Drug-induced liver injury (DILI) is one of the most common adverse drug reactions that may seriously threaten the health of children and is receiving increasing clinical attention day by day. There is still no independent diagnosis and treatment guideline for DILI in children, but its clinical features are not completely similar to those in adults. This article reviews the epidemiology, clinical features, diagnosis, and treatment progress in order to provide a reference for the management of DILI in children.
Child ; Humans ; Chemical and Drug Induced Liver Injury/therapy* ; Drug-Related Side Effects and Adverse Reactions ; Liver/pathology* ; Risk Factors

Objective: To observe the treatment response of a two-dose regimen of inotuzumab ozogamicin (inotuzumab), a monoclonal antibody targeting CD22, for patients with heavily treated relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), including those failed or relapsed after chimeric antigen receptor (CAR) -T-cell therapy. Methods: Pediatric and adult patients who received two doses of inotuzumab and who were evaluated after inotuzumab treatment were included. Antibody infusions were performed between March 2020 and September 2022. All patients expressed CD22 antigen as detected by flow cytometry (>80% leukemic cells displaying CD22) before treatment. For adults, the maximum dosage per administration was 1 mg (with a total of two administrations). For children, the maximum dosage per administration was 0.85 mg/m(2) (no more than 1 mg/dose; total of two administrations). The total dosage administered to each patient was less than the standard dosage of 1.8 mg/m(2). Results: Twenty-one patients with R/R B-ALL were included, including five children (<18 years old) and sixteen adults. Seventeen patients presented with 5.0% -99.0% leukemic blasts in the bone marrow/peripheral blood or with extramedullary disease, and four patients were minimal residual disease (MRD) -positive. Fourteen patients underwent both CD19 and CD22 CAR-T-cell therapy, four underwent CD19 CAR-T-cell therapy, and three underwent blinatumomab therapy. Eleven patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). After inotuzumab treatment, 14 of 21 patients (66.7% ) achieved a complete response (CR, one was MRD-positive CR), and all four MRD-positive patients turned MRD-negative. Four of six patients who failed recent CD22 CAR-T-cell therapy achieved a CR after subsequent inotuzumab treatment. Seven patients (33.3% ) demonstrated no response. Grade 1-3 hepatotoxicity occurred in five patients (23.8% ), one child with no response experienced hepatic veno-occlusive disease (HVOD) during salvage transplantation and recovered completely. Conclusion: For patients with heavily treated R/R B-ALL, including those who had undergone allo-HSCT and CD19/CD22 CAR-T-cell therapy, the two-dose regimen of inotuzumab resulted in a CR rate of 66.7%, and the frequency of hepatotoxicity and HVOD was low.
Adult ; Humans ; Child ; Adolescent ; Inotuzumab Ozogamicin ; Receptors, Chimeric Antigen ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Antibodies, Monoclonal ; Adaptor Proteins, Signal Transducing ; Antigens, CD19 ; Chemical and Drug Induced Liver Injury

Humans ; Child ; COVID-19/complications* ; Brain Diseases ; Myositis/complications* ; Kidney ; Liver Failure, Acute/complications* ; Acute Kidney Injury/complications*

Objective: The kidney disease: improving global outcome (KDIGO) and pediatric reference change value optimized for acute kidney injury (pROCK) criteria were used to evaluate the incidence, stages and mortality of acute kidney injury (AKI). The differences between the 2 criteria were compared for exploring the value of pROCK criteria in diagnosing pediatric AKI and predicting adverse outcomes. Methods: In the multicenter prospective clinical cohort study, we collected general data and clinical data such as serum creatinine values from 1 120 children admitted to 4 PICUs of Children's Hospital of Soochow University, Children's Hospital of Fudan University, Anhui Provincial Children's Hospital, and Xuzhou Children's Hospital from September 2019 to February 2021. AKI was defined and staged according to the KDIGO and pROCK criteria. The incidence of AKI, the consistency of AKI definite diagnosis and stages, and the mortality in PICU were compared between the 2 groups. The chi-square test or Fisher's exact test was applied for comparison between 2 groups. The Cohen's Kappa and Weighted Kappa analyses were used for evaluating diagnostic consistency. The Cox regression analysis was used to evaluate the correlation between AKI and mortality. Results: A total of 1 120 critically ill children were included, with an age of 33 (10, 84) months. There are 668 boys and 452 girls. The incidence of AKI defined by the KDIGO guideline was higher than that defined by pROCK criteria (27.2%(305/1 120), 14.7%(165/1 120), χ²=52.78, P<0.001). The concordance rates of the 2 criteria for the diagnosis of AKI and AKI staging were 87.0% (κ=0.62) and 79.7% (κ=0.58), respectively. Totally 63 infants with AKI stage 1 defined by the KDIGO guideline were redefined as non-AKI by following the pROCK criteria. The PICU mortality rate of these infants was similar to patients without AKI defined by KDIGO guideline(P=0.761). After adjusting for confounders, AKI defined by KDIGO or pROCK criteria was an independent risk factor of death in PICU (AHR=2.04, 2.73,95%CI 1.27-3.29, 1.74-4.28, both P<0.01), and the risk of death was higher when using the pROCK compared with the KDIGO criteria. As for the KDIGO criteria, mild AKI was not associated with the mortality in PICU (P=0.702), while severe AKI was associated with increased mortality (P<0.001). As for the pROCK criteria, both mild and severe AKI were risk factors of PICU death in children (HR=3.51, 6.70, 95%CI 1.94-6.34, 4.30-10.44, both P<0.001). In addition, The AKI severity was positively associated with the mortality. Conclusions: The AKI incidence and staging varied depending on the used diagnostic criteria. The KDIGO definition is more sensitive, while the pROCK-defined AKI is more strongly associated with high mortality rate.
Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Acute Kidney Injury/epidemiology* ; Cohort Studies ; Critical Illness ; Prospective Studies ; Risk Factors

Acute Kidney Injury/therapy* ; Anticoagulants/therapeutic use* ; Blood Coagulation ; Child ; Citrates ; Citric Acid/therapeutic use* ; Continuous Renal Replacement Therapy ; Humans ; Renal Replacement Therapy

OBJECTIVES: To evaluate the effect of fluid load on the prognosis of children with sepsis-associated acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). METHODS: A total of 121 children who underwent CRRT for sepsis-associated AKI from August 2018 to March 2021 were enrolled in the retrospective study. According to the fluid load from admission or disease progression to CRRT, they were divided into three groups: low fluid load (fluid load: <5%; n=35), high fluid load (fluid load: 5% - <10%; n=35), and fluid overload (fluid load: ≥10%; n=51). Baseline data and clinical biochemical data before CRRT were collected for comparison and analysis. The Kaplan-Meier survival curve analysis was used for comparison of 28-day survival between groups. The multivariate logistic regression model was used to identify the influencing factors for the prognosis of the children. RESULTS: The survival analysis showed that the fluid overload group had a significantly higher 28-day mortality rate than the low fluid load and high fluid load groups (P<0.05). The multivariate logistic regression analysis showed that an increase in fluid overload volume was a risk factor for increased 28-day mortality in the fluid overload group, while earlier initiation of CRRT was a protective factor (P<0.05). CONCLUSIONS Fluid overload before CRRT may increase the mortality in children with sepsis-associated AKI, and CRRT should be performed for these children as early as possible.
Acute Kidney Injury/therapy* ; Child ; Continuous Renal Replacement Therapy ; Humans ; Prognosis ; Retrospective Studies ; Sepsis/therapy*

INTRODUCTION: Wheeled recreational devices (WRDs) include tricycles, bicycles, scooters, inline skates, skateboards, longboards and waveboards, and can cause significant morbidity and mortality. This study aimed to describe the epidemiology and nature of injuries sustained by children from WRD use, and risk factors for severe injury. METHOD: We described injuries relating to WRD use in children <18 years who presented to the emergency department of an Asian tertiary hospital between 2016 and 2020. Demographic data, site and nature of the injury, and historical trends were analysed. Risk factors for severe injury (defined as fractures or dislocations), Injury Severity Score ≥9, and injuries resulting in hospitalisation, surgery or death were evaluated. RESULTS: A total of 5,002 patients with 5,507 WRD-related injuries were attended to over the 5-year study period. Median age was 4.7 years. Injuries related to bicycles (54.6%) and scooters (30.3%) were most frequent, followed by skateboards and waveboards (7.4%), inline skates (4.7%), and tricycles (3.0%). Injuries occurred most frequently in public spaces. Soft tissue injuries (49.3%) and fractures (18.7%) were the most common diagnoses. Upper limb (36.4%) and head and neck (29.0%) regions were the most common sites of injury. Among the patients, 1,910 (38%) had severe injuries with potential morbidity. On multivariate analysis, heavier children of the school-going age who use either scooters, skateboards or inline skates are more prone to severe injuries. Involvement in a vehicular collision was a negative predictor. CONCLUSION WRD use in children can result in severe injuries. Wrist and elbow guards, as well as helmets are recommended, along with adequate parental supervision.
Child ; Child, Preschool ; Emergency Service, Hospital ; Fractures, Bone/etiology* ; Head Protective Devices ; Humans ; Injury Severity Score ; Retrospective Studies ; Risk Factors ; Singapore/epidemiology*

OBJECTIVES: To investigate the incidence rate of acute kidney injury (AKI) in children with type 1 diabetes and diabetic ketoacidosis (DKA) and the risk factors for AKI in children with DKA. METHODS: A retrospective analysis was performed on 45 children with type 1 diabetes and DKA who attended Children's Hospital of Nanjing Medical University from 2018 to 2020. According to the presence or absence of AKI on admission, they were divided into two groups: non-AKI (n=37) and AKI (n=8). Socio-demographic data and physical examination data on admission were collected, including height, weight, blood pressure, and heart rate. Chemiluminescence particle immunoassay was used to determine the levels of serum creatinine and blood urea nitrogen on admission and at discharge. The multivariate logistic regression model was used to assess the risk factors for AKI in children with type 1 diabetes and DKA. RESULTS: The 45 children had a median age of 9.2 years at diagnosis. Among the 8 children (18%) with AKI on admission, 6 had stage 1 AKI and 2 had stage 3 AKI. An increase in corrected serum sodium level was an independent risk factor for AKI in children with type 1 diabetes and DKA (P<0.05), and a relatively high insulin level on admission was an independent protective factor against AKI (P<0.05). CONCLUSIONS There is a high incidence rate of AKI in children with type 1 diabetes and DKA. It is important to correct DKA actively, control blood glucose in time, and perform renal function tests and follow-up regularly in such children.
Acute Kidney Injury ; Blood Glucose ; Child ; Diabetes Mellitus, Type 1 ; Diabetic Ketoacidosis ; Humans ; Retrospective Studies

OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) in children. METHODS: A retrospective analysis was performed on the medical data of 111 children who underwent HSCT from January 2018 to January 2020. A multivariate logistic regression analysis was used to identify the risk factors for AKI. The Kaplan-Meier survival analysis was used to compare the prognosis in children with different grades of AKI. RESULTS: Graft-versus-host disease (grade Ⅱ-Ⅳ) (OR=4.406, 95%CI: 1.501-12.933, P=0.007), hepatic veno-occlusive disease (OR=4.190, 95%CI: 1.191-14.740, P=0.026), and thrombotic microangiopathy (OR=10.441, 95%CI: 1.148-94.995, P=0.037) were closely associated with the development of AKI after HSCT. The children with stage Ⅲ AKI had a lower 1-year survival rate than those without AKI or with stage Ⅰ AKI or stage Ⅱ AKI (28.6%±12.1% vs 82.8%±5.2%/81.7%±7.4%/68.8%±11.6%; P<0.05). CONCLUSIONS Children with stage Ⅲ AKI after HSCT have a higher mortality rate. Graft-versus-host disease, hepatic veno-occlusive disease, and thrombotic microangiopathy are closely associated with the development of AKI after HSCT.
Child ; Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Graft vs Host Disease/complications* ; Risk Factors ; Acute Kidney Injury/therapy* ; Thrombotic Microangiopathies/complications*

OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) in children with cardiac arrest (CA) and the influencing factors for prognosis. METHODS: A retrospective analysis was performed on the medical records of the children who developed CA in the pediatric intensive care unit (PICU) of Hunan Children's Hospital from June 2016 to June 2021. According to the presence or absence of AKI within 48 hours after return of spontaneous circulation (ROSC) for CA, the children were divided into two groups: AKI (n=50) and non-AKI (n=113). According to their prognosis on day 7 after ROSC, the AKI group was further divided into a survival group (n=21) and a death group (n=29). The multivariate logistic regression analysis was used to investigate the risk factors for early AKI in the children with CA and the influencing factors for prognosis. RESULTS: The incidence rate of AKI after CA was 30.7% (50/163). The AKI group had a 7-day mortality rate of 58.0% (29/50) and a 28-day mortality rate of 78.0% (39/50), and the non-AKI group had a 7-day mortality rate of 31.9% (36/113) and a 28-day mortality rate of 58.4% (66/113). The multivariate logistic regression analysis showed that long duration of cardiopulmonary resuscitation (OR=1.164, 95%CI: 1.088-1.246, P<0.001), low baseline albumin (OR=0.879, 95%CI: 0.806-0.958, P=0.003), and adrenaline administration before CA (OR=2.791, 95%CI: 1.119-6.961, P=0.028) were closely associated with the development of AKI after CA, and that low baseline pediatric critical illness score (OR=0.761, 95%CI: 0.612-0.945, P=0.014), adrenaline administration before CA (OR=7.018, 95%CI: 1.196-41.188, P=0.031), and mechanical ventilation before CA (OR=7.875, 95%CI: 1.358-45.672, P=0.021) were closely associated with the death of the children with AKI after CA. CONCLUSIONS Albumin should be closely monitored for children with ROSC after CA, especially for those with long duration of cardiopulmonary resuscitation, low baseline pediatric critical illness score, adrenaline administration before CA, and mechanical ventilation before CA, and such children should be identified and intervened as early as possible to reduce the incidence of AKI and the mortality rate.
Child ; Humans ; Prognosis ; Retrospective Studies ; Critical Illness ; Heart Arrest/complications* ; Acute Kidney Injury/epidemiology* ; Intensive Care Units, Pediatric ; Risk Factors ; Epinephrine ; Albumins