Israel Medical Association Journal

Background: Treatment guidelines for well-differentiated papillary thyroid carcinoma (PTC) are based on retrospective studies and vary among different professional thyroid associations.

Objectives: To evaluate physician adherence to guidelines, overall and by specialty.

Methods: Questionnaires on the approach to low risk PTC were distributed among 51 surgeons and endocrinologists treating patients with PTC in tertiary medical centers.

Results: A wide range of answers was recorded among physicians regarding the danger posed by low risk PTC to the patient’s life, urgency with which treatment should be administered, type of treatment, and risks associated with this treatment. There was a significant between-group difference in treatment preference: endocrinologists chose total thyroidectomy with radioactive iodine, while surgeons favored hemithyroidectomy alone.

Conclusions: There is a wide difference in treatment recommendations between treating physicians and different specialties with regard to low risk PTC. The wide variation within and between specialties may be explained by biases. 

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of the innate and adaptive immune systems with the production of autoantibodies by stimulated B lymphocytes. The BLyS protein (B lymphocyte stimulator) is secreted mainly by monocytes and activated T cells and is responsible for the proliferation, maturation and survival of B cells.

Objectivs: To study sera BLyS level and its clinical significance in Israeli lupus patients over time.

Methods: The study population included 41 lupus patients (8 males, 33 females; mean age 35.56 ± 15.35 years) and 50 healthy controls. The patients were followed for 5.02 ± 1.95 years. We tested 221 lupus sera (mean 5.4 samples/patient) and 50 normal sera for BLyS levels by a capture ELISA. Disease activity was determined by the SLEDAI score.

Results: Sera BLyS levels were significantly higher in SLE patients than in controls (3.37 ± 3.73 vs. 0.32 ± 0.96 ng/ml, P < 0.05). BLyS levels were high in at least one sera sample in 80.5% of the patients but were normal in all sera in the control group. There was no correlation between sera BLyS and anti-ds-DNA autoantibody levels. BLyS levels fluctuated over time in sera of lupus patients with no significant correlation to disease activity.

Conclusions: Most of our lupus patients had high sera BLyS levels, suggesting a role for BLyS in the pathogenesis and course of SLE. Our results support the current novel approach of targeting BLyS (neutralization by antibodies or soluble receptors) in the treatment of active lupus patients.

Objectives: To examine the effect of meloxicam, a selective COX-2 inhibitor, or low dose aspirin on the development of experimental atherosclerosis in apoE knockout (KO) compared to wild-type (WT) mice. We aimed to test the hypothesis that meloxicam, a potential vasculitis inducer, would exacerbate atherosclerotic lesions while aspirin, which is known to reduce the incidence of thrombosis occlusive events, would increase protection in this model.

Methods: We randomly divided 36 male apoE KO and 36 WT mice, 8 weeks old. Mice were treated for 10 weeks with 0.1 mg/ml aspirin, or 0.05 mg/ml meloxicam, dissolved in their drinking water. Control groups received regular drinking water. At sacrifice, the hearts were removed for histochemical staining and plaque size and composition were examined.

Results: Aspirin-treated animals displayed a decreased atherosclerotic lesion area compared to the untreated control mice, while meloxicam had a null effect on the extent of atherosclerosis in Apo E KO mice.

Conclusions: These results suggest that low dose aspirin reduces early atherosclerosis, while inhibition of COX-2 by meloxicam is not associated with an increase in atherosclerotic plaque size in this mouse model.

Objectives: To present our initial experience with MitraClip implantation in 20 high risk patients at Sheba Medical Center.

Methods: Twenty high surgical risk patients with symptomatic significant MR underwent MitraClip implantation. Clinical and echocardiographic parameters were recorded at baseline and at follow-up.

Results: The patients’ mean age was 76 years and 65% were male. Coronary artery disease was present in 85% and 45% had previous bypass surgery. Renal failure was present in 65%, atrial fibrillation in 60%, and 30% had an implantable cardioverter defibrillator/cardiac resynchronization therapy device. Mean left ventricular ejection fraction was 36%. Grade III-IV MR was present in all patients with the vast majority suffering from functional MR secondary to ventricular remodeling. New York Heart Association (NYHA) class was III-IV in 90%. Patients were followed for a mean of 231 days. Acute reduction of MR grade to ≤ 2 was accomplished in 19 of the 20 patients (95%) with a 30 day mortality of 5%. At follow-up MR was reduced to ≤ 2 in 64% of patients, and NYHA class improved in 70% of patients. An additional 2 patients (11%) died during follow-up.

Conclusions: MitraClip implantation is feasible and safe in high risk highly symptomatic patients with significant MR. Acute and mid-term results are comparable to similar high risk patient cohorts in the literature. Continued surveillance and longer follow-up are needed to elucidate which patients are most likely to benefit from the procedure.

Methods: In this retrospective multicenter open-label study we examined the efficacy and tolerability of VNS in patients in five adult and pediatric epilepsy centers in Israel. All patients had drug-resistant epilepsy and after VNS implantation in 2006–2007 were followed for a minimum of 18 months. Patients were divided into two age groups: < 21 and > 21 years old.

Results: Fifty-six adults and children had a stimulator implanted in 2006–2007. At 18 months post-VNS implantation, none of the patients was seizure-free, 24.3% reported a reduction in seizures of ≥ 75%, 19% reported a 50–75% reduction, and 10.8% a 25–50% reduction. The best response rate occurred in patients with complex partial seizures. Among these patients, 7 reported a ≥ 75% reduction, 5 patients a 50–75% reduction, 3 patients a 25–50% reduction, and 8 patients a < 25% reduction. A comparison of the two age groups showed a higher reduction in seizure rate in the older group (< 21 years old) than the younger group.

Conclusions: VNS is a relatively effective and safe palliative method for treating refractory epilepsy in both adults and children. It is an alternative treatment for patients with drug-resistant epilepsy, even after a relatively longed disease duration, who are not candidates for localized epilepsy surgery.

Background: Trans-catheter aortic valve implantation (TAVI) has emerged as a novel therapeutic approach for patients with severe tricuspid aortic stenosis (AS) not suitable for aortic valve replacement.

Objectives: To describe our initial single-center experience with TAVI in patients with "off-label" indications.

Methods: Between August 2008 and December 2011 we performed TAVI in 186 patients using trans-femoral, trans-axillary, trans-apical and trans-aortic approaches. In 11 patients (5.9%) TAVI was undertaken due to: a) pure severe aortic regurgitation (AR) (n=2), b) prosthetic aortic valve (AV) failure (n=5), c) bicuspid AV stenosis (n=2), and d) prosthetic valve severe mitral regurgitation (MR) (n=2).

Results: Implantation was successful in all: six patients received a CoreValve and five patients an Edwards-Sapien valve. In-hospital mortality was 0%. Valve hemodynamics and function were excellent in all patients except for one who received an Edwards-Sapien that was inside a Mitroflow prosthetic AV and led to consistently high trans-aortic gradients. No significant residual regurgitation in AR and MR cases was observed.
Conclusions: TAVI is a good alternative to surgical AV replacement in high risk or inoperable patients with severe AS. TAVI for non-classical indications such as pure AR, bicuspid AV, and failed prosthetic aortic and mitral valves is feasible and safe and may be considered in selected patients. 

Objectives: To review our use of ECMO over a 10 year period.

Methods: All children supported with ECMO from 2000 to 2010 were reviewed. Most of these children suffered from cardiac anomalies. The patients were analyzed by age, weight, procedure, RACHS-1 when appropriate, length of support, and outcome.

Results: Sixty-two children were supported with ECMO; their median age was 3 months (range 0–216 months) and median weight 4.3 kg (range 1.9–51 kg). Thirty-four patients (52.3%) needed additional hemofiltration or dialysis due to renal failure. The children requiring ECMO support represented a wide spectrum of cardiac lesions; the most common procedure was arterial switch operation 27.4% (n=17). ECMO was required mainly for failure to separate from the heart-lung machine (n=55). The median duration of ECMO support was 4 days (range 1–14 days); 29 (46.7%) patients were weaned successfully from ECMO during this time period, and 5 of them died during hospitalization, yielding an overall hospital survival rate of 38.7%.

Conclusions: ECMO support has significant survival benefit for patients with post-cardiotomy heart failure. Its early deployment should be considered in cardiopulmonary resuscitation.

Background: Multidrug-resistant tuberculosis (MDR-TB) presents a difficult therapeutic problem due to the failure of medical treatment. Pulmonary resection is an important adjunctive therapy for selected patients with MDR-TB.

Objectives: To assess the efficacy of pulmonary resection in the management of MDR-TB patients.

Methods: We retrospectively reviewed the charts of MDR-TB patients referred for major pulmonary resections to the departments of thoracic surgery at Assaf Harofeh and Wolfson Medical Centers. For the period under study, 13 years (from 1998 to 2011), we analyzed patients’ medical history, bacteriological, medical and surgical data, morbidity, mortality, and short-term and long-term outcome.

Results: We identified 19 pulmonary resections (8 pneumonectomies, 4 lobectomies, 1 segmentectomy, 6 wedge resections) from among 17 patients, mostly men, with a mean age of 32.9 years (range 18–61 years). Postoperative complications developed in six patients (35.3%) (broncho-pleural fistula in one, empyema in two, prolonged air leak in two, and acute renal failure in one). Only one patient (5.8%) died during the early postoperative period, three (17.6%) in the late postoperative period, and one within 2 years after the resection. Of 12 survivors, 9 were cured, 2 are still under medical treatment, and 1 is lost from follow-up because of poor compliance.

Conclusions: Pulmonary resection for MDR-TB patients is an effective adjunctive treatment with acceptable morbidity and mortality.
 

Background: Determining the prognosis of patients with heart failure is essential for patient management and clinical trial conduct. The relative value of traditional prognostic criteria remains unclear and the assessment of long-term prognosis for individual patients is problematic.

Objectives: To determine the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of patients with idiopathic dilated cardiomyopathy.

Methods: We investigated the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of individual patients in a large, representative, contemporary cohort of idiopathic dilated cardiomyopathy (IDCM) patients referred to Johns Hopkins from 1997 to 2004 for evaluation of cardiomyopathy. In all patients a baseline history was taken, and physical examination, laboratory studies, echocardiogram, right heart catheterization and endomyocardial biopsy were performed.

Results: In 171 IDCM patients followed for a median 3.5 years, there were 50 long-term event-free survivors (LTS) (median survival 6.4 years) and 34 patients died or underwent ventricular assist device placement or transplantation within 5 years (NLTS; non-long-term survivors) (median time to event 1.83 years. Established risk factors (gender, race, presence of diabetes, serum creatinine, sodium) and the use of accepted heart failure medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers) were similar between the two groups. Although LTS had younger age, higher ejection fraction (EF) and lower New York Heart Association (NYHA) class at presentation, the positive predictive value of an EF< 25% was 64% (95% CI 41%–79%) and of NYHA class > 2 was 53% (95% CI 36–69%). A logistic model incorporating these three variables incorrectly classified 29% of patients.

Conclusions: IDCM exhibits a highly variable natural history and standard clinical predictors have limited ability to classify IDCM patients into broad prognostic categories. These findings suggest that there are important host-environmental factors still unappreciated in the biology of IDCM.
 

Background: There is a striking increase in the number of people with metabolic syndrome (MetS) as a result of the global epidemic of obesity and diabetes. Increasing evidence suggests that uric acid may play a role in MetS.

Objectives: To assess the prevalence of MetS in a large cohort from Israel and its association with hyperuricemia using the latest three definitions of MetS.

Methods: We conducted a retrospective analysis of the database from a screening center in Israel, using the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF) and the Harmonizing definitions of MetS, to assess 12,036 subjects with an age range of 20–80 years.

Results: The mean age of the study sample was 46.1 ± 10.2 years and 69.8% were male. The prevalence of MetS was 10.6%, 18.2% and 20.2% in the revised NCEP ATP III, the IDF and the Harmonizing definitions respectively. The prevalence of hyperuricemia in subjects with MetS, for all three MetS definitions, was similar: 20.0%, 19.9% and 19.1% respectively. There was a graded increase in the prevalence of MetS among subjects with increasing levels of uric acid. The increasing trend persisted after stratifying for age and gender and after multivariate analysis (P for trend < 0.001).

Conclusions: This large cohort shows a high prevalence of MetS in Israel, but is still lower than the prevalence in western countries. Hyperuricemia is common in those subjects and might be considered a potential clinical parameter in the definition of MetS.