Israel Medical Association Journal

Background: Late nephrology referral, before initiation of dialysis treatment, is associated with adverse outcome.

Objectives: To investigate the implications of late nephrology referral on mortality among dialysis patients in Israel.

Methods: We retrospectively analyzed 200 incident dialysis patients. Patients were defined as late referrals if they started dialysis less than 3 months after their first nephrology consultation. Survival rates and risk factors for mortality were analyzed

Results: The early referral (ER) group comprised 118 patients (59%) and the late referral (LR) group 82 patients (41%). The mortality rate was 44.5% (53 patients) in the ER and 68% (n=56) in the LR group. The 4 year survival rate was 41.1% in the ER and 18.7% in the LR group (P < 0.0001). The mortality rate increased with late nephrology referral (HR 1.873, 95%CI 1.133–3.094), with age (HR 1.043 for each year, 95%CI 1.018–1.068), with diabetes (HR 2.399, CI 1.369-4.202), and with serum albumin level (HR 0.359 for an increase of each 1 g/dl, 95%CI 0.242–0.533). The median survival time was higher for the ER group in women, in patients younger than 70, and in diabetic patients. A trend for longer survival time was found in non-diabetic patients. Survival time was not increased in early referred patients older than 70 and in male patients.

Conclusions: Late nephrology referral is associated with an overall higher mortality rate in dialysis patients. The survival advantage of early referral may have a different significance in specific subgroups. The timing of nephrology referral should be considered as a modifiable risk factor for mortality in patients with end-stage renal disease. 

* Israel Glaucoma Screening Group 2009-2010 (in alphabetical order):

Applebaum E, Arodi A, Avidar A, Barkana Y, Beiran I, Bracha Z, Burgansky Z, Cotlear D, Dafna O, Drori L, ElNaddaf H, Epstein E, Garzozi H, Gawi H, Geffen N, Glovinsky Y, Hadayer A, Jubran R, Kalev-Landoy M, Kaniezer B, Kratz A, Kurtz S, Matanes M, Mazover A, Mazzawi N, Naveh L, Nesher R, Neuman H, Pedut T, Pikel Y, Rachmiel R, Rath E, Robinson A, Segev E, Shemesh G, Shoham N, Silverston B, Tam G, Tessler Z, Tiosano B, Vidan A, Vishinevski I, Zalish M, Zarfati D, Zorani Y.

Background: Early detection of glaucoma enables early initiation of treatment. Screening populations at risk is likely to help achieve this goal.

Objectives: To increase public awareness regarding early detection of glaucoma, and estimate the prevalence of increased intraocular pressure (IOP) and optic disk cupping in the screened population.

Methods: A public awareness campaign was carried out in Israel during the 2009 and 2010 World Glaucoma Week, culminating each year in a one-day, free-of-charge screening of individuals in 13 outreach public locations. Screening was performed by 45 ophthalmologists and included a brief medical history, slit-lamp exam with measurement of intraocular pressure (IOP), and evaluation of cup/disk ratio.

Results: A total of 2560 individuals were screened; the mean age was 59 ± 13 years. IOP ≥ 21 mmHg was found in 4.8%, and 12.3% had cupping ≥ 0.5. IOP ≥ 21 mmHg together with cupping ≥ 0.5 were present in 1.4% and this rate increased with age: 3.7% of cases in the age group ≥ 70 years compared to 1% and 0.6% in the age groups 50–69 and < 50 years, respectively (P < 0.001). Likewise, the prevalence of cupping ≥ 0.7 and of IOP ≥ 24 mmHg increased significantly with age. The prevalence of IOP ≥ 21 mmHg increased in cases with a family history of glaucoma in first-degree relatives (10.5% compared to 3.9%, P < 0.001). The prevalence of IOP ≥ 21 mmHg was also increased in diabetic patients (8.3% vs. 4.3% in non-diabetics, P = 0.002). Further ophthalmologic evaluation was recommended to 13% of the screened individuals.

Conclusions: Outreach screening for glaucoma is a valuable tool for detecting glaucoma, pre-perimetric glaucoma, or ocular hypertension in a meaningful number of previously undiagnosed cases. Yet, cost-effectiveness issues should also be considered. The yield of such screening increases with age and seems to be most advantageous in cases with diabetes or a family history of glaucoma. 

Background: Chronic spontaneous urticaria (CSU) is a common, debilitating disease that is frequently resistant to standard therapy. Omalizumab, anti-immunoglobulin-E humanized monoclonal antibody, was recently shown to be effective in treating resistant CSU.

Objectives: To investigated the treatment of CSU with omalizumab in Israel.

Methods: We conducted a multicenter retrospective analysis of patients with refractory CSU treated with omalizuamb in Israel during 2012–2013. Complete improvement was defined as resolution of symptoms with no need for other medications, or satisfactory when patients’ condition improved but required regular or intermittent doses of antihistamines.

Results: Forty-three patients received omalizumab off-label for refractory CSU. Their mean age was 45 ± 12 years and CSU duration was 4.3 ± 4 years. In this cohort, 98% were unsuccessfully treated with high dose H(1)-antihistamines, 88% with systemic glucocorticoids and 30% with cyclosporine and/or other immune-modulators. Fourteen patients received only one injection of omalizumab, while the other 29 received on average of 4.3 ± 3.2 injections; 30 patients received 150 mg/month and 13 received 300 mg/month. Following omalizumab therapy, disease remitted within weeks in 86% of patients, of whom half achieved complete remission. The latter was associated with usage of high dose omalizumab, 300 mg/month vs. 150 mg/month (P = 0.02) and repeated therapy (i.e., multiple injections vs. a single injection) (P = 0.0005).

Conclusions: Omalizumab is an effective and safe treatment for refractory CSU with rapid onset of action for inducing and maintaining remission. Treating CSU patients mandates an individual approach, because while low dose omalizumab will suffice for some patients others might need higher doses and prolonged therapy. 

Background: Removal of retained placental tissue postpartum and retained products of conception (RPOC) abortion is done by uterine curettage or hysteroscopy. Trauma to the endometrium from surgical procedures, primarily curettage, can cause intrauterine adhesions (Asherman's syndrome) and subsequent infertility. The incidence of malpractice claims relating to intrauterine adhesions is rising, justifying reevaluation of the optimal way of handling these complications. 

Objectives: To review malpractice claims regarding intrauterine adhesions, and to explore the clinical approach that might reduce those claims or improve their medical and legal outcomes.

Methods: We examined 42 Asherman's syndrome claims handled by MCI, the largest professional liability insurer in Israel. The clinical chart of each case was reviewed and analyzed by the event preceding the adhesion formations, timing and mode of diagnosis, and outcome. We also assessed whether the adverse outcome was caused by substandard care and it it could have been avoided by different clinical practice. The legal outcome was also evaluated.

Results: Forty-seven percent of the cases occurred following vaginal delivery, 19% followed cesarean section, 28% were RPOC following a first-trimester pregnancy termination, and 2% followed a second-trimester pregnancy termination.

Conclusions: It is apparent that due to a lack of an accepted management protocol for cases of RPOC, it is difficult to legally defend those cases when the complication of Asherman syndrome develops. 

Background: Serum lactate dehydrogenase (LDH) is elevated in various diseases. 

Objectives: To analyze serum LDH as a distinguishing clinical biomarker and as a predictor of in-hospital outcome in admitted medical patients.

Methods: We analyzed a cohort of all 158 patients with very high isolated LDH (LDH ≥ 800 IU/ml – without concomitant elevations of alanine aminotransferase and aspartate aminotransferase) – admitted to our internal medicine department during a 3 year period. Epidemiologic and clinical data, as well as the final diagnosis and outcome were recorded and compared with those of a cohort of all 188 consecutive control patients.

Results: Very high isolated LDH was a distinguishing biomarker for the presence of cancer (27% vs. 4% in the LDH group and controls respectively, P < 0.0001), liver metastases (14% vs. 3%, P < 0.0001), hematologic malignancies (5% vs. 0%, P = 0.00019), and infection (57% vs. 28%, P < 0.0001). Very high isolated LDH was a marker for a severe prognosis, associated with more admission days (9.3 vs. 4.1, P < 0.0001), significantly more in-hospital major complications, and a high mortality rate (26.6% vs. 4.3%, P < 0.0001). Finally, very high isolated LDH was found in a multivariate regression analysis to be an independent predictor of mortality.

Conclusions: The presence of very high isolated LDH warrants thorough investigation for the presence of severe underlying disease, mostly metastatic cancer, hematologic malignancies and infection. Moreover, it is a marker for major in-hospital complications and is an independent predictor of mortality in admitted medical patients. 

Smoking is a risk factor for thromboangiitis obliterans (TAO, Buerger’s disease) and arteriosclerosis, but there are few cases of coronary heart disease (CAD)-associated Buerger's disease. A literature search for articles in English, Spanish and French published between 1966 and 2012 on patients with coronary involvement and TAO revealed 12 patients. We describe an additional case with involvement of the central nervous system, myocardium and large-diameter proximal arteries. The main clinical manifestations in these 13 cases were lower limb claudication and acute thoracic pain. The histologic findings showed thrombosis with unbroken internal elastic lamina and intimal clusters of granulocytes; coronary angiography revealed predominant involvement of the left anterior descending and right coronary artery. Treatment included coronary bypass procedures, coronary angioplasty, smoking cessation, and anticoagulant therapy. A complete therapeutic response was observed in half the patients. This review of all published cases of TAO patients with coronary symptoms, together with our patient, demonstrates the rarity of this clinical association. Patients under age 40 with CAD but no prominent cardiovascular risk factors besides smoking should be evaluated for the presence of Buerger's disease.

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.