Giorgos Chouliaras

Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major

Cardiac and endocrine disorders are common sequelae of iron overload in transfused thalassaemia patients. Combined chelation with desferrioxamine (DFO) and deferiprone (DFP) is well tolerated and produces an additive/synergistic effect superior to either drug alone. 52 thalassaemia major patients were transitioned from DFO to combined chelation with DFO and DFP. Serum ferritin, cardiac and hepatic iron levels were monitored regularly for up to 7 years, as were cardiac and endocrine function. Patients’ iron load normalized, as judged by ferritin and cardiac and hepatic magnetic resonance imaging findings. In all 12 patients receiving treatment for cardiac dysfunction, symptoms reversed following combined chelation, enabling nine patients to discontinue heart medications. In the 39 patients with abnormal glucose metabolism, 44% normalized. In 18 requiring thyroxine supplementation for hypothyroidism, 10 were able to discontinue, and four reduced their thyroxine dose. In 14 hypogonadal males on testosterone therapy, seven stopped treatment. Of the 19 females, who were hypogonadal on DFO monotherapy, six were able to conceive. Moreover, no patients developed de novo cardiac or endocrine complications. These results suggest that intensive combined chelation normalized patients’ iron load and thereby prevented and reversed cardiac and multiple endocrine complications associated with transfusion iron overload.

Survival in a large cohort of Greek patients with transfusion‐dependent beta thalassaemia and mortality ratios compared to the general population

Background:  With transfusions and chelation therapy, the prognosis for transfusion‐dependent beta thalassaemia has changed from being fatal in early childhood to a chronic disorder with prolonged survival.

Impact of magnetic resonance imaging on cardiac mortality in thalassemia major

To evaluate whether the introduction of magnetic resonance imaging (MRI) in the management of thalassemia major (TM) patients has affected the risk of cardiac death.

Bone Health in Children With Celiac Disease Assessed By Dual X-ray Absorptiometry: Effect of Gluten-free Diet and Predictive Value of Serum Biochemical Indices

Objectives: In the present study, we aimed to assess bone status and the effect of gluten-free diet (GFD) in children with celiac disease (CD), and to evaluate the predictive value of standard serum biochemical indices in the diagnosis of bone mineral density (BMD) disturbances. Methods: Forty-five children at the time of diagnosis of CD (group A, 77.8% girls) and 36 children receiving GFD for >2 years (group B, 75% girls) were included. Sixteen children in group A were reexamined 12 months after initiation of GFD. Serum measurements of biochemical bone health indices and BMD, assessed by dual x-ray absorptiometry, were obtained. Results: Patients after 1 year of receiving GFD had higher BMD z scores compared with baseline (−1.45 ± 0.28 vs −0.61 ± 0.25, respectively, P = 0.004). BMD z scores were significantly lower than expected for the normal population, after 1 (P = 0.03) or at least 2 (P < 0.001) years of receiving GFD. In group B, BMD z score was positively correlated with 25-hydroxy vitamin D levels (P = 0.009). In the repeated measurements group, 25-hydroxy vitamin D differed between pre- and post-GFD (P = 0.018). No biochemical index was capable of predicting an abnormal BMD z score (receiver operating characteristic curve analysis, all of the areas under the curve <0.66). Conclusions: GFD has a beneficial effect on bone health. Two years receiving diet do not ensure normalization. Biochemical markers are not indicative of BMD disturbances. Dual x-ray absorptiometry should be included in the standard management of children with CD.

Relation of chelation regimes to cardiac mortality and morbidity in patients with thalassaemia major: an observational study from a large Greek Unit

Objectives:  Cardiac complications because of transfusional iron overload are the main cause of death in thalassaemia major. New chelators and iron monitoring methods such as cardiac magnetic resonance (CMR) became available after the year 2000. We evaluated the impact of these new management options on cardiac mortality and morbidity.

The Prevalence of Helicobacter pylori Gastritis in Newly Diagnosed Children with Inflammatory Bowel Disease

Recent studies have shown that patients with inflammatory bowel disease (IBD) are less likely to be infected with Helicobacter pylori compared with non‐IBD patients. We aimed to study the prevalence of H. pylori‐positive and H. pylori‐negative gastritis in newly diagnosed children with IBD in comparison to those with non‐IBD in Greece.

Cardiac magnetic resonance in transfusion dependent thalassaemia: assessment of iron load and relationship to left ventricular ejection fraction

Cardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR‐derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0·57, P < 0·001). The prevalence of CD was 32·9% in patients with T2* ≤ 8 ms, 12·5% in patients with T2* > 8 ms and ≤14 ms and reduced to 9·1% in patients with T2* between 14–20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for CD (Receiver operating characteristic analysis, area under the curve = 0·68). Patients with cardiac T2* ≤ 8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible.

HLA class II high-resolution genotyping in Greek children with celiac disease and impact on disease susceptibility.

Background:Celiac disease (CD) has been associated with HLA class II heterodimers. This study aimed at determining the HLA genotypic and allelic distribution in Greek children with CD as compared with the general population.Methods:A total of 118 children with CD and 120 healthy individuals serving as controls were included in the study.Results:Higher frequencies for HLA-DQB1*02:01 (40.25 vs. 9.58%, P < 0.001) and DQB1*02:02 (20.34 vs. 5.42%, P < 0.001) were observed in patients with CD, whereas HLA-DQB1*03:01 (16.53 vs. 30.42%, P < 0.001), DQB1*05:01 (0.85 vs. 10%, P < 0.001), and DQB1*05:02 (5.51 vs. 17.92%, P < 0.001) were significantly lower, as compared with the controls. DQA1*02:01 (patients with CD vs. controls: 20.76 vs. 6.67%, P < 0.001) and DQA1*05:01 (40.25 vs. 9.58%, P < 0.001) were significantly more frequent in patients. The frequencies of HLA-DQA1* 01:01, *01:02, *01:04, and *05:05 were significantly lower in patients (P < 0.001). The haplotype mainly associated with CD was DRB1*03-DQB1*02:01-DQA1*05:01; patients with CD vs. controls: 39.83 vs. 9.58%, P < 0.001. In total, 84.75% of patients carried DQ2 (vs. 21.67% in controls, P < 0.001), whereas 11.02% were DQ8 positive/DQ2 negative.Conclusion:This study confirms the existing data and provides additional evidence supporting a strong genetic predisposition for CD associated with the class II alleles DQB1*02 and DQA1*05 encoding the serological specificity DQ2.

The value of focally enhanced gastritis in the diagnosis of pediatric inflammatory bowel diseases.

BACKGROUND AND AIMS Focally enhanced gastritis (FEG) has been suggested as a diagnostic marker for patients with Crohns disease. In this study we evaluated the prevalence of FEG in children with inflammatory bowel diseases (IBD) and assessed the ability of FEG to distinguish IBD from non-IBD patients. METHODS A retrospective study of the children who underwent esophagogastroduodenal endoscopy (EGD) during 2004-2011 was performed, after excluding individuals with H. pylori infection and celiac disease. Two groups were studied: patients with IBD (IBD group, n=185) and non-IBD patients who underwent endoscopy of the upper gastrointestinal tract for various abdominal complaints (non-IBD group, n=684). Relation of FEG to age and gender was also assessed. RESULTS FEG was found significantly more frequently among children with IBD (35.7% vs 3.4%, respectively, p<0.001). Children with FEG were 15.4 times more likely to have IBD than to belong in the non-IBD group. All types of IBD had significantly higher frequencies of FEG compared to non-IBD individuals (Crohns disease: 54.1%, ulcerative colitis: 21.6%, IBD unclassified: 18.4%, all three comparisons with the non-IBD group: p-values<0.001). FEG positivity was more common in females compared to males with Crohns disease and ulcerative colitis and in children younger than 2 years in the IBD-unspecified group. FEG achieved a sensitivity of 35.7% and specificity of 96.6% in distinguishing between IBD from non-IBD patients. CONCLUSIONS FEG has significantly higher prevalence in children with IBD, particularly Crohns disease and can be a valuable supporting finding in cases of indefinite diagnosis.

Thirty-year experience in preventing haemoglobinopathies in Greece: achievements and potentials for optimisation.

Beta thalassaemia major (β‐TM) and sickle‐cell disease (SCD) are severe haemogobinopathies requiring life‐lasting, advanced medical management. In the Mediterranean region, both conditions occur with high frequency. We assessed the efficacy of the National Program for the Prevention of Haemoglobinopathies in Greece during the last 30 yrs.