Israel Medical Association Journal

 Background:  Pomegranate extract (POMx) consumption has been shown to reduce the incidence and severity of collagen-induced arthritis in mice.

Objectives:  To investigate whether pomegranate consumption affects disease activity in patients with rheumatoid arthritis (RA), in relation to their serum oxidative status.

Methods:  In this pilot 12 week open-labeled study eight patients with active RA consumed POMx (10 ml/day) for 12 weeks. Patients’ joint status and serum oxidative status (lipid peroxidation, total thiols group, paraoxonase 1 activity) were evaluated at baseline and at week 12.

Results:  Six patients completed the study. POMx consumption significantly (P < 0.02) reduced the composite Disease Activity Index (DAS28) by 17%, which could be related mostly to a significant (P < 0.005) reduction in the tender joint count (by 62%). These results were associated with a significant (P < 0.02) reduction in serum oxidative status and a moderate but significant (P < 0.02) increase in serum high density lipoprotein-associated paraoxonase 1 (PON1) activity. The addition of POMx to serum from RA patients reduced free radical-induced lipid peroxidation by up to 25%.

Conclusions:  The pomegranate consumption reduced DAS28 in RA patients, and this effect could be related to the antioxidative property of pomegranates. Dietary supplementation with pomegranates may be a useful complementary strategy to attenuate clinical symptoms in RA patients.

Background: Rapid reperfusion of an infarct-related artery is crucial for the successful treatment of ST elevation myocardial infarction. Every effort should be made to shorten door-to-balloon time.

Objectives: To investigate whether bypassing the emergency room (ER) has a positive influence on door-to-balloon time in patients presenting with ST elevation myocardial infarction (STEMI) and whether the reduction in door-to-balloon time improves patients’ clinical outcome.

Methods: We analyzed data of 776 patients with STEMI[1] from the 2004 and the 2006 Acute Coronary Syndrome Israeli Survey (ACSIS) registry. The ACSIS[2] is a biennial survey on acute myocardial infarction performed in all 25 intensive cardiac care units in Israel during a 2-month period. Twenty-five percent of patients (193 of 776) arrived directly to the intensive cardiac care unit (ICCU) and 75% (583 of 776) were assessed first in the ER[3]. We compared door-to-balloon time, ejection fraction, 30 days MACE (major adverse cardiac and cerebrovascular events) and 30 days mortality in the two study groups.

Results: There was significantly shorter door-to-balloon time in the direct ICCU group as compared with the ER group (45 vs. 79 minutes, P < 0.002). Patients in the direct ICCU group were more likely to have door-to-balloon time of less than 90 minutes in accordance with ACC/AHA guidelines (88.7% vs. 59.2%, P < 0.0001). Moreover, patients in the direct ICCU group were less likely to have left ventricular ejection fraction < 30% (5.4% vs. 12.2%, P = 0.045) and less likely to have symptoms of overt congestive heart failure. Lastly, 30 days MACE[4] was significantly lower in the direct ICCU group (22 vs. 30%, P < 0.004).

Conclusions: There is significant reduction of the door-to-balloon time in the direct ICCU admission strategy. This reduction translates into improvement in clinical outcome of patients. It is reasonable to apply the direct ICCU strategy to patients with STEMI.

Background: Concomitant human immunodeficiency virus and human papillomavirus infection increases both HPV[1] persistence and the risk of invasive cervical cancer. An estimation of HPV prevalence among HIV[2]-positive women in Israel would contribute to improving care for this population and preventing morbidity and mortality related to cervical cancer.

Objectives: To determine the prevalence of HPV infection and cervical cytology abnormalities, and to assess the possible influence of HIV infection on HPV carriage in HIV-positive women attending the Infectious Disease Clinic at Soroka University Medical Center.

Methods: The study population included 84 HIV-seropositive women. They were examined by a gynecologist and screened for HPV genotyping, and Pap smears were obtained for cervical cytology. Demographic, behavioral, and HIV infection variables were also recorded and analyzed.

Results: Forty-nine (58.3%) of the study participants were HPV-positive; 34 of them had oncogenic genotypes. Young age (< 16 years) at first sexual intercourse was the only variable significantly associated with HPV infection (P < 0.05). Abnormal cervical cytology was present in 17 women (20.3%); 21 women were referred to colposcopy, which was abnormal in 9 (10.7%).

Conclusions: The prevalence of HPV carriage among HIV-positive woman in our study was slightly higher than published elsewhere. The prevalence of pathological cervical cytology was much higher than in the general population. An extremely high prevalence of pathological colposcopies requiring further treatment was found. Screening for HPV and premalignant changes in the uterine cervix is highly recommended in the HIV-seropositive population. We suggest that colposcopy be considered part of the routine workup in HIV-seropositive woman.

Background: Appropriate antibiotic use is of both clinical and economic significance to any health system and should be given adequate attention. Prior to this study, no in-depth information was available on antibiotic use patterns in the emergency department of Hadassah Medical Center.

Objectives: To describe the use and misuse of antibiotics and their associated costs in the emergency department of Hadassah Medical Center.

Methods: We analyzed the charts of 657 discharged patients and 45 admitted patients who received antibiotics in Hadassah Medical Center’s emergency department during a 6 week period (29 April – 11 June 2007). A prescription was considered appropriate or inappropriate if the choice of antibiotic, dose and duration by the prescribing physician after diagnosis was considered suitable or wrong by the infectious diseases consultant evaluating the prescriptions according to Kunin’s criteria.

Results: The overall prescribing rate of antibiotics was 14.5% (702/4830) of which 42% were broad- spectrum antibiotics. The evaluated antibiotic prescriptions numbered 1105 (96 prescriptions containing 2 antibiotics, 2 prescriptions containing 3 antibiotics), and 54% of them were considered appropriate. The total inappropriate cost was 3583 NIS[1] (1109 USD PPP[2]) out of the total antibiotic costs of 27,300 NIS (8452 USD PPP). The annual total antibiotic cost was 237,510 NIS (73,532 USD PPP) and the annual total inappropriate cost was 31,172 NIS (9648 USD PPP). The mean costs of inappropriate prescriptions were highest for respiratory (112 NIS, 35 USD PPP) and urinary tract infection (93 NIS, 29 USD PPP). There were more cases when the optimal cost was lower than the actual cost (N=171) than when optimal cost was higher than the actual cost (N=9). In the first case, the total inappropriate costs were 3805 NIS (1,178 USD PPP), and in the second case, -222 NIS (68.7 USD PPP).

Conclusions: The use of antibiotics in emergency departments should be monitored, especially in severely ill patients who require broad-spectrum antibiotics and for antibiotics otherwise restricted in the hospital wards. Our findings indicate that 12% of the total antibiotic costs could have been avoided if all prescriptions were optimal.

Background: Coronary CT angiography is an accurate imaging modality; however, its main drawback is the radiation dose. A new technology, the "step and shoot," which reduces the radiation up to one-eighth, is now available.

Objectives: To assess our initial experience using the "step-and-shoot" technology for various vascular pathologies.

Methods: During a 10 month period 125 consecutive asymptomatic patients (111 men and 14 women aged 25–82, average age 54.9 years) with various clinical indications that were appropriate for step-and-shoot CCTA[1] (regular heart rate < 65 beats/minute and body weight < 115 kg) were scanned with a 64-slice multidetector computed tomography Brilliance scanner (Philips, USA). The preparation protocol for the scan was the same as for the regular coronary CTA. All examinations were interpreted by at least one experienced radiologist and one experienced interventional cardiologist. The quality of the examinations was graded from 1 (excellent imaging quality of all coronary segments) to 4 (poor quality, not diagnostic). There were 99 patients without a history of coronary intervention, 13 after coronary stent deployment (19 stents), and 3 after coronary artery bypass graft.

Results: Coronary interpretation was obtained in 122 examinations (97.6%). The imaging quality obtained was as follows: 103 patients scored 1 (82.4%), 15 scored 2 (12%), 4 scored 3 (3.2%) and 3 scored 4 (2.4%). The grades were unrelated to cardiac history or type of previous examinations. Poor image quality occurred because of sudden heart rate acceleration during the scan (one patient), movement and respiration (one patient), and arrhythmia and bad scan timing (in one). Two patients were referred to percutaneous coronary intervention based on the CCTA findings, which correlated perfectly.

Conclusions: Step-and-shoot CCTA is a reliable technique and CCTA algorithm comparable to the regular CCTA. This technique requires the lowest radiation dose, as compared to other coronary imaging modalities, that can be used for all CCTA indications based on the inclusion criteria of low (> 65 bpm) and stable heart rate.

Background: On-site cardiac surgery is not widely available in developing countries despite a high prevalence of coronary artery disease.

Objectives: To analyze the safety, feasibility and cost-effectiveness of transradial percutaneous coronary intervention without on-site cardiac surgery in a community hospital in a developing country.

Methods: Of the 174 patients who underwent PCI[1] for the first time in our center, we analyzed two groups: stable coronary disease and acute myocardial infarction. The primary endpoint was the rate of complications during the first 24 hours after PCI. We also analyzed the length of hospital stay and the rate of hospital readmission in the first week after PCI, and compared costs between the radial and femoral approaches.

Results: The study group comprised 131 patients with stable coronary disease and 43 with acute MI[2]. Among the patients with stable coronary disease 8 (6.1%) had pulse loss, 12 (9.16%) had on-site hematoma, and 3 (2.29%) had bleeding at the site of the puncture. Among the patients with acute MI, 3 (6.98) had pulse loss and 5 (11.63%) had bleeding at the site of the puncture. There were no cases of atriovenous fistula or nerve damage. In the stable coronary disease group, 130 patients (99%) were discharged on the same day (2.4 ± 2 hours). In the acute MI group, the length of stay was 6.6 ± 2.5 days with at least 24 hours in the intensive care unit. There were no hospital readmissions in the first week after the procedure. The total cost, which includes equipment related to the specific approach and recovery room stay, was significantly lower with the radial approach compared to the femoral approach (US$ 500 saving per intervention).

Conclusions: The transradial approach was safe and feasible in a community hospital in a developing country without on-site cardiac surgery backup. The radial artery approach is clearly more cost effective than the femoral approach.

Background: Trans-aortic pressure gradient in patients with aortic stenosis and left ventricular systolic dysfunction is typically low but occasionally high.

Objectives: To examine the distribution of trans-aortic PG[1] in patients with severe AS[2] and severe LV[3] dysfunction and compare the clinical and echocardiographic characteristics and outcome of patients with high versus low PG.

Methods: Using the echocardiographic laboratory database at our institution, 72 patients with severe AS (aortic valve area ≤ 1.0 cm²) and severe LV dysfunction (LV ejection fraction ≤ 30%) were identified. The characteristics and outcome of these patients were compared.

Results: PG was high (mean PG ≥ 35 mmHg) in 32 patients (44.4%) and low (< 35 mmHg) in 40 (55.6%). Aortic valve area was slightly smaller in patients with high PG (0.63 ± 0.15 vs. 0.75 ± 0.16 cm² in patients with low PG, P = 0.003), and LV ejection fraction was slightly higher in patients with high PG (26 ± 5 vs. 22 ± 5% in patients with low PG, P = 0.005). During a median follow-up period of 9 months 14 patients (19%) underwent aortic valve replacement and 46 patients (64%) died. Aortic valve replacement was associated with lower mortality (age and gender-adjusted hazard ratio 0.19, 95% confidence interval 0.05–0.82), whereas trans-aortic PG was not (P = 0.41).

Conclusions: A large proportion of patients with severe AS have relatively high trans-aortic PG despite severe LV dysfunction, a finding partially related to more severe AS and better LV function. Trans-aortic PG is not related to outcome in these patients.

Background: Kidney disease and cardiovascular disease seem to be lethally synergistic and both are approaching the epidemic level. A reduced glomerular filtration rate is associated with increased mortality risk in patients with heart failure. Many patients with congestive heart failure are anemic. Anemia is very often associated with chronic kidney disease.

Objectives: To assess – in relation to New York Heart Association class – the prevalence of anemia and chronic kidney disease in patients with normal serum creatinine in a cohort of 526 consecutive patients with coronary artery disease undergoing percutaneous coronary interventions.

Methods: GFR[1] was estimated using the simplified MDRD formula, the Cockcroft-Gault formula, the Jeliffe and the novel CKD-EPI formula.

Results: According to the WHO definition the prevalence of anemia in our study was 21%. We observed a progressive decline in GFR and hemoglobin concentration together with a rise in NYHA[2] class. Significant correlations were observed between eGFR[3] and systolic blood pressure, diastolic blood pressure, age, NYHA class, complications of PCI[4], including bleeding, and major adverse cardiac events.

Conclusions: The prevalence of anemia and chronic kidney disease is high in patients undergoing PCI despite normal serum creatinine, particularly in higher NYHA class. Lower eGFR and hemoglobin are associated with more complications, including bleeding after PCI and higher prevalence of major adverse cardiac events. In patients with risk factors for cardiovascular disease, GFR should be estimated since renal dysfunction and subsequent anemia are important risk factors for cardiovascular morbidity and mortality.

Background: Clinical and epidemiologic features of coronary heart disease may not be explained solely by established risk factors. The role of infectious pathogens in the development and rupture of atherosclerotic plaques remains elusive but an association between Chlamydia pneumoniae, Mycoplasma pneumoniae and CHD[1] has been previously reported

Objectives: To determine whether there is an association between mycoplasmal infections and CHD.

Methods: We conducted a prospective cohort analysis of 150 consecutive hospitalized patients with CHD (85 with acute coronary syndrome and 65 admitted for unrelated reasons) and 98 healthy blood donors. Antibody titers for Mycoplasma pneumoniae, M. fermentans, M. hominis and Ureaplasma urealyticum were measured with the agglutination test or specific enzyme-linked immunosorbent assay in all three groups of patients.

Results: Analysis of the antibody titers did not reveal any significant difference in the presence of mycoplasmal antibodies between the patients with ACS[2], patients with known stable CHD hospitalized for non-CHD reasons, and healthy blood donors.

Conclusions: Determination of specific antibodies did not reveal a significant association among different types of mycoplasmal infection and CHD.





[1] CHD = coronary heart disease

[2] ACS = acute coronary syndrome

Background: Myocardial blush grade is a useful marker of microvascular reperfusion that may influence left ventricular dilatation.

Objectives: To assess the impact of myocardial blush grade on LV[1] remodeling in patients undergoing successful primary  PCI³ for first anterior ST elevation myocardial infarction.

Methods: In 26 consecutive patients MB[2] grade was evaluated immediately after primary PCI[3]. Each patient underwent transthoracic echocardiography at 24 hours and 6 months after PCI for evaluation of LV volumes. LV remodeling was defined as an increase in end-diastolic volume by ≥ 20%.

Results: The presence of myocardial reperfusion (MB 2-3) after primary PCI was associated with a significantly lower rate of remodeling than the absence of myocardial reperfusion (MB 0-1) (17.6% vs. 66.6%, P = 0.012). Accordingly, at 6 months, patients with MB 2-3 had significantly smaller LV end-diastolic volume (94 ± 21.5 ml vs. 115.2 ± 26) compared with patients with MB 0-1. In univariate analysis, only MB (0-1 versus 2-3) was associated with increased risk of LV remodeling (odds ratio 9.3, 95% confidence interval 1.45–60.21, P = 0.019).

Conclusions: Impaired microvascular reperfusion, as assessed by MB 0-1, may be associated with LV remodeling in patients with STEMI[4] treated successfully with primary PCI.

Background: The incidence of stroke varies among ethnically and culturally diverse groups.

Objectives: To examine the ethnic-geographic patterns of stroke incidence in men and women with coronary heart disease in Israel, focusing on the extent to which this variability can be explained by known differences in risk factors for stroke.

Methods: Patients with documented coronary heart disease were followed for 6–8 years for incident cerebrovascular events. Baseline medical evaluation included assessment of vascular risk factors and measures of blood lipids. Among 15,052 patients, a total of 1110 were identified with any incident ischemic cerebrovascular event by ICD-9 codes, of whom 613 had confirmed ischemic stroke or transient ischemic attack.

Results: A major excess of ischemic cerebrovascular events among Israeli Arab women as compared to males, and an inverse finding among Israeli born Jews, were noted. The high risk in the Arab population in Israel reflected an unfavorable risk profile, since predicted rates by multivariate analysis and observed rates were 69 and 68 per 1000, respectively. High ischemic cerebrovascular event rates were identified among patients born in the Balkan countries and North Africa (89 and 90 per 1000) but unfavorable risk factor levels of these individuals did not explain them. Most trends appeared similar in male and female patients. A comparison of observed and accepted-according-to-risk-profile rates of ischemic cerebrovascular events yielded significant differences (P = 0.04), consistent with an additional role of geographic/ethnic origin, resulting from factors that remain unrecognized,or with variables unassessed in this study.

Conclusions: We identified an ethnic diversity in stroke risk among Israeli born in different parts of the world beyond what could be expected on the basis of differences in known risk factors. These findings call for detailed research aimed at identifying additional differences in the risk profile of patients with atherothrombotic disease exposed to an increased risk of stroke.