Cardiac iron overload evaluation in thalassaemic patients using T2* magnetic resonance imaging following chelation therapy: a multicentre cross-sectional study

Abstract Introduction Magnetic resonance imaging (MRI) T2* technique is used to assess iron overload in the heart, liver and pancreas of thalassaemic patients. Optimal iron chelation and expected tissue iron response rates remain under investigation. The objective of this study was to analyse serum ferritin and the iron concentration in the heart, liver and pancreas measured by MRI T2*/R2* during regular chelation therapy in a real-world cohort of patients with thalassemia. Methods We evaluated thalassaemic patients ≥ 7 years old undergoing chelation/transfusion therapy by MRI and assessed serum ferritin at baseline and follow-up from 2004-2011. Results We evaluated 136 patients, 92% major thalassaemic, with a median age of 18 years, and median baseline ferritin 2.033ng/ml (range: 59-14,123). Iron overload distribution was: liver (99%), pancreas (74%) and heart (36%). After a median of 1.2 years of follow-up, the iron overload in the myocardium reduced from 2,63 Fe mg/g to 2,05 (p 0.003). The optimal R2* pancreas cut-off was 148 Hertz, achieving 78% sensitivity and 73% specificity. However, when combining the R2* pancreas cut off ≤ 50 Hertz and a ferritin ≤ 1222 ng/ml, we could reach a negative predictive value (NPV) of 98% for cardiac siderosis. Only 28% were undergoing combined chelation at baseline assessment, which increased up to 50% on follow up evaluation. Conclusions Chelation therapy significantly reduced cardiac siderosis in thalassaemic patients. In patients with moderate/severe liver iron concentration undergoing chelation therapy, ferritin levels and myocardium iron improved earlier than the liver siderosis.

A rare case of bronze diabetes in a patient with thalassemia

Secondary haemochromatosis (also known as bronze diabetes) is a perilous medical condition that can occur as a complication of frequent blood transfusions. Thalassemia major which occurs due to a decrease in the beta globulin chain can lead to severe anemia, extramedullary hematopoiesis and splenomegaly. Becauseof this, the affected patients requiredcontinuous blood transfusions throughout their life and as a consequence, it may lead to iron overload. A 26-year-old male presented with a complaint of darkening skin, joint pain and fever. He was a known case of thalassemia major and was undergoing blood transfusions three times a week. Further laboratory findings revealed decreased hemoglobin, abnormal liver function tests and increased blood glucose levels. The patient was managed with IV insulin and chelation therapy. The patient responded to treatment and was better on subsequent follow-up. The diagnostic and therapeutic challenges along with the epidemiological dataemphasize the need of raising the awareness of physicians to this devastating condition.

Influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome: A retrospective study / 中华血液学杂志

Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.

Effects of lead exposure and chelation therapy in different developmental stages on mouse short-term and long-term cognitive functions / 环境与职业医学

Background Lead (Pb) exposure impairs cognitive functions of children. Whether Pb exposure in different developmental stages induces long-term cognitive impairment, and whether chelation therapy could mitigate the cognitive impairment is rarely reported. Objective This experiment is designed to investigate effects of Pb exposure and chelation therapy during different developmental stages (breastfeeding, weaning, and early puberty periods) on mouse short-term and long-term cognitive functions. Methods C57BL/6 male mice in breastfeeding period, weaning period, and early puberty period (postnatal day 2, 21, and 41; PND 2, PND 21, and PND 41, n=30, respectively) were randomly divided into control, Pb exposure, and Pb+dimercaptosuccinic acid (DMSA) treatment groups (n=10 in each group). The control groups received standard food and deionized water. The Pb exposure mice received standard food and free drinking water containing Pb acetate (0.1% for dams, and 0.05% for pups). After receiving Pb acetate for 19 d, the Pb+DMSA treatment groups were given 1 mmol·kg−1·d−1 DMSA for 6 d with gastric infusion. Whole blood Pb levels were measured after DMSA treatment on experimental day 25. The effects on short-term cognitive function were tested in the Morris Water Maze task by the analyses of escape latency on PND 75−79, as well as target quadrant time and times of platform-crossing on PND 80. Hippocampal long-term potentiation of field excitatory postsynaptic potential (fEPSP) of mice on PND 365 was induced to demonstrate the effects on long-term cognitive function. Results The blood Pb levels among the Pb, Pb+DMSA, and control groups were statistically different for each developmental stage (Fbreastfeeding period=43.47, Fweaning period=228.6, Fearly period of puberty=274.2, all P<0.001). Compared to the counterpart control groups, blood Pb levels of the pb exposure groups (386.4, 265.0, and 178.1 μg·L−1 in breastfeeding period, weaning period, and early puberty period, respectively) were significantly higher for all stages. After the chelation therapy, the blood Pb significantly decreased for all stages (28.68, 47.29, and 20.93 μg·L−1 in the three periods, respectively, all P<0.001) and the Pb levels of the mice exposed in the breastfeeding period decreased most (by 92.58%, 82.15%, and 88.25% in the three periods, respectively, P<0.01). In the water maze task, the mice exposed to Pb in the breastfeeding period had a gentler decrease in escape latency (from 54.20 s on day 1 to 30.54 s on day 5, by 43.65 % decrease) than the control group (from 32.44 s on day 1 to 15.20 s on day 5, by 53.14 % decrease) (P<0.01) and a significant decrease in target quadrant time (P<0.05). After the chelation therapy, the escape latency of the DMSA-treated mice in the breastfeeding period (from 40.94 s on day 1 to 20.87 s on day 5, by 48.99 % decrease) was steeper than that of the Pb-exposed mice (P<0.05). The differences in the escape latency, target quadrant time, and times of platform-crossing were not significant between the Pb-exposed mice and the control mice in the weaning period and early period of puberty (all P>0.05). After the chelation therapy, such differences were also not significant compared with before therapy. Due to the small sample size, data were merged for different developmental stages in the long-term potentiation test. The amplitudes of fEPSP induced in the control, Pb-exposed, and DMSA treatment groups were significantly different (Fgroups=212.2, Ftime=11.36. P<0.001). The average fEPSP amplitude induced in the last 10 min recorded in the hippocampal slices in the Pb exposure group was significantly lower than that in the control group (P<0.05). After the DMSA treatment, no significant differences were observed in the fEPSP amplitudes between the Pb exposure group and the DMSA treatment group (P>0.05). When observing the fEPSP data by developmental stages, the fEPSP amplitude in the breastfeeding Pb-exposure group was 27.2% lower than that of the breastfeeding control group, while such changes were not obvious in the weaning period or in the early period of puberty. The fEPSP amplitude in breastfeeding DMSA treatment group was 44.3% higher than that of the breastfeeding Pb exposure group, while such changes were not observed in the weaning period or in early period of puberty. Conclusion Pb exposure during different developmental stages, especially in breastfeeding period, could affect short-term and long-term cognitive functions of mice. The harmful effects may be partially reversed by DMSA chelation therapy, especially being treated in breastfeeding period.

Diving deep into chelation therapy for coronary artery disease: a review

Chelation therapy is still a mainstay therapy when it comes to dealing with heavy metal intoxication. The ability of various chelators to bind metal and other chemical molecules led to the idea whether chelation therapy can be used as an alternative therapy to enchain calcium element that is known to be present in the atherosclerotic plaque. Various studies have been conducted, one of which is a large trial to assess chelation therapy study to show in case ethylenediaminetetraacetic acid (EDTA) chelator can be proven by evidence-based in managing coronary heart disease. Despite the favorable results that were found in many literature studies, the results of the study are still under debate in various aspects. To address this issue, we conducted a review article to discuss comprehensively the general description of EDTA as chelation therapy, various mechanisms that can explain the use of EDTA in the management of coronary heart disease, the pharmacokinetic aspects of EDTA chelation therapy, as well as describing various existing studies with a good level of evidence to review the effectiveness of these therapies against coronary artery disease.

Prospecção de sideróforos do tipo hidroxamato e quinona para terapia de sobrecarga de ferro / Prospection of hydroxamate and quinone-type siderophores for iron overload chelation therapy

A sobrecarga de ferro é uma condição prejudicial para os pacientes, que apresentam uma diminuição significativa na qualidade de vida. Os fármacos quelantes são moléculas que têm capacidade de uso clínico para atuar como atenuadores da sobrecarga de metais. Neste trabalho apresentamos uma análise de sideróforos do tipo hidroxamato e quinona, com o objetivo de ampliar a gama de terapia de sobrecarga de ferro. Para cada composto foi realizado um ensaio competitivo com a sonda calce- ína para verificar a capacidade de ligação do ferro, e um ensaio antioxidante baseado na supressão da oxidação dependente de ferro da dihidrorrodamina (DHR) sob ascorbato. Foi observado que o hidroxamato cíclico piridoxatina apresentou capacidade de sequestrar ferro de substratos de alta afinidade, tanto em meio tamponado quanto em meio intracelular. Em ambas as situações também se mostrou um antioxidante eficiente. Entretanto, parece ser o mais tóxico do grupo dos hidroxamatos (que ainda continha o hidroxamato linear desferricoprogênio e o aromático desferriastercromo). Outros compostos naturais também foram estudados como possíveis candidatos a fármacos para sobrecarga de ferro. Complexos de ferro foram caracterizados por espectrofotometria para avaliar a estequiometria possível, considerando os sítios de ligação para cada composto. Ensaios de fluorescência revelaram que entre os quatro compostos em estudo (ácido clorogênico, lapachol, hemateína e hematoxilina), o complexo entre ferro e hemateína apresenta maior estabilidade relativa do que outros

Iron overload is a harmful condition for patients, who have a significant decrease in life quality. Chelating drugs are molecules that have the capacity for clinical use to act as attenuators of metal overload. In this work we present an analysis of hydroxamate and quinone-type siderophores, intending to broaden the range of iron overload therapy. For each compound it was conducted a competitive assay with the fluorescent probe calcein to verify the iron binding ability, and an antioxidant assay based on suppression of the iron-dependent oxidation of dihydrorhodamine (DHR) under ascorbate. It was observed that cyclic hydroxamate pyridoxatin displayed good ability to scavenge iron from high affinity substrates both in buffer and in intracellular medium. It was also an efficient antioxidant in both setups. However, pyridoxatin seems to be the most toxic from the hydroxamate group (composed also by the linear desferricoprogen and the aromatic desferriasterchrome). Other natural compounds have also been studied as possible candidates for iron-overload drug therapy. Iron complexes were characterized by spectrophotometry to assess the possible stoichiometry considering the binding sites for each compound. Fluorescence assays revealed that among the four compounds in study (chlorogenic acid, lapachol, hematein and hematoxylin), the complex between iron and hematein has higher relative stability than others

Study of iron overload assessment by T2* magnetic resonance imaging in patients with myelodysplastic syndromes / 中华血液学杂志

Objectives: To analyze the cardiac T2* value, liver iron concentration (LIC) , and related laboratory parameters in myelodysplastic syndrome (MDS) with iron overload and evaluate the changes of organ functions after iron chelation therapy. To explore the value of magnetic resonance imaging (MRI) T2* in making early diagnosis and assessing organs iron overload. Methods: Retrospective investigation was used to observe the cardiac T2* value, LIC, iron metabolism parameters and related laboratory parameters of 85 MDS patients from Nov 2014 to Jan 2018. Among them, 7 MDS patients with Low/Int-1 have received iron chelation therapy for 6 months during two MRI examinations. The above parameters were collected before and after iron chelation therapy for comparison. Results: Correlations were found between heart T2* value and age (rs=-0.290, P=0.007) and left ventricular ejection fraction (LVEF) (rs=0.265, P=0.009) . There was a significant negative correlation between heart T2* value and blood transfusion units (rs=-0.701, P<0.001) . There was a significant positive correlation between LIC and serum ferritin (SF) (rs=0.577, P<0.001) . There was also a correlation between LIC and ALT (rs=0.268, P=0.014) and blood transfusion units (rs=0.244, P=0.034) . There was no correlation between heart T2* and pro-BNP, SF (all P>0.05) , and no correlation between LIC and age (P>0.05) . The increase of heart T2* between the normal and abnormal groups was statistically significant (P=0.005) , but the iron overload ratio of the heart T2*<20 ms was not significant between the two groups. There was statistical significance in the proportion of severe liver iron overload (LIC>15 mg/g DW) (P=0.045) . After iron chelation therapy, the values of SF, transferrin saturation, ALT, AST, pro-BNP and LIC of 7 patients were decreased compared with values before iron chelation therapy, and the peripheral blood cell level was increased. However, the changes of LVEF and T2* values after iron chelation were not obvious. Conclusion: MRI T2* may be a predictor of iron overload in patients with MDS in early stage, and may be more valuable compare with LVEF, SF and other laboratory indicators. The safety and repeatability of MRI cardiac T2* examination are recognized, and it can be used as an ideal detection for patients with iron overload.

Study of iron overload assessment by T2* magnetic resonance imaging in patients with myelodysplastic syndromes / 中华血液学杂志

Objectives@#To analyze the cardiac T2* value, liver iron concentration (LIC) , and related laboratory parameters in myelodysplastic syndrome (MDS) with iron overload and evaluate the changes of organ functions after iron chelation therapy. To explore the value of magnetic resonance imaging (MRI) T2* in making early diagnosis and assessing organs iron overload.@*Methods@#Retrospective investigation was used to observe the cardiac T2* value, LIC, iron metabolism parameters and related laboratory parameters of 85 MDS patients from Nov 2014 to Jan 2018. Among them, 7 MDS patients with Low/Int-1 have received iron chelation therapy for 6 months during two MRI examinations. The above parameters were collected before and after iron chelation therapy for comparison.@*Results@#Correlations were found between heart T2* value and age (rs=-0.290, P=0.007) and left ventricular ejection fraction (LVEF) (rs=0.265, P=0.009) . There was a significant negative correlation between heart T2* value and blood transfusion units (rs=-0.701, P<0.001) . There was a significant positive correlation between LIC and serum ferritin (SF) (rs=0.577, P<0.001) . There was also a correlation between LIC and ALT (rs=0.268, P=0.014) and blood transfusion units (rs=0.244, P=0.034) . There was no correlation between heart T2* and pro-BNP, SF (all P>0.05) , and no correlation between LIC and age (P>0.05) . The increase of heart T2* between the normal and abnormal groups was statistically significant (P=0.005) , but the iron overload ratio of the heart T2*<20 ms was not significant between the two groups. There was statistical significance in the proportion of severe liver iron overload (LIC>15 mg/g DW) (P=0.045) . After iron chelation therapy, the values of SF, transferrin saturation, ALT, AST, pro-BNP and LIC of 7 patients were decreased compared with values before iron chelation therapy, and the peripheral blood cell level was increased. However, the changes of LVEF and T2* values after iron chelation were not obvious.@*Conclusion@#MRI T2* may be a predictor of iron overload in patients with MDS in early stage, and may be more valuable compare with LVEF, SF and other laboratory indicators. The safety and repeatability of MRI cardiac T2* examination are recognized, and it can be used as an ideal detection for patients with iron overload.

Comparative Efficacy and Safety of Oral Iron Chelators and their Novel Combination in Children with Thalassemia.

Objective: To compare the efficacy and safety of oral iron chelators (Deferiprone and Deferasirox) when used singly and in combination in multi-transfused children with thalassemia. Design: Prospective comparative study. Setting: Thalassemia Center of a medical college affiliated hospital Participants and Intervention: 49 multi-transfused children with thalassemia with a mean (SD) age 11.6 (6.21) y received daily chelation therapy with either deferiprone alone (75 mg/kg/day in 3 divided doses), deferasirox alone (30 mg/kg/day single dose) or their daily combination (same dose as monotherapy) for 12 months. Outcome measures: Serum ferritin levels at the start of study, after 6 months and after 12 months. MRI T2* of liver and heart initially and after 6 months of follow up. 24-hour urinary iron excretion values at the outset and after 12 months of chelation therapy. At every visit for blood transfusion, all patients were clinically assessed for any adverse effects; liver and renal functions were monitored 6-monthly. Results: After 12 months of respective chelation therapy, serum ferritin values decreased from a mean of 3140.5 ng/mL to 2910.0 ng/mL in deferiprone alone group, 3859.2 ng/mL to 3417.4 ng/mL in deferasirox alone group and from 3696.5 ng/mL to 2572.1 ng/mL in the combination group. The combination therapy was more efficacious in causing fall in serum ferritin levels compared to deferiprone and deferasirox monotherapy (P=0.035 and 0.040, respectively). Results of MRI T2* were equivocal. Combined drug usage produced maximum negative iron balance in the body by maximally increasing the iron excretion in urine from 61.1 µmol/day to 343.3 µmol/day (P=0.002). No significant adverse reactions were noticed in either the monotherapy or the combination group. Conclusion: Oral combination therapy of deferiprone and deferasirox appears to be an efficacious and safe modality to reduce serum ferritin in multi-transfused children with thalassemia.

Acute inhalational metallic nickel poisoning / 中华急诊医学杂志

Objective To investigate the clinical characteristics of acute inhalational metallic nickel poisoning and its treatment effect.Methods Data including epidemiology,clinical features,laboratory tests,imaging examinations,therapy protocol as well as prognosis were collected and analyzed.Results Thoracic CT scan of all patients demonstrated as bilateral diffuse infiltration.Nickel concentration in both blood and urine were high in all patients and the concentration was positively associated with poisoning severity.All 4 patients received glucocorticoid treatment,2 of whom with acute respiratory distress syndrome were admitted to ICU to initiate mechanical ventilation and were given sodium dimercaptopropanesulfonate.All patients survived to hospital discharge.Conclusions Acute inhalational metallic nickel poisoning is uncommon and early symptoms are inconclusive.The blood and urine nickel concentration is helpful to judge the severity of the disease.Pulmonary diffuse infiltration is the main clinical feature.Glucocorticoid,chelation therapy as well as symptomatic treatment are effective therapies to relief disease severity.

Correlation Between Mean Red Cell Transfusion Demand And Chelation Therapy In Multiply Transfused Thalassemia Major Patients.

Abstracts: Background & Objective: Life long red blood transfusion remains the main treatment for β thalassemia major patients. Transfusion-dependent patients, in the absence of chelation therapy, develop progressive accumulation of iron, which is responsible for tissue damage and, eventually, death. The factors, which influence the iron burden are type of chelation therapy and mean red cell transfusion requirement. Increasing red cell transfusion requirement, iron deposit and development of all antibodies complicates transfusion therapy in thalassemia patients. Aim is to investigate the patients for the red cell transfusion requirement compared on the basis of iron overload and type of chelation therapy. Methodology: Ninety eights patients were included in this study and samples collected and investigated for the red cell transfusion requirement, compared on the basis of iron overload and type of chelation therapy.Conclusion: Combination of two iron chelators (such as parenteral desferroxamine plus oral deferiprone) have been shown to produce additive and synergistic effects, may produce enhanced iron excretion, minimize side effects, decrease mean red cell transfusion requirement and improve compliance is strongly recommended in transfusion dependent thalassemia patients.

Ocular abnormalities in multi‑transfused beta‑thalassemia patients.

Aims: The aim of this study was to assess ocular changes in thalassemia patients who have received multiple transfusions and chelate binding therapy in order to avoid iron accumulation. Settings and Design: A cross‑sectional study. Subjects and Methods: A total of 54 thalassemia major patients were selected as case group, and 54 age‑ and sex‑matched healthy subjects were regarded as a control group. Ocular examination included visual acuity, refraction testing, slit lamp examination, funduscopy, tonometry, perimetry, tear break‑up time test, and color vision testing were performed for all the participants. We computed the frequency and duration of blood transfusion, the mean serum ferritin level, pretransfusion hemoglobin concentration, and type, duration, and daily dose of chelation therapy for thalassemia patients based on their records. Statistical Analysis Used: All data analysis was performed using SPSS, version 19. Results: All the thalassemic patients were asymptomatic, but abnormal ocular findings (dry eye (33.3%), cataract (10.2%), retinal pigment epithelium degeneration (16.7%), color vision deficiency (3.7%), and visual field defects (33.7%)) were seen in 68.5% of thalassemic group. The prevalence of ocular abnormalities in normal group was 19.4%, which was significantly lower than that in thalassemia patients (P = 0.000). No significant correlation was found between ocular abnormalities and mean serum ferritin level (P = 0.627) and mean hemoglobin concentration (P = 0.143). Correlation of number of blood transfusion with the presence of ocular abnormalities was found to be statistically significant (P = 0.005). Conclusions: As life expectancy for beta‑thalassemia patients extends, regular ophthalmological evaluation to detect early changes in their ocular system is recommended.

Brain 1H-MRS study on the effects of copper chelation therapy on WD patients / 中国神经精神疾病杂志

Objective To examine the brain metabolic changes in WD patients receiving copper chelation by us?ing 1H-MRS. Method Thirty-nine patients with WD was randomly divided into four groups: non-brain type group (18 cases), brain type prior-treatment group and short-term treatment group (21 cases), long-term treatment group (20 cases) from short-term treatment group, and 20 healthy volunteers served as a control group. 1H-MRS and MRI were performed on patients on 1.5/MR/MRS system to detect these above-mentioned items before and after treatment. Result The mean of NAA/Cr was significantly lower in the left putamen and head of the caudate nucleus than in the left basal ganglion in the 39 patients with WD. The mean of NAA/Cr and Cho/Cr in the left putamen and basal ganglion was significantly lower in non-brain type group than in control group(P0.05). The mean of NAA/Cr and NAA/Cho in the left putamen and basal ganglion was much higher in long-term treatment group than in brain type group(P<0.01 or P<0.05). The mean of Cho/Cr in the left head of caudate nucleus were much higher after treatment compared with prior-treatment group(P<0.05). The mean of NAA/Cr in the left putamen, head of the left caudate nucleus and basal ganglion in all groups was negatively correlated with course of the disease. Conclusion There are significant differences in brain metabolism among different type of WD. The long-term but not short-term copper chelation significantly improves brain metabolism. NAA/Cr may be used as a non-invasive indicator to examine the efficacy of treatment.

Polineuropatía motora subaguda secundaria a intoxicación por plomo / Subacute motor polyneuropathy secondary to lead poisoning

Las manifestaciones clínicas de la intoxicación por plomo son variadas e inespecíficas y continúan siendo un reto diagnóstico, en especial cuando son producto de presentaciones tan infrecuentes como las secundarias a fragmentos por proyectiles de arma de fuego intraarticulares. En suamplio espectro de manifestaciones se han descrito cambios que van desde el déficit de atenciónhasta estados más avanzados como las polineuropatías. El diagnóstico se basa principalmente enla medición del metal en distintos elementos del paciente y el tratamiento en medidas generales desoporte y terapia de quelación. Describimos el caso de un hombre con el antecedente de una herida por arma de fuego en caderaderecha, con un cuadro clínico progresivo de dolor abdominal, anemia acompañada de punteadobasófilo y manifestaciones neurológicas. Con un estudio por electromiografía que reporto unapolineuropatía axonal desmielinizante motora y sensitiva. Sus niveles séricos de plomo fueron 113µg/dL (Rango normal hasta 10 µg/dL) y después de un esquema de tratamiento con edetato calciodisódico (EDTA) más D penicilamina los síntomas neurológicos mejoraron asociado a un controlsérico de plomo de 49.1 µg/dL. Conclusión: la intoxicación por plomo es causa de polineuropatía motora subaguda especialmente en pacientes con exposición prolongada y niveles séricos altos de plomo. (Acta Med Colomb2014; 39: 185-190).

The clinical manifestations of lead poisoning are varied and nonspecific and remain a diagnostic challenge, especially when they are product of infrequent presentations such as the secondary to intraarticular gun fire fragments. In its broad spectrum of manifestations, changes ranging from attention deficit disorder to more advanced states like polyneuropathies have been described. The diagnosis is based mainly on the measurement of metal in various elements of the patient, and treatment in general supportive measures and chelation therapy. The case of a man with a history of gunshot wound in right hip with a progressive clinical picture of abdominal pain, anemia accompanied by basophilic stippling and neurological manifestations is described. The electromyography reported a motor and sensory axonal demyelinating polyneuropathy. Serum levels of lead were 113 µg/dL (normal range up 10 µg/dL) and after a treatment regimen with calcium disodium edetate (EDTA ) plus D penicillamine, the neurological symptoms improved, associated with a serum lead control of 49.1 µg/dL. Conclusion: lead poisoning causes subacute motor polyneuropathy especially in patients with prolonged exposure and high serum lead levels. (Acta Med Colomb 2014; 39: 185-190).

Saturnismo por retenção de projétil de arma de fogo em articulação:relato de caso / Saturnism caused by retained intra-articular bullet: case report

A intoxicação por chumbo, também conhecida como saturnismo, que ocorre em razão do projétil retido em ferimento por arma de fogo, é uma complicação já conhecida e descrita na literatura. O risco dessa intoxicação endógena por chumbo está associado ao contato do projétil com o líquido sinovial ou líquido cefalorraquidiano. O tratamento é feito com terapia de quelação, sendo definitivo com a retirada cirúrgica do projétil. Relatamos aqui um caso clínico de um paciente que desenvolveu intoxicação por chumbo em razão de projétil retido em contato com líquido sinovial. Paciente do gênero masculino, 24 anos, internado para investigação de quadro de dor abdominal associada a náuseas, vômitos e febre há 7 dias. Diagnosticado saturnismo, que foi confirmado por meio de exames laboratoriais e de imagem. Procedeu-se, então, à retirada dos fragmentos, além do segmento clínico de suporte. Apresentou evolução favorável após tratamento

Lead poisoning, also known as saturnism, caused by a retained bullet, is a well-known complication, and has also been described in literature. This endogenous intoxication is associated with the contact of the projectile with synovial liquid or cerebrospinalfluid. Chelation therapy is advised as a course of treatment in addition to the surgical removal of the projectile, both all- together sums up to a definitive optimum outcome. We discuss here a clinical case of a patient who developed lead poisoning due to a retained projectile within synovial liquid. Male patient,24 years old, admitted with the symptoms of abdominal pain, nausea, vomiting and fever for 7 days for investigation. He was diagnosed with saturnism, that was confirmed by laboratorial and imaging exams. The following procedure was the removal of fragments in addition to the continuous clinical follow-up. The patient presented with positive response to treatment.

Expulsion by Ionic Complexation: Benchmark Therapy for Atherosclerosis A Review.

Ethylenediamine tetraacetic acid (EDTA) chelation therapy has been practiced since longtime for the treatment of cardiovascular diseases, alone or in combination with other treatments. It has been recommended as a harmless, relatively inexpensive and non-surgical method of restoring blood flow in atherosclerotic vessels. Ability of EDTA to form complex with heavy metals like calcium, lead, copper is used to remove calcium from arthrosclerosis plaques which ultimately improves the condition. It can be concluded that chelation therapy is emerging form of complementary or alternative medicine to surgery and can be used in safe manner. Still there is insufficient evidence to decide on the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of patients with atherosclerotic cardiovascular disease.

Recent advances in treatment of aplastic anemia

Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.

Sobrecarga de ferro em adolescente com xerocitose: a importância da ressonância nuclear magnética / Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging

Relatar um caso de sobrecarga de ferro secundária à xerocitose, uma doença rara, em uma adolescente, diagnosticada por meio de ressonância magnética em T2*. Relatamos o caso de uma paciente sintomática com xerocitose, nível de ferritina de 350ng/mL e sobrecarga de ferro cardíaca significativa. Ela foi diagnosticada por ressonância magnética em T2* e recebeu terapia de quelação. Análise por ectacitometria confirmou o diagnóstico de xerocitose hereditária. Na sequência, a ressonância magnética em T2* demonstrou resolução completa da sobrecarga de ferro em vários órgãos e novo ecocardiograma revelou resolução completa das alterações cardíacas anteriores. A paciente permanece em terapia de quelação. Xerocitose é uma desordem genética autossômica dominante rara, caracterizada por estomatocitose desidratada. O paciente pode apresentar fadiga intensa e sobrecarga de ferro. Sugerimos o uso regular de ressonância magnética em T2* para o diagnóstico e controle da resposta à quelação de ferro em xerocitose e acreditamos que o exame pode ser útil também em outras anemias hemolíticas que necessitam de transfusões.

To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

Brazilian Thalassemia Association protocol for iron chelation therapy in patients under regular transfusion

In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox) providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA), presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams) and the role of T2* magnetic resonance imaging (MRI) to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.

Uncommon Sources and Some Unsual Manifestations of Lead Poisoning in a Tropical Developing Country

Lead-containing cooking utensils, sometimes used in South Indian homes, and indigenous medications, widely used in India and increasingly in developed countries, may be responsible for lead intoxication in adults. We report chronic lead poisoning in five adult patients. Not all patients had abdominal colic, while dramatic weight loss, depression and encephalopathy were seen. Once recognized, lead poisoning is treatable and sometimes preventable. Response to chelation therapy with agents such as calcium ethylenediaminetetraacetate (CaEDTA) is impressive, although several courses of therapy may be necessary.