Khaled M Musallam

Novartis, Bâle, Basel-City, Switzerland

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Publications (153)733.13 Total impact

  • Blood Cells Molecules and Diseases 12/2015; 55(4):419. DOI:10.1016/j.bcmd.2015.09.004 · 2.65 Impact Factor
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    ABSTRACT: Background: Patients with non-transfusion-dependent thalassemia (NTDT) present with a spectrum of disease severities. Since there are multiple pathophysiologies in such patients, tailoring treatment remains essential. Therefore, one simple, reliable tool would be beneficial to assess disease severity and tailor therapy, particularly for internal medicine specialists who may treat a variety of NTDT patients with a multitude of complications. This would allow for standardization of assessments leading to timely interventions and prevention of complications. Methods: A working group of NTDT experts was formed to develop a new disease severity scoring system for adult and pediatric patients with NTDT, based on parameters considered to be most pertinent in defining disease severity. Results: 20 parameters were selected for inclusion in the disease severity scoring system. An additional six parameters, largely related to growth and development, were selected specifically for pediatric patients (≤16years of age). Consensus of expert opinion was used to establish the selected methods of assessment for each parameter, based on feasibility and availability of technology, cost containment, and avoidance of patient risk. Conclusion: We propose that this new disease severity scoring system for adult and pediatric NTDT patients could be developed into a practical tool for widespread clinical use.
    European Journal of Internal Medicine 11/2015; DOI:10.1016/j.ejim.2015.10.003 · 2.89 Impact Factor

  • Blood Cells Molecules and Diseases 08/2015; 55(2). DOI:10.1016/j.bcmd.2015.05.011 · 2.65 Impact Factor
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    ABSTRACT: To evaluate the effect of preoperative anaemia and blood transfusion on 30-day postoperative morbidity and mortality in patients undergoing gynecological surgery. Data were analyzed from 12,836 women undergoing operation in the American College of Surgeons National Surgical Quality Improvement Program. Outcomes measured were; 30-day postoperative mortality, composite and specific morbidities (cardiac, respiratory, central nervous system, renal, wound, sepsis, venous thrombosis, or major bleeding). Multivariate logistic regression models were performed using adjusted odds ratios (ORadj) to assess the independent effects of preoperative anaemia (hematocrit <36.0%) on outcomes, effect estimates were performed before and after adjustment for perioperative transfusion requirement. The prevalence of preoperative anaemia was 23.9% (95%CI: 23.2-24.7). Adjusted for confounders by multivariate logistic regression; preoperative anaemia was independently and significantly associated with increased odds of 30-day mortality (OR: 2.40, 95%CI: 1.06-5.44) and composite morbidity (OR: 1.80, 95%CI: 1.45-2.24). This was reflected by significantly higher adjusted odds of almost all specific morbidities including; respiratory, central nervous system, renal, wound, sepsis, and venous thrombosis. Blood Transfusion increased the effect of preoperative anaemia on outcomes (61% of the effect on mortality and 16% of the composite morbidity). Preoperative anaemia is associated with adverse post-operative outcomes in women undergoing gynecological surgery. This risk associated with preoperative anaemia did not appear to be corrected by use of perioperative transfusion.
    PLoS ONE 07/2015; 10(7):e0130861. DOI:10.1371/journal.pone.0130861 · 3.23 Impact Factor
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    ABSTRACT: Little research has been done on the current cut-off international normalized ratio (INR) value of 1.5 for patients undergoing surgery. The objectives of this study are to assess the association between INR and postoperative major bleeding and mortality in patients undergoing surgery and to identify an ideal pre-operative INR for surgical patients. We analyzed data from the American College of Surgeons' National Surgical Quality Improvement Program database between 2008 and 2011 (636,231 patients). The primary outcomes were major bleeding and mortality at 30 days postoperatively. Multivariate logistic regression analyses were carried out to assess these associations. Compared to an INR of <1, the adjusted odds ratio (aOR) for major bleeding was 1.22 (95 % CI 1.18-1.25) for INR 1-1.49, 1.48 (95 % CI 1.40-1.56) for INR 1.5-1.9, and 1.49 (95 % CI 1.39-1.60) for INR ≥2. The aOR for mortality at 30 days post-operation compared to INR of <1 was 1.51 (95 % CI 1.41-1.62), 2.31 (95 % CI 2.12-2.52), and 2.81 (95 % CI 2.56-3.10) for INR 1-1.49, 1.5-1.9, and ≥2, respectively. The ideal pre-operative INR value to predict an increased risk for major bleeding was 1.10 and 1.13 for mortality. In conclusion, preoperative INR is significantly and independently associated with postoperative major bleeding and mortality.
    Journal of Thrombosis and Thrombolysis 06/2015; DOI:10.1007/s11239-015-1235-1 · 2.17 Impact Factor
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    ABSTRACT: Long-term controlled studies are needed to inform on the clinical benefit of chelation therapy for myocardial iron removal in transfusion-dependent beta thalassemia patients. In a 1-year non-randomized extension to the CORDELIA study, data collected from patients with myocardial siderosis provided additional information on deferasirox or deferoxamine (DFO) efficacy and safety. Myocardial (m)T2* increased from baseline 11.6 to 15.9 ms in patients receiving deferasirox for 24 months (n=74; Geometric mean [Gmean] ratio of month 24/baseline 1.38 [95% confidence interval 1.28, 1.49]) and from 10.8 to 14.2 ms in those receiving DFO (n=29; Gmean ratio 1.33 [1.13, 1.55]; P=0.93 between groups). Improved mT2* with deferasirox was evident across all subgroups evaluated irrespective of baseline myocardial (mT2* <10 vs ≥10 ms) or liver (LIC <15 vs ≥15 mg Fe/g dw) iron burden. Mean LVEF was stable and remained within normal limits with deferasirox or DFO. Liver iron concentration decreased from high baseline values of 30.6 ± 18.0 to 14.4 ± 16.6 mg Fe/g dw at month 24 in deferasirox patients and from 36.8 ± 15.6 to 11.0 ± 12.1 mg Fe/g dw in DFO patients. The long-term safety profile of deferasirox or DFO was consistent with previous reports; serious drug-related AEs were reported in 6.8% of deferasirox and 6.9% of DFO patients. Continued treatment of severely iron-overloaded beta thalassemia patients with deferasirox or DFO led to sustained improvements in myocardial iron irrespective of high or low baseline myocardial or liver iron burden, in parallel with substantial improvements in liver iron. ( identifier: NCT00600938)
    American Journal of Hematology 02/2015; 90(2). DOI:10.1002/ajh.23876 · 3.80 Impact Factor
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    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; 38(5). DOI:10.3109/03630269.2014.939279 · 0.79 Impact Factor
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    Haematologica 07/2014; 99(11). DOI:10.3324/haematol.2013.097220 · 5.81 Impact Factor
  • Sally Temraz · Valeria Santini · Khaled Musallam · Ali Taher ·
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    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 07/2014; 91(1). DOI:10.1016/j.critrevonc.2014.01.006 · 4.03 Impact Factor
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    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. Identifier: NCT01496963.
    Circulation 09/2013; 129(3). DOI:10.1161/CIRCULATIONAHA.113.002124 · 14.43 Impact Factor
  • Bassem N Matta · Khaled M Musallam · Joseph E Maakaron · Suzanne Koussa · Ali T Taher ·
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    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; 19(4). DOI:10.1179/1607845413Y.0000000120 · 1.25 Impact Factor

  • Blood Cells Molecules and Diseases 09/2013; 52(2-3). DOI:10.1016/j.bcmd.2013.08.006 · 2.65 Impact Factor
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    Shahina Daar · Khaled M Musallam · Anil Pathare · Ali Taher ·

    Blood Cells Molecules and Diseases 09/2013; 52(1). DOI:10.1016/j.bcmd.2013.08.001 · 2.65 Impact Factor
  • K M Musallam · J B Porter · P M Sfeir · H M Tamim · T Richards · L A Lotta · F Peyvandi · F R Jamali ·
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    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. DOI:10.1002/bjs.9176 · 5.54 Impact Factor
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    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; 148(8):1-8. DOI:10.1001/jamasurg.2013.2360 · 3.94 Impact Factor
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    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. DOI:10.3324/haematol.2012.066845 · 5.81 Impact Factor

  • Blood Cells Molecules and Diseases 05/2013; 51(3). DOI:10.1016/j.bcmd.2013.05.001 · 2.65 Impact Factor
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    Ali T Taher · Vip Viprakasit · Khaled M Musallam · M Domenica Cappellini ·
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    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 05/2013; 88(5). DOI:10.1002/ajh.23405 · 3.80 Impact Factor
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    ABSTRACT: Background. Identification and management of risk factors for stroke following isolated coronary artery bypass grafting (CABG) could potentially lower the risk of such serious morbidity. Methods. We retrieved data for 30-day stroke incidence and perioperative variables for patients undergoing isolated CABG and used multivariate logistic regression to assess the adjusted effect of preoperative hematocrit concentration on stroke incidence. Results. In 2,313 patients (mean age 65.9 years, 73.6% men), 43 (1.9%, 95% CI: 1.4–2.5) developed stroke within 30 days following CABG (74.4% within 6 days). After adjustment for a priori defined potential confounders, each 1% drop in preoperative hematocrit concentration was associated with 1.07 (95% CI: 1.01–1.13) increased odds for stroke (men, OR: 1.08, 95% CI: 1.01–1.16; women, OR: 1.02, 95% CI: 0.91–1.16). The predicted probability of stroke for descending preoperative hematocrit concentration exceeded 2% for values <37% (<37% for men (adjusted OR: 2.39, 95% CI: 1.08–5.26) and <38% for women (adjusted OR: 2.52, 95% CI: 0.53–11.98), with a steeper probability increase noted in men). The association between lower preoperative hematocrit concentration and stroke was evident irrespective of intraoperative transfusion use. Conclusion. Screening and management of patients with low preoperative hematocrit concentration may alter postoperative stroke risk in patients undergoing isolated CABG.
    Anemia 04/2013; 2013:206829. DOI:10.1155/2013/206829
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    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; 161(6). DOI:10.1111/bjh.12340 · 4.71 Impact Factor

Publication Stats

2k Citations
733.13 Total Impact Points


  • 2015
    • Novartis
      Bâle, Basel-City, Switzerland
  • 2012-2015
    • University of Milan
      Milano, Lombardy, Italy
  • 2007-2015
    • American University of Beirut
      • • Department of Internal Medicine
      • • Division of Hematology/Oncology
      • • Department of Obstetrics and Gynecology
      Beyrouth, Beyrouth, Lebanon
  • 2011-2013
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      • • Medicine and Medical Specialties
      • • “Angelo Bianchi Bonomi” Haemophilia Regional Reference Centre for Haemorrhagic and Thrombotic Diseases
      Milano, Lombardy, Italy