Age, Race, and Income Are Associated With Lower Screening Rates at a Safety Net Hospital.

BACKGROUND: While lung cancer screening improves cancer-specific mortality and is recommended for high-risk patients, barriers to screening still exist. We sought to determine our institution's (an urban safety net hospital) screening rate and to identify socioeconomic barriers to lung cancer screening. METHODS: We identified 8935 smokers 55 to 80 years of age evaluated by a primary care physician between March 2015 and March 2017 at our institution. We randomly selected one-third of these (n = 2978) to review for eligibility using the U.S. Preventive Services Task Force criteria for lung cancer screening. Using our institution's Lung Cancer Screening Program clinical tracking database, we identified patients who were screened from March 2015 to March 2017. We collected demographic information (race, primary language, education status, and median income) and evaluated possible associations with screening. RESULTS: Among our institution population, 99 patients meeting U.S. Preventive Services Task Force screening criteria underwent screening computed tomography, whereas 516 eligible patients were not screened, making our institution's estimated screening rate 16.1%. Comparing the unscreened population with those who received screening at our institution, the unscreened population was significantly older (median age of screened patients was 63 years, of unscreened patients was 66 years; P < .001). African Americans had a lower screening rate (37.6% of the screened population and 47.5% of the unscreened population; P < .001). Unscreened patients had a lower annual household income. CONCLUSIONS: The lung cancer screening rate at our hospital is 16.1%. Unscreened patients were older, were more likely to be African American, and had a lower median income. These findings highlight possible screening barriers and potential areas for targeted strategies to decrease disparities in lung cancer screening.

Prostaglandin signaling suppresses beneficial microglial function in Alzheimer's disease models.

Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer's disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aß peptides and determined that microglia-specific deletion of the gene encoding the PGE2 receptor EP2 restores microglial chemotaxis and Aß clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE2/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD.

Inflammatory prostaglandin E2 signaling in a mouse model of Alzheimer disease.

OBJECTIVE: There is significant evidence for a central role of inflammation in the development of Alzheimer disease (AD). Epidemiological studies indicate that chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD in healthy aging populations. As NSAIDs inhibit the enzymatic activity of the inflammatory cyclooxygenases COX-1 and COX-2, these findings suggest that downstream prostaglandin signaling pathways function in the preclinical development of AD. Here, we investigate the function of prostaglandin E(2) (PGE(2) ) signaling through its EP3 receptor in the neuroinflammatory response to Aß peptide. METHODS: The function of PGE(2) signaling through its EP3 receptor was examined in vivo in a model of subacute neuroinflammation induced by administration of Aß(42) peptides. Our findings were then confirmed in young adult APPSwe-PS1ΔE9 transgenic mice. RESULTS: Deletion of the PGE(2) EP3 receptor in a model of Aß(42) peptide-induced neuroinflammation reduced proinflammatory gene expression, cytokine production, and oxidative stress. In the APPSwe-PS1ΔE9 model of familial AD, deletion of the EP3 receptor blocked induction of proinflammatory gene and protein expression and lipid peroxidation. In addition, levels of Aß peptides were significantly decreased, as were ß-secretase and ß C-terminal fragment levels, suggesting that generation of Aß peptides may be increased as a result of proinflammatory EP3 signaling. Finally, deletion of EP3 receptor significantly reversed the decline in presynaptic proteins seen in APPSwe-PS1ΔE9 mice. INTERPRETATION: Our findings identify the PGE(2) EP3 receptor as a novel proinflammatory, proamyloidogenic, and synaptotoxic signaling pathway, and suggest a role for COX-PGE(2) -EP3 signaling in the development of AD.