Autoimmune pancreatitis in patients with inflammatory bowel disease: A real-world multicentre collaborative ECCO CONFER study

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMAutoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP–IBD and predictors of complicated AIP course have rarely been reported. Methods: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. Results: We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ± 16 years]. The majority of Crohn’s disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred. Conclusions: In this large international cohort of patients with concomitant AIP–IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP cours

Anti‑TNF agents and new biological agents (Vedolizumab and Ustekinumab) in the prevention and treatment of postoperative recurrence after surgery in crohn’s disease

Surgery for Crohn’s disease (CD) is not curative, as postoperative recurrence (POR) after ileocolonic resection is the rule in the absence of prophylactic treatment. In the present article, we critically review available data on the role of anti-tumour necrosis factor (TNF) agents and new biologics (including vedolizumab and ustekinumab) in the prevention and treatment of POR after surgery in CD. Several studies (summarised in various meta-analyses) have confrmed the efcacy of anti-TNFs in the prevention of POR. We identifed 37 studies, including 1863 CD patients, with mean endoscopic POR at 6–12 months of 29%. Only few randomised controlled trials (RCTs) have directly compared thiopurines and anti-TNFs, with controversial results, although the superiority of the latter is supported by several meta-analyses. Infiximab and adalimumab seem equally efective. The combination of anti-TNFs and immunosuppressives should be considered in patients previously exposed to anti-TNFs. Several studies have shown that anti-TNFs remain an efective option to prevent POR also in patients with anti-TNF failure before surgery. In fact, the use of the same anti-TNF before and after surgery might be efective for the prevention of POR. Prophylactic anti-TNF treatment, once started, should be continued long term. Anti-TNFs are also efective for the treatment of established POR. Retreatment with anti-TNFs for POR is a valid strategy even after their preoperative failure. In six studies (including 156 patients) evaluating vedolizumab, mean endoscopic POR at 6–12 months was 41%. The non-randomised comparison of anti-TNFs and vedolizumab has provided controversial results. One placebo-controlled RCT confrmed that vedolizumab is quite efective in preventing POR in CD patients with increased risk of recurrence. Seven studies (including 162 patients) evaluated ustekinumab, with a mean endoscopic POR at 6–12 months of 41%. The comparative efcacy of ustekinumab and anti-TNFs is still unclear. Ustekinumab and vedolizumab seem to be equally efective, although the experience is very limited. In conclusion, to date, anti-TNFs are the most efective agents in preventing and treating POR in CD. Anti-TNFs remain an efective option to prevent POR also in patients with anti-TNF failure before surgery. Vedolizumab seems to be quite efective in the prevention of POR in patients with increased risk of recurrence. Ustekinumab is probably also efective in the postoperative setting, although the comparative efcacy with anti-TNFs or vedolizumab is still unclea

Validación de la colonografía por tomografía computarizada para el diagnóstico de los pólipos y masas colorrectales

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 24 de Junio de 200

Effectiveness and safety of Ustekinumab in ulcerative colitis: real-world evidence from the ENEIDA registry

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMThe development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods: Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results: A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions: Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinuma

Long-term safety of in utero exposure to anti-TNFα drugs for the treatment of inflammatory bowel disease: Results from the multicenter European TEDDY study

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMThe long-term safety of exposure to anti-tumor necrosis factor (anti-TNF alpha) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNF alpha drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNF alpha medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNF alpha agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNF alpha agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNF alpha drugs does not seem to be associated with increased short-term or long-term risk of severe infections in childrenTh is research has been funded by grant from the Instituto de Salud Carlos III (PI13/00041

Tofacitinib in ulcerative colitis: real-world evidence from the ENEIDA registry

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMTo evaluate the effectiveness and safety of tofacitinib in ulcerative colitis [UC] in real life. Methods Patients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score [PMS]. Short-term response/remission was assessed at Weeks 4, 8, and 16. Results, A total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio [OR] = 0].2; 95% confidence interval [CI] = 0].1–0.4) was the only variable associated with lower likelihood of achieving remission at Week 8. Higher PMS at Week 4 [OR = 0.5; 95% CI = 0.3–0.7] and higher PMS at Week 8 [OR = 0.2; 95% CI = 0.1–0.5] were associated with lower probability of achieving remission at Week 16. A total of 45 patients [40%] discontinued tofacitinib over time. Higher PMS at Week 8 was the only factor associated with higher tofacitinib discontinuation [hazard ratio = 1.5; 95% CI = 1.3–1.6]. A total of 34 patients had remission at Week 8; of these, 65% had relapsed 52 weeks after achieving remission; the dose was increased to 10 mg/12 h in nine patients, and five of them reached remission again. Seventeen patients had adverse events. Conclusions: Tofacitinib is effective and safe in UC patients in real practice, even in a highly refractory cohort. A relevant proportion of patients discontinue the drug over time, mainly due to primary failur

Variantes genéticas en la región 3’UTR de los genes BRCA1 y BRCA2 y su reconocimiento por miARNs en cáncer de mama y ovario hereditario

El síndrome de cáncer de mama y ovario hereditario (HBOC) es una patología causada principalmente por mutaciones en los genes BRCA1 y BRCA2. La región 3'UTR de los genes permite la unión de la mayoría de los microARNs involucrados en la regulación genética fina. El objetivo de esta tesis doctoral fue identificar variantes alélicas en los sitios de unión de miARN en las regiones 3'UTR en los genes BRCA1 y BRCA2 en pacientes diagnosticados con HBOC. La estrategia experimental consistió en colectar muestras de sangre de 50 pacientes con HBOC y de 50 controles de una población del Noreste de México y obtener el ADN genómico. Las regiones 3'UTR de BRCA1 y BRCA2 se amplificaron por PCR punto final y se secuenciaron para identificar variantes genéticas utilizando herramientas de bioinformática. Los resultados mostraron nueve polimorfismos (SNPs): cuatro en BRCA1 (rs3092995 (C/G), rs8176318 (C/T), rs111791349 (G/A) y rs12516 (C/T)) y cinco en BRCA2 (rs15869 (A/C), rs7334543 (A/G), rs1157836 (A/G) y rs75353978 (TT/del TT). También se identificó una nueva variante en la posición c.* 457 (A / C) en 3'UTR de BRCA2. Las variantes rs111791349-A, rs15869-C y c.*457-C aumentaron el riesgo de HBOC en la población de estudio: (odds ratio (OR) rango 3.7- 15.4; p <0.05). Las variantes genéticas en el 3'UTR de BRCA1 y BRCA2 aumentaron el riesgo de HBOC entre 3.7-15.4 veces en la población con esta condición. La presencia/ausencia de estos SNPs puede influir en la pérdida / creación de sitios de unión de miARN, como hsa-miR-1248 en BRCA1 3'UTR o el sitio de unión de la familia hsamiR-548 en BRCA2. Estos resultados agregan nuevas pruebas de participación de miARN en la patogénesis de HBOC. En conclusión la presencia los SNPs rs8176318 (G/T), rs15869 (A/C) y la variante c.*457 (A/C) fueron significativas y están relacionadas a un aumento en el riesgo en el grupo de HBOC. La nueva variante descrita en la región 3’UTR de BRCA2, tanto en pacientes HBOC como en los controles, ubicada en sitio c.*457 posiblemente sea específica para población de la región del Noreste de México. Finalmente, el análisis in silico se postula la pérdida/creación de sitios de unión de miARN, como hsa-miR-1248 en BRCA1 3'UTR o el sitio de unión de la familia hsa-miR548 en BRCA2 que sugiere la participación de miARNs en la patogénesis del HBOC. Abstract Hereditary breast and ovarian cancer (HBOC) syndrome are mainly caused by mutations in the BRCA1 and BRCA2 genes. The 3’UTR region allows the binding of microRNAs, which are involved in genetic tune regulation. We aimed to identify allelic variants on 3’UTR miRNA-binding sites in the BRCA1 and BRCA2 genes in HBOC patients. Blood samples were obtained from 50 patients with HBOC and from 50 controls. The 3’UTR regions of BRCA1 and BRCA2 were amplified by PCR and sequenced to identify genetic variants using bioinformatics tools. We detected nine polymorphisms in 3’UTR, namely: four in BRCA1 (rs3092995 (C/G), rs8176318 (C/T), rs111791349 (G/A), and rs12516 (C/T)) and five in BRCA2 (rs15869 (A/C), rs7334543 (A/G), rs1157836 (A/G), and rs75353978 (TT/del TT)). A new variant in position c.*457 (A/C) on 3’UTR of BRCA2 was also identified. The following three variants increased the risk of HBOC in the study population: rs111791349-A, rs15869-C, and c.*457-C (odds ratio (OR) range 3.7–15.4; p < 0.05). Genetic variants into the 3’UTR of BRCA1 and BRCA2 increased the risk of HBOC between 3.7–15.4 times in the study population. The presence/absence of these polymorphisms may influence the loss/creation of miRNA binding sites, such as hsa-miR1248 in BRCA1 3′UTR or the hsa-miR-548 family binding site in BRCA2. Our results add new evidence of miRNA participation in the pathogenesis of HBOC

Spanish media coverage of journalistic artificial intelligence: relevance, topics and framing

La inteligencia artificial (IA) se ha convertido en un tema muy discutido debido a su implementación en muchas áreas, incluida la periodística. Se examina la cobertura de la IA periodística en medios escritos españoles, particularmente la relevancia otorgada, los temas tratados y el encuadre desde el que se aborda, mediante un análisis de contenido cuantitativo y un análisis estadístico. La IA periodística solo aparece como tema principal en un tercio de los casos, está cada vez más presente, se distribuye en más secciones y aparece principalmente en piezas escritas por periodistas de los medios. Predominan los textos informativos, pero son los periodistas quienes escriben la mayoría de los interpretativos y prácticamente todos los opinativos, promoviendo así el conocimiento y el debate público. Se ocupan principalmente de la aplicación más extendida de la IA, que es la automatización, muy por encima de los problemas laborales y éticos. La IA periodística suele enmarcarse más desde sus beneficios que de sus riesgos, pero recientemente se observan algunos cambios: una creciente preocupación por sus peligros e implicaciones éticas; la detección de abundantes piezas con encuadre personal, donde los periodistas hablan de su profesión y del uso de ChatGPT; y una creciente relevancia del encuadre episódico con el desarrollo de productos de IA. Este estudio podría haber examinado todo tipo de medios, aunque habría ido más allá de la naturaleza exploratoria de esta investigación pionera. Con este trabajo ampliamos la producción científica sobre IA periodística en España, donde esta perspectiva no ha sido analizada.Artificial intelligence (AI) has become a much-discussed topic due to its implementation in many areas, including journalism. This article examines the coverage of journalistic AI in Spanish written media, in particular the relevance allocated to it, the topics that are addressed, and the framing from which it is approached. Quantitative content analysis and statistical analysis were used. Although journalistic AI only appears as the main topic in a third of cases, it is increasingly present, it is distributed across more sections, and it mostly appears in self-written articles. Despite informative texts prevailing, journalists author the majority of interpretative and practically all opinion pieces, thus increasing knowledge and promoting public debate. They deal largely with the most widespread application of AI, which is news automation, ranking well above the issues of job loss and ethics. Although journalistic AI is generally framed from a perspective of its benefits rather than from its risks, some recent changes are observed: growing concern about its dangers and its ethical implications; the detection of numerous pieces with a Personal Frame, where journalists reflect on their profession and the use of ChatGPT; and the growing relevance of the Episodic Frame as specific AI products develop. This study could have examined all types of media, although that approach would have gone beyond the exploratory nature of this pioneering research. With this work we extend scientific production on journalistic AI in Spain, where this perspective has not been analysed.Este artículo forma parte del proyecto PR3/23-30837 financiado por la Universidad Complutense de Madrid

Risk factors for COVID-19 in inflammatory bowel disease: A national, ENEIDA-based case–control study (COVID-19-EII)

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, y los autores pertenecientes a la UAMScant 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 cautionThis study was funded by the Carlos III Health Institute (COV20/00227: Co-IP Dra. Maria Esteve and Dra. Yamile Zabana), FEDER (Fondo Europeo de Desarrollo Regional) and supported by GETECCU. The ENEIDA Registry of GETECCU is supported by Takeda, Pfizer, Galápagos, AbbVie and Bioge

Benefits of paediatric to adult transition programme in onflammatory bowel disease: The BUTTERFLY study of GETECCU and SEGHNP

Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017–2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients’ outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcome