Clinical Value of Liquid Biopsy in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma During Targeted Therapy.

PURPOSE: FGFR2 fusions occur in 10% to 15% of patients with intrahepatic cholangiocarcinoma (iCCA), potentially benefiting from FGFR inhibitors (FGFRi). We aimed to assess the feasibility of detecting FGFR2 fusions in plasma and explore plasma biomarkers for managing FGFRi treatment. EXPERIMENTAL DESIGN: We conducted a retrospective study in 18 patients with iCCA and known FGFR2 fusions previously identified in tissue samples from prior FGFRi treatment. Both tissue and synchronous plasma samples were analyzed using a custom hybrid capture gene panel with next-generation sequencing (VHIO-iCCA panel) and validated against commercial vendor results. Longitudinal plasma analysis during FGFRi was performed. Subsequently, we explored the correlation between plasma biomarkers, liver enzymes, tumor volume, and clinical outcomes. RESULTS: Sixteen patients (88.9%) were positive for FGFR2 fusion events in plasma. Remarkably, the analysis of plasma suggests that lower levels of ctDNA are linked to clinical benefits from targeted therapy and result in improved progression-free survival and overall survival. Higher concentrations of cell-free DNA before FGFRi treatment were linked to worse overall survival, correlating with impaired liver function and indicating compromised cell-free DNA removal by the liver. Additionally, increased ctDNA or the emergence of resistance mutations allowed earlier detection of disease progression compared with standard radiologic imaging methods. CONCLUSIONS: VHIO-iCCA demonstrated accurate detection of FGFR2 fusions in plasma. The integration of information from various plasma biomarkers holds the potential to predict clinical outcomes and identify treatment failure prior to radiologic progression, offering valuable guidance for the clinical management of patients with iCCA.

New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases.

Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production. (J Histochem Cytochem XX.XXX-XXX, XXXX).

Incidence of confusional syndrome (delirium) in a Latin American university hospital.

BACKGROUND: Little is known about the incidence of delirium and its subtypes in patients admitted to different departments of university hospitals in Latin America. OBJECTIVE: To determine the incidence of delirium and the frequency of its subtypes, as well as its associated factors, in patients admitted to different departments of a university hospital in Bogotá, Colombia. METHODS: A cohort of patients over 18 years of age admitted to the internal medicine (IM), geriatrics (GU), general surgery (GSU), orthopaedics (OU) and intensive care unit (ICU) services of a university hospital was followed up between January and June 2018. To detect the presence of delirium, we used the CAM (Confusion Assessment Method) and the CAM-ICU if the patient had decreased communication skills. The delirium subtype was characterised using the RASS (Richmond Agitation and Sedation Scale). Patients were assessed on their admission date and then every two days until discharged from the hospital. Those in whom delirium was identified were referred for specialised intra-institutional interdisciplinary management. RESULTS: A total of 531 patients admitted during the period were assessed. The overall incidence of delirium was 12% (95% CI, 0.3-14.8). They represented 31.8% of patients in the GU, 15.6% in the ICU, 8.7% in IM, 5.1% in the OU, and 3.9% in the GSU. The most frequent clinical display was the mixed subtype, at 60.9%, followed by the normoactive subtype (34.4%) and the hypoactive subtype (4.7%). The factors most associated with delirium were age (adjusted RR = 1.07; 95% CI, 1.05-1.09), the presence of four or more comorbidities (adjusted RR = 2.04; 95% CI, 1.31-3.20), and being a patient in the ICU (adjusted RR = 2.02; 95% CI, 1.22-3.35). CONCLUSIONS: The incidence of delirium is heterogeneous in the different departments of the university hospital. The highest incidence occurred in patients that were admitted to the GU. The mixed subtype was the most frequent one, and the main associated factors were age, the presence of four or more comorbidities, and being an ICU patient.

Incidencia del Síndrome Confusional (delirio) en un Hospital Universitario Latinoamericano / Incidence of confusional syndrome (delirium) in a Latin American university hospital

resumen Introducción: Poco se conoce acerca de la incidencia del delirio en pacientes hospitalizados en diferentes servicios de hospitales universitarios en Latinoamérica y de los subtipos que se presentan. Objetivo: Determinar la incidencia del delirio, la frecuencia de los subtipos motores y los factores asociados en pacientes hospitalizados en diferentes servicios de un hospital uni versitario en Bogotá, Colombia. Métodos: Se dio seguimiento a una cohorte de pacientes mayores de 18 arios hospitalizados en los servicios de Medicina Interna, Geriatría, Cuidado Intensivo, Cirugía General y Orto pedia de un hospital universitario entre enero y junio de 2018. Para identificar la presencia de delirio, se utilizó la escala CAM (Confusion Assessment Method) y la CAM-ICU si el paciente presentaba disminución de las capacidades de comunicación. El subtipo de delirio se carac terizó utilizando la escala RASS (Richmond Agitation and Sedation Scale). Los pacientes fueron valorados el día de ingreso y luego cada 2 días hasta su alta hospitalaria. Se derivó a los pacientes en quienes se identificó delirio para tratamiento especializado interdisciplinario intrainstitucional. Resultados: Se evaluó a 531 pacientes que ingresaron durante ese periodo a los servicios mencionados. La incidencia global del delirio fue del 12% (IC95%, 0,3-14,8). En orden des cendiente, el 31,8% de los pacientes hospitalizados en el servicio de Geriatría, el 15,6% en Cuidado Intensivo, el 8,7% en Medicina Interna, el 5,1% en Ortopedia y el 3,9% en Cirugía. El subtipo motor más frecuente fue el mixto (60,9%), seguido por el normoactivo (34,4%) y el hipoactivo (4,7%). Los factores asociados con la incidencia del delirio fueron la edad (RR ajustada = 1,07; IC95%, 1,05-1,09), la presencia de 4 o más comorbilidades (RR ajustada = 2,04; IC95%, 1,31-3,20) y la hospitalización en Cuidado Intensivo (RR ajustada = 2,02; IC95%, 1,22 3,35). Conclusiones: La incidencia del delirio es heterogénea en los diferentes servicios del hospital universitario. La mayor incidencia se presentó en pacientes ingresados en el servicio de Geriatría; el subtipo más frecuente fue el mixto y los principales factores asociados fueron la edad, la presencia de 4 o más comorbilidades y la hospitalización en Cuidado Intensivo.

abstract Bacfeground: Little is known about the incidence of delirium and its subtypes in patients admitted to different departments of university hospitals in Latin America. Objective: To determine the incidence of delirium and the frequency of its subtypes, as well as its associated factors, in patients admitted to different departments of a university hospital in Bogotá, Colombia. Methods: A cohort of patients over 18 years of age admitted to the internal medicine (IM), geriatrics (GU), general surgery (GSU), orthopaedics (OU) and intensive care unit (ICU) ser vices of a university hospital was followed up between January and June 2018. To detect the presence of delirium, we used the CAM (Confusion Assessment Method) and the CAM-ICU if the patient had decreased communication skills. The delirium subtype was characterised using the RASS (Richmond Agitation and Sedation Scale). Patients were assessed on their admission date and then every two days until discharged from the hospital. Those in whom delirium was identified were referred for specialised intra-institutional interdisciplinary management. Results: A total of 531 patients admitted during the period were assessed. The overall incidence of delirium was 12% (95% CI, 0.3-14.8). They represented 31.8% of patients in the GU, 15.6% in the ICU, 8.7% in IM, 5.1% in the OU, and 3.9% in the GSU. The most frequent clinical display was the mixed subtype, at 60.9%, followed by the normoactive subtype (34.4%) and the hypoactive subtype (4.7%). The factors most associated with delirium were age (adjusted RR = 1.07; 95% CI, 1.05-1.09), the presence of four or more comorbidities (adjusted RR = 2.04; 95% CI, 1.31-3.20), and being a patient in the ICU (adjusted RR = 2.02; 95% CI, 1.22-3.35). Conclusions: The incidence of delirium is heterogeneous in the different departments of the university hospital. The highest incidence occurred in patients that were admitted to the GU. The mixed subtype was the most frequent one, and the main associated factors were age, the presence of four or more comorbidities, and being an ICU patient.

Estudio Histológico en Embriones de Cobayo (Cavia porcellus) y su Utilidad como Modelo para la Comprensión del Desarrollo Embrionario Humano / Histological Study in Guinea Pig Embryos (Cavia porcellus) and its Usefulness as a Model for Understanding Human Embryonic Development

El cobayo es un modelo animal ampliamente utilizado en la investigación biomédica debido a sus similitudes biológicas con los seres humanos. El objetivo de nuestro estudio es proporcionar sustento morfológico para utilizar preparados histológicos de embriones de cobayo como modelo de estudio para comprender los procesos del desarrollo embrionario humano. Nuestros resultados muestran que los embriones de cobayo presentan características morfológicas similares a las observadas en los embriones humanos, lo que sugiere que pueden utilizarse como un modelo efectivo para estudiar el desarrollo embrionario humano. Este hallazgo tiene importantes implicancias para la investigación y la docencia utilizando este modelo animal. Se analizaron preparados histológicos de embriones de cobayo teñidos con hematoxilina eosina, adquiridos por la Universidad Autónoma de Chile. Se tomaron microfotografías de preparados histológicos de cobayo en diferentes estadios del desarrollo y se seleccionaron las mejores imágenes para la descripción de estructuras y establecer estimados de la embriogénesis. Del análisis de los preparados se desprende que órganos como esófago, médula espinal y corazón presentan similitudes anatómicas e histológicas que hacen posible compararlas con el desarrollo embrionario humano y la edad de gestación en etapas tempranas. El uso de preparados de embriones de cobayo y su análisis desde un aspecto histológico resulta ser una estrategia metodológica factible debido a las similitudes en la embriogénesis de los mamíferos y las concordancias morfológicas con el desarrollo de los órganos entre humanos y roedores. Esto permite implementar este modelo animal como una herramienta para comprender el desarrollo embrionario humano.

SUMMARY: The guinea pig is an animal model widely used in biomedical research due to its biological similarities with humans. The objective of our study is to provide morphological support to use histological preparations of guinea pig embryos as a study model to understand the processes of human embryonic development. Our results show that guinea pig embryos present morphological characteristics similar to those observed in human embryos, suggesting that they can be used as an effective model to study human embryonic development. This finding has important implications for research and teaching using this animal model. Histological preparations of guinea pig embryos stained with hematoxylin eosin, acquired by the Autonomous University of Chile, were analyzed. Photomicrographs of histological preparations of guinea pigs at different stages of development were taken and the best images were selected to describe structures and establish estimates of embryogenesis. From the analysis of the preparations it is clear that organs such as the esophagus, spinal cord and heart present anatomical and histological similarities that make it possible to compare them with human embryonic development and gestation age in early stages. The use of guinea pig embryo preparations and their analysis from a histological aspect turns out to be a feasible methodological strategy due to the similarities in mammalian embryogenesis and the morphological concordances with the development of organs between humans and rodents. This allows this animal model to be implemented as a tool to understand human embryonic development.

Differential roles of eNOS in late effects of VEGF-A on hyperpermeability in different types of endothelial cells.

Vascular endothelial growth factor (VEGF)-A induces endothelial hyperpermeability, but the molecular pathways remain incompletely understood. Endothelial nitric oxide synthase (eNOS) regulates acute effects of VEGF-A on permeability of endothelial cells (ECs), but it remains unknown whether and how eNOS regulates late effects of VEGF-A-induced hyperpermeability. Here we show that VEGF-A induces hyperpermeability via eNOS-dependent and eNOS-independent mechanisms at 2 days after VEGF-A stimulation. Silencing of expression of the eNOS gene (NOS3) reduced VEGF-A-induced permeability for dextran (70 kDa) and 766 Da-tracer in human dermal microvascular ECs (HDMVECs), but not in human retinal microvascular ECs (HRECs) and human umbilical vein ECs (HUVECs). However, silencing of NOS3 expression in HRECs increased permeability to dextran, BSA and 766 Da-tracer in the absence of VEGF-A stimulation, suggesting a barrier-protective function of eNOS. We also investigated how silencing of NOS3 expression regulates the expression of permeability-related transcripts, and found that NOS3 silencing downregulates the expression of PLVAP, a molecule associated with trans-endothelial transport via caveolae, in HDMVECs and HUVECs, but not in HRECs. Our findings underscore the complexity of VEGF-A-induced permeability pathways in ECs and the role of eNOS therein, and demonstrate that different pathways are activated depending on the EC phenotype.

Risk factors associated with hemorrhagic cerebrovascular accident: A cross-sectional study in patients from a hospital in Peru.

In Peru, cardiovascular accidents (CVA) cause around 15% of premature death, with an increase in CVA due to the prevalence of risk factors for CVA in the Peruvian population. Hemorrhagic CVA presents higher mortality compared to ischemic. This research aimed to identify the risk factors associated with hemorrhagic CVA. We carried out a retrospective cross-sectional study using the medical records of patients with a diagnosis of CVA treated at the Regional Hospital of Ica during the years 2018 and 2019. Independent variables included age, sex, type 2 diabetes, dyslipidemia, hypertension, smoking, obesity, and intracranial carotid artery calcification. To identify factors associated with an increased probability for hemorrhagic CVA compared to ischemic CVA, a generalized linear model with logit link and binomial family, obtaining the odds ratio (OR) and its 95% confidence interval (CI). we evaluated the data from 132 patients. Of them, 46 (34.85%) had hemorrhagic CVA. Only systolic blood pressure (OR: 1.04; 95% CI: 1.02-1.06) and hypertension (OR: 0.29; 95% CI: 0.10-0.89) were significantly associated with hemorrhagic CVA compared to ischemic CVA. Hypertension is associated with hemorrhagic CVA compared to ischemic CVA. These results are consistent with the literature.

Durvalumab-induced Pure White Cell Aplasia.

Immune checkpoint inhibitors (ICI) have gained approval as a treatment for a wide array of cancers. Their mechanism of action prevents the inactivation of cytotoxic T-cells, allowing for its cytotoxic response. However, the upregulation of the immune system by ICI also leads to many undesired adverse events known as immune-related adverse events (irAEs), ranging from dermatologic manifestations, such as rashes, to inflammation of mucous membranes, to hematologic toxicities. Here, we report a case of ICI-induced pure white cell aplasia, secondary to the agent durvalumab, which responded to treatment with filgrastim, prednisone, and cyclosporine. ICI-neutropenia accounts for 0.6% of all irAEs or 17% of hematologic irAEs. Given the rarity of hematologic irAEs, the available treatment guidelines are based on expert consensus. As ICI becomes more widely used, we can expect an increase in the prevalence of rare irAEs as well. This case report aims to present a rare side effect of ICI and demonstrate its response to immunosuppressive therapy while providing guidance for future clinicians and further elucidating the mechanism behind these irAEs.

Dilatación idiopática de la aurícula derecha. Reporte de caso y revisión de la literatura / Idiopathic dilatation of the right atrium. Case report and literature review

Resumen La dilatación idiopática de la aurícula derecha (DIAD) es una malformación poco frecuente caracterizada por un crecimiento desproporcionado de la aurícula derecha en ausencia de una causa estructural o funcional que la justifique. Presentamos el caso de una paciente con DIAD con diagnóstico desde la etapa prenatal.

Abstract Idiopathic dilatation of the right atrium is a rare malformation characterized by disproportionate growth of the right atrium in the absence of a cause that justifies it. We present the case of a patient with idiopathic dilatation of the right atrium diagnosed since fetal life.

The Hippo signaling pathway effector YAP promotes salivary gland regeneration after injury.

Salivary glands are damaged by radiotherapy for head and neck cancers, which often culminates in radiation-induced hyposalivation and xerostomia that may be permanent. Here, we identified a central role for YAP in the regenerative response of the salivary gland. Activation of the Hippo signaling pathway inhibits the phosphorylation of YAP, leading to its nuclear translocation and transcriptional activity. Using mice with salivary gland injury induced by surgical ligation and salivary gland­derived organoids, we found that YAP nuclear localization in the salivary gland epithelium changed dynamically between homeostasis and regeneration. Whereas local injury had no effect on nuclear YAP localization in saliva-producing acinar cells, it triggered nuclear accumulation of YAP in saliva-transporting ductal cells. Injury also stimulated the proliferation of ductal cells, which were mainly quiescent under homeostatic conditions and in nonregenerating areas distal to the injury site, thus enabling salivary gland regeneration. Overexpressing YAP or driving YAP nuclear translocation by inhibiting upstream Hippo pathway kinases increased the capacity of mouse and human salivary gland cells, including human cells that had been irradiated, to form lobed organoids in vitro. Our results identify a YAP-driven regeneration program in salivary gland ductal cells that could be used to promote salivary gland regeneration after irradiation-induced damage.

Nivelación propedéutica y rendimiento académico en la Universidad Bernardo O'Higgins de Chile / Preparatory leveling and academic performance in Bernardo O'Higgins University of Chile

Introducción: Esta investigación presenta los resultados preliminares del plan de Nivelación académica de la Universidad Bernardo O´Higgins, realizado en 2018 y denominado Nivelación Cero. Este proyecto es parte de la estrategia institucional, diseñada como una extensión del programa de nivelación de la universidad, para apoyar a los estudiantes nuevos en el repaso de contenidos escolares y estrategias de autogestión, para afrontar las exigencias del primer año de estudios. Objetivo: Exponer en qué medida un plan de acompañamiento propedéutico contribuye con la mejora del rendimiento en los estudiantes de nuevo ingreso. Métodos: En marzo de 2018 se llevó a cabo un estudio comparativo basado en un análisis estadístico multivariado (hj-Biplot), sobre los resultados obtenidos en la aprobación semestral general y en las asignaturas críticas de la formación, situados en el primer semestre de carrera. Resultado: La aplicación del programa de Nivelación Cero en el primer semestre de 2018 determinó de forma positiva la cantidad de aprobación en materias críticas de la carrera elegida. Conclusiones: Esta experiencia da cuenta de la importancia que tiene la realización de procesos de nivelación, tendientes a hacer del sistema universitario un espacio que promueva la equidad(AU)

ABSTRACT Introduction: This research presents the preliminary results of Bernardo O'Higgins University's academic leveling plan, carried out in 2018 and called "Nivelación Cero" [Zero Leveling]. This project is part of the institutional strategy designed as an extension of the university's leveling program, in order to support new students in reviewing school content and regarding self-management strategies, to face the demands of the first academic year. Objective: To expose to what extent a preparatory support plan contributes to improving the performance of new students. Methods: In March 2018, a comparative study was carried out based on a multivariate statistical analysis (hj-Biplot), on the results obtained in the general semester completion qualification as well as in the critical subjects of the training, located in the first semester of the major. Results: The application of the "Nivelación Cero" program in the first semester of 2018 positively determined the amount of completion qualification in critical subjects of the chosen major. Conclusions: This experience shows the importance of carrying out leveling processes, aimed at making the university system a space that promotes equity.

Optimal Allocation of Chemotherapy Schemes for Metastatic Colon Cancer in Colombia.

OBJECTIVES: This study aims to determine the optimal proportion for different chemotherapy schemes in patients with metastatic colorectal cancer who have undergone surgical resection in Colombia. METHODS: A linear programming model was used to quantify the optimal proportion of the chemotherapy schemes that maximize quality-adjusted life-years (QALYs). The model was evaluated in 6 different scenarios using parametric and dynamic optimization with different budget restriction constraints. The results were compared to the current mixture of schemes used in our country. RESULTS: The results show that 63%, 37%, and 0.8% of the population should receive the FOLFOXIRI scheme (fluorouracil + leucovorin + oxaliplatin + irinotecan), FOLFIRI (irinotecan + leucovorin + fluorouracil), and FOLFIRI plus cetuximab, respectively. With these proportions, 8734 QALYs and universal coverage of the population are obtained. In an optimistic scenario (high QALYs, low costs, and budget of $40 million), the entire population should receive the FOLFIRI scheme. A pessimistic scenario (low QALYs, high costs, and budget of $15 million) would benefit only 46% of the population with the fluorouracil plus leucovorin scheme. In the other 3 scenarios with higher budget constraints, 52%, 69%, and 86% of the population should receive FOLFIRI, respectively. Dynamic optimization revealed that FOLFIRI and FOLFOX (oxaliplatin + leucovorin + fluorouracil) schemes are more likely to generate higher QALYs with lower costs and a limited budget. CONCLUSIONS: The current use of chemotherapy schemes is not optimal. An increasing proportion of FOLFIRI, FOLFOX, and FOLFOXIRI should be used more often as schemes to treat metastatic colorectal cancer in Colombia.

The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways.

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.

Mouse parotid salivary gland organoids for the in vitro study of stem cell radiation response.

OBJECTIVE: Hyposalivation-related xerostomia is an irreversible, untreatable, and frequent condition after radiotherapy for head and neck cancer. Stem cell therapy is an attractive option of treatment, but demands knowledge of stem cell functioning. Therefore, we aimed to develop a murine parotid gland organoid model to explore radiation response of stem cells in vitro. MATERIALS AND METHODS: Single cells derived from murine parotid gland organoids were passaged in Matrigel with defined medium to assess self-renewal and differentiation potential. Single cells were irradiated and plated in a 3D clonogenic stem cell survival assay to assess submandibular and parotid gland radiation response. RESULTS: Single cells derived from parotid gland organoids were able to extensively self-renew and differentiate into all major tissue cell types, indicating the presence of potential stem cells. FACS selection for known salivary gland stem cell markers CD24/CD29 did not further enrich for stem cells. The parotid gland organoid-derived stem cells displayed radiation dose-response curves similar to the submandibular gland. CONCLUSIONS: Murine parotid gland organoids harbor stem cells with long-term expansion and differentiation potential. This model is useful for mechanistic studies of stem cell radiation response and suggests similar radiosensitivity for the parotid and submandibular gland organoids.

Evolving Landscape of Molecular Prescreening Strategies for Oncology Early Clinical Trials.

Most academic precision oncology programs have been designed to facilitate enrollment of patients in early clinical trials with matched targeted agents. Over the last decade, major changes were seen both in the targetable molecular alteration landscape and in drug development trends. In this article, we describe how the Vall d'Hebron Institute of Oncology molecular prescreening program adapted to a dynamic model of biomarker-drug codevelopment. We started with a tumor-agnostic hotspot mutation panel plus in situ hybridization and immunohistochemistry of selected markers and subsequently transitioned to tumor-specific amplicon-based next-generation sequencing (NGS) tests together with custom copy number, fusion, and outlier gene expression panels. All assays are optimized for archived formalin-fixed paraffin-embedded tumor tissues without matched germline sequencing. In parallel, biomarker-matched trials evolved from a scenario of few targets and large populations (such as PI3K inhibitors in PIK3CA mutants) to a complex situation with many targets and small populations (such as multiple targetable fusion events). Recruitment rates in clinical trials with mandatory biomarkers decreased over the last 3 years. Molecular tumor board meetings proved critical to guide oncologists on emerging biomarkers for clinical testing and interpretation of NGS results. The substantial increase of immunotherapy trials had a major impact in target prioritization and guided clinical implementation of new markers, such as tumor mutational burden, with larger exon-based NGS assays and gene expression signatures to capture microenvironment infiltration patterns. This new multiomics era of precision oncology is expected to increase the opportunities for early clinical trial matching.

Depresión del adulto mayor peruano y variables sociodemográficas asociadas: análisis de endes 2017 / Depression of the peruvian elderly adult and associated sociodemographical variables, analysis of endes 2017

Objetivo: Determinar las variables sociodemográficas asociadas a la depresión en el adulto mayor peruano a partir de la información obtenida mediante la Encuesta Demográfica y de Salud Familiar (ENDES) del año 2017 realizada por el Instituto Nacional de Estadística e Informática (INEI). Métodos: Estudio observacional, correlacional y de corte transversal que usó una muestra probabilística de 4917 adultos mayores (60 años a más). Para la determinación de depresión en la población se usó como instrumento el Patient Health Questionnaire (PHQ) de 9 preguntas, incluido en el cuestionario de salud en la sección de salud mental del ENDES 2017. Resultados: La prevalencia de depresión en el adulto mayor peruano en el año 2017 fue de 14,2%. Como variables sociodemográficas asociadas a la depresión fueron el sexo femenino [ORaj 1,995 (1,684 -2,364)]; carecer de instrucción [ORaj 2,524 (2,126 - 2,996)]; la edad mayor de 75 años [ORaj 1,763 (1,494 - 2,080)]; vivir en una zona rural [ORaj 1,410 (1,198 -1,659)]; y ser pobre [ORaj 1,456 (1,229 - 1,724)]. No hubo asociación entre depresión y discapacidad (p=0,704). [ORaj 1,103 (0,663 - 1,835)]. Conclusión: La prevalencia de depresión en el adulto mayor peruano es alta. Las variables sociodemográficas que estuvieron asociadas como factores de riesgo para el desarrollo de depresión en el adulto mayor fueron de sexo femenino, el carecer de instrucción, edad mayor de 75 años, vivir en zona rural y ser pobre.

Objective: To determine the sociodemographic variables associated with depression in the elderly of Peru based on the information obtained through the Demographic and Family Health Survey (ENDES) of the year 2017 carried out by the National Institute of Statistics and Informatics (INEI). Methods: An observational, correlational and cross-sectional study that used a probabilistic sample of 4917 older adults (60 years and over). For the determination of depression in the population, the Patient Health Questionnaire (PHQ) of 9 questions included in the health questionnaire in the mental health section of ENDES 2017 was used as an instrument. Results: The prevalence of depression in the Peruvian elderly in 2017 was 14.2%. As sociodemographic variables associated with depression were the female sex [OR 1.995 (1.684 -2.364)]; lack instruction [ORaj 2.524 (2.126-2996)]; the age over 75 years [ORaj 1.763 (1.494 2.080)]; live in a rural area [ORaj 1.410 (1.198 -1.659)]; and be poor [ORaj 1.456 (1.229 - 1.724)]. It was not associated with disability (p = 0.704). [ORaj 1.103 (0.663-1835)]. Conclusion: It was concluded that the prevalence of depression in the Peruvian adult is high. Among the sociodemographic variables that were identified as risk factors for presenting depression were female sex, lacking education, age over 75, living in rural areas and being poor.

Análisis de género de clases de la autodeterminación del rendimiento y la motivación en clase de Educación Física / Gender analysis of motivation and performance self-assessment in physical education class

Introducción: En la actualidad los estudiantes no se motivan para realizar actividad física en la clase de Educación Física y esto se agrava en el género femenino, dado que tienen mayores índices de obesidad y desmotivación, es un tema contingente en la actualidad de la educación chilena que debe ser abordado. Objetivo: Analizar los factores que inciden en la escasa motivación de estudiantes de género femenino de octavo grado básico en Educación Física. Métodos: El diseño de investigación fue de carácter mixto, ya que estuvo basado en la combinación de metodologías y técnicas de recolección de información cuantitativas y cualitativas. Resultados: Se realizaron análisis y evaluación de diagnóstico rendimiento mujeres y hombres de octavo grado básico en Educación Física. Análisis multivariados de las variables: práctica educativa, metodología y motivación de resultados validados que mostraron una tendencia en sus resultados. Conclusiones: El análisis confirma que las alumnas de octavo básico no se motivan y tampoco participan de forma regular en la clase de Educación Física, porque las actividades no se vinculan a sus intereses e inquietudes propias de una adolescente. Además, presentan desgano en realizar actividades deportivas aludiendo a las exigencias del profesor y actividades que están orientadas hacia los intereses del sexo masculino en desmedro del sexo femenino(AU)

Introduction: Current lack of motivation by students to actively engage in physical activity during physical education class is more marked among girls, given their higher obesity and disinterest indices. This urgent problem of Chilean education requires immediate analysis. Objective: Analyze the teaching and methodological factors affecting the scant motivation of female 8th grade junior high school students for physical education classes, as well as their variability and dispersion. Methods: A mixed research design was used based on a combination of quantitative and qualitative data collection methodologies and techniques. Results: Diagnostic analysis and evaluation were conducted of the performance of 8 th grade junior high school male and female students in physical education. Multivariate analysis was performed of the variables educational practice, methodology and motivation of validated results showing a trend in their values. Conclusions: Analysis confirmed that female 8th grade students lack motivation and do not attend physical education class regularly, since those activities have little to do with the likes and interests of adolescents. The students stated that their reluctance to participate in sport activities is due to the demands of teachers and the activities themselves, geared as they are to the interests of the male sex at the expense of female students(AU)

Hemorragia digestiva e insuficiencia hepática aguda por leptospirosis: una entidad que no debemos olvidar / Gastrointestinal bleeding and acute hepatic failure by leptospirosis: an entity that should not be forgotten

La leptospirosis es una enfermedad causada por la espiroqueta Leptospira. Se trata de una zoonosis de distribución mundial, con predominio en los trópicos. En España no es frecuente pero sí se observan casos en zonas más húmedas o con presencia de ríos, lagos o estanques, como son Cataluña, Andalucía o la Comunidad Valenciana, donde se relaciona con los arrozales. Los transmisores son múltiples animales como vacas o ratas, contagiándose el ser humano mediante contacto directo con estos animales o su orina, o bien de forma indirecta al consumir o estar en contacto con agua contaminada por la orina de éstos. Las manifestaciones clínicas son muy variables, siendo asintomática o poco sintomática en la mayoría de los pacientes. Aunque no ocurre siempre, la leptospirosis cursa con una primera fase con fiebre, mialgias, afectación renal o hemorragia de distintos órganos, seguida de una segunda fase con presencia de ictericia por afectación hepática. La enfermedad de Weil es una forma de leptospirosis grave caracterizada por afectación hepática con ictericia e insuficiencia renal aguda, asociada a una considerable mortalidad. El diagnóstico se basa en técnicas serológicas y detección de DNA mediante PCR. El tratamiento consta de medidas de soporte y antibioticoterapia. Presentamos un paciente con enfermedad de Weil y hemorragia digestiva por leptospirosis, con una evolución clínica fulminante, y hacemos hincapié en la necesidad de tener presente esta entidad, especialmente en ambientes epidemiológicos favorables como el de este paciente, con el fin de lograr un diagnóstico precoz.

Leptospirosis disease is caused by the spirochete Leptospira. It is a worldwide distribution zoonosis, with predominance in the tropics. In Spain, it is not frequent but some cases have been noticed especially in humid areas surrounded by rivers, lakes or ponds, such as Catalonia, Andalucia or the Valencian Community. It is transmitted by a variety of animals such as cows or rats, that are infected either by direct contact with these animals or their urine, or indirectly by consuming or being in contact with water contaminated by their urine. The clinical manifestations are very variable, being asymptomatic or not very symptomatic in most of the patients. Unusually, leptospirosis presents with a first phase with fever, myalgias, liver injury or different organs hemorrhage, followed by a second phase with the presence of jaundice due to hepatic failure. Weil's disease is a kind of severe leptospirosis characterized by hepatic failure with jaundice and acute renal failure, associated with high mortality rates. The diagnosis is based on serological techniques and DNA detection by PCR. The treatment consists of life support measures and antibiotic therapy. A patient with Weil's disease and leptospirosis digestive bleeding is presented, with a fulminant clinical course. In order to achieve an early diagnosis, the need to keep this entity in mind must be emphasized, especially in favorable epidemiological environments as the one of this patient.

Use of Iodine to Biofortify and Promote Growth and Stress Tolerance in Crops.

Iodine is not considered essential for land plants; however, in some aquatic plants, iodine plays a critical role in antioxidant metabolism. In humans, iodine is essential for the metabolism of the thyroid and for the development of cognitive abilities, and it is associated with lower risks of developing certain types of cancer. Therefore, great efforts are made to ensure the proper intake of iodine to the population, for example, the iodization of table salt. In the same way, as an alternative, the use of different iodine fertilization techniques to biofortify crops is considered an adequate iodine supply method. Hence, biofortification with iodine is an active area of research, with highly relevant results. The agricultural application of iodine to enhance growth, environmental adaptation, and stress tolerance in plants has not been well explored, although it may lead to the increased use of this element in agricultural practice and thus contribute to the biofortification of crops. This review systematically presents the results published on the application of iodine in agriculture, considering different environmental conditions and farming systems in various species and varying concentrations of the element, its chemical forms, and its application method. Some studies report beneficial effects of iodine, including better growth, and changes in the tolerance to stress and antioxidant capacity, while other studies report that the applications of iodine cause no response or even have adverse effects. We suggested different assumptions that attempt to explain these conflicting results, considering the possible interaction of iodine with other trace elements, as well as the different physicochemical and biogeochemical conditions that give rise to the distinct availability and the volatilization of the element.