Khaled M Musallam

American University of Beirut, Beyrouth, Beyrouth, Lebanon

Are you Khaled M Musallam?

Claim your profile

Publications (141)677.46 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Thalassemia continues to be a major health burden. The chronicity of the disease and the high cost of life-long treatment make prevention strategies crucial in the management of this disease. In this article, we revisit different successful prevention strategies, and underline the Lebanese model. The Chronic Care Center (CCC), Beirut, is the only specialized center in Lebanon for the treatment and prevention of thalassemia. The current number of patients registered up to August 2013 was 724, representing cases from all over Lebanon. In 1994, the center launched a national prevention program following the World Health Organization (WHO) recommendations. The major activities of the program include awareness campaigns, screening for thalassemia carriers in the general population and high risk groups, registry of new cases and follow-up on the mandatory premarital law (established at the same time). Screening programs showed a carrier rate of around 2.3% in the general population, and 4.0–41.0% in high risk groups. The major pitfall in the law is that only persons with a mean corpuscular volume (MCV) of >70.0 fL are asked to perform further hemoglobin (Hb) testing. A significant decrease in the number of new cases of thalassemia patients in Lebanon reflects the efforts deployed in the prevention of the disease. However, some limitations are faced in reaching a complete eradication of the disease, mainly due to the fact that abortion is illegal and due to pitfalls and incorrect implementation of the premarital law.
    Hemoglobin 07/2014; · 0.89 Impact Factor
  • Haematologica 07/2014; · 5.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Iron overload remains a concern in MDS patients especially those requiring recurrent blood transfusions. The consequence of iron overload may be more relevant in patients with low and intermediate-1 risk MDS who may survive long enough to experience such manifestations. It is a matter of debate whether this overload has time to yield organ damage, but it is quite evident that cellular damage and DNA genotoxic effect are induced. Iron overload may play a critical role in exacerbating pre-existing morbidity or even unmask silent ones. Under these circumstances, iron chelation therapy could play an integral role in the management of these patients. This review entails an in depth analysis of iron overload in MDS patients; its pathophysiology, effect on survival, associated risks and diagnostic options. It also discusses management options in relation to chelation therapy used in MDS patients and the impact it has on survival, hematologic response and organ function.
    Critical reviews in oncology/hematology 01/2014; · 5.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pulmonary arterial hypertension (PAH) remains a concern in patients with β-thalassemia major (TM) and intermedia (TI); however, studies evaluating its prevalence and risk factors using systematic confirmation on right heart catheterization are lacking. This was a multicenter cross-sectional study of 1309 Italian β-thalassemia patients (mean age 36.4 ± 9.3 years; 46% men; 74.6% TM, 25.4% TI). Patients with a tricuspid-valve regurgitant jet velocity (TRV) ≥3.2 m/s (3.6%) on transthoracic echocardiography further underwent right heart catheterization to confirm the diagnosis of PAH (mean pulmonary arterial pressure ≥25 mm Hg and pulmonary capillary wedge pressure ≤15mm Hg). The confirmed PAH prevalence on right heart catheterization was 2.1% (95%CI: 1.4-3.0); and was higher in TI (4.8%, 95%CI: 3.0-7.7) than TM (1.1%, 95%CI: 0.6-2.0). The positive predictive value for the TRV ≥3.2 m/s threshold for the diagnosis of pulmonary hypertension was 93.9%. Considerable functional limitation and decrease in the 6-minute walk distance were noted in patients with confirmed PAH. On multivariate logistic regression analysis, independent risk factors for confirmed PAH were age (OR: 1.102 per 1-year increase, 95%CI: 1.06-1.15) and splenectomy (OR: 9.31, 95%CI: 2.57-33.7). The prevalence of PAH in β-thalassemia patients as confirmed on right heart catheterization was 2.1%, with a ~5-fold higher prevalence in TI than TM. Advanced age and splenectomy are risk factors for PAH in this patient population. ClinicalTrials.gov. Identifier: NCT01496963.
    Circulation 09/2013; · 15.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with beta-thalassemia intermedia tend to present later in life with milder anemia than beta-thalassemia major patients. The incidence of mortality and its causes in this patient population remains unknown. We aim to reveal the incidence and most common causes of death in this population. We reviewed the charts of all of the beta-thalassemia intermedia patients who had been followed at the Chronic Care Center in Hazmieh, Lebanon during a 10-year period. A total of 18 patients out of 127 had died during the follow-up period giving a cumulative 10-year mortality incidence of 14%. The most common causes of cardiac deaths were due to renal and cardiac causes. Most causes of death have been linked to the high levels of iron coupled with anemia present in this patient population. Many of deaths could be prevented by adequate treatment. Larger studies with more comprehensive data capture on risk factors of mortality in this patient population are called for.
    Hematology (Amsterdam, Netherlands) 09/2013; · 1.33 Impact Factor
  • Blood Cells Molecules and Diseases 09/2013; · 2.26 Impact Factor
  • Shahina Daar, Khaled M Musallam, Anil Pathare, Ali Taher
    Blood Cells Molecules and Diseases 09/2013; · 2.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Preoperative anaemia is associated with adverse postoperative outcomes. Data on raised preoperative haematocrit concentration are limited. This study aimed to evaluate the effect of raised haematocrit on 30-day postoperative mortality and vascular events in patients undergoing major surgery. This was a cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Thirty-day mortality and vascular events, demographics and perioperative risk factors were obtained for adults undergoing major surgery. The adjusted effect of raised (over 0·50) compared with normal (0·41-0·50, American Medical Association reference range) preoperative haematocrit concentration on postoperative outcomes was assessed. Separate sex-specific analyses were also conducted, using haematocrit concentration thresholds commonly used in the diagnosis and management of apparent or absolute erythrocytosis. Some 3961 (2·0 per cent) of 197 469 patients had a raised haematocrit concentration before surgery. After adjustment, the 30-day postoperative mortality rate was higher in patients with raised haematocrit than in those without (odds ratio (OR) 2·23, 95 per cent confidence interval 1·77 to 2·80). Thirty-day rates of deep vein thrombosis (OR 1·95, 1·44 to 2·64) and pulmonary embolism (OR 1·79, 1·17 to 2·73), but not myocardial infarction or stroke, were also higher in patients with a raised haematocrit concentration. The effect on mortality was noted beyond the haematocrit thresholds of 0·48 in women and 0·52 in men; the effect estimates were considerably higher for values exceeding 0·54. Values between 0·41 and 0·45 were not associated with increased mortality risk. Similar observations were noted for venous thrombosis, although with apparent sex differences. A raised haematocrit concentration was associated with an increased risk of 30-day mortality and venous thrombosis following major surgery.
    British Journal of Surgery 07/2013; 100(8):1030-6. · 4.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE The effects of smoking on postoperative outcomes in patients undergoing major surgery are not fully established. The association between smoking and adverse postoperative outcomes has been confirmed. Whether the associations are dose dependent or restricted to patients with smoking-related disease remains to be determined. OBJECTIVE To evaluate the association between current and past smoking on the risk of postoperative mortality and vascular and respiratory events in patients undergoing major surgery. DESIGN Cohort study using the American College of Surgeons National Surgical Quality Improvement Program database. We obtained data on smoking history, perioperative risk factors, and 30-day postoperative outcomes. We assessed the effects of current and past smoking (>1 year prior) on postoperative outcomes after adjustment for potential confounders and effect mediators (eg, cardiovascular disease, chronic obstructive pulmonary disease, and cancer). We also determined whether the effects are dose dependent through analysis of pack-year quintiles. SETTING AND PARTICIPANTS A total of 607 558 adult patients undergoing major surgery in non-Veterans Affairs hospitals across the United States, Canada, Lebanon, and the United Arab Emirates during 2008 and 2009. MAIN OUTCOMES AND MEASURES The primary outcome measure was 30-day postoperative mortality; secondary outcome measures included arterial events (myocardial infarction or cerebrovascular accident), venous events (deep vein thrombosis or pulmonary embolism), and respiratory events (pneumonia, unplanned intubation, or ventilator requirement >48 hours). RESULTS The sample included 125 192 current (20.6%) and 78 763 past (13.0%) smokers. Increased odds of postoperative mortality were noted in current smokers only (odds ratio, 1.17 [95% CI, 1.10-1.24]). When we compared current and past smokers, the adjusted odds ratios were higher in the former for arterial events (1.65 [95% CI, 1.51-1.81] vs 1.20 [1.09-1.31], respectively) and respiratory events (1.45 [1.40-1.51] vs 1.13 [1.08-1.18], respectively). No effects on venous events were observed. The effects of smoking mediated through smoking-related disease were minimal. The increased adjusted odds of mortality in current smokers were evident from a smoking history of less than 10 pack-years, whereas the effects of smoking on arterial and respiratory events were incremental with increased pack-years. CONCLUSIONS AND RELEVANCE Smoking cessation at least 1 year before major surgery abolishes the increased risk of postoperative mortality and decreases the risk of arterial and respiratory events evident in current smokers. These findings should be carried forward to evaluate the value and cost-effectiveness of intervention in this setting. Our study should increase awareness of the detrimental effects of smoking-and the benefits of its cessation-on morbidity and mortality in the surgical setting.
    JAMA surgery. 06/2013;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration.
    Haematologica 06/2013; 98(6):833-44. · 5.94 Impact Factor
  • Blood Cells Molecules and Diseases 05/2013; · 2.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We conducted a cross-sectional study on 924 β-thalassaemia major patients (mean age 30·1 years) treated at nine Italian centres using the webthal software, to evaluate real-life application of iron overload assessment and management standards. Serum ferritin <2500 ng/ml was a risk factor for never having liver iron concentration (LIC) measurement, while absence of cardiac disease and siderosis were risk factors for a delay in LIC measurement >2 years. Patients who never had a cardiac MRI (CMR) T2* measurement were <18 years, had iron intake ≤0·4 mg/kg per day, or a serum ferritin <2500 ng/ml. A history of normal CMR T2* was the main risk factor for a delay in subsequent assessment of >2 years. Deferoxamine (22·8%) was more commonly used in patients with Hepatitis C Virus or high serum creatinine. Deferiprone (20·6%) was less commonly prescribed in patients with elevated alanine aminotransferase; while a deferoxamine + deferiprone combination (17·9%) was more commonly used in patients with serum ferritin >2500 ng/ml or CMR T2* <20 ms. Deferasirox (38·3%) was more commonly prescribed in patients <18 years, but less commonly used in those with heart disease or high iron intake. These observations largely echoed guidelines at the time, although some practices are expected to change in light of evolving evidence.
    British Journal of Haematology 04/2013; · 4.94 Impact Factor
  • Blood Cells Molecules and Diseases 04/2013; · 2.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Efforts to optimize the management of patients with β-thalassemia major (TM) continue to expand. Evidence from biomedical research evaluating safe and careful processing measures of blood products, the efficacy and safety of oral iron chelators, and noninvasive techniques for the assessment of iron overload are translated into better patient outcomes. The construction of TM management guidelines facilitated the incorporation of such evidence into practice. However, as several aspects of the management of TM remain controversial or governed by resource availability, a concern regarding potential variations in recommendations made by the different guidelines becomes rational, especially for physicians treating TM patients outside countries where the guidelines were constructed. In this work, we overview currently available guidelines for the management of TM and explore apparent similarities and differences between them. The evaluated guidelines included the Thalassaemia International Federation, US, Canadian, UK, Italian and Australian guidelines. We noted a general consensus for most aspects of management, although some guidelines provided more comprehensive and contemporary recommendations than others. We did not identify differences warranting concern, although minor differences in iron overload assessment strategy and more notable variations in the recommendations for iron chelation therapy were observed.
    Acta Haematologica 03/2013; 130(2):64-73. · 0.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Improvement of survival in patients with β-thalassemia has allowed several clinical morbidities to manifest, including renal complications. Patients may experience proximal tubular dysfunctions and abnormalities in glomerular filtration rate. Several risk factors have been proposed. Hypoxia may lead to renal damage with resulting proximal tubular epithelial cell dysfunction and interstitial fibrosis, while anemia induces renal hemodynamic changes. Iron overload secondary to regular transfusion therapy can also result in an increase in oxidative stress and direct cytotoxicity to the kidney. Moreover, the use of certain iron-chelating agents is associated with a transient, nonprogressive increase in serum creatinine levels. However, most available evidence comes from small, cross-sectional studies. Longitudinal follow-up of patients is needed to better understand the mechanisms of renal abnormalities in this patient population.
    Journal of nephrology 03/2013; · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease characterized by acute episodes of widespread microvascular thrombosis. The discovery that the plasmatic activity of the von Willebrand factor cleaving protease, ADAMTS13, is severely deficient in patients with TTP partially clarified the pathophysiology of the disease. However, the finding of severe deficiency of ADAMTS13 alone is unable to fully explain the clinical heterogeneity of the disease. The recent development of methods that measure ADAMTS13 activity with great analytical precision offers the opportunity to define the relationships between levels of ADAMTS13 activity below 10% (herein defined as "residual ADAMTS13 activity") and the clinical manifestations of the disease. Recent studies suggest that the amount of residual activity of ADAMTS13 may be a major determinant of the clinical heterogeneity of TTP. Herein, we review the recent findings on residual ADAMTS13 activity and their implications for research and clinical practice in the field.
    Blood reviews 03/2013; 27(2):71-6. · 7.19 Impact Factor
  • Khaled M Musallam, Maria D Cappellini, Ali T Taher
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE OF REVIEW: The aim is to overview recent evidence on consequences, assessment, and management of iron overload in transfusion-independent patients with β-thalassemia intermedia. RECENT FINDINGS: Despite their transfusion-independence, β-thalassemia intermedia patients can still accumulate iron due to increased intestinal absorption. Recent observational studies show that iron burden in this group of patients can ultimately reach considerably high thresholds, and leads to a variety of serious morbidities involving the liver, endocrine glands, and arguably the vascular system. The diagnosis of iron overload in this patient population can follow established guidelines from β-thalassemia major patients, although with careful interpretation of spot serum ferritin levels. Data from a recent randomized clinical trial demonstrated the efficacy and safety of iron chelation therapy in decreasing liver iron concentration in this group of patients, which may ultimately help in reducing morbidity risk. SUMMARY: Iron overload in transfusion-independent patients with β-thalassemia intermedia deserves careful attention, and prompt diagnosis and management are recommended.
    Current opinion in hematology 02/2013; · 5.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Iron overload may still occur in transfusion-independent patients with β-thalassemia intermedia due to increased intestinal iron absorption. In this study, we evaluated the association between iron overload, using a liver iron concentration threshold of therapeutic significance (≥5mg/g), and morbidity in 168 chelation naive patients with β-thalassemia intermedia. We demonstrated that patients with a liver iron concentration ≥5mg/g have a significantly higher prevalence of several serious vascular and endocrine/bone morbidities than do patients with <5mg/g, and we established absolute morbidity risk values differentiating both groups. We also demonstrated that the association between iron overload and morbidity in such patients is independent of the effects of advancing age and disease severity. These findings suggest that treating iron burden in β-thalassemia intermedia may be associated with reduction in serious morbidity risk.
    Blood Cells Molecules and Diseases 02/2013; · 2.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite receiving no or only occasional blood transfusions, patients with non-transfusion-dependent thalassemia (NTDT) have increased intestinal iron absorption and can accumulate iron to levels comparable with transfusion-dependent patients. This iron accumulation occurs more slowly in NTDT patients compared to transfusion-dependent thalassemia patients, and complications do not arise until later in life. It remains crucial for these patients' health to monitor and appropriately treat their iron burden. Based on recent data, including a randomized clinical trial on iron chelation in NTDT, a simple iron chelation treatment algorithm is presented to assist physicians with monitoring iron burden and initiating chelation therapy in this group of patients. Am. J. Hematol., 2013. © 2013 Wiley Periodicals, Inc.
    American Journal of Hematology 02/2013; · 4.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent molecular studies of fetal hemoglobin (HbF) regulation have reinvigorated the field and shown promise for the development of clinical HbF inducers to be used in patients with β-thalassemia and sickle cell disease. However, while numerous promising inducers of HbF have been studied in the past in β-thalassemia patient populations, with limited success in some cases, no universally effective agents have been found. Here we examine the clinical studies of such inducers in an attempt to systematically review the field. We examine trials of agents including 5-azacytidine, hydroxyurea, short-chain fatty acids, and others in this review. This review highlights the heterogeneity of clinical studies done on these agents, including both the patient populations examined and the study end points. By examining the published studies of these agents, we hope to provide a resource that will be valuable for the design of future studies of HbF inducers in β-thalassemia patient populations.
    Blood 01/2013; · 9.78 Impact Factor

Publication Stats

1k Citations
677.46 Total Impact Points

Institutions

  • 2008–2014
    • American University of Beirut
      • • Department of Internal Medicine
      • • Division of Hematology/Oncology
      • • Department of Emergency Medicine
      Beyrouth, Beyrouth, Lebanon
    • Makassed General Hospital
      Beyrouth, Beyrouth, Lebanon
  • 2013
    • Sultan Qaboos University
      • Department of Hematology
      Muscat, Muhafazat Masqat, Oman
  • 2011–2013
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      • Medicine and Medical Specialties
      Milano, Lombardy, Italy
    • Shiraz University of Medical Sciences
      • Department of Pediatrics
      Shīrāz, Fars, Iran
    • University of Padova
      • Department of Cardiac, Thoracic and Vascular Sciences
      Padova, Veneto, Italy
  • 2009–2013
    • University of Milan
      • Department of Internal Medicine
      Milano, Lombardy, Italy
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
    • Cairo University
      • Department of Pediatrics
      Cairo, Muhafazat al Qahirah, Egypt
    • Azienda Ospedaliera Niguarda Ca' Granda
      • Department of Cardiology
      Milano, Lombardy, Italy
  • 2012
    • United Arab Emirates University
      Al Ain, Abu Dhabi, United Arab Emirates
  • 2009–2011
    • Rafik Hariri University Hospital
      Beyrouth, Beyrouth, Lebanon