ABSTRACT
BACKGROUND: Sepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as endotoxins, producing endotoxemia. Disseminated intravascular coagulation (DIC) is frequently observed in septic patients and is associated with organ failure and death. Sepsis activates endothelial cells (ECs), promoting a prothrombotic phenotype contributing to DIC. Ion channel mediated calcium permeability participates in coagulation. The transient reception potential melastatin 7 (TRPM7) non-selective divalent cation channel that also contains an α-kinase domain, which is permeable to divalent cations including Ca2+, regulates endotoxin-stimulated calcium permeability in ECs and is associated with increased mortality in septic patients. However, whether endothelial TRPM7 mediates endotoxemia-induced coagulation is not known. Therefore, our aim was to examine if TRPM7 mediates coagulation during endotoxemia. RESULTS: The results showed that TRPM7 regulated endotoxin-induced platelet and neutrophil adhesion to ECs, dependent on the TRPM7 ion channel activity and by the α-kinase function. Endotoxic animals showed that TRPM7 mediated neutrophil rolling on blood vessels and intravascular coagulation. TRPM7 mediated the increased expression of the adhesion proteins, von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1), and P-selectin, which were also mediated by the TRPM7 α-kinase function. Notably, endotoxin-induced expression of vWF, ICAM-1 and P-selectin were required for endotoxin-induced platelet and neutrophil adhesion to ECs. Endotoxemic rats showed increased endothelial TRPM7 expression associated with a procoagulant phenotype, liver and kidney dysfunction, increased death events and an increased relative risk of death. Interestingly, circulating ECs (CECs) from septic shock patients (SSPs) showed increased TRPM7 expression associated with increased DIC scores and decreased survival times. Additionally, SSPs with a high expression of TRPM7 in CECs showed increased mortality and relative risk of death. Notably, CECs from SSPs showed significant results from the AUROC analyses for predicting mortality in SSPs that were better than the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores. CONCLUSIONS: Our study demonstrates that sepsis-induced DIC is mediated by TRPM7 in ECs. TRPM7 ion channel activity and α-kinase function are required by DIC-mediated sepsis-induced organ dysfunction and its expression are associated with increased mortality during sepsis. TRPM7 appears as a new prognostic biomarker to predict mortality associated to DIC in SSPs, and as a novel target for drug development against DIC during infectious inflammatory diseases.
Subject(s)
Animals , Rats , Sepsis , Endotoxemia , Disseminated Intravascular Coagulation , TRPM Cation Channels , von Willebrand Factor , Calcium , Intercellular Adhesion Molecule-1 , P-Selectin , Endothelial Cells , EndotoxinsABSTRACT
RESUMEN El objetivo del presente estudio está dirigido a analizar los presupuestos teóricos acerca del aprendizaje basado en problemas como metodología activa para la enseñanza de las ciencias naturales en la Educación Superior cubana. Se realizó una revisión bibliográfica en la que se consideraron artículos originales y de revisión publicados entre 2000 y 2020 a partir de los descriptores aprendizaje basado en problemas, aprendizaje por descubrimiento y construcción, aprendizaje basado en proyectos y en retos. La búsqueda fue realizada en las bases de datos SciELO y Google académico de abril a junio de 2020, en función del establecimiento de los presupuestos teóricos y metodológicos de una investigación desarrollada en el Departamento de Química de la Facultad de Ciencias Aplicadas perteneciente a la Universidad de Camagüey Ignacio Agramonte Loynaz. Se concluye que resulta pertinente asumir por parte del profesor esta metodología, ya que se concreta en una gestión docente enfocada en el aprendizaje centrado en el estudiante, por consiguiente, es necesario seguir investigando en esta temática y proceder al desarrollo y la aplicación de instrumentos que permitan evaluarla de modo fiable y eficaz.
ABSTRACT The objective of the actual research is to analyze the theoretical bases about problem-based learning as an active methodology for the teaching of natural sciences in Cuban Higher Education. With the descriptors learning based on problems, learning by discovery and construction, learning based on projects and challenges, a bibliographic review was carried out in which original and review articles published between 2000 and 2020 were considered. The search was carried out in the databases of SciELO and Google academic data from April to June 2020. It is concluded that it is pertinent to assume this methodology by the teacher, since it is specified in a teaching management focused on student-centered learning, therefore, it is necessary to continue investigating in this area and proceed to the development and application of instruments that allow them to be evaluated reliably and effectively.
ABSTRACT
RESUMEN Objetivo: determinar la prevalencia del compro miso ganglionar de pacientes con cáncer de endometrio y hacer una exploración de los factores asociados a la invasión ganglionar. Materiales y métodos: estudio de prevalencia con análisis exploratorio. Se incluyeron pacientes con cáncer de endometrio llevadas a histerectomía abdominal total más salpingooforectomía bilateral y linfadenectomía pélvica, con o sin linfadenectomía paraaórtica en siete centros de oncología de Colombia, en el periodo 2009-2016. Se excluyeron pacientes con radioterapia o quimioterapia previa, diagnóstico histológico de tumores neuroendocrinos, carcinosarcomas, tumores sincrónicos o metacrónicos. Muestreo no probabilístico. Tamaño muestral n = 290. Variables medidas: sociodemográficas, clínicas e histopatológicas y compromiso ganglionar pélvico o paraaórtico. Se presenta la prevalencia de periodo; el análisis exploratorio se realizó por medio de odds ratio (OR) crudo y el ajustado mediante un modelo multivariado (regresión logística no condicional). Resultados: se obtuvieron 467 casos de los cuales se excluyeron 163 por no presentar la totalidad de las variables, se estudiaron 304 pacientes. La prevalencia del compromiso ganglionar fue del 15,8 % (48/304). Los factores asociados al compromiso ganglionar en el análisis crudo y ajustado fueron la invasión linfovascular (OR ajustado = 9,32; IC 95 %: 4,27-21,15) e invasión miometrial (OR ajustado = 3.95; IC 95 %: 1,29-14,98). Conclusión: el 15 % de las pacientes sometidas a linfadenectomía tienen compromiso ganglionar. Se deben evaluar alternativas diagnósticas menos invasivas que la cirugía radical para establecer la invasión ganglionar.
ABSTRACT Objective: To determine the prevalence of lymph node involvement in patients with endometrial cancer and to explore factors associated with lymph node invasion. Materials and methods: Prevalence study with exploratory analysis. The study included patients with endometrial cancer who underwent total abdominal hysterectomy plus bilateral salpyingooophorectomy and pelvic lymphadenectomy with or without para-aortic lymphadenectomy in seven oncology centers in Colombia between 2009 and 2016. Patients who had received prior radiotherapy or chemotherapy, with a histological diagnosis of neuroendocrine tumors, carcinosarcomas or synchronous or metachronous lesions were excluded. Non-probabilistic sampling. Sample size n=290. Measured variables: sociodemographic, clinical and histopathological, and pelvic or para-aortic lymph node involvement. The prevalence for the period is presented. The exploratory analysis was conducted using crude odds ratio (OR) and adjusted OR by means of a multivariate model (unconditional logistic regression). Results: Overall, 467 cases were retrieved. Of them, 163 were excluded because of non-availability of all the variables. In total, 304 patients were studied. The prevalence of lymph node involvement was 15.8 % (48/304). In the crude and adjusted analysis, factors associated with lymph node involvement were lymphovascular invasion (adjusted OR: 9.32; 95 % CI 4.27-21.15) and myometrial invasion (adjusted OR: 3.95; 95 % CI 1.29-14.98). Conclusion: Of the patients undergoing lymphadenectomy, 15 % have lymph node involvement. Less invasive diagnostic options than radical surgery to ascertain lymph node invasion should be assessed.
Subject(s)
Endometrial Neoplasms , Pathology, Surgical , Lymph NodesABSTRACT
INTRODUCCIÓN: el carcinoma endometrial es la sexta entidad maligna más común a nivel mundial. En la mayoría de casos se diagnóstica de forma temprana. Recurre principalmente a cúpula vaginal y a nivel linfático, sin embargo, se han descrito metástasis a vagina, peritoneo y pulmones, entre otros. PRESENTACIÓN DEL CASO: paciente femenina adulta mayor con antecedente de carcinoma endometrial hace 7 años, tratado quirúrgicamente con estudio histopatológico que evidenciaba un miometrio infiltrado en un 95% sin invasión a otros órganos y linfadenectomía libre de lesión (estadio FIGO IB), quien consulta por dolor abdominal localizado en mesogastrio y deposiciones melénicas, evidenciándose una lesión gástrica, con resultado de biopsia que reporta carcinoma pobremente diferenciado con positividad focal para vimentina compatible con metástasis gástrica secundaria a carcinoma endometrial. Se indica manejo sistémico con quimioterapia, se documenta respuesta total de la lesión. DISCUSIÓN: las lesiones tumorales a nivel de estómago son primarios en su gran mayoría, una metástasis a este nivel es inusual. En el momento del diagnóstico de una metástasis gástrica, la mitad de las pacientes presentan concomitante compromiso de otros órganos. El carcinoma endometrial no está descrito dentro de los primarios que generan este compromiso. CONCLUSIÓN: el caso expuesto es un reto clínico, que representa un vacío en la evidencia actual; se comparte la experiencia de un manejo exitoso. Son necesarios más estudios para evaluar el pronóstico, opciones de tratamiento y definir la pertinencia de métodos de tamización para la detección temprana de estos casos.
INTRODUCTION: the endometrial carcinoma is the sixth cancer worldwide. Usually it is diagnosed in early stages. The sites of recurrence includes vaginal cuff and lymph nodes, however some metastasis have been described to vagina, peritoneum and lungs, among others. CASE REPORT: Elder female with history of an endometrial carcinoma 7 years ago, surgically treated. With histopathology that reported myometrial infiltration in a 95% without invasion to other organs and lymphadenectomy free of neoplasm (FIGO IB), who consult at the emergency room due to abdominal pain and black stool, with further studies that make evident a gastric lesion with biopsy reported as a poorly differentiated carcinoma, vimentin positive, compatible with gastric metastasis secondary to an endometrial carcinoma. Chemoterapy was indicated, documenting total posterior response of the lesion. DISCUSSION: Secondary lessions in stomach are rare. If they are present at the moment of diagnosis half of the patients concomitantly have metastasis in other organs. The endometrial carcinoma hasn't been described as a common localization that result in this compromise. CONCLUSION: the case exposed is a clinical challenge, a therapeutic success is shared. Limited evidence is available. Further studies are necessary to evaluate the prognosis, therapeutic options and to define the relevance of screening tests for early detection.
Subject(s)
Humans , Female , Aged , Carcinoma/secondary , Endometrial Neoplasms/pathology , Gastrointestinal Neoplasms/secondary , Carcinoma/diagnostic imaging , Gastrointestinal Neoplasms/diagnostic imagingABSTRACT
La enfermedad trofoblástica gestacional (ETG) comprende un grupo de lesiones trofoblásticas benignas, anormalidades en la formación de la placenta como son las molas hidatiformes (MH) completas y parciales, y la neoplasia trofoblástica gestacional maligna (NTGM). La ETG, es un fenómeno que se ha visto favorecido por los avances y el desarrollo de la medicina, ya que su diagnóstico es cada vez más temprano gracias a la implementación del estudio ecográfico en el primer trimestre de gestación, así mismo, el seguimiento con la subunidad ί de la Gonadotropina Coriónica Humana ( hCG) ha permitido la detección temprana de un gran número de mujeres quienes posterior a la evacuación de una MH, progresan hacia una NTGM. Ante el diagnóstico de MH, siempre debe buscarse su evacuación y posterior seguimiento para la detección precoz del desarrollo de NTGM; en cuanto al tratamiento es importante individualizarlo en mujeres con NTGM basándose en los factores de riesgo usando un régimen menos tóxico en pacientes de bajo riesgo y terapia combinada agresiva más cirugía en pacientes de alto riesgo.
Gestational trophoblastic disease (GTD) includes a group of benign trophoblastic disorders which compromise the abnormal placental formation like: complete and partial hydatidiform mole and gestational trophoblastic neoplasia (GTN). Patients with GTD have benefited by the progress and development of medicine, since earlier diagnosis with BhCG levels, ultrasonography and histopathology allows a prompt and appropriate management. BhCG follow up has to be performed in all post molar pregnancies to rule out development of postmolar gestational trophoblastic neoplasia and the right choice of assay kit is mandatory to avoid false negative or positive results. It is important to individualize treatment for women with malignant GTN based on risk factors, using a single agent such as methotrexate in low risk group and multiple agents such as EMA-CO in high risk group, treatments that usually result in a high cure rate.