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RESUMEN Los inhibidores de la tirosina quinasa han cambiado drásticamente la perspectiva clínica de los pacientes con cáncer de pulmón de células no pequeñas avanzado con mutaciones del receptor del factor de crecimiento epidérmico. Sin embargo, existen aún retos en el manejo de los pacientes con esta mutación en un escenario metastásico, como es la resistencia intrínseca y adquirida a inhibidores de tirosina quinasa. Se discutirán los últimos avances y nuevas estrategias en primera línea de tratamiento, resistencia a osimertinib y tratamiento en mutación, en el exón 20.

ABSTRACT Tyrosine kinase inhibitors have dramatically changed the clinical outcomes for patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutations. However, there are still challenges in the management of patients with this mutation in a metastatic setting, such as intrinsic and acquired resistance to tyrosine kinase inhibitors. We will discuss the latest advances and new strategies in first-line treatment, osimertinib resistance, and exon 20 mutation treatment.

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Background: Erythroblast erythroferrone (ERFE) secretion inhibits hepcidin expression by sequestering several bone morphogenetic protein (BMP) family members to increase iron availability for erythropoiesis. Methods: To address whether ERFE functions also in bone and whether the mechanism of ERFE action in bone involves BMPs, we utilize the Erfe-/- mouse model as well as ß-thalassemic (Hbbth3/+) mice with systemic loss of ERFE expression. In additional, we employ comprehensive skeletal phenotyping analyses as well as functional assays in vitro to address mechanistically the function of ERFE in bone. Results: We report that ERFE expression in osteoblasts is higher compared with erythroblasts, is independent of erythropoietin, and functional in suppressing hepatocyte hepcidin expression. Erfe-/- mice display low-bone-mass arising from increased bone resorption despite a concomitant increase in bone formation. Consistently, Erfe-/- osteoblasts exhibit enhanced mineralization, Sost and Rankl expression, and BMP-mediated signaling ex vivo. The ERFE effect on osteoclasts is mediated through increased osteoblastic RANKL and sclerostin expression, increasing osteoclastogenesis in Erfe-/- mice. Importantly, Erfe loss in Hbbth3/+mice, a disease model with increased ERFE expression, triggers profound osteoclastic bone resorption and bone loss. Conclusions: Together, ERFE exerts an osteoprotective effect by modulating BMP signaling in osteoblasts, decreasing RANKL production to limit osteoclastogenesis, and prevents excessive bone loss during expanded erythropoiesis in ß-thalassemia. Funding: YZG acknowledges the support of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01 DK107670 to YZG and DK095112 to RF, SR, and YZG). MZ acknowledges the support of the National Institute on Aging (U19 AG60917) and NIDDK (R01 DK113627). TY acknowledges the support of the National Institute on Aging (R01 AG71870). SR acknowledges the support of NIDDK (R01 DK090554) and Commonwealth Universal Research Enhancement (CURE) Program Pennsylvania.

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El linfoma difuso de células B grandes es el subtipo más común de los linfomas no Hodking. La presentación clínico-patológica es heterogénea, los exámenes de inmunohistoquímica y moleculares genéticas son pieza clave en el diagnóstico. Entre las presentaciones cutáneas de este linfoma, la más común es la tipo piernas. Sin embargo, en el presente artículo se reporta un caso de una mujer con presentación facial y compromiso grave _ El diagnóstico definitivo se da por suma de criterios patológicos y por inmunohistoquímica. La paciente recibió esquema CHOP (ciclofosfamida, doxorrubicina, vincristina, prednisona), y en los dos primeros meses presentó una excelente respuesta.

Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphomas. The clinical-pathological presentation is heterogeneous, immunohistochemistry and molecular genetics test are so important in diagnosis. Among the cutaneous presentations of this lymphoma, the most common is in the leg, however, on this occasion we reported a case of facial presentation with severe compromise. The definitive diagnosis is given by the sum of pathological and immunohistochemical criterias, the patient received CHOP scheme, which in the first two months had an excellent response.

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OBJETIVO: Conocer las características de uso y los niveles de dependencia al internet de estudiantes de medicina de Lima; y determinar la relación entre estas variables. MATERIAL Y MÉTODOS: Estudio descriptivo, observacional, en estudiantes de medicina del tercer año de tres universidades: Universidad San Martin de Porres, Universidad Nacional Mayor de San Marcos y Universidad Peruana Cayetano Heredia (N=308). Se utilizaron dos instrumentos: 1) Cuestionario sobre las características de uso del internet; 2) Test de dependencia, IAT modificado y validado (alfa de Cronbach=0.91). RESULTADOS: La edad media fue 20 años. Uso diario, con un promedio de 4 horas por día. El tipo de uso fue predominantemente académico (100%), seguido de la comunicación-interacción social y recreativa. Según el género, se pudo observar que los hombres tuvieron más problemas sobre el control del uso de internet (36.5%). Mayor número de usuarios con problemas frecuentes se encontró en la UNMSM (35.4%), proseguido por la UPCH (32.7%). La correlación de las paginas o aplicaciones más usadas y el nivel de dependencia (p<0.05), se obtuvieron: Yahoo respuestas, Pokerstart, Facebook aplicaciones y Seriesyonkis. CONCLUSIONES: La población no presentó nivel alto de dependencia al Internet. Un tercio (30.7%), mostró problemas frecuentes respecto al uso. No se determinó correlación entre el nivel de dependencia y las horas de uso.

OBJETIVE: To determine the characteristics of use and levels of dependency Internet in medical students of Lima, and determine the relationship between these variables. MATERIALS AND METHODS: A descriptive, observational, and medical students the third year of three universities: Universidad San Martin de Porres, Universidad Nacional Mayor de San Marcos and Universidad Peruana Cayetano Heredia (N = 308). Two instruments were used: 1) Questionnaire on the characteristics of Internet use, 2) dependence test, IAT modified and validated (CronbachÆs alpha = 0.91). RESULTS: The mean age was 20 years. There is a daily use with an average of 4 hours per day. The type of use was predominantly academic (100%), followed by communication, social interaction and recreation. By gender, it was observed that men had more problems on the control of Internet usage (36.5%). Most users with common problems found in the San Marcos University (35.4%), continued by the UPCH (32.7%). The correlation of the pages orapplications used and the level of dependence (p <0.05) were obtained: Yahoo answers, Pokerstart, Facebook applications and Seriesyonkis.CONCLUSIONS: The population does not have high levels of dependence on the Internet. One third of the population (30.7%) had frequent problems about use. Not determined a correlation between the level of dependency and hours of use, this may be a characteristic of the population.

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