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עמוד בית
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October 2014
Elisabetta Borella MD, Lavinia Palma MD, Margherita Zen MD, Silvano Bettio MD, Linda Nalotto MD, Mariele Gatto MD, Marta Domeneghetti MD, Luca Iaccarino MD, Leonardo Punzi and Andrea Doria MD
Autoinflammatory (AIF) and autoimmune (AIM) diseases are chronic immune disorders characterized by dysregulation of the immune system. Most AIF diseases are monogenic diseases which lead to hyperactivation of the inflammasome and release of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and IL-18, resulting in tissue inflammation. Besides, the main feature of autoimmune diseases is the loss of tolerance of the adaptive immune cells against self antigens. Most AIF diseases are polygenic and numerous immune pathogens are involved in organ damage. The involvement of some AIF-associated mechanisms in AIM diseases, i.e., the activation of the inflammasome and the role of IL-1, was recently recognized. Moreover, some single nucleotide polymorphisms of the inflammasome genes have been proven to be involved in the development of AIF-related inflammatory features in autoimmune patients. These observations raise the possibility of using some anti-inflammatory drugs, like IL-1 antagonists, in autoimmune diseases with autoinflammatory features. 
Orit Barrett MD, Ella Abramovich MD, Jacob Dreiher MD MPH, Victor Novack MD PhD and Mahmoud Abu-Shakra MD
Piercarlo Sarzi-Puttini MD and Fabiola Atzeni MD PhD
Laura Andreoli MD, Rossella Reggia MD, Lara Pea MD, Micol Frassi MD, Alessandra Zanola PhD, Stefania Cartella MD, Franco Franceschini MD and Angela Tincani MD
Carlo Perricone MD, Shunit Rinkevich-Shop PhD, Miri Blank PhD, Natalie Landa-Rouben PhD, Cristiano Alessandri MD, Fabrizio Conti MD, PhD, Jonathan Leor MD, Yehuda Shoenfeld MD FRCP and Guido Valesini MD
M. Galeazzi, L. Bazzichi, G.D. Sebastiani, D. Neri, E. Garcia Gonzalez, N. Ravenni, L. Giovannoni, J. Wilton, M. Bardelli, C. Baldi, E. Selvi, A. Iuliano, G. Minisola, R. Caporali, E. Prisco and S. Bombardieri
September 2014
Liora Ore MD MPH, Hanna J. Garzozi MD, Naama Schwartz MA and Michal Cohen-Dar MD MPH

Background: The detection and correction of refractive errors is one of the priorities of the World Health Organization Initiative Vision 2020.

Objectives: To determine the factors related to a child having an ocular abnormality (poor vision, refractive error or other abnormality) among schoolchildren in northern Israel.

Methods: A cross-sectional population-based study was conducted among 2113 students aged 6-7 and 13-14 years old in 70 schools in northern Israel. Medical examination included vision history, clinical eye examination and vision testing. If a parent’s informed consent was available, eye drops (cycloplegia) were delivered for fundus and retinoscopy testing. An ophthalmologist was asked to determine the need for the child’s referral for further diagnostic procedures, treatment and/or follow-up. Multivariate analysis was limited to 1708 children, using data pertaining to the ophthalmologist’s decision regarding referral, as well as vision and retinoscopy results.

Results: Vision and/or ocular abnormality was prevalent in 21.5% (95% confidence interval 17.4–26.6%), predominantly among 13-14 year olds and Jewish children. Abnormal clinical findings were found in 5.7% of the students. Retinoscopy showed a higher prevalence of hypermetropia among 6-7 year olds and a higher prevalence of myopia and astigmatism among the 13-14 year olds. The multivariate analysis suggests an independent effect of retinoscopy abnormality (odds ratio = 3.85), vision abnormality (OR [1]= 2.42), Jewish ethnicity (OR = 1.62) and 13-14 year old age group (OR = 1.26) on the ophthalmologist’s referral decision.

Conclusions: Vision and/or ocular abnormality is an important health problem among schoolchildren in northern Israel. The independent effect of ethnicity and age on the ophthalmologist’s referral decision should be further explored.


 





OR = odds ratio 



Smadar Gertel MD and Howard Amital MD MHA

The major autoantigens in the inflamed synovium in rheumatoid arthritis (RA) are citrullinated peptides. Citrullinated peptides are employed in diagnostic kits for detection of anti-citrullinated protein antibodies (ACPA), a serological marker with high specificity and sensitivity in the diagnosis of RA, and have been included in the new ACR/EULAR classification criteria for RA. ACPA-positive RA patients suffer from an erosive and more aggressive disease compared to ACPA-negative patients. In view of the mounting indications that ACPA plays a seminal role in the pathogenesis of RA, it might be valuable to pursue a specific treatment aiming ACPA as a target. We found that citrullinated peptides, which contain a unique amino acid, citrulline, alter the protein structure within the connective tissue, leading to tolerance breakdown and triggering the autoimmune response in RA. However, with different doses and routes of administration, citrullinated peptides can promote immune tolerance rather than induction of disease. 

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. 

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. 

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.  
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