An evolving role for endobronchial ultrasonography in the intensive care unit.

Endobronchial ultrasound (EBUS) bronchoscopy is an established minimally-invasive modality for visualization, characterization, and guidance of sampling of paratracheal and parabronchial structures and tissues. In the intensive care unit (ICU), rapidly obtaining an accurate diagnosis is paramount to the management of critically ill patients. In some instances, diagnosing and confirming terminal illness in a critically ill patient provides needed closure for patients and their loved ones. Currently available data on feasibility, safety, and yield of EBUS bronchoscopy in critically ill patients is based on single center experiences. These data suggest that in select ICU patients convex and radial probe-EBUS bronchoscopy can serve as useful tools in the evaluation of mediastinal lymphadenopathy, central airway obstruction, pulmonary embolism, and peripheral lung lesions. Barriers to the use of EBUS bronchoscopy in the ICU include: (I) requirement for dedicated equipment, prolonged procedure time, and bronchoscopy team expertise that may not be available; (II) applicability to a limited number of patients and conditions in the ICU; and (III) technical difficulty related to the relatively large outer diameter of the convex probe-EBUS bronchoscope and an increased risk for adverse cardiopulmonary consequences due to intermittent obstruction of the artificial airway. While the prospects for EBUS bronchoscopy in critically ill patients appear promising, judicious patient selection in combination with bronchoscopy team expertise are of utmost importance when considering performance of EBUS bronchoscopy in the ICU setting.

Talimogene Laherparepvec (T-VEC) and Other Oncolytic Viruses for the Treatment of Melanoma.

Many mammalian viruses have properties that can be commandeered for the treatment of cancer. These characteristics include preferential infection and replication in tumor cells, the initiation of tumor cell lysis, and the induction of innate and adaptive anti-tumor immunity. Furthermore, viruses can be genetically engineered to reduce pathogenicity and increase immunogenicity resulting in minimally toxic therapeutic agents. Talimogene laherparepvec (T-VEC; Imlygic™), is a genetically modified herpes simplex virus, type 1, and is the first oncolytic virus therapy to be approved for the treatment of advanced melanoma by the US FDA. T-VEC is attenuated by the deletion of the herpes neurovirulence viral genes and enhanced for immunogenicity by the deletion of the viral ICP47 gene. Immunogenicity is further supported by expression of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, which helps promote the priming of T cell responses. T-VEC demonstrated significant improvement in durable response rate, objective response rate, and progression-free survival in a randomized phase III clinical trial for patients with advanced melanoma. This review will discuss the optimal selection of patients for such treatment and describe how therapy is optimally delivered. We will also discuss future directions for oncolytic virus immunotherapy, which will likely include combination T-VEC clinical trials, expansion of T-VEC to other types of non-melanoma skin cancers, and renewed efforts at oncolytic virus drug development with other viruses.