A panel of plasma microRNAs improves the assessment of surrogate markers of cardiovascular disease in rheumatoid arthritis patients.

OBJECTIVE: Patients with RA present increased risk of cardiovascular (CV) disease compared with the general population. Moreover, CV risk factors that have a causal relationship with atherosclerosis do not seem to fully explain the accelerated process that they exhibit. We evaluated the association of a 10 microRNAs panel with surrogate markers of subclinical arteriosclerosis [carotid intima-media thickness (cIMT), carotid plaque presence (cPP), pulse wave velocity (PWV) and distensibility] in a cohort of RA patients. MATERIAL AND METHODS: A total of 199 patients with RA were included. Surrogate markers of arteriosclerosis were measured with My Lab 60 X-Vision sonographer. MicroRNAs were extracted from plasma and quantified with qPCR. Multivariate models and classification methods were performed. RESULTS: Multivariate models showed that microRNAs-24 (ß = 15.48), 125a (ß = 9.93), 132 (ß = 11.52), 146 (ß = 15.12), 191 (ß = 13.25) and 223 (ß = 13.30) were associated with cIMT globally. MicroRNA-24 [odds ratio (OR) = 0.41], 146 (OR = 0.36) and Let7a (OR = 0.23) were associated with cPP in men. Including the microRNAs in a partial least square discriminant analysis model properly classified men with and without cPP. MicroRNA-96 (ß = -0.28) was associated with PWV in male patients. Finally, several miRNAs were also associated with cIMT, cPP and arterial stiffness in the high DAS28 group and in the earlier tertile groups of disease duration. CONCLUSION: Plasmatic expression of microRNA-24, 96, 103, 125a, 132, 146, 191, 223 and Let7a were associated with surrogate markers of CV disease and could be predictors of CV risk in patients with RA.

Plasma Expression of Carotid Plaque Presence-Related MicroRNAs Is Associated with Inflammation in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with problems beyond the joints such as cardiovascular (CV) disease. MicroRNA-24, -146 and -Let7a are associated with carotid plaque presence in RA patients. We evaluated whether these microRNAs were involved in the inflammatory state of RA, and we studied their gene targets to understand their role in inflammation and atherosclerosis. A total of 199 patients with RA were included. Inflammatory variables such as disease activity score 28 (DAS28) and erythrocyte sedimentation rate (ESR) were quantified. MicroRNAs were extracted from plasma and quantified with qPCR. Multivariate models and classification methods were used for analysis. The multivariate models showed that diminished expression of microRNA-146 was associated with inferior levels of DAS28-ESR, and the decreased expression of microRNA-24, -146 and -Let7a were associated with lowered ESR in the overall cohort. When microRNAs were evaluated globally, a global increase was associated with increased DAS28-ESR and ESR in the overall cohort. Sex-stratified analyses showed different associations of these microRNAs with the inflammatory variables. Finally, random forest models showed that microRNAs have a pivotal role in classifying patients with high and low inflammation. Plasmatic expressions of microRNA-24, -146 and -Let7a were associated with inflammatory markers of RA. These microRNAs are associated with both inflammation and atherosclerosis and are potential therapeutic targets for RA.

Characterization of 1H NMR Plasma Glycoproteins as a New Strategy To Identify Inflammatory Patterns in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease associated with a high index of morbidity and mortality from cardiovascular diseases. We used 1H NMR to characterize the plasma glycoprotein and lipoprotein profiles of a cohort of patients with RA ( n = 210) versus healthy individuals ( n = 203) to associate them with the RA disease and its severity. Using 1H NMR, we developed a line-shape method to characterize the two peaks associated with glycoproteins (GlycA and GlycB) and its derived variables: areas of GlycB (Area GlycB) and GlycA (Area GlycA), shape factors of these two peaks (H/W = height/width), and the distance between them (Distance GlycB-GlycA). We also used the advanced lipoprotein test Liposcale (CE) to characterize the lipoprotein subclasses. The standard lipid panel and traditional inflammatory markers such as C-reactive protein, the erythrocyte sedimentation rate, fibrinogen, the rheumatoid factor, anticitrullinated peptide antibodies, and the DAS28 index have also been determined. RA patients presented a significant 10.65% increase in the GlycA associated area compared with the control group ( p = 2.21 × 10-10). They also presented significantly higher H/W GlycA and GlycB ratios than the control population (H/W GlycB p = 7.88 × 10-8; H/W GlycA p = 5.61 × 10-8). The prediction model that uses the traditional inflammatory variables and the 1H NMR-derived parameters presented an AUC that was almost 10% higher than the model that only uses the traditional inflammatory variables (from 0.7 to 0.79 AUC). We have demonstrated that GlycA and GlycB variables derived from 1H NMR, along with classic inflammatory parameters, help to improve the classification of individuals with high RA disease activity.

Unravelling and Quantifying the "NMR-Invisible" Metabolites Interacting with Human Serum Albumin by Binding Competition and T2 Relaxation-Based Decomposition Analysis.

Quantitative profiling of low-molecular-weight metabolites (LMWMs) by 1H NMR is routinely used in high-throughput serum metabolomics. First, the protein background is attenuated using a T2 filter; then, the LMWM signals are resolved by line-shape fitting. However, protein-binding modifies the motional properties of LMWM, and their signal partially attenuates with the T2 filter, along with the protein background. Consequently, the quantified LMWM signals do not reflect the total concentration in serum but the nonbinding part. Here we present a novel strategy based on binding competition to promote the release of the "NMR-invisible" metabolites from serum proteins and achieve quantifications closer to total concentrations. The study focuses on five clinically relevant amino acids with different binding properties (valine, isoleucine, leucine, tyrosine, and phenylalanine). We analyzed their binding affinity to human serum albumin (HSA) in serum mimic samples and promoted the release of their bound fraction by TSP titration. Furthermore, we used a novel combination of pseudo-2D CPMG and multivariate curve resolution analysis, allowing the separation of LMWM and protein signals and providing LMWM quantifications corrected for transverse relaxation effects. We found that TSP concentrations larger than 3 mM released most of the bound fraction and validated these findings in real serum/plasma samples.

Plasma expression of microRNA-425-5p and microRNA-451a as biomarkers of cardiovascular disease in rheumatoid arthritis patients.

To validate in a cohort of 214 rheumatoid arthritis patients a panel of 10 plasmatic microRNAs, which we previously identified and that can facilitate earlier diagnosis of cardiovascular disease in rheumatoid arthritis patients. We identified 10 plasma miRs that were downregulated in male rheumatoid arthritis patients and in patients with acute myocardial infarction compared to controls suggesting that these microRNAs could be epigenetic biomarkers for cardiovascular disease in rheumatoid arthritis patients. Six of those microRNAs were validated in independent plasma samples from 214 rheumatoid arthritis patients and levels of expression were associated with surrogate markers of cardiovascular disease (carotid intima-media thickness, plaque formation, pulse wave velocity and distensibility) and with prior cardiovascular disease. Multivariate analyses adjusted for traditional confounders and treatments showed that decreased expression of microRNA-425-5p in men and decreased expression of microRNA-451 in women were significantly associated with increased (ß = 0.072; p = 0.017) and decreased carotid intima-media thickness (ß = -0.05; p = 0.013), respectively. MicroRNA-425-5p and microRNA-451 also increased the accuracy to discriminate patients with pathological carotid intima-media thickness by 1.8% (p = 0.036) in men and 3.5% (p = 0.027) in women, respectively. In addition, microRNA-425-5p increased the accuracy to discriminate male patients with prior cardiovascular disease by 3% (p = 0.008). Additionally, decreased expression of microRNA-451 was significantly associated with decreased pulse wave velocity (ß = -0.72; p = 0.035) in overall rheumatoid arthritis population. Distensibility showed no significant association with expression levels of the microRNAs studied. We provide evidence of a possible role of microRNA-425-5p and microRNA-451 as useful epigenetic biomarkers to assess cardiovascular disease risk in patients with rheumatoid arthritis.

Assessment of arterial stiffness variables in patients with rheumatoid arthritis: A mediation analysis.

We aimed to study arterial stiffness variables in patients with rheumatoid arthritis (RA), specifically considering their associations with path model mediation analysis. We examined arterial stiffness expressed by the pulse wave velocity (PVW), augmentation index (AIx), distensibility, and clinical and biochemical characteristics in a cohort of 214 RA patients. Variable associations were analysed using multivariate linear regression analysis. We also used path model mediation analysis for PWV variable. Our results indicate that age, systolic blood pressure (SBP), and body mass index (BMI) were significantly associated with PWV, and collectively accounted for 32% of PWV variability. The parallel mediation analysis showed that SBP and BMI accounted for 21% and 7% (a total of 28%) of the total effect of age on PWV, respectively, indicating a partial mediation effect. The associated variables with AIx were age and tender joint count, while those with distensibility were BMI and sex, overall accounting for 16.5% and 4.7% of the variation in AIx and distensibility, respectively. We observed no associations of arterial stiffness with inflammatory variables, disease activity and duration, or cholesterol levels. In conclusion, in our population of RA patients, age is the most important variable that determines the increase in PWV. We have also shown that a significant proportion of the negative effects of age on PWV occurs through increases in SBP and BMI. In our study, lipid and inflammation variables were not associated with an increase in arterial stiffness.

[Efficacy of gabapentin in the treatment of carpal tunnel syndrome]. / Eficacia de la gabapentina en el tratamiento del síndrome del túnel carpiano.

BACKGROUND AND OBJECTIVE: To evaluate the analgesic efficacy and safety of gabapentin in the treatment of carpal tunnel syndrome (CTS), as well as the electromyographic (EMG) evolution after 6 months. PATIENTS AND METHOD: A prospective study with a 6-month follow-up of patients with EMG diagnosis of primary CTS starting treatment with 1.800 mg/day of gabapentin. At baseline visit and after 6 months of treatment a complete clinical evaluation and an EMG study were performed. Adverse effects of gabapentin were also registered. RESULTS: Twenty-five patients were included, mean age (standard deviation) 58.88 (7.69) years. After 6 months of treatment, a statistically significant reduction of pain (p = 0.001) and improvement of severity of symptoms (p = 0.008) were observed, although functional capacity did not change. EMG was performed in 19 patients at 6 months. Compared to baseline EMG: 52.6% patients showed no changes in EMG findings, while 5.3% patients showed improvement and in 26.3% the EMG was normal. Progression was only seen in 15.8% of patients after 6 months of treatment. In 28% of the patients gabapentin was stopped because of side effects. CONCLUSIONS: In our series, gabapentin was effective in the reduction of pain and improvement of the severity of the symptoms. Results of EMG after 6 months of treatment showed no changes, with improvement and/or remission in 84.2% of the cases. The drug was safe and well tolerated.

Variables associated with subclinical atherosclerosis in a cohort of rheumatoid arthritis patients: Sex-specific associations and differential effects of disease activity and age.

OBJECTIVE: To advance the study of variables associated with subclinical atherosclerosis in rheumatoid arthritis (RA) with special consideration for the degree of disease activity, age and gender. METHODS: The carotid intima-media thickness (cIMT) and the presence of carotid atherosclerotic plaques along with clinical and biochemical characteristics were determined in 214 RA patients. RESULTS: Adjusted analysis reveals that men had a 0.059 mm significantly increased cIMT compared with women (p = 0.001; R2 = 3.8%) and that age was associated with cIMT (ß = 0.0048 mm; p = 0.0001; R2 = 16%). Interestingly, we observed a significant interaction between gender and age. Thus, the effect of age on cIMT was significantly increased (12%) in men compared with women (p-value for interaction term = 0.041). Moreover, adjusted multivariable linear regression analysis revealed that disease activity score (DAS28) was significantly associated with cIMT in women (ß = 0.021; p = 0.018: R2 = 0.03) but not men. In particular, women with high disease activity had a 0.079 mm increased cIMT compared with women in remission (p = 0.026). In addition, men in remission had a 0.134 mm increased cIMT compared with women in remission (p = 0.003; R2 = 8.7%). Active patients did not exhibit differences in cIMT values. Furthermore, 43% of patients presented carotid plaques. The variables independently associated with carotid plaques were age, smoking, health assessment questionnaire, erythrocyte sedimentation rate and rheumatoid factor (p<0.0001; R2 = 46%). CONCLUSION: In our cohort of patients with RA, DAS28 and age are differentially associated with cIMT in men and women. Our findings could explain the contradictory results that have previously been published in the literature.

[Dyspnea in a patient with systemic lupus erythematosus]. / Disnea en una paciente con lupus eritematoso sistémico.

A 33-year-old woman with a previous history of systemic lupus erythematosus complained of exerptional dyspnea and pleuritic chest pain accompanied by polyarthritis. Chest-X-rays revealed an elevation of the right hemidiaphragm. We discuss the diagnostic and therapeutic approach.

Fe de errores de “Artritis séptica por Propionbacterium acnes” / No disponible

No disponible

Disnea en una paciente con lupus eritematoso sistémico / Dyspnea in a patient with systemic lupus erythematosus

Paciente de 33 años, con antecedentes de lupus eritematoso sistémico que consulta por disnea progresiva de moderados esfuerzos acompañada de dolor torácico derecho de características pleuríticas. En la radiografía simple de tórax se evidenció elevación del hemidiafragma derecho. Se discute a continuación el abordaje diagnóstico y terapéutico de la paciente (AU)

A 33-year-old woman with a previous history of systemic lupus erythematosus complained of exertional dyspnea and pleuritic chest pain accompanied by polyarthritis. Chest-X-rays revealed an elevation of the right hemidiaphragm. We discuss the diagnostic and therapeutic approach (AU)

Eficacia de la gabapentina en el tratamiento del síndrome del túnel carpiano / Efficacy of gabapentin in the treatment of carpal tunnel syndrome

Fundamento y objetivo: Evaluar la eficacia analgésica y la seguridad de la gabapentina en el tratamiento del síndrome del túnel carpiano (STC), así como la evolución electromiográfica (EMG) a los 6 meses. Pacientes y método: Estudio prospectivo de 6 meses de duración en los pacientes con diagnóstico EMG de STC primario en tratamiento con gabapentina a dosis de 1.800 mg/día. En la visita basal y a los 6 meses se realizaron valoración clínica, exploración y EMG, y se registraron los efectos adversos. Resultados: Se incluyó en el estudio a 25 pacientes con una edad media (desviación estándar) de 58,88 (7,69) años. A los 6 meses se observó una reducción del dolor (p = 0,001) y de la intensidad de los síntomas (p = 0,008), sin cambios en la capacidad funcional. El EMG se realizó a los 6 meses en 19 pacientes, de los que no se observaron cambios respecto a EMG basal en un 52,6%, se apreció mejoría en un 5,3%, progresión en un 15,8% y curación en un 26,3%. En un 28% se retiró el tratamiento por efecto adverso. Conclusiones: En nuestra serie la gabapentina fue eficaz en la reducción del dolor y en la mejoría de la intensidad de los síntomas. El EMG a los 6 meses de tratamiento demostró estabilidad, mejoría y/o curación en el 84,2% de los casos. La gabapentina resultó segura y bien tolerada

Background and objective: To evaluate the analgesic efficacy and safety of gabapentin in the treatment of carpal tunnel syndrome (CTS), as well as the electromyographic (EMG) evolution after 6 months. Patients and method: A prospective study with a 6-month follow-up of patients with EMG diagnosis of primary CTS starting treatment with 1.800 mg/day of gabapentin. At baseline visit and after 6 months of treatment a complete clinical evaluation and an EMG study were performed. Adverse effects of gabapentin were also registered. Results: Twenty-five patients were included, mean age (standard deviation) 58.88 (7.69) years. After 6 months of treatment, a statistically significant reduction of pain (p = 0.001) and improvement of severity of symptoms (p = 0.008) were observed, although functional capacity did not change. EMG was performed in 19 patients at 6 months. Compared to baseline EMG: 52.6% patients showed no changes in EMG findings, while 5.3% patients showed improvement and in 26.3% the EMG was normal. Progression was only seen in 15.8% of patients after 6 months of treatment. In 28% of the patients gabapentin was stopped because of side effects. Conclusions: In our series, gabapentin was effective in the reduction of pain and improvement of the severity of the symptoms. Results of EMG after 6 months of treatment showed no changes, with improvement and/or remission in 84.2% of the cases. The drug was safe and well tolerated

Meningitis aséptica con ADA elevado tras interrupción del tratamiento antirretroviral / Aseptic meningitis with elevated adenosine deaminase (ADA) after interruption of antiretroviral treatment

No disponible