The influence of NUDT15 variants on 6-mercaptopurine-induced neutropenia in Vietnamese pediatric acute lymphoblastic leukemia.

6-Mercaptopurine (6-MP) serves as the backbone of maintenance therapy in acute lymphoblastic leukemia. The nucleoside diphosphate-linked moiety X-type motif 15 genes (NUDT15) affects the metabolism of 6-MP and thiopurine-related neutropenia in the Asian population. This study reports the influence of these variants on 6MP-induced neutropenia in children with acute lymphoblastic leukemia (ALL). A total of 102 children were enrolled in this retrospective cohort study. NUDT15 variants on exon 1 and exon 3 were identified by Sanger sequencing. We divided the intermediate metabolizer group and the normal metabolizer group base on NUDT15 diplotypes. During the first 3 months of maintenance treatment, medical reports measured treatment-related toxicity (neutropenia) and 6-MP dose decreases. NUDT15 genotyping showed two categories of mutations: wild type (75.5%) and heterozygous variant (24.5%). Neutropenia during the early phase of maintenance therapy in the intermediate metabolizer group (68%) was significantly higher than the normal metabolizer group (18.2%) with 10-fold greater odds. Especially, the c.415C>T heterozygous variant was extremely associated with neutropenia compared with the C>C genotype (odds ratio [OR]: 12; 95% confidence interval [CI]: 3.5-41.7). The tolerated doses of 6-MP after the first 3 months of maintenance therapy related to the intermediate metabolizer group and the normal metabolizer group were 48.7 and 64.3 mg/m2/day, respectively (p < 0.001). One-fourth of individuals had NUDT15 variations. All NUDT15 heterozygous mutations cause neutropenia and need 6-MP dose optimization. Given the frequency of NUDT15 mutations in Vietnamese children and their connection with early neutropenia, testing is indicated.

A Simple, Rapid, and Cost-Effective PCR Procedure for Detection of NUDT15 Gene Variants in Vietnamese Patients with Acute Lymphoblastic Leukemia.

Objective The NUDT15 variants impact thiopurine dose selection in acute lymphoblastic leukemia patients. The ability to rapidly detect variants is important in clinical practice. This study aims to develop a simple polymerase chain reaction (PCR) procedure for detecting NUDT15 variants in Vietnamese patients. Materials and Methods Sanger sequencing was used to determine NUDT15 variants from 200 patients. We designed primers and optimized the PCR procedure for detection of wild-type and variant alleles and compared with Sanger sequencing results. Results The inserted variant c.55_56insGAGTCG was detected by differences in size through conventional PCR. The tetra-primer amplification refractory mutation system PCR was successful in detecting two variations, c.52G > A and c.415C > T. The sensitivity and specificity of PCR procedure achieved 100% when compared to 200 Sanger sequencing results. Conclusion Our PCR procedure is suitable for replacing Sanger sequencing to detect the NUDT15 variants in clinical setting.

Cardiovascular injury and clinical features of multisystem inflammatory syndrome in children (MIS-C) related to Covid-19 in Vietnam.

BACKGROUND: This study aimed to describe the cardiovascular injury and clinical features of multisystem inflammatory syndrome in children (MIS-C) related to coronavirus disease 2019 (COVID-19) in Ho Chi Minh City, Vietnam. METHODS: This was a retrospective cohort study of children with MIS-C (from September 1, 2021 to February 28, 2022) in Children's Hospital 1, Ho Chi Minh City. Demographics, clinical history, significant underlying conditions, clinical manifestations, laboratory investigations, and medical management were analyzed. RESULTS: A total of 76 patients were included (median age, 5.9 years old, 2 months-16 years). The male/female ratio was 1.6/1. Most patients (75/76) had no previous medical conditions. The mean time from acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to symptom onset was 39 days. During an acute SARS-CoV-2 infection, these patients are either asymptomatic or mildly symptomatic. In addition to fever, gastrointestinal symptoms were also prominent, as observed in our study, with 75%, 73.7%, and 72.3% of patients presenting with abdominal pain, vomiting, and loose stools, respectively. The levels of inflammatory markers increased upon admission and returned to normal levels after treatment. Echocardiography revealed decreased myocardial contractility and coronary injury in 16 (21.1%) and 32 (42.1%) patients, respectively. Most cases (72/76) had no fever within 3 days of intravenous immunoglobulin (IVIG) and methylprednisolone treatment. No deaths occurred in this study. The mean duration of hospitalization was 7.2 days. CONCLUSION: Cardiovascular involvement was observed in approximately 53.9% of the patients. Anti-inflammatory treatment with IVIG and methylprednisolone had a favorable short-term outcome. However, long-term follow-up studies on post-discharge MIS-C cases are needed to make appropriate treatment recommendations in the acute phase.

The Role of Lung Ultrasonography in Etiologic Diagnosis of Acute Dyspnea in a Resource Limited Setting.

The aim of the current study was to describe lung ultrasonography (LUS) characteristics and to evaluate the agreement between LUS and chest radiography (CXR) in diagnosis of four conditions causing most acute dyspnea in children, namely, pneumonia, pleural effusion, pneumothorax and acute pulmonary edema in children at a teaching hospital in Vietnam. We reviewed the records of the chidren between January and June 2018, who presented to emergency department (ED) or pediatric intensive care unit (PICU) at children hospital 1 (CH1) with acute dyspnea and had final diagnosis of one of four etiologies including pneumonia, pleural effusion, pneumothorax and acute pulmonary edema. All patients underwent CXR and LUS at the time of admission. Eighty-one children with acute dyspnea including pneumonia (n=65, 80%), pleural effusion (n=9, 11%), pneumothorax (n=3, 4%) and acute pulmonary edema (n=4, 5%) were enrolled. LUS was identified among 100% of cases with pleural effusion and pneumothorax (CXR only showed 73.3% and 50%, respectively); 92.3% of cases with pneumonia (CXR showed 93.8%) and only 75% of cases with acute pulmonary edema (CXR showed 50%). When comparing LUS with CXR, we noticed a good agreeement between the 2 methods in the diagnosis of pneumonia (kappa=0.64, p<0.001). LUS was shown to be a feasible and non-invasive technique which can help clinicians to comfirm the etiology of acute pulmonary dyspnea.