bluuebunny/crossref_metadata_2025 huggingface dataset:
Early and intermediate outcomes for surgical management of infective endocarditis
Authors: Volk Lindsay , Verghis Nina , Chiricolo Antonio , Ikegami Hirohisa , Lee Leonard Y. , Lemaire Anthony
Published: December 2019

Objective

The treatment of active infective endocarditis (IE) presents a clinical dilemma with uncertain outcomes. This study sets out to determine the early and intermediate outcomes of patients treated surgically for active IE at an academic medical center.

Methods

A retrospective chart review was conducted to identify patients who underwent surgical intervention for IE at our institution from July 1st, 2011 to June 30th, 2018. In-patient records were examined to determine etiology of disease, surgical intervention type, postoperative complications, length of stay (LOS), 30-day in-hospital mortality, and 1-year survival.

Results

Twenty-five patients underwent surgical intervention for active IE. The average age of the patients was 47 ± 14 years old and most of the patients were male (N = 15). The majority of the patients had the mitral valve replaced (N = 10), with the remaining patients having tricuspid (N = 8) and aortic (N = 7) valve replacements. The etiology varied and included intravenous drug use (IVDU), and presence of transvenous catheters. The 30-day in-hospital mortality was 4% with 1 patient death and the 1-year survival was 80%. The average LOS was 27 days ±15 and the longest LOS was 65 days.

Conclusions

Surgical management of IE can be difficult and challenging however mortality can be minimized with acceptable morbidity. The most common complication was CVA. The average LOS is longer than traditional adult cardiac surgery procedures and the recurrence rate of valvular infection is not minimal especially if the underlying etiology is IVDU.
Optimizing sequestered carbon in forest offset programs: balancing accounting stringency and participation
Authors: Wise Lindsey , Marland Eric , Marland Gregg , Hoyle Jason , Kowalczyk Tamara , Ruseva Tatyana , Colby Jeffrey , Kinlaw Timothy
Published: December 2019

Background

Although there is broad agreement that negative carbon emissions may be required in order to meet the global climate change targets specified in the Paris Agreement and that carbon sequestration in the terrestrial biosphere can be an important contributor, there are important accounting issues that often discourage forest carbon sequestration projects. The legislation establishing the California forest offset program, for example, requires that offsets be “real, additional, quantifiable, permanent, verifiable, and enforceable”. While these are all clearly desirable attributes, their implementation has been a great challenge in balancing complexity, expense, and risk. Most forest offset protocols carry similar accounting objectives, but often with different details, (e.g. Richards and Huebner in Carbon Manag 3(4):393–410, 2012 and Galik et al. in Mitig Adapt Strateg Glob Change 14:677–690, 2009). The result is that the complexity, expense, and risk of participation discourage participation and make it more difficult to achieve climate mitigation goals. We focus on the requirements for accounting and permanence to illustrate that current requirements disproportionately disadvantage small landowners.

Results

The simplified 1040EZ filing system for U.S. income taxes may provide insight for a protocol model that balances reward, effort, and risk, while still achieving the overall objectives of standardized offset protocols. In this paper, we present initial ideas and lay the groundwork behind a “2050EZ” protocol for forest carbon sequestration as a complement to existing protocols.

Conclusion

The Paris Agreement states that “Parties should take action to conserve and enhance, as appropriate, sinks and reservoirs of greenhouse gases.” The Paris Agreement also refers to issues such as equity, sustainable development, and other non-carbon benefits. The challenge is to provide incentives for maintaining and increasing the amount of carbon sequestered in the biosphere. Monitoring and verification of carbon storage need to be sufficient to demonstrate sequestration from the atmosphere while providing clear incentives and simple accounting approaches that encourage participation by diverse participants, including small land holders.
Clinical and genetic characteristics of Chinese patients with cerebrotendinous xanthomatosis
Authors: Tao Qing-Qing , Zhang Yun , Lin Hui-Xia , Dong Hai-Lin , Ni Wang , Wu Zhi-Ying
Published: December 2019

Background

Cerebrotendinous xanthomatosis (CTX) is a rare inborn lipid-storage disease caused by mutations in the sterol 27-hydroxylase (CYP27A1) gene with an autosomal recessive pattern of inheritance. To date, only 19 CTX patients from 16 families have been reported in the Chinese population.

Results

Three novel likely pathogenic mutations (c.368_374delCCAGTAC, c.389 T > A and c.571C > T) and 7 previously reported pathogenic mutations (c.379C > T, c.435G > T, c.1016C > T, c.1214G > A, c.1263 + 1G > A, c.1420C > T and c.1435C > T) were identified. In addition, we summarized the genotypes and phenotypes of reported Chinese CTX patients. The most predominant mutations inCYP27A1were c.410G > A and c.379C > T, and the most common clinical manifestations were pyramidal signs, xanthomatosis, cerebellar ataxia, and cognitive impairment.

Conclusion

Our study broadens the genetic and clinical spectrum of CTX and provides insightful information to help better diagnose and understand the disease.
Developmental hypomyelination in Wolfram syndrome: new insights from neuroimaging and gene expression analyses
Authors: Samara Amjad , Rahn Rachel , Neyman Olga , Park Ki Yun , Samara Ahmad , Marshall Bess , Dougherty Joseph , Hershey Tamara
Published: December 2019

Wolfram syndrome is a rare multisystem disorder caused by mutations in WFS1 or CISD2 genes leading to brain structural abnormalities and neurological symptoms. These abnormalities appear in early stages of the disease. The pathogenesis of Wolfram syndrome involves abnormalities in the endoplasmic reticulum (ER) and mitochondrial dynamics, which are common features in several other neurodegenerative disorders. Mutations in WFS1 are responsible for the majority of Wolfram syndrome cases. WFS1 encodes for an endoplasmic reticulum (ER) protein, wolframin. It is proposed that wolframin deficiency triggers the unfolded protein response (UPR) pathway resulting in an increased ER stress-mediated neuronal loss. Recent neuroimaging studies showed marked alteration in early brain development, primarily characterized by abnormal white matter myelination. Interestingly, ER stress and the UPR pathway are implicated in the pathogenesis of some inherited myelin disorders like Pelizaeus-Merzbacher disease, and Vanishing White Matter disease. In addition, exploratory gene-expression network-based analyses suggest that WFS1 expression occurs preferentially in oligodendrocytes during early brain development. Therefore, we propose that Wolfram syndrome could belong to a category of neurodevelopmental disorders characterized by ER stress-mediated myelination impairment. Further studies of myelination and oligodendrocyte function in Wolfram syndrome could provide new insights into the underlying mechanisms of the Wolfram syndrome-associated brain changes and identify potential connections between neurodevelopmental disorders and neurodegeneration.
A post-translational modification signature defines changes in soluble tau correlating with oligomerization in early stage Alzheimer’s disease brain
Authors: Ercan-Herbst Ebru , Ehrig Jens , Schöndorf David C. , Behrendt Annika , Klaus Bernd , Gomez Ramos Borja , Prat Oriol Nuria , Weber Christian , Ehrnhoefer Dagmar E.
Published: December 2019

Tau is a microtubule-binding protein that can receive various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. Hyperphosphorylation of tau is linked to its aggregation and the formation of neurofibrillary tangles (NFTs), which are a hallmark of Alzheimer’s disease (AD). While more than 70 phosphorylation sites have been detected previously on NFT tau, studies of oligomeric and detergent-soluble tau in human brains during the early stages of AD are lacking. Here we apply a comprehensive electrochemiluminescence ELISA assay to analyze twenty-five different PTM sites as well as tau oligomerization in control and sporadic AD brain. The samples were classified as Braak stages 0–I, II or III–IV, corresponding to the progression of microscopically detectable tau pathology throughout different brain regions. We found that soluble tau multimers are strongly increased at Braak stages III–IV in all brain regions under investigation, including the temporal cortex, which does not contain NFTs or misfolded oligomers at this stage of pathology. We additionally identified five phosphorylation sites that are specifically and consistently increased across the entorhinal cortex, hippocampus and temporal cortex in the same donors. Three of these sites correlate with tau multimerization in all three brain regions, but do not overlap with the epitopes of phospho-sensitive antibodies commonly used for the immunohistochemical detection of NFTs. Our results thus suggest that soluble multimers are characterized by a small set of specific phosphorylation events that differ from those dominating in mature NFTs. These findings shed light on early PTM changes of tau during AD pathogenesis in human brains.
Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas
Authors: Goldenberg Alice , Marguet Florent , Gilard Vianney , Cardine Aude-Marie , Hassani Adnan , Doz François , Radi Sophie , Vasseur Stéphanie , Bou Jacqueline , Branchaud Maud , Houdayer Claude , Baert-Desurmont Stéphanie , Laquerriere Annie , Frebourg Thierry
Published: December 2019

The contribution of mosaic alterations to tumors of the nervous system and to non-malignant neurological diseases has been unmasked thanks to the development of Next Generation Sequencing (NGS) technologies. We report here the case of a young patient without any remarkable familial medical history who was first referred at 7 years of age, for an autism spectrum disorder (ASD) of Asperger type, not associated with macrocephaly. The patient subsequently presented at 10 years of age with multiple nodular lesions located within the trigeminal, facial and acoustic nerve ganglia and at the L3 level. Histological examination of this latter lesion revealed a glioneuronal hamartoma, exhibiting heterogeneous PTEN immunoreactivity, astrocyte and endothelial cell nuclei expressing PTEN, but not ganglion cells. NGS performed on the hamartoma allowed the detection of a PTEN pathogenic variant in 30% of the reads. The presence of this variant in the DNA extracted from blood and buccal swabs in 3.5 and 11% of the NGS reads, respectively, confirmed the mosaic state of the PTEN variant. The anatomical distribution of the lesions suggests that the mutational event affecting PTEN occurred in neural crest progenitors, thus explaining the absence of macrocephaly. This report shows that mosaic alteration of PTEN may result in multiple central and peripheral nervous system hamartomas and that the presence of such alteration should be considered in patients with multiple nervous system masses, even in the absence of cardinal features of PTEN hamartoma tumor syndrome, especially macrocephaly.
Recent advances in melanin-like nanomaterials in biomedical applications: a mini review
Authors: Park Jihyo , Moon Haeram , Hong Seonki
Published: December 2019

Background

Melanins are a group of biopigments in microorganisms that generate a wide range of colorants. Due to their multifunctionality, including ultraviolet protection, radical scavenging, and photothermal conversion, in addition to their intrinsic biocompatibility, natural melanins and synthetic melanin-like nanomaterials have been suggested as novel nano-bio platforms in biomedical applications.

Main body

Recent approaches in the synthesis of melanin-like nanomaterials and their biomedical applications have briefly been reviewed. Melanin-like nanomaterials have been suggested as endogenous chromophores for photoacoustic imaging and radical scavengers for the treatment of inflammatory diseases. The photothermal conversion ability of these materials under near-infrared irradiation allows hyperthermia-mediated cancer treatments, and their intrinsic fluorescence can be an indicator in biosensing applications. Furthermore, catechol-rich melanin and melanin-like nanomaterials possess a versatile affinity for various functional organic and inorganic additives, allowing the design of multifunctional hybrid nanomaterials that expand their range of applications in bioimaging, therapy, theranostics, and biosensing.

Conclusion

Melanin-like natural and synthetic nanomaterials have emerged; however, the under-elucidated chemical structures of these materials are still a major obstacle to the construction of novel nanomaterials through bottom-up approaches and tuning the material properties at the molecular level. Further advancements in melanin-based medical applications can be achieved with the incorporation of next-generation chemical and molecular analytical tools.
Ictal semiology, functional anatomy and multimodal diagnostic in patients with insular epilepsies
Authors: Stefan Hermann , Gollwitzer Stephanie
Published: December 2019

Background

The insula is a hidden part in the cerebral cortex. Insular epilepsy is underrecognized and it bears a special risk for misdiagnosis with regard to nonepileptic seizures or wrong localization of epileptic seizures.

Case presentations

The manuscript describes 2 cases with ictal semiology of paresthesia and pain followed by hyperkinetic movements, noninvasive findings of source localization and/or invasive SEEG exploration.

Conclusion

Magnetic source imaging, ictal SPECT as noninvasive and invasive recordings with depth electrodes (SEEG) can provide important preoperative information for the involvement of insular and periinsular regions in focal pharmacoresistant epilepsies. The optimal use of these methods presupposes extensive knowledge of ictal semiology and other clinical characteristics. The clinical localization hypothesis can be optimally proofed by SEEG exploration.
Genome-Wide Analysis Identifies Two Susceptibility Loci for Positive Thyroid Peroxidase and Thyroglobulin Antibodies
Authors: Matana Antonela , Boutin Thibaud , Torlak Vesela , Brdar Dubravka , Gunjača Ivana , Kolčić Ivana , Boraska Perica Vesna , Punda Ante , Polašek Ozren , Barbalić Maja , Hayward Caroline , Zemunik Tatijana
Published: December 2019

Introduction

Thyroid peroxidase (TPO) and thyroglobulin (Tg) are main components of the thyroid gland and play an essential role in thyroid hormone synthesis. The development of antibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) is the major diagnostic hallmark and early indicator of autoimmune thyroid disease. TPOAb and TgAb are under strong genetic influence; however, genetic factors that determine thyroid antibody positivity are largely unknown.

Materials and Methods

To identify novel loci associated with TPOAb and/or TgAb positivity, we performed a genome-wide meta-analysis in a total of 2613 individuals from Croatia. Participants with elevated plasma TPOAb and/or TgAb were defined as cases (N = 619) and those with TPOAb and TgAb within reference values were defined as controls (N = 1994).

Results

We identified 2 novel loci, of which 1 is located within the YES1 gene (rs77284350, P = 1.50 × 10–8), and the other resides within the IRF8 gene (rs16939945, P = 5.04 × 10–8).

Conclusions

Although the observed variants were associated with TPOAb and TgAb positivity for the first time, both YES1 and IRF8 were previously linked to susceptibility to other autoimmune diseases, and represent plausible biological candidates. This study adds to the knowledge of genetics underlying thyroid antibodies and provides a good basis for further research.
“Spirit in Opposition”
Authors: Baig Hamzah
Published: December 2019

Contemporary political events in Palestine and the United States have drawn renewed interest in the long history of militant Black-Palestinian solidarity. Although many historical accounts typically begin in the post-1967 Arab-Israeli War moment with the Student Nonviolent Coordinating Committee and the Black Panthers in Algiers, this article traces a foundational period of Black radical coalition building with Palestine through Malcolm X and the Nation of Islam. In doing so, it privileges systems of intergenerational exchange and emphasizes the ways in which broader political developments, from Egyptian anti-imperialism to the birth of the Third World project, helped establish the basis for the Black Power movement’s identification with Palestine. The article argues that the Nation of Islam and Malcolm X’s border crossing and concomitant efforts to forge ties with Arab-world liberation movements explicitly rendered Palestine a referent of the Black Radical Tradition.
Diagnosis of non-tuberculous mycobacterial pulmonary disease (NTM-PD): modern challenges
Authors: Musaddaq Besma , Cleverley Joanne R
Published: December 2019

Non-tuberculous mycobacterial pulmonary disease is growing in incidence and prevalence. However, it is frequently overlooked as a differential diagnosis by both clinicians and radiologists alike due to its non-specific clinical features, wide spectrum of radiological findings and difficulty in isolating the causative organism. The aim of this article is to illustrate the spectrum and follow-up of the radiological findings of non-tuberculous mycobacterial pulmonary disease and the challenges involved in making a diagnosis.
Latest developments in in-vivo imaging for proton therapy
Authors: Parodi Katia
Published: December 2019

Owing to the favorable physical and biological properties of swift ions in matter, their application to radiation therapy for highly selective cancer treatment is rapidly spreading worldwide. To date, over 90 ion therapy facilities are operational, predominantly with proton beams, and about the same amount is under construction or planning.

Over the last decades, considerable developments have been achieved in accelerator technology, beam delivery and medical physics to enhance conformation of the dose delivery to complex shaped tumor volumes, with excellent sparing of surrounding normal tissue and critical organs. Nevertheless, full clinical exploitation of the ion beam advantages is still challenged, especially by uncertainties in the knowledge of the beam range in the actual patient anatomy during the fractionated course of treatment, thus calling for continued multidisciplinary research in this rapidly emerging field.

This contribution will review latest developments aiming to image the patient with the same beam quality as for therapy prior to treatment, and to visualize in-vivo the treatment delivery by exploiting irradiation-induced physical emissions, with different level of maturity from proof-of-concept studies in phantoms and first in-silico studies up to clinical testing and initial clinical evaluation.
Introduction to pedagogical activity. Practicum
Authors: Орлов Александр , Orlov Aleksandr , Агафонова Алла , Agafonova Alla
Published: December 2019

The training manual presents a system of individualized tasks for all forms of professional training of future teachers. Performance of tasks will allow students with the help of the teacher to choose the pace, direction and forms of advancement in the study of pedagogical disciplines.
The content and methodological apparatus of the workshop will help students to engage in productive independent work, the purpose of which is the development of motives and skills of teaching, the formation of professional thinking, professional value orientations and ethical positions, as well as stimulating the need for professional self-education and self-education.
For students and teachers of pedagogical universities.
Balance in our thinking
Authors: Allingham Sue
Published: December 2019

It is important to continue to question media coverage which promotes a narrow view of early education. In order to get it right for our youngest children we need to be open to the broad perspectives that only experts can provide.
A cultural revolution
Authors: Marsh Sian , Mason Gill
Published: December 2019

A focus on the unique child is key to understanding how cultural capital relates to best practice. Here Sian Marsh of Best Practice Network highlights the approach of Kids Planet Day Nurseries.
Through the looking glass
Authors: MacConville Ruth
Published: December 2019

Worrying about weight and physical appearance can start at a very early age. In this book extract, Ruth MacConville defines what constitutes a positive body image and how it can be influenced.
Help them to stay focused
Authors: Brown Paula
Published: December 2019

Paula Brown outlines the most recent research behind executive functions and explores how practitioners can support children to make plans, reach goals and review their progress and success.
‘We make the most of our space’
Authors: Rook Olivia
Published: December 2019

Running two busy settings has its challenges, but Kim Benham (pictured below), the owner of Sparkles and Millies Pre-schools, gets the balance right with the help of a supportive team.
Steps to better behaviour
Authors: Smith Nick
Published: December 2019

Latest figures on school exclusions due to bullying show wide disparity between the regions. Nick Smith unpicks the underlying trends and gives his view on the strategies which are proving to have a positive effect.
Tokens of friendship
Authors: Hart Karen
Published: December 2019

Both girls and boys will enjoy making friendship bracelets, using their imaginations to create their own unique designs and deciding which friends and family to gift them to. Observe how they persevere and are proud of what they have made.
Where does this waste go?
Authors: Waters Rebecca
Published: December 2019

Possessing the relevant knowledge on effective waste disposal to keep you, your employees and your patients safe, while also minimising your clinic's impact on the environment is important. Rebecca Waters outlines the Department of Health and Care's colour code for best practice waste management that aims to make the different types of waste and their disposal methods clear
The complexities of compliance: tax authority processes and making an appeal
Authors: Bernstein Adam
Published: December 2019

For obvious reasons, HM Revenue & Customs maintains a series of penalty-backed regimes to ensure compliance with tax law. However, with penalties being automatic, Adam Bernstein stresses the importance of taxpayers understanding the tax authority's processes and how appeals can be lodged
Laura de Mello e Souza
Authors: Santos Pérez José Manuel
Published: December 2019

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Brasil y la mirada extranjera del Mundial: el análisis de las narrativas de El País
Authors: Soares De Almeida Paulo Henrique
Published: December 2019

Este trabajo consiste en un análisis de las representaciones de la identidad brasileña construida por el diario español El País durante la Copa Mundial de 2014. El objetivo es estudiar el concepto de identidad nacional en la comunicación contemporánea y descubrir la opinión que la prensa extranjera tiene de Brasil en tiempos de la globalización y mundialización de la cultura. El estudio utiliza como referente teórico un análisis crítico de la narrativa como propone Motta (2013), teniendo en cuenta el texto periodístico como un género narrativo que construye significados sobre la realidad del Brasil actual, examinando su etapa de crecimiento económico y sus referencias culturales a partir de la mirada del otro, el extranjero.
La búsqueda de la eficacia de derechos humanos: un análisis de los objetivos del milenio de la ciudad de Aquiraz (Ceará, Brasil)
Authors: Alves Veira De Melo Renato
Published: December 2019

El objetivo de este artículo es ayudar a comprender y conocer la coyuntura actual de los Objetivos del Milenio dando especial énfasis a la pobreza y la educación en el municipio de Aquiraz. Con ese fin, este trabajo muestra la implantación de las estrategias seguidas por el municipio para alcanzar los Objetivos del Milenio, con el foco puesto, específicamente, en la reducción de la pobreza y en la educación fundamental, mostrando las herramientas utilizadas por el estado de Ceará y el municipio de Aquiraz para alcanzar sus objetivos de crecimiento económico, probando los avances conseguidos y lo que todavía falta para alcanzar y cumplir las metas de los ODM. El planeta ya no soporta el uso intensivo de los recursos naturales insostenibles y los Objetivos de Desarrollo Sostenible necesitan concretar el camino en dirección a un modelo de desarrollo sostenible, partiendo de los consensos establecidos entre los países en la Conferencia para el Desarrollo Sostenible del 2012, Río+ 20.
Los Sertones, o la construcción del Brasil en la obra de Euclides da Cunha
Authors: Bautista Lucca Juan
Published: December 2019

El presente artículo tiene como objetivo central recuperar la lectura de uno de los principales exponentes del ensayismo brasileño (Euclides da Cunha) a partir de su obra nodal (“Los sertones”) para desentrañar la morfología que adquiere la construcción de la nación brasileña en el viraje del siglo XIX y XX en la pluma de uno de los principales literatos de la naciente República Federativa de Brasil. A tal fin, la propuesta analítica de este escrito radica en desandar dos dimensiones para abordar la complejidad de la propuesta del periodista: por un lado, tomar en cuenta las aristas que ofrece el texto para construir un espacio-tiempo con densidad antropológica y política que el autor llama Sertón; y, por el otro, analizar la múltiple y extensa intertextualidad que ofrece esta obra en sí, pero también como la producción de Da Cunha reverbera en otros exponentes de la literatura como D. F. Sarmiento, J. Guimarães Rosa, M. Vargas Llosa o G. Freyre.
La escritura de Raduan Nassar: palabra rígida, palabra maleable
Authors: De Sousa ElesbÃo Juliane
Published: December 2019

En esta investigación, nos acercaremos a la escritura de Raduan Nassar, fijándonos en el modus operandi del escritor. Teniendo en cuenta la prosa-poética, nos adentraremos en el tejido textual de la novela Lavoura Arcaica, publicada en 1975, con el fin de entender cómo se generaron los temas elegidos en un lenguaje lírico ambientado en la prosa, así como de analizar la ambivalencia de los discursos de los protagonistas de esta obra tan poco conocida. De ese modo, el objetivo de esta investigación es conocer algo más la creación literaria nassariana, cuya escritura artística y literaria tiene en cuenta temas densos y claves para el ser humano, a través de un lenguaje lírico-poético muy fuerte y en constante diálogo con otros discursos.
Una interpretación Informacional del Niño Salvaje de Aveyron: L’enfant sauvage (1970)
Authors: Contreras Pulache Hans , Joya Quispe Alexa Ivonne , Moya Maldonado Dafne Solange , Oscanoa Chávez Angello Jesús , Pérez Ly Yumi Shannon , Moya Salazar Jeel
Published: December 2019

Sobre la base del film: L’enfant Sauvage (1970) de François Truffaut, se propone discutir los siguientes conceptos: humanización y socialización, desde la perspectiva de la Teoría Sociobiológica Informacional. Y luego, se elabora una interpretación de los cambios que ocurren en el sistema nervioso de un niño salvaje (feral) en el inicio (tardío) de su socialización. En síntesis, buscamos respondernos las siguientes preguntes: i. ¿Qué es lo que busca Itard en Víctor: humanizarlo o socializarlo?; y ii. ¿Cómo puede interpretarse neurológicamente los cambios que le ocurren a Víctor luego de su encuentro con Itard?
P009 Characterization of Health Services That Provide Nursing Care for Inflammatory Bowel Disease Patients in Brazil
Authors: Barros Jaqueline , Ramdeen Madhoor , Baima Julio , Alencar Rubia , Saad-Hossne Rogerio , Sassaki Ligia
Published: December 2019

BACKGROUND:

Nursing care in inflammatory bowel disease (IBD) is essential to the success of the treatment. IBD patients need continuous and specialized care and the characterization of health services is necessary to identify the deficiencies for further resolution in the future. The aim of the study is to identify the characteristics of health services that provide nursing care for IBD patients in Brazil.

METHODS:

A descriptive study was performed. Participants were nurses who treat IBD patients. The identification of nurses was performed through: analysis of national curricula registered with the National Council for Scientific and Technological Development in Brazil, access to the Brazilian IBD Study Group records and referral by colleagues. A specific online survey questionnaire consisting of 37 questions was developed.

RESULTS:

74 nurses were identified. Health services are located in the following Brazilian regions: Southeast (66.22%), Northeast (13.51%), South (9.46%), North (6.76%) and Midwest (4.05%). The most frequent services were public hospital (45.95%), IBD outpatient clinic (25.68%), private clinic (21.62%) and infusion center (10.81%). In the infusion centers were identified emergency trolley (45.95%), bathroom for the patient (43.24%), refrigerator for storing medications (43.24%), comfortable chair for infusion (43.24%) and post nursing (40.54%). Health services are integrated with endoscopic dilation service (40.54%), magnetic resonance imaging (52.70%), pathology department (54.05%), urgency and emergency room (58.11%), endoscopy (70.27%), computed tomography (59.46%), surgical inpatient unit (67.57%) and clinical inpatient unit (72.97%). The services have telephone consultation (28.38%) and communication by email (20.27%). The team is composed of nurses (71.62%), coloproctologist (64.86%), gastroenterologist (58.11%), dietician (56.76%), psychologist (41.89%) and stomatherapist (40.54%).

CONCLUSION(S):

Most health services are located in the southeast region; the type of service provided is public with access to specific tests. Infusion centers have the minimum required resources recommended. Some health services feature telemedicine service. The multidisciplinary team is present in most services. These findings suggest the need for prompt expansion and improvement to the delivery of services and care for all IBD patients across the nation.
P012 Successful Use of Combination Biologic Therapy in Medically Refractory Pediatric Crohn's Disease and Sacroiliitis
Authors: Bass Julie , Goyal Alka
Published: December 2019

CASE:

We present a patient with medically refractory Crohn’s disease, sacroiliitis and growth failure who showed remarkable response to combination therapy using two different biological agents along with an immunomodulator and no significant adverse events. A 14-year old male presented for 2nd opinion regarding management of refractory ileocolonic Crohn’s disease. He was diagnosed with Crohn’s disease at an outside center at 9 years of age. Initial treatment with systemic steroids and azathioprine was unsuccessful. He had sub-optimal clinical improvement on anti-tumor necrosis factor (TNF) therapy that included infliximab for 1 year, followed by adalimumab for 1.5 years. He subsequently struggled with repeated episodes of Clostridium difficile (CDI) requiring prolonged vancomycin taper. His therapy was then switched to vedolizumab, systemic steroids and azathioprine which provided some symptomatic relief, but he was noted to be persistently anemic with elevated inflammatory markers and poor growth. At the time of presentation to our center he was steroid dependent on prednisone 5 mg daily for 6 months while still on vedolizumab and azathioprine. He had mildly active clinical disease but severe growth failure and was negative for CDI. Repeat disease assessment noted severe granulomatous colitis and terminal ileitis with worsening disease in the distal colon. He was treated with Budesonide MMX and mesalamine enemas with no improvement. Vedolizumab levels were noted to be low and therefore therapy escalated to every 4-week intervals. Azathioprine was stopped due to lack of efficacy despite adequate levels. Due to body mass index (BMI) z-score of -2.4, exclusive enteral therapy was implemented for 3 months followed by transition to regular diet. His weight improved but there was no change in clinical activity or laboratory abnormalities. He subsequently developed leg and hip pain. Rheumatology evaluation was pursued, and he was diagnosed with sacroiliitis based on physical examination and a lumbosacral MRI. At this point a decision was made to use combination of two biologicals due to prior history of GI disease refractory to anti-TNF therapy. Adalimumab and oral methotrexate were given in addition to vedolizumab. He has been on this combination for last 9 months with no adverse events. Patient has shown excellent clinical response with normalization of inflammatory markers and resolution of anemia. His BMI z-score improved to 0.76 with weight gain of 25 kilograms in the past year. Combination biologicals are rarely utilized due to concerns for side effects and high cost making it difficult to obtain insurance approval. When used judiciously in patients with medically refractory disease it can be safe and effective. A paucity of literature exists regarding the use of combination biologicals especially in children.
P013 Characteristics of Fecal Microbiota Transplantation Use in Inflammatory Bowel Disease cohort
Authors: Bauer Christina , Long Millie , Zhang Xian , Sandler Robert
Published: December 2019

BACKGROUND:

There is a growing interest in the role of gut bacteria in a variety of diseases and an emerging hypothesis that inflammatory bowel disease (IBD) is triggered by microbial dysbiosis in genetically susceptible individuals. Currently fecal microbiota transplantation (FMT) is utilized for the treatment of C. difficile colitis. Data on the efficacy of FMT for IBD are mixed, but patients are interested in its use for treatment of IBD. We sought to describe the use of FMT (self or medical professional administered) in individuals with IBD using IBD Partners, an internet-based cohort.

METHODS:

A total of 3,247 patients enrolled in the IBD Partners cohort were offered the opportunity to complete an optional survey on use of FMT. Bivariate statistics were used to determine factors associated with use of FMT including IBD disease characteristics, indication for FMT, and mode of FMT delivery.

RESULTS:

Of the 3,247 patients eligible to complete the FMT survey, 51 (1.6%) people responded that they had an FMT in the past. Of patients undergoing FMT, 22 patients had the FMT for C. difficile while 29 reported that the FMT was for another indication. Most patients receiving FMT for an indication other than C. difficile had UC/IC (25, 86.2%). Colonoscopy (68.2%) and nasogastric tube (18.2%) were the most common routes of administration for patients receiving FMT for C. difficile colitis. Self-administration (72.4%) and enemas (17.2%) were the most common routes of administration in patients receiving FMT for an alternate indication. Patients reporting FMT for an indication other than C. difficile were less likely to have a physician directing their FMT treatment (20.6%) as compared to patients receiving FMT for C. difficile (86.3%). Patient reported efficacy was lower for FMT given for a non-C. difficile indication.

CONCLUSION(S):

Patients undergoing FMT for an indication other than C. difficile infection were more likely to have UC, self-administer FMT, and were less likely to be receiving FMT under the guidance of a medical professional. FMT was not as effective for symptoms when given for a non-C. difficile indication. Patients should be counseled on potential harms and lack of efficacy data associated with FMT for IBD indications to try to discourage self-administered FMT without proper medical oversite.
P022 Factors Associated With Proximal Disease Extension in Ulcerative Proctitis: Experience From an IBD Tertiary Center in Southeastern Brazil
Authors: Ferreira Sandro , Parra Rogerio , Feitosa Marley , de Mendonça Rafaella , Borges Ingrid , Aprile Lílian , Cardoso Pedro , Féres Omar , José Joaquim Rocha , Troncon Luiz Ernesto
Published: December 2019

BACKGROUND:

Ulcerative proctitis (UP) accounts for a significant proportion of cases of ulcerative colitis (UC) and implies limited involvement of the rectum. Some patients presenting initially with UP may progress to more extensive colitis (inflammation found distally to the rectum-sigmoid junction). Although several predictive factors for this progression have been described, none has been established as definitive. We aimed at determining risk factors predictive of proximal disease extension in UP.

METHODS:

Retrospective analysis of data from 97 patients (67% female) with UP (Montreal Classification: E1) with at least 12 months of follow-up at the local University Hospital from January 2001 up to December 2018. Proximal extension was evaluated endoscopically during follow-up and was defined as E1 progressing to E2/E3. Factors examined comprised age, gender, race, presence of extraintestinal manifestations, Mayo endoscopic score, disease relapse, use of corticosteroids, immunosuppressive and biological agents and colectomy. We used univariate analysis (Chi-square test) to assess the association of individual factors to proximal disease extension.

RESULTS:

A total of 29 (29.9%) patients experienced proximal disease extension during a mean follow-up of 137.36 ± 86.63 months. The following factors were significantly associated with proximal disease extension: higher initial Mayo score (P = 0.035) and higher initial disease severity (P = 0.0024). Use of corticosteroids initially (86.2% vs 41.2%, P < 0.0001), increased disease relapse rate (86.2% vs 20.6%, P < 0.0001) and the need for immunosuppressive agents (57.1% vs 13.6%, P < 0.0001) or biological agents (42.9% vs 10.3%, P < 0.0001) were all significantly higher among UP patients with disease proximal extension, when compared to non-extensors. Colectomy was also associated with proximal disease extension (P = 0.0002). No significant association was found between UP proximal extension and gender, race, age at diagnosis and extraintestinal manifestations.

CONCLUSION(S):

UP is a dynamic disease that may progress over time. UP patients with increased clinical and endoscopic severity at the diagnosis are likely to evolve with proximal extension and should be more carefully followed up.
P024 Clinical Aspects and Associated Factors With Surgical Resection in Crohn's Disease Patients
Authors: Ferreira Sandro , Xavier Luana Dias , Borges Ingrid , de Mendonça Rafaella , Lemos Priscila , Aprile Lílian , Parra Rogerio , Feitosa Marley , Féres Omar , Rocha José Joaquim , Troncon Luiz Ernesto
Published: December 2019

BACKGROUND:

Despite the numerous advances in medical treatment, it is estimated that a significant percentage of patients with Crohn's disease (CD) requires bowel resection at least once. The aim of this study was to evaluate patient characteristics and factors associated to surgical resection in patients with Crohn's disease in a tertiary IBD unit in Southeastern Brazil.

METHODS:

Retrospective analysis of data from 247 patients with Crohn's disease in follow-up at the University Hospital, Ribeirão Preto Medical School, from January 2000 up to December 2016. Medical records data comprised age, gender, disease location, disease behavior, disease duration and smoking. Patients were divided into two groups: presence or absence of surgical resection.

RESULTS:

Out of the 247 patients with CD, 111 underwent surgical resection (53.2% female, 82.9% Caucasians, mean age: 45.49 ± 13.30 years). More than one surgical procedure was performed in 15.3% of patients. Main indications for surgery were: stenosis (10.3%), clinical intractability (6.5%) and massive hemorrhage (2.7%). Smoking (P = 0.0109, OR = 2.244; 95% CI: 1.237 to 4.056), stenotic phenotype (P < 0.0001, OR = 5.294; 95% CI: 3.073 to 9.1212), ileo-colonic location (P < 0.0001, OR = 3.447; 95% CI: 2.061 to 5.698), longer disease duration (P < 0.0001) and more advanced age (P = 0.001) were significantly associated with operations for CD. No significant differences were observed in relation to gender, race, age at diagnosis and previous use of corticosteroids.

CONCLUSION(S):

Need for surgical treatment is still frequent in patients with CD. Smoking (current or past), longer disease time, stenotic phenotype and ileo-colonic localization in CD patients were associated with a higher risk of surgery in our IBD Unit. Awareness about factors associated with unfavorable outcome allows these patients to be treated more appropriately.
P026 Investigating Predictors of Antibodies to Infliximab Formation in Inflammatory Bowel Disease – The Importance of Immunomodulators
Authors: Freitas Marta , Magalhaes Rui , Dias de Castro Francisca , Moreira Maria João , Cotter José
Published: December 2019

BACKGROUND:

Anti-tumor necrosis factor (TNF)-α have revolutionized the treatment of inflammatory bowel diseases (IBD), modifying their natural history. Loss of response to anti-TNFs is a clinical challenge and has been associated with formation of antibodies.

AIM:

To identify predictive factors of antibodies to infliximab (ATI) formation in IBD patients.

METHODS:

Retrospective single-center study including all consecutive IBD patients being treated with infliximab with at least one ATI and infliximab level determination and with a minimum follow-up of six months after the first testing. Presence of ATI was considered if at least one determination was positive during the follow-up and infliximab levels at this testing were registered. Clinical and demographic data obtained included disease phenotype, surgical background, duration of infliximab therapy, use of premedication, concomitant immunomodulator therapy at the time of testing, compliance, occurrence of an infusion reaction and biochemical assessment at the time of first induction treatment.

RESULTS:

104 patients were included, 56 females (53.8%) with mean age of 38.2 ± 13.1 years. The overall prevalence of detectable ATI was 28.8% (30) and the mean time to its formation was 32.8 ± 24.3 months. Most (66.7%) patients with ATI had simultaneously nontherapeutic levels of infliximab. Patients treated with concomitant immunomodulators were less likely to develop ATI (33% versus 88%, P < 0.001). Additionally, it was found that patients with Ulcerative Colitis (UC) were more likely to have detectable ATI than those with Crohn Disease (CD) (44.4% vs 23.4%, P = 0.04). However, UC patients were less treated with concomitant immunomodulators (48.1% vs 80.5%, P = 0.001). At logistic regression analysis only lack of immunomodulator use (P < 0.001; OR 13.5, CI 95%, 4.63–40.0) was independently associated with ATI formation.

CONCLUSION(S):

Concomitant immunomodulator therapy was the only protective factor for the ATI formation, supporting its institution to prevent loss of response to anti-TNFs.
P038 Comparing the Efficacy and Safety of Subcutaneous Vedolizumab Versus Adalimumab for the Treatment of Ulcerative Colitis: A Network Meta-Analysis
Authors: Jairath Vipul , Chan Keith , Lasch Karen , Keeping Sam , Agboton Christian , Blake Aimee , Jansen Jeroen , Patel Haridarshan
Published: December 2019

BACKGROUND:

Vedolizumab (VDZ), a gut-selective monoclonal α4β7 integrin antibody, is approved for the treatment of moderately to severely active ulcerative colitis (UC) and Crohn’s disease. Intravenous (IV) VDZ was recently shown to be superior to subcutaneous (SC) adalimumab (ADA) in VARSITY (1), the first head-to-head randomized controlled trial (RCT) of biological therapies in UC. No comparative efficacy or safety data versus ADA exist for VDZ SC, a new formulation in development (2). To generate estimates of the comparative efficacy and safety of VDZ SC versus ADA, we conducted a network meta-analysis (NMA) of RCTs.

METHODS:

The NMA was conducted using results from a targeted literature review that identified RCTs of both VDZ and ADA: GEMINI 1, VISIBLE 1, ULTRA-2, and VARSITY. In the former two trials, responders were rerandomized at the end of induction, whilst the latter two trials were treat-through designs. To adequately analyze these trials in one network of evidence, efficacy outcomes were assessed conditionally upon response at start of maintenance. For treat-through studies, this was response at 6/8 weeks. Efficacy outcomes in the maintenance period were response and remission at 52/54 weeks. Safety outcomes were overall adverse events (AEs), serious AEs (SAEs), overall infections, serious infections, and AEs leading to discontinuation as reported at 52 weeks. Odds ratios (OR) with 95% credible intervals (CrI) were estimated using probit and binomial NMA models. ADA SC 40 mg Q2W, VDZ IV 300 mg Q4W, and VDZ IV 300 mg Q8W were all compared against VDZ SC 108 mg Q2W (reference group).

RESULTS:

ADA had lower rates for maintenance of response and remission relative to VDZ SC, but this was not statistically significant (ORs with 95% Crl: 0.60 [0.33, 1.08] and 0.59 [0.33, 1.09], respectively). Although overall AEs were significantly higher with ADA compared with VDZ SC (OR 2.02 [1.04, 3.89]), other safety outcomes were similar: overall infections, OR 1.86 (0.94, 3.77); serious AEs, OR 1.41 (0.54, 3.75); serious infections, OR 0.39 (0.05, 2.73); AEs leading to discontinuation, OR 2.58 (0.80, 9.44). As expected, VDZ IV had similar maintenance efficacy and safety outcomes relative to VDZ SC.

CONCLUSION(S):

Results from this indirect treatment comparison suggest that VDZ SC may achieve higher rates of maintenance response and remission among responders at start of maintenance than ADA and is associated with a lower risk of overall AEs. In the absence of a head-to-head trial between VDZ SC and ADA SC, these findings support a favorable benefit-risk profile of VDZ SC in UC.