24 results on '"Dan Caspi"'
Search Results
2. Soluble ST2 and CXCL-10 may serve as biomarkers of subclinical diastolic dysfunction in SLE and correlate with disease activity and damage
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A. Polachek, Ori Elkayam, Daphna Paran, Yan Topilsky, Smadar Gertel, Sara Borok, Sevan Letourneau-Shesaf, Ehud Chorin, Ofir Elaluof, Ilana Kaufman, Dan Caspi, Irena Wigler, Shlomo Berliner, Michal Laufer-Perl, Uri Arad, Jonathan Wollman, David Levartovsky, Eihab Ghantous, Aviram Hochstadt, Irena Litinsky, and Valerie Aloush
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Adult ,Male ,Diastole ,030204 cardiovascular system & hematology ,Risk Assessment ,Severity of Illness Index ,Ventricular Function, Left ,Disease activity ,03 medical and health sciences ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Rheumatology ,Risk Factors ,Medicine ,Humans ,Lupus Erythematosus, Systemic ,Prospective Studies ,Subclinical infection ,030203 arthritis & rheumatology ,Systemic lupus ,business.industry ,Stroke Volume ,Middle Aged ,Interleukin-1 Receptor-Like 1 Protein ,Echocardiography, Doppler ,Chemokine CXCL10 ,Cross-Sectional Studies ,Immunology ,Linear Models ,Female ,business ,Biomarkers - Abstract
Objective Subclinical myocardial dysfunction has been reported to occur early in systemic lupus erythematous (SLE). The study aim was to search for biomarkers of subclinical myocardial dysfunction which may correlate with disease activity in SLE patients. Methods This is a prospective, controlled, cross-sectional study of 57 consecutive patients with SLE and 18 controls. Serum samples were obtained to determine serum soluble ST2 (sST2), CXCL-10 and high-sensitivity troponin (hs-troponin) levels. All participants underwent an echocardiographic tissue Doppler study. Results sST2, CXCL-10 and hs-troponin levels were higher in patients with higher SLE disease activity (SLEDAI). sST2 and CXCL-10 levels were higher in patients with more disease damage as measured by the SLE damage index. Measures of diastolic dysfunction, as assessed by echocardiographic tissue Doppler negatively correlated with log CXCL-10: including E/A; E/e′lateral and E/e′septal, while E/e′ positively correlated with CXCL-10. Diastolic dysfunction parameters also correlated with log sST2 levels, a negative correlation was seen with E/e′lateral and a positive correlation was seen with E/e′. Systolic dysfunction parameters positively correlated with hs-troponin: LVED, LVES, IVS, LVMASS and LVMASS index. In a multivariate analysis, sST2 and CXCL-10 were found to be significantly different in SLE vs. healthy controls, independent of each other and independent of cardiovascular risk factors. Conclusions Soluble ST2 and CXCL-10 are markers of disease activity and accrued damage in SLE and may serve as sensitive biomarkers for detection of subclinical diastolic dysfunction, independent of traditional cardiovascular risk factors.
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- 2020
3. AB0032 DIFFERENTIAL IMPACT OF BIOLOGICS AND GLUCOCORTICOIDS ON TNF SECRETION AND CD14+CD16+ MONOCYTES PERCENTAGE IN CULTURE DERIVED FROM SYNOVIAL FLUIDS OF PATIENTS WITH PSORIATIC ARTHRITIS-IN VITRO RESEARCH
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K. Meridor, A. Polachek, David Levartovsky, Victoria Furer, R. Tzemach, Dan Caspi, Ori Elkayam, and Smadar Gertel
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business.industry ,Immunology ,TNF secretion ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,In vitro ,Psoriatic arthritis ,Rheumatology ,Immunology and Allergy ,Cd14 cd16 monocytes ,Medicine ,business ,Differential impact - Abstract
Background:Inflammatory joint diseases, such as psoriatic arthritis (PsA), are frequently treated by biologics. Assessment of treatment efficacy is based upon change in clinical activity scores and in tender and swollen joint counts. Although the response to these agents may be attributed to their central anti-inflammatory effects, synovial response may be operating in parallel. The potential beneficial role of intra-articular injection of tumor necrosis factor (TNF) blockers compared to glucocorticoids (GCs) in reducing synovitis was shown by means of clinical and instrumental validated measures (1). The inflamed synovial fluid is rich in mononuclear cells, however, the different mode of action of the in vitro response of these cells to drugs may contribute to the understanding of cellular response to therapeutic agents in central as opposed to peripheral compartments.Objectives:To evaluate the effect of biologics used in the management of PsA on synovial fluid mononuclear cells (SFMCs) in vitro, and to compare their modes of action to GCs that are used to locally alleviate synovial inflammation.Methods:SFMCs were obtained from PsA patients (n=11) during therapeutic knee arthrocentesis. The cells were cultured in vitro for 7 days in the presence of biologics (adalimumab, infliximab, secukinumab and ustekinumab, 10ug/ml) and GCs (betamethasone and methylprednisolone, 1 ug/ml and 10ug/ml) or medium as control. Levels of the secreted TNF were measured by ELISA. Changes in %CD14+CD16+ monocytes were analyzed by flow cytometry.Results:Both TNF inhibitors (adalimumab pp=0.0003) and GCs (betamethasone and methylprednisolone at 1ug/ml pp+CD16+ SFMCs derived from PsA patients (n=11) were significantly reduced by TNF inhibitors (p=0.0003) compared to medium, however, other biologics and GCs did not display similar activity (Fig. 1B).Figure 1.Both TNF inhibitors and GCs block TNF secretion but exhibit different activity on inflammatory CD14+CD16+ monocytes derived from SFMCs of PsA patients. SFMCs were co-cultured for 7 days in the presence of adalimumab, infliximab, secukinumab and ustekinumab at 10ug/ml or with betamethasone and methylprednisolone at 1ug/ml and 10ug/ml. Medium alone was used as a control. (A) Culture supernatants were analyzed for TNF levels by ELISA (n=8). (B) Cells were analyzed for %CD14+CD16+ monocytes by flow cytometry (n=11). All p values were calculated by the non-parametric one-way ANOVA Kruskal-Wallis test and Dunn’s multiple comparison test, *ppp=0.0003.Conclusion:Our data demonstrated marked activity mediated by TNF inhibitors in comparison with other biologics tested for their ability to suppress TNF secretion and inflammatory CD14+CD16+ monocytes. In contrast, GCs suppressed TNF secretion but did not significantly change the proportion of inflammatory CD14+CD16+ monocytes. These findings suggest an additional mechanism of action exerted directly by TNF inhibitors on synovial monocytes and which differs from that of GCs. These results warrant further studies of the therapeutic potential of local peripheral activity of TNF inhibitors for clinical application.Reference:[1]Carubbi F, Zugaro L, Cipriani P, Conchiglia A, Gregori L, Danniballe C, et al. Safety and efficacy of intra-articular anti-tumor necrosis factor alpha agents compared to corticosteroids in a treat-to-target strategy in patients with inflammatory arthritis and monoarthritis flare. Int J Immunopathol Pharmacol. 2016;29:252-66.Disclosure of Interests:None declared
- Published
- 2021
4. FRONT MATTER
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Dan Caspi and Daniel Rubinstein
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- 2017
5. Prevalence of Axial Spondyloarthritis Among Patients With Fibromyalgia: A Magnetic Resonance Imaging Study With Application of the Assessment of SpondyloArthritis International Society Classification Criteria
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Mark Berman, I Wigler, Valerie Aloush, Jacob N. Ablin, Iris Eshed, Maria Likhter, Daphna Paran, Marina Anouk, Dan Caspi, Ori Elkayam, and Jonathan Wollman
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musculoskeletal diseases ,030203 arthritis & rheumatology ,medicine.medical_specialty ,Ankylosing spondylitis ,medicine.diagnostic_test ,business.industry ,Spondyloarthropathy ,Radiography ,Sacroiliitis ,Magnetic resonance imaging ,medicine.disease ,Rheumatology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Fibromyalgia ,Severity of illness ,Physical therapy ,Medicine ,030212 general & internal medicine ,business - Abstract
Objective To evaluate the prevalence of sacroiliitis, the radiographic hallmark of inflammatory spondyloarthropathy, among patients diagnosed with fibromyalgia syndrome (FMS), using the current Assessment of SpondyloArthritis International Society (ASAS) criteria and magnetic resonance imaging. Methods Patients experiencing FMS (American College of Rheumatology 1990 criteria) were interviewed regarding the presence of spondyloarthritis (SpA) features and underwent HLA–B27 testing, C-reactive protein (CRP) level measurement, and magnetic resonance imaging examinations of the sacroiliac joints. FMS severity was assessed by the Fibromyalgia Impact Questionnaire and the Short Form 36 health survey. SpA severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index. Results Sacroiliitis was demonstrated among 8 patients (8.1%) and ASAS criteria for diagnosis of axial SpA were met in 10 patients (10.2%). Imaging changes suggestive of inflammatory involvement (e.g., erosions and subchondral sclerosis) were demonstrated in 15 patients (17%) and 22 patients (25%), respectively. The diagnosis of axial SpA was positively correlated with increased CRP level and with physical role limitation at recruitment. Conclusion Imaging changes suggestive of axial SpA were common among patients with a diagnosis of FMS. These findings suggest that FMS may mask an underlying axial SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such comorbidities.
- Published
- 2017
6. Expression levels of selected genes can predict individual rheumatoid arthritis patient response to tumor necrosis factor alpha blocker treatment
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Uri Arad, Victoria Furer, Ilana Kaufman, David Levartovsky, Jonathan Wollman, Shlomo Pundak, Adi Broyde, Dan Caspi, Ofir Elalouf, Yoav Smith, Daphna Paran, Ori Elkayam, and Sara Pel
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0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Treatment response ,Alpha (ethology) ,Patient response ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Genetic Testing ,Prospective Studies ,Israel ,Gene ,Aged ,Retrospective Studies ,030203 arthritis & rheumatology ,business.industry ,Tumor Necrosis Factor-alpha ,Interferon-stimulated gene ,Gene Expression Profiling ,General Medicine ,Middle Aged ,medicine.disease ,Pharmacogenomic Testing ,030104 developmental biology ,Rheumatoid arthritis ,Antirheumatic Agents ,Tumor necrosis factor alpha ,Female ,Reagent Kits, Diagnostic ,business - Abstract
Rheumatoid arthritis (RA) patients have many therapeutic options; however, tools to predict individual patient response are limited. The Genefron personal diagnostic kit, developed by analyzing large datasets, utilizes selected interferon stimulated gene expressions to predict treatment response. This study evaluates the kit's prediction accuracy of individual RA patients' response to tumor necrosis alpha (TNFα) blockers.A retrospective analysis was performed on RA patients reported in published datasets. A prospective analysis assessed RA patients, before and 3 months after starting a TNFα blocker. Clinical response was evaluated according to EULAR response criteria. Blood samples were obtained before starting treatment and were analyzed utilizing the kit which measures expression levels of selected genes by quantitative real time polymerase chain reaction (PCR). ROC analysis was applied to the published datasets and the prospective data.The Genefron kit analysis of retrospective data predicted the response to a TNFα blocker in 53 of 61 RA patients (86.8% accuracy). In the prospective analysis, the kit predicted the response in 16 of 18 patients (89% accuracy) achieving a EULAR moderate response, and in 15 of 18 patients achieving a EULAR good response (83.3% accuracy). ROC analysis applied to the two published datasets yielded an AUC of 0.89. ROC analysis applied to the prospective data yielded an AUC of 0.83 (sensitivity - 100%, specificity - 75%) The statistical power obtained in the prospective study was .9.The diagnostic kit predicted the response to TNFα blockers in a high percentage of patients assessed retrospectively or prospectively. This personal kit may guide selection of a suitable biological drug for the individual RA patient.
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- 2018
7. The In/Outsiders—Political Control on Media in Israel: A Theoretical Framework
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Yehiel Limor and Dan Caspi
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Politics ,Political science ,Political economy ,Control (linguistics) - Published
- 2018
8. Sputum Anticitrullinated Protein Antibodies in Patients With Long-standing Rheumatoid Arthritis
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Daphna Paran, Wilma Vree Egberts, Ori Elkayam, I Wigler, Elizabeth Fireman, David Levartovsky, Dan Caspi, Ido Druckman, Moshe Stark, Ilana Kaufman, Ari Polachek, and Ger J. M. Pruijn
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Adult ,Male ,musculoskeletal diseases ,Peptides, Cyclic ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,medicine ,Humans ,In patient ,skin and connective tissue diseases ,Aged ,Autoantibodies ,030203 arthritis & rheumatology ,biology ,business.industry ,Sputum ,Autoantibody ,Bio-Molecular Chemistry ,Middle Aged ,medicine.disease ,Control subjects ,Cross-Sectional Studies ,030228 respiratory system ,Rheumatoid arthritis ,Immunology ,biology.protein ,Female ,Antibody ,medicine.symptom ,business ,Biomarkers - Abstract
The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis (RA).Nineteen consecutive RA patients and 16 age- and sex-matched control subjects participated in this cross-sectional study. All underwent complete lung function tests and provided induced sputum. Antibodies to citrullinated (CitP) and the corresponding norleucine-containing (NorP) peptides in the sputum of the RA patients and control subjects, as well as in the serum of the RA patients, were determined by enzyme-linked immunosorbent assay.Patients with RA had the following characteristics: mean disease duration of 12 years, Disease Activity Score for 28 joints of 3.44, and Sharp-van der Heijde score of 57.5. Ten of the 19 RA patients showed high titers of ACPAs in their sera. Four of the seropositive (40%), none of the seronegative RA patients, and only 1 of the control subjects showed detectable levels of ACPAs in their sputum. The ratio between the reactivity with CitP and NorP peptides in the sputum was significantly higher in RA sputum than in control sputum (1.33 ± 1.2 vs. 0.64 ± 0.14, P = 0.02). A positive correlation was found between sputum ACPAs and age, serum ACPAs, sputum anti-NorP, serum anti-CitP/NorP reactivity ratio, and the proportion of neutrophils and lymphocytes in the sputum. No significant correlation was found between sputum ACPAs and disease severity, history of smoking, lung function tests, or treatment for RA.Anticitrullinated protein/peptide antibodies can be detected in the sputum of RA patients and are correlated with the presence in the serum.
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- 2018
9. Reporting The Middle East: Challenges And Chances
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Dan Caspi, Daniel Rubinstein, Dan Caspi, and Daniel Rubinstein
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- Arab-Israeli conflict--Press coverage, Arab-Israeli conflict--Mass media and the conflict, Palestine question (1948-)
- Abstract
Numerous studies address the flow of information between nations and states — especially in the era of globalization — and its contribution to the development of relations across physical borders. By contrast, little attention has been paid to the circumstances under which parties in conflict initiate and build barriers to free flow of information. The conflict in the Middle East may serve as a test bed of controlled disruption of information flow, as covered in Reporting the Middle East: Challenges and Chances. Two parallel types of confrontations appear to take place in the Middle East: the actual physical conflict, and the'war of words,'conducted via the media, with each side firing its own verbal missiles. Reporting the Middle East: Challenges and Chances aims to show that the media arena is a key element in understanding the Middle East conflict. Media coverage of Middle Eastern affairs remains critical, if only because of its power in determining sources of information, setting decision makers'agendas, and influencing management of the physical confrontation.
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- 2018
10. Galectin-3 is a sensor-regulator of toll-like receptor pathways in synovial fibroblasts
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Dan Caspi, Ori Elkayam, Sharon Amir, Avital Angel-Korman, Ortal Segal, Aviram Gold, Sharon Tzadok, Noa Madar-Balakirski, Aharon Menachem, and Uri Arad
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Lipopolysaccharides ,medicine.medical_specialty ,animal structures ,Galectin 3 ,Inflammatory arthritis ,Immunology ,Arthritis ,Biochemistry ,Proinflammatory cytokine ,Lipopeptides ,Synovitis ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Humans ,Immunology and Allergy ,Secretion ,Receptor ,Chemokine CCL5 ,Molecular Biology ,Toll-like receptor ,Interleukin-6 ,business.industry ,Synovial Membrane ,Toll-Like Receptors ,Hematology ,Fibroblasts ,medicine.disease ,Cell biology ,stomatognathic diseases ,Endocrinology ,Gene Knockdown Techniques ,Tetradecanoylphorbol Acetate ,Matrix Metalloproteinase 3 ,business ,Cell activation ,Signal Transduction - Abstract
Galectin-3 is a β-galactoside-binding lectin that plays an important role in the modulation of immune responses. It has been shown to aggravate joint inflammation and destruction in experimental arthritis. We investigated the role of galectin-3 in TLR-induced cell activation in human synovial fibroblasts (SF) in order to better understand the mechanism(s) of the proinflammatory function of galectin-3 in arthritis. Galectin-3 expression in SF obtained from rheumatoid arthritis and osteoarthritis patients was inhibited by siRNA mediated gene-knockdown. Galectin-3 was also inhibited with modified citrus pectin (MCP), a polysaccharide galectin-3 ligand. Galectin-3 knockdown inhibited TLR-2, -3 and -4-induced IL-6 secretion, but not TLR-2, -3 and -4-mediated matrix metalloproteinase-3 or CC chemokine ligand-5 secretion. When the SF were stimulated with phorbol 12-myristate 13-acetate, a protein kinase C activator that bypasses the membranal receptors, galectin-3 knockdown no longer influenced IL-6 secretion. MCP reduced IL-6 levels in a dose-dependent manner. Our results indicate that galectin-3 is a positive sensor-regulator of TLR-induced IL-6 secretion in human synovial fibroblasts, thus adding new insights into the mechanisms by which galectin-3 augments synovial inflammation. These findings corroborate the potential role of glycan inhibitors of galectin-3 as a therapeutic approach for the treatment of inflammatory arthritis.
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- 2015
11. The fine line between Takayasu arteritis and giant cell arteritis
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Rachel Pauzner, Hagit Sarvagyl-Maman, Marina Anouk, Ari Polachek, Gideon Nesher, Ori Elkayam, Uri Arad, Dan Caspi, Gabriel S. Breuer, Galia Rosen, Ilana Kaufman, and David Levartovsky
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Male ,Aortic arch ,medicine.medical_specialty ,Biopsy ,Giant Cell Arteritis ,Diagnosis, Differential ,Rheumatology ,medicine.artery ,Ascending aorta ,medicine ,Humans ,Arteritis ,Aorta ,Aged ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Abdominal aorta ,Angiography ,Arteries ,General Medicine ,Middle Aged ,medicine.disease ,Takayasu Arteritis ,Temporal Arteries ,Surgery ,Giant cell arteritis ,Treatment Outcome ,cardiovascular system ,Female ,Radiology ,Tomography, X-Ray Computed ,business ,Vasculitis - Abstract
The objective of this study is to describe a series of patients above the age of 50 years with large vessel arteritis and vascular involvement typical of TAK. A retrospective review of 18 patients (median age 64 years) with emphasis on clinical characteristics, laboratory values, and vascular involvement by CT, MRI, or planar angiography. Five patients fulfilled the ACR criteria for GCA, five for TAK, three both GCA and TAK, while five patients did not fulfill the criteria for either disease. The dominant presenting symptoms were constitutional, while only a few patients had cranial or peripheral symptoms. Sixty-one percent had physical signs of vascular compromise. Temporal artery biopsy showed giant cell arteritis in six out of nine biopsies. Arterial involvement: 78 % had either involvement of the ascending aorta, the aortic arch, descending or/and abdominal aorta, 9 carotid, 12 subclavian, 5 axillary, 3 renal, 7 iliac, and 2 femoral arteries; 7 mesenteric or celiac trunk. All the patients were treated with prednisone and 50 % with steroid-sparing drug. Nine out of 15 patients (60 %) achieved remission after 1 year of follow-up. No substantial differences in the distribution of vascular involvement, type of treatment, or outcome measures were observed between patients fulfilling criteria for GCA or TAK. Vascular involvement typical of TAK in patients above the age of 50 years with large vessel arteritis seems to be more frequent than previously assumed. Our findings support the assumption that TAK and GCA represent a spectrum of the same disease.
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- 2014
12. Introduction — Conflict Mediatization in the Middle East
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Daniel Rubinstein and Dan Caspi
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Middle East ,History ,Ethnology - Published
- 2017
13. Competing Trends in the Arab Press in Israel: From Print to the Internet
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Mustafa Kabha and Dan Caspi
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History ,business.industry ,Media studies ,Library science ,The Internet ,Performance art ,business - Published
- 2017
14. Another View of the Information Wall in the Israeli-Arab Conflict
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Daniel Rubinstein and Dan Caspi
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Political economy ,Political science - Published
- 2017
15. Just Like in America: New Media in the 18th Knesset Election Campaign 1
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Dan Caspi and Eleanor Lev
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Political science ,Knesset ,Media studies ,New media - Published
- 2017
16. AB0203 Expression levels of selected genes can predict the individual rheumatoid arthritis patient response to tumor necrosis factor alpha blocker treatment
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Adi Broyde, Uri Arad, Victoria Furer, Yoav Smith, David Levartovsky, S Pundak, Sara Pel, Ilana Kaufman, Ofir Elalouf, Dan Caspi, Jonathan Wollman, Ori Elkayam, and Daphna Paran
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Oncology ,medicine.medical_specialty ,Response to therapy ,business.industry ,Real life setting ,medicine.disease ,Patient response ,Retrospective data ,Quantitative Real Time PCR ,Internal medicine ,Rheumatoid arthritis ,Immunology ,medicine ,Tumor necrosis factor alpha ,business ,Moderate Response - Abstract
Background Rheumatoid arthritis (RA) patients have many therapeutic options. However, there are limited tools to predict the individual patient9s response to therapy. The Genefron personal diagnostic kit (IFR 300) has been developed based on analysis of large databases to select interferon stimulated gene (ISG) expressions which could predict response to a biologic agent Objectives This study aims to evaluate the ability of the Genefron diagnostic kit to predict the individual RA patient response to TNFα blockers. Methods Two separate analyses were performed, one retrospective and one prospective analysis. The response of 61 RA patients reported in 2 published data sets was analyzed retrospectively utilizing the Genefron kit. In addition, 18 patients with RA were assessed prospectively, before and 3 months after starting treatment with a TNFα blocker. Clinical assessment included swollen and tender joint counts, patient and physician assessments of disease activity. Patients9 blood samples were obtained before administration of the TNFα blocker and were analyzed utilizing the Genefron diagnostic kit which measures expression levels of selected genes by quantitative real time PCR. Results Genefron kit analysis of retrospective data correctly predicted the response to a TNFα blocker in 53 of 61 RA patients (accuracy - 86.8%). In the prospective analysis 6 patients achieved a moderate EULAR response, 6 achieved a good EULAR response and 6 did not respond. According to the EULAR moderate response, the Genefron diagnostic kit predicted the response correctly in 16 of 18 patients (accuracy-89%, sensitivity -100%, specificity - 67%). According to the EULAR good response, the kit predicted the response correctly in 15 of 18 patients (accuracy - 83.3%, sensitivity - 100%, specificity - 75%). Conclusions The Genefron diagnostic kit predicted the response to TNFα blockers in a high percentage of RA patients assessed either retrospectively or prospectively in a real life setting. This personal diagnostic kit has the ability to guide selection of a suitable biological drug for the individual RA patient Disclosure of Interest None declared
- Published
- 2017
17. AB0138 Interferon-gamma challenge of PBMC from patients with lupus nephritis in remission decreases suppressor of cytokine signaling 1 (SOCS1) and regulatory t cells (TREGS) and promotes immune activation
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Amir Sharabi, Ilana Kaufman, Daphna Paran, J Wallman, S Jacky, Valerie Aloush, Uri Arad, G. Gibor, Ori Elkayam, Dan Caspi, and Jacob N. Ablin
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030203 arthritis & rheumatology ,0301 basic medicine ,business.industry ,Suppressor of cytokine signaling 1 ,Lupus nephritis ,medicine.disease ,Peripheral blood mononuclear cell ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immunology ,medicine ,Interferon gamma ,business ,medicine.drug ,Immune activation - Published
- 2017
18. Reporting the Middle East
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Dan Caspi and Daniel Rubinstein
- Published
- 2017
19. Prevalence of Axial Spondyloarthritis Among Patients With Fibromyalgia: A Magnetic Resonance Imaging Study With Application of the Assessment of SpondyloArthritis International Society Classification Criteria
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Jacob N, Ablin, Iris, Eshed, Mark, Berman, Valerie, Aloush, Irena, Wigler, Dan, Caspi, Maria, Likhter, Jonathan, Wollman, Daphna, Paran, Marina, Anouk, and Ori, Elkayam
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Adult ,Male ,Fibromyalgia ,Sacroiliac Joint ,Middle Aged ,Magnetic Resonance Imaging ,Severity of Illness Index ,C-Reactive Protein ,Spondylarthritis ,Prevalence ,Humans ,Female ,Sacroiliitis ,HLA-B27 Antigen - Abstract
To evaluate the prevalence of sacroiliitis, the radiographic hallmark of inflammatory spondyloarthropathy, among patients diagnosed with fibromyalgia syndrome (FMS), using the current Assessment of SpondyloArthritis International Society (ASAS) criteria and magnetic resonance imaging.Patients experiencing FMS (American College of Rheumatology 1990 criteria) were interviewed regarding the presence of spondyloarthritis (SpA) features and underwent HLA-B27 testing, C-reactive protein (CRP) level measurement, and magnetic resonance imaging examinations of the sacroiliac joints. FMS severity was assessed by the Fibromyalgia Impact Questionnaire and the Short Form 36 health survey. SpA severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index.Sacroiliitis was demonstrated among 8 patients (8.1%) and ASAS criteria for diagnosis of axial SpA were met in 10 patients (10.2%). Imaging changes suggestive of inflammatory involvement (e.g., erosions and subchondral sclerosis) were demonstrated in 15 patients (17%) and 22 patients (25%), respectively. The diagnosis of axial SpA was positively correlated with increased CRP level and with physical role limitation at recruitment.Imaging changes suggestive of axial SpA were common among patients with a diagnosis of FMS. These findings suggest that FMS may mask an underlying axial SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such comorbidities.
- Published
- 2016
20. Longterm Efficacy of an Antipneumococcal Polysaccharide Vaccine among Patients with Autoimmune Inflammatory Rheumatic Diseases
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Dan Caspi, Ilana Kaufman, Adi Broyde, Uri Arad, David Levartovsky, Daphna Paran, Irena Wigler, Noa Madar-Balakirski, and Ori Elkayam
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Adult ,Male ,medicine.medical_specialty ,Spondyloarthropathy ,Immunology ,Inflammatory bowel disease ,Gastroenterology ,Pneumococcal Infections ,Autoimmune Diseases ,Pneumococcal Vaccines ,03 medical and health sciences ,Psoriatic arthritis ,Young Adult ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Rheumatic Diseases ,Immunology and Allergy ,Medicine ,Humans ,030212 general & internal medicine ,Aged ,030203 arthritis & rheumatology ,Aged, 80 and over ,Ankylosing spondylitis ,business.industry ,Vaccination ,Antibody titer ,Middle Aged ,medicine.disease ,Treatment Outcome ,Rheumatoid arthritis ,Antirheumatic Agents ,Methotrexate ,Female ,business ,medicine.drug - Abstract
Objective.To estimate the longterm humoral response of an antipneumococcal polysaccharide vaccine (PPSV23) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or inflammatory bowel disease (IBD)-associated spondyloarthropathy (SpA), and the effect of demographic and clinical factors and treatment on the longterm efficacy of the vaccine.Methods.A total of 145 consecutive patients treated with biologics [tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) receptor inhibitors] or methotrexate (MTX) participated in this study. Fifteen were excluded because of absent information regarding their vaccination status (n = 9) or because of technical problems in obtaining their serum sample (n = 6). They were diagnosed with RA (n = 63, 48.5%), PsA (n = 29, 22.3%), AS (n = 28, 21.5%), or IBD-associated SpA (n = 3, 2.3%). Their mean age was 54.6 years, and 61.5% were women. Data were collected on the timing of vaccination, demographic and clinical characteristics, and treatment, and patients’ serum antipneumococcal antibody levels were tested.Results.Two-thirds of the patients (67.7%) had received PPSV23 45 months (mean) earlier. Treatment included TNF-α inhibitors (73.9%), IL-6 receptor inhibitors (13.1%), or MTX without a biological treatment (13%). The uptake of vaccination was significantly higher in the older population (> 65 yrs). Vaccinated patients had significantly higher antibody levels compared with vaccine-naive patients. The antibody levels had been preserved after 10 years. MTX use, but not biologics, was associated with significantly lower antibody levels.Conclusion.The longterm efficacy of the PPSV23 vaccination seems to be preserved among patients with RA, PsA, AS, and IBD-associated SpA for at least 10 years. Efficacy is slightly impaired by MTX, but it is not affected by biologics. These findings suggest that revaccination after 5 years might not be needed for all, and testing the antibody titers should be considered to identify those who may benefit from revaccination.
- Published
- 2015
21. Impaired diffusion tensor imaging findings in the corpus callosum and cingulum may underlie impaired learning and memory abilities in systemic lupus erythematosus
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Irena Litinsky, Elissa L. Ash, Talma Hendler, Maya Weinstein, Marina Anouk, Irit Shapira-Lichter, Dan Caspi, Valerie Aloush, Daphna Paran, and N Lustgarten
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Adult ,Pathology ,medicine.medical_specialty ,Corpus callosum ,behavioral disciplines and activities ,Brain mapping ,Gyrus Cinguli ,Corpus Callosum ,Pathogenesis ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Rheumatology ,Antiphospholipid syndrome ,medicine ,Cingulum (brain) ,Humans ,Lupus Erythematosus, Systemic ,030203 arthritis & rheumatology ,Brain Mapping ,medicine.diagnostic_test ,business.industry ,Lupus Vasculitis, Central Nervous System ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Diffusion Tensor Imaging ,Female ,business ,Functional magnetic resonance imaging ,030217 neurology & neurosurgery ,Diffusion MRI - Abstract
Background Memory impairment is prevalent in systemic lupus erythematosus (SLE); however, its pathogenesis is unknown. In a previous functional magnetic resonance imaging (fMRI) study we demonstrated altered brain activity dynamics and less brain deactivation in patients with SLE as compared with healthy controls, when performing a learning and memory task. Our findings localized this impairment to the default mode network (DMN), and particularly to its anterior medial prefrontal cortex node. In addition, altered networking of the hippocampal subsystem of the DMN was seen in patients with SLE when performing this task, as well as atrophy of the left hippocampus. The present study aimed to search for a structural substrate for the altered recruitment pattern observed in fMRI studies using diffusion tensor imaging (DTI). Patients and methods Using DTI, we characterized brain diffusivity in 10 patients with SLE and nine healthy controls. Two tracts associated with the DMN were reconstructed: the corpus callosum (CC) and the cingulum bundle. The CC was segmented according to the Witelson segmentation scheme and the cingulum was segmented into superior and descending bundles. Results A significant increase in mean diffusivity (MD) was seen in patients with SLE without neuropsychiatric SLE (NPSLE) as compared with healthy controls in all five segments of the CC (segment 1: p = 0.043; segment 2: p = 0.005; segment 3: p = 0.003; segment 4: p = 0.012; segment 5: p = 0.023) as well as in the descending portion of the left cingulum bundle ( p = 0.026). Conclusions Increased MD values in the CC and the left cingulum may indicate impaired organization/reduced integrity of these tracts, which may underlie the abnormal pattern of brain activity recruitment of the DMN observed during a verbal learning and memory task. Taking into account the central role of the left hippocampus in verbal memory, the abnormal integrity of the left cingulum may contribute to the reduced performance of patients with SLE on verbal memory tasks.
- Published
- 2015
22. Measurement of Cellular Immunity to Influenza Vaccination in Rheumatoid Arthritis; Comparison of Three Assays
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Noa Madar-Balakirski, Ella Mendelson, Ori Elkayam, elboim, Michal M, Dan Caspi, Sharon Amir, and Uri Arad
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Cellular immunity ,education.field_of_study ,Hemagglutination assay ,Influenza vaccine ,business.industry ,Immunology ,Population ,Antibody titer ,Virology ,Vaccination ,Immune system ,Immunity ,Drug Discovery ,Immunology and Allergy ,Medicine ,business ,education - Abstract
Objective: Monitoring of immune responses is essential in the care of immunosuppressed individuals, including rheumatic patients. Evaluation of cellular immunity is essential for confirming virus-specific effector cell functions, but it is poorly standardized, and suffers from technical limitations and inaccurate results. There is, therefore, a need for reliable techniques for assessing cell-mediated immunity. In this study we compared the cell-mediated immunity response to influenza vaccine between a population of rheumatoid arthritis (RA) patients and healthy subjects by three methods. Methods: Trivalent influenza subunit vaccine was administered to 18 RA patients who were taking disease-modifying antirheumatic drugs and to 18 healthy controls. Peripheral blood mononuclear cells (PBMCs) and sera were obtained immediately before and ~28 days after vaccination. Cell-mediated immunity responses to vaccination were evaluated by (1) flow cytometric analysis of IL-2/IFN-γ production in activated CD4/CD8 T-cells, (2) enzyme-linked immunosorbent assay for the analysis of IFN-γ secretion, and (3) Granzyme B activity assay. Humoral response was evaluated by the hemagglutination inhibition assay. Results: Vaccination induced a significant increase in PBMC IFN-γ secretion and Granzyme B activity in the RA patients. Granzyme B activity also significantly increased in the controls, but there was no change in the levels of secreted IFN-γ. No group differences in the frequencies of IFN-γ/IL-2-producing activated CD4/CD8 T-cells were observed by flow cytometry. The geometric mean of hemagglutination inhibition antibody titers increased significantly for the H1N1/H3N2 influenza strains in both groups. Conclusions: Granzyme B activity assay was the only method to detect a significant cell-mediated immunity response in both groups while significant increase in IFN-γ secretion was demonstrated only in RA patients. Flow cytometric analysis failed to show IL-2 and IFN-γ production in both groups. Currently available methods for measuring cellular responsiveness to influenza vaccination are inconsistent and limited in their ability to reflect acquired cellular immunity.
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- 2015
23. Prevalence of TNF-α blocker immunogenicity in psoriatic arthritis
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Michael Zisapel, Hagit Matz, Ilana Kaufman, Hagit Padova, Noa Madar-Balakirski, Ori Elkayam, Devy Zisman, Uri Arad, Dan Caspi, Ira Litinsky, Joy Feld, Irena Wigler, Hagit Maman-Sarvagyl, and Daphna Paran
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Adult ,Male ,medicine.medical_specialty ,Immunology ,Arthritis ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Receptors, Tumor Necrosis Factor ,Etanercept ,Psoriatic arthritis ,Young Adult ,Rheumatology ,Internal medicine ,medicine ,Adalimumab ,Immunology and Allergy ,Humans ,Aged ,Aged, 80 and over ,biology ,business.industry ,Tumor Necrosis Factor-alpha ,Immunogenicity ,Arthritis, Psoriatic ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Antibodies, Neutralizing ,Infliximab ,Cross-Sectional Studies ,Methotrexate ,Antirheumatic Agents ,Immunoglobulin G ,biology.protein ,Female ,Antibody ,business ,medicine.drug - Abstract
Objective.The longterm use of tumor necrosis factor (TNF)-α blockers is limited by the formation of neutralizing antibodies. To the best of our knowledge, immunogenicity in psoriatic arthritis (PsA) has not been investigated in depth. Our objective was to evaluate the prevalence and significance of TNF-α blocker immunogenicity in PsA.Methods.Consecutive patients with PsA treated with either infliximab (IFX), adalimumab (ADA), or etanercept (ETN) > 3 months participated in our cross-sectional study. Their demographic and clinical characteristics, skin and joint disease activity, and records of use of methotrexate (MTX) and other medications were collected. Drug levels (ELISA) and antidrug antibodies (ADAb; Bridging ELISA) were evaluated before the next injection or infusion.Results.A total of 93 patients with PsA were recruited (48 receiving ADA, 24 IFX, and 21 ETN), with a mean age of 53 years (range 21–83 yrs), composed of 53% women. One-fourth of the patients were concomitantly treated with MTX. Altogether, 77% of the patients demonstrated therapeutic drug levels. High levels of ADAb were found in 29% of patients taking ADA, 21% taking IFX, and 0% taking ETN. ADAb significantly correlated with lower drug levels, higher 28-joint Disease Activity Scores, and higher global assessments. MTX use correlated significantly with a lower prevalence of ADAb.Conclusion.Significant levels of ADAb were present in up to 29% of patients with PsA treated with ADA or IFX. ADAb clearly correlated with low therapeutic drug levels and higher disease activity variables. The use of MTX significantly decreased ADAb prevalence, and its use should be strongly considered in combination with TNF-α blocker antibodies in patients with PsA.
- Published
- 2014
24. THU0316 Frequency of Axial Spondyloarthropathy Among Patients Suffering from Fibromyalgia. A Magnetic Resonance Imaging Study Applying the Assessment of Spondylo-Arthritis International Society Classification Criteria: Table 1
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Amir Sharabi, Sara Borok, M. Likhter, Daphna Paran, Valerie Aloush, Y. Wolman, Ori Elkayam, Jacob N. Ablin, Marina Anouk, Mark Berman, Dan Caspi, A. Rom-Broyde, David Levartovsky, I Wigler, and Iris Eshed
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,medicine.diagnostic_test ,Spondyloarthropathy ,business.industry ,Immunology ,Sacroiliitis ,Enthesitis ,Physical examination ,Dolorimeter ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Dactylitis ,Rheumatology ,Fibromyalgia ,Internal medicine ,medicine ,Physical therapy ,Immunology and Allergy ,medicine.symptom ,business ,BASDAI - Abstract
Background Fibromyalgia Syndrome (FMS), considered the result of increased processing of pain by the central nervous system, is a non-inflammatory condition characterized by chronic, widespread musculoskeletal pain and tenderness.Axial spondyloarthritis (SpA) is a group of inflammatory joint disease primarily involving the sacroiliac joints and axial spine. Although FMS and axial SpA differ vastly in their pathogenesis, a considerable clinical overlap may exist between these conditions. Chronic nocturnal back pain and disturbed sleep may accompany either condition. The Assessment of Spondylo-Arthritis international Society (ASAS) has published updated classification criteria for axial SpA with an imaging and clinical arms. We have previously described an increased prevalence of secondary FMS among female SpA patients. Objectives To evaluate the prevalence of axial SpA among FMS patients, utilizing the 2010 ASAS criteria (1). Methods Patients suffering from FMS (ACR 1990 classification criteria) were recruited consecutively from a specialized FMS clinic. Patients were interviewed regarding the presence of SpA features, as defined by the ASAS group (IBP, arthritis, enthesitis, uveitis, dactylitis, psoriasis, Crohn9s/colitis, good response to NSAIDS, family history of SpA) and underwent HLA-B27 testing and CRP measurement. MRI examinations of the sacroiliac joints were performed on a 1.5 T MRI unit using semicoronal T1 weighted, STIR and FSPGR pre- and post-contrast injection sequences. FMS severity was assessed by the FIQ and SF-36 questionnaires and physical examination of the tender points using a dolorimeter. SpA symptom severity was assessed by the BASDAI questionnaire Results 99 unselected patients were recruited and MRI results were available for 74. Sacroiliitis, based on ASAS definition (2), was found among 7 patients, 7 of which fulfilled ASAS SpA classification criteria. 6 patients fulfilled the criteria based on sacroiliitis on imaging and SpA features, one additional patient fulfilled SpA criteria based on HLA-B27 positivity and additional SpA features. Conclusions Imaging findings suggestive of inflammatory SpA were not uncommon among patients presenting with a clinical diagnosis of FMS. Definite sacroiliitis and ASAS criteria SpA positivity were diagnosed among 9.5% of patients and additional changes typical of SpA were frequent. These findings suggest that FMS may mask an underlying SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such co-morbidities. References Sieper J et al. Ann Rheum Dis 2009;68:8(Suppl II):ii1–ii44 Rudwaleit M et al. Ann Rheum Dis 2009; 68(10):1520 Disclosure of Interest J. Ablin Speakers bureau: Pfizer Inc., I. Eshed: None declared, M. Berman: None declared, V. Aloush: None declared, I. Wigler: None declared, D. Caspi: None declared, M. Likhter: None declared, A. Sharabi: None declared, A. Rom-Broyde: None declared, S. Borok: None declared, D. Levartovsky: None declared, Y. Wolman: None declared, D. Paran: None declared, M. Anouk: None declared, O. Elkayam: None declared
- Published
- 2015
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