Cardiorespiratory fitness and age-related arterial stiffness in women with systemic lupus erythematosus.

BACKGROUND: The aim of this study was twofold: (i) to examine the association of cardiorespiratory fitness with arterial stiffness in women with systemic lupus erythematosus; (ii) to assess the potential interaction of cardiorespiratory fitness with age on arterial stiffness in this population. MATERIALS AND METHODS: A total of 49 women with systemic lupus erythematosus (mean age 41.3 [standard deviation 13.8] years) and clinical stability during the previous 6 months were included in the study. Arterial stiffness was assessed through pulse wave velocity (Mobil-O-Graph® 24 hours pulse wave velocity monitor). Cardiorespiratory fitness was estimated with the Siconolfi step test and the 6-minute walk test. RESULTS: Cardiorespiratory fitness was inversely associated with pulse wave velocity in crude analyses (P < .05), although this relationship was attenuated when age and other cardiovascular risk factors were controlled. There was a cardiorespiratory fitness × age interaction effect on pulse wave velocity, regardless of the test used to estimate cardiorespiratory fitness (P < .001 for the Siconolfi step test; P = .005 for the 6-minute walk test), indicating that higher cardiorespiratory fitness was associated with a lower increase in pulse wave velocity per each year increase in age. CONCLUSIONS: The results of this study suggest that cardiorespiratory fitness might attenuate the age-related arterial stiffening in women with systemic lupus erythematosus and might thus contribute to the primary prevention of cardiovascular disease in this population. As the cross-sectional design precludes establishing causal relationships, future clinical trials should confirm or contrast these findings.

Association between perceived level of stress, clinical characteristics and psychopathological symptoms in women with systemic lupus erythematosus.

OBJECTIVES: To evaluate psychopathological status and stress level from a sample with SLE; compare mental functioning and stress levels between women with SLE and healthy women; determine whether disease duration, disease activity, cumulative organ damage and stress have an influence on psychopathological symptoms in SLE patients; and evaluate whether perception of stress is related to SLE severity. METHODS: We conducted a cross-sectional study of 425 participants; 202 women with SLE, with an average age (SD) of 36.61 (10.15), and 223 healthy women, with age-matched controls. The assessment included the clinical characteristics (disease duration, SLE activity, cumulative organ damage, pharmacotherapy), the Symptom Checklist-90-Revised (SCL-90-R) and the Perceived Stress Scale. Descriptive, comparative, univariate and multivariate analysis were performed. RESULTS: SLE patients showed psychopathological alterations in the somatisation, obsessive-compulsive and positive discomfort subscales of SCL-90-R. Women with SLE reported significantly higher scores on the psychopathological dimensions and perceived stress compared to healthy women, except for paranoid ideation. Disease duration, SLE activity, cumulative organ damage, and perceived stress were shown to be significant predictors of psychopathological manifestations, explaining a range, between 20 and 43%, of variance across SCL-90-R dimensions. Moreover, perceived stress was related to SLE activity, after controlling for psychopathological dimensions. CONCLUSIONS: The psychopathological manifestations in SLE appeared to be influenced by perceived stress, disease duration, disease activity and cumulative organ damage. In turn, perceived stress was associated with disease severity. This knowledge may contribute to a more comprehensive perspective of these manifestations in the SLE population in the clinical setting.

Effect of ethnicity on clinical presentation and risk of antiphospholipid syndrome in Roma and Caucasian patients with systemic lupus erythematosus: a multicenter cross-sectional study.

AIM: To determine if there are ethnic differences in the prevalence of antiphospholipid syndrome (APS), clinical presentation and autoantibody profile between Roma and Caucasian patients with systemic lupus erythematosus (SLE). METHOD: A cross-sectional study was conducted including data from Roma and Caucasian SLE patients consecutively attending six hospitals in Spain. Socio-demographic characteristics, prevalence of APS, clinical and analytical features of SLE and APS were compared between ethnic groups. RESULTS: Data from 52 Roma and 98 Caucasian SLE patients were included. Roma SLE patients had a higher risk (odds ratio 2.56, 95% CI 1.02-6.39) and prevalence of APS (28.8% vs. 13.3%, P = 0.027). Furthermore, Roma SLE patients had a statistically significant higher prevalence of abortions (23.5% vs. 10.2%, P = 0.049). In relation to other APS diagnostic criteria, Roma SLE patients had a non-statistically significant higher prevalence of fetal deaths (14.3% vs. 5.1%, P = 0.106) and thrombotic events (21.1% vs. 12.2%, P = 0.160). In relation to SLE clinical features, Roma patients had a significantly higher prevalence of arthritis (75% vs. 57.1%, P = 0.034) and non-significant higher prevalence of serositis (44.2% vs. 29.6%, P = 0.104), discoid lesions (11.5% vs. 5.1%, P = 0.191), oral ulcers (46.1% vs. 34.7%, P = 0.218) and livedo reticularis (21.1% vs. 15.3%, P = 0.374). No statistically significant differences were found in the Systemic Lupus International Collaborating Clinics Damage Index or the autoimmune serological profile. CONCLUSION: Prevalence and risk of APS were significantly higher in Roma SLE patients. Furthermore, Roma patients had a significantly higher prevalence of abortions and a non-significant higher prevalence of fetal deaths and thrombotic events.

Potentially inappropriate prescribing according to STOPP-2 criteria among patients discharged from Internal Medicine: prevalence, involved drugs and economic cost.

AIM: This study aims to determine the prevalence of potentially inappropriate prescribing (PIP) among patients discharged from Internal Medicine, the drugs and factors associated and economic cost of PIP. METHODS: This retrospective cross-sectional, single-center study included participants aged ≥65 years consecutively discharged from the Internal Medicine Unit in a tertiary hospital of Southern Spain. PIP was defined by the Screening Tool for Older Persons Prescriptions (STOPP-2) criteria version 2 (2015 update). The association of PIP with chronic conditions was analyzed using multilevel logistic regression model. Data on economic cost associated to PIP were determined according to the computerized prescribing database of Andalusia ("Receta XXI"). RESULTS: Out of the 275 patients studied, a total of 249 PIPs were detected in 114 (41.5%) patients of whom 79 (28.7%) had one or two STOPP-2 criteria and 35 (12.7%) 3 or more criteria. The most involved drugs were benzodiazepines (45.5%); antithrombotics (14.5%), including anticoagulants or antiplatelets, and opioids (11.4%). The multivariate logistic regression analysis identified polypharmacy (OR=11.00; 95% CI 1.41-85.52) and extreme polypharmacy (OR=26.25; 95% CI 3.34-206.07) as independent risk factors for PIP. The mean cost of PIP was €18.75±4.24 per patient and month. Opioids accounted for the highest percentage expenditure of PIP (39.02%), followed by inhaled bronchodilator drugs (30.30%), antithrombotics (12.20%) and benzodiazepines (7.92%). CONCLUSIONS: PIP is frequent among patients discharged from Internal Medicine. The number of prescribed drugs was independently associated to PIP and benzodiazepines were the most involved drugs. PIP was associated to a significant economic cost.

Una causa no habitual de distrés respiratorio del adulto / An unusual cause of adult respiratory distress

No disponible

Off-label use of rituximab for systemic lupus erythematosus in Europe.

OBJECTIVES: Rituximab (RTX) is a biological treatment used off-label in patients with systemic lupus erythematosus (SLE). This survey aimed to investigate the off-label use of RTX in Europe and compare the characteristics of patients receiving RTX with those receiving conventional therapy. METHODS: Data on patients with SLE receiving RTX were taken from the International Registry for Biologics in SLE retrospective registry and complemented with data on patients with SLE treated with conventional therapy. For nationwide estimates of RTX use in patients with SLE, investigators were asked to provide data through case report forms (CRFs). Countries for which no data were submitted through CRFs, published literature and/or personal communication were used, and for European countries where no data were available, estimates were made on the assumption of similarities with neighbouring countries. RESULTS: The estimated off-label use of RTX in Europe was 0.5%-1.5% of all patients with SLE. In comparison with patients with SLE on conventional therapy, patients treated with RTX had longer disease duration, higher disease activity and were more often treated with immunosuppressives. The most frequent organ manifestations for which either RTX or conventional therapy was initiated were lupus nephritis followed by musculoskeletal and haematological. The reason for treatment was, besides disease control, corticosteroid-sparing for patients treated with conventional therapy. CONCLUSIONS: RTX use for SLE in Europe is restrictive and appears to be used as a last resort in patients for whom other reasonable options have been exhausted.

Relationship between QT Interval Length and Arterial Stiffness in Systemic Lupus Erythematosus (SLE): A Cross-Sectional Case-Control Study.

INTRODUCTION AND OBJECTIVES: The QT interval on the electrocardiogram has been shown to be longer in patients with systemic lupus erythematosus (SLE) compared to that of the general population. The clinical significance of this finding is unknown. The aim of this study was to assess the relationship between QT interval and subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. MATERIAL AND METHODS: 93 patients with SLE and 109 healthy women with similar basal characteristics were studied. All patients underwent a 12- lead electrocardiogram, and corrected QT interval (QTc) was measured using the Bazett's formula. The presence of atherosclerosis was evaluated by carotid-femoral pulse-wave velocity. RESULTS: Clinical basal characteristics were similar in both groups. QTc interval was 415 ± 21.4 milliseconds in all patients, and 407 ± 19.1 milliseconds in the control group (p = 0.007). There was a positive correlation between QTc interval and carotid-femoral pulse-wave velocity (r = 0.235; p = 0.02) in patients with SLE. This association was independent of hypertension and age in a multivariate analysis. CONCLUSION: QTc interval measured by electrocardiogram is prolonged in SLE patients; it is related to subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. This measure may help stratify risk in routine clinical practice and select the patients that might benefit from a more aggressive therapy in the prevention of cardiovascular events.

Cumulated organ damage is associated with arterial stiffness in women with systemic lupus erythematosus irrespective of renal function.

OBJECTIVES: To determine whether there is an association between cumulated organ damage and arterial stiffness in women with systemic lupus erythematosus (SLE) with normal renal function and without renal damage. METHODS: Eighty-eight SLE women with normal renal function and without renal damage, and 102 sex- and age-matched controls with no history of coronary heart disease or peripheral arterial disease were studied. Cumulated organ damage and arterial stiffness were measured using the SLICC/ACR Damage Index (SDI) and pulse wave velocity (PWV), respectively. Patients were categorised as with (SDI ≥1) or without cumulated organ damage (SDI=0) and bivariate analyses were performed to compare both groups. A multivariate logistic regression was carried out to analyse the independent factors associated with cumulated organ damage. A multiple linear regression analysis was used to investigate the correlation between SDI and PWV, adjusted for appropriate confounders. RESULTS: PWV was significantly higher in patients with respect to controls (p=0.007). Also, patients with SDI ≥1 had significantly higher PWV than those with SDI=0 (p=0.007). In the multivariate analysis, cumulated organ damage was significantly associated with PWV (p=0.006) and obesity (p=0.003). Furthermore, PWV correlated with SDI after adjustment for age, SLE duration, systolic blood pressure, body mass index, renal function, prednisone and homocysteine (r=0.283, p=0.011). Patients with increased PWV were more likely to have organ damage (SDI ≥1) than those with normal PWV (67% vs. 36%, p=0.023). CONCLUSIONS: Cumulated organ damage was found to be independently associated with the arterial stiffness in SLE women without renal involvement.

Nighttime Blood Pressure Patterns and Subclinical Atherosclerosis in Women with Systemic Lupus Erythematosus.

OBJECTIVE: To compare 24-h ambulatory blood pressure (BP) monitoring (ABPM) values and patterns in women with systemic lupus erythematosus (SLE) with those of a matched control group and their relationship with the presence of subclinical atherosclerosis. METHODS: ABPM was assessed in 70 women with SLE and in 65 sex- and age-matched controls without a history of clinic cardiovascular disease (CVD). Carotid-femoral pulse wave velocity (PWV), which is a marker of subclinical atherosclerosis and a predictor of future CVD, was measured. Multivariate logistic analysis was used to determine which explanatory variables were independently associated with the non-dipper pattern and the presence of nocturnal hypertension (HTN) in women with SLE. RESULTS: No differences in PWV were found between patients and controls [median 7.3, interquartile range (IQR) 6.5-8.1 m/s vs median 7.1, IQR 6.5-7.8 m/s, p = 0.474]. The frequency of nondipper pattern (p = 0.025) and nocturnal HTN (p = 0.004) was significantly higher in women with SLE than in controls. White-coat and masked HTN were present in 10% and 11% of patients and in 20% and 8% of controls, respectively (p > 0.05 in all cases). The concordance between office and ambulatory HTN in the SLE and control groups was modest (κ = 0.325 and κ = 0.451, respectively). PWV and chronic kidney disease, and PWV and the Systemic Lupus Erythematosus Disease Activity Index were found to be independently associated with nocturnal HTN and nondipper pattern, respectively. CONCLUSION: Women with SLE were more likely to have an altered nighttime BP pattern than controls. In women with SLE, nondipper pattern and nocturnal HTN were independently associated with increased subclinical atherosclerosis measured by PWV.

Acción inmunomoduladora de las células madre mesenquimales en las enfermedades autoinmunitarias / Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases

Las enfermedades autoinmunitarias son un grupo de trastornos en los que existe un fallo en la tolerancia inmunitaria y, con ello, una hiperactivación del sistema inmunológico, de lo que se deriva un estado de inflamación crónica y un potencial daño multiorgánico. Los fármacos empleados en la actualidad para el tratamiento de este grupo de enfermedades son agentes con mayor o menor efecto inmunodepresor, con importante toxicidad sistémica y potencial riesgo de infecciones oportunistas. Se han descrito, en distintos estudios, las propiedades inmunomoduladoras de las células madre mesenquimales, características que las hacen candidatas a ser empleadas en el tratamiento de las enfermedades autoinmunitarias. Realizamos una revisión de la situación actual de esta línea terapéutica en lupus eritematoso sistémico, síndrome de Sjögren, esclerosis sistémica, enfermedad de Crohn y esclerosis múltiple, así como de los potenciales riesgos derivados de su empleo (AU)

Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use (AU)

Prevalence of and factors associated with increased arterial stiffness in patients with primary Sjögren's syndrome.

OBJECTIVE: To compare the presence of subclinical atherosclerosis measured by means of pulse wave velocity (PWV) in women with primary Sjögren's syndrome (SS) versus a healthy age- and sex-matched control group, and to identify factors independently associated with PWV in primary SS. METHODS: Forty-four women with primary SS and 78 age-matched healthy women without overt cardiovascular (CV) diseases were assessed for traditional and nontraditional CV risk factors. PWV was also performed. A linear regression analysis was used to identify factors independently associated with PWV in primary SS. RESULTS: Women with primary SS had significantly higher PWV than controls (P = 0.030), and the frequency of increased PWV was significantly higher in this group (25% versus 8%; P = 0.013). The proportion of patients ages ≤50 years (ratio 4.6) with increased PWV was almost 2-fold higher than those ages >50 years (ratio 2.4) with respect to controls. Positivity for anti-SSB was more frequent in patients with normal PWV than in those with increased PWV (61% versus 18%; P = 0.034). Women with primary SS and increased PWV had lower levels of 25-hydroxyvitamin D (25[OH]D; P = 0.047) than primary SS patients with normal PWV. In addition, 25(OH)D levels tended to correlate inversely with PWV in women with primary SS (P = 0.067), but not in controls (P = 0.97). In multivariate analysis, the Framingham Risk Score (FRS) and Sjögren's Syndrome Damage Index emerged as factors independently correlated with PWV. CONCLUSION: Women with primary SS had higher PWV than controls, but a similar FRS. The FRS and chronic damage were found to be independently associated with PWV.

[Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases]. / Acción inmunomoduladora de las células madre mesenquimales en las enfermedades autoinmunitarias.

Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use.