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עמוד בית
Wed, 27.11.24

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June 2014
Tal Zilberman MD, Tanya Zahavi MD, Alexandra Osadchy MD, Naomi Nacasch MD and Ze'ev Korzets MBBS
Hagit Peleg MD, Benjamin Koslowski MD, Nurit Hiller MD and Samuel N. Heyman MD
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.

Bonaguri Chiara PHD, Orsoni Jelka Gabriella MD, Russo Annalisa PHD, Rubino Pierangela MD, Bacciu Salvatore MD, Lippi Giuseppe MD Melegari Alessandra PHD, Zavota Laura MD, Ghirardini Stella AO and Mora Paolo MD

Background: Cogan’s syndrome (CS) is a rare autoimmune vasculitis characterized by ocular inflammation and sensorineural hearing loss. CS is divided into a “typical” form with non-syphilitic interstitial keratitis and audiovestibular symptoms, and an “atypical” form with ocular involvement affecting structures other than the cornea. Anti-Hsp70 antibodies were found at variable levels in patients presenting with various forms of autoimmune sensorineural hearing loss (ASNHL).

Objectives: To assess the correlation between anti-Hsp70 antibodies and specific ASNHL subgroups.

Methods: We divided 112 subjects into four groups: 14 subjects with typical CS, 24 with atypical CS, 55 with ASNHL, and 19 control subjects (healthy subjects and patients with systemic autoimmune diseases but no sensorineural hearing or audiovestibular alterations). Patients were tested for serological autoimmunity markers including anti-Hsp70.

Results: Positivity of the anti-Hsp70 antibody test was highest in the typical CS group (92.9%) and lowest in the control group (5.2%). The test was positive in 52.7% of patients in the ASNHL group and 16.6% in the atypical CS group. The paired comparison analysis between groups showed that sensitivity of anti-Hsp70 in the typical CS group was significantly higher, as compared to the other three study groups.

Conclusions: Anti-Hsp70 antibodies can be considered a serological marker of “typical” CS. “Atypical” CS is conceivably a sort of “melting pot” of different forms of autoimmune diseases still characterized by ocular inflammation and sensorineural hearing loss but whose antigenic characteristics need to be further defined.

Timna Agur MD MSc, Yair Levy MD, Eleonora Plotkin MD and Sydney Benchetrit MD
Donato Rigante MD PhD, Aurora Rossodivita MD PhD and Luca Cantarini MD PhD
Cassandra Ocampo MD, Molebedi L. Segwagwe MB ChB MRCP, Julian Deonarain MB ChB FCPath, Francesca Cainelli MD and Sandro Vento MD
May 2014
Lior Koren MD, Adi Barak RN, Doron Norman MD, Ofer Sachs MD and Eli Peled MD
Background: Proximal hip fractures in the elderly are common and have serious implications for health resources. Researching the timing of these fractures could contribute to diverting resources towards peaks in incidence and investing in prevention at certain times.

Objectives: To examine the effect of seasonality, weather and holidays on hip fracture incidence in older adults. The study population comprised 2050 patients aged 65 years or more who sustained a proximal hip fracture.

Methods: The computerized files of the patients were reviewed for trends in incidence by season, precipitation, minimum and maximum temperatures, day of the week, and certain Jewish festivals.

Results: Hip fractures were more likely to occur in the winter than in the summer (P < 0.0001). Factors that significantly correlated with hip fracture were the maximum daily temperature (r = -0.746, P = 0.005) followed by the minimum daily temperature (r = -0.740, P = 0.006) and precipitation (r = 0.329, P = 0.02). There were fewer fractures on Saturdays (the Sabbath) as compared to other days of the week (P = 0.045). Researching the incidence on Jewish festivals, we found an elevated incidence on Passover (P < 0.0001) and a reduced incidence on the Day of Atonement (Yom Kippur) (P = 0.013).

Conclusions: In older people there is an elevated incidence of proximal hip fractures during the winter and on the Jewish festivals. On weekends and on the Day of Atonement the incidence of proximal hip fractures was reduced.

April 2014
Eyal Bercovich MD, Lital Keinan-Boker MD PhD and Shaul M. Shasha MD
 Background: Previous studies suggest that exposure to starvation and stress between conception and early infancy may have deleterious effects on health later in life; this phenomenon is termed fetal origin of adult disease.

Objectives: To determine whether exposure to the Holocaust from preconception to early infancy is a cause of chronic morbidity in adulthood.

Methods: This pilot study involved 70 European Jews born in countries under Nazi rule (exposed group) during the period 1940–1945 who were interviewed to determine the presence of chronic diseases. A control group of 230 Israeli-born individuals of the same descent, age, and gender distribution were extracted from the Israel National Health Interview Survey-2 (unexposed group). The prevalence of selected risk factors and chronic diseases was compared between the groups.

Results: The prevalence of cardiovascular risk factors and morbidity was significantly higher in the exposed group: body mass index (BMI) (29.06 ± 3.2 vs. 26.97 ± 4.42, P = 0.015), hypertension (62.9% vs. 43%, P = 0.003), dyslipidemia (72.9% vs. 46.1%, P < 0.001), diabetes (32.9% vs. 17.4%, P = 0.006), angina pectoris (18.6% vs. 4.8%, P = 0.001) and congestive heart failure (8.6% vs. 1.7%, P = 0.013). The prevalence of cancer (30.0% vs. 8.7% P < 0.001), peptic ulcer disease (21.4% vs. 7%, P = 0.001), headaches/migraines (24.3% vs. 12.6%, P < 0.001) and anxiety/depression (50.0% vs. 8.3%, P < 0.001) was also higher in the exposed group.

Conclusions: These results suggest that exposure to Holocaust conditions in early life may be associated with a higher prevalence of obesity, dyslipidemia, diabetes, hypertension, cardiovascular morbidity, malignancy and peptic diseases in adulthood. These findings set the stage for further research, which might define those exposed as a high risk group for chronic morbidity.

George M. Weisz MD FRACS MA and William R. Albury BA PhD
 Reinhard Heydrich, architect of the “Final solution of the Jewish problem,” had a meteoric career in the SS. He organized the Wannsee Conference and created the SS killing squads. Under his leadership as Reich Protector of Bohemia and Moravia, the suppression of the Czech community was brutal. An attempt on his life in Prague was unsuccessful but it left him severely injured and he died eight days later. Reviewing the available information on his hospital treatment and the autopsy report, it is suggested that Heydrich received substandard medical treatment, quite likely a result of political interference from rival members of the SS hierarchy.

Tania Sezin MSc, Emily Avitan-Hersh MD, Margarita Indelman MSc, Roni Moscona MD, Edmond Sabo MD, Rina Katz MSc, Shimon Pollack MD and Reuven Bergman MD
 Background: Human amnion membrane (HAM) was suggested to be a superior antigenic substrate for immunoblotting in detecting autoantibodies of autoimmune bullous skin diseases.

Objectives: To determine the properties of HAM as an antigenic substrate for the detection of autoantibodies in pemphigus vulgaris and bullous pemphigoid.

Methods: Immunomapping and tandem liquid chromatography mass spectrometry were used to delineate the antigenic structure of HAM in 25 pemphigus patients, 41 pemphigoid patients, and 36 controls. Immunoblotting and indirect immunofluorescence were used to study the diagnostic utility of HAM, and the results were compared to those of indirect immunofluorescence on monkey esophagus, immunoblotting using normal human skin, and enzyme-linked immunosorbent assay (ELISA).

Results: Immunomapping demonstrated the presence of all the antigens known to be targeted in autoimmune bullous skin diseases, in both normal human skin and HAM, except for the absence of BP230, and low threshold levels of Dsg1, Dsg3 and Dsc3 in HAM. HAM indirect immunofluorescence demonstrated anti-basement membrane zone antibodies in 48.7% of the pemphigoid patients, and anti-intercellular space antibodies in 72.0% of the pemphigus patients. HAM immunoblotting did not demonstrate anti-BP230 antibodies, but detected anti-BP180 antibodies in 53.6% of the pemphigoid patients. It did not demonstrate anti-Dsg1 and/or anti-Dsg3 antibodies in any of the pemphigus patients. These results were inferior to those of ELISA and monkey esophagus indirect immunofluorescence.

Conclusions: Compared to other studied methods, HAM does not offer advantages in detecting autoantibodies in bullous pemphigoid and pemphigus vulgaris. 

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. 

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