Alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutation is an uncommon but biologically relevant molecular feature in glioblastoma (GBM), linked to tumor heterogeneity, DNA damage response pathways, and treatment-relevant biology. Noninvasive prediction of ATRX status remains challenging, and the incremental value of physiologic MRI beyond structural imaging is unclear.

Chronic diseases in children require long-term management and affect physical, psychological, and social well-being. Treatment adherence and self-management skills in children remain a challenge, particularly in conditions such as thalassemia, which require lifelong treatment. Innovative approaches such as gamification are being developed to improve children's engagement and health behaviors, but their application in thalassemia remains limited. This study aimed to map gamification-based interventions addressing treatment adherence and self-management in children with chronic diseases and identify their implications for thalassemia. This scoping review followed the Joanna Briggs Institute (JBI) methodology and PRISMA-ScR guidelines. A literature search was conducted in five databases (PubMed, Scopus, ScienceDirect, Sage Journals, and MEDLINE) covering the years 2016-2026. Article selection followed the PCC framework (Population: children with chronic diseases; Concept: gamification-based interventions for treatment adherence and self-management; Context: pediatric chronic disease management). A total of 16 studies involving children with various chronic diseases were included. Interventions included gamified mobile applications, serious games, augmented reality (AR), virtual reality (VR), and digital therapeutic platforms. Across the included studies, treatment adherence and self-management were the most frequently reported outcomes, followed by improvements in disease-related knowledge, technical skills, engagement, and health literacy. Several studies also reported improvements in selected clinical indicators. However, substantial heterogeneity in intervention design, outcomes, and follow-up duration limited comparisons across studies. Evidence specific to thalassemia was limited to one study, which reported improvements in health literacy, self-management, and decision-making. The mapped evidence suggests that gamification-based interventions may support treatment adherence and self-management in children with chronic diseases. Thalassemia appears to be a promising target for future digital health intervention development. However, further theory-based studies with robust designs and longer follow-up are needed.

Thalassemia represents a spectrum of rare, inherited blood disorders associated with a range of disease- and treatment-related complications. Thalassemia can have a significant effect on the female reproductive system, and obstetrics and gynecology specialists have a key role to play in managing the disease as part of a multidisciplinary team. Here, we review the role of obstetrics and gynecology specialists in thalassemia from puberty to pregnancy and postnatal support, including diagnosis and management of complications, supporting patients through pubertal and fertility issues and the risks associated with pregnancy.

Β-thalassemia trait (β-TT) is a common hemoglobin disorder that is frequently confused with iron deficiency anemia (IDA), leading potentially low-yield confirmatory hemoglobin fraction analysis and increased use of healthcare resources. To assess the appropriateness of β-TT screening in patients with microcytic hypochromic anemia and to detect laboratory and clinical predictors of potentially low yield testing. A total of 12,622 patients with microcytic hypochromic anemia who underwent hemoglobin fraction analysis by HPLC between February 2023 to July 2025 were included in this retrospective cross-sectional study. Data on complete blood counts, Pathologist remarks, and HPLC results were collected. Red cell indices (Mentzer Index) , HbA2 levels, and recorded clinical context were used to operationally classify testing appropriateness. Multivariable multinomial logistic regression was used to identify predictors of test appropriateness. Among the 12,622 patients, 3932 (31.2%) had confirmed β-TT, 8312 (65.9%) had non-β-TT microcytic anemia, and 378 (3.0%) had borderline HbA2 values. Testing was categorized as appropriate in 2544 cases (20.2%), potentially low-yield in 5678 cases (45.0%), and unclear in 4400 cases (34.9%) based on red cell indices, HbA2 levels, and clinical context. While suspected β-TT significantly predicted appropriate testing, suspected IDA (OR 4.00, p < 0.001), female sex (OR 1.50, p < 0.001), and post-transfusion samples (OR 4.27, p < 0.001) were independently associated with potentially low-yield testing. The possible masking effect of iron deficiency on β-TT detection was reflected by the fact that 490 patients (3.9%) were recommended to undergo a repeat HPLC after iron supplementation to rule out iron deficiency-mediated suppression of HbA2 as a potential masking factor for β-TT. A significant portion of β-TT screening my be potentially low-yield, which may affect clinical results and available resources. Test utilization may be optimized and diagnostic accuracy may be improved by evaluating iron status, repeating testing after iron correction when indicated and interpreting red cell indices in appropriate clinical setting.

Hydroxyurea (HU) is the most widely prescribed disease-modifying treatment in sickle cell disease (SCD), though treatment responses vary due to metabolism and adherence. We examined HU blood levels and treatment response in patients with homozygous sickle cell disease (HbSS). We measured HU in whole blood of 955 SCD patients enrolled in GenoMed4All using mass spectrometry. HU detection was defined as Z-score > 2.5 relative to untreated healthy controls. Among HbSS patients not receiving recent transfusion therapy (n = 539), HU was detected in 39% (143/369) of HU-prescribed patients ≥ 10 years (median age 31.8 [10.0-69.9]). In only 24% (23/109) of young patients (< 10 years, median age 5.9 [1.2-9.9]), HU was detected, despite comparable HU dosing (18.8 vs. 20.3 mg/kg/day). Detectable HU was associated with increased MCV (p < 0.001), and in patients ≥ 10 years also with increased HbF, despite low HbF (< 10%) in 25%. Neutropenia occurred in 8.0% of patients with detectable HU, 4.5% with undetected HU. Only one patient had severe neutropenia (< 0.5 × 10e9/l). In young patients, neutropenia occurred in 1.4% with undetected HU, and in 8.7% with detected HU. This is the largest study to date that reports data on HU levels in HbSS patients. Most HU-prescribed patients, particularly young patients, had undetectable HU levels. Low MCV, HbF, and absent toxicity in children and limited toxicity in adults suggest that treatment for patients with undetectable HU is suboptimal. These findings warrant the need to optimize dosing and adherence to improve treatment in SCD, especially in young patients.

Adipsic hypernatremia is a rare hypothalamic disorder characterized by impaired thirst despite preserved renal concentrating ability and may coexist with multisystem neuroendocrine and sleep disturbances. We report a 20-year-old male with beta-thalassemia minor presenting with severe hypernatremia with serum sodium of 170 mEq/L (SI: 170 mmol/L) (reference range 133-146 mEq/L [SI: 133-146 mmol/L]), absent thirst, weight loss, fatigue, hypogonadotropic hypogonadism, and hyperprolactinemia, along with excessive daytime sleepiness, hypnagogic hallucinations, and emotion-triggered cataplexy. Laboratory evaluation confirmed preserved renal concentrating ability, and pituitary magnetic resonance imaging was normal. Findings were consistent with adipsic hypernatremia due to functional hypothalamic dysfunction, with coexisting severe obstructive sleep apnea confirmed on polysomnography (apnea-hypopnea index [AHI] 35.9 events/hour) and presumed narcolepsy with cataplexy. Management included structured fluid intake, testosterone replacement, cabergoline, wake-promoting agents (modafinil, methylphenidate), and continuous positive airway pressure therapy. This case underscores the complex interplay between hypothalamic dysfunction, endocrine abnormalities, and sleep disorders, highlighting the importance of early recognition and structured management to prevent recurrent hypernatremia and optimize clinical outcomes.

We assessed the effect of hepatic iron levels on liver apparent diffusion coefficient (ADC) values assessed by magnetic resonance imaging (MRI) and the influence of different b-values on the extent of this association. We prospectively enrolled 110 patients (60 women, 33.05 ± 7.86 years) with beta-thalassemia. Single-shot echoplanar diffusion-weighted imaging (DWI) with different b values was acquired, and ADC_200 (b-values 0/200 s/mm2), ADC_600 (b-values 0/600 s/mm2), and ADC_1000 (b-values 0/1000 s/mm2) were obtained. Liver T2* values were measured with a gradient-echo multiecho sequence and were converted into liver iron concentration (LIC) values. There was a significant difference among the three different ADC values (p < 0.0001). Mean MRI LIC values were 7.99 ± 10.09 mg/g dw, and 64 (58.2%) patients had liver iron overload (LIC > 3 mg/g dw). Significant negative correlation was found between MRI LIC values and ADC_200 values (R = -0.284, p = 0.003), ADC_600 values (R = -0.645, p < 0.00001), and ADC_1000 values (R = -0.842, p < 0.0001). MRI LIC was more strongly correlated with both ADC_600 and ADC_1000 than with ADC_200 (p < 0.00001 for both comparisons) and with ADC_600 than with ADC_200 (p < 0.0001). ADC_200 values were comparable between patients without and with liver iron overload (2.11 ± 0.53 vs. 1.87 ± 0.89 × 10-3 mm2/s, p = 0.081), while patients with liver iron overload had significantly decreased ADC_600 values (0.91 ± 0.72 vs. 1.52 ± 0.49 × 10-3 mm2/s, p < 0.0001), and ADC_1000 values (0.48 ± 0.38 vs. 1.23 ± 0.23 × 10-3 mm2/s, p < 0.0001). In conclusion, the demonstrated inverse correlation between LIC and liver ADC values, accentuated at higher diffusion b-values, has relevant clinical implications, indicating that liver iron overload acts as a confounding factor in quantitative DWI and should be accounted for to avoid misinterpretation of liver ADC measurements in diagnostic and therapeutic workflows.

β-thalassemia major induces chronic immune dysregulation driven by persistent anemia, iron overload, and repeated blood transfusions. It is associated with a complex and dynamic reshaping of immune homeostasis. In this context, immune checkpoints, CTLA-4, LAG-3, and TIM-3, have emerged as critical regulators of the balance between immune activation and tolerance. This study aimed to evaluate their expression and association with alloantibody formation. Pediatric β-thalassemia major patients on regular transfusions, including 22 alloimmunized and 22 nonalloimmunized, along with 22 healthy controls, were recruited for this study. Expression of CTLA-4, LAG-3, and TIM-3 was analyzed using reverse transcription PCR. TIM-3 expression was lower in patients than in controls (P = .003). This reduction was particularly evident in alloimmunized patients compared with the nonalloimmunized group (P = .001). Using random forest machine learning, cross-validated variable importance identified TIM-3 and CTLA-4 as important variables in the alloimmunization process. The pooled receiver operating characteristic (ROC) curve for the 3 studied markers in the patient groups demonstrated good discriminative performance between alloimmunized and non alloimmunized patients, with an area under the curve of 0.779, specificity 90.9%, and sensitivity 68.2%, outperforming conventional statistical analysis. In conclusion, downregulation of TIM-3 and CTLA-4 in pediatric β-thalassemia major patients may contribute to alloantibody formation.