Israel Medical Association Journal

Background: Although fat grafting is a common technique to repair defects after breast cancer reconstruction surgery and has a low complication rate, the relation between fat grafting and the risk of breast cancer is unknown. Clinical trials to investigate this connection can elucidate the benefits and potential risks of fat grafting in oncology patients.

Objectives:To establish an efficient experimental model, using magnetic resonance imaging (MRI) scans, for comparing different breast tumor study groups post-fat grafting. 

Methods: Breast tumor cells were injected into immunocompromised mice. After tumors formed they were removed. Liposuction was performed in a female human donor and fat was collected. Cells were extracted from the fat by enzymatic digestion. Immunocompromised mice were randomized into four groups: a preliminary experiment group and three equal groups according to the type of fat graft: (i) fresh fat enriched with adipose-derived mesenchymal stem cells (AdMSCs), (ii) fresh fat without cell enrichment, and (iii) no fat injected. Tumor volume was assessed by serial MRI scans. 

Results: The rate of tumor growth was higher in the enriched fat group compared to the non-enriched fat group. 

Conclusions: This experimental model is an effective measurable method, allowing future investigation of the effect of autologous fat on breast cancer.

 

Background: Radial artery occlusion (RAO) may occur following transradial catheterization, precluding future use of the vessel for vascular access or as a coronary bypass graft. Recanalization of RAO may occur; however, long-term radial artery patency when revascularization is more likely to be required has not been investigated. Transradial catheterization is usually performed via 5-Fr or 6-Fr catheters. Insertion of 7-Fr sheaths into the radial artery enables complex coronary interventions but may increase the risk of RAO. 

Objective: To assess the long-term radial artery patency following transradial catheterization via 7-Fr sheaths.

Methods: Antegrade radial artery blood flow was assessed by duplex-ultrasound in 43 patients who had undergone transradial catheterization via a 7-Fr sheath. 

Results: All patients had received intravenous unfractionated heparin with a mean activated clotting time (ACT) of 247 ± 56 seconds. Twenty-four patients (56%) had received a glycoprotein IIbIIIa inhibitor and no vascular site complications had occurred. Mean time interval from catheterization to duplex-ultrasound was 507 ± 317 days. Asymptomatic RAO was documented in 8 subjects (19%). Reduced body weight was the only significant univariate predictor of RAO (78 ± 11 vs. 89 ± 13 kg, P = 0.031). In a bivariate model using receiver operator characteristic (ROC) curves, the combination of lower weight and shorter ACT offered best prediction of RAO (area under the ROC curve 0.813). 

Conclusions: Asymptomatic RAO was found at late follow-up in approximately 1 of 5 patients undergoing transradial catheterization via a 7-Fr sheath and was associated with lower body weight and shorter ACT. 

 

Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that it is very difficult to diagnose in the early phase, resulting in a critical delay in therapy which is often begun when internal organ involvement is already irreversible. The ACR or LeRoy criteria have a low sensitivity for the early phases; these criteria were replaced by the ACR/EULAR 2013 criteria which improved the disease classification. Therefore, the SSc diagnosis may be delayed for several years after the onset of Raynaud’s phenomenon (RP) and even after the onset of the first non-RP symptom. RP, antinuclear antibodies (ANA) positivity, and puffy fingers were recently indicated as “red flags” (by the VEDOSS project) – that is, the main elements for suspicion of SSc in the very early phase of the disease. Confirming the diagnosis requires further tests, particularly nailfold videocapillaroscopy and evaluation of specific disease antibodies (anti-centromere and anti-topoisomerase I). In this way, the VEDOSS project identified patients in the very early phase of disease enabling a ‘‘window of opportunity’’ whereby the physician can act with effective drugs to block or at least slow the progression of the disease. The principal challenge in the fight against SSc is to detect valid predictors of disease evolution in order to treat patients in the early stage of disease. While waiting to find valid predictors, a close follow-up of the patients with the VEDOSS red flags is essential, as is a close collaboration between rheumatologists and general practitioners in order to identify all potential SSc patients as soon as possible.

Physical, mental and social well-being are important outcomes in patients with chronic rheumatic diseases, including systemic lupus erythematosus (SLE). The MOS SF-36 and the WHO QoL Bref are appropriate for assessing quality of life (QoL) in patients with SLE.  The QoL of patients with SLE is impaired compared with that of controls. Fibromyalgia adversely affects the QoL of SLE patients. Women with SLE had significantly lower scores on subscales of the sense of coherence (SoC) compared with matched controls. This reduced SoC in SLE women represents impaired adaptive coping and is independently associated with reduced QoL in women with SLE. Depression and anxiety are common among SLE patients, and the frequency is similar to that in patients with rheumatoid arthritis. A reciprocal longitudinal relationship between depression and illness intrusiveness was found in patients with SLE. Disease activity and damage are not associated with depression. The subjective experience, not the illness per se, causes depression.

Background: Antiphospholipid antibodies (aPL) have been advocated as potential mediators of unexplained female infertility, but no evidence has yet been raised to support such an association.

Objectives: To test the hypothesis that aPL might interfere with uterine decidualization, a gene expression study was performed on decidual stromal cells treated with different aPL preparations.

Methods: Decidual stromal cells were isolated from first-trimester deciduas obtained from two women undergoing elective abortion, and treated with: (i) a β2GPI-dependent aPL monoclonal antibody (IS3); (ii) IS3 plus TIFI, a synthetic peptide mimicking PL-binding region of β2GPI; and (iii) IgG from healthy subjects (NHS). Gene expression data were acquired using human HT-12 v3 beadchip arrays (Illumina). Differential expression analysis was performed by fitting a gene-wise linear model using the treatment group and decidual source as covariates.

Results: In the comparison of IS3 versus IgG NHS-treated decidual cells, gene ontology (GO) enrichment was expressed in terms relating to well-characterized aPL-mediated cellular effects: “inflammatory response,” “immune response,” “response to stress,” “oxydoreductase activity,” “metalloendopeptidase activity,” and “cytokine/chemokine activity.” As expected, almost all genes were up-regulated by IS3 treatment. The same GO categories appeared to be differentially expressed when IS3 treatment was compared to IS3 + TIFI, but with most genes being down-regulated.

Conclusions: Given the inflammatory response evinced at gene expression analysis on decidual stromal cells treated with a β2GPI -dependent aPL monoclonal antibody, it is feasible that aPL might interfere with uterine decidualization, affecting the early stages of implantation and ultimately resulting in female infertility.

 

Sjögren’s syndrome (SS), a chronic systemic autoimmune inflammatory condition involving the exocrine glands, has been suggested to be part of the spectrum of the “Autoimmune/inflammatory Syndrome Induced by Adjuvants” (ASIA). ASIA incorporates an umbrella of clinical conditions including siliconosis, macrophage myofasciitis syndrome, and post-vaccination phenomena that occur after the exposure to a substance, namely the adjuvant. Interestingly, SS and ASIA share several common features. Firstly, a shared pathogenic mechanism involving a disruption of the immune system balance, with B cell proliferation, cytokine production and tissue infiltration, have been proposed. Patients with ASIA often present clinical features resembling those of SS; dry mouth and dry eyes have also been included in the proposed classification criteria for ASIA. Finally, several case reports have suggested that both vaccines and silicone may trigger the development of SS. Unveiling these common pathways will contribute considerably to our understanding and managing of both conditions.

Long-term extension studies and observational drug registers have revealed an increased risk of serious infections in patients treated with anti-tumor necrosis factor agents, particularly infliximab, etanercept and adalimumab. The same may be true for the newer biological drugs rituximab, tocilizumab and abatacept, although this has yet to be confirmed by long-term observational studies. We review the risk of tuberculosis, herpes zoster and other opportunistic infections, and the recommendations for screening for tuberculosis and hepatitis B and C infections in patients affected by rheumatoid arthritis, with the aim of informing patients and encouraging greater awareness among physicians.

There is growing interest in the contribution of vitamin D deficiency to autoimmunity. Several studies have shown an association between low levels of vitamin D and autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes, autoimmune thyroid diseases, celiac disease, and systemic lupus erythematosus (SLE). Vitamin D receptor ligands can mediate immunosuppressive effects. It has been suggested that low levels of this hormone contribute to the immune activation in lupus and other autoimmune diseases. This review updates and summarizes the literature on the association between vitamin D and SLE, and discusses the various correlations between vitamin D and SLE activity, clinical expressions, serology, and gene polymorphisms of vitamin D receptors.

In recent years, salivary gland ultrasonography (SGUS) has emerged as a promising tool for the diagnosis and prognostic stratification of patients with primary and secondary Sjögren’s syndrome. Several studies have emphasized that salivary ultrasonography could be a highly specific tool for the diagnosis of the disease. However, before it can be used in daily clinical practice the SGUS procedure needs standardization and validation in larger disease-control groups. In this review we provide an update on the role of SGUS in the diagnostic algorithm of primary Sjögren’s syndrome.

Autoimmune diseases are classic examples of multifactorial disorders in which a large number of genes interact with environmental factors to form the final phenotype. Identification of the genes involved in these diseases is a daunting challenge. Initially the search involved the candidate approach where polymorphisms in suspected genes were tested for association in large cohorts of patients and controls. Today, the most widely used method is genome-wide association studies (GWAS), a method based on screening large panels of patients and controls with hundreds of thousands of single nucleotide polymorphisms (SNPs), with microarray-based technology. Unique families in which autoimmune diseases are caused by single genes are another alternative. The identification of candidate genes is often followed by studies that provide biologic plausibility for the findings. The widely expanding list of genes involved in autoimmune conditions show that the same genes frequently underlie the pathogenesis of different autoimmune diseases. Despite all available resources, the main void of heritability in autoimmune conditions is yet to be discovered. Identification of these genes will help define new biological pathways and identify novel targets for the development of new therapeutic drugs.