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: The prevalence of ADHD is controversial, with many feeling that this disorder is over- or under-diagnosed.

Objectives: To study the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its association with socio-demographic characteristics, comorbid mental disorders, medical services, and methylphenidate use in the Israeli adolescent population.

Methods: The Israel Survey of Mental Health among Adolescents was conducted in a representative national sample of 14–17 year olds and their mothers. The Development and Well-Being Assessment was administered to identify DSM-IV diagnoses of ADHD and comorbid mental and learning disorders, and the results were verified by senior child psychiatrists. Respondents were also asked about their use of medical services and psychotropic drug intake in the past 12 months.

Results: Three percent of the adolescents met the DSM-IV criteria for ADHD. ADHD was significantly associated with gender (higher prevalence in boys than girls), ethnicity (higher prevalence in Jews than Arabs/Druze), referral to a medical professional, and maternal help-seeking for the emotional or behavioral problems of the adolescent. Medication was prescribed to 2.9% of adolescents: 34.6% with a diagnosis of ADHD had not been prescribed methylphenidate in the past year, and 34.6% of the medicated subjects did not have a diagnosis of ADHD. None of the Arab/Druze adolescents was receiving stimulants compared to 3.7% of the Jewish adolescents.

Conclusions: Despite advances in public awareness of mental disorders in youth, a substantial proportion of older Israeli adolescents, especially from minority groups, are under-diagnosed or untreated. At the same time, many, especially from the Jewish majority, are over-diagnosed and potentially over-treated. Ethnic disparities in rates of mental health care highlight the urgent need to identify and overcome barriers to the recognition and treatment of these conditions.

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 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.