clinically invasive pulmonary aspergillosis. Sputum culture was the key point to clinical diagnosis. The patients in whom the antifungal therapy was initiated early had a good outcome.