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עמוד בית
Thu, 18.07.24

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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. 

Marina Pekar, Gilad Twig MD, Alex Levin MD and Howard Amital MD MHA
March 2014
Tal Bergman-Levy, Jeremia Heinik and Yuval Melamed
Testamentary capacity refers to an individual's capability to write his or her own will. Psychiatrists are required occasionally to give expert opinions regarding the testamentary capacity of individuals with a medical history or suspected diagnosis of a mental illness. This may stem from the patient/lawyer/family initiative to explore the current capacity to testate in anticipation of a possible challenge, or may be sought when testamentary capacity of a deceased has been challenged. In this article we examine the medico-legal construct of testamentary capacity of the schizophrenic patient, and discuss the various clinical situations specific to schizophrenic patients, highlighting their impact on the medical opinion regarding testamentary capacity through examining the rulings of the Israeli Supreme Court in a specific case where the testamentary capacity of a mentally ill individual who was challenged postmortem, and provide a workable framework for the physician to evaluate the capacity of a schizophrenia patient to write a will.

Aleksandra Djokovic, Ljudmila Stojanovich, Milica Kontic, Natasa Stanisavljevic, Slavica Radovanovic and Dragomir Marisavljevic
Background: Antiphospholipid syndrome (APS, also known as Hughes syndrome) may manifest itself as a primary or secondary disease, most commonly with systemic lupus erythemathosus (SLE) and various cardiac manifestations. 

Objectives: To report the first results from the Serbian National Cohort study, which was started in January 2000.

Methods: Our study included 374 patients: 260 primary APS patients and 114 SLE patients with secondary APS. Antiphospholipid antibody (aPL) analysis included detection of anticardiolipin antibodies (aCL) (immunoglobulin G and M), ß2-glycoprotein 1, and lupus anticoagulant. Echocardiography was performed in all patients, and data on myocardial infarction, unstable angina, chronic cardiomyopathy and acute heart failure were collected.

Results: There were 30.7% secondary APS patients and 9.2% primary APS patients with pseudo-infective endocarditis (P = 0.0001). Cardiac manifestations were observed in 28.7% of patients who had more than one type of antibody (category I), in 24.1% with category IIa, in 23.1% with category IIb, and in 27.8% with category IIc (P = 0.78). Age was confirmed as a significant factor for cardiac manifestations in APS patients (52.3 and 43.3 years, respectively, P = 0.001). aCL IgG and IgM positivity was related to valvular changes in all APS patients and high levels of those antibodies increased the risk of these manifestations.

Conclusions: Patients with secondary APS had a higher prevalence of valvular lesions, and some aPL types and high levels of aPL were risk factors for specific cardiac manifestations in APS patients.

Yigal Helviz, Moshe Hersch, David Raveh, Lev Shmulovich and Sharon Einav
Hasan Kais MD, Yehuda Hershkovitz MD, Judith Sandbank MD and Ariel Halevy
Bernardo Melamud, Yoav Lurie, Eran Goldin, Izhar Levi and Yaacov Esayag
January 2014
Johad F. Khoury, Myriam Weyl Ben-Arush, Michael Weintraub, Elisha Waldman, Boris Futerman, Eugene Vlodavsky and Sergey Postovsky
 Background: In osteosarcoma the histological response, measured by the percentage of tumor necrosis, constitutes one of the most significant predictive factors, with better survival in patients whose tumor necrosis is ≥ 90%.

Objectives: To determine if the decrease rate of serum alkaline phosphatase (SAP) levels during the first month of neoadjuvant chemotherapy could serve as a predictive indicator of tumor necrosis and clinical outcome.

Methods: We analyzed the medical files of 53 osteosarcoma patients (19 females, 34 males) (median age 16 years, range 8–24); the disease was metastatic in 12 and localized in the other 41.

Results: The histological responses were good in 38 patients (71.7%) and poor in 15 (28.3%). At a median follow-up of 50 months, 34 patients (64.2%) had no evidence of disease and 19 (35.8%) had died from the disease. High levels of SAP at diagnosis correlated with worse survival (P = 0.002). There was no difference in overall survival between patients whose SAP decrease rate was > 25% and those with a rate < 25% (P = 0.14). Among female patients, "rapid" SAP responders had better survival than "slow" responders (P = 0.026). In patients with metastases the SAP decrease rate was positively correlated with survival (P = 0.042).

Conclusions: There was no evidence that "rapid" SAP responders had a higher percentage of tumor necrosis than "slow" responders, although female "rapid" SAP responders had a better prognosis than "slow" responders. Patients with metastases at presentation and "rapid" SAP response had better prognoses.

Emily Lubart, Arthur Leibovitz, Vadim Shapir and Refael Segal
Background: Musculoskeletal and joint disorders are extremely common in the elderly. They directly affect mobility, gait stability, quality of life, and independence.

Objectives: To assess the nature of joint problems encountered in a geriatric inpatient population and evaluate the contribution of a rheumatologist.

Methods: We reviewed the rheumatology consultations that were conducted in a geriatric medical center over a 10 year period.

Results: A total of 474 consultations were held; most of these patients (86%) were hospitalized in the acute geriatric departments, 10% in the rehabilitation ward and 4% in the long-term care wards. Some patients were seen more than once. The rheumatologic joint problem was the main reason for hospitalization in 53% of these patients. Monoarthritis was the most frequent complaint (50%), followed by pauci-articular arthritis (two to five joints) in 30% of patients. Arthrocentesis, diagnostic and therapeutic, was performed in 225 patients, most of them on knee joints (81%). The most frequent diagnosis was osteoarthritis with acute exacerbation (28%), followed by gout (18%), pseudo-gout (9%) and rheumatoid arthritis (9%). In 86 cases (18%) the diagnosis was a non-specific rheumatologic problem: arthralgia, non-specific generalized pain, or fibromyalgia.

Conclusions: Prompt and appropriate evaluation, as well as arthrocentesis and treatment initiation, including local injections, were made possible by the presence of an in-house rheumatologist. 

Alon Eisen, Eli Lev, Zaza Iakobishvilli, Avital Porter, David Brosh, David Hasdai and Aviv Mager
Background: Treatment with HMG-CoA reductase inhibitors (statins) is often complicated by muscle-related adverse effects (MAEs). Studies of the association between low plasma vitamin D levels and MAEs have yielded conflicting results.

Objectives: To determine if low plasma vitamin D level is a risk factor for MAEs in statin users.

Methods: Plasma levels of 25(OH) vitamin D were measured as part of the routine evaluation of unselected statin-treated patients attending the coronary and lipid clinics at our hospital during the period 2007–2010. Medical data on muscle complaints and statin use were retrieved from the medical files. Creatine kinase (CK) levels were derived from the hospital laboratory database.

Results: The sample included 272 patients (141 men) aged 33–89 years. Mean vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 ± 20.5 vs. 44.7 ± 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 11 patients (4%) had both. There was no difference in plasma vitamin D levels between patients with and without myalgia (46.3 ± 17.7 vs. 48.9 ± 21.0 nmol/L, P = 0.31), with and without CK elevation (50.2 ± 14.6 vs. 47.8 ± 20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 ± 15.0 vs. 47.8 ± 10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient gender and presence/absence of coronary artery disease, and when using a lower vitamin D cutoff (< 25 nmol/L).

Conclusions: There is apparently no relationship between plasma vitamin D level and risk of MAEs in statin users.

Joao L. P. Vaz, Mirhelen M. Abreu and Roger A. Levy
 Background: The presence of anti-citrullinated peptide/protein antibody (ACPA) has a high specificity and predictive value for the development of rheumatoid arthritis (RA). Some studies have shown decreased titers of this antibody after treatment with infliximab.

Objectives: To assess the changes in ACPA titers in patients with RA after treatment with infliximab as a first biological agent, and to correlate these variations with non-infusion-related adverse effects.

Methods: In a prospective multicenter observational study involving 48 research centers, we assessed 139 patients with established moderate-to-severe RA diagnosed according to American College of Rheumatology criteria. Samples were collected before and 6–12 months after treatment.

Results: The mean age of the study patients was 50.6 years old, and 118 were female (84.9%). Statistically significant variations in ACPA titers were noted in 47 patients (before and after treatment) (P = 0.012). Overall, ACPA titers were decreased in 32 (65.3%) and increased in 15 (34.7%). No correlation was found between severe or mild adverse effects in patients presenting variations in ACPA titers.

Conclusions: The present study showed that infliximab affected ACPA titers, promoting mainly a decrease; however, this was not related to the occurrence of non-infusion-related adverse effects.

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. 

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