Background：Authoritative clinical practice guidelines and expert consensus have recommended the use of rituximab (RTX) in the treatment of children with frequent relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS) of steroid-sensitive nephrotic syndrome(SSNS). However, there is a discrepancy in terms of clinical indications, treatment, and follow-up protocols.
Objective：To comprehensively examine relapse and steroid therapy during over one year follow-up in patients diagnosed with FRNS/SDNS who were administered the initial course of RTX while being in remission.
Design：Systematic review and meta-analysis.
Methods：Keywords of SSNS, FRNS, SDNS, and RTX were used to search China Biology Medicine Database, PubMed, Embase, Scopus, and Cochrane from the inception to June 26, 2022. The preliminary and full-text screening were conducted by two independent reviewers, who also extracted the relevant data. Unsure or controversial literature underwent a third-party review. At least one RTX intervention for children aged between 1 and 22 years with SSNS was included.
Main outcome measures：The frequency of relapse, time to the first relapse, cumulative steroid dosage, and percentage of patients who withdrew from steroids in those who were followed-up for more than 1 year after receiving RTX intervention.
Results：A total of 26 studies (1 in Chinese and 25 in English) were eligible including 8 randomized controlled trials (RCT), 1 non-randomized study of interventions (NRSI), 8 cohort studies, and 9 case series reports. Two subgroups were defined as FRNS/SDNS+ group in which immunosuppressants were used before RTX intervention and FRNS/SDNS- group in which no other immunosuppressants were used before RTX intervention. Meta-analysis of 9 studies on the relapse rate of FRNS/SDNS during at least 1-year follow-up showed a 78% reduction in the relapse rate of RTX compared to the control group (OR=0.22, 95%CI: 0.09 to 0.53). In FRNS/SDNS+ group， RTX reduced the relapse rate by 67 % compared to the control group (OR=0.33, 95%CI: 0.12 to 0.94). In FRNS/SDNS- group, RTX reduced the relapse rate by 85 % compared to the control group (OR=0.15, 95%CI: 0.03 to 0.68) in the absence of other immunosuppressants. Additionally, the meta-analysis of 20 studies indicated that the relapse rate after RTX was 42% (95% CI: 32 to 53). The meta-analysis of 9 studies on the time to the first relapse of FRNS/SDNS+ during at least 1-year follow-up indicated that the median time to the first relapse was 9.89 months (95%CI: 7.14 to 12.65). According to the meta-analysis of 3 studies on the median relapse free survival (RFS) from the initiation of FRNS/SDNS- to at least 1-year follow-up, RTX (1-2 doses) had a longer median RFS of 20 days compared to the control, with a median survival ratio (MSR) of 0.69 (95%CI: 0.52 to 0.87). The meta-analysis of four studies on the reduction of FRNS/SDNS cumulative steroid dose over a 1-year period found that RTX produced a significant decrease compared to the control group with a statistically significant difference (SMD=-1.12, 95%CI: -1.49 to -0.74). According to the meta-analysis of two studies on FRNS/SDNS steroid withdrawal rate within a three-month follow-up, the rate of RTX was 14.6 times higher compared to the control group (CNI or CTX) (OR=14.62, 95% CI: 5.43 to 39.39). The meta-analysis of three studies on the steroid withdrawal rate of FRNS/SDNS+ during a six-month follow-up after RTX showed a withdrawal rate of 68% (95% CI: 56 to 79).
Conclusions：Compared with controls, RTX showed limited benefits in terms of relapse rate and first relapse time from the initiation of treatment to 1-year follow-up, and it could provide benefits in steroid reduction rather than steroid withdrawal. Addition of RTX in FRNS/SDNS patients, as compared with placebo or blank control, can reduce the 1-year follow-up relapse rate by at least 88%. The overall relapse rate for FRNS/SDNS patients who received RTX treatment at the 1-year follow-up was 43%. The addition of RTX treatment for FRNS/SDNS can provide 10 months of relapse-free survival time.
Background：Over the past 20 years, rituximab (RTX) has shown better efficacy than other immunosuppressants in the treatment of children with steroid-sensitive nephrotic syndrome (SSNS), but reports of adverse events still need to be accumulated.
Objective：To understand the adverse events of rituximab for children with SSNS.
Design：Systematic review and meta-analysis.
Methods：PubMed, Embase, Cochrane, Scopus and Chinese Biology Medicine databases were searched from the inception to June 26, 2022, with the keywords of SSNS and RTX. The preliminary screening, full text screening and data extraction were all completed by the same two reviewers. Unsure or controversial literature was submitted to a third reviewer. At least one RTX intervention for children aged between 1 and 22 years with SSNS was included.
Main outcome measures：The incidences of adverse events.
Results：A total of 47 studies (5 in Chinese and 42 in English) were included in the analysis, including 7 doublearm intervention studies (5 randomized controlled trials, 2 nonrandomized study) and 40 case series reports. Comparing RTX with placebo or conventional immunosuppressants (control group) in SSNS children, there were no statistically significant differences in the incidences of adverse events (7 studies, 130/184 vs 107/177), serious adverse events (4 studies, 14/140 vs 9/122), infusion reaction (1 study, 19/24 vs 13/24) and infection (2 studies, 33/56 vs 23/38). In case series reports of SSNS children treated with RTX, the incidences of adverse events, serious adverse events, infusion reaction, infection and serum sickness were 59 percent (95%CI: 55 percent to 63percent), 7 percent (95%CI: 6 percent to 9 percent),31 percent (95%CI: 28 percent to 35 percent), 21 percent (95%CI: 18 percent to 24 percent) and 5 percent (95%CI: 2 percent to 10 percent), respectively. Studies reporting both neutropenia and agranulocytosis revealed the incidence of neutropenia was 9 percent (95%CI: 5 percent to 17 percent) and the incidence of agranulocytosis was 4 percent (95%CI: 2 percent to 10 percent). Studies focusing on hypogammaglobulinemia revealed the incidence of hypogammaglobulinemia was 51 percent (95%CI: 42 percent to 60 percent).
Conclusions：RTX treatment of SSNS did not increase the incidences of adverse events, serious adverse events and infection, but hypogammaglobulinemia and serum sickness should be of concern.
Background：The use of dezocine, a new opioid agonistantagonist, for postoperative analgesia in children is poorly reported, and there is no accepted reference dose for its use in children.
Objective：To investigate the efficacy and safety of dezocine in postoperative analgesia in children, and to provide a suitable reference dose for analgesia in postoperative children.
Design：Singlecenter randomized controlled study.
Methods：With the preoperative classification of ⅢⅣ by the American Society of Anesthesiologists (ASA), patients directly transferred to PICU after congenital heart disease (CHD) were enrolled from Children's Hospital of Chongqing Medical University at the age of >28 d at the time of surgery. A random number table was used and the grouping results were sealed in an envelope. The PICU physician on duty was responsible for the subject assignment, and the bedside nurse performed the intervention. All patients were randomized into 5 groups. Subjects in the experimental group were continuously injected with lowdose (group D1), mediumdose (group D2), or highdose (group D3) dezocine after the operation, and those in the control group were injected with sufentanil (group SF) or morphine (group M). The postoperative pain and sedation scores were observed. The outcome observers and data analysts were not blinded. Invasive ventilatorassisted ventilation, symptomatic management, and midazolam sedation were performed after admission to the PICU in both five groups. D1, D2, and D3 groups received dezocine 20, 30, 40 μg·kg-1·h-1 respectively, SF group received sufentanil 0.08 μg·kg-1·h-1, and M group received morphine 20 μg·kg-1·h-1. All intravenous injection was administrated through a syringe pump. Face Pain Scale (FPS) and Child Revised Impact of Events Scale (CRIES) were used to evaluate pain, and Ramsay and ComfortB were used to score sedation. All scales were completed by PICU specialist nurses.
Main outcome measures：The percentage of satisfaction with analgesia/sedation at 1 h, 4 h, 8 h, 12 h, and 24 h after the operation.
Results：A total of 152 children with congenital heart disease were enrolled, 30, 30, 31, 31, and 30 in groups D1, D2, D3, SF, and M, respectively, all of whom completed the designed intervention and observation. There were no significant differences in age, weight, sex, extracorporeal circulation time, pediatric critical illness score (PCIS) and preoperative ASA grading among the 5 groups. Compared with group M, the FPS scores were higher in the D2 group at 24h and the D3 group at 4 h and 24 h; the CRIES scores were higher in the D1 and D2 groups at 1 h and 4 h and in the D3 group at 4 h and 24 h ; the Ramsay scores were higher in the D2 and D3 groups at 1 h and 4 h; the ComfortB scores were higher in the D1 group at 4 h and 12 h, in the D2 group at 1h and 4 h and in the D3 group at 1 h, 4 h, and 12 h. All the differences were statistically significant. There was no statistically significant difference in analgesia/sedation satisfaction between the D group(D1, D2, D3) and the SF group in terms of the four scales. The differences in vital signs and related indexes were not statistically significant among the 5 groups at each postoperative time point. The proportion of additional sedative/analgesic drugs was lower in groups D1 and D2 than in groups M and SF, and the differences were statistically significant. Two cases of hypotension and one case of respiratory depression were observed in group M.
Conclusions：The analgesic effect of dezocine in postoperative children with congenital heart disease is better than that of morphine and comparable to that of sufentanil. Dezocine has fewer adverse reactions.
Background：Severe coronary artery lesions (CAL) caused by Kawasaki disease (KD) can lead to coronary events or death in children and has an important impact on long-term prognosis and quality of life.
Objective：To summarize and analyze the medium-term and long-term clinical outcomes of KD children with severe CAL and provide the basis for long-term follow-up management and prognosis evaluation of KD children.
Design：Cohort study.
Methods：The HIS system of Children's Hospital of Fudan University was searched to include children < 18 years of age who were discharged from the hospital from January 2008 to December 2019 with a diagnosis of KD and were diagnosed with severe CAL due to KD by coronary angiography (CAG) in our hospital. Patients with other diseases causing severe CAL and affecting the prognosis of severe CAL were excluded. All children were followed up by senior cardiovascular specialists in the outpatient clinic and ward, and were given medical treatment. Children with severe coronary artery stenosis and myocardial ischemia were treated surgically after multidisciplinary discussion. Children with myocardial ischemia, myocardial infarction or death during diagnosis and follow-up were taken as the poor prognosis group, and the opposite was the good prognosis group. The poor prognosis and the evolution of CAL were observed, and the influencing factors of poor prognosis were analyzed.
Main outcome measures：Poor prognosis and improvement of CAL.
Results：A total of 144 children with severe CAL due to KD were included in this analysis. Among them, 117(81.2%) were males and 27 were females with a median KD onset age of 2.2(1.0, 4.5) years, a median follow-up time of 1.6(0, 3.4) years, and a disease duration of 5.0(3.0, 21.3) months at the diagnosis of severe CAL. A total of 276 coronary arteries were involved in 144 children with KD and severe CAL. Single coronary arteries and ≥2 coronary arteries were involved in 56 cases(38.9%) and 88 cases(61.1%) respectively. There were 122 cases of giant coronary artery aneurysm(GCAA), 8 cases of multiple small and medium-sized coronary artery aneurysms(CAA) in the single coronary artery, 6 cases of GCAA with multiple small and medium-sized CAA in the single coronary artery, and 8 cases of stenosis in all affected coronary arteries. Sixty-two cases developed coronary artery stenosis, including 31 cases of coronary artery occlusion. Fifty-four of 144 children(37.5%) developed poor prognosis, and myocardial ischemia was present in all 54 cases, 14 of which had developed recorded acute myocardial infarction at the ischemic myocardium, and one child died of severe heart failure due to myocardial infarction. The results of multivariate analysis showed that the risk of poor prognosis was 2.6 times higher in children with ≥2 coronary artery involvement than in those with only 1 coronary artery involvement(OR=2.602, 95% CI: 1.201 to 5.634), and 3 times higher in children with coronary artery stenosis than in those without coronary artery stenosis(OR=3.055, 95% CI: 1.450 to 6.437). Among 179 CAG, 114 patients(208 affected coronary arteries) underwent one CAG, and 30 patients(68 affected coronary arteries) underwent≥2 CAG. When 68 affected coronary arteries were first diagnosed, 51 of them were GCAA and the improvement rate was 4.0% at the last follow-up; 3 of them were multiple small and medium-sized CAAs and the improvement rate was 66.6% at the last follow-up; 2 were single small and medium-sized CAAs and developed stenosis(stenosis degree about 50%) until the last follow-up; and 12 were stenosis and did not improve until the last follow-up.
Conclusions：GCAA is the main type of KD with severe CAL, and it is difficult to recover. The improvement rate of multiple small and medium-sized CAAs in the single coronary artery is high. Coronary artery stenosis and multivessel coronary artery involvement are factors leading to the poor prognosis of children with severe CAL caused by KD.
Background：Family financial burden due to childhood acute lymphoblastic leukemia (ALL) is high.
Objective：To explore the factors affecting the medical costs of children with ALL and to provide a basis for reasonable cost control.
Design：Cross-sectional study.
Methods：Children with newly diagnosed ALL were retrospectively enrolled at the Department of Hematology and Oncology of Children's Hospital of Chongqing Medical University. The total medical expenses during remission induction therapy were analyzed, and the factors affecting medical burden were analyzed using rank correlation analysis and generalized linear model statistics.
Main outcome measures：The total hospitalization costs during the remission induction course in children with ALL.
Results：A total of 1 081 children with newly diagnosed ALL were included in this analysis, including 622 males (57.5%) and 459 females with an average age of (70.5±44.5) months. The average total cost of diagnosis and treatment in the remission induction course was 59 860 yuan, the average daily hospitalization cost was (1 244±581) yuan, and the average blood product transfusion cost was (7 106±5 391) yuan. Univariate rank correlation coefficients showed there was a statistically significant difference between the medical costs during the remission induction and age, disease immunotype, risk stratification at initial diagnosis, nosocomial infection, fungal infection and sepsis, non-hematology admission, PICU admission, length of hospitalization and cost of blood product transfusion. Generalized linear model construction indicated that transfer to PICU, non-hematology admission, nosocomial infection, immunotype, fungal infection, length of hospital stay and cost of blood transfusion were independent risk factors affecting the total medical expenses in the remission induction course.
Conclusions：The medical costs of ALL children were influenced by disease severity, complication severity, and factors related to medical management such as nosocomial infection and specialty admissions.
Background: Great heterogeneity exists in studies on the relationship between adolescents' mental health and 24-h movement consisting of sleep, sedentary behavior, and physical activity. Therefore, it is difficult to obtain high-quality evidence synthesis sufficient to guide clinical practice.
Objective: To summarize and evaluate the current status of research on the relationship between 24-hour movement (sleep, sedentary behavior, and physical activity) and mental health in children and adolescents, as well as the problems in research design, so as to provide a reference for future research.
Design: Scoping review.
Methods: PubMed, Embase, Web of Science, and CNKI databases were searched from the inception to September 28, 2022, with the keywords of sleep, sedentary behavior, physical activity, 24-h movement, mental health, and adolescents to identify research on the correlation or causal inference between 24-h movement and mental health in healthy children and adolescents. Data extraction forms for movement type, measurement methods, classification of measurement items, and specific item measurement were gradually refined in the process of data extraction and synthesis after reading the text title, abstract, and full text for screening.
Main outcome measures: Study types and measurement instruments for the relationship between 24-h movement and mental health in adolescents.
Results: A total of 927 articles were retrieved from the English and Chinese databases, and after de-duplication, initial screening and full-text screening, 55 articles were finally included with 45 (82%) cross-sectional studies and 10 prospective cohort studies; 47 (85%) subjective reports and 8 objective monitoring articles. For sleep, 54 described sleep duration and 4 assessed sleep quality, sleep latency, daytime sleepiness, and sleep disruption. For sedentary behavior, there were 50 subjective reports, 5 objective reports, and 46 studies about screen exposure. For physical activity, hours of moderate-to-vigorous physical activity were assessed in 47 subjective reports and 8 objective reports. A total of 32 studies focused on depression, 9 on anxiety, 5 on stress, and 35 on other mental health outcomes (positive mood, behavioral problems, life satisfaction or health-related quality of life, mental illness and symptoms, emotion regulation skills, and cell phone addiction). Forty-four papers explored the correlation between 24-h movement and mental health, 8 papers explored changes in the structure of 24-h movement using isochronous substitution models, and 3 explored mediators of 24-h movement affecting mental health.
Conclusions: There are few studies on the association between 24-h movement and mental health in adolescents, and the measurement tools used need to be standardized. In the future, isochronous substitution models or real-world intervention studies are needed to find the recommended 24-h movement packages that can maximize the health effects of the movement and are easy to achieve at the same time.
Background: The International Study of Kidney Diseases in Children (ISKDC) classification is often used clinically in purpura nephritis (HSPN), but it can only reflect active inflammation of the kidney at the onset, instead of chronic leisons.
Objective: To investigate the application value of the Oxford classification of IgA nephropathy (MEST-C) scale in children with HSPN.
Design: Case series report.
Methods: Children aged ≤14 years who were hospitalized in the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2015 to December 2017, who met the diagnostic criteria for HSPN and underwent renal biopsy were retrospectively collected. General information, laboratory indicators of urine and blood samples before renal biopsy, clinical manifestations, ISKDC grading, and immunofluorescence typing based on pathology reports were collected. The renal pathology was re-evaluated based on the pathology report with reference to the MEST-C scale under the guidance of the pathologist. Since there were no T1/T2 lesions in this study, the renal tubulointerstitial lesions were classified into acute (Ta) and chronic (Tc) scores. All patients were divided into the groups of mesangial cell hyperplasia (M0/M1), endothelial cell hyperplasia (E0/E1), segmental sclerosis/adhesion (S0/S1), Ta0/Ta1, Tc0/Tc1, crescent formation (C0/C1 /C2). The kappa concordance test was performed for MEST-C and ISKDC grading and immunofluorescence pathology.
Main outcome measures: The consistency of different pathological types of HSPN.
Results: A total of 341 children with HSPN were analyzed incuding 191 males and 150 females, with a median age of onset of 9(8,11) years and an interval of 10 (3, 21) days between the first symptoms and abnormal urine test resutls. Clinical typing was most common for hematuria and proteinuria, with a higher proportion of hematuria and proteinuria in the C1 group, a higher proportion of nephrotic syndrome in the M1, E1, and Ta1 groups, and a higher proportion of chronic nephritis in the S1 and Tc1 groups (all with P < 0.05). M1, Ta1, and C2 groups were associated with more severe microscopic hematuria(P < 0.05). M1, E1, Ta1, and C2 groups were associated with large amounts of proteinuria(P < 0.05). M1, Ta1, C1/C2 groups were associated with decreased eGFR levels(P < 0.05). ISKDC grade II and III were the most common, and there were no cases of grade I, V, and VI. E1 and C1 pathological changes were more common in MEST-C score. MEST-C was correlated with ISKDC grading. M1, E1, Ta1, C1/C2 groups had higher ISKDC grading, and that of S1 and Tc1 groups were lower.
Conclusions: The consistency of MEST-C scores with clinical manifestations and laboratory indicators of HSPN in children was in accordance with clinical expectations. All MEST-C pathological indices were consistent with ISKDC grading, and Ta and E indices were consistent with the severity of complement C3 deposition and fibrinogen, respectively.
Background: It is unclear whether the use of pacification strategies before MR scanning can improve the examination cooperation of children in a non-sedated state.
Objective: To explore the effectiveness of an intelligent pacification strategy information system based on assisted decision-making in reducing the sedation rate of short-term MR scans in preschool children.
Design: Quality improvement study.
Methods: Patients at the age of 3-5 years were enrolled from those who attended the outpatient (excluding emergency) and inpatient MR appointments in the Radiology Department at the Xiamen Branch of Children's Hospital of Fudan University. Regular plain scans of common parts were performed with conventional sequences, and the total scanning time was about 10 minutes. Those who were unable to communicate and maintain a quiet state due to mental or psychological illness or intellectual disability were excluded and those who needed urgent MR examination due to acute and severe illness without time and conditions to receive pacification were excluded. Before the quality improvement, specialists at pacification made a plan based on their own experience and discussion with the family member. After the quality improvement, the intelligent pacification strategy information system was used to assist the decision-making. Accompanied by the pacification specialist to perform the plan, patients first received the simulated MR scan. If they succeeded in finishing the scan, a formal MR scan was performed. If the simulated MR failed twice, or patients failed to receive formal MR, patients would be sedated with medication to complete the scan. The pacification success rate, pacification time, and image quality were compared before and after quality improvement.
Main outcome measures: The pacification success rate.
Results: One hundred and twenty-five children aged 3 to 5 years were included, with 62 before improvement and 63 after improvement. There were 65 males (52%). Simulated MR was completed by pacification in 111 cases, 52 before improvement and 59 after improvement, and formal MR was completed by pacification in 99 cases, 46 before improvement and 53 after improvement. A total of 26 cases completed MR after sedation by enema, 16 cases before improvement, and 10 cases after improvement. The pacification success rate after quality improvement was higher than that before(84.1% vs 74.2%), and the pacification time was shorter than that before ［ (42.91±5.43) min vs (54.35±7.02) min］. The differences were statistically significant. There was no statistically significant difference in image quality between the success subgroup and the failure subgroup as well as before and after improvement.
Conclusions: The application of an intelligent pacification strategy information system based on assisted decision-making can help reduce the use of sedative drugs in preschool children during short-term MR scans and improve the efficiency of pacification.
Background: Orthopedic outcomes after craniosynostosis surgery are dependent on helmet orthopedic treatment.
Objective: To investigate the effect of continuing treatment with an orthopedic helmet in children with non-syndromic craniosynostosis after surgery.
Design: Case series report.
Methods: A retrospective analysis was performed for clinical data of children with non-syndromic craniosynostosis who underwent continuous correction with orthopedic helmets at the Children's Health and Development Center of Peking University Third Hospital from January 2019 to December 2021.
Main outcome measures: Head circumference, cranial asymmetry index (CVAI) and cranial ratio (CR).
Results: Forty-five children with non-syndromic craniosynostosis treated with orthopedic helmets were included in the analysis with 24 males and 21 females. There were 16 cases of premature closure of the coronal suture, 18 cases of premature closure of the sagittal suture, 9 cases of premature closure of the herringbone suture, and 2 cases of premature closure of the frontal suture. Before wearing the orthopedic helmet, 15 cases were diagnosed as plagiocephaly, 6 cases as brachycephaly, 16 cases as scaphocephaly, 5 cases as asymmetric brachycephaly and 3 cases of normal skull shape. Minimally invasive craniosynostosis was performed in 12 cases, and craniotomy and cranial remodeling were performed in 33 cases. The average age at operation was 8.5 (6, 12) months. The average time to start wearing the orthopedic helmet was 20 (14, 26) d after surgery, and the average wearing time was 7 (4.5, 10) months. All 45 children were able to wear the orthopedic helmet as required, with a median follow-up time of 7.5 (5, 10.5) months. Compared with the before, significant improvement was identified in head circumference ［(445±10.5) mm vs (469±6.5) mm］ for all 45 children, CVAI of children with plagiocephaly ［(6.1±2.5) vs (3.1±1.2)］, CR in children with brachycephaly ［(0.95±0.08) vs (0.82±0.06)］ and CR in children with scaphocephaly ［(0.72±0.02) vs (0.79±0.03)］ after 2-week orthopedic helmet wearing. Forty-one cases completed neuromotor and psychological development scoring at the age of 12 to 24 months, with an average score of (97.9±7.5), all of which were within the normal range. There were no complications such as skin ulcer necrosis, severe rash, and skin allergy.
Conclusions: After non-syndromic craniosynostosis, the orthopedic helmet has a positive effect on the treatment of cranial abnormalities, and it is safe and will not cause head growth restriction.
Background: The high prevalence of hearing loss in China is associated with a high carrier rate of pathogenic variants in genes for hearing loss. At present, there is a lack of screening data on carriers of pathogenic genes for hearing loss among newborns in neonatal intensive care units (NICU).
Objective: To investigate the carrier rate of GJB2 and SLC26A4, pathogenic genes for hearing loss, in NICU newborns.
Design: Cross-sectional survey.
Methods: Newborns were enrolled in the NICU at Children's Hospital of Fudan University from January 2016 to December 2021, with admission days≤28 d and high-throughput sequencing completed before discharge. Those with positive hearing-loss-associated genetic findings after birth were excluded. The sex, gestational age and birth weight were collected from electronic medical records. The number of cases identified with pathogenic variants in GJB2 and SLC26A4 and the standard terminology of the human phenotype of the children were extracted from the sequencing database. Carrier rate(%)=the number of heterozygous pathogenic or likely pathogenic (P/LP) variants/total number of study subjects. PubMed, Embase, and Wanfang databases were searched. Literature that previously reported the carrier status of the GJB2 gene and/or SLC26A4 gene P/LP mutations in NICU patients, newborns and pregnant women in China were included and reviewed.
Main outcome measures: Carrier rate of P/LP variants in the GJB2 gene and SLC26A4 gene.
Results: A total of 14 924 neonates were included, including 8 587 males (57.5%) and 6 337 females, with a gestational age of (35.6±3.7) weeks and a birth weight of (2 711.7±887.1) g. A total of 18 heterozygous P/LP mutations were detected in 2 009 children (13.462%) carrying P/LP mutations of the GJB2 gene, among which c.109G>A was the most common (10.902%), followed by c.235del (1.749 %), c.299_300del (0.409%), c.176_191del (0.154%), c.508_511dup (0.074%) and c.257C>G. There were 305 children (2.044%) carrying P/LP mutations of the SLC26A4 gene. A total of 31 heterozygous P/LP mutations were detected, and the six highest carrier rates were for c.919-2A>G (1.139%), c. .2168A>G (0.181%), c.1226G>A (0.100%), c.1229C>T (0.094%), c.1174A>T (0.080%) and c.1003T>C, respectively.
Conclusions: It is suggested that c.109G>A, c.508_511dup and c.257C>G on the GJB2 gene and c.1003T>C on the SLC26A4 gene should be included in the carrier screening for pathogenic genes for hearing loss among newborns in NICU.
Background: There is controversy at home and abroad as to whether delayed high-dose methotrexate (MTX) excretion should be rescued by hemodialysis.
Objective: To investigate the effectiveness of high-flux hemodialysis (HF-HD) on MTX clearance in children with tumors.
Design: Case series report.
Methods: A retrospective analysis was performed for consecutive cases with blood levels >10 μmol·L-1 at 44 h after MTX chemotherapy at the Department of Hematology Oncology at Shanghai Children's Medical Center affiliated with Shanghai Jiao Tong University School of Medicine between January 2016 to June 2021. The children with calcium folinate (CF) alone were in the non-HF-HD group, and those with HF-HD + CF were in the HF-HD group. Gastrointestinal tracts, liver and kidney function as well as hematologic toxicity indicators were compared between the two groups.
Main outcome measures: The incidence of adverse reactions to liver and kidney function.
Results: There were 20 times delayed MTX excretion with 9 in the non-HF-HD group and 11 in the HF-HD group. According to Common Terminology Criteria for Adverse Events v4.0, there was no significant difference in creatinine, uric acid, ALT, AST, mucositis, 24 h MTX concentration, and the time required for MTX concentration to return to normal between the CF group and the HF-HD group. There was no significant difference in the incidence of hematologic adverse events between the two groups, while the differences in incidences of abnormalities of AST, ALT, fever, mucositis, WBC, NE, Hb, and PLT were not statistically significant between the two groups.
Conclusions: If the kidney function is normal, CF rescue can be used for children with tumors to clear MTX effectively and safely, and dialysis is not recommended unless it is necessary.
