RESUMEN
BACKGROUND: Fentanyl is a synthetic opioid fueling the current opioid crisis in the United States. While emergency department (ED) visits due to opioid-related overdoses, injection complications, and withdrawals become increasingly more frequent, fentanyl is not detected in routine toxicology testing. We evaluated 2 FDA-approved fentanyl immunoassays in a sampled ED population. METHODS: De-identified, remnant urine specimens (n = 213) collected from patients presenting to a large ED were analyzed using ARK Fentanyl II (ARK II) and Immunalysis SEFRIA (SEFRIA) fentanyl immunoassays on an Architect c16000 (Abbott) analyzer. All discrepant specimens were evaluated by LC-MS/MS. Additionally, polysubstance abuse patterns and trends were analyzed. RESULTS: While intra-assay imprecision was comparable for ARK II and SEFRIA, inter-assay imprecision for ARK II and SEFRIA varied from 8.0% to 1.8% and from 37% to 12.5%, respectively. SEFRIA had a marginally higher false-positivity rate (3%) than ARK II (1%). Both assays had equivalent sensitivity of 95%, with ARK II (99%) having greater specificity than SEFRIA (97%). Fentanyl was detected in 13.7% of drug-panel-positive patient samples and most frequently observed in patients also testing positive for amphetamines and cocaine. Notably, fentanyl was detected in 5.3% of patient samples that were negative for all other drugs in our standard toxicology panel. CONCLUSIONS: A sizable portion of drug-positive samples from our ED were positive for fentanyl, with a subset of patients testing positive for fentanyl alone. Implementation of fentanyl testing into routine toxicology panels can elucidate polysubstance abuse paradigms and capture ED patients that would go undetected in standard panels.
RESUMEN
Expression of PDL1 on the surface of tumor cells can blunt the efficacy of many cancer immunotherapies. For example, our lab has previously shown that tumors derived from malignant cells incapable of expressing PDL1 are highly susceptible to immunotherapy induced by oncolytic virus treatment while tumors derived from PDL1 capable cells are highly resistant. In patient biopsies, however, expression of PDL1 on malignant cells is often not uniform with some cells expressing PDL1 while others do not. Importantly, how this partial PDL1 positivity influences the outcomes of immunotherapy remains largely unknown. In the current work, we expand on our previous findings by generating partially PDL1 positive tumors in immune competent animals and asking what percentage of tumor cells must express PDL1 for a tumor to become functionally resistant to oncolytic treatment. Our results indicate that the responsiveness of partially PDL1+ tumors correlates linearly with the percentage of PDL1 capable cells present at the initiation of treatment. Additionally, we observe that tumors which relapse after treatment display a significant increase in the numbers of PDL1 capable cells present suggesting that specific editing of mixed tumors might play a role in disease relapse. These data indicate that varying levels of PDL1 expression can play a significant role in the outcomes of oncolytic immunotherapy and challenges the concept that tumors should be viewed as simply PDL1+ or PDL1-.