Background The collective living environment during the preschool period is associated with a high incidence of acute upper respiratory tract infections (AURTIs).
Objective To explore the effectiveness of physiological saline nasal irrigation (seawater) in preventing AURTIs in healthy preschool children entering childcare centers, providing a theoretical basis for improving hygiene and healthcare in childcare institutions.
Design Singlecenter randomized controlled trial (RCT).
Methods Healthy children in the middle class of kindergartens were selected as the study subjects, and cluster random sampling was conducted at the class level. The study was not blinded. The intervention group received nasal care with seawater nasal irrigation at room temperature, with one spray before entering and leaving the kindergarten each day, for a semester of kindergarten attendance (192 times over 96 days). The operation was performed according to the recommended methods in the Expert Consensus on Nasal Saline Irrigation in Children with Upper Respiratory Tract Infections (2023). The control group received organized interventions when entering and leaving the kindergarten each day. The kindergarten healthcare doctors recorded nasal irrigation twice daily and adverse reactions. Interrupted nasal irrigation time, the first report of AURTIs, onset time of nasal symptoms, relief time, disappearance time, and withdrawal time were also recorded. Those meeting the following criteria were excluded: children in the intervention group with nasal irrigation interruption ≥1 week (including Saturdays and Sundays); children with absenteeism exceeding 20% of the school days during the study period (19 days); children who withdrew from the study halfway (e.g., transferring schools); children who used antibiotics, antiviral drugs, or antichlamydial infection drugs based on medical records during the study period; children whose first occurrence of AURTI or nasal symptoms was not reported to the kindergarten within 24 hours according to the CRF table.
Main outcome measures Incidence of AURTIs (the number of children who developed AURTI within 48 hours of enrollment divided by the number of enrollees).
Results A total of 234 children in the middle class of kindergartens who met the inclusion and exclusion criteria were included in the analysis, with 120 in the intervention group and 114 in the control group. There were no statistically significant differences in gender, age, weight, and actual days in kindergarten between the two groups of children. The incidence of AURTIs during the study period ［55 (45.8%) vs. 81 (71.0%)］and the average number of AURTIs ［(0.7±1.0) vs. (1.4±1.3)］ in the intervention group were significantly lower than those in the control group (P<0.05). There were no statistically significant differences in the incidence of AURTIs between boys and girls in the intervention group. It is the same with the control group. However, there were statistically significant differences in the incidence of AURTIs between two groups in both boys and girls. The intervention group showed statistically significant differences in the relief time ［(2.3±1.0 days) vs. (2.8±0.9 days)］ and disappearance time ［(5.4±1.1 days) vs. (5.8±1.0 days)］ of nasal symptoms compared to the control group. Three cases of mild nasal bleeding occurred in the intervention group, but nasal irrigation intervention continued because of the children's tolerance, and no nasal irritation or ear pain was found.
Conclusion Physiological seawater nasal irrigation can reduce the incidence and frequency of AURTIs in healthy preschool children entering childcare centers. It can also effectively relieve nasal symptoms associated with AURTIs and shorten the duration of symptoms. The clinical operation is simple and convenient with few adverse reactions.
Background Despite that numerous researches have investigated the pathogenesis of Kawasaki disease (KD), including epidemiology, genetics, infection, immunity, and inflammation. However, the causes of KD is still not well underlined.
Objective We analyzed the blood samples of KD patients and control cases using modified highthroughput metagenomics sequencing to identify the bacterial and viral composition and relative abundances, aiming to demonstrate the potential pathogenic virus of KD.
Design Casecontrol study.
Methods We collected the blood samples from KD patients and controls, then purification, extraction and sequencing of viruslike particles had been completed. After quality control of raw data, macrogenome was assembled by MEGAHIT software and species annotating was performed on kraken2. Obtaining relative abundance of each sample at different taxonomic levels (phylum, order, family, genus, and species), we normalized taxon abundance with the online tool Wekemo Bioincloud. The top 20 taxa were displayed and analyzed comparatively using linear discriminant analysis. LDA>2 was set as the criteria of significant differences in abundance between groups for filtering potential pathogenic species.
Main outcome measures Relative abundance of each sample at different taxonomic levels (phylum, order, family, genus, and species).
Results We found that there was little difference between KDs and the controls in terms of overall microorganism. Only phylum Cossaviricota and species Bacillussp Y1 were significantly different. However, there was a great significant difference between viral population annotations. The relative abundances of Uroviricota, Nucleocytoviricota, and Taleaviricota were significantly higher in controls compared with KD patients. Various genera, such as Orthohepadnavirus, Pegunavirus, Montyvirus, Orthonairovirus, Toursvirus, showed significantly higher relative abundance in KDs. In KD patients, the relative abundance of Woodchuckhepatitis virus, Propionibacterium virus (PHL112N00, ATCC29399BT, Pirate, and P105), Diadromus pulchellus toursvirus, and so on were significantly more abundant than that in controls.
Conclusion Summarily, we screened out several candidates KD pathogenic viruses, like WHV, Orthonairovirus, and DpTV1. These viruses may be responsible for acute febrile illness or liver damage in KD patients, or they may be able to disrupt patients' immune systems, but further investigations are required.
Background The number of pediatric patients undergoing prolonged mechanical ventilation (PMV) in pediatric intensive care units (PICUs) has been rapidly increasing, but the factors influencing mortality among these patients remain unclear.
Objective To analyze the factors affecting mortality in pediatric patients receiving PMV in PICUs.
Design Retrospective cohort study.
Methods This study included consecutive cases of invasive mechanical ventilation for ≥14 days with ≥6 hours of ventilation per day at the PICU of the Children's Hospital of Chongqing Medical University from October 1, 2020, to June 30, 2021. Patients were followed for one month after discharge with survival and mortality as outcomes. Data were collected at PICU admission, during PICU treatment, and at discharge. Cox regression analysis was used to explore factors influencing mortality.
Main outcome measures Factors influencing mortality in children undergoing PMV.
Results During the study period, 1 815 patients were admitted to the PICU with 1 144 requiring mechanical ventilation. One hundred and twenty-seven patients met the inclusion criteria for PMV, among which 99 survived and 28 (22.0%) died during the first month of discharge. A multivariable Cox proportional hazards model was constructed using 10 variables from information at PICU admission, during treatment, and at discharge. The results showed that for risk of death during the first month of discharge, a PELOD-2 score ≥4 during the course was associated with a 2.9-fold increased risk (HR=2.893, 95% CI: 1.182-7.079), blood transfusion therapy with a 2.8-fold increased risk (HR=2.766, 95% CI: 1.012-7.558), blood purification therapy with a 3-fold increased risk (HR=2.978, 95% CI: 1.108-8006), and mechanical ventilation duration ≥30 days with a 3.1-fold increased risk (HR=3.062, 95% CI: 1.282-7.312), while hospital stay length≥35 days was associated with an 89% reduction in the risk of death (HR=0.112, 95% CI: 0.037-7.312).
Conclusion The mortality rate among children receiving PMV in the PICU was 22%. Factors such as a PELOD-2 score ≥4, blood transfusion, blood purification therapy, and mechanical ventilation duration ≥30 days were associated with approximately a threefold increase in the risk of death during the first month after discharge, while hospital stay length ≥35 days was associated with a decreased risk of death.
Background Trends in growth and development of children and adolescents are considered to be a " biological standard of living conditions", reflecting the combined effects of genetic trajectories, environmental factors centered on nutrition and disease, and socio-economic circumstances. Objective The aim of this study was to construct a non-invasive equation for the prediction of maturity offsets and to assess the level of physiological maturity of individuals through a longitudinal study. Design Mixed longitudinal study. Methods From the 2015-2021 cohort of the Child and Adolescent Growth and Development Longitudinal Study, children and adolescents with four or more monitoring records who could accurately calculate the age of peak height velocity (aPHV) were selected for the prediction of maturity offsets using the lasso method. After supplementing the data in 2022-2023, children and adolescents were selected based on the same selection criteria, and the equations were validated. All statistics were performed in R and GraphPad software. Main outcome Maturity offset equations. Results Male equation = -15.553 + 0.705 × age + 0.067 × sitting height + 0.063 × BMI, with a SEE of 0.625; female equation = -14.240 + 0.668 × age + 0.084 × sitting height + 0.002 × quetelet index, with a SEE of 0.542. These equations were more suitable for the current cohort of children and adolescents in Shanghai. Conclusion At the present period, children and adolescents still maintain the long-term trend of growth characterized by the advancement of the pubertal spurt. It is necessary to seize this strong momentum to give full expression to the growth potential and to promote the healthy development of the population. Maturity offset equations applicable to the current population could be adopted for the evaluation of individual physiological maturity, in order to achieve fair competition and early screening of sports talents during training and competition, and to promote the long-term development of youth sports literacy and ability level.
Background It is of great significance to predict the mortality of children with severe infection scientifically and effectively. In the past, the relationship between illness and death in critically ill children was mostly predicted by scores with poor accuracy like the Pancreatitis Complications and Severity Index.
Objective To explore the sensitive indicators for the early warning of the death in children with severe infection by machine learning combined with feature screening.
Design Cohort study.
Methods We conducted the cohort study based on the pediatric Multi-center Infectious Diseases Collaboration Network database of 54 PICUs in 20 provincial administrative regions of China. In total, 122 clinical features of 11 clinical dimensions were collected from children aged > 28 days after birth to 18 years, with confirmed infection and at least one organ dysfunction. A risk prediction model for mortality in critically ill children with infections was established by constructing logistic regression models (LR), random forest models (RF), extreme gradient boosting tree models (XGB), and backpropagation neural network models (BP) through machine learning techniques and screening important clinical features.
Main outcome measures AUROC and the performance of the model in screening clinical characteristics.
Results From April 1, 2022 to December 31, 2023, there were 1 738 cases of severe infection with complete records at PICU admission, at PICU 24h stay and at discharge from PICU, of whom 1 396 patients survived or improved, and 342(19.6%) died or deteriorated. After data preprocessing by outlier processing, missing value filling, mandatory value interval range testing, normalization processing, 1 738 pieces of information were entered into machine learning to build the model. According to the ration of 4∶1, 1 390 patients were enrolled in training sets and 348 were in validation sets. In training sets, 1 116 patients survived (or cured) and 274 died (or worsened), and in validation sets, 280 patients survived (or cured), and 68 died (or worsened). In training sets, a total of 122 clinical features were input. After machine learning and feature screening, the range of AUROC of LR, RF and XGB was 0.74-0.78 in validation sets after 50 rounds of 5-fold stratified cross-validation. Features with greater importance than the mean value were selected to construct the optimal clinical features in LR, RF, and XGB models. At present, there is no good method to measure the importance of BP characteristics. Clinical features constructed by the LR model were closer to clinical expectations than by RF and XGB.
Conclusion Machine learning is less than perfect in predicting death of severe infectious diseases in children, and the clinical futures screened by predictive model are still far from clinical expectations.
Background Foreign studies have reported that tubulointerstitial nephritis-uveitis (TINU) syndrome accounts for a relatively high proportion of acute interstitial nephritis (AIN) in children, but some children have atypical clinical manifestations and are likely to be misdiagnosed. At present, the proportion and prognosis of TINU syndrome in children with AIN are not clear in China.
Objective To analyze the clinical and pathological characteristics of TINU syndrome in AIN children.
Design Retrospective cohort study.
Methods The clinical and pathological manifestations in AIN children confirmed by renal biopsy in our hospital from January 2012 to December 2022 were retrospectively collected and analyzed. According to the final diagnosis at the last follow-up, the patients were divided into the TINU syndrome group and the non-TINU syndrome group. The age of onset, sex, past history, history of prodromal infection, medication history, clinical manifestations at onset and return visit, ophthalmic consultation results, laboratory examination results at the first visit, pathological data of kidney biopsy, and treatment and follow-up were intercepted.
Main outcome measures Kidney and ocular manifestations as well as the associated treatment and prognosis in children with TINU.
Results Twenty-one AIN children were included in this study, accounting for 16% of AIN children confirmed by renal biopsy. There were ten cases (48%) in the TINU syndrome group and 11 cases in the non-TINU syndrome group including 2 for Sjogren syndrome, 1 for drug induction, 1 for sarcoidosis, and 7 for unclear reasons. Among the TINU children, uveitis was diagnosed before or simultaneously with renal biopsy in 5 cases , and 1 to 12 months after renal biopsy in the other 5 cases with binocular involvement. There were 4 cases of anterior uveitis and 6 cases of panuveitis. One child with sarcoidosis in the non-TINU group was diagnosed with uveitis at the beginning. Among the 10 children with TINU, 5 cases were males and the others were female with the onset age of 8 to 15 years old, among which 3 had a history of precursor infection, 4 had a history of medication treatment with weight loss or poor appetite at admission, 4 had fever, 2 had joint pain, 2 had conjunctival congestion, pain and tears, 4 had foam urine, 6 had increased urine volume or new nocturia, and 2 had increased blood pressure. After systemic and ocular application of corticosteroids, the renal manifestations of 10 TINU cases improved or disappeared, and 6 cases of uveitis improved. As the symptoms of uveitis did not improve, one case received corticosteroid eye drops and three cases combined with other immunosuppressive therapy. At a follow-up of 11 (4,21) months, two had repeated AIN symptoms of after prednisone withdrawal or reduction, and improved after reveiving glucocorticoids and immunosuppressive agents again; two had ocular complications (one for secondary glaucoma in both eyes with bilateral visual field defects, the other one for cataract), and three still had uveitis. Compared with children with AIN caused by TINU and non-TINU, there were no statistically significant differences in demographic data, age of onset, history of prodromal infection, medication history, the proportion of children with ocular symptoms at first diagnosis, other clinical symptoms, laboratory indicators, renal pathological manifestations, and the proportion of renal recurrence.
Conclusion Besides specific ocular lesions, AIN by TINU syndrome exhibits similar clinical manifestations, laboratory findings, and pathological changes to AIN by non-TINU syndrome. The clinical symptoms of uveitis are often subtle and may appear several months after renal symptoms. Ophthalmic history data of all pediatric AIN patients should be collected, and these patients should undergo systematic ophthalmic examination and receive regular follow-up visits from ophthalmologists.
Background Rare cases of immunodeficiency disease-related vaccine-derived poliomyelitis (iVAPP) have been reported in China.
Objective To analyze the clinical features, immunodeficiency phenotype, treatment as well as prognosis among different iVAPP patients.
Design Case series report.
Methods Retrospective analysis was performed for the clinical data of 4 children with iVAPP admitted to Department of Clinical Immunology at Children's Hospital of Fudan University from May 2018 to June 2023. The intercepted information from medical records included poliovirus (PV) vaccination, clinical manifestations, immune-related indicators, etiological test results, treatment, outcome and muscle strength recovery.
Main outcome measures Clinical manifestations and immunology-related indicators.
Results All 4 patients with iVAPP were boys. Their paralysis symptoms were presented at 4-7 months after taking OPV, and the first dose was received at 3 months of age. Case 1, 2, 4 received 1, 2, and 3 doses of OPV respectively, and case 3 received 2 doses of OPV and 1 dose of IPV. Two cases of combined immunodeficiency-related vaccine-derived polio (CID-VAPP) were admitted to the hospital due to lung infection and axillary lymph node inflammation with severely reduced counts of T and B cells. Their paralysis of multiple limbs and muscle weakness of multiple limbs could not be relieved by active treatment. The infections involved multiple sites and were caused by various pathogens. Mycobacterium tuberculosis complex and severe pneumonia were found. Deaths occurred within the first year of life due to severe infections. The other 2 cases were primary antibody deficiency disease (PAD)-VAPP, who were admitted to the hospital at the age of 12 months and 9 months respectively due to limb disability, showing a decrease in the number of B cells as well as impaired antibody secretion. The symptoms of limb paralysis involved one or more sides of the body, and the muscle strength could return to normal after treatment, with mild infection symptoms and a good prognosis.
Conclusion Intaking OPV may lead to iVAPP in both CID and PAD children, and the prognosis mainly depends on the primary disease.
Background：The clinical manifestations of children with cerebral palsy are diverse, and there are few studies analyzing the characteristics of children with cerebral palsy of different genders with large sample data in China.
Objective：To explore the gender differences in clinical data of children with cerebral palsy.
Design：Case series report.
Methods：General information, perinatal risk factors, and clinical features of children with cerebral palsy who were hospitalized in the Third Affiliated Hospital of Zhengzhou University from January 2019 to February 2022 were retrospectively collected.
Main outcome measures：Gender differences in clinical features of children with cerebral palsy.
Results：A total of 486 children with cerebral palsy were included, including 323 males and 163 females. The proportion of cesarean section, premature infants and macrosomia in males was significantly higher than that in females, while the proportion of normal birth weight children was significantly lower than that in females. In the comparison of birth seasons between groups, the proportion of males born in spring was significantly lower than that of females, while the proportion of winter births was significantly higher than that of females. The proportion of pregnancy complication, asphyxia, cerebral hemorrhage, hypoxic-ischemic encephalopathy and hypoglycemia in males was significantly higher than that in females. The proportion of grade IV and V in the Gross Motor Function Classification System was significantly higher than that in females, and the proportion of abnormal white matter in MRI classification was significantly higher than that in female children. Differences were statistically significant across all comparisons.
Conclusion：There are gender differences in some clinical data of children with cerebral palsy. Most of the children with cerebral palsy are males and the severity is more serious than that of females.
Background：6-mercaptopurine (6-MP) is one of the main drugs used in the maintenance therapy of acute lymphoblastic leukemia (ALL), and its metabolism enzyme gene polymorphism is associated with the degree of bone marrow suppression caused by the drug.
Objective：To investigate the relationship between the dose of 6-MP use and TPMT and NUDT15 gene polymorphisms during maintenance therapy in children with ALL.
Design：Retrospective cohort study.
Methods：Children with a clear diagnosis of ALL at the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were included, who achieved complete remission after prior chemotherapy and entered the maintenance therapy stage with oral 6-mercaptopurine (6-MP) treatment. Before starting oral 6-MP, genetic testing for TPMT and NUDT15 genotypes was conducted to analyze the dosage and bone marrow suppression of 6-MP treatment in children with different TPMT and NUDT15 genotypes.
Main outcome measures：6-MP dosage.
Results：This study analyzed 61 pediatric ALL patients undergoing maintenance therapy. Among them, 48 patients were included in the statistical analysis of TPMT gene polymorphism (excluding 13 cases with NUDT15 gene mutations), with 45 wild-type cases and 3 mutant cases. Additionally, 58 patients were included in the statistical analysis of NUDT15 gene polymorphism (excluding 3 cases with TPMT gene mutations), with 45 CC genotype cases, 9 CT genotype cases, and 4 TT genotype cases. During the maintenance therapy with 6-MP, significant differences in WBC, Hb, and PLT counts were observed among patients with different TPMT and NUDT15 genotypes (all P< 0.05). Patients experienced varying degrees of neutropenia after medication, including 15 cases with wild-type TPMT and 3 mutant TPMT cases, as well as 15 CC genotype cases, 5 CT genotype cases, and 4 TT genotype cases of NUDT15 gene. The differences in bone marrow suppression among patients with different TPMT and NUDT15 genotypes were statistically significant (all P< 0.05). Furthermore, there were significant differences in the dosage of 6-MP among patients with different TPMT and NUDT15 genotypes (all P< 0.05). Specifically, the maintenance therapy dosage of 6-MP for patients with wild-type TPMT and mutant TPMT was (40.81 ± 6.02) and (16.25 ± 4.42) mg·m-2·d-1, respectively. For patients with CC genotype, CT genotype, and TT genotype of the NUDT15 gene, the 6-MP dosage was (40.81 ± 6.02), (34.28 ± 4.53), and (10.00 ± 1.28) mg·m-2·d-1, respectively.
Conclusion：Patients with mutations in the TPMT and NUDT15 genes experience more severe bone marrow suppression compared to those with the wild-type genotype. The dosage of 6-MP used during maintenance therapy in pediatric ALL patients is associated with TPMT and NUDT15 gene polymorphisms.
Background：PTEN gene mutation can lead to a variety of syndrome phenotypes. At present, there are many studies on the phenotypic spectrum in adults, but few studies in children.
Objective：To summarize the genotypes and clinical phenotypes of children with PTEN gene mutation and their correlation.
Design：Case series report.
Methods：Children with PTEN gene mutations, rated as being pathogenic or possibly pathogenic, discovered by high-throughput sequencing in the Molecular Medicine Center of the Children's Hospital of Fudan University from January 1, 2016 to January 31, 2023 were included. Their clinical data and gene testing results were intercepted.
Main outcome measures：Clinical manifestations and PTEN gene mutations.
Results：A total of 51 children with confirmed PTEN gene pathogenic mutations were included, including 33 males. The median age at the time of gene testing was 2 years (1d-13 years), and the median follow-up age was 5.2 years (3.6-6.5 years). The main complaints were developmental delay or communication disorder (24 cases in total, 47.0%). Forty-one pathogenic or suspected pathogenic variants were detected in the PTEN gene, including 28 missense mutations (68.3%), 5 nonsense mutations, 4 frameshift mutations, 3 classical splice site mutations, and 1 initiation codon mutation. Twenty-eight variants were located in the phosphatase domain (68.3%), 11 in the C2 domain (24.4%), and 1 in each of the PIP2 binding motif (PBD) and C-tail domains. c.388C>T(p.R130X) (5 cases) and c.302T>C(p.I101T) (3 cases) were hotspot mutation sites. Twelve mutation sites had not been previously reported. Mutation sources were verified in 22 children, of which 17 (77.3%) were de novo mutations. Macrocephaly was identified in 48 cases (94.1%). Forty-two cases (82.3%) were diagnosed with neurodevelopmental disorders, including language development delay in 36 cases (70%), large motor development delay in 25 cases (49.0%), fine motor development delay in 2 cases, poor balance in 3 cases, ASD in 14 cases (27.4%), intellectual disability in 13 cases (25.5%), attention deficit and hyperactivity disorder in 1 case, learning difficulty in 1 case, and epilepsy in 3 cases (5.8%). Tumor diseases were detected in 11 children (21.6%), with a median age of 4.0(1.0-5.0) years at the time of detection. Eight cases (15.7%) showed skin manifestations including penile freckles, café au lait spots, nevi, and hair follicle keratosis. Thirty-nine patients underwent cranial MRI, and 35 (89.7%) showed abnormalities, mainly including widened perivascular spaces (18 cases), white matter abnormalities (6 cases), and enlarged ventricles (4 cases). There was no significant difference in clinical phenotype, mutation type, and domain distribution of mutation sites.
Conclusion：Children with PTEN gene mutations mainly present with macrocephaly with neurodevelopmental disorders such as developmental delay, intellectual disability, and autism spectrum disorder, and may have tumorigenesis, dermatological manifestations, and abnormal cranial MRI findings.
