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[Abstract] Background: Hospitalized COVID-19 patients are prone to develop persistent symptoms and to show reduced quality of life following hospital admission. Methods: Prospective cohort study of COVID-19 patients admitted to a hospital from March 1 to April 30, 2020. The primary outcome was to compare health related quality of life and persistent symptoms six months after hospital admission, of COVID-19 patients who required ICU admission with those who did not. Results: Among the 242 patients hospitalized during the defined period of time, 44 (18.2%) needed ICU admission. Forty (16.5%) patients died during hospital admission. Two hundred and two (83.5%) patients were discharged alive from the hospital. At six months, 183 (75.6%) patients completed the questionnaires (32 ICU patients and 151 non ICU patients). Ninety-six (52.4%) reported decreased quality of life and 143 (78.1%) described persistent symptoms. More ICU patients showed worsening of their quality of life (71.9 vs. 43.7%, P = 0.004). There were no differences in the proportion of patients with persistent symptoms between ICU and non ICU patients (87.5 vs. 76.2%, P = 0.159). ICU patients showed more frequently dyspnea on exertion (78.1 vs. 47.7%, P = 0.02), dyspnea on light exertion (37.5 vs. 4.6%, P < 0.001), and asthenia (56.3 vs. 29.1, P = 0.003). Conclusions: Survivors of COVID-19 needing hospitalization had persistent symptoms and a decline in the quality of life. ICU patients referred a large decrease of their quality of life compared with non ICU patients. [Resumen] Antecedentes/Contexto. Existe una tendencia en los pacientes hospitalizados por COVID-19 a desarrollar síntomas persistentes y a presentar una disminución en su calidad de vida tras el ingreso hospitalario. Métodos. Estudio de cohorte prospectivo de pacientes COVID-19 con ingreso hospitalario entre el 1 de marzo al 30 de abril de 2020. El objetivo primario fue comparar la calidad de vida relacionada con la salud y la presencia de síntomas persistentes seis meses después del ingreso, comparando los pacientes que requirieron ingreso en UCI con los que no lo precisaron. Resultados. De los 242 pacientes hospitalizados durante el período de estudio, 44 (18,2%) necesitaron ingreso en UCI. 40 (16,5%) pacientes fallecieron durante el ingreso hospitalario. 202 (83,5%) pacientes fueron dados de alta del hospital. A los seis meses, 183 (75,6%) pacientes completaron los cuestionarios (32 pacientes UCI y 151 pacientes no UCI). 96 (52,4%) refirieron disminución de la calidad de vida y 143 (78,1%) describieron síntomas persistentes. Un número mayor de pacientes de UCI mostraron un empeoramiento de su calidad de vida (71,9% vs 43,7%, P = 0,004). No hubo diferencias en la proporción de pacientes con síntomas persistentes entre los pacientes con UCI y sin UCI (87,5% vs 76,2%, P = 0,159). Los pacientes de UCI mostraron con mayor frecuencia disnea de esfuerzo (78,1% vs 47,7%, P = 0,02), disnea de pequeños esfuerzos (37,5% vs 4,6%, P < 0,001) y astenia (56,3 vs 29,1, P = 0,003). Conclusiones. Los supervivientes de COVID-19 que necesitaron hospitalización presentaron síntomas persistentes y un deterioro de su calidad de vida. Los pacientes de UCI refirieron una mayor disminución de su calidad de vida en comparación con los pacientes que no precisaron UCI.

• Several cardiovascular/hemostatic disturbances haves been reported in patients with COVID-19, but the real frequency and their potential association with the pathogenic mechanisms of SARS-CoV-19 still remain to be defined. • We investigated the relative frequency of acute coronary syndrome, deep venous thrombosis, pulmonary embolism, stroke and upper gastrointestinal bleeding in COVID patents attending emergency departments (EDs), before hospitalization and compared them with frequencies in the general ED population attending 50 Spanish EDs. • We found that the risk of pulmonary embolism is clearly increased in COVID patients, with an OR of 4.53 with respect to non-COVID patients (95% confidence interval 4.03- 5.10). Additionally, the diagnosis of pulmonary embolism was 2 fold more frequent among ED comers in 2020 compared to 2019, suggesting a SARS-CoV-2 role in such increment of cases.. The remaining entities studied were not found to be unequivocally increased in the present study and need further investigation.

Objective We investigated the incidence, predictor variables, clinical characteristics, and stroke outcomes in patients with COVID-19 seen in emergency departments (EDs) before hospitalization. Methods We retrospectively reviewed all COVID-19 patients diagnosed with stroke during the COVID-19 outbreak in 62 Spanish EDs. We formed two control groups: COVID-19 patients without stroke (control A) and non-COVID-19 patients with stroke (control B). We compared disease characteristics and four outcomes between cases and controls. Results We identified 147 strokes in 74,814 patients with COVID-19 seen in EDs (1.96 parts per thousand, 95% confidence interval [CI] = 1.66 parts per thousand to 2.31 parts per thousand), being lower than in non-COVID-19 patients (6,541/1,388,879, 4.71 parts per thousand, 95% CI = 4.60 parts per thousand to 4.83 parts per thousand; odds ratio [OR] = 0.42, 95% CI = 0.35 to 0.49). The estimated that standardized incidences of stroke per 100,000 individuals per year were 124 and 133 for COVID-19 and non-COVID-19 individuals, respectively (OR = 0.93 for COVID patients, 95% CI = 0.87 to 0.99). Baseline characteristics associated with a higher risk of stroke in COVID-19 patients were hypertension, diabetes mellitus, and previous cerebrovascular and coronary diseases. Clinically, these patients more frequently presented with confusion, decreased consciousness, and syncope and higher D-dimer concentrations and leukocyte count at ED arrival. After adjustment for age and sex, the case group had higher hospitalization and intensive care unit (ICU) admission rates (but not mortality) than COVID-19 controls without stroke (OR = 3.41, 95% CI = 1.27 to 9.16; and OR = 3.79, 95% CI = 1.69 to 8.50, respectively) and longer hospitalization and greater in-hospital mortality than stroke controls without COVID-19 (OR = 1.55, 95% CI = 1.24 to 1.94; and OR = 1.77, 95% CI = 1.37 to 2.30, respectively). Conclusions The incidence of stroke in COVID-19 patients presenting to EDs was lower than that in the non-COVID-19 reference sample. COVID-19 patients with stroke had greater need for hospitalization and ICU admission than those without stroke and longer hospitalization and greater in-hospital mortality than non-COVID-19 patients with stroke.

OBJECTIVE: We investigated the incidence, risk factors, clinical characteristics and outcomes of acute pancreatitis (AP) in patients with COVID-19 attending the emergency department (ED), before hospitalization. METHODS: We retrospectively reviewed all COVID patients diagnosed with AP in 62 Spanish EDs (20% of Spanish EDs, COVID-AP) during the COVID outbreak. We formed two control groups: COVID patients without AP (COVID-non-AP) and non-COVID patients with AP (non-COVID-AP). Unadjusted comparisons between cases and controls were performed regarding 59 baseline and clinical characteristics and 4 outcomes. RESULTS: We identified 54 AP in 74,814 patients with COVID-19 attending the ED (frequency=0.72‰, 95%CI=0.54-0.94‰). This frequency was lower than in non-COVID patients (2,231/1,388,879, 1.61‰, 95%CI=1.54-1.67; OR=0.44, 95%CI=0.34-0.58). Etiology of AP was similar in both groups, being biliary origin in about 50%. Twenty-six clinical characteristics of COVID patients were associated with a higher risk of developing AP: abdominal pain (OR=59.4, 95%CI=23.7-149), raised blood amylase (OR=31.8; 95%CI=1.60-632) and vomiting (OR=15.8, 95%CI=6.69-37.2) being the strongest, and some inflammatory markers (C-reactive protein, procalcitonin, platelets, D-dimer) were more increased. Compared to non-COVID-AP, COVID-AP patients differed in 23 variables; the strongest ones related to COVID symptoms, but less abdominal pain was reported, pancreatic enzymes raise was lower, and severity (estimated by BISAP and SOFA score at ED arrival) was higher. The in-hospital mortality (adjusted for age and sex) of COVID-AP did not differ from COVID-non-AP (OR=1.12, 95%CI=0.45-245) but was higher than non-COVID-AP (OR=2.46, 95%CI=1.35-4.48). CONCLUSIONS: Acute pancreatitis as presenting form of COVID-19 in the ED is unusual (

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

Highlights • Long outcomes of a large sample of hospitalized CPVID-19 patients were analyzed. • A large proportion of hospitalized COVID-19 patients had a reduced functional status six months after hospitalization. • ICU patients referred a large decrease of their functional status compared with not ICU patients six months after hospitalization. • Female sex, age, length of hospital stay, mechanical ventilation, and ICU admission were associated with limitations in everyday life .

Objective Introducing a new, simple and inexpensive portable equipment for lifeguards, consisting of a pre-assembled full-size plastic blanket with a mask and HEPA filter, which could offer significant time-saving advantages to reduce COVID-19 risk transmission in the first few minutes of CPR after water rescue, avoiding the negative impact of delayed ventilation. Method A pilot study was carried out to determine the feasibility of the pre-assembled kit of face-mask and HEPA filter adapted on a pre-set plastic-blanket. The first step consisted of washing hands, putting on safety glasses and gloves as the first personal protection equipment (PPE) and then covering the victim with an assembled plastic blanket. The second step consisted of 10 min of cardiopulmonary resuscitation (CPR) with PPE and plastic blanket, following the technical recommendations for ventilation during COVID-19. Results Ten rescuers took part in the pilot study. The average time to wear PPE and place the pre-assembly kit on the victim was 82 s [IC 58–105]. After 10 min the quality of the resuscitation (QCPR) was 91% [87–94]. Quality chest compressions (CC) were 22% better than ventilations (V). Most of the rescuers (60%) thought that placing the plastic blanket on the victim on the beach was somewhat simple or very simple. Conclusions Resuscitation techniques in COVID-19 era at the beach have added complexities for the correct use of PPE. Plastic blanket plus basic ventilations equipment resource could be a new alternative to be considered for lifeguards to keep ventilation on use while reducing risk transmission., Highlights • Pre-assembled kit to avoid delaying CPR in the Covid-19 Era • An easy and low-cost equipment • For prehospital environments without immediate EMS assistance

Leprosy, or Hansen’s disease, is a chronic granulomatous disease caused by Mycobacterium leprae and the recently discovered Mycobacterium lepromatosis. In Spain and other countries, where leprosy has been eliminated, an increasing number of imported cases have been documented, especially from South Africa and South America. The diagnosis of leprosy is mainly clinical, based on the signs established by the World Health Organization (WHO), although laboratory tools can be useful for diagnostic confirmation. The treatment is based on the administration of multi-drug therapy, and involves the multidisciplinary work of experts in ophthalmology, orthopedics, and physiotherapy. We studied the confirmed cases by microbiological and /or histopathological diagnosis in the health area of Santiago de Compostela (456,874 inhabitants in Galicia, in the Northwest of Spain), analyzing their clinical, microbiological, and epidemiological characteristics (2006–2015). In our study, we describe five cases of leprosy, four of them imported and one that, in the absence of more data, is native. Although we have only documented five cases during the 10 years of the study, our experience highlights the importance of considering the country of origin, travel history, and contacts in patients or staff working with leprosy patients. Despite the decrease of leprosy in our environment, it is important to enhance suspicion of the disease among health personnel, especially in those patients from countries where leprosy is endemic and those in close contact with the diagnosed patients.

The prognosis of a patient with Covid-19 pneumonia is uncertain. Our objective was to establish a predictive model of disease progression to facilitate early decision-making. A retrospective study was performed of patients admitted with Covid-19 pneumonia, classified as severe (admission to the intensive care unit, mechanic invasive ventilation, or death) or non-severe. A predictive model based on clinical, analytical, and radiological parameters was built. The probability of progression to severe disease was estimated by logistic regression analysis. Calibration and discrimination (receiver operating characteristics curves and AUC) were assessed to determine model performance. During the study period 1,152 patients presented with Covid-19 infection, of whom 229 (19.9%) were admitted for pneumonia. During hospitalization, 51 (22.3%) progressed to severe disease, of whom 26 required ICU care (11.4); 17 (7.4%) underwent invasive mechanical ventilation, and 32 (14%) died of any cause. Five predictors determined within 24 hours of admission were identified: Diabetes, Age, Lymphocyte count, SaO2, and pH (DALSH score). The prediction model showed a good clinical performance, including discrimination (AUC 0.87 CI 0.81, 0.92) and calibration (Brier score = 0.11). In total, 0%, 12%, and 50% of patients with severity risk scores ≤5%, 6-25%, and >25% exhibited disease progression, respectively. A simple risk score based on five factors predicts disease progression and facilitates early decision-making according to prognosis. Carlos III Health Institute, Spain, Ministry of Economy and Competitiveness (SPAIN) and the European Regional Development Fund (FEDER) Instituto de Salud Carlos III

Background: The prognosis of a patient with Covid-19 pneumonia is uncertain. Our objective was to establish a predictive model of disease progression to facilitate early decision-making. Methods: A retrospective study was performed of patients admitted with Covid-19 pneumonia, classified as severe (admission to the intensive care unit, mechanic invasive ventilation, or death) or non-severe. A predictive model based on clinical, analytical, and radiological parameters was built. The probability of progression to severe disease was estimated by logistic regression analysis. Calibration and discrimination (receiver operating characteristics curves and AUC) were assessed to determine model performance. Findings: During the study period 1,152 patients presented with Covid-19 infection, of whom 229 (19.9%) were admitted for pneumonia. During hospitalization, 51 (22.3%) progressed to severe disease, of whom 26 required ICU care (11.4); 17 (7.4%) underwent invasive mechanical ventilation, and 32 (14%) died of any cause. Five predictors determined within 24 hours of admission were identified: Diabetes, Age, Lymphocyte count, SaO2, and pH (DALSH score). The prediction model showed a good clinical performance, including discrimination (AUC 0.87 CI 0.81, 0.92) and calibration (Brier score = 0.11). In total, 0%, 12%, and 50% of patients with severity risk scores ≤5%, 6-25%, and >25% exhibited disease progression, respectively. Interpretation: A simple risk score based on five factors predicts disease progression and facilitates early decision-making according to prognosis. Funding Statement: This project was funded by the Carlos III Health Institute, Spain, Grant/Award Number: COV20/00404; Ministry of Economy and Competitiveness (SPAIN) and the European Regional Development Fund (FEDER). Declaration of Interests: The authors declare no conflicts of interest associated with this publication. Ethics Approval Statement: The study was conducted in accordance with the guidelines of the Declaration of Helsinki and the principles of good clinical practice and was approved by the Institutional Review Board (IRB) of the Galician Health Service on April 3, 2020 (#2020/194). Informed consent forms were waived by the IRB.

In patients with coronavirus disease 2019 (COVID-19) infection, common drugs may exacerbate symptoms and negatively impact outcomes. However, the role of chronic medications on COVID-19 effects remains poorly understood. We hypothesized that certain chronic pain medications would influence outcomes in patients with COVID-19. The main aim is to assess the effect of these medications on the course of the disease in COVID-19 patients. Secondary aims are to compare disease severity and outcomes in patients with COVID-19 receiving chronic treatment with analgesics or other medications versus untreated patients and to determine prevalence of chronic pain medications in specific subgroups of hospitalized patients for COVID-19. Multicenter case-population study in 15 care centers for patients =18 years of age diagnosed and hospitalized with COVID-19. Controls will include patients treated at participating centers for chronic pain during the six-month period prior to March 15th, 2020. Each case will be age- and sex-matched to 10 controls. Patients will be grouped according to disease severity criteria. The primary outcome measures in patients admitted for COVID-19 will be: 1. statistical association between chronic pain medication and disease severity; 2. association between chronic pain treatment and survival. Secondary outcome measures include: 1. prevalence of chronic pain medications in patients with COVID-19 by age and sex; 2. prevalence of chronic pain medications in patients with COVID-19 vs controls. Patients and controls will be paired by age, sex, and geographic residence. Odds ratios with 95% confidence intervals will be calculated to determine the association between each drug and clinical status. Univariate and multivariate analyses will be performed. This is a study protocol. Data is actually being gathered and results are yet not achieved. There is no numerical data presented, so the conclusions cannot be considered solid at this point. Pain medications are likely to influence severity of COVID-19 and patient survival. Identifying those medications that are most closely associated with severe COVID-19 will provide clinicians with valuable data to guide treatment and reduce mortality rates and the long-term sequelae of the disease.

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).

Servicio de Otorrinolaringologia, Hospital Universitario Nino Jesus, Madrid, Espana Servicio de Anatomia Patologica, Hospital Universitario Nino Jesus, Madrid, Espana Servicio de Otorrinolaringologia, Hospital Universitario Virgen del Rocio, Sevilla, Espana ado de http://www.elsevier.es el 21/06/2016. Copia para uso personal, se prohibe la transmision de este documento por cualquier medio o formato.

Objective.To study the qualitative and quantitative phenotypic changes that occur in molecules involved in antigen presentation and costimulation in synovial B cells from rheumatoid arthritis (RA) and psoriatic arthritis (PsA).Methods.The presence of HLA-DR, CD86, and CD40 in CD20+ cells was studied in RA synovium biopsies using immunohistochemistry and immunofluorescence. Expression was assessed by flow cytometry of the Class II molecules CD40, CD86, CD23, and CD27 on B cells from the synovial fluid (SF), with respect to peripheral blood, from 13 patients with RA and 15 patients with PsA. Expression of interferon-induced protein with tetratricopeptide repeats 4 (IFIT4) in immune-selected CD20+ cells from patients with RA was assessed by quantitative realtime PCR.Results.Infiltrating synovial RA, B cells expressed HLA-DR, CD40, and CD86. Increased expression of CD86, HLA-DR, and HLA-DQ in B cells from SF was found in patients with RA and PsA. HLA-DP was also elevated in rheumatoid SF B cells; conversely, a significantly lower expression was observed in SF from patients with PsA. CD40 expression was increased in SF B cells from PsA, but not in patients with RA. Interestingly, CD20 surface expression level was significantly lower in SF B cells (CD19+, CD138−) from RA, but not in patients with PsA. CD27 upregulation and CD23 downregulation were observed in synovial B cells in both pathologies. Finally, a 4-fold increase in IFIT4 mRNA content was shown in B cells from SF in patients with RA.Conclusion.Synovial B cells from patients with RA and patients with PsA express different antigen-presenting cell phenotypes, suggesting that this cell type plays a dissimilar role in the pathogenesis of each disease.

Objectives Rheumatoid Arthritis (RA) patients show alterations in cholesterol and lypoproteins levels. These disturbances seem to be related to the inflammation that takes place in the disease, but the pathological mechanisms that leed to it are unknown. Cholesterol ester transfer protein (CETP) is an enzyme that allows transference of cholesterol ester from HDL to LDL-cholesterol particles. CETP has recently gained interest as therapeutic goal of new treatments developed to treat dyslipidemia. The aim of this study is to describe the role of this enzyme in a model of chronic inflammation associated dyslipidemia as it occurs in rheumatoid arthritis. Methods 101 RA patients and 115 sex and age-matched controls were included. Serum levels of CEPT were measured by an enzimelinked inmunoassay and the enzymatic activity by a specific kit (Roar CEPT activity assay kit). In both patients and controls classical lipidic profile (cholesterol, triglycerides, HDL and LDL cholesterol, apolipoprotein A1, apolipoprotein B and lipoprotein A) was defined. Also ESR and CRP were determined. In RA patients disease activity indexes like DAS28 and HAQ were collected, as well as, sociodemographic variables, comorbidility and anthropometric variables. Multivariate analysis was performed to compare results between patients and controls adjusting for corticosteroids intake and for classical dyslipidemia risk factors. Results Serum protein levels were correlated with the enzimatic activity (r=0,5, p=0,00), showing that serum levels could be enough to express the activity of this enzime. Patients show lower CETP activity levels after adjusting for sex and age (beta coefficient -0,52 pmol/l, CI95% -0,87–0,18, p=0,01). In patients, CRP levels show a negative correlation with CETP activity (r=-0.34, p=0,03); in controls this correlation did not achieve the stadistic significance. Disease activity scores like DAS28 did not show association with CETP. Conclusions CETP is underexpressed in RA patients. Differencial characteristics of dyslipIdemia in RA could be partly explained by this fact. Disclosure of Interest None Declared

Objectives It has been suggested that resistance to insulin action is a feature that accompanies rheumatoid arthritis (RA), a disease where chronic inflammation predominates and classical triggers for insulin resistance (IR) like obesity and diabetes are absents. However, data regarding characterization of RA features associated with this insulin resistance (IR) are lacking. The aim of this study was to investigate how sensitivity to insulin and markers of beta cell dysfunction (proinsulin processing metabolites) are expressed in RA. Methods 101 non-diabetic RA patients and 99 non-diabetic sex and age-matched controls were included in this study. Insulin sensitivity function through homeostatic model assessment (HOMA2), and beta cell secretion through insulin, split and intact proinsulin, and C-peptide were assessed in both groups. We performed multiple regression analysis to compare IR between groups and to explore the relation between RA features and IR. Data were adjusted for glucocorticoids intake and for IR classical risk factors. Results RA patients compared to controls show higher HOMA-IR ( log HOMA-IR, beta coefficient, 0.40 [95% CI 0.20-0.59], p=0.00). When this data was adjusted for glucocorticoids intake, non-on corticosteroid patients maintained a higher IR index (beta coef. 0.14 [95% CI 0.05-0.24], p=0.00). Current prednisone treatment was not associated with higher IR in the patients’ intragroup comparison (beta coef. 0.56 [1.13-1.19], p=0.22). Insulin processing signaling in RA patients showed impaired features via an elevated intact proinsulin levels (beta coef. 3.13 [0.81-5.44] pMol/L, p=0.03 for the comparison between patients and controls). Split proinsulin levels were also higher in RA patients (beta coef. 13.7 pmol/L [3.57-9.40], p=0.00) even adjusting for prednisone intake (beta coef. 2.66 pmol/L [95%CI 1.62-5.95] for non steroids RA patients when compared to controls). In multiple regression analysis, RA features (disease duration, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, disease activity through HAQ and DAS28 scores, and current non-biologic disease modifying antirheumatic drug), when adjusted for sex, age and body mass index, were not associated with IR or insulin propeptides. Conclusions Beta cell signaling is impaired in non-diabetic and non-corticoids RA patients. Disclosure of Interest None Declared

Objectives To explore the influence of body composition and abdominal adiposity on endothelial dysfunction and radiological damage in Rheumatoid Arthritis (RA) patients. Methods A total of 100 patients, 54 RA patients and 46 controls, adjusted for sex, body mass index (BMI), age and comorbidity, were included. Total body composition was measured by dual energy X-ray absorptiometry; total and regional lean mass, fat mass, fat free mass index (fat free mass/m2) and fat mass index (fat mass/m2) were established. Quantification of visceral and parietal abdominal fat area was determined using magnetic resonance imaging, as well as visceral/parietal fat index. Endothelial dysfunction was assessed by brachial artery flow-mediated dilatation (FMD) as the dilator response to 5 minutes distal cuff occlusion and after sublingual nitroglycerine administration, and the Sharp Score defined radiological damage. The 28-joint DAS (DAS-28) and disability using HAQ (Health Assessment Questionnaire) scores, erythrocyte sedimentation rate (ESR) and C-reactive protein were collected. Multivariate analysis was performed to compare body composition between controls and patients and the relationship between those and endothelial dysfunction and radiological damage, everything adjusted for demographic and comorbidity variables. Results In the univariate analysis RA patients showed less flow-mediated dilatation (5.9 vs 9.8 mm, p=0.03). Similarly, fat free mass index was higher in patients than in controls (beta coefficient 0,94 (CI95% 0,08-1,80), P=0,03) after adjusting for BMI, sex and age; on the other hand fat mass index tended to be higher in patients than in controls (beta coefficient 2,51 (CI95% -0,82-5,84), p=0.13). Parietal and visceral abdominal fat values did not show differences between controls and patients. Fat mass, lean mass and abdominal fat did not correlate with DAS-28, HAQ, ESR or CRP. Parietal abdominal fat through resonance imaging in RA patients showed a negative relation with flow-mediated dilatation (beta coefficient -0.045 mm FMD/cm2 parietal area, p=0.02) after adjusting for BMI. This relation was not found with visceral abdominal fat. Radiological damage was negatively correlated with total bone mass (beta coefficient -1,13, CI95% -2,05-0,22, p=0.02) and showed a negative trend to do it also with total lean mass (beta coefficient -1.11 CI95% 2,42-0,21, p=0,09). Conclusions Changes in body composition take place in RA patients. These changes can be related to the endothelial dysfunction and radiological damage that occurs in this disease. Disclosure of Interest None Declared

Objectives The retinol binding protein 4 (RBP4) has recently been described as a protein highly related with insulin resistance (IR) states like obesity and diabetes. The chronic inflammatory states, like in rheumatoid arthritis (RA), are linked also to insulin resistance by mechanisms that are unknown. Therefore, RA is considered as an insulin resistance model related with a chronic inflammatory state, where diabetes and obesity, classical factors for IR, are absent. The objective of this study is to estimate RBP4 expression in RA patients. Methods 101 RA patients and 115 age and sex-matched controls were included. Pancreatic beta cell function was estimated by classical insulinresistance indexes like HOMA (homeostatic model assessment 2). RBP4, C peptide and insuline levels were measured in patients and controls by a specific enzyme-linked immunosorbent assay (ELISA). Multivariate analysis was performed to compare results between patients and controls and the data were adjusted for glucocorticoids intake and for IR classical risk factors. Results RBP4 levels did not show differences between controls and patients, after adjusting for sex, age, body mass index (BMI) and waist circumference (lnRBP4 2,83 mcg/dl in patients vs. 2,70 mcg/dl, p=0,33). On going steroids patients showed higher RBP4 levels (lnRBP4 3,03 vs 2,61 mcg/dl, p=0.00), after adjusting for age, sex, BMI and waist circumference. Similarly, in the univariate analysis, RBP4 levels tended to correlate with steroid average dose (r=0,20, p=0,14). In our serie, RBP4 levels were not related with the classical IR characteristics, like abdominal waist and BMI, both in controls and patients. Nor these levels showed relation with ESR, CRP, insuline levels or disease activity indexes. Conclusions The molecular mechanisms that lead to IR in RA patients appear to be different from those that ocurr in obesity and diabetes status. RBP4 does not seem to play a role in IR in patients with RA. Disclosure of Interest None Declared

The case of a 7-year-old boy with the normotensive form of “chloride-shunt” syndrome is described. An unusual feature was the clinical presentation with lithiasis, caused by marked hypercalciuria of renal origin. The present studies were carried out to investigate the nature of the renal tubular defect. Indices for proximal and distal sodium chloride reabsorption were increased during hypotonic saline diuresis. Baseline sodium chloride excretion was low but increased above the range of control values after acute furosemide administration. Baseline potassium excretion was low, was not modified by the infusion of sodium chloride and increased significantly during infusions of sodium sulphate or sodium bicarbonate. Calcium excretion remained unchanged during sodium chloride, sodium sulphate or sodium bicarbonate infusions, but increased after furosemide administration. Nasal insufflation of 1-desamino-8-d-arginine-vasopressin induced both an increase in potassium excretion and a decrease in calcium and magnesium excretion. Plasma atrial natriuretic peptide was increased and was not significantly modified by infusion of hypertonic saline or acute administration of furosemide. These findings indicate that the primary renal abnormality appears to be an enhanced tubular reabsorption of sodium chloride, apparently present in the proximal tubule and the ascending loop of Henle. The associated presence of hypercalciuria also suggests a transport defect in the distal tubule. Decreased potassium excretion probably depends on a voltage-shunting defect in the cortical collecting tubule, which can be reversed by increasing the delivery of non-reabsobable anions or by enhancing the conductance of the luminal membrane. Treatment with hydrochlorothiazide was successful in correcting most biochemical abnormalities but did not result in catch-up growth.