Israel Medical Association Journal

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.

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 number of patients treated with intravitreal injections has increased significantly over the past few years, mainly following the introduction of anti-vascular endothelial growth factor antibody intraocular medications. Bevacizumab is mostly used in this group of medications.

Objectives: To describe persistent elevation of intraocular pressure (IOP) following intravitreal injection of bevacizumab.

Methods: We reviewed consecutive cases of persistent IOP elevation after intravitreal bevacizumab injection for exudative age-related macular degeneration (AMD). A total of 424 patients (528 eyes) met the inclusion criteria and received 1796 intravitreal injections of bevacizumab. Persistent IOP elevation was found in 19 eyes (3.6%, 19/528) of 18 patients (4.2%, 18/424) with IOP elevated 30–70 mmHg, 3–30 days after injection.

Results: Mean IOP was 42.6 mmHg (range 30–70); IOP elevations occurred after an average of 7.8 injections of bevacizumab (range 3–13). Injected eyes (19/528) had a significantly higher incidence of elevated IOP than uninjected eyes (fellow eyes), 1/328, P < 0.001.

 Conclusions: Like other anti-vascular endothelial growth factor (VEGF) substances reported in a few recent studies, intravitreal injection of bevacizumab for neovascular AMD may be associated with persistent IOP elevation. Providers should be aware that significant IOP elevation might occur after repeated treatments. 

Objectives: To evaluate glycemic control, prevalence of diabetic ketoacidosis (DKA) at presentation, diabetic complications rate, and associated autoimmune diseases in a pediatric T1DM patient population in the Negev area.

Methods: Clinical and demographic details of 168 T1DM patients were evaluated, including HbA1C levels, long-term complications, related autoimmune diseases, and insulin pump usage. The data were analyzed and the Jewish and Bedouin patient groups compared.

Results: Only 13.1% of the patients had reached the HbA1C levels recommended by the current guidelines at the first and second year follow-up visits, and 9.5% and 7.1% at the third and fourth year visits, respectively. A significant difference in HbA1c levels between Jewish and Bedouin patients was found (P = 0.045 at the first year follow-up, P ≤ 0.01 thereafter). Significant difference was found between the Jewish and the Bedouin groups regarding presentation with DKA, 33% and 56% of the patients respectively (P = 0.01).

Conclusions: Existent glycemic control in daily practice is far from the guideline goals. Bedouin ethnicity was associated with less favorable diabetes control, emphasizing the need for better awareness of T1DM and its treatment options in this population. More resources should be directed to address T1DM in the general population, especially among the Bedouin.

 Background: Hemorrhagic radiation cystitis (HRC) is a significant clinical problem that occurs after pelvic radiation therapy and is often refractory.

Objectives: To evaluate the efficacy and safety of hyperbaric oxygen therapy (HBO) for HRC.

Methods: Daily 90 minute sessions of HBO at 2 ATM 100% oxygen were given to 32 HRC patients with American Society of Therapeutic Radiology and Oncology (ASTRO) grades 3-4 hematuria.

Results: The median age was 72.5 (48–88 years). The median time interval between radiation therapy and HBO was 4 years (1–26 years). The patients received a median of 30 HBO sessions (3–53). Hematuria resolved in 27 patients (84%) and persisted in 5. Cystectomy was required in two, and ileal-conduit and bilateral percutaneous nephrostomies were performed in one and two patients, respectively. With a median follow-up of 12 months (5–74 months), the hematuria cleared completely in 16 patients (59%) and mild hematuria requiring no further treatment recurred in 10 others. Another patient with ASTRO grade 4 hematuria needed bladder irrigation and blood transfusions. Complications included eardrum perforation in four patients and transient vertigo and mild hemoptysis in one case each. None of them required HBO discontinuation.

Conclusions: HBO controlled bleeding in 84% of the patients. A durable freedom from significant hematuria was achieved in 96% of the patients. HBO seems to be an effective and safe modality in patients with HRC.