• IMA sites
  • IMAJ services
  • IMA journals
  • Follow us
  • Alternate Text Alternate Text
עמוד בית
Tue, 26.11.24

Search results


August 2014
Menachem Rottem MD, Ramit Segal MD, Shmuel Kivity MD, Laliv Shamshines MD, Yael Graif MD, Meir Shalit MD, Aharon Kessel MD, Josef Panasoff MD, Shai Cohen MD, Elias Toubi MD and Nancy Agmon-Levin MD

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. 

Daniel Elbirt MD*, Ilan Asher MD*, Keren Mahlab-Guri MD, Shira Bezalel-Rosenberg MD, Victor Edelstein MD and Zev Sthoeger MD

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.

Gilad Allon MD, Nir Seider MD, Eytan Z. Blumenthal MD and Itzchak Beiran MD
July 2014
Michael Arad MD, Tamar Nussbaum MD, Ido Blechman BA, Micha S. Feinberg MD, Nira Koren-Morag PhD,Yael Peled MD and Dov Freimark MD

Background: Contemporary therapies improve prognosis and may restore left ventricular (LV) size and function.

Objectives: To examine the prevalence, clinical features and therapies associated with reverse remodeling (RR) in dilated cardiomyopathy (DCM).

Methods: The study group comprised 188 DCM patients who had undergone two echo examinations at least 6 months apart. RR was defined as increased LV ejection fraction (LVEF) by ≥ 10% concomitant with ≥ 10% decreased LV end-diastolic dimension.

Results: RR occurred in 50 patients (26%) and was associated with significantly reduced end-systolic dimension, left atrial size, grade of mitral regurgitation, and pulmonary artery pressure. NYHA class improved in the RR group. RR was less common in familial DCM and a long-standing disease and was more prevalent in patients with prior exposure to chemotherapy. Recent-onset disease, lower initial LVEF and normal electrocardiogram were identified as independent predictors of RR. Beta-blocker dose was related to improved LVEF but not to RR. Over a mean follow-up of 23 months, 16 patients (12%) from the 'no-RR' group died or underwent heart transplantation compared to none from the RR group (P < 0.01).

Conclusions: Contemporary therapies led to an an improvement in the condition of a considerable number of DCM patients. A period of close observation while optimizing medical therapy should be considered before deciding on invasive procedures. 

Arie Soroksky MD, Sergey Nagornov MD, Eliezer Klinowski MD, Yuval Leonov MD, Eduard Ilgiyaev MD, Orit Yossepowitch MD and Galina Goltsman M

Background: The role of routine active surveillance cultures (ASCs) in predicting consequent blood stream infections is unclear.

Objectives: To determine prospectively whether routine screening ASCs obtained on admission to the intensive care unit (ICU) can predict the causative agent of subsequent bloodstream infections.

Methods: We prospectively studied a cohort of 100 mechanically ventilated patients admitted consecutively to a 16-bed ICU. On admission, ASCs were obtained from four sites: skin cultures (swabs) from the axillary region, rectal swabs, nasal swabs, and deep tracheal aspirates. Thereafter, cultures were obtained from all four sites daily for the next 5 days of the ICU stay.

Results: Of the 100 recruited patients 31 (31%) had culture-proven bacteremia; the median time to development of bacteremia was 5 days (range 1–18). Patients with bacteremia had a longer median ICU stay than patients without bacteremia: 14 days (range 2–45) vs. 5 days (1–41) (P < 0.001). ICU and 28 day mortality were similar in patients with and without bacteremia. Most ASCs grew multiple organisms. However, there was no association between pathogens growing on ASCs and eventual development of bacteremia.

Conclusions: ASCs obtained on ICU admission did not identify the causative agents of most subsequent bacteremia events. Therefore, bloodstream infections could not be related to ASCs.

Igor Rabin MD, Uri Shpolanski PhD, Allon Leibovitz MD and Arie Bass MD

Background: Claudication is one of the sequelae of peripheral arterial disease (PAD). To date, no effective treatment has been found for this condition.

Objectives: To investigate a new device to treat PAD. The device administers pre-programmed protocols of oscillations to the foot.

Methods: Fifteen patients aged 40–70 years who suffered from intermittent claudication secondary to PAD were recruited to an open prospective study. Each patient was treated once for 30 minutes. The following parameters were evaluated: pain-free and maximal walking distances, skin blood flux by laser-Doppler, skin temperature, ankle-brachial and toe-brachial indices, transcutaneous oxygen pressure (tcpO2) and transcutaneous carbon dioxide pressure (tcpCO2). Non-parametric signed-rank test was applied for testing differences between baseline assessment and post-treatment assessments for quantitative parameters.

Results: Mean pain-free walking distance was 122 ± 33 m and increased to 277 ± 67 m, after the treatment session (P = 0.004). Mean maximal walking distance was 213 ± 37 m and it increased to 603 ± 77 m (P < 0.001). Foot skin perfusion also improved, as demonstrated by an increase in tcpO2 by 28.6 ± 4.1 mmHg (P < 0.001), a decrease in tcpCO2 by 2.8 ± 1.3 (P = 0.032), and up to twofold improvement in blood flux parameters, and an increase in skin temperature by 1.9 ± 0.5°C (P < 0.001). Ankle-brachial index increased by 0.06 ± 0.01 (P = 0.003) and toe-brachial index by 0.17 ± 0.02 (P < 0.001).

Conclusions: Preprogrammed oscillations applied to the foot had a positive effect on microcirculation, tissue oxygenation and CO2 clearance; they had a smaller though significant effect on arterial blood pressure indices, and the change in the arterial-brachial index correlated with the change in the pain-free walking distance. 

Natalya Bilenko MD PhD MPH, Drora Fraser PhD, Hillel Vardy BA and Ilana Belmaker MD MPH
Background: A high prevalence of iron deficiency anemia persists in Bedouin Arab and Jewish pediatric populations in southern Israel.

Objectives: To compare the effect of daily use of multiple micronutrient supplementation (MMS), "Sprinkles," a powdered formulation of iron, vitamins A and C, folic acid and zinc, with liquid iron and vitamins A and D on iron deficiency at 12 months of age.

Methods: The 621 eligible Bedouin and Jewish infants in the study were assigned to the MMS and control arms and received their supplementations from age 6 to 12 months. We examined the change in hemoglobin, hematocrit, mean cell volume, red blood cell distribution, serum ferritin and transferrin saturation. In addition, we used the high Iron Deficiency Index (IDI) if two or more of the above six parameters showed abnormal levels. 

Results: Rates of anemia decreased significantly over the 6 month period, from 58.8% to 40.6% among Bedouin infants (P = 0.037) and from 40.6 to 15.8% among Jewish infants (P = 0.017). In Bedouin infants the prevalence of high IDI decreased significantly from 79.2% to 67.4% (P = 0.010) in the MMS group, but there was no change in the controls. Among Jewish infants, the high IDI prevalence decreased from 67% to 55.6% with no statistically significant difference in the two study arms. In the multivariate analysis in Bedouin infants MMS use was associated with a reduced risk of 67% in high IDI at age 12 months as compared to controls (P = 0.001). Fewer side effects in the intervention groups in both ethnic populations were reported.

Conclusions: MMS fortification of home food can be recommended as an effective and safe method for preventing iron deficiency anemia at 12 months of age. 
Aharon Erez MD, Omri Shental MD, Joseph Z. Tchebiner MD, Michal Laufer-Perl MD, Asaf Wasserman MD, Tal Sella MD and Hanan Guzner-Gur MD

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. 

A. Nobre MD, Walber P. Vieira MD, Francisco E.S. da Rocha MD, Jozelio F. de Carvalho MD PhD and Carlos E.M. Rodrigues MD PhD

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.

Gideon Nesher MD
Giant cell arteritis (GCA) is considered to be a T cell-dependent disease. Autoantibodies have not consistently been found in GCA. The exception is antiphospholipid antibodies (APLA), which were found in 30–80% of GCA cases. Recently, efforts have been made to seek autoantibodies in GCA using newer methods of detection: serological identification of antigens by recombinant cDNA expression cloning, and a proteomic approach. In these studies, lamin C (a nuclear envelope antigen) was recognized by antibodies in 32% of GCA sera and none of the controls. Other autoantigenic proteins were also identified: lamin A, vinculin (a cytoskeleton antigen), and annexin 5 (an endothelial protein). In a recent study, 92% of 36 patients with GCA and/or polymyalgia rheumatica (PMR) had autoantibodies to a human ferritin peptide (the heavy chain N-terminal); 89% had antibodies to bacterial ferritin peptide of Staphylococcus epidermidis. The significance of these findings needs to be studied further. GCA may be a part of the newly described ASIA syndrome (autoimmune syndrome induced by adjuvants). A recent study from Italy reported 10 cases of GCA/PMR within 3 months of influenza vaccination. These comprised 50% of all cases of GCA/PMR diagnosed during the 6 year period of the study. Another 11 cases of GCA following influenza vaccinations were reported. GCA pathogenesis involves all branches of the immune system, including antigen-presenting cells, T cells and B cells, and autoantibody formation is not uncommon. GCA etiology remains unknown, but may be associated with exposure to bacterial or viral antigens.  
Ori Toker MD, Ariella Tvito MD, Jacob M. Rowe MD, Jacob Ashkenazi MD, Chezi Ganzel MD, Yuval Tal MD and Meir Shalit MD
Legal Disclaimer: The information contained in this website is provided for informational purposes only, and should not be construed as legal or medical advice on any matter.
The IMA is not responsible for and expressly disclaims liability for damages of any kind arising from the use of or reliance on information contained within the site.
© All rights to information on this site are reserved and are the property of the Israeli Medical Association. Privacy policy

2 Twin Towers, 35 Jabotinsky, POB 4292, Ramat Gan 5251108 Israel