Correlation between PD-L1 expression and MET gene amplification in patients with advanced non-small cell lung cancer and no other actionable oncogenic driver.

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.

Dendritic Cells From the Cervical Mucosa Capture and Transfer HIV-1 via Siglec-1.

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.

Acute histological inflammatory activity is associated with clinical relapse in patients with ulcerative colitis in clinical and endoscopic remission.

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.

An Epidemic Outbreak of Cutaneous Leishmaniasis Presenting as Suppurative Folliculitis: A Study of 6 Cases.

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.

Initial experience with real-time elastography using an ultrasound bronchoscope for the evaluation of mediastinal lymph nodes.

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.