Search Results (39)

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/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 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

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

Beta thalassemia is an inherited blood disorder that results in inefficient erythropoiesis due to genetic mutation that leads to the reduction or absence of the hemoglobin beta-globulin protein. Approximately 8.5% of UAE residents suffer from β-thalassemia, a significant health and financial problem. The treatment options available for β-Thalassemia major are limited and associated with a wide range of complications. β-thalassemia gene therapy is emerging as a potential novel treatment option that eliminates the complications caused by the current long-term treatment modalities and the associated economic burden. This paper reviews the scientific literature related to emerging gene therapy for β-Thalassemia by analyzing all the articles published from January 2010 to December 2023 in the English language on Databases like PubMed, Scopus, ProQuest, and CINAHL. The use of gene therapy has demonstrated promising outcomes for a permanent cure of β-Thalassemia. To conclude, gene therapy is an innovative solution. It demonstrates a promising future, but does come with its own setbacks and is something that must be tackled in order to revolutionize it in the medical world. FDA-approved ZYNTEGLO is a potentially one-time curative treatment for β-Thalassemia. Although cutting-edge, its use is limited because of the high cost—a price of USD 2.8 million per patient. Full article

HbF induction is an appropriate strategy to ameliorate the severity of β-thalassemia symptoms. Hydroxyurea (HU) is the most common chemical agent introduced as an HbF inducer but responsiveness to HU is variable and the introduction of HbF inducers alternative to HU with low cytotoxicity has been a crucial challenge. Resveratrol is an HbF inducer agent that may have favorable effects on the differentiation of hematopoietic erythroid progenitors (HEPs). The present study aimed to investigate the effect of resveratrol on γ-globin, stress response, and anti-apoptotic gene expression among hydroxyurea (HU)-responders and HU-nonresponders (HU-NR). Four cases of HU-R and four cases of HU-NR were studied. HEPs of the patients were cultured, and the expression of γ-globin, Foxo3, and Bclxl was assessed. Moreover, the differentiation and apoptotic rate of the cells were investigated using flow cytometry analysis. In three cases, the γ-globin gene expression increased after resveratrol treatment. All of the HU-NR patients were also non-responders to resveratrol (Res-NR). The expression of Foxo3 and Bclxl genes was higher in responders to resveratrol (Res-R) compared to non-responders (Res-NR). The rate of apoptosis in Res-R patients was also lower than in Res-NR. Responders to resveratrol also had a higher rate of HEP maturation. The cells of both HU–NR and Res-NR patients could not adapt to stress conditions and proceed to the erythroid differentiation. In conclusion, resveratrol increased the γ-globin expression in HEPs of β-thalassemia patients. The response was observed only in R-HU patients with similar cellular pathways. Full article

We investigated depression and anxiety levels and related psychological disorders in adolescents with transfusion-dependent thalassemia (TDT) in this study. The study was conducted in two pediatric hematology outpatient clinics and included adolescents with TDT (14.8 ± 2.4 years, n = 40) in the study and compared them with the healthy age-matched control group (14.3 ± 2.3 years, n = 62). The Turkish version of the Revised Child Anxiety and Depression Scale (RCADS) was used to determine depression, anxiety, and related psychologic disorders (obsession, panic disorder, social phobia). Depression, anxiety, obsession, panic disorder, and social phobia scores were significantly higher in the patient group compared with the control (all p < 0.05). Ferritin levels were positively correlated with total depression, general anxiety, separation anxiety, and social phobia scores, but transfusion frequency and young age were the confounding factors. Patients in early adolescence and those who require more frequent blood transfusions are at higher risk of developing psychological disorders; routine screening for mood disorders should be warranted. Serum ferritin level may be a good warning indicator for early recognition of psychologic disorders in TDT patients. Full article

We evaluated the association of vitamin D and parathormone (PTH) levels with cardiac iron and function in beta-thalassemia major (β-TM) patients. Two-hundred and seventy-eight TM patients (39.04 ± 8.58 years, 56.8% females) underwent magnetic resonance imaging for the assessment of iron overload (T2* technique), biventricular function parameters (cine images), and replacement myocardial fibrosis (late gadolinium enhancement technique). Vitamin D levels were deficient (<20 ng/dL) in 107 (38.5%) patients, insufficient (20–30 ng/dL) in 96 (34.5%) patients, and sufficient (≥30 ng/dL) in 75 (27.0%) patients. Deficient vitamin D patients had a significantly higher frequency of myocardial iron overload (MIO; global heart T2* < 20 ms) than patients with sufficient and insufficient vitamin D levels and a significantly higher left ventricular end-diastolic volume index and mass index than patients with sufficient vitamin D levels. PTH was not associated with cardiac iron, function, or fibrosis. In the multivariate regression analysis, vitamin D, serum ferritin, and pancreatic iron levels were the strongest predictors of global heart T2* values. In receiver operating characteristic curve analysis, a vitamin D level ≤ 17.3 ng/dL predicted MIO with a sensitivity of 81.5% and a specificity of 75.3% (p < 0.0001). In TM, the periodic and regular assessment of vitamin D levels can be beneficial for the prevention of cardiac iron accumulation and subsequent overt dysfunction. Full article

Matched hematopoietic stem cell transplantation (HSCT) is a feasible and curative treatment in pediatric patients with beta thalassemia major (β-TM). However, little data are available regarding patients and their parents’ health-related quality of life (HRQoL) after the procedure. As such, we investigated the HRQoL of pediatric patients with β-TM after HSCT compared to that of patients treated with blood transfusions and iron chelation. The health-related quality of life of 43 β-TM pediatric patients and 43 parents were evaluated using the Pediatric Quality of Life Inventory (PedsQL). A total of 25 patients underwent HSCT: 15 from a sibling and 10 from an HLA-matched donor. The median follow-up time from HSCT was 5 years (range 1–13 years). The mean ages at the survey were 10.1 years (range 5–15) and 9.6 years (range 5–15) for transfused and transplanted patients, respectively. A significant reduction in HRQoL was reported in the group of transfused patients compared with that of patients transplanted in the following PedsQL domains: children’s and parents’ physical functions, Δ = −15.4, p = 0.009 and Δ = −11.3, p = 0.002, respectively; children’s and parents’ emotional functioning, Δ = −15.2, p = 0.026 and Δ = −15.2, p = 0.045, respectively; child’s and parents’ school functioning, Δ = −25, p = 0.005 and Δ = −22.5, p = 0.011, respectively; total child and parents scores, Δ = −14.5, p = 0.004 and Δ = −13.2, p = 0.005, respectively. The results of a multivariable analysis showed that the HSCT procedure was significantly associated with a higher total child PedsQL score (adjusted mean difference = 15.3, p = 0.001) and a higher total parent PedsQL score (adjusted mean difference = 14.1, p = 0.006). We found no significant difference in the HRQoL measured after sibling or unrelated human leukocyte antigen (HLA)-matched HSCT. Finally, a significant positive correlation across all the PedsQL domains was found between the scores reported by the children and those reported by their parents. In conclusion, our study shows that HSCT in pediatric patients with β-TM is associated with a good overall HRQoL profile. This information further supports physicians when counseling patients and their parents before the HSCT procedure. Full article

Few data are available on the efficacy and safety of splenectomy in patients with transfusion-dependent Beta-Thalassemia Major (β-TM) and on its impact on a patient’s health-related quality of life (HRQoL). We examined the long-term HRQoL of adult patients with β-TM in comparison with those treated with medical therapy by using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). We also evaluated the safety and efficacy of splenectomy. Overall, 114 patients with a median age of 41 years (range 18–62) were enrolled in this cross-sectional study. Twenty-nine patients underwent splenectomy (25.4%) at a median age of 12 years (range 1–32). The median follow-up after splenectomy was 42 years (range 6–55). No statistically significant differences were observed in any of the scales of the SF-36 between splenectomized and not-splenectomized patients. The majority of surgical procedures (96.6%) were approached with open splenectomy. Post-splenectomy complications were reported in eight patients (27.5%): four overwhelming infections, three with pulmonary hypertension, and one with thrombosis. A significantly higher prevalence of cardiovascular comorbidities (58.6 vs. 21.2%, p < 0.001) and diabetes (17.2 vs. 3.5%, p = 0.013) was observed in splenectomized patients. These patients, however, required fewer red blood cell units per month, with only 27.6% of them transfusing more than 1 unit per month, compared with 72.9% of the not-splenectomized group. Overall, our data suggest that physicians should carefully consider splenectomy as a possible treatment option in patients with β-TM. Full article

Genetic polymorphisms in Quantitative Trait Loci (QTL) genes such as BCL11A, HBS1L-MYB and KLF1 have been reported to influence fetal hemoglobin (HbF) levels. This prospective study was planned to evaluate the role of genetic polymorphisms in QTL genes as determinant of HbF levels in beta thalassemia major patients. The study was carried out on 100 thalassemia major patients. Blood samples were collected in EDTA and plain vials for biochemical and molecular evaluation. The BCL11A, HBS1L-MYB and KLF1 genotypes were determined using a polymerase chain reaction (PCR)-based method. Red Blood Cell (RBC) indices and HbF levels were assessed. In silico analysis was assessed using loss-of-function tool (Lof Tool). Statistical difference and genetic comparisons between groups were evaluated by using SPSS for Windows, version 16.0 (SPSS Inc., Chicago, IL, USA). Comparisons between quantitative variables were carried out after data explored for normality using Kolmogorov–Smirnov test of normality. Logistic regression was used for computation of ORs and 95% CIs (Confidence Interval). We observed association of HbF levels in thalassemia major patients with the polymorphisms in BCL11A (rs11886868 rs7557939; rs1427407 and rs766432) and HBS1L-MYB (rs9399137) gene. The results of this study indicated that the presence of polymorphisms on modifier genes are strongly associated with an increase in HbF levels in thalassemia major patients. Further research with a larger sample size and with other genes of modifier genes is required. Full article

Background: Beta thalassemia major (Beta-TM) is an inherited condition which presents at around two years of life. Patients with Beta-;TM may develop cardiac iron toxicity secondary to transfusion dependence. Cardiovascular magnetic resonance (CMR) T2*, a technique designed to quantify myocardial iron deposition, is a driving component of disease management. A decreased T2* value represents increasing cardiac iron overload. The clinical manifestation is a decline in ejection fraction (EF). However, there may be early subclinical changes in cardiac function that are not detected by changes in EF. CMR-derived strain assesses myocardial dysfunction prior to decline in EF. Our primary aim was to assess the correlation between CMR strain and T2* in the Beta-TM population. Methods: Circumferential and longitudinal strain was analyzed. Pearson’s correlation was calculated for T2* values and strain in the Beta-TM population. Results: We identified 49 patients and 18 controls. Patients with severe disease (low T2*) were found to have decreased global circumferential strain (GCS) in comparison to other T2* groups. A correlation was identified between GCS and T2* (r = 0.5; p < 0.01). Conclusion: CMR-derived strain can be a clinically useful tool to predict early myocardial dysfunction in Beta-TM. Full article

Background and Objectives: Beta-thalassemia (BT) has a high prevalence in Mediterranean, Southeast Asian, and African countries. Studies stated that thalassemia is an endemic disease that causes significant health problems in Cyprus. This study aimed to measure the contact angle between the implant and blood samples from BT major patients and healthy individuals to compare the contact angles and wettability of Grade 5 titanium implant surfaces. Materials and Methods: Grade 5 titanium discs that were 10 mm in diameter were used since they mimic the surface of dental implants. Following receiving informed consent, blood samples were taken from the patients’ index fingers in each group with lancet needles and a photo of the contact angle between the blood samples and the titanium surface was taken; the collected blood was transferred to a titanium disc with a medical pipette. ImageJ software with a specific contact angle plugin was used for the contact angle measurements. Results: Theta-mean, theta-circular, and theta-ellipse values were compared between all groups, and no significant difference was found (p > 0.05). Conclusions: In this study, it was hypothesized that the patients’ rheological property of decreased deformability would affect the wettability of implant surfaces in vitro; however, no such finding was reached in this study. Since in-depth studies associated with dental implant success in BTM patients are absent in the literature and Cyprus is one of the Mediterranean countries with a high prevalence of BTM, this study was conducted to enrich the literature. While some systemic diseases may affect the contact angle between the implant surface and blood, it can be concluded that this condition was not present for BTM patients in our study. Last but not least, we emphasize that this experiment was done on a single surface type and the results can be totally different when using other surface types. Full article