RESUMEN
Non-small cell lung cancers (NSCLC) are the most common type of lung cancer and can be classified according to the presence of mutually exclusive oncogenic drivers. The majority of NSCLC patients present a non-actionable oncogenic driver, and treatment resistance through the amplification of the MET proto-oncogene (MET) or the expression of programmed cell death protein 1 ligand (PD-L1) is common. Herein, we investigated the relation between MET gene amplification and PD-L1 expression in patients with advanced NSCLC and no other actionable oncogenic driver (i.e., EGFR, ALK, ROS1). Our retrospective observational study analyzed data from 48 patients (78% men, median age 66 years) admitted to the Germans Trias i Pujol Hospital, Spain, between July 2015 and February 2019. Patients presenting MET amplification showed a higher proportion of PD-L1 expression (93% vs. 39%; p < 0.001) and overexpression (64% vs. 27%; p = 0.020) than those with non-amplified MET. PD-L1 expression was not significantly different when analyzed by sex (p = 0.624), smoking history (p = 0.429), and Eastern Cooperative Oncology Group Performance Status (p = 0.597) Overall survival rates were not significantly affected by MET amplification (high and intermediate amplification vs low amplification and non-amplificated) (p = 0.252) nor PD-L1 expression (> vs =< 50%) (p = 0.893). In conclusion, a positive correlation was found between MET gene amplification and PD-L1 expression and highly expressed (above 50%) in patients with NSCLC and no other actionable oncogenic driver. It could be translated as new guided-treatment oportunities for these patients.
RESUMEN
Antigen presenting cells from the cervical mucosa are thought to amplify incoming HIV-1 and spread infection systemically without being productively infected. Yet, the molecular mechanism at the cervical mucosa underlying this viral transmission pathway remains unknown. Here we identified a subset of HLA-DR+ CD14+ CD11c+ cervical DCs at the lamina propria of the ectocervix and the endocervix that expressed the type-I interferon inducible lectin Siglec-1 (CD169), which promoted viral uptake. In the cervical biopsy of a viremic HIV-1+ patient, Siglec-1+ cells harbored HIV-1-containing compartments, demonstrating that in vivo, these cells trap viruses. Ex vivo, a type-I interferon antiviral environment enhanced viral capture and trans-infection via Siglec-1. Nonetheless, HIV-1 transfer via cervical DCs was effectively prevented with antibodies against Siglec-1. Our findings contribute to decipher how cervical DCs may boost HIV-1 replication and promote systemic viral spread from the cervical mucosa, and highlight the importance of including inhibitors against Siglec-1 in microbicidal strategies.
Asunto(s)
Cuello del Útero/inmunología , Células Dendríticas/inmunología , Infecciones por VIH/inmunología , VIH-1/fisiología , Lectina 1 Similar a Ig de Unión al Ácido Siálico/inmunología , Replicación Viral/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Transporte Biológico Activo/inmunología , Cuello del Útero/patología , Cuello del Útero/virología , Células Dendríticas/patología , Células Dendríticas/virología , Femenino , Células HEK293 , Infecciones por VIH/patología , Humanos , Interferón Tipo I/inmunología , Persona de Mediana Edad , Membrana Mucosa/inmunología , Membrana Mucosa/patología , Membrana Mucosa/virologíaRESUMEN
BACKGROUND: It has been suggested that acute histological activity has a prognostic value in the outcome of ulcerative colitis (UC) patients in clinical and endoscopic remission. Our aim was to assess the role of histology as a risk factor for clinical relapse (CR) in patients in both clinical and endoscopic remission. METHODS: Patients with left-sided or extensive UC in clinical and endoscopic remission (Mayo endoscopic subscore ≤1) undergoing colonoscopy for dysplasia surveillance with random colonic biopsies between 2005-2015 were included. Basal plasmacytosis, acute (AHA), and the chronic (CHA) histological inflammatory activity of all biopsy sets were evaluated. RESULTS: One hundred and thirteen patients were included. Median time in clinical remission at inclusion was 27 months (IQR 15-56). Eight percent of patients relapsed within the first year and 33% during the whole follow-up period. In the univariate analysis, the presence of AHA, alone (P=0.048) or together with a past flare within the previous 12 months (P=0.01), was associated with CR within the first year of follow-up. In the multivariate analysis, AHA, together with a flare within the previous 12 months, remained the only risk factor for relapse (RR=7.5; IC95%; 1.8-29.9; P=0.005). CONCLUSIONS: In UC patients in clinical and endoscopic remission, the presence of AHA is a risk factor for clinical relapse.
Asunto(s)
Colitis Ulcerosa/patología , Mucosa Intestinal/patología , Cicatrización de Heridas , Adulto , Anciano , Biomarcadores/metabolismo , Colitis Ulcerosa/terapia , Colonoscopía , Determinación de Punto Final , Heces/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , España , Centros de Atención TerciariaRESUMEN
Folliculitis is defined as the inflammation of the follicles. The most common cause of folliculitis is infection. Here, we report an unusual cause of suppurative infundibulitis-which had not yet been described in the literature-due to Leishmania infection, and exemplified by 6 cases that occurred in the setting of an epidemic outbreak. The 6 individuals were immigrants from Morocco. Most of them were men (4 men and 2 women), and most of them were less than 30 years old (apart from one 40-year-old woman). In all cases, a cutaneous biopsy was performed. There was a granulomatous folliculitis with suppurative granulomas in all the cases. All cases showed prominence of plasma cells in the inflammatory infiltrate, and leishmanias were found in all cases. They were mainly seen in the abscessified central areas. The amount of organisms varied from a few to a moderate amount. They were stained by the anti-CD1a antibody (Novocastra) and by a polyclonal homemade anti-leishmania antibody. In addition, in 1 case, microbiological culture was performed, and Leishmania major was demonstrated as the causative agent of the infection.
Asunto(s)
Brotes de Enfermedades , Foliculitis/epidemiología , Foliculitis/patología , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/patología , Adolescente , Adulto , Biopsia con Aguja , Estudios de Cohortes , Diagnóstico Diferencial , Femenino , Foliculitis/diagnóstico , Humanos , Inmunohistoquímica , Incidencia , Leishmaniasis Cutánea/diagnóstico , Masculino , Persona de Mediana Edad , España/epidemiologíaAsunto(s)
Autoanticuerpos/sangre , Miositis/inmunología , Miositis/patología , Partícula de Reconocimiento de Señal/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Humanos , Inmunosupresores , Persona de Mediana Edad , Miositis/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Muestreo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Partícula de Reconocimiento de Señal/análisis , Resultado del TratamientoRESUMEN
La elastografía en tiempo real realizada durante la ultrasonografía endoscópica digestiva es una técnica relativamente nueva que permite caracterizar la dureza de los tejidos, y ha sido utilizada con éxito como predictor de malignidad en ganglios mediastínicos. En la presente nota clínica se describe nuestra experiencia práctica en la técnica de la elastografía con ecobroncoscopio en el estudio de los ganglios linfáticos mediastínicos. Presentamos un caso realizado mediante ultrasonografía endobronquial sectorial y el primer caso publicado de elastografía por ultrasonografía endoscópica con ecobroncoscopio, en 2 pacientes con carcinoma de pulmón no microcítico. El patrón cualitativo en color del tejido se obtuvo en ambos casos y se correlacionó con la evaluación anatomopatológica. Los resultados de viabilidad iniciales son prometedores y las aplicaciones ecobroncoscópicas, como la estadificación ganglionar guiada, requieren ser evaluadas. Categorizar el riesgo de malignidad puede ser importante para ayudar a tomar decisiones en la obtención de muestras
Real-time elastography performed during endoscopic ultrasonography is a relatively new method for characterizing tissue stiffness, and has been used successfully as a predictor of malignancy in mediastinal lymph nodes. This case report describes our practical experience with this technique using an ultrasound bronchoscope to examine mediastinal lymph nodes. We present a case of sectorial endobronchial ultrasound and the first published case of endoscopic ultrasound elastography using ultrasound bronchoscope in two patients with non-small cell lung carcinoma. Qualitative tissue color pattern was obtained in both cases and correlated with pathological evaluation. The initial feasibility results are promising and suggest that ultrasound bronchoscopy techniques, such s guided nodal staging, merit additional studies. It may be importantto categorize the risk of malignancy to facilitate sampling decisions
Asunto(s)
Humanos , Masculino , Anciano , Diagnóstico por Imagen de Elasticidad , Endosonografía , Broncoscopía , Neoplasias del Mediastino/diagnóstico , Neoplasias Pulmonares/patología , Metástasis Linfática , Estadificación de NeoplasiasRESUMEN
Real-time elastography performed during endoscopic ultrasonography is a relatively new method for characterizing tissue stiffness, and has been used successfully as a predictor of malignancy in mediastinal lymph nodes. This case report describes our practical experience with this technique using an ultrasound bronchoscope to examine mediastinal lymph nodes. We present a case of sectorial endobronchial ultrasound and the first published case of endoscopic ultrasound elastography using ultrasound bronchoscope in two patients with non-small cell lung carcinoma. Qualitative tissue color pattern was obtained in both cases and correlated with pathological evaluation. The initial feasibility results are promising and suggest that ultrasound bronchoscopy techniques, such as guided nodal staging, merit additional studies. It may be important to categorize the risk of malignancy to facilitate sampling decisions.