Therapeutic yoga reduces pro-tumorigenic cytokines in cancer survivors.

INTRODUCTION: Chronic inflammation can remain many years after the completion of cancer treatment and is associated with cancer recurrence. The purpose of this study was to examine how a 16-week therapeutic yoga program (TYP) modulates the cytokine profile in heterogeneous cancer survivors. METHODS: Eligible participants were 18 years of age or older and clinically diagnosed with cancer. Consenting participants were asked to attend three, 75-min sessions weekly of TYP with meditation. Seventeen patients provided blood samples at baseline and end of study. Eight cytokines (interferon (IFN)-γ; interleukin (IL)-1b, IL-1ra, IL-4, IL-6, IL-8, IL-10; and tumor necrosis factor (TNF)-α), three receptors (sIL-6R, sTNFRI, sTNFRII), and C-reactive protein (CRP) were quantified. RESULTS: Patients were 59.6 ± 7.3 years old; over half (56%) were overweight or obese BMI ≥ 25 kg/m2); majority were female (71%) and breast cancer survivors (65%), of which 44% were Hispanic. Marked reductions were observed in all cytokines except IL-4, with significant reductions (p < 0.05) found in IL-1b (- 13%) and IL-1ra (- 13%). No significant changes were observed in soluble cytokine receptors or CRP. CONCLUSIONS: TYP led to significant reduction in circulating cytokines associated with chronic inflammation in a heterogeneous sample of cancer survivors.

Synthesis and evaluation of HfO2 as a prospective filler in inorganic-organic hybrid membranes based on Nafion for PEM fuel cells.

Hybrid inorganic-organic Nafion membranes modified with metal oxides (typically TiO2, ZrO2, WO3) are a good alternative for fuel cell applications. However, one of their main limitations is associated with their relative low proton conductivity at temperatures above 80 °C. In this work, we overcome this issue using HfO2 as a filler. HfO2 was prepared by a sol-gel method, and it was compared with a recast Nafion membrane (named as recast). Deconvolved XPS spectra confirmed the presence of hafnia, while EDS analysis was used to determine its weight content resulting in a 1.88 wt%. FT-IR ATR experiments indicated that the HfO2 hybrid membrane possess a higher capability to retain water than the recast. Thus, the water uptake, swelling degree, conductivity tests and fuel cell evaluations were performed. The water uptake analysis revealed that the hybrid membrane presented a higher retention percentage at 100 °C (61%) than recast (29%). This improvement enabled a higher ionic conductivity at 80 °C and 100 °C. The hybrid membrane displayed a higher conductivity at 100 °C than the recast membrane (112 versus 82 mS cm-1), increasing the cell performance to 0.36 W cm-2; being this performance almost two-fold higher to that obtained for the recast membrane. In summary, herein we demonstrated that HfO2 can be considered as an excellent substitute to conventional fillers.

Encapsulation of allogeneic mesenchymal stem cells in alginate extends local presence and therapeutic function.

Bone marrow derived mesenchymal stem cells (MSCs) have immunomodulatory and trophic capacities. For therapeutic application in local chronic inflammatory diseases, MSCs, preferably of allogeneic origin, have to retain immunomodulatory properties. This might be achieved by encapsulation of MSCs in a biomaterial that protects them from the host immune system. Most studies investigating the properties of MSCs for therapeutic application use short term cultures of cells in monolayer. Since the physical environment of MSCs can influence their functionality, we evaluated the feasibility of preserving the immunomodulatory properties of MSCs encapsulated in a three-dimensional alginate construct. After 5 weeks of implantation in immunocompetent rats, active allogeneic MSCs encapsulated in alginate were still detectable by Bio Luminescence Imaging and Magnetic Resonance Imaging of luciferase transduced and superparamagnetic iron oxide labelled MSCs. MSCs injected in saline were only detectable up to 1 week after injection. Moreover, the MSCs encapsulated in alginate responded to inflammatory stimuli similarly to MSCs in monolayer culture. In addition, MSC-alginate beads secreted immunomodulatory and trophic factors and inhibited T-cell proliferation after 30 d of in vitro culture. Our data indicate that allogeneic MSCs encapsulated in alginate persist locally and could act as an interactive immunomodulatory or trophic factor release system for several weeks, making this an interesting system to investigate for application in inflammatory disease conditions.

Netrin-1 and multiple sclerosis: a new biomarker for neuroinflammation?

BACKGROUND AND PURPOSE: Netrin-1, an axon guidance protein, reduces serum levels of pro-inflammatory mediators and stabilizes the blood-brain barrier limiting the entrance of immune cells into the central nervous system. The aim was to investigate its presence in the experimental autoimmune encephalomyelitis (EAE) model and in multiple sclerosis (MS) patients with and without clinical activity. METHODS: Netrin-1 levels were evaluated in EAE mouse tissues. Afterwards, serum netrin-1 was cross-sectionally quantified in 90 patients with different MS phenotypes and 30 control subjects. An additional group of 10 relapsing-remitting MS (RRMS) patients was longitudinally evaluated throughout a relapse (RRMSr) with an interval of 60 days. Tumour necrosis factor α (TNFα), a reference inflammatory cytokine, and netrin-1 were quantified by enzyme-linked immunosorbent assay. RESULTS: Experimental autoimmune encephalomyelitis mice showed significantly lower netrin-1 levels and higher TNFα amounts in sera, spinal cord and cerebella than healthy control mice. MS patients showed significantly lower serum netrin-1 levels than controls (511.62 ± 209.30 and 748.32 ± 103.24 pg/ml, respectively; P ≤ 0.005). The lowest protein levels were found in RRMSr, remaining significantly lower throughout the relapse. TNFα serum concentrations were higher in MS patients compared to controls, and negatively correlated with netrin-1 levels (r = -0.3734, P ≤ 0.0001). CONCLUSIONS: Netrin-1 decreased in EAE and in MS patients, mainly during relapse, suggesting an anti-inflammatory role of netrin-1. Further research should be performed in a larger cohort of patients to validate netrin-1 as a biomarker of MS inflammatory activity.

A genome-wide association study identifies a new locus associated with the response to anti-TNF therapy in rheumatoid arthritis.

Anti-Tumor Necrosis Factor (anti-TNF) drugs are biologic agents commonly used to treat rheumatoid arthritis (RA). However, anti-TNFs are not effective in approximately one out of four treated patients. We conducted a Genome-Wide Association Study (GWAS) to identify the genetic variation associated with the response to anti-TNF therapy in RA. In the discovery stage, 372 RA patients treated with an anti-TNF agent (infliximab, adalimumab or etanercept) were analyzed and treatment response was defined at 12 weeks of therapy. We found a genome-wide significant association in the MED15 gene with the response to etanercept (P<1.5e-8). Using an independent cohort of 245 RA patients, we performed a replication study of the most significant GWAS associations. We replicated the association at the MED15 locus and found suggestive evidence of association in the previously associated MAFB locus. The results of this study suggest novel mechanisms associated with the response to anti-TNF therapies.

Uncovered secret of a Vasseur-Tramond wax model.

The technique of anatomical wax modelling reached its heyday in Italy during the 18th century, through a fruitful collaboration between sculptors and anatomists. It soon spread to other countries, and prestigious schools were created in England, France, Spain and Austria. Paris subsequently replaced Italy as the major centre of manufacture, and anatomical waxes were created there from the mid-19th century in workshops such as that of Vasseur-Tramond. This workshop began to sell waxes to European Faculties of Medicine and Schools of Surgery around 1880. Little is known of the technique employed in the creation of such artefacts as this was deemed a professional secret. To gain some insight into the methods of construction, we have studied a Vasseur-Tramond wax model in the Valladolid University Anatomy Museum, Spain, by means of multi-slice computerised tomography and X-ray analysis by means of environmental scanning electron microscopy. Scanning electron microscopy was used to examine the hair. These results have revealed some of the methods used to make these anatomical models and the materials employed.

JC virus reactivation in patients with autoimmune rheumatic diseases treated with rituximab.

OBJECTIVES: To evaluate the presence of John Cunningham virus (JCV) DNA in patients with autoimmune rheumatic diseases (ARDs) treated with rituximab (RTX). METHOD: We assessed the JCV DNA levels in peripheral blood mononuclear cell (PBMC), serum, and urine samples by quantitative real-time polymerase chain reaction (qPCR) in a cohort of 42 ARD patients (20 of whom were being treated with RTX) and 42 healthy donors. Approximately 1 year later, we collected further samples from 32 of these 42 ARD patients, all of whom were being treated with RTX. We studied the association between these viral DNA prevalences and various clinical and demographic variables. RESULTS: The viral prevalence in PBMC, serum, and urine samples was 2.4% (1/42), 0%, and 50% (21/42), respectively, in the healthy donors, and 26% (8/31), 16% (5/31), and 86% (25/29), respectively, in the patients treated with RTX. The viral prevalences were not associated with any of the demographic or clinical variables included in the study. CONCLUSIONS: We detected a viral reactivation in PBMCs and serum during the RTX treatment that did not seem to be influenced by either use of immunosuppressive drugs or the length of treatment with the monoclonal antibody. Although this reactivation was asymptomatic, the viral presence in blood could increase the probability of the appearance of a neurotrophic variant of JCV.

[Randomised clinical trial to compare two tracheotomy care methods in an Intensive Care Unit]. / Ensayo clínico aleatorizado para la comparación de dos métodos de cura de traqueotomía en una Unidad de Cuidados Intensivos.

INTRODUCTION: Tracheotomy is a common technique in Intensive Care Units (ICU). It is known that nursing care during and after that procedure is directly related to its success, by reducing the possible complications to a minimum, such as the stoma infection, and contributing to a favourable outcome in critical patients. OBJECTIVES: To compare the use of polyhexanide (PLX) versus saline+povidone iodine (PY) as antiseptics and infection incidence in tracheostomies performed in Intensive Care Units. MATERIAL AND METHOD: A 2-year, experimental, randomised, open-label trial carried out in a multidiscipline ICU with 32 beds. The study was approved by the Research Ethics Committee of Principality of Asturias. RESULTS: The overall infection rate observed for every hundred patients was 1.34 (95% CI; 0.81-2.01), with 1.46 when using PLX and 1.21 for PY (P=.685). CONCLUSIONS: In spite of the experimental treatment (PLX) was shown to be effective in other types of wounds in our study. No significant differences were found between this technique and the standard one. Since there is no national registry of tracheotomy- associated infections, it is not possible to know whether the rate observed is within the usual parameters.

Burden of skeletal-related events in prostate cancer: unmet need in pain improvement.

PURPOSE: Up to 75% of patients with prostate cancer experience metastatic bone disease, which leads to an increased risk for skeletal-related events (SREs) including pathological bone fracture, spinal cord compression, and hypercalcemia of malignancy. Our objective was to systematically review the literature on the impact of SREs on quality of life (QOL), morbidity, and survival with a primary focus on the impact of SREs on pain in prostate cancer patients. METHODS: We searched PubMed, limiting to peer-reviewed English-language human studies published in 2000-2010. The search was based on the US Food and Drug Administration and European Medicines Agency definition of an SRE, which includes pathologic fracture, spinal cord compression (SCC), hypercalcemia of malignancy, and radiotherapy or surgery to bone resulting from severe bone pain. RESULTS: A total of 209 articles were screened, of which 173 were excluded, and 36 were included in this review. Patients with SREs had more pain and worse survival compared with no SREs. Pathologic bone fractures worsened QOL and were associated with shorter survival. Radiation therapy of SCC alleviated pain and improved morbidity. SCC was associated with decreases in patient survival. Radiation therapy and surgery to bone improved pain. CONCLUSIONS: Specific SREs are associated with worse outcomes, including increased pain, poorer QOL, morbidity, and survival. Treatment of SREs is associated with improved pain, although there remains a need for more effective treatment of SREs in prostate cancer patients.

Oleanolic acid modulates the immune-inflammatory response in mice with experimental autoimmune myocarditis and protects from cardiac injury. Therapeutic implications for the human disease.

Myocarditis and dilated cardiomyopathy (DCM) are inflammatory diseases of the myocardium, for which appropriate treatment remains a major clinical challenge. Oleanolic acid (OA), a natural triterpene widely distributed in food and medicinal plants, possesses a large range of biological effects with beneficial properties for health and disease prevention. Several experimental approaches have shown its cardioprotective actions, and OA has recently been proven effective for treating Th1 cell-mediated inflammatory diseases; however, its effect on inflammatory heart disorders, including myocarditis, has not yet been addressed. Therefore, the present study was undertaken to determine the effectiveness of OA in prevention and treatment of experimental autoimmune myocarditis (EAM). The utility of OA was evaluated in vivo through their administration to cardiac α-myosin (MyHc-α614-629)-immunized BALB/c mice from day 0 or day 21 post-immunization to the end of the experiment, and in vitro through their addition to stimulated-cardiac cells. Prophylactic and therapeutic administration of OA dramatically decreased disease severity: the heart weight/body weight ratio as well as plasma levels of brain natriuretic peptide and myosin-specific autoantibodies production were significantly reduced in OA-treated EAM animals, compared with untreated ones. Histological heart analysis showed that OA-treatment diminished cell infiltration, fibrosis and dystrophic calcifications. OA also decreased proliferation of cardiac fibroblast in vitro and attenuated calcium and collagen deposition induced by relevant cytokines of active myocarditis. Furthermore, in OA-treated EAM mice the number of Treg cells and the production of IL-10 and IL-35 were markedly increased, while proinflammatory and profibrotic cytokines were significantly reduced. We demonstrate that OA ameliorates both developing and established EAM by promoting an antiinflammatory cytokine profile and by interfering with the generation of cardiac-specific autoantibodies, as well as through direct protective effects on cardiac cells. Therefore, we envision this natural product as novel helpful tool for intervention in inflammatory cardiomyopathies including myocarditis.

Stain-free detection as loading control alternative to Ponceau and housekeeping protein immunodetection in Western blotting.

It is currently a routine practice to require a measurement of a housekeeping reference, including actin, glyceraldehyde-3-phosphate dehydrogenase, ß-tubulin, among others, in Western blots, as it is the rule in RNA blots. Reversible Ponceau staining has been applied successfully to check equal loading of gels. Here we test a new technique, with the Stain-Free gels from Bio-Rad, against both Ponceau staining and housekeeping protein immunodetection under different conditions. Our results show that Stain-Free gels outperform Ponceau staining and that both are more consistent than housekeeping proteins as a loading control.

Single-nucleotide polymorphisms at the 9p21.3 genomic region not associated with the risk of cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic polygenic inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular disease (CVD). In this study, we evaluated the potential association of 9p21.3 single-nucleotide polymorphisms (SNPs) - previously linked to coronary artery disease - and CVD risk in 2001 Spanish RA patients genotyped for 9p21.3 SNPs using TaqMan™ assays. Carotid intima media thickness (cIMT) and presence of carotid plaques were also analyzed. Cox regression model did not disclose significant differences between patients who experienced CVD and those who did not. Neither association was found between cIMT or carotid plaques and SNPs allele distribution. In conclusion, results do not support a role of rs10116277 or rs1537375 SNPs in CVD risk in Spanish RA patients.

The 11q23.3 genomic region-rs964184-is associated with cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease associated with high risk of cardiovascular (CV) events. Recently, the rs964184 polymorphism has been associated with coronary artery disease in nonrheumatic Caucasian individuals. 2160 Spanish RA patients were genotyped for the rs964184 polymorphism. Sex, age at diagnosis and traditional CV risk factors (diabetes mellitus, dyslipidemia and smoking habit) were associated with increased risk of CV events. Interestingly, RA patients carrying the rs964184 GG genotype had significantly higher risk of CV events than those with CC genotype [hazard ratio (HR) = 2.91, 95% confidence interval (CI): 1.36-6.26, P = 0.006] after adjusting the results for sex, age at diagnosis and traditional CV risk factors. Our results indicate that rs964184 polymorphism is associated with CV disease in RA.

Leflunomide discontinuation in rheumatoid arthritis and influence of associated disease-modifying anti-rheumatic drugs: a survival analysis.

OBJECTIVES: The aims of this study were to describe the rate of leflunomide discontinuation in rheumatoid arthritis (RA) patients, in standard clinical practice, and to analyse which factors could influence this rate, paying particular attention to the concomitant treatment with other disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We selected RA patients, diagnosed according to the 1987 American College of Rheumatology (ACR) criteria, attending the rheumatology outpatient clinic of the San Carlos Clinical Hospital (Madrid, Spain), who had started treatment with leflunomide between 1 January 2006 and 1 January 2011. Clinical records were examined until withdrawal of the drug, loss of follow-up, or 1 October 2011. Kaplan-Meier curves were set to account for leflunomide withdrawal. Cox bivariate and multivariate regression models were conducted to examine risk factors for leflunomide discontinuation. RESULTS: The incident rate (IR) for leflunomide discontinuation, regardless of the cause, was 27 per 100 patient-years [95% confidence interval (CI) 22-31]. We observed, in both the bivariate and multivariate regression analysis, that those aged > 75 years at the start of the leflunomide treatment and undergoing concurrent treatment with methotrexate (MTX) and/or hydroxychloroquine (HC) had a significantly higher risk of leflunomide discontinuation. CONCLUSIONS: An older age at the start of the treatment with leflunomide, or concomitant treatment with MTX and/or HC, could be associated with a higher risk of leflunomide discontinuation, regardless of the cause. Therefore, when taking MTX or HC, patients receiving leflunomide should be closely monitored early to detect the occurrence of adverse reactions, and hence prevent their aggravation.

Expression of human endogenous retrovirus HERV-K18 is associated with clinical severity in osteoarthritis patients.

OBJECTIVES: The aim of this study was to evaluate the involvement of human endogenous retrovirus K18 (HERV-K18) in osteoarthritis (OA), by genotyping the HERV-K18 env locus in OA patients and controls, and analysing HERV-K18 RNA expression and its association with OA risk and clinical variables. METHOD: We recruited 558 patients with symptomatic OA and 600 controls. We performed the genotyping by TaqMan assays and the analysis of expression by quantitative real-time polymerase chain reaction (qRT-PCR). Scores on the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), the Lequesne index, and the Stanford Health Assessment Questionnaire (HAQ) were analysed with regard to the expression levels of HERV-K18. RESULTS: The 18.3 haplotype tended towards an association with OA risk and concordantly this haplotype was associated with a higher HERV-K18 expression (p = 0.05). We found statistically significant differences when we compared the scores on the WOMAC, the Lequesne index for knee and hip, and the HAQ between OA patients with higher expression [normalization ratio (NR) > 10] and OA patients without HERV-K18 expression (p = 0.0003, 0.0005, 0.002, and 0.05, respectively), and also when the comparison was made between OA patients with higher expression (NR > 10) and OA patients with low expression of HERV-K18 (NR = 1) for the WOMAC and the Lequesne index for knee and hip (p = 0.002, 0.013, and 0.006, respectively). CONCLUSIONS: We found an association between health status measurement systems and severity index for OA and the levels of expression of HERV-K18. These results suggest the possible involvement of HERV-K18 in the aetiopathogenesis of the disease.

Comparison of measurements made on dry bone and digital measurements in Anatomage for the sacral bone in a Spanish population.

The use of osteometry for human identification is a key element in the field of forensic sciences. Currently, the osteometry focuses on the use of digital techniques such as photography or 3D scans, to study and measure bones, offering advantages like easy access, preservation of bones, and worldwide collaboration possibilities. The study aims to analyze whether digital tools such as Anatomage can be used to collect reliable data. The study compares measurements of the sacral bone from 41 individuals from Orgiva Collection using both traditional and digital methods. The variables analyzed were described previously, including landmarks and positions, and were coded by differentiating the measurements between dry bone (caliper) and digital measurement (Anatomage). Results indicate minimal differences between digital and dry bone measurements, with only one variable showing a significant differences in the effect size analysis (d > 0.80). The TEM analysis showed four variables as non-acceptable (rTEM > 1.5), possibly due to the landmark location or the experience using the tool to locate landmarks. Digital resources are valuable for morphometric evaluations and human identification within forensic sciences. However, caution is necessary to ensure accurate landmark localization and validate these tools across various bone types and larger sample sizes.

Pharmacological therapy in the secondary prevention of ischemic stroke in the oldest-old patients: has it improved in recent decades?

INTRODUCTION: Population aging has caused an increase in strokes in very elderly patients (VEP). We assess how secondary prevention of ischemic stroke has changed in VEP in recent decades. METHOD: Retrospective study of discharges due to ischemic stroke in the Virgen Macarena, Virgen del Rocio and Valme hospitals in Seville (Spain), during the periods 1999-2001, 2014-16 and 2019-2020. VEP were considered those with ≥80 years. RESULT: We studied 1806 patients, 349 (19.3%) were VEP. Over the years, VEPs have doubled (13.5% vs. 25.9% and 28% p = 0.0001) and age has increased (83.3 ±â€¯3 vs. 84.1 ±â€¯3 vs. 85.2 ±â€¯4 p = 0.001). Comparing the periods, the VEPs have more hypertension (69.9% vs. 84.8% vs. 84.6%; p = 0.0001) and dyslipidemia (12% vs. 41.7% vs. 52.3%; p = 0.0001) and have prescribed more antihypertensives (69.1% vs. 86.7% vs. 92.3%; p = 0.0001), statins (5.3% vs. 78% vs. 81.5%; p = 0.0001) and anticoagulants (16.5% vs. 19.4% vs. 53.1%; p = 0.001), increasing the number of antihypertensives (1 ±â€¯0.9 vs. 1.6 ±â€¯0, 9 vs. 1.9 ±â€¯0.8 drugs p = 0.0001), and high-intensity statins (2.3% vs. 42.7 vs. 69.2% p = 0.0001). Comparing the VEPs with the younger ones, there were no differences in antihypertensive treatment in any period, there were differences in antithrombotic treatment in the first period, and with statins the differences were maintained until the end. CONCLUSIONS: In the last 20 years the number of VEPs has doubled, exceeding a quarter of the discharges. Although there is improvement in secondary stroke prevention in VEPs, there is room for improvement.

Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis.

OBJECTIVE: The methionine sulfoxide reductase A (MSRA) gene is related to oxidative stress that has been involved in the susceptibility to rheumatoid arthritis (RA) in genome-wide pathway analysis and replication studies. The aim of the present study was to determine whether the MSRA gene is implicated in susceptibility to cardiovascular (CV) disease in RA patients. METHODS: A total of 1302 patients fulfilling the 1987 American College of Rheumatism classification criteria for RA were genotyped for the MSRA rs10903323 (G/A) polymorphism. Two hundred and thirty-three (17.9%) patients experienced CV events. Human leucocyte antigen (HLA)-DRB1 genotyping was performed using molecular-based methods. Multiple logistic regression models were constructed with adjustments for gender, age at RA diagnosis, follow-up, rheumatoid shared epitope, and traditional CV risk as potential confounders. RESULTS: There were no statistically significant differences in the allele or genotype frequencies for the MSRA rs10903323 polymorphism between RA patients who experienced CV events and those who did not. However, an adjusted logistic regression model disclosed that the minor allele G yielded a marginally significant increased risk of CV events in this series of patients with RA [p = 0.05, odds ratio (OR) 1.68, 95% confidence interval (CI) 1.00-2.85]. When the logistic regression model was adjusted for anti-cyclic citrullinated peptide (anti-CCP) antibody status instead of for shared epitope, an increased risk of having ischaemic heart disease was found in patients carrying the minor allele G (p = 0.04, OR 2.00, 95% CI 1.03-3.88). CONCLUSION: The MSRA rs10903323 gene polymorphism may be implicated in the increased risk to develop CV events, in particular ischaemic heart disease, observed in RA patients.

Influence of MHCIITA rs3087456 and rs4774 polymorphisms in the susceptibility to cardiovascular disease of patients with rheumatoid arthritis.

OBJECTIVES: MHCIITA is a major regulator of MHC expression that has been reported to be involved in the susceptibility to rheumatoid arthritis (RA) and myocardial infarction. In this study we investigated the potential association of two MHCIITA gene polymorphisms with cardiovascular (CV) risk in patients with RA. METHODS: 1302 patients fulfilling the 1987 ACR classification criteria for RA were genotyped for the MHCIITA rs3087456 and rs4774 gene polymorphisms to determine the influence of MHCIITA variants in the development of CV events. The potential influence of these polymorphisms in the development of subclinical atherosclerosis was also analysed in a subgroup of patients with no history of CV events by the assessment of two surrogate markers of atherosclerosis; brachial and carotid ultrasonography to determine endothelial function and carotid artery intima-media thickness, respectively. RESULTS: No statistically significant differences in the allele or genotype frequencies for each individual MHCIITA gene polymorphism between RA patients who experienced CV events, or not, were found. This was also the case when each polymorphism was assessed according to results obtained from surrogate markers of atherosclerosis. Also, in assessing the combined influence of both MHCIITA gene polymorphisms in the risk of CV disease after adjustment for gender, age at time of disease diagnosis, follow-up time, traditional CV risk factors, and shared epitope status, patients with CV events only showed a marginally decreased frequency of the MHCIITA rs3087456-rs4774 G-G allele combination (p=0.08; odds ratio: 0.63 [95% confidence interval: 0.37-1.05]). CONCLUSIONS: Our data do not support an influence of MHCIITA rs3087456 and rs4774 polymorphisms in the increased risk of CV events of patients with RA.