Estrategia educativa intercultural para la prevención del cáncer de cuello cérvico uterino en el resguardo de Paujil, Amazonia Colombiana / Intercultural educational strategy for the prevention of cervical cancer in Paujil Resguardo Amazonía colombiana

RESUMEN Los pueblos indígenas siguen sufriendo inequidades, a pesar de los avances relacionados con la protección de la diversidad étnica y cultural, siendo las mujeres uno de los grupos de mayor riesgo, sobre todo, en lo referente a la salud sexual y reproductiva, situación contemplada como un compromiso de acción en los objetivos de desarrollo sostenible. En ese contexto, esta investigación acción participativa buscó construir una estrategia educativa intercultural, sostenible y segura culturalmente que, a propósito de la prevención del cáncer de cuello uterino, aportará al empoderamiento y la conservación de la salud de las mujeres habitantes del resguardo de Paujil -Colombia. La iniciativa surgió de mujeres indígenas preocupadas por mejorar la salud de sus congéneres y un grupo de investigadores. La construcción de una estrategia educativa intercultural representa un reto, pues la pedagogía occidental no necesariamente corresponde a las concepciones de enseñanza aprendizaje de las indígenas del resguardo. Hay dificultades lingüísticas, pues cada etnia tiene su propia lengua. Las indígenas lideresas se convirtieron en las facilitadoras del proceso que se centró más en el uso de la oralidad y encuentros entre mujeres, que se conocen entre sí. Las mujeres prefieren estrategias didácticas basadas en compartir experiencias y el uso de cartillas y videos. El trabajo permitió concluir que cualquier estrategia educativa intercultural que se proponga debe ser específica y acorde a las necesidades de las comunidades.

ABSTRACT Despite the advances related to the protection of ethnic and cultural diversity, indigenous people continue to suffer inequities, with women being one of the groups most at risk, especially concerning sexual and reproductive health, a situation considered as a problem, a commitment to action in the sustainable development goals. In this context, this Participatory action research searched to build an intercultural educational strategy, sustainable and culturally safe, which, concerning the prevention of cervical cancer, would contribute to the empowerment and conservation of the health of the women who live in the Paujil reservation-Colombia. The initiative arose from indigenous women concerned about improving the health of their peers, and a group of researchers. The construction of an intercultural educational strategy represents a challenge since western pedagogy does not necessarily correspond to the teaching-learning conceptions of the indigenous people of the reservation. There are linguistic difficulties because each ethnic group has its language. The indigenous leaders became the facilitators of the process that focused more on the use of orality and meetings between women who know each other. Women prefer a didactic strategy based on sharing experiences, and the use of primers, and videos. The work allowed to conclude that any proposed of intercultural educational strategy must be specific and according to the needs of the communities.

Mortalidad por cáncer de cuello uterino en la amazonia de Colombia / Cervical cancer mortality in the Colombian Amazon

Resumen OBJETIVO: Analizar el pico de mortalidad por cáncer de cuello uterino registrado en 2018 en Guainía, Colombia. MATERIALES Y MÉTODOS: Estudio ecológico basado en los datos de todas las instituciones con información de la morbilidad y mortalidad y atenciones relacionadas con el cáncer de cuello uterino en Colombia, entre enero de 2009 y diciembre de 2019. Se incluyeron todos los datos disponibles para Guainía. Se excluyeron las bases sin datos entre 2016 y 2018. Se analizaron la morbilidad y mortalidad, atenciones y procedimientos, y se compararon con el comportamiento en 2018 respecto de los demás años. RESULTADOS: Las personas atendidas, las atenciones y los procedimientos relacionados con cáncer de cuello uterino disminuyeron en 2016 y 2017. La concentración de atenciones por persona más baja del periodo se dio en 2017. En 2019, aumentó la cantidad de personas con diagnóstico de infección por papilomavirus. CONCLUSIONES: La reducción en el tamiz, las atenciones y los procedimientos relacionados con el cáncer de cuello uterino, en un territorio, puede ocasionar aumentos en la mortalidad por este tipo de cáncer. Es fundamental sostener en el tiempo las acciones de prevención, diagnóstico y tratamiento, para evitar esta mortalidad.

Abstract OBJECTIVE: To analyze the cervical cancer mortality peak, in Guainía, in 2018. MATERIALS AND METHODS: Ecological study. Data from all institutions with cervical cancer morbidity, mortality and attention information in Colombia, between January/2009 and December/2019, were analyzed. All available data for Guainía were included. The databases with no data between 2016 and 2018 were excluded. Morbidity, mortality, attention, and procedures were analyzed, comparing the behavior in 2018 to the other years. RESULTS: Cervical cancer-related patients, care and procedures decreased in 2016 and 2017. The lowest concentration of care per person in the period was in 2017. In 2019, the number of people diagnosed with papillomavirus infection increased. CONCLUSIONS: The reduction in screenings, care and procedures related to cervical cancer, in a territory, can lead to increases in mortality from this type of cancer. It is essential to sustain prevention, diagnosis, and treatment actions over time to avoid this mortality.

Consumption of Alcohol, Tobacco and Psychoactive Substances in Adolescents from an Indigenous Territory in the Colombian Amazon. / Consumo de alcohol, tabaco y sustancias psicoactivas de los adolescentes de un territorio indígena en la Amazonía colombiana.

INTRODUCTION: There are very few studies on the consumption of psychoactive substances (PAS) among young people from indigenous territories and evening or blended learning students. In Inírida, a municipality in the Colombian Amazon, there were concerns about a possible consumption issue that had never been characterised before. OBJECTIVE: To characterise the consumption of alcohol, tobacco and PAS in Inírida among teenage evening and blended learning students. METHODS: The Inter-American Uniform Drug Use Data System (SIDUC) survey developed by the Inter-American Drug Abuse Control Commission (CICAD) was adapted to the cultural context and carried out on 95% of 284 evening and blended learning students (262). Descriptive statistics and multiple correspondence analyses were used. RESULTS: Currently, 59% consume alcohol; 28% tobacco; 21% marijuana; 3% cocaine paste; 1% ecstasy (MDMA); 1% cocaine; and 1% inhalants. Also, 61% believe that drugs are available inside and around the vicinity of their school, and that marijuana (62%) and cocaine paste (35%) are easily acquired. Drugs are most commonly offered in neighbourhoods (56%) and at parties (30%). Those offering the highest quantity of drugs are acquaintances (35%) and friends (29%). And 51% stated that they had participated in preventive activities related to consumption. CONCLUSIONS: The population has a higher consumption of the substances studied in comparison with the national reference, that of Orinoquía and Amazonía, with the exception of cocaine and inhalants. The consumption situation was confirmed, so participatory actions are proposed.

Consumo de alcohol, tabaco y sustancias psicoactivas de los adolescentes de un territorio indígena en la Amazonía colombiana,

Introducción: Existen muy pocos estudios sobre el consumo de sustancias psicoactivas (SPA) en jóvenes de territorios indígenas y en estudiantes semipresenciales o nocturnos. En Inírida, municipio de la Amazonía colombiana, preocupaba un posible problema de consumo nunca caracterizado. Objetivo: Caracterizar el consumo de alcohol, tabaco y SPA en adolescentes de Inírida esco larizados en jornada nocturna y semipresencial. Métodos: Encuesta CICAD/SIDUC, ajustada al contexto cultural, al 95% de los 284 estudiantes de la jornada elegida (n = 262). Se utilizó estadística descriptiva y análisis de corresponden cias múltiples. Resultados: Actualmente consume alcohol el 59%; cigarrillo, el 28%; marihuana, el 21%; basuco, el 3%; éxtasis, el 1%; cocaína, el 1%, e inhalables, el 1%. El 61% considera que en el colegio y alrededores hay disponibilidad de drogas y es fácil conseguir marihuana (62%) y basuco (35%). Se ofrecen drogas con mayor frecuencia en el barrio (56%) y las fiestas (30%). Las personas que más les ofrecen drogas son conocidos (35%) y amigos (29%). El 51% manifiesta haber recibido actividades de prevención del consumo. Conclusiones: La población presenta mayor consumo de las sustancias estudiadas que el refe rente nacional y de la Orinoquía y Amazonía, excepto en cocaína e inhalables. Se corrobora la situación de consumo y se proponen acciones participativas.

Introduction: There are very few studies on the consumption of psychoactive substances (PAS) among young people from indigenous territories and evening or blended learning students. In Inírida, a municipality in the Colombian Amazon, there were concerns about a possible consumption issue that had never been characterised before. Objective: To characterise the consumption of alcohol, tobacco and PAS in Inírida among teenage evening and blended learning students. Methods: The Inter-American Uniform Drug Use Data System (SIDUC) survey developed by the Inter-American Drug Abuse Control Commission (CICAD) was adapted to the cul tural context and carried out on 95% of 284 evening and blended learning students (262). Descriptive statistics and multiple correspondence analyses were used. Results: Currently, 59% consume alcohol; 28% tobacco; 21% marijuana; 3% cocaine paste; 1% ecstasy (MDMA); 1% cocaine; and 1% inhalants. Also, 61% believe that drugs are available inside and around the vicinity of their school, and that marijuana (62%) and cocaine paste (35%) are easily acquired. Drugs are most commonly offered in neighbourhoods (56%) and at parties (30%). Those offering the highest quantity of drugs are acquaintances (35%) and friends (29%). And 51% stated that they had participated in preventive activities related to consumption. Conclusions: The population has a higher consumption of the substances studied in com parison with the national reference, that of Orinoquía and Amazonía, with the exception of cocaine and inhalants. The consumption situation was confirmed, so participatory actions are proposed.

Condiciones en la frontera sur entre Colombia y Venezuela ante la pandemia de COVID-19 / Underlying conditions on the southern border between Colombia and Venezuela to face the COVID-19 pandemic

RESUMEN Objetivos Dimensionar la migración humana en la frontera sur entre Colombia y Venezuela (Departamento de Guainía), y caracterizar las condiciones sociales, de acceso y de atención en salud frente a la pandemia de COVID-19. Métodos Estudio mixto, epidemiológico y etnográfico. Se calcularon: tasa de migrantes venezolanos (según Migración Colombia al 31 de diciembre de 2019), acceso efectivo a atención médica y dotación en puestos de salud (según datos recolectados entre junio de 2017 y julio de 2019, en todos los puestos de salud de Guainía, mediante entrevistas semiestructuradas, observación participante y el uso de Google Earth™ y Wikiloc™). Los tiempos medianos se calcularon y graficaron en Stata™. Se describieron dinámicas culturales y de atención en salud a partir del trabajo de campo y de una permanente revisión documental. Resultados Guainía ocupa el puesto 23 en número total de venezolanos, pero es el cuarto departamento en densidad de venezolanos (14,4%). En ausencia del centro de salud de San José, en el río Guainía los tiempos medianos hasta la institución de referencia real son de 8,7 horas en invierno y 12,3 en verano y los casos complejos requieren remisión aérea. En el río Inírida, sin el centro de Chorro Bocón, los tiempos reales son de 11,9 horas en invierno y 16,1 en verano. Solo el 57% de los puestos de salud tenía insumos para manejar infección respiratoria aguda. Conclusiones Ante la llegada de COVID-19 a territorios sur-fronterizos, es necesario fortalecer inmediatamente servicios médicos y de salud pública para evitar elevadas tasas de letalidad.(AU)

ABSTRACT Objectives To size human migration on the southern border between Colombia and Venezuela (Guainía department), and characterize the social, access and health care conditions relevant to the COVID-19 pandemic. Methods Mixed epidemiological and ethnographic study. Rate of Venezuelan migrants was calculated according to Migration Colombia data until December 31st, 2019, also effective access to medical care, and provision of health posts were calculated, with information from each Guainía health post collected from June 2017 to June 2019, through semi-structured interviews, participant observations, Google Earth™ and Wikiloc™. Stata™ was used to calculate and graph median times of effective access. Cultural dynamics and health care conditions were described by the field work information and a permanent documentary review. Results Guainía is the 23rd department, according to the total number of Venezuelans, but the fourth in Venezuelans density (14,4%). In the Guainía river, the median times to the real reference health institution were 8,7 hours in winter and 12,3 in summer, and complex cases require air referrals. In the Inírida river, the median times to the real reference health institution were 11,9 hours in winter and 16,1 in summer. Only 57% of the health posts had supplies for acute respiratory infections. Conclusions Facing COVID-19 in south border territories, it is necessary to immediately strengthen medical and public health services to avoid high fatality rates.(AU)

Condiciones en la frontera sur entre Colombia y Venezuela ante la pandemia de COVID-19 / Underlying conditions on the southern border between Colombia and Venezuela to face the COVID-19 pandemic

RESUMEN Objetivos Dimensionar la migración humana en la frontera sur entre Colombia y Venezuela (Departamento de Guainía), y caracterizar las condiciones sociales, de acceso y de atención en salud frente a la pandemia de COVID-19. Métodos Estudio mixto, epidemiológico y etnográfico. Se calcularon: tasa de migrantes venezolanos (según Migración Colombia al 31 de diciembre de 2019), acceso efectivo a atención médica y dotación en puestos de salud (según datos recolectados entre junio de 2017 y julio de 2019, en todos los puestos de salud de Guainía, mediante entrevistas semiestructuradas, observación participante y el uso de Google Earth™ y Wikiloc™). Los tiempos medianos se calcularon y graficaron en Stata™. Se describieron dinámicas culturales y de atención en salud a partir del trabajo de campo y de una permanente revisión documental. Resultados Guainía ocupa el puesto 23 en número total de venezolanos, pero es el cuarto departamento en densidad de venezolanos (14,4%). En ausencia del centro de salud de San José, en el río Guainía los tiempos medianos hasta la institución de referencia real son de 8,7 horas en invierno y 12,3 en verano y los casos complejos requieren remisión aérea. En el río Inírida, sin el centro de Chorro Bocón, los tiempos reales son de 11,9 horas en invierno y 16,1 en verano. Solo el 57% de los puestos de salud tenía insumos para manejar infección respiratoria aguda. Conclusiones Ante la llegada de COVID-19 a territorios sur-fronterizos, es necesario fortalecer inmediatamente servicios médicos y de salud pública para evitar elevadas tasas de letalidad.(AU)

ABSTRACT Objectives To size human migration on the southern border between Colombia and Venezuela (Guainía department), and characterize the social, access and health care conditions relevant to the COVID-19 pandemic. Methods Mixed epidemiological and ethnographic study. Rate of Venezuelan migrants was calculated according to Migration Colombia data until December 31st, 2019, also effective access to medical care, and provision of health posts were calculated, with information from each Guainía health post collected from June 2017 to June 2019, through semi-structured interviews, participant observations, Google Earth™ and Wikiloc™. Stata™ was used to calculate and graph median times of effective access. Cultural dynamics and health care conditions were described by the field work information and a permanent documentary review. Results Guainía is the 23rd department, according to the total number of Venezuelans, but the fourth in Venezuelans density (14,4%). In the Guainía river, the median times to the real reference health institution were 8,7 hours in winter and 12,3 in summer, and complex cases require air referrals. In the Inírida river, the median times to the real reference health institution were 11,9 hours in winter and 16,1 in summer. Only 57% of the health posts had supplies for acute respiratory infections. Conclusions Facing COVID-19 in south border territories, it is necessary to immediately strengthen medical and public health services to avoid high fatality rates.(AU)

Mielinolisis extrapontina en una paciente embarazada, con hiperémesis e hiponatremia. Reporte de un caso / Extrapontine myelinolysis in a pregnant with hyperemesis and hyponatremia. A case report

Resumen: ANTECEDENTES: La mielinolisis extrapontina forma parte del síndrome de desmielinización osmótica que lesiona los oligodendrocitos y ocasiona la pérdida de mielina en regiones del sistema nervioso central diferentes al puente del tronco encefálico. Se origina por la corrección rápida de sodio en pacientes con hiponatremia y en mujeres embarazadas se asocia con hiperémesis gravídica. CASO CLÍNICO: Paciente indígena, de 32 años, enviada a un hospital universitario de alta complejidad en Bogotá, desde un territorio de la Amazonia colombiana, en el marco de un nuevo modelo de salud, con embarazo de 15 semanas, quien tuvo un episodio convulsivo, afasia y automatismo bucal, con antecedente de hiperémesis gravídica y otro episodio de hiperémesis con hiponatremia un mes antes. Inicialmente se sospechó eclampsia y neuroinfección; se implementó tratamiento para la corrección rápida del sodio y prescripción de anticonvulsivos. La resonancia magnética cerebral fue compatible con mielinolisis extrapontina. Luego de un mes regresó a su territorio de origen para rehabilitación. Tuvo parto domiciliario a las 38.3 semanas y acudió al hospital para el alumbramiento. CONCLUSIONES: La mielinolisis extrapontina debe considerarse en el diagnóstico diferencial entre embarazo con cuadro neurológico agudo y antecedente de hiperémesis e hiponatremia. Es importante integrar, sistemáticamente, hospitales universitarios o de alta complejidad en los territorios rurales para optimizar el diagnóstico y tratamiento de estas pacientes.

Abstract: BACKGROUND: Extrapontine myelinolysis is part of the osmotic demyelination syndrome, being an acute non-inflammatory demyelinating disease caused by hyperosmotic stress that injures oligodendrocytes and causes myelin loss in regions of the central nervous system other than the pons of the brain stem. Primarily caused by a rapid sodium correction in patients with hyponatremia, in pregnant women its most frequent association is with hyperemesis gravidarum. CLINICAL CASE: A 32-year-old indigenous woman was referred to a university hospital of high complexity, in Bogotá, from a territory of the Colombian Amazon, within the framework of a new health care model, with a 15-week pregnancy, who had a convulsive episode, aphasia and oral automatism, and a recent history of hyperemesis gravidarum. Another history of hyperemesis and hyponatremia a month ago. Initially, eclampsia and neuroinfection were suspected, a rapid correction of sodium, anticonvulsant, remission and management in the intensive care unit was performed. MRI was compatible with extrapontin myelinolysis. After a month she returned to the territory of origin for rehabilitation. She had a home delivery at 38.3 weeks and went to the hospital for placental delivery. CONCLUSION: Extrapontin myelinolysis should be considered in the differential diagnosis between pregnancy with acute neurological symptoms conditions and a history of hyperemesis or hyponatremia. In case of a repeated history of acute hyponatremia in pregnant women with hyperemesis, chronicity should be considered. It is recommended to integrate university hospitals to rural territories to optimize the diagnosis and management of this type of cases.

CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions.

BACKGROUND: Squamous intraepithelial lesions/cervical intraepithelial neoplasias (SIL/CIN) are high-risk human papilloma virus (hrHPV)-related lesions which are considered as high grade (HSIL/CIN2-3) or low grade (LSIL/CIN1) lesions according to their risk of progression to cervical cancer (CC). Most HSIL/CIN2-3 are considered as transforming hrHPV infections, so truly CC precursors, although some clear spontaneously. hrHPV testing has a high sensitivity for the detection of HSIL/CIN2-3 but a relatively low specificity for identifying transforming lesions. We aimed to determine whether the combination of CADM1, MAL and miR124 promoter methylation status assessed in histological samples can be used as a biomarker in the identification of transforming HSIL/CIN lesions. DESIGN: 131 cervical biopsies, including 8 cases with no lesion and a negative hrHPV test result (control group), 19 low-grade (L)SIL/CIN1, 30 HSIL/CIN2, 60 HSIL/CIN3, and 14 CC were prospectively collected. hrHPV was detected and genotyped using the polymerase chain reaction (PCR)-based technique SPF10 HPV LIPA. A multiplex quantitative methylation-specific PCR (qMSP) was used to identify the methylation status of the CADM1, MAL, and miR124 promoter genes. RESULTS: Significantly higher methylation levels of CADM1, MAL and miR-124 were found in HSIL/CIN2-3 and CC compared with normal and LSIL lesions. DNA methylation of at least one gene was detected in 12.5% (1/8) of normal samples, 31.5% (6/19) of LSIL/CIN1, 83.3% (25/30) of HSIL/CIN2, 81.6% (49/60) of HSIL/CIN3 and 100% (14/14) of CC (p < 0.001). The sensitivity and specificity for HSIL/CIN2-3 and CC of having at least one methylated gene were 84.6% and 74.0%, respectively. The sensitivity and specificity of the combination of at least one methylated gene and a positive hrHPV test were 80.7% and 85.1% for HSIL/CIN2-3 and CC, respectively. CONCLUSIONS: The methylation rate of CADM1, MAL and miR124 increases with the severity of the lesion. Further research is warranted to evaluate the usefulness of these biomarkers for the identification of transforming HSIL/CIN.

Clinicopathological evaluation of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in post-transplant lymphoproliferative disorders: association with Epstein-Barr virus, PD-L1 copy number alterations, and outcome.

AIMS: The clinical implications of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in patients with post-transplant lymphoproliferative disorders are largely unknown, and its association with Epstein-Barr virus (EBV) status and PD-L1 copy number alterations (CNAs) has not been thoroughly studied. METHODS AND RESULTS: PD1/PD-L1 expression was studied in 50 adult post-transplant lymphoproliferative disorders, and the correlations with PD-L1 CNAs, EBV, clinicopathological features and outcome were evaluated. Thirty-seven (74%) cases were classified as diffuse large B-cell lymphoma (DLBCL), nine (18%) cases were classified as polymorphic, and four (8%) cases were classified as classic Hodgkin lymphoma. Thirty-four cases were EBV-positive, with 29 of 34 (85%) having latency II or III, and 15 of 34 (44%) having viral replication. PD-L1 expression in tumour cells and tumour-associated macrophages was observed in 30 (60%) and 37 (74%) cases, respectively. PD1 positivity was seen in 16 (32%) cases. PD-L1 expression was associated with EBV with latency II or III (P = 0.001) and organ rejection (P = 0.04), and, in DLBCL, with non-germinal centre type DLBCL (P < 0.001). Cases with PD-L1-positive tumour cells showed a higher number of PD-L1 CNAs than PD-L1-negative cases (P = 0.001). Patients with EBV/latency III/replication and simultaneous PD-L1 expression showed the worst overall survival (P < 0.001). CONCLUSIONS: The PD1/PD-L1 axis is deregulated in post-transplant lymphoproliferative disorders, with frequent PD-L1 expression and PD1 negativity. PD-L1 expression is associated with EBV latency II or III and PD-L1 CNAs, and probably reflects a proinflammatory tumour microenvironment. The combined analysis of EBV status and PD-L1 expression may help to identify deeply immunosuppressed patients who can benefit from immune reconstitution approaches.

Pacientes procedentes de un territorio disperso que fallecieron en un hospital universitario: serie de casos / Patients from a scattered territory who died in a university hospital. A case series / Pacientes de um territorio disperso, que morreram em um hospital universitário. Série de casos

Introducción: Guainía, departamento con población dispersa, pluriétnico y multifronterizo, fue seleccionado en 2016 como piloto del Modelo Integral de Atención en Salud (MIAS). Dentro de la operación del MIAS se encuentra el Hospital de San José (HSJ), hospital universitario ubicado en Bogotá, que recibe pacientes remitidos por aire desde Guainía para atención especializada. Objetivo: Describir las características de los pacientes remitidos de Guainía que murieron en el HSJ, en el marco del MIAS. Métodos: Estudio tipo serie de casos de los pacientes procedentes de Guainía y remitidos al HSJ que fallecieron durante la estancia hospitalaria entre el 1 de julio de 2016 y el 31 de diciembre de 2017. Se analizaron variables demográficas y clínicas mediante estadística descriptiva. Para identificar muertes evitables se usó el inventario de indicadores de mortalidad evitable adaptado a Colombia (INIME). Resultados: De los 238 pacientes recibidos, 18 fallecieron, 3 de los cuales murieron antes de 48 horas de estancia hospitalaria. La mayoría requirió unidad de cuidado intensivo. Entre los diagnósticos de ingreso predominó la neumonía en el grupo de las patologías infecciosas y la desnutrición en las no infecciosas. Las muertes de todos los menores de 18 años y del 70 % de adultos tenían causas potencialmente evitables según los grupos del INIME. Discusión: El predominio de causas de mortalidad evitables, con muertes por desnutrición infantil y enfermedad diarreica aguda, indica la necesidad de actividades que impacten los determinantes sociales y la determinación social de la salud. Conclusión: La alta frecuencia de muertes evitables sugiere que la implementación de la estrategia de atención primaria en salud no fue óptima en el periodo estudiado. Además, para los casos graves, el estrés del desplazamiento aéreo a Bogotá no parece una buena opción. Es necesario incrementar las capacidades del Hospital de Inírida para reducir remisiones de casos.

Introduction: Guainía, a department with a dispersed, multi-ethnic and multi-border population, was selected in 2016 as a pilot of the Integral Model of Health Care (MIAS). Within the MIAS operation is the Hospital de San José (HSJ), a university hospital located in Bogotá, which receives air-remited patients from Guainía for specialized care. Objective: To describe the characteristics of Guainía patients who died in HSJ, under the MIAS. Methods: Serial case study of patients from Guainía referred to HSJ, who died during the hospital stay, between July 01, 2016 and December 31, 2017. Demographic and clinical variables were analyzed using descriptive statistics. The inventory of Colombia-adapted avoidable mortality indicators (INIME) was used to identify preventable deaths. Results: Of the 238 patients received, 18 died, 3 of them died before 48 hours of hospital stay. Most required Intensive Care Unit. Among the entrance diagnoses, pneumonia prevailed in the group of infectious pathologies and malnutrition in non-infectious ones. The deaths of all children under the age of 18 and 70 % of adults had potentially avoidable causes according to INIME groups. Discussion: The prevalence of preventable causes of mortality, with deaths from child malnutrition and acute diarrhoeal disease, indicates the need for activities that impact social determinants and social determination of health. Conclusion: The high frequency of avoidable deaths suggests that the implementation of the Primary Health Care strategy was not optimal in the period studied. Moreover, for severe cases, the stress of air travel to Bogotá does not seem like a good option. It is necessary to increase the capacities of Inírida Hospital to reduce critical case referrals.

Introdução: Guainía, departamento com população dispersa, multiétnica e multi-fronteira, foi selecionado em 2016 como piloto do Modelo de Atenção Integral à Saúde (MIAS). Dentro da operação do MIAS, encontra-se o Hospital San José (HSJ), um hospital universitário localizado em Bogotá, que recebe pacientes encaminhados por via aérea de Guainía para atendimento especializado. Objetivo: Descrever as características dos pacientes encaminhados por Guainía que morreram no HSJ, no âmbito do MIAS. Métodos: Estudo de série de casos de pacientes de Guainia e encaminhados ao HSJ que faleceram durante a internação hospitalar, entre 1 de julho de 2016 e 31 de dezembro de 2017. As variáveis demográficas e clínicas foram analisadas por estatística descritiva. Para identificar mortes evitáveis, foi utilizado o inventário de indicadores de mortalidade evitável adaptados à Colômbia (INIME). Resultados: Dos 238 pacientes recebidos, 18 morreram, 3 dos quais morreram dentro de 48 horas após a internação hospitalar. A maioria necessitava de unidade de terapia intensiva. Entre os diagnósticos de admissão, a pneumonia predominou no grupo de doenças infecciosas e a desnutrição em doenças não infecciosas. As mortes de todos os menores de 18 e 70 % dos adultos tiveram causas potencialmente evitáveis, de acordo com os grupos do INIME. Discussão: A prevalência de causas evitáveis de mortalidade, com mortes por desnutrição infantil e doença diarréica aguda, indica a necessidade de atividades que impactem os determinantes sociais e a determinação da saúde social. Conclusão: A alta frequência de mortes evitáveis sugere que a implementação da estratégia de Atenção Primária à Saúde não foi ótima no período estudado. Além disso, em casos graves, o estresse nas viagens aéreas para Bogotá não parece ser uma boa opção.

Value of HPV 16/18 Genotyping and p16/Ki-67 Dual Staining to Predict Progression to HSIL/CIN2+ in Negative Cytologies From a Colposcopy Referral Population.

OBJECTIVES: To assess the prognostic value of human papillomavirus (HPV) 16/18 genotyping and p16/Ki-67 dual staining cytology in high-risk HPV (hrHPV)-positive women with no lesion or minor abnormalities. METHODS: We evaluated progression to high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grades 2 to 3 or cervical cancer (HSIL/CIN2+), persistence/regression of hrHPV infection in women referred to colposcopy showing hrHPV infection, histology diagnosis different from HSIL/CIN2+, and negative cytology. HPV 16/18 genotyping and dual staining were performed in liquid-based cytologic specimens obtained on the first visit. RESULTS: Progression was observed in 16 (8.0%) of 200 women. Those with HPV 16/18 infection had an increased risk of progression compared with women infected by other hrHPV types, and they also showed more persistence. However, no association was observed between progression or persistence and the result of the dual staining. CONCLUSIONS: HPV 16/18-positive women with no lesions or minor abnormalities are at high risk of progression to HSIL/CIN2+ and hrHPV persistence.

Role of Human Papillomavirus in Vulvar Cancer.

Human papillomavirus (HPV) is involved in one of the at least 2 pathways leading to vulvar squamous cell carcinoma (VSCC). Inactivation of p53 and retinoblastoma by the viral products E6 and E7 is involved in malignant transformation. The percentage of HPV-positive VSCCs ranges from 18% to 75%, depending on the geographical area. HPV-associated tumors affect relatively young women and arise from high-grade intraepithelial lesions, identical to other HPV-associated premalignant lesions of the anogenital tract. HPV-independent tumors tend to affect older women and usually arise in a background of inflammatory skin disorders and a subtle variant of in situ lesion called differentiated vulvar intraepithelial neoplasia. HPV-positive tumors tend to be of basaloid or warty types, whereas HPV-independent tumors tend to be of keratinizing type, but there is frequent overlap between histologic types. There is no conclusive evidence yet on the best strategy in terms of determining HPV attribution. HPV DNA detection is generally considered the gold standard although there is some concern about misclassification when using this technique alone. p16 immunostaining has shown to be an excellent surrogate marker of HPV infection. Positive results for both techniques are considered the best evidence for HPV-association. The prognostic role of HPV in VSCC is still contradictory, but increasing evidence suggests that HPV-associated tumors are less aggressive. Currently, there are no differences in treatment between HPV-associated and HPV-independent VSCC, but novel immunological strategies based on anti-HPV antigens are being evaluated in clinical trials.

Renal graft survival according to Banff 2013 classification in indication biopsies. / Supervivencia del injerto renal según la categoría de Banff 2013 en biopsia por indicación.

INTRODUCTION: The impact of acute rejection in kidney graft survival is well known, but the prognosis of other diagnoses is uncertain. We evaluated the frequency and impact on graft survival of different diagnostic categories according to the Banff 2013 classification in a cohort of renal transplant recipients. MATERIAL AND METHODS: Retrospective study of 495 renal biopsies by indication in 322 patients from 1990-2014. Two independent observers reviewed the histological reports, reclassifying according to the Banff 2013 classification. RESULTS: Of 495 biopsies, 28 (5.7%) were not diagnostic. Of the remaining 467, 10.3% were «normal¼ (category 1), 19.6% antibody-mediated changes (category 2), 5.9% «borderline¼ changes (category 3), 8.7% T-cell-mediated rejection (category 4), 23.4% interstitial fibrosis/tubular atrophy (IFTA) (category 5) and 26.5% with other diagnoses (category 6). As time after transplantation increases, diagnoses of categories 1, 3 and 4 decrease, while categories 5 and 2 increase. Worse graft survival with category 2 diagnosis was observed (45% at 7.5 years, HR 4.29 graft loss [95% CI, 2.39-7.73]; P≤.001, compared to category 1). Grafts with «unfavourable histology¼ (chronic antibody-mediated rejection, moderate-severe IFTA) presented worse survival that grafts with «favourable histology¼ (normal, acute tubular necrosis, mild IFTA). CONCLUSIONS: The Banff 2013 classification facilitates a histological diagnosis in 95% of indication biopsies. While diagnostic category 6 is the most common, a change in the predominant histopathology was observed according to time elapsed since transplantation. Antibody-mediated changes are associated with worse graft survival.

Disforia de género, presentación de un caso masculino a femenino (MTF) en el Hospital de San José / Gender dysphoria: Presentation of a male to female (MTF) case in San José Hospital, Bogotá, Colombia

La identidad de género es el sentido de masculinidad o feminidad que puede tener una persona o una combinación de ambas; desde 1940 Harry Benjamín plantea el término transexualidad o trastorno de identidad de género (TIG) cuando hay alteración de esta. Su manejo debe hacerse de manera multi e interdisciplinaria a través del proceso de reasignación de género. A continuación se presenta el caso de una paciente de 50 anos con diagnóstico de disforia de género masculino a femenino (MTF), quien desde la infancia presentaba insatisfacción con su sexo asignado al nacimiento, lo cual la hace candidata a terapia de reemplazo hormonal, tratamiento quirúrgico de feminización y asignación de sexo.

Gender identity is a person concept of self as being male or female, or ambivalent sex. Trans-sexuality or gender identity disorder was given that name by Harry Benjamin since 1940. The treatment should be multi and inter-disciplinary through a process of a gender reassignment. A case is presented of a 50 year-old patient with a diagnosis of male to female (MTF) gender dysphoria, who felt dissatisfied since childhood with her gender assigned at birth, thus being a candidate for hormone replacement therapy, surgical feminisation treatment, and gender assignment.

Characterization and prognostic implication of 17 chromosome abnormalities in myelodysplastic syndrome.

The prognosis of chromosome 17 (chr17) abnormalities in patients with primary myelodysplastic syndrome (MDS) remains unclear. The revised International Prognostic Scoring System (IPSS-R) includes these abnormalities within the intermediate cytogenetic risk group. This study assessed the impact on overall survival (OS) and risk of acute myeloid leukemia transformation (AMLt) of chr17 abnormalities in 88 patients with primary MDS. We have compared this group with 1346 patients with primary MDS and abnormal karyotype without chr17 involved. The alterations of chr17 should be considered within group of poor prognosis. The different types of alterations of chromosome 17 behave different prognosis. The study confirms the intermediate prognostic impact of the i(17q), as stated in IPSS-R. The results of the study, however, provide valuable new information on the prognostic impact of alterations of chromosome 17 in complex karyotypes.

CPT1c is localized in endoplasmic reticulum of neurons and has carnitine palmitoyltransferase activity.

CPT1c is a carnitine palmitoyltransferase 1 (CPT1) isoform that is expressed only in the brain. The enzyme has recently been localized in neuron mitochondria. Although it has high sequence identity with the other two CPT1 isoenzymes (a and b), no CPT activity has been detected to date. Our results indicate that CPT1c is expressed in neurons but not in astrocytes of mouse brain sections. Overexpression of CPT1c fused to the green fluorescent protein in cultured cells demonstrates that CPT1c is localized in the endoplasmic reticulum rather than mitochondria and that the N-terminal region of CPT1c is responsible for endoplasmic reticulum protein localization. Western blot experiments with cell fractions from adult mouse brain corroborate these results. In addition, overexpression studies demonstrate that CPT1c does not participate in mitochondrial fatty acid oxidation, as would be expected from its subcellular localization. To identify the substrate of CPT1c enzyme, rat cDNA was overexpressed in neuronal PC-12 cells, and the levels of acylcarnitines were measured by high-performance liquid chromatography-mass spectrometry. Palmitoylcarnitine was the only acylcarnitine to increase in transfected cells, which indicates that palmitoyl-CoA is the enzyme substrate and that CPT1c has CPT1 activity. Microsomal fractions of PC-12 and HEK293T cells overexpressing CPT1c protein showed a significant increase in CPT1 activity of 0.57 and 0.13 nmol.mg(-1).min(-1), respectively, which is approximately 50% higher than endogenous CPT1 activity. Kinetic studies demonstrate that CPT1c has similar affinity to CPT1a for both substrates but 20-300 times lower catalytic efficiency.

A new LC-ESI-MS/MS method to measure long-chain acylcarnitine levels in cultured cells.

The quantitative evaluation of long-chain acylcarnitines in lipid extracts from cultured cells or tissues is a prerequisite to study carnitine palmitoyltransferase (CPT) activity. There is thus a need for the accurate measurement of the concentration of long-chain acylcarnitines at the lowest concentration present in lipid extracts. Here we report a fast and reliable quantitative method based on the use of weak acid extraction and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to quantify acylcarnitines through hydrophilic interaction chromatography. The method was validated using isotopic dilution and the results allow the analysis of a large number of samples at low concentration levels (down to 0.35 nmol L(-1) for palmitoylcarnitine) with good inter- and intra-day precision. The method was used for the quantitative study of changes in concentration of palmitoylcarnitine and other acylcarnitines in PC-12 cells over-expressing CPT1a gene. It was also used to measure CPT1 activity in mitochondria isolated from transfected cells, giving similar results to the more common radiometric method, but with higher sensitivity.

C-terminal end and aminoacid Lys48 in HMG-CoA lyase are involved in substrate binding and enzyme activity.

3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase adopts a (betaalpha)(8) TIM barrel structure with an additional beta9, alpha11 and alpha12 helices. Location of HMG part of the substrate has been suggested but the binding mode for the CoA moiety remains to be resolved. As mutation F305 fs(-2), which involves the last 21 residues of the protein, and mutation K48N caused 3-hydroxy-3-methylglutaric aciduria in two patients, we examined the role of the C-terminal end and Lys(48) in enzyme activity. Expression studies of various C-terminal-end-deleted and K48N-mutated proteins revealed that residues 311-313 (localized in the loop between alpha11 and alpha12 helices) and Lys(48) are essential for enzyme activity. An in silico docking model locating HMG-CoA on the surface of the enzyme implicates Asn(311) and Lys(313) in substrate binding by establishing multiple polar contacts with phosphate and ribose groups of adenosine, and Lys(48) by contacting the carboxyl group of the panthotenic acid moiety.

Gamma interferon levels and antibody production induced by two PvMSP-1 recombinant polypeptides are associated with protective immunity against P.vivax in Aotus monkeys.

Effector mechanisms responsible for providing protective immunity against Plasmodium vivax (Pv) infection were examined in Aotus monkeys vaccinated with two Pv Merozoite Surface Protein-1 (PvMSP-1) recombinant polypeptides that had previously been shown to protect vaccines against parasite challenge. Vaccine efficacy was reproducible in this trial, showing that one out of the five monkeys immunised with the recombinant protein mixture was partially protected while three others controlled parasitaemia. Antibodies reactive to the parasite's native proteins, the recombinant polypeptides and peptides spanning both recombinant fragments were detected in most vaccinees. Despite substantial Peripheral Blood Mononuclear Cell (PBMC) antigen-specific cellular proliferation not being detected, high rPvMSP-1(20) specific gamma interferon (IFN-gamma) production was found in the three animals that controlled parasitaemia. Altogether the results suggest that antibody titres and antigen-specific IFN-gamma production mediate protective immunity against P. vivax.