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Iron-overload-associated cardiomyopathy has been one of the primary causes of mortality in thalassemia patients with iron burden. There is growing evidence citing the beneficial effects of ebselen as an antioxidant selectively blocking the divalent metal transporter 1 (DMT-1) to deter iron ingress into cardiomyocytes, raising internets in viewing this component in this population in order to treat and even prevent cardiomyopathy occurring from iron surplus. In this article, we reviewed the potential advantageous effects of ebselen in thalassemia patients who suffer from iron excess, susceptible to cardiomyopathy induced by iron overload. A systematic search in several databases, including PubMed, Scopus, and Web of Science, was conducted to explore the role of ebselen in controlling iron-overload-related cardiomyopathy in thalassemia patients by the keywords of Ebselen AND iron. The inclusion criteria were English-written preclinical and clinical studies investigating the efficacy and side effects of ebselen in an iron-overload context. After searching the databases, 44 articles were found. Next, of 19 published articles, 3 were included in this article. After reviewing the references of the included studies, no articles were added. In conclusion ebselen can be a promising adjuvant therapy in patients with thalassemia alongside the standard treatment with iron chelators, particularly in severe cases with cardiomyopathy, due to falling iron inflow by inhibiting DMT-1 and increasing ferroportin-1 expression and antioxidant properties. However, clinical studies need to be carried out to reach a definite conclusion.

Abstract Ferritin is frequently used to screen some dire consequences of iron overload in β-thalassemia patients. The study aimed to define the best cutoff point of ferritin to screen for cardiac and liver hemosiderosis in these cases. This was a registry-based study on β-thalassemia patients living throughout Mazandaran province, Iran (n = 1959). In this diagnostic research, the index test was ferritin levels measured by a chemiluminescent immunoassay. As a reference test, T2*-weighted magnetic resonance imaging (T2*-weighted MRI) was applied to determine cardiac and liver hemosiderosis. A cutoff point of 2027 ng/mL for ferritin showed a sensitivity of 50%, specificity 77.4%, PPV 42.1%, and NPV 82.5% for cardiac hemosiderosis (area under curve [AUC] 0.66, 95% CI 0.60–0.71, adjusted odds ratio [OR] 2.05, 95% CI 1.05–4.01). At an optimum cutoff point of 1090 ng/mL, sensitivity 66.7%, specificity 68%, PPV 82.9%, and NPV 46.8% for liver hemosiderosis were estimated (AUC 0.68, 95% CI 0.63–0.73, adjusted OR 3.93, 95% CI 2.02–7.64. The likelihood of cardiac hemosiderosis serum ferritin levels below 2027 ng/mL is 17.5%. Moreover, 82.9% of β-thalassemia patients with serum ferritin levels above 1090 ng/mL may suffer from liver hemosiderosis, regardless of the grades.

Background and Aims: Several studies have highlighted the potent antioxidant properties of N‐acetyl cysteine (NAC). This review aimed to assess the impact of NAC on oxidative stress biomarkers in patients with β‐thalassemia. Methods: The review included articles published before 2024 that investigated the effects of NAC on oxidative stress in individuals with β‐thalassemia. A comprehensive search was conducted across various databases, including Scopus, PubMed, Web of Science, Trip, and CENTRAL. Only English‐language clinical trials were considered for inclusion in this review. Besides, the number needed to treat (NNT) was calculated based on the included studies. Results: Ninety‐nine articles were retrieved from electronic databases, and after a thorough review, eight articles were selected for comprehensive text analysis. The highest dose of NAC administered was 10 mg/kg/day (equivalent to 600 mg/day) over a period of 3–6 months. All the studies assessing the impact of NAC on oxidative stress indicators in β‐thalassemia patients demonstrated positive effects during the 3‐month follow‐up period. Most estimated NNTs fell into 1–5, suggesting significant clinical therapeutic value in this context. Conclusion: The current potency of NAC alone appears to be effective in ameliorating oxidative stress in patients with β‐thalassemia major. While a 3‐month duration seems adequate to demonstrate the antioxidant properties of NAC in this population, larger and well‐designed clinical trials are warranted. Current clinical evidence possesses a high risk of bias. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and aim: Hypozincemia is a prevalent adverse consequence in diabetes mellitus (DM) and β-Thalassemia patients. We aimed to evaluate the level of serum zinc in β-thalassemia patients with DM and a risk assessment for hypozincemia. Methods: The study population included transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) with overt DM (fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-h plasma glucose≥200 mg/dL). Serum zinc concentration was measured by the colorimetric method, and the values below 70 μg/dL were defined as hypozincemia. Myocardial and liver T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) were valued by a free contrast MRI. The demographic, clinical, paraclinical, and laboratory data were also recorded. The data belonged to the period from December 2018 until December 2020. Results: Of 64 diabetic β-thalassemia patients, 41 cases had zinc data in their medical files (aged 38 ± 9 years, 48.8% female). 78.05% of patients (n = 32) were TDT, and 21.95% were NTDT (n = 9). The mean ± standard deviation of zinc level was 110.2 ± 127.6 μg/dL. The prevalence of hypozincemia was 9.76%, 95% confidence interval [CI] 0.27 to 19.24 (four cases). After controlling age, the odds of hypozincemia for using deferasirox (DFX) was 8.77, 95% CI 0.60 to 127.1. In β-thalassemia patients, the age-adjusted risk of hypozincemia was calculated at 15.85, 95% CI 0.47 to 529.3 for hepatitis C. The adjusted risk of hypozincemia based on age for antacid use was 6.34, 95% CI 0.39 to 102.7. Conclusion: In light of this study, as well as hepatitis C, using DFX and antacids is associated with a high risk of hypozincemia amid diabetic β-thalassemia cases. However, upward bias should be taken into consideration. Author summary: [ABSTRACT FROM AUTHOR]

Background: Electronic registry system of beta-thalassemia patients was run by Thalassemia Research Center (TRC) in 2017. The aim of the current study was presentation of therapeutic status in these patients at Mazandaran Province, Iran. Methods: Therapeutic status variables including: Name of cities and hospitals, age and sex of patients, dependent and non-transfusion-dependent, starting age of the blood transfusion and iron-chelating agents, blood group and Rh, washed blood transfusion, abnormal antibody, transfusion reactions, mean hemoglobin during the last 3 months, type of iron chelators, iron chelators dosage, serum ferritin, and the use of hydroxyurea. Results: Overall, 1831 patients were registered [891 male (48.7%)]. Mean age of patients was 30±9.7 yr. Average of hemoglobin levels for female and male were 9.1±5.1 and 9.4±6.3 gr/dl, respectively. Seventy-six percent of transfusion-dependent patients (1385) have received iso-group PRBC (packed red blood cells), after crossmatch. The most common blood group among patient was type O-positive (35.7%). Monotherapy with desferrioxamine was most type of used iron-chelating agent in these patients (47.2%). Mean of ferritin was 3300±7800 (ng/ml). Twenty-eight percent of patients (484) have received hydroxyurea; proportion of male and female was approximately equal. T2 weighted magnetic resonance imaging (MRIT2*) was measured in 62.2% of patients. Moderate and severe hepatosiderosis was 10.1% and 2.9%, respectively. Patients with moderate and severe cardiac siderosis were 11% and 5%, respectively. Conclusion: Registry findings are valuable for treatment management and ensuring patients medications. It will also provide accessibility to various levels of patients’ information for health care managers and experts to help them make appropriate decisions.

Background: Hepatitis B surface antigen (HBsAg) is one of the main proteins of HBV envelop and its serum quantitative measurement is the most common quantitative test for monitoring the progress of Chronic Hepatitis B. Although measurement of serum HBV DNA copy number is a gold standard method for displaying viral load, the test is relatively expensive and it is not readily available everywhere in the world, while quantitative detection of HBsAg is fairly easy and inexpensive. The aim of this study was to investigate the correlation between serum HBsAg level and HBV DNA copy number in patients with chronic HB. Materials and Methods: Quantitative HBsAg, quantitative HBV DNA, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels were tested in 74 patients with chronic hepatitis B infection - who were HBsAg-positive for more than 6 months. In order to find any correlation between the results of these methods, Spearman and Kruska-Wallis correlation coefficient tests were applied. Results: No significant correlation was observed between quantitative HBsAg and HBV DNA measurements. Also, we could not find any correlation between serum HBsAg and ALT levels. But, serum HBV DNA content and AST level had a significant positive correlation. Conclusion: There are many factors affecting the correlation between serum HBV DNA copy number and HBsAg level such as genotype of HBV virus, phase of infection, methods of measurement, HBeAg status, and drug and types of treatment procedures. Therefore, these factors should be considered in further studies dealing with the correlation between quantitative HBV DNA and HBsAg tests.

Context: Vitamin D deficiency is a common nutritional disorder in Iran. Vitamin D is an essential health factor from birth onward. This study was conducted to summarize epidemiologic researches regarding vitamin D deficiency in different parts of the country and to conclude if food fortification is necessary. Evidence Acquisition: The study was designed in Thalassemia Research Center, Sari, Iran. It was a narrative review on the current situation of vitamin D deficiency in Iran. Related literature of the studies, in Farsi and English, conducted in the recent decade were explored. Data source of the study was Medline, SID, PubMed, Scopus, Request, Web-of-knowledge, Springer, Ovid, and Google Scholar. Results: Twenty five cross-sectional researches were found regarding vitamin D status in Iran from 2003 to 2013. There was also a Meta-analysis conducted in 2008. The total amount of 25(OH) D3 was measured mostly by radio immune assay (RIA) method. Most of the studies were done on adults. Definition of vitamin D deficiency was based on cut off of the kit in most studies; however in some studies the serum parathyroid hormone (PTH) was measured and cut off for diagnosis based on increased PTH. Maximum rate of sever vitamin D deficiency was reported as 47% in 2011. Conclusions: Vitamin D deficiency is very frequent in Iran. Dealing with a national important nutritional problem is important. One way is to fortify suitable foods or edible products such as milk or cooking oil. Increasing public awareness about the problem and motivating people to do something on their expense is another option. In the current case taking vitamin D supplements on a regular basis, daily, weekly, or any other routines which could be available and cost effective may solve the problem. For people above one year old it is recommended to take 300’000 IU (as intramuscular injection or oral dose) of vitamin D as a starting dose, then 50,000 IU oral dose every three months.

Background: Chronic hepatitis C infection used to be one of the most important burdens on patients with transfusion-dependent beta thalassemia major (TDTM). Chronic active hepatitis reduces quality of life, and liver cirrhosis and cancer shorten life expectancy in many cases. Objectives: We compared the characteristics of our patients at the Thalassemia Research Center (TRC) regarding hepatitis C infection at two time points. Patients and Methods: A review was conducted in a cohort of 390 TDTM patients with a history of at least one blood transfusion in 2014. Type of treatment protocol for hepatitis C virus (HCV) and the number of courses were defined. Descriptive statistics were performed using SPSS software (V16). Results: Screening for HCV started in 1995 at the TRC. Seventy-seven (15%) patients were antibody-positive in 1995. Tests for virus detection were not available at the time. Patients have been examined using serum AST, ALT, bilirubin, PT, PTT, and liver biopsy, and 45 were treated using alpha interferon alone. A second liver biopsy was performed at the end of treatment for 21 patients, and a blinded pathologist compared the histology according to the Knodell score. According to normalization of liver enzymes, the treatment was successful (McNemar test, P < 0.02). Based on the Knodell score, 54%, 31%, and 11% had complete, partial, and no response, respectively. A quantitative test for viremia became available thereafter. Thirteen patients who were resistant to alpha interferon have been treated using “Pegasys”™ ± ribavirin. Ten patients responded; however, three have been resistant and are still viremic. Twenty-seven patients received no treatment. Twenty-two (81.4%) had negative PCR tests. Five viremic patients refused treatment. A second screening test for HCV antibody was introduced in 2001, and, since then, annual screening for HCV antibody has been performed for all patients. No new case has been found since 2001. During the follow-up period, two deaths have been recorded in the cohort; none was a direct consequence of liver disease. Both patients had negative PCR tests for viremia. In 2014, there were 72 patients (52% men) with positive antibody tests, with a mean age of 30.5 ± 5.7 years. They mean age at the first blood transfusion was 2.8 ± 2.5 years. At the time of publishing, 15 patients (3.8%; 95% confidence interval 2 - 5.6) had viremia. Five patients had documented liver cirrhosis. Conclusions: The prevalence of hepatitis C virus has decreased dramatically owing to primary prevention (donor blood screening and discarding infected blood) and antiviral treatment of affected patients. Better clinical management with iron chelating agents and supportive therapy for cirrhotic patients is also in place.

Abstract Background and Objective: Diabetes mellitus is one of complications that thalassemia major patients face with. Hence, blood glucose monitoring is of vital importance to these patients. Because of high level of fetal hemoglobin in these patients, the measurement of hemoglobin A1c is not reliable and should be displaced by fructosamine test. Material and Methods: The current descriptive study was carried out on 33 beta-thalassemia major patients afflicted with diabetes mellitus (21 female and 12 male cases). Blood glucose level, fructosamine, hemoglobin A1c, serum ferritin and fetal hemoglobin were measured. Results: Blood glucose levels are 204±103 mg/dL and 221±101 mg/dL (p=0.63) fetal hemoglobin levels are 9%±7% and 13%±9% (p=0.22) serum ferritin levels are 1744±1534 ng/mL and 3253±1773 ng/mL (p=0.96) in female and male patients, respectively. The level of fructosamine (42±124 mmol/L) and glycosylated hemoglobin (8.9%±1.8%) are correlated significantly (r=0.69, p

Major β-thalassemia (β-TM) is one of the most common inherited hemolytic types of anemia which is caused as a result of absent or reduced synthesis of β-globin chains of hemoglobin. This defect results in red blood cells lysis and chronic anemia that can be treated by multiple blood transfusions and iron chelation therapy. Without iron chelation therapy, iron overload will cause lots of complications in patients. Antioxidant components play an important role in the treatment of the disease. Silymarin is an antioxidant flavonoid isolated from Silybum marianum plant. In the present study, we reviewed clinical and experimental studies investigating the use of silymarin prior to September 1, 2015, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases and we evaluated the potential effects of silymarin on controlling the complications induced by iron overload in patients with β-TM. Based on the results of the present study, we can conclude that silymarin may be useful as an adjuvant for improving multiple organ dysfunctions.

While thalassemia major (TM) used to be a prevalent genetic disease in the past, however, (PKU) is quite rare in spite of consanquiness marriage rate of about 40% in the region. Preventive efforts for TM started >20 years ago but neonatal screening for PKU started since 2007. This is the first report of co-existence of thalassemia and PKU in Middle East and in consideration of the prevalence of each genes, this chance association is a very unusual event. We report a case of having PKU and TM

AbstractBackground and Purpose: β-thalassaemia is the most frequent inherited disorder in the world, especially in Iran and Mazandaran Province. It is caused by mulation in β-globin gene on chromosome 11 with more than 150 different mulations causing β-thalassaemia, has been identified in the β-globin gene to date. Hydroxyurea, is one of the drugs used in Thalassemia patient’s treatment, however, it is not effective in all patients. The mechanisms of the hydroxyuea effect in not clear yet. This study compared different β-globin gene mutations in β-thalassaemia patients who were referred to the Thalassemia Research Center in Sari in two groups, good responder and non-responder, to the hydroxyurea.Materials and Methods: This was a case-control study, comparing two groups of 30 thalassaemic patients who received hydroxyurea. Two groups were included, 30 good responders to hydroxyurea treatment (control) and 30 who did not respond to the treatment (case). First, DNA was extracted from peripheral blood. Then, two different methods for mutation detection were used. In the Thalassaemia Research Center in Sari, mutations in 60 patients were identified using ARMS-PCR. Also the results were confirmed in Genetic laboratory of Amirkola, using two mutation detection methods, reverse-dot blot hybridization and ARMS-PCR.Results: In the group of good responder (control), the average patient’s age were 28/1 ± 7/78 years, and the average age at the onset of blood transfusion was reported to be 8/5 ± 8/56 year. In this group, the mean comparison of the hemoglobin level and red blood size (MCV) prior and after drug consumption were statistically significant. In the group of non-responder (case), the mean age was 21.3 ± 6.43, the mean age starting blood transfusions was 3.3 ± 3.75, and the mean of drug consumption was 2.3 ± 0.8 months. From the mutations identified, IVSII-1G>A was the most common type in both case and control group, while of 30 of control group, 22 individuals were homozygous, and 7 individuals were heterozygous for this mutation (frequency % 42.5). For the 30 case patients, 11 individuals were homozygous, while 11 were heterozygous (frequency % 27.5). Comparison between two groups, case and control group, were statistically significance (PA mutation in good responder patients to hydroxyurea as compared to the non responder group, is significant and similar to the previous findings. Key words: β-thalassaemia, Hydroxyurea, MutationJ Mazand Univ Med Sci 2008; 18(64): 1-10 (Persian)

(Received 6 Aug, 2008; Accepted 3 Dec, 2008) Abstract Background and purpose: Beta-thalassemia is the most common inherited disorder in the world, especially in Iran. According to Iranian thalassemia society registry, 18616 thalassemia patients now living in Iran, which Mazandaran and Fars provinces have the most patients. Previous reports have shown that the frequency of b-thalassemia carriers is more than 10% in Mazandaran province. Although b-thalassemia is very heterogenous in the molecular level, but in each population, 5 to 10 mutations are more common. In this research common mutation in eastern area of Mazadaran province was investigated. Materials and methods: 5 to 10 ml peripheral blood samples were collected from volunteer patients who were referred to Boali Sina Hospital in Sari. DNA was extracted from blood, then 20 different mutations were screened and detected using two different methods, ARMS-PCR and Reverse-Dot Blot in Thalassemia Research Center in Sari and Amir Kola Thalassemia Center. Results: From 240 chromosomes investigated in 120 b-thalassemia patients in total, 96.25% mutations were identified. 13 different mutations were identified from 231 chromosomes. Among different mutations investigated, IVSII-1G>A was detected as the most common with frequency of 68/3%, which was homozygous in 64 individuals (53/3%) and compound heterozygous with other mutations in 34 individuals (28/3%) respectively. Mutations C8(-AA), codon22(G>A)/ FSC 22/23/24(-7bp), codon 30(G>A), and IVSII-1G>A were identified in 83% of chromosomes which were studied (200 chromosomes from 240). Conclusion: Mutation IVSII-1G>A is the most common mutation in northern provinces (Gilan, mazandaran, Golestan) in recent study. Also, comparison of these results with the similar finding from other provinces showed that the distributions of mutations in the northern area are different with northwest, south or southeast of the country.

Iron-overload-associated cardiomyopathy has been one of the primary causes of mortality in thalassemia patients with iron burden. There is growing evidence citing the beneficial effects of ebselen as an antioxidant selectively blocking the divalent metal transporter 1 (DMT-1) to deter iron ingress into cardiomyocytes, raising internets in viewing this component in this population in order to treat and even prevent cardiomyopathy occurring from iron surplus. In this article, we reviewed the potential advantageous effects of ebselen in thalassemia patients who suffer from iron excess, susceptible to cardiomyopathy induced by iron overload. A systematic search in several databases, including PubMed, Scopus, and Web of Science, was conducted to explore the role of ebselen in controlling iron-overload-related cardiomyopathy in thalassemia patients by the keywords of Ebselen AND iron. The inclusion criteria were Englishwritten preclinical and clinical studies investigating the efficacy and side effects of ebselen in an iron-overload context. After searching the databases, 44 articles were found. Next, of 19 published articles, 3 were included in this article. After reviewing the references of the included studies, no articles were added. In conclusion ebselen can be a promising adjuvant therapy in patients with thalassemia alongside the standard treatment with iron chelators, particularly in severe cases with cardiomyopathy, due to falling iron inflow by inhibiting DMT-1 and increasing ferroportin-1 expression and antioxidant properties. However, clinical studies need to be carried out to reach a definite conclusion. [ABSTRACT FROM AUTHOR]

Byline: Farshad. Hasanzadeh Kiabi, Abbas. Alipour, Hadi. Darvishi-Khezri, Aily. Aliasgharian, Amir. Emami Zeydi Background: Ventilator-associated pneumonia (VAP) is a type of lung infection that typically affects critically ill patients undergoing [...]