A cross-sectional analysis of the PURE study on minerals intake among Malaysian adult population with hypertension.

Hypertension (HPT) is the leading modifiable risk factor for cardiovascular diseases and premature death worldwide. Currently, attention is given to various dietary approaches with a special focus on the role of micronutrient intake in the regulation of blood pressure. This study aims to measure the dietary intake of selected minerals among Malaysian adults and its association with HPT. This cross-sectional study involved 10,031 participants from the Prospective Urban and Rural Epidemiological study conducted in Malaysia. Participants were grouped into HPT if they reported having been diagnosed with high blood pressure [average systolic blood pressure (SBP)/average diastolic blood pressure (DBP) ≥ 140/90 mm Hg]. A validated food frequency questionnaire (FFQ) was used to measure participants' habitual dietary intake. The dietary mineral intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, sodium, and zinc was measured. The chi-square test was used to assess differences in socio-demographic factors between HPT and non-HPT groups, while the Mann-Whitney U test was used to assess differences in dietary mineral intake between the groups. The participants' average dietary intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, selenium, sodium, and zinc was 591.0 mg/day, 3.8 mg/day, 27.1 mg/day, 32.4 mg/day, 0.4 mg/day, 1431.1 mg/day, 2.3 g/day, 27.1 µg/day, 4526.7 mg/day and 1.5 mg/day, respectively. The intake was significantly lower among those with HPT than those without HPT except for calcium and manganese. Continuous education and intervention should be focused on decreasing sodium intake and increasing potassium, magnesium, manganese, zinc, and calcium intake for the general Malaysian population, particularly for the HPT patients.

Congenital Methemoglobinemia in a 33-Year-Old Patient: A Case Report on a Rare Presentation and a Review of the Literature.

Cyanosis and dyspnea are common complaints in adults and have broad differential diagnoses, of which rare ones such as congenital methemoglobinemia should always be considered in the differential diagnosis. Methemoglobinemia might be acquired or congenital. Patients' symptoms vary from severe shortness of breath, mental status changes, and cyanosis to none. The diagnosis of congenital methemoglobinemia is challenging and requires high index of suspension, especially in older patients. In addition, when diagnosed the treatment of congenital methemoglobinemia is oral ascorbic acid which is readily available. We present a rare case of a 33-year-old lady, who had a long history of recurrent episodes of cyanosis, headache, and fatigue. After excluding cardiopulmonary causes, methemoglobin levels were measured and found to be high, and the chart review revealed high levels of methemoglobin in all her previous episodes, without exposure to any offending agent. This raised the concern of a late diagnosis of congenital methemoglobinemia. The patient was treated with a high dose of ascorbic acid resulting in resolution of the symptoms. Congenital methemoglobinemia is a rare diagnosis that needs a high index of suspicion, especially in adults. A thorough history, physical examination, and multiple laboratory tests are needed to confirm the diagnosis and rule out other causes.

A Short Review on Growth and Endocrine Long-term Complications in Children and Adolescents with ß-Thalassemia Major: Conventional Treatment versus Hematopoietic Stem Cell Transplantation.

The conventional treatment of ß-thalassemia (ß-TM) patients is based on the correction of anemia through regular blood transfusions and iron chelation therapy. However, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only currently available technique that has curative potential. Variable frequency and severity of long-term growth and endocrine changes after conventional treatment as well as after HSCT have been reported by different centers. The goal of this mini-review is to summarize and update knowledge about long-term growth and endocrine changes after HSCT in patients with ß-TM in comparison to those occurring in ß-TM patients on conventional treatment. Regular surveillance, early diagnosis, treatment, and follow-up in a multi-disciplinary specialized setting are suggested to optimize the patient's quality of life (www.actabiomedica.it).

Blood transfusion and iron overload in patients with Sickle Cell Disease (SCD): Personal experience and a short update of diabetes mellitus occurrence.

The conventional treatment of ß-thalassemia (ß-TM) patients is based on the correction of anemia through regular blood transfusions and iron chelation therapy. However, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only currently available technique that has curative potential. Variable frequency and severity of long-term growth and endocrine changes after conventional treatment as well as after HSCT have been reported by different centers. The goal of this mini-review is to summarize and update knowledge about long-term growth and endocrine changes after HSCT in patients with ß-TM in comparison to those occurring in ß-TM patients on conventional treatment. Regular surveillance, early diagnosis, treatment, and follow-up in a multi-disciplinary specialized setting are suggested to optimize the patient's quality of life (www.actabiomedica.it).

Untargeted Metabolomics Identifies a Novel Panel of Markers for Autologous Blood Transfusion.

Untargeted metabolomics was used to analyze serum and urine samples for biomarkers of autologous blood transfusion (ABT). Red blood cell concentrates from donated blood were stored for 35−36 days prior to reinfusion into the donors. Participants were sampled at different time points post-donation and up to 7 days post-transfusion. Metabolomic profiling was performed using ACQUITY ultra performance liquid chromatography (UPLC), Q-Exactive high resolution/accurate mass spectrometer interfaced with a heated electrospray ionization (HESI-II) source and Orbitrap mass analyzer operated at 35,000 mass resolution. The markers of ABT were determined by principal component analysis and metabolites that had p < 0.05 and met ≥ 2-fold change from baseline were selected. A total of 11 serum and eight urinary metabolites, including two urinary plasticizer metabolites, were altered during the study. By the seventh day post-transfusion, the plasticizers had returned to baseline, while changes in nine other metabolites (seven serum and two urinary) remained. Five of these metabolites (serum inosine, guanosine and sphinganine and urinary isocitrate and erythronate) were upregulated, while serum glycourdeoxycholate, S-allylcysteine, 17-alphahydroxypregnenalone 3 and Glutamine conjugate of C6H10O2 (2)* were downregulated. This is the first study to identify a panel of metabolites, from serum and urine, as markers of ABT. Once independently validated, it could be universally adopted to detect ABT.

Use of rivaroxaban in sickle cell disease and venous thromboembolism: A case report.

INTRODUCTION: Sickle cell disease (SCD) is a hematological disorder characterized by sickling of red blood cells. Patients are at increased risk of venous thromboembolism. There are no guidelines for the management of venous thromboembolism in sickle cell disease specifically in terms of the anticoagulant of choice. PATIENT CONCERNS: Here, we report a case of a 30-year-old lady with past medical history of sickle cell disease who came with chest pain and shortness of breath. DIAGNOSIS: We found that she has bilateral pulmonary embolism (PE). INTERVENTION: She was started on rivaroxaban. OUTCOME: The patient was followed for 18 months, she did not suffer from recurrence of PE, and she did not develop any complications related to rivaroxaban. CONCLUSION: We concluded that rivaroxaban is effective in treating PE in sicklers and also it is safe.

Rickets Due to Severe Vitamin D and Calcium Deficiency During the COVID-19 Pandemic in Malaysia.

BACKGROUND Rickets is the deficiency in mineralization of the bone associated with lack of sunlight exposure and inadequate dietary calcium and/or vitamin D in children. Important efforts to eradicate rickets include appropriate sunlight exposure advice and fortification of food and milk with vitamin D. However, there is a growing concern that the current Coronavirus Disease 2019 (COVID-19) pandemic will increase the incidence of rickets due to inadequate sunlight exposure resulting from movement restriction measures imposed by governments across the world. CASE REPORT A 22-month-old girl presented to our primary care clinic in Selangor, Malaysia with abnormal gait and bowing of the legs during the COVID-19 pandemic. She had a history of inadequate sun exposure as she lived in an apartment and there was a Movement Control Order in place because of the pandemic. Calcium intake was also poor as she could not tolerate formula milk and did not consume any other dairy products. Investigations revealed severe hypocalcemia and low vitamin D level. She was diagnosed with nutritional rickets and was referred for admission to correct the hypocalcemia. She was subsequently discharged with oral calcium and vitamin D supplementation. Her calcium and vitamin D levels improved and at her 6-month review, her bilateral bowed legs had improved significantly. CONCLUSIONS This case highlights the importance of having a high degree of suspicion for vitamin D deficiency and rickets in young children growing up during the COVID-19 pandemic. Public health messages on preventing the spread of COVID-19 should also be interlaced with messages addressing the possible effects of our new norms such as inadequate sunlight exposure.

Evaluation of Hepatitis B Reactivation Among Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors.

Hepatitis B reactivation (HBVr) in cancer patients is a well-established complication due to chemotherapy-induced immunosuppression. Studies have reported HBVr associated with immunosuppressive medications, such as rituximab, methotrexate, and high dose steroids. There are different risks for different types of chemotherapy with rituximab carrying one of the highest risks for hepatitis B reactivation. Tyrosine kinase inhibitors (TKIs) are the standard of care in patients with chronic myeloid leukemia (CML). The risk of HBVr in chronic myeloid leukemia has been reported in many studies, but to this date, there are no clear guidelines or recommendations regarding screening and monitoring of HBV in CML patients receiving TKIs. We conducted this review to identify the risk of HBVr in patients with CML who are treated with tyrosine kinase inhibitors. We recommend testing for HBV status in patients who are to be treated with TKIs and to consider giving prophylaxis in those who are positive for HBsAg at baseline. More studies are needed to assess the risk of reactivation in patients with Hepatitis B core antibody positive receiving TKIs. Currently, monitoring such patients for reactivation may be the best strategy.

COVID-19 and thalassemia beta major in splenectomized patient: Clinical case progression and literature review.

Although the possibility of asymptomatic course for COVID-19 infection in splenectomized thalassemia beta major patients is present, screening them for COVID-19 is important as the progression is still not clear.

Iron-Induced Thrombocytopenia: A Mini-Review of the Literature and Suggested Mechanisms.

Anemia constitutes a major global health burden, and iron deficiency is the most common cause of it. Iron deficiency and replacement affect not only hemoglobin (Hb) levels but also other hematological parameters such as platelet count. In this mini-review, we explore thrombocytopenia as a side effect of iron replacement therapy. We searched for relevant articles published in English, and all case reports/series of iron-induced thrombocytopenia were collected and analyzed. A total of 11 case reports and one case series were found relating to very low Hb at a baseline level of 5.25 +/- 2.2 g/dl and variable platelet count at baseline that dropped in 9 +/-3 days to an average of 121 +/- 112 x 109/L, which in most of the cases was self-corrected. The parenteral route was more commonly reported to be associated with thrombocytopenia, and discontinuation of therapy was needed in two patients. The mechanisms, prevalence, and clinical significance of thrombocytopenia associated with iron replacement are unknown; several effects of iron on the primary hematopoietic cells and stromal cell lines have been proposed, such as influence on common progenitors, effects on cytokines, and thrombopoietic effect of erythropoietin, which is directly affected by iron levels. Iron replacement can lead to significant thrombocytopenia. Further research is needed to describe the exact incidence, mechanism, and clinical significance of thrombocytopenia associated with iron supplementation.

A Rare Case of Acquired Hemolytic Anemia and Pancytopenia Secondary to Pernicious Anemia.

The commonest etiologies of new-onset pancytopenia are congenital bone marrow failure syndromes, marrow space-occupying lesions, infections, and peripheral destruction. Nutritional deficiencies, including folate and vitamin B12, can occasionally cause pancytopenia. We report a 48-year-old gentleman who presented with a 1-week history of dizziness and upper gastrointestinal bleeding. Laboratory evaluation revealed pancytopenia, macrocytosis, toxic neutrophils, hemolysis, suppressed reticulocyte count, positive direct anti-globulin test (DAT), severely reduced B12 levels, and positive anti-intrinsic factor and anti-parietal cell antibodies. He was started on weekly intramuscular B12 supplementation and showed improvement in blood cell counts during follow-up. Recognition of B12 deficiency as a cause of pancytopenia and DAT-positive autoimmune hemolytic anemia can help to avoid unwanted investigations and aid in early diagnosis and treatment.

Anti-saprolegnia potency of some plant extracts against Saprolegnia diclina, the causative agent of saprolengiasis.

Saprolegnosis of fresh water fishes caused by Saprolegnia diclina often results in serious economic losses to fish hatcheries. Despite the proven efficiency of malachite green as a potential fungicide in prevention and control of fish saprolegnosis, there is a strong debate about its safety aspects in use since it was documented to be responsible for many carcinogenic and teratogenic attributes. Bioactivity of four ethanolic plant extracts were assessed to attain a natural alternative to the traditional fungicide currently used in saprolegnosis control. Ethanolic extracts of Punica granatum and Thymus vulgaris exhibited a potential efficacy in suppressing mycelial growth of S. diclina at concentration of 0.5 mg/ml while extracts of Nigella sativa and Zingiber officinales were not effective respectively. The extract of pomegranate showed the highest antifungal potency with minimum inhibitory concentration (MIC) of 200 ppm while thyme extract was less effective and recorded MIC of 400 ppm against S. diclina. The acute fish toxicity of the plant extracts indicated the low toxicity of P. granatum and T. vulgaris extracts as no fish mortalities were detected at aquaria containing 200, 400 and 800 ppm of plant extracts respectively. Considering the low toxicity of these plant extracts, it may be concluded that 200 and 400 ppm of pomegranate and thyme extracts which suppressed the mycelial growth of the S. diclina could be safely used for saprolegniasis control. Both of pomegranate and thyme extracts which proved to possess a potential antifungal activity can be considered as a natural alternative fungicides to control saprolegniasis avoiding carcinogenic malachite green application.

Short-Term Outcome and MRI Changes in Three Adult Patients with Sickle Cell Disease and Aseptic Osteonecrosis after Treatment with Hyperbaric Oxygen Therapy: A Preliminary Report.

BACKGROUND: Musculoskeletal manifestations are common in sickle cell disease (SCD). Vaso-occlusive crisis can manifest acutely as joint and bone pain, osteomyelitis and/or arthritis. It can also lead to chronic bone aches, bone deformities, degenerative arthritis, pathological fractures, and osteoporosis. Hyperbaric oxygen (HBO) therapy is a mode of treatment in which the patient is exposed to very high arterial and tissue oxygen pressure, during multiple sessions. It has been used as primary or adjunctive therapy for a variety of medical disorders, including necrotizing infection and sickle cell crisis. CASE REPORT: In this case series, 3 patients with SCD and avascular necrosis were treated with 15-40 sessions of HBO and were assessed 6-12 months by MRI after treatment. They showed different clinical outcomes and MRI changes. CONCLUSION: We concluded that HBO can result in some subjective improvement, especially in early stages. Further studies on severe cases are needed.

A Rare Case of Severe Copper Deficiency in an Infant with Exclusive Breast Feeding Mimicking Myelodysplastic Syndrome.

An 11-month-old full-term female infant was referred to the hematology clinic due to marked anemia and neutropenia. She was almost exclusively breastfed and rejecting all trials for supplementary food including artificial formulas. Bone marrow aspirate revealed cytoplasmic vacuolization in precursors of the myeloid and erythroid series with significant dysgranulopoiesis and dyserythropoiesis and ringed sideroblasts. Flow cytometry analysis revealed increased hematogones with aberrant loss/downregulation of CD33 on granulocytes and monocytes (sign of dysmyelopoiesis). Laboratory investigation revealed low serum copper and ceruloplasmin. Administration of a multivitamin including a high concentration of copper for only 1 week improved her hemoglobin and absolute neutrophil count up to 1.9 × 103/µL, then dropped to 0.3 103/µL after she stopped taking the copper multivitamin. Her blood counts improved till total normalization and up to the time this report is issued. The probable role of unrecognized copper deficiency in causing anemia in infants more than 6 months of age is discussed, and the importance of serum copper examination in refractory anemia and neutropenia is emphasized. This case shows that copper deficiency should be an integral part of the differential diagnosis of refractory anemia including sideroblastic anemia and dysplasia. To the best of our knowledge, no such case has previously been described in the literature.

In vitro anticandidal potency of Syzygium aromaticum (clove) extracts against vaginal candidiasis.

BACKGROUND: Candida vaginitis is a global health hazard that increases morbidity among women of childbearing age. Recent studies have revealed a high incidence of drug-resistant Candida strains. Additionally, treating Candida vulvovaginitis during pregnancy is challenging as antifungal therapy is associated with fetal abnormalities. Hence, it is important to develop novel therapeutic strategies to treat vulvovaginal candidiasis. METHODS: In this study, we used the disc diffusion method to evaluate the anticandidal activity of different Syzygium aromaticum extracts (methanol, ethyl acetate, n-hexane, and diethyl ether) against C. albicans, C. glabrata, and C. tropicalis. Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis of different S. aromaticum extracts was performed to determine active components exhibiting anticandidal activity. Cytotoxicity of different clove extracts against the HUH7 cell line was evaluated. RESULTS: The ethyl acetate extract exhibited the highest antifungal activity against C. albicans, C. glabrata, and C. tropicalis with inhibition zone diameters of 20.9, 14.9, and 30.7 mm, respectively. The minimum inhibitory concentration of the S. aromaticum ethyl acetate extract was 250 µg/disc against C. tropicalis, and 500 µg/disc against C. albicans and C. glabrata, while the minimum fungicidal concentration was 0.5 mg/disc against C. tropicalis and 1 mg/disc against the C. albicans and C. glabrata. GC-MS analysis of the ethyl acetate extract revealed the main bioactive compound as eugenol (58.88%), followed by eugenyl acetate (23.86%), trans-caryophyllene (14.44%), and α-humulene (1.88%). The cytotoxicity assay indicated that the diethyl ether extract demonstrated the lowest toxicological effect against the HUH7 cell line, with a relative IC50 of 62.43 µg/ml; the methanolic extract demonstrated a higher toxicity (IC50, 24.17 µg/ml). CONCLUSION: As the S. aromaticum extract exhibited high antifungal activity at low concentrations, it can be a potential source of natural antifungal drugs.

Marital status and paternity in patients with Transfusion- Dependent Thalassemia (TDT) and Non Transfusion-Dependent Thalassemia (NTDT): an ICET - A survey in different countries.

BACKGROUND: More than five decades ago, thalassemia major (TDT) was fatal in the first decade of life. Survival and quality of life have improved progressively thanks to the implementation of a significant advance in diagnostic and therapeutic methods, consisting mainly of a frequent transfusion program combined with intensive chelation therapy. Improvement also includes imaging methods used to measure liver and cardiac iron overload. Improved survival has led to a growing number of adults requiring specialised care and counselling for specific life events, such as sexual maturity and acquisition of a family. AIMS OF THE STUDY: The main aim is to present the results of a survey on the marital and paternity status in a large population of adult males with TDT and NTDT living in countries with a high prevalence of thalassemia and a review of current literature using a systematic search for published studies. RESULTS: Ten out of 16 Thalassemia Centres (62.5%) of the ICET-A Network, treating a total of 966 male patients, aged above 18 years with ß- thalassemias (738 TDT and 228 NTDT), participated in the study. Of the 966 patients, 240 (24.8%) were married or lived with partners, and 726 (75.2%) unmarried. The mean age at marriage was 29.7 ± 0.3 years. Of 240 patients, 184 (76.6%) had children within the first two years of marriage (2.1 ± 0.1 years, median 2 years, range 1.8 - 2.3 years). The average number of children was 1.32 ± 0.06 (1.27 ± 0.07 in TDT patients and 1.47 ± 0.15 in NTDT patients; p: >0.05). Whatever the modality of conception, 184 patients (76.6%) had one or two children and 1 NTDT patient had 6 children. Nine (4.8%) births were twins. Of 184 patients, 150 (81.5%) had natural conception, 23 (12.5%) required induction of spermatogenesis with gonadotropins (hCG and hMG), 8 (4.3%) needed intracytoplasmic sperm injection (ICSI) and 3 adopted a child. 39 patients with TDT and NTDT asked for medical help as they were unable to father naturally: 7 TDT patients (17.9%) were azoospermic, 17 (37.7%) [13 with TDT and 4 with NTDT] had dysspermia and 15 (33.3%) [13 with TDT and 2 with NTDT] had other "general medical and non-medical conditions". CONCLUSIONS: Our study provides detailed information in a novel area where there are few contemporary data. Understanding the aspects of male reproductive health is important for physicians involved in the care of men with thalassemias to convey the message that prospects for fatherhood are potentially good due to progressive improvements in treatment regimens and supportive care.

Final Height and Endocrine Complications in Patients with ß-Thalassemia Intermedia: Our Experience in Non-Transfused Versus Infrequently Transfused Patients and Correlations with Liver Iron Content.

BACKGROUND: ß-thalassemia intermedia (TI) spans a wide spectrum of severity and carries higher morbidity than previously recognized, including extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis, secondary heart failure, pulmonary hypertension, skeletal deformity, growth retardation and endocrine abnormalities, such as diabetes mellitus, hypothyroidism, osteoporosis, and hypogonadism. OBJECTIVES: To evaluate the final height and the endocrine complications encountered in young adult patients with TI followed at Hematology Section, Doha (Qatar) in relation to liver iron content in non-transfused versus infrequently transfused TI patients. PATIENTS AND METHODS: This retrospective cohort study was performed on 28 young adults with TI who were randomly selected from the Hematology Clinic of the Hematology Section, National Centre for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar).Eligibility criteria for this retrospective analysis included TI patients diagnosed by complete blood count, hemoglobin electrophoresis and young adult age ( ≥ 18 years).Group 1 included nine patients who did not receive any blood transfusion, and Group 2 included 19 patients who infrequently received blood transfusions.Data recorded from charts included demographic characteristics (gender, date of birth, ethnicity), disease and treatment characteristics (e.g., transfusion frequency, history of chelation therapy, and splenectomy), auxological and pubertal data [growth percentiles and pubertal stages, and body mass index (BMI)], laboratory data and target organ complications (including endocrinopathies and liver disease). Iron overload was assessed by direct (liver iron content; LIC) and indirect methods (SF), and bone mass index (BMA) by dual-energy X-ray absorptiometry (DXA). RESULTS: Short stature [Final Height (Ht) SDS < -2] occurred in 25% of patients with no difference between the two groups of patients. Insulin growth factor 1 (IGF-1) SDS was low in 35.7 % of patients with no statistical difference among the two groups. Impaired fasting blood glucose occurred in 17.8% of patients, diabetes mellitus in 25% and hypogonadotropic hypogonadism in 10.7% of them. Morning cortisol was low in one patient. No thyroid or hypo-parathyroid abnormalities were detected in any patient. Liver iron content (LIC) > 15 mg/g dry weight and SF > 2,000 ng/mL were detected in 75% of the patients. The values resulted significantly higher in the transfused group (Group 2). High liver enzyme level (ALT) was detected in 42.8 % of patients, and the values were significantly higher in the transfused group (Group 2). Total and fetal Hb was significantly higher in group 1 versus group 2. Osteopenia was diagnosed in 14.3% of patients. Females had significantly better final height SDS, higher IGF-1 SDS, lower LIC and fasting blood glucose level compared to males. Significant correlations were found between Ht-SDS and IGF-1 SDS; LIC and SF, level; ALT and LIC, SF levels. Total and fetal Hb did not correlate significantly with Ht-SDS or IGF-1 level. CONCLUSIONS: A significant number of TI patients have high LIC, short stature and endocrine disorders. Patients who require occasional transfusions have more liver iron overload and higher hepatic dysfunction. Females appear to attain a better final adult height and have higher IGF1-SDS versus males. Our data emphasize the need for long term surveillance for identification of organ-specific risk factors and early disease manifestations. We also recommend close monitoring of endocrine and other complications, according to the international guidelines.

Severe Liver Iron Concentrations (LIC) in 24 Patients with ß-Thalassemia Major: Correlations with Serum Ferritin, Liver Enzymes and Endocrine Complications.

INTRODUCTION: Chronic blood transfusion is the mainstay of care for individuals with ß-thalassemia major (BTM). However, it causes iron-overload that requires monitoring and management by long-term iron chelation therapy to prevent endocrinopathies and cardiomyopathies, which can be fatal. Hepatic R2 MRI method (FerriScan®) has been validated as the gold standard for evaluation and monitoring liver iron concentration (LIC) that reflects the total body iron-overload. Although adequate oral iron chelation therapy (OIC) is promising for the treatment of transfusional iron-overload, some patients are less compliant with it, and others suffer from long-term effects of iron overload. OBJECTIVE: The aim of our study was to evaluate the prevalence of endocrinopathies and liver dysfunction, in relation to LIC and serum ferritin level, in a selected group of adolescents and young adult BTM patients with severe hepatic iron overload (LIC from 15 to 43 mg Fe/g dry weight). PATIENTS AND METHODS: Twenty-four selected BTM patients with severe LIC, due to transfusion-related iron-overload, followed at the Haematology Section, National Centre for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar), from April 2015 to July 2017, were retrospectively evaluated. The prevalence of short stature, hypogonadism, hypothyroidism, hypoparathyroidism, impaired fasting glucose (IFG), diabetes, and adrenal insufficiency was defined and assessed according to the International Network of Clinicians for Endocrinopathies in Thalassemia (ICET) and American Diabetes Association criteria. RESULTS: Patients' most common transfusion frequency was every three weeks (70.8%). At the time of LIC measurements, their median age was 21.5 years with a mean age of 21.7 ± 8.0 years. Mean LIC was 32.05 ± 10.53 mg Fe/g dry weight (range: 15 to 43 mg Fe/g dry weight), and mean serum ferritin level was 4,488.6 ± 2,779 µg/L. LIC was correlated significantly with serum ferritin levels (r = 0.512; p = 0.011). The overall prevalence of short stature was 26.1% (6/23), IFG was 16.7% (4/24), sub-clinical hypothyroidism was 14.3% (3/21), hypogonadotropic hypogonadism was 14.3% (2/14), diabetes mellitus was 12.5% (3/24), and biochemical adrenal insufficiency was 6.7% (1/15). The prevalence of hepatitis C positivity was 20.8% (5/24). No case of clinical hypothyroidism, adrenal insufficiency or hypoparathyroidism was detected in this cohort of patients. The prevalence of IFG impaired fasting glucose was significantly higher in BTM patients with very high LIC (>30 mg Fe/g dry liver) versus those with lower LIC (p = 0.044). The prevalence of endocrinopathies was not significantly different between the two groups of patients with LIC above and below 15 mg Fe/g dry weight. CONCLUSIONS: A significant number of BTM patients, with high LIC and endocrine disorders, still exist despite the recent developments of new oral iron chelating agents. Therefore, physicians' strategies shall optimize early identification of those patients to optimise their chelation therapy and to avoid iron-induced organ damage. We believe that further studies are needed to evaluate if serial measurements of quantitative LIC may predict the risk for endocrine complications. Until these data are available, we recommend a close monitoring of endocrine and other complications, according to the international guidelines.

Jadenu® Substituting Exjade® in Iron Overloaded ß-Thalassemia Major (BTM) Patients: A Preliminary Report of the Effects on the Tolerability, Serum Ferritin Level, Liver Iron Concentration and Biochemical Profiles.

INTRODUCTION: Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade® is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of patients with chronic iron overload. This may significantly improve the compliance to treatment of patients with ß-thalassemia major (BMT). The aim of this study was to evaluate the drug tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload. PATIENTS AND METHODS: Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular red cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade® therapy (30 mg/kg per day) for two years or more before starting Jadenu® therapy (14-28 mg/kg/day). The reason for shifting from Deferasirox® to Jadenu® therapy was lack of tolerability, as described by patients, such as nausea, vomiting, diarrhea, stomach pain. Most of them also reported that Deferasirox® was not palatable. Lab investigations included monthly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year after starting Jadenu ® therapy, were also assessed. RESULTS: Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment. Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade® therapy in 8 out of 12 BMT patients. A non-significant decrease in LIC measured by FerriScan® and serum ferritin levels was observed after one year of treatment with Jadenu®. A significant positive correlation was found between serum ferritin level and LIC measured by the FerriScan® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters. CONCLUSIONS: Our study shows that short-term treatment with Jadenu ® is safe but is associated with a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and the longterm outcomes of new deferasirox formulation.

Hypogonadism in male thalassemia major patients: pathophysiology, diagnosis and treatment.

Failure of pubertal growth, delay or absence of sexual development, infertility and sexual dysfunction due to hypogonadism and defective spermatogenesis are frequent and well recognized disturbances among male patients with transfusion dependent (TD) thalassaemia major (ß-thal). These problems are attributed mainly to the damage caused by chronic anaemia and the deposition of excess iron in the pituitary gland and testicles. This is a short review of male pubertal disorders in patients with ß-thal written by pediatric endocrinologists and haematologists with an interest and active involvement, in the diagnosis and management of these complications in this group of patients. A vigilant clinical evaluation of growth and puberty, as well as an appropriate hormonal evaluation in poly-transfused (TD ß-thal) patients is strongly recommended for early detection and treatment of endocrine dysfunction. Of crucial importance also, is the implementation of an efficient chelation regime from early life, to prevent severe iron load and permanent damage to the endocrine glands, particularly those responsible for gonadal function.