Silibinin Suppresses Tumor Cell-Intrinsic Resistance to Nintedanib and Enhances Its Clinical Activity in Lung Cancer.

The anti-angiogenic agent nintedanib has been shown to prolong overall and progression-free survival in patients with advanced non-small-cell lung cancer (NSCLC) who progress after first-line platinum-based chemotherapy and second-line immunotherapy. Here, we explored the molecular basis and the clinical benefit of incorporating the STAT3 inhibitor silibinin-a flavonolignan extracted from milk thistle-into nintedanib-based schedules in advanced NSCLC. First, we assessed the nature of the tumoricidal interaction between nintedanib and silibinin and the underlying relevance of STAT3 activation in a panel of human NSCLC cell lines. NSCLC cells with poorer cytotoxic responses to nintedanib exhibited a persistent, nintedanib-unresponsive activated STAT3 state, and deactivation by co-treatment with silibinin promoted synergistic cytotoxicity. Second, we tested whether silibinin could impact the lysosomal sequestration of nintedanib, a lung cancer cell-intrinsic mechanism of nintedanib resistance. Silibinin partially, but significantly, reduced the massive lysosomal entrapment of nintedanib occurring in nintedanib-refractory NSCLC cells, augmenting the ability of nintedanib to reach its intracellular targets. Third, we conducted a retrospective, observational multicenter study to determine the efficacy of incorporating an oral nutraceutical product containing silibinin in patients with NSCLC receiving a nintedanib/docetaxel combination in second- and further-line settings (n = 59). Overall response rate, defined as the combined rates of complete and partial responses, was significantly higher in the study cohort receiving silibinin supplementation (55%) than in the control cohort (22%, p = 0.011). Silibinin therapy was associated with a significantly longer time to treatment failure in multivariate analysis (hazard ratio 0.43, p = 0.013), despite the lack of overall survival benefit (hazard ratio 0.63, p = 0.190). Molecular mechanisms dictating the cancer cell-intrinsic responsiveness to nintedanib, such as STAT3 activation and lysosomal trapping, are amenable to pharmacological intervention with silibinin. A prospective, powered clinical trial is warranted to confirm the clinical relevance of these findings in patients with advanced NSCLC.

Trastornos plaquetarios hereditarios poco frecuentes: patología molecular y aspectos diagnósticos / Infrequent hereditary platelets disorders: molecular pathology and diagnostic aspects

Introducción: Las plaquetas tienen una función clave en la hemostasia primaria a través de cuatro mecanismos fundamentales: adhesión, agregación, secreción y actividad procoagulante, todos controlados genéticamente por más de 50 genes asociados que han sido identificados. Las manifestaciones clínicas en las alteraciones hereditarias de las plaquetas suelen ser variables; aunque estas alteraciones de la coagulación suelen presentarse con una trombocitopenia notoria, también pueden exhibir trombocitopatías, en las cuales la capacidad hemostática de las plaquetas resulta afectada sin variar su número. Por tanto, existen gran variedad de manifestaciones fenotípicas y mutaciones en relación con la función plaquetaria, algunas de las cuales se explicarán más adelante. Objetivo: Realizar revisión práctica sobre mutaciones plaquetarias hereditarias de baja incidencia y destacar la importancia de su conocimiento, correcto diagnóstico, y tratamiento precoz. Métodos: Se realizó revisión literaria en inglés y españolen MEDLINE, EMBASE, Lilacs y ScienceDirect desde mayo 2019 hasta abril 2020, con el uso de combinación de palabras clave y términos MeSH relacionados con trombastenia, genética médica, hemostasis, agregación plaquetaria, trombopoyesis. Se efectuó análisis y resumen de la bibliografía revisada. Conclusión: Entre las alteraciones hereditarias de las plaquetas se pueden encontrar defectos en todos los mecanismos en que participan; sin embargo, la confirmación diagnóstica sigue siendo complicada por el tiempo y el costo que representa lo que ocasiona diagnósticos inadecuados que impactan en el manejo clínico y la evolución(AU)

Introduction: Platelets have a key role in primary hemostasis through four main mechanisms: adhesion, aggregation, secretion and procoagulant activity, all of these controlled by over 50 associated genes that have been identified. Clinical signs of hereditary platelets alterations are usually variable; even though these disorders of hemostasis generally course with a notorious thrombocytopenia, they also might have thrombocytopathies, in which the hemostatic capacity of platelets is affected without altering its number. According to this, there's a great variety of phenotypic manifestations and mutations that affect platelet function, some of these will be explained later on. Objective: To make a practical review of hereditary platelets mutations that have low incidence in population and to highlight the importance of knowing about them, how to diagnose them and early treatment. Methods: A review of literature in both Spanish and English, was done based on MEDLINE, EMBASE, Lilacs and ScienceDirect, during May 2019 and April 2020 using key words and MeSH terms such as thrombasthenia, medical genetics, hemostasis, platelets aggregation, thromopoiesis. Then, an analysis and summary of the reviewed bibliography was carried out. Conclusion: Among the hereditary alterations of platelets, many defects can be found in every mechanism involved; however, diagnostic confirmation is still complicated due to time and cost, causing inaccurate diagnoses that impact on clinic management and evolution(AU)

Etnoeducación: educación para la salud desde la diversidad cultural / Ethnoeducation: health education from cultural diversity / Etnoeducação: educação para a saúde a partir da diversidade cultural

Introducción. En un país multicultural como Colombia, la etnoeducación es un importante elemento en la educación médica, pues favorece la calidad de vida de minorías étnicas a partir de potencialidades comunitarias, prácticas, hábitos, experiencias y enfoques que promuevan el sentido global de la salud. El objetivo de este artículo fue realizar una revisión narrativa sobre los antecedentes de la etnoeducación y su impacto en la salud. El desarrollo de competencias interculturales en los estudiantes del área de la salud permitiría a los futuros profesionales desempeñar su rol con adecuada pertinencia cultural, respetando los valores, tradiciones e historia de las comunidades. Temas tratados: A nivel mundial, la etnoeducación ha sido un aspecto relevante, organizaciones internacionales han trabajado durante décadas para su implementación. A nivel nacional, se han creado diversos instrumentos normativos y reglamentación para la implementación de la etnoeducación, sin embargo, cerca del 86% de las poblaciones étnicas no cuentan con acceso a educación que cumpla con los principios establecidos. La importancia de la etnoeducación se ha evidenciado en varios países, brindando resultados positivos como la disminución de la morbimortalidad con actividades educativas de promoción de la salud y prevención de la enfermedad. Para ello, es crucial que las acciones planteadas se integren con las percepciones culturales de las comunidades. Conclusión: Existen muchos lineamientos a nivel local, nacional e internacional, sin embargo, la etnoeducación continúa siendo un reto. Es necesario aumentar los esfuerzos para que la etnoeducación logre los objetivos que están planteados desde el punto de vista teórico. Cómo citar: Hernández-Martínez A, Cuartas-Agudelo YS, Herrera-Almanza L, Roldan-Tabares MD, Martínez- Sánchez LM. Etnoeducación: educación para la salud desde la diversidad cultural. MedUNAB. 2021; 24(1): 80- 91.Doi: https://doi.org/10.29375/01237047.3899

Introduction. In a multicultural country such as Colombia, ethnoeducation is an important component of health education, because it promotes the quality of life of ethnic minorities based on the community's potential, practices, habits, experiences and approaches that promote overall health awareness. The purpose of this article is to perform a narrative review on the background of ethnoeducation and its impact on health. The development of inter-cultural skills among students in health fields would enable the future professional to perform their roles with adequate cultural relevancy, respecting the values, traditions and history of the communities. Topics discussed: Worldwide, ethnoeducation has been highly relevant, and some international organizations have worked on its implementation for decades. In Colombia, several legal and regulatory instruments have been developed to implement ethnoeducation. However, close to 86 % of the ethnic populations do not have access to education in accordance with the established principles. The importance of ethnoeducation has been highlighted in several countries in that it has achieved positive results such as a reduction of morbidity and mortality through educational activities that promote health and help prevent diseases. To achieve this, it is essential that the planned activities be integrated into the communities' cultural perceptions. Conclusion: Although local, national and international guidelines have been established, ethnoeducation continues to be a challenge. It is necessary to increase efforts in order for ethnoeducation to achieve the objectives that have been set out from a theoretical perspective. Cómo citar: Hernández-Martínez A, Cuartas-Agudelo YS, Herrera-Almanza L, Roldan-Tabares MD, Martínez- Sánchez LM. Etnoeducación: educación para la salud desde la diversidad cultural. MedUNAB. 2021; 24(1): 80- 91.Doi: https://doi.org/10.29375/01237047.3899

Introdução. Em um país multicultural como a Colômbia, a etnoeducação é um elemento importante na educação médica, pois favorece a qualidade de vida das minorias étnicas a partir das potencialidades comunitárias, das práticas, dos hábitos, das experiências e abordagens que promovem o sentido global da saúde. O objetivo deste artigo foi realizar uma revisão narrativa sobre os antecedentes da etnoeducação e seu impacto na saúde. O desenvolvimento de competências interculturais nos alunos da área da saúde permitirá aos futuros profissionais desempenharem seu papel com adequada relevância cultural, respeitando os valores, tradições e história das comunidades. Tópicos discutidos: Em nível global, a etnoeducação tem sido um aspecto relevante e organizações internacionais trabalharam durante décadas para implementá-la. A nível nacional foram criados diversos instrumentos normativos e reguladores para a implementação da etnoeducação, no entanto, cerca de 86% das etnias não tem acesso a uma educação que cumpra os princípios estabelecidos. A importância da etnoeducação é evidente em diversos países, proporcionando resultados positivos como a redução da morbimortalidade com atividades educativas de promoção da saúde e prevenção de doenças. Para isso, é fundamental que as ações propostas estejam integradas às percepções culturais das comunidades. Conclusão: Existem muitas diretrizes a nível local, nacional e internacional, ainda assim, a etnoeducação continua a ser um desafio. É necessário aumentar os esforços para que a etnoeducação atinja os objetivos que são levantados a partir do ponto de vista teórico. Cómo citar: Hernández-Martínez A, Cuartas-Agudelo YS, Herrera-Almanza L, Roldan-Tabares MD, Martínez- Sánchez LM. Etnoeducación: educación para la salud desde la diversidad cultural. MedUNAB. 2021; 24(1): 80- 91.Doi: https://doi.org/10.29375/01237047.3899

High-performance athletes’ attitude towards doping: Validation of the Spanish version of the Performance Enhancement Attitude Scale for Colombia / Actitud frente al dopaje de deportistas de alto rendimiento: Validación de la versión española de la Performance Enhancement Attitude Scale para Colombia

BACKGROUND: Doping is the use of substances to achieve a better performance in sports. This practice is considered to be growing worldwide. Despite regulations by the World Anti-Doping Agency, 14-39% of high-performance athletes have consumed prohibited substances at least once in their sports career. The attitudes towards this type of consumption are used as predictors of the intent of usage of prohibited substances to improve physical performance. OBJECTIVE: This study aimed to validate the Spanish Version of the Performance Enhancement Attitude Scale of high-performance athletes in the Colombian context. METHODOLOGY: A cross-sectional study was performed with a convenience sampling of 112 athletes aged 15 and older, registered in a State Sports Institute in Medellín, Colombia in 2016. The participants self-completed Petróczi and Aidman instrument, Performance Enhancement Attitude Scale, adapted into Spanish by Morente-Sánchez, et al. in 2014. The reliability of the scale was assessed using Cronbach's Internal Consistency Coefficient and an exploratory and confirmatory factor analysis (CFA) was conducted to evaluate the scale's structure. RESULTS: The scale had a reliability of 0.87 and the factor analysis confirmed the unidimensionality. Of all the athletes participating in the research, the Performance Enhancement Attitude Scale average was 35.8 of 102 points, indicating a low tendency of attitudes towards doping. CONCLUSION: The psychometric properties of the 17 items of the Performance Enhancement Attitude Scale are adequate and could be used when assessing attitudes towards doping of high-performance athletes in similar contexts. This information could be used for the purposes of developing educational strategies for doping prevention in our athletes

INTRODUCCIÓN: El dopaje es el uso de sustancias para lograr un mejor desempeño en los deportes. Esta práctica parece estar creciendo en todo el mundo. A pesar de las regulaciones de la World Anti-Doping Agency, 14-39% de los deportistas de alto rendimiento han consumido sustancias prohibidas al menos una vez durante su carrera deportiva. las actitudes hacia este tipo de consumo se emplean como predictores de la intención de uso de sustancias prohibidas para mejorar el rendimiento físico. OBJETIVO: El objetivo del estudio fue validar en deportistas de alto rendimiento en el contexto colombiano la versión española de la escala de Actitudes frente al mejoramiento del rendimiento. DISEÑO: Se realizó un estudio de corte transversal en 2016 con una muestra por conveniencia de 112 deportistas de 15 y más años inscritos en un instituto deportivo estatal en Medellín (Colombia). METODOLOGÍA: Los participantes autodiligenciaron el instrumento de Petróczi y Aidman Performance Enhancement Attitude Scale (PEAS), adaptado al español por Morente-Sánchez et al. Se evaluó la confiabilidad de la escala con el coeficiente de consistencia internal de Cronbach y se hicieron análisis factorial exploratorio y confirmatorio para evaluar la estructura de la escala. RESULTADOS: Los resultados indicaron que la escala tenía una confiabilidad de 0,87 y el análisis factorial confirmó la unidimensionalidad. En los deportistas participantes en la investigación el promedio de la PEAS fue de 35,8 de 102 puntos posibles, indicando baja tendencia de actitudes hacia el dopaje. CONCLUSIÓN: Las propiedades psicométricas de los 17 ítems de la PEAS son adecuadas, y podría ser utilizada en la evaluación de actitudes hacia el dopaje en deportistas de alto rendimiento en contextos similares. Esta información podría ser utilizada para el desarrollo de estrategias educativas para la prevención del dopaje en nuestros deportistas

Hemocomponentes en urgencias: tratamiento vital para los pacientes politraumatizados / Blood products in the emergency room: vital treatment for polytraumatized patients

Introducción: La principal causa de mortalidad temprana en pacientes politraumatizados es la hipovolemia secundaria a hemorragia masiva. La terapia con hemocomponentes y cristaloides constituye un mecanismo esencial y salvavidas en estas situaciones como medida de reemplazo de volumen. De la misma manera los pacientes con lesiones traumáticas graves tienen una disminución aguda significativa en el recuento de plaquetas circulantes que los hace candidatos a la transfusión de componentes plaquetarios; sin embargo, el uso de estos componentes sanguíneos puede traer consigo desenlaces no deseados como aumento en la mortalidad. Si bien muchos estudios revelan un aumento de la mortalidad como desenlace asociado al uso de hemocomponentes, otros establecen su uso como una medida reductora de este desenlace. Objetivo: Exponer las principales indicaciones de hemocomponentes en los pacientes politraumatizados, así como relacionar los eventos adversos asociados a su uso que influyen sobre la mortalidad y el tiempo de hospitalización de estos pacientes. Desarrollo: La mortalidad asociada al uso de hemocomponentes aún es un tema controvertido. En la hemorragia masiva el apoyo transfusional rápido y eficiente es esencial en el tratamiento y la atención de politraumatismos, de ahí que sea necesario contar con protocolos de transfusión que mejoren los resultados y disminuyan las complicaciones. Además, se identificó la necesidad de nuevos estudios sobre el tema para mejorar estos protocolos y reducir las complicaciones.(AU)

Introduction: The main cause of early mortality in polytrauma patients is hypovolemia secondary to massive hemorrhage. Hemocomponent and crystalloid therapy is an essential and life-saving mechanism in these situations as a measure of volume replacement. In the same way, patients with severe traumatic injuries have a significant acute decrease in circulating platelet counts that makes them candidates for transfusion of platelet components; However, the use of these blood components can lead to unwanted outcomes such as increased mortality. Although many studies reveal an increase in mortality as an outcome associated with the use of blood components, others establish its use as a reducing measure of this outcome. Objective: to present the main indications of blood components in polytrauma patients, as well as to relate the adverse events associated with their use that influence the mortality and hospitalization time of these patients. Devlopment: Mortality associated with the use of blood components is still a controversial issue. In massive hemorrhage, rapid and efficient transfusion support is essential in the treatment and care of polytrauma, hence it is necessary to have transfusion protocols that improve results and reduce complications. In addition, the need for new studies on the subject to improve these protocols and reduce complications was identified(AU)

Leucemia de manifestación aguda y las nuevas alternativas terapéuticas / Leukemia of acute presentation and the new therapeutic alternatives

Resumen La leucemia forma parte de un sinnúmero de malignidades hematológicas que afectan la diferenciación de los leucocitos en la médula ósea. Esta enfermedad se puede clasificar de acuerdo con las características morfológicas, citoquímicas e inmunológicas que expresen los blastos. Las manifestaciones clínicas de la enfermedad, como: anemia, trombocitopenia, dolores óseos, sangrado, procesos infecciosos, hepatoesplenomegalia, entre otros, son consecuencias del proceso de infiltración de los blastos en la médula ósea. La leucemia comprende un grupo heterogéneo de malignidades que representan un desafío diagnóstico y terapéutico, que a la larga generan un efecto biopsicosocial en las familias y los pacientes.

Abstract Leukemia is a part of a lot of hematologic malignancies that affect leukocyte differentiation in the bone marrow. This illness can be classified according to morphologic, cytochemical and immunological characteristics expressed by blast cells. Clinical manifestations, such as: anemia, thrombocytopenia, bone pains, bleeding, infectious processes, hepatosplenomegaly, among others, are a consequence of blast cell infiltration processes in the bone marrow. Leukemia comprises a heterogeneous group of malignancies that represent a diagnostic and therapeutic challenge, which in the long term generates a biospsycosocial impact on families and patients.

Coagulación intravascular diseminada: Una revisión de tema / Disseminated intravascular coagulation: A review of the topic

Resumen Introducción: La Coagulación Intravascular Diseminada, es un síndrome secundario a patologías subyacentes, donde la activación localizada de la coagulación y la respuesta inflamatoria generalizada, pueden llevar a daños tisulares y microvasculares. Se ha reportado una prevalencia del 10,8% en varias unidades de cuidados intensivos de Colombia; su presentación en el contexto de sepsis es diferente según el tipo de infección. Objetivo: Realizar una revisión de la literatura de los conceptos más destacados de la Coagulación Intravascular Diseminada. Materiales y métodos: Se realizó una revisión por medio de la búsqueda de artículos originales, revisiones sistemáticas y narrativas, en las bases de datos PubMed y ScienceDirect y en el buscador Google Académico; se seleccionaron 80 artículos, de los cuales se incluyeron 51. Se tuvo en cuenta publicaciones en español, inglés y francés, con fecha de publicación menor o igual a 5 años. Resultados: Se realizó la descripción sobre tratamiento, etiología, presentación clínica y diagnóstico de la Coagulación Intravascular Diseminada, haciendo especial énfasis en los estudios sobre marcadores moleculares y nuevas alternativas terapéuticas. Conclusión: La Coagulación Intravascular Diseminada es una complicación que contribuye a aumentar la morbilidad y la mortalidad, cuyo pronto diagnóstico y tratamiento aportan significativamente a una mejor evolución clínica.

Abstract Introduction: Disseminated intravascular coagulation is a secondary syndrome to underlying pathologies, where localized coagulation activation and generalized inflammatory response can lead to tissue and microvascular damage. A prevalence of 10.8% has been reported in several intensive care units in Colombia. Its presentation in the context of sepsis is different depending on the type of infection. Objective: To conduct a review of literature of the most outstanding concepts of disseminated intravascular coagulation. Materials and methods: A review was made by means of the search of original articles, systematic and narrative reviews, in the PubMed and ScienceDirect databases and in the Google Scholar search engine; 80 articles were selected, of which 51 were included. Publications were taken into account in Spanish, English and French, with a publication date of less than or equal to 5 years. Results: The description of treatment, etiology, clinical presentation and diagnosis of Disseminated Intravascular Coagulation was made, with special emphasis on the studies on molecular markers and new therapeutic alternatives. Conclusion: Disseminated intravascular coagulation is a complication which contributes to increase morbidity and mortality, whose early diagnosis and treatment contribute significantly to better clinical evolution.

Anemia de Fanconi / Fanconi anemia

Resumen: La anemia de Fanconi es una enfermedad hereditaria con patrón de transmisión autosómico recesivo, asociada con múltiples mutaciones en al menos 20 genes cuyos productos forman parte de los mecanismos de reparación del material genético en las células. Estas mutaciones generan inestabilidad cromosomal que resulta en manifestaciones clínicas muy diversas, las más características son la insuficiencia de médula ósea, anormalidades congénitas y alta predisposición a neoplasias. El diagnóstico clínico de este trastorno es difícil, no sólo por su heterogeneidad, sino también porque es poco sospechado, se necesitan pruebas de laboratorio específicas para poder confirmarlo. De la misma manera, el tratamiento de la enfermedad es difícil porque está enfocado principalmente al manejo de los síntomas y a la prevención de afecciones asociadas, por lo que la anemia de Fanconi debe ser conocida para poder dar a los pacientes el seguimiento correcto.

Abstract Fanconi anemia is a hereditary disease with an autosomal recessive transmission pattern, associated with multiple mutations on at least 20 genes whose products are part of the cell's genetic material repair mechanisms. These mutations produce chromosomal instability, which results in diverse clinical manifestations; the most characteristic is bone marrow failure, congenital abnormalities and a high predisposition to neoplasms. Clinical diagnosis of this disorder is difficult, not only due to its heterogeneity but also because is little suspected, being necessary laboratory test to allow confirmation. In like manner, treatment of the disease is difficult as its mainly focused on symptoms management and prevention of associated conditions, therefore Fanconi anemia needs to be known in order to be able to give patients a correct follow up.

Probable drug-drug interaction between erlotinib and amiodarone causes severe neurotoxicity in a patient with advanced lung cancer.

Drug-drug interactions (DDIs) are of great concern in the treatment of cancer, especially when target therapies, such as tyrosine kinase inhibitors, are being used. Here, we report a case of probable DDI between erlotinib and amiodarone leading to severe neurotoxicity. Amiodarone inhibits P-glycoprotein (P-gp), for which erlotinib is a substrate. P-gp is an important drug transporter that is involved in limiting the blood-brain barrier penetration of erlotinib. Clinicians should be aware of emerging data characterizing the effect of the P-gp transport system on drug exposure and its potential for DDI.

[Guillain-Barré syndrome. Its association with alpha tumor necrosis factor]. / Síndrome de Guillain-Barré. Asociación con antagonista de FNT?

BACKGROUND: adalimumab, a human recombinant monoclonal antibody against tumoral necrosis factor alpha (TNFα), has been associated with central nervous system demyelinating diseases and peripheral neuropathic syndrome. The Guillain-Barré Syndrome (GBS) is one of them. CLINICAL CASE: we presented the case of a 65 year old woman, with diabetes mellitus and psoriasic arthritis, treated with adalimumab; after the fourth infusion, she developed paresthesia and mild weakness in lower limbs, these symptoms persisted three days after each infusion and each time remitted spontaneously; following the eight dose, presented a characteristic clinical picture of the GBS, confirmed with neurophysiological studies that showed an axonal motor-sensitive polyneuropathy. The treatment consisted in intravenous immunoglobulin, with good outcome. CONCLUSIONS: the synergy among cellular and humoral immune responses, against peripheral nerve antigens is responsible of immunopathogenesis related to GBS. The prolonged and intensified pathologic immune response induced by adalimumab, may be associated to the development of GBS.

Primary sacral hydatid cyst. A case report.

This case report highlights an unusual osseous spinal presentation of a well described disease, hydatidosis. A 59-year-old woman presented with increasing back pain and bilateral radiculopathy. Examination disclosed symptoms of spinal stenosis and urinary incontinence. Radiographs showed an expansive lytic lesion affecting the pelvic bones with destruction of the bone cortex. Laboratory analyses were performed and the patient underwent CT and MRI studies. Serology for Echinococcus was positive. When assessing sciatica, low back pain or lower limb weakness the pelvic cavity should be examined for hidden disease that might explain the neurological symptoms. Hydatid disease of bone should be considered in the differential diagnosis of any bone mass discovered in the human body. Diagnosis was delayed in this case because the pelvic cavity was not studied when radiculopathy symptoms started and there was no coexisting visceral involvement.