The kinome, cyclins and cyclin-dependent kinases of pituitary adenomas, a look into the gene expression profile among tumors from different lineages.

BACKGROUND: Pituitary adenomas (PA) are the second most common intracranial tumors and are classified according to hormone they produce, and the transcription factors they express. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. METHODS: Here we performed transcriptome and proteome analysis of tumors derived from POU1F1 (GH-, TSH-, and PRL-tumors, N = 16), NR5A1 (gonadotropes and null cells adenomas, n = 17) and TBX19 (ACTH-tumors, n = 6) lineages as well as from silent ACTH-tumors (n = 3) to determine expression of kinases, cyclins, CDKs and CDK inhibitors. RESULTS: The expression profiles of genes encoding kinases were distinctive for each of the three PA lineage: NR5A1-derived tumors showed upregulation of ETNK2 and PIK3C2G and alterations in MAPK, ErbB and RAS signaling, POU1F1-derived adenomas showed upregulation of PIP5K1B and NEK10 and alterations in phosphatidylinositol, insulin and phospholipase D signaling pathways and TBX19-derived adenomas showed upregulation of MERTK and STK17B and alterations in VEGFA-VEGFR, EGF-EGFR and Insulin signaling pathways. In contrast, the expression of the different genes encoding cyclins, CDK and CDK inhibitors among NR5A1-, POU1F1- and TBX19-adenomas showed only subtle differences. CDK9 and CDK18 were upregulated in NR5A1-adenomas, whereas CDK4 and CDK7 were upregulated in POUF1-adenomas. CONCLUSIONS: The kinome of PA clusters these lesions into three distinct groups according to the transcription factor that drives their terminal differentiation. And these complexes could be harnessed as molecular therapy targets.

Bioethical implications of end-of-life decision-making in patients with dementia: a tale of two societies.

End-of-life decision-making in patients with dementia is a complex topic. Belgium and the Netherlands have been at the forefront of legislative advancement and progressive societal changes concerning the perspectives toward physician-assisted death (PAD). Careful consideration of clinical and social aspects is essential during the end-of-life decision-making process in patients with dementia. Geriatric assent provides the physician, the patient and his family the opportunity to end life with dignity. Unbearable suffering, decisional competence, and awareness of memory deficits are among the clinical considerations that physicians should incorporate during the end-of-life decision-making process. However, as other societies introduce legislature granting the right of PAD, new social determinants should be considered; Mexico City is an example. Current perspectives regarding advance euthanasia directives (AED) and PAD in patients with dementia are evolving. A new perspective that hinges on the role of the family and geriatric assent should help culturally heterogeneous societies in the transition of their public health care policies regarding end-of-life choices.

Posición prono en pacientes con síndrome de insuficiencia respiratoria progresiva aguda por COVID-19 / Prone position in patients with acute respiratory failure syndrome due to COVID-19 / Posição prona em pacientes com síndrome da insuficiência respiratória aguda devido ao COVID-19

Resumen: Aproximadamente hasta 5% de los pacientes afectados por la infección por SARS-CoV-2 (COVID-19) requieren estancia en la Unidad de Cuidados Intensivos. De ellos, hasta 71% presentarán Síndrome de Insuficiencia Respiratoria Progresiva Aguda (SIRPA). Colocar a los pacientes en posición prono es una técnica que ha demostrado resultados favorables en aquéllos con hipoxemia refractaria por SIRPA grave. Las Guías Americanas y Europeas actuales del manejo del COVID-19 recomiendan posición prono para mejorar la hipoxemia con resultados variables. Ésta es una técnica de bajo costo que podría mejorar el pronóstico de estos pacientes. Presentamos cinco pacientes con resultados variables en posición prono y concluimos que, al menos en esta primera muestra, hay mejoría de todos en la oxigenación, así como en la imagen radiográfica, lo cual no necesariamente se correlaciona con una mejoría global del paciente.

Abstract: Approximately, up to 5% of the patients infected with SARS-CoV-2 (COVID-19) need to be treated in the Critical Care Unit. Of all these patients, up to 71% will develop Acute Respiratory Distress Syndrome (ARDS). The technique of placing the patients in prone position has had good results in patients with refractory hypoxemia secondary to severe ARDS. The American and European guidelines recommend the use of prone position to improve sever hypoxemia of COVID-19 patients. It is a low cost technique that could improve the outcome in this patients. We present the results of 5 of our first patients with COVID-19 using prone position concluding that at least, in this first sample, there is a good response with improvement of hypoxemia as well as improvement in the chest X-ray images but we cannot conclude if it has an impact in the outcome of the patient, defined as survival or days in mechanical ventilation.

Resumo: Aproximadamente 5% dos pacientes afetados pela infecção por SARS-CoV-2 (COVID-19) necessitam de uma internação na Unidade de Terapia Intensiva. Desse modo, até 71% apresentarão Síndrome da Insuficiência Respiratória Progressiva Aguda (SIRPA). A colocação de pacientes em decúbito ventral é uma técnica que demonstrou resultados favoráveis em pacientes com hipoxemia refratária devido à SIRPA grave. As diretrizes americanas e européias atuais para o manejo do COVID-19 recomendam uma posição propensa a melhorar a hipoxemia com resultados variáveis. É uma técnica de baixo custo que poderia melhorar o prognóstico desses pacientes. Apresentamos 5 pacientes com resultados variáveis em decúbito ventral e concluímos que, pelo menos nessa primeira amostra, há uma melhora na oxigenação e na imagem radiográfica, que não necessariamente se correlaciona com uma melhora geral no paciente.

Acute myocardial infarction with ST-segment elevation. / Infarto agudo al miocardio con elevación del segmento ST en época de COVID-19.

Coronavirus disease 19 (COVID-19) is the infection caused by the SARS-CoV-2 virus and it has become a global emergency. The disease has a hughe impact on cardiopaths. Under regular conditions, patients entering the emergency room with a ST-segment elevation myocardial infarction (STEMI) must be urgently treated with reperfusion strategy. However, due to the scarce knowledge about COVID-19, there have not being yet established the guidelines for management of patients with STEMI and COVID-19. In this review we expose the main conclusions of relevant articles published about STEMI management during this pandemic. We aim to provide a review to guide the decisions about the management of STEMI during the COVID-19 emergency.

La infección por coronavirus SARS-CoV-2 es una emergencia sanitaria global que puede afectar gravemente a las personas cardiópatas. En condiciones normales, los pacientes que se presentan en las unidades médicas con diagnóstico de infarto agudo al miocardio con elevación del segmento ST (IAM-CEST) deben ser atendidos con estrategia de reperfusión coronaria de manera urgente. Sin embargo, no existen lineamientos bien establecidos sobre el tratamiento de los pacientes con IAM-CEST y COVID-19 debido a la aún escasa información al respecto, dada la súbita aparición de la enfermedad. En este artículo se exponen los principales aspectos de los artículos más relevantes sobre el manejo del IAM-CEST en el contexto de esta pandemia. El objetivo de esta publicación es apoyar en la toma de decisiones para el manejo del IAM-CEST en el contexto de la emergencia por COVID-19.

Pharmacological treatment of obesity / Tratamiento farmacológico de la obesidad

More than 70% of the population in Mexico is overweight or obese, affecting mainly people in productive age. Obesity is associated with the development of diseases that increase cardiovascular risk (diabetes mellitus, hypertension or atherogenic dyslipidemia), diseases that limit the quality of life of the patient (osteoarthrosis or sleep apnea) and even with the increase in the incidence of certain types of cancer (breast or colon). It is evident that the decrease of at least 5% of body weight induces improvement in all these factors; however, in some patients it is difficult to achieve this goal only with lifestyle modifications. In this review we analyze some drugs approved for weight control by national and international agencies that can serve as an auxiliary in conjunction with diet and exercise. Treatment must be individualized according to each patient characteristics, with an adequate evaluation of their risks and benefits.

Más del 70% de la población en México padece sobrepeso u obesidad, que afectan principalmente a personas en edad productiva. La obesidad se asocia con el desarrollo de enfermedades que incrementan el riesgo cardiovascular (diabetes mellitus, hipertensión arterial o dislipidemia aterogénica), así como a enfermedades que limitan la calidad de vida del paciente (osteoartrosis o apnea del sueño) y al incremento en la incidencia de ciertos tipos de cáncer (mama o colon). Es evidente que la disminución de al menos 5% del peso corporal induce mejoría en todos estos factores; sin embargo, en algunos pacientes es difícil alcanzar esta meta únicamente con modificaciones en el estilo de vida. En esta revisión se analizan algunos medicamentos aprobados para el control de peso por organismos nacionales e internacionales que pueden servir como auxiliares en conjunto con la dieta y el ejercicio. El tratamiento debe ser individualizado y deben evaluarse adecuadamente sus riesgos y beneficios.