Israel Medical Association Journal

Background: The VEGFR/PDGFR inhibitor sunitinib was approved in Israel in 2008 for the treatment of metastatic renal cell carcinoma (mRCC), based on an international trial. However, the efficacy of sunitinib treatment in Israeli mRCC patients has not been previously reported.

Objectives: To report the outcome and associated factors of sunitinib treatment in a large cohort of Israeli mRCC patients.

Methods: We conducted a retrospective study of an unselected cohort of mRCC patients who were treated with sunitinib during the period 2006–2013 in six Israeli hospitals. Univariate and multivariate analyses were performed to determine the association between treatment outcome and clinicopathologic factors.

Results: We identified 145 patients; the median age was 65 years, 63% were male, 80% had a nephrectomy, and 28% had prior systemic treatment. Seventy-nine percent (n=115) had clinical benefit (complete response 5%, n=7; partial response 33%, n= 48; stable disease 41%, n=60); 21% (n=30) were refractory to treatment. Median progression-free survival (PFS) was 12 months and median overall survival 21 months. Factors associated with clinical benefit were sunitinib-induced hypertension: [odds ratio (OR) 3.6, P = 0.042] and sunitinib dose reduction or treatment interruption (OR 2.4, P = 0.049). Factors associated with PFS were female gender [hazard ratio (HR) 2, P = 0.004], pre-sunitinib treatment neutrophil to lymphocyte ratio ≤ 3 (HR 2.19, P = 0.002), and active smoking (HR 0.19, P < 0.0001). Factors associated with overall survival were active smoking (HR 0.25, P < 0.0001) and sunitinib-induced hypertension (HR 0.48, P = 0.005). To minimize toxicity, the dose was reduced or the treatment interrupted in 39% (n=57). 

Conclusions: The efficacy of sunitinib treatment for mRCC among Israeli patients is similar to that of international data.

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. 

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: High levels of plasma homocysteine constitute a risk for cardiovascular disease. Physical activity, known to reduce CVD[1] risk, has been related to levels of Hcy[2]. Recently, higher Hcy was shown to be associated with lower cardiovascular fitness in women but not in men.

Objectives: To further explore the relationship between cardiorespiratory fitness and plasma total homocysteine levels in a large cohort of adult males and females.

Methods: This cross-sectional study included 2576 fitness and Hcy examinations in adults (62% males) aged 30–59 years, randomly drawn from a population undergoing a periodic health examination in the Sheba Medical Center's Executive Screening Survey. Blood tests were collected for tHcy[3] and a sub-maximal exercise test was performed to estimate cardiorespiratory fitness. Information on CVD/CVD risk factors (coronary heart disease, cerebrovascular accident, diabetes, hypertension or dyslipidemia) was self-reported.

Results: Mean tHcy plasma levels were 14.4 ± 7.7 and 10.2 ± 3.0 µmol/ml, and mean maximal oxygen uptake 36.5 ± 11.7 and 29 2 ± 9.5 ml/kg/min for males and females, respectively. A multiple regression analysis, adjusting for age, body mass index and CVD/CVD risk factors, showed no association between cardiorespiratory fitness and level of tHcy in males (P = 0.09) or in females (P = 0.62).

Conclusions: In this sample no relationship was found between level of cardiorespiratory fitness and plasma tHcy in men or women. The inconsistency of findings and the small number of studies warrant further research of the association between cardiorespiratory fitness and tHcy, an association that may have clinical implications for the modifications of cardiovascular risk factors.

Objectives: To compare the outcomes of two groups of CICF[1] patients who underwent two different treatment protocols.

Methods: The study cohort included 72 infants treated in our hospital from August 1998 to December 2002. Group 1 comprised 40 infants (61 clubfeet) who were treated by a traditional method (a modification of the Kite and Lovell technique), and group 2 consisted of 32 infants (48 clubfeet) who were treated with the Ponseti technique. Both groups were similar in age, gender and severity of the deformity (Dimeglio scoring system)

Results: After an average follow-up of 54.9 months (range 44–68), 35 (57%) clubfeet in group 1 required surgical intervention and 27 (44%) clubfeet had a residual deformity at last follow-up. In the Ponseti group, 45 (94%) clubfeet were fully corrected at last follow-up (average 29.2 months, range 16–45) while 3 (6%) clubfeet had residual deformity and required surgery. Tendo-Achilles tenotomy was performed with no complications in 47 clubfeet (in group 2) at an average age of 2.4 months (range 2–4 months).

Conclusions: Even after a relatively short follow‑up period, our success rate with the Ponseti approach already appears to be significantly higher and to bear fewer complications than the traditional treatment, in agreement with the results published by other medical centers. We now endorse the Ponseti technique of conservative manipulative treatment for congenital idiopathic clubfoot in our department.

Background: Bladder exstrophy is a severe congenital defect that requires a multidisciplinary treatment approach. Soft tissue repair may be successful during the first few days after birth but a combination of pelvic osteotomies and bladder reconstruction is necessary later in life. The combination of externally fixed anterior and posterior osteotomies has biomechanical advantages over previous techniques for achieving primary bladder closure.

Objectives: To describe our experience with a combined vertical and horizontal pelvic osteotomy approach for the repair of bladder exstrophy.

Methods: Four children underwent bladder exstrophy closure; the mean age at surgery was 19 months (range 9–33 months)... We stabilized the osteotomies with a small Synthes AO external fixator, 4.0 mm rod diameter.

Results: All four patients had successful bladder repair with no dehiscence; two of them achieved partial continence, and bladder neck reconstruction is planned for the other two. Three of the four patients sustained neurologic injury; two completely recovered, and the third continues to suffer from right drop foot. The average follow-up was 39 months (range 10–60 months).

Conclusions: Vertical and horizontal pelvic osteotomies stabilized by external fixator and bladder repair is an effective treatment for bladder exstrophy.

Background: The more patients know about their medications the higher their compliance with drug therapy, reflecting an effective communication between health professionals and their patients. Numerous studies on this subject have been published, but none has been conducted in Israel.

Objectives: To evaluate patients’ perceptions of drug counseling by health professionals – the prescribing physician and dispensing pharmacist – and to determine whether there is a difference in the patient’s perception according to his or her place of birth and mother tongue.

Methods: A total of 810 patients were interviewed following receipt of their medications from in-house pharmacies at two community clinics of Israel’s largest sick fund. Each patient was interviewed in his or her mother tongue according to a constructed questionnaire, which included the patient’s demographic background, type of medications received, the patient’s perceptions of drug counseling given by both the physician and the pharmacist, and the patient’s perception of non-prescription drug counseling given by the dispensing pharmacist.

Results: Of the 810 patients enrolled in this study, 32% received three or more medications at each physician visit. The main therapeutic classes of medications prescribed and dispensed were for neurological disorders, cardiovascular diseases, gastrointestinal problems and respiratory diseases. While 99% of the patients claimed that they knew how to use their medications, only 96% reported receiving an explanation from either physician or pharmacist. The quality of counseling, as evaluated by the patients, was ranked above average for 75% of the consultations with the prescribing physician and 63% with the dispensing pharmacist.

Conclusions: Although few conclusions can be drawn from this study based on the initial statistical analysis of the data, the major findings were that patients value highly the counseling they receive and that 99% believe they have the requisite knowledge for using their medications. Compared to the international literature, our results – based on the patients' perceptions – indicate that counseling by pharmacists is a common and well-accepted activity in Israel and occurs at a high rate.