Shared epitope classification methods according to Gregersen and de Vries allow adequate characterization of patients with rheumatoid arthritis in a Colombian population

Introduction: The most important genetic association in rheumatoid arthritis (RA) is presented with some alleles from the HLA-DRB1 gene that encode the shared epitope (SE). Objectives: To apply the SE classification methods of Gregersen, de Vries, Raychaudhuri, Mattey, and Tezenas du Montcel in a group of Colombian patients with RA and determine the most common HLA-DRB1 alleles in the population. Methods: RA diagnosis, genetic study of the HLA-DRB1 region using Luminex technology in 50 RA and 50 healthy subjects. For the classification analysis, Fisher's exact test and chi-squared test were applied. Tables were created to count the RA-related alleles. We used odds ratio to determine the risk between the presence of the shared epitope (SE) and anti-cyclic citrullinated peptides (Anti-CCP). Results: Gregersen and de Vries methods were suitable for the characterization of RA in this population (p = .006). The most prevalent HLA-DRB1 alleles in the RA group were 14:02,04:04, 08:02,04:05, and 10:01. High frequencies of the 07:01, 03:01,13:02,01:02, and 12:01 HLA-DRB1 alleles were found in the healthy population. HLA-DRB1 alleles with similar distribution in both populations were 04:07, 15:01, 11:01, 16:02, and 01:01. A high frequency of SE + was observed in Anti-CCP + individuals (63.15%); however, this was not statistically significant [OR2.4 (.63-9.01); p = .19]. Conclusion: The SE classification methods of Gregersen and de Vries were adequate in characterizing RA in a Colombian population group. An equivalence of 100% was verified between the susceptibility alleles defined by de Vries and the alleles assigned as SE according to Gregersen.

Introducción: La asociación genética más importante en artritis reumatoide (AR) se presenta con algunos alelos del gen HLA DRB1 que codifican el epítope compartido (EC). Objetivos: Aplicar los métodos de clasificación de EC de Gregersen et al., de Vries et al., Raychaudhuri et al., Mattey et al., y Tezenas du Montcel et al., en un grupo de pacientes colombianos con AR, y determinar los alelos HLA DRB1 más frecuentes en esta población. Métodos: Diagnóstico para AR, estudio genético de la región HLA DRB1 por tecnología Luminex® de 50 sujetos AR y 50 sanos. Para análisis comparativos de clasificaciones EC, se aplicaron las pruebas test exacto de Fisher y Chi-cuadrado y se realizaron tablas de conteos para los alelos relacionados con AR. Se estimó la razón de odds para determinar el riesgo entre la presencia de EC y los anticuerpos antipéptidos cíclicos citrulinados (anti-PCC). Resultados: Los métodos de Gregersen et al. y de Vries et al. fueron adecuados para la caracterización de AR en esta población (p = 0,006). Los alelos HLA DRB1 más prevalentes en el grupo AR fueron 14:02, 04:04, 08:02, 04:05 y 10:01. Se encontraron altas frecuencias de los alelos HLA DRB1 07:01, 03:01,13:02, 01:02 y 12:01 en población sana. Alelos HLA DRB1 con distribución similar en ambas poblaciones fueron: 04:07, 15:01, 11:01, 16:02 y 01:01. Se observó alta frecuencia de individuos EC+ en el grupo AR anti-PCC+ (63,15%); no obstante, sin asociación estadística (OR: 2,4 [0,63-9,01]; p = 0,19). Conclusión: Los métodos de clasificación para EC de Gregersen et al. y de Vries et al. fueron adecuados caracterizando AR en un grupo de población colombiana. Se corroboró equivalencia del 100% entre los alelos de susceptibilidad definidos por de Vries y los alelos asignados como EC según Gregersen et al.

Análisis de posibles peligros en leche materna donada. Revisión / Analysis of potential hazards in donated breast milk. Review

La leche materna donada es un recurso de alto valor que puede ser utilizado para la alimentación de neonatos hospitalizados y a término, por tanto, garantizar su inocuidad es imperativo. Esta revisión de literatura reúne los principales peligros de naturaleza física, química y microbiológica identificados en leche materna, con la intención de proveer una referencia que los consolide de tal forma que la información pueda ser utilizada por bancos de leche humana, gobiernos y agencias regulatorias para establecer mecanismos para su prevención y control. Se realizó una revisión de literatura entre agosto del 2021 y octubre del 2022, utilizando buscadores y descriptores específicos para peligros de transmisión alimentaria en leche materna. Se incluyeron estudios publicados en español o en inglés. Se identificaron 31 agentes biológicos patógenos incluyendo bacterias, virus y parásitos. Como peligros químicos se reportaron medicamentos, drogas, cafeína, infusiones herbales, micotoxinas, alérgenos, especias, suplementos nutricionales, contaminantes ambientales y desinfectantes. Se alerta sobre la presencia potencial de plástico y vidrio de tamaño menor a 7 mm proveniente del ambiente de extracción y recipientes. La presencia de peligros microbiológicos y químicos en leche materna puede darse por transmisión vertical, temperaturas inadecuadas durante el almacenamiento y contaminación en el proceso. La presencia de peligros físicos se relaciona con la manipulación de los implementos en etapas posteriores a la extracción. Se requiere prestar atención a los hábitos de la madre para prevenir peligros químicos, así como más investigación relacionada con micotoxinas en leche materna(AU)

Donated breast milk is a highvalue resource which can be used to feed hospitalized neonates and full-term infants, therefore, ensuring its safety is imperative. This literature review presents the main hazards of physical, chemical and microbiological nature identified in human milk, with the intention of providing a reference that consolidates the reported hazards reported, so the information can be used by human milk banks, governments and regulatory agencies to establish prevention and control mechanisms. A literature review was carried out between August 2021 and October 2022, using search engines and specific descriptors for foodborne hazards in breast milk. Studies published in Spanish and English were considered. 31 pathogenic biological agents including bacteria, viruses and parasites were identified. Medications, drugs, caffeine, herbal infusions, mycotoxins, allergens, spices, nutritional supplements, contaminants of environmental origin and disinfectants were reported as chemical hazards. No physical hazards were identified, however the potential presence of plastic and glass smaller than 7 mm from the extraction environment or containers is alerted. Presence of microbiological and chemical hazards can be due to vertical transmission, inadequate temperature of storing, contamination during extraction, packaging, and infant feeding. Whereas presence of physical hazards is related to implements handling after extraction. Attention to hygiene and habits of the mother to prevent chemical hazards and further research related to mycotoxins in human milk is required(AU)

Grupo multifamiliar em transtornos alimentares durante a primeira onda da pandemia de covid-19: transição para a modalidade online / Multifamily group on eating disorders during the first wave of the covid-19 pandemic: transitioning to the online modality / Grupo multifamiliar de trastornos alimentarios durante la primera ola de la pandemia de la covid-19: transición a la modalidad en línea

As restrições impostas pela pandemia de covid-19 levaram os serviços de saúde a reorganizarem seu funcionamento, ajustando-se à modalidade remota. A transição repentina e sem o devido preparo técnico impôs desafios adicionais para usuários e profissionais. Para aprimorar as estratégias assistenciais, torna-se imprescindível dar voz aos usuários dos serviços, para que narrem suas experiências e possam manifestar suas facilidades e dificuldades com essa passagem. Este estudo tem como objetivo investigar como os principais cuidadores familiares de pessoas com transtornos alimentares vivenciaram a transição do grupo de apoio para o formato remoto e identificar vantagens e desvantagens percebidas nesse modelo. Estudo clínico-qualitativo, exploratório, realizado em um serviço de atendimento especializado de um hospital terciário. O cenário investigado foi o grupo de apoio psicológico aberto a familiares que, desde o início da pandemia de covid-19, passou a ser oferecido na modalidade online. Participaram do estudo cinco mães e três pais presentes em 13 sessões grupais consecutivas. Entrevistas individuais foram aplicadas com a Técnica do Incidente Crítico logo após o término de cada encontro grupal, totalizando 26 entrevistas audiogravadas, transcritas e submetidas à análise temática. A transição para o online foi vivenciada pelos participantes como um recurso válido para permitir que o grupo funcionasse em tempos de grave crise sanitária. Como vantagens, foram mencionadas: a continuidade do cuidado, maior acessibilidade e facilidade em relação à logística da participação. Como limitações do formato online, foram destacadas: nem todos os familiares contam com conexão de internet de qualidade e possível dificuldade para manusear a tecnologia digital. Apesar dos desafios impostos pela súbita mudança para a modalidade online, na perspectiva dos usuários do serviço os esforços de adaptação foram bem-sucedidos, possibilitando a continuidade do cuidado à saúde mental.(AU)

The constraints imposed by the COVID-19 pandemic led health services to reorganize their operation, adjusting to the online modality. The sudden and unprepared technical transition has imposed additional challenges for both users and professionals. To improve care strategies, it is essential to give voice to services users, so that they can narrate their experiences and express their facilities and difficulties with this transition. This study aims to investigate how main family caregivers of people with eating disorders experienced the transition of the support group to the remote modality and to identify perceived advantages and disadvantages in this model. This is a clinical-qualitative, exploratory study carried out in a specialized care service of a tertiary hospital. The investigated setting was the psychological support group open to family members, which since the beginning of the COVID-19 pandemic has been offered online. Five mothers and three fathers who attended 13 consecutive group sessions participated in the study. Individual interviews were carried out with the Critical Incident Technique shortly after the end of each group meeting with all members, totaling 26 audio-recorded interviews. Data were subjected to thematic analysis. Transition was experienced as a valid resource to maintain the group active in times of a severe health crisis. As advantages of the remote modality were mentioned: continuity of care, greater accessibility, and ease in relation to the logistics of participation. As limitations of the online format were highlighted: not everyone has a good-quality connection to the internet, and difficulty in handling the digital technology. Despite the challenges imposed by the sudden shift to the online modality, from the service users' perspective the adaptation efforts were successful, enabling continuity of mental health care.(AU)

Las limitaciones que impuso la pandemia de la COVID-19 llevaron a los servicios sanitarios a reorganizar su funcionamiento adaptándose a la modalidad remota. El súbito cambio y sin la preparación técnica adecuada implicó retos adicionales a los usuarios y profesionales. Para mejorar las estrategias de atención es fundamental dar voz a los usuarios de los servicios, para que puedan narrar sus experiencias y expresar sus facilidades y dificultades con esta transición. Este estudio pretende investigar cómo han vivido los cuidadores de personas con trastornos alimentarios la transición del grupo de apoyo presencial al formato remoto e identificar las ventajas y desventajas percibidas en este modelo. Se trata de un estudio clínicocualitativo, exploratorio. El escenario investigado fue el grupo de apoyo psicológico abierto a los familiares en la modalidad en línea. Cinco madres y tres padres participaron en 13 sesiones de grupo consecutivas. Se realizaron entrevistas individuales con la técnica de incidentes críticos inmediatamente después de cada reunión del grupo, con un total de 26 entrevistas grabadas en audio, transcritas y sometidas a análisis temático. La transición a la red fue experimentada como un recurso válido para permitir que el grupo funcione en tiempos de crisis sanitaria grave. Las ventajas de la modalidad remota fueron conexión segura en tiempos de confinamiento físico, continuidad, mayor accesibilidad y facilidad en relación con la logística de la participación. Las limitaciones del formato en línea fueron la falta de una conexión de calidad a Internet y la posible dificultad de manejo de la tecnología digital. A pesar de las dificultades impuestas por el cambio repentino a la modalidad en línea, desde la perspectiva de los usuarios del servicio los esfuerzos de adaptación fueron un éxito, lo que permitió seguir con la atención de salud mental.(AU)

Bioseguridad y autocuidado: prioridad en la formación universitaria en momentos de pandemia / Biosafety and self-care: a priority in university training during pandemic times

Introducción: La bioseguridad y el autocuidado son dos prácticas importantes en el proceso de formación. Estas deben reforzarse permanentemente, ya que se relacionan de manera directa no solo con el riesgo de infecciones, sino con la calidad de la atención. Objetivo: Identificar la evidencia científica sobre los procesos de formación en bioseguridad y autocuidado en el marco de la pandemia. Métodos: Se hizo una revisión de la literatura científica publicada entre 2016 y 2020 sobre medidas de bioseguridad y autocuidado. La búsqueda se realizó en español, inglés y portugués, en la Biblioteca Virtual en Salud, Pubmed, Science Direct y el motor de búsqueda de Google Académico. Se aplicó la metodología PRISMA y se evaluaron en total 25 artículos científicos. Resultados: El año 2020 tuvo mayor frecuencia. La generalidad de los estudios se realizó en el contexto universitario en programas de salud. La higiene de las manos y el uso de guantes fueron las medidas de bioseguridad más informadas; mientras que las medidas de precaución se conocen e implementan. Las publicaciones denotan moderado conocimiento en cuanto a prevención de factores de riesgos biológicos, especialmente en prácticas clínicas. Conclusiones: En los procesos de formación debe tenerse en cuenta la relevancia de reforzar las medidas de bioseguridad y autocuidado para favorecer el ejercicio profesional. Es importante diseñar y repensar estos procesos, tanto en docentes como estudiantes, a través de nuevos métodos y cambios curriculares. La salud mental puede verse afectada no solo por la situación, sino por desconocimiento, miedo a infectarse y sobrecarga laboral(AU)

Introduction: Biosafety and self-care are two important practices in the training process. These should be permanently reinforced, since they are directly related not only to the risk of infections, but also to the quality of care. Objective: To identify the scientific evidence on the biosafety and self-care training processes in the context of the pandemic. Methods: A review of the scientific literature published between 2016 and 2020 on biosafety and self-care measures was carried out. The search was performed in Spanish, English and Portuguese, in the Virtual Health Library, PubMed, Science Direct, and the Google Scholar search engine. The PRISMA methodology was applied and a total of 25 scientific articles were assessed. Results: The year 2020 had the highest frequency. Most of the studies were carried out in the university context in health programs. Hand hygiene and glove-wearing were the most reported biosafety measures, while warning measures are known and implemented. The publications are indicative of moderate knowledge regarding prevention of biological risk factors, especially in clinical practices. Conclusions: The relevance of reinforcing biosafety and self-care measures to favor professional practice should be taken into account in training processes. It is important to design and rethink these processes, both in professors and students, through new methods and curricular changes. Mental health may be affected not only by the situation, but also by ignorance, fear of infection and work overload(AU)

Construção e validação de instrumento para avaliação das medidas de biossegurança em bioterrorismo pelos bombeiros / Construction and validation of and assessment tool for biosafety measures in bioterrorism for firefighters / Construcción y validación de un instrumento para evaluar las medidas de bioseguridad en el bioterrorismo de los bomberos

Objetivo: Este estudo teve como objetivo desenvolver e validar um instrumento de avaliação das medidas de Biossegurança adotadas pelos bombeiros militares, para a contenção dos agentes biológicos frente a um evento de bioterrorismo. Métodos: Tratou-se de um estudo descritivo de abordagem quantitativa, de desenvolvimento metodológico e do tipo de validação de conteúdo de um instrumento de avaliação. O estudo foi dividido nas fases de desenvolvimento e validação do instrumento. Para o desenvolvimento do instrumento foram feitas revisões da literatura e para a validação do instrumento foi utilizado o método Delphi. Para o estudo foram incluídos 6 juízes que avaliaram o instrumento através da escala numérica tipo Likert. Resultados: Os juízes avaliaram que o instrumento proposto está bem estruturado, possuindo boa clareza e coesão de escrita, com aplicabilidade no campo de estudo e de grande relevância, principalmente em vista a ausência desse tipo de instrumento para a população de bombeiros militares. Para avaliar a concordância entre os juízes foi utilizado o índice de Validade de Conteúdo, que alcançou 98% de concordância e o Índice de Fidedignidade Interavaliadores, que alcançou os conceitos bom e muito bom, mostrando baixa variância das respostas dos juízes, sendo estatisticamente válido. Conclusão: O estudo descreveu o processo de construção e validação do instrumento, provando ser apropriado e confiável para ser utilizado.

Objective: This study aimed to develop and validate an instrument to assess the Biosafety measures adopted by firefighters, for the containment of biological agents in the face of a bioterrorism event. Methods: This is a descriptive study with a quantitative approach, methodological development, and the type of content validation of an assessment instrument. The study was divided into instrument development and validation phases. For the development of the instrument, literature reviews were conducted and for the instrument validation, the Delphi method was used. For the study, 6 judges were included who evaluated the instrument using the Likert-type numerical scale. Results: The judges evaluated that the proposed instrument is well structured, with good clarity and cohesion of writing, with applicability in the field of study and of great relevance, especially considering the absence of this type of instrument for the military firefighter population. To evaluate the agreement between the judges, we used the Content Validity Index which reached 98% of agreement and the Interrate agreement, which reached the concepts good and very good, showing low variance of the judges' answers, being statistically valid. Conclusion: The study described the process of construction and validation of the instrument, proving to be appropriate and reliable to be used.

Objetivo: Este estudio tenía como objetivo desarrollar y validar un instrumento para evaluar las medidas de bioseguridad adoptadas por los bomberos militares para contener los agentes biológicos durante un evento de bioterrorismo. Métodos: Se trata de un estudio descriptivo de abordaje cuantitativo, de desarrollo metodológico y del tipo de validación de contenido de un instrumento de evaluación. El estudio se dividió en las fases de desarrollo y validación del instrumento. Para la elaboración del instrumento se realizaron revisiones bibliográficas y para la validación del mismo se utilizó el método Delphi. Para el estudio se incluyeron 6 jueces que evaluaron el instrumento mediante una escala numérica tipo Likert. Resultados: Los jueces evaluaron que el instrumento propuesto está bien estructurado, poseyendo buena claridad y cohesión de redacción, con aplicabilidad en el campo de estudio y de gran relevancia, especialmente en vista de la ausencia de este tipo de instrumento para la población de bomberos militares. Se utilizó el Índice de Validez de Contenido para evaluar la concordancia entre los jueces, alcanzando un 98% de acuerdo y el Índice de Fiabilidad Inter-registrador, que alcanzó conceptos buenos y muy buenos, mostrando una baja varianza en las respuestas de los jueces, siendo estadísticamente válido. Conclusión: El estudio describió el proceso de construcción y validación del instrumento, demostrando ser apropiado y confiable para ser utilizado.

Spondyloarthritis: Characterization of a cohort. Pablo Tobón Uribe Hospital. Medellín, Colombia / Espondiloartritis: caracterización de la cohorte del Hospital Pablo Tobón Uribe, Medellín, Colombia

ABSTRACT Introduction: Spondyloarthritis is a group of chronic inflammatory diseases. Several factors of the disease remain unknown, including clinical and radiological behavior, the demographic characteristics and burden of disease in Colombian patients. Objective: To characterize the demographic aspects, the clinical and paraclinical behaviour, and the therapeutic requirements of a cohort of patients with spondyloarthritis followed-up in the Hospital Pablo Tobón Uribe from January 1, 2005 to December 31, 2017. Methodology: Cohort study. The population was characteriszed using descriptive statistics, qualitative variables using simple and relative frequencies, and quantitative variables using means and standard deviation or medians with their interquartile ranges. Results: The cohort consisted of 181 patients, 100 men (54.9%) and 81 women (44.5%). Just under one half (45.1%) had ankylosing spondylitis, 18.1% undifferentiated spondyloarthritis, 17.1% psoriatic arthropathy, 14.8% reactive arthritis, and 4.4% inflammatory bowel disease. More than two-thirds (69.8%) of the patients had peripheral manifestations, and 67% had axial. A positive HLAB27 was observed in 55.6% of patients. The MRI showed acute and chronic changes in the sacroiliac in 69% and 37%, respectively, with radiological sacroiliitis being observed in 59.5% of cases. The large majority (91.1%) of the patients were treated with PII of original article: S0121-8123(21)00018-9 NSAIDs, 60.1% with sulfasalazine, 43.4% with COX2 inhibitors, and 33.7% with methotrexate. TNFa inhibitors were required by 56.6% of the subjects 3 years after the onset of symptoms. The most commonly used biological drugs were Adalimumab (31.1%), etanercept (21.7%), infliximab (13.1%), golimumab 6.1%, and certolizumab 0.5%. Conclusions: Ourpopulation was characterized by a high activity and functional compromise demonstrated by the high scores of BASDAI and BASFI, and because 56.6% of the patients required anti-TNFa agents.

RESUMEN Introducción: Las espondiloartritis son un grupo de enfermedades inflamatorias crónicas. Se desconoce su comportamiento en nuestro medio, al igual que el comportamiento clínico y radiológico, las características demográficas y la carga de enfermedad en los pacientes colombianos. Objetivos: Caracterizar los aspectos demográficos, el comportamiento clínico y paraclínico y los requerimientos terapéuticos de la cohorte de pacientes con espondiloartritis seguidos en el Hospital Pablo Tobón Uribe desde el 1.° de enero del 2005 hasta el día 31 de diciembre del 2017. Metodología: Estudio de cohorte. La población se caracterizó mediante estadística descrip tiva, las variables cualitativas mediante frecuencias simples y relativas, en tanto que para las cuantitativas se emplearon medias y desviación estándar o medianas con sus rangos intercuartílicos. Resultados: La cohorte está constituida por 181 pacientes, 100 hombres (54,9%) y 81 mujeres (44,5%). El 45,1% tenía espondilitis anquilosante, el 18,1% espondiloartritis indiferenciada, el 17,1% artropatía psoriásica, el 14,8% artritis reactiva y el 4,4% enfermedad inflamatoria intestinal. El 69,8% de los pacientes tenía manifestaciones periféricas y el 67% axiales. El 55,6% de los pacientes tuvo HLAB27 positivo. La RMN mostró cambios agudos y crónicos en las sacroilíacas en el 69% y 37%, respectivamente; en el 59,5% de los casos se observó sacroileítis radiológica. el 91,1% de los pacientes se trató con AINE, el 60,1% con sulfasa lazina, el 43,4% con inhibidores COX2 y el 33,7% con metotrexato. El 56,6% de los sujetos requirió inhibidores-TNFa 3 arios después del inicio de los síntomas. Los biológicos más uti lizados fueron adalimumab (31,1%), etanercept (21,7%), infliximab (13,1%), golumimab (6,1%) y certolizumab (0,5%). Conclusiones: Nuestra población se caracterizó por una alta actividad y gran compromiso funcional, lo que se refleja en altos puntajes de Basdai y Basfi y en que el 56,6% de los pacientes requirió agentes anti-TNFa.

Environmental influences on the ichthyoplankton in hypersaline estuaries located in a Semiarid Northeastern Brazilian coast

Hypersaline estuaries are commonly found in the Semiarid Northeast Brazilian coast. However, the utilization of these estuaries by early life stages of fishes is less well documented. This study aimed to evaluate the effects of environmental factors on the ichthyoplankton, and to describe their spatial and temporal variation in two estuaries (Tubarão and Casqueira). The sampling were diurnally in four excursions carried out during two dry-season months (November and December 2017) and two rainy-season months (May and July 2018). A total of 423 larvae representing 30 species (14 families) and 2,762 eggs (five families) were collected. Although the community structures were similar in both estuaries, there was strong seasonal variation, with higher abundances observed during the dry season. Low rainfall was the primary environmental driver affecting ichthyoplankton in both estuaries. Other environmental factors, such as depth, water temperature, and channel width, were also predictor variables for the distribution of eggs and larvae. The ichthyoplankton was dominated by marine estuarine-dependent species in both estuaries, accounting for 76% of individuals. The presence of the early life stages of typically marine species suggests that hypersaline environments provide important nursery areas and play an essential role for some coastal fish species.(AU)

Os estuários hipersalinos são comumente encontrados na região semiárida da costa nordestina brasileira. No entanto, a utilização desses estuários pelos primeiros estágios de vida dos peixes é pouco documentada. O objetivo deste estudo foi avaliar os efeitos de fatores ambientais sobre o ictioplâncton e descrever sua variação espacial e temporal em dois estuários (Tubarão e Casqueira). As amostragens foram diurnas em quatro excursões realizadas em dois meses da estação seca (novembro e dezembro de 2017) e dois meses da estação chuvosa (maio e julho de 2018). Um total de 423 larvas representando 30 espécies (14 famílias) e 2.762 ovos (cinco famílias) foram coletadas. Embora as estruturas das comunidades fossem semelhantes em ambos os estuários, houve fortes diferenças de variação sazonal, com maiores abundâncias observadas durante a estação seca. A baixa precipitação foi o principal fator ambiental que afetou o ictioplâncton em ambos os estuários. Outros fatores, como profundidade, temperatura da água e largura do canal, também foram preditoras para a distribuição de ovos e larvas. O ictioplâncton foi dominado por espécies marinhas dependentes em ambos os estuários, representando 76% dos indivíduos. A presença de estágios iniciais de espécies tipicamente marinhas sugere que ambientes hipersalinos fornecem áreas de berçário importantes e desempenham um papel essencial para algumas espécies de peixes costeiros.(AU)

Depleción de eosinófilos: muchas implicaciones en modelos múridos, pocas estudiadas en humanos / Eosinophil depletion: many implications in murine models, few studied in humans

The eosinophil is a cell of the immune system, with an arsenal of substances that can alter the balance that exists in the different organs where they are found. With the advent of monoclonal antibodies, concern about their depletion has become an important turning point in their formulation. For this reason, it is of vital importance to investigate the consequences of the mechanism of action of biological agents, in the short and long term. This review tries to show the role of eosinophils in both homeostasis and disease, and their relationship and interaction with monoclonal drugs in diseases focused on the Th2 profile. It is expected that this article can be useful when making the decision to start treatment with monoclonals, specifically anti-interleukin-5 or against its receptor

Expresión génica de mediadores moleculares para potencial terapia celular en el síndrome gastrointestinal inducido por radiación / Genetic expression of molecular mediators for potential cell therapy in radiation-induced gastrointestinal syndrome

Antecedentes: Las células madres intestinales generan las distintas estirpes celulares a dicho nivel. Estas se regulan por interacciones entre el epitelio y las células del nicho celular anexo. Estas se pueden ver dañadas en tratamientos con radiación, generando el síndrome gastrointestinal inducido por radiación. Se ha visto que células madre mesenquimales (MSC) y macrófagos de médula ósea (BMM) tienen propiedades de regeneración tisular. Objetivos: Evaluar la expresión génica de IL-4, Wnt6, VEGF y bFGF, a partir de cultivos celulares primarios independientes de MSC derivadas de tejido adiposo y BMM de ratones C57BL/6, por medio de PCR en tiempo real (qRT-PCR). Diseño experimental: A partir de un análisis in silico, se confeccionaron primers para evaluar la expresión génica de las moléculas propuestas, en los cultivos primarios por medio de qRT-PCR y electroforesis. Resultados y proyecciones: IL-4 y Wnt6 no son expresadas en las muestras de BMM y MSC. VEGF y bFGF son expresadas por diferentes células, dando expresión diferenciada. A futuro, se deben evaluar las mismas estirpes celulares en un ambiente inflamatorio y su efecto en la expresión génica, en especial VEGF y bFGF. Limitaciones: El número de moléculas en estudio es limitado y la expresión se evalúo solo a nivel genético.

Background: Intestinal stem cell generates diferents cellular types in their niche. They're regulated by interactions between epithelium and niche's cells, and can be damaged by medical radiation treatments causing radiation-induced gastrointestinal syndrome. It has seen that mesenchymal stem cells (MSC) d and bone marrow-derived macrophages (BMM) have propierties of tissular regeneration. Objectives: Determinated genetic expression of IL-4, Wnt6, VEGF and bFGF, in primary cellular cultures of MSC derivated of adipose tissue and BMM of C57BL/6 mice, through real time PCR (qRT-PCR). Methods: By an in silico analysis, we created primers to evaluate the proposed molecules in the primary cellular cultives, with qRT-PCR and electrophoresis. Results and projections: IL-4 and Wnt6 were not expressed in the MSC and BMM samples. VEGF and bFGF were expressed by different cells, giving differential expression. In the future, the same samples should be analyzed in an inflammatory environment, especially VEGF and bFGF. Limitations: The number of molecules are limited and the expression of them is only in a genetic level.

Variabilidad intrasujeto de la prueba de caminata de seis minutos / Within-subject variability of the 6-minute walk test

Introducción: la prueba de caminata de seis minutos evalúa la capacidad para hacer ejercicio y es de amplio uso, bajo costo y variabilidad diversa. Objetivo: definir la utilidad de una segunda prueba de caminata de seis minutos realizada a 30 minutos de la primera. Material y métodos: se llevó a cabo un estudio observacional, longitudinal y analítico de sujetos nacidos y habitantes de la Ciudad de México, de ambos géneros, sin enfermedad cardiopulmonar. Se registraron sus variables demográficas. Las diferencias se calcularon con la prueba t para grupos independientes y la variabilidad con el estadístico de BlandAltman; su magnitud, con el coeficiente de correlación intraclase e intervalos de confianza del 95% (IC 95%). Una p < 0.05 se consideró significativa. Resultados: se estudiaron 200 pruebas de 100 sujetos. La edad promedio fue de 36 ± 11 años. La media del índice de masa corporal fue 24.71 ± 3.24 kg/m2. Fueron 43 hombres (43%). La actividad más frecuente fueron las artes y los oficios en 38 (38%). Solo en 55 (55%) incrementaron en 24 los metros caminados en la segunda prueba. Los metros caminados totales de la caminata 1 frente a la 2 fueron 437.65 ± 48.84 frente a 441.62 ± 11.49. La diferencia media (sesgo) fue de −4 (57.9, −65.9) y el coeficiente de correlación intraclase de 0.800 (IC 95% 0.717-0.861). Conclusiones: la prueba de caminata de seis minutos es reproducible con variabilidad amplia. Estos resultados sugieren realizar solo una prueba de caminata de seis minutos

Background: The 6-minute walk test assesses the ability to perform exercise and it is widely used, of low cost, and of diverse variability. Objective: To define the usefulness of a second 6-minute walk test performed 30 minutes from the first. Material and methods: An observational, longitudinal and analytical study was carried out in subjects born and inhabitants from Mexico City, both genders, without cardiopulmonary disease. Their demographic variables were recorded. Differences were calculated with the t test for independent groups and variability with the Bland-Altman statistic; its magnitude, with the intraclass correlation coefficient and 95% confidence intervals (95% CI). A p < 0.05 was considered significant. Results: 200 tests from 100 subjects were studied. Average age was 36 ± 11 years. Body mass index average was 24.71 ± 3.24 kg/m2. 43 subjects were male (43%). The most frequent activity was arts and crafts in 38 (38%). Only 55 subjects (55%) increased by 24 the number of meters walked in the second test. Total of meters walked on walk 1 vs. 2 were: 437.65 ± 48.84 vs. 441.62 ± 11.49. Mean difference (bias) was of −4 (57.9, −65.9) and intraclass correlation coefficient of 0.800 (95% CI, 0.717-0.861). Conclusions: The 6-minute walk test is reproducible with wide variability. These results suggest to do only one 6-minute walk test

Clinical analysis of 5 cases of systemic juvenile idiopathic arthritis with coronary artery dilatation / 中华儿科杂志

Objective: To investigate the clinical characteristics of systemic juvenile idiopathic arthritis combined with coronary artery dilatation. Methods: A retrospective analysis was performed on the clinical data, including clinical manifestations, blood routine, inflammatory factors, echocardiography, vascular ultrasound and CT angiography, treatment and outcomes, etc, of 5 cases with systemic juvenile idiopathic arthritis combined with coronary artery dilation admitted to Department of Rheumatology in the affiliated Children's Hospital of Capital Institute of Pediatrics from May 2019 to June 2021. Results: There were 2 males and 3 females among 5 cases. The onset age ranged from 7 months to 4 years 7 months.The diagnostic time ranged from 1.5 months to 3.0 months.Four cases were diagnosed as atypical Kawasaki disease. Three cases showed unilateral coronary artery dilation.Two cases showed bilateral coronary artery dilation.Four cases developed multiple organ injuries.Three cases developed macrophage activation syndrome.Three cases developed lung injury.Two cases developed pericardial effusion.One case developed pulmonary hypertension.As for treatment, 3 cases treated with methylprednisolone pulse therapy and methotrexate combined with cyclosporine, improved after the final application of biological agents, and have stopped prednisone. The other 2 cases were treated with adequate oral prednisone and gradually reduced, and methotrexate was added at the same time, 1 case relapsed in the process of reduction. No other vascular involvement was found in 5 cases. Coronary artery dilation recovered completely after 1 to 3 months of treatment. Conclusions: Systemic juvenile idiopathic arthritis combined with coronary artery dilatation has the clinical characteristics of small onset age, long diagnostic time, prone to multiple organ injuries. Corticosteroids and conventional immunosuppressive agents are not sensitive, and biological agents should be used as soon as possible.The prognosis of coronary artery dilation is good after timely treatment.

Disfunción sexual femenina: una mirada a los últimos 44 años. Análisis bibliométrico / Female Sexual Dysfunction: Looking Back at the Last 44 Years. A Bibliometric Analysis

Objetivo La disfunción sexual femenina (DSF) es un trastorno prevalente que afecta la calidad de vida de las mujeres y combina factores biológicos, psicológicos e interpersonales. Su estudio ha sido de poco interés, en campos como la investigación y el tratamiento, debido a la dificultad en la medición de las respuestas sexuales en las mujeres y otros factores, como el tabú acerca de la sexualidad femenina. Este estudio caracteriza las tendencias de publicaciones científicas acerca del tema, para que los urólogos puedan comprender la necesidad de realizar la búsqueda de este trastorno en la práctica diaria. Métodos Se realizó una búsqueda de la literatura en las bases de datos PubMed, FABUMED y Scopus, utilizando la estrategia «((«female sexual dysfunction¼ [Title/Abstract])¼. Se realizó un análisis bibliométrico descriptivo, de corte retrospectivo, de la literatura médica obtenida en MEDLINE. A través de las herramientas estadísticas FABUMED, PubReminer y Scopus, se recopilaron los datos y se obtuvo los resultados de las variables que posteriormente fueron analizadas de forma estadística y descriptiva. Con base en esta información, elaboramos tablas y gráficas en Microsoft Office Excel 2017. Adicionalmente, realizamos un análisis de mapeo bibliométrico utilizando el programa VOSviewer. Para la obtención del factor de impacto (FI), utilizamos el Journal Citation Reports 2017/2018. Resultados Desde 1975 hasta 2019, se publicaron 1.292 estudios, y la tasa anual de publicación permaneció estable entre 1975 y 2000. Pero, a partir del año 2000, se evidenció un aumento en el número de publicaciones, con un crecimiento del 92,1%. De las veinte revistas con más publicaciones, sólo cuatro son de urología. Los países con más publicaciones fueron: Estados Unidos (31,4%), Reino Unido (12,9%), Italia (8,9%), Turquía (5,9%), y Australia (4%). Estos datos son muy diferentes a los de los países de América Latina, en los que se encontraron muy pocas publicaciones, como Colombia, con tan sólo tres estudios. Conclusiones Este análisis bibliométrico mostró las diferentes tendencias y tasas de publicación de estudios sobre DSF, y evidenció una baja tasa de producción con relación a otras temáticas, sobre todo en las revistas urológicas, con predominio de mujeres como autores, aunque en los últimos años se ha identificado un crecimiento importante y sostenido. Se hace evidente la necesidad de desarrollar estrategias para mejorar la formación tanto en los niveles de posgrado como de pregrado y, así, generar más adhesión a este tema en una especialidad quirúrgica como la nuestra.

Objectives Female sexual dysfunction (FSD) is a prevalent disorder that affects the quality of life of women and combines biological, psychological, and interpersonal factors. There has been a lack of interest in studying FSD in such fields as research and treatment, due to the difficulty in measuring the sexual responses of women and other factors such as the taboo surrounding female sexuality. The present study portrays the trends in the scientific publications on the subject, so urologists can perceive and understand the need for research about this disorder in the daily practice. Methods A comprehensive review on the topic was performed through a PubMed, FABUMED, and Scopus databases using the search strategy "female sexual dysfunction", as well as a retrospective, descriptive, bibliometric analysis of the medical literature retrieved from MEDLINE. Data was collected through the FABUMED, PubReMiner, and Scopus statistical tools, and, based on the results obtained for the variables, which were later submitted to a statistical and descriptive analysis. Based on this data, tables and graphs were developed using the Microsoft Office Excel 2017 software. Moreover, we performed a bibliometric mapping analysis using the VOSviewer software. In order to obtain the impact factor (IF), we used the Journal Citation Reports 2017/2018. Results From 1975 to 2019, 1,292 studies were published; yearly publication rate remained stable from1975 to 2000, but after year 2000, an increase in the number of publications was evidenced, with a growth of 92.1%. But as of the year 2000, an increase in the number of publications was evidenced, with a growth of 92.1%. Of the twenty journals with the most publications, only four are on urology. The countries with the greatest number of publications were: the United States (31.4%), the United Kingdom (12.9%), Italy (8.9%), Turkey (5.9%), and Australia (4%). This data differs from that of Latin American countries, in which few publications were found, such as in Colombia, with only three studies. Conclusions The present bibliometric analysis showed the different trends and publication rates of studies on FSD, showing a low production rate as compared with that of other urological topics, especially in Urological journals, with a predominance of women as authors, although in recent years an important and sustained growth has been identified. The need to develop strategies to improve training at both the graduate and undergraduate levels and thus generate more adherence to these issues in a surgical specialty like ours is evident.

Fatores associados à infecção pelo vírus da estomatite vesicular em equídeos no estado do Rio Grande do Norte, Brasil / Factors associated with infection by the vesicular stomatitis virus in equines in the state of Rio Grande do Norte, Brazil

Objetivou-se investigar a presença do Vírus da Estomatite Vesicular (VEV) e seus fatores de risco para ocorrência e disseminação da enfermidade em equídeos das mesorregiões Leste e Oeste Potiguar do estado do Rio Grande do Norte, Brasil. Foram analisadas pela técnica de virusneutralização, 809 amostras sanguíneas de equídeos provenientes de noventa propriedades de dezesseis municípios Potiguares durante os meses de julho de 2018 a fevereiro de 2019. Os fatores de riscos associados ao VEV foram avaliados por meio de questionário epidemiológico e os dados submetidos a análise estatística no programa IBM SPSS Statistics versão 21.0 com nível de confiança de 95%. Posteriormente, todas as variáveis estatisticamente significantes foram submetidas a análise de regressão de Poisson. A soroprevalência de anticorpos anti-VEV foi 24,6% (199/809), sendo 3,2% (13/402) de soropositivos na mesorregião Leste e 45,7% (186/407) na do Oeste Potiguar. Com relação aos sorotipos, observou-se uma prevalência de 3,8% (31/809) e 24,5% (198/809) para Indiana 2 e 3 respectivamente, com 15,1% (30/198) de coinfecção. Equídeos criados na mesorregião Oeste, em propriedades que não realizam quarentena e onde os animais enfermos são mantidos no rebanho, foram consideradas fatores predisponentes a infecção pelo VEV. Esses resultados demonstram a circulação do VEV em equídeos no Rio Grande do Norte, com destaque ao Oeste Potiguar, e sendo necessário a aplicação de medidas sanitárias que impeçam introdução e disseminação do vírus ente as espécies susceptíveis, principalmente em condições climáticas favoráveis para a sua manutenção, no ambiente de criação e pastagens.

This study aimed to investigate the presence of Vesicular stomatitis virus (VSV) and risk factors for its occurrence and dissemination in equines from the Eastern and Western mesoregions of the state of Rio Grande do Norte, Brazil. Blood samples were analyzed, by Serum Virus Neutralization Assay, from 809 animals belonging to 90 properties distributed in sixteen municipalities from July 2018 to February 2019. Risk factors were assessed using an epidemiological questionnaire. Data were submitted to statistical analysis using the software IBM SPSS Statistics, version 21.0 with a 95% confidence level. Also, all statistically significant variables were subjected to Poisson regression analysis. The occurrence of anti-VSV antibodies was 24.6% (199/809) with 3.2% (13/402) and 45.7% (186/407) of seropositivity in the Western and Eastern mesoregion, respectively. Regarding serotypes, there were an occurrence of 3.8% (31/809) and 24.5% (198/809) for Indiana 2 and 3, respectively, and 15.1% (30/198) of co-infection for both. Equines kept of the Western mesoregion, on properties that do not quarantine, and where sick animals are kept in the herd, were considered risk factors for LVV infection. These results demonstrate the presence of VSV in equines in Rio Grande do Norte, with emphasis on Oeste Potiguar, and that sanitary measures must be adopted to prevent the introduction and viral spreading among susceptible species, especially due to favorable climatic conditions for the maintenance of VSV in the breeding and pasture environment.

Características pessoais e do ambiente associadas com transtorno do desenvolvimento da coordenação / Personal and environmental characteristics associated with coordination development disorder

RESUMO Identificar a associação entre características pessoais e ambientais de crianças com provável transtorno do desenvolvimento da coordenação (TDC). Participaram 42 pais, 32 professores e 42 pré-escolares (3,4±0,5 anos). Como instrumentos foram utilizados o Movement Assessment Battery for Children 2 (MABC-2), o Teste de Maturidade Mental Columbia (EMMC), o Questionário da Associação Brasileira de Empresas de Pesquisas (ABEP), o Strengths and Difficulties Questionnaire (SDQ), o Swanson Nolan and Pelham IV Scale (SNAP-IV), o Questionário de percepção de pais/responsáveis sobre habilidades motoras, acadêmicas, emocionais e comportamentais e o Early Years Movement Skills Checklist. Na análise foi utilizado o teste Shapiro Wilk e Regressão Logística Binária (p<0,05). Os resultados demostraram diferença estatisticamente significativa para as seguintes características associadas às crianças com persistência de TDC: 1) características pessoais: o peso ao nascer, a idade de sentar, o desenvolvimento cognitivo, os problemas de linguagem e os problemas de conduta; 2) características ambientais da família: a união estável dos pais, a melhor qualidade do ambiente domiciliar; 3) no ambiente escolar o nível de escolaridade do professor. Conclui-se que as crianças que nasceram com maior peso, que apresentaram desenvolvimento cognitivo superior, vivem com pais em união estável, que possuem professor de sala especialista e apresentaram menores chances de persistir no TDC.

ABSTRACT Identify the associtation among personal and environmental characteristics on the motor development of children with probable developmental coordination disorder (DCD). The participants were 42 parents, 32 teachers and 42 preschoolers' (3.4±0.5years). As measurement instruments: The Movement Assessment Battery for Children 2 (MABC2), the Columbia Mental Maturity test (EMMC), the Questionnaire of the Brazilian Association of Research Companies (ABEP), the Strengths and Difficulties Questionnaire (SDQ), the Swanson Nolan and Pelham IV Scale (SNAP-IV), Structured Questionnaire for parents on motor, academic, emotional and behavioral skills and Early Years Movement Skills Checklist were used. For data analysis, the Shapiro Wilk test and Binary Logistic Regression were used, adopting p <0.05. Results shown statistically significant difference for the personal characteristics associated with children with persistence DCD: 1) birth weight, age to sit, cognitive development, language problems and conduct problems; 2) For home characteristics: quality of the home environment and the parents' stable union were taken into account; 3) For day care center, the education of the classroom teacher was considered. In conclusion, children who were born with greater weight, who had higher cognitive development, live with parents in a stable relationship and who have a specialized classroom teacher were less likely to persist in DCD.

Recomendaciones de expertos para el tratamiento biológico en pacientes con psoriasis / Expert recommendations for biological treatment in patients with psoriasis

Resumen En los últimos años, la introducción de diversos medicamentos biológicos para el tratamiento de la psoriasis ha aumentado considerablemente el arsenal terapéutico del médico, con lo cual se ha logrado un fuerte impacto positivo en el control de la enfermedad. Con el fin de proveer de las mejores recomendaciones para el uso de estos biológicos en los pacientes afectados de psoriasis, el grupo mexicano de expertos en psoriasis PSOMEX ha formulado recomendaciones para mejorar la comprensión y el posicionamiento terapéutico de este tipo de medicamentos.

Abstract In recent years, the introduction of a series of biological drugs for the treatment of psoriasis has considerably increased the therapeutic armamentarium of doctors, and thus a strongly positive impact on the control of this condition has been achieved. With the purpose to provide the best recommendations for the use of these biological agents in patients with psoriasis, the Mexican group of psoriasis experts, PSOMEX, has developed recommendations in order to improve the understanding and therapeutic positioning of this type of medications.

Análise crítica do uso dos anti-TNF na era dos novos agentes biológicos na doença inflamatória intestinal / Critical analysis of anti-tnf use in the era of new biological agents in inflammatory bowel disease

ABSTRACT BACKGROUND: Inflammatory bowel diseases (IBD), both Crohn's disease and ulcerative colitis, are chronic immune-mediated diseases that present a relapsing and remitting course and requires long-term treatment. Anti-tumor necrosis factor (anti-TNF) therapy has changed the management of the disease by reducing the need for hospitalizations, surgeries and improving patient´s quality of life. OBJECTIVE: The aim of this review is to discuss the role of anti-TNF agents in IBD, highlighting the situations where its use as first-line therapy would be appropriate. METHODS: Narrative review summarizing the best available evidence on the topic based on searches in databases such as MedLine and PubMed up to April 2020 using the following keywords: "inflammatory bowel disease'', "anti-TNF agents" and ''biologic therapy''. CONCLUSION: Biological therapy remains the cornerstone in the treatment of IBD. In the absence of head-to-head comparisons, the choice of the biological agent may be challenging and should take into account several variables. Anti-TNF agents should be considered as first line therapy in specific scenarios such as acute severe ulcerative colitis, fistulizing Crohn's disease and extra-intestinal manifestations of IBD, given the strong body of evidence supporting its efficacy and safety in these situations.

RESUMO CONTEXTO: As doenças inflamatórias intestinais (DII), tanto a doença de Crohn (DC) como a retocolite ulcerativa (RCU), são doenças crônicas imunomediadas que se apresentam com períodos de surto e remissão e requerem terapia a longo prazo. A terapia com anti-fator de necrose tumoral (anti-TNF) tem mudado o manejo da doença reduzindo a necessidade de hospitalizações, cirurgias e melhorando a qualidade de vida dos pacientes. OBJETIVO: O objetivo do presente trabalho é apresentar uma revisão sobre a importância dos agentes anti-TNF no contexto da DII, levando em consideração situações em que essas drogas são usadas como terapia de primeira linha. MÉTODOS: Revisão narrativa baseada nas melhores evidências disponíveis na literatura através de buscas feitas nas bases de dados MedLine e PubMed até abril de 2020, utilizando as seguintes palavras chaves: "doença inflamatória intestinal'', "agentes anti-TNF" e "terapia biológica". CONCLUSÃO: A terapia biológica permanece sendo fundamental no tratamento da DII. Na ausência de estudos "head-to-head'' comparando os biológicos entre si, a escolha do agente biológico pode ser um desafio na prática clínica e múltiplas variáveis devem ser levadas em consideração. Os agentes anti-TNF devem ser considerados terapia de primeira linha em situações específicas como na colite ulcerativa aguda grave, na doença de Crohn fistulizante e nas manifestações extra-intestinais da doença inflamatória intestinal, uma vez que há evidências científicas robustas que sustentam a sua eficácia e segurança nessas situações.

Utility of biomarkers in traumatic brain injury: a narrative review / Utilidad de los biomarcadores en trauma craneoencefálico: una revisiOn narrativa

Abstract Introduction: With the evolution of diagnostic techniques in traumatic brain injury (TBI), the study of neurological injury has made progress based on the concepts of primary and secondary injury, leading to the era of proteomics to understand the complex molecular events involved in the process. Objectives: This narrative review is intended to discuss the state of the art of the most frequently used biomarkers in TBI, their clinical utility, and the implications for therapeutic decision-making protocols. Materials and methods: In order to fulfill the objective of this paper, a literature review was conducted of the most important databases. Results: Several biomarkers have been studied as prognostic factors in patients with TBI. Learning about their sensitivity and specificity in neurological injury, and its post-trauma evolution over time, has been the goal of various papers in the past few years. Conclusion: Breakthroughs in the study of protein degradation make it necessary to broaden the spectrum and knowledge of new diagnostic methods in TBI. Further studies are needed to define the role of biomarkers and to promote protocols integrating specific values.

Resumen Introducción: Con la evolución de las técnicas diagnósticas en el trauma craneoencefálico, el estudio de la lesión neurológica ha progresado sobre los conceptos de lesión primaria y secundaria, para entrar así en la era de la proteómica y, con ella, entender los complejos eventos moleculares existentes en su proceso. Objetivos: En esta revisión narrativa se pretende presentar el estado actual de los biomarcadores que más se usan en lesión cerebral traumática, su utilidad clínica y las implicaciones en protocolos de decisión terapéutica. Materiales y métodos: Para dar respuesta al objetivo de este trabajo, se realizó una revisión de la literatura en las principales bases de datos. Resultados: Se han estudiado varios biomarcadores como factor pronóstico en pacientes con trauma craneoencefálico. Conocer su sensibilidad y especificidad para la lesión neurológica, así como su evolución en el tiempo tras el traumatismo, ha sido el objetivo de diversos trabajos en los últimos años. Conclusión: El avance en el estudio de los productos de degradación de las proteínas hace necesario ampliar el espectro y el conocimiento en el campo de los nuevos métodos diagnósticos en el trauma craneoencefálico. Se requieren más estudios para definir la función de los biomarcadores y proponer protocolos que integren valores específicos.

Persistencia a largo plazo de agentes biológicos en el tratamiento de pacientes con Artritis Reumatoidea: una revisión sistemática de la literatura / Long-term persistence of biological agents in the treatment of patients with Rheumatoid Arthritis: a systematic literature review

La persistencia en el tratamiento es un marcador subrogante de éxito de tratamiento a largo plazo. Objetivo: Evaluar la persistencia de los agentes biológicos utilizados para el tratamiento de pacientes con artritis reumatoidea (AR) a un tiempo de 5 años y determinar las principales causas asociadas a persistencia o discontinuación. Material y métodos: Se realizó una revisión sistemática de la literatura (RSL), según las recomendaciones PRISMA, en las bases de datos Pubmed, Cochrane y Lilacs, y estudios presentados en los congresos ACR, EULAR, PANLAR (2018/2019) hasta Enero 2020. Dos revisoras independientes, evaluaron todas las publicaciones identificadas, por título y abstract y por full text, de acuerdo a la metodología PICO. Los criterios de elegibilidad fueron estudios de pacientes ≥ 18 años con diagnóstico de AR, en tratamiento con agentes biológicos, que midieran persistencia/discontinuación en un período de tiempo igual o superior a 5 años y que estuvieran en idioma inglés o español. En el caso de falta de acuerdo entre las dos revisoras, un tercer revisor fue consultado. La información extraída fue analizada mediante estadística descriptiva, se calculó el porcentaje promedio de persistencia de cada agente biológico a los 5 años. Resultados: Se seleccionaron 56 artículos luego de la remoción de los duplicados y de la exclusión por título/abstract, y por full text. De ellos 13, eran fase de extensión a largo plazo de estudios randomizados controlados, 15 cohortes retrospectivas, 18 cohortes prospectivas y 10 cohortes retro-prospectivas y correspondían a un total de 72177 (rango: 79-10396) pacientes con AR, con una edad media 53.8 años ± 12.1, 78.2% de sexo femenino y un tiempo promedio de evolución de la AR de 9.7 años ± 8.4. En 33.9% de los estudios, la terapia biológica estaba combinada con drogas modificadoras de la AR convencionales (DMARs-c), en 3.6% en monoterapia, 48.2% ambas modalidades y en 14.3% no informaba. Un estudio fue realizado en 1° línea (metotrexato näive), 29 estudios en 2° línea (respuesta inadecuada a MTX y/o DMARs-c), 5 en 3° línea (respuesta inadecuada a DMARs biológicas-b-), 12 en ≥2° línea terapéutica y en 9 no especificaban. En 30 estudios que evaluaron 2° línea terapéutica, la mayor persistencia correspondió a tocilizumab (TCZ) 66.41% (IC95% 57.8-79.94), abatacept (ABA) 57.91% (IC95% 50.96-64.87) y golimumab (GOL) 54.38% (IC95% 48.58-60.19). Y 10 estudios, en los cuales el DMAR-b había sido analizado en 3° línea terapéutica, las mayores tasas de retención correspondieron a rituximab (RTX) 61.19% (IC95% 57.53-66.22) y TCZ 61.1% (IC95% 58.81-63.32). Entre los estudios que evaluaron predictores, los más frecuentemente asociados a mayor sobrevida fueron: tratamiento combinado con DMAR-c, etanercept versus infliximab y adalimumab y 2° línea de tratamiento vs 3° o 4° línea y los asociados a menor sobrevida fueron: mayor uso de esteroides, mayor actividad basal de la enfermedad y sexo femenino. Conclusiones: En esta RSL, la persistencia de los DMAR-b a 5 años en pacientes con respuesta inadecuada a DMARs-c y DMARs-b fue numéricamente mayor para los agentes no TNFi. Y entre los TNFi, GOL presentó mayor retención en 2° línea terapéutica.

Treatment persistence is a surrogate marker for long-term treatment success. Objective: To assess the persistence of the biological agents used for treatment of patients with rheumatoid arthritis (RA) over 5 years period and to determine the main causes associated with persistence or discontinuation. Material and methods: A systematic literature review (SLR) was carried out, according to PRISMA recommendations, including Pubmed, Cochrane and Lilacs databases, and studies presented at the ACR, EULAR, PANLAR congresses (2018/2019) until January 2020. Two independent reviewers evaluated the identified publications, by title and abstract and full text, according to PICO methodology. Eligibility criteria were: studies including RA patients ≥ 18 years, treated with biological agents, which measured persistence/ discontinuation for a period of time equal to or greater than 5 years and who were in English or Spanish language. In the case of lack of agreement between the two reviewers, a third reviewer was consulted. The extracted information was analyzed using descriptive statistics, an average percentage of persistence for each biological agent at 5 years was calculated. Results: 56 articles were selected after removal of duplicates and exclusion by title/abstract, and by full text. Long-term extension phase of randomized controlled studies were 13, another 15 retrospective cohorts, 18 prospective cohorts and 10 retro-prospective cohorts and corresponded to a total of 72177 (range: 79-10396) patients with RA, with a mean age of 53.8 years ± 12.1, 78.2% female and an average RA disease duration of 9.7 years ± 8.4. In 33.9% of the studies, biological therapy was combined with conventional disease modifying anti-rheumatic drugs (c-DMARDs), in 3.6% monotherapy, 48.2% both modalities, and in 14.3% not reported. One study was in the 1st line (methotrexate näive), 29 studies in 2nd line (inadequate response to MTX and/or c-DMARDs), 5 in 3rd line (inadequate response to biological b-DMARDs), 12 in ≥2nd therapeutic line and in 9 studies did not specify this condition. In 30 studies which evaluated the 2nd therapeutic line, the highest persistence corresponded to tocilizumab (TCZ) 66.41% (95% CI 57.8-79.94), abatacept (ABA) 57.91% (95% CI 50.96-64.87) and golimumab (GOL) 54.38% (95% CI 48.58-60.19). In 10 studies, in which b-DMARD had been analyzed in 3rd therapeutic line, highest retention rates corresponded to rituximab (RTX) 61.19% (95% CI 57.53-66.22) and TCZ 61.1% (95% CI 58.81-63.32). Among studies that evaluated predictors, the most frequently associated with higher survival were: combined treatment with c-DMARD, etanercept versus infliximab and adalimumab and 2nd line of treatment vs. 3rd or 4th line whereas those associated with lower survival rates were: greater use of steroids, higher baseline disease activity, and female gender. Conclusions: In this SLR, the 5-year persistence of b-DMARD in patients with inadequate response to DMARs-c and DMARs-b was numerically greater for non-TNFi agents. And among TNFi, GOL presented a higher retention in 2nd therapeutic line.

Correlación entre características clinicopatológicas e inmunohistoquímicas del cáncer de mama en mujeres argentinas / Correlation between clinicopathological and immunohistochemical characteristics of breast cancer in Argentine women

Introducción: El cáncer de mama se clasifica en 4 subgrupos moleculares de tumores. Estos factores biológicos junto al grado histológico, han tomado importancia en la nueva clasificación TNM ya que permite establecer pronósticos de sobrevida. Objetivo: Analizar la correlación entre los distintos subtipos moleculares de los carcinomas de mama con factores clínico-patológico, la presencia de metástasis axilares y en la re-estadificación de los tumores según la nueva Clasificación TNM de la AJCC. Material y método: Estudio observacional y descriptivo de series de casos, registrados en Registro de Cáncer de Mama (RCM), en Argentina entre los años 2006 a 2016. Resultados: La mayoría de los tumores fueron Luminales. Los estadios avanzados fueron en edades tempranas. El mayor compromiso axilar perteneció a HER2 neu positivos. Se consiguió re estadificar las pacientes aumentando el número de pacientes con estadios IA y IB y descendiendo los estadios IIA, IIIA, IIIB y IIIC. Conclusiones: De los subtipos moleculares con factores clinicopatológicos más desfavorables fueron los Triples Negativos y Her2 neu. La importancia de los factores biológicos a la hora de re estadificar los pacientes según TNM 8° edición, favorece los tratamientos conservadores y específicos contra el tumor evitando el sobre tratamiento e implican menores costos que las plataformas genómcias.

Introduction: Breast cancer is classified into 4 molecular subgroups. These biological factors, together with the histological grade, are important factors in the 8th edition of the TNM Classification, and allow establishing survival prognoses in patients with breast cancer. Objetive: The main objetive was to analyse the correlation between different molecular subtypes of breast carcinomas, the presence of axillary metastases and the correlation of tumours in the new TNM Classification. Material and method: Observational and descriptive restrospective study of case series registred in RCM, in Argentina between 2006 and 2016. Results: Most of the tumours were Luminals. The clinical presentation of advanced stages was more frequent at early ages. The molecular subtypes with the highest axillary involvement were HER2 neu tumours. We managed to re-stage the patients to the TNM Classification 8th edition, increasing the number of patients with stages IA and IB and decreasing the stage IIA, IIIA, IIIB and IIIC. Conclusions: Triples negative tumours were diagnosed in more advanced stages, according to the new TNM Classification, than the Luminals. The surgical decision was not modified according to the molecular subtype. We conclude the importance of biological factors when re-staging patients according to the new TNM Classification 8th edition because it increases the number of conservative treatments, and more targets treatment.

Factores biológicos relacionados con la masa ósea en hombres de edad mediana / Biological Factors Associated to Bone Mass in Middle-Aged Men

RESUMEN Introducción: La osteoporosis masculina es una enfermedad clínica heterogénea y subdiagnosticada, con múltiples factores de riesgo. Requiere un proceso de diagnóstico en ocasiones más complejo que en las mujeres. Objetivo: Identificar factores biológicos relacionados con la masa ósea en hombres de edad mediana. Métodos: Se realizó estudio descriptivo, transversal, en 43 hombres de edad mediana (40-59 años) entre abril de 2017 y mayo de 2018, que fueron atendidos en el Policlínico Universitario Vedado. Se estudiaron los antecedentes patológicos familiares (APF) de osteoporosis masculina o fracturas por fragilidad, índice de masa corporal (IMC), circunferencia de la cintura (CC), presión arterial (PA), glucemia, colesterol, triglicéridos, creatinina, hormona luteinizante, folículo estimulante, estradiol, testosterona (T), prolactina y paratohormona (PTH) y densitometría dual de Rx (DXA). Según edad y resultado de la DXA, se crearon 4 grupos (de 40-49 y de 50-59 años, en L1-L4 y fémur). Se identificaron hombres con hueso normal y mala masa ósea (MMO). Se determinaron distribuciones de frecuencia (variables cualitativas), y mediana y rango (cuantitativas). Se empleó chi cuadrado para determinar relación entre variables cualitativas y Mann-Whitney para cuantitativas. Para establecer correlación entre variables cuantitativas, se calculó el test de Pearson. Resultados: En hombres de 50-59 años, con antecedentes patológicos familiares de fracturas por fragilidad, predominó la mala masa ósea (75 por ciento). La mediana del índice de masa corporal en hombres de 40-49 años fue mayor (26,7 Kg/m2sc) en los que tenían hueso normal en L1-L4; en los de 50-59 años con aumento de la circunferencia de la cintura predominó la mala masa ósea (3; 75 por ciento). La presión arterial sistólica y diastólica se correlacionaron positivamente con la densidad mineral ósea en L1-L4 ([r = 0,225; p = 0,009], [r = 0,263; p = 0,002]). Hubo correlación positiva entre colesterol y contenido mineral óseo en fémur (r = 0,164; p = 0,002). La testosterona resultó más baja en hombres con hueso normal (40-49 años: 15,3 nmol/L; 50-59 años: 12,5 nmol/L). Se observó correlación negativa entre paratohormona y contenido mineral óseo en fémur (r = -0,324; p = 0,000). Conclusiones: Se puede concluir que, de los factores biológicos estudiados en los hombres de edad mediana del Policlínico Universitario Vedado, los niveles más elevados de presión arterial y colesterol, y más bajos de paratohormona, se asociaron con mejor masa ósea(AU)

ABSTRACT Introduction: Male osteoporosis is a heterogeneous and underdiagnosed clinical condition and with multiple risk factors, which requires a diagnostic process that is sometimes more complex than for women. Objective: To identify biological factors related to bone mass in middle-aged men from "Vedado" University Polyclinic. Methods: A cross-sectional and descriptive study was carried out with 43 middle-aged (40-59 years old) men, between April 2017 and May 2018. The variables were family pathological history of osteoporosis or fragility fractures, body mass index, waist circumference, blood pressure, glycemia, cholesterol, triglycerides, creatinine, luteinizing hormone, stimulating follicle, estradiol, testosterone, prolactin and parathyroid hormone, and dual x-ray densitometry. According to age and results of the dual x-ray densitometry, four groups were created (40-49 and 50-59 years old, in L1-L4 and femur). The men with normal bone and poor bone mass were identified. Frequency distributions (qualitative variables), as well as median and range (quantitative variables) were determined. The chi-square test was used to determine the relationship between qualitative variables, and the Mann-Whitney test was used for quantitative variables. To establish correlation between quantitative variables, the Pearson test was used. Results: Among men aged 50-59 years and with a family pathological history of fragility fractures, poor bone mass prevailed (75 percent). The median body mass index among men aged 40-49 years was higher (26.7 kg/m2sc) in those with normal bone in L1-L4; among those aged 50-59 years and with increased waist circumference, poor bone mass predominated (3; 75 percent). Systolic and diastolic blood pressure were correlated positively with bone mineral density in L1-L4 [(r = 0.225, p = 0.009), (r = 0.263, p = 0.002)]. There was a positive correlation between cholesterol and bone mineral content in the femur (r = 0.164, p = 0.002). T was lower among men with normal bone (15.3 nmol/L for the group 40-49 years old, and 12.5 nmol/L for the group 50-59 years old). A negative correlation was observed between the parathyroid hormone and bone mineral content values in the femur (r = -0.324, p = 0.000). Conclusions: Among the biological factors studied in middle-aged men from "Vedado" University Polyclinic, higher levels of blood pressure and cholesterol, as well as lower levels of the parathyroid hormone were concluded to be associated with better bone mass(AU)