Limited English proficiency and head and neck cancer outcomes.

PURPOSE: Limited English proficiency (LEP) is common among hospitalized patients and may impact clinical care and outcomes. This study aimed to examine the relationship between LEP and clinical oncological outcomes for patients with head and neck cancer (HNC). MATERIALS AND METHODS: A single center retrospective review was conducted including adult patients with squamous cell carcinoma of the head and neck who received treatment with curative intent between January 1, 2014 and July 1, 2019. Clinical data collected included patient demographics and clinical variables. Univariate and multivariate analysis was performed to determine whether there was an association between LEP and demographic and clinical factors. RESULTS: There were 477 patients included in the study; 426 (81%) were English proficient (EP) while 51 (10.7%) were LEP. The LEP patients were diagnosed with cancer at a later overall stage (p = 0.03) and less frequently treated with surgery alone compared to English speaking patients (p < 0.001). After adjusting for overall stage and primary site, LEP patients were significantly more likely to receive primary surgical management compared to primary non-surgical management [OR = 2.29 95% CI (0.93, 5.58), p = 0.008]. There was also a significant association between LEP and primary site of tumor (p < 0.01). Kaplan-Meyer curves for overall survival and disease specific survival showed no significant differences between the two cohorts (p = 0.8063 and p = 0.4986, respectively). CONCLUSIONS: LEP may impact access to care resulting in more advanced overall tumor stage at presentation and treatment with primary surgery compared to non-surgical management after adjusting for tumor stage and primary site. Interventions to provide better access to care, awareness of HNC in the LEP populations, and earlier detection may improve outcomes for LEP patients.

PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function.

The orphan nuclear receptor Nurr1 is critical for the development, maintenance and protection of midbrain dopaminergic (mDA) neurons. Here we show that prostaglandin E1 (PGE1) and its dehydrated metabolite, PGA1, directly interact with the ligand-binding domain (LBD) of Nurr1 and stimulate its transcriptional function. We also report the crystallographic structure of Nurr1-LBD bound to PGA1 at 2.05 Å resolution. PGA1 couples covalently to Nurr1-LBD by forming a Michael adduct with Cys566, and induces notable conformational changes, including a 21° shift of the activation function-2 helix (H12) away from the protein core. Furthermore, PGE1/PGA1 exhibit neuroprotective effects in a Nurr1-dependent manner, prominently enhance expression of Nurr1 target genes in mDA neurons and improve motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse models of Parkinson's disease. Based on these results, we propose that PGE1/PGA1 represent native ligands of Nurr1 and can exert neuroprotective effects on mDA neurons, via activation of Nurr1's transcriptional function.