This review discussesed the application of healthcare simulation in the post-graduation education of pediatric emergency and critical care medicine in China,puting forward the necessity of its application,introducing the application scenarios from four aspects:basic skills simulation training,specialized skills simulation training,situational simulation training and screen simulation training,and analyzing the existing problems from three aspects:teaching staff,curriculum research and training equipment.Some suggestions are put forward to strengthen the system guarantee,concentrate the development of multidisciplinary forces,and integrate the strength of domestic industry,university and research.

Objective:To investigate the clinical characteristics, treatment process and prognosis of children with severe side effects after chimeric antigen receptor T cell immunotherapy(CAR-T), so as to provide evidence for timely intervention after CAR-T treatment.Methods:From June 1, 2015 to May 31, 2020, children with cytokine release syndrome(CRS)or immune cell related neurotoxicity syndrome(ICANS)who were treated with CAR-T therapy in our hospital and revealed severe effects transferred to PICU were included in the study, and their clinical course and multiple laboratory examination data were systematically analyzed.Results:Seventeen children showed CRS reaction and entered PICU after CAR-T therapy.The most common clinical symptoms were respiratory distress(13 cases) and circulatory disorder(10 cases), of which 7 cases were complicated with severe ICANS.Serum interferon -γ(IFN-γ)and interleukin-6(IL-6)levels significantly increased after CAR-T cell infusion, reaching the peak at (5.1±1.6)days.The serum levels of IFN-γ and IL-6 in children with severe CRS were significantly higher than those in children with mild CRS(all P<0.05). The level of serum IL-6 in children with high tumor load was significantly higher than that in children with low tumor load( P<0.05). The mortality rate of children with elevated level of serum TNF-α was higher(5/5 vs.3/11, P<0.05). Children with severe CRS were more likely to develop grade 4 ICANS(4/4 vs.0/3, P<0.05). The mortality rate of children with oxygenation index(P/F value)<200 mmHg(1 mmHg=0.133 kPa) was higher(5/5 vs.2/12, P<0.05). The vasoactive inotropic score[ M( Min, Max)] in the death group was significantly higher than that in survival group[29.5(14.0, 50.0) vs.1.5(0, 25.0), Z=8.000, P=0.027]. Conclusion:Serum IL-6 and IFN-γ are crucial causes of CRS.High tumor load is one of the factors causing high level of serum inflammatory factors.Respiration and circulation systems are the most frequently involved systems.Therefore, the evaluation indexes of these two systems can help us judge the prognosis of children.

Objective:To explore any changes in the topology of the brain′s resting-state functional networks after an ischemic stroke causing cognitive impairment (iPSCI) and their relationship with the impairment.Methods:Twenty-one patients with impaired cognition after a stroke were recruited into an iPSCI group, and 21 healthy counterparts matched in gender, age and the education level formed the control (HC) group. Three-dimensional T1-weighted anatomical images and resting state functional magnetic resonance images of all of the subjects were collected and any differences in brain network topology were analyzed using graph theory. The degree of centrality (DC), between centrality (BC) and the global topological properties of each brain region were compared using independent-sample t-tests. Spearman correlation coefficients were computed to analyze the significance of any correlation between topology differences and Montreal Cognitive Assessment Scale (MoCA) or Mini-Mental Status Examination (MMSE) scores.Results:Compared with the HC group, a significant DC increase was observed in the orbital part of the right of middle frontal gyrus (ORBmid.R), the right hippocampus (HIP.R), and the right thalamus (THA.R). There was a significant decrease in the left Rolandic operculum (ROL.L), the left postcentral gyrus (PoCG.L), the left supramarginal gyrus (SMG.L), the left angular gyrus (ANG.L), the left and right caudate nucleus (CAU.L and CAU.R), the putamen of the left lenticular nucleus (PUT.L), the left Heschl gyrus (HES.L), the left superior temporal gyrus (STG.L), and the temporal pole of the left superior temporal gyrus (TPOsup.L). Compared with the HC group, the brain regions of the iPSCI group in which the BC had increased significantly were the orbital part of the left middle frontal gyrus (ORBmid.L), the left cuneus (CUN.L), and the right precuneus (PCUN.R). DC was significantly decreased in the left caudate nucleus (CAU.L), the left temporal pole of the superior temporal gyrus (TPOsup.L), and the left of inferior temporal gyrus (ITG.L). Compared with the HC group, the area under the receiver operating curve (AUC) of the shortest path length (Lp) and the normalized Lp (λ) of the iPSCI group increased significantly, and the AUC of the normalized clustering coefficient (γ) and small-worldness (σ) decreased significantly. The DCs of the ROL.L, PoCG.L, CAU.L, HES.L, STG.L and TPOsup.L regions showed moderate positive correlation with the MoCA and MMSE scores ( r>0.4), as did the BC of the CAU.L and TPOsup.L regions ( r>0.4). Conclusions:Cognitive impairment is mainly associated with decreased nodal properties in the brain regions related to language and in the caudate nucleus. The topology of the frontal lobe, hippocampus, thalamus, striatum and default networks may self-repair after an iPSCI. The brain′s functional network after an iPSCI still has small-world properties, but with low efficiency and high cost.

Objective:To explore the implementation of individualized lung protection ventilation strategy in pediatric acute respiratory distress syndrome(pARDS)guided by transthoracic electrical impedance tomography(EIT)and critical care ultrasound(CCU).Methods:We retrospectively analyzed the therapeutic process of protective ventilation strategy in one case of severe pARDS.EIT and CCU were used to guide the implementation of lung protective ventilation strategy.Results:EIT was used to guide lung recruitment and optimal positive end-expiratory pressure titration.CCU was used to assess hemodynamics and lung status of ARDS patient, and guide the implementation of right ventricular protective ventilation and circulatory protective ventilation.Finally, the patient eventually survived.Conclusion:The idea of ARDS protective ventilation has changed from traditional lung protective ventilation to right heart protective ventilation and circulatory protective ventilation, and finally achieved the protection of pulmonary vascular endothelium.EIT and CCU enrich the understanding of the pathophysiology and protective ventilation strategy in pARDS.

Objective:To investigate the immunity markers related to nosocomial infection in children with sepsis.Methods:A retrospective study including 155 cases diagnosed as sepsis from September 2015 to June 2020 in children′s intensive care unit (PICU) of Shanghai Children′s Medical Center was conducted. According to the presence of nosocomial infection occurred in PICU, septic children were divided into two groups: no nosocomial infection and nosocomial infection group. The differences about helper T-cells 1 and 2 cytokines, T cells subgroup absolute count, the proportion of CD14 + human leukocyte antigen DR (CD14 +HLA-DR), the proportion of regulatory T cells, pediatric risk of mortality Ⅲ (PRISM-Ⅲ), the treatment and outcome between the two groups were compared. Through propensity score matching (PSM), the disease severity and treatment of the two groups were matched to analyze the differences between the above indicators. Chi-square test or U test was used for comparison between groups. Receiver operating characteristic (ROC) curve was used to predict the occurrence of nosocomial infection. Results:There were 104 cases in no nosocomial infection group and 51 cases in nosocomial infection group. The first PICU-acquired infections occurred at (12±7) days after PICU admission. The most common PICU-acquired infections were pneumonia (26 cases, 51.0%) and bloodstream infections (15 cases, 29.4%). PRISM-Ⅲ of nosocomial infection group was significantly higher than that in no nosocomial infection group (8 (0-31) vs. 4 (0-17), Z=3 913.00, P<0.01).The proportion of using vasoactive drugs and invasive mechanical ventilation of nosocomial infection group was significantly higher (35.3% (18/51) vs. 10.6% (11/104), χ2=13.77, P<0.01; 86.3% (44/51) vs. 38.5% (40/104), χ2=31.51, P<0.01).The PICU length of stay of nosocomial infection group was significantly longer (20 (3-94) vs.7 (2-41) days, Z=4 585.50, P<0.01). The mortality of the nosocomial infection group was significantly higher than that of the group without nosocomial infection (29.4% (15/51) vs. 6.7% (7/104), χ2=14.45, P<0.01). Interleukin-6 and interleukin-10 of the nosocomial infection group were significantly higher than that in no nosocomial infection group (37.83 (2.23-7 209.99) vs. 13.45 (0.80~50 580.64) ng/L, Z=3 390.50, P=0.01; 10.42 (1.11-6 052.21) vs.4.10 (0.16-409.28) ng/L, Z=3 212.00, P=0.03). CD4 +/CD8 + and the percentage of CD14 +HLA-DR were significantly lower in the nosocomial infection group compared with the no nosocomial infection group (1.16 (0.44-4.96) vs. 1.61 (0.15-6.37), Z=1 955.00, P=0.01; 0.48 (0.08-0.99) vs. 0.67 (0.09-0.98), Z=1 915.50, P<0.01). After PSM, the percentage of CD14 +HLA-DR of nosocomial infection group was significantly lower than that in no nosocomial infection group (0.44 (0.08-0.99) vs. 0.64 (0.09-0.98), Z=758.00, P=0.02). The ROC curve analysis of the percentage of CD14 +HLA-DR in predicting nosocomial infection showed that the area under the curve was 0.642, the cut-off value was 0.39, and the 95% CI was 0.528-0.755. Conclusion:The level of the percentage of CD14 +HLA-DR maybe is related to the occurrence of nosocomial infection in children with sepsis.

Objective:To analyze the clinical characteristics, diagnosis and treatment strategies of cryptococcus neoformans infection in children, and to explore the application value of PCR and high-throughput gene analysis in the diagnosis and treatment of cryptococcus neoformans infection.Methods:The clinical data of children with cryptococcus neoformans infection were retrospectively analyzed, who were hospitalized in Shanghai Children′s Medical Center from July 1998 to December 2018, including epidemiological characteristics (age, gender, underlying disease, and contact history, etc.), clinical manifestations, laboratory tests, imaging studies, pathogen detection methods, and treatment and prognosis.Results:A total of ten children were enrolled in the survey, including five males and five females, and the median age was 6.28(4.08, 12.02) years; four cases had a history of poultry/soil/corrosion exposure; seven cases were diagnosed as cryptococcus neoformans meningitis, three cases were diagnosed as disseminated cryptococcal disease; five cases had underlying disease, including two cases of which were found to have primary immunodeficiency through high-throughput genetic analysis; headache with fever was the most common clinical symptom of cryptococcus neoformans meningitis.All three cases of disseminated cryptococcosis had primary or secondary immunodeficiency.All children were treated with 5-fluorocytosine + amphotericin B/amphotericin B liposome in induction therapy, and fluconazole in consolidation therapy.Notably, two cases showed hypokalemia during induction therapy, and one case showed mild renal dysfunction during consolidation treatment; five cases were cured, three cases were abandoned, one case was relapsed, and one case died.Conclusion:Children with cryptococcosis neoformans infection who are considered to have normal immune function may have primary immunodeficiency caused by gene mutation.PCR can improve the detection rate of cryptococcus neoformans and shorten the detection time.A significant increase in eosinophils may indicate the spread of infection.Hydration and regular potassium supplementation may reduce the toxicity of amphotericin B. Control of intracranial hypertension is the key to improve the success rate of treatment.

Objective:To explore the application value of FilmArray detection in children with acute lower respiratory tract infection and conduct economics analysis.Methods:From December 1, 2016 to November 30, 2017, 1 380 patients were enrolled in our study.Some children(FilmArray group) were tested for respiratory pathogens with FilmArray, while others (control group) were tested by 7-box antigen test of respiratory virus, gold colloid test of influenza and mycoplasma antibody.Those with underlying diseases were excluded.A total of 160 cases in the FilmArray group and 160 cases in the control group were obtained with tendency score matching method.The physical examination of pathogens, clinical indicators, usage of anti-infective drugs and hospitalization related costs were compared.Results:The positive rate of FilmArray test was significantly higher than that in control group (86.88% vs. 45.91%). The most common pathogens detected by FilmArray were adenovirus(39 cases), rhinovirus(34 cases), and parainfluenza virus(30 cases). In the FilmArray group, nine cases were positive for botulinum pertussis, accounting for 5.6% of the total.The hospitalization time of FilmArray group was shorter than that in control group [(8.89±6.23 days vs.(11.51±14.43)days]. In FilmArray group, the antibiotics were used for a shorter time, and 18 children did not use antibiotics during hospitalization.Compared with the control group, the hospitalization cost had no significant difference in the FilmArray group, but the antibiotic cost was less, as well as hospitalization time was shorter.The average hospitalization cost saved by using the FilmArray test was nearly 2 000 yuan per person. Conclusion:The application of FilmArray detection in children with acute lower respiratory tract infection can quickly and accurately identify a various infections of virus, bacteria and atypical pathogen, which guides using anti-infective drugs more reasonably.The application of FilmArray detection shortens the average hospitalization days of children, increases the utilization efficiency of medical resources, and reduces the medical cost and indirect economic loss of children’s families, which has certain economics significance.

Objective: To investigate the safety, feasibility and operation key points of whole lung lavage in infants with pulmonary alveolar proteinosis. Methods: The clinical manifestations, genetic screening, therapeutic interventions and outcome of an infant with pulmonary alveolar proteinosis complicated with respiratory failure who received whole lung lavage in November 2018 in Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine were reported. Websites including PubMed, Springer Link, China National Knowledge Infrastructure (CNKI), Weipu Database, and Wanfang Database were searched using the key words of "whole lung lavage" "pediatric" and "pulmonary alveolar proteinosis" for articles published from their establishments to April 2019. Relevant literature was reviewed. Results: A 3-month-old boy had experienced cough, shortness of breath and cyanosis for 1 week prior to admission to pediatric intensive care unit. Physical examination showed hepatosplenomegaly. Complete blood cell count showed mild anemia (hemoglobin 96 g/L) and normal white blood cells. The patient had normal C-reactive protein and normal blood platelet. Biochemical panel showed hypoalbuminemia (31 g/L), mildly elevated glutamic oxaloacetic transaminase (115 U/L) and blood ammonia (165 μmol/L), extremely elevated lactate dehydrogenase (>6 600 U/L) and hyperferritinemia (>4 500 μg/L). Chest computed tomography (CT) revealed decreased transmittance of both lungs, patchy high density shadow and ground glass opacity. Genetic testing revealed a mutation of c.625+1G>A in SLC7A7. Schiff reaction (PAS staining) in bronchoalveolar lavage fluid was positive. The patient was diagnosed with severe pneumonia, respiratory failure, lysinuria urinary protein intolerance, and pulmonary alveolar proteinosis. The patient received sequential unilateral whole lung lavage in 2 days and was successfully weaned from ventilator. He was discharged home breathing room air. Eleven articles (11 in English and non in Chinese) were reviewed. Twenty-one patients were included. After whole lung lavage, 76% (16/21) of the patients had improvement in respiratory function. Conclusions Whole lung lavage can effectively improve respiratory failure caused by pulmonary alveolar proteinosis in infant patients. The procedure is feasible and safe.

Objective:To investigate the sedation weaning strategies in critically ill patients with mechanical ventilation in pediatric intensive care unit (PICU) and to explore the effect of different sedative weaning patterns on withdrawal syndrome.Methods:A single-center prospective cohort study was conducted from April 1, 2016 to April 30, 2017. One hundred and twelve patients who required mechanical ventilation and benzodiazepines and (or) opioids for at least 5 consecutive days in PICU of Shanghai Children's Medical Center were enrolled. Twenty patients (17.9%) had an intermittent weaning pattern, defined as a 50% or greater increase in daily benzodiazepine and (or) opioid dose after the start of weaning, and the remaining 92 cases (82.1%) had a steady weaning pattern. The demographic and clinical features, duration and dose of sedative and analgesics, and the incidence of withdrawal syndrome were evaluated. Mann-Whitney U test was used for comparison about clinical features between different weaning pattern groups and children with withdrawal syndrome or not. Logistic regression was used to explore the risk factors of withdrawal syndrome. Results:Among the 112 patients, 46 (41.1%) had withdrawal syndrome. The patients with the intermittent weaning pattern had a high score of pediatric risk of mortality Ⅲ (PRISM-Ⅲ) (10.0 (3.5, 12.0) vs. 6.0 (2.0, 10.0), U=654.50, P=0.043) and were prone to re-intubation (35.0% (7/20) vs. 7.6% (7/92), P=0.003). The patients with withdrawal syndrome had longer duration of sedation (19.5 (16.8, 24.3) vs. 10.0 (7.0, 17.3) days, U=743.50, P<0.01), higher incidence of intermittent weaning pattern (32.6% (15/46) vs. 7.6% (5/66),χ 2=11.58, P=0.001), longer PICU hospitalization (19.0 (15.8, 25.3) vs. 12.0 (8.8, 17.0) days, U=755.00, P<0.01) and higher cost (89 (57,109) vs. 53 (32, 79) thousand yuan, U=804.00, P<0.01). Logistic regression showed that intermittent weaning pattern (odds ratio ( OR) =4.85, 95 % confidence interval ( CI) 1.39-16.91, P=0.013), perioperative period of liver transplantation ( OR=6.97, 95 %CI 1.25-39.04, P=0.027) and a cumulative dose of midazolam ≥ 34.7 mg/kg ( OR=8.12, 95 %CI 3.09-21.37, P<0.01) were risk factors of withdrawal syndrome. Conclusions:Withdrawal syndrome is more likely to occur in children who are intermittently weaned from sedation. Steady weaning strategy may help prevent iatrogenic withdrawal syndrome.

Objective To explore the characteristics and value for predicting prognosis of cytokines in septic children with or without neutropenia.Methods Totally 138 septic children were divided into the neutropenia and non-neutropenia groups according to absolute neutropenic count.Septic children were divided into the shock and non-shock groups according to circulation function and organ perfusion.The levels of C-reactive protein,procalcitonin,cytokines,PRISM-Ⅲ and clinical outcomes were analyzed between the relative groups.Results (1) Totally 138 septic children were recruited,64 with neutropenia and 74 without neutropenia.The level of PRISM-Ⅲ of the neutropenia group was significantly higher than that of the non-neutropenia group (P=0.048).Mortality showed no significant difference between the two groups,but hospital stay in the neutropenia group was longer than that in the non-neutropenia group.The levels of C-reactive protein,IL-6,and IL-10 ihe neutropenia group were significantly higher than those of the non-neutropenia group (P=0.001;P=0.001;P=0.032).The level of TNF-α in the neutropenia group was significantly lower than that of the non-neutropenia group (P=0.032).(2)Among the 64 septic children with neutropenia,23 were combined with shock.The PRISM-Ⅲ level of the shock group was significantly higher than that of the non-shock group (P=0.001).The mortality of the shock group (43.5％,10/23) was significantly higher than the non-shock group (2.4％,1/41) (P=0.001).C-reactive protein,procalcitonin,IL-6,IL-10 and TNF-α in the shock group elevated obviously than those in the non-shock group (P=0.001;P=0.001;P=0.001;P=0.005;P=0.019).The area under receiver operating characteristic curve was 0.8 for IL-6 (cut-offvalue 315.38 pg/mL),0.8 for IL-10 (cutoff value 45.18 pg/mL),and 0.85 for TNF-α (cut-off value 1.95 pg/mL).(3) Among the 74 septic children without neutropenia,19 were combined with shock The PRISM-Ⅲ level of the shock group was significantly higher than that of the non-shock group (P=0.022).There was no significant difference of mortality between the two groups (P=0.3).IL-10 level in the shock group elevated obviously than that in the non-shock group (P=0.015).(4) Among the 42 children with sepsis shock,23 were combined with neutropenia.The PRISM-Ⅲ level of the neutropenia group was significantly higher than that of the non-neutropenia group (P=0.005).There was no significant difference of mortality between the two groups (P=0.29).The levels of C-reactive protein,procalcitonin,IL-6 and IL-10 in the neutropenia group were significantly higher than those in the non-neutropenia group (P=0.001;P=0.001;P=0.001;P=0.035).There was no difference of TNF-α level between the two groups.(5) Among the 96 children without sepsis shock,41 were combined with neutropenia.No difference of PRISM-Ⅲ level was observed between the neutropenia and nonneutropenia groups.The mortality of the neutropenia group was significantly lower than that in the non-neutropenia group (2.4％ vs 20％,P=0.02).The levels of C-reactive protein and IL-6 in the neutropenia group were significantly higher than those in the non-neutropenia group (P=0.005;P=0.033).The TNF-α level was significantly lower than that in the non-neutropenia group (P=0.007).Conclusions Compared to children without neutropenia,septic children combined with neutropenia have longer hospital stay,and septic shock children combined with neutropenia have higher mortality,and levels of IL-6,IL-10 and TNF-α were also significantly increased.The levels of IL-6,IL-10 and TNF-α can help to predict prognosis of children with sepsis.