Israel Medical Association Journal

Background: Multiple sclerosis (MS) is a common demyelinating disorder of the central nervous system (CNS) and although it is a well-established autoimmune disease its ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity.

Objectives: To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease.

Methods: Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls.

Results: Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P ≤ 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05)

Conclusions: Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.
 

Background: ST-elevation myocardial infarction is caused by occlusive coronary thrombosis where antecedent plaque disruption occurs. When treating STEMI[1] the main goal is to achieve prompt reperfusion of the infarction area. Several studies have demonstrated the efficacy of an aspiration device before percutaneous coronary intervention in patients with acute myocardial infarction.

Objectives: To determine the added value of thrombus aspiration prior to primary PCI[2] by comparing AMI[3] patients with totally occluded infarct-related artery treated with routine primary PCI to those treated with extraction device prior to primary PCI.

Methods: The study group comprised 122 consecutive patients with AMI and a totally occluded infarct artery (TIMI flow 0) who underwent primary PCI. The patients were divided into two groups: 68 who underwent primary PCI only (control group) and 54 who underwent primary thrombus extraction with an extraction device before PCI (extraction group). Baseline clinical and lesion characteristics were similar in both groups. Final TIMI grade flow and myocardial blush as well as 1 year mortality, target lesion revascularization, recurrent myocardial infarction, unstable angina and stroke were compared between the two groups.

Results: Primary angiographic results were better for the extraction group versus the control group: final grade 3 TIMI flow was 100% vs. 95.6% (P = 0.03) and final grade 3 myocardial blush grade 50% vs. 41.18% (although P was not significant). Long-term follow-up total MACE[4] showed a non-significant positive trend in the extraction group (12.96% vs. 24.71%, P = 0.26).

Conclusions: The use of extraction devices for intracoronary thrombectomy during primary PCI in patients with totally occluded infarct artery significantly improved epicardial reperfusion in the infarct-related vessel and showed a trend for more favorable long-term outcome.

Background: Infiltrating ductal carcinoma and infiltrating lobular carcinoma account for more than 90% of all invasive breast cancer histological types. The rate of ILC[1] is reported to be increasing steadily in the United States and Europe.

Objectives: To describe the trend in the incidence of ILC in a large cohort of patients who underwent surgery in a single institution over an 18 year period.

Methods: Our comprehensive database of 2175 consecutive patients with invasive breast cancer diagnosed during the period 1992–2009 served for the analysis. Several potential factors associated with lobular carcinoma as compared with ductal carcinoma were evaluated.

Results: During this period, a 2.4-fold increase in the incidence of pure ILC was noted, from 4.6% in the years 1992–1994 to 10.9% in 2004–2006, followed by a modest decrease to 8.7% in 2007–2009. A significant association of lobular malignancies with external hormonal use was noted, including hormone replacement therapy exposure in patients diagnosed at age 50–64, and ovarian overstimulation during in vitro fertilization in those diagnosed at age 50 or less.  

Conclusions: Better diagnostic tools – such as the liberal use of ultrasound and magnetic resonance imaging – and more accurate pathological definition for ILC type appear to influence the changes in the incidence of ILC in the subgroups of invasive breast cancer.

Background: In compliance with public health measures initiated by the Israel Ministry of Health following an outbreak of influenza, amantadine was administered to all patients in the psychogeriatric department of Lev Hasharon Mental Health Center to reduce transmission and illness severity in this susceptible population.

Objectives: To evaluate the potential beneficial effects of amantadine on elderly hospitalized patients with persistent schizophrenia.

Methods: We conducted a retrospective case review of the treatment effects of amantadine on the mental, cognitive and clinical states of elderly chronic schizophrenic patients who received concomitant amantadine treatment and were routinely evaluated with the Positive and Negative Syndrome Scale, the Mini Mental State Examination, and Sandoz Clinical Assessment Geriatric Scale.

Results: No significant differences before and after amantadine treatment were noted. Conclusion: Amantadine did not influence the mental, cognitive and clinical states of elderly schizophrenia patients and thus can be considered as an anti-influenza preventive measure for this population, when indicated.

survey. A tailor-made CME program may have contributed to the improvement in skills and quality of care.

Background: The prevalence of aortic stenosis increases with advancing age. Once symptoms occur the prognosis in patients with severe aortic stenosis is poor. The current and recommended treatment of choice for these patients is surgical aortic valve replacement. However, many patients, mainly the very elderly and those with major comorbidities, are considered to be at high surgical risk and are therefore denied treatment. Recently, a transcatheter alternative to surgical AVR[1] has emerged.

Objectives: To describe the first year experience and 30 day outcome of transcatheter aortic self-expandable CoreValve implantation in Israel.

Methods: Transcatheter aortic valve implantation using the CoreValve system has been performed in Israel since September 2008. In the following year 55 patients underwent CoreValve TAVI[2] in four Israeli centers.

Results: Patients' mean age was 81.7 ± 7.1 years; there were 35 females and 20 males. The mean valve area by echocardiogram was 0.63 ± 0.16 cm². The calculated mean logistic Euroscore was 19.3 ± 8%. Following TAVI, mean transvalvular gradient decreased from baseline levels of 51 ± 13 to 9 ± 3 mmHg. The rate of procedural success was 98%. One patient died on the first day post-procedure (1.8%) and all-cause 30 day mortality was 5.5% (3 of 55 patients). One patient had a significant post-procedural aortic regurgitation of > grade 2. Symptomatic improvement was evident in most patients, with reduction in functional capacity grade from 3.2 ± 0.6 at baseline to 1.4 ± 0.7. The most common post-procedural complication was complete heart block, which necessitated permanent pacemaker implantation in 37% of patients.

Conclusions: The Israeli first year experience of transcatheter aortic valve implantation using the CoreValve self-expandable system demonstrates an effective and safe procedure for the treatment of severe aortic stenosis in patients at high surgical risk.

Background: Continuous use of combined oral contraceptives is currently attracting growing interest as a means of improving menstrual related symptoms and reducing the number of bleeding days.

Objectives: To evaluate bleeding patterns, menstrual symptoms and quality of life with an extended 84/7 oral contraceptive regimen versus 21/7 cycles.

Methods: In two consecutive run-in cycles, 30 µg ethinyl estradiol and 3 mg drospirenone tablets taken on days 1–21 were followed by a tablet-free period from days 22 to 28 of each cycle and then by two 84 day cycles of pill use with a 7 day tablet-free interval. The primary outcome was the total number of bleeding/spotting days. Secondary outcomes were severity of daily symptoms, general well-being determined by the PGWBI questionnaire, and overall treatment satisfaction.

Results: Of the 137 women invited to participate in the study 109 (aged 18–40 years) were enrolled. The number of bleeding days decreased by about one-third from a calculated 31.8 days of bleeding under a cyclic 21/7 regimen to an expected total of 21.8 days for the extended 84/7 regimen. The incidence of menorrhagia, intermenstrual bleeding, dysmenorrhea, abdominal bloating, breast tenderness, depressive moods and irritability – when compared at enrollment and at the end of the second extended study period – was significantly lower (P < 0.005) among women on the continuous pill regimen. The median (range) global PGWBI scores were not substantially different before and after the extended use cycles: 78.2 (39.1–96.4) and 77.3 (30.9–96.4), respectively. Body weight and skin condition also remained constant. At the completion of the study: 65.5% of the women were either highly satisfied (41.4%) or satisfied (24.1%) with the extended regimen.

Conclusions: The extended 84/7 regimen was found to be satisfactory for the majority of participants and was associated with a decrease in the number of bleeding days and an improvement in menstrual symptoms compared to 21/7 cycles. 

[1] MHC = mother and child health

Background: Most data on the incidence of rheumatic fever come from hospital records. We presumed that there may be cases of RF[1] that do not require hospitalization, especially in countries with high quality community health care. 

Objectives: To explore the incidence and characteristics of RF using community-based data. 

Methods: A retrospective descriptive study was conducted among the members (more than 450,000) of the Clalit Health Services, Central district, during 2000–2005. The electronic medical files of members up to 40 years old with a diagnosis of RF in hospital discharge letters or during community clinic visits were retrieved. Patients with a first episode of RF according to the modified Jones criteria were included.

Results: There were 44 patients with a first episode of RF. All patients were under the age of 29. The annual incidence among patients aged 0–30 years was 3.2:100,000; the highest incidence was among children aged 5–14 years (7.5:100,000), and in males the incidence was 2.26 times higher than in females. The incidence was higher among patients from large families, of non-Jewish ethnicity, and from rural areas. Twenty-five percent of the patients were both diagnosed and treated in an ambulatory care setting.

Conclusions: Although the incidence of RF in the western world and in Israel is low, the disease still occurs and mainly affects children. Any future estimates of disease incidence should take into account that RF is becoming an ambulatorily treated disease.  

Background: Research on synergistic effects of patient-targeted interventions combined with physician-targeted interventions has been limited.

Objectives: To compare a combined physician-patient intervention to physician feedback alone on a composite outcome of glycemic, lipid and blood pressure control.

Methods: In this cluster study 417 patients with adult-type 2 diabetes from four primary care clinics were randomized to receive either a physician-only intervention or a combined physician-plus-patient intervention. Physicians in all clinics received diabetes-related quality performance feedback during staff meetings. Patients at combined-intervention clinics also received a letter encouraging them to remind their doctors to address essential aspects of diabetes care at the next visit. At 1 year follow-up, outcome measurements included hemoglobin A1c, low density lipoprotein-cholesterol and systolic blood pressure; the proportion of patients with HbA1c[1] < 9%, LDL[2] < 130 mg/dl and SBP[3] < 140 mmHg both as separate outcomes and combined.

Results: After adjusting for patient characteristics and baseline measures, follow-up levels of HbA1c (7.5% vs. 7.8%, P = 0.09), LDL (104.7 vs. 110.7 mg/dl, P < 0.05) and SBP (135.6 vs. 139.9, P = 0.10) were marginally better for combined-intervention patients compared to physician-only intervention patients. Significantly more patients in the combined-intervention (38.8%) than physician-only intervention (24.2%) met all three targets (HbA1c < 9%, LDL < 130 mg/dl and SBP < 140 mmHg) as a single combined outcome (adjusted odds ratio 2.4, P < .01).

Conclusions: Compared to physician-feedback alone, a dual intervention combining a patient letter with physician feedback produced modest improvements in glycemic, lipid and blood pressure control individually, but substantial improvement in a combined measure of these three outcomes together. Using composite outcomes may detect meaningful improvements in the management of complex chronic disease. 

Background: Patients with thick melanomas > 4 mm deep are at great risk for regional and distant metastatic disease. Historically, the appropriate management of thick melanomas has remained unclear and there is no consensus in the literature. Many have taken the nihilistic view that surgical intervention to excise regional nodal basins is not justified in light of the poor overall prognosis and risk of occult distant disease.

Objectives: To review the outcome of patients with thick node negative melanoma treated at a multidisciplinary academic center

Methods: We retrospectively reviewed a database of melanoma patients to identify patients with thick melanomas, > 4 mm, who were either clinically or sentinel node biopsy negative, staged T4N0, stage IIb or IIc. The charts of these patients were reviewed and updated, with a median follow-up of 4 years.

Results: We identified 23 patients who fit these criteria. Of these, 18 (78%) remain alive with a median follow-up of 4 years. Five patients died of metastatic disease. Of the 18 surviving patients, 14 remained with no evidence of disease after initial resection of their primary lesions. The majority of the recurrences were non-nodal.
Conclusions: The overall survival of patients in our study remains above 75%, at median follow-up of 4 years, even with thick initial index tumor depths. Most of the failures were due to hematogenous spread with lymphatic sparing. Tumor biology that may inhibit lymphatic spread could be a target of future investigation

Background: Critical limb ischemia is an increasingly common condition that has high surgical morbidity and limited non-surgical options.  

Objectives: To evaluate the use of silicon carbide-coated Motion stents, as compared to reported data for bare metal stents, in elderly patients with infrapopliteal artery stenoses causing critical limb ischemia after failed or complicated percutaneous transluminal angioplasty.

Methods: Between January 2003 and March 2004, 41 stents were inserted into 17 consecutive patients (11 males, 6 females, mean age 82 years, range 75–93) following unsuccessful or complicated PTA[1]. Seven patients had one-vessel run-off, six had two-vessel and four had three vessel run-off. All patients suffered from CLI[2], had up to three lesions and more than one co-morbid condition, and were considered at high surgical risk. Silicon carbide-coated Motion coronary stents, 2.5–4 mm diameter and 25 and 30 mm length, were used. Pre-intervention assessment included clinical condition, ankle brachial index, Doppler ultrasound and digital subtracted angiography. Post-intervention evaluation included clinical condition, ABI[3], and Doppler ultrasound at 3, 6 and 12 months.

Results: The technical success rate per lesion was 100% (41/41). Two patients died of unrelated causes after 2 and 8 months respectively. Primary patency rates with duplex ultrasound were 68.7% (11/16) at 3 months, 43.7% (7/16) at 6 months and 40% (6/15) after 12 months. Nine patients developed complete occlusion in 13 stents; three of these patients underwent a below-knee amputation and two patients a partial foot amputation. Re-intervention (PTA only) was performed in 7 patients (43.7%). Secondary patency rate was 81.2% (13/16) at 6 months and 60% (9/15) at one year. Mean ABI index had improved at 6 months from 0.32 to 0.67, and to 0.53 at one year. Clinical improvement was evident in 87.5% (14/16) at 6 months and in 66.6% (10/15) at one year.

Conclusions: Silicon carbide-coated stents are comparable to bare metal stents after 6 and 12 months in infrapopliteal interventions in CLI when stenting is indicated.