AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans.

Polyubiquitinated proteins are primarily degraded by the ubiquitin-proteasome system (UPS). Proteasomes are present both in the cytoplasm and nucleus. Here, we investigated mechanisms coordinating proteasome subcellular localization and activity in a multicellular organism. We identified the nuclear protein-encoding gene akir-1 as a proteasome regulator in a genome-wide Caenorhabditis elegans RNAi screen. We demonstrate that depletion of akir-1 causes nuclear accumulation of endogenous polyubiquitinated proteins in intestinal cells, concomitant with slower in vivo proteasomal degradation in this subcellular compartment. Remarkably, akir-1 is essential for nuclear localization of proteasomes both in oocytes and intestinal cells but affects differentially the subcellular distribution of polyubiquitinated proteins. We further reveal that importin ima-3 genetically interacts with akir-1 and influences nuclear localization of a polyubiquitin-binding reporter. Our study shows that the conserved AKIR-1 is an important regulator of the subcellular function of proteasomes in a multicellular organism, suggesting a role for AKIR-1 in proteostasis maintenance.

BAP1 Malignant Pleural Mesothelioma Mutations in Caenorhabditis elegans Reveal Synthetic Lethality between ubh-4/BAP1 and the Proteasome Subunit rpn-9/PSMD13.

The deubiquitinase BAP1 (BRCA1-associated protein 1) is associated with BAP1 tumor predisposition syndrome (TPDS). BAP1 is a tumor suppressor gene whose alterations in cancer are commonly caused by gene mutations leading to protein loss of function. By CRISPR-Cas, we have generated mutations in ubh-4, the BAP1 ortholog in Caenorhabditis elegans, to model the functional impact of BAP1 mutations. We have found that a mimicked BAP1 cancer missense mutation (UBH-4 A87D; BAP1 A95D) resembles the phenotypes of ubh-4 deletion mutants. Despite ubh-4 being ubiquitously expressed, the gene is not essential for viability and its deletion causes only mild phenotypes without affecting 20S proteasome levels. Such viability facilitated an RNAi screen for ubh-4 genetic interactors that identified rpn-9, the ortholog of human PSMD13, a gene encoding subunit of the regulatory particle of the 26S proteasome. ubh-4[A87D], similarly to ubh-4 deletion, cause a synthetic genetic interaction with rpn-9 inactivation affecting body size, lifespan, and the development of germ cells. Finally, we show how ubh-4 inactivation sensitizes animals to the chemotherapeutic agent Bortezomib, which is a proteasome inhibitor. Thus, we have established a model to study BAP1 cancer-related mutations in C. elegans, and our data points toward vulnerabilities that should be studied to explore therapeutic opportunities within the complexity of BAP1 tumors.

Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans.

Cisplatin is the most common drug in first-line chemotherapy against solid tumors. We and others have previously used the nematode Caenorhabditis elegans to identify genetic factors influencing the sensitivity and resistance to cisplatin. In this study, we used C. elegans to explore cisplatin effects on mitochondrial functions and investigate cisplatin-induced neurotoxicity through a high-resolution system for evaluating locomotion. First, we report that a high-glucose diet sensitizes C. elegans to cisplatin at the physiological level and that mitochondrial CED-13 protects the cell from cisplatin-induced oxidative stress. Additionally, by assessing mitochondrial function with a Seahorse XFe96 Analyzer, we observed a detrimental effect of cisplatin and glucose on mitochondrial respiration. Second, because catechol-O-methyltransferases (involved in dopamine degradation) are upregulated upon cisplatin exposure, we studied the protective role of dopamine against cisplatin-induced neurotoxicity. Using a Tierpsy Tracker system for measuring neurotoxicity, we showed that abnormal displacements and body postures in cat-2 mutants, which have dopamine synthesis disrupted, can be rescued by adding dopamine. Then, we demonstrated that dopamine treatment protects against the dose-dependent neurotoxicity caused by cisplatin.

Presence and interaction of free-living amoebae and amoeba-resisting bacteria in water from drinking water treatment plants.

Free-living amoebae (FLA) are ubiquitous and many isolates have been shown to be infected with amoeba-resisting bacteria, as the example of Acanthamoeba and Legionella interaction. Due to the high environmental prevalence of Acanthamoeba. in the Castilian Plateau (Spain), the aims of this work were to investigate the occurrence of Acanthamoeba and other FLA in water from several sampling points from four Drinking Water Treatment Plants (DWTP) and to investigate the presence of Legionella spp. and other amoeba-resisting bacteria in biofilms in raw and finished water, taking into account that no legislation exists for this protozoa control. Acanthamoeba was detected at different sampling points, and sand filters seemed to contribute to amoebic enrichment. After ozonation, a temporary decrease in viable amoebae was observed. The genotypes detected were T3, T4, and T5, revealing the first report of genotype T5 in waters from this region. Moreover, Balamuthia mandrillaris, Vermamoeba vermiformis and Paravahlkampfia sp. were detected. Regarding Legionella, PCR detection in raw and finished water was higher than by agar culture, but even higher after Acanthamoeba co-culture. Also, Legionella's presence was higher in raw water than in finished water. The decrease of free Legionella observed from raw (27.5%, by PCR) to finished water (3.4% by PCR) contrasted with the increase of Legionella-infected FLA from raw (30.7%) to finished water (52%). At biofilm, free Legionella was not detected, and the percentage of infected FLA was low (3.8%). Legionella species identified in these samples were L. drozanskii, L. donaldsonii and L. feeleii. Additionally, Acanthamoeba co-culture led to the isolation of Pseudomonas aeruginosa, P. stutzeri, P. fluorecens, Achromobacter xylosoxidans and Stenotrophomonas maltophilia. The highly disseminated presence of Acanthamoeba and the detection of amoeba-resisting bacteria inside amoebae highlight the importance of developing methods for controlling FLA in order to limit human pathogenic amoeba-resisting bacteria survival to the water purification processes.

Efficient Generation of Endogenous Fluorescent Reporters by Nested CRISPR in Caenorhabditis elegans.

CRISPR-based genome-editing methods in model organisms are evolving at an extraordinary speed. Whereas the generation of deletion or missense mutants is quite straightforward, the production of endogenous fluorescent reporters is more challenging. We have developed Nested CRISPR, a cloning-free ribonucleoprotein-driven method that robustly produces endogenous fluorescent reporters with EGFP, mCherry or wrmScarlet in Caenorhabditis elegans This method is based on the division of the fluorescent protein (FP) sequence in three fragments. In the first step, single-stranded DNA (ssDNA) donors (≤200 bp) are used to insert the 5' and 3' fragments of the FP in the locus of interest. In the second step, these sequences act as homology regions for homology-directed repair using a double-stranded DNA (dsDNA) donor (PCR product) containing the middle fragment, thus completing the FP sequence. In Nested CRISPR, the first step involving ssDNA donors is a well-established method that yields high editing efficiencies, and the second step is reliable because it uses universal CRISPR RNAs (crRNAs) and PCR products. We have also used Nested CRISPR in a nonessential gene to produce a deletion mutant in the first step and a transcriptional reporter in the second step. In the search for modifications to optimize the method, we tested synthetic single guide RNAs (sgRNAs), but did not observe a significant increase in efficiency. To streamline the approach, we combined all step 1 and step 2 reagents in a single injection and were successful in three of five loci tested with editing efficiencies of up to 20%. Finally, we discuss the prospects of this method in the future.

Barreras y facilitadores en la implantación de estándares de calidad en las unidades de hospital de día reumatológicas. Análisis cualitativo del proyecto VALORA / Barriers to and facilitators of implementing quality standards in Hospital Day Care Units in Rheumatology: Qualitative approach to the VALORA study

Objetivo: Identificar las barreras y los facilitadores en la implantación de estándares de calidad en las unidades de hospital de día (UHdD) reumatológicas. Material y métodos: Se analizaron las valoraciones sobre UHdD clasificadas en torno a estándares de estructura, procesos y resultados. La aproximación cualitativa se llevó a cabo mediante 13 grupos de discusión (GD) formados por profesionales de Reumatología (7), de Enfermería (4) y pacientes (2) de UHdD. La captación de informantes se realizó mediante muestreo intencionado atendiendo a variables que configuran las percepciones de las UHdD. El análisis de los datos se realizó siguiendo una perspectiva descriptiva-interpretativa. Resultados: La especialización de las UHdD monovalentes y la formación específica en Reumatología para Enfermería se perciben como los principales facilitadores para la implantación de estándares. Por el contrario, la demora en la disponibilidad de los fármacos en las UHdD se identifica como una barrera que prolonga la estancia de pacientes y desaprovecha recursos. Las diferencias en regulaciones locales se perciben como una posible barrera para el acceso equitativo a fármacos. El elemento mejor valorado por los pacientes fue la atención recibida, por encima de las variables estructurales o de proceso. Conclusiones: Los hallazgos de este estudio sugieren que las mejoras para la implantación de estándares de calidad en las UHdD pueden incluir 3 niveles de actuación: la propia UHdD, el centro hospitalario, y un tercero relacionado con regulaciones locales de acceso a fármacos

Objective: To identify barriers and facilitators in the implementation of quality standards in hospital day care units (HDCU) in rheumatology. Material and methods: We analyzed appraisals of HDCU in terms of standards for structure, processes and results. The qualitative approach was conducted through 13 discussion groups created by rheumatology health professionals (7), nursing professionals (4) and HDCU patients (2). The recruitment of informants was done through purposive sampling, attending to variables that form the perceptions of the HDCU. Data analysis was performed using a descriptive-interpretive method. Results: The specialization of the HDCU and specific training in rheumatology for nursing are perceived as the main facilitator for the implementation of standards. Conversely, the delay in the availability of medicines at the HDCU is identified as a barrier that prolongs patient stay and wastes resources. Differences in local regulations are perceived as a potential barrier to equitable access to medicines. The patients gave higher ratings to the care received than to structural variables or those related to process. Conclusions: The findings of this study suggest that improvements in the implementation of quality standards in HDCU may include three levels of action: the HDCU, the hospital and a third related to local regulations to access to medicines

Genetic and cellular sensitivity of Caenorhabditis elegans to the chemotherapeutic agent cisplatin.

Cisplatin and derivatives are commonly used as chemotherapeutic agents. Although the cytotoxic action of cisplatin on cancer cells is very efficient, clinical oncologists need to deal with two major difficulties, namely the onset of resistance to the drug and the cytotoxic effect in patients. Here, we used Caenorhabditis elegans to investigate factors influencing the response to cisplatin in multicellular organisms. In this hermaphroditic model organism, we observed that sperm failure is a major cause of cisplatin-induced infertility. RNA sequencing data indicate that cisplatin triggers a systemic stress response, in which DAF-16/FOXO and SKN-1/NRF2, two conserved transcription factors, are key regulators. We determined that inhibition of the DNA damage-induced apoptotic pathway does not confer cisplatin protection to the animal. However, mutants for the pro-apoptotic BH3-only gene ced-13 are sensitive to cisplatin, suggesting a protective role of the intrinsic apoptotic pathway. Finally, we demonstrated that our system can also be used to identify mutations providing resistance to cisplatin and therefore potential biomarkers of innate cisplatin-refractory patients. We show that mutants for the redox regulator trxr-1, ortholog of the mammalian thioredoxin reductase 1 TRXR1, display cisplatin resistance. By CRISPR/Cas9, we determined that such resistance relies on the presence of the single selenocysteine residue in TRXR-1.This article has an associated First Person interview with the first author of the paper.

Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent.

Purpose: To investigate the genetic basis of cisplatin resistance as efficacy of cisplatin-based chemotherapy in the treatment of distinct malignancies is often hampered by intrinsic or acquired drug resistance of tumor cells.Experimental Design: We produced 14 orthoxenograft transplanting human nonseminomatous testicular germ cell tumors (TGCT) in mice, keeping the primary tumor features in terms of genotype, phenotype, and sensitivity to cisplatin. Chromosomal and genetic alterations were evaluated in matched cisplatin-sensitive and their counterpart orthoxenografts that developed resistance to cisplatin in nude mice.Results: Comparative genomic hybridization analyses of four matched orthoxenografts identified recurrent chromosomal rearrangements across cisplatin-resistant tumors in three of them, showing gains at 9q32-q33.1 region. We found a clinical correlation between the presence of 9q32-q33.1 gains in cisplatin-refractory patients and poorer overall survival (OS) in metastatic germ cell tumors. We studied the expression profile of the 60 genes located at that genomic region. POLE3 and AKNA were the only two genes deregulated in resistant tumors harboring the 9q32-q33.1 gain. Moreover, other four genes (GCS, ZNF883, CTR1, and FLJ31713) were deregulated in all five resistant tumors independently of the 9q32-q33.1 amplification. RT-PCRs in tumors and functional analyses in Caenorhabditis elegans (C. elegans) indicate that the influence of 9q32-q33.1 genes in cisplatin resistance can be driven by either up- or downregulation. We focused on glucosylceramide synthase (GCS) to demonstrate that the GCS inhibitor DL-threo-PDMP resensitizes cisplatin-resistant germline-derived orthoxenografts to cisplatin.Conclusions: Orthoxenografts can be used preclinically not only to test the efficiency of drugs but also to identify prognosis markers and gene alterations acting as drivers of the acquired cisplatin resistance. Clin Cancer Res; 24(15); 3755-66. ©2018 AACR.

Nuevas tendencias en el manejo quirúrgico del agujero macular / New trends in the surgical management of macular holes

El agujero macular es un desorden de la interfase vitreorretinal definido como un defecto de espesor completo desde la membrana limitante interna hasta los segmentos externos de los fotorreceptores que normalmente involucra a la fóvea. Es más frecuente en mujeres mayores de 55 años y existe un riesgo de un 10-15 por ciento de afectación del ojo contralateral. Con el aumento de la esperanza de vida, se demandan nuevos retos y técnicas quirúrgicas para este problema de salud. Se realizó una revisión de artículos publicados e indexados en la base de datos de PubMed, que se refirieran a las características y clasificación por tomografía de coherencia óptica del agujero macular y las opciones terapéuticas para este. Nuevas técnicas quirúrgicas se han descrito para los agujeros maculares idiopáticos. El surgimiento de la tomografía de coherencia óptica, sobre todo la de dominio espectral, ha aumentado las posibilidades diagnósticas de tratamiento y seguimiento en las enfermedades de la interfase vitreorretinal, específicamente el agujero macular(AU)

A macular hole is a disorder of the vitreous-retina interface defined as a full-thickness defect from the internal limiting membrane to the external segments of photoreceptors which typically involves the fovea. It is more common among women aged over 55 years, and there is a 10-15 percent risk that the contralateral eye is affected. As life expectancy increases, new challenges come up and new surgical techniques are required for this health problem. A review was conducted of papers published and indexed in the database PubMed which referred to the optical coherence tomography classification and characteristics of macular holes, as well as the therapeutic options to treat it. New surgical techniques have been described for idiopathic macular holes. Introduction of optical coherence tomography, especially spectral domain OCT, has increased the diagnostic possibilities of the treatment and follow-up of vitreous-retina interface disorders, particularly macular holes(AU)

Nuevas tendencias en el manejo quirúrgico del agujero macular / New trends in the surgical management of macular holes

El agujero macular es un desorden de la interfase vitreorretinal definido como un defecto de espesor completo desde la membrana limitante interna hasta los segmentos externos de los fotorreceptores que normalmente involucra a la fóvea. Es más frecuente en mujeres mayores de 55 años y existe un riesgo de un 10-15 por ciento de afectación del ojo contralateral. Con el aumento de la esperanza de vida, se demandan nuevos retos y técnicas quirúrgicas para este problema de salud. Se realizó una revisión de artículos publicados e indexados en la base de datos de PubMed, que se refirieran a las características y clasificación por tomografía de coherencia óptica del agujero macular y las opciones terapéuticas para este. Nuevas técnicas quirúrgicas se han descrito para los agujeros maculares idiopáticos. El surgimiento de la tomografía de coherencia óptica, sobre todo la de dominio espectral, ha aumentado las posibilidades diagnósticas de tratamiento y seguimiento en las enfermedades de la interfase vitreorretinal, específicamente el agujero macular(AU)

A macular hole is a disorder of the vitreous-retina interface defined as a full-thickness defect from the internal limiting membrane to the external segments of photoreceptors which typically involves the fovea. It is more common among women aged over 55 years, and there is a 10-15 percent risk that the contralateral eye is affected. As life expectancy increases, new challenges come up and new surgical techniques are required for this health problem. A review was conducted of papers published and indexed in the database PubMed which referred to the optical coherence tomography classification and characteristics of macular holes, as well as the therapeutic options to treat it. New surgical techniques have been described for idiopathic macular holes. Introduction of optical coherence tomography, especially spectral domain OCT, has increased the diagnostic possibilities of the treatment and follow-up of vitreous-retina interface disorders, particularly macular holes(AU)

Barriers to and facilitators of implementing quality standards in Hospital Day Care Units in Rheumatology: Qualitative approach to the VALORA study. / Barreras y facilitadores en la implantación de estándares de calidad en las unidades de hospital de día reumatológicas. Análisis cualitativo del proyecto VALORA.

OBJECTIVE: To identify barriers and facilitators in the implementation of quality standards in hospital day care units (HDCU) in rheumatology. MATERIAL AND METHODS: We analyzed appraisals of HDCU in terms of standards for structure, processes and results. The qualitative approach was conducted through 13 discussion groups created by rheumatology health professionals (7), nursing professionals (4) and HDCU patients (2). The recruitment of informants was done through purposive sampling, attending to variables that form the perceptions of the HDCU. Data analysis was performed using a descriptive-interpretive method. RESULTS: The specialization of the HDCU and specific training in rheumatology for nursing are perceived as the main facilitator for the implementation of standards. Conversely, the delay in the availability of medicines at the HDCU is identified as a barrier that prolongs patient stay and wastes resources. Differences in local regulations are perceived as a potential barrier to equitable access to medicines. The patients gave higher ratings to the care received than to structural variables or those related to process. CONCLUSIONS: The findings of this study suggest that improvements in the implementation of quality standards in HDCU may include three levels of action: the HDCU, the hospital and a third related to local regulations to access to medicines.

Recommendations for infectious disease screening in migrants to Western Europe with inflammatory arthropathies before starting biologic agents. Results from a multidisciplinary task force of four European societies (SIR, SER, SIMET, SEMTSI) facing the largest impact of the flow of migrants today.

OBJECTIVES: Inflammatory arthritis needs infectious disease screening before starting a biologic agent, however, few data are known about migrant patients, who represent a peculiar population which requires a multidisciplinary approach among international health specialists and should also be considered by health authorities. For this reason, the Italian and Spanish Societies of Rheumatology (SIR and SER) and Tropical Medicine (SIMET and SEMTSI) promoted a multidisciplinary task force in order to produce specific recommendations about screening and advices to be considered in migrant patients with inflammatory arthritis candidate to receive biological therapy, according to their geographical origin. METHODS: The experts provided a prioritised list of research questions and the eligible spectrum of inflammatory arthritis, biologic drugs and infectious disease were defined in order to perform a systematic literature review. A search was made in Medline, Embase and Cochrane library, updated to March 2015. Ubiquitous infections and HBV, HCV, HIV and tuberculosis that are already considered in national and international recommendations, were not included. The strength of each recommendation was determined. RESULTS: The task force members agreed on 7 overarching principles. The risk of reactivation of selected potentially latent infectious disease was addressed in migrants with inflammatory arthritis candidates for biologics was considered and 15 potentially relevant infections were identified. CONCLUSIONS: Fifteen disease-specific recommendations were formulated on the basis of high level of agreement among the experts panel.

The utility of C-reactive protein and procalcitonin for sepsis diagnosis in critically burned patients: A preliminary study.

OBJECTIVE: To assess the utility of C-reactive protein (CRP) and procalcitonin (PCT) as biomarkers of infection in patients with severe burn injury. METHODS: The present study included severe burn injury patients consecutively admitted to the Virgen del Rocío University Hospital (Andalucia, Spain) intensive care unit during a 12-month period. The variables of interest were: age, sex, mechanism of injury, percentage of burned body surface area, the Abbreviated Burn Severity Index (ABSI) and the absence/presence of sepsis. The authors analyzed serum levels of CRP and PCT at admission and every 48 h thereafter until intensive care unit discharge or death. Each determination was considered to be a sample or unit of analysis. RESULTS: A total of 157 determinations were analyzed from 17 severe burn injury patients. Fifty-four samples were considered to be septic, 25 of which corresponded to the first day of a new onset of sepsis. The mean duration of these symptoms was four days (interquartile range two to five days). Significant differences were found in the distributions of CRP and PCT values between sepsis and no-sepsis samples. Analysis of the changes in these biomarkers over time showed that PCT increase (ΔPCT) differentiated these diagnoses, whereas CRP increase (ΔCRP) did not. ROC curve analysis revealed that ΔPCT could predict positive sepsis samples (area under the curve 0.75 [95% CI 0.58 to 0.90]; P=0.003). CONCLUSION: These preliminary results showed that PCT had a better discriminatory capacity than CRP for identifying infectious processes in patients with severe burn injury. A larger sample size would be needed to confirm these results.

OBJECTIF: Évaluer l'utilité de la protéine C réactive (PCR) et de la procalcitonine (PCT) comme biomarqueurs de l'infection chez des grands brûlés. MÉTHODOLOGIE: La présente étude portait sur des grands brûlés admis consécutivement à l'unité de soins intensifs de l'hôpital universitaire Virgen del Rocío d'Andalousie, en Espagne, sur une période de 12 mois. Les variables étudiées étaient l'âge, le sexe, le mécanisme de brûlure, le pourcentage de surface corporelle brûlée, l'indice abrégé de gravité des brûlures (ABSI) et l'absence ou la présence de sepsis. Les auteurs ont analysé les taux sériques de PCR et de PCT des patients à l'admission, puis toutes les 48 heures jusqu'à leur congé des soins intensifs ou à leur décès. Chaque déterminant était considérée comme un échantillon ou une unité d'analyse. RÉSULTATS: Au total, les auteurs ont analysé 157 déterminants chez 17 grands brûlés. Cinquante-quatre échantillons étaient considérés comme septiques, dont 25 correspondaient au premier jour d'apparition du sepsis. Les symptômes duraient en moyenne quatre jours (plage interquartile de deux à cinq jours). Les auteurs ont constaté des différences importantes dans la répartition des valeurs de PCR et de PCT entre les échantillons de sepsis et sans sepsis. L'analyse des changements de ces biomarqueurs au fil du temps a révélé que l'augmentation de la PCT (ΔPCT) distinguait ces diagnostics, contrairement à l'augmentation de la PCR (ΔPCR). L'analyse de la courbe ROC a révélé que la ΔPCT pouvait prédire des échantillons de sepsis positifs (aire sous la courbe de 0,75 [95% IC 0,58 à 0,90]; P=0,003). CONCLUSION: Les résultats préliminaires démontrent que la PCT avait une meilleure capacité discriminatoire que la PCR pour dépister les processus infectieux chez des grands brûlés. Il faudrait un plus gros échantillon pour confirmer ces résultats.

Resultados de dos encuestas dirigidas a inmigrantes y nativos del sureste español: salud, uso de servicios y necesidad de asistencia médica / Results of two surveys of immigrants and natives in Southeast Spain: health, use of services, and need for medical assistance

Objetivo. Comparar la salud, uso de servicios sanitarios y necesidad insatisfecha de atención médica (NIAM) entre inmigrantes y nativos del sureste español. Material y métodos. Estudio transversal de dos muestras representativas de población: inmigrante (n=1150) y nativa (n=1303; Encuesta Nacional de Salud). Se creó una única base de datos con ponderación específica para cada muestra y se estimaron razones de prevalencia (RP) mediante regresión multivariante. Resultados. Marroquíes, ecuatorianos y europeos del este (EE) declararon peor salud que los nativos (RPs [IC95%]: 2.45 [1.91-3.15]; 1.51 [1.28-1.79] y 1.44 [1.08-1.93], respectivamente). Los inmigrantes hicieron mayor uso de las urgencias (excepto EE) y consumieron menos fármacos. Los marroquíes mostraron la mayor diferencia en la frecuencia de NIAM (RP [IC95%]: 12.20 [5.25-28.37]), principalmente por razones laborales (46%). Conclusiones. La salud y el uso de servicios sanitarios difirieron significativamente entre inmigrantes y nativos. Destaca la NIAM alta en marroquíes por causa laboral.

Objective. To compare the self-perceived health, use of health services and unmet need for health care (UNHC) among immigrants and native populations of Southeast Spain. Materials and methods. Cross-sectional study of two representative samples of 1150 immigrants, and 1303 native participants from the National Health Survey. A single database was created with specific weights for each sample, and prevalence ratios (PR) were estimated by multivariate regression. Results. Moroccans, Ecuadorians and Eastern Europeans (EE) reported poorer health than the native population (PRs [CI95%]: 2.45 [1.91-3.15]; 1.51 [1.28-1.79] and 1.44 [1.08-1.93], respectively). Immigrants made greater use of emergencies that natives (except for EE) and had lower use of medication. Moroccan showed the greatest difference in the frequency of UNHC (PR [CI95%]:12.20 [5.25 - 28.37]), mainly because of working limitations (46%). Conclusions. The health status and use of health services among immigrants differ significantly from those of natives. Results highlight the higher frequency of UNHC among immigrants, especially high in Moroccans.

[Results of two surveys of immigrants and natives in Southeast Spain: health, use of services, and need for medical assistance]. / Resultados de dos encuestas dirigidas a inmigrantes y nativos del sureste español: salud, uso de servicios y necesidad de asistencia médica.

OBJECTIVE: To compare the self-perceived health, use of health services and unmet need for health care (UNHC) among immigrants and native populations of Southeast Spain. MATERIALS AND METHODS: Cross-sectional study of two representative samples of 1150 immigrants, and 1303 native participants from the National Health Survey. A single database was created with specific weights for each sample, and prevalence ratios (PR) were estimated by multivariate regression. RESULTS: Moroccans, Ecuadorians and Eastern Europeans (EE) reported poorer health than the native population (PRs [CI95%]: 2.45 [1.91-3.15]; 1.51 [1.28-1.79] and 1.44 [1.08-1.93], respectively). Immigrants made greater use of emergencies that natives (except for EE) and had lower use of medication. Moroccan showed the greatest difference in the frequency of UNHC (PR [CI95%]:12.20 [5.25 - 28.37]), mainly because of working limitations (46%). CONCLUSIONS: The health status and use of health services among immigrants differ significantly from those of natives. Results highlight the higher frequency of UNHC among immigrants, especially high in Moroccans.

Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations for biologics optimization in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.

OBJECTIVE: The aim of this study was to establish guidelines for the optimization of biologic therapies for health professionals involved in the management of patients with RA, AS and PsA. METHODS: Recommendations were established via consensus by a panel of experts in rheumatology and hospital pharmacy, based on analysis of available scientific evidence obtained from four systematic reviews and on the clinical experience of panellists. The Delphi method was used to evaluate these recommendations, both between panellists and among a wider group of rheumatologists. RESULTS: Previous concepts concerning better management of RA, AS and PsA were reviewed and, more specifically, guidelines for the optimization of biologic therapies used to treat these diseases were formulated. Recommendations were made with the aim of establishing a plan for when and how to taper biologic treatment in patients with these diseases. CONCLUSION: The recommendations established herein aim not only to provide advice on how to improve the risk:benefit ratio and efficiency of such treatments, but also to reduce variability in daily clinical practice in the use of biologic therapies for rheumatic diseases.

Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en el lupus eritematoso sistémico / SER Consensus statement on the use of biologic therapy for systemic lupus erythematosus

Objetivo: Elaborar unas recomendaciones que sirvan de referencia a los reumatólogos y otros profesionales implicados en el tratamiento del lupus eritematoso sistémico (LES) que vayan a utilizar o consideren la utilización de terapias biológicas en su manejo. Métodos: Las recomendaciones se emitieron siguiendo la metodología de grupos nominales y basadas en revisiones sistemáticas. El nivel de evidencia y el grado de recomendación se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por técnica Delphi. Resultados: Se realizan recomendaciones sobre el uso de belimumab, actualmente única terapia biológica con aprobación para el tratamiento del LES, y otras terapias biológicas sin indicación aprobada en LES. El objetivo del tratamiento es la respuesta clínica completa, entendida como la ausencia de actividad clínica percibida o constatable. Se matiza el uso de terapias biológicas en LES y cuál debe ser la evaluación previa y la vigilancia del paciente que recibe estos fármacos. Conclusiones: Se presentan las recomendaciones SER sobre el uso de terapias biológicas en el LES(AU)

Objective: To provide a reference to rheumatologists and other physicians involved in the treatment of systemic lupus erythematosus (SLE) who are using, or about to use biologic therapies. Methods: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to a model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. Results: We have produced recommendations on the use of belimumab, the only biological agent with approved indications for SLE, and other biological agents without an indication for SLE. The objective of treatment is to achieve a complete clinical response, taken as the absence of perceived or evident disease activity. Nuances regarding the use of biologic therapies in SLE were reviewed as well, such as the evaluation that should be performed prior to administration and the follow up of patients undergoing these therapies. Conclusions: We present the SER recommendations for the use of biological therapies in patients with SLE(AU)

SER consensus statement on the use of biologic therapy for systemic lupus erythematosus.

OBJECTIVE: To provide a reference to rheumatologists and other physicians involved in the treatment of systemic lupus erythematosus (SLE) who are using, or about to use biologic therapies. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to a model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. RESULTS: We have produced recommendations on the use of belimumab, the only biological agent with approved indications for SLE, and other biological agents without an indication for SLE. The objective of treatment is to achieve a complete clinical response, taken as the absence of perceived or evident disease activity. Nuances regarding the use of biologic therapies in SLE were reviewed as well, such as the evaluation that should be performed prior to administration and the follow up of patients undergoing these therapies. CONCLUSIONS: We present the SER recommendations for the use of biological therapies in patients with SLE.

Blebitis asociada a endoftalmitis: presentación de casos / Blebytis associated to endophthalmitis: presentation of a case

La endoftalmitis se conoce como una de las complicaciones más graves y temidas por los oftalmólogos. El 70 por ciento de ellas se presentan después de un proceder quirúrgico. Las infecciones relacionadas con la bula de filtración en la cirugía del glaucoma son infrecuentes y representan el 0,1 por ciento de todas la endoftalmitis, aunque se consideran potencialmente graves. Comprenden la flebitis, que es un término introducido para describir la infección de la bula de filtración, de aspecto mucopurulento, acompañada de una mediana actividad en cámara anterior y en ausencia de vitritis. Este último signo es la diferencia más importante con la blebitis asociada a endoftalmitis, en la cual sí hay compromiso del vítreo, que se asocia a hipopión y severa pérdida visual. Se presentan tres pacientes operados por cirugía filtrante de glaucoma, quienes presentaron un cuadro de blebitis asociada a endoftalmitis en los dos restante, necesitando tratamiento tópico más intraviteo y quirúrgico, respectivamente. Si se realiza un diagnóstico, tratamiento adecuado y oportuno, en estas entidades poco frecuentes pero devastadoras, se minimizan los riesgos y las complicaciones graves, obteniendo un mejor pronóstico visual, lo que llevó a los autores a presentar esta serie de casos(AU)

The endophthalmitis is known a one of the most serious complications feared by the ophthalmologists. 70 per cent of them appear after a surgical procedure. The infections related with the filtration bulla in the glaucoma surgery are infrequent and represent 0,1 per cent of all the endophthalmitis, though they are considered potentially serious. They comprehend the blebytis, a term introduced to describe the infection of the filtration bulla, with mucous purulent aspect, accompanied with a medium activity in the anterior chamber and lacking vitritis. This last sign is the most important difference with the blebytis associated to endophthalmitis, in which the vitreous humor is involved, associated to hypopyon and severe visual loss. We present three patients operated by glaucoma filtrating surgery who presented a picture of blebytis associated to endophthalmitis in the other two, needing topical treatment plus intravitreous and surgical, respectively. If an opportune and adequate diagnosis and treatment is made in these infrequent but devastating entities, the serious risks and complications are minimized, obtaining a better visual prognosis. Those were the reasons leading the authors to present these cases(AU)

Blebitis asociada a endoftalmitis. Presentación de casos / Blebytis associated to endophthalmitis. Presentation of a case

La endoftalmitis se conoce como una de las complicaciones más graves y temidas por los oftalmólogos. El 70 % de ellas se presentan después de un proceder quirúrgico. Las infecciones relacionadas con la bula de filtración en la cirugía del glaucoma son infrecuentes y representan el 0,1 % de todas la endoftalmitis, aunque se consideran potencialmente graves. Comprenden la flebitis, que es un término introducido para describir la infección de la bula de filtración, de aspecto mucopurulento, acompañada de una mediana actividad en cámara anterior y en ausencia de vitritis. Este último signo es la diferencia más importante con la blebitis asociada a endoftalmitis, en la cual sí hay compromiso del vítreo, que se asocia a hipopión y severa pérdida visual. Se presentan tres pacientes operados por cirugía filtrante de glaucoma, quienes presentaron un cuadro de blebitis asociada a endoftalmitis en los dos restante, necesitando tratamiento tópico más intraviteo y quirúrgico, respectivamente. Si se realiza un diagnóstico, tratamiento adecuado y oportuno, en estas entidades poco frecuentes pero devastadoras, se minimizan los riesgos y las complicaciones graves, obteniendo un mejor pronóstico visual, lo que llevó a los autores a presentar esta serie de casos.

The endophthalmitis is known a one of the most serious complications feared by the ophthalmologists. 70 % of them appear after a surgical procedure. The infections related with the filtration bulla in the glaucoma surgery are infrequent and represent 0,1 % of all the endophthalmitis, though they are considered potentially serious. They comprehend the blebytis, a term introduced to describe the infection of the filtration bulla, with mucous purulent aspect, accompanied with a medium activity in the anterior chamber and lacking vitritis. This last sign is the most important difference with the blebytis associated to endophthalmitis, in which the vitreous humor is involved, associated to hypopyon and severe visual loss. We present three patients operated by glaucoma filtrating surgery who presented a picture of blebytis associated to endophthalmitis in the other two, needing topical treatment plus intravitreous and surgical, respectively. If an opportune and adequate diagnosis and treatment is made in these infrequent but devastating entities, the serious risks and complications are minimized, obtaining a better visual prognosis. Those were the reasons leading the authors to present these cases.