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עמוד בית
Sun, 25.09.22

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October 2021
Rotem Shpatz MD, Yolanda Braun-Moscovici MD, and Alexandra Balbir-Gurman MD

Background: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease with the presence of autoantibodies, rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPA). The presence of RF or ACPA predicts RA severity. Data on the influence of ACPA titer on RA course are limited.

Objectives: To determine the correlation between ACPA titers at the time of RA diagnosis to RA features and severity during 3 years of follow-up.

Methods: We performed a retrospective study of RA patients treated at our institution during the years 2006–2015 with known ACPA titers at RA diagnosis who completed at least 3 years of follow-up. Patients (N=133) were divided according to ACPA titer: seronegative (< 15 U/ml, n=55), weakly positive (15–49 U/ml, n=18), moderately positive (50–300 U/ml, n=29), and strongly positive (> 300 U/ml, n=31). Patient data, including disease activity score (DAS28), bone erosion on hand and/or foot X-rays, treatments with corticosteroids and disease-modifying-anti-rheumatic drugs (DMARDs), and hospitalizations, were recorded. Chi-square and Mann-Whitney method were used for statistical analysis. P < 0.05 was considered as statistically significant.

Results: Male gender, smoking, and RF positivity correlated with ACPA positivity and higher ACPA titers. There was no correlation between ACPA titer and the variables defined as representing RA severity: higher DAS28, bone erosions, hospitalizations, need for corticosteroids, and conventional and biological DMARDs.

Conclusions: Titer of ACPA was not identified as a predictive factor for RA severity

May 2021
Lea Kahanov MD, José E. Cohen MD, Shifra Fraifeld MBA, Cezar Mizrahi MD, Ronen R. Leker MD, Samuel Moscovici MD, and Sergey Spektor MD PhD

Background: Superficial temporal artery-middle cerebral artery microvascular bypass (STA-MCA MVB) is an important strategy for the management of selected patients.

Objective: To present our 19-year experience with STA-MCA MVB.

Methods: Data for consecutive patients who underwent STA-MCA MVB from 2000–2019 due to moyamoya/moyamoya-like disease, complex intracranial aneurysms, or intractable brain ischemia due to internal carotid artery or MCA occlusive disease with repeated ischemic events were retrospectively analyzed under a waiver of informed consent. Key surgical steps and the important role of neuroendovascular interventions are presented. Surgical results and late outcomes were analyzed.

Results: The study included 32 patients (17 women [53%], 15 men [47%]), mean age 42.94 years (range 16–66). The patients underwent 37 STA-MCA MVB procedures during the study period: 22 with moyamoya/moyamoya-like disease (69%) underwent 27 surgeries (five bilateral); 7 patients with complex aneurysms (22%) and 3 patients with vascular occlusive disease (9%) underwent unilateral bypass. Five of seven aneurysms were treated with coiling or flow-diverter stent implant prior to bypass surgery; two were clipped during the bypass procedure. There were no surgical complications, no perioperative mortality, and no death from complications related to neurovascular disease at late follow-up. Transient neurological deficits following 7/37 surgeries (19%) resolved with no permanent neurologic sequelae. Transient ischemic attacks occurred only in the immediate postoperative period in four patients (11%).

Conclusions: In specific cases, STA-MCA MVB is a feasible and clinically effective procedure. It is important to preserve this technique in the surgical armamentarium

November 2020
Katya Dolnikov MD, Gai Milo MD, Suheir Assady MD, Robert Dragu MD, Yolanda Braun-Moscovici MD, and Alexandra Balbir-Gurman MD
August 2020
Yolanda Braun-Moscovici MD, Devy Zisman MD and Alexandra Balbir-Gurman MD
May 2020
Yolanda Braun-Moscovici MD, Yonit Tavor MD, Doron Markovits MD PhD, Kohava Toledano MD, Alexander Rozin MD, Menahem A. Nahir MD PhD and Alexandra Balbir-Gurman MD

Background: Behçet's disease is a multi-systemic chronic relapsing inflammatory disease, classified among the vasculitides. The heterogeneity of clinical manifestations challenges the disease management.

Objectives: To assess efficacy and safety of adalimumab in patients with active persistent Behçet's arthritis who did not respond to disease-modifying anti-rheumatic drugs and to assess the impact of treatment on the cytokine milieu.

Methods: Our cohort comprised 10 patients with active arthritis who received adalimumab in a 24-week investigator-initiated prospective open-label study. Patients who relapsed within 12 weeks following adalimumab discontinuation could enter a 3-year extension study. The patients underwent a comprehensive assessment including questionnaires and measurement of inflammatory cytokines, adalimumab serum levels, and anti-drug antibodies.

Results: A significant improvement was observed in arthritis, disease activity visual analogue scales, Behçet's disease current activity form, and interleukin-6 (IL-6) levels, but not in health assessment questionnaire and functional assessment of chronic illness therapy fatigue scale questionnaire. Resolution of oral and urogenital ulcers was achieved in all patients. Significant reduction of pain was reported by 40% of patients. The disease relapsed in 9 of 10 patients, within 2–6 weeks following adalimumab discontinuation. Of the 7 patients who continued the study, arthritis was resolved in 5. Two patients with high neutralizing antidrug antibodies titer relapsed.

Conclusions: Adalimumab treatment achieved a significant improvement in arthritis, mucocutaneous manifestations, and IL-6 levels in all study patients but only 40% reported significant pain reduction. The arthritis relapsed in 90% of patients following adalimumab discontinuation and long-term treatment was required.

January 2019
Alexandra Balbir-Gurman MD, Vika Shataylo BSc and Yolanda Braun-Moscovici MD

Background: The aggregation of autoimmune diseases in relatives (AID-R) of patients with systemic sclerosis (SSc) has been reported.

Objectives: To analyze the prevalence of autoimmune diseases in SSc relatives and to compare their features to those of SSc patients without AID-R (controls).

Methods: A case-control analysis compared SSc patients with AID-R to those without AID-R (25 patients) with similar disease duration.

Results: Among 322 patients, 25 (7.7%; 21 females, 41.4 ± 15.6 years of age, disease duration 11 ± 8.6 years) had AID-R (21 had a first-degree relative, 4 had a second-degree relative, and 2 had both). Fourteen patients (56%) and five controls (20%) had an additional autoimmune disease (P < 0.009). Diffuse SSc (48% vs. 24%) and arthritis (72% vs. 28%) were more frequent among the patients with AID-R than the controls (P < 0.05). No significant differences were found regarding lung, heart, vascular, and digestive system involvement. The mean number of additional autoimmune diseases was 0.84 ± 0.94 in AID-R vs. 0.24 ± 0.52 in controls (P < 0.038). The mean number of autoantibodies was 2.8 ± 1.5 and 2.2 ± 0.9 (P < 0.047). Five patients died during follow-up, four of whom had AID-R. Relatives of SSc patients had diverse autoimmune diseases; the prevalence of SSc in scleroderma relatives was 1.86% (2 in first-degree and 6 in second-degree relatives). SSc patients with AID-R had an obvious tendency to polyautoimmunity.

Conclusion: A precise family history is an important clue in prognosis and prediction of autoimmune diseases in SSc patients and their relatives.

February 2016
Avi Moscovici MD, Michael Kogan MD, Iris Kliers MD, Olga Kukuy MD and Gad Segal MD
September 2015
Rina Elimelech BDS, Yaniv Mayer DMD, Yolanda Braun-Moscovici MD, Eli E. Machtei DMD and Alexandra Balbir-Gurman MD

Background: Systemic sclerosis (SSc) is a chronic disease with prominent vasculopathy, inflammation, production of autoantibodies, and tissue fibrosis. Periodontitis is a chronic inflammatory oral condition manifesting as microbial infection, inflammation and destruction of the alveolar bone. In both conditions tumor necrosis factor-alpha (TNFα) and other pro-inflammatory cytokines play an important role in pathogenesis. 

Objectives: To assess the periodontal status in SSc patients and compare these parameters to TNFα level in gingival crevicular fluid (GCF) of SSc patients and healthy controls.

Methods: Twenty SSc patients and 20 controls underwent periodontal examination, including probing depth (PD), plaque index (PI), gingival index (GI), bleeding on probing (BOP), and measurement of TNFα levels in collected GCF. 

Results: SSc patients had a greater PD (3.74 ± 0.32 mm vs. 3.35 ± 0.31 mm, P > 0.003), GI (1.53 ± 0.34 vs. 1.12 ± 0.54, P > 0.049), and non-significantly higher BOP than controls. TNFα levels in GCF were higher in SSc patients (1.63 ± 0.36 vs. 1.15 ± 0.34 pg/ml, P = 0.001). Periodontitis parameters correlated with several SSc variables; PI in particular was higher in patients with longer disease duration, sclerodactyly, more severe skin involvement, and SSc activity score.

Conclusions: Patients with SSc have higher indices of periodontal inflammation and higher TNFα level in GCF than did healthy individuals. These changes probably reflect the complexity of factors that influence oral health in SSc. Common pathologic pathways may be responsible for the association between SSc and periodontitis, which requires further study.

 

March 2015
Alexandra Balbir-Gurman MD, Mordechai Yigla MD, Ludmila Guralnik MD, Emilia Hardak MD, Anna Solomonov MD, Alexander P. Rozin MD, Kohava Toledano MD, Amir Dagan MD, Rema Bishara MD, Doron Markovits MD PhD, Menahem A. Nahir MD and Yolanda Braun-Moscovici MD

Abstract

Background: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12–24 months in most reports.

Objectives: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.

Methods: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1, 4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed.

Results: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0–4 and 4–7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G).

Conclusions: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

 

August 2013
A. Dagan, D. Markovits, Y. Braun-Moscovici, A. Rozin, K. Toledano and A. Balbir-Gurman
December 2012
August 2011
A. Balbir-Gurman, B. Fuhrman, Y. Braun-Moscovici, D. Markovits and M. Aviram

 Background:  Pomegranate extract (POMx) consumption has been shown to reduce the incidence and severity of collagen-induced arthritis in mice.

Objectives:  To investigate whether pomegranate consumption affects disease activity in patients with rheumatoid arthritis (RA), in relation to their serum oxidative status.

Methods:  In this pilot 12 week open-labeled study eight patients with active RA consumed POMx (10 ml/day) for 12 weeks. Patients’ joint status and serum oxidative status (lipid peroxidation, total thiols group, paraoxonase 1 activity) were evaluated at baseline and at week 12.

Results:  Six patients completed the study. POMx consumption significantly (P < 0.02) reduced the composite Disease Activity Index (DAS28) by 17%, which could be related mostly to a significant (P < 0.005) reduction in the tender joint count (by 62%). These results were associated with a significant (P < 0.02) reduction in serum oxidative status and a moderate but significant (P < 0.02) increase in serum high density lipoprotein-associated paraoxonase 1 (PON1) activity. The addition of POMx to serum from RA patients reduced free radical-induced lipid peroxidation by up to 25%.

Conclusions:  The pomegranate consumption reduced DAS28 in RA patients, and this effect could be related to the antioxidative property of pomegranates. Dietary supplementation with pomegranates may be a useful complementary strategy to attenuate clinical symptoms in RA patients.

January 2011
A. Balbir-Gurman and Y. Braun-Moscovici

Background: Overlap syndrome is an entity that satisfies the criteria of at least two connective tissue diseases. These conditions include systemic sclerosis, dermatomyositis or polymyositis, Sjogren's syndrome, rheumatoid arthritis and systemic lupus erythematosus. A combined pathology has impact on the clinical features, diagnosis and treatment.

Objectives: To analyze the features of SSc[1] patients with overlap syndrome registered in the European (EUSTAR) database at our center and to review the literature focusing on clinical and diagnostic issues and new treatments.

Methods: We studied the medical records of 165 consecutive SSc patients and reviewed cases with scleroderma overlap syndrome. Using the key words “overlap syndrome," "systemic sclerosis," “connective tissue disease” and “biological agents” we conducted a PubMed search for the period 1977 to 2009.

Results: Forty patients satisfied the criteria for scleroderma overlap syndrome. The incidence of additional connective tissue diseases in the whole group and in the overlap syndrome group respectively was: dermatomyositis or polymyositis 11.5% and 47.5%, Sjogren's syndrome 10.3% and 42.5%, rheumatoid arthritis 3.6% and 15.4%, and systemic lupus erythematosus 1.2% and 5.0%. Coexistence of SSc and another CTD[2] aggravated the clinical course, especially lung, kidney, digestive, vascular and articular involvement. Non-rheumatic complications mimicked SSc complications. An additional rheumatic or non-rheumatic disease affected treatment choice.

Conclusions: The definition of scleroderma overlap syndrome is important, especially in patients who need high-dose corticosteroids for complications of a CTD. The use of novel biological therapies may be advocated in these patients to avoid the hazardous influences of high-dose steroids, especially renal crisis. In some overlap syndrome cases, biological agents serve both conditions; in others one of the conditions may limit their use. In the absence of formal clinical trials in these patients a cautious approach is preferred.






[1] SSc = systemic cclerosis

[2] CTD = connective tissue disease


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