Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case-control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March-July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3-5.9), occupational risk (OR: 2.9; 95%CI: 1.8-4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2-2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09-0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

Experiencias en el aula: tercer encuentro de prácticas pedagógicas innovadoras.

Experiencias de profesores en su quehacer en los distintos ambientes de aprendizaje presenciales y a distancia.Para el Centro de Excelencia Docente aeiou constituye un honor presentar la publicación del Tercer Encuentro de Prácticas Pedagógicas Innovadoras en el que se destacan cuarenta trabajos de profesores de UNIMINUTO provenientes de diferentes sedes. Con este encuentro son ya tres que bajo la dirección de aeiou los profesores han compartido su quehacer en los distintos ambientes de aprendizaje presenciales y a distancia. Cada año el Centro de Excelencia Docente invita a los profesores a participar en este evento, para el 2108 además de la inscripción voluntaria por parte de cada profesor, se invitó al estudiantado a que postularan a sus profesores que consideraban eran innovadores y creativos en el cumplimiento de su función docente y se obtuvo una respuesta importante por parte de los estudiantes, que para algunos profesores resultó sorpresiva porque quizás no habían considerado que el trabajo que hacían en su ambiente de aprendizaje era diferente, fuera de lo común. Luego de una evaluación de jurados nacionales e internacionales de las prácticas presentadas y de la realización del evento, que tuvo como novedad hacerlo de forma simultánea en cuatro sedes donde UNIMINUTO tiene presencia: Buga, Ibagué, Pereira y Bogotá, se comparte la presente publicación para tener como referencia y evidencia el trabajo que los profesores hacen a diario

Estudios actuales de literatura comparada. Teorías de la literatura y diálogos interdisciplinarios

Estos dos volúmenes constituyen una contribución al desarrollo de la comparatística que se realiza, principalmente, desde América Latina. El primer volumen está organizado en tres partes y consta de 22 artículos, mientras que el segundo reúne 24 capítulos.UCR::Vicerrectoría de Docencia::Artes y Letras::Facultad de Letras::Escuela de Filología, Lingüística y LiteraturaUCR::Vicerrectoría de Docencia::Ciencias Básicas::Sistema de Educación General::Escuela de Estudios GeneralesUCR::Vicerrectoría de Investigación::Sistema de Estudios de Posgrado::Artes y Letras::Maestría Académica en Literatura FrancesaUCR::Vicerrectoría de Investigación::Sistema de Estudios de Posgrado::Artes y Letras::Maestría Académica en Literatura LatinoamericanaUCR::Vicerrectoría de Docencia::Artes y Letras::Facultad de Letras::Escuela de Lenguas Moderna

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC &gt; 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Cuentos de nunca acabar. Aproximaciones desde la interculturalidad

Cuentos de nunca acabar. Aproximaciones desde la interculturalidad, surge después de la pandemia y su imposibilidad de socializar “en persona” con los compañeros de eventuales encuentros, porque la Comprensión Lectora tenía que reinventarse para su nueva reflexión cognitiva, adaptación contextual y reconstrucción del conocimiento. Este renovado enfoque de la realidad postpandemia, concebido en el marco de la educación intercultural comunitaria, busca potencializar los entornos naturales, sociales y culturales como recursos de aprendizaje multidisciplinario a través del lenguaje animado de los cuentos. En este marco, había que dinamizar la asignatura de Comunicación Oral y Escrita, que se dicta en los Primeros Niveles de los Centros de Apoyo de Otavalo, Cayambe, Latacunga y Riobamba, mediante un eje transversal donde los estudiantes escriban fundamentados en valores de la cosmovisión andina, considerando que provienen de varios lugares de la sierra y amazonía ecuatoriana. Todo surgió del encuentro presencial de un sábado cualquiera donde los estudiantes realizaban ejercicios narrativos, logrando una apreciable respuesta de imaginación, más emotiva que la clásica tarea de las Unidades, tanto así que, pasados unos días, seguían llegando sus escritos a mi correo. Entonces nos pusimos manos a la obra, cada estudiante tendría dos opciones como Actividad Integradora, la primera consistía en escribir un cuento de su propia inspiración, y la segunda analizar un clásico para comentar sus valores y antivalores. La mayor parte de estudiantes decidió escribir su propio cuento, de donde se escogieron algunas participaciones que podrían considerarse originales, para una edición que, respetando la transcripción de la tradición oral que prima en los sectores comunitarios, nos concretamos en revisar la puntuación y ortografía para publicarlos. Con esto buscamos innovar la Actividad Integradora, por algo más práctico y operativo para configurar los Objetos de Aprendizaje que buscamos. Así nació, en medio del camino, este libro de Cuentos de nunca acabar. Aproximaciones desde la interculturalidad, que ponemos en sus manos. Hernán Hermosa Mantilla Quito, junio de 202

Adelante / Endavant

Séptimo desafío por la erradicación de la violencia contra las mujeres del Institut Universitari d’Estudis Feministes i de Gènere "Purificación Escribano" de la Universitat Jaume