Predisposing factors for advanced liver fibrosis in patients with sickle cell disease.

Sickle cell disease (SCD) is one of the most common monogenic disorders worldwide and liver complications are common in this group of patients. Our study aims to highlight the prevalence of chronic liver complications and the main predisposing factors for advanced liver fibrosis in SCD patients. For this purpose, 219 patients from eight Thalassemia and Sickle Cell Units across Greece enrolled in our study and history of liver related disease complications was recorded, as well as a full laboratory and imaging analysis concerning their liver function. 13.6% of the patients had advanced liver fibrosis. The presence of liver fibrosis was significantly correlated with advanced age, male gender, cholelithiasis and higher LDH, γ-GT, INR, direct and indirect bilirubin levels. These patients had exhibited significantly more episodes of liver crises and acute intrahepatic cholestasis. No correlation was observed with right heart failure or previous viral hepatitis. Patients with advanced liver fibrosis were receiving a more intensive transfusion therapy for a longer period of time and had higher Liver Iron Concentration levels. Our study shows that liver complications and cirrhosis is a significant cause of morbidity in patients with SCD and it is primarily associated with intravascular hemolysis and vaso-occlusive phenomena and secondarily with iron overload.

Invasive Mucormycosis in Children With Malignancies: Report From the Infection Working Group of the Hellenic Society of Pediatric Hematology-Oncology.

Mucormycosis is an invasive, life-threatening fungal infection that mainly affects immunocompromised hosts. We collected data of pediatric mucormycosis cases from all 7 Greek Hematology-Oncology Departments for the years 2008-2017. Six cases of invasive mucormycosis diagnosed during treatment for malignancies were included in the study. In 4 children (66%) mucormycosis occurred within the first 20 days after diagnosis of the underlying disease. Two cases were classified as proven mucormycosis and 4 as probable. The most frequently recorded species was Rhizopus arrhizus (2 patients), followed by Mucor spp (1), and Lichtheimia spp (1). All patients received liposomal amphotericin B. Combined antifungal treatment was used in 5 cases. Surgical excision was performed in 4 cases (66%). Two patients died at 6 and 12 months after the diagnosis, respectively, 1 (17%) because of mucormycosis. Our data suggest that mucormycosis may occur early after the initiation of intensive chemotherapy in children with malignancies.

Successful long-term hematological and immunological reconstitution by autologous cord blood transplantation combined with post-transplant immunosuppression in two children with severe aplastic anemia.

aUCBT is a valuable curative option in pediatric patients with refractory idiopathic SAA and no available matched sibling or unrelated donors. Experience in the use of autologous cord blood units in patients with SAA is limited and private for-profit cord blood-banking programs are controversial. We report the successful treatment of two patients with SAA, aged 15 and 24 months, with autologous cord blood combined with immunosuppression. After conditioning with 200 mg/kg cyclophosphamide and ATG, 7.5 mg/kg, 32.2 × 107 /kg, and 3.8 × 107 /kg autologous cord blood nucleated cells were infused, respectively. One of our patients underwent transplantation after failure of IST. Both patients received post-transplant immunosuppression with cyclosporine for 12 months. They remain disease-free 6 years post-transplantation.

Voriconazole Antifungal Prophylaxis in Children With Malignancies: A Nationwide Study.

BACKGROUND: Antifungal prophylaxis (AFP) is recommended in at-risk hematology-oncology patients. We evaluated the safety of AFP with voriconazole (VRC) in pediatric hematology/oncology patients. MATERIALS AND METHODS: A retrospective study of VRC AFP in children with malignancies hospitalized in all 7 Greek pediatric hematology/oncology centers during 2008 to 2012 was conducted. Patients' demographics, outcome, and adverse event (AE) data were recorded. RESULTS: Four hundred twenty-nine VRC AFP courses in 249 patients (median age 6 y, 55% boys) were studied. The most common underlying diseases were acute lymphoblastic leukemia (51%), non Hodgkin lymphoma (8.6%), and acute myeloid leukemia (7.7%). The median number of VRC courses per patient was 1.7, whereas the median VRC dose was 7 mg/kg (range, 5 to 7 mg/kg) every 12 hours. During the last 2 weeks before AFP, 51% of the patients had received corticosteroids, 43% suffered from severe neutropenia, and 17.3% from mucositis. The median duration of VRC AFP was 17 days (range, 1 to 31 d). A single breakthrough fungemia due to Candida glabrata was recorded. Only 1 patient died due to the underlying disease. The most common AEs reported in 70/429 (16.3%) courses with ≥1 AE were elevated liver enzymes (50%), hypokalemia (24.3%), and ophthalmological disorders (14.3%). The median time of AE onset was 5 days (range, 1 to 21 d). Among 70 AEs reported, 38.5%, 48.4%, and 12.8% were of grade I, II, and III, respectively. CONCLUSIONS: VRC prophylaxis in pediatric hematology/oncology patients appears to be well tolerated.

Correlation of NT-proBNP levels and cardiac iron concentration in patients with transfusion-dependent thalassemia major.

Iron-induced cardiotoxicity remains the leading cause of morbidity and mortality in patients with transfusion-dependent ß-thalassemia major. Heart failure in these patients, which may be reversible but has a poor prognosis, is characterized by myocardial iron deposition-related early diastolic dysfunction. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker for the detection of asymptomatic left ventricular dysfunction. In this study, we prospectively evaluated plasma NT-proBNP levels in 187 adult patients aged 19-54 years with ß-TM. Possible correlations with the proposed recently cardiac iron concentration based on an equation derived from heart T2* assessment by MRI: [Fe] = 45.0 × [T2*](-1.22) with [Fe] in milligrams per gram dry weight and T2* in milliseconds were explored. We found that: 143 patients had no cardiac hemosiderosis, defined as [Fe] < 1.1 mg/g dry weight, corresponding to T2* > 20 ms and 44 patients had cardiac hemosiderosis, defined as [Fe] > 1.2mg/g dry weight. The main results of the study showed that: a) NT-proBNP levels were markedly increased in thalassemic patients (152.2 ± 190.1 pg/mL, ranged from 6.0 to 1336.0 pg/mL compared to normal control levels 40.1 ± 19.7 pg/mL, p < 0.001, b) NT-proBNP levels were significantly higher in patients with cardiac hemosiderosis compared to patients without cardiac hemosiderosis (185.1 ± 78.0 vs 128.9 ± 20.2 pg/mL, p < 0.05), c) NT-proBNP levels correlated with [Fe] values (r = 0.387, p < 0.001). This correlation was significant in patients with cardiac hemosiderosis (r = 0.520, p < 0.001), but not in patients without cardiac hemosiderosis (p > 0.1), and d) no significant correlation was found between NT-proBNP levels and left ventricular ejection fraction values, (p > 0.3). Our study demonstrated for first time the significant association of NT-proBNP levels and cardiac iron concentration in patients with ß-thalassemia major linking blood chemistry and imaging techniques. Multicenter studies of these parameters during iron chelation therapies are needed to validate their association and further exploit its clinical use.

Assessment of oxidative stress in patients with sickle cell disease: The glutathione system and the oxidant-antioxidant status.

Continuous reactive oxygen species (ROS) production in individuals with sickle cell disease (SCD) may alter their overall redox status and cause tissue damage. The aim of this study was to evaluate oxidative stress in patients with SCD using two new assays, FORT (free oxygen radical test) and FORD (free oxygen radical defense) along with assessment of glutathione system including superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities, vitamins A, C and E, malondialdehyde (MDA), non-transferrin bound iron (NTBI) and nitric oxide (NO) concentrations. A total of 40 patients with SCD and 25 apparently healthy volunteers (control group) were enrolled in the study. Components of glutathione system, vitamins A, C, and E, and malondialdehyde were determined with reverse-phase HPLC, non-transferrin bound iron (NTBI) was assessed with atomic absorption spectroscopy using graphite furnace, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities were determined spectrophotometrically in red cell lysates, nitric oxide (NO) was detected colorimetrically, while FORT and FORD using colorimetric assays, as two point-of-care tests. The findings revealed significant impairment of the glutathione system indicated by reduced GSH(total) (p<0.00001), GSH(reduced) (p<0.00001) and GSSG (p>0.056) values of SCD patients compared to the control group. ROS expressed as FORT were significantly increased (p<0.00001), while antioxidant defense expressed as FORD was significantly reduced (p<0.02) in SCD group compared to the control group. Age and genotype of the patients as well as therapy of their disease appeared to play no role in their oxidative status.

Disturbances of biomarkers of iron and oxidant-antioxidant homeostasis in patients with beta-thalassemia intermedia.

BACKGROUND: Disturbances of oxidative stress and antioxidant status have been reported in patients with Β-ThM and in a limited number of patients with ThI. OBJECTIVES: To I) study relevant biomarkers of iron metabolism, oxidative stress and antioxidant status, in untransfused patients with ThI and II) evaluate the relation of changes in biomarkers to the clinicalhematological phenotype and genotype. DESIGN: Biomarkers of iron metabolism (ferritin, NTBI, sTfR), of oxidant activity (MDA, GSSG, GSSC/GSHT, NO) and of antioxidant enzymes (GR, GPx, SOD) and Vitamins (E, C, A) were estimated and analyzed in 20 controls and 33 patients with ThI, sub-classified into mild (17) and severe (16) types. All but five were untransfused. RESULTS: Clinical phenotypes of mild and severe ThI were related to distinct genotypes, 11 for mild and 14 for severe. The three iron biomarkers were significantly increased in both ThI types compared to controls and in severe compared to mild types. The ferritin levels (total iron load) had a highly significant positive correlation with age (p〈0.001) and sTfR. Biomarkers with oxidant activity were also significantly increased in ThI patients compared to controls; significantly higher levels for MDA, NTBI, and GSSG/GSHT were found in severe ThI. The activity of antioxidant enzymes GR, GP and SOD, was significantly significantly reduced in patients, especially in the severe type. Vitamin C was mildly reduced in both types of ThI. CONCLUSIONS: Activity of relevant biomarkers of iron and oxidant-antioxidant homeostasis was significantly increased in untransfused patients with ThI. These changes coincide with the severity of clinical phenotype, genotype and bone marrow erythroid activity evaluated by sTfR levels.

Invasive Fungal Infections in Children with Haematological Malignancies: Diagnostic and Therapeutic Challenges.

The incidence of invasive fungal infections (IFIs) has dramatically increased over the last few decades in parallel with the increased number of immunocompromised patients [...].

Low- and High-Attenuation Lung Volume in Quantitative Chest CT in Children without Lung Disease.

In contrast to studies of adults with emphysema, application of fixed thresholds to determine low- and high-attenuation areas (air-trapping and parenchymal lung disease) in pediatric quantitative chest CT is problematic. We aimed to assess age effects on: (i) mean lung attenuation (full inspiration); and (ii) low and high attenuation thresholds (LAT and HAT) defined as mean attenuation and 1 SD below and above mean, respectively. Chest CTs from children aged 6-17 years without abnormalities were retrieved, and histograms of attenuation coefficients were analyzed. Eighty examinations were included. Inverse functions described relationships between age and mean lung attenuation, LAT or HAT (p < 0.0001). Predicted value for LAT decreased from -846 HU in 6-year-old to -950 HU in 13- to 17-year-old subjects (cut-off value for assessing emphysema in adults). %TLCCT with low attenuation correlated with age (rs = -0.31; p = 0.005) and was <5% for 9-17-year-old subjects. Inverse associations were demonstrated between: (i) %TLCCT with high attenuation and age (r2 = 0.49; p < 0.0001); (ii) %TLCCT with low attenuation and TLCCT (r2 = 0.47; p < 0.0001); (iii) %TLCCT with high attenuation and TLCCT (r2 = 0.76; p < 0.0001). In conclusion, quantitative analysis of chest CTs from children without lung disease can be used to define age-specific LAT and HAT for evaluation of pediatric lung disease severity.

Diagnostic Capacity for Invasive Fungal Infections in the Greek Paediatric Haematology-Oncology Units: Report from the Infection Working Group of the Hellenic Society of Paediatric Haematology-Oncology.

An audit based on a specific questionnaire was attempted, in order to investigate the mycology laboratory diagnostic capacity for invasive fungal diseases (IFDs) in Greek Paediatric Haematology-Oncology departments/units. The study provided the relevant information for the years 2019 and 2020 and included data from all units, concerning culture-based methods and direct microscopy, phenotypic and molecular identification, sensitivity testing, serology and molecular diagnosis, as well as therapeutic drug monitoring. The target was mostly to reveal the level of laboratory coverage for hospitalised paediatric patients, independently of the possibility of performing the tests in the host hospital, or otherwise to refer the specimens elsewhere. In total, the current study demonstrated that the most important facilities and services regarding the IFD diagnostics for paediatric haematology-oncology patients in Greece are available and relatively easily accessible, with a reasonable turnaround time. Acting as an initial registry for further improvements, the audit can serve as a valuable approach to the actual situation and future perspectives. A national clinical mycology network under the auspices of the relevant scientific societies will probably facilitate collaboration between all the departments (clinical and laboratory) involved in invasive fungal infections and provide an easier approach to any necessary test for any hospitalised patient.

Evaluation of liver fibrosis in patients with thalassemia: the important role of hyaluronic acid.

Patients with transfusion-dependent thalassemia major often develop liver fibrosis due to liver iron overload and/or hepatitis virus C (HCV) infection. Hyaluronic acid (HA) plays a prominent role in the pathogenesis of liver fibrosis and the elevation of serum HA concentration is due to either increased synthesis by inflammatory cells and hepatic stellate cells or impaired degradation by sinusoidal endothelial cells (SECs) and thus is proposed as a non-invasive biomarker of liver fibrosis either by itself and/or included in the Hepascore formula. In this study we evaluated prospectively a screening of liver fibrosis in 201 adult patients aged 19-54 years with transfusion-dependent thalassemia major, based on HA measurements. 41/201 patients were HCV-RNA (+). HA was measured with a turbidimetric assay applied on a clinical chemistry analyzer. The Hepascore was computed from the results by using the model previously published. The main results of the study showed that: a) HA levels were increased in 110/201 (55%) thalassemia patients 85.0 ± 10.3 ng/ml, ranged from 15.0 to 1495.0 µg/l, compared to 20.8 ± 7.4 µg/l reference laboratory values, p<0.001, b) HA levels were significantly higher in HCV-RNA(+) compared to HCV-RNA(-) patients, 171.6 ± 202 vs 53.8 ± 35.5 µg/l, p<0.0001 c) no significant correlations were found between HA levels and/or Hepascore with ferritin and liver iron content (LIC) assessed with MRI (p>0.324 and p>0.270, respectively). Our findings indicate that hyaluronic acid measurements contribute to the assessment of liver fibrosis in patients with thalassemia and might be helpful for further evaluation of patients with liver biopsy if this is truly needed. Furthermore, liver fibrosis in thalassemia seems to be independent from liver siderosis.

Candidemia in Children with Malignancies: Report from the Infection Working Group of the Hellenic Society of Pediatric Hematology-Oncology.

Candidemia is an important cause of morbidity and mortality especially in immunocompromised and hospitalized patients. We retrospectively collected data of candidemia cases that occurred in the seven Hematology-Oncology Departments/Units of Greece and the Stem Cell Transplant Unit between 2015 and 2019. In total, 19 episodes of candidemia in 19 patients were recorded. The majority of the patients (78.9%) had at least one risk factor for candidemia. The most frequent risk factors associated with candidemia observed in our patients were prolonged duration of hospitalization (30 days, range 1-141), presence of a central venous catheter at diagnosis of candidemia (73.7%) and antibiotics use during the last two weeks (84.2%). Candida parapsilosis was the most common species isolated accounting for 42.1%, followed by C. albicans (26.3%) and C. famata (15.8%). Nearly all of the patients (84.2%) received antifungal monotherapy with liposomal amphotericin B or echinocandins. The central venous catheter was removed in 78.6% of patients and the median time between the first positive blood culture and catheter removal was 3 days (range 1-9). Mortality at 28 days was 26.3%. In conclusion, a predominance of non-albicans species was observed in our study in conformity with the global trend.

Evaluation of endocrine complications in beta-thalassemia intermedia (ß-TI): a cross-sectional multicenter study.

BACKGROUND: Data on the prevalence and type of endocrine disorders in ß-thalassemia intermedia (ß-TI) patients are scarce. This multicenter study was designed to determine the prevalence of endocrine complications and the associated risk factors in a large group of ß-TI patients. METHODS: In this cross-sectional multicenter study, 726 ß-TI patients, aged 2.5-80 years, registered at 12 thalassemic centers, from nine countries, were enrolled during 2017. In a subgroup of 522 patients (mean age 30.8 ± 12.1; range: 2.5-80 years) from Qatar, Iran, Oman, Cyprus, and Jordan detailed data were available. RESULTS: Overall, the most prevalent complications were osteopenia/osteoporosis (22.3%), hypogonadism (10.1%), and primary hypothyroidism (5.3%). In the subgroup multivariate analysis, older age was a risk factor for osteoporosis (Odds ratio: 7.870, 95% CI: 4.729-13.099, P < 0.001), hypogonadism (Odds ratio: 6.310, 95% CI: 2.944-13.521, P < 0.001), and non-insulin-dependent diabetes mellitus (NIDDM; Odds ratio: 17.67, 95% CI: 2.217-140.968, P = 0.007). Splenectomy was a risk factor for osteoporosis (Odds ratio: 1.736, 95% CI: 1.012-2.977, P = 0.045). Hydroxyurea was identified as a "protective factor" for NIDDM (Odds ratio: 0.259, 95% CI: 0.074-0.902, P = 0.034). CONCLUSIONS: To the best of our knowledge, this is the largest cohort of ß-TI patients with endocrine disorders evaluated in extremely heterogenic thalassemic populations for age, clinical, hematological, and molecular composition. The study demonstrates that endocrine complications are less common in patients with ß-TI compared with ß-TM patients. However, regular monitoring with timely diagnosis and proper management is crucial to prevent endocrine complications in ß-TI patients.

The experience of a tertiary unit on the clinical phenotype and management of hypogonadism in female adolescents and young adults with transfusion dependent thalassemia.

BACKGROUND: Transfusion-dependent ß-thalassemia (TDT) is associated with several complications necessitating a multidisciplinary approach for diagnosis, treatment and follow-up. Hypogonadism in female TDT patients is one of the most common endocrine complications, requiring hormone replacement therapy (HRT) throughout reproductive life. Little is known about the balance of benefits versus risks of treatment with sex steroids. AIM: The aim of this manuscript is to review the action and the associated adverse effects of HRT in hypogonadal TDT females. DESIGN: Retrospective medical database records from a single centre, over a period of 38 years (January 1980 to June 2018), were reviewed. STUDY POPULATION: Forty-two cases of hypogonadism in TDT females followed in a pediatric and adolescent outpatient clinics, were in included in the study. METHODS: Auxological, clinical, laboratory, hormonal and imaging investigations were reviewed, as well as all adverse events registered during HRT. MAIN RESULTS: In general, HRT was safe for most patients. There were few minor side effects and a couple of rare but serious adverse events. CONCLUSIONS: The study provides a representative clinical profile of long-term effects of HRT in hypogonadal adolescents and young adult TDT women. Our results highlight also the need for further research in other areas for which HRT may have a role.  We hope this will contribute to a wider understanding, and potential improvement, of patient safety and quality of life.

Pregnancy Complications in a-Thalassemia (Hemoglobinopathy H): A Case Study.

Thalassemia intermedia (TI) is a clinical definition which represents a wide spectrum of thalassemia genotypes but mainly includes patients who do not require or only occasionally require transfusion. An uncommon case of a 32-year-old Greek woman, para 1, at the 22nd week + day 3 of gestation with thalassemia intermedia (she was splenectomized), where her pregnancy was complicated with portal vein thrombosis, splenic thrombosis, and partial HELLP, is described. This is a generally uncommon event in thalassemia intermedia. She had no transfusion as her hematologist consulted and she took anticoagulation therapy. Thus, we present for the first time in the literature a case of HbH a-thalassemia pregnant woman whose pregnancy was complicated with portal vein thrombosis, splenic vein thrombosis, and partial HELLP; she was treated with anticoagulation therapy and she had a successful outcome.

Plasma neutrophil gelatinase-associated lipocalin levels are markedly increased in patients with non-transfusion-dependent thalassemia: Lack of association with markers of erythropoiesis, iron metabolism and renal function.

BACKGROUND: Neutrophil Gelatinase-Associated Lipocalin (NGAL) (known as NGAL, Lipocalin 2, Siderocalin, Uterocalin, proteinase-3 and 24p3) is a mammalian small 25-kD peptide that belongs to the lipocalin superfamily, which consists of about 20 small lipoproteins. NGAL was initially discovered as an antibacterial factor of natural immunity and an acute-phase protein. NGAL is also an iron trafficking protein, a member of the non-transferrin-bound iron (NTBI) pool and an alternative to the transferrin-mediated iron-delivery pathway. Of note, NTBI, which is elevated in thalassemic patients, induces cellular toxicity. In this study we investigated the possible association of NGAL with parameters of erythropoiesis, iron metabolism and renal injury in patients with non-transfusion-dependent thalassemia (thalassemia intermedia or TI). PATIENTS AND METHODS: Thirty-five patients with TI, 13 men and 22 women, aged 8-63 years, were included in the study, while, 20 healthy individuals served as controls. Plasma NGAL levels were determined using an immunoenzymatic technique. Erythroid marrow activity was estimated by measuring soluble transferrin receptors (sTfR) levels with a turbidimetric technique. NTBI levels were determined using electrothermal atomic absorption spectrometry. Cystatin C, ß2-microglobulin and hs-CRP concentrations were measured by means of immunonephelometric techniques. RESULTS: The main results of the study showed: a) NGAL levels were significantly higher in patients with TI compared to controls (139.1 ± 86.1 vs 51.2 ± 11.8 µg/L, p<0.0001), without significant effect of splenectomy or hydroxyurea on NGAL levels. Only 4 patients had NGAL levels within the control group range, b) no correlation was found between NGAL levels and either the parameters of erythropoiesis Hb, Hb F, reticulocytes and sTfR (p>0.66, p>0.67, p>0.63 and p>0.81 respectively), or with those of iron metabolism ferritin and NTBI (p>0.90 and p>0.95 respectively). CONCLUSIONS: The increased NGAL levels reported for the first time in TI patients in this study are in agreement with the elevated expression of NGAL observed in TI mouse models. We postulate that the induction of NGAL in these patients may represent either a survival response, facilitating the survival of the less damaged thalassemic erythroid precursors, or a consequence of the abnormal iron regulation in TI.

The reproducibility of cardiac and liver T2* measurement in thalassemia major using two different software packages.

In b-thalassemia major (TM) multiple blood transfusions are needed for survival. As a consequence these patients present iron overload in different organs, including heart and liver. Magnetic resonance imaging using a bright blood gradient echo sequence has been successfully used for the quantification of tissue iron. The aim is to evaluate of the accuracy and precision in the evaluation of liver and myocardial T2* values in TM using two different analytical software solutions. Thirty TM patients aged 20-56 years (mean age 37, 11M/19F) were scanned in a GE 1.5 T CVI system. Each scan included the measurement of heart and liver T2* and the left ventricular ejection fraction using standard techniques. The analysis of T2* of heart and liver was done using the two different analytical software solutions: the "Functool" protocol by GE and the T2* module of QMassMR v7.4 by Medis medical imaging systems bv, Leiden, The Netherlands. The cardiac and liver T2* measurements showed that both software solutions allow reproducible measurements with low intra-observer variations (accuracy < 0.3 ms, precision < 2 ms). There is a small but significant difference between the two solutions of 2.4 ms in cardiac and of 1.5 ms in liver measurements. However, from the clinical point of view these differences (<2 ms) are small with negligible impact on the patient's treatment management. The comparison of the T2* measurements using the two analytical software solutions proved that both techniques enable reproducible measurements for the evaluation of iron overload in heart and liver.

The Greek cardiac magnetic resonance experience: a comparison with the EuroCMR Registry.

INTRODUCTION: We carried out an evaluation of Greek cardiovascular magnetic resonance (CMR) data in order to analyse the indications, safety, quality, and impact on management, in comparison with the EuroCMR registry. METHODS: A retrospective analysis was performed of Greek CMR data from patients referred from 6 Greek cardiac clinics to 6 different MRI units in Athens that offer CMR services. A total of 10,000 CMR examinations carried out from 1995 to 2010 were evaluated retrospectively and included in the study. RESULTS: Fifty percent of patients underwent evaluation for thalassaemic syndromes. In the remaining 50%, the most important indications were: a) workup of myocarditis/cardiomyopathies (40%), b) assessment of viability (5%), and c) congenital heart disease (5%). Image quality was good in 75%, moderate in 15%, and inadequate in 10% of cases. Complications occurred in 0.02%, including allergic reactions, dyspnoea, and panic attack. No death or cardiac complication was observed during or due to CMR; however, stress testing was not used in any of the cases. In 65% of all CMR studies, the initial diagnosis made by a non SCMR-trained person had no impact on the patients' management and did not offer any diagnostic contribution to referral clinicians, discouraging them from referring for CMR again. However, after the re-evaluation performed by an SCMR-trained person, the results of the Greek CMR were capable of satisfying all imaging needs in a percentage of patients equivalent to that presented in the EuroCMR registry (83% vs. 86%, p=NS), so that no further non-invasive imaging procedures would be required after CMR. CONCLUSIONS: Thalassaemia and myocarditis were the most frequent CMR indications in Greece. However, the lack of training according to SCMR guidelines lowers the diagnostic efficacy significantly and leads to under-use of the technique.

Statins, bone formation and osteoporosis: hope or hype?

Osteoporosis is a major health problem affecting both men and women. Statins, besides their action as lipid-lowering agents, seem to have additional pleiotropic properties, among them a beneficial effect on bone mineral density. The entirety of experimental and the majority of clinical studies as well as the only relevant meta-analysis suggest that statins have an anabolic effect on bone metabolism. Statins, osteoporosis and adipogenesis share the same pathway, RANKL/OPG. It would appear that an imbalance in this pathway could be responsible for the manifestation of some metabolic disorders such as diabetes mellitus, atherogenesis, multiple myeloma, osteoporosis. Possibly in the future, drugs which can intervene in this biochemical and pathophysiological cascade, like statins, in a variety of doses, could be used for the management of ectopic ossification syndromes and other bone disorders, even as an additive treatment. Until then, further large longitudinal randomized controlled studies for each statin separately are required to confirm this hypothesis.

Observation of a rare hemoglobin variant [Hb Lulu island, beta107(G9)Gly-->Asp, GGC-->GAC] co-inherited with a beta+-thalassemia mutation [IVS-I-110 (G-->A)] or in the heterozygous state in a Greek-Albanian family.

We report clinical, hematological, biochemical, functional and molecular studies carried out on two first cousins from a Greek-Albanian family who have clinical and hematological findings consistent with the diagnosis of thalassemia intermedia. DNA studies determined that they had co-inherited a common Mediterranean beta-thalassemia (thal) mutation, IVS-I-110 (G-->A), in trans to a beta-globin gene mutation at codon 107 (GGC-->GAC), predicted to give rise to a rare unstable beta chain variant Hb Lulu Island or beta107(G9)Gly-->Asp.