Israel Medical Association Journal

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 assess whether a new herbal-based potentially wake-promoting beverage is effective in counteracting somnolence and reduced post-lunch performance.

Methods: Thirty healthy volunteers were studied on three different days at the sleep clinic. On each visit they ate a standard lunch at noontime, followed by a drink of "Wake up®," 50 mg caffeine, or a placebo in a cross-over double-blind regimen. At 30 and 120 minutes post-drinking, they underwent a battery of tests to determine the effects of the beverage. These included: a) a subjective assessment of alertness and performance based on a visual analog scale, and b) objective function tests: the immediate word recall test, the digit symbol substitution test (DSST), and hemodynamic measurements. The results of the three visits were compared using one-way analysis of variance, with P < 0.05 considered statistically significant.

Results: In all performance tests, subjective vigilance and effectiveness assessment, both Wake up® and caffeine were significantly superior to placebo 30 minutes after lunch. However, at 2 hours after lunch, performance had deteriorated in those who drank the caffeine-containing drink, while Wake up® was superior to both caffeine and placebo. Blood pressure and pulse were higher 2 hours after caffeine ingestion, compared to both Wake up® and placebo.

Conclusions: These results suggest that a single dose of Wake up® is effective in counteracting the somnolence and reduced performance during the post-lunch hours. In the current study it had no adverse hemodynamic consequences.

Objectives: To review our experience with laparoscopic repair of GDH, emphasizing preoperative investigation, technical aspects, and outcome.

Methods: We conducted a retrospective review of patients operated on for GDH who were diagnosed when at least half the stomach was found in the mediastinum at surgery. Technical aspects and surgical outcomes were evaluated.

Results: Fifty patients underwent laparoscopic GDH repair during an 8 year period. Four patients admitted with acute symptomatic volvulus of the stomach were initially treated by endoscopic decompression followed by surgery during the same admission. Two cases were converted to open surgery. Initial surgery was successful in 45 patients; 3 had an immediate recurrence, 1 was reoperated for dysphagia during the same admission, and 1 had a mediastinal abscess. During long-term follow-up, six patients required reoperation for recurrent hernias. Another four patients had asymptomatic partial herniation of the stomach. The main reason for failure was incomplete reduction of the hernia sac, especially the posterior component. No correlation was found between the type of repair and surgical failure. Most patients who did not undergo an anti-reflux procedure had postoperative reflux unrelated to their preoperative workup.

Conclusions: Laparoscopic repair of GDH is challenging, but practical and safe. It should be the treatment of choice for this potentially life-threatening condition. Careful attention to pitfalls, such as the posterior element of the sac, and routine performance of an anti-reflux procedure are crucial.

Objectives: To evaluate the feasibility of induction chemotherapy with docetaxel-cisplatin-5-flurouracil (TPF) followed by external beam radiotherapy (EBRT) with concomitant chemotherapy (CRT) or cetuximab (ERT) in the treatment of patients with advanced SCCHN.

Methods: We reviewed the data of all patients with advanced SCCHN, stage III and IV, treated in 2007–2010. Tolerability was assessed and scored according to the proportion of patients completing the planned study protocol. Toxicity was scored using the U.S. National Cancer Institute Common Toxicity Criteria (version 4) for classification of adverse events.

Results: The study included 53 patients. TPF was initiated at a reduced dose in 13 patients (25%). Twenty-two patients (41.5%) received primary prophylaxis with granulocyte colony-stimulating factor (GCSF) and 42 (77%) completed treatment according to schedule. During the induction phase one patient (2%) died and 24 (45%) had one or more grade 3-4 complications. The number of patients who developed neutropenia was lower in the group that received primary GCSF prophylaxis. Secondary dose reductions were required in 21% of the patients.

Conclusions: Induction TPF was associated with grade 3-4 toxicity. Prophylaxis with GCSF should be part of the treatment regimen.

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.