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Abstract: Introduction: Expedient pathological diagnosis is crucial in selection of appropriate treatment in patients presented with superior vena cava syndrome (SVCS). The performance and safety of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in this setting is unknown. Methods: Over a 4-year period, patients presented with SVCS in the presence of mediastinal mass and referred for EBUS-TBNA were enrolled for the study. The procedure was performed under local anaesthesia with conscious sedation. TBNA was performed under real-time with the curvilinear probe of EBUS. Rapid on site cytological examination (ROSE) was not available. Results: Eighteen procedures of EBUS-TBNA were performed in 17 patients. Malignancy was confirmed in 16 patients (diagnostic yield 94.1%). There was no major complication including significant bleeding or pneumothorax related to the procedures. Conclusions: EBUS-TBNA has high diagnostic yield and is safe in patients presented with SVCS and mediastinal mass. [Copyright &y& Elsevier]

Summary: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has recently been shown to be accurate in diagnosis and staging of mediastinal lymph node metastases. We report a case of squamous cell carcinoma diagnosed by endobronchial biopsy with concomitant contralateral hilar lymph node metastasis from small cell carcinoma being confirmed by EBUS-TBNA. The diagnosis of synchronous primary lung cancers in this case, which altered the treatment strategy, would not be made if pathological staging of intrathoracic lymph node was not pursued. The unique role of EBUS-TBNA in diagnosis of hilar lymphadenopathy was underscored. The potential pitfall of missing synchronous lung tumour if the diagnosis is based either on sampling from intrathoracic lymph node or from endobronchial lesion alone is discussed. [Copyright &y& Elsevier]

The link between the gut microbiome and responsiveness to immune checkpoint inhibitor (ICI) therapy is now well established. New therapeutic opportunities exploiting this relationship are being developed with the goal of augmenting ICI efficacy. In this review, we summarize the foundational research establishing these interactions and discuss the mechanisms and novel therapeutic options associated with this gut microbiome-ICI connection. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNPs) are currently the most effective in vivo delivery systems for silencing target genes in hepatocytes employing small interfering RNA. Antigen-presenting cells (APCs) are also potential targets for LNP siRNA. We examined the uptake, intracellular trafficking, and gene silencing potency in primary bone marrow macrophages (bmMΦ) and dendritic cells of siRNA formulated in LNPs containing four different ionizable cationic lipids namely DLinDAP, DLinDMA, DLinK-DMA, and DLinKC2-DMA. LNPs containing DLinKC2-DMA were the most potent formulations as determined by their ability to inhibit the production of GAPDH target protein. Also, LNPs containing DLinKC2-DMA were the most potent intracellular delivery agents as indicated by confocal studies of endosomal versus cytoplamic siRNA location using fluorescently labeled siRNA. DLinK-DMA and DLinKC2-DMA formulations exhibited improved gene silencing potencies relative to DLinDMA but were less toxic. In vivo results showed that LNP siRNA systems containing DLinKC2-DMA are effective agents for silencing GAPDH in APCs in the spleen and peritoneal cavity following systemic administration. Gene silencing in APCs was RNAi mediated and the use of larger LNPs resulted in substantially reduced hepatocyte silencing, while similar efficacy was maintained in APCs. These results are discussed with regard to the potential of LNP siRNA formulations to treat immunologically mediated diseases. [ABSTRACT FROM AUTHOR]