Point Shear Wave Elastography Detected Liver Stiffness Increased in Pediatric Patient With Thalassemia Major.

ABSTRACT: Transient elastography (TE) and point shear wave elastography (pSWE) are 2 elastographic ultrasound examinations used in liver stiffness (LS) measurement. It was shown that the LS value detected by TE in pediatric ß-thalassemia major patients has increased, and there was no LS evaluation obtained with pSWE in literature. Thus, in this study, it was aimed to evaluate LS with pSWE examination in children with thalassemia major and to determine LS-related parameters in these patients. Sixty-three schoolchildren with a diagnosis of ß-thalassemia major and 21 healthy controls between the ages of 7 and 18 years were included. In addition to routine anamnesis, physical examination, and laboratory examinations, renal and liver ultrasounds were performed. Liver stiffness values were measured by pSWE examination. Serum levels of urea, aspartate-aminotransferase, alanine-aminotransferase, iron, and ferritin were significantly higher in patients, and serum creatinine, iron binding capacity, and hemoglobin levels were found to be significantly lower (P < 0.05 for each). Liver stiffness values were significantly higher in patients compared with healthy controls. In linear regression analysis, serum iron and iron binding capacity values were found to be closely related with LS (P < 0.001 vs. ß = 0.482 and P = 0.047 vs. ß = 0.237, respectively). Liver stiffness values obtained by pSWE examination increase significantly in patients. According to the results of our study, in addition to the previously known TE method, we think that the LS evaluation obtained by pSWE, a new method that can make more accurate measurements, can be used in the possible early detection of target organ damage in children with thalassemia major.

Pancreatic iron in pediatric transfusion-dependent beta-thalassemia patients: A longitudinal MRI study.

BACKGROUND: In pediatric transfusion-dependent thalassemia (TDT) patients, we evaluated the prevalence, pattern, and clinical associations of pancreatic siderosis and the changes in pancreatic iron levels and their association with baseline and changes in total body iron balance. PROCEDURE: We considered 86 pediatric TDT patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload (IO) was quantified by R2* magnetic resonance imaging (MRI). RESULTS: Sixty-three (73%) patients had pancreatic IO (R2* > 38 Hz). Global pancreas R2* values were significantly correlated with mean serum ferritin levels, MRI liver iron concentration (LIC) values, and global heart R2* values. Global pancreas R2* values were significantly higher in patients with altered versus normal glucose metabolism. Thirty-one patients also performed the follow-up MRI at 18 ± 3 months. Higher pancreatic R2* values were detected at the follow-up, but the difference versus the baseline MRI was not significant. The 20% of patients with baseline pancreatic IO showed no pancreatic IO at the follow-up. The 46% of patients without baseline pancreatic IO developed pancreatic siderosis. The changes in global pancreas R2* between the two MRIs were not correlated with baseline serum ferritin levels, baseline, final, and changes in MRI LIC values, or baseline pancreatic iron levels. CONCLUSIONS: In children with TDT, pancreatic siderosis is a frequent finding associated with hepatic siderosis and represents a risk factor for myocardial siderosis and alterations of glucose metabolism. Iron removal from the pancreas is exceptionally challenging and independent from hepatic iron status.

Bone densitometry in Thalassemia major: a closer look at pitfalls and operator-related errors in a 10-year follow-up population.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the gold standard for measuring bone mineral density (BMD) with tolerable error rate, high precision, and excellent consistency. Our objective was to investigate the frequency and distribution of errors in a cohort of patients with Thalassemia major (TM). METHODS: We reviewed the DXA examinations of 340 patients with ß-TM followed by our institution, acquired in different imaging centers between 2009 and 2019. We collected sex and age at the time of the first examination and at the last visit, as well as BMD, T-score, and Z-score values. Errors were analyzed by anatomical site (lumbar spine, total hip, femoral neck). RESULTS: Out of 5099 total DXA scans, 11.85% presented one or more errors. Specifically, the incorrect examinations were 315 out of 1707 (18.45%) at the lumbar spine level, 113 out of 1697 (6.66%) at the total hip, 176 out of 1695 (10.38%) at the femoral neck. Errors in vertebral inclusion were the most frequently registered (45.86%). A significant difference resulted from the comparison of the T-score and Z-score median values of all the lumbar spine DXA examinations and the correct ones (p value 0.037 and 0.0003, respectively). CONCLUSION: Although not directly involved in the performance and interpretation of DXA, physicians interested in osteoporosis management should be familiar with the protocols to minimize errors and allow the proper use of bone densitometry. DXA obtained at the spine level is more frequently affected by errors in patients with TM, potentially influencing the diagnostic assessment of bone health status.

Longitudinal prospective comparison of pancreatic iron by magnetic resonance in thalassemia patients transfusion-dependent since early childhood treated with combination deferiprone-desferrioxamine vs deferiprone or deferasirox monotherapy.

BACKGROUND: In transfusion-dependent thalassemia patients who started regular transfusions in early childhood, we prospectively and longitudinally evaluated the efficacy on pancreatic iron of a combined deferiprone (DFP) + desferrioxamine (DFO) regimen versus either oral iron chelator as monotherapy over a follow-up of 18 months. MATERIALS AND METHODS: We selected patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network who received a combined regimen of DFO+DFP (No.=28) or DFP (No.=61) or deferasirox (DFX) (No.=159) monotherapy between the two magnetic resonance imaging scans. Pancreatic iron overload was quantified by the T2* technique. RESULTS: At baseline no patient in the combined treatment group had a normal global pancreas T2* (≥26 ms). At follow-up the percentage of patients who maintained a normal pancreas T2* was comparable between the DFP and DFX groups (57.1 vs 70%; p=0.517).Among the patients with pancreatic iron overload at baseline, global pancreatic T2* values were significantly lower in the combined DFO+DFP group than in the DFP or DFX groups. Since changes in global pancreas T2* values were negatively correlated with baseline pancreas T2* values, the percent changes in global pancreas T2* values, normalized for the baseline values, were considered. The percent changes in global pancreas T2* values were significantly higher in the combined DFO+DFP group than in either the DFP (p=0.036) or DFX (p=0.030) groups. DISCUSSION: In transfusion-dependent patients who started regular transfusions in early childhood, combined DFP+DFO was significantly more effective in reducing pancreatic iron than was either DFP or DFX.

Four­Dimensional Echocardiographic Evaluation of Cardiac Iron Overload in Patients with Beta-Thalassemia Major.

Cardiac magnetic resonance imaging is the gold standard to detect cardiac iron overload in patients with beta-thalassemia. The aim of this study was to evaluate cardiac iron overload using four-dimensional transthoracic echocardiography in thalassemia patients with and without cardiac involvement detected by T2* value and to compare the two techniques. This cross-sectional and observational study was conducted in 44 patients diagnosed with thalassemia major. Left ventricular systolic function was assessed using four-dimensional speckle tracking echocardiography-derived global longitudinal (GLS), circumferential, radial, and area strain indices. Left ventricular ejection fraction, volumes, and mass index were similar between the patients with T2* values less than 20 ms as compared to those with T2* values greater than 20 ms. However, patients with lower T2* values had significantly higher GLS values (- 17.0% vs. - 19.8%, p < 0.001) compared with those with higher T2* values. GLS demonstrated a sensitivity of 91.7% and a specificity of 71.9% at a cut-off value of - 18.5%; however, sensitivity was 75%, and the specificity was 84.4% at a cut-off value of - 17.5%. For - 18.5%, the positive predictive value was 55%, and the negative predictive value was 95.8%; for - 17.5%, these values were 64.2 and 90%, respectively. This novel echocardiographic method, tested for the first time in our study in comparison with cardiac MRI in an adult patient group, has been shown to predict cardiac iron overload in thalassemia patients in the subclinical period without LVEF decline. Four-dimensional GLS is a marker with high sensitivity and negative predictive value.

Magnetic resonance imaging assessment of the changes of cardiac and hepatic iron load in thalassemia patients before and after hematopoietic stem cell transplantation.

To investigate the value of T2* technique on 3.0 T magnetic resonance imaging (MRI) in evaluating the changes of cardiac and hepatic iron load before and after hematopoietic stem cell transplantation (HSCT) in patients with thalassemia (TM), the 141 TM patients were divided into 6 group for subgroup analysis: 6, 12, 18, 24 and > 24 months group, according to the postoperative interval. The T2* values of heart and liver (H-T2*, L-T2*) were quantified in TM patients before and after HSCT using 3.0 T MRI T2* technology, and the corresponding serum ferritin (SF) was collected at the same time, and the changes of the three before and after HSCT were compared. The overall H-T2* (P = 0.001) and L-T2* (P = 0.041) of patients after HSCT were higher than those before HSCT (mean relative changes = 19.63%, 7.19%). The H-T2* (P < 0.001) and L-T2* (P < 0.001) > 24 months after HSCT were significantly higher than those before HSCT (mean relative changes = 69.19%, 93.73%). The SF of 6 months (P < 0.001), 12 months (P = 0.008), 18 months (P = 0.002) and > 24 months (P = 0.001) were significantly higher than those before HSCT (mean relative changes = 57.93%, 73.84%, 128.51%, 85.47%). There was no significant improvement in cardiac and liver iron content in TM patients within 24 months after HSCT, while the reduction of cardiac and liver iron content in patients is obvious when > 24 months after HSCT.

Left Ventricular Myocardial Dysfunction Evaluation in Thalassemia Patients Using Echocardiographic Radiomic Features and Machine Learning Algorithms.

Heart failure caused by iron deposits in the myocardium is the primary cause of mortality in beta-thalassemia major patients. Cardiac magnetic resonance imaging (CMRI) T2* is the primary screening technique used to detect myocardial iron overload, but inherently bears some limitations. In this study, we aimed to differentiate beta-thalassemia major patients with myocardial iron overload from those without myocardial iron overload (detected by T2*CMRI) based on radiomic features extracted from echocardiography images and machine learning (ML) in patients with normal left ventricular ejection fraction (LVEF > 55%) in echocardiography. Out of 91 cases, 44 patients with thalassemia major with normal LVEF (> 55%) and T2* ≤ 20 ms and 47 people with LVEF > 55% and T2* > 20 ms as the control group were included in the study. Radiomic features were extracted for each end-systolic (ES) and end-diastolic (ED) image. Then, three feature selection (FS) methods and six different classifiers were used. The models were evaluated using various metrics, including the area under the ROC curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE). Maximum relevance-minimum redundancy-eXtreme gradient boosting (MRMR-XGB) (AUC = 0.73, ACC = 0.73, SPE = 0.73, SEN = 0.73), ANOVA-MLP (AUC = 0.69, ACC = 0.69, SPE = 0.56, SEN = 0.83), and recursive feature elimination-K-nearest neighbors (RFE-KNN) (AUC = 0.65, ACC = 0.65, SPE = 0.64, SEN = 0.65) were the best models in ED, ES, and ED&ES datasets. Using radiomic features extracted from echocardiographic images and ML, it is feasible to predict cardiac problems caused by iron overload.

Myocardial tissue characterization by segmental T2 mapping in thalassaemia major: detecting inflammation beyond iron.

AIMS: We measured myocardial T2 values by a segmental approach in thalassaemia major (TM) patients, comparing such values against T2* values for the detection of myocardial iron overload (MIO), evaluating their potential in detecting subclinical inflammation, and correlating with clinical status. METHODS AND RESULTS: One-hundred and sixty-six patients (102 females, 38.29 ± 11.49years) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network underwent magnetic resonance imaging for the assessment of hepatic, pancreatic, and cardiac iron overload (T2* technique), of biventricular function (cine images), and of replacement myocardial fibrosis [late gadolinium enhancement (LGE)]. T2 and T2* values were quantified in all 16 myocardial segments, and the global value was the mean of all segments. Global heart T2 values were significantly higher in TM than in a cohort of 80 healthy subjects. T2 and T2* values were significantly correlated. Out of the 25 patients with a decreased global heart T2* value, 11 (44.0%) had reduced T2 values. No patient with a normal T2* value had a decreased T2 value.Eleven (6.6%) patients had a decreased global heart T2 value, 74 (44.6%) a normal global heart T2 value, and 81 (48.8%) an increased global heart T2 value. Biventricular function was comparable amongst the three groups, whilst LGE was significantly more frequent in patients with reduced vs. increased global heart T2 value. Compared with the other two groups, patients with reduced T2 values had significantly higher hepatic and pancreatic iron deposition. CONCLUSION: In TM, T2 mapping does not offer any advantage in terms of sensitivity for MIO assessment but detects subclinical myocardial inflammation.

Pancreatic fatty replacement as risk marker for altered glucose metabolism and cardiac iron and complications in thalassemia major.

OBJECTIVES: This multicenter study assessed the extent of pancreatic fatty replacement and its correlation with demographics, iron overload, glucose metabolism, and cardiac complications in a cohort of well-treated patients with thalassemia major (TM). METHODS: We considered 308 TM patients (median age: 39.79 years; 182 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Magnetic resonance imaging was used to quantify iron overload (IO) and pancreatic fat fraction (FF) by T2* technique, cardiac function by cine images, and to detect replacement myocardial fibrosis by late gadolinium enhancement technique. The glucose metabolism was assessed by the oral glucose tolerance test. RESULTS: Pancreatic FF was associated with age, body mass index, and history of hepatitis C virus infection. Patients with normal glucose metabolism showed a significantly lower pancreatic FF than patients with impaired fasting glucose (p = 0.030), impaired glucose tolerance (p < 0.0001), and diabetes (p < 0.0001). A normal pancreatic FF (< 6.6%) showed a negative predictive value of 100% for abnormal glucose metabolism. A pancreatic FF > 15.33% predicted the presence of abnormal glucose metabolism. Pancreas FF was inversely correlated with global pancreas and heart T2* values. A normal pancreatic FF showed a negative predictive value of 100% for cardiac iron. Pancreatic FF was significantly higher in patients with myocardial fibrosis (p = 0.002). All patients with cardiac complications had fatty replacement, and they showed a significantly higher pancreatic FF than complications-free patients (p = 0.002). CONCLUSION: Pancreatic FF is a risk marker not only for alterations of glucose metabolism, but also for cardiac iron and complications, further supporting the close link between pancreatic and cardiac disease. KEY POINTS: • In thalassemia major, pancreatic fatty replacement by MRI is a frequent clinical entity, predicted by a pancreas T2* < 20.81 ms and associated with a higher risk of alterations in glucose metabolism. • In thalassemia major, pancreatic fatty replacement is a strong risk marker for cardiac iron, replacement fibrosis, and complications, highlighting a deep connection between pancreatic and cardiac impairment.

Incidental osteonecrosis in the distal left femur in a case of beta-thalassemia with COVID-19: Role of [99mTc]Tc-MDP whole-body bone scan.

Secondary anemia in hemoglobinopathies like thalassemia can cause expansion of the bone marrow cavities because of compensatory marrow hyperplasia. This case demonstrates spontaneous osteonecrosis of the distal left femur in a patient with ß-thalassemia that may be secondary to ischemic infarction secondary to occlusion of the microvasculature within the expanded cancellous bone. This subject was referred to Hazrat Rasool Akram Hospital because of fever, cough, and bone pain. In the CT scan she had scattered peripheral CGO in both lungs due to COVID-19 with two paravertebral masses due to extramedullary hematopoiesis. The patient had also generalized bone pain so the physician asked for a whole-body bone scan and incidentally, we found a cold lesion with a rim of increased uptake in the distal left femur that with bone biopsy it was consistent with osteonecrosis. This case illustrates the importance of performing a whole-body bone scan in ß-thalassemia for the management of patients and diagnosis of occult osteonecrosis.

Echocardiographic evaluation of left atrial strain for predicting iron overload in pediatric patients with ß-thalassemia with preserved ejection fraction.

Pediatric patients with ß-thalassemia (ß-TM) with preserved ejection fraction may experience early myocardial damage. This prospective study aimed to investigate left atrial (LA) function restructure in pediatric patients with ß-TM by two-dimensional speckle tracking echocardiography (2D-STE) and evaluate the value of LA strain for predicting myocardial iron overload (MIO). We recruited 50 ß-TM pediatric patients and 30 healthy children aged 3-14 years. The patients were assigned to a normal left ventricular (LV) lesion group (n = 20) and an enlarged LV lesion group (n = 30). Subjects all underwent echocardiography to measure conventional cardiac function parameters and LA strain parameters. The results displayed that LA reservoir strain (LASr), conduit strain (LAScd), contractile strain (LASct) and strain rate were significantly reduced in pediatric patients with ß-TM with preserved ejection fraction. LASr, LAScd, and LASct were negatively correlated with the E/e' ratio, of which LASr had the most significant correlation (r = - 0.69, P < 0.001). LASr and LASct correlated positively with T2* (r = 0.70 and 0.62, respectively, all P < 0.001). In the multiple regression, LASr and LASct were independent predictors for T2*. The areas under the curve for LASr and LASct were 0.87 (P < 0.001) and 0.78 (P = 0.004), respectively. Our results demonstrated that LA strains were dramatically impaired in pediatric patients with ß-TM, and LASr is an efficient indicator for detecting LV early diastolic dysfunction in ß-TM pediatric patients and reflects early myocardial damage. LASr and LASct were independently predictive of MIO, but LASr was a more sensitive predictor.

The effect of ferritin levels on distal femoral cartilage thickness in patients with beta thalassaemia major.

INTRODUCTION: To the best of our knowledge, the present study is the first in the literature to assess distal femoral cartilage thickness and its relationship with ferritin levels in adult patients with beta thalassaemia major (BTM). MATERIALS AND METHODS: 45 patients with BTM and 45 healthy controls were included in the study. Ferritin and haemoglobin levels of the patient and healthy groups were determined by blood analysis and distal femoral cartilage thicknesses were measured via ultrasound. Then, the patient group was divided into subgroups according to whether their ferritin levels were below or above 2500 µg/L. They were then compared among themselves and with the healthy control group using the available data. RESULTS: Distal femoral cartilage thickness values were statistically significantly lower in the BTM group compared to the healthy control group (p values < 0.001). Patients with a ferritin level below 2500 µg/L had statistically significantly higher right and left average distal femoral cartilage thickness values than the patients with a ferritin level above 2500 µg/L (p = 0.029 and p = 0.019, respectively). The right and left average distal femoral cartilage thickness values of the patient subgroup with low ferritin levels were statistically similar to the control group (p = 0.146 and p = 0.164, respectively). CONCLUSION: Our study showed that thalassaemia patients are more likely to develop osteoarthritis (OA) than the normal population and possible OA development can be prevented by keeping the ferritin levels of these patients in the optimum range.

The frequency of synovitis and calcium pyrophosphate deposition with ultrasound is increased in transfusion-dependent beta-thalassaemia patients: effect of iron accumulation?

OBJECTIVES: To determine the frequency of synovitis and calcium pyrophosphate deposition (CPDD) with ultrasound (US) in the wrists of transfusion dependant (TD) beta-thalassaemia patients and to investigate the associated factors with these pathologies. METHODS: Eighty-seven beta-thalassaemia patients (46 thalassaemia major and 41 thalassaemia minor patients) were grouped into two as TD and transfusion non-dependent (TND)-thalassaemia patients. Under bilateral wrist US the presence of synovial hypertrophy (SH), power Doppler signal (PD) combined synovitis (SH+PD), tenosynovitis, and triangular fibrocartilage complex (TFC)-cartilage calcification (CC) were examined. SH, PD, and combined synovitis in the US were classified as Grade-0 (no), Grade-1 (minimal), Grade-2 (moderate), and Grade-3 (severe). RESULTS: The incidence of moderate/severe SH, PD, and combined synovitis with US was 34.8%, 17.4%, and 34.8% in TD-thalassaemia patients, respectively, but none in TND patients (p<0.001, p=0.006, p<0.001). The frequency of TFC-CC with US was 32.6% in TD and 2.4% in TND-thalassaemia patients (p<0.001). Ferritin level was positively correlated with SH (r=0.414, p<0.001), PD (r=0.279, p=0.009) and combined synovitis scores (r=0.402, p<0.001). Ferritin level (OR:1.001, CI:1.000-1.002) and the presence of TFC-CC (OR:25.048, CI:5.187-120.951) were determined as to be associated with moderate/severe combined synovitis. CONCLUSIONS: The presence of synovitis and TFC-CC with the US is common in patients with beta-thalassaemia who have had recurrent blood transfusions. Iron overload in beta-thalassaemia patients may cause CPDD and synovial inflammation.

Cardiac iron overload detection using longitudinal strain in asymptomatic children with beta thalassemia major.

Cardiomyopathy mediated by iron disposition in cardiomyocytes is a dreadful cause of morbidity and mortality in patients with beta thalassemia major (BTM). Conventional transthoracic echocardiography (TTE) parameters are preserved at late stages of cardiomyopathy induced by iron overload. Therefore, cardiac imaging modalities based on myocardial deformation such as strain imaging are used for early detection of cardiac iron overload. To demonstrate the contribution of longitudinal strain (LS) in early detection of cardiac iron overload in children with BTM. Sixty children (30 children with BTM and 30 healthy controls) were enrolled in this study. Conventional TTE study was performed in both patient and control groups. LV regional longitudinal strain (RLS) were determined and compared between the two study groups. Mean age was 10.4 ± 5 years in BTM group compared to 10.2 ± 5 years in control group (p = 0.876). Compared to control group, there was no significant difference in conventional TTE parameters except for indexed left atrium (LA) area and volume. LA was significantly larger in BTM children (27.59 ± 13.1 ml/m2 vs. 18.23 ± 4.33 ml/m2, p = 0.001). RLS was lower in anterior, septal and inferior walls in basal and middle segments of LV in BTM group while there was no significant difference in RLS in apical segment between the two groups (- 27.30 ± 5.1 vs.- 28.83 ± 4.33, p = 0.22). In asymptomatic BMT children with normal conventional TTE parameters, LS could be used for the detection of subclinical myocardial dysfunction.

Quantitative T2* MRI for bone marrow iron overload: normal reference values and assessment in thalassemia major patients.

PURPOSE: We evaluated the feasibility and reproducibility of bone marrow T2* values and established the lower limit of normal in a cohort of healthy subjects. We investigated the clinical correlates of bone marrow T2* values in patients with thalassemia major (TM). MATERIAL AND METHODS: Thirty healthy subjects and 274 consecutive TM patients (38.96 ± 8.49 years, 151 females) underwent MRI at 1.5T. An axial slice in the upper abdomen was acquired by a T2* gradient-echo multiecho sequence and the T2* value was calculated in a circular region of interest defined in the visible body of the first or second lumbar vertebra. In patients, also liver and heart T2* values were assessed. RESULTS: In healthy subjects bone marrow T2* values were independent of age and gender. The lower limit of normal for bone marrow T2* was 13 ms. In both healthy subjects and 30 randomly selected patients, the coefficient of variation for inter-operator-reproducibility was < 10%. TM patients exhibited significantly lower bone marrow T2* values than healthy subjects (7.47 ± 5.18 ms vs. 17.08 ± 1.89 ms; p < 0.0001). A pathological bone marrow T2* was detected in 82.8% of TM patients. In TM, the female sex was associated with reduced bone marrow T2* values. Bone marrow T2* values were inversely correlated with mean serum ferritin levels (R = -0.431; P < 0.0001) and hepatic iron load (R = - 0.215; P < 0.0001). A serum ferritin level > 536 ng/ml predicted the presence of a pathological bone marrow T2*. A positive correlation was found between bone marrow and heart T2* values (R = 0.143; P = 0.018). A normal bone marrow T2* showed a negative predictive value of 100% for cardiac iron. CONCLUSION: Bone marrow T2* measurements can be easily obtained using the same sequences acquired for liver iron quantification and may bring new insights into the pathophysiology of iron deposition; hence, they should be incorporated into clinical practice.

The role of opportunistic quantitative computed tomography in the evaluation of bone disease and risk of fracture in thalassemia major.

OBJECTIVE: Dual-energy X-ray absorptiometry (DXA) remains the cornerstone for osteoporosis evaluation in Thalassemia major. However, several drawbacks have been observed in this unique setting. We sought to determine the correlation between quantitative CT (QCT) and DXA-derived parameters; secondarily, we aimed to investigate the role of the two techniques in predicting the risk of fracture. METHODS: We retrospectively included patients with ß-thalassemia major who had undergone both lumbar and femoral DXA examinations, and CT scans including the lumbar spine, performed for disparate diagnostic issues, within 4 months from the DXA. CT data were examined employing a phantom-less QCT method for bone mineral density (BMD) assessment. We also retrieved any spontaneous or fragility fractures occurring from 1 year before up to 5 years after the date of DXA scans. RESULTS: The 43 patients were included. QCT measures were significantly higher than those determined by DXA. The gap between QCT and DXA values was strongly associated with patient age. The most powerful predictive variable for risk of fracture was the ACR classification based on volumetric BMD obtained by QCT. CONCLUSIONS: DXA provided more negative measures than those determined by QCT. However, QCT seemed to evaluate thalassaemic osteopathy better than DXA, since volumetric BMD was a stronger predictor of fracture.

Aortic Intima Media Thickness is Increased and Closely Related to Elevated Oxidative Stress Increases in Beta Thalassemia Minor. / Aumento da Espessura Médio-intimal Aórtica e sua Relação com Estresse Oxidativo Elevado em Pacientes com Talassemia Menor.

BACKGROUND: Abdominal aortic intima media thickness (A-IMT) may be an early marker of subclinical atherosclerosis and an objective indicator of increased oxidative stress in beta-thalassemia minor patients. OBJECTIVE: To evaluate whether aortic and carotid IMTs change with oxidative stress and to assess the relationship between these parameters in beta-thalassemia minor patients. METHODS: The study included 80 patients diagnosed with beta-thalassemia minor, and 50 healthy individuals with similar age and gender. After routine procedures, blood samples were collected from the study groups for thiol-disulfide hemostasis and ischemia-modified albumin (IMA). C-IMT measurements were performed in four different regions (right and left internal and external carotid artery) by ultrasonography. In addition, A-IMT measurement was performed by abdominal ultrasonography. Statistically significant p value was set as <0.05 for all comparisons. RESULTS: In beta-thalassemia minor patients, native thiol, total thiol and native thiol / total thiol ratio were lower, and the IMA, disulfide / native thiol ratio and disulfide / total thiol ratios were higher than in healthy control group. A-IMT measurement was significantly higher in beta-thalassemia minor group than controls (1.46±0.37 vs 1.23±0.22 and p<0.001). When the parameters associated with A-IMT in univariate analysis were evaluated by multivariate linear regression analysis, A-IMT was positively related, and native thiol and total thiol levels were negatively and closely related to IMA (p<0.01). CONCLUSION: We demonstrated, for the first time, that oxidative stress status increased with increased A-IMT, while C-IMT remained unchanged in beta-thalassemia minor patients.

FUNDAMENTO: A espessura médio-intimal (EMI) da artéria aorta abdominal (EMI-A) pode ser um marcador precoce de aterosclerose subclínica e um indicador objetivo de estresse oxidativo em pacientes com talassemia menor. OBJETIVO: Avaliar se as EMIs da artéria aorta e da artéria carótida (EMI-C) se alteram com estresse oxidativo, e examinar a relação entre esses parâmetros em pacientes com talassemia menor. MÉTODOS: O estudo incluiu 80 pacientes diagnosticados com talassemia menor, e 50 indivíduos sadios com idade e sexo similares. Após procedimentos de rotina, as amostras de sangue foram coletadas dos grupos de estudo para a medida da homeostase tiol/dissulfeto e da albumina modificada pela isquemia (AMI). As medidas da EMI-C foram realizadas a partir de quatro regiões diferentes (artéria carótida externa direita e esquerda e artéria carótida interna direita e esquerda) por ultrassonografia, e a medida da EMI-A foi realizada por ultrassonografia abdominal. Um valor de p<0,05 foi definido como estatisticamente significativo. RESULTADOS: Nos pacientes com talassemia menor, os níveis de tiol nativo e tiol total, e a razão tiol nativo/tiol total foram mais baixos, e os valores de AMI, razão dissulfeto/tiol nativo, e razão dissulfeto/tiol total foram mais altos que no grupo controle. A EMI-A foi significativamente maior no grupo de pacientes com talassemia menor que nos controles (1,46±0,37 vs 1,23±0,22 e p<0,001). Quando os parâmetros associados com EMI-A na análise univariada foram avaliados por regressão linear multivariada, EMI-A apresentou uma relação positiva, e os níveis de tiol nativo e tiol total apresentaram uma forte relação negativa com AMI (p<0,01). CONCLUSÃO: Nós demonstramos, pela primeira vez, um aumento no estresse oxidativo com a elevação da EMI-A, e valores inalterados da EMI-C em pacientes com talassemia menor.

Dual gradient echo in-phase and out of phase sequences in assessment of hepatic iron overload in patients with beta-thalassemia, would be better?

PURPOSE: To evaluate the diagnostic accuracy of the dual gradient-echo (GRE) in- and out-of-phase sequences as a quantitative tool for hepatic iron overload in comparison with MRI R2* relaxometry in paediatric patients with beta-thalassemia. METHOD: Sixty-three patients with beta-thalassemia major (transfusion-dependent) or beta-thalassemia intermedia (transfusion- and non-transfusion-dependent) were referred from the paediatric department (haematology unit) to the radiology department at a university hospital. The paediatrician conducted a clinical examination for the studied group, assessed their laboratory data, conducted R2* relaxometry and dual gradient echo sequences to calculate R2* and relative signal intensity index at the axial mid-section of the liver, and studied their correlation. A 1.5 Tesla MR scanner was used (Achieva; Philips Medical Systems, the Netherlands). Data were fed to the computer and analysed using the IBM SPSS software package version 20.0 (Armonk, NY: IBM Corp). The Kolmogorov-Smirnov test was used to verify the normality of distribution. The significance of the results was determined at the 5% level. The Chi-square, Fisher's exact correction, Pearson coefficient, and Bland-Altman tests were used. RESULTS: Dual gradient-echo in- and out-of-phase sequences using visual assessment accurately assessed 93.65% of our patient group with hepatic iron overload. A significant correlation was found between the relative signal intensity index and hepatic MRI R2* relaxometry (p < 0.001, r = 0.861). CONCLUSIONS: Dual gradient-echo in and out-of-phase sequences are good imaging tools for hepatic iron detection and quantification. These sequences showed good correlation with R2* relaxometry (r = 0.861, p < 0.001).

Symphysis morphology and mandibular alveolar bone thickness in patients with ß-thalassemia major and different growth patterns.

OBJECTIVE: The present study aimed to assess the morphology of symphysis and alveolar bone thickness (ABT) surrounding mandibular incisors in thalassemic patients, as compared to unaffected individuals. METHODS: This case-control study was conducted on lateral cephalograms of 60 thalassemic and 60 unaffected patients with Class II malocclusion seeking orthodontic treatment at Dental School, Shiraz University of Medical Sciences. The sample was divided into three subgroups including hyperdivergent, normodivergent, and hypodivergent, according to the Jarabak index. Symphysis dimensions and alveolar bone thickness surrounding mandibular incisors were measured using AutoCad software. Finally, the correlation between alveolar bone thickness and symphysis morphology was assessed. RESULTS: In general, chin dimensions and bone thickness at different levels of mandibular incisor roots (cervical, middle, apical) were smaller in thalassemic adolescents than controls. Concerning the total sample as well as the normodivergent subgroup, significantly lower values were observed in thalassemic patients for symphysis width, total ABT at the cervical, and lingual ABT at the apical root area compared to controls (p < 0.05). The hypodivergent growth pattern was not associated with any statistical differences between the groups (p> 0.05). In both thalassemic and control subjects, symphysis width showed a weak to moderate positive correlation with ABT of lower incisors (p< 0.05), whereas symphysis height showed a moderate positive correlation with cervical ABT in only ß-thalassemia patients (p< 0.05). CONCLUSIONS: Compared to controls, ß-thalassemia patients showed thinner alveolar bone at different levels of lower incisor roots and smaller symphysis dimensions. There were significant correlations between symphysis dimensions and alveolar bone thickness of mandibular incisors in the sample.

Left atrial deformation indices in ß-thalassemia major patients.

The presence of atrial cardiomyopathy in ß-thalassemia major (ß-TM) patients complicates their clinical condition. The diagnosis is challenging even with cardiac magnetic resonance (CMR) imaging. Novel echocardiographic techniques are applied to increase the diagnostic yield. Fifty-six ß-TM patients and thirty age and sex-matched controls were included in the present cross-sectional study. Heart rate, PR duration, and P axis were measured by electrocardiography, left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD), ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e'), left atrial volume index (LAVI), left atrial strain at reservoir (LASr), conduit (LAScd) and contraction (LASct) phases respectively, left ventricular global longitudinal strain (GLS) by echocardiography, and T2* calculation in patient group by CMR. PR duration, LVEF, LAVI, E/e', GLS, and left atrial deformation parameters differed between patients and controls (p <0.05). In patient group, left atrial strain was correlated with PR duration, LAVI, E/e', GLS, and T2* (p <0.05). T2* was correlated only with left atrial deformation indices (p <0.05). Patients with a history of atrial fibrillation were older, had lower heart rate, prolonged PR, increased E/e' and LAVI, and impaired left atrial strain (p <0.05). LASct differed relative to the presence of atrial fibrillation and myocardial iron overload. Atrial strain could be of clinical use in the early detection of atrial cardiomyopathy. An impaired LASct could identify ß-TM patients with undetected episodes of atrial fibrillation. Finally, left atrial strain may be helpful in myocardial iron load estimation.