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עמוד בית
Thu, 18.07.24

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May 2014
Ilan Ben-Zvi MD and Avi Livneh MD
Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease characterized by spontaneous short attacks of fever, elevated acute-phase reactants, and serositis. Approximately 5%–10% of FMF patients do not respond to colchicine treatment and another 5% are intolerant to colchicine because of side effects. Recently, following the discovery of the inflammasome and recognition of the importance of interleukin-1β (IL-1β) as the major cytokine involved in the pathogenesis of FMF, IL-1β blockade has been suggested and tried sporadically to treat FMF, with good results. To date, case reports and small case series involving colchicine-resistant FMF patients and showing high efficacy of IL-1β blockade have been reported. At the Israel Center for FMF at the Sheba Medical Center the first double-blind randomized placebo-controlled trial of anakinra in FMF patients who are resistant or intolerant to colchicines is underway. In this report we discuss the mechanism of colchicine resistance in FMF patients, the data in the literature on IL1β blockade in these patients, and the anakinra trial inclusion criteria and study protocol.

Cassandra Ocampo MD, Molebedi L. Segwagwe MB ChB MRCP, Julian Deonarain MB ChB FCPath, Francesca Cainelli MD and Sandro Vento MD
April 2014
Arie Apel MD, Meirav Kedmi MD, Etai Levi MD, Miriam Berkowicz MD, Yaron Davidovitz MD, Abraham Kneller MD, Elena Ribakovsky MD, Avichai Shimoni MD, Arnon Nagler MD MSc and Abraham Avigdor MD
 Background: Acute lymphocytic leukemia (ALL) is a rare disease with a poor outcome in adults. Over the years different protocols have been developed with the aim of improving the outcome. The German study group protocols (GMALL), which are the most frequently used in our institutions, changed significantly between the periods 1989–93 and 1999–2003.

Objectives: To investigate whether the change in protocols over the years resulted in an outcome difference at two hospitals in Israel.

Methods: We thoroughly reviewed the records of 153 patients from Sheba Medical Center and Soroka Medical Center, of whom 106 comprised the study group. The patients were divided into two groups according to the treatment protocol used: 40 patients with the 1989/93 protocol and 66 with the 1999/2003 protocol. Outcome was analyzed for the two groups.

Results: We found a significant difference in disease-free survival (DFS) between the two groups for B cell-ALL (B-ALL) patients who achieved complete remission after induction. There was no difference in overall survival. We did not find any difference in outcome for T cell-ALL patients or for CD20-positive patients.

Conclusions: In our retrospective analysis, GMALL 99/2003 led to a better DFS for B-ALL patients who were in complete remission after induction. This is possibly related to the differences in medications between the protocols, but may also be due to better supportive care. Despite the proven advantage of the newer protocols regarding overall survival, in our experience there was no other significant difference between the two regimens. 

Eyal Kramer MD, Oscar Herman MD, Jacob Frand MD, Lior Leibou MD, Letizia Schreiber MD and Hananya Vaknine MD
 Background: Basal cell carcinoma (BCC) is the most common malignancy in humans. Several factors have been associated with the biological behavior of these tumors, including histopathologic type, depth of tumor invasion, perineural invasion, and the expression of several biologic markers including Ki67, a proliferative marker. Previous studies assessing the relationship between the proliferative fraction, as expressed by Ki67, and the histologic variants of BCC as well as its association with the tendency to recur, failed to illustrate significant statistical correlation.

Objectives: To examine the proliferative index, as expressed by Ki67, in various subtypes of basal cell carcinoma, and to assess its relationship to various histological and clinical variables.

Methods: In this retrospective study 51 lesions of BCC were examined. In each case, the following data were gathered: demographic (age and gender), anatomic location, size of the lesion, and clinical follow-up.  Each case was stained immunohistochemically with anti-Ki67 antigen (MIB-1), and the proliferative index was determined. Histologic analysis was performed for the following data: presence of an ulcer, intensity of inflammatory infiltrate, histologic subtype, mitotic count, and the presence of perineural invasion.

Results: Basal cell carcinoma exhibited a wide variation of proliferative indices, ranging from 1% to 61%. A significant statistical correlation was observed between the proliferative index and the mitotic activity, tumor ulceration and brisk tumor-infiltrating lymphocytes.

Conclusions: The wide variation in the degree of proliferation (from almost no activity to highly proliferative tumors) suggests that basal cell carcinoma exhibits a wide spectrum of biological characteristics. Ulcerated lesions were characterized by high proliferative index. No true correlation was demonstrated between the proliferative index and the aggressive histologic subtypes, implying that other factors were more biologically significant. The degree of proliferation also showed significant statistical correlation with the degree of tumor infiltration by lymphocytes. The significance of this proliferation-associated increased immunogenicity needs to be further studied.

Ori Galante MD, Ella Abramovich MD, Anat Nevo-Shor MD and Yaniv Almog MD
Maitseo Kuno Nwako-Mohamadi MBChB BAO MSc, Vidushi Madan MD, Matthew N. Tanko MBBS FMCPath (Nig) and Sandro Vento MD
March 2014
Ilan Goldberg, Oksana Finkel, Andrea GatD, Eli Sprecher and Helena Martinez de Morentin
Erythema nodosum and pyoderma gangrenosum are common skin manifestations in inflammatory bowel diseases. Curiously, these two cutaneous features have seldom been reported to occur simultaneously.  We present three patients affected with inflammatory bowel disease, with concomitant erythema nodosum and pyoderma gangrenosum.

Avraham Unterman, Anat Achiron, Itai Gat, Oren Tavor and Amitai Ziv
 Background: Physicians are often insufficiently trained in bedside teaching and mentoring skills. Objectives: To develop, implement and assess a simulation-based training program designed to improve clinical teaching among physicians.

Methods: We developed a one-day tutor training program based on six simulated scenarios with video-based debriefing. The program's efficacy was assessed using questionnaires completed by the participating physicians and their students. Main outcome measures were self-perceived teaching skills at baseline, after participation in the program, and following completion of the tutor role. Secondary outcome measures were the students' perceptions regarding their tutor skills.

Results: Thirty-two physicians (mean age 35.5, 56% females) participated in the program. Self-assessment questionnaires indicated statistically significant improvement following the program in 13 of 20 measures of teaching skills. Additional improvement was observed upon completion of the tutor role, leading to significant improvement in 19 of the 20 measures. Questionnaires completed by their students indicated higher scores in all parameters as compared to a matched control group of tutors who did not participate in the program, though not statistically significant. Most participants stated that the program enhanced their teaching skills (88%), they implement program-acquired skills when teaching students (79%), and they would recommend it to their peers (100%). Satisfaction was similar among participants with and without previous teaching experience.

Conclusions: A novel one-day simulation-based tutor training program was developed and implemented with encouraging results regarding its potential to improve clinical teaching and mentoring skills. 

Lela Migirov, Gahl Greenberg, Ana Eyal and Michael Wolf
Cholesteatoma is an epidermoid cyst that is characterized by independent and progressive growth with destruction of adjacent tissues, especially the bone tissue, and tendency to recurrence. Treatment of cholesteatoma is essentially surgical. The choice of surgical technique depends on the extension of the disease, and preoperative otoscopic and radiological findings can be decisive in planning the optimal surgical approach. Cholesteatoma confined to the middle ear cavity and its extensions can be eradicated by use of the minimally invasive transmeatal endoscopic approach. Computerized tomography of the temporal bones fails to distinguish a cholesteatoma from the inflammatory tissue, granulations, fibrosis or mucoid secretions in 20–70% of cases showing opacification of the middle ear and mastoid. Using the turbo-spin echo (TSE), also known as non-echo planar imaging (non-EPI) diffusion-weighted (DW) magnetic resonance imaging, cholesteatoma can be distinguished from other tissues and from mucosal reactions in the middle ear and mastoid. Current MRI sequences can support the clinical diagnosis of cholesteatoma and ascertain the extent of the disease more readily than CT scans. The size determined by the TSE/HASTE (half-Fourier acquisition single-shot turbo-spin echo) DW sequences correlated well with intraoperative findings, with error margins lying within 1 mm. Our experience with more than 150 endoscopic surgeries showed that lesions smaller than 8 mm confined to the middle ear and its extension, as depicted by the non-EPI images, can be managed with transmeatal endoscopic approach solely. We call upon our otolaryngologist and radiologist colleagues to use the newest MRI modalities in the preoperative evaluation of candidates for cholesteatoma surgery.

February 2014
Godfrey M. Rwegerera, Wahhab Chowdhury MPhil Path, Mpho A. Setime and Sandro Vento
December 2013
Sergiu C. Blumen, Anat Kesler, Ron Dabby, Stavit Shalev, Chaiat Morad, Yechoshua Almog, Joseph Zoldan, Felix Benninger, Vivian E. Drory, Michael Gurevich, Menachem Sadeh, Bernard Brais and Itzhak Braverman
 Background: Oculopharyngeal muscular dystrophy (OPMD) produced by the (GCG)13 expansion mutation in the PABPN1 gene is frequent among Uzbek Jews in Israel.

Objectives: To describe the phenotypic and genotypic features in five Bulgarian Jewish patients, from different families, with autosomal dominant OPMD.

Methods: We performed clinical follow-up, electrodiagnostic tests and mutation detection. Blood samples were obtained after informed consent and DNA was extracted; measurement of GCG repeats in both PABPN1 alleles and sequencing of OPMD mutations were performed according to standard techniques.

Results: We identified five patients (four females), aged 58 to 71 years, with bilateral ptosis, dysphagia, dysphonia (n=3) and myopathic motor units by electromyography. In all patients we noticed proximal weakness of the upper limbs with winging scapulae in three of them. All cases shared the (GCG)13-(GCG)10 PABPN1 genotype.

Conclusions: OPMD among Bulgarian Jews is produced by a (GCG)13 expansion, identical to the mutation in Uzbek Jews and French Canadians. In addition to the classical neurological and neuro-ophthalmological features, early shoulder girdle weakness is common in Bulgarian Jewish patients; this is an unusual feature during the early stages of OPMD produced by the same mutation in other populations. We suggest that besides the disease-producing GCG expansion, additional ethnicity-related genetic factors may influence the OPMD phenotype. OPMD is a rare disease, and the identification of five affected families in the rather small Bulgarian Jewish community in Israel probably represents a new cluster; future haplotype studies may elucidate whether a founder effect occurred. 

Osamah Hussein, Jamal Zidan, Michael Plich, Hana Gefen, Roberto Klein, Karina Shestatski, Kamal Abu-Jabal and Reuven Zimlichman

Background: Coronary slow flow phenomenon (CSFP) is a functional and structural disease that is diagnosed by coronary angiogram.    



Objectives: To evaluate the possible association between CSFP and small artery elasticity in an effort to understand the pathogenesis of CSFP.

Methods: The study population comprised 12 patients with normal coronary arteries and CSFP and 12 with normal coronary arteries without CSFP. We measured conjugated diene formation at 234 nm during low density lipoprotein (LDL) oxidation, as well as platelet aggregation. We estimated, non-invasively, arterial elasticity parameters. Mann-Whitney non-parametric test was used to compare differences between the groups. Data are presented as mean ± standard deviation.

Results: Waist circumference was 99.2 ± 8.8 cm and 114.9 ± 10.5 cm in the normal flow and CSFP groups, respectively (P = 0.003). Four patients in the CSFP group and 1 in the normal flow group had type 2 diabetes. Area under the curve in the oral glucose tolerance test was 22% higher in the CSFP than in the normal group (P = 0.04). There was no difference in systolic and diastolic blood pressure, plasma concentrations of total cholesterol, triglycerides, high density lipoprotein, LDL and platelet aggregation parameters between the groups. Lag time required until initiation of LDL oxidation in the presence of CuSO4 was 17% longer (P = 0.02) and homocysteine fasting plasma concentration was 81% lower (P = 0.05) in the normal flow group. Large artery elasticity was the same in both groups. Small artery elasticity was 5 ± 1.5 ml/mmHgx100 in normal flow subjects and 6.1 ± 1.9 ml/mmHgx100 in the CSFP patients (P = 0.02).

Conclusions: Patients with CSFP had more metabolic derangements. Arterial stiffness was not increased in CSFP.

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