Disseminated Cunninghamella elegans Infection Diagnosed by mNGS During Induction Therapy in a Child With Intermediate-risk Acute Lymphoblastic Leukemia: A Case Report and Review of Literature.

We described a 14-year-old girl with acute lymphoblastic leukemia who developed disseminated mucormycosis during induction therapy. Disseminated Cunninghamella elegans infection was confirmed by histopathology, microbiological culture, and metagenomic next-generation sequencing analysis of skin tissue, blood, and cerebrospinal fluid. Subsequently, the patient received a combination of liposomal amphotericin B, posaconazole, and caspofungin for antifungal treatment, but eventually died because of severe fungal pneumonia, respiratory failure, and septic shock. Moreover, case reports of pulmonary mucormycosis in children published since 1959 were reviewed. In summary, metagenomic next-generation sequencing is an effective diagnostic method for Cunninghamella with high speed and sensitivity.

Diagnosis, treatment, and prevention of severe acute hepatitis of unknown etiology in children.

BACKGROUND: Severe acute hepatitis of unknown etiology in children has recently exhibited a global trend of concentrated occurrence. This review aimed to summarize the current available information regarding the outbreak of severe acute hepatitis and introduce our hospital's previous experiences with the diagnosis and treatment of severe acute hepatitis for reference. DATA SOURCES: Websites including the UK Health Security Agency, European Centre for Disease Prevention and Control, CDC, WHO, and databases including PubMed/Medline, Cochrane Library, Embase and Web of Science were searched for articles on severe acute hepatitis in children. RESULTS: As of May 26, 2022, a total of 650 cases have been reported in 33 countries; at least 38 (6%) children required liver transplantation, and nine (1%) died. Cases are predominantly aged between 3 and 5 years old, and there are no epidemiological links among them. The common manifestations are jaundice, vomiting and pale stools. Adenovirus tested positive in most cases, and SARS-CoV-2 and other viruses were detected in a few cases, but virus particles were not found in liver tissue. Adenovirus immunohistochemistry showed immunoreactivity in the intrasinusoidal lumen from some liver samples. The hierarchical treatment includes symptomatic and supportive therapy, management of coagulation disorders and hepatic encephalopathy, artificial liver support, and liver transplantation (approximately 6%-10% of cases require liver transplant). CONCLUSIONS: The etiology of this severe acute hepatitis in children is not clear. The clinical features are severe acute hepatitis with significantly elevated liver enzymes. Clinicians need to be alert to children with hepatitis.

Performance of Three Mortality Prediction Scores and Evaluation of Important Determinants in Eight Pediatric Intensive Care Units in China.

Background: The mortality prediction scores were widely used in pediatric intensive care units. However, their performances were unclear in Chinese patients and there were also no reports based on large sample sizes in China. This study aims to evaluate the performances of three existing severity assessment scores in predicting PICU mortality and to identify important determinants. Methods: This prospective observational cohort study was carried out in eight multidisciplinary, tertiary-care PICUs of teaching hospitals in China. All eligible patients admitted to the PICUs between Aug 1, 2016, and Jul 31, 2017, were consecutively enrolled, among whom 3,957 were included for analysis. We calculated PCIS, PRISM IV, and PELOD-2 scores based on patient data collected in the first 24 h after PICU admission. The in-hospital mortality was defined as all-cause death within 3 months after admission. The discrimination of mortality was assessed using the area under the receiver-operating characteristics curve (AUC) and calibrated using the Hosmer-Lemeshow goodness-of-fit test. Results: A total of 4,770 eligible patients were recruited (median age 18.2 months, overall mortality rate 4.7%, median length of PICU stay 6 days), and 3,957 participants were included in the analysis. The AUC (95% confidence intervals, CI) were 0.74 (0.71-0.78), 0.76 (0.73-0.80), and 0.80 (0.77-0.83) for PCIS, PRISM IV, and PELOD-2, respectively. The Hosmer-Lemeshow test gave a chi-square of 3.16 for PCIS, 2.16 for PRISM IV and 4.81 for PELOD-2 (p ≥ 0.19). Cox regression identified five predictors from the items of scores better associated with higher death risk, with a C-index of 0.83 (95%CI 0.79-0.86), including higher platelet (HR = 1.85, 95% CI 1.59-2.16), invasive ventilation (HR = 1.40, 1.26-1.55), pupillary light reflex (HR = 1.31, 95% CI 1.22-1.42) scores, lower pH (HR 0.89, 0.84-0.94), and extreme PaO2 (HR 2.60, 95% CI 1.61-4.19 for the 1st quantile vs. 4th quantile) scores. Conclusions: Performances of the three scores in predicting PICU mortality are comparable, and five predictors were identified with better prediction to PICU mortality in Chinese patients.

[Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)].

The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.

Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus.

Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV (the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children's Regional Medical Center, Children's Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.

Acinetobacter baumannii meningitis in children: a case series and literature review.

INTRODUCTION: The incidence of Acinetobacter baumannii meningitis, which typically occurs after neurosurgery, has increased in recent years. Pediatric Acinetobacter baumannii meningitis due to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has important clinical significance. METHODOLOGY: We retrospectively reviewed the clinical course and outcome of nine cases of meningitis due to Acinetobacter baumannii in children and reviewed the relevant literature. RESULTS: Seven patients had a history of neurosurgery, and the average time from the first surgery to cerebrospinal fluid (CSF) culture in these seven patients was 23.71 ± 17.43 days. Of all nine patients, four patients showed MDR isolates, two showed XDR isolates, and one showed pan-drug-resistant (PDR) isolates. Three patients received an intrathecal injection of amikacin. Two patients received intravenous colistin (5 mg/kg), and one received polymyxin B (2 mg/kg). The mean hospitalization duration was 39.44 days. Four patients eventually died: two with MDR Acinetobacter, one with PDR Acinetobacter, and one with susceptible Acinetobacter. Two of them still had positive CSF cultures at death. CONCLUSION: Acinetobacter baumannii meningitis is usually associated with neurosurgery and the placement of foreign material, and it usually has a high mortality. Intrathecal or intraventricular polymyxin administration is expected to be an effective choice for meningitis but requires further study.

Preliminary experience with tigecycline treatment for severe infection in children.

Severe infection is a primary cause of mortality in children facing challenges from multidrug-resistant (MDR) pathogens, particularly MDR Acinetobacter baumannii. Tigecycline has an expanded spectrum of antibacterial activity, and some successful instances of its use in children have been reported. We conducted a retrospective chart review of children treated at a tertiary hospital between May 1, 2012 and May 1, 2017 to examine the efficacy and safety of tigecycline in children with severe infection. A total of 110 patients (69 males) were enrolled in this study, including 46 MDR A. baumannii infection patients, encompassing 51 A. baumannii strains. Totally, the median duration of tigecycline therapy was 10 days (range, 2-47 days), with a clinical improvement rate of 47.27% (52/110). In A. baumannii infection group, the clinical improvement rate was 50% (23/46) and the microbiology eradication rate was 50.98% (26/51). No adverse events were reported during therapy; however, in one case, a 9-year-old boy with hematologic disease developed tooth discoloration.Conclusion: Although some patients benefited from tigecycline, the efficacy and safety of tigecycline should not be overvalued. Additional data from randomized controlled trials are required to assess the administration of tigecycline. What is Known: • Severe infection is a primary cause of mortality in pediatric patients and its treatment is facing challenges from an increasing number of multidrug-resistant (MDR) pathogens. • Tigecycline has an expanded spectrum of antibacterial activity. • Several case reports have indicated that tigecycline could be used as a salvage therapy in children when options are limited or non-existent. What is New: • We found that rate of clinical improvement was different in various groups of different infection. The efficacy of tigecycline should not be overvalued. • Six dosage models and different infection types were observed in our series, with different improvement and eradication rate, indicating that more data are required to identify a proper tigecycline dosage.

Preliminary experience of tigecycline treatment for infection in children with hematologic malignancies.

Background Severe infection is life-threatening in children with hematologic malignancies and its treatment is challenging because of an increasing number of multidrug-resistant pathogens. Tigecycline has an expanded antibacterial activity spectrum; some successful cases of tigecycline treatment have been reported in the literature. Objective To examine the efficacy and safety of tigecycline in children. Setting Department of hematologic malignancies in a tertiary hospital. Method A retrospective chart review from May 1, 2012 to May 1, 2017. The patients were identified by the hospital information system and a custom-made Microsoft Excel 2007 database of patients was created to record demographic and medical data. Main outcome measure Efficacy and safety of tigecycline use in severe infection children with hematologic malignancies. Results Thirty-seven patients were enrolled and the predominant diagnosis was acute lymphoblastic leukemia. The median duration of tigecycline therapy was 9 days. Most prescriptions were empirical. Eighteen patients received a maintenance dose of 2 mg/kg q12 h, without a loading dose. Sulperazone was the most frequently prescribed concomitant drug. At the end of tigecycline therapy, improvement was observed in 48.7% of cases. After treatment, interleukin-10 levels notably decreased. The only reported adverse event was a case of tooth discoloration. Conclusion Tigecycline can be used as salvage therapy in children with hematologic malignancy and seems tolerable. Prospective controlled studies are required to definitively evaluate the efficacy and safety of tigecycline in children.

Are platelet volume indices related to mortality in hospitalized children on mechanical ventilation?

Objectives To investigate platelet volume indices and in-hospital mortality in children on mechanical ventilation. Methods This retrospective study included children aged <16 years on mechanical ventilation, and compared parameters, measured on admission, between survivors and non-survivors. Dynamic platelet volume indices over the first 7 days were visualized. Independent risk factors of mortality were identified using multivariate logistic regression analysis. Results Out of 2 319 children aged 28 days-3 years, serum albumin (odds ratio [OR] 0.9, 95% confidence interval [CI] 0.85, 0.96), bilirubin (OR 1.01, 95% CI 1.0, 1.77), and lactic acid (OR 1.22, 95% CI 1.05, 1.38) levels were associated with mortality. Out of 2 415 children aged > 3 years, procalcitonin (OR 1.01, 95% CI 1.0, 1.01) and lactic acid (OR 1.22, 95% CI 1.09, 1.35) were associated with mortality. Platelet volume indices on admission were not independently associated with mortality in either group. Mean platelet volume (MPV) and platelet distribution width (PDW) showed different trends in non-survivors versus survivors over 1 week in both age groups. Conclusions Platelet volume indices may be associated with mortality in critically ill children receiving mechanical ventilation.

Combined application of extracorporeal membrane oxygenation and an artificial pacemaker in fulminant myocarditis in a child.

Fulminant myocarditis is severe and aggressive, but it is self-limited and usually has a favorable prognosis if the patients can survive the acute phase. When drug treatment is not effective, extracorporeal membrane oxygenation technology should be applied to support cardiopulmonary function. Extracorporeal membrane oxygenation can simultaneously support function of the left ventricle, right ventricle, and lungs, and provide stable blood circulation for patients with heart and respiratory failure, which allows sufficient time for the cardiopulmonary system to recover. Fulminant myocarditis affects cardiac systolic function, as well as the function of autorhythmic cells and the conduction system. If severe bradycardia or atrioventricular block appears, a pacemaker needs to be installed. We report a child with fulminant myocarditis who was treated with extracorporeal membrane oxygenation combined with an artificial pacemaker.

Effect of Antipyretic Therapy on Mortality in Critically Ill Patients with Sepsis Receiving Mechanical Ventilation Treatment.

Purpose. The study aimed to investigate the effectiveness of antipyretic therapy on mortality in critically ill patients with sepsis requiring mechanical ventilation. Methods. In this study, we employed the multiparameter intelligent monitoring in intensive care II (MIMIC-II) database (version 2.6). All patients meeting the criteria for sepsis and also receiving mechanical ventilation treatment were included for analysis, all of whom suffer from fever or hyperthermia. Logistic regression model and R language (R version 3.2.3 2015-12-10) were used to explore the association of antipyretic therapy and mortality risk in critically ill patients with sepsis receiving mechanical ventilation treatment. Results. A total of 8,711 patients with mechanical ventilator were included in our analysis, and 1523 patients died. We did not find any significant difference in the proportion of patients receiving antipyretic medication between survivors and nonsurvivors (7.9% versus 7.4%, p = 0.49). External cooling was associated with increased risk of death (13.5% versus 9.5%, p < 0.001). In our regression model, antipyretic therapy was positively associated with mortality risk (odds ratio [OR]: 1.41, 95% CI: 1.20-1.66, p < 0.001). Conclusions. The use of antipyretic therapy is associated with increased risk of mortality in septic ICU patients requiring mechanical ventilation. External cooling may even be deleterious.

Clinical application of extracorporeal membrane oxygenation in children with refractory cardiopulmonary failure.

BACKGROUND: This study aimed to discribe the experience in supporting children with refractory cardiopulmonary failure with extracorporeal membrane oxygenation (ECMO). METHODS: We retrospectively reviewed 12 children with refractory cardiopulmonary failure supported with ECMO from February 2009 to August 2015 in the Pediatric Intensive Care Unit (PICU), Children's Hospital, Zhejiang University School of Medicine. RESULTS: Seven of the 12 patients were weaned successfully from ECMO and dischaged from the hospital, with a survival rate of 58.3% (7/12). Among them, five patients had acute fulminant myocarditis (AFM). Complications during ECMO included hemorrhage, hemolysis, thrombosis, acute kidney injury, and secondary hematogenous infection. During 1-24 month follow-up, the seven surviving patients recovered with normal cardiopulmonary function. CONCLUSIONS: ECMO is useful for supporting children with refractory cardiopulmonary failure, especially for treatment of AFM.

[A multicenter prospective clinical study on continuous blood purification in treating childhood severe sepsis].

OBJECTIVE: To evaluate efficacy of continuous blood purification (CBP) in childhood severe sepsis through the analysis of organ function, inflammatory mediators and prognosis. METHOD: Forty-seven children with severe sepsis aged 29 days -16 years who were treated in PICU of Shanghai and Zhejiang five hospitals during October 1, 2011 and September 30, 2012 were enrolled; 30 cases treated with CBP were recorded as logged group , 17 cases without CBP as unlogged group. Changes in the cardiovascular, respiratory function, renal function, inflammatory markers, PRISM score III, PCIS and survival were observed and compared between the two groups at baseline (d0), first days (d1), second days (d2), third days (d3), fifth days (d5). RESULT: (1) Cardiovascular function: In d3 and d5, heart rate (HR) and mean arterial pressure (MAP) were improved as compared to unlogged group (121, 119 vs. 138, 137; 71, 80 mmHg vs. 63, 62 mmHg, P < 0.05), with no statistical significance in arterial blood lactate concentration. (2) Oxygenation index (PaO2/FiO2) and arterial oxygen saturation (SaO2) increased as compared to unlogged group, but did not reach statistical significance. (3) Blood urea nitrogen (BUN) and creatinine (Cr) were improved as compared with unlogged group from d1 (P < 0.05). (4) Inflammatory mediators did not show significant differences. (5) Twenty-eight days survival rate: logged group was 70.0%, unlogged group was 52.9%, but the difference was not statistically significant (P = 0.242). CONCLUSION: CBP can improve circulatory function, oxygenation, and renal function in children with severe sepsis. No evidence was found that CBP could decrease the level of inflammatory mediators, improve critical score and 28 days survival rate.

Lower mannose-binding lectin contributes to deleterious H1N1 2009 infection in children.

Mannose-binding lectin (MBL) has broad range of activity against viruses through the mechanisms of neutralization, opsonization, and complement activation. Prior studies have demonstrated that MBL inactivated the season's influenza virus. Due to the fact that children have no neutralizing antibody against H1N1 2009 virus, innate immunity may be crucial in the defense against influenza. Therefore, we studied whether MBL levels played a role in H1N1 2009 infection in children. In a prospective survey, we revealed that MBL levels in ICU influenza cases were significantly lower than in children with influenza from infection disease ward. MBL may be involved in innate immune responses to H1N1 2009 infection in children.

Local experience with extracorporeal membrane oxygenation in children with acute fulminant myocarditis.

To analyze the clinical effect of extracorporeal membrane oxygenation (ECMO) in children with acute fulminant myocarditis, we retrospectively analyzed the data of five children with acute fulminant myocarditis in the intensive care unit (ICU) at the Affiliated Children's Hospital, Zhejiang University from February 2009 to November 2012. The study group included two boys and three girls ranging in age from 9 to 13 years (median 10 years). Body weight ranged from 25 to 33 kg (mean 29.6 kg). They underwent extracorporeal membrane oxygenation (ECMO) through a venous-arterial ECMO model with an average ECMO supporting time of 89.8 h (40-142 h). Extracorporeal circulation was established in all five children. After treatment with ECMO, the heart rate, blood pressure, and oxygen saturation were greatly improved in the four children who survived. These four children were successfully weaned from ECMO and discharged from hospital machine-free, for a survival rate of 80% (4/5). One child died still dependent on the machine. Cause of death was irrecoverable cardiac function and multiple organ failure. Complications during ECMO included three cases of suture bleeding, one case of acute hemolytic renal failure and suture bleeding, and one case of hyperglycemia. During the follow-up period of 4-50 months, the four surviving children recovered with normal cardiac function and no abnormal functions of other organs. The application of ECMO in acute fulminant myocarditis, even in local centers that experience low incidence of this disease, remains an effective approach. Larger studies to determine optimal timing of placement on ECMO to guide local centers are warranted.

Successful rescue of a child with fall-related multi-organ injuries.

BACKGROUND: Fall-related injury is a major cause of accidental death and is rarely reported in children. Even successful treatment of children with multi-organ injuries caused by fall from the extreme height has been rarely reported. METHODS: We herein report a 2-year-old girl who fell from the 10th floor, had multi-organ injuries, and was successfully rescued. RESULTS: The girl sustained multi-organ injuries, such as head injury, closed abdominal injury, as well as fractures of the left limbs, and successfully recovered after two surgeries and supportive treatment. CONCLUSIONS: This case illustrates that a child who falls from extreme heights can occasionally be rescued. Early neuroprotective strategies help to improve neurological recovery.