Can we validate a clinical score to predict the risk of severe infection in patients with systemic lupus erythematosus? A longitudinal retrospective study in a British Cohort

OBJECTIVE: Severe infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Our primary objective was to use data from a large Spanish cohort to develop a risk score for severe infection in SLE, the SLE Severe Infection Score (SLESIS) and to validate SLESIS in a separate cohort of 699 British patients. DESIGN AND SETTING: Retrospective longitudinal study in a specialist tertiary care clinic in London, UK. PARTICIPANTS: Patients fulfilling international classification criteria for SLE (n=209). This included 98 patients who had suffered severe infections (defined as infection leading to hospitalisation and/or death) and 111 randomly selected patients who had never suffered severe infections. OUTCOMES: We retrospectively calculated SLESIS at diagnosis for all 209 patients. For the infection cases we also calculated SLESIS just prior to infection and compared it to SLESIS in 98 controls matched for disease duration. We carried out receiver operator characteristic (ROC) analysis to quantify predictive value of SLESIS for severe infection. RESULTS: Median SLESIS (IQR) at diagnosis was higher in the infection group than in the control group (4.27 (3.18) vs 2.55 (3.79), p=0.0008). Median SLESIS prior to infection was higher than at diagnosis (6.64 vs 4.27, p<0.001). In ROC analysis, predictive value of SLESIS just before the infection (area under the curve (AUC)=0.79) was higher than that of SLESIS at diagnosis (AUC=0.63). CONCLUSIONS: We validated the association of SLESIS with severe infection in an independent cohort. Calculation of SLESIS at each clinic visit may help in management of infection risk in patients with SLE. Prospective studies are needed to confirm these findings

Red cell distribution width correlates with fatigue levels in a diverse group of patients with systemic lupus erythematosus irrespective of anaemia status

Objectives: Fatigue remains a debilitating feature of systemic lupus erythematosus (SLE). Although in some cases this may be the result of intercurrent fibromyalgia, mood disorder or untreated metabolic syndrome, in many cases the cause is unclear. The aim of this study was to investigate the relationship between fatigue and red cell distribution width (RDW), a measure of variability in erythrocyte size and volume. Method: A total of 225 patients were recruited from three clinics in England and Australia. Patients completed the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score or 12-item Short Form survey (SF-12) to measure fatigue, which was compared with RDW and haemoglobin. In a subgroup of 72 patients, markers of disease activity were also assessed for correlation with fatigue using univariate and multivariate analysis with fatigue as the dependent variable. Results: In all three groups, significant correlations between fatigue and RDW were observed (p<0.001; p=0.02; p<0.001 respectively) and this was preserved in multivariate analysis. There was no correlation between fatigue and haemoglobin in two groups (with the correlation between RDW and fatigue remaining significant in non-anaemic patients in the third group). In subgroup analysis, fatigue was not associated with any measures of disease activity. Conclusions: We report a reproducible, statistically significant association between RDW and fatigue levels in a diverse population of patients with SLE. The findings of this study raise the possibility of a potential novel biological basis for fatigue in those in whom there is a lack of an alternate explanation

Influence of elevated-CRP level-related polymorphisms in non-rheumatic Caucasians on the risk of subclinical atherosclerosis and cardiovascular disease in rheumatoid arthritis

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA

Incretins in patients with rheumatoid arthritis

Background: The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients. Methods: We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects. Results: Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (? coefficient 46, 95% CI 6?87, p = 0.026) and Clinical Disease Activity Index (? coefficient 7.74, 95% CI 1.29?14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with ?-cell function (HOMA2 of ?-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response. Conclusions: The incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA.This work was supported by grants from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 Instituto de Salud Carlos III [ISCIII] PI14/00394) and by the Fondo Europeo de Desarrollo Regional (FEDER) (to IFA). The research of MAGG was supported by European Union FEDER funds and by the “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748, PI12/00060, and PI15/00525) of the Instituto de Salud Carlos III (ISCIII; Spanish Health Ministry). The research of MAGG was also partially supported by RETICS Programs RD12/0009 (RIER) and RD12/0009/0013 from the ISCIII (Spanish Health Ministry)

Innovación en las enseñanzas universitarias: experiencias presentadas en las III Jornadas de Innovación Educativa de la ULL

En este libro se recoge un conjunto de experiencias de innovación educativa desarrolladas en la ULL en el curso 2011-12. Se abordan distintos ámbitos y ramas del conocimiento, y ocupan temáticas variadas que han sido desarrolladas con rigor, y con un claro potencial para su extrapolación a efectos de la mejora educativa en el ámbito universitario. Esta publicación constituye una primera edición de una serie que irá recogiendo las experiencias de innovación educativa de la ULL. Este es un paso relevante para su impulso en nuestra institución, como lo es el de su vinculación con la investigación educativa, para potenciar su publicación en las revistas científicas en este ámbito cada vez más pujante y relevante para las universidades. Sobre todo representan el deseo y el compromiso del profesorado de la ULL para la mejora del proceso educativo mediante la investigación, la evaluación y la reflexión compartida de nuestras prácticas y planteamientos docentes

Can we validate a clinical score to predict the risk of severe infection in patients with systemic lupus erythematosus? A longitudinal retrospective study in a British Cohort

OBJECTIVE: Severe infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Our primary objective was to use data from a large Spanish cohort to develop a risk score for severe infection in SLE, the SLE Severe Infection Score (SLESIS) and to validate SLESIS in a separate cohort of 699 British patients. DESIGN AND SETTING: Retrospective longitudinal study in a specialist tertiary care clinic in London, UK. PARTICIPANTS: Patients fulfilling international classification criteria for SLE (n=209). This included 98 patients who had suffered severe infections (defined as infection leading to hospitalisation and/or death) and 111 randomly selected patients who had never suffered severe infections. OUTCOMES: We retrospectively calculated SLESIS at diagnosis for all 209 patients. For the infection cases we also calculated SLESIS just prior to infection and compared it to SLESIS in 98 controls matched for disease duration. We carried out receiver operator characteristic (ROC) analysis to quantify predictive value of SLESIS for severe infection. RESULTS: Median SLESIS (IQR) at diagnosis was higher in the infection group than in the control group (4.27 (3.18) vs 2.55 (3.79), p=0.0008). Median SLESIS prior to infection was higher than at diagnosis (6.64 vs 4.27, p<0.001). In ROC analysis, predictive value of SLESIS just before the infection (area under the curve (AUC)=0.79) was higher than that of SLESIS at diagnosis (AUC=0.63). CONCLUSIONS: We validated the association of SLESIS with severe infection in an independent cohort. Calculation of SLESIS at each clinic visit may help in management of infection risk in patients with SLE. Prospective studies are needed to confirm these findings