Colombian Consensus on the Treatment of Placenta Accreta Spectrum (PAS) / Consenso Colombiano de Tratamiento del Espectro de Acretismo Placentario (EAP)

Introduction: Placenta accreta spectrum (PAS) is a condition associated with massive postpartum bleeding and maternal mortality. Management guidelines published in high income countries recommend the participation of interdisciplinary teams in hospitals with sufficient resources for performing complex procedures. However, some of the recommendations contained in those guidelines are difficult to implement in low and medium income countries. Objectives: The aim of this consensus is to draft general recommendations for the treatment of PAS in Colombia. Materials and methods: Twenty-three panelists took part in the consensus with their answers to 31 questions related to the treatment of PAS. The panelists were selected based on participation in two surveys designed to determine the resolution capabilities of national and regional hospitals. The modified Delphi methodology was used, introducing two successive discussion rounds. The opinions of the participants, with a consensus of more than 80%, as well as implementation barriers and facilitators, were taken into consideration in order to issue the recommendations. Results: The consensus draftedfive recommendations, integrating the answers of the panelists. Recommendation 1. Primary care institutions must undertake active search of PAS in patients with risk factors: placenta praevia and history of myomectomy or previous cesarean section. In case of ultrasound signs suggesting PAS, patients must be immediately referred, without a minimum gestational age, to hospitals recognized as referral centers. Online communication and care modalities may facilitate the interaction between primary care institutions and referral centers for PAS. The risks and benefits of telemedicine modalities must be weighed. Recommendation 2. Referral hospitals for PAS need to be defined in each region of Colombia, ensuring coverage throughout the national territory. It is advisable to concentrate the flow of patients affected by this condition in a few hospitals with surgical teams specifically trained in PAS, availability of specialized resources, and institutional efforts at improving quality of care with the aim of achieving better health outcomes in pregnant women with this condition. To achieve this goal, participants recommend that healthcare regulatory agencies at a national and regional level should oversee the process of referral for these patients, expediting administrative pathways in those cases in which there is no prior agreement between the insurer and the selected hospital or clinic. Recommendation 3. Referral centers for patients with PAS are urged to build teams consisting of a fixed group of specialists (obstetricians, urologists, general surgeons, interventional radiologists) entrusted with the care of all PAS cases. It is advisable for these interdisciplinary teams to use the "intervention bundle" model as a guidance for building PAS referral centers. This model comprises the following activities: service preparedness, disease prevention and identification, response to the occurrence of the disease, and debriefing after every event. Telemedicine facilitates PAS treatment and should be taken into consideration by interdisciplinary teams caring for this disease. Recommendation 4. Obstetrics residents must be instructed in the performance of maneuvers that are useful for the prevention and treatment of massive intraoperative bleeding due to placenta praevia and PAS, including manual aortic compression, uterine tourniquet, pelvic packing, retrovesical bypass, and Ward maneuver. Specialization Obstetrics and Gynecology programs in Colombia must include the basic concepts of the diagnosis and treatment of PAS. Referral centers for PAS must offer online and in-person training programs for professionals interested in improving their competencies in PAS. Moreover, they must offer permanent remote support (telemedicine) to other hospitals in their region for patients with this condition. Recommendation 5. Patients suspected of having PAS and placenta praevia based on imaging, with no evidence of active vaginal bleeding, must be delivered between weeks 34 and 36 6/7. Surgical treatment must include sequential interventions that may vary depending on the characteristics of the lesion, the clinical condition of the patient and the availability of resources. The surgical options (total and subtotal hysterectomy, one-stage conservative surgical management and watchful waiting) must be included in a protocol known by the entire interdisciplinary team. In situations in which an antepartum diagnosis is lacking, that is to say, in the face of intraoperative finding of PAS (evidence of purple bulging or neovascularization of the anterior aspect of the uterus), and the participation of untrained personnel, three options are considered: Option 1: In the absence of indication of immediate delivery or of vaginal delivery, the recommendation is to postpone the cesarean section (close the laparotomy before incising the uterus) until the recommended resources for safe surgery are secured. Option 2: If there is an indication for immediate delivery (e.g., non-reassuring fetal status) but there is absence of vaginal bleeding or indication for immediate PAS management, a two-stage management is suggested: cesarean section avoiding placental incision, followed by uterine repair and abdominal closure, until the availability of the recommended resources for safe surgery is ascertained. Option 3: In the event of vaginal bleeding that prevents definitive PAS management, the fetus must be delivered through the uterine fundus, followed by uterine repair and reassessment of the situation. Sometimes, fetal delivery diminishes placental flow and vaginal bleeding is reduced or disappears, enabling the possibility to postpone definitive management of PAS. In case of persistent significant bleeding, hysterectomy should be performed, using all available resources: manual aortic compression, immediate call to the surgeons with the best available training, telemedicine support from expert teams in other hospitals. If a patient with risk factors for PAS (e.g., myomectomy or previous cesarean section) has a retained placenta after vaginal delivery, it is advisable to confirm the possibility of such diagnosis (by means of ultrasound, for example) before proceeding to manual extraction of the placenta. Conclusions: It is our hope that this first Colombian consensus on PAS will serve as a basis for additional discussions and collaborations that can result in improved clinical outcomes for women affected by this condition. Additional research will be required in order to evaluate the applicability and effectiveness of these recommendations.

Introducción: el espectro de acretismo placentario (EAP) es una condición asociada a sangrado masivo posparto y mortalidad materna. Las guías de manejo publicadas en países de altos ingresos recomiendan la participación de grupos interdisciplinarios en hospitales con recursos suficientes para realizar procedimientos complejos. Sin embargo, algunas de las recomendaciones de estas guías resultan difíciles de aplicar en países de bajos y medianos ingresos. Objetivos: este consenso busca formular recomendaciones generales para el tratamiento del EAP en Colombia. Materiales y métodos: en el consenso participaron 23 panelistas, quienes respondieron 31 preguntas sobre el tratamiento de EAP. Los panelistas fueron seleccionados con base en la participación en dos encuestas realizadas para determinar la capacidad resolutiva de hospitales en el país y la región. Se utilizó la metodología Delphi modificada, incorporando dos rondas sucesivas de discusión. Para emitir las recomendaciones el grupo tomó en cuenta la opinión de los participantes, que lograron un consenso mayor al 80 %, así como las barreras y los facilitadores para su implementación. Resultados: el consenso formuló cinco recomendaciones integrando las respuestas de los panelistas. Recomendación 1. Las instituciones de atención primaria deben realizar búsqueda activa de EAP en pacientes con factores de riesgo: placenta previa e historia de miomectomía o cesárea en embarazo previo. En caso de haber signos sugestivos de EAP por ecografía, las pacientes deben ser remitidas de manera inmediata, sin tener una edad gestacional mínima, a hospitales reconocidos como centros de referencia. Las modalidades virtuales de comunicación y atención en salud pueden facilitar la interacción entre las instituciones de atención primaria y los centros de referencia para EAP. Se debe evaluar el beneficio y riesgo de las modalidades de telemedicina. Recomendación 2. Es necesario que se definan hospitales de referencia para EAP en cada región de Colombia, asegurando el cubrimiento de la totalidad del territorio nacional. Es aconsejable concentrar el flujo de pacientes afectadas por esta condición en unos pocos hospitales, donde haya equipos de cirujanos con entrenamiento específico en EAP, disponibilidad de recursos especializados y un esfuerzo institucional por mejorar la calidad de atención, en busca de tener mejores resultados en la salud de las gestantes con esta condición. Para lograr ese objetivo los participantes recomiendan que los entes reguladores de la prestación de servicios de salud a nivel nacional, regional o local vigilen el proceso de remisión de estas pacientes, facilitando rutas administrativas en caso de que no exista contrato previo entre el asegurador y el hospital o la clínica seleccionada (IPS). Recomendación 3. En los centros de referencia para pacientes con EAP se invita a la creación de equipos que incorporen un grupo fijo de especialistas (obstetras, urólogos, cirujanos generales, radiólogos intervencionistas) encargados de atender todos los casos de EAP. Es recomendable que esos grupos interdisciplinarios utilicen el modelo de "paquete de intervención" como guía para la preparación de los centros de referencia para EAP. Este modelo consta de las siguientes actividades: preparación de los servicios, prevención e identificación de la enfermedad, respuesta ante la presentación de la enfermedad, aprendizaje luego de cada evento. La telemedicina facilita el tratamiento de EAP y debe ser tenida en cuenta por los grupos interdisciplinarios que atienden esta enfermedad. Recomendación 4. Los residentes de Obstetricia deben recibir instrucción en maniobras útiles para la prevención y el tratamiento del sangrado intraoperatorio masivo por placenta previa y EAP, tales como: la compresión manual de la aorta, el torniquete uterino, el empaquetamiento pélvico, el bypass retrovesical y la maniobra de Ward. Los conceptos básicos de diagnóstico y tratamiento de EAP deben incluirse en los programas de especialización en Ginecología y Obstetricia en Colombia. En los centros de referencia del EAP se deben ofrecer programas de entrenamiento a los profesionales interesados en mejorar sus competencias en EAP de manera presencial y virtual. Además, deben ofrecer soporte asistencial remoto (telemedicina) permanente a los demás hospitales en su región, en relación con pacientes con esa enfermedad. Recomendación 5. La finalización de la gestación en pacientes con sospecha de EAP y placenta previa, por imágenes diagnósticas, sin evidencia de sangrado vaginal activo, debe llevarse a cabo entre las semanas 34 y 36 6/7. El tratamiento quirúrgico debe incluir intervenciones secuenciales que pueden variar según las características de la lesión, la situación clínica de la paciente y los recursos disponibles. Las opciones quirúrgicas (histerectomía total y subtotal, manejo quirúrgico conservador en un paso y manejo expectante) deben incluirse en un protocolo conocido por todo el equipo interdisciplinario. En escenarios sin diagnóstico anteparto, es decir, ante un hallazgo intraoperatorio de EAP (evidencia de abultamiento violáceo o neovascularización de la cara anterior del útero), y con participación de personal no entrenado, se plantean tres situaciones: Primera opción: en ausencia de indicación de nacimiento inmediato o sangrado vaginal, se recomienda diferir la cesárea (cerrar la laparotomía antes de incidir el útero) hasta asegurar la disponibilidad de los recursos recomendados para llevar a cabo una cirugía segura. Segunda opción: ante indicación de nacimiento inmediato (por ejemplo, estado fetal no tranquilizador), pero sin sangrado vaginal o indicación de manejo inmediato de EAP, se sugiere realizar manejo en dos tiempos: se realiza la cesárea evitando incidir la placenta, seguida de histerorrafia y cierre de abdomen, hasta asegurar la disponibilidad de los recursos recomendados para llevar a cabo una cirugía segura. Tercera opción: en presencia de sangrado vaginal que hace imposible diferir el manejo definitivo de EAP, es necesario extraer el feto por el fondo del útero, realizar la histerorrafia y reevaluar. En ocasiones, el nacimiento del feto disminuye el flujo placentario y el sangrado vaginal se reduce o desaparece, lo que hace posible diferir el manejo definitivo de EAP. Si el sangrado significativo persiste, es necesario continuar con la histerectomía haciendo uso de los recursos disponibles: compresión manual de la aorta, llamado inmediato a los cirujanos con mejor entrenamiento disponible, soporte de grupos expertos de otros hospitales a través de telemedicina. Si una paciente con factores de riesgo para EAP (por ejemplo, miomectomía o cesárea previa) presenta retención de placenta posterior al parto vaginal, es recomendable confirmar la posibilidad de dicho diagnóstico (por ejemplo, realizando una ecografía) antes de intentar la extracción manual de la placenta. Conclusiones: esperamos que este primer consenso colombiano de EAP sirva como base para discusiones adicionales y trabajos colaborativos que mejoren los resultados clínicos de las mujeres afectadas por esta enfermedad. Evaluar la aplicabilidad y efectividad de las recomendaciones emitidas requerirá investigaciones adicionales.

Consenso Colombiano de Tratamiento del Espectro de Acretismo Placentario (EAP) / Colombian Consensus on the Treatment of Placenta Accreta Spectrum (PAS)

RESUMEN Introducción: el espectro de acretismo placentario (EAP) es una condición asociada a sangrado masivo posparto y mortalidad materna. Las guías de manejo publicadas en países de altos ingresos recomiendan la participación de grupos interdisciplinarios en hospitales con recursos suficientes para realizar procedimientos complejos. Sin embargo, algunas de las recomendaciones de estas guías resultan difíciles de aplicar en países de bajos y medianos ingresos. Objetivos: este consenso busca formular recomendaciones generales para el tratamiento del EAP en Colombia. Materiales y métodos: en el consenso participaron 23 panelistas, quienes respondieron 31 preguntas sobre el tratamiento de EAP. Los panelistas fueron seleccionados con base en la participación en dos encuestas realizadas para determinar la capacidad resolutiva de hospitales en el país y la región. Se utilizó la metodología Delphi modificada, incorporando dos rondas sucesivas de discusión. Para emitir las recomendaciones el grupo tomó en cuenta la opinión de los participantes, que lograron un consenso mayor al 80 %, así como las barreras y los facilitadores para su implementación. Resultados: el consenso formuló cinco recomendaciones integrando las respuestas de los panelistas. Recomendación 1. Las instituciones de atención primaria deben realizar búsqueda activa de EAP en pacientes con factores de riesgo: placenta previa e historia de miomectomía o cesárea en embarazo previo. En caso de haber signos sugestivos de EAP por ecografía, las pacientes deben ser remitidas de manera inmediata, sin tener una edad gestacional mínima, a hospitales reconocidos como centros de referencia. Las modalidades virtuales de comunicación y atención en salud pueden facilitar la interacción entre las instituciones de atención primaria y los centros de referencia para EAP. Se debe evaluar el beneficio y riesgo de las modalidades de telemedicina. Recomendación 2. Es necesario que se definan hospitales de referencia para EAP en cada región de Colombia, asegurando el cubrimiento de la totalidad del territorio nacional. Es aconsejable concentrar el flujo de pacientes afectadas por esta condición en unos pocos hospitales, donde haya equipos de cirujanos con entrenamiento específico en EAP, disponibilidad de recursos especializados y un esfuerzo institucional por mejorar la calidad de atención, en busca de tener mejores resultados en la salud de las gestantes con esta condición. Para lograr ese objetivo los participantes recomiendan que los entes reguladores de la prestación de servicios de salud a nivel nacional, regional o local vigilen el proceso de remisión de estas pacientes, facilitando rutas administrativas en caso de que no exista contrato previo entre el asegurador y el hospital o la clínica seleccionada (IPS). Recomendación 3. En los centros de referencia para pacientes con EAP se invita a la creación de equipos que incorporen un grupo fijo de especialistas (obstetras, urólogos, cirujanos generales, radiólogos intervencionistas) encargados de atender todos los casos de EAP. Es recomendable que esos grupos interdisciplinarios utilicen el modelo de "paquete de intervención" como guía para la preparación de los centros de referencia para EAP. Este modelo consta de las siguientes actividades: preparación de los servicios, prevención e identificación de la enfermedad, respuesta ante la presentación de la enfermedad, aprendizaje luego de cada evento. La telemedicina facilita el tratamiento de EAP y debe ser tenida en cuenta por los grupos interdisciplinarios que atienden esta enfermedad. Recomendación 4. Los residentes de Obstetricia deben recibir instrucción en maniobras útiles para la prevención y el tratamiento del sangrado intraoperatorio masivo por placenta previa y EAP, tales como: la compresión manual de la aorta, el torniquete uterino, el empaquetamiento pélvico, el bypass retrovesical y la maniobra de Ward. Los conceptos básicos de diagnóstico y tratamiento de EAP deben incluirse en los programas de especialización en Ginecología y Obstetricia en Colombia. En los centros de referencia del EAP se deben ofrecer programas de entrenamiento a los profesionales interesados en mejorar sus competencias en EAP de manera presencial y virtual. Además, deben ofrecer soporte asistencial remoto (telemedicina) permanente a los demás hospitales en su región, en relación con pacientes con esa enfermedad. Recomendación 5. La finalización de la gestación en pacientes con sospecha de EAP y placenta previa, por imágenes diagnósticas, sin evidencia de sangrado vaginal activo, debe llevarse a cabo entre las semanas 34 y 36 6/7. El tratamiento quirúrgico debe incluir intervenciones secuenciales que pueden variar según las características de la lesión, la situación clínica de la paciente y los recursos disponibles. Las opciones quirúrgicas (histerectomía total y subtotal, manejo quirúrgico conservador en un paso y manejo expectante) deben incluirse en un protocolo conocido por todo el equipo interdisciplinario. En escenarios sin diagnóstico anteparto, es decir, ante un hallazgo intraoperatorio de EAP (evidencia de abultamiento violáceo o neovascularización de la cara anterior del útero), y con participación de personal no entrenado, se plantean tres situaciones: Primera opción: en ausencia de indicación de nacimiento inmediato o sangrado vaginal, se recomienda diferir la cesárea (cerrar la laparotomía antes de incidir el útero) hasta asegurar la disponibilidad de los recursos recomendados para llevar a cabo una cirugía segura. Segunda opción: ante indicación de nacimiento inmediato (por ejemplo, estado fetal no tranquilizador), pero sin sangrado vaginal o indicación de manejo inmediato de EAP, se sugiere realizar manejo en dos tiempos: se realiza la cesárea evitando incidir la placenta, seguida de histerorrafia y cierre de abdomen, hasta asegurar la disponibilidad de los recursos recomendados para llevar a cabo una cirugía segura. Tercera opción: en presencia de sangrado vaginal que hace imposible diferir el manejo definitivo de EAP, es necesario extraer el feto por el fondo del útero, realizar la histerorrafia y reevaluar. En ocasiones, el nacimiento del feto disminuye el flujo placentario y el sangrado vaginal se reduce o desaparece, lo que hace posible diferir el manejo definitivo de EAP. Si el sangrado significativo persiste, es necesario continuar con la histerectomía haciendo uso de los recursos disponibles: compresión manual de la aorta, llamado inmediato a los cirujanos con mejor entrenamiento disponible, soporte de grupos expertos de otros hospitales a través de telemedicina. Si una paciente con factores de riesgo para EAP (por ejemplo, miomectomía o cesárea previa) presenta retención de placenta posterior al parto vaginal, es recomendable confirmar la posibilidad de dicho diagnóstico (por ejemplo, realizando una ecografía) antes de intentar la extracción manual de la placenta. Conclusiones: esperamos que este primer consenso colombiano de EAP sirva como base para discusiones adicionales y trabajos colaborativos que mejoren los resultados clínicos de las mujeres afectadas por esta enfermedad. Evaluar la aplicabilidad y efectividad de las recomendaciones emitidas requerirá investigaciones adicionales.

ABSTRACT Introduction: Placenta accreta spectrum (PAS) is a condition associated with massive postpartum bleeding and maternal mortality. Management guidelines published in high income countries recommend the participation of interdisciplinary teams in hospitals with sufficient resources for performing complex procedures. However, some of the recommendations contained in those guidelines are difficult to implement in low and medium income countries. Objectives: The aim of this consensus is to draft general recommendations for the treatment of PAS in Colombia Materials and Methods: Twenty-three panelists took part in the consensus with their answers to 31 questions related to the treatment of PAS. The panelists were selected based on participation in two surveys designed to determine the resolution capabilities of national and regional hospitals. The modified Delphi methodology was used, introducing two successive discussion rounds. The opinions of the participants, with a consensus of more than 80 %, as well as implementation barriers and facilitators, were taken into consideration in order to issue the recommendations. Results: The consensus drafted five recommendations, integrating the answers of the panelists. Recommendation 1. Primary care institutions must undertake active search of PAS in patients with risk factors: placenta praevia and history of myomectomy or previous cesarean section. In case of ultrasound signs suggesting PAS, patients must be immediately referred, without a minimum gestational age, to hospitals recognized as referral centers. Online communication and care modalities may facilitate the interaction between primary care institutions and referral centers for PAS. The risks and benefits of telemedicine modalities must be weighed. Recommendation 2. Referral hospitals for PAS need to be defined in each region of Colombia, ensuring coverage throughout the national territory. It is advisable to concentrate the flow of patients affected by this condition in a few hospitals with surgical teams specifically trained in PAS, availability of specialized resources, and institutional efforts at improving quality of care with the aim of achieving better health outcomes in pregnant women with this condition. To achieve this goal, participants recommend that healthcare regulatory agencies at a national and regional level should oversee the process of referral for these patients, expediting administrative pathways in those cases in which there is no prior agreement between the insurer and the selected hospital or clinic. Recommendation 3. Referral centers for patients with PAS are urged to build teams consisting of a fixed group of specialists (obstetricians, urologists, general surgeons, interventional radiologists) entrusted with the care of all PAS cases. It is advisable for these interdisciplinary teams to use the "intervention bundle" model as a guidance for building PAS referral centers. This model comprises the following activities: service preparedness, disease prevention and identification, response to the occurrence of the disease, and debriefing after every event. Telemedicine facilitates PAS treatment and should be taken into consideration by interdisciplinary teams caring for this disease. Recommendation 4. Obstetrics residents must be instructed in the performance of maneuvers that are useful for the prevention and treatment of massive intraoperative bleeding due to placenta praevia and PAS, including manual aortic compression, uterine tourniquet, pelvic packing, retrovesical bypass, and Ward maneuver. Specialization Obstetrics and Gynecology programs in Colombia must include the basic concepts of the diagnosis and treatment of PAS. Referral centers for PAS must offer online and in-person training programs for professionals interested in improving their competencies in PAS. Moreover, they must offer permanent remote support (telemedicine) to other hospitals in their region for patients with this condition. Recommendation 5. Patients suspected of having PAS and placenta praevia based on imaging, with no evidence of active vaginal bleeding, must be delivered between weeks 34 and 36 6/7. Surgical treatment must include sequential interventions that may vary depending on the characteristics of the lesion, the clinical condition of the patient and the availability of resources. The surgical options (total and subtotal hysterectomy, one-stage conservative surgical management and watchful waiting) must be included in a protocol known by the entire interdisciplinary team. In situations in which an antepartum diagnosis is lacking, that is to say, in the face of intraoperative finding of PAS (evidence of purple bulging or neovascularization of the anterior aspect of the uterus), and the participation of untrained personnel, three options are considered: Option 1: In the absence of indication of immediate delivery or of vaginal delivery, the recommendation is to postpone the cesarean section (close the laparotomy before incising the uterus) until the recommended resources for safe surgery are secured. Option 2: If there is an indication for immediate delivery (e.g., non-reassuring fetal status) but there is absence of vaginal bleeding or indication for immediate PAS management, a two-stage management is suggested: cesarean section avoiding placental incision, followed by uterine repair and abdominal closure, until the availability of the recommended resources for safe surgery is ascertained. Option 3: In the event of vaginal bleeding that prevents definitive PAS management, the fetus must be delivered through the uterine fundus, followed by uterine repair and reassessment of the situation. Sometimes, fetal delivery diminishes placental flow and vaginal bleeding is reduced or disappears, enabling the possibility to postpone definitive management of PAS. In case of persistent significant bleeding, hysterectomy should be performed, using all available resources: manual aortic compression, immediate call to the surgeons with the best available training, telemedicine support from expert teams in other hospitals. If a patient with risk factors for PAS (e.g., myomectomy or previous cesarean section) has a retained placenta after vaginal delivery, it is advisable to confirm the possibility of such diagnosis (by means of ultrasound, for example) before proceeding to manual extraction of the placenta. Conclusions: It is our hope that this first Colombian consensus on PAS will serve as a basis for additional discussions and collaborations that can result in improved clinical outcomes for women affected by this condition. Additional research will be required in order to evaluate the applicability and effectiveness of these recommendations.

Transcriptome dataset of omental and subcutaneous adipose tissues from gestational diabetes patients.

Gestational diabetes (GD) is one of the most prevalent metabolic diseases in pregnant women worldwide. GD is a risk factor for adverse pregnancy outcomes, including macrosomia and preeclampsia. Given the multifactorial etiology and the complexity of its pathogenesis, GD requires advanced omics analyses to expand our understanding of the disease. Next generation RNA sequencing (RNA-seq) was used to evaluate the transcriptomic profile of subcutaneous and omental adipose tissues (AT) collected from patients with gestational diabetes and matched controls. Samples were harvested during cesarean delivery. Results show differences based on anatomical location and provide whole-transcriptome data for further exploration of gene expression patterns unique to GD patients.

Evisceración intestinal transvaginal por dehiscencia de la cúpula vaginal posterior a la histerectomía: reporte de caso / Transvaginal bowel evisceration due to vaginal vault deshicence following a hysterectomy: case report

Resumen ANTECEDENTES: La dehiscencia de la cúpula vaginal es una complicación rara de la histerectomía, secundaria a factores de riesgo que alteran la cicatrización. Su incidencia y prevalencia son bajas y cuando ocurre es una urgencia quirúrgica. OBJETIVO: Reportar el caso clínico de una paciente con evisceración intestinal transvaginal y revisar el procedimiento diagnóstico y terapéutico y compararlo con lo registrado en la bibliografía. CASO CLÍNICO: Paciente de 67 años, con un cuadro clínico de cuatro horas de dolor abdominal asociado con sensación de masa vaginal. Antecedente de cirugía oncológica. En el examen físico se identificó una evisceración intestinal, sin necrosis. Durante el procedimiento quirúrgico se evidenció un defecto en la cúpula vaginal de tres centímetros. Por acceso abdominal y vaginal se efectuó la reparación, sin complicaciones. En el posoperatorio cursó con desaturación de oxígeno multifactorial, se trató, controló y se dio de alta del hospital. Acudió a los controles posoperatorios en los que se la encontró con adecuada evolución clínica. CONCLUSIÓN: La evisceración transvaginal es poco frecuente, cuando ocurre requiere diagnosticarse y tratarse de inmediato, para contrarrestar las complicaciones asociadas. En este caso, la paciente recibió atención multidisciplinaria con adecuada evolución posoperatoria. En virtud de la baja incidencia no se dispone de evidencia suficiente para recomendar una vía de acceso ideal para el tratamiento quirúrgico.

Abstract BACKGROUND: Vaginal vault dehiscence is a rare complication of hysterectomy, secondary to risk factors that alter healing. Its incidence and prevalence are low and when it occurs it is a surgical emergency. OBJECTIVE: To report the clinical case of a patient with transvaginal intestinal evisceration and to review the diagnostic and therapeutic procedure and compare it with that reported in the literature. CLINICAL CASE: A 67-year-old female patient with a four-hour clinical picture of abdominal pain associated with vaginal mass sensation. History of previous oncologic surgery. Physical examination revealed intestinal evisceration without necrosis. During the surgical procedure a three centimeter defect of the vaginal vault was evidenced. The repair was performed by abdominal and vaginal access, without complications. Postoperatively she presented with multifactorial oxygen desaturation, was treated, monitored and discharged from the hospital. She attended postoperative controls in which she was found with adequate clinical evolution. CONCLUSION: Transvaginal evisceration is rare, when it occurs it needs to be diagnosed and treated immediately, to counteract associated complications. In this case, the patient received multidisciplinary care with adequate postoperative evolution. Due to the low incidence, there is insufficient evidence to recommend an ideal access route for surgical treatment.

Reporte de caso: placenta percreta con previa embolización de vasos anómalos / Case Report: Placenta Percreta With Previous Embolization of Anomalous Vessels / Relato de caso: placenta percrete com embolização prévia de vasos anómalos

Resumen: el acretismo placentario es una de las complicaciones obstétricas más temidas. Se entiende como el proceso de inserción placentaria anormal, secundario a un procedimiento quirúrgico, lo que ocasiona un error de decidualización en el área cicatricial que lleva a la profundización anormal del trofoblasto. La frecuencia de esta patología ha ido en aumento debido al incremento en la tasa de cesáreas en los últimos años. El caso se presenta en el hospital Universitario Clínica San Rafael en Bogotá, se trata de una paciente de 36 años, gestación de 37,1 semanas, con antecedente de cesárea previa, en quien se evidenció percretismo placentario; luego del nacimiento, se dejó placenta in situ y así el servicio de cirugía endovascular realizó embolización de vasos anómalos, lo que disminuyó el sangrado en la histerectomía diferida. Se comprobó evolución favorable y seguimiento de la paciente hasta ser dada de alta de la institución sin complicaciones. Actualmente existen diversos abordajes terapéuticos, entre ellos la histerectomía posterior de la cesárea y el manejo médico hasta involución de la placenta e histerectomía diferida, todos encaminados a disminuir complicaciones asociadas, entre las cuales las más frecuentes son la hemorragia, los requerimientos de transfusión y los días de hospitalización e infección, con el fin de disminuir la morbimortalidad materna extrema.

Abstract: placental accretism is one of the most feared obstetric complications. It is understood as the process of abnormal placental insertion, secondary to a surgical procedure, which causes a decidualization error in the scar area leading to abnormal deepening of the trophoblast. The freguency of this pathology has been increasing due to the increase in the rate of cesarean sections in recent years. The case is presented in the hospital Universitario Clínica San Rafael in Bogotá, it is a 36-year-old patient, 37,1 weeks gestation, with a history of previous cesarean section, with an evident case of placenta percreta; after birth, placenta was left in place and thus the endovascular surgery service performed embolization of anomalous vessels, which reduced bleeding in the deferred hysterectomy. A favorable evolution was verified, and the patient was followed up until she was discharged from the institution without complications. Currently, there are several therapeutic approaches, including hysterectomy after cesarean section and medical management up to placental involution and delayed hysterectomy, all aimed at reducing associated complications, among which the most frequent are hemorrhage, transfusion requirements and days of hospitalization and infection, in order to reduce extreme maternal morbimortality.

Resumo: o acretismo placentário é urna das complicações obstétricas mais temidas. Entende-se como o processo de inserção placentária anormal, secundário a um procedimento cirúrgico, que causa um erro de decidualização na área cicatricial levando ao aprofundamento anormal do trofoblasto. A frequência dessa patologia vem aumentando devido ao aumento da taxa de cesarianas nos últimos anos. O caso é apresentado no Hospital Universitário Clínica San Rafael, em Bogotá, é uma paciente de 36 anos, 37,1 semanas de gestação, com história de cesariana anterior, na qual foi evidenciado percretismo placentário; após o nascimento, a placenta foi deixada in situ e, portanto, uma cirurgia endovascular foi feita para que fosse possível embolizar os vasos anómalos, o que diminuiu o sangramento na histerectomia tardia. Evolução favorável e acompanhamento da paciente até receber alta da instituição sem complicações. Atualmente, existem várias abordagens terapêuticas, incluindo histerectomia pós-cesariana e manejo médico até involução placentária e histerectomia tardia, todas com o objetivo de reduzir as complicações associadas, dentre as quais as mais comuns são sangramento, necessidade de transfusão e dias de internação e infecção, a fim de reduzir a mortalidade materna extrema.

Culture time and reagent minimization in the chemical PCC assay.

The possibility to reduce the culture time and volume of blood and reagents required for the chemical Premature Chromosome Condensation (PCC) assay is demonstrated in this work. Peripheral whole blood was exposed to gamma radiation (1-20 Gy). Lymphocytes were cultured for 40 h, using 50 µl of blood and 450 µl of culture medium. The dose-response curves were adjusted, using length ratio (LR) of the longest to the shortest chromosome piece, and the frequency of rings per cell. No statistical differences were found between the results obtained with this method and those reported with the classical PCC assay culture. The minimization of culture time and reagents in combination with the automatic measurement of the LR of the chromosome pieces, or the scoring of rings, can be a valuable biodosimetry tool in a mass casualty scenario.

Automatic Detection of Mitosis and Nuclei From Cytogenetic Images by CellProfiler Software for Mitotic Index Estimation.

Mitotic Index (MI) estimation expressed as percentage of mitosis plays an important role as quality control endpoint. To this end, MI is applied to check the lot of media and reagents to be used throughout the assay and also to check cellular viability after blood sample shipping, indicating satisfactory/unsatisfactory conditions for the progression of cell culture. The objective of this paper was to apply the CellProfiler open-source software for automatic detection of mitotic and nuclei figures from digitized images of cultured human lymphocytes for MI assessment, and to compare its performance to that performed through semi-automatic and visual detection. Lymphocytes were irradiated and cultured for mitosis detection. Sets of images from cultures were analyzed visually and findings were compared with those using CellProfiler software. The CellProfiler pipeline includes the detection of nuclei and mitosis with 80% sensitivity and more than 99% specificity. We conclude that CellProfiler is a reliable tool for counting mitosis and nuclei from cytogenetic images, saves considerable time compared to manual operation and reduces the variability derived from the scoring criteria of different scorers. The CellProfiler automated pipeline achieves good agreement with visual counting workflow, i.e. it allows fully automated mitotic and nuclei scoring in cytogenetic images yielding reliable information with minimal user intervention.

Shortening the culture time in cytogenetic dosimetry using PCC-R assay.

The fast assessment of the dose received by exposed persons is crucial in radiological accidents, so the 48 h of cell culture in conventional cytogenetic dosimetry in addition to some limitations after high doses becomes a disadvantage. The premature chromosome condensation (PCC) assay permits to analyse enough cells after high radiation exposure, and the score of PCC-R may reduce the culture time up to 40-42 h. Peripheral whole-blood samples were exposed to 1-10 Gy of gamma radiation and cultured during 40 and 42 h. No statistical difference between frequencies was obtained between 40, 42 and 48 h of culture time, and PCC index decreased with the increase of the dose and increased with the culture time. The protocol proposed allows reduce the culture time down to 40 or 42 h when using the PCC-R assay with adequate precision in dose estimation.

Maternity in adolescents and its association with caesarean labor / Adolescencia materna y su asociación con la realización de cesárea / Mãe adolescente e sua associação com cesariana

Objective: to evaluate the association between adolescence and cesarean section in women aged 10-19 years compared with those found in ages between 19 and 25 years, patients in a hospital, and determine its association with sociodemographic variables and neonatal in terms of prematurity, and Apgar low birth weight. Materials and Methods: a case-control study was performed using a simple random sampling, considering the calculation of a statistical sample. a total of 1,304 cases and 2,608 controls were included. First time mom patients treated at an institution x over a period of three years, to determine associations of risk through analysis of hypothesis testing is included. Results: the risk of caesarean section in teenagers is (OR 1.13, 95% CI 1.10 to 1.51). In addition, it was determined that there is an increased risk of low birth weight (OR 9.4, 95% CI 7.59 to 11.76), with no difference in adolescents in the risk of Apgar down score at minute and 5 minutes later. Conclusion: there is an increased risk of low birth weight and require termination of pregnancy via cesarean in adolescents compared to young adults, especially if they are under 14. It is necessary to promote campaigns to prevent teenage pregnancy, as the main measure of control over these population.

Objetivo: evaluar la asociación entre adolescencia y la realización de cesárea en mujeres de 10 a 19 años, en comparación con las que se encuentran en edades entre 19 y 25 años, atendidas en un hospital X, y determinar su asociación con variables sociodemográficas y neonatales en términos de prematurez, Apgar y bajo peso al nacer. Materiales y Métodos: se realizó un estudio de casos y controles, mediante un muestreo simple aleatorio, teniendo en cuenta el cálculo de una muestra estadística. Se incluyeron un total de 1.304 casos y 2.608 controles. Se incluyeron pacientes primigestantes atendidas en una institución X en un período de tres años, para determinar asociaciones de riesgo mediante análisis de contraste de hipótesis. Resultados: el riesgo de cesárea en adolescentes es de (OR 1,13, IC 95% 1,10-1,51). Además, se determinó que en las adolescentes existe un riesgo mayor de bajo peso al nacer (OR 9,4, IC 95% 7,59-11,76), sin diferencia en cuanto al riesgo de Apgar bajo al minuto y los 5 minutos. Conclusión: existe un mayor riesgo de presentar bajo peso neonatal y requerir terminación de la gestación por vía cesárea en adolescentes, en comparación con las adultas jóvenes, especialmente si son menores de 14 años. Se requiere

Objetivo: avaliar a associação entre a adolescência ea cesariana em mulheres com idade entre 10 a 19 anos, em comparação com aqueles encontrados na faixa etária entre 19 e 25 anos, servido em um hospital, e determinar associação STI com variáveis neonatais e sociodemográficos em termos de prematuridade, Apgar e baixo peso ao nascer. Materiais e Métodos: um estudo de caso-controle foi realizado utilizando amostragem aleatória simples, Considerando o cálculo de uma amostra estatística. Um total de 1.304 casos e 2.608 controles foram incluídos. Primigestas pacientes tratados em uma instituição x ao longo de um período de três anos, para determinar associações de risco através da análise dos testes de hipóteses está incluído. Resultados: o risco de cesariana em adolescentes é (ou CI 1,13, 95% 1,10-1,51). Além disso, determinou-se que há um aumento do risco de baixo peso ao nascer (OR 9,4, IC 95% 7,59-11,76), não havendo diferença em adolescentes no risco de baixo índice de Apgar no minuto 5 minutos. Conclusão: há um aumento do risco de baixo peso ao nascer e exigem a interrupção da gravidez através de cesariana em adolescentes em comparação com adultos jovens, especialmente se eles estão sob 14. É necessário promover campanhas de prevenção da gravidez na adolescência, como a principal medida de controle sobre a população.

Pharmacokinetics and Biodistribution Study of 7A7 Anti-Mouse Epidermal Growth Factor Receptor Monoclonal Antibody and Its F(ab')(2) Fragment in an Immunocompetent Mouse Model.

Immunocompetent mice, Fc receptor γ-chain deficient mice (Fcer1g(-/-)), and molecular tools as F(ab')(2) bivalent fragments appear as the most suitable biological models to study the mechanisms of the action of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs). In vivo experiments contrasting antitumor effects of whole Abs and their bivalent fragments commonly involve a previous comparative pharmacokinetics study. In this paper, pharmacokinetics and biodistribution of an anti-mouse EGFR Ab were assessed using immunocompetent mice. (125)I-labeled 7A7 mAb holds an elimination half-life (t(1/2)ß) of 23.1 h in C57BL/6 mice. Accumulation of mAb was found in liver, spleen, kidneys, and mostly in lungs. We used an ELISA method to determine the t(1/2)ß of a 7A7 mAb using the same experimental setting. Results from this new analysis revealed a t(1/2)ß of 23.9 h, supporting this method as a safer and easier system to evaluate pharmacokinetics parameters of mAbs targeting mouse EGFR. Using this system we also studied pharmacokinetics of 7A7 F(ab')(2) fragment. A tenfold difference between the mAb and fragment t(1/2)ß was found. These data support the use of the 7A7 F(ab')(2) fragment in in vivo studies to explore the contribution of the EGFR signaling blockade and the Fc region to the antitumor effect of 7A7 mAb in this autologous scenario.

Quantitative image analysis of gamma-H2AX foci induced by ionizing radiation applying open source programs.

OBJECTIVE: To test a CellProfiler pipeline for automated counting and characterization of gamma-H2AX foci in color images of human cultured cells. STUDY DESIGN: A431 cells were irradiated and stained for gamma-H2AX foci detection. Sets of color images were analyzed visually, and findings were compared with those using FociCounter and CellProfiler software. RESULTS: The CellProfiler pipeline includes some proprieties not present in FociCounter, such as the automatic detection of nuclei, the detection of touching nuclei and the rejection of nuclei that touch the border of the image. The time required for manual operation is associated with the number of images analyzed visually or by FociCounter but not for the CellProfiler program. CellProfiler reduced manual operation time and is about 4 times faster than semiautomatic detection using FociCounter and 10 times faster than visual counting. CONCLUSION: We conclude that CellProfiler and FociCounter are reliable tools for measuring gamma-H2AX foci. However, CellProfiler overcomes the limitations of the FociCounter program and is able to detect nuclei automatically, saving considerable manual operation.

Radiosensitization induced by the anti-epidermal growth factor receptor monoclonal antibodies cetuximab and nimotuzumab in A431 cells.

Epidermal growth factor receptors (EGFR) are overexpressed in a wide range of malignancies including head and neck, colon, and breast cancers. It has been identified that carcinomas with high expression levels of EGFR are more resistant to radiotherapy. Therefore, inhibiting nuclear translocation of EGFR to increase the radiosensitivity of malignant cells expressing EGFR offers the potential for increasing the therapeutic index of radiotherapy. The purpose of the present study was to quantify and to compare the radiosensitizing properties of the well-known anti-EGFR antibodies, cetuximab and nimotuzumab in human epidermoid A431 overexpressing EGFR cells. Cells were treated with two concentrations of the antibodies and then irradiated with a single dose of 4 Gy. The results indicated that the two antibodies induced radiosensitization increasing the percentage of dead/dying cells and the yield of γ-H2AX foci 24 h after irradiation. Whereas cetuximab exhibited a significant increase in radiosensitization at the highest concentration, the effects of nimotuzumab were more modest. A correlation between γ-H2AX foci signals and dead/dying cells was observed. The disparity in modulation of radiation-induced DNA damage by the two antibodies could be associated with the level of their respective intrinsic cytotoxic properties. Overall, the findings highlight the potential therapeutic benefit of combination therapy with anti-EGFR antibodies and radiotherapy for relevant carcinomas.

Visual estimation of the percentage of DNA in the tail in the comet assay: evaluation of different approaches in an intercomparison exercise.

One of the difficulties in the comparison of results between laboratories working with the comet assay is the great diversity of parameters used to express DNA damage and the lack of conversion factors between the majority of them. Here we report a scorer-independent conversion curve to transform the values of DNA damage reported in arbitrary units (AU) into estimated percentage of DNA in the tail (E%T), and the results obtained in an intercomparison exercise where the effectiveness of this curve and two others proposed in the literature (E%T=AU/4 and E%T=(AU/5)+10) were tested. To obtain the conversion curve, human lymphocytes were first treated with radiation or H(2)O(2). Percentage of DNA in tail (%T) was then measured in 2100 comets (300 comets per treatment) using Casp image analysis software. Subsequently, using these values of %T, categories of 0, 1, 2, 3, and 4 were assigned to comets with %T [0-1), [1-25), [25-45), [45-70), and >70, and DNA damage was calculated in AU, as usual. DNA damage was induced in the interval 24-315AU (1.54-65.23%T). The best-fit conversion curve obtained by regression analysis was E%T=(AU-25.87)/4.46. In the intercomparison exercise, ten scorers from nine laboratories analyzed the same comet images (recorded on a compact disc) visually. The values reported in comet categories were transformed into AU and subsequently into E%T, using the three approaches mentioned above. The best agreement between E%T and %T measured by the software (S%T) was obtained with the conversion curve reported here, where the slope of E%T versus S%T from the ten scorers was not different from 1. Using this conversion curve, the overall mean difference between E%T and S%T was 1.4±2.62 and 57 (81%) of E%T values differ from S%T by less than 5 units. These findings show the strength of the scorer-independent conversion curve as a tool to compare results reported in AU or %T by different laboratories.

Genotoxic assessment of aqueous extract of Rhizophora mangle L (mangle rojo) by spermatozoa head assay / Evaluación genotóxica del extracto acuoso de Rhizophora mangle L (mangle rojo) mediante el ensayo de la cabeza del espermatozoide

INTRODUCTION: the aqueous extract bark of Rhizophora mangle L. (red mangrove) has traditionally been used in Cuban folk medicine due to its wide array of curative properties: astringent, haemostatic, febrifuge and antifungal. Previous chemical characterization studies of the liophylized aqueous extract bark, revealed that tannins are the main components, although the presence of other compounds such as epicatechin, catechin, clorogenic, gallic and ellagic acids, as well as galotannins have been also described. OBJECTIVE: this work was designed to determine if any components of the extracts has the ability to produce genotoxic effects in germ cells of Cenp:NMRI mouse models using the abnormal shape of spermatozoa test. METHODS: the lyophilized aqueous extract bark was given by oral gavages (500, 1000 and 2000 mg of total solids /kg bw) in three series of the classical protocol of Wyrobeck and Bruce, in intervals of 24 hrs for 5 days. RESULTS: in series I, the animals were sacrificed on day 4 after starting the administration. In series II the animals were sacrificed on day 21 while in series III the day of sacrificed was the 35th. CONCLUSIONS: no cytotoxic effect was observed in the 3 series and in all doses proved and only the highest dose of the extract in the series I provoked a slight genotoxic effect when increase the percentage in the number of abnormal spermatozoa.

INTRODUCCIÓN: el extracto acuoso de Rhizophora mangle L. (mangle rojo), se ha usado tradicionalmente en Cuba por su amplio espectro de propiedades curativas: como astringente, hemostático, febrífugo y antifúngico. Los estudios previos de caracterización química del extracto acuoso liofilizado de la corteza de la planta revelaron que los taninos son los componentes principales, aunque también se ha descrito la presencia de otros compuestos como las epicatequinas, el ácido clorogénico, ácido gálico y ácido elágico, así como galotaninos. OBJETIVO: el presente estudio fue diseñado para determinar si alguno de los componentes del extracto tiene la capacidad para producir efectos genotóxicos en células germinales de ratones Cenp:NMRI utilizando el ensayo de anormalidades de la cabeza del espermatozoide. MÉTODOS: el extracto liofilizado fue administrado por vía oral (500, 1 000 y 2 000 mg de material vegetal/kg) en 3 series del protocolo clásico de Wyrobeck y Bruce, en intervalos de 24 h por 5 d consecutivos. RESULTADOS: en la serie I los animales fueron sacrificados el dia 4 después de iniciada la administración. En la serie II los animales fueron sacrificados el día 21, mientras que en la serie III fueron sacrificados el día 35. CONCLUSIONES: no se observó efecto citotóxico en las 3 series y en todas las dosis probadas, y solamente la dosis mayor del extracto en la serie I provocó un ligero efecto genotóxico al incrementar el porcentaje de espermatozoides anormales.

Genotoxic assessment of aqueous extract of Rhizophora mangle L (mangle rojo) by spermatozoa head assay / Evaluación genotóxica del extracto acuoso de Rhizophora mangle L (mangle rojo) mediante el ensayo de la cabeza del espermatozoide

INTRODUCTION: the aqueous extract bark of Rhizophora mangle L. (red mangrove) has traditionally been used in Cuban folk medicine due to its wide array of curative properties: astringent, haemostatic, febrifuge and antifungal. Previous chemical characterization studies of the liophylized aqueous extract bark, revealed that tannins are the main components, although the presence of other compounds such as epicatechin, catechin, clorogenic, gallic and ellagic acids, as well as galotannins have been also described. OBJECTIVE: this work was designed to determine if any components of the extracts has the ability to produce genotoxic effects in germ cells of Cenp:NMRI mouse models using the abnormal shape of spermatozoa test. METHODS: the lyophilized aqueous extract bark was given by oral gavages (500, 1000 and 2000 mg of total solids /kg bw) in three series of the classical protocol of Wyrobeck and Bruce, in intervals of 24 hrs for 5 days. RESULTS: in series I, the animals were sacrificed on day 4 after starting the administration. In series II the animals were sacrificed on day 21 while in series III the day of sacrificed was the 35th. CONCLUSIONS: no cytotoxic effect was observed in the 3 series and in all doses proved and only the highest dose of the extract in the series I provoked a slight genotoxic effect when increase the percentage in the number of abnormal spermatozoa(AU)

INTRODUCCIÓN: el extracto acuoso de Rhizophora mangle L. (mangle rojo), se ha usado tradicionalmente en Cuba por su amplio espectro de propiedades curativas: como astringente, hemostático, febrífugo y antifúngico. Los estudios previos de caracterización química del extracto acuoso liofilizado de la corteza de la planta revelaron que los taninos son los componentes principales, aunque también se ha descrito la presencia de otros compuestos como las epicatequinas, el ácido clorogénico, ácido gálico y ácido elágico, así como galotaninos. OBJETIVO: el presente estudio fue diseñado para determinar si alguno de los componentes del extracto tiene la capacidad para producir efectos genotóxicos en células germinales de ratones Cenp:NMRI utilizando el ensayo de anormalidades de la cabeza del espermatozoide. MÉTODOS: el extracto liofilizado fue administrado por vía oral (500, 1 000 y 2 000 mg de material vegetal/kg) en 3 series del protocolo clásico de Wyrobeck y Bruce, en intervalos de 24 h por 5 d consecutivos. RESULTADOS: en la serie I los animales fueron sacrificados el dia 4 después de iniciada la administración. En la serie II los animales fueron sacrificados el día 21, mientras que en la serie III fueron sacrificados el día 35. CONCLUSIONES: no se observó efecto citotóxico en las 3 series y en todas las dosis probadas, y solamente la dosis mayor del extracto en la serie I provocó un ligero efecto genotóxico al incrementar el porcentaje de espermatozoides anormales(AU)