Perfil de consulta ambulatoria otorrinolaringológica en pandemia por COVID-19 / Profile of patients in otorhinolaryngological consultation in a COVID-19 pandemic

Introducción: La patología otorrinolaringológica (ORL) presenta alta incidencia en atención primaria, alcanzando hasta 49% de las consultas, sin embargo, la pandemia por SARS-CoV-2 repercutió de manera transversal en los servicios sanitarios, pudiendo haber influido en el perfil de consulta, por lo que se requiere un análisis para la elaboración de estrategias que permitan asegurar la atención sanitaria ante eventos de esta magnitud. Objetivo: Analizar el perfil de consulta libre por patología ORL ambulatoria en un centro médico privado en La Serena durante los años 2019 y 2020. Material y Método: Estudio analítico de corte transversal sobre consultas ambulatorias durante los años 2019 y 2020 realizadas en un centro privado de atención abierta en La Serena. Se estimaron frecuencias en números absolutos y proporciones, estimación de promedios y medianas. Resultados: Durante 2019 hubo un total de 11.932 consultas y en 2020 hubo 9.576. Se observó un predominio de sexo femenino en las consultas de 51% en ambos años. La mediana en 2019 fue de 35 años y en 2020 de 39 años. En 2020 las patologías con mayor consulta fueron nariz (44%), oído (37%) y faringolaringe (14%). Existió un aumento significativo en la consulta por patología cocleovestibular durante 2020. Conclusión: En 2020 hubo una disminución del 19,7% de las consultas dado, probablemente, a las restricciones de movilidad y aforos. Existió un aumento significativo en la proporción de consultas por patologías cocleovestibulares, como vértigo periférico, hipoacusia súbita y tinnitus, atribuido probablemente al estrés emocional generado por la pandemia.

Introduction: Otolaryngological (ENT) pathology presents high incidence in primary care reaching up to 49% of morbidity consultations, however, the pandemic by SARS-CoV-2 had a transversal impact on health services, and may have influenced the consultation profile, so an analysis is required for the development of strategies to ensure health care in the face of events of this magnitude. Aim: To analyze the profile of spontaneous consultation for outpatient ENT pathology in a medical center in La Serena city during 2019 and 2020. Material and Methods: Cross-sectional analytical study of outpatient consultations during the years 2019 and 2020 performed in a private open care center in the commune of La Serena. Frequencies were estimated in absolute numbers and proportions; averages and medians were estimated. Results: During 2019 there were a total of 11,932 consultations and in 2020 there were 9,576. There was a predominance of female sex in the consultations of 51%. The median in 2019 was 35 years and in 2020 it was 39 years. In 2020, the pathologies with the highest number of consultations were nose (44%), ear (37%) and laryngopharynx (14%). There was an increase in consultation for cochleovestibular pathology during 2020. Conclusion: In 2020 there was a 19.7% of consultation decrease probably due to mobility and capacity restrictions. There was a significant increase in the proportion of consultations for cochleovestibular pathologies such as peripheral vertigo, hearing loss and tinnitus, probably attributed to the emotional stress generated by the pandemic.

Disección endoscópica submucosa para el tratamiento del cáncer esofágico / Endoscopic submucosal dissection for the treatment of esophageal cancer

Resumen Introducción: El cáncer de esófago (CE) constituye la sexta causa de muerte por cáncer en el mundo. La disección endoscópica submucosa (DES) es una técnica que permite la resección en bloque de lesiones del tubo digestivo. Tiene rol curativo en pacientes seleccionados y potenciales ventajas sobre la esofagectomía. Objetivo: Describir los resultados perioperatorios y oncológicos de la DES como tratamiento del CE en nuestro centro. Materiales y Método: Estudio retrospectivo de pacientes sometidos a DES por CE entre los años 2010-2020. Resultados: Diez pacientes fueron tratados con DES por CE entre los años 2010 y 2020. El 80% eran hombres y la edad promedio fue de 72 años (63-84). La resección en bloque fue lograda en todos los casos y no se presentó morbimortalidad perioperatoria. Todas las disecciones fueron R0 y el 90% cumplió con estándares de curación. El seguimiento promedio fue de 38 meses (3,5-123). La sobrevida global fue de 90%. La sobrevida específica por cáncer y libre de recurrencia fue de 100%. Discusión: La morbimortalidad asociada a la esofagectomía es alta. La DES sería una alternativa más segura, que permite lograr un R0 y eventualmente la curación en pacientes seleccionados con CE limitado a la mucosa o submucosa. Conclusión: La presente constituye la primera serie reportada de pacientes con cáncer esofágico sometidos a DES en nuestro país. Muestra excelentes resultados oncológicos y seguridad del procedimiento, comparables a las grandes series descritas en la literatura internacional.

Introduction: Esophageal cancer is the sixth leading cause of death by cancer worldwide. Endoscopic submucosal dissection (ESD) is a technique that allows en bloc resection of early lesions of the digestive tract. It has curative potential in selected patients and potential benefits over esophagectomy for the treatment of esophageal cancer (EC). Aim: To report the results of ESD for EC in a high-volume center in Chile. Materials and Method: Retrospective descriptive study of patients who underwent ESD for EC at our center. Results: A total of 10 patients were treated with ESD for EC between 2010 and 2020. Eighty percent were male patients, the average age was 72 years (63-84). En bloc resection was achieved in all cases and there were no complications or mortality. All of the dissections were classified as R0 and 90% met curative standards. The mean follow-up was 38 months (3.5-123). Overall survival was 90%. Cancer-specific survival was 100% and recurrence-free survival was 100%. Discussion: The rate of morbidity and mortality of esophagectomy is high. ESD would be a safer technique, which allows R0 resections and eventually curation in selected patients with EC limited to the mucosa or submucosa. Conclusion: This is the first report of ESD for the treatment of EC in our country, it shows excellent oncologic results and safety of the procedure, comparable to those reported in the larger series published to date.

Actualización y controversias en el tratamiento de las malformaciones congénitas de la vía aérea pulmonar / Update and disagreements in the treatment of congenital pulmonary airway malformations

Congenital pulmonary airway malformations (CPAM) are rare and occur due to a failure in lung embryological development. They are classified according to their pathological characteristics and their anatomical origin. They can occur from the antenatal period to adulthood, can be associated with hydrops fetalis, respiratory distress, recurrent infections, or in an otherwise asymptomatic patient. In this article we carry out a scope review of the literature to answer frequent questions of the clinical teams in charge of patients with CPAM, such as the antenatal approach, the different types of surgeries and the management of asymptomatic patients. Although the indication for surgery is clear in symptomatic patients, little is known about its natural history of this condition, including the possibility of spontaneous resolution and the development of complications or neoplasm. So, the treatment of asymptomatic patients continues to be controversial. Therapeutic decisions must be made by multidisciplinary teams with the informed participation of parents and patients. In our opinion, considering the excellent results of minimally invasive surgery, its low incidence of complications, and practically zero mortality when performed by experienced groups, it seems reasonable to consider elective resection of a MCVAP in asymptomatic patients.

Las malformaciones congénitas de la vía aérea pulmonar (MCVAP) son infrecuentes y ocurren debido a una falla en el desarrollo embriológico pulmonar. Se clasifican de acuerdo con sus características patológicas y a su origen anatómico. Se pueden presentar desde el periodo antenatal hasta la adultez, asociarse a cuadros de hidrops fetal, distrés respiratorio, infecciones recurrentes, o como un hallazgo en pacientes asintomáticos. En este artículo realizamos una revisión bibliográfica exploratoria para responder dudas frecuentes de los equipos clínicos a cargo de pacientes con MCVAP, como el enfrentamiento antenatal, los distintos tipos de cirugía y su abordaje, y el manejo de pacientes asintomáticos. Si bien la indicación de cirugía es clara en pacientes sintomáticos, poco se conoce acerca de su historia natural, incluyendo la posibilidad de resolverse de forma espontánea, de complicarse o de evolucionar hacia el desarrollo de una neoplasia, por lo que el tratamiento de pacientes asintomáticos continúa siendo controversial. Las decisiones terapéuticas deben ser tomadas por equipos multidisciplinarios con la participación informada de los padres y de los pacientes. En nuestra opinión, considerando los excelentes resultados de la cirugía mínimamente invasiva, su baja incidencia de complicaciones y prácticamente nula mortalidad, al ser realizada por grupos con experiencia, nos parece razonable plantear la resección electiva de una MCVAP en un paciente asintomático.

Epidemiología, tratamiento y mortalidad en pacientes infectados por enterobacterias productoras de carbapenemasas: estudio retrospectivo / Epidemiology, treatment and mortality in infection by carbapenemase-producing Enterobacteriaceae: retrospective study

Resumen Introducción: Las enterobacterias productoras de carbapenemasas (EPC) suponen un reto para la salud pública y la práctica clínica. Objetivo: Analizar la epidemiología, el tratamiento y la mortalidad en pacientes infectados por EPC. Material y Métodos: Análisis retrospectivo de 163 pacientes infectados por EPC en un hospital universitario desde julio de 2013 a octubre de 2015. Resultados: Klebsiella pneumoniae fue aislada en 95,1% de los casos, y la mayoría de las carbapenemasas pertenecían al grupo OXA-48 (93%). La adquisición fue nosocomial en 124 casos (77%), asociada a cuidados sanitarios en 30 (18,6%), y 7 (4,3%) fueron de adquisición comunitaria. Las infecciones más frecuentes fueron las del tracto urinario (48,4%) y las respiratorias (19,5%). Aproximadamente, la mitad de los pacientes recibieron monoterapia antimicrobiana. La tasa de mortalidad a los 30 días fue de 23,3%. El análisis multivariante identificó que la presencia de shock séptico al diagnóstico (OR 4,2; IC 95% 1,5-11) estaba asociada de manera independiente con mayor mortalidad en el primer mes, sin lograr identificar asociación con el tratamiento antimicrobiano inapropiado. Discusión: Son necesarios más estudios para aclarar si el tratamiento antimicrobiano de las infecciones por EPC debe ser combinado o si podría ser suficiente la monoterapia en infecciones leves.

Abstract Background: Carbapenemase-producing Enterobacteriaceae (CPE) has become a significant problem in terms of public health and clinical outcome. Objective: To assess the epidemiology, treatment and mortality in patients with infection due to CPE. Material and Methods: A retrospective analysis of 163 patients with CPE infection was carried out in a university hospital from July 2013 to October 2015. Results: A total of 163 patients were included over the study period. Klebsiella pneumoniae was isolated in 95.1% of cases, and most of carbapenemases belonged to the OXA-48 group (93.0%). Acquisition was nosocomial in 124 cases (77.0%), healthcare-associated in 30 (18.6%), and 7 cases (4.3%) were community-acquired. The most frequent infections identified in this study were urinary tract (48.4%) and respiratory (19.5%) infections. Approximately half of the patients received antibiotic monotherapy. The 30-day mortality rate was 23.3%. Multivariate analysis revealed that the presence of septic shock at diagnosis (OR 4.2; IC 95% 1.5-11) was independently associated with an increase in death during the first month, unable to identify association with inappropriate antibiotic treatment. Discussion: Further studies are needed to clarify whether antibiotic treatment of EPC infections should be combined or if monotherapy might be sufficient in mild infections.

[Pleuro-pulmonary blastoma presenting as a chest wall deformity: a case report]. / Deformación de la pared torácica como presentación de un blastoma pleuropulmonar, caso clínico.

INTRODUCTION: Pleuropulmonary blastema (PPB) is the most common primary malignancy of the lungs in childhood. It occurs more frequently in children between one and four years of age, and respiratory symptoms are a common manifestation. Three types have been defined (type I, II and III), which are related to survival and prognosis. OBJECTIVE: To report the first case of a patient with a PPB who presented with a chest wall deformity. CASE REPORT: One year old male patient who had a chest wall deformity at ten months of age. Imaging revealed a giant cyst in the right hemithorax. He did not develop respiratory symptoms until hospital admission. A right upper lobectomy was perfor med and the biopsy confirmed a type I pleuropulmonary blastoma. He was considered successfully treated with complete surgical excision and routine follow-up with thoracic imaging is conducted. CONCLUSIONS: PPB is a very rare cancer that needs to be considered in the differential diagnosis of cystic lung diseases in children. The recognition of this lesion as a malignant tumour rather than a developmental cystic malformation is vital so the child can receive complete excision and appropriate follow-up care.

Deformación de la pared torácica como presentación de un blastoma pleuropulmonar, caso clínico / Pleuro-pulmonary blastoma presenting as a chest wall deformity: a case report

INTRODUCCIÓN: El blastema pleuropulmonar (BPP) es la neoplasia primaria maligna más común de los pulmones en la infancia. Se presenta con mayor frecuencia en niños entre 1 y 4 años, con sínto mas respiratorios. Han sido definidos tres tipos por histopatología (tipo I, II y III), relacionados con sobrevida y pronóstico. OBJETIVO: Reportar el primer caso de un paciente con un BPP que se presentó como una deformación de la pared torácica. CASO CLÍNICO: Paciente de un año de vida que se presentó con una deformidad de la pared torácica a los 10 meses de edad. El estudio imagenológico reveló una gran masa quística en el hemitórax derecho. No desarrolló sintomatología respiratoria hasta el ingreso hospitalario. Se realizó una lobectomía superior derecha y la biopsia confirmó un BPP tipo I. Se trató con resección quirúrgica y realización periódica de imágenes torácicas como seguimiento. CONCLUSIONES: Se reporta el caso de un BPP que se manifestó con deformidad torácica, forma de presentación no descrita previamente en la literatura. El BPP es un cáncer poco frecuente que debe ser considerado en el diagnóstico diferencial de lesiones quísticas pulmonares, sobre todo en la edad pediátrica. Reconocerlo como un tumor maligno en vez de una anomalía del desarrollo, es determinante para que el paciente sea sometido a resección quirúrgica, terapia adyuvante y seguimiento apropiado.

INTRODUCTION: Pleuropulmonary blastema (PPB) is the most common primary malignancy of the lungs in childhood. It occurs more frequently in children between one and four years of age, and respiratory symptoms are a common manifestation. Three types have been defined (type I, II and III), which are related to survival and prognosis. OBJECTIVE: To report the first case of a patient with a PPB who presented with a chest wall deformity. CASE REPORT: One year old male patient who had a chest wall deformity at ten months of age. Imaging revealed a giant cyst in the right hemithorax. He did not develop respiratory symptoms until hospital admission. A right upper lobectomy was perfor med and the biopsy confirmed a type I pleuropulmonary blastoma. He was considered successfully treated with complete surgical excision and routine follow-up with thoracic imaging is conducted. CONCLUSIONS: PPB is a very rare cancer that needs to be considered in the differential diagnosis of cystic lung diseases in children. The recognition of this lesion as a malignant tumour rather than a developmental cystic malformation is vital so the child can receive complete excision and appropriate follow-up care.

Epidemiology and Risk Factors for Cancer After Lung Transplantation.

Cancer is the third most common cause of death among lung transplant (LT) recipients who survive for more than 1 year. The purpose of this study was to analyze the incidence and risk factors for cancer after LT in a Spanish cohort. The epidemiology and risk factors for cancer were retrospectively analyzed in LT recipients from 2 cities in Spain, Madrid and Barcelona. Of the 1353 LT patients initially included in the study, 125 (9.2%) developed cancer after a mean of 3.7 years. This frequency was 5-fold higher than in the general population. The most prevalent tumors were skin cancer (32%), lymphoproliferative disease (18%), and lung cancer (16.5%). In 4 patients, lung cancer was diagnosed on the day of the operation. The risk of cancer increased with age >55 year (hazard ratio [HR] 2.89 [1.64-5.09]; P < .001), in men (HR 2.8 [1.4-5.6]; P = .004), and in heavy smokers (>20 pack-years) (HR 2.94 [1.64-5.27]; P < .001). Other factors such as sun exposure were not found to be risk factors. In conclusion, prevalence of cancer is high in LT recipients in a Mediterranean country. Skin tumors, lymphoproliferative disease, and lung cancer are the most prevalent cancers. Age, male sex, and smoking were the main risk factors for cancer in this population.

Miotomía endoscópica por vía oral (POEM) para el tratamiento de la acalasia: experiencia clínica inicial y resultados a corto plazo / Per-oral endoscopic myotomy (POEM) for the treatment of achalasia: initial clinical experience and short term results

Resumen Introducción: La acalasia es el trastorno motor primario más frecuente del esófago. El estándar de tratamiento actual es la miotomía de Heller laparoscópica. En los últimos años, el desarrollo de técnicas endoscópicas avanzadas ha permitido el posicionamiento de la técnica POEM (del inglés: per-oral endoscopic myotomy) como una nueva alternativa terapéutica con resultados promisorios. Objetivo: Presentar nuestra experiencia clínica, con descripción de la técnica utilizada, resultados perioperatorios y seguimiento a corto plazo en el desarrollo de esta alternativa terapéutica. Materiales y métodos: Se realizó un análisis retrospectivo de datos obtenidos en forma prospectiva de 15 pacientes intervenidos mediante POEM en 3 hospitales docentes asociados. Se recopilaron variables demográficas preoperatorias, detalle del intraoperatorio y registro de morbimortalidad operatoria. Se realizó un seguimiento clínico dirigido registrando el puntaje de Eckardt y la presencia de síntomas de reflujo gastroesofágico. Resultados: Entre agosto de 2015 y noviembre de 2016 se realizaron 15 POEM. Seis de estos pacientes eran mujeres, y la edad promedio fue de 49 años. El tiempo operatorio promedio fue de 110 min; no hubo morbimortalidad operatoria. La estadía hospitalaria promedio fue de 2,8 días. El seguimiento fue de entre 1 y 15 meses. El puntaje de Eckardt promedio en el preoperatorio y en el postoperatorio fue de 10,5 y 0,4 puntos, respectivamente. Tres pacientes presentaban síntomas de reflujo gastroesofágico al momento del seguimiento. Conclusión: Los resultados obtenidos en nuestra serie apoyan la efectividad y seguridad del POEM a corto plazo. Se requiere de un seguimiento mayor para determinar el rol definitivo de esta técnica.

Abstract Introduction: Achalasia is the most common primary motor disorder of the esophagus. The current standard of treatment is laparoscopic Heller's myotomy. Recently the development of advanced endoscopic techniques has allowed the positioning of the POEM (per-oral endoscopic myotomy) technique as a new therapeutic alternative with promising results. Objective: To present our clinical experience in POEM, with description of the technique used, peri-operative results and short-term follow-up in the development of this therapeutic alternative. Materials and methods: We performed a retrospective analysis of data obtained prospectively from 15 patients undergoing POEM in three clinical centers in our country. Preoperative demographic variables, intraoperative detail, and operative morbidity and mortality were collected. Clinical follow-up was performed with controls recording Eckardt score and presence of gastroesophageal reflux symptoms. Results: Between August 2015 and November 2016, 15 POEM were performed, six of these patients were women, average age was 49 years. The average operative time was 110 min, we did not have any perioperative morbimortality. Hospital stay was 2.8 days. Follow-up was between 1 and 15 months, Eckardt's preoperative and postoperative score was on average 10.5 and 0.4 points, respectively. Three patients had gastroesophageal reflux symptoms at the time of follow-up. Conclusion: Our results support the effectiveness and security of POEM in short-term follow up. Further monitoring is required to determine the definitive role of this technique.

Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action.

Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.

Predictores clínicos de bacteriemia en adultos inmunocompetentes hospitalizados por neumonía adquirida en la comunidad / Clinical predictors of bacteremia in immunocompetent adult patients hospitalized for community-acquired pneumonia

Background: The clinical usefulness of blood cultures in the management of patients hospitalized with community-acquired pneumonia (CAP) is controversial. Aim: To determine clinical predictors of bacteremia in a cohort of adult patients hospitalized for community-acquired pneumonia. Material and Methods: A prospective cohort of 605 immunocompetent adult patients aged 16 to 101 years (54% male) hospitalized for CAP was studied. The clinical and laboratory variables measured at admission were associated with the risk of bacteremia by univariate and multivariate analysis using logistic regression models. Results: Seventy seven percent of patients had comorbidities, median hospital stay was 9 days, 7.6% died in hospital and 10.7% at 30 days. The yield of the blood cultures was 12.6% (S. pneumoniae in 69 patients, H. influenzae in 3, Gram negative bacteria in three and S. aureus in one). These results modified the initial antimicrobial treatment in one case (0.2%). In a multivariate analysis, clinical and laboratory variables associated with increased risk of bacteremia were low diastolic blood pressure (Odds ratio (OR): 1.85, 95% confidence intervals (CI) 1.02 to 3.36, p < 0.05), leukocytosis e" 15,000/mm³ (OR: 2.18, 95% CI 1.22 to 3.88, p < 0.009), serum urea nitrogen e" 30 mg/dL (OR: 2.23, 95% CI 1.22 to 4.05, p < 0.009) and serum C-reactive protein e" 30 mg/dL (OR: 2.20, 95% CI 1.22 to 3.97, p < 0.01). Antimicrobial use before hospital admission significantly decreased the blood culture yield (OR: 0.14, 95% CI 0.04 to 0.46, p < 0.002). Conclusions: Blood cultures do not contribute significantly to the initial management of patients hospitalized for community-acquired pneumonia. The main clinical predictors of bacteremia were antibiotic use, hypotension, renal dysfunction and systemic inflammation.

Evaluación de los músculos respiratorios en la parálisis diafragmática bilateral / Assessment of respiratory muscle strength in bilateral diaphragmatic paralysis

Measurement of respiratory muscle strength is useful in order to detect respiratory muscle weakness and to quantify its severity. Apropos of a patient with bilateral diaphragmatic paralysis, we review the clinical manifestations and methods for assessing the strength of the respiratory muscles. In patients with severe respiratory muscle weakness, vital capacity and total lung capacity are reduced but are a non-specific and relatively insensitive measure. Conventionally, inspiratory and expiratory muscle strength has been assessed by maximal inspiratory and expiratory mouth pressures sustained for one second (PIMax and PEMax). The sniffmanoeuvre is natural and probably easier to perform. Sniff pressures are more reproducible and useful measure of diaphragmatic strength. However, the PIMax-PEMax and sniff manoeuvres are volition dependent, and submaximal efforts are most likely to occur in patients who are ill or breathless. Non-volitional tests include measurements of twitch esophageal, gastric and transdiaphragmatic pressure during bilateral electrical and magnetic phrenic nerve stimulation. Electrical phrenic nerve stimulation is technically difficult and is also uncomfortable and painful. Magnetic phrenic nerve stimulation is less painful and transdiaphragmatic pressure is reproducible in normal subjects. Systematic clinical evaluation and additional laboratory tests allow the diagnosis in most patients with respiratory muscle weakness.

La evaluación de la fuerza de los músculos respiratorios permite diagnosticar y cuantificar la gravedad de la debilidad muscular en diferentes enfermedades. A propósito de un paciente con parálisis diafragmática bilateral, hemos revisado el cuadro clínico y los procedimientos diagnósticos para evaluar la fuerza de los músculos respiratorios. En los pacientes con debilidad muscular respiratoria severa, disminuye la capacidad vital y la capacidad pulmonar total, pero es una medida inespecífica y relativamente insensible. Tradicionalmente, la fuerza muscular respiratoria es evaluada midiendo la presión inspiratoria y espiratoria máximas en la boca sostenidas durante un segundo (PIMax y PEMax). La medición de la presión inspiratoria máxima en la nariz (SNIP) es una maniobra natural, más simple de medir y más reproducible, siendo útil en la evaluación de la fuerza diafragmática. Sin embargo, estas técnicas no invasivas son operador dependiente, por lo tanto, esfuerzos submáximos es más probable que ocurran en pacientes graves o con disnea. Las mediciones de las presiones esofágica, gástrica y transdiafragmática mediante estimulación eléctrica o magnética del nervio frénico no son dependientes de la voluntad y son más confiables. Sin embargo, la estimulación eléctrica del nervio frénico es técnicamente difícil y puede ser incómoda y dolorosa. La estimulación magnética del nervio frénico es menos dolorosa y la medición de la presión transdiafragmática es reproducible en sujetos normales. La evaluación clínica sistemática y los exámenes de laboratorio complementarios permiten establecer el diagnóstico en la mayoría de los pacientes con debilidad de los músculos respiratorios.

Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC).

BACKGROUND: BRCA1-associated breast cancers have been associated to a triple-negative phenotype. The prevalence of BRCA1 germline mutations in young onset TNBC based on informativeness of family history has not been reported. PATIENTS AND METHODS: From January 2008 to May 2009 were collected blood and tumor samples from patients with TNBC younger than 50 years and without a family history of breast and ovarian cancer in first- and second-degree relatives. Analysis of BRCA1 germline mutations was made. Age at diagnosis and informativeness of family history (presence of female in first- and second-degree relatives alive until age 45) was collected in all cases. Immunohistochemistry of basal-like features was performed centrally in all available tumors. RESULTS: Seven pathogenic mutations were detected in 92 patients (7.6 %), two of them in patients younger than 35 years (28.6 %) (Fisher's exact test, p = 0.631). Three non-classified variants were detected (3.2 %). Family history was informative in two patients with a pathogenic mutation (28.6 %) and not informative in five (71.4 %) (Fisher's exact test, p = 0.121). Of the seven patients with a pathogenic mutation, four had a basal-like phenotype. CONCLUSION: Patients with apparently sporadic TNBC younger than 50 years and a non-informative family history are candidates for germline genetic testing of BRCA1.

Classical cadherins control survival through the gp130/Stat3 axis.

Stat3 (Signal Transducer and Activator of Transcription-3) is activated by a number of receptor and nonreceptor tyrosine kinases. We recently demonstrated that engagement of E-cadherin, a calcium-dependent, cell to cell adhesion molecule which is often required for cells to remain tightly associated within the epithelium, also activates Stat3. We now examined the effect of two other classical cadherins, cadherin-11 and N-cadherin, whose expression often correlates with the epithelial to mesenchymal transition occurring in metastasis of carcinoma cells, upon Stat3 phosphorylation and activity. Our results indicate that engagement of these two cadherins also, can trigger a dramatic surge in Stat3 activity. This activation occurs through upregulation of members of the IL6 family of cytokines, and it is necessary for cell survival, proliferation and migration. Interestingly, our results also demonstrate for the first time that, in sharp contrast to Stat3, the activity of Erk (Extracellular Signal Regulated kinase) was unaffected by cadherin-11 engagement. Further examination indicated that, although IL6 was able to activate Erk in sparsely growing cells, IL6 could not induce an increase in Erk activity levels in densely growing cultures. Most importantly, cadherin-11 knock-down did allow Erk activation by IL6 at high densities, indicating that it is indeed cadherin engagement that prevents Erk activation by IL6. The fact that the three classical cadherins tested so far, E-cadherin, N-cadherin and cadherin11, which are present in essentially all tissues, actually activate Stat3 regardless of their role in metastasis, argues for Stat3 as a central survival, rather than invasion factor.

Synthesis and biological activity of new bispyridinium salts of 4,4'-bispyridyl-5,5'-perfluoroalkyl-2,2'-bisoxazoles.

A series of bispyridinium compounds were synthesized by a short sequence of reactions from symmetric diamides. All compounds were tested for their antiproliferative activity against HT-29, a cell line derived from a human colon adenocarcinoma, and their inhibitory activity against choline kinase (ChoK), a novel anticancer molecular target already in clinical trials. Most of the compounds analyzed showed good antiproliferative activities, in the micromolar range, with the identification of promising lead molecules as a new family of potential inhibitors of ChoK.

Dendritic cell uptake of iron-based magnetic nanoparticles.

We have investigated the internalization of magnetic nanoparticles (NPs) into dendritic cells (DCs) in order to assess both the final location of the particles and the viability of the cultured cells. The particles, consisting of a metallic iron core covered with carbon, showed no toxic effects on the DCs and had no effect in their viability. We found that mature DCs are able to incorporate magnetic nanoparticles in a range of size from 10 nm to ca. 200 nm, after 24 h of incubation. We describe a method to separate cells loaded with NPs, and analyze the resulting material by electron microscopy and magnetic measurements. It is found that NPs are internalized in lysosomes, providing a large magnetic signal. Our results suggest that loading DCs with properly functionalized magnetic NPs could be a promising strategy for improved vectorization in cancer diagnosis and treatment.

Synthesis of antitumor dendritic imides.

Dendritic imides were synthesized and evaluated as antitumor compounds. Compounds 8 and 11 showing a promising profile as inhibitors of lck but their antiproliferative activity against HT-29 was not so relevant.