Eficacia de la nutrición enteral exclusiva en la enfermedad de Crohn pediátrica: factores predictivos de respuesta y de mantenimiento de la remisión

Pese a que la eficacia de la nutrición enteral exclusiva (NEE) para la inducción a la remisión en la enfermedad de Crohn pediátrica se conoce desde la década de los 80 muy pocos han sido los estudios publicados hasta la fecha en España. Además, sólo unos pocos trabajos han utilizado la calprotectina fecal como marcador de respuesta a la NEE. Un aspecto ampliamente debatido es si el empleo precoz de inmunomoduladores (AZA o 6MP) modifica el curso de la enfermedad en todos los pacientes afectos de EC o sólo en casos seleccionados. No se han publicado datos sobre la incidencia de EII pediátrica en la provincia de Málaga. Los objetivos propuestos para la elaboración del presente trabajo son: 1. Estimar la tasa de remisión y de respuesta tras el tratamiento de inducción a la remisión con NEE. 2. Evolución de los parámetros clínicos, antropométricos y de laboratorio tras la NEE. 3. Estimar los factores predictivos de respuesta a la NEE. 4. Estimar el porcentaje de pacientes en remisión libre de esteroides a la semana 52 y determinar los factores predictivos de remisión libre de esteroides en semana 52. 5. Efecto del tratamiento precoz con inmunomoduladores en el curso de la enfermedad. 6. Estimar la tasa de incidencia de EII y su tendencia en la población pediátrica de la provincia de Málaga durante el periodo de estudio. Material y método Estudio unicéntrico observacional ambispectivo que incluye a los pacientes diagnosticados de EC y que recibieron al menos 6 semanas de NEE durante su primer brote de enfermedad atendidos la Unidad de Gastroenterología y Nutrición Infantil del Hospital Materno Infantil de Málaga. El periodo retrospectivo transcurrió desde enero 2002 a diciembre 2006 siendo prospectivo con posterioridad hasta junio 2014. Se han incluido los pacientes de edades comprendidas entre 0 y 14 años ya que a partir de esta edad los pacientes son derivados al digestivo de adultos. Resultados Constatamos un incremento en la incidencia de EII durante el periodo de estudio, de 1,78 /105 hab. en el año 2002 a 4,56 /105 hab. en 2013. Se incluyeron 50 pacientes, 32 niños (64%) y 18 niñas (36%), con una edad al diagnóstico de 10,8 ± 2,9 años. El tiempo transcurrido desde el inicio de los síntomas hasta el diagnostico fue de 4,9 meses (RIQ 2,5 - 12,1). La duración de la NEE fue de 7,71 semanas (RIQ 6,5-8,5). De los 48 pacientes que completaron el periodo de NEE, 42 (87,5%, análisis por protocolo) alcanzaron la remisión clínica, este porcentaje de respuesta desciende hasta el 84% en el análisis por intención de tratar. La tasa de cumplimentación fue del 96%. Tras finalizar el periodo de NEE hubo un incremento significativo de talla, cifras plasmáticas de albúmina, hemoglobina y hematocrito junto con un descenso significativo en los valores de CF, PCR, VSG, cifras de leucocitos y plaquetas. La NEE fue bien tolerada en todos los casos y no aconteció ningún efecto adverso durante el periodo de estudio. Al final del periodo de NEE la dieta fue reintroducida de forma progresiva sin ningún incidente. Conclusiones La incidencia de enfermedad inflamatoria intestinal pediátrica en la provincia de Málaga ha aumentado en la última década. La NEE administrada durante 6-8 semanas es efectiva para inducir la remisión clínica y bioquímica en pacientes con EC en su primer brote. La NEE disminuye el grado de inflamación de la mucosa intestinal, mejorando los niveles de CF. La remisión libre de esteroides a los 12 meses es superior en pacientes que reciben tratamiento precoz con tiopurínicos durante el tratamiento con NEE. El periodo de NEE es esencial para actualizar el calendario vacunal y solicitar los exámenes complementarios previos al inicio del tratamiento inmunosupresor

EEN Yesterday and Today … CDED Today and Tomorrow.

The treatment of Pediatric Crohn's Disease (CD) requires attention both to achieve mucosal healing and to optimize growth, while also maintaining proper bone health. Exclusive Enteral Nutrition (EEN) is recommended as first-line treatment in luminal CD. The therapeutic mechanisms of EEN are being discovered by advances in the study of the gut microbiota. Although the total exclusion of a normal diet during the time of EEN continues to be of high importance, new modalities of dietary treatment suggest a successful future for the nutritional management of CD. In this sense, Crohn's Disease Exclusion Diet (CDED) is a long-term strategy, it apparently acts on the mechanisms that influence the appearance of inflammation (reducing dietary exposure to products negatively affecting the microbiota), but does so using specific available whole foods to achieve this goal, increases the time of clinical remission and promotes healthy lifestyle habits. The development of CDED, which partly minimizes the problems of EEN, has enabled a turnaround in the treatment of pediatric CD. This review highlights the role of enteral nutrition in the treatment of Crohn's disease with special emphasis on newer dietary modalities such as CDED

Whole transcription profile of responders to anti-tnf drugs in pediatric inflammatory bowel disease

Background: Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged 0.6 or <−0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05). Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBDInstituto de Salud Carlos III número de becas PI16 / 00559 y PI19 / 00792Consejería de Educación y Deporte de la Comunidad de Madrid PEJ16 / MED / AI-1260Instituto de Investigaciones Sanitarias Gregorio Marañón PRE2018-2Fondos Europeos de Desarrollo Regional (FEDER) del Comisión Europe

La zona patrimonial de la Cuenca Minera de Riotinto-Nerva: trayectoria y retos patrimoniales de futuro

Este estudio pretende analizar la trayectoria de la Zona Patrimonial, como figura de reciente creación y reducida aplicación a través del caso de la Cuenca Minera de Riotinto-Nerva. La singularidad tanto paisajística como jurídica de este Bien de Interés Cultural hacen de su estudio una oportunidad para avanzar en futuras declaraciones. La evolución del panorama legislativo patrimonial, incluyendo esta novedosa figura de protección plantea la necesidad de evaluar su resultado en términos de gestión patrimonial. En la concurrencia de una serie de agentes patrimoniales y con la convivencia de diferentes normativas y declaraciones previas, se estima necesario analizar la pluralidad de acciones que plantea la administración, incluyendo aspectos fundamentales como la gestión, la evolución en la percepción de los diferentes elementos patrimoniales, su valorización social o las estrategias de difusión aplicadas desde su inscripción. La Cuenca Minera de Riotinto-Nerva constituye uno de los enclaves mineros más antiguos y representativos a nivel mundial. Complementariamente se propone ahondar en las directrices necesarias para su inscripción en la Lista de Patrimonio Mundial, justificándose también su carácter excepcional desde su particularidad cromática, hecho diferencial toponímico e hito identitario para la comunidad local. Se indagará en la definición de sus Valores Universales Excepcionales (VUE) potenciales, sus atributos y posibles límites.This study aims to analyse the trajectory of the Heritage Zone, as a recently created and reduced application figure through the case of the Riotinto-Nerva Mining Basin. The unique landscape and legal characteristics of this Asset of Cultural Interest make this study an opportunity to advance in future statements. The evolution of the legislative panorama of heritage, including this novel preservation figure, raises the need to evaluate its result in terms of heritage management. In the concurrence of a series of heritage agents and with the coexistence of different regulations and previous inscriptions, it is considered necessary to analyse the plurality of actions proposed by the administration, including fundamental aspects such as management, the evolution in the perception of the different heritage elements, their social appreciation or the dissemination strategies applied since their registration. The Riotinto-Nerva Mining Basin is one of the oldest and most representative mining sites in the world. It is also proposed that the guidelines necessary for its inscription on the World Heritage List be further developed, justifying its exceptional character by its colouring, toponymic differentiation and identity landmark for the local community. The definition of its potential Outstanding Universal Values (OUV), their attributes and possible limits will be investigated

Guía de práctica clínica SENPE/SEGHNP/SEFH sobre nutrición parenteral pediátrica

Introduction: Parenteral nutrition (PN) in childhood is a treatment whose characteristics are highly variable depending on the age and pathology of the patient. Material and methods: The Standardization and Protocols Group of the Spanish Society for Parenteral and Enteral Nutrition (SENPE) is an interdisciplinary group formed by members of the SENPE, the Spanish Society of Gastroenterology, Hepatology and Pediatric Nutrition (SEGHNP) and the Spanish Society of Hospital Pharmacy (SEFH) that intends to update this issue. For this, a detailed review of the literature has been carried out, looking for the evidences that allow us to elaborate a Clinical Practice Guide following the criteria of the Oxford Center for Evidence-Based Medicine. Results: This manuscript summarizes the recommendations regarding indications, access routes, requirements, modifications in special situations, components of the mixtures, prescription and standardization, preparation, administration, monitoring, complications and home NP. The complete document is published as a monographic number. Conclusions: This guide is intended to support the prescription of pediatric PN. It provides the basis for rational decisions in the context of the existing evidence. No guidelines can take into account all of the often compelling individual clinical circumstances.Introducción: la nutrición parenteral (NP) en la infancia es un tratamiento cuyas características son muy variables en función de la edad y la patología que presente el paciente. Material y métodos: el grupo de Estandarización y Protocolos de la Sociedad Española de Nutrición Parenteral y Enteral (SENPE) es un grupo interdisciplinar formado por miembros de la SENPE, Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP) y Sociedad Española de Farmacia Hospitalaria (SEFH) que pretende poner al día este tema. Para ello, se ha realizado una revisión pormenorizada de la literatura buscando las evidencias que nos permiten elaborar una Guía de Práctica Clínica siguiendo los criterios del Oxford Centre for Evidence-Based Medicine. Resultados: este manuscrito expone de forma resumida las recomendaciones en cuanto a indicaciones, vías de acceso, requerimientos, modificaciones en situaciones especiales, componentes de las mezclas, prescripción y estandarización, preparación, administración, monitorización, complicaciones y NP domiciliaria. El documento completo se publica como número monográfico. Conclusiones: esta guía pretende servir de apoyo para la prescripción de la NP pediátrica. Constituye la base para tomar decisiones en el contexto de la evidencia existente. Ninguna guía puede tener en cuenta todas las circunstancias clínicas individuale

Dossier y guía de autoayuda para la mejora del malestar docente

Este trabajo tiene como objetivo dar una panorámica sobre el burnout en el ámbito docente y aportar herramientas para la prevención y afrontamiento de situaciones de estres laboral del profesorado, así como el desarrollo de altos niveles de resieliencia, todo desde un enfoque multidisciplinar.127 p

Gene signatures of early response to anti-TNF drugs in pediatric inflammatory bowel disease

T. Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged &lt;18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value &lt; 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.This work was funded by Instituto de Salud Carlos III (grants numbers PI16/00559 and PI19/00792), Consejería de Educación y Deporte de la Comunidad de Madrid (grant number PEJ16/MED/AI-1260), and by the Gregorio Marañón Health Research Institute (grant number PRE-2018-2), The study was cofunded by ERDF Funds (FEDER) from the European Commission, “A way of making Europe

Predicting Outcomes in Pediatric Crohn’s Disease for Management Optimization: Systematic Review and Consensus Statements from PIBD-Ahead Program

A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce complications. We aimed to identify evidence-based predictors of outcomes with the goal of optimizing individual patient management. A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence. Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density. These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk

Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014–2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6–8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn’s Disease activity index [wPCDAI] 15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6–8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn’s disease regardless of the location of disease and disease activityS

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group