Liver Iron Concentration Research Articles

Analysis of liver iron concentration in an elderly female undergoing hemodialysis with calcific uremic arteriolopathy does not support the role of iron overload in calciphylaxis: lesson for the clinical nephrologist

Analysis of liver iron concentration in an elderly female undergoing hemodialysis with calcific uremic arteriolopathy does not support the role of iron overload in calciphylaxis: lesson for the clinical nephrologist

The Oral Ferroportin Inhibitor VIT-2763 Improves Erythropoiesis without Interfering with Iron Chelation Therapy in a Mouse Model of β-Thalassemia.

In β-thalassemia, ineffective erythropoiesis leads to anemia and systemic iron overload. The management of iron overload by chelation therapy is a standard of care. However, iron chelation does not improve the ineffective erythropoiesis. We recently showed that the oral ferroportin inhibitor VIT-2763 ameliorates anemia and erythropoiesis in the Hbbth3/+ mouse model of β-thalassemia. In this study, we investigated whether concurrent use of the iron chelator deferasirox (DFX) and the ferroportin inhibitor VIT-2763 causes any pharmacodynamic interactions in the Hbbth3/+ mouse model of β-thalassemia. Mice were treated with VIT-2763 or DFX alone or with the combination of both drugs once daily for three weeks. VIT-2763 alone or in combination with DFX improved anemia and erythropoiesis. VIT-2763 alone decreased serum iron and transferrin saturation (TSAT) but was not able to reduce the liver iron concentration. While DFX alone had no effect on TSAT and erythropoiesis, it significantly reduced the liver iron concentration alone and in the presence of VIT-2763. Our results clearly show that VIT-2763 does not interfere with the iron chelation efficacy of DFX. Furthermore, VIT-2763 retains its beneficial effects on improving ineffective erythropoiesis when combined with DFX in the Hbbth3/+ mouse model. In conclusion, co-administration of the oral ferroportin inhibitor VIT-2763 and the iron chelator DFX is feasible and might offer an opportunity to improve both ineffective erythropoiesis and iron overload in β-thalassemia.

COPPER AND IRON SUPPLEMENTATION IN THE TROPICAL ENVIRONMENT EFFECTS ON HAEMATOLOGICAL MEASUREMENTS, ORGAN WEIGHTS, TISSUE COPPER AND IRON

The study which lasted 3 months was a factorial arrangement in which nine dietary treatments resulting from supplementation of a commercial layers diet with 0, 200 or 400 mg/kg Copper and 0, 100 or 200 mg/kg Iron were fed to 135 fifty two-week old laying hens of the Golden Hubbard Connect Strain. After 12 weeks on the diets, three birds, randomly selected from each treatment, were slaughtered and their blood, liver, spleen and heart analysed for effect of supplementary copper and iron on haemoglobin content, packed cell volume and weights of the liver, spleen and heart and their copper and iron concentrations. No significant effects of supplementary copper or Iron or their interaction were observed on haemoglobin, packed cell volume or weights of the liver, spleen and heart. However, dietary iron supplementation produced significant (P<0.05) effects on iron storage in the liver and spleen but not on copper storage. On the other hand, copper addition significantly (P<0.05) increased liver storage of copper and spleen storage of iron. Supplementary copper and iron Interaction effects which were not significant for all other measurements, were observed to be significant (P<0.05) for liver copper and Iron concentrations and spleen copper concentration and highly significant (P<0.01) for spleen iron concentration.

The serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia: is there a good correlation?

ABSTRACT Introduction Liver iron overload is common in patients with thalassemia. In patients with beta-thalassemia, the correlation between serum ferritin and liver iron concentration is well established. The correlation between serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia remains limited. Methods This is a cross-sectional study in patients with alpha-thalassemia aged ≥ 18 years old at Srinagarind Hospital, Khon Kaen University, Thailand. Liver iron concentration (LIC) was evaluated by the MRI-T2* technique. Linear logistic regression analysis was used to determine the correlation between serum ferritin levels and liver iron concentrations. Results One hundred and thirty-one of the MRI-T2* measurements from 65 patients with alpha-thalassemia were evaluated. Patients with non-deletional alpha-thalassemia had higher LIC compared to patients with deletional alpha-thalassemia. The serum ferritin levels were relatively low at the same levels of LIC in patients with non-deletional alpha-thalassemia compared to deletional alpha-thalassemia. Conclusions The correlation of serum ferritin levels and LIC was modest and different among alpha-thalassemia genotypes. A different serum ferritin threshold is needed to guide iron chelation therapy in patients with alpha-thalassemia. Evaluation of liver iron concentration is necessary for patients with alpha-thalassemia, especially in patients with non-deletional alpha-thalassemia.

Hepatocellular carcinoma in transfusion dependent thalassemia patients: a review from a clinical perspective

Survival in patients with transfusion-dependent thalassemias (TDT) has increased, and complications such as hepatocellular carcinoma (HCC) are emerging. Risk factors include viral infection, mainly hepatitis C virus (HCV), iron overload, the presence of cirrhosis, and immune dysregulation. Median survival after HCC occurrence has been estimated at 12 months, while data regarding the incidence of HCC in this population are minimal. Implementing effective hepatitis B virus (HBV)/HCV antiviral treatment and universal HBV vaccination programs is expected to decrease the risk for hepatocarcinogenesis substantially. Significant hemosiderosis and hepatic fibrosis are common in patients with TDT despite chelation therapy and have been correlated with HCC development. Thus, iron overload should be monitored with liver iron concentration and ferritin levels, and effective chelation therapy should be applied. In addition, all TDT patients, particularly those with cirrhosis, should be under surveillance every six months with abdominal ultrasound ± alpha-fetoprotein levels, as this combination seems to provide better sensitivity for early HCC detection.

Effects of dietary chromium-yeast level on growth performance, blood metabolites, meat traits and muscle fatty acids profile, and microminerals content in liver and bone of lambs

To assess the effect of dietary supplement levels of chromium-yeast (Cr-yeast) on growth performance, blood glucose and triglycerides, fatty acid (FA) profile in intramuscular fat, carcase and meat traits, iron, copper, chromium and zinc concentrations in liver and bone, 24 Rambouillet male lambs (29.2 ± 0.17 kg body weight) were randomly assigned to four diets with 0, 0.2, 0.4 and 0.6 mg Cr/kg DM. The growth performance trial lasted 49 d. Supplemental Cr-yeast did not affect growth performance and carcase characteristics (p > .05), but reduced (p < .05) perirenal and intramuscular fat, as well as 3 h post-feeding blood glucose and triglycerides concentration. In liver, Fe and Cu concentration decreased (p < .05), while Cr concentrations in liver increased with increasing Cr-yeast dietary levels. In bone, Fe decreased (p < .05) as Cr-yeast dietary levels increasing, and Cr-yeast supplementation increased Cr concentrations (p < .05). As Cr-yeast dietary level increased, palmitic (C16:0) and stearic (C18:0) SFA decreased linearly (p < .05), while palmitoleic (C16:1n-7), vaccenic (C18:1n-7), linoleic (C18:2n-6) and arachidic (C20:4) unsaturated fatty acids (UFA) increased linearly (p < .01). In conclusion, Cr-yeast did not affect growth performance and carcase quality, but decreased the perirenal and intramuscular fat, blood glucose and triglyceride content, and Fe and Cu concentrations in liver as increased Cr-yeast levels in the diet. Because supplemental Cr-yeast improved index of atherogenicity and unsaturated to saturated FA ratio in muscle of lambs, it could be of human nutritional interest. HIGHLIGHTS Cr-yeast supplementation reduced blood glucose and triglyceride concentration. In liver, Fe and Cu content decreased while Cr increased with increasing Cr-yeast dietary levels. Cr-yeast modified the FA profile of human nutritional interest and improved the unsaturated to saturated FA ratio in intramuscular fat.

Long-Term Efficacy of α-Interferon in β-Thalassemics With Chronic Hepatitis C

AbstractHepatitis C virus (HCV) infection is a common cause of liver disease among polytransfused thalassemics. We treated a cohort of subjects with β-thalassemia major and chronic hepatitis C with α-interferon. The aims of the study were to assess the long-term biochemical and virologic efficacy of α-interferon and to evaluate the influence of HCV type and liver siderosis on the outcome of therapy. Seventy subjects (mean age, 14.1 years) with chronic HCV infection and abnormal aminotransferases received recombinant α-interferon for 12 months and were observed after therapy for at least 24 months. Sixty-three subjects (90%) were HCV-RNA positive at the start of therapy. HCV type 1b was found in 41 subjects (65.1%), non-1b types in 13 (20.6%), and mixed HCV types in 9 (14.3%). Liver biopsy showed cirrhosis in 11 subjects (15.7%) and siderosis grade 3-4 in 24 patients (34.2%). Three patients stopped therapy due to adverse events. Twenty-eight subjects (40%) had normal aminotransferases and had cleared HCV-RNA when last observed (mean follow-up, 36.5 months; range, 25 to 49 months). Of 41 patients who did not normalize aminotransferases, 9 had become HCV-RNA negative at the end of follow-up. The absence of cirrhosis, low liver iron content, and infection with non-1b HCV type were independently associated to complete sustained response upon multivariable analysis. In conclusion, α-interferon may induce a sustained virologic and biochemical remission of hepatitis in β-thalassemic patients with chronic HCV infection and nonadvanced liver disease.

Characterization of Iron Complexes in the Red Blood Cells of β-thalassaemia patients using 57Fe Mössbauer Spectroscopy

Red Blood Cells (RBCs) samples from healthy volunteers, β-thalassaemia major and β-thalassaemia intermedia patients were studied by means of 57Fe Mössbauer Spectroscopy (MS). The MS spectra from the RBCs of the thalassaemia patients showed the existence of significant amounts of ferritin-like iron, and in particular in the 82% of the β-thalassaemia intermedia ones. Also, β-thalassaemia intermedia patients were found to have higher Liver Iron Concentration (LIC) when compared to the β-thalassaemia major patients, as assessed by MRI exams, even though they had on an average about half the serum ferritin levels.

R2 and R2* MRI assessment of liver iron content in an undifferentiated diagnostic population with hyperferritinaemia, and impact on clinical decision making

PurposeTo confirm the linear correlation between Ferriscan® R2 (1/T2 Relaxomatry) and R2* (1/T2* Relaxometry) derived 3D Gradient echo (GRE) mDIXON-Quant sequence (Philips) with simultaneous production of a proton density fat fraction (PDFF) in undifferentiated patients with hyperferritinaemia, and to prospectively determine the clinical utility of this tool in these patients by recording the impact on clinical decision-making. Materials and MethodsParticipants referred to a hospital haematology outpatient clinic for investigation and management of elevated serum ferritin (two serum ferritin levels > 500 μg/L 4 weeks apart) were included in the study. Exclusion criteria: contraindications to MRI; clinically relevant investigations for alternative causes of hyperferritinaemia pending; and terminal illness. Thirty-two participants were recruited: 27 men, 5 women. All MRIs performed at 1.5 T. For R2* quantification, 3D six echo GRE sequence (mDIXON-Quant) was acquired. R2 images were acquired over 20 min as dictated and reported by the licensee (Ferriscan®). Clinician interpretation and patient management based on R2* and liver iron content derived from R2 (LICR2) was recorded. Pearson’s correlations, linear regression analyses, and ROC curves were calculated. P value <0.05 was considered significant. ResultsA high degree of correlation between mean R2* and LICR2 was observed in this novel patient population (slope ± SE of 43.35 ± 1.88 s−1 permg/g; 95 % CI 39.5–47.2; P < 0.001; R2 = 0.87). Clinical decision making was amended in 14/32 (44 %) patients with hyperferritinaemia following the disclosure of R2* results to clinicians, compared with serum ferritin alone. Liver biopsy was avoided in one patient based on LICR2 and R2*. Unrecognised hepatic steatosis was diagnosed in one patient from the PDFF map. ConclusionWe have confirmed the linear correlation between R2 and R2* in a real-world diagnostic population with hyperferritinaemia. Non-invasive assessment of liver iron content (LIC) by R2 and R2* MRI is a useful clinical tool and alters management in these patients.

Liver cT1 decreases following direct-acting antiviral therapy in patients with chronic hepatitis C virus

PurposeDirect-acting antiviral therapies (DAAs) for treatment of chronic hepatitis C virus (HCV) have excellent rates of viral eradication, but their effect on regression of liver fibrosis is unclear. The primary aim was to use magnetic resonance imaging (MRI) and spectroscopy (MRS) to evaluate changes in liver fibrosis, liver fat and liver iron content (LIC) in patients with chronic HCV following treatment with DAAs.MethodsIn this prospective study, 15 patients with chronic HCV due to start treatment with DAAs and with transient elastography (TE) > 8 kPa were recruited consecutively. Patients underwent MRI and MRS at baseline (before treatment), and at 24 weeks and 48 weeks after the end of treatment (EoT) for the measurement of liver cT1 (fibroinflammation), liver fat and T2* (LIC).ResultsAll patients achieved a sustained virological response. Liver cT1 showed significant decreases from baseline to 24 weeks post EoT (876 vs 806 ms, p = 0.002, n = 15), baseline to 48 weeks post EoT (876 vs 788 ms, p = 0.0002, n = 13) and 24 weeks post EoT to 48 weeks post EoT (806 vs 788 ms, p = 0.016, n = 13). Between baseline and 48 weeks EoT significant reduction in liver fat (5.17% vs 2.65%, p = 0.027) and an increase in reported LIC (0.913 vs 0.950 mg/g, p = 0.021) was observed.ConclusionLiver cT1 decreases in patients with chronic HCV undergoing successful DAA treatment. The relatively fast reduction in cT1 suggests a reduction in inflammation rather than regression of fibrosis.

Iron and zinc homeostases in female rats with physically active and sedentary lifestyles.

To determine the effects of repeated physical activity on iron and zinc homeostases in a living system, we quantified blood and tissue levels of these two metals in sedentary and physically active Long-Evans rats. At post-natal day (PND) 22, female rats were assigned to either a sedentary or an active treatment group (n = 10/group). The physically active rats increased their use of a commercially-constructed stainless steel wire wheel so that, by the end of the study (PND 101), they were running an average of 512.8 ± 31.9 (mean ± standard error) min/night. After euthanization, plasma and aliquots of liver, lung, heart, and gastrocnemius muscle were obtained. Following digestion, non-heme iron and zinc concentrations in plasma and tissues were measured using inductively coupled plasma optical emission spectroscopy. Concentrations of both non-heme iron and zinc in plasma and liver were significantly decreased among the physically active rats relative to the sedentary animals. In the lung, both metals were increased in concentration among the physically active animals but the change in zinc did not reach significance. Similarly, tissue non-heme iron and zinc levels were both increased in heart and muscle from the physically active group. It is concluded that repeated physical activity in an animal model can be associated with a translocation of both iron and zinc from sites of storage (e.g. liver) to tissues with increased metabolism (e.g. the lung, heart, and skeletal muscle).

Evaluation of Liver Iron Content by Magnetic Resonance Imaging in Children with Acute Lymphoblastic Leukemia after Cessation of Treatment

Objective:There are a limited number of studies evaluating iron overload in childhood leukemia by magnetic resonance imaging (MRI). The aim of this study was to determine liver iron content (LIC) by MRI in children with acute lymphoblastic leukemia (ALL) who had completed treatment and to compare those values with serum iron parameters.Materials and Methods:A total of 30 patients between the ages of 7 and 18 who had completed ALL treatment were included in the study. Serum iron parameters (serum iron, serum ferritin [SF], and total iron-binding capacity) and liver function tests were studied. R2 MRI was performed for determining LIC.Results:Normal LIC was detected in 22 (63.4%) of the cases. Seven (23.3%) had mild and 1 (3.3%) had moderate liver iron deposition. In contrast, severe iron overload was not detected in any of the cases. LIC levels were correlated with the numbers of packed red blood cell (pRBC) transfusions (r=0.637, p<0.001), pRBC transfusion volume (r=0.449, p<0.013), SF levels (r=0.561, p=0.001), and transferrin saturation (r=0.353, p=0.044). In addition, a positive correlation was found between the number of pRBC transfusions and SF levels (r=0.595, p<0.001).Conclusion: We showed that the frequency of liver iron deposition was low and clinically less significant after the end of treatment in childhood ALL patients. LIC was demonstrated to be related to SF and transfusion history. These findings support that SF and transfusion history may be used as references for monitoring iron accumulation or identifying cases for further examinations such as MRI.

Reproducibility of liver iron concentration estimates in MRI through R2* measurement determined by least-squares curve fitting.

Measuring transverse relaxation rate (R2* = 1/T2*) via MRI allows for noninvasive evaluation of multiple clinical parameters, including liver iron concentration (LIC) and fat fraction. Both fat and iron contribute to diffuse liver disease when stored in excess in the liver. This liver damage leads to fibrosis and cirrhosis with an increased risk of developing hepatocellular carcinoma. Liver iron concentration is linearly related to R2* measurements using MRI. A phantom was constructed to assess R2* quantification variability on 1.5 and 3 T MRI systems. Quantification was executed using least‐squares curve fitting techniques. The phantom was created using readily available, low‐cost materials. It contains four vials with R2* values that cover a clinically relevant range (100 to 420 Hz at 1.5 T). Iron content was achieved using ferric chloride solutions contained in glass vials, each affixed in a three‐dimensional (3D)‐printed polylactide (PLA) structure, surrounded by distilled water, all housed in a sealed acrylic cylinder. Multiple phantom stands were also 3D‐printed using PLA for precise orientation of the phantom with respect to the direction of the static magnetic field. Acquisitions at different phantom angles, across multiple MRI systems, and with different pulse sequence parameters were evaluated. The variability between any two R2* measurements, taken in the same vial under these various acquisition conditions, on a 1.5 T MRI system, was <7% for each of the four vials. For 3 T MRI systems, variability was less than 14% in all cases. Variability was <6% for both 1.5 and 3 T acquisitions when unchanged pulse sequence parameters were used. The phantom can be used to mimic a range of clinically relevant levels of R2* relaxation rates, as measured using MRI. These measurements were found to be reproducible relative to the gold‐standard method, liver biopsy, across several different image acquisition conditions.

Predictive Value of Serum Ferritin in Combination with Alanine Aminotransferase and Glucose Levels for Noninvasive Assessment of NAFLD: Fatty Liver in Obesity (FLiO) Study.

The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or in combination with other routine biochemical parameters. Subjects with overweight/obesity and ultrasound-confirmed liver steatosis (n = 112) from the Fatty Liver in Obesity (FLiO) study were assessed. The hepatic evaluation considered magnetic resonance imaging, ultrasonography, and credited routine blood liver biomarkers. Anthropometry and body composition, dietary intake (by means of a validated 137-item food frequency questionnaire), and specific biochemical markers were also determined. Serum ferritin levels were analyzed using a chemiluminescent microparticle immunoassay kit. Lower serum ferritin concentrations were associated with general better liver health and nutritional status. The evaluation of ferritin as a surrogate of liver damage by means of quantile regression analyses showed a positive association with alanine aminotransferase (ALT) (β = 19.21; p ≤ 0.001), liver fat content (β = 8.70; p = 0.008), and hepatic iron (β = 3.76; p ≤ 0.001), after adjusting for potential confounders. In receiver operating characteristic (ROC) analyses, the panel combination of blood ferritin, glucose, and ALT showed the best prediction for liver fat mass (area under the curve (AUC) 0.82). A combination of ferritin and ALT showed the higher predictive ability for estimating liver iron content (AUC 0.73). This investigation demonstrated the association of serum ferritin with liver health as well as with glucose and lipid metabolism markers in subjects with NAFLD. Current findings led to the identification of ferritin as a potential noninvasive predictive biomarker of NAFLD, whose surrogate value increased when combined with other routine biochemical measurements (glucose/ALT).

Brain Iron Content in Egyptian Patients with Sickle Cell Disease: Impact on Neurocognitive Functions

Background:Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment which may be due to iron overload in brain tissue or hemoglobin polymerization and endothelial dysfunction.Primary objectivewas measuring brain iron content (using R2* values) in the caudate and thalamic regions through quantitative brain MRI in Egyptian adolescents and young adults with multi-transfused SCD in comparison to beta thalassemia major (BTM) and age- and sex-matched healthy controls.Secondary objectiveswere evaluating the impact of brain iron content on neurocognitive functions of SCD patients and its association with MRI assessment of liver iron concentration (LIC) and cardiac iron (myocardial T2*).Methods: 32 children and young adults with SCD (mean age: 15.3 ± 3.7, 19 males and 13 females), 15 BTM (mean age: 19.4 ± 4.3, 7 males and 8 females) and 11 healthy control age- and gender-matched were recruited. Thorough clinical assessment, hematological and serum ferritin were performed. Brain MRI study using multi-echo fast gradient echo sequence was performed only for 15 patients with SCD, 15 patients with BTM and 11 controls and brain R2* values of both caudate and thalamic regions (right and left sides) were calculated. LIC and myocardial T2 were performed for; 15 with SCD and 15 with BTM. 32 SCD patients were examined for the neurocognitive functions; Wechsler IV Intelligence scale (verbal, perceptual, memory, processing and total IQ), Benton Visual Retention Test and Brief Psychiatric Rating Scale (BPRS).Results:For SCD patients their mean transfusion index was 174.70±63.98ml/kg/year and mean iron overload/day 0.30±0.12 mg/kg. 30 (93.8%) all SCD patients were on regular chelation therapy; 16 were on deferiprone and 16 were on combined chelation over last 5 years. Of those 32 SCD patients; 20 received concomitantly hydroxyurea therapy. Mean total IQ for SCD patients was 86.9±10.7; 68.9% had under- threshold &amp;lt;90 IQ and 27.5% had average (90-109) IQ. 12.5% of SCD patients had moderate to severe anxiety and 60.8% had of SCD patients had depression. No significant differences were found between SCD, BTM as regards LIC (p=0.102) No significant differences were found between SCD, BTM and control group in all regions of interests in brain MRI except that left thalamus R2* higher in BTM patients than both SCD and controls (p=0.032). R2* values of different regions of brain in relation with the studied parameters of SCD patients was not significant except that mean right caudate R2* was higher in female 17.4±0.8 than male 15.6±1.7 (p=0.044). The correlation coefficients showed no significant association between brain R2* and LIC or heart R2* values of SCD patients. There were positive correlation between left caudate R2* and both age and HbS%, negative correlation between transfusion index and right thalamus R2*, negative correlation between HbA% and left caudate R2* among SCD patients.Conclusion:Brain iron content in adolescents and young adults with SCD was not significantly different from either controls or BTM; SCD had high prevalence of neurocognitive dysfunction, which could not be explained by brain iron content or distribution. Figure 1 Disclosures No relevant conflicts of interest to declare.

Long-Term Efficacy and Safety of Betibeglogene Autotemcel Gene Therapy for the Treatment of Transfusion-Dependent β-Thalassemia: Results in Patients with up to 6 Years of Follow-up

Long-Term Efficacy and Safety of Betibeglogene Autotemcel Gene Therapy for the Treatment of Transfusion-Dependent β-Thalassemia: Results in Patients with up to 6 Years of Follow-up

Is Normal Growth and Development Achieved By Current Management Approaches to Thalassemia Major in the New Era?

Introduction: Growth retardation (GR) and pubertal disturbances are the earliest consequences of iron toxicity resulting from the pituitary iron deposition in children and adolescents with thalassemia major (TM). It is suggested that adequate transfusion regimens together with appropriate management of iron chelation with timely initiation and dose tailoring by close monitoring using surrogate markers of the iron load may achieve a normal pattern of complication-free survival in TM. Objectives: The purpose of this study was to evaluate the fact that the current approach to the management of the disease has provided a normal growth progression and sexual development in patients (pts) with TM. Methods: We recruited male (M) and female (F) TM pts born after 2000 and followed-up (FU) in Ege University Thalassemia Center. The pts. with an acute or chronic illness that may interfere with growth and development or stem cell transplantation recipients were excluded. The Committee of Clinical Investigation at Ege University Hospital (19.02.2020, 20-2.1T/2) approved this study. Height (H) and weight (W) assessments were performed by using the Harpenden stadiometer and puberty was evaluated by Tanner staging at 3 monthly intervals. H-standard deviation scores (h-SDS) were calculated. Target-H based on mid-parental-H for M &amp; F pts was estimated. All pts. were evaluated annually for bone mineral density (BMD) using dual-energy X-ray absorptiometry (Hologic QDR-4500W, USA) after 8 years (y) of age. The mean SDS of the lumbar spine (L1-4) BMD between -1 and -2.5 was defined as osteopenia and &amp;lt;-2.5 as osteoporosis. Growth hormone (GH) secretion was evaluated by L-dopa and insulin tests in pts. with standing-H below the -2 SD. Pts whose GH response to both stimulation tests were less than 5 ng/ml with the monoclonal assay were considered as GH deficient. Transfused pRBC units (U) and average pre-transfusion hemoglobin (Hb) per year were recorded. Serum ferritin (SF) was monitored at monthly intervals. Myocardial (T2*) and liver (R2) iron were assessed by a 1.5 Tesla magnetic resonance imaging (MRI) machine (Siemens, Symphony Vision 16034 scanner) after 8 y. Annual median SF, prescribed chelator(s), mean chelator doses were recorded by reviewing pts' records. Transfusional iron intake (TII) was estimated as the total amount of pure RBCs (each U, 250 ml with 57% Hct) transfused in a y (ml) x 1.08. Daily TII was expressed as annual TII (mg)/ mean kg b.w./days of the y. Results: We recruited 30 TM (28 β/β, 1 β/δβ, and 1 non-deletional HbH) pts (13 F and 17 M). Demographics for the population are summarized in Table1. All pts maintained annual mean pre-transfusion Hb&amp;gt; 9 g/dl. Twenty-two of 24 pts maintained Deferasirox (DFX) chelation during 9 ± 3.6 y (median 9, range 2-13 y) and achieved optimum SF levels at all times (Figure a). The dose tailoring of DFX found parallel to the changes in TII during FU (Figure b). Liver iron concentration (LIC) and myocardial T2* (mT2*) in 22 pts on DFX chelation were between 0.9-5.4 (2.1 ± 1.3 SD) mg Fe/g d.w. and 19.4-43.5 (28 ± 6.7 SD) ms, respectively, in all assessments. The only pt with mT2* of 19.4 ms revealed mT2* of &amp;gt;20 ms on FU scans. The puberty initiated at 12.8 ± 1.1 y in M (n=12) &amp; 11.2 ± 1.3 y in F (n=12) and progressed without hormone replacement in all, regardless of the chelator. Overall, growth reduced compared to the non-thalassemic population after 8 y with clear evidence of growth catch-up by the introduction of puberty. h-SDS detected &amp;lt;-2 in 6 pts in whom one had a familial GR and 5 found GH deficient and received GH therapy. All pts but one developed h-SDS&amp;lt; -2 at 10-12 y-old when they had S1/2 puberty. The pt no 4 who was entirely unresponsive to GH stimulation tests, developed GR at 1 y-old. He remained unresponsive to GH therapy (Table 2). The 14 (%58) and 5 (21%) of 24 pts demonstrated osteopenia and osteoporosis, respectively. Improvement in BMD-SDS was observed following pubertal spurt. Conclusions: Puberty was the main determinant of growth and bone maturation in TM. Despite, puberty has achieved within physiological limits in M &amp; F pts, a slight delay was observed compared to the non-thalassemic population. The relative delay in pubertal spurt may lead to overdiagnosis of growth and bone-maturation failure and unnecessary intervention in adolescent TM pts. This hypothesis as well as the appropriateness of current management guidelines remains to be elucidated. Disclosures No relevant conflicts of interest to declare.

Outcome of Sibling's and Unrelated Umbilical Cord Blood Stem Cell Transplantation Combined PBSC in Thalassemia Major and Related Factors Analysis:76 Cases Reported in Single Center

Objectives: At present, allogeneic hematopoietic stem cell transplantation is still the only way to cure thalassemia major (TM) patients. But in fact, less than half of the patients can find matched sibling or unrelated donors.Umbilical cord blood stem cells(UCB) is a potential source of stem cells.This paper was to explore effectiveness and compare the outcomes of sibling's and unrelated cord blood stem cell transplantation combined with PBSC in TM. Methods: From Jan. 2008 to Oct. 2019, the clinical data of 76 children with TM who were first underwent cord blood stem cell transplantation was analyzed retrospectively. As of Dec.31, 2019, the median follow-up time was 53 months. The NF-08-TM protocol with CY + Bu + flu + TT in conditioning, was used for sibling cord blood transplantation(CBT) in which the graft including fresh cord blood and PBSC from newborns. Haploid peripheral blood stem cells combined unrelated cord blood transplantation was carried out with NF-14-TM protocol added CY in day +3, day+ 4 days ,followed infusion of unrelated cord blood in + 6 day.The average infusion of cord blood mononuclear cells was 8.50×10^7 (2.73-20.30×10^7), of which CD34+cells were 2.42×10^5 (0.26-8.06×10^5). Unrelated cord blood mononuclear cells were 5.90×10^7 (0.77-11.35×10^7), of which CD34+ cells were 1.78×10^5 (0.17-4.44×10^5). The number of haploid mononuclear cells was 27.70×10^8 (8.80-63.18×10^8). SPSS 20.0 software was used to analyze the subjects' clinical characteristics, long-term survival rate, factors affecting umbilical cord blood implantation and related complications Results:Total of 45 cases of sibling CBT and 31 cases of unrelated CBT combined with haploid PBSC were enrolled. Two of the 76 thalassemia children died, with an OS of 96.3±2.6%, TFS93.8±3.1%; TMR was 3.7%. The OS of the sibling CBT group and the unrelated CBT group were 97.8 ± 2.2% and 90.0±9.9%, P=0.586; Meanwhile TFS were 93.3 ± 3.7% and 92.9±6.9%, P=0.589. Liver iron concentration (MRI-T2) in the unrelated CBT group was significantly correlated with delayed implantation of stem cells and delayed reconstruction of platelets (P=0.013 and P=0.034).There was no significant difference in the rate of delayed implantation of stem cells and granulocyte reconstruction between the unrelated CBT group and the sibling CBT group, but the rate of delayed platelet reconstruction in the unrelated CBT group was significantly higher than that in the sibling CBT group (P=0.002). The time of umbilical cord blood implantation in the unrelated CBT group was shorter than that in the sibling CBT group (24.32 days vs 37.67 days, P=0.058), but the platelet reconstruction in this group was slower than that in the sibling CBT group, with no statistically significant difference (P=0.061). In the ferritin level, the platelet reconstruction time in the unrelated CBT group was significantly higher than that in the sibling CBT group (P=0.031). Logistic regression analysis showed that ferrimin, umbilical cord blood sources, dose of umbilical cord blood mononuclear cells and acute GVHD were not risk factors for delayed implantation of stem cells (over 30 days).The incidence of acute and chronic GVHD in the unrelated CBT group was significantly higher than that in the sibling CBT group (P &amp;lt; 0.001 and P=0.034). The virus infection rate of the unrelated CBT group was significantly higher than that of the sibling CBT group (P=0.008). The infection of herpes simplex virus type I was common in sibling CBT, while cytomegalovirus was the main infectious virus in unrelated CBT. Conclusion:By increasing the dose of stem cells, the outcomes of TM after transplantation was favorable both in sibling and unrelated CBT group. Unrelated CBT combined with haploid PBSC can potentially reduce implantation time compared with sibling CBT. The strategies of prophylaxis and treatment of GVHD and cytomegalovirus infection should be strengthened. Iron overload may affect umbilical cord blood stem cell implantation and hematopoietic recovery. Figure 1 Disclosures No relevant conflicts of interest to declare.

Longitudinal Effect of Luspatercept Treatment on Iron Overload and Iron Chelation Therapy (ICT) in Adult Patients (Pts) with β-Thalassemia in the Believe Trial

Longitudinal Effect of Luspatercept Treatment on Iron Overload and Iron Chelation Therapy (ICT) in Adult Patients (Pts) with β-Thalassemia in the Believe Trial

Effect of iron oxide nanoparticles on vascular function and nitric oxide production in acute stress-exposed rats.

We investigated whether polyethylene glycol-coated Fe3O4 nanoparticles (IONs), acute stress and their combination modifies vascular functions, nitric oxide synthase (NOS) activity, mean arterial pressure (MAP) as well as hepcidin and ferritin H gene expressions in Wistar-Kyoto rats. Rats were divided into control, ION-treated rats (1 mg Fe/kg i.v.), repeated acute air-jet stress-exposed rats and IONs-and-stress co-exposed rats. Maximal acetylcholine (ACh)-induced and sodium nitroprusside (SNP)-induced relaxations in the femoral arteries did not differ among the groups. IONs alone significantly elevated the N?-nitro-L-arginine methyl ester (L-NAME)-sensitive component of ACh-induced relaxation and reduced the sensitivity of vascular smooth muscle cells to SNP. IONs alone also elevated NOS activity in the brainstem and hypothalamus, reduced NOS activity in the kidneys and had no effect in the liver. Acute stress alone failed to affect vascular function and NOS activities in all the tissues investigated but it elevated ferritin H expression in the liver. In the ION-and-stress group, NOS activity was elevated in the kidneys and liver, but reduced in the brainstem and hypothalamus vs. IONs alone. IONs also accentuated air-jet stress-induced MAP responses vs. stress alone. Interestingly, stress reduced ION-originated iron content in blood and liver while it was elevated in the kidneys. In conclusion, the results showed that 1) acute administration of IONs altered vascular function, increased L-NAME-sensitive component of ACh-induced relaxation and had tissue-dependent effects on NOS activity, 2) ION effects were considerably reduced by co-exposure to repeated acute stress, likely related to decrease of ION-originated iron in blood due to elevated decomposition and/or excretion.