Introduction: Beta-thalassemia is a group of inherited hemolytic anemias and one of the most common genetic disorders in Thailand. The clinical spectrum of beta-thalassemia disease ranges from mild to severe clinical symptoms including mild beta-thalassemia intermedia (TI) and severe beta-thalassemia major (TM). Objective: This study aimed to determine the correlation between beta-globin gene (HBB) mutations and their phenotypic manifestations by evaluating patients’ clinical characteristics, transfusion requirements, growth and hematologic parameters, and hemoglobin typing among pediatric patients treated at Phramongkutklao Hospital. Materials and methods: Seventy beta-thalassemia patients, including 63 with beta-thalassemia/hemoglobin E (HbE) and 7 with either homozygous or compound heterozygous beta-thalassemia, were enrolled in this study. Their clinical presentation, growth parameters and laboratory findings were reviewed and analyzed. The mean follow-up time was 10.52±5.62 years. Mutation analysis in each individual was performed using multiplex amplification refractory mutation system (M-ARMS), direct DNA sequencing of beta-globin gene and gap PCR for 3.4 kb deletion detection. Results: All 7 homozygous and compound heterozygous beta-thalassemia patients were classified in TM. Among 63 patients with beta-thalassemia/HbE, 58 were classified in TM and 4 were classified in TI. Mean age at diagnosis was 0.8±0.49 years for homozygous or compound heterozygous beta-thalassemia and 3.43±3.5 years for beta-thalassemia/HbE. The most common HBB mutation was HBB:c.126_129delCTTT [codon 41/42 (-TCTT)] found in 34 alleles (48.6%). The height for age was also lower in homozygous beta-thalassemia patients (<3rd percentile) compared to compound heterozygous beta-thalassemia patients (25–50th percentile).
Conclusion: This study revealed a genotype–phenotype correlation of the most prevalent beta-thalassemia in Thai children using diagnostic capacity in genotypic analysis of HBB mutation. Our findings can provide a better prediction of clinical manifestation and severity by early identification of the type of the HBB mutations.

Clinical and molecular genetic features of Hb H and AE-Bart’s diseases in central Thai children Chanchai Traivaree,1,* Boonchai Boonyawat,2,* Chalinee Monsereenusorn,1 Piya Rujkijyanont,1 Apichat Photia1 1Division of Hematology/Oncology, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand; 2Division of Genetics, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand *These authors contributed equally to this work Background: α-Thalassemia, one of the major thalassemia types in Thailand, is caused by either deletion or non-deletional mutation of one or both α-globin genes. Inactivation of three α-globin genes causes hemoglobin H (Hb H) disease, and the combination of Hb H disease with heterozygous hemoglobin E (Hb E) results in AE Bart’s disease. Objective: This study aimed to characterize the clinical and hematological manifestations of 76 pediatric patients with Hb H and AE Bart’s diseases treated at Phramongkutklao Hospital, a tertiary care center for thalassemia patients in central Thailand.Patients and methods: Seventy-six unrelated pediatric patients, 58 patients with Hb H disease and 18 patients with AE Bart’s disease, were enrolled in this study. Their clinical presentations, transfusion requirement, laboratory findings, and mutation analysis were retrospectively reviewed and analyzed.Results: A total of 76 pediatric patients with Hb H and AE Bart’s diseases who mainly lived in central Thailand were included in this study. The clinical severities of patients with non-deletional mutations were more severe than those with deletional mutations. Eighty-six percent of patients with non-deletional AE Bart’s disease required more blood transfusion compared to 12.5% of patients with deletional AE Bart’s disease. Non-deletional AE Bart’s disease also had a history of urgent blood transfusion with the average of 6±0.9 times compared to 1±0.3 times in patients with deletional Hb H disease. The difference was statistically significant.Conclusion: This study revealed the differences in clinical spectrum between patients with Hb H disease and those with AE Bart’s disease in central Thailand. The differentiation of α-thalassemia is essential for appropriate management of patients. The molecular diagnosis is useful for diagnostic confirmation and genotype–phenotype correlation. Keywords: genotype, phenotype, Hb H disease, AE Bart’s disease, Thai children

Background: High-dose methotrexate (HD-MTX) is widely used as a standard chemotherapeutic agent in pediatric cancers. Most research studies have confirmed the therapeutic efficacy of HD-MTX; however, strategies to prevent side effects vary among institutions, especially in developing countries, with limited monitoring of plasma methotrexate level. Objective: To evaluate the effect of intravenous hydration during HD-MTX administration on plasma methotrexate clearance in pediatric oncology patients. Materials and methods: This study retrospectively reviewed 165 courses of HD-MTX administered to children with acute lymphoblastic leukemia (ALL), non-Hodgkin’s lymphoma (NHL), or osteosarcoma. Demographic data of patients were collected. Adverse complications related to HD-MTX and 72-hour plasma methotrexate level were analyzed between patients receiving intravenous hydration ≥3,000 mL/m²/day and those receiving hydration <3,000 mL/m²/day. Results: Among 56 HD-MTX (1.5 g/m²) courses in ALL, delayed methotrexate clearance was only found in one course administered with hydration <3,000 mL/m²/day. However, no correlation was observed between adverse complications and methotrexate levels. Of 34 HD-MTX (1.5–3 g/m²) courses in NHL, no significant correlation was observed between methotrexate levels and intravenous hydration. However, increased adverse complications were found in the course with delayed methotrexate clearance. Interestingly, among 75 HD-MTX (10–12 g/m²) courses in osteosarcoma, normal methotrexate clearance was successfully achieved in all courses administered with hydration ≥3,000 mL/m²/day compared with those administered with hydration <3,000 mL/m²/day (P=0.007). Furthermore, the courses administered with hydration <3,000 mL/m²/day and had delayed methotrexate clearance were more likely to develop adverse complications. Conclusion: Intravenous hydration of ≥3,000 mL/m²/day during HD-MTX administration is essentially required in osteosarcoma and can be considered as optional in ALL with HD-MTX <1.5 g/m², especially in developing countries with limited monitoring of plasma methotrexate level.

A wide variety of materials are used for lumbar interbody fusion, but there is no unified consensus on the superiority of one material over another. The aim of this systematic review and network meta-analysis (NMA) is to compare and rank the various TLIF interbody materials based on fusion rates. We queried PubMed, EMBASE and Scopus from inception until August 2023, in which 2135 studies were identified. Inclusion criteria were applied based on the PRISMA guidelines. The fusion assessment employed the Bridwell's criteria with a length of follow-up of at least 12 months. The NMA was conducted to compare multiple approaches from multiple studies using the frequentist framework with STATA16. In total, 13 TLIF studies involving 1919 patients with 1981 lumbar interbody levels fulfilled our eligibility criteria. Seven different cage materials were utilized: polyetheretherketone (PEEK, as the reference), allograft, autograft, PEEK with titanium coating (TiPEEK), titanium, carbon/carbon fiber reinforced polymer (CFRP) and 3D-printed titanium. The average patient age was 60.9 (SD = 7.5) years old. When compared to PEEK, the other six materials did not have a significantly different rate of lumbar fusion. However, the SUCRA number of the 3D-printed titanium, TiPEEK, Ti, allograft, autograft, CFRP, and PEEK were 0.8, 0.6, 0.5, 0.5, 0.4, 0.4, and 0.3 consecutively. Based on a network meta-analysis within the confines of our clinical study, 3D-printed titanium interbody cage may promote the highest success rate of fusion while PEEK may be the material with the least success rate of fusion in TLIF.

Congenital factor VII (FVII) deficiency is a rare inherited coagulopathy. The clinical manifestations and clinical findings vary widely, ranging from asymptomatic to life-threatening bleeding, including intracranial hemorrhage (ICH), with prolonged prothrombin time, normal partial thromboplastin time and normal platelet counts, which are confirmed by the low level of FVII assay. Treatment consists of fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), and recombinant activated FVII to treat bleeding and prophylactic therapy. Here, we report four patients with FVII levels T was the most common (50%) mutation identified in our study, followed by the K376X nonsense mutation (37.5%). In our study, we found that genetic information affected the severity of congenital FVII deficiency with ICH.

Background: The most common complication among pediatric oncology patients is febrile neutropenia (FN). Invasive fungal disease (IFD) is suspected when fever persists > 4– 7 days after empirical antibiotics. Its clinical characteristics and predictive factors associated with IFD among pediatric oncology patients with FN were thus explored. Methods: Pediatric oncology patients with FN between January 1, 2012 and December 31, 2016 were enrolled in this study. Clinical characteristics, including laboratory investigations, treatment modalities, and final outcomes of IFD were retrospectively reviewed and analyzed. Results: In all, 73 patients with 180 episodes of confirmed diagnosis of FN were studied. Median age at diagnosis was 6.2 years, with equal sex distribution. The most common diagnosis was acute lymphoblastic leukemia (n=91, 51%), followed by acute myeloid leukemia (n=47, 26%), Burkitt’s lymphoma (n=7, 4%) and neuroblastoma (n=7, 4%). Median absolute neutrophil count at FN diagnosis was 0 (0– 806) cells/mm³. IFD was diagnosed for 25 (14%) episodes. Mortality rates for FN and IFD were 4% and 20%, respectively. Respiratory compromise, oxygen requirement, hypotension, prolonged hospitalization, duration of fever and neutropenia, bacteremia, bacteriuria, funguria, abnormal liver-function results, and prolonged broad-spectrum antibiotic administration were factors associated with IFD (P< 0.05). Prolonged duration between initiation of fever and antifungal administration for nearly 10 days was an independent factor in prediction of IFD occurrence (P= 0.014). Conclusion: Respiratory compromise, oxygen requirement, hypotension, prolonged hospitalization, duration of fever and neutropenia, bacteremia, bacteriuria, funguria, abnormal liver-function results and prolonged broad-spectrum antibiotic administration were factors associated with IFD. Duration between initiation of fever and antifungal administration of nearly 10 days were considered a risk factors of IFD among patients with FN. IRB Reference Number: IRBRTA 825/2560.