Background: Repetitive transcranial magnetic stimulation (rTMS) combined with antidepressants has emerged as a novel therapy for treating depression in children and adolescents. However, predicting early treatment efficacy remains a significant challenge.
Objective: To explore potential factors that could predict long-term efficacy during rTMS combined with antidepressant therapy.
Design: Retrospective cohort study.
Methods: The cohort included children and adolescents under 18 years of age who were newly diagnosed with moderate to severe unipolar or bipolar depression, received rTMS treatment continuously for at least 20 sessions during hospitalization, had daily symptom index (DI-5) scores recorded, and had Hamilton Depression Rating Scale (HAMD) scores recorded before and after the 20th rTMS session. Participants were divided into response and non-response groups based on whether their final HAMD score showed a reduction of ≥50% from baseline. Correlation analysis was conducted between DI-5 and HAMD scores. If a strong correlation was found, the potential of DI-5 assessments during rTMS treatment to predict early response was evaluated.
Main outcome measures: Correlation between DI-5 and HAMD scores.
Results: A total of 228 children and adolescents with moderate to severe unipolar or bipolar depression met the inclusion and exclusion criteria. The mean age was 14.0 ± 3.0 years, and 111 (48.6%) were male. The Pearson correlation coefficients between DI-5 and HAMD scores before and after rTMS treatment were 0.70 and 0.72, respectively, with both being statistically significant (P< 0.001). After 20 rTMS sessions, there were 101 participants in the response group and 127 in the non-response group. There were no statistically significant differences between the two groups in gender distribution, age, single-parent household proportion, left-behind children proportion, family psychiatric history, age of symptom onset, symptom duration, learning disabilities, language disorders, motor development disorders, weight, height, medication duration, counseling sessions, thyroid dysfunction, time to fall asleep, frequency of dreaming, and picky eating habits (P>0.05). Baseline DI-5 and HAMD scores also showed no statistically significant differences between the response and non-response groups (P>0.05). However, DI-5 scores after the 20th rTMS session were significantly different between the response and non-response groups (P<0.001), as were the final HAMD scores (P<0.001). On the 11th session, the DI-5 scores showed a statistically significant difference between the response and non-response groups (P<0.001). A median reduction of 2 points in DI-5 scores was used as a stratification basis. In the group with a reduction of <2 points on the DI-5 scale, 107 participants (46.9%) had a 98.1% probability of being in the non-response group by the 20th rTMS session. In the group with a reduction of ≥2 points, 64 participants (87.4%) had an 89.2% probability of being in the response group by the 20th rTMS session.
Conclusion: A reduction of ≥2 points on the DI-5 scale by the 11th rTMS session may serve as an early predictor of treatment efficacy for rTMS combined with antidepressants in children and adolescents with depression.
Background: Minimal residual disease (MRD) is used to monitor and assess the treatment response in pediatric acute lymphoblastic leukemia (ALL) and to stratify risk based on MRD levels.
Objective: To investigate the prognostic value of regularly monitoring MRD during and after chemotherapy in predicting relapse in children with ALL.
Design: Retrospective cohort study
Methods: The clinical data of 224 ALL children received CCCG-ALL2015 chemotherapy from January 2015 to February 2020 were retrospectively included in our study. MRD was detected using flow cytometry to analyze the association between regular monitoring of MRD and prediction of recurrence.
Main outcome measures: Recurrence free survival (RFS)
Results: A total of 224 children were included in this analysis, with 134 males and 90 females, and a median age of 4.8 years. On day 19 (D19) of induction remission, 104 cases (46.4%) were MRD-positive, and on day 46 (D46), 23 cases (10.3%) were MRD-positive. From post-induction remission (week 16) to the end of chemotherapy (week 125), 145 cases remained MRD-negative. During follow-up after the end of chemotherapy (weeks 152-287), 13 cases became MRD-positive, of which 11 (84.6%) relapsed. A total of 28 children relapsed, with a median relapse time of 33 months. Among them, 14 survived, 12 died, and 2 were lost to follow-up. There were 20 cases of bone marrow relapse, including 2 with concurrent testicular relapse and 1 with CNSL and 8 with CNSL alone. The median follow-up time for the 224 children was 52 months (IQR: 36.5-69.5 months), and the 5-year RFS was (84.5±2.8)%. There were statistically significant differences in the 5-year RFS between children with D46 MRD ≥0.01% and <0.01%, as well as between those who remained MRD-negative throughout chemotherapy and those who were MRD-positive at least once (P<0.05).
Conclusion: Children with D46 MRD ≥0.01% and those who were MRD-positive at least once during chemotherapy had a poorer prognosis. Regular MRD monitoring during chemotherapy is crucial.
Objective: To investigate the association between body composition and blood pressure in children.
Design: Systematic review/Meta-analysis.
Methods: We conducted computer searches in four Chinese databases (CNKI, Wanfang Data, VIP and CBM), as well as four international databases (PubMed, Web of Science, and EBSCO) from inception to August 8, 2023. We included longitudinal cohort studies examining the relationship between body composition and childhood blood pressure. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. We summarized the results quantitatively and qualitatively.
Main outcome measures: Association between body composition and childhood hypertension.
Results: A total of 9 longitudinal cohort studies were included, investigating the longitudinal relationship between body composition and systolic and diastolic blood pressure in children. Seven of these studies reported the association of fat mass-related indicators with blood pressure in children, showing a positive correlation between childhood fat mass percentage and blood pressure. However, conclusions regarding other fat mass indicators were inconsistent. Two studies reported on the relationship between non-fat mass and childhood blood pressure with inconsistent findings. Three studies reported a positive correlation between fat mass and the occurrence of high systolic and diastolic blood pressure in childhood, although the risk of hypertension may be negatively correlated with neonatal fat mass.
Conclusion: The percentage of body fat in children is positively correlated with both diastolic and systolic blood pressure. Body composition has a significant impact on blood pressure in children.
Background：Adolescents with congenital heart disease (CHD) face physical and psychological challenges during their growth. Self-empowerment is an important indicator of their self-management ability and quality of life. Currently, there is a lack of relevant assessment tools in China.
Objective：To translate the Gothenburg Young Persons Empowerment Scale-Congenital Heart Disease (GYPES-CHD) into Chinese and test its reliability and validity.
Design：Reliability and validity analysis.
Methods:The Brislin translation model was used to translate the scale through forward translation, back translation, and back-translation comparison. A purposive sampling method was used to select 15 CHD adolescents of different ages and educational levels for cognitive interviews. a purposive sampling method was used to select 15 CHD adolescents of different ages and educational levels for cognitive interviews. Adolescents with congenital heart disease (CHD) aged between 10 to 18 years, who were diagnosed at our hospital, had long-term follow-up, possessed certain reading and writing abilities, and were able to understand the questionnaire, were included. Adolescents with comorbidities affecting intellectual development, other systemic diseases requiring multiple surgeries, or conditions leading to mental disorders were excluded. Participants completed a general information survey, the Chinese version of the GYPES-CHD, and the General Self-Efficacy Scale (GSES).
Participants completed a general information survey, the Chinese version of the GYPES-CHD, and the General Self-Efficacy Scale (GSES).
Main outcome measures：Reliability and validity of the Chinese version of GYPES-CHD.
Results：A total of 166 questionnaires were distributed, and 153 were returned (response rate of 92.16%) to be included in the analysis.The Chinese version of GYPES-CHD consists of 5 dimensions and 15 items. Item analysis showed that the Pearson correlation coefficients between the scores of each item, dimension and the total score of the Chinese version of GYPES-CHD ranged from 0.210 to 0.538 (P<0.001). The critical ratio (CR) for the 15 items was between 4.218 and 12.358 (P<0.001). The Cronbach's α coefficient of the Chinese version of GYPES-CHD was 0.905, and the Cronbach's α coefficients for the five dimensions ranged from 0.740 to 0.851. The test-retest reliability was 0.869, and the Cronbach's α coefficients for the five dimensions were between 0.783 and 0.837, with a correlation coefficient of 0.841 between the total scores of the two administrations. The content validity index at the scale level and item level were 0.906 and 0.947, respectively. The correlation coefficient between the total GSES score and the total score of the Chinese version of GYPES-CHD was 0.52 (P<0.01), and the criterion-related validity with the five dimensions ranged from 0.375 to 0.495 (P<0.01).
Conclusion：The Chinese version of GYPES-CHD has good reliability and validity and can be used to assess the empowerment level of CHD adolescents in the context of Chinese culture.
Background: The traditional treatment for activated phosphoinositide 3-kinase δ (PI3Kδ) syndrome (APDS) has shown limited efficacy in preventing infections. Recently, rapamycin has been used in the clinical treatment of children with APDS type1 (APDS1) caused by PIK3CD gene mutations.
Objective: To investigate the efficacy and safety of rapamycin in the treatment of APDS1.
Design: Case series report.
Methods: This study included consecutive cases diagnosed with APDS1 via genetic testing and treated with oral rapamycin from June 2017 to June 2023 at the Children's Hospital of Zhejiang University School of Medicine. The use of rapamycin for treating non-tumorous lymphoproliferation due to APDS in children is off-label in China. Before treatment, parents were fully informed of the risks and signed informed consent. The oral dosage of rapamycin was 1 mg·m-2·d-1.
Main outcome measures: The number of pneumonia episodes within 12 months and ultrasound assessment of liver, spleen, and lymph node enlargement.
Results: Among the four children treated with rapamycin for APDS1, three were male and one was female. The average age of onset was 35.5±17.9 months, and the average age at diagnosis was 56.5±35.0 months. Whole-exome sequencing revealed a de novo heterozygous mutation in the PIK3CD gene (c.3061G>A, p.E1021K) in all cases. All presented with recurrent coughing and had hepatosplenomegaly and lymphadenopathy. All had pneumonia. There were 2 cases of recurrent mumps, 2 cases of growth retardation, and one case each of atopic dermatitis, inflammatory bowel disease, and Wegener's granulomatosis. Bronchoscopy showed cobblestone-like bulge in the bronchial mucosa in three cases. All had reduced CD19+ B cells and inverted CD4+/CD8+ ratios; three had elevated IgM levels, and one had decreased IgG. Prior to rapamycin, all received IVIG, anti-infective treatment and corticosteroids, yet continued to suffer from recurrent respiratory infections and hepatosplenomegaly. Additionally, three developed thrombocytopenia and two had anemia. Rapamycin was administered orally to all children from 1 to 44 months after diagnosis for 12 to 58 months. Following 12 months of rapamycin treatment, the average annual number of pneumonia episodes decreased from 5.3 to 1.0. There was significant improvement in hepatosplenomegaly and superficial lymphadenopathy, and Hb and PLT levels returned to normal. However, there were no statistically significant differences in immunological parameters before and after treatment. No rapamycin-related adverse effects, tumors, or deaths were observed during follow-up.
Conclusion: Rapamycin is relatively safe and has some efficacy in treating APDS1.
Background: Some critically ill children with influenza A virus (IAV) infection may have severe sequelae or even die, but its early clinical manifestations are non-specific. At present, there is a lack of relevant prediction models at home and abroad.
Objective: To establish a nomogram prediction model for critical IAV infection in children to help early clinical identification of critical IAV infection.
Design: Case-control study.
Methods: Consecutive patients with IAV infection who were hospitalized in Children's Hospital Affiliated to Zhengzhou University from January 2018 to November 2023 were enrolled. According to the discharge diagnosis and clinical data, they were divided into critically ill children and non-critically ill children. The demographic data, symptoms on admission, laboratory tests on admission, and co-infection with other pathogens were collected. According to the incidence of IAV in Henan Province, the samle size should be greater than 320 cases. The enrolled children were randomly divided into a modeling group and a validation group at a ratio of 7∶3. The influencing factors of critical IAV infection were screened in the modeling group, and the R 4.3.2 software package was used to construct a nomogram prediction model for critical IAV infection.
Main outcome measures: Risk factors for critically ill children with influenza A virus (IAV) infection.
Results: Among 391 hospitalized children with IAV infection, 134 cases were critically ill, of whom 20 cases (14.9%) had sequelae, all of them were nervous system damage, and 12 cases (9.0%) died. All the non-critically ill children were cured and discharged. There were 274 cases in the modeling group and 117 cases in the validation group. There was no significant difference in clinical data between the two groups. Multivariate Logistic regression analysis showed that neurological symptoms (OR=6.923, 95%CI: 2.569-18.656), co-infection with other pathogens (OR=3.092, 95%CI: 1.379-6.934), and elevated NLR (OR=1.404, 95%CI: 1.029-1.914) and increased IL-6 (OR=1.009, 95%CI: 1.000-1.018) are risk factors, and propagated rise (OR=0.925, 95%CI: 0.862-0.992) is a protection factor. Taking critical IAV infection as the prediction outcome, a nomogram prediction model was constructed based on neurological symptoms, combined with other pathogen infections, and laboratory indicators such as NLR, IL-6, and ALB. The AUC of the model was 0.949 (95%CI: 0.915-0.982) in the modeling group and 0.912 (95%CI: 0.871-0.952) in the validation group. The nomogram model fitted well (χ2=5.077，P=0.749), the predicted probability was in good agreement with the actual probability, and had a high net clinical benefit rate.
Conclusion: The nomogram prediction model based on neurological symptoms, infection with other pathogens and laboratory indexes of NLR, IL-6 and ALB is effective and has good discriminative ability.
Background: Historically, infectious diseases have been the primary focus of pediatric gastrointestinal disorders. However, in recent years, the diagnosis rate of genetic metabolic diseases has gradually increased.
Objective: To summarize the clinical phenotypes and genotypes of common genetic metabolic diseases affecting the digestive system.
Design: Case series report.
Methods: This study included children who presented with gastrointestinal symptoms and had abnormal whole-exome sequencing results at a single center between January 1, 2015, and December 31, 2019. Demographic data, clinical information, and genetic testing results were extracted from the medical records system.
Main outcome measures: Clinical phenotypes and genotypes.
Results: Among the 320 children who underwent genetic testing in the gastroenterology department, 111 (34.7%) had abnormal results. The mean age at diagnosis was 2.4±2.8 years, and 68 (61.3%) were male. The main disease phenotypes included hereditary liver diseases in 70 cases (63.1%), with Wilson's disease and glycogen storage diseases each accounting for 15 cases, Citrin deficiency for 13 cases, Alagille syndrome, progressive familial intrahepatic cholestasis (PFIC), and bilirubin metabolism disorders for 9 cases each. Other conditions included very early-onset inflammatory bowel disease (VEO-IBD) in 8 cases (7.2%) and progressive muscular dystrophy in 10 cases (9.1%).Wilson's disease commonly presented as asymptomatic persistent transaminase elevation (53.3%), with the ATP7B gene c.2333G>T (p.R778L) being the most common mutation site (53.3%). Glycogen storage disease patients mainly exhibited hypoglycemia, hepatomegaly, abnormal liver function (93.3% for all), and elevated triglycerides (60.0%). Subtypes included type Ⅸa (6 cases), type Ⅲ (5 cases), and one case each of GSD Ⅰa, GSD Ⅱ, GSD Ⅵ, and GSD ⅩⅤ. Alagille syndrome was associated with abnormal liver function in all 9 cases, and 8 (88.9%) visited the hospital due to yellowish discolouration of the skin and sclera. The JAG1 gene mutation (Alagille syndrome type 1) was found in 8 cases (88.9%), and the NOTCH2 gene mutation (Alagille syndrome type 2) was found in 1 case. Citrin deficiency patients were mostly admitted due to yellowish discolouration of the skin and mucous membrane (92.3%) and exhibited abnormal liver enzymes, cholestasis, and hypoglycemia. All 13 cases had mutations in the SLC25A13 gene, with c.851_854del (38.5%) and c.852_855del (30.8%) being the most common mutations. Progressive familial intrahepatic cholestasis (PFIC) was characterized by hepatomegaly, elevated ALT, AST, and total bile acids in all 9 cases. The subtypes included type 2 (6 cases with ABCB11 gene mutations), type 3 (2 cases with ABCB4 gene mutations), and type 1 (1 case with ATP8B1 gene mutation). Bilirubin metabolism disorders were identified in 9 cases presenting with jaundice and/or abnormal liver function, all of which had UGT1A1 gene mutations. The most common mutation sites were c.211G>A (p.G71R) (66.7%) and A(AT)6TAAinsTA (55.6%). VEO-IBD was primarily characterized by chronic diarrhea in all 8 cases, with elevated WBC counts and CRP levels. Endoscopic findings showed cobblestone-like changes and deep ulcers in the colonic mucosa. Seven cases had IL10-RA gene mutations, with c.301C>T (p.R101W) (62.5%) and c.537G>A (p.T179T) (50%) being the most common, and one case had a heterozygous mutation in the IL10-RB gene.
Conclusion: Genetic testing plays a crucial role in the diagnosis and treatment of genetic metabolic diseases affecting the digestive system in children.
Background: Multisystem inflammatory syndrome in children (MIS-C) is associated with SARS-CoV-2 infection. Most previous studies on MIS-C are case reports or reviews, with refractory MIS-C only documented in individual case reports.
Objective: To explore the differences between refractory MIS-C and non-refractory MIS-C and to enhance understanding of the disease.
Design: Case-control study.
Methods: Consecutive cases of MIS-C from six hospitals in Zhejiang Province were collected. Refractory MIS-C was defined as persistent fever and/or terminal organ involvement after first-line treatment (case group), while the remaining cases were classified as non-refractory MIS-C (control group). The basic information, clinical manifestations, laboratory tests, imaging findings, treatment, and efficacy of the two groups were summarized and analyzed using univariate analysis.
Main outcome measures: Clinical characteristics of MIS-C.
Results: A total of 23 children with MIS-C were included in this analysis, with an average onset age of 4.8±3.4 years. The interval between SARS-CoV-2 infection or exposure and MIS-C diagnosis was 30±9 days. The case group included 4 children (2 males and 2 females), while the control group included 19 children (10 males and 9 females). There were no statistically significant differences between the two groups in terms of basic information, clinical manifestations, or severe complications. In imaging findings, the case group had higher proportions of involvement in ≥2 serous cavities (75% vs . 16%) and pericardial effusion (75% vs . 11%) compared to the control group. In laboratory tests, the case group showed lower platelet (PLT) counts, higher procalcitonin (PCT), and D-dimer levels, as well as elevated levels of IL-6, IL-10, and IFN-γ, all of which were statistically significant. In the control group, 8 cases (42%) were treated with IVIG alone, 4 cases (21%) with corticosteroids alone, and 6 cases (32%) with a combination of IVIG and corticosteroids. In the case group, all 4 children received additional tocilizumab treatment on top of corticosteroids and IVIG. All 23 children improved and were discharged, with no fatalities. One child in the control group experienced severe intracranial hemorrhage and was left with hemiplegia at discharge and during a 6-month follow-up, but was lost to follow-up thereafter. Another child with coronary artery dilation returned to normal after 1 month of post-discharge follow-up.
Conclusion: MIS-C can lead to severe complications such as intracranial hemorrhage, macrophage activation syndrome (MAS), and coronary artery dilation, but generally has a relatively good prognosis. Children with refractory MIS-C exhibit more intense inflammatory responses and more significant multisystem involvement. Tocilizumab is effective in treatment.
