Udon Thani Hospital

In addition to the Human Leukocyte Antigen B*58:01(HLA-B*58:01), several non-genetic factors have been associated with allopurinol hypersensitivity syndrome, particularly severe cutaneous adverse drug reactions (SCAR), which are clinically serious. However, the magnitude of the impact of these non-genetic factors on the development of SCAR remains unclear. This study aimed to develop a non-genetic risk prediction model for predicting allopurinol-induced SCAR. This retrospective observational study was performed during the same time period. SCAR cases were collected from tertiary care hospital centers, while the non-SCAR cases were collected from primary and tertiary care hospital centers. Non-genetic factors including sex, age, renal function, concomitant use of diuretics, starting dose of allopurinol, and serum urate (SU) were used for the development of the prediction models. Of the 23,294 cases, 209 were SCAR and 23,085 were non-SCAR cases. Three risk stratification models were developed. Models 1A and 1B were applied for patients who did not have and had SU level at the time of starting allopurinol, respectively. Model 2 was applied for patients who had all non-genetic risk factors, started allopurinol within 60 days, but had not yet developed SCAR. The area under the receiver operating characteristic curve for Models 1A, 1B, and 2 was 0.73 (95

The nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) has been identified as a key genetic determinant of 6-mercaptopurine (6-MP)-induced hematopoietic toxicity in populations with a high frequency of NUDT15 variants but a low frequency of thiopurine S-methyltransferase (TPMT) variants. However, evidence remains limited in populations where both genetic variants are prevalent. This study aimed to characterize the impact of NUDT15 and TPMT polymorphisms on 6-MP-induced hematopoietic toxicity in Thai pediatric patients, a population with a high prevalence of both variants. A total of 215 Thai pediatric patients undergoing maintenance-phase therapy with 6-MP were enrolled. Genotyping for TPMT and NUDT15 was performed, and phenotypes were determined based on the genotype data. The results showed that the absolute neutrophil count (ANC), white blood cell (WBC) count, and platelet count during the first 6 months of the maintenance phase were significantly lower in intermediate metabolizers (IM) of NUDT15 compared to normal metabolizers (NM). The risk of 6-MP-induced severe neutropenia increased by 6.8-24.5-fold in IM/PM of NUDT15. The suitable tolerance doses of 6-MP in the IM/PM of NUDT15 were lower than the normal starting dose while the tolerance dose of 6-MP in the indeterminate metabolizers (IDM) of NUDT15 or IM of TPMT was not significantly different from the normal starting dose. In conclusion, NUDT15 plays a more prominent role than TPMT in 6-MP-induced hematopoietic toxicity in Thai pediatric patients. Determining NUDT15 phenotypes is essential to ensure appropriate 6-MP dosage adjustments and to mitigate the risk of severe hematopoietic toxicity in this population.

Background:Ablation is increasingly used to treat atrial fibrillation (AF), and recognizing potential complications is essential. We present a case of left atrial intramural haematoma after radiofrequency ablation (RFA), successfully managed with a conservative approach. Case summary:A 39-year-old man underwent pulmonary vein isolation (PVI). During RFA with a contact-force catheter, the areas close to the left superior pulmonary vein, including the left atrial appendage, roof, and posterior wall, showed absent electrical signal. Left atrial scarring was suspected. PVI was completed. On the following day, the patient had chest pain. Transthoracic echocardiography revealed pericardial effusion and a large left atrial mass. Computed tomography confirmed a left atrial intramural haematoma extending into the left atrial cavity. Anticoagulation was discontinued. The patient developed worsening chest tightness on postoperative day 2 due to increasing of pericardial effusion. Pericardiocentesis was performed to relieve symptoms, and 400 mL of bloody fluid was drained. The effusion did not progress further. The drain was removed three days later, and the haematoma was managed conservatively with a favourable outcome. Discussion:Left atrial intramural haematoma can occur following left atrial RFA. Diagnosis relies on multimodality imaging, including echocardiogram and computed tomography. Furthermore, intra-procedural mapping abnormalities, such as a large low-voltage area, may indicate an evolving complication. Early recognition of this rare but potentially life-threatening complication can guide prompt and appropriate management. In stable patients, close clinical and imaging follow-up is appropriate, as shown in our case. In severe cases with haemodynamic compromise, urgent surgical intervention may be required.

BACKGROUND:The survival outcomes among children with acute myeloid leukemia (AML) in low- and middle-income countries are still poor despite adopting modern treatment regimens from developed countries. The study aimed to identify additional potential determinant factors for relapse and death among children with AML in Thailand. METHODS:In all, data from 282 children newly diagnosed with AML between 2015 and 2019 across Thailand were retrospectively reviewed. Data, including initial white blood cell numbers, genetic analysis, post-induction minimal residual disease (MRD), hematopoietic stem cell transplantation, and supportive care, were analyzed. RESULTS:The probability of 5-year, event-free survival, overall survival, and cumulative incidence of relapse were 40.5%, 42.3%, and 47.4%, respectively. The risk of death was significantly increased among patients stratified as high-risk AML with an adjusted hazard ratio (HR) of 1.8 (95% confidence interval [CI]: 1.1-2.9, p = 0.01). The accessibility to MRD was significantly associated with the risk of death with an adjusted HR of 1.7 (95% CI: 1.1-2.5, p = 0.01). Patients with low-risk AML did carry a significant risk for both death, with an adjusted HR of 1.8 (95% CI: 1.1-3.0, p = 0.02), and relapse, with an adjusted HR of 2.6 (95% CI: 1.5-4.7, p < 0.001) for initial WBC greater than 100,000/mm3. CONCLUSION:Elevated initial WBC numbers and accessibility to MRD could be considered additional risk factors for unfavorable outcomes in childhood AML.