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.

Epidemiology of Cardiopulmonary Arrest and Outcome of Resuscitation in PICU Across China: A Prospective Multicenter Cohort Study.

Objective: To investigate the epidemiology and the effectiveness of resuscitation from cardiopulmonary arrest (CPA) among critically ill children and adolescents during pediatric intensive care unit (PICU) stay across China. Methods: A prospective multicenter study was conducted in 11 PICUs in tertiary hospitals. Consecutively hospitalized critically ill children, from 29-day old to 18-year old, who had suffered from CPA and required cardiopulmonary resuscitation (CPR) in the PICU were enrolled (December 2017-October 2018). Data were collected and analyzed using the "in-hospital Utstein style." Neurological outcome was assessed with the Pediatric Cerebral Performance Category (PCPC) scale among children who had survived. Factors associated with the return of spontaneous circulation (ROSC) and survival at discharge were evaluated using multivariate logistic regression. Results: Among 11,599 admissions to PICU, 372 children (3.2%) had CPA during their stay; 281 (75.5%) received CPR, and 91 (24.5%) did not (due to an order of "Do Not Resuscitate" requested by their guardians). Cardiopulmonary disease was the most common reason for CPA (28.1% respiratory and 19.6% circulatory). The most frequent initial dysrhythmia was bradycardia (79%). In total, 170 (60.3%) of the total children had an ROSC, 91 had (37.4%) survived till hospital discharge, 28 (11.5%) had survived 6 months, and 19 (7.8%) had survived for 1 year after discharge. Among the 91 children who were viable at discharge, 47.2% (43/91) received a good PCPC score (1-3). The regression analysis results revealed that the duration of CPR and the dose of epinephrine were significantly associated with ROSC, while the duration of CPR, number of CPR attempts, ventricular tachycardia/ventricular fibrillation (VT/VF), and the dose of epinephrine were significantly associated with survival at discharge. Conclusion: The prevalence of CPA in critically ill children and adolescents is relatively high in China. The duration of CPR and the dose of epinephrine are associated with ROSC. The long-term prognosis of children who had survived after CPR needs further improvement.

Clinical Application of Whole Exome Sequencing for Monogenic Disorders in PICU of China.

OBJECTIVES: Whole exome sequencing (WES) has been widely used to detect genetic disorders in critically ill children. Relevant data are lacking in pediatric intensive care units (PICUs) of China. This study aimed to investigate the spectrum of monogenic disorders, the diagnostic yield and clinical utility of WES from a PICU in a large children's hospital of China. METHODS: From July 2017 to February 2020, WES was performed in 169 critically ill children with suspected monogenic diseases in the PICU of Beijing Children's Hospital. The clinical features, human phenotype ontology (HPO) terms, and assessment of clinical impact were analyzed. RESULTS: The media age of the enrolled children was 10.5 months (range, 1 month to 14.8 years). After WES, a total of 43 patients (25%) were diagnosed with monogenic disorders. The most common categories of diseases were metabolic disease (33%), neuromuscular disease (19%), and multiple deformities (14%). The diagnosis yield of children with "metabolism/homeostasis disorder" and "growth delay" or "ocular anomalies" was higher than that of children without these features. In addition, the diagnosis rate increased when more features were observed in children. The results of WES had an impact on the treatment for 30 cases (70%): (1) change of treatment (n = 11), (2) disease monitoring initiation (n = 18), (3) other systemic evaluation (n = 3), (4) family intervention (n = 2), and (5) rehabilitation and redirection of care toward palliative care (n = 12). CONCLUSION: WES can be used as an effective diagnostic tool in the PICU of China and has an important impact on the treatment of patients with suspected monogenic conditions.

A novel de novo CASZ1 heterozygous frameshift variant causes dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is the most common cardiomyopathy with a common presentation of heart failure. It has been reported that CASZ1 loss-of-function mutation contributes to familial DCM and congenital ventricular septal defect (VSD). To date, only two pathogenic variants in CASZ1 have been previously reported worldwide. METHODS: To identify the causative variant in an 11-month-old Chinese boy with DCM and left ventricular noncompaction cardiomyopathy (LVNC), trio-whole-exome sequencing was performed followed by mutational analysis and Sanger sequencing. RESULTS: An unreported de novo heterozygous frameshift variant (c.2443_2459delGTGGGCACCCCCAGCCT, p.Val815Profs*14) in CASZ1 was idenitified in the proband. The frameshift mutation in CASZ1 not only led to DCM but also presented an LVNC phenotype. CONCLUSION: We have identified a novel CASZ1 variant in a patient with combined DCM and LVNC for the first time, thus broadening the phenotypic spectrum of CASZ1 variants. Furthermore, this study emphasized the usefulness of whole-exome sequencing for genetic diagnosis of cardiomyopathy.

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.

On-line lung volume measurement during high-frequency oscillatory ventilation.

OBJECTIVE: A bag-in-box system using a closed-circuit helium-dilution technique was used to determine the functional residual capacity during conventional mechanical ventilation. The purpose of this study was to determine whether the bag-in-box system could be used to measure mean lung volume without interrupting high-frequency oscillatory ventilation. DESIGN: Laboratory study. SETTING: Hospital intensive care medical research laboratory. SUBJECTS: Six mechanical lung models and ten New Zealand adult rabbits. INTERVENTIONS: The bag-in-box system was introduced into the respiratory circuit during the study. The rabbits were randomly divided into a healthy group and an acute lung injury group. Acute lung injury was induced by intravenously infusing oleic acid during conventional mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: In a lung model study, a series of rebreathing processes were performed. By measuring the helium concentration in each process, the rebreathing time needed for equilibration was found to be about 50 secs. We compared the measured volume with a known lung volume to test the method's accuracy. The volumes differed by -0.5% to 4.4%. Measured and known volumes of different size lung models correlated well (p <.001). Equilibration of helium in the system occurred after 40-50 secs of rebreathing in healthy rabbits and 30-40 secs of rebreathing in rabbits with acute lung injury. Of 45 mean lung volume determinations in ten rabbits, the coefficient of variation ranged from 0.5% to 6.5%. When mean airway pressure changed, the mean lung volume alteration was detected by the method, but it was inconsistent in each mean airway pressure variation. CONCLUSION: A bag-in-box apparatus using a helium-dilution technique could be evaluated as a method to measure gas-containing lung volumes ranging from 10 to 60 mL in patients receiving high-frequency oscillatory ventilation.

The epidemiology and resuscitation effects of cardiopulmonary arrest among hospitalized children and adolescents in Beijing: an observational study.

AIM: To investigate the epidemiology and resuscitation effects of cardiopulmonary arrest among hospitalized children and adolescents in Beijing. METHODS: A prospective multicentre study was conducted in four hospitals in urban/suburban areas of Beijing. Patients aged 1 month-18 years with cardiopulmonary arrest and received cardiopulmonary resuscitation (CPR) who were consecutively hospitalised during the study period (1 September 2008-31 December 2010) were enrolled. Data was collected and analyzed using the "in-hospital Utstein style". Neurological outcome was assessed with the pediatric cerebral performance category (PCPC) among patients who survived. RESULT: 201 of 108,673 hospitalized patients (0.18%) had cardiopulmonary arrest during their hospitalization. Of these, 174 patients underwent CPR. The most common causes of cardiopulmonary arrest were the diseases of respiratory system (29.3%) and circulatory system (19.0%). The most common initial rhythm was bradycardia (72.4%). About 108 patients (62.1%) had restoration of spontaneous circulation (ROSC). Forty-nine patients (28.2%) survived to hospital discharge, 25 (14.5%) survived 6 months post discharge, and 21 (12.1%) survived 1 year post discharge. Out of the 21 patients who survived 1 year after hospital discharge, 18 had good neurological outcome. Multivariate logistic regression analysis showed age, duration of CPR and endotracheal intubation performed before cardiopulmonary arrest were independent factors of cardiopulmonary resuscitation effect. CONCLUSION: The prevalence of in-hospital cardiopulmonary arrest in children and adolescents is low. The long-term result of children and adolescents survived from cardiopulmonary resuscitation is quite good. Age, CPR duration and endotracheal intubation performed before cardiopulmonary arrest were independent factors of cardiopulmonary resuscitation effect.