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Browsing by Author "Saliba, Antoine N."
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Item 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 MedicineItem Combination of sorafenib, vorinostat and bortezomib for the treatment of poor-risk AML: report of two consecutive clinical trials(Elsevier, 2019-02) Sayar, Hamid; Cripe, Larry D.; Saliba, Antoine N.; Abu Zaid, Mohammad; Konig, Heiko; Boswell, H. Scott; Medicine, School of MedicineItem 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 MedicineItem Does Race Play a Role in Complications and Outcomes of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms?(2021) Peseski, Andrew M.; Saliba, Antoine N.; Althouse, Sandra K.; Sayar, Hamid; Medicine, School of MedicineBACKGROUND: Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of hematologic malignancies with known vascular complications. The role race and ethnicity play in these complications is less defined. We aimed to further evaluate the role of race in patients without a history of previous thrombotic or hemorrhagic events. METHODS: In this retrospective study, 300 adult patients with MPN were included; 270 (90.0%) were White and 30 (10.0%) were non-White. The non-White group primarily consisted of African American or Black (26 patients), followed by others. Median age at diagnosis was 58 years for White patients and 61.5 years for non-White patients. The interaction between outcomes and vascular events with race was evaluated using multivariate logistical regression models. RESULTS: The incidence of thrombotic events was inversely correlated with age at diagnosis, with younger patients demonstrating a higher rate of thrombotic events over time (p < .001). The incidence of thrombotic or hemorrhagic events did not differ between White and non-White patients. A statistically significant difference in median survival was observed between White and non-White patients: 29 years (95% confidence interval [CI]: 21.8-not reached) versus 13 years (95% CI: 5.7-22.7), respectively (p = .016). CONCLUSION: This study did not find a significant difference in the rate of thrombotic or hemorrhagic events between White and non-White patients with MPN but suggested that non-White patients had significantly shorter median survival than White patients. Such observations may inform future studies to further characterize racial disparities in outcomes.Item 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 MedicineThalassemic 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.Item 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 MedicinePatients 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.Item 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 MedicineOur 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.