Browsing by Author "Taher, Ali T."

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    Causes of hospital admission in β-thalassemia (CHAT) in Lebanon from 1995 to 2015: A pilot retrospective study from a tertiary care center
    (Wiley, 2017) Saliba, Antoine N.; Moukhadder, Hassan M.; Harb, Afif; Beydoun, Hassan; Bou-Fakhredin, Rayan; Taher, Ali T.; Department of Medicine, School of Medicine
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    Disparities in the risk of septic events in patients undergoing splenectomy for hematological malignancies (D‐ROSE‐PUSH): A study based on ACS‐NSQIP database
    (Wiley, 2019) Saliba, Antoine N.; Tamim, Hani; Mailhac, Aurelie; Jamali, Faek R.; Taher, Ali T.; Medicine, School of Medicine
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    Iron overload in thalassemia: different organs at different rates
    (American Society of Hematology, 2017-12-08) Taher, Ali T.; Saliba, Antoine N.; Medicine, School of Medicine
    Thalassemic disorders lie on a phenotypic spectrum of clinical severity that depends on the severity of the globin gene mutation and coinheritance of other genetic determinants. Iron overload is associated with increased morbidity in both patients with transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). The predominant mechanisms driving the process of iron loading include increased iron burden secondary to transfusion therapy in TDT and enhanced intestinal absorption secondary to ineffective erythropoiesis and hepcidin suppression in NTDT. Different organs are affected differently by iron overload in TDT and NTDT owing to the underlying iron loading mechanism and rate of iron accumulation. Serum ferritin measurement and noninvasive imaging techniques are available to diagnose iron overload, quantify its extent in different organs, and monitor clinical response to therapy. This chapter discusses the general approach to iron chelation therapy based on organ involvement using the available iron chelators: deferoxamine, deferiprone, and deferasirox. Other novel experimental options for treatment and prevention of complications associated with iron overload in thalassemia are briefly discussed.
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    Non-Transfusion-Dependent Thalassemia: An Update on Complications and Management
    (MDPI, 2018-01-08) Sleiman, Joseph; Tarhini, Ali; Bou-Fakhredin, Rayan; Saliba, Antoine N.; Cappellini, Maria Domenica; Taher, Ali T.; Medicine, School of Medicine
    Patients with non-transfusion-dependent thalassemia (NTDT) experience many clinical complications despite their independence from frequent transfusions. Morbidities in NTDT stem from the interaction of multiple pathophysiological factors: ineffective erythropoiesis, iron overload (IOL), and hypercoagulability. Ineffective erythropoiesis and hemolysis are associated with chronic hypoxia and a hypercoagulable state. The latter are linked to a high prevalence of thromboembolic and cerebrovascular events, as well as leg ulcers and pulmonary hypertension. IOL in NTDT patients is a cumulative process that can lead to several iron-related morbidities in the liver (liver fibrosis), kidneys, endocrine glands (endocrinopathies), and vascular system (vascular disease). This review sheds light on the pathophysiology underlying morbidities associated with NTDT and summarizes the mainstays of treatment and some of the possible future therapeutic interventions.
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    Safety and Pharmacokinetics of the Oral Iron Chelator SP-420 in β-thalassemia
    (Wiley, 2017-12) Taher, Ali T.; Saliba, Antoine N.; Kuo, Kevin H.; Giardina, Patricia J.; Cohen, Alan R.; Neufeld, Ellis J.; Aydinok, Yesim; Kwiatkowski, Janet L.; Jeglinski, Brenda I.; Pietropaolo, Keith; Berk, Gregory; Viprakasit, Vip; Medicine, School of Medicine
    Our phase I, open-label, multi-center, dose-escalation study evaluated the pharmacokinetics (PK) of SP-420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent β-thalassemia. SP-420 was administered as a single dose of 1.5 (n = 3), 3 (n = 3), 6 (n = 3), 12 (n = 3), and 24 (n = 6) mg/kg or as a twice-daily dose of 9 mg/kg (n = 6) over 14-28 days. There was a near dose-linear increase in the mean plasma SP-420 concentrations and in the mean values for Cmax and AUC0-τ over the dose range evaluated. The median tmax ranged from 0.5 to 2.25 h and was not dose dependent. The study was prematurely terminated by the sponsor due to renal adverse events (AE) including proteinuria, increase in serum creatinine, and one case of Fanconi syndrome. Other adverse effects included hypersensitivity reactions and gastrointestinal disturbances. Based on current dose administration, the renal AE observed outweighed the possible benefits from chelation therapy. However, additional studies assessing efficacy and safety of lower doses or less frequent dosing of SP-420 over longer durations with close monitoring would be necessary to better explain the findings of our study and characterize the safety of the study drug.