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עמוד בית
Wed, 07.06.23

Search results

October 2018
Howard S. Oster MD PhD, Shani Svorai-Litvak MD, Ilya Kirgner MD, Albert Kolomansky MD, Robert S. Siegel MD and Moshe Mittelman MD

Background: With advances in myelodysplastic syndromes (MDS), patient cohorts from different time periods might be different.

Objectives: To compare presentation and outcomes between two cohorts.

Methods: Data were collected from George Washington University Medical Center, Washington, DC, USA 1986–1987 (DC), and Tel Aviv Medical Center, Israel 1999–2009 (TA).

Results: The study comprised 227 patients (139 TA, 88 DC). TA patients were older (75.4 ± 9.8 vs. 63.8 ± 14.3 years, P < 0.001) and had more cardiovascular diseases (56.8% vs. 14.8%, P < 0.001), fewer cytopenias (1.67 ± 0.82 vs. 2.0 ± 0.93, P = 0.003), and lower mean corpuscular volume (94.3 ± 9.9 fl vs. 100.5 ± 15.3 fl, P < 0.001). Hemoglobin, leukocyte, neutrophil, and platelet counts were similar. More TA patients had dysplasias. Bone marrow cellularity and cytogenetics were similar, but more TA patients had blasts < 5% (73.4% vs. 50.6%, P = 0.003). More TA patients had early French-American-British (FAB) disease (66.9% vs. 40.9%, P < 0.001) and lower risk disease per International Prognostic Scoring System (81% vs. 50%, P < 0.001). The 5 year survival (5YS) of TA patients was not significantly greater (62% vs. 55%). 5YS by FAB was also slightly greater for TA patients (77% vs. 65% for early FAB; 43% vs. 37% for advanced FAB, P > 0.05).

Conclusions: Although patients diagnosed with MDS at a later period were older and had more cardiovascular co-morbidities, they had fewer cytopenias, tended to have earlier disease, and had minimally greater, but not significant, 5YS.

October 2015
Uri Rozovski MD, Ofira Ben-Tal MD, Ilya Kirgner MD, Moshe Mittelman MD and Mara Hareuveni PHD

Background: Approximately 80% of patients with myelodysplastic syndromes (MDS) receive multiple red blood cells (RBC), often multiple transfusions, and are therefore prone to develop alloantibodies against RBC. Because of increasing evidence for the role of immune dysregulation in the pathobiology of MDS, we hypothesized that in patients with MDS there is an increase in alloantibody formation beyond that expected by multiple transfusions.

Objectives: To determine the prevalence rates of alloantibodies in patients with MDS who are transfusion dependent and compare them to those of non-MDS patients matched for number of RBC units they received. 

Methods: The blood bank database was screened to identify non-MDS patients matched for age and number of units transfused. Logistic regression analysis was applied to determine factors affecting alloantibody formation. 

Results: Of 60 patients with MDS, 18 (30%) developed alloantibodies against RBC. Transfusion-dependent MDS and non-MDS patients (N=56 each), matched for number of RBC units and age, were compared. Fifteen MDS patients (27%) but only 12 non-MDS patients (12%) developed alloantibodies (P = 0.057). The relative risk for developing antibodies in MDS patients was 2.14, and MDS was the strongest predictor for formation of alloantibodies during transfusion therapy (odds ratio 3.66, confidence interval 1.4–9.3). 

Conclusions: Patients with MDS are at increased risk to develop RBC alloantibodies, partly because these patients receive multiple RBC transfusions. Whether matching for RH and KEL would lead to lower rates of RBC alloantibodies remains to be determined.


July 2013
H.S. Oster, M. Benderly, M. Hoffman, E. Cohen, A. Shotan and M. Mittelman
 Background: Anemia is common in heart failure (HF), but there is controversy regarding its contribution to morbidity and mortality.

Objective: To examine the association of mild and severe anemia with acute HF severity and mortality.

Methods: Data were prospectively collected for patients admitted to all departments of medicine and cardiology throughout the country during 2 months in 2003 as part of the Heart Failure Survey in Israel. Anemia was defined as hemoglobin (Hb) < 12 g/dl for women and < 13 g/dl for men; Hb < 10 g/dl was considered as severe anemia. Mortality data were obtained from the Israel population registry. Median follow-up was 33.6 months.

Results: Of 4102 HF patients, 2332 had acute HF and available hemoglobin data. Anemia was common (55%) and correlated with worse baseline HF. Most signs and symptoms of acute HF were similar among all groups, but mortality was greater in anemic patients. Mortality rates at 6 months were 14.9%, 23.7% and 26.3% for patients with no anemia, mild anemia, and severe anemia, respectively (P < 0.0001), and 22.2%, 33.6% and 39.9% at one year, respectively (P < 0.0001). Compared to patients without anemia, multivariable adjusted hazard ratio was 1.35 for mild anemia and 1.50 for severe anemia (confidence interval 1.20–1.52 and 1.27–1.77 respectively).

Conclusions: Anemia is common in patients with acute HF and is associated with increased mortality correlated with the degree of anemia.

May 2008
M. Mittelman, G. Lugassy, D. Merkel, H. Tamary, N. Sarid, E. Rachmilewitz and C. Hershko
April 2007
M. Garty, A. Shotan, S. Gottlieb, M. Mittelman, A. Porath, B.S. Lewis, E. Grossman, S. Behar, J. Leor, M. S. Green, R. Zimlichman and A. Caspi

Background: Despite improved management of heart failure patients, their prognosis remains poor.

Objectives: To characterize hospitalized HF[1] patients and to identify factors that may affect their short and long-term outcome in a national prospective survey.

Methods: We recorded stages B-D according to the American College of Cardiology/American Heart Association definition of HF patients hospitalized in internal medicine and cardiology departments in all 25 public hospitals in Israel.

Results: During March-April 2003, 4102 consecutive patients were recorded. Their mean age was 73 ± 12 years and 57% were males; 75.3% were hypertensive, 50% diabetic and 59% dyslipidemic; 82% had coronary artery disease, 33% atrial fibrillation, 41% renal failure (creatinine ³ 1.5 mg/dl), and 49% anemia (hemoglobin £ 12 g/dl). Mortality rates were 4.7% in-hospital, 7.6% at 30 days, 18.7% at 6 months and 28.1% at 12 months. Multiple logistic regression analysis revealed that increased 1 year mortality rate was associated with New York Heart Association III–IV (odds ratio 2.07, 95% confidence interval 1.78–2.41), age (for 10 year increment) (OR[2] 1.41, 95% CI[3] 1.31–1.52), renal failure (1.79, 1.53–2.09), anemia (1.50, 1.29–1.75), stroke (1.50, 1.21–1.85), chronic obstructive pulmonary disease (1.25, 1.04–1.50) and atrial fibrillation (1.20, 1.02–1.40).

Conclusions: This nationwide heart failure survey indicates a high risk of long-term mortality and the urgent need for the development of more effective management strategies for patients with heart failure discharged from hospitals.


[1] HF = heart failure

[2] OR = odds ratio

[3] CI = confidence interval

B. S. Lewis, A. Shotan, S. Gottlieb, S. Behar, D. A. Halon, V. Boyko, J. Leor, E. Grossman, R. Zimlichman, A. Porath, M. Mittelman, A. Caspi and M. Garty

Background: Heart failure with preserved systolic left ventricular function is a major cause of cardiac disability.

Objectives: To examine the prevalence, characteristics and late clinical outcome of patients hospitalized with HF-PSF[1] on a nationwide basis in Israel.

Methods: The Israel nationwide HF survey examined prospectively 4102 consecutive HF patients admitted to 93 internal medicine and 24 cardiology departments in all 25 public hospitals in the country. Echocardiographic LV function measurements were available in 2845 patients (69%). The present report relates to the 1364 patients who had HF-PSF (LV ejection fraction ≥ 40%).

Results: Mortality of HF-PSF patients was high (in-hospital 3.5%, 6 months 14.2%, 12 months 22.0%), but lower than in patients with reduced systolic function (all P < 0.01). Mortality was higher in patients with HF as the primary hospitalization diagnosis (16.0% vs. 12.5% at 6 months, P = 0.07 and 26.2% vs. 18.0% at 12 months, P = 0.0002). Patients with HF-PSF who died were older (78 ± 10 vs. 71 ± 12 years, P < 0.001), more often female (P = 0.05) and had atrial fibrillation more frequently (44% vs. 33%, P < 0.01). There was also a relationship between mortality and pharmacotherapy: after adjustment for age and co-morbid conditions, mortality was lower in patients treated with angiotensin-converting enzyme inhibitors (P = 0.0003) and angiotensin receptor blockers (P = 0.002) and higher in those receiving digoxin (P = 0.003) and diuretic therapy (P = 0.009).

Conclusions: This nationwide survey highlights the very high late mortality rates in patients hospitalized for HF without a decrease in systolic function. The findings mandate a focus on better evidence-based treatment strategies to improve outcome in HF-PSF patients.


[1] HF-PSF = heart failure with preserved systolic left ventricular function

December 2006
A. Jotkowitz, A. Porath, A. Shotan, M. Mittelman, E. Grossman, R. Zimlichman, B.S. Lewis, A. Caspi, S. Gottlieb and M. Garty, for the Steering Committee of the Israeli Heart Failure National Survey 2003

Background: Despite significant advances in the therapy of heart failure, many patients still do not receive optimal treatment.

Objectives: To document the standard of care that patients hospitalized with HF[1] in Israel received during a 2 month period.

Methods: The Heart Failure Survey in Israel 2003 was a prospective 2 month survey of patients admitted to all 25 public hospitals in Israel with a diagnosis of HF.

Results: The mean age of the 4102 patients was 73 years and 43% were female. The use of angiotensin-converting enzyme/angiotensin receptor blockers and beta blockers both declined from NYHA class I to IV (68.8% to 50.6% for ACE[2]-inhibitor/ARB[3] and 64.1% to 52.9% for beta blockers, P < 0.001 for comparisons). The percentage of patients by NYHA class taking an ACE-inhibitor or ARB and a beta blocker at hospital discharge also declined from NYHA class I to IV (47.5% to 28.8%, P < 0.002 for comparisons). The strongest predictor of being discharged with an ACE-inhibitor or ARB was the use of these medications at hospital admission. Negative predictors for their usage were age, creatinine, disease severity class, and functional status.

Conclusions: Despite the dissemination of guidelines many patients did not receive optimal care for HF. Reasons for this discrepancy need to be identified and modified.

[1] HF = heart failure

[2] ACE = angiotensin-converting enzyme

[3] ARB = angiotensin receptor blocker

October 2006
H.S. Oster, M. Hoffman, S. Prutchi-Sagiv, O. Katz, D. Neumann and M. Mittelman
 Recombinant human erythropoietin has become an essential part of the management of anemic patients with end-stage renal disease. It is also used to treat the anemia associated with cancer and other diseases, and it improves quality of life. In recent years, studies in animals and humans have focused on the use of rHuEPO[1] for other indications. It has been found to play a role in both cardioprotection and neuroprotection. It has effects on the immune system, and can cause regression in hematologic diseases such as multiple myeloma. It may also improve the response of solid tumors to chemotherapy and radiation therapy. On the other hand, concerns have been raised following two studies of patients with solid tumors in whom those treated with rHuEPO had diminished survival. Criticism of the design of these studies makes it clear that large, well-designed, randomized trials must be performed to determine the role of rHuEPO in the treatment of cancer, and more generally to clarify the full clinical benefits of the drug, while minimizing the harm.

[1] rHuEPO = recombinant human erythropoietin

January 2004
A. Zeidman, Z. Fradin, A. Blecher, H.S. Oster, Y. Avrahami and M. Mittelman

Background: Anemia is a known risk factor for ischemic heart disease. Based on knowledge of the physiologic role of oxygen delivery to the myocardium, anemia may be a cause of more severe cardiovascular diseases or a marker of other processes occurring in the body that induce more severe disease.

Objectives: To investigate the relationship between anemia and the clinical picture of IHD[1], including manifestations, severity and complications.

Methods: The population studied comprised 417 similarly aged patients with IHD and anemia. The patients were categorized into subgroups of IHD according to disease severity: namely, angina pectoris, acute ischemia, acute myocardial infarction, congestive heart failure or cardiac arrhythmias. Two populations served as control groups: patients with anemia but no IHD (C-I) and patients with IHD without anemia (C-II). A standard anemia workup was conducted in all patients with IHD and anemia and a correlation was made between the hematologic parameters and the manifestations and complications of IHD.

Results: The common presenting symptom was chest pain in the study group and in C-II (94% and 86% respectively) and weakness (90%) in C-I. Patients with IHD and anemia tended to suffer from a more advanced degree of IHD (80%) compared to patients with IHD alone who had milder disease (46%). Hematologic values including hemoglobin, mean cell volume, serum iron and total iron binding capacity correlated inversely with disease severity among anemic patients with IHD. There were significant differences between the study group and C-II regarding CHF[2] (31% and 18% respectively) and arrhythmias (41% and 16% respectively). The mortality rate was higher in patients with IHD and anemia than in patients with IHD alone (13% and 4% respectively).

Conclusions: Anemia is a significant risk factor in IHD. It correlates with advanced IHD, CHF, rhythm disturbance and higher mortality rate. An aggressive therapeutic and preventive approach might improve the outcome of this disease.

[1] IHD = ischemic heart disease

[2] CHF = congestive heart failure

December 2003
V. Teplitsky, D. Huminer, J. Zoldan, S. Pitlik, M. Shohat and M. Mittelman

Background: Transcobalamin II is a serum transport protein for vitamin B12. Small variations in TC-II[1] affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B12 deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes.

Objectives: To study 23 members of a four-generation family with hereditary vitamin B12 deficiency and neurologic disorders.

Methods: Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members.

Results: Partial TC-II deficiency was found in 19 subjects. Apo TC- II (free TC-II unbound to vitamin B12) and total unsaturated B12 binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B12) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B12 levels but were not anemic. Low serum B12 levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B12 injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency.

Conclusions: We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease the amount of stored cobalamin, resulting in increased susceptibility to impaired intestinal delivery of cobalamin and predisposing to clinically expressed megaloblastic anemia at a later age. Partial TC-II deficiency should be suspected in families with megaloblastic anemia and in individuals with neurologic and mental disturbances – despite normal serum vitamin B12 levels. Low serum UBBC[2] and apo TC-II should confirm the diagnosis. Early vitamin B12 therapy may prevent irreversible neurologic damage.

[1] TC II = transcobalamin II

[2] UBBC = unsaturated B12 binding capacity

April 2003
S. Behar, A. Battler, A. Porath, J. Leor, E. Grossman, Y. Hasin, M. Mittelman, Z. Feigenberg, C. Rahima-Maoz, M. Green, A. Caspi, B. Rabinowitz and M. Garty

Background: Little information is available on the clinical practice and implementation of guidelines in treating acute myocardial infarction patients in Israel.

Objective: To assess patient characteristics, hospital course, management, and 30 day clinical outcome of all AMI[1] patients hospitalized in Israel during a 2 month period in 2000.

Method: We conducted a prospective 2 month survey of consecutive AMI patients admitted to 82 of 96 internal medicine departments and all 26 cardiac departments operating in Israel in 2000. Data were collected uniformly by means of a hospital and 30 day follow-up form.

Results: During the survey 1,683 consecutive patients with a discharge diagnosis of AMI were included. Their mean age was 66 years; 73% were male. The electrocardiographic pattern on admission revealed ST elevation, non-ST elevation and an undetermined ECG[2] in 63%, 34% and 4% of patients respectively. Aspirin and heparin were given to 95% of patients. Beta-blockers and angiotensin-converting enzyme inhibitors were given to 76% and 65% of patients respectively. Among hospital survivors, 45% received lipid-lowering drugs. Thrombolytic therapy was administered in 28% of patients, coronary angiography was used in 45%, and 7% of patients underwent primary percutaneous coronary intervention. The 7 and 30 day mortality rates were 7% and 11% respectively.

Conclusions: This nationwide survey shows that one-third of the AMI patients in Israel are elderly (≥ 75 years). The survey suggests that clinical guidelines for the management of patients with AMI are partially implemented in the community. Data from large surveys representing the "real world" practice are of utmost importance for the evaluation of clinical guidelines, research and educational purposes.

[1] AMI = acute myocardial infarction

[2] ECG = electrocardiogram

November 2002
Jacob Cohen, MSc, Lia Supino-Rosin, MSc, Eran Barzilay, BSc, Ronit Eisen-Lev, DMD, Moshe Mittelman, MD and Drorit Neumann, PhD
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