Search Results (150)

Diabetes, a major global healthcare challenge, is characterized by chronic hyperglycemia and significantly exacerbates the severity of systemic complications. Iron, an essential element ubiquitously present in biological systems, is involved in many biological processes facilitating cell proliferation and growth. However, excessive iron accumulation promotes oxidative damage through the Fenton reaction, thereby increasing the incidence of diabetes and worsening diabetic complications. Notably, ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key mechanism underlying diabetes and diabetic complications. In this review, we provide an update on the current understanding of iron metabolism dysregulation in diabetes risk, and disclose the mechanistic links between iron overload and diabetes evidenced in hereditary hemochromatosis and thalassemia. We particularly highlight iron-mediated oxidative stress as a central nexus impairing glucose metabolism and insulin sensitivity. Furthermore, we discuss the significance of dysmetabolic iron and ferroptosis activation in the progression of diabetes and diabetic complications, as well as the possible application of natural products for iron metabolism regulation and ferroptosis-inhibition-targeted therapeutic strategies to treat diabetes and diabetic complications. 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

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

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/Objective: Patients with beta-thalassemia are more susceptible to iron overload and have altered neutrophil function. This study investigated the connections between iron metabolism in neutrophils, neutrophil functionality, and overall iron status in individuals with β-thalassemia and sickle cell anemia. Methods: We recruited 18 patients with β-thalassemia, 5 patients with sickle cell anemia, and 15 healthy controls. Our evaluation included measurements of iron and hepcidin concentrations in the serum, along with an analysis of neutrophil function, specifically their phagocytic and oxidative burst capabilities. In addition, we examined the expression of iron transport proteins in neutrophils. Results: Patients with β-thalassemia showed significant iron overload, reduced neutrophil counts, and decreased oxidative burst activity and phagocytosis. Systemic iron status is inversely correlated with the phagocytic capacity of β-thalassemia neutrophils. Regression analysis indicated a significant association between serum iron level, transferrin iron binding capacity, transferrin saturation, and neutrophil percentage. These findings elucidate the essential role of systemic iron levels in neutrophil efficacy against infections. Furthermore, FPN1B and DMT1A mRNA levels were upregulated, and IRP2 was downregulated in the neutrophils of patients with β-thalassemia major and intermedia compared to controls. Conclusions: Elevated systemic iron levels were associated with reduced neutrophil counts and impaired neutrophil function in patients with β-thalassemia. These findings highlight a critical role of systemic iron overload in neutrophil dysfunction. Full article

Cardiovascular complications are a major concern in thalassemia patients, primarily driven by endothelial dysfunction. This systematic review and meta-analysis evaluated endothelial biomarkers as indicators of cardiovascular disease risk in thalassemia. A systematic search of PubMed, Scopus, and Embase identified 41 studies comparing biomarkers in thalassemia patients and healthy individuals. The biomarkers analyzed included ICAM-1, VCAM-1, E-selectin, P-selectin, von Willebrand factor (vWF), endothelial microparticles (EMPs), nitric oxide (NO), nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), and endothelin-1 (ET-1). Using random effects modeling, pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated. The results showed significantly elevated levels of ICAM-1 (SMD 2.15, 95% CI: 1.09–3.22), VCAM-1 (SMD 2.50, 95% CI: 1.35–3.66), E-selectin (SMD 1.21, 95% CI: 0.92–1.50), P-selectin (SMD 1.62, 95% CI: 0.83–2.42), and ET-1 (SMD 1.23, 95% CI: 0.03–2.42) in thalassemia patients. However, NO, ADMA, and vWF showed no significant differences. No studies on NOS were identified, while only one study found significantly elevated EMPs in thalassemia patients. This review highlights ICAM-1, VCAM-1, E-selectin, P-selectin, and ET-1 as key biomarkers for cardiovascular complications in thalassemia. Further research on EMPs and NOS is essential to enhance the understanding of endothelial dysfunction in this population. Full article

Survival analysis is a statistical approach widely employed to model the time of an event, such as a patient’s death. Classical approaches include the Kaplan–Meier estimator and Cox proportional hazards regression, which assume a linear relationship between the model’s covariates. However, the linearity assumption might pose challenges with high-dimensional data, thus stimulating interest in performing survival analysis using neural network models. In the present work, we implemented a deep Cox neural network (Cox-net) to predict the time of a cardiac event using patient data collected from the Myocardial Iron Overload in Thalassemia (MIOT) project. Cox-net achieved a concordance index (c-index) of 0.812 ± 0.036, outperforming the classical Cox regression (0.790 ± 0.040), and it demonstrated resilience to varying levels of censored patients. A permutation feature importance analysis identified fibrosis and sex as the most significant predictors, aligning with clinical knowledge. Cox-net was able to represent the nonlinear relationships between covariates and maintain reliable survival curve predictions in datasets with a large number of censored patients, making it a promising tool for determining the appropriate clinical pathway for thalassemic patients. Full article

Cardiovascular diseases are a leading cause of death worldwide, and they are becoming even more frequent due to the aging of society. Due to this fact, new parameters that are useful in diagnosing, as well as in assessing, the risk of cardiovascular events, and in future prognosis estimation, should be developed. The left atrioventricular coupling index (LACI) has been recently introduced as the one parameter meeting these criteria. The current review aims to collect all available data and assess whether the LACI may be a valuable tool in daily clinical practice, and, simultaneously, to direct future research on the subject. The LACI is a parameter that can be calculated based on echocardiographic, cardiac CT and CMR examinations. It appears to be of use in several cardiovascular diseases, especially heart failure and atrial fibrillation, both in diagnostics and as a prognostic marker. Moreover, the LACI is a useful marker in cardiomyopathies, myocardial infarction, beta-thalassemia major and light-chain amyloidosis. However, the number of studies on the subject of LACI is limited, and some of these studies are based on the same cohort of patients. Future studies should take up the subject of the LACI, especially when it comes to the value of calculating the LACI based on various imaging techniques, including echocardiography. Full article

Objectives: This study aimed to compare the pancreatic volume between beta-thalassemia major (β-TM) and beta-thalassemia intermedia (β-TI) patients and between thalassemia patients and healthy subjects and to determine the predictors of pancreatic volume and its association with glucose metabolism in β-TM and β-TI patients. Methods: We considered 145 β-TM patients and 19 β-TI patients enrolled in the E-MIOT project and 20 healthy subjects. The pancreatic volume and pancreatic and hepatic iron levels were quantified by magnetic resonance imaging. Results: The pancreatic volume indexed by body surface area (PVI) was significantly lower in both β-TI and β-TM patients compared to healthy subjects and in β-TM patients compared to β-TI patients. The only independent determinants of PVI were pancreatic iron in β-TM and hepatic iron in β-TI. In β-TM, there was an association between alterations of glucose metabolism and PVI, and PVI was a comparable predictor of altered glucose metabolism compared to pancreatic iron. Only one β-TI patient had an altered glucose metabolism and showed a reduced PVI and pancreatic iron overload. Conclusions: Thalassemia syndromes are characterized by a reduced pancreatic volume, associated with iron levels. In β-TM, the pancreatic volume and iron deposition are associated with the development and progression of alterations of glucose metabolism. Full article

Background/Objectives: This study aimed to determine the frequency of osteoporosis in children and adolescents with thalassemia major (TM) and to identify risk factors for the early development of osteoporosis. Methods: This retrospective study included 27 patients under 18 years of age receiving regular blood transfusions and chelation therapy for TM at our hospital. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry, and a lumbar spine Z-score <−2 was considered osteoporotic. Patients with osteoporosis were classified as Group 1 and those without osteoporosis as Group 2. Results: Osteoporosis was detected in 22.2% of the study population. The mean age was 13.83 ± 2.85 years in Group 1 and 7.95 ± 5.05 years in Group 2 (p = 0.012). Body weight and height were significantly lower in Group 1 (p = 0.012 and p = 0.004). Ferritin levels were 5306 ± 1506 ng/mL in Group 1 and 2020 ± 1205 ng/mL in Group 2, and the difference was significant (p = 0.001). Group 1 had significantly lower Ca and P levels (p < 0.001, p = 0.038). BMD was negatively correlated with ferritin (r = −0.791, p < 0.001) and positively correlated with calcium (r = 0.499, p = 0.008). Conclusions: Osteoporosis is a common condition in TM patients. Patients with risk factors should be followed more closely. These patients should be identified before BMD decreases. To prevent osteoporosis, regular BMD scans should be performed, calcium and vitamin D supplementation should be provided, and physical activity should be encouraged. Full article

β-thalassemia, a hereditary hemoglobinopathy, is caused by reduced or absent synthesis of the β-globin chains of hemoglobin. Three clinical conditions are recognized: β-thalassemia major, β-thalassemia intermedia, and β-thalassemia minor (β-Thal⁺). This latter condition occurs when an individual inherits a mutated β-globin gene from one parent. In erythrocytes from β-Thal⁺ subjects, the excess α-globin chains produce unstable α-tetramers, which can induce substantial oxidative stress leading to plasma membrane and cytoskeleton damage, as well as deranged cellular function. In the present study, we hypothesized that increased oxidative stress might lead to structural rearrangements in erythrocytes from β-Thal⁺ volunteers and functional alterations of ion transport proteins, including band 3 protein. The data obtained showed significant modifications of the cellular shape in erythrocytes from β-Thal⁺ subjects. In particular, a significantly increased number of elliptocytes was observed. Interestingly, iron overload, detected in erythrocytes from β-Thal⁺ subjects, provoked a significant production of reactive oxygen species (ROS), overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase, and glutathione depletion, resulting in (a) increased lipid peroxidation, (b) protein sulfhydryl group (-SH) oxidation. Iron overload-related oxidative stress affected Na⁺/K⁺-ATPase activity, which in turn may have contributed to impaired β-Thal⁺ erythrocyte deformability. As a result, alterations in the distribution of cytoskeletal proteins, including α/β-spectrin, protein 4.1, and α-actin, in erythrocytes from β-Thal⁺ subjects have been detected. Significantly, oxidative stress was also associated with increased phosphorylation and altered band 3 ion transport activity, as well as increased oxidized hemoglobin, which led to abnormal clustering and redistribution of band 3 on the plasma membrane. Taken together, these findings contribute to elucidating potential oxidative stress-related perturbations of ion transporters and associated cytoskeletal proteins, which may affect erythrocyte and systemic homeostasis in β-Thal⁺ subjects. Full article

Background and Objectives: This study aimed to identify asymptomatic brain lesions in patients with β-thalassemia major (TM) and sickle cell anemia (SCA) and evaluate the correlation of these lesions with factors such as splenectomy, thrombocytosis, and blood transfusions. Materials and Methods: A total of 26 patients with thalassemia major and 23 patients with sickle cell anemia were included. Ischemic lesions were categorized as lacunar, small vessel, or multifocal. Variables including age, years of education, presence and type of MRI-detected ischemia, smoking status, hemoglobin, hematocrit, platelet count, ferritin levels, vitamin B12 levels, fasting blood sugar, splenectomy status, chelation therapy, and hydroxyurea treatment were compared between the two groups. Results: The mean age was 27.33 years in the thalassemia major group and 32.65 years in the sickle cell anemia group (p = 0.010). No statistically significant difference was observed in the distribution of ischemia types between the groups (p = 0.303). The thalassemia major group had a lower mean hemoglobin level (8.37 g/dL) compared to the sickle cell anemia group (9.57 g/dL) (p = 0.003). Ferritin levels were significantly higher in the thalassemia major group (2018.92 ng/mL) than in the sickle cell anemia group (660.39 ng/mL) (p < 0.001). Conclusions: Although ischemic lesions were more frequently observed in patients with sickle cell anemia, the difference was not statistically significant. These findings emphasize the importance of ongoing surveillance and individualized management to mitigate cerebrovascular risks in both patient populations. Full article

Background: This study aimed to describe Sickle Cell Disease (SCD) phenotypes, sociodemographic characteristics, healthcare, and clinical outcomes of patients with SCD attending Mnazi Mmoja Hospital (MMH) in Zanzibar. Methods: Individuals who visited MMH between September 2021 and December 2022 and were known or suspected to have SCD were enrolled in the clinic. Sociodemographic characteristics and clinical features were documented, and laboratory tests were performed. A two-sample test of proportions was used to ascertain the significance of differences in the distribution of clinical outcomes between the follow-up visits. Results: A total of 724 patients with SCD were enrolled: 367 (50.7%) were male, and 357 (49.3%) were female. Most patients—713 (98.5%) in total—were homozygous (Hb SS), 9 (1.2%) had the Hb SC phenotype, and 2 (0.3%) had HbS β+ thalassemia. The majority of patients were aged 13 years and below—520 (71.8%) in total—and most did not have health insurance—582 (80.4%) in total. While all patients received folic acid, only a quarter received pneumococcal prophylaxis and hydroxyurea. Attendance at the third visit was associated with a reduced frequency of self-reported episodes of pain (24 patients [4.3%] vs. 11 patients [1.9%]). Conclusion: The population of patients with SCD in Zanzibar mostly comprised children who were Hb SS. Basic care services are still suboptimal, although they are associated with better outcomes when present. Thorough evaluation of SCD prevalence in Zanzibar through newborn screening programs is warranted. Full article

Thalassemia is an autosomal recessive hereditary chronic hemolytic anemia characterized by a partial or complete deficiency in the synthesis of alpha- or beta-globin chains, which are essential components of adult hemoglobin. Mutations in the globin genes lead to the production of unstable globin chains that precipitate within cells, causing hemolysis. This shortens the lifespan of mature red blood cells (RBCs) and results in the premature destruction of RBC precursors in the bone marrow. Regular red blood cell transfusions are the standard treatment for thalassemia. However, these transfusions can lead to increased iron overload, which can impair vital systems such as the liver, heart, ovaries, and endocrine system. Focusing on female reproductive endocrinology, recurrent blood transfusions can cause iron accumulation in the pituitary and hypothalamus, leading to hypogonadotropic hypogonadism (HH), the most common endocrinopathy in these patients, affecting 40–91% of women. Recurrent transfusions and the resulting iron overload can also lead to oxidative stress and ovarian damage in patients with beta-thalassemia major (BTM). Despite advancements in iron chelation therapy, hypothalamic–pituitary damage associated with HH contributes to subfertility and sexual dysfunction, often with little to no recovery. In women exposed to gonadotoxic drugs, particularly those with BTM, anti-Mullerian hormone (AMH)—a marker of ovarian reserve—is frequently used to assess ovarian damage. This review aims to explore the pathophysiology of β-thalassemia and its major clinical manifestations, with a focus on endocrine complications and their impact on ovarian reserve. It also investigates how metabolomics can provide insights into the disease’s metabolic alterations and inform current and emerging therapeutic strategies to mitigate complications and optimize patient outcomes, potentially leading to more effective and personalized treatments. Full article

Background/Objectives: We aimed to establish biatrial and biventricular reference ranges using cardiac magnetic resonance (CMR) parameters in SCD patients without heart damage. Methods: This study compared CMR parameters, quantified by cine SSFP sequences, in 48 adult SCD patients without apparent cardiac involvement (defined by the absence of known risk factors, normal electrocardiogram, and no macroscopic myocardial fibrosis or significant cardiac iron on T2* CMR) to matched cohorts of 96 healthy controls and 96 thalassemia major (TM) patients without cardiac damage. Nine paediatric SCD patients were also analysed and compared to age- and gender-matched groups of nine TM patients and nine healthy subjects. Results: In all groups, studied males displayed higher biventricular volumes and mass indexes than females. Male SCD patients showed significantly higher left ventricular (LV) end-diastolic volume index (EDVI), LV end-systolic volume index (ESVI), LV stroke volume index (SVI), cardiac index, LV and right ventricular (RV) mass index, and atrial areas than healthy subjects. Females with SCD exhibited increased LV EDVI, LV SVI, RV mass index, and left atrial area index compared to healthy controls. SCD and TM patients showed comparable biatrial areas and biventricular volumes and function. When compared to TM, SCD males exhibited a larger mass index, while SCD females showed an increased RV mass index. CMR parameters were similar across all paediatric groups. Conclusions: By establishing the biatrial and biventricular reference ranges through CMR for adult male and female SCD patients, we aimed to prevent possible misdiagnosis of cardiomyopathy in this population by taking into account cardiac adaptation due to anaemia. Full article