Disease Phenotype and Outcome Depending on the Age at Disease Onset in Patients Carrying the R92Q Low-Penetrance Variant in TNFRSF1A Gene

Aparició en l'adult; Malalties autoinflamatòries; Variants de baixa penetrànciaAparición en el adulto; Enfermedades autoinflamatorias; Variantes de baja penetranciaAdult onset; Autoinflammatory diseases; Low-penetrance variantsBackground: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal-dominant autoinflammatory disease caused by mutations in the TNFRSF1A gene. R92Q, a low-penetrance variant, is usually associated with a milder TRAPS phenotype than structural or pathogenic mutations. No studies differentiating R92Q-related disease in patients with pediatric and adult onset have been performed to date. Objective: To analyze clinical features and disease outcomes in patients diagnosed with TRAPS associated with R92Q variant and to investigate differences between patients with pediatric and adult disease onset. Methods: A retrospective review of patients with R92Q-related disease from four reference centers for autoinflammatory diseases was performed. Clinical and laboratory features, family history of autoinflammatory diseases, treatments received, and outcomes during follow-up were recorded and separately analyzed in pediatric and adult patients. Our results were included in the analysis with other reported pediatric and adult R92Q-related disease series. Results: Our series encompassed 18 patients (9 females and 9 males) with R92Q variant. In 61% of patients, disease onset occurred during infancy and in 39%, during adulthood, with a median diagnostic delay of 5 years and a follow-up of 5.4 years. A positive family history of autoinflammatory disease was detected in 28% of patients. All patients presented with febrile recurrent episodes. Other common symptoms included arthralgia/arthritis (61%), myalgia (39%), asthenia/fatigue (44%), abdominal pain (39%), headache (33%), odynophagia (33%), skin rash (28%), and chest pain (22%). During attacks, 80% of patients increased acute phase reactants levels. No patient had developed amyloidosis during the study period. At the end of follow-up, 28% of patients were asymptomatic and treatment free, 50% were receiving non-steroidal anti-inflammatory drugs or glucocorticoids on demand, and 22% were being treated with biologic agents. When differences between pediatric and adult patients were globally analyzed, adults tended to have longer attacks duration and presented more frequently with chest pain and headache, while abdominal pain, vomiting, cervical adenitis, and pharyngitis predominated in pediatric patients. No differences in outcomes and treatment requirements were observed in both age groups. Conclusion: This study has contributed to characterize R92Q-related disease by identifying trends in disease phenotypes depending on the age at disease onset.This study has been supported by Ministerio de Economía y Competitividad (SAF 14/57708-R) and co-funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, and Una manera de hacer Europa (JH-R)

Case study and cooperative learning at university

Diseñar los planes de estudio en función del desarrollo de competencias demanda cambios metodológicos importantes. El método de caso es una de las estrategias de enseñanza y aprendizaje más adecuadas para desarrollar las competencias orientadas al trabajo en equipo y al fomento de la colaboración. El artículo que se presenta es un resumen del proyecto de innovación “El estudio de caso y el aprendizaje cooperativo en la universidad” (PIE-2010-2012) financiado por la Universidad del País Vasco. El objetivo general del proyecto es implementar el método de caso en las asignaturas de Organización de Centros (Socio)Educativos (titulaciones de Pedagogía y Educación Social). MÉTODO: Se han seleccionado dos grupos de segundo curso de la titulación de Educación Social (uno en euskera y otro en castellano) y otros dos del mismo curso de Pedagogía en ambos idiomas. En uno de los grupos de cada titulación se trabajaron técnicas de dinámica de grupo y en otro se desarrolló la estrategia del método de caso sin la ayuda de ellas. El alumnado evaluó la experiencia mediante un diario de grupo. RESULTADOS: Los datos indican que el alumnado está satisfecho con las actividades de aprendizaje realizadas en clase, las competencias de la titulación se desarrollan de manera satisfactoria y el funcionamiento de los grupos experimentales, en general, es mejor que el de los grupos control. La eficacia del trabajo grupal está estrechamente vinculada con variables de tipo relacional. DISCUSIÓN: La cooperación, la ayuda y la supervisión de tareas entre los miembros del grupo fomentan la interacción y el sentimiento de seguridad entre los estudiantes que tienen dificultades para lograr los objetivos de aprendizaje. Un alumno o alumna que se siente respaldado por su grupo a nivel académico, afectivo y relacional probablemente va a percibir un contexto de trabajo más seguro, inclusivo y acogedor.Designing syllabuses according to how competences develop demands major methodological changes. The case method is one of the most suitable teaching and learning strategies that can be used to develop competences geared towards teamwork and encouraging collaboration. METHOD: Two groups from the second year leading to the Social Education qualification were selected (one in Basque and the other in Spanish), together with a further two from the same year leading to the Pedagogy qualification in both languages. Group enabling techniques were used in one of the two degree course groups, while the strategy to be pursued for the case method was developed in the other group without their help. Students assessed the experience using a group diary. RESULTS: Data shows that students are satisfied with the learning activities carried out in class, the competences attached to the qualification are developed satisfactorily, and, generally speaking, the experimental groups function better than the control groups. The effectiveness of group work is closely linked to variables of a relational nature. DISCUSSION: Cooperation, help and the supervision of tasks among group members encourage interaction and a sense of security among students who are experiencing difficulties in achieving learning objectives. Students who feel that they are being backed up by their group on an academic, affective and relational level are probably going to find themselves in a more secure, inclusive and cosy working context.Grupo FORCE (HUM-386). Departamento de Didáctica y Organización Escolar de la Universidad de Granada

Donostialdeko gizarte eta hezkuntza arloko zerbitzuetako profesionalen laneko asegabetasuna

Los profesionales de los servicios socioeducativos y asistenciales desarrollan su labor en contextos problemáticos. Las actividades relacionadas con la intervención socioeducativa exigen mucha implicación y causan un desgaste físico y emocional importante. La insatisfacción en el trabajo influye en la salud de los trabajadores, en la calidad de la prestación de servicios y, en definitiva, en el funcionamiento de las organizaciones sociales. El estudio que se presenta a continuación se ha reali;:.ado durante el curso 2011-2012 y es parte de una investigación más amplia que ha tratado de analizar las características de los sectores sociales en riesgo de exclusión y de los profesionales que trabajan con estos colectivos. El objetivo de este artículo es analizar las causas y reflexionar en torno al fenómeno de la insatisfacción laboral de los profesionales que trabajan en los servicios socioeducativos de la zona de Donostia. Se ha administrado un cuestionario de 120 preguntas a los trabajadores de los servicios sociales recogiéndose las respuestas de 141 profesionales. La insatisfacción laboral está estrechamente relacionada con la conducta inadecuada en el trabajo, las características de la tarea (complejidad, cantidad de trabajo ... ), ratios y hacinamiento, malas relaciones con los compañeros-as y usuarios-as, inseguridad laboral (agresiones, insultos, conflictos ... ) y ambigüedad de la tarea que realiza el profesional (falta de proyecto y de criterios claros)

Efficacy and Safety of Anakinra Plus Standard of Care for Patients With Severe COVID-19: A Randomized Phase 2/3 Clinical Trial

Efficacy; Safety; COVID-19Eficacia; Seguridad; COVID-19Eficàcia; Seguretat; COVID-19Importance COVID-19 pneumonia is often associated with hyperinflammation. The efficacy and safety of anakinra in treating patients with severe COVID-19 pneumonia and hyperinflammation are still unclear. Objective To assess the efficacy and safety of anakinra vs standard of care alone for patients with severe COVID-19 pneumonia and hyperinflammation. Design, Setting, and Participants The Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to COVID-19 (ANA-COVID-GEAS) was a multicenter, randomized, open-label, 2-group, phase 2/3 clinical trial conducted at 12 hospitals in Spain between May 8, 2020, and March 1, 2021, with a follow-up of 1 month. Participants were adult patients with severe COVID-19 pneumonia and hyperinflammation. Hyperinflammation was defined as interleukin-6 greater than 40 pg/mL, ferritin greater than 500 ng/mL, C-reactive protein greater than 3 mg/dL (rationale, ≥5 upper normal limit), and/or lactate dehydrogenase greater than 300 U/L. Severe pneumonia was considered if at least 1 of the following conditions was met: ambient air oxygen saturation 94% or less measured with a pulse oximeter, ratio of partial pressure O2 to fraction of inspired O2 of 300 or less, and/or a ratio of O2 saturation measured with pulse oximeter to fraction of inspired O2 of 350 or less. Data analysis was performed from April to October 2021. Interventions Usual standard of care plus anakinra (anakinra group) or usual standard of care alone (SoC group). Anakinra was given at a dose of 100 mg 4 times a day intravenously. Main Outcomes and Measures The primary outcome was the proportion of patients not requiring mechanical ventilation up to 15 days after treatment initiation, assessed on an intention-to-treat basis. Results A total of 179 patients (123 men [69.9%]; mean [SD] age, 60.5 [11.5] years) were randomly assigned to the anakinra group (92 patients) or to the SoC group (87 patients). The proportion of patients not requiring mechanical ventilation up to day 15 was not significantly different between groups (64 of 83 patients [77.1%] in the anakinra group vs 67 of 78 patients [85.9%] in the SoC group; risk ratio [RR], 0.90; 95% CI, 0.77-1.04; P = .16). Anakinra did not result in any difference in time to mechanical ventilation (hazard ratio, 1.72; 95% CI, 0.82-3.62; P = .14). There was no significant difference between groups in the proportion of patients not requiring invasive mechanical ventilation up to day 15 (RR, 0.99; 95% CI, 0.88-1.11; P > .99). Conclusions and Relevance In this randomized clinical trial, anakinra did not prevent the need for mechanical ventilation or reduce mortality risk compared with standard of care alone among hospitalized patients with severe COVID-19 pneumonia.Funding for this study was received from the Regional Government of Navarra, Spain (project 0011-3597-2020-000028 to Dr Fanlo), and drugs were provided by the company Swedish Orphan Biovitrum (Sobi)

Donostialdeko gizarte eta hezkuntza arloko zerbitzuetako profesionalen laneko asegabetasuna

Los profesionales de los servicios socioeducativos y asistenciales desarrollan su labor en contextos problemáticos. Las actividades relacionadas con la intervención socioeducativa exigen mucha implicación y causan un desgaste físico y emocional importante. La insatisfacción en el trabajo influye en la salud de los trabajadores, en la calidad de la prestación de servicios y, en definitiva, en el funcionamiento de las organizaciones sociales. El estudio que se presenta a continuación se ha reali;:.ado durante el curso 2011-2012 y es parte de una investigación más amplia que ha tratado de analizar las características de los sectores sociales en riesgo de exclusión y de los profesionales que trabajan con estos colectivos. El objetivo de este artículo es analizar las causas y reflexionar en torno al fenómeno de la insatisfacción laboral de los profesionales que trabajan en los servicios socioeducativos de la zona de Donostia. Se ha administrado un cuestionario de 120 preguntas a los trabajadores de los servicios sociales recogiéndose las respuestas de 141 profesionales. La insatisfacción laboral está estrechamente relacionada con la conducta inadecuada en el trabajo, las características de la tarea (complejidad, cantidad de trabajo ... ), ratios y hacinamiento, malas relaciones con los compañeros-as y usuarios-as, inseguridad laboral (agresiones, insultos, conflictos ... ) y ambigüedad de la tarea que realiza el profesional (falta de proyecto y de criterios claros)

Spanish cohort of VEXAS syndrome : clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism

The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms

Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes

Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are dominantly inherited autoinflammatory diseases associated to gain-of-function NLRP3 mutations and included in the cryopyrin-associated periodic syndromes (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ≈35% of patients with CINCA. However, no data are currently available regarding the relevance of this mechanism in other CAPS phenotypes. OBJECTIVE: To evaluate somatic NLRP3 mosaicism as the disease-causing mechanism in patients with clinical CAPS phenotypes other than CINCA and NLRP3 mutation-negative. METHODS: NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. Apoptosis-associated Speck-like protein containing a CARD (ASC)-dependent nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. RESULTS: A variable degree (5.5-34.9%) of somatic NLRP3 mosaicism was detected in 12.5% of enrolled patients, all of them with a MWS phenotype. Six different missense variants, three novel (p.D303A, p.K355T and p.L411F), were identified. Bioinformatics and functional analyses confirmed that they were disease-causing, gain-of-function NLRP3 mutations. All patients treated with anti-interleukin1 drugs showed long-lasting positive responses. CONCLUSIONS: We herein show somatic NLRP3 mosaicism underlying MWS, probably representing a shared genetic mechanism in CAPS not restricted to CINCA syndrome. The data here described allowed definitive diagnoses of these patients, which had serious implications for gaining access to anti-interleukin 1 treatments under legal indication and for genetic counselling. The detection of somatic mosaicism is difficult when using conventional methods. Potential candidates should benefit from the use of modern genetic tool

Case study and cooperative learning in the university

Designing syllabuses according to how competences develop demands major methodological changes. The case method is one of the most suitable teaching and learning strategies that can be used to develop competences geared towards teamwork and encouraging collaboration. METHOD:Two groups from the second year leading to the Social Education qualification were selected (one in Basque and the other in Spanish), together with a further two from the same year leading to the Pedagogy qualification in both languages. Group enabling techniques were used in one of the twodegree course groups, while the strategy to be pursued for the case method was developed in the other group without their help. Students assessed the experience using a group diary. RESULTS: Data shows that students are satisfied with the learning activities carried out in class, the competences attached to the qualification are developed satisfactorily, and, generally speaking, the experimental groups function better than the control groups. The effectiveness of group work is closely linked to variables of a relational nature. DISCUSSION: Cooperation, help and the supervision of tasks among group members encourage interaction and a sense of security amongstudents who are experiencing difficulties in achieving learning objectives. Students who feel that they are being backed up by their group on an academic, affective and relational level are probably going to find themselves in a more secure, inclusive and cosy working context

Estudio de caso y aprendizaje cooperativo en la universidad

Diseñar los planes de estudio en función del desarrollo de competencias demanda cambios metodológicos importantes. El método de caso es una de las estrategias de enseñanza y aprendizaje más adecuadas para desarrollar las competencias orientadas al trabajo en equipo y al fomento de la colaboración. El artículo que se presenta es un resumen del proyecto de innovación “El estudio de caso y el aprendizaje cooperativo en la universidad” (PIE-2010-2012) financiado por la Universidad del País Vasco. El objetivo general del proyecto es implementar el método de caso en las asignaturas de Organización de Centros (Socio)Educativos (titulaciones de Pedagogía y Educación Social). MÉTODO: Se han seleccionado dos grupos de segundo curso de la titulación de Educación Social (uno en euskera y otro en castellano) y otros dos del mismo curso de Pedagogía en ambos idiomas. En uno de los grupos de cada titulación se trabajaron técnicas de dinámica de grupo y en otro se desarrolló la estrategia del método de caso sin la ayuda de ellas. El alumnado evaluó la experiencia mediante un diario de grupo. RESULTADOS: Los datos indican que el alumnado está satisfecho con las actividades de aprendizaje realizadas en clase, las competencias de la titulación se desarrollan de manera satisfactoria y el funcionamiento de los grupos experimentales, en general, es mejor que el de los grupos control. La eficacia del trabajo grupal está estrechamente vinculada con variables de tipo relacional. DISCUSIÓN: La cooperación, la ayuda y la supervisión de tareas entre los miembros del grupo fomentan la interacción y el sentimiento de seguridad entre los estudiantes que tienen dificultades para lograr los objetivos de aprendizaje. Un alumno o alumna que se siente respaldado por su grupo a nivel académico, afectivo y relacional probablemente va a percibir un contexto de trabajo más seguro, inclusivo y acogedor.