Background：Electroencephalogram (EEG) monitoring has been widely used in the assessment of brain development in preterm infants and brain function in children with brain injury. There are few clinical reports on the changes of EEG in highrisk fullterm neonates without clinical symptoms in the early stage after birth.
Objective：To investigate the necessity of early electroencephalogram (EEG) screening in asymptomatic highrisk neonates after birth.
Design：Retrospective cohort study.
Methods：The information at birth, maternal information, intrapartum information, discharge diagnosis, aEEG and vEEG results within 72 hours after birth of highrisk infants who underwent electrophysiological monitoring were retrospectively collected. vEEG was used as the gold standard for EEG monitoring, and aEEG was used as the screening method. Based on the five domains of language, gross motor, fine motor, problem solving and personalsocial in the Developmental Questionnaire (3), a selfmade neurobehavioral development screening questionnaire was made using the common similar questions in the BayleyScales of Infant Development at the age of 12 months. The outcome was neurobehavioral prognosis at 12 months of age.
Main outcome measures：To evaluate the screening effect of early electroencephalogram (EEG) monitoring on neurobehavioral outcomes at 12 months of age.
Results：A total of 398 highrisk infants who met the inclusion and exclusion criteria were enrolled in this study. There were 205 males (51.5%) and a gestational age of 38.9±1.1 (37+041+2) weeks, all of whom had stable vital signs, no hypoxia or nervous system clinical manifestations.aEEG and vEEG examinations were performed within 72h after birth. With vEEG as the gold standard and aEEG as the screening method, 46 cases were true positive, 325 cases were true negative, 0 case was false positive, and 27 cases were false negative. The sensitivity of aEEG was 63.0%(95%CI：51.7%74.4%), and the specificity was 100%(95%CI：100%100%). The vEEG abnormal group included 46 true positive cases and 27 false negative cases, and the vEEG normal group included 325 true negative cases and no false positive cases. A total of 386 cases (97.0%) completed the telephone followup of neurobehavioral questionnaire at 12 months of age. There was a significant difference in the total score of 8090 in the five domains of the Neurobehavioral Development Questionnaire between the normal vEEG group and the abnormal vEEG group (4.1% vs 40.3%).The scores of language, gross motor, fine motor, problem solving and personalsocial ability were significantly different. There were significant differences in birth weight, small for gestational age, length of hospital stay, vaginal delivery, forceps delivery, intrauterine distress, fetal heart rate <100 beats/min, umbilical artery blood gas pH value, BE value and lactic acid between the two groups.
Conclusions：With vEEG as the gold standard, the sensitivity and specificity of aEEG were 63.0% and 100%, respectively. In total，4.1% and 40.3% of highrisk infants with normal and abnormal EEG had abnormal neurobehavioral development at 12 months of age, respectively. Therefore，aEEG screening is necessary for highrisk infants early after birth.
Background：Weaning management of patients with prolonged mechanical ventilation （PMV） and subsequent transition to home mechanical ventilation have been complex challenges for critical care teams.
Objective：To explore the application of multidisciplinary treatment (MDT) model in the diagnosis and treatment of pediatric PMV and to analyze its clinical value and the significance of promotion for individualized weaning plan and transition from PMV to HMV.
Design：Quality improvement.
Methods：Patients with PMV in PICU were observed, and were divided into control group and intervention group according to 18 months before and after July 2020. The diagnosis and treatment measures of PMV in our hospital mainly include: prevention of ventilatorassociated pneumonia, sedation, analgesia, fluid management, nutritional support, early rehabilitation, individualized weaning program, education and followup of PMV transition to HMV, and establishment of outpatient and emergency followup for HMV specific diseases. The control group was empirically treated by different doctors or teams in the PICU. In the intervention group, the PMVMDT team led the treatment. Taking the PICU as the platform, PMVMDT parttime liaisons and core team members (respiratory therapists, rehabilitation physicians, ent physicians, nutrition physicians, etc.) were set up. The HMV special followup and emergency clinics were established.
Main outcome measures：PMV transition to HMV and the application of individualized weaning technology.
Results：There were 101 cases of PMV in the intervention group and 124 cases in the control group. There was no statistical difference in gender, age, weight and the primary disease causing PMV between the two groups. In the control group, 36 cases died in hospital, 67 cases were improved and discharged (44 cases discharged after weaning and extubation , 14 cases still dependent on mechanical ventilation, and 7 cases still dependent on artificial airway without mechanical ventilation), and 21 patients gave up treatment. In the intervention group, 26 cases died in hospital, 64 cases were improved and discharged (38 cases discharged after weaning and extubation, 19 cases still dependent on mechanical ventilation, and 7 cases still dependent on artificial airway without mechanical ventilation), and 11 patients gave up treatment (9 deaths, 1 case still dependent on mechanical ventilation, 1 case successfully extubated). Compared with the control group, there were more use of diaphragm ultrasound (97.0% vs 12.7%), diaphragm electrical activity monitoring technology (5% vs 0) and external diaphragm pacer (26.7% vs 0) in the intervention group, and the differences were statistically significant. There was no significant difference in the number of cases of bronchoscopy between the two groups. The esophageal pressureguided strategy and neurally adjusted ventilator assist (NAVA) mode were the first of their kind. Among 19 HMV patients in the intervention group, 3 cases were readmitted by green channel due to aggravation of pulmonary infection caused by irregular airway clearance, 1 case died, and the rest of them still insisted on HMV during followup. Fourteen cases with HMV in control group were lost to followup. In the intervention group, there were 7 cases dependent on artificial airway without mechanical ventilation, of which 1 case were extubation 3 months after discharge, and the rest were all alive during followup. There were 7 cases dependent on artificial airway without mechanical ventilation, and they were all lost to followup. There was no statistical difference between the two groups in the number of patients discharged from hospital, extubation at discharge, dependent on mechanical ventilation at discharge, dependent on artificial airway without mechanical ventilation, length of stay in ICU and duration of mechanical ventilation.
Conclusions：PMVMDT model can provide systematic and individualized clinical diagnosis, treatment and weaning plan for children with ventilator dependent as early as possible. It also provides home care training before discharge and regular followup after discharge for children with HMV. All these can ensure the effectiveness and continuity of treatment strategies for children with longterm mechanical ventilation.
Background：Patients with congenital heart disease need lifelong followup, and lack of disease knowledge may lead to interruption of followup. Effective assessment of patients' and caregivers' disease knowledge and accurate education can reduce unintended complications and facilitate their transition to adulthood.
Objective：To translate English Leuven knowledge questionnaire for congenital heart disease (LKQCHD) into Chinese version,and explore its application effect in parents of CHD patients.
Design：English to Chinese translation and a crosssectional survey.
Methods：After permission from the original author, a new Brislin translation model was applied to translate English LKQCHD into Chinese through literal translation, back translation and contrast back translation. A content validity evaluation was conducted by 7 healthcare experts. After confirming the content and face validity of the questionnaire, the LKQCHD was distributed to parents of CHD patients. Logistic regressive analysis was performed to investigate the factors influencing the disease knowledge of parents of CHD children.
Main outcome measures：Disease knowledge questionnaire scores.
Results：The Chinese version of LKQCHD contained 27 items. The item content validity index（ICVI）was 0.97 , the universal agreement of scale level content validity index（SCVI/UA）was 0. 85，the mean scale level content validity index(SCVI/AVE) was 0.97, and the interrater agreement（IR）was 0.85. A total of 302 Chinese version LKQCHD questionnaires were send out and taken back 301 effective questionnaires with the accuracy of (65.2±23.5) %. Multivariate analysis showed that the mother's education level, the family's economic level and the times of surgeries were the main influencing factors of the score of LKQCHD.
Conclusions：The Chinese version of the LKQCHD is valid to assess the level of knowledge mastery in parents and caregivers of CHD patients.
Background：The 2019 international consensus on central precocious puberty (CPP) proposed that random serum luteinizing hormone (LH) has important reference value for the confirmation or exclusion of CPP, but there is no corresponding diagnostic criteria in China.
Objective：By verifying the diagnostic value of the cutoff value of serum LH basal value proposed in the international consensus in 2019 for CPP, it is expected to reduce unnecessary GnRH stimulation tests and provide guidance for clinical practice.
Design：Diagnostic accuracy study.
Methods：According to the Chinese Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty (2022 edition) (referred to as the Chinese consensus), the recommended value of LH (chemiluminescence method) (peak LH ≥5 IU·L-1and peak LH /FSH ≥0.6 combined with clinical) was used as the gold standard for the diagnosis of CPP. According to the two cutoff values (0.83 and 0.20 IU·L-1) recommended by the international consensus, girls aged 49 years who met the diagnostic criteria of precocity, did not have menarche, had breast development Tanner stage Ⅲ or below, and underwent GnRH stimulation test were enrolled. Peripheral precocity was excluded. The clinical data of age, height, weight, body mass index (BMI), Tanner stage, gonadal axis hormones and sex hormones, bone age (TW3), pituitary MR and uterine and ovarian ultrasound were collected.
Main outcome measures：Sensitivity and specificity of different basic luteinizing hormone cutoff values for diagnosing CPP.
Results：A total of 352 girls with precocious puberty were included in the analysis. Among them, 203 cases were diagnosed as CPP and 149 cases were diagnosed as PT according to the gold standard. The average age of precocious puberty was (7.3±1.0) years, and the average height was (130.6±10.3) cm. The CPP girls had significantly higher mean age, height and bone age, and baseline serum LH, FSH, LH/FSH, and E2 levels than the PT girls. The differences were statistically significant. The specificity of baseline serum LH value ≥0.83 IU·L-1 (100%, 95%CI:97%100%) was better than that of baseline serum LH value <0.20 IU·L-1(45%, 95%CI:37%53%) and from 0.20 to 0.82 IU·L-1 (56%, 95%CI:47%63%). The CPP girls with a baseline LH level of ≥0.83 IU·L-1 had significantly higher breast Tanner stage, bone age, and bone agechronological age difference than those with a baseline LH level of <0.83 IU·L-1 (P<0.05), and a significantly lower pituitary height than those with a baseline LH level of < 0.83 IU·L-1 (P<0.05).
Conclusions：When chemiluminescence method is used to detect gonadal hormone in children with precocious puberty, CPP can be diagnosed with serum LH base value ≥ 0.83 IU·L-1, and GnRH excitation test is not required LH <0.20 IU·L-1 cannot be used as the exclusion criteria for CPP, and sexual GnRH excitation test should be selected to assist diagnosis based on clinical characteristics.
Background：Neuroblastoma is the most common extracranial solid tumor in children, and its clinical presentation and prognosis vary widely.
Objective：To investigate the clinical features and prognostic analysis of different international neuroblastoma pathology classification in children with nonhighrisk neuroblastoma.
Design：Retrospective cohort study.
Methods：We retrospectively collected clinical data of nonhighrisk neuroblastoma children admitted to the medical oncology ward at Beijing Children's Hospital, Capital Medical University from March 2007 to December 2020. We divided the children into favorable histology（FH）group and unfavorable histology（UH）group according to the INPC classfication system. We analyzed the clinical features of the different international neuroblastoma pathology classification and performed a prognostic analysis. Survival analysis was carried out using the KaplanMeier method.
Main outcome measures：3year and 5year overall survival(OS) and eventfree survival(EFS) rates.
Results：A total of 445 children were included in the clinical data, including 313 children in the FH group. There were 164 cases (52.4%) younger than 18 months of age; the mediastinum was the most common site of origin (52.7%), with distant metastases in 52 cases (16.6%). In the UH group, there were 132 cases, with 25 cases (18.9%) younger than 18 months of age; the primary site was most common in the retroperitoneum (49.2%) and 10 cases (7.6%) had distant metastases. The differences in age distribution, primary site and incidence of distant metastases between the two groups were statistically significant, while the differences in gender, maximum diameter of the tumour and LDH level were not statistically significant. The median followup time was 34 (0.16166) months. The 3year EFS was 96.4% and 92% in the FH and UH groups, respectively, and 5year EFS was 95.4% and 87.8%, respectively, with statistically significant differences (χ2was 1.63 and 4.75, P was 0.046 and 0.029 , respectively). The 3year OS was 98.3% and 98.4% in the FH and UH groups, respectively, and 5year OS was 98% and 98.8%, respectively, with no statistically significant difference (χ2was 0.76 and 0.54, P was 1.53 and 0.82, respectively).
Conclusions：Among children with nonhighrisk neuroblastoma, patients in the UH group are older than those in the FH group, have more retroperitoneal primary tumours and a lower incidence of distant metastases. Children with FH have better OS and EFS than children with UH and may be considered for less intensive chemotherapy.
Background： Crescents are a common pathological feature in patients with purpura nephritis (HSPN), but there are few reports on the correlation between the proportion of crescents and the clinical and pathological features of children with HSPN.
Objective：To compare the clinical and pathological features of HSPN children with different crescentic ratios.
Design：Case series report.
Methods：The hospitalized children were enrolled between January 2013 to December 2017 at the Pediatric Nephrology Center of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine where they were diagnosed with HSPN and underwent the first renal biopsy with a crescent ratio ≤ 50%. According to the crescent proportion in the pathological report of renal biopsy, patients were divided into no crescent group, crescent <25% group and crescent 25% to 50% group. The general information, clinical manifestations, laboratory test indicators before renal biopsy, and pathological report of the renal biopsy were intercepted from the medical records, and compared between groups.
Main outcome measures：The relationship between crescent ratio and clinical manifestations and renal pathological features.
Results：A total of 416 children with HSPN were included in the analysis, including 167 cases in the no crescent group, 222 cases in the crescent <25% group, and 27 cases in the crescent 25% to 50% group. For clinical manifestations, the incidence of edema in the crescent <25% group and the crescent 25% to 50% group was higher than that in the no crescent group. Hematuria plus proteinuria was the main clinical type in the three groups. The proportion of nephrotic syndrome in the crescent 25% to 50% group was higher than that in the other two groups, and the differences were statistically significant. For laboratory examination indicators, the 24h urine protein quantification and BUN level in the crescent 25% to 50% group were higher than those in the other two groups, and the eGFR was lower than that in the other two groups. The levels of CRP and Ddimer in the crescent <25% group and the crescent 25% to 50% group were higher than those in the no crescent group. Scr in the crescent 25% to 50% group was higher than that in the no crescent group. The differences were statistically significant. According to the glomerular pathology, the proportions of fibrinoid necrosis and endothelial cell hyperplasia in the crescent <25% and 25% to 50% groups were higher than those in the no crescent group. The proportion of interstitial pathology graded as + and the proportion of C3 and fibrinogen (FIB) graded as ++ gradually increased with the growing crescent ratio. The differences were statistically significant. There is a positive correlation between the crescent proportion and the degree of renal tubular interstitial pathological grade (r=0.308, P<0.001), and a weak positive correlation with the degree of C3 deposition (r=0.139, P=0.005) and the degree of FIB deposition (r=0.177, P<0.001).
Conclusions：There is a parallel relationship between the crescent proportion and the severity of glomerular pathology, tubular interstitial injury, C3 and FIB deposition, and clinical staging in HSPN children.
Background:Enterovirus (EV) is one of the common pathogens that cause neonatal infection. Understanding the positive rate of EV nucleic acid detection and the disease distribution of hospitalized newborns will facilitate the development of rational therapeutic strategies.
Objective:To investigate the positive rate of enterovirus nucleic acid swabs in hospitalized neonates and its distribution in diseases.
Design:A crosssectional study.
Methods:For patients hospitalized in neonatal medical ward at Beijing Children′s Hospital from October 1, 2020 to September 30, 2021,the throat swabs were taken on the day of admission. Realtime PCR was used to detected general enterovirus (EV)EV71/CA16(Coxsackievirus A16). The positive rate of EV nucleic acid test and its distribution in disease was calculated. Clinical manifestations and laboratory tests between the EV positive group and the negative group were compared.
Main outcome measures:Positive rate of EV nucleic acid detection and disease distribution in hospitalized neonates.
Results:A total of 1,095 neonates (accounting for 91.2% of the hospitalized patients during the same period) were enrolled, including 605 males (55.3%) and 976 term infants (89.1%). The median age of admission was 11 (419) days and the median hospital stay was 8 (612) days. The first three orders of admission diagnosis were neonatal hyperbilirubinemia, neonatal pneumonia, and neonatal septicemia. The positive rate of EV nucleic acid test was 9.1‰ (10/1095). The positive rate of EV nucleic acid in infectious diseases was (9/483, 18.6‰). Among them, 5 cases (50%), 3 cases (30%) and 2 cases (20%) were presented with respiratory symptoms, jaundice and gastrointestinal symptoms as the first symptoms, respectively. Ten children were cured or improved and discharged. There were no statistically significant differences between children with positive and negative EV nucleic acid tests in gender, birth weight, gestational age, preterm delivery, delivery mode, feeding mode, maternal risk factors of perinatal infection, maternal gestational diabetes, age of onset, length of hospital stay and hospitalization cost (P>0.05). The incidence of contact with family members with symptomatic infection before onset was 60% in children with positive EV nucleic acid test, higher than 7% in children with negative EV test, and the difference was statistically significant (P<0.001). The proportion of central nervous system infection in children with positive and negative EV nucleic acid test was 20% and 3.1%, respectively, and the difference was statistically significant (P<0.05), but there was no significant difference in the incidence of fever, pathological jaundice, respiratory symptoms, digestive symptoms and nervous system symptoms (P>0.05). The proportion of children with infectious disease was 90% in EV positive children, higher than 43.7% in EV negative children, but there was no statistical significance. There was no statistical significance in the total number of white blood cells, incidence of hemoglobin, thrombocytopenia, incidence of myocardial enzyme and glutamicpyruvic transaminase, serum total bilirubin value, albumin, serum creatinine and blood urea nitrogen in the positive and negative children with EV nucleic acid test (P>0.05).
Conclusions:The positive rate of nucleic acid test of EV throat swabs was 9.1‰ at admission, and there was no specific change in clinical manifestations and laboratory routine test results. Transmission from family members may be the main cause of positive EV nucleic acid test in neonates. Children with positive EV nucleic acid test have a higher risk of central nervous system infection.
Background:Intestinal perforation in neonates with necrotizing enterocolitis（NEC） may lead to adverse neonatal outcomes.
ObjectiveTo analyze the risk factors for intestinal perforation in neonates with necrotizing enterocolitis.
Design:Casecontrol study
Methods:The retrospective study was conducted in infants with NEC(Bell stage≥Ⅱ) admitted to the neonatal department, Children's Hospital of Chongqing Medical University during January 1st, 2011 to December 31st, 2021. The positive group was 153 NEC with intestinal perforation. By 1:1 random proportioning method,153 NEC with nonintestinal perforation were enrolled in negative group. The clinical characteristics between two groups were compared to analyze the risk factors for intestinal perforation in neonates with necrotizing enterocolitis. The fitting curve was used to determine the cutoff and the receiver operating characteristics curve(ROC) was used to evaluate the predictive value of risk factors for intestinal perforation.
Main outcome measures:The risk factors of intestinal perforation in neonates with necrotizing enterocolitis.
Results:There were significant differences in birth weight, gestational age, small for gestational age infants, fever, hypotension, abdominal distension, bloody stools, thrombocytopenia, hypoproteinemia, hyperbilirubinemia, hypofibrinogenemia, renal impairment, coagulopathy, patent ductus arteriosus, proportion of ibuprofen usage before the diagnosis of NEC and proportion of dopamine usage within 1 week before the diagnosis of NEC in positive group and negative group(P＜0.05). Abdominal distension （OR=17.869，95%CI：4.97264.213）, blood in stool （OR=4.836，95%CI：1.77313.188）, thrombocytopenia （OR=16.657，95%CI：6.17344.943）, hyperbilirubinemia （OR=4.485，95%CI：1.80911.120）, hypofibrinogenia （OR=5.034，95%CI：1.50516.832）, sepsis （OR=12.385，95%CI：4.714~32.537）were the independent risk factors for intestinal perforation. ROC curve analysis showed that the combination of 6 independent risk factors and 6 risk factors had predictive value for intestinal perforation in neonates with necrotizing enterocolitis(P<0.05). The combination of the 6 independent risk factors mentioned above has the highest predictive value for intestinal perforation in neonates with necrotizing enterocolitis. The area under the curve of ROC was 0.961.
Conclusions:Abdominal distension, blood in stool, thrombocytopenia, hyperbilirubinemia, hypofibrinogenia, sepsis were the independent risk factors for intestinal perforation.
LI Miao, DU Shuxu, WANG Shumei, GONG Xiaojun, REN Siqi, ZHANG Jin, ZHANG Zhen, SUN Huaying, SUN Yanling, QIU Xiaoguang, LIU Wei, LI Chunde, WU Wanshui, SUN Liming
Background:Choroid plexus carcinoma (CPC) is very rare in children, and there are few reports in China about this special cohort.
Objective:To investigate the clinical features, treatment and survival outcome in pediatric CPC patients.
Design:Case series report.
Methods:Children with CPC confirmed by pathology after tumor resection, who were admitted to pediatric department of Beijing Shijitan Hospital from January 2017 to October 2022, were retrospectively analyzed. The last followup was December 31, 2022. The sex, age at diagnosis, clinical features, treatment and followup were collected. KaplanMeier method was adopted for survival analysis.
Main outcome measures:Overall survival (OS) and progressionfree survival (PFS).
Results:Among the 12 included patients, four were males and eight were females. The median age at diagnosis was 29.7 (range, 5.8119.6) months, with 8 cases less than 3 years old at the time of diagnosis, tumor diameter ≥5cm in 8 cases, and <5cm in 4 cases. Nine cases were supratentorial, and 3 were infratentorial. The tumor was located in ventricular system in 6 cases, and external involvement of brain parenchyma in 6 cases. Two cases experienced metastases (M+) and 10 patients without metastasis (M0) at the time of diagnosis. All the patients received tumor resection with 8 cases under gross total resection (GTR) and 4 near total resection (NTR). Five (42%) cases received chemotherapy only and 7 patients (58%) were treated with both radiotherapy and chemotherapy after surgery. At the time of last followup, 8 cases experienced tumor recurrence or progression, and 4 cases died. The mean OS were (56.7±8.8) months. The 1, 3, 5year OS were (83.3%±10.8)%、(66.7%±13.6)%, and (66.7%±13.6)%, respectively. The mean PFS time were（24.3±7.2）months. The 1, 3year PFS were (41.7%±14.2)% and (33.3%±13.6)%, respectively. The KaplanMeier univariate analysis showed the 3year OS was poorer in children with infratentorial tumors than those with supratentorial tumors (χ2=8.562, P=0.003). And the 3year OS was also lower in patients who received chemotherapy only than those who received radiotherapy in combination with chemotherapy (χ2=8.488, P =0.004). The difference in 3year PFS was not satistically significant in gender,age at diagnosis(< 3 years old and 318 years old) , tumor diameter (<5 cm and ≥5 cm), GTR and NTR, metastasis or not, chemotherapy only or in combination with radiotherapy (P>0.05).
Conclusions:CPC is very rare with poor prognosis in children. Children with infratentorial tumors and who received chemotherapy only tend to have poorer OS.
Background:Invasive bloodstream infections with nontyphoid salmonella (NTS) can result in septicemia, and untimely diagnosis and treatment can lead to severe complications and death.
Objective:To summarize and analyze the clinical features and treatment experience of NTS septicemia in children.
Design:Case series report.
Methods:Children diagnosed with NTS septicemia by blood culture at the Sichuan University West China Second University Hospital from November 2017 to October 2022 were enrolled. Data on general information, clinical manifestations, laboratory examinations, treatments, and prognosis of the children were collected through the hospital medical record system.
Main outcome measures:Discharge with improvement or death.
Results:A total of 13 children with NTS septicemia were enrolled, and the age of onset was 1 year (0.9, 6 years), of which 10 were <5 years. Five were males and 7 had comorbidities. The source of infection was unknown except for one patient who had eaten infected food. The time of onset was from July to September（76.9%）. All patients had a high fever, and 10 (76.9%) had a fever as their first symptom; 6 had diarrhea and 6 had cough. The rest symptoms included shortness of breath, depression, convulsions, vomiting, bloody stools, rash, bone and joint pain, wheezing, cyanosis, and jaundice. There were 6 cases of gastroenteritis, 5 cases of pneumonia, and 1 case of meningitis and 1 case of osteomyelitis. Laboratory result showed increased WBC in 3 cases, increased PLT in 3 cases, increased CRP in 8 cases, increased PCT in 6 cases, decreased Hb in 6 cases, and increased ALT/AST in 6 cases. Blood cultures obtained 3 cases of Salmonella Enteritidis and Salmonella Typhimurium respectively, and 1 case of Salmonella Derby, Salmonella Dublin and Salmonella Newlands respectively, and 4 untyped cases. The blood culture turned negative at 5 (4.5, 13.5) days. Twelve were drugresistant and 7 were multidrugresistant. High resistance rates were observed for amikacin (92.3%), tobramycin (92.3%), and gentamicin (92.3%), followed by ampicillin (69.2%) and sulfamethoxazole/trimethoprim (30.8%). No carbapenems were resistant. Most were sensitive to third and fourthgeneration cephalosporins and aztreonam. The duration of the antibiotic therapy was 17 (14, 21.5) days. All of 13 children recovered and were discharged.
Conclusions:NTS septicemia occurs mostly in children under 5 years old with a high fever as the common clinical manifestation and is likely to be accompanied by gastrointestinal symptoms. The diagnosis depends on pathogenetic testing. Thirdgeneration cephalosporins are recommended for empirical treatment, and most patients can obtain a good clinical outcome. Carbapenems are recommended for patients with ineffective firstline therapy and severe infections.
Background：USP53 gene deficiency disease is a newly discovered rare genetic disorder characterized by cholestasis. Few cases have been reported and more cases need to be accumulated to fully describe the clinical and genetic features.
Objective：To investigate the clinical and genetic characteristics of children with USP53 gene deficiency.
Design：Case series report.
Methods：This retrospective study enrolled children with USP53 gene deficiency who were admitted to the Children's Hospital of Fudan University from January 2019 to December 2022.The clinical data were collected and analyzed. Medical literature published before December 2022 was searched with the keywords of USP53, ubiquitin-specific peptidase 53 and cholestasis in PubMed, Wanfang database and China National Knowledge Infrastructure.
Main outcome measures：USP53 gene variation sites and clinical phenotypes.
Results：Six patients with USP53 gene deficiency were enrolled (3 males and 3 females). All 6 patients presented with jaundice onset at infancy and liver function tests showed low GGT cholestasis. Whole exome sequencing (WES) were performed and compound heterozygous or homozygous USP53 gene variants were found in these patients. After treatment with ursodeoxycholic acid and cholestyramine, jaundice in 5 cases was completely regressed and liver function tests were normal followed up to the age of 7 to 34 months. One case presented at the with jaundice age of 5 months and completely regressed at last follow-up(12 months) with high total bile acid（257 μmol·L-1）. A total of 3 compound heterozygous and 3 homozygous USP53 gene variants were found through WES in these 6 patients (c.1012C>T in 3 patients, c.1558C>T and c.1426C>T in 2 patients). Except for c.725C>G, which was classified as a variant of uncertain clinical significance, other variants were classified as pathogenic variants. Among all the variants, c.1815_1816dupTA and c.725C>G were novel, which have never been reported before. Thirty-three of 38 USP53-deficient patients presented with jaundice, cholestasis and pruritus and other symptoms including hearing loss (4 cases), speech and developmental delay (2 cases), heart failure (1 case), hypocalcemia (1 case), hypothyroidism (1 case), leukocytosis and thrombocytosis (1 case) and fundus oculi lesion (1 case). A total of 25 pathogenic variants in five types were reported, including nine frameshift variants, six nonsense variants, five missense variants, three splice site mutations and two gross deletion variants.
Conclusions：USP53-deficient patients often present with jaundice and cholestasis, and the prognosis is good. Among all the USP53 variants, frameshift variants and nonsense variants are common.
Background: SMARCA2 gene mutations can lead to different neurodevelopmental disorders.
Objective: To summarize the clinical and genetic characteristics of SMARCA2 related disorders.
Design: Case Series Report.
Methods: Cases were enrolled who met the following inclusion criteria: aged 0-18 years who were included in the databases of Clinical Big Data of Children with Mental Disorders/Developmental Delays and Clinical Big Data of Children with Epilepsy in the Department of Pediatrics, Xiangya Hospital, Central South University from January 2017 to December 2021; the genetic test results showed that the SMARCA2 gene mutation was pathogenic or likely pathogenic; there were follow-up records after the first visit. Children's demography information, maternal pregnancy history, birth history and past history, seizure types and frequency, anti-seizure medications, physical examination, EEG, growth and development assessment data were collected. The last follow-up was January 2022. Based on previous literature reports, the clinical and genetic characteristics of SMARCA2 related diseases were summarized.
Main outcome measures: Frequency of epileptic seizures.
Results: Among the 6 cases of SMARCA2 related nervous system disease, 3 cases were male and 3 cases were female. Case 6 was diagnosed as Lennox-Gastaut syndrome(LGS), and case 1-5 were diagnosed as Nicolaides-Baraitser syndrome(NCBRS). The follow-up period was 1.75 (0.58-3.25) years. They all denied any previous history of heat shock, other intracranial lesions, or similar family history. All had varying degrees of developmental delay. The median onset age of seizure was 9 (8-19)months. In case 6, seizures manifested as spasms, tonic spasm, atypical absence seizure and myoclonus seizure. In cases 1-5, there were four instances of generalized tonic-clonic seizures, three instances of focal seizures, two instances of spasms, two instances of cluster seizures, and one instance of status epilepticus. All five cases exhibited distinct facial characteristics, such as a triangular face, prominent eyelashes, broad nasal base, and broad philtrum. Additionally, they all presented with stunted growth and microcephaly. In contrast, case six only displayed a broad nasal base. Six cases were treated with antiepileptic drugs such as sodium valproate, adrenocorticotropin, chlorhexidine, and levetiracetam. The seizures were completely controlled in two cases, and significant improvement was observed in four cases. All were detected with SMARCA2 (NM_003070) de novo heterozygous missense mutation. The missense mutations were located in the ATPase/C-terminal Helicase domain in cases 1 to 5, and were in HSA domain in case 6. The missense variation in cases 1 to 6 is: c.2554G>A/pathogenic, c.2564G>A/pathogenic, c.3394G>A/pathogenic, c.2551G>A/pathogenic, c.2830C>A/likely pathogenic, c.1399C>T/likely pathogenic. Cases 3-6 have not been reported.
Conclusions: The SMARCA2 gene mutation can lead to neurodevelopmental disorders with NCBRS as the main phenotype. There are genotype-phenotype associations in SMARCA2 related neurodevelopmental disorders. The common features including developmental delay/intellectual disability and epilepsy. Children with NCBRS also have special rough facial features and developmental abnormalities, and prominent language deficits.
