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Mortality rates among critically ill pediatric patients remain a persistent challenge. It is imperative to identify patients at higher risk to effectively allocate appropriate resources. Our study aimed to develop a prediction score based on clinical parameters and hemogram to predict pediatric intensive care unit (PICU) mortality. We conducted a retrospective study to develop a clinical prediction score using data from children aged 1 month to 18 years admitted for at least 24 hours to the PICU at Chiang Mai University between January 2018 and December 2022. PICU mortality was defined as death within 28 days of admission. The score was developed using multivariable logistic regression and assessed for calibration and discrimination. There were 29 deaths in 330 children (8.8%). Our model for predicting 28-day ICU mortality uses four key predictors: male gender, use of vasoactive drugs, red blood cell distribution width (RDW) ≥15.9%, and platelet distribution width (PDW), categorized as follows: <10% (0 points), 10-14.9% (2 points), and ≥15% (4 points). Scores range from 0 to 8, with a cutoff value of 5 to differentiate low-risk (<5) from high-risk (≥5) groups. The tool demonstrates excellent performance with an AuROC curve of 0.86 (95% CI: 0.80-0.91, p<0.001) showing excellent discrimination and calibration, 82.8% sensitivity, and 73.1% specificity, respectively. The score, developed from clinical data and hemogram, demonstrated potential in predicting ICU mortality among critically ill children. However, further studies are necessary to externally validate the score before it can be confidentially implemented in clinical practices.

Background l -Asparaginase is a crucial component of acute lymphoblastic leukemia (ALL) treatment. However, hypersensitivity is a common adverse event. This study aimed to identify risk factors for l -asparaginase hypersensitivity in childhood ALL. Methods Children treated for ALL at Chiang Mai University Hospital, Thailand, between 2005 and 2020 were included. Demographic data, clinical characteristics, and factors related to l -asparaginase were retrospectively reviewed. Results l -Asparaginase hypersensitivity was observed in 24 of 216 children with ALL (11.1%). All patients received native l -asparaginase intramuscularly, and events occurred exclusively during the post-induction phase without concurrent corticosteroid use. Univariable analysis showed that relapsed ALL, higher accumulated doses, increased exposure days, and longer interval between drug administrations were potential risk factors. In multivariable logistic regression analysis, interruption of l -asparaginase administration for ≥ 52 weeks and exposure duration of ≥ 15 days were independent risk factors, with adjusted odds ratio of 16.481 (95% CI 3.248–83.617, p  = 0.001) and 4.919 (95% CI 1.138–21.263, p  = 0.033), respectively. Conclusions Children with ALL who require re-exposure to l -asparaginase after 52-week interruption or who have received l -asparaginase for ≥ 15 exposure days are at risk of developing l -asparaginase hypersensitivity. Further management strategies in this setting should be evaluated.

Hemophilia is an inherited bleeding disorder caused by deficiency of a specific coagulation factor. Factor VIII deficiency is responsible for hemophilia A while factor IX deficiency is responsible for hemophilia B. As per the 2020 annual global survey by the World Federation of Hemophilia, only 1828 Thai hemophiliacs have been registered to the national healthcare system. The reason for the low number is the underdiagnosis which is a major concern in the real-world practice among Asian countries. In Thailand, most hemophiliacs are diagnosed by general practitioners, pediatricians or internists at rural hospitals and are referred to hemophilia specialists at the Hemophilia Treatment Centers (HTCs). Despite the challenges pertaining to infrastructure and cost of treatment, Thailand has progressed substantially in providing the required hemophilia care, as evidenced by an evolution in acquiring and sharing knowledge as well as collaborative efforts among multiple stakeholders over the past three decades. In this letter-to-the-editor, the authors have summarized the practices for and challenges faced with hemophilia management in Thailand.

AimsAnalysis of the F8 gene helps predict the risk of developing factor VIII (FVIII) inhibitors and the depth of phenotype in haemophilia A (HA) patients. Since data in Southeast Asian countries remain scarce, we aim to study F8 variation correlated with HA phenotypes in Thailand.MethodsThai patients with HA were enrolled from seven haemophilia treatment centres during 2022–2023. Using peripheral blood DNA, inverse shifting-polymerase chain reaction (IS-PCR) for F8-intron 22 inversion (Inv22) and F8-intron 1 inversion (Inv1) was performed. Whole exome sequencing (WES) was explored in cases without Inv22/Inv1.ResultsOf 124 patients with HA, 91.9% were detected with a causative F8 variant, including Inv22 (30.6%), Inv1 (1.6%), missense (23.4%), nonsense (16.9%) and small insertion/deletion (16.1%) mutations. Inv22, small insertion/deletion and nonsense were associated with severe HA, compared with missense variants, by the ORs of 13.9 (95% CI, 4.2 to 56.7), 14.7 (95% CI, 3.4 to 104.7) and 15.6 (95% CI, 3.6 to 110.2), respectively. While nonsense variants affecting the light chain increased the risk of developing FVIII inhibitors (OR, 6.8; 95% CI, 1.5 to 32.6) compared with the low-risk (small insertion/deletion, missense and splice-site) variants. Twelve patients (9.7%) harboured novel F8 variants, comprising five missense (p.Pro540Leu, p.Ser564Pro, p.Leu668Pro, p.Ala1721Glu, p.His2024Pro), five small insertion/deletion (p.Val502SerfsTer13, p.Ile522PhefsTer13, p.Phe992LysfsTer11, p.Leu1223PhefsTer18, c.6427_6429+3delATGGTA) and one nonsense mutations (p.Glu1292Ter).ConclusionsIS-PCR followed by WES successfully assesses F8 alterations in most HA cases. With several unique variants, severe HA in Thailand is considerably caused by Inv22, small insertion/deletion and nonsense, whereas missense variants are more responsible for nonsevere HA phenotypes.

Background/Objectives: Red blood cell distribution width (RDW) and mean platelet volume (MPV) are well-established prognostic biomarkers across various medical conditions. However, their role in predicting mortality among critically ill pediatric patients remains unclear. This study investigates the association between RDW, MPV, and 28-day mortality in pediatric intensive care unit (PICU) patients. Methods: This retrospective cohort study analyzed data from children aged 1 month to 18 years who were admitted to the PICUs at Chiang Mai University Hospital for ≥24 h between January 2018 and December 2022. The primary outcome was 28-day PICU mortality. A log-binomial regression analysis was conducted to assess the association of RDW and MPV with 28-day PICU mortality, adjusting for age, sex, mechanical ventilation, vasoactive drug use, continuous renal replacement therapy, and multiorgan failure. Results: A total of 580 PICU patients were included, 55.3% male, with a median age of 5.9 (IQR: 4.7–10.4) months. The 28-day PICU mortality rate was 9.8% (57/580). Respiratory failure and acute respiratory distress syndrome were the most common admission diagnoses (72.1%). Elevated RDW (≥15%) and MPV (≥10 fL) were independently associated with increased 28-day PICU mortality (adjusted RR: 2.73, 95% CI: 1.45–5.13 and 2.38, and 95% CI: 1.43–3.93, respectively). Both markers demonstrated high negative predictive values (RDW: 96.0% and MPV: 94.6%). Conclusions: Elevated RDW (≥15%) and MPV (≥10 fL) were independently associated with increased 28-day PICU mortality. These findings highlight their potential utility as accessible and cost-effective biomarkers for early risk stratification in critically ill pediatric patients.

Background This study aimed to determine the elements and the extent of information that child participants and their parents would like to read in an informed assent form (IAF)/informed consent form (ICF) of a pediatric drug trial. Methods A descriptive survey was conducted to determine the perceived importance of each element of the ICF content from child participants and their parents who underwent informed assent/consent of a multi-center pediatric drug trial. The respondents were asked to indicate the level of importance of each item in a questionnaire, by giving a rating scale from 1 (not important) to 5 (very important). Results A total of 22 families, 17 child participants with the diagnosis of hematology or oncology diseases and 27 parents, were enrolled. Among 30 items, risk–benefit aspects (i.e., direct health benefit [mean: 4.71 for child respondents, 4.89 for parent respondents], indirect/societal benefit [mean: 4.65, 4.85], major foreseeable risk [mean: 4.47, 4.78], post-trial benefit/provision [mean: 4.59, 4.74], and all adverse effects of the drug including uncommon adverse effects [mean: 4.53, 4.74]) were perceived to be of most concerning items from both child participants’ and parents’ viewpoint. None of the items were considered ‘slightly important’ or lower by more than 20% of the respondents. Conclusions For pediatric drug trials, risk–benefit information (including direct health benefit, indirect/societal benefit, and post-trial benefit/provision, as well as major foreseeable risk and adverse effects of the drug) should be made a salient feature of an IAF/ICF. This empirical data could help related stakeholders arrange essential information in order of importance and tailor an IAF/ICF to better suit child participants’ and parents’ needs, particularly for pediatric drug trials involving children with the diagnosis of hematology or oncology diseases. Key points Informed assent/consent remains one of the most challenging issues in pediatric drug trials, with no trustworthy clue or guidance to determine what type of information and the extent of information to be provided in an informed assent/consent form. Based on our empirical data, risk–benefit aspects related to trial participation were perceived to be more important than general information or technical details of the trial, although all the elements are deemed useful, to a certain degree, to both child participants and their parents. Both child participants and their parents did not want to read an unduly long form, with the maximum acceptable page length of no more than 5–8 pages.

Background Clinical outcomes of patients with osteosarcoma remain unsatisfactory, with little improvement in a 5-year overall survival over the past three decades. There is a substantial need for further research and development to identify and develop more efficacious agents/regimens in order to improve clinical outcomes of patients for whom the prognosis is unfavorable. Recently, mycophenolate mofetil, a prodrug of mycophenolic acid, has been found to have anticancer activity against osteosarcoma in both in vitro and animal experiments, so that further investigation in humans is warranted. Methods A total of 27 patients with high-grade locally advanced or metastatic osteosarcoma will be enrolled into this phase II, multi-center, open-label, single-arm, two-stage clinical trial. The main objectives of this study are to determine the efficacy and safety of mycophenolate mofetil in the patients. The primary endpoint is progression-free survival at 16 weeks; the secondary endpoints include progression-free survival, overall survival, overall response rate, safety parameters, pharmacokinetic parameters, biomarkers, pain score, and quality of life. Mycophenolate mofetil at the initial dose of 5 g/day or lower will be administered for 4 cycles (28 days/cycle) or until disease progression or unacceptable toxicity. The dose of mycophenolate mofetil may be reduced by 1–2 g/day or withheld for some Grade 3 or Grade 4 toxicities whenever clinically needed. The duration of study participation is approximately 4–5 months, with a minimum of 12 study visits. If mycophenolate mofetil proves beneficial to some patients, as evidenced by stable disease or partial response at 16 weeks, administration of mycophenolate mofetil will continue in the extension period. Discussion This trial is the first step in the translation of therapeutic potential of mycophenolate mofetil emerging from in vitro and animal studies into the clinical domain. It is designed to assess the efficacy and safety of mycophenolate mofetil in patients with high-grade locally advanced or metastatic osteosarcoma. The results will provide important information about whether or not mycophenolate mofetil is worth further development. Trial registration This trial was prospectively registered on Thai Clinical Trials Registry (registration number: TCTR20190701001 ). The posted information will be updated as needed to reflect protocol amendments and study progress.

Hemophilia cannot be diagnosed in most laboratories of economically less-developed countries leading to high mortality and morbidity rates. A diagnostic tool was established ranging from bleeding assessment and a simple bedside test of mixing venous clotting time (VCT) to comprehensive DNA analysis for patients with hemophilia. Patients with known (n=80) and suspected hemophilia (n=14) were included. Their bleeding symptoms were initially evaluated using verified translated-Thai ISTH bleeding assessment tool. Then, blood samples were drawn using a two-syringe technique, 2 mL each was placed in three tubes, for the mixing VCT and citrate blood was kept for coagulogram and coagulation factor assay. Finally, DNA analysis was determined. A total of 94 patients with hemophilia (A68, B26) defined as severe (A 57, B 17), moderate (A 7, B 5), and mild degrees (A 4, B 4) with the mean (SD) age of 14.0 (11.7) years and 24 normal controls aged 25.5 (4.5), were enrolled in the study. The mean (SD) bleeding score of patients with hemophilia was 13.5 (5.5), which did not significantly differ between patients with hemophilia A and B. The mixing venous clotting time offered the presumptive diagnosis of hemophilia A and B, which were subsequently confirmed by the prolonged APTT, low FVIII:C and FIX:C and mutations on the factor VIII and IX genes. A diagnostic tool for bleeding assessment, mixing venous clotting time, coagulogram, coagulation factor assay, and DNA analysis for patients with hemophilia has been established in the existing health-care system.

Orbital involvement is one of the extramedullary manifestations in acute leukemia. It is common in acute myeloid leukemia, but rare in acute lymphoblastic leukemia (ALL). We described a 3-year-old girl who presented with progressive proptosis of the right eye and was later diagnosed with precursor B-cell ALL. Initial blood count showed Hb 6.9 g/dL, WBC 42,000/mm3, lymphoblast 50%, and platelet count 185,000/mm3. Bone marrow aspiration revealed 90% lymphoblasts with positivity for CD10, CD19, CD20, CD22, and HLA-DR markers. Computed tomography (CT) scan of the brain and orbit revealed a homogeneous enhancing mass involving the right orbit with intracranial extension. The cytogenetic study showed 46,XX chromosomes. After 4 weeks of induction chemotherapy for very high-risk ALL, although the bone marrow was in remission, the proptosis was partially resolved. CT scan confirmed a decrease in size of the right orbital mass and degree of intracranial extension. Unfortunately, the patient abandoned the treatment after the induction chemotherapy. The actual incidence of orbital involvement in ALL is unknown. Previous case reports describe diverse manifestations of orbital involvement in ALL. The involvement may be unilateral or bilateral, may occur at first diagnosis or at relapse, and may be seen in isolation or with other systemic symptoms. There is no standard treatment protocol. Chemotherapy with or without radiotherapy is generally suggested. The role of upfront hematopoietic stem cell transplantation remains inconclusive. The previously reported prognosis of ALL with orbital involvement is poor.