Search Results (573)

Prognostic scores that help allocate resources and time to the most critical patients could have potentially improved the response to the SARS-CoV-2 pandemic. We assessed the performance of five risk scores in predicting death or transfer to the intensive care unit (ICU) or sub-intensive care unit (SICU) in hospitalised patients with SARS-CoV-2 infection, with the three aims of retrospectively analysing the effectiveness of these tools, identifying frail patients at risk of death or complications due to infection, and applying these tools in the event of future pandemics. A retrospective observational study was conducted by evaluating data from patients hospitalised with SARS-CoV-2 infection. Among 134 patients considered, 119 were enrolled. All patients were adults, with a mean age of 64 years, and were hospitalised in the Infectious Diseases Division. We compared the five scores using receiver operating characteristic curves and calculation of the areas under the curve (AUCs) to determine their predictive performance. Four of the five scores demonstrated a high accuracy in predicting mortality among COVID-19-positive patients, with AUCs between 0.749 and 0.885. However, only two of the five scores showed good performance in predicting transfer to the ICU or SICU, with AUCs ranging from 0.740 to 0.802. The 4C Mortality Score and COVID-GRAM presented the highest performance for both outcomes. These two scores are easy to apply and low cost. They could still be used in clinical practice as predictive tools for frail and elderly patients with SARS-CoV-2 infection, as well as in the event of future pandemics. Full article

During carcinogenesis, cells must acquire a telomere maintenance mechanism in order to avoid telomere shortening-induced replicative senescence. While most tumors activate telomerase, a minority of them employ a recombinational mechanism called Alternative Lengthening of Telomeres (ALT). One of the most investigated features is the association between ALT and ATRX mutations, since this has been shown to be the gene with the highest rate of mutations among ALT tumors. However, most of these studies, and in particular, mechanistic studies in vitro, have been carried out on mesenchymal tumors (sarcomas). In the present study, using genomic and expression data from the DepMap portal, we identified several non-mesenchymal ALT cell lines, and we compared the incidence of ATRX and other gene mutations between ALT cell lines of different origins (mesenchymal, neural, epithelial, hematopoietic). We confirmed that ATRX is frequently mutated in mesenchymal and neural ALT cell lines but not in epithelial ones. Our results showed that mutations of ATRX or other proteins involved in the maintenance of telomere integrity are needed for ALT activation in all cell types, and ATRX is preferentially mutated in mesenchymal ALT cells. Besides a more precise interpretation of the role of ATRX loss in ALT establishment, we proposed a model in which mutation of this gene impairs differentiation in mesenchymal and neural cells (but not in epithelial ones). Therefore, we explained the high incidence of ATRX mutations in mesenchymal and neural tumors with the fact that they both trigger ALT and impair differentiation, thus promoting two steps at once in the process of carcinogenesis. Full article

Beta-thalassemia major is an inherited disorder that requires lifelong blood transfusions, with the risk of complications including poor oral health and dental caries. The objective of this study was to compare the oral microbiome diversity and composition in transfusion-dependent thalassemia patients and relate it to oral hygiene and dental caries. A cross-sectional analysis of 35 patients of beta-thalassemia major aged 6–18 years was performed. The status of oral hygiene was examined through the Oral Hygiene Index—Simplified (OHI-S) and Decayed, Missing, and Filled Teeth (DMFT) index. Saliva was taken for DNA extraction, followed by the 16S rRNA sequencing of V3-V4 hypervariable regions. The bioinformatics pipeline in QIIME2 was utilized for analyzing the comparison of microbial composition and diversity in groups of varying oral hygiene status and severity of caries. Metagenomic analysis revealed 3334 Amplicon Sequence Variants (ASVs), of which the most prevalent genera were Streptococcus, Haemophilus, Veillonella, Rothia, and Prevotella. High-oral-hygiene groups presented increased levels of cariogenic bacteria, while moderate-oral-hygiene groups presented an equilibrated microbiome. No statistically significant differences in microbial diversity were found between the study groups (p > 0.05). This study sheds light on the critical importance of oral hygiene in microbiome diversity in patients with beta-thalassemia major. Full article

The risk of anemia and iron overload is a global concern in beta (β)-thalassemia. The β-thalassemia primary treatment includes blood transfusion and iron chelation therapy; however, both are associated with risks such as anemia, iron depletion, overload, and oxidative stress if not adequately monitored. Therefore, this study investigates the effects of curcumin on anemia, iron overload, and oxidative stress in β-thalassemia. In this meta-analysis, search terms including “curcumin,” “Curcuma longa,” “curcuminoids,” “turmeric,” and “thalassemia” were used in Scopus and PubMed to identify studies published from inception to 15 February 2025. The quantitative analysis was performed using a meta-analysis web tool, and the effect estimates were reported as the mean difference (MD) or standardized mean difference (SMD), along with 95% confidence intervals (CI). Our analysis showed no significant effect on hemoglobin (p = 0.1788) and red blood cell count (p = 0.9534). In contrast, there was a significant decrease in serum ferritin [SMD = −0.24 (−0.46, −0.02), p = 0.0335], non–transferrin bound iron (NTBI), [SMD = −0.59 (−0.98, −0.19), p = 0.0039] and serum iron, [SMD = −0.30 (−0.60, −0.01), p = 0.0425]. Furthermore, there was a reduction in reactive oxygen species; [SMD = −0.83 (−1.23, −0.44), p < 0.0001] and malonaldehydes, [MD = −343.85 nmol/g Hb (−465.94, −221.76), p < 0.0001]. A dose of 500 mg of curcumin was found to be more effective in reducing the NTBI. The findings suggest that curcumin may help reduce iron overload and oxidative stress in β-thalassemia; however, its effect on improving anemia appears to be limited. Given the small sample size of the included studies, we recommend that future research involve larger cohorts and employ rigorous methodologies to evaluate the therapeutic potential of curcumin in β-thalassemia thoroughly. Additionally, we recommend using curcumin-enhancing strategies to improve its bioavailability and administer an optimal yet effective dose. Full article

The aberrant localization of the mutated nucleophosmin (NPM1) protein in the cytoplasm is the hallmark of the development of acute myeloid leukemia (AML); the gene, located in the nucleolus, codes for a protein that normally shuttles between the nucleus and the cytoplasm of the normal hematopoietic cells. Patients harboring NPM1 mutations are diagnosed as having NPM1-mutated AMLs, which are types of leukemia with distinct clinical and laboratory characteristics. The essential diagnostics for investigating NPM1-mutated AMLs, the interactions with concomitant mutations affecting prognosis and the therapeutic interventions that the treatment of such patients requires are discussed in this review. Novel investigational agents in current clinical trials are also highlighted, along with the roles of exportin 1 (XPO1), menin-KMT2A inhibitors and immunotherapy in NPM1-mutated AMLs. This review focuses on critically evaluating the available data and aims to reveal the secrets of NPM1-mutated AMLs. Full article

Iron overload is a significant concern for patients with thalassemia and often necessitates the use of iron-chelating agents to mitigate the associated complications. Selecting the most appropriate chelation therapy from the available options is a complex decision for healthcare professionals. To support this decision-making process, this study investigates the application of the “Fuzzy Analytic Hierarchy Process” (FAHP) for medication selection in thalassemia patients requiring iron-chelation therapy. In this study, 20 hematologists participated, and matrices related to the FAHP model were used to evaluate three primary iron chelators: deferoxamine, deferasirox, and deferiprone. The results revealed that deferiprone was the most effective choice, while deferasirox outperformed the others in terms of cost and patient satisfaction. Notably, deferoxamine exhibits the highest rate of side effects, followed by deferiprone and deferasirox. The results obtained from the FAHP analysis indicated a consensus among experts and highlighted deferasirox as the optimal choice for treating chronic iron overload in thalassemia patients. The study demonstrates the practical applicability of the FAHP methodology in guiding informed decisions for iron-chelation therapy. It provides insights to help healthcare professionals optimize treatment strategies for patients with thalassemia. Full article

Sickle-cell disease (SCD) is a group of inherited blood disorders in which a mutation in the β-globin (HBB) gene causes red blood cells to produce abnormal hemoglobin, known as Hb S. SCD is characterized by an autosomal-recessive pattern of inheritance, implying that for a child to manifest the condition, they must inherit an Hb S allele from both parents (HbSS) or one Hb S allele and another β-globin variant, such as Hb C or β-thalassemia (HbSC, HbS/β-thal). It has been observed that (heterozygote) carriers of one copy of the sickle-cell trait (HbAS) are typically healthy and can even gain partial protection from severe malaria. The term “severe and complicated malaria” is delineated based on specific clinical and laboratory characteristics in the presence of Plasmodium falciparum parasitemia. The prevalent forms of severe malaria among African children include cerebral malaria, respiratory distress, and severe malaria anemia. Cerebral malaria is a rare complication of malaria infection and is associated with a high mortality rate. Full article

Background/Objectives: Chronic anemia and iron overload in thalassemia lead to organ failures, including the heart, liver, endocrine glands, and spleen. Comprehensive multidisciplinary management is pivotal in improving patients’ clinical outcomes and well-being. The report aims to present a rare case of improved clinical condition in a transfusion-dependent thalassemia patient. Methods: Medical summaries were collected to compare patients’ conditions at various time frames. Furthermore, the report was composed in chronological order. Results: A 31-year-old male diagnosed with beta-thalassemia major and multiple comorbidities, including diabetes with a history of diabetic ketoacidosis, heart failure with a history of cardiac arrest, hepatomegaly, severe thoracolumbar scoliosis, and depression, exhibited a high physical endurance. The patient managed to maintain a strong treatment adherence and undergo intensive regular multidisciplinary follow-ups. The patient gained cardiac function improvement and metabolic stabilization, leading to completing a 5 k marathon without complication. Conclusions: Intensive management of iron overload through double oral chelation allows organ function improvement. Better mental health attenuates the patient’s overall well-being and is attributed to the ability to gain high physical endurance. Full article

Objectives: We compared changes in hepatic and cardiac iron levels, left ventricular (LV) and right ventricular (RV) dimensions and function, and bi-atrial areas, all assessed through magnetic resonance imaging (MRI), between patients with non-transfusion-dependent thalassemia (NTDT) and those with neo-transfusion-dependent thalassemia (neo-TDT) over an 18-month follow-up period. Methods: We included 32 NTDT patients (42.78 ± 12.62 years, 53.1% females) and 58 neo-TDT (>4 transfusions per year) patients (44.08 ± 14.13 years, 46.6% females), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. Iron overload was quantified by T2* technique, biventricular function and atrial areas by cine images. Macroscopic myocardial fibrosis was detected by the late gadolinium enhancement technique. Results: Changes in cardiac and hepatic iron levels, in biventricular ejection fractions, in LV mass index, and bi-atrial areas were comparable between the two groups. A trend of worsening biventricular dimensions was observed in the NTDT group, while the neo-TDT group showed an improvement (decrease) in biventricular size (LV stroke volume index: p = 0.036; LV cardiac index: p = 0.031; RV end-diastolic volume index: p = 0.034; RV stroke volume index: p = 0.033). The inter-group comparison showed significant differences in the changes of biventricular end-diastolic volume indexes (LV: p = 0.011 and RV: p = 0.034) and stroke volume indexes (LV: p = 0.036 and RV: p = 0.033) and in the cardiac index (p < 0.0001). At both MRI scans, the frequency of replacement myocardial fibrosis was comparable between the two groups. Conclusions: Our 18-month longitudinal data revealed distinct patterns of cardiac remodeling in NTDT and neo-TDT patients. The progressive ventricular dilation observed in NTDT patients highlights the need for careful MRI monitoring and potential interventions to address the long-term cardiac consequences of anemia. Full article

Nucleic acid detection technology is crucial for molecular diagnosis. The advent of CRISPR/Cas12a-based nucleic acid detection has considerably broadened its scope, from the identification of infectious disease-causing microorganisms to the detection of disease-associated biomarkers. This innovative system capitalizes on the non-specific single-strand cleavage activity of Cas12a upon target DNA recognition. By employing a fluorescent probe in the form of a single-stranded DNA/RNA, this technology enables the observation of fluorescence changes resulting from nonspecific cleavage, thereby facilitating detection. CRISPR/Cas12a-based detection systems can be regarded as a new type of biosensor, offering a practical and efficient approach for nucleic acid analysis in various diagnostic settings. CRISPR/Cas12a-based biosensors outperform conventional nucleic acid detection methods in terms of portability, simplicity, speed, and efficiency. In this review, we elucidate the detection principle of CRISPR/Cas12a-based biosensors and their application in disease diagnostics and discuss recent innovations and technological challenges, aiming to provide insights for the research and further development of CRISPR/Cas12a-based biosensors in personalized medicine. Our findings show that although CRISPR/Cas12a-based biosensors have considerable potential for various applications and theoretical research, certain challenges remain. These include simplifying the reaction process, enhancing precision, broadening the scope of disease detection, and facilitating the translation of research findings into clinical practice. We anticipate that ongoing advancements in CRISPR/Cas12a-based biosensors will address these challenges. Full article

Testicular orphan receptors TR2 and TR4 serve as central regulators of erythropoiesis, orchestrating the entire continuum of erythroid progenitor cell proliferation, differentiation, and maturation. As core components of the direct repeat erythroid determinant (DRED) complex, they activate erythroid-specific transcriptional programs to dynamically control the spatiotemporal expression of globin genes. These nuclear receptors not only engage in functional interactions with key erythroid transcription factors GATA1 and KLF1 to coregulate erythroid differentiation and maturation but also recruit epigenetic modifier complexes such as DNMT1 and LSD1 to modulate chromatin states dynamically. Research has established that dysfunctions in TR2/TR4 are implicated in β-thalassemia and sickle cell disease (SCD): β-thalassemia is associated with the defective silencing of γ-globin genes, while in SCD, TR2/TR4 antagonizes BCL11A to reactivate fetal hemoglobin (HbF) expression. This review systematically dissects the molecular regulatory networks of TR2/TR4 in erythroid cells, interprets their dual regulatory properties across different stages of erythroid differentiation, and explores the therapeutic potential of targeting TR2/TR4 for treating erythroid-related disorders such as β-thalassemia and SCD, thereby providing novel directions for hematological disorder therapy. Full article

Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid. Material & Methods: A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and APTw imaging with a 3T MR scanner. Receiver operating characteristic (ROC) curves were calculated for the APTw% mean, median, and max signal for the different molecular biomarkers. A logistic regression model was constructed for combined mean and median APTw% signals for p53 expression. Results: The whole-tumor max APTw% signal could significantly differentiate MGMTp from non-MGMTp HGG, p = 0.035. A cutoff of 4.28% max APTw% signal yielded AUC (area under the curve) = 0.702, with 70.6% sensitivity and 66.7% specificity. The mean/median APTw% signals differed significantly in p53 normal versus p53-overexpressed HGG s: 1.81%/1.83% vs. 1.15%/1.18%, p = 0.002/0.006, respectively. Cutoffs of 1.25%/1.33% for the mean/median APTw% signals yielded AUCs of 0.786/0.757, sensitivities of 76.9%/76.9%, and specificities of 50%/66.2%, p = 0.002/0.006, respectively. A logistic regression model with a combined mean and median APTw% signal for p53 status yielded an AUC = 0.788 and 76.9% sensitivity and 66.2% specificity. ATRX-, IDH- wild type (wt) vs. mutation (mut), and the level of Ki-67 did not differ significantly, but trends were found: IDH-wt and low Ki-67 showed higher mean/median/max APTw% signals vs. IDH-mut and high Ki-67, respectively. ATRX-wt vs. mutation showed higher mean and median APTw% signals but lower max APTw% signal. Conclusions: APTw imaging can potentially be a useful marker for the stratification of p53 expression and MGMT status in high-grade glioma in the preoperative setting and potentially aid surgical decision-making. Full article

Background: This study aimed to investigate the effects of allogeneic hematopoietic stem cell transplantation (HSCT) on quality of life and behavioral problems in children diagnosed with leukemia and β-thalassemia major, with a focus on post-transplant diagnosis-specific differences in psychosocial adjustment. Method: This study included 112 children (63 children with acute leukemia, 49 children with β-thalassemia major) aged 6–18 years, along with a control group of 30 healthy children within the same age range. The Pediatric Quality of Life Inventory (PedsQL) and the Child Behavior Checklist for Ages 6–18 (CBCL) were administered. Participants were categorized into five groups, and the outcomes were compared accordingly. Results: The emotional functioning subscale scores of the PedsQL were significantly lower in children with leukemia and those who had undergone HSCT for leukemia, when compared to children with thalassemia (p < 0.05). The social functioning subscale scores were also significantly lower in children with leukemia who underwent HSCT compared to those with thalassemia (p < 0.05). The CBCL internalizing scores were higher in children with leukemia and post-HSCT leukemia patients than in their healthy peers (p < 0.05). Over time, both diagnostic groups showed improvements, with total PedsQL scores increasing and total CBCL scores decreasing after HSCT. Conclusions: This study demonstrates that quality of life improved and behavioral problems diminished over time following HSCT. However, the psychosocial impact of HSCT varied depending on the underlying disease, with children diagnosed with leukemia being slightly more adversely affected. These findings suggest that interventions aimed at improving quality of life and addressing behavioral issues should be tailored to the specific diagnosis. Full article

Background/Objectives: Red blood cell (RBC) parameters are routinely used to screen for α- and β-thalassemia traits as part of prenatal diagnosis for severe fetal thalassemia in countries with a high prevalence of the disease. In clinical practice, the same cut-off values for these parameters are applied to both females and males. However, given that the normal reference ranges for some RBC parameters differ significantly between sexes, sex-specific cut-off values may be more appropriate, especially in combination. To date, the effectiveness of RBC indices in males for predicting α- and β-thalassemia traits has not been evaluated. The objectives of this study are to assess the diagnostic performance of individual and combined RBC parameters in detecting α⁰-thalassemia traits among non-anemic males. Methods: This diagnostic study is a secondary analysis of prospectively collected data from our project on prenatal control of severe thalassemia. The study population comprised male partners of pregnant women who underwent thalassemia screening during their first antenatal visit. RBC parameters, including hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), and RBC count, were measured for each participant. Carrier status for the α0-thalassemia Southeast Asian (SEA) genotype was confirmed by using a polymerase chain reaction (PCR)-based method. The diagnostic performance of each RBC parameter and their combinations, based on predictive models generated using logistic regression, was evaluated and compared using receiver operating characteristic (ROC) curves. Results: A total of 486 Thai males were recruited for the study, including 137 individuals with the α⁰-thalassemia trait and 349 with a normal α-thalassemia genotype (control group). All RBC parameters, except for Hct, differed significantly between the two groups. Among the individual indices, MCH exhibited the highest diagnostic accuracy, followed by MCV, with areas under the curve (AUCs) of 0.981 and 0.973, respectively. An MCH cut-off value of 26 pg and an MCV cut-off value of 80 fL provided a sensitivity of 100% for both indices, with specificities of 88.5% and 86.8%, respectively. The combination predictive model provided the best diagnostic performance, achieving an AUC of 0.987, which was slightly but significantly higher than that of any individual parameter. This model yielded a sensitivity of 100% and a significantly higher specificity of 90.8% at a cut-off probability of 7.0%. Conclusions: MCH and MCV demonstrated excellent screening performance for identifying α0-thalassemia carriers in males. However, the combination model exhibited even greater accuracy while reducing the false-positive rate. Implementing this model could minimize the need for unnecessary PCR testing, leading to substantial cost savings. Full article

Hemoglobin disorders are among the most common inherited diseases worldwide. Their clinical manifestations range from anemia to more severe forms associated with neurological impairments. These complications can result as secondary consequences of the disease’s clinical manifestations or be directly linked to genetic mutations. In this study, we present two families with neurological impairments who were referred to us for complementary hematological and biochemical analyses. Complete blood count, methemoglobin level, and methemoglobin reductase activity were assessed. Molecular analyses were performed using whole-exome sequencing, and the segregation of the identified mutations was confirmed with direct sequencing. Their pathogenicity and conservation were evaluated using various bioinformatics tools. Clinical and hematological findings suggested X-linked alpha-thalassemia/impaired intellectual development syndrome in the first family and recessive congenital methemoglobinemia type II in the second. This was confirmed by the identification of pathogenic mutations ATRX: p.Arg2131Gln and CYB5R3: p.Ala179Thr, respectively. Although these variants have been previously reported worldwide, they were identified for the first time in our population. Our results contribute to the understanding of the pathogenesis of these rare disorders and provide a basis for diagnosis, treatment, and genetic counseling. The mechanisms by which these mutations contribute to neurological symptoms are discussed. Full article