Estudio de la regulación de la expresión de quimioquinas en fibroblastos dérmicos en la esclerosis sistémica

Tesis de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Microbiología I, leída el 06-03-2001Depto. de Inmunología, Oftalmología y ORLFac. de MedicinaTRUEpu

Complement as a Therapeutic Target in Systemic Autoimmune Diseases

The complement system (CS) includes more than 50 proteins and its main function is to recognize and protect against foreign or damaged molecular components. Other homeostatic functions of CS are the elimination of apoptotic debris, neurological development, and the control of adaptive immune responses. Pathological activation plays prominent roles in the pathogenesis of most autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, dermatomyositis, and ANCA-associated vasculitis. In this review, we will review the main rheumatologic autoimmune processes in which complement plays a pathogenic role and its potential relevance as a therapeutic target

The interaction of amino acids with macrocyclic pH probes of pseudopeptidic nature

The fluorescence quenching, by a series of amino acids, of pseudopeptidic compounds acting as probes for cellular acidity has been investigated. It has been found that amino acids containing electron-rich aromatic side chains like Trp or Tyr, as well as Met quench the emission of the probes mainly via a collisional mechanism, with Stern–Volmer constants in the 7–43 M−1 range, while other amino acids such as His, Val or Phe did not cause deactivation of the fluorescence. Only a minor contribution of a static quenching due to the formation of ground-state complexes has been found for Trp and Tyr, with association constants in the 9–24 M−1 range. For these ground-state complexes, a comparison between the macrocyclic probes and an open chain analogue reveals the existence of a moderate macrocyclic effect due to the preorganization of the probes in the more rigid structure

Diseño de programa de inducción y entrenamiento para la empresa de servicios públicos Paz de Ariporo S.A E.S. P

No aplicaEn este trabajo podemos conocer de la empresa Paz De Ariporo S.A E.S. P tanto en su funcionamiento y como la prestación de servicios a la cual se dedica la empresa, de esta analizamos el proceso de inducción y entrenamiento del cual podemos ver que existen algunas falencias que se presentan y como se puede implementar estrategias de mejoramiento para que el desarrollo de las actividades sean cada vez mejor y con un buen desempeño por parte de los empleados, así mismo resaltar la importancia que tiene el proceso de inducción y entrenamiento a los empleados que ingresan a la empresa. Igualmente se realiza un estudio a los empleados para poder evaluar las falencias que se perciben y cuales son algunos de los factores que hacen que se presenten dichas fallas en el proceso de inducción y entrenamiento a los empleados que van ingresando. Luego de realizar una pequeña encuesta a los empleados el grupo de trabajo realiza un análisis a los factores que son objeto de estudio y que nos ayuda a la identificación de aspectos que están causando falencias en el proceso de inducción y entrenamiento y que hacen que algunas actividades en la prestación de servicios se vean afectadas. Se espera dar a conocer y plantear estrategias que contribuyan con el mejoramiento de las falencias que se vienen presentando en dichos procesos.In this work we can learn about the company Paz De Ariporo S.A E.S. P both in its operation and as the provision of services to which the company is dedicated, from this we analyze the induction and training process of which we can see that there are some shortcomings that arise and how improvement strategies can be implemented so that the development of activities are better and better and with a good performance by the employees, likewise highlighting the importance of the induction and training process for employees who enter the company. Likewise, a study is carried out on the employees to be able to evaluate the perceived shortcomings and what are some of the factors that cause these failures to appear in the induction and training process to the employees who are entering. After conducting a small survey of the employees, the work group performs an analysis of the factors that are the object of study and that helps us to identify aspects that are causing shortcomings in the induction and training process and that make some activities in the provision of services are affected. It is expected to publicize and propose strategies that contribute to the improvement of the shortcomings that have been presented in these processes

Trends in hip fracture in patients with rheumatoid arthritis: Results from the Spanish National Inpatient Registry over a 17-year period (1999–2015). TREND-AR study

Purpose T o analyse trends in hip fracture (HF) rates in patients with rheumatoid arthritis (RA) over an extended time period (17 years). Methods T his observational retrospective survey was performed by reviewing data from the National Surveillance System for Hospital Data, which includes more than 98% of Spanish hospitals. All hospitalisations of patients with RA and HF that were reported from 1999 to 2015 were analysed. Codes were selected using the Ninth International Classification of Diseases, Clinical Modification: ICD-9-CM: RA 714.0 to 714.9 and HF 820.0 to 820.3. The crude and age-adjusted incidence rate of HF was calculated by age and sex strata over the last 17 years. General lineal models were used to analyse trends. Results Between 1999 and 2015, 6656 HFs occurred in patients with RA of all ages (84.25% women, mean age 77.5 and 15.75% men, mean age 76.37). The ageadjusted osteoporotic HF rate was 221.85/100 000 RA persons/ year (women 227.97; men 179.06). The HF incidence rate increased yearly by 3.1% (95% CI 2.1 to 4.0) during the 1999–2015 period (p<0.001) and was more pronounced in men (3.5% (95% CI 2.1 to 4.9)) than in women (3.1% (95% CI 2.3 to 4.1)). The female to male ratio decreased from 1.54 in 1999 to 1.14 in 2015. The average length of hospital stays (ALHS) decreased (p<0.001) from 16.76 days (SD 15.3) in 1999 to 10.78 days (SD 7.72) in 2015. Age at the time of hospitalisation increased (p<0.001) from 75.3 years (SD 9.33) in 1999 to 79.92 years (SD 9.47) in 2015. There was a total of 326 (4.9%) deaths during admission, 247 (4.4%) in women and 79 (7.5%) in men (p<0.001). Conclusion I n Spain, despite the advances that have taken place in controlling disease activity and in treating osteoporosis, the incidence rate of HF increased in both male and female patients with RA.This work has a help for the research provided by the Society of Rheumatology of the Community of Madrid (SORCOM)

Prevalence of hospital PCR-confirmed COVID-19 cases in patients with chronic inflammatory and autoimmune rheumatic diseases

[Abstract] Background: The susceptibility of patients with rheumatic diseases and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown. Methods: We performed a retrospective study with patients under follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with severe acute respiratory syndrome coronavirus 2-positive PCR tests performed in the hospital to the same reference populations. Rates of PCR+ confirmed COVID-19 were compared among groups. Results: Patients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Patients with systemic autoimmune or immune-mediated disease (AI/IMID) showed a significant increase, whereas patients with inflammatory arthritis (IA) or systemic lupus erythematosus did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. Patients with IA on targeted-synthetic or biological disease-modifying antirheumatic drugs (DMARDs), but not those on conventional-synthetic DMARDs, had a greater prevalence despite a similar age distribution. Conclusion: Patients with AI/IMID show a variable risk of hospital-diagnosed COVID-19. Interplay of ageing, therapies and disease-specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyse the specific factors involved in COVID-19 susceptibility.Instituto de Salud Carlos III; RD16/0012 RETICS Progra

Cardiovascular events in Systemic Lupus Erythematosus: a nationwide study in Spain from the RELESSER Registry

This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis. RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis. From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2-66.1], and SLE duration of 212.0 months [120.8-289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02-1.04]), hypertension (1.71 [1.20-2.44]), smoking (1.48 [1.06-2.07]), diabetes (2.2 [1.32-3.74]), dyslipidemia (2.18 [1.54-3.09]), neurolupus (2.42 [1.56-3.75]), valvulopathy (2.44 [1.34-4.26]), serositis (1.54 [1.09-2.18]), antiphospholipid antibodies (1.57 [1.13-2.17]), low complement (1.81 [1.12-2.93]), and azathioprine (1.47 [1.04-2.07]) as risk factors for CV events. We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows-for the first time-an association between diabetes and CV events in SLE patients

Incidence, associated factors and clinical impact of severe infections in a large, multicentric cohort of patients with systemic lupus erythematosus

OBJECTIVES: To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ?4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. RESULTS: A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ?1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (?10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999). CONCLUSIONS: Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect.Spanish Foundation of Rheumatology. FIS/ISCIII (grant number PI11/02857). Dr. Pego-Reigosa is supported by Grant 316265 (BIOCAPS) from the European Union 7th Framework Programme (FP7/REGPOT-2012–2013.1)

Primary respiratory disease in patients with systemic lupus erythematosus: data from the Spanish rheumatology society lupus registry (RELESSER) cohort

Background The purpose of this study was to assess the prevalence, associated factors, and impact on mortality of primary respiratory disease in a large systemic lupus erythematosus (SLE) retrospective cohort. Methods All adult patients in the RELESSER-TRANS (Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology [SER], cross-sectional phase) registry were retrospectively investigated for the presence of primary pleuropulmonary manifestations. Results In total 3215 patients were included. At least one pleuropulmonary manifestation was present in 31% of patients. The most common manifestation was pleural disease (21%), followed by lupus pneumonitis (3.6%), pulmonary thromboembolism (2.9%), primary pulmonary hypertension (2.4%), diffuse interstitial lung disease (2%), alveolar hemorrhage (0.8%), and shrinking lung syndrome (0.8%). In the multivariable analysis, the variables associated with the development of pleuropulmonary manifestation were older age at disease onset (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.02-1.04), higher SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) scores (OR 1.03, 95% CI 1.00-1.07), the presence of Raynaud's phenomenon (OR 1.41, 95% CI 1.09-1.84), secondary antiphospholipid syndrome (OR 2.20, 95% CI 1.63-2.97), and the previous or concomitant occurrence of severe lupus nephritis, (OR 1.48, 95% CI 1.12-1.95) neuropsychiatric manifestations (OR 1.49, 95% CI 1.11-2.02), non-ischemic cardiac disease (OR 2.91, 95% CI 1.90-4.15), vasculitis (OR 1.81, 95% CI 1.25-2.62), hematological manifestations (OR 1.31, 95% CI 1.00-1.71), and gastrointestinal manifestations, excluding hepatitis (OR 2.05, 95% CI 1.14-3.66). Anti-RNP positivity had a clear tendency to significance (OR 1.32, 95% CI 1.00-1.75; P = 0.054). The development of pleuropulmonary manifestations independently contributes to a diminished survival (hazard ratio of 3.13). However, not all complications will influence the prognosis in the same way. Whereas the occurrence of pleural disease or pulmonary thromboembolism has a minimal impact on the survival of these patients, the remaining manifestations have a major impact on mortality. Conclusion Except for pleural disease, the remaining respiratory manifestations are very uncommon in SLE (<4%). Pleuropulmonary manifestations independently contributed to a decreased survival in these patients