LIU Gongbao, GU Ying, ZHANG Xiaobo, WANG Chuanqing, ZENG Mei, SHEN Guomei, LU Guoping, CAO Yun, ZHANG Mingzhi, WANG Zhonglin, MA Jian, GE Yanling, ZHANG Lan, LI Zhihua, XIA Aimei, ZHAI Xiaowen, ZHOU Wenhao, GUI Yonghao, XU Hong, HUANG Guoying
Background：As Omicron variant is extremely infectious, the pandemic of Omicron variant in Shanghai from March to May this year is complex, dynamic and uncertain, therefore it is more challenging for hospitals.
Objective：To summarize the experience of bubble management of preventing and controlling nosocomial infection and occupational exposure of COVID19.
Design：Observational study.
Methods：In this pandemic, our hospital is designed as a big bubble. Six key medical departments are designed as medium bubbles, including the outpatient of COVID19, fever clinic, emergency department, special ward of COVID19, neonatal isolation ward and transition ward. Several important departments of medium bubbles are designed as small bubbles. Those with a red code, positive results of coronavirus nucleic acid or antigen tests, or infection history of COVID19, and the close contacts of COVID19 were admitted to the outpatient of COVID19. According to the condition and epidemic history, they were arranged to different functional small bubbles. Those fever patients with a green code or a yellow code were admitted to fever clinic. Those with emergent conditions but without fever were admitted to the emergency department which was further divided into two small bubbles named as the buffer area and general area . The backup was also available. Patients with a positive PCR result were admitted to the special ward of COVID19 while those with severe critical illness were in the ICU, and the other with mild or common type were in the general ward. All newly admitted children except critical illness and neonates were in the transition ward. Neonates with negative primary screening nucleic acid from pregnant women with COVID19 were admitted to neonatal isolation ward while all neonates were arranged in the small bubble of negative pressure area first. After daily nucleic acid tests for 3 days, those with negative resulst were transferred to nonnegative pressure area and the other with positive results were transferred to special ward of COVID19. The flow of personnel and meterial with different risk rate was not allowed. The staff with the lower risk moving to the higher level risk should be reported to the department of medical affairs. Meanwhile the plan of the bubble burst is ready. Standard training contents and assessment requirements were formulated according to different posts of staff, and checked through voice and video monitoring system and onsite supervision.
Main outcome measures：Nosocomial infection and occupational exposure of COVID19.
Results：A total of 432 patients with COVID19 were admitted to our hospital, including 341 patients with mild type (78.9%), 88 patients with common type(20.4%), and 3 patients with critical illness. Each critical illness had invasive mechanical ventilation while one patient had additional CRRT and ECMO .None of them died from COVID19. Twentynine patients had underlying disease and 109 staff successively worked in outpatient and inpatient of COVID19 including 46 doctors, 49 nurses, 9 medical technicians and 5 auxiliary medical personnel, none of which had nosocomial infection and occupational exposure of COVID19. A total of 189 persons with a red code were intercepted at the entrance of the hospital. All patients with red codes were guided to the outpatient of COVID19, therefore, none of them was permitted into the general outpatient and emergency department. The total number of outpatient and emergency patients was 253 571, 12 114 of which was admitted to emergency. Six emergency patients were positive of primary nucleic acid test. Three patients with COVID19 entered the general area of emergency, resulting in the closed disinfection and sterilization for 3 times, activating the backup emergency area. A total of 8 328 patients were admitted to fever clinic, 50 of which were transferred to the outpatient of COVID19 after positive nucleic acid test. The total number of outpatient of COVID19 was 763. According to grade V triage,3 of 4 cases of grade I /II were critical illness. In total, 690 neonates were admitted to our hospital including 516 cases of lowrisk epidemic history and 174 cases of highrisk epidemic history, 2 cases of which were positive of nucleic acid test. Six hundred and ninetythree patients were admitted to the transition ward including 223 emergency cases and 470 selective cases, 1 of which was positive of nucleic acid test. All staff working in the isolation ward participated in theoretical training and special training on highrisk bubbles was carried out for 29 times for 291 people. Both theoretical training and operation training were qualified.Video monitoring and onsite supervision were performed for 304 people.
Conclusion：There was neither nosocomial infection nor cupational exposure of COVID19 in this bubble management.
ZHANG Lan , YANG Tongling , WANG Jin , LI Zhihua , YUAN Hao , ZHU Xiaoting , JIANG Siyuan , ZHANG Rong , LI Liling , ZHOU Jianguo , LU Chunmei , WANG Laishuan , HU Xiaojing , CAO Yun
Background：Children's Hospital of Fudan University was the designated hospital for newborns in the SARSCoV2 omicron variant wave in Shanghai from March to May 2022. Facing the complexity of the current pandemic, it was a challenge for special populations such as newborns to coordinate pandemic control and medical treatment.
Objective：To implement and improve the bubble strategy for newborns on the basis of the overall strategy in the hospital.
Design：Observational study.
Methods：Four small bubbles were developed in the bubble management of newborns in the hospital.The COVID19 ward in Shanghai Public Health Clinical Center, as a small red bubble, was used to admit the infants with nucleic acid or antigen positive results, in accordance with the protocol set by Children's Hospital of Fudan University. The isolation ward, as a small orange bubble, was set in a separate building in the hospital including negative pressure rooms. Infants with highrisk epidemic history were admitted. All infants in the small orange bubble were required to complete a 7day medical observation and perform nucleic acid test every day. The negative pressure rooms and the nonnegative pressure rooms had their own independent places for storing materials. The staff were protected by grade II and grade I (+4) standard protective equipment respectively. The transportation of stuff and specimens was carried out by special "ferrymen". The transition ward with single rooms and multiperson rooms, as a small yellow bubble, was set to admit lowrisk epidemic history infants. Nucleic acid testing was performed every 24 hours and medical observation would be ended if nucleic acid was negative for 3 consecutive days. The single rooms and the multiperson rooms had their own independent places for storing materials. The staff were protected by grade II and grade I (+4) standard protective equipment respectively. The transportation of stuff and specimens was carried out by special "ferrymen". The clean wards, as the small green bubbles, were the areas for routine hospitalized infants as usual. They admitted defined riskfree infants from orange and yellow bubbles. The transport of infants was uniformly taken by 120 emergency vehicles of the whole city. The infants were transported to the bubble by the transport team of the corresponding bubble. Infants came out of the the small red bubble according to the protocol of COVID19 ward in the other article of the whole hospital in this issue. Infants came out of small orange bubble according to the following protocols: a.The 7days medical observation was completed; b. There was no COVID19 patients in the building of the family where the infants lived after being discharged; c. The health code of the home caregivers and the coresidents was green, or the isolation had been removed; d. The health code of the family members who took the infants out of the hospital was green, and the nucleic acid within 48 hours was negative. Infants could come out of small yellow bubble after 72h medical observation. During the hospitalization of the infants, the medical staff conveyed humanistic care to the parents of the newborn through WeChat to relieve the doubts, anxieties and difficulties of parents at any time.
Main outcome measures：No occupational exposure and nosocomial infections among medical staff.
Results：A total of 677 infants were admitted, of which 158 (130 from Shanghai Public Health Clinical Center, 21 from other medical institutions, and 7 transported by small orange bubble team) were admitted into the small orange bubble for management. There were 10(6.4%) premature infants out of them. The remaining 519 infants (375 from the community, 144 transported by the small yellow bubble team) admitted into the yellow bubble for management. There were 173 (33.3%) preterm infants, 82 (15.8%) infants with intubation, 45(8.7%) with noninvasive ventilation, all of whom entered the small green bubbles after medical observation, including 137 in the NICU and 382 in the general ward. The average length of stay was 13.5 days. One infant was diagnosed as complex congenital heart disease in the small orange bubble and transported to CCU after medical observation. Two infants with positive nucleic acid test in the small orange bubble who had contact history with COVID19 mothers after birth were and transported to the red bubble for management. There were 324 medical staff participating in the work of the small red, orange, yellow and green bubbles, and no occupational exposure or hospital infection occurred.
Conclusion：It is feasible to implement newborn bubble management in this pandemic wave, and the effect of preventing and controlling occupational exposure and hospital infection is good.
Background：The Omicron pandemic in Shanghai from March to May 2022 is very challenging for the emergency department to attach equal importance to emergency rescue and pandemic prevention and control.
Objective：To explore the effect of bubble strategy on emergency rescue and pandemic prevention and control.
Design：Observational study.
Methods：During this pandemic period, the hospital is designed as a big bubble, and the emergency department is designed as a medium bubble. The buffer zone, resuscitation room, consulting room and observation room are designed as small bubbles. Based on "four zones, two channels and twice triage", the original layout and process of emergency department were modified. The four zones were as the following: a. the clean zone mainly included personnel living room and personal protective equipment (PPE) donning room; b. the potentially contaminated zone was set between the contaminated zone and clean zone, including PPE doffing room 1 and 2; c. the contaminated zone included the second triage area, waiting area, resuscitation room, consulting rooms and observation room; d. the highrisk contaminated zone included the first triage area and buffer zone. Two channels were clean and contamination channels. Twice triage referred to the initial screening at the entrance of the emergency department, and fivelevel triage after admission to the emergency department. The buffer zone was used for those who were diagnosed with critical illness but had a red health code and no negative nucleic acid test results within 48 hours. Level Ⅰ/Ⅱ patients with negative nucleic acid test results within 48 hours were admitted to the resuscitation room. Level ⅢⅤ patients with negative nucleic acid test results within 48 hours or negative onsite antigen test results were arranged to the consulting room. Patients who had negative nucleic acid test results on the day of entering the hospital and requirements for observation are admitted to the observation room. The second emergency room was set up as a backup emergency room when the major emergency department needed to be closed temporarily because of the presence of COVID19 infection patients. The bubble rupture plan was established. If a patient treated in the consulting room or resuscitation room was confirmed to be COVID19 infection, the first environmental sampling was performed at the exposure site to evaluate the degree of environmental contamination, and a second sampling was performed after terminal disinfection to evaluate the environmental safety. The second emergency room was activated if necessary.
Main outcome measures：Nosocomial infection and occupational exposure of medical staff.
Results：A total of 12 114 patients were admitted to the emergency department of our hospital, including 15 level Ⅰ patients, 310 level Ⅱ patients, 8 728 level Ⅲ patients, 2 564 level Ⅳ patients and 497 level Ⅴ patients. There were 7 major rescues, 32 medium rescues and 1 070 minor rescues. Fiftyeight patients were admitted to the PICU and 3 patients died in the emergency department. A total of 36 doctors, 38 nurses and 3 sanitation workers participated in the emergency department bubble, rotating every 5 days. Neither nosocomial infection nor occupational exposure occurred. Twentynine patients were admitted to the buffer zone, among which 3 patients were confirmed to be COVID19 infection and 3 patients were transferred to the PICU because of critical illness. In total, 652 patients were admitted to the observation room, among which 12 patients were transferred to PICU because of illness deterioration. Fiftyfive patients were guided to the COVID19 clinic by the initial screening, of which 4 patients were positive for nucleic acid test. A total of 6 patients with novel coronavirus infection were admitted to the emergency department. Among them, 3 children with positive nucleic acid test results were admitted to the consulting room, which caused environmental contamination. Terminal disinfection and environmental sampling were performed and the emergency department reopened when all environmental samples were tested negative.
Conclusion：By adjusting the layout of emergency department and modifying the treatment process, it is possible to meet the needs of emergency care and pandemic prevention and controlat the same time, and to achieve the double zero of nosocomial infection and occupational exposure. The risk of bubble rupture existed, so it was necessary to make a plan.
Background：Rehabilitation of children and adolescents with cerebral palsy（CP） needs highquality clinical practice guidelines to provide effective assessment and intervention to improve the health condition of children and adolescents with CP.
Objective：To improve and perfect the topic structure of Clinical Practice Guidelines for Children and Adolescents with Cerebral Palsy (CANDLE).
Design：A Scoping review
Methods：We searched English literature in Google Scholar and Chinese literature in CNKI, WangFang and VIP from January 1, 2010 to May 2, 2022 to get literature about children and adolescents with CP including guidelines, expert consensus, systematic review, and scoping review. Grey literature was searched in Google and BAIDU. According to intelligent sorting of Google scholar, researchers preliminarily screened literature by reading titles and abstracts until consecutive 50 articles of failed to match the inclusion criteria. The included literature was rescreened by reading full texts. References of the included literature after the second screening were compared with the final list of the included studies to find differences. Those unduplicated ones were screened by reading titles and abstracts. Researchers extracted data about questions proposed by the scoping review to a selfmade Excel sheet. The sheet consists of items of the application condition of The International Classification of Functioning, Disability and Health for Children and Youth（ICFCY）, function assessment, development, intervention, and functional influencing factor of children and adolescents with CP. The consistency of extracted data by 6 researchers was requested to be over 80%. Qualitative and quantitative methods were used to analyze data, and the core member of the CANDLE team answered the questions proposed by the scoping review.
Main outcome measures：Questions proposed by the scoping review.
Results：A total of 372 articles were enrolled in this scoping review. There has been a gradual increase in the number of guidelines, expert consensus, systematic reviews and scoping reviews in the past years. We got 7 English scoping reviews from 2010 to 2018, and 42 from 2018 to 2022. The majority of English literature focuses on intervention techniques, assessment techniques, and function status. Intervention techniques in Chinese literature accounted for 66.7%. There were 37 kinds of intervention techniques in 181 English articles. Four articles adopted ICFCY or ICF concept, and 78 articles partially used ICF concept in their structure. A total of 47 guidelines and expert consensus were enrolled. Among them, 9 expert consensus and 7 guidelines used function as a starting point. In 6 comprehensive guidelines, contents about function related to posture and motor were shown by muscular tension, mobility, hand activity, secondary musculoskeletal, daily living and leisure activities. There were 104 articles (31%) discussing the assessment method separately within 20 articles using COSMIN. Nine articles (3%) independently elaborated the effect of development characteristics on function. A total of 41 articles (12.1%) analyzed the interaction between function and background factors through the methods of correlation and influencing factors.
Conclusion：The overall structure of CANDLE was initially formed through this scoping review. Eight domains were established with function as the core, each of which is shown through five elements (ICFCY as the framework, assessment, development, interaction, and intervention). Questions of interest within the scope are built on the elements.
Background：Though screening techniques for neonatal major congenital heart disease (mCHD) are becoming increasingly mature, their widespread acceptance and application still need to be built on economic factors. Currently, there are few studies related to the health economics of mCHD screening, and most of the data are from developed countries.
Objective：To investigate the effectiveness and economics of mCHD screening.
Design：Systematic review.
Methods：The search strategy was established according to the rule of PIROS participant for neonatal, index for pulse oximetry (POX), reference for echocardiography and surgery, outcome for neonatal mCHD, and study design for cost analysis, costeffectiveness analysis, costutility analysis, and costbenefit analysis. Web of Science, The Cochrane Library, MedLine, Embase, SinoMed, CNKI, and Wanfang Databases were searched from 2000 to April 28, 2022. By reading the title, abstract, and full text, relevant information was extracted including health economics indicators evaluation method, research perspective, cost collection range, sensitivity analysis type, discount rate, and health economics evaluation results such as the cost of saving one Life year (LYS), the cost of gaining a quality adjusted life year (QALY), the cost of avoiding a disability adjusted life year (DALY), the cost of an additional case diagnosed on time, and the incremental costeffectiveness/utility ratio(ICER). The quality of literature was evaluated by the Quality of Health Economic Studies (QHES) instrument.
Main outcome measures:The cost and costeffectiveness of screening.
Results：Eleven articles were included from 2007 to 2020, of which 7 were able to extract the data of POX screening, 4 were able to extract the data of clinical evaluation (CE) , and POX+CE screening, and 1 was able to extract the data of POX+MUR screening. There were 2 about social science, 9 about medical system, 4 about population, 7 about models, 1 with both direct cost and indirect cost, and 10 with only direct cost. Based on the exchange rate of USD in June 2022, the cost of POX screening is 224.5 USD, in which the labor cost is 2.537.4 USD, the cost of onetime probe is 13.422 USD, and the cost of reusable probe is 0.10.9 USD. CE screening costs 0.504.50 USD. MUR screening costs 1.302.0 USD. Echocardiography (ECHO) costs 301300 USD for screening positive cases. CEA/CUA (costeffectiveness/utility analysis) was used in 8 articles, among which 2 articles evaluated POX screening, 5 for POX+CE screening, and 1 for POX+MUR. The cost of using a probe and echocardiography was the main cost of screening without considering labor costs. POX, POX+MUR, and POX+CE have cost effectiveness. POX+MUR has cost effectiveness compared with ECHO. When ECHO+CE can detect other congenital defects, it has cost effectiveness compared with POX+CE.
Conclusion：The cost of mCHD screening is mainly reflected in whether to use a onetime probe and echocardiography. POX, POX+MUR, and POX+CE have cost effectiveness. Neonatal mCHD screening is economically acceptable at different economic development levels.
Background：Currently in clinical genetic diagnosis, both exome capture sequencing (ES) and whole genome sequencing (WGS) have a wide range of application scenarios. Each has its own advantages in terms of either better costeffective performance or a wider variant detection range. The establishment of an integrative genetic diagnosis process that supports two different library preparation and sequencing protocols is essential to further improve the sensitivity and efficiency of genetic testing.
Objective：By integrating the analysis of various variant types fitting both ES and WGS scenarios, the normalization and structuring of complex clinical phenotypes of genetic diseases, and the phenotypeoriented genetic variation analysis system to establish an integrated process from the application of genetic test to the feedback of a diagnostic report.
Design：Process development.
Methods：An integrated fullprocess closedloop analysis system for highthroughput sequencing data (Fudan Process 3.0) was established including the modules of processing the medical history, extracting structured terms of phenotype, sequencing experiment, detecting variants, interpretating variants, checking quality control, and analyzing both genotypes and phenotypes. In terms of testretest analysis of representative cases, we selected representative cases with various type of conclusive pathogenic variants and diagnosis difficulties to present the analysis process from sequencing experiments and clinical history to the generation of a draft report.
Main outcome measures：The structured phenotype terms of patients, the data quality control parameters, the status of variant detection and interpretation, and the final diagnosis during the analysis of representative cases.
Results：During the reanalysis of 3 representative cases, the optimized trio genome sequencing, probandonly WGS and CES were carried out respectively. The structured phenotype was successfully extracted from the medical history. The data quality of FastQ and BAM files was well controlled. After interpretation, a combined genotype and phenotype analysis was performed to detect the complex inheritance pattern of three cases respectively. In example 1, detected point mutation NM_058172 (c. 1294C>T and 4q21.22 about 13 kb structural variant deletion on ANTXR2) matched the recessive inheritance model. In example 2, a pathogenic variant m. 14459G>A on mitochondrial gene MTND6 with heterogeneity>99.5% was detected. In example 3, a homozygous pathogenic variant NM_000344（c. 863G>T combined with a single-copy deletion of SMN1 gene）was detected.
Conclusion：The Fudan Process 3.0 is well functioned in processing either ES or WGS data to analyze various variant types and draw genetic diagnosis conclusions, especially in handling cases with complex variant types.
Background：Fetal lung development is later than other organs, and the maturity of lung development is closely related to pregnancy outcome.
Objective：To investigate the relationship between the ratio of systolic acceleration time/ejection time (AT/ET) of fullterm fetal main pulmonary artery ultrasound and neonatal lung maturity and its predictive value.
Design：Casecontrol study.
Methods：Pregnant women who underwent ultrasound examination of fetal main pulmonary arteries in Xinxiang Central Hospital of Henan Province from October 2019 to October 2020 were taken as the research objects. According to fetal amniotic fluid or tracheal aspiration liquid lamellar bodies (LB)≥50×109·L-1 after delivery, they were divided into mature and immature groups. The clinical data and AT/ET ratio of fetal main pulmonary artery were compared between the two groups. Multivariate logistic regression analysis was used to analyze the factors affecting neonatal lung maturity. Spearman correlation analysis to explore the correlation between AT/ET ratio and neonatal lung maturity. ROC curve was drawn to analyze the predictive value of AT/ET ratio on neonatal lung maturity.
Main outcome measures：The relationship between AT/ET ratio of fetal main pulmonary artery and neonatal lung maturity.
Results：Ultrasound images of 102 pregnant women and their pulmonary aorta and LB data of newborns were analyzed in this paper, aged from 23 to 36 (29.4±1.0) years, with 37+138+6 (38.3±0.1) weeks of ultrasonic examination of main pulmonary artery. There were 76 cases in mature lung group and 26 cases in immature lung group. There were significant differences in nutritional status, fetal respiratory motor score, PSV and AT/ET in the middle of fetal main pulmonary artery between the two groups (P<0.05). Multivariate logistic regression analysis showed that AT/ET in the middle segment of fetal main pulmonary artery was an independent factor affecting neonatal lung maturity (OR=0.881, 95%CI:0.6780.983). Spearman correlation analysis showed that AT/ET ratio in the middle of fetal main pulmonary artery was positively correlated with neonatal lung maturity (r=0.678, P=0.003). ROC curve showed that the best cutoff value of AT/ET in the middle of fetal main pulmonary artery for predicting neonatal lung maturity was 0.22. At this time, the sensitivity was 92.1% (95%CI：84.1%97.4%), the specificity was 84.6% (95%CI:70.9%93.4%), and the AUC was 0.818 (95%CI:71.5%92.7%). The kappa value of lung maturity predicted by AT/ET ratio was 0.812 (P<0.05).
Conclusion：AT/ET in the main pulmonary artery of fullterm fetus is closely related to the lung maturity of newborns, and has certain predictive value for the lung maturity of newborns.
Background：The longterm survival of children with neuroblastoma (NB) associated with MYCN amplification is not promising, and few studies have been previously reported in China.
Objective：To summarize the related factors of clinical characteristics, therapeutic effect and prognosis in NB children with MYCN amplification and to further improve the recognization of this group in NB.
Design：Case series report.
Methods：The clinical information of NB with MYCN amplification, diagnosed and treated from Feb 2007 to Jan 2020, were analyzed retrospectively, and the tumor location, size, metastasis, treatment, and risk factors affecting the prognosis were analyzed.
Main outcome measures：Factors affecting the 3year survival of NB with MYCN amplification.
Results：A total of 133 NB patients with MYCNAmp were included in this study, accounting for 12.02% of total NB patients in the same period in our center. The median age of onset was 35.7±9.8 months. There were 129 cases (97%) located in abdomen region and 4 cases (3%) in posterior mediastinal region. There were 81 cases (60.9%) with bone marrow metastasis, 80 cases (60.2%) with bone metastasis and 24 cases (18.1%) with central nerves system metastasis. Serum LDH ≥1 500 U·L-1was shown in 99 cases (74.4%). NES ≥100 ng·mL-1was found in 126 cases (94.7%). The largest tumor diameter (>10 cm) was in 89 cases (66.9%). The 3year OS and EFS were 19.7% and 19.0%. There were 78 cases of progressive recurrence, 8, 20, 46 and 4 cases of progressive recurrence happened at induction, consolidation, maintenance and withdrawal, respectively. Primary tumor, bone marrow, central nervous system and bone were the most common sites of progressive recurrence. The median time of first progression was 11.3 months. Bone marrow and bone metastasis, deletion of 1p36 were risk factors.
Conclusion：A single center with large sample of MYCNAmp NB showed that the primary tumor was predominantly located in the retroperitoneal adrenal region, with a high rate of early distant metastasis, and more than 50% of the children developed tumor progression during maintenance therapy with 3year OS of 19.7%. These children urgently need targeted therapy and other new treatment to further improve the efficacy and the prognosis.
Background：The quantitative analysis focused on virus shedding duration of immunocompromised (IC) children infected with SARSCoV2 during the Omicron wave is rare.
Objective：To investigate the differences in virus shedding duration between IC and nonIC patients infected with Omicron and to provide firstline information for public health policy making and precise epidemic prevention strategy.
Design：Retrospective cohort study.
Methods：The study population was Omicron infected inhospital pediatric patients. According to their immune condition, these patients were divided into IC and nonIC groups. The immunocompromised state was divided into complete immunocompromised condition, relative immunocompromised condition, and immunosuppressive therapy. The nonIC group was matched with gender, age, type of SARSCoV2 infection, and 1:3 ratio in the IC group. The SARSCoV2 genome PCR test detected nasal swab samples. Cycle threshold (Ct) value ≥35 was the endpoint.
Main outcome measures：SARSCoV2 virus shedding time.
Results：From April 12 to May 12, 2022, we enrolled 728 patients hospitalized in Renji Hospital, School of Medicine, Shanghai Jiao Tong University, the dedicated hospital in Shanghai. Among them, 33 patients were in the IC group, including 8 cases in complete immunocompromised state and 23 cases in a relative immunocompromised state. Two patients without complete or relative immunocompromised state received immunosuppressive therapy. Ninetynine patients were included in the nonIC group. No significant differences were detected in clinical phenotypes, treatment, and vaccination between the two groups. The virus shedding time between IC and nonIC groups had a significant difference (16.5±6.8 vs. 10.3±4.4 days). The virus shedding duration of mild type was (14.0±8.3) and (9.7±3.1) days, (18.3±4.9) and (11.2±5.9) days in moderate type. Significant differences were detected. The virus shedding duration of the two groups had significant differences during the 9th14th days (P=0.0050.039). The virus shedding duration of moderate type in two groups had significant differences during the 10th15th days. Three patients (9%) in the IC group had positive PCR test results again after two weeks. The disease type of these three patients were milder than the previous infection. All three patients were unvaccinated.
Conclusion：Virus shedding duration of IC patients was significantly longer than that of nonIC patients in Omicron wave. The prolonged virus shedding duration in IC patients was mainly in the 9th14th days. The IC patients had a higher risk of recurrent positive PCR results, which indicated longer isolation time and a strict nucleic acid test strategy after negative PCR test results.
Background：Coronavirus Disease 2019 (COVID19) vaccination plays an important role in controlling the pandemic and protecting population from developing into a severe type. The vaccination safety in children with a history of allergy has been a common concern.
Objective：To provide the best immunization practice and recommendations for children with a history of allergy.
Design：Case series report.
Methods：Children and adolescents aged 3 to 17 who were consulted at the designated pediatric COVID19 vaccine advisory clinic in Children's Hospital of Fudan University between August 12nd, 2021 and December 3rd, 2021 were included. Based on individual's past medical history, current health status, and parental concerns, individualized assessments are made, and recommendations for deferring and recommending vaccinations are given. Telephone followup was conducted to collect adverse events following immunization (AEFI) within 72 h and 28 d after vaccination and any unsolicited adverse events reported by parents. The causal association between AEFI and vaccine was assessed.
Main outcome measures：AEFI of COVID19 vaccine.
Results：A total of 116 children consulted for COVID19 vaccination, including 67 boys (57.8%) and 49 girls, aged (10.1±3.1) years old. Seventyseven (66.4%) were recommended to start vaccination, and 39 were recommended to defer vaccination after individualized assessment in the immunization advisory clinic. The followings were recommended to defer the vaccination 25 cases in the acute phase of allergic disease among 70 cases (60.3%) with a history of allergy, 5 cases of severe allergic reactions among 11 cases (9.5%) with a history of other vaccine or drug allergy, 5 cases in the acute phase of the disease in 13 cases (11.2%) with a history of nondrug allergy, and 3 cases of acute illness (respiratory tract infection) among 21 cases (18.1%) with atopy, and 1 case（0.9%）with a history of allergic to the first dose of COVID19 vaccine. All patients in the deferring vaccination group completed the telephone followup 3 months after the consultation. Seventyseven children in the recommended starting vaccination group were followed up for 3 times, among which 54 cases were in the vaccinated subgroup (47 children receiving 2 doses of vaccine, 7 children receiving 1 dose of vaccine), and 23 cases were in the unvaccinated subgroup. There were no significant differences in gender, allergic disease history, other vaccine or drug allergy history, nondrug allergy history and atopy between the two subgroups. The age ［(10.4±3.0) years vs (9.0±3.1) years old, P=0.04］ between the two subgroups had statistically significant difference. No severe allergic reactions were collected during the telephone followup at 4 d and 28 d after vaccination. Within 72 hours after vaccination, 18 cases (17.8%) were solicited with 10 systemic adverse events, 5 cases (5.0%) of rash and cough respectfully, 4 cases (4.0%) of runny nose, 3 cases (3.0%) of anorexia and fever respectfully, 2 cases (2.0%) of sore throat, 1 case (1.0%) of fatigue, myalgia, nausea and vomiting respectively. There was a causal relationship with the AEFIs and COVID19 vaccine after preliminary judgement. No additional solicited adverse reactions were reported in the 28 d and 3month telephone followup. Within 28 days after vaccination, parents voluntarily reported 5 cases of unsolicited adverse events, 3 cases (3.0%) of idiopathic dermatitis or eczema, and 2 cases (2.0%) of allergic rhinitis. No causal relationship with COVID19 vaccine was found. The incidence of AEFIs of COVID19 vaccine within 28 days was 33.3% (18/54).
Conclusion：It is safe for children whose allergic diseases are in remission status, those who had nonsevere allergic reactions to nonCOVID19 vaccines or other drugs, those who had nondrug allergy history, and those who had atopy to receive inactivated COVID19 vaccines. The systemic adverse reactions of AEFIs of COVID19 vaccine all occurred within 72 hours after vaccination, and were causally related to the COVID19 vaccination.
Background：The primary hyperoxalurias (PHs) is a rare hereditary nephrolithiasis and nephrocalcinosis caused by different gene mutations of enzymes that control the glyoxylate metabolism. PH1 and PH2 have already been paid more attention, while PH3 is the most recently identified type and there are only a few PH3 cases reported to date.
Objective：To summarize the clinical phenotypes of PH3 patients and to explore the putative mutation hotspot regions in different ethnic groups.
Design：Case series report.
Methods：From January 2015 to December 2021, the PH3 patients diagnosed by genetic testing in Children's Hospital of Fudan University were enrolled. Clinical and molecular biological data were collected from inpatient medical history. The Chinese and English literature of PH3 cases was searched in PubMed, Embase, Wanfang database and CNKI database to collect case source (country), gender, number of cases, onset age, diagnosis age, clinical manifestations (urolithiasis, nephrocalcinosis, hypercalciuria, hyperoxaluria), followup time, kidney function (chronic kidney disease stage 2, chronic kidney disease stage 3, chronic kidney disease stage 45), followup, outcome of urinary tract stones (active stones, asymptomatic stones or disappearance of stones), and HOGA1 gene mutation type.
Main outcome measures：Clinical phenotypes and hotspot variation in different ethnic groups.
Results：Eight PH3 patients were enrolled (7 boys, 1 girl). The median age of onset was 10 months, and the median diagnosis age was 16 months. Initial symptoms showed urinary tract infection in 5 patients and gross hematuria in 3 patients. Imaging evaluation identified the diagnosis of nephrolithiasis in 8 cases, and none of them showed nephrocalcinosis. Three patients were tested for urinary excretion of oxalate, and 1 showed hyperoxaluria. Six patients conducted urinary calcium test and 5 of them showed hypercalciuria. One patient was loss to follow up and the other 7 cases were followed up for a median of 25 months. The glomerular filtration rate remained stable. Furthermore, 3 cases showed kidney stones disappearing during the followup. All the 8 cases had HOGA1 gene variant, including compound heterozygous variants in 5 cases and homozygous variants in the other 3 cases. According to ACMG classification, 6 variants were identified as likely pathogenic variants and the other 4 were identified as pathogenic variants. Among 82 articles related to PH3, 23 were case reports or case series reports which included 321 cases of PH3. Among these cases, 36 patients from China and 293 patients form Europe and America. The percentage of nephrolithiasis in Chinese group and EuropeanAmerican group were 83 percent(30/36) and 85 percent(195/230) respectively. The percentage of nephrocalcinosis in these two groups were 3 percent (1/29) and 8 percent (20/261). There was no difference in hyperoxaluria between the two groups ［90 percent (26/29) vs 96percent (66/69)］. There was significant difference in hypercalciuria between the two groups ［44 percent (11/25) vs 23 percent (34/150)］. In Chinese group, one patient progressed to endstage renal disease when he was 25 years old. In EuropeAmerica group, there were 2 patients progressed to endstage renal disease at the age of 8 and 33 respectively. The percentage of active stone in these two groups were 13 percent (3/23) and 37 percent (22/59), and the difference was significant. The hotspot variants of the Chinese group were c.834G>A (splice site), c.834_c.834+1GG>TT (splice site) and c.769T＞G (p.C257G), accounting for 28 percent(20/72), 21percent(15/72) and 11 percent(8/72), respectively. The hotspot variants of the EuropeanAmerican populations were c.700+5G>T (splice site) and c.944_946delAGG (p. E315del), accounting for 40 percent(236/586) and 12 percent(73/586), respectively.
Conclusion：The age of onset and diagnosis of PH3 is quite earlier, and the overall prognosis is better than that of PH1 and PH2. Chinese and EuropeanAmerican PH3 patients may have different hotspot variants for HOGA1 gene.
Background：Sirolimus (SRL) is used in children for organ transplantation, autoimmune diseases, lymphatic malformation, vascular malformation, tuberous sclerosis and other diseases. However, it has great pharmacokinetic variability, which requires therapeutic drug monitoring (TDM).
Objective：To reveal the causes of abnormal serum concentration of sirolimus.
Design：Case report.
Methods：We described the clinical data of 2 children with immunodeficiency treated with SRL for 6 months, analyzed the causes of abnormal drug concentration in children, and reviewed the literature.
Main outcome measures：Whole blood trough concentration (Cmin) reached the target range of 510 ng·mL-1.
Results：For child A, the drug interaction between SRL and voriconazole and CYP3A5 rs776746C/C genotype were the reasons for the slow drug metabolism and abnormal increase of Cmin. The dose decreased to 20% of the initial dose and gradually returned to the standard range. For child B, CYP3A5 rs776746 C/C genotype and ABCB1 gene rs1045642 T /T genotype were the reasons for the decrease of drug clearance rate and the abnormal increase of Cmin. After reducing the initial dose to 50%, the serum concentration of SRL gradually decreased to normal, and the treatment concentration was within the standard range.
Conclusion：Systematic method will help to determine the cause of Cmin abnormal value of SRL. The sample factors, clinical factors and genetic factors should be considered before adjusting the treatment plan, and the comprehensive treatment management (CMM) of SRL should be optimized.
