Polymorphisms indicating risk of inflammatory bowel disease or antigenicity to anti-TNF drugs as biomarkers of response in children

Crohn’s disease; Polymorphism; PediatricEnfermedad de Crohn; Polimorfismo; PediátricoMalaltia de Crohn; Polimorfisme; PediatriaFew genetic polymorphisms predict early response to anti-TNF drugs in inflammatory bowel disease (IBD), and even fewer have been identified in the pediatric population. However, it would be of considerable clinical interest to identify and validate genetic biomarkers of long-term response. Therefore, the aim of the study was to analyze the usefulness of biomarkers of response to anti-TNFs in pediatric IBD (pIBD) as long-term biomarkers and to find differences by type of IBD and type of anti-TNF drug. The study population comprised 340 children diagnosed with IBD who were treated with infliximab or adalimumab. Genotyping of 9 selected SNPs for their association with early response and/or immunogenicity to anti-TNFs was performed using real-time PCR. Variants C rs10508884 (CXCL12), A rs2241880 (ATG16L1), and T rs6100556 (PHACTR3) (p value 0.049; p value 0.03; p value 0.031) were associated with worse long-term response to anti-TNFs in pIBD. DNA variants specific to disease type and anti-TNF type were identified in the pediatric population. Genotyping of these genetic variants before initiation of anti-TNFs would enable, if validated in a prospective cohort, the identification of pediatric patients who are long-term responders to this therapy.This research was funded by Instituto de Salud Carlos III, grant number PI19/00792 and PI22/00584 (L.L-F.), both cofunded by the European Union, by Instituto de Investigación Sanitaria Gregorio Marañón, grant number 2021-II-postdoc-01 (S.S-M.), and by Consejería de Educación, Universidades, Ciencia y Portavocía Comunidad de Madrid, grant number PEJ-2021-AI/BMD-21866 (P.Z-C.)

Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort

Adalimumab; Infliximab; PharmacogeneticsAdalimumab; Infliximab; FarmacogenèticaAdalimumab; Infliximab; FarmacogenéticaThe genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab.This research was funded by Instituto de Salud Carlos III, grant number PI19/00792 (L.A.L.-F.) and Juan Rodes program JR19/00005 (E.L.-M.), by Instituto de Investigación Sanitaria Gregorio Marañón, grant number 2021-II-postdoc-01 (S.S.-M.), and by Consejería de Educación, Universidades, Ciencia y Portavocía Comunidad de Madrid, grant number PEJ-2021-AI/BMD-21866 (P.Z.-C.). The study was co-funded by the European Union

Similarities and differences in extracellular vesicle profiles between ischaemic stroke and myocardial infarction

Extracellular vesicles (EVs) are involved in intercellular signalling through the transfer of molecules during physiological and pathological conditions, such as ischaemic disease. EVs might therefore play a role in ischaemic stroke (IS) and myocardial infarction (MI). In the present study, we analysed the similarities and differences in the content of circulating EVs in patients with IS and MI. This prospective observational study enrolled 140 participants (81 patients with IS, 37 with MI and 22 healthy controls [HCs]). We analysed the protein and microRNA content from EVs using proteomics and reverse transcription quantitative real-time polymerase chain reaction and compared it between the groups. In the patients with IS and MI, we identified 14 common proteins. When comparing IS and MI, we found differences in the protein profiles (apolipoprotein B, alpha-2-macroglobulin, fibronectin). We also found lower levels of miR-340 and miR-424 and higher levels of miR-29b in the patients with IS and MI compared with the HCs. Lastly, we found higher miR-340 levels in IS than in MI. In conclusion, proteomic and miRNA analyses suggest a relationship between circulating EV content and the patient’s disease state. Although IS and MI affect different organs (brain and heart) with distinct histological characteristics, certain EV proteins and miRNAs appear to participate in both diseases, while others are present only in patients with ISThis work was sponsored by a grant from Miguel Servet (CP15/00069 to María Gutiérrez- Fernández), a predoctoral fellowship (FI17/00188 to Mari Carmen Gómez-de Frutos;FI18/00026 to Fernando Laso-García), a Sara Borrell postdoctoral fellowship (CD19/00033 to María Pérez-Mato), the INVICTUS PLUS network grant (RD16/0019/0005) from the Carlos III Health Institute Health Care Research Fund and was co-funded by the European Regional Development Fund (ERDF) and Juan de la Cierva postdoctoral fellowship (IJCI-2017-33505 to Laura Otero-Ortega, Spanish State Research Agency) and the Spanish Ministry of Science and Innovatio

Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP

Inflammatory bowel diseases; Transition to adult care; Transitional careEnfermedad inflamatoria intestinal; Tránsito a la atención adulta; Cuidados de transiciónMalaltia inflamatòria intestinal; Trànsit a l'atenció adulta; Cures de transicióBackground: 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 outcomes.This work was supported by a grant from the Young Group of the Spanish Gastroenterology Association (AEG)

Salud escolar en tiempos de Covid

El regreso a los centros educativos tras los meses de confinamiento por la pandemia de COVID-19 ha supuesto un reto para todos los países del mundo. En el caso de Europa, y concretamente España, la vuelta a las aulas ha sido un proceso complejo en el que el papel de la enfermera escolar ha sido fundamental. El objetivo del proyecto es analizar el impacto de la pandemia sobre los estudiantes de todos los niveles, así como las dificultades más relevantes encontradas en la incorporación a la educación y el papel de la enfermera en ello. Los resultados detallan los problemas más prevalentes a nivel sanitario, socioeconómico y legislativo que han surgido a raíz de la pandemia a nivel europeo, estatal y comunitario en el caso de la Comunidad de Madrid y desarrollan la labor fundamental de las enfermeras escolares en el cumplimiento de los protocolos elaborados para la reincorporación de los estudiantes a la educación semi-presencial. En las conclusiones se recogen las principales consecuencias sobre la salud bio-psico-social de los estudiantes de todos los niveles a raíz de la pandemia, la repercusión que tuvo sobre su educación, el cambio a la modalidad virtual durante el confinamiento iniciado en el mes de marzo y la posterior adaptación al sistema semi-presencial, donde uno de los protagonistas es la enfermera escolar. Su labor se basa en asegurar el cumplimiento de los protocolos y medidas de protección instauradas en todos los centros educativos y velar por la seguridad de todas las personas implicadas.Coming back to schools after months of lockdown due to the COVID-19 pandemic has been a challenge for all countries in the world. In the case of Europe, and specifically Spain, the return to the classroom has been a complex process in which the role of the school nurse has been key. The aim of the project is to analyse the impact of the pandemic on students at all levels, as well as the most relevant difficulties encountered in the incorporation into education and the role of the nurse in this. The results detail the most prevalent problems at a health, socio-economic and legislative level that have arisen as a result of the pandemic at a European, Spanish and regional level in the case of the Community of Madrid and develop the fundamental work of school nurses in the fulfilment of the protocols drawn up for the reincorporation of students into semi-attendance education. The conclusions include the main consequences on the bio-psycho-social health of students at all levels as a result of the pandemic, the impact on their education of the change to the virtual modality during the confinement that began in March and the subsequent adaptation to the blended learning system, where one of the protagonists is the school nurse. Their work is based on ensuring compliance with the protocols and protective measures established in all educational centres and ensuring the safety of all those involved

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.Peer reviewe

La escuela y el fenómeno multimedia

Trata la aplicación de las nuevas tecnologías a la práctica educativa en las áreas de Ciencias Naturales, Física, Química, Matemáticas, Lengua, Historia y Dibujo. Pretende abrir nuevas vías para el proceso educativo fomentando nuevas formas de trabajar en el aula que acerquen al profesorado y al alumnado al mundo laboral actual. Desarrolla cuatro actividades orientadas al aprendizaje del manejo de un procesador de texto, de un multimedia, acceso a base de datos a través del teléfono y obtención de documentos gráficos con el escáner, en todas ellas hay una primera etapa para la formación del profesorado que luego aplicará sus conocimientos en el aula; las dos últimas actividades se centran en la utilización de estas tecnologías con alumnado con determinadas deficiencias y en talleres de Matemáticas y Ciencias de la Naturaleza. La evaluación se realiza sobre los resultados de las encuestas a profesores, alumnos y padres.Madrid (Comunidad Autónoma). Consejería de Educación y CulturaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

COVID-19 Gastrointestinal Manifestations Are Independent Predictors of PICU Admission in Hospitalized Pediatric Patients.

Multicenter study conducted in 15 hospitals including 101 COVID-19 pediatric inpatients aiming to describe associated gastrointestinal (GI) manifestations. GI symptoms were present in 57% and were the first manifestation in 14%. Adjusted by confounding factors, those with GI symptoms had higher risk of pediatric intensive care unit admission. GI symptoms are predictive of severity in COVID-19 children admitted to hospitals

COVID-19 Gastrointestinal Manifestations Are Independent Predictors of PICU Admission in Hospitalized Pediatric Patients

Multicenter study conducted in 15 hospitals including 101 COVID-19 pediatric inpatients aiming to describe associated gastrointestinal (GI) manifestations. GI symptoms were present in 57% and were the first manifestation in 14%. Adjusted by confounding factors, those with GI symptoms had higher risk of pediatric intensive care unit admission. GI symptoms are predictive of severity in COVID-19 children admitted to hospitals