Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology.

Introduction: Gastric cancer is one of the most prevalent types of cancer worldwide. The World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and the Global Cancer Statistics (GLOBOCAN) reported an age standardized global incidence rate of 9.2 per 100,000 individuals for gastric cancer in 2022, with a mortality rate of 6.1. Despite considerable progress in precision oncology through the efforts of international consortia, understanding the genomic features and their influence on the effectiveness of anti-cancer treatments across diverse ethnic groups remains essential. Methods: Our study aimed to address this need by conducting integrated in silico analyses to identify actionable genomic alterations in gastric cancer driver genes, assess their impact using deleteriousness scores, and determine allele frequencies across nine global populations: European Finnish, European non-Finnish, Latino, East Asian, South Asian, African, Middle Eastern, Ashkenazi Jewish, and Amish. Furthermore, our goal was to prioritize targeted therapeutic strategies based on pharmacogenomics clinical guidelines, in silico drug prescriptions, and clinical trial data. Results: Our comprehensive analysis examined 275,634 variants within 60 gastric cancer driver genes from 730,947 exome sequences and 76,215 whole-genome sequences from unrelated individuals, identifying 13,542 annotated and predicted oncogenic variants. We prioritized the most prevalent and deleterious oncogenic variants for subsequent pharmacogenomics testing. Additionally, we discovered actionable genomic alterations in the ARID1A, ATM, BCOR, ERBB2, ERBB3, CDKN2A, KIT, PIK3CA, PTEN, NTRK3, TP53, and CDKN2A genes that could enhance the efficacy of anti-cancer therapies, as suggested by in silico drug prescription analyses, reviews of current pharmacogenomics clinical guidelines, and evaluations of phase III and IV clinical trials targeting gastric cancer driver proteins. Discussion: These findings underline the urgency of consolidating efforts to devise effective prevention measures, invest in genomic profiling for underrepresented populations, and ensure the inclusion of ethnic minorities in future clinical trials and cancer research in developed countries.

The pharmacoepigenetic paradigm in cancer treatment.

Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role in the development and progression of cancer by significantly influencing gene activity and cellular function. This insight has led to the development of a novel class of therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, histone methyltransferase inhibitors, and DNA methyltransferase inhibitors, aim to modulate gene expression to curb cancer growth by uniquely altering the epigenetic landscape of cancer cells. Ongoing research and clinical trials are rigorously evaluating the efficacy of these drugs, particularly their ability to improve therapeutic outcomes when used in combination with other treatments. Such combination therapies may more effectively target cancer and potentially overcome the challenge of drug resistance, a significant hurdle in cancer therapy. Additionally, the importance of nutrition, inflammation control, and circadian rhythm regulation in modulating drug responses has been increasingly recognized, highlighting their role as critical modifiers of the epigenetic landscape and thereby influencing the effectiveness of pharmacological interventions and patient outcomes. Epigenetic drugs represent a paradigm shift in cancer treatment, offering targeted therapies that promise a more precise approach to treating a wide spectrum of tumors, potentially with fewer side effects compared to traditional chemotherapy. This progress marks a step towards more personalized and precise interventions, leveraging the unique epigenetic profiles of individual tumors to optimize treatment strategies.

Hacia una atención de calidad integral en las maternidades con perspectiva de derechos humanos / Towards a comprehensive quality of care in birthing facilities with human rights perspective

Resumen La calidad de la atención obstétrica hoy no solo se limita a tener profesionales con competencias técnicas basadas en evidencia científica, sino que incluye la atención centrada en la mujer, persona gestante y su familia, como expresión del respeto de sus derechos humanos. Este artículo revisa cómo el tema ha sido abordado globalmente y nacionalmente desde la Conferencia de Fortaleza en 1985 hasta la presentación reciente de proyectos de ley en el parlamento chileno.

Abstract Obstetric quality of care today means not only having skilled providers with evidence-based competences but it includes woman, pregnant person and family-centered reproductive health as expression of respect of their human rights. This article reviews how this issue has been approached in a global and national level since Fortaleza Conference in 1985 until recent bills of law proposed before Chilean parliament.

A Web Platform (MOSAICO) to Design, Perform, and Assess Collaborative Clinical Scenarios for Medical Students: Viewpoint.

BACKGROUND: The collaborative clinical simulation (CCS) model is a structured method for the development and assessment of clinical competencies through small groups working collaboratively in simulated environments. From 2016 onward, the CCS model has been applied successfully among undergraduate and graduate medical students from the Universidad de Talca, Chile; the Universität de Barcelona, Spain; and the Universidad de Vic-Manresa, Spain. All the templates for building the clinical cases and the assessment instruments with CCS were printed on paper. Considering the large number of CCS sessions and the number of participating students that are required throughout the medical degree curriculum, it is impossible to keep an organized record when the instruments are printed on paper. Moreover, with the COVID-19 pandemic, web platforms have become important as safe training environments for students and medical faculties; this new educational environment should include the consolidation and adaptation of didactic sessions that create and use available virtual cases and use different web platforms. OBJECTIVE: The goal of this study is to describe the design and development of a web platform that was created to strengthen the CCS model. METHODS: The design of the web platform aimed to support each phase of the CCS by incorporating functional requirements (ie, features that the web platform will be able to perform) and nonfunctional requirements (ie, how the web platform should behave) that are needed to run collaborative sessions. The software was developed under the Model-View-Controller architecture to separate the views from the data model and the business logic. RESULTS: MOSAICO is a web platform used to design, perform, and assess collaborative clinical scenarios for medical students. MOSAICO has four modules: educational design, students' collaborative design, collaborative simulation, and collaborative debriefing. The web platform has three different user profiles: academic simulation unit, teacher, and student. These users interact under different roles in collaborative simulations. MOSAICO enables a collaborative environment, which is connected via the internet, to design clinical scenarios guided by the teacher and enables the use of all data generated to be discussed in the debriefing session with the teacher as a guide. The web platform is running at the Universidad de Talca in Chile and is supporting collaborative simulation activities via the internet for two medical courses: (1) Semiology for third-year students (70 students in total) and (2) Medical Genetics for fifth-year students (30 students in total). CONCLUSIONS: MOSAICO is applicable within the CCS model and is used frequently in different simulation sessions at the Universidad de Talca, where medical students can work collaboratively via the internet. MOSAICO simplifies the application and reuse of clinical simulation scenarios, allowing its use in multiple simulation centers. Moreover, its applications in different courses (ie, a large part of the medical curriculum) support the automatic tracking of simulation activities and their assessment.

Left ventricular assist device (LVAD) program in Chile: first successful experience in South America.

BACKGROUND: The need to have a variety of tools to deal with end-stage heart failure (ES-HF), along with the limited heart transplantation availability encouraged us to create a pilot Left ventricular assist device (LVAD) program in a public health care system hospital in Chile. METHODS: A retrospective analysis of the first nine patients of an ongoing LVAD program initiated on August 2013 was performed, completing an average of 30 months of follow-up. The most important events regarding to morbidity and mortality are described. RESULTS: Nine patients with ES-HF underwent LVAD implantation surgery; one of them died 23 days after surgery and another died after 11 months. One patient successfully underwent heart transplantation after 16 months of HeartWare ventricular assist device (HVAD) support; the other six patients remain in the program and have an average follow-up of 846 days at the time of this study (range, 23-1,481 days). The survival rate at 6, 12 and 18 months follow-up was 89%, 78% and 78% respectively. CONCLUSIONS: This new pioneering LVAD program in Chile has been successful and now constitutes a vital adjunct to all who work in heart transplantation and ES-HF programs. It offers an effective therapeutic alternative when there is a severe donor shortage, in cases of atypical blood types, emergencies, exceptional cases with contraindication for heart transplantation or when there is important donor-receiver size mismatch.

Reacción tuberculínica en lactantes sanos vacunados con BCG al nacer / Tuberculin reaction in healthy infants vaccinated with at birth

Doscientos veintiocho lactantes sanos, vacunados con BCG al nacer, sin antecedentes de contacto con TBC ni de condición anergizante alguna, fueron estudiados consecutivamente mediante prueba cutánea de tuberculina con 2 UT de PPD RT 23, con detergente (Tweenn 80) agregado. El propósito de este estudio fue evaluar la respuesta a 2 UT de PPD que, a esta edad, es principalmente inducida por la vacuna BCG. Solamente 8,8% de los lactantes estudiados tuvieron reacción positiva al PPD. No se encontró cicatriz BCG en 16,2% de los pacientes, y en 14,9% no hubo reacción al PPD ni de cicatriz. Estos resultados son significativamente diferentes y fueron estudiados con PPD 2 UT del mismo origen, sugieren la necesidad de evaluar las vacunas actualmente en uso y también de determinar la existencia de factores que pudieran alterar su eficacia, o influir en la evaluación del grado de protección otorgado por tales vacunas