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https://www.readbyqxmd.com/read/28924413/pseudovitelliform-maculopathy-associated-with-deferoxamine-toxicity-multimodal-imaging-and-electrophysiology-of-a-rare-entity
#1
Kelly M Bui, SriniVas R Sadda, Hani Salehi-Had
Deferoxamine is a commonly used chelating agent for secondary hemochromatosis. We report a rare retinal manifestation of deferoxamine toxicity in a 68-year-old man and provide supporting multimodal imaging and electrophysiology. The patient had iron overload related to transfusion-dependent myelodysplastic syndrome and developed a pseudovitelliform macular lesion related to deferoxamine toxicity. We also describe for the first time the worsening of this maculopathy on deferasirox, an alternative chelating agent...
2017: Digital Journal of Ophthalmology: DJO
https://www.readbyqxmd.com/read/28900315/efficacy-and-safety-of-deferasirox-in-pediatric-patients-of-thalassemia-at-a-tertiary-care-teaching-hospital
#2
Dhaval R Thakor, Chetna K Desai, Jigar D Kapadia, Ram K Dikshit, K M Mehariya
OBJECTIVE: To evaluate efficacy, safety and utilization pattern of deferasirox in paediatric patients of transfusion dependant β Thalassemia Major at a tertiary care teaching hospital in Gujarat. MATERIALS AND METHODS: This observational, prospective-retrospective, single centre, continuous study was conducted in a tertiary care teaching hospital among paediatric patients of transfusion dependent β Thalassemia Major. Patients treated with deferasirox for not more than 12 weeks were enrolled...
April 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/28875336/progression-of-liver-fibrosis-can-be-controlled-by-adequate-chelation-in-transfusion-dependent-thalassemia-tdt
#3
D Maira, E Cassinerio, A Marcon, M Mancarella, M Fraquelli, P Pedrotti, M D Cappellini
A substantial proportion of patients with transfusion-dependent beta-thalassemia major suffer from chronic liver disease. Iron overload resulting from repeated transfusions and HCV infection has been implicated in the development of liver fibrosis. Hepatic siderosis and fibrosis were assessed in 99 transfusion-dependent thalassemia (TDT) patients using transient elastography (TE) and liver iron concentration (LIC) assessed by T2*MRI at baseline and after 4 years. Data were analyzed retrospectively. At baseline, the overall mean liver stiffness measurement (LSM) was 7...
September 5, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28864815/eltrombopag-a-powerful-chelator-of-cellular-or-extracellular-iron-iii-alone-or-combined-with-a-second-chelator
#4
Evangelia Vlachodimitropoulou, Yu-Lin Chen, Maciej Garbowski, Pimpisid Koonyosying, Bethan Psaila, Martha Sola-Visner, Nichola Cooper, Robert Hider, John Porter
Eltrombopag (ELT) is a thrombopoietin receptor agonist, also reported to decrease labile iron in leukemia cells. Here we examine the previously undescribed iron(III)-coordinating and cellular iron-mobilizing properties of ELT. We find a high binding constant for iron(III) (log β2=35). Clinically achievable concentrations (1μM) progressively mobilised cellular iron from hepatocyte, cardiomyocyte and pancreatic cell lines, rapidly decreasing intracellular ROS and also restoring insulin secretion in pancreatic cells...
September 1, 2017: Blood
https://www.readbyqxmd.com/read/28820004/drug-induced-liver-injury-in-children-clinical-observations-animal-models-and-regulatory-status
#5
Qiang Shi, Xi Yang, James J Greenhaw, Alec Thomas Salminen, Gary M Russotti, William F Salminen
Drug-induced liver injury in children (cDILI) accounts for about 1% of all reported adverse drug reactions throughout all age groups, less than 10% of all clinical DILI cases, and around 20% of all acute liver failure cases in children. The overall DILI susceptibility in children has been assumed to be lower than in adults. Nevertheless, controversial evidence is emerging about children's sensitivity to DILI, with children's relative susceptibility to DILI appearing to be highly drug-specific. The culprit drugs in cDILI are similar but not identical to DILI in adults (aDILI)...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28818403/heavy-metal-levels-in-patients-with-ineffective-erythropoiesis
#6
Turan Bayhan, Şule Ünal, Eyüp Çırak, Onur Erdem, Cemal Akay, Orhan Gürsel, İbrahim Eker, Erdem Karabulut, Fatma Gümrük
OBJECTIVES: Iron is taken into enterocytes at the duodenum via apical divalent metal-ion transporter 1 protein. Besides iron, divalent metal-ion transporter 1 also transports other divalent metals. We aimed to investigate blood heavy metal levels in patients with ineffective erythropoiesis. METHODS: Blood levels of heavy metals including Pb, Al, Cd, Cr, Co, Cu, and Zn were measured in patients with thalassemia major (TM), thalassemia intermedia (TI), congenital dyserythropoietic anemia (CDA), and age- and sex-matched healthy controls...
August 2, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28815805/intracellular-iron-overload-leading-to-dna-damage-of-lymphocytes-and-immune-dysfunction-in-thalassemia-major-patients
#7
Jyoti Shaw, Ayan Chakraborty, Arijit Nag, Arnab Chattopadyay, Anjan Kr Dasgupta, Maitreyee Bhattacharyya
OBJECTIVES: To investigate the cause and effects of intracellular iron overload in lymphocytes of thalassemia major patients. METHODS: 66 thalassemia major patients having iron overload and 10 age matched controls were chosen for the study. Blood sample was collected and serum ferritin, oxidative stress, lymphocyte DNA damage were examined as well as infective episodes were also counted. RESULTS: Case-control analysis revealed significant oxidative stress, iron overload, DNA damage and rate of infections in thalassemia cases as compared to controls...
August 16, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28809446/deferasirox-for-managing-iron-overload-in-people-with-thalassaemia
#8
REVIEW
Claudia Bollig, Lisa K Schell, Gerta Rücker, Roman Allert, Edith Motschall, Charlotte M Niemeyer, Dirk Bassler, Joerg J Meerpohl
BACKGROUND: Thalassaemia is a hereditary anaemia due to ineffective erythropoiesis. In particular, people with thalassaemia major develop secondary iron overload resulting from regular red blood cell transfusions. Iron chelation therapy is needed to prevent long-term complications.Both deferoxamine and deferiprone are effective; however, a review of the effectiveness and safety of the newer oral chelator deferasirox in people with thalassaemia is needed. OBJECTIVES: To assess the effectiveness and safety of oral deferasirox in people with thalassaemia and iron overload...
August 15, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28781827/deferasirox-associated-with-liver-failure-and-death-in-a-sickle-cell-anemia-patient-homozygous-for-the-1774delg-polymorphism-in-the-abcc2-gene
#9
Caroline C B Braga, Bruno Deltreggia Benites, Dulcineia M de Albuquerque, Marisa C Alvarez, Tiago Seva-Pereira, Bruno K L Duarte, Fernando F Costa, Simone C O Gilli, Sara T O Saad
This manuscript describes the case of a patient with sickle cell anemia who died of fulminant hepatitis after therapy with the iron chelator Deferasirox. The patient was homozygous for the -1774delG polymorphism in the Abcc2 gene, which raises the concern about the use of hepatotoxic drugs in this specific context.
August 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28753129/glomerular-and-tubular-functions-in-children-and-adults-with-transfusion-dependent-thalassemia
#10
Agageldi Annayev, Zeynep Karakaş, Serap Karaman, Altan Yalçıner, Alev Yılmaz, Sevinç Emre
OBJECTIVE: This study aimed at assessing renal functions in patients with transfusion dependent thalassemia (TDT). MATERIALS AND METHODS: Fifty patients and 30 controls were enrolled in this prospective study. Serum levels of electrolytes and albumin were measured by a spectrophotometer. Serum levels of cystatin-C and urinary levels of β2-microglobulin were measured by nephelometric method. Thirty-eight patients were receiving Deferasirox, 8 were on Deferiprone...
July 28, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28706555/advances-in-iron-chelation-therapy-transitioning-to-a-new-oral-formulation
#11
Nirmish R Shah
Iron overload is a concern for patients who require repeated red-blood-cell transfusions due to conditions such as sickle cell disease, thalassemia, or myelodysplastic syndromes. The recommended treatment for removing excess iron in these patients is iron chelation therapy. Currently available iron chelators include deferoxamine, which is administered by injection, and deferasirox and deferiprone, both of which are administered orally. Adherence to iron chelator therapy is an important consideration and may be affected by side effects...
2017: Drugs in Context
https://www.readbyqxmd.com/read/28687016/safety-and-tolerability-of-deferasirox-in-pediatric-hematopoietic-stem-cell-transplant-recipients-one-facility-s-five-years-experience-of-chelation-treatment
#12
Natalia Maximova, Massimo Gregori, Roberto Simeone, Aurelio Sonzogni, Giulia Boz, Carmen Fucile, Valeria Marini, Antonietta Martelli, Francesca Mattioli
42 pediatric patients with iron overload, who underwent liver biopsy and DFX treatment after hematopoietic stem cell transplantation were included in the study group. The patients were divided into two groups diversified according to deferasirox trough plasma concentrations (DFX Ctrough) with cut-off equal to10 mcg/mL. The average dose of DFX was 25.9 mg/kg in the DFX Ctrough < 10 mcg/mL group versus 19.2 mg/kg in the DFX Ctrough > 10 mcg/mL group (p=0,0003). The mean duration of DFX treatment was 135...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28683697/assessment-of-off-label-prescribing-profile-evidence-and-evolution
#13
Encarnación Blanco-Reina, Azucena Muñoz-García, Manuel Jesús Cárdenas-Aranzana, Ricardo Ocaña-Riola, José Ramón Del Prado-Llergo
OBJECTIVES: The objectives of the study were to describe the extent and profile of off-label prescriptions, to evaluate the level of evidence supporting these indications, to assess the research activity in these conditions, and to determine to what extent these were authorized as new indications five years after the application. METHODS: A cross-sectional study including all applications conducted in the Hospital Universitario Reina Sofía in Córdoba during 2010...
July 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/28673501/management-of-iron-overload-in-hemoglobinopathies
#14
S Allali, M de Montalembert, V Brousse, M Chalumeau, Z Karim
Hemoglobinopathies, thalassemia and sickle cell disease are among the most frequent monogenic diseases in the world. Transfusion has improved dramatically their prognosis, but provokes iron overload, which induces multiple organ damages. Iron overload is related to accumulation of iron released from hemolysis and transfused red cell, but also, in thalassemic patients, secondary to ineffective erythropoiesis, which increases intestinal iron absorption via decreased hepcidin production. Transfusion-related cardiac iron overload remains a main cause of death in thalassemia in well-resourced countries, and is responsible for severe hepatic damages in sickle cell disease...
June 30, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28651884/-transfusions-in-myelodysplastic-syndromes
#15
C Rose
PRBC transfusion remains the mainstay of treatment of anemia in MDS after failure of erythropoiesis stimulating agents. The most common transfusion trigger in transfusion-dependent MDS patients is 80g/L. This level is based only on expert consensus; a randomized controlled trial comparing restrictive against liberal policy is required to evaluate potential impact of transfusion policy on with QoL and survival. Prophylactic antigen matching for RhCE and K must be used in order to reduce the risk of red blood cell (RBC) alloimmunization...
September 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28644630/expanding-the-therapeutic-potential-of-the-iron-chelator-deferasirox-in-the-development-of-aqueous-stable-ti-iv-anticancer-complexes
#16
Sergio A Loza-Rosas, Alexandra M Vázquez-Salgado, Kennett I Rivero, Lenny J Negrón, Yamixa Delgado, Josué A Benjamín-Rivera, Angel L Vázquez-Maldonado, Timothy B Parks, Charlene Munet-Colón, Arthur D Tinoco
The recent X-ray structure of titanium(IV)-bound human serum transferrin (STf) exhibiting citrate as a synergistic anion reveals a difference in Ti(IV) coordination versus iron(III), the metal endogenously delivered by the protein to cells. This finding enriches our bioinspired drug design strategy for Ti(IV)-based anticancer therapeutics, which applies a family of Fe(III) chelators termed chemical transferrin mimetic (cTfm) ligands to inhibit Fe bioavailability in cancer cells. Deferasirox, a drug used for iron overload disease, is a cTfm ligand that models STf coordination to Fe(III), favoring Fe(III) binding versus Ti(IV)...
July 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28621205/neurocognitive-dysfunction-in-children-with-%C3%AE-thalassemia-major-psychometric-neurophysiologic-and-radiologic-evaluation
#17
M S Elalfy, R H Aly, H Azzam, K Aboelftouh, R H Shatla, M Tarif, M Abdatty, R M Elsayed
OBJECTIVE: To evaluate the impact of iron chelating drugs and serum ferritin on the neurocognitive functions of patients with β thalassemia major (β-TM), using psychometric, neurophysiologic and radiologic tests. METHODS: Eighty children with β-TM were enrolled into the study and were compared to 40 healthy controls. All participants were evaluated by measuring serum ferritin, neurocognitive assessment by Benton Visual Retention Test, Wechsler Intelligence Scale for Children, Wisconsin Card Sort Test, P300 and magnetic resonance spectroscopy (MRS)...
June 16, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28556939/a-case-of-fanconi-syndrome-due-to-a-deferasirox-overdose-and-a-trial-of-plasmapheresis
#18
L Shah, J L Powell, J J Zaritsky
WHAT IS KNOWN AND OBJECTIVE: Deferasirox has nephrotoxic effects in the context of chronic therapy. This case report illustrates proximal tubular dysfunction (Fanconi syndrome) due to an acute deferasirox overdose. CASE DESCRIPTION: In response, we trialled plasmapheresis to eliminate the drug. Deferasirox levels were obtained in the context of three rounds of plasmapheresis. Given the half-life model of decay, we concluded that plasmapheresis may not have been successful...
May 29, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28421266/reactive-oxygen-species-mediated-t-lymphocyte-abnormalities-in-an-iron-overloaded-mouse-model-and-iron-overloaded-patients-with-myelodysplastic-syndromes
#19
Jie Chen, Wen-Yi Lu, Ming-Feng Zhao, Xiao-Li Cao, Yan-Yu Jiang, Xin Jin, Ping Xu, Ting-Ting Yuan, Yu-Chen Zhang, Xiao Chai, Juan-Xia Meng, Qing Li, Xia Xiao, Juan Mu, De-Guan Li, Ai-Ping Qi
The adverse effects of iron overload have raised more concerns as a growing number of studies reported its association with immune disorders. This study aimed to investigate alterations in the immune system by iron overload in patients with myelodysplastic syndrome (MDS) and an iron-overloaded mouse model. The peripheral blood from patients was harvested to test the effect of iron overload on the subsets of T lymphocytes, and the level of reactive oxygen species (ROS) was also evaluated. The data showed that iron-overloaded patients had a lower percentage of CD3(+) T cells and disrupted T cell subsets, concomitant with higher ROS level in lymphocytes...
July 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28419408/iron-chelating-therapy-with-deferasirox-in-transfusion-dependent-higher-risk-myelodysplastic-syndromes-a-retrospective-multicentre-study
#20
MULTICENTER STUDY
Pellegrino Musto, Luca Maurillo, Vittorio Simeon, Antonella Poloni, Carlo Finelli, Enrico Balleari, Alessandra Ricco, Flavia Rivellini, Agostino Cortelezzi, Giuseppe Tarantini, Oreste Villani, Giovanna Mansueto, Maria R Milella, Daniele Scapicchio, Gioacchino Marziano, Massimo Breccia, Pasquale Niscola, Alessandro Sanna, Cristina Clissa, Maria T Voso, Susanna Fenu, Adriano Venditti, Valeria Santini, Emanuele Angelucci, Alessandro Levis
Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000 mg/day (range 375-2500 mg) for a median of 11 months (range 0·4-75)...
June 2017: British Journal of Haematology
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