Israel Medical Association Journal

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.
 

Background: High sensitivity C-reactive protein, a marker of inflammation, has been proposed to stratify coronary artery disease risk and is lowered by HMG-CoA reductase (statin) therapy. However, the reproducibility of persistently elevated hs-CRP[1] levels and association with other markers of inflammation in patients with stable CAD[2] on aggressive statin therapy is unknown.

Objectives: To determine the reproducibility of hs-CRP levels measured within 2 weeks in patients with documented CAD with stable symptoms and to identify associations with other markers of inflammation.

Methods: Levels of hs-CRP were measured twice within 14 days (7 ± 4) in 23 patients (22 males and 1 female, average age 66 ± 10 years) with stable CAD and hs-CRP ≥ 2.0 mg/L but ≤ 10 mg/L at visit 1. All patients had received statins for cholesterol management (low density lipoprotein-cholesterol 84 ± 25 mg/dl) with no dose change for > 3 months. None had a history or evidence of malignancy, chronic infection or inflammation, or recent trauma. There was no change in medications between visits 1 and 2, and no patient reported a change in symptoms or general health during this interval. White blood cell count and pro- and anti-inflammatory cytokines were measured at both visits.

Results: hs-CRP levels tended to be lower at visit 2 (median 2.4 mg/L, range 0.8–11 mg/L) than at visit 1 (median 3.3 mg/L, range 2.0–9.7 mg/L; P = 0.1793). However, between the two visits hs-CRP levels decreased by more than 1.0 mg/L in 10 patients and increased by more than 1.0 mg/L in 4 patients. Changes in hs-CRP levels were unrelated to changes in levels of white blood cells (P = 0.4353). Of the cytokines tested, only the anti-inflammatory cytokine interleukin-1 receptor antagonist and the pro-inflammatory cytokine interleukin-8 were above lower limits of detection, but there were no correlations between changes in these values and changes in hs-CRP (both P > 0.5).

Conclusions: In stable CAD patients on aggressive statin therapy, hs-CRP levels may fluctuate over brief periods in the absence of changes in health, cardiac symptom status and medications, and without corroboration with other measures of inflammation. Accordingly, elevated hs-CRP levels should be interpreted with caution in this setting.

Background: Stent thrombosis is a rare but devastating complication of coronary stent implantation. The incidence and potential predictors were assessed in a "real world” single center.

 Objectives: To examine whether socioeconomic status indeed affects the occurrence of stent thrombosis.

Methods: We searched our database for cases of "definite" stent thrombosis (according to the ARC Dublin definitions). Each case was matched by procedure date, age and gender; three cases of stenting did not result in stent thrombosis. Demographic and clinical parameters were compared and socioeconomic status was determined according to a standardized polling and market survey database.

Results: A total of 3401 patients underwent stent implantation in our hospital during the period 2004–2006. Their mean age was 63 ± 11 years, and 80% were males. Twenty-nine cases (0.85%) of “definite” sub-acute/late stent thrombosis were recorded. Mortality at 30 days was recorded in 1 patient (3.5%). Thrombosis occurred 2 days to 3 years after stent implantation. All patients presented with acute myocardial infarction. Premature clopidogrel discontinuation was reported in 60%. Patients with stent thrombosis had significantly higher rates of AMI[1] at the time of the initial procedure (76 vs. 32%, P < 0.001) and were cigarette smokers (60 vs. 28%, P < 0.001). Drug-eluting stents were used less in the stent thrombosis group. There was no difference in stent diameter or length between the two groups. Socioeconomic status was significantly lower at the stent thrombosis group, 3.4 ± 2.4 vs. 5.4 ± 2.6 (mean ± SD, scale 1–10, P < 0.01).

Conclusions: The incidence rate of stent thrombosis is at least 0.85% in our population. It appears in patients with significantly lower socioeconomic status and with certain clinical predictors. These results warrant stricter follow-up and support the policy of healthcare providers regarding patients at risk for stent thrombosis.

Background: Although the comprehensive evaluation of the fetal heart includes echocardiography by an experienced pediatric cardiologist, economic constraints sometimes dictate the need to select patients.

Objectives: To analyze the usefulness of fetal echocardiography in the detection of congenital heart disease according to the referral indication.

Methods: This retrospective survey relates to all 3965 FE studies performed in our center from January 2000 to December 2004. The diagnosed cardiac anomalies were classified as significant and non-significant malformations. All FE[1] studies were done by a single operator (A.L.) at Meir Medical Center, a referral center for a population of about 400,000. The 3965 FE studies were performed for the following indications: abnormal obstetric ultrasound scans, maternal and family history of cardiac malformations, medication use during the pregnancy, and maternal request. The relative risk of detecting CHD[2] was calculated according to the various referral indications.

Results: Overall, 228 (5.8%) cases of CHD were found. The most common indication for referral was suspicion of CHD during a four-chamber view scan in a basic system survey or during a level II ultrasound survey. No correlation was found between maternal age and gestational age at the time of scanning and the likelihood of finding CHD.

Conclusions: Our data suggest that a suspicious level-II ultrasound or the presence of polyhydramnios is an important indication for FE in the detection of significant CHD.

Background: Chronic heart failure is associated with excessive hospitalizations and poor prognosis.

Objectives: To summarize the 5 year experience of a single-center CHF[1] day care service, detect the cardiovascular and non-cardiovascular events, and evaluate the safety of the treatments provided.

Methods: We retrospectively studied all patients admitted to the CHF day care service of the Sheba Medical Center between September 2000 and September 2005.

Results: Advanced (New York Heart Association class III-IV) CHF patients (n=190), mean age 65 ± 12 years and left ventricular ejection fraction 25 ± 11%, were treated for 6 hourly biweekly visits; 77% had ischemic and 23% had non-ischemic cardiomyopathy. Treatment included: intravenous diuretic combinations (91%), intermittent low dose (≤ 5 mg/kg/min) dobutamine (87%), low dose (≤ 3 mg/kg/min) dopamine (38%), intravenous iron preparation and/or blood (47%), and intravenous nitropruside (36%). Follow-up of at least 1 year from initiation of therapy was completed in 158 of 190 patients (83%). Forty-six (29.3%) died: 23% due to CHF exacerbation, 5.7% from infection, 4.4% from sudden cardiac death, 3.8% from malignancy, 2.5% from malignant arrhythmias, 1.9% from renal failure, 1.3% from stroke, and 0.6% from myocardial infarction. There were only 0.68 rehospitalizations/patient/year; the most frequent cause being CHF exacerbation (16.5%).

Conclusions: Our study demonstrates the safety and potential benefits of a supportive day care service for advanced CHF patients. Multidrug intravenous treatment, accompanied by monitoring of electrolytes, hemoglobin and cardiac rhythm, along with education and psychological support, appear to reduce morbidity in advanced CHF patients and may have contributed to the lower than expected mortality/hospitalization rate.

Background: Unicompartmental knee replacement has become a surgical alternative for treating isolated medial or lateral osteoarthritis of the knee or avascular necrosis of the femoral condyls.

Objectives: To evaluate the short-term results of the Oxford Phase 3^® unicompartmental knee replacement for unicompartmental knee arthrosis or avascular necrosis of the medial

femoral condyle.

Methods: During the period 2003–2005 a total of 59 patients (59 knees) underwent medial Oxford Phase 3^® unicompartmental knee replacement in our unit. The patients were interviewed and examined, and standing anteroposterior and lateral X-rays were taken. All patients completed the Western Ontario and McMaster Universities Index of Osteoarthritis and the Short Form 12 questionnaire, and the International Knee Society score was evaluated. The data were collected and statistical analysis was performed.

Results: X-rays were performed and scores for the WOMAC[1] and IKS[2] were assessed for 42 patients (31 females, 11 males). At an average of 32 months after surgery, the total WOMAC score was 30. The mean SF[3]12 physical score was 38 and the mean SF12 mental score was 51. The mean IKS score was 166. Ninety-one percent of the patients had active flexion of 120 degrees or more. Of 59 knees 7 were converted to total knee arthroplasty – all of them within the first 2 years of starting the procedure and all of them in relatively young patients.

Conclusions: Despite the higher revision rate to TKR[4] in this study, our findings confirm the short-term results reported in other studies of the Oxford medial unicompartmental knee and our early failure rate could be explained by a performance learning curve. This study confirms that this bone-preserving procedure should be considered in end-stage isolated unicompartmental osteoarthritis or avascular necrosis by surgeons who have the adequate training and experience.

Background: Stem cell-based therapy is a promising approach for the treatment of neurodegenerative disease. In our laboratory, a novel protocol has been developed to induce bone marrow-derived mesenchymal stem cells into neurotrophic factor-secreting cells. These cells produce and secrete factors such as BDNF (brain-derived neurotrophic factor) and GDNF (glial-derived neurotrophic factor).

Objectives: To evaluate the migratory capacity and efficacy of NTF-SC[1] in animal models of Parkinson's disease and Huntington's disease.

Methods: MSCs[2] underwent two-phase medium-based induction. An efficacy study was conducted on the 6-hydroxydopamine-induced lesion, a rat model for Parkinson's disease. Cells were transplanted on the day of 6-OHDA[3] administration, and amphetamine-induced rotations were measured as a primary behavioral index. In a second experiment, migratory behavior was examined by transplanting cells a distance from a quinolinic acid-induced striatal lesion, a rat model for Huntington's disease. Migration, in vivo, was monitored using longitudinal magnetic resonance imaging scans followed by histology.

Results: NTF-SCs attenuated amphetamine-induced rotations by 45%. HPLC analysis demonstrated a marked decrease in dopamine depletion, post-cellular treatment. Moreover, histological assessments revealed that the engrafted cells migrated and acted to regenerate the damaged striatal dopaminergic nerve terminal network. In a preliminary work on an animal model for Huntington's disease, we demonstrated by high resolution MR images and correlating histology that induced cells migrated along the internal capsule towards the QA[4]-induced lesion.

Conclusions: The induced MSCs are a potential therapy for neurodegenerative diseases, due both to their NTF secretion and their ability to migrate towards the diseased tissue.

The histopathology of severe persistent asthma and chronic obstructive pulmonary disease is predominantly characterized by neutrophilic inflammation. It is posited that chronic hypoxia from hypoventilation in combination with hypoperfusion and hypercapnia are associated with induction of pulmonary tissue acidosis in SPA[1] and COPD[2], which in turn provide ideal conditions to induce danger-associated molecular patterns, i.e., crystallized and calcium pyrophosphate. These stimuli in combination with other danger-related biochemical signals are capable of stimulating an innate immune receptor (cryopyrin inflammasome, NALP3) and cause interleukin-1β secretion with subsequent neutrophilic inflammation. There is evidence to suggest that the mechanisms and pathobiology associated with chronic hypoxia, reduced perfusion and reoxygenation in SPA/COPD may exhibit similarities to the biphasic pathobiology involved in ischemia-reperfusion injury. A rationale is suggested for trials of IL-1β[3] targeted therapies as an adjunct strategy to control neutrophilic inflammation in these conditions.