Carbapenem-resistant Enterobacteriaceae（CRE）is one of the common pathogens of hospital-acquired infections and has been widely spread in various countries，becoming one of the important public health problems worldwide.With the increase in the proportion of pediatric patients with CRE infections，studies related to the prevention and the control of CRE nosocomial infections have focused more on this group in recent years.Early prevention is particularly important because of the very limited treatment options for CRE infections and the high morbidity and mortality rates.Active screening，as a core measure to prevent CRE infection，has been implemented in several countries in recent years and has been shown to have a positive effect on the prevention and control of nosocomial infection in CRE.The target population of active screening generally includes people in close contact with CRE patients and people at high risk of CRE infection；screening specimens are mostly used in perianal swabs or rectal swabs；detection methods include bacterial culture and molecular detection techniques，with the former being the main method；the timing of screening is to collect the initial specimen within 24 hours of new admission，and follow up people at high risk of infection with regular testing.

Objective:To analyze the clinical characteristics of three patients with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.Methods:Three patients with IPEX syndrome diagnosed at the Children′s Hospital of Fudan University from January 24, 2013 to July 29, 2019 were selected as the study subjects. Their clinical features, laboratory investigations and results of genetic testing were summarized. Treatment and prognosis were also explored.Results:All of the three children had developed the disorder during infancy. One child had initial features including diabetes and diabetic ketoacidosis, whilst the other two had initiated by diarrhea. All patients had gastrointestinal involvement, and one was diagnosed as very early onset inflammatory bowel disease by colonoscopy and biopsy. Two children also had endocrine glands involvement. One child had manifested type 1 diabetes and positivity for thyroglobulin and thyroid peroxidase antibodies, though his thyroid function had remained normal. Another one had hypothyroidism and was treated by levothyroxine. Genetic testing revealed that all children had harbored missense variants of the FOXP3 gene, including c. 1222G>A (p.V408M), c. 767T>C (p.M256T) and c. 1021A>G (p.T341A). The clinical symptoms of one patient were alleviated following allogeneic hematopoietic stem cell transplantation. One patient was stable after treatment with infliximab plus insulin, and one child had died of refractory septic shock and multiple organ dysfunction syndrome at 3 months old. Conclusion:FOXP3 gene variant-associated IPEX syndrome may have very early onset and diverse clinical manifestations. For male patients with infantile onset chronic diarrhea, multiple endocrine or multiple system involvement, genetic testing is recommended, which may facilitate early diagnosis, treatment and genetic counseling.

Objective To analyze the concentration and exposure of vancomycin in children with gram-positive coccal infection,and the corresponding clinical efficacy and safety to support rational use of vancomycin in children.Methods We prospectively collected the clinical and laboratory data of 87 children with gram-positive coccal infection in the Children's Hospital of Fudan University from January 2012 to March 2021.Therapeutic drug monitoring(TDM)was conducted for vancomycin simultaneously,to acquire the data of serum through concentration(Cmin),peak concentration(Cmax),the area under the drug concentration-time curve in a 24-h interval(AUC0-24h)and the ratio ofAUC0-24h to the minimum inhibitory concentration(AUC0-24h/MIC).Results The median(P25,P75)age of the children enrolled in this study was 3.60(1.20,20.00)months.The median dose of vancomycin was 39.23(30.00,46.51)mg/kg.The median serum Cmin was 3.30(1.50,7.10)mg/L.Cmin achieved the target(5-15 mg/L)in 23 cases(26.4％).The median AUC0-24h was 213(174,293)mg·h/L and the median AUC0-24h/MIC was 221(128,349).Adaily dose of above 60 mg/kg in children could achieve the median value of AUC0-24h and AUC0-24h/MIC greater than 400,and the corresponding median age was 28.50(6.85,36.00)months.Multivariate logistic analysis showed a good correlation between Cmin and AUC0-24h(P=0.002).At the end of treatment,the clinical efficacy rate was 85.1％(74/87)and the bacterial eradication rate was 95.4％(83/87).No renal injury occurred during the treatment.Conclusions In this study,the median daily dosage,Cmin and A UC0-24h/MIC of vancomycin were below the recommended range at home and abroad.However,good clinical and microbiological efficacy were achieved in children at low vancomycin exposure.The probability of target attainment(PTA)for A UC0-24h and AUC0-24h/MIC ≥400 increased when the daily dose of vancomycin was＞60 mg/kg(corresponding to the median age of 28.50 months)or Cmin ≥ 5 mg/L.

Objective:To explore the factors affecting the prognosis of severe pediatric acute respiratory distress syndrome (ARDS) after receiving extracorporeal membrane oxygenation (ECMO) support.Methods:It was a multicenter prospective observational study. A total of 95 children with severe ARDS who were treated with ECMO salvage therapy from January 2018 to December 2022 in 9 pediatric ECMO centers in China were enrolled in the study. The general data, disease severity, organ function, comprehensive treatment and prognosis were recorded, and they were divided into survival group and death group according to the outcome at discharge. T test, chi-square test, multivariate Logistic regression and mixed linear model were used to analyze the relationship among baseline before ECMO treatment, some important indicators (pediatric critical scores, platelet count, albumin, fibrinogen, etc) during ECMO treatment and prognosis. Results:Among the 95 children with severe ARDS who received ECMO, 55 (58%) were males and 40 (42%) were females, aged 36.9 (0.5, 72.0) months. Twelve children (13%) were immunodeficient. Sixty-eight (72%) children were treated with venous artery (VA) mode and 27 (28%) with venous vein (VV) mode. The discharge survival rates of overall, VA, and VV mode children were 51% (48/95), 47% (32/68), and 59% (16/27), respectively. The number of immunodeficient children in the death group was higher, and there were lower pediatric critical scores, platelet count, albumin, fibrinogen and arterial oxygen partial pressure/fraction of inspired oxygen (PaO 2/FiO 2), higher ventilator driving pressure (ΔP), oxygenaion index (OI), and longer ARDS duration before ECMO (all P<0.05). There were no statistically significant differences in other indicators, including age, gender, weight, and ECMO mode among different prognostic groups (all P>0.05). High ΔP, high OI, low P/F, and low albumin were high-risk factors affecting prognosis(all P<0.05). After further grouping, it was found that ΔP≥25 cmH 2O (1 cmH 2O=0.098 kPa), P/F≤67 mmHg (1 mmHg=0.133 kPa) and OI≥35 were the thresholds for predicting poor prognosis ( P<0.05). From 24 h after ECMO, there were significant differences in ΔP, P/F and OI between the dead group and the survival group (all P<0.05), and the differences gradually increased with the ECMO process. The platelet level was significant from 7 days after ECMO ( P<0.05) and gradually expanded. Blood lactate levels showed a significant difference between the 2 groups on before and after ECMO ( P<0.05) and gradually increased from 24 h after ECMO. Conclusions:The risk factors affecting the prognosis of severe ARDS in ECMO include high ΔP, high OI, low P/F and low albumin purification therapy before ECMO. The gradual decrease of ΔP, OI and increase of P/F from 24 h of ECMO predicted a good prognosis, while the gradual increase of lactate after ECMO application showed a poor prognosis.

Objective:To explore the genetic etiology of pediatric intensive care unit (PICU) mortality cases and summarize their clinical characteristics.Methods:This was a retrospective cohort study. The study population consisted of 234 children who died within 7 d after admitted to the PICU of Children′s Hospital of Fudan University from January 2017 to December 2021. The clinical diagnoses, laboratory test results, and genetic testing results were collected. These patients were divided into the pathogenic gene variation positive (PGVP) group and the pathogenic gene variation negative (PGVN) group according to the results of genetic testing. The Mann-Whitney U test and Pearson′s chi-square test or Fisher′s exact probability method were used to compare the clinical characteristics between the groups. Results:A total of 234 cases were enrolled, including 139 (59.4%) males and 95 (40.6%) females. The age at death was 1.0 (0.4, 3.7) years old and the length of PICU stay was 16 (6, 33) days. There were 62 cases (26.5%) PGVP, and the mutated pathogenic genes included immune genes (23 cases (37.1%)), metabolic genes (11 cases (17.7%)), neuromuscular genes (11 cases (17.7%)), cardiovascular genes (4 cases (6.5%)), and genes of other systems (13 cases (21.0%)). The age at death in PGVP cases was significantly lower than in PGVN cases (0.6 (0.3, 1.4) vs. 1.3(0.5, 4.3) years old, Z=3.85, P<0.001). Compared with the PGVN group, the PGVP group had a higher incidence of family history and chronic complex conditions (CCC) than the PGVN group (6.5% (4/62) vs. 0.6% (1/172) and 93.5% (58/62) vs. 76.2% (131/172), χ2=8.87, P=0.018 and 0.003, respectively). Children in the PGVP group were admitted with higher incidence of severe infection, decreased consciousness or coma, moderate-to-severe anemia, thrombocytopenia, protracted diarrhea, and abnormalities in muscle strength or tone than those in the PGVN group (74.2%(46/62) vs. 45.9%(79/172), 50.0%(31/62) vs. 35.5%(61/172), 32.3%(20/62) vs. 18.0%(31/172), 21.0%(13/62) vs. 10.5%(18/172), 25.8%(16/62) vs. 4.1%(7/172), 16.1%(10/62) vs. 5.2%(9/172), χ2=14.63, 4.04, 5.41, 4.37, 24.30, 7.25, all P<0.05). Pathogenic genes that occurred more than twice included IL2RG (5 cases), SMN1 (4 cases), and SH2D1A (3 cases, including 2 single gene varients and 1 copy number varient). Conclusions:Among the deceased cases in the PICU, the main genetic causes are immune-related, metabolic, and neuromuscular genetic disorders. Critically ill children with a family history, CCC, and early features such as severe infections, decreased consciousness or coma, moderate to severe anemia, thrombocytopenia, protracted diarrhea, or abnormalities in muscle strength or tone should be closely monitored and undergo early genetic testing.

Objective:To investigate the characteristics and changes of bacterial infection and drug resistance in PICU at Children′s Hospital of Fudan University from 2016 to 2020.Methods:All the strains were collected at Children′s Hospital of Fudan University from January 1 st, 2016 to December 31 st, 2020.Antimicrobial susceptibility test was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were analyzed according to CLSI 2020 breakpoints. Results:(1)Bacterial distribution: 2 551 bacteria were monitored from 2016 to 2020 in our center.The top 3 bacteria were all gram-negative bacteria.Among them, Burkholderia cepacian showed a tortuous downward trend(13.45% to 1.18%), and Klebsiella pneumoniae showed an upward trend(6.05% to 10.61%).The most common infected site was respiratory tract, although the strains in the respiratory tract decreased year by year.Baumanii was the most common bacteria in respiratory infections.Staphylococcus epidermidis was the most common bacteria from 2016 to 2017 in blood infections, but Achromobacter xylosoxidans were became the most common bacteria from 2018 to 2020.Enterococcus faecium was the most common bacteria in urinary infections.(2) Drug resistance: Baumanii had a high drug resistance rate to amikacin, gentamicin, cefepime, and cefitadine, with no obvious changes over the years, which had a gradually decreasing drus resistance rate to cefoperazone sulbactam, showing a tortuous upward trend to imipenem and meropenem.Baumanii and Pseudomonas aeruginosa had a low drug resistance to levofloxacin over the years, but with high resistance rates in 2020.Escherichia coliand and Klebsiella pneumoniae still had high resistance rates to beta-lactam antibiotics, and their resistance rates to levofloxacin were decreasing.Escherichia coli and Klebsiella pneumoniae showed decreasing resistance rates to imipenem and increased resistance rates to meropenem.The resistance rate of Enterococcus faecium to levofloxacin decreased and always showed a high susceptibility rate to polypeptide antibiotics.Neither Staphylococcus epidermidis nor Staphylococcus aureus were currently resistant to tetracycline antibiotics, and the resistance rates of aminoglycoside antibiotics, such as gentamicin, was also declining.Conclusion:The bacterial infection in PICU shows as the main characteristics of respiratory infection and gram-negative bacteria infection.Carbapenem-resistant Enterobacteriaceae bacteria, Enterococci and Staphylococcus species are becoming increasingly more resistant.

Objective To explore the common CT signs of acquired immune deficiency syndrome(AIDS)-associated pneumocystis jirovecii pneumonia(PJP).Methods The chest CT data of 123 patients with AIDS-associated PJP were analyzed retrospectively.Results Multifocal lesions in both lungs were found in all cases.Distribution characteristics were as follows:diffuse and symmetrical distribution in both lungs in 100 cases(81.3％),diffuse and asymmetrical distribution in both lungs in 15 cases(12.2％),and scattered distribution in both lungs in 8 cases(6.5％).The density and morphological features were as follows:ground glass opacity in 120 cases(97.6％);"lunate arch sign"in 25 cases(20.3％);pulmonary interstitial proliferation in 103 cases(83.7％);crazy paving pattern in 14 cases(11.4％);patchy or consolidation shadow in 55 cases(44.7％);pulmonary cysts in 26 cases(21.1％);and nodular in 26 cases(21.1％).Other rare signs included pleural effusion in 11 cases,pericardial effusion in 6 cases,mediastinal and hilar lymphadenopathy in 9 cases,and mediastinal emphysema in 1 case.Conclusion The chest CT manifestations of AIDS-associated PJP have certain characteristics,including diffuse and symmetrical distribution of lesions in both lungs,as well as ground glass opacity and interstitial hyperplasia as common signs,especially,"lunate arch sign"and pulmonary cysts are more specific signs.

Objective:To understand the current situations and existing problems of pediatric emergency in Shanghai city and provide a basis for the construction and management of pediatric emergency.Methods:The questionnaire survey was used to investigate the current situations of pediatric emergency department in secondary and tertiary public hospitals in Shanghai city.Results:A total of 28 questionnaires were delivered, and 28 were responded.Six of the 28 hospitals had no administratively independent pediatric emergency or no separate pediatric emergency area.Of the 22 hospitals, each had an average of 9.7 professional emergency pediatricians, with the exception of one secondary hospital that lacked professional emergency pediatricians.Professional emergency pediatricians accounted for an average of 70.0% of all pediatricians.Of the 22 hospitals, 18(81.8%) were open 24 hours a day.Fourteen(63.6%) had independent triage.Eight children′s emergency rooms(36.4%) were shared with adults.Among the 22 hospitals, 20 hospitals filled in the annual total number of pediatric emergency visits, and the total number of pediatric emergency visits ranged from 2 791 to 467 428, with an average of 93 966.65.Conclusion:There are still some problems in the development of pediatric emergency department in secondary and tertiary public hospitals in Shanghai city, such as insufficient human resources, substandard personnel training, incomplete equipment and lack of critical first-aid techniques.Therefore, the construction and management of pediatric emergency department still need to be improved.

Infectious diseases are clinically very common, among which bacterial infections are the most common ones.Therefore, antibiotics have become ones of the most widely used drugs in clinical practice.While saving lives of many infected patients, antibiotics can also lead to adverse reactions, which can cause damage to organs function in severe cases and even life-threatening.Common adverse reactions include allergic reactions and various organs damage.In this review, we aimed to focus on the evaluation of common adverse reactions and organs damage caused by antibiotics, in order to improve the prevention and treatment of adverse reactions and promote rational use of antibiotics.

Objective:To prospectively investigate the prevalence of heparin-induced thrombocytopenia (HIT) in critically ill children during extracorporeal membrane oxygenation(ECMO) and explore the clinical characteristics and prognosis of HIT during ECMO.Methods:A total of 22 critically ill children, who had received ECMO support for more than 96 hours in the Intensive Care Unit at the Children′s Hospital of Fudan University from March 2019 to December 2020, were enrolled.According to the 4T score and the heparin/platelet factor 4(PF4) antibody, children whose 4T scores were not less than 6 and heparin/ PF4 antibodies were positive, were classified into HIT group ( n=6), and non-HIT group ( n=16). The clinical outcomes and the incidence of thrombotic events were compared between two groups. Results:The incidence of HIT during ECMO in critically ill children was 27% in this study.The incidence of thrombosis in the ECMO circuit in the HIT group was higher (100% vs.63%, P=0.133), and the average time to the first thrombosis in ECMO circuit in the HIT group was shorter than that in the non-HIT group (3.70 d vs.5.44 d, P=0.06). During the first 14 days of ECMO, the proportion of children with thrombotic events no less than twice was higher in the HIT group (67% vs.19%, P=0.054). There was no significant difference regarding the survival rate at 28 days after ECMO withdrawal between two groups (33% vs.50%, P=0.664). Conclusion:The prevalence of HIT during ECMO in critically ill children is high.Thrombosis events tend to occur earlier and more extensively in children with HIT during ECMO.No significant effect of HIT on the survival rate of children during ECMO is found.Whether HIT has effect on the survival rate of children with ECMO requires a prospective and large clinical study.