NA.

Chronic lung diseases, such as pulmonary emphysema, are increasingly recognized complications of infection with the human immunodeficiency virus (HIV). Emphysema in HIV may occur independent of cigarette smoking, via mechanisms that are poorly understood but may involve lung endothelial cell apoptosis induced by the HIV envelope protein gp120. Recently, we have demonstrated that lung endothelial apoptosis is an important contributor to the development of experimental emphysema, via upregulation of the proinflammatory cytokine endothelial monocyte-activating polypeptide II (EMAP II) in the lung. Here we investigated the role of EMAP II and its receptor, CXCR3, in gp120-induced lung endothelial cell apoptosis. We could demonstrate that gp120 induces a rapid and robust increase in cell surface expression of EMAP II and its receptor CXCR3. This surface expression occurred via a mechanism involving gp120 signaling through its CXCR4 receptor and p38 MAPK activation. Both EMAP II and CXCR3 were essentially required for gp120-induced apoptosis and exposures to low gp120 concentrations enhanced the susceptibility of endothelial cells to undergo apoptosis when exposed to soluble cigarette smoke extract. These data indicate a novel mechanism by which HIV infection causes endothelial cell loss involved in lung emphysema formation, independent but potentially synergistic with smoking, and suggest therapeutic targets for emphysema prevention and/or treatment.

A retrospective review of 100 sequential patients (2009-2012) with head and neck cancer was performed to determine the frequency of 5 types of diagnostic delays and errors outlined by the Institute of Medicine. There were a total of 105 diagnostic delays/errors. The most common was delay in being seen in the otolaryngology clinic after referral placement (28.6%), followed by diagnostic error by the referring physician (22%), delay in referral of a symptomatic patient to the otolaryngology clinic (16.2%), delay in employing an appropriate diagnostic test or procedure (15.2%), delay in action following reporting of pathology or imaging results for an incidental lesion (11.4%), diagnostic error by the otolaryngology clinic (2.8%), delay in action following reporting of pathology or imaging results for the symptomatic lesion (2.8%), and use of outmoded tests or therapy (1%). Increased awareness of these types of delays/errors will direct actions and processes to reduce or eliminate them.

Objective The primary objective was to define and quantify the relationship between immunosuppression and prognosis in patients with cutaneous squamous cell carcinoma of the head and neck. Data Sources Ovid/Medline, PubMed, Embase, and Scopus were searched from inception through June 5, 2017, with cross-referenced subject headings of squamous cell carcinoma, skin neoplasms, head and neck neoplasms, and prognosis. Additional gray literature was queried. Review Methods All prospective, retrospective, and cohort studies in the English literature investigating prognosis in patients with head and neck cutaneous squamous cell carcinoma were eligible for inclusion. Meta-analysis data were pooled using the fixed-effects model. The main outcome measures were hazard ratios detailing subgroup analysis between immunosuppressed and immunocompetent patients. Results Seventeen studies were eligible for inclusion; 317 of the 2886 patients were immunosuppressed. Meta-analysis with pooled hazard ratios was performed for all outcome variables with at least 3 reported hazard ratios. Immunosuppression portended a worse prognosis across all outcome variables of interest: locoregional recurrence (2.20; 95% confidence interval [CI], 1.45-3.36), disease-free survival (2.69; 95% CI, 1.60-4.51), disease-specific survival (3.61; 95% CI, 2.63-4.95), and overall survival (2.09; 95% CI, 1.64-2.67). Conclusion This is the largest investigation into the impact of immunosuppression on head and neck cutaneous squamous cell carcinoma. Immunosuppressed patients experience worse recurrence and survival outcomes compared to immunocompetent counterparts. The data support formal inclusion of immunosuppression in head and neck cutaneous squamous cell carcinoma staging systems.