RESUMO
BACKGROUND: Recent literature suggests that state-level legislation is effective in reducing postoperative opioid prescribing after total joint arthroplasty but has not addressed the effect on opioid antagonist coprescribing. This study aims to describe the change in postoperative opioid and opioid antagonist prescribing patterns after total joint arthroplasty following passage of state-level opioid-limiting legislation and to determine the comorbidities associated with increased opioid prescribing in this population. METHODS: Billing data were used to identify all patients who underwent primary total hip or knee arthroplasty admitted between March 2016 and March 2018 at our institution. The data were divided into 2 cohorts comprising the year before (671 subjects) and after (713 subjects) the legislation. Discharge prescriptions were reviewed, and the median morphine milligram equivalents (MME) per day and naloxone prescriptions were recorded. International Classification of Diseases codes were used to identify comorbid conditions of interest present during previous inpatient or outpatient encounters. RESULTS: There was a significant reduction in both the minimum and maximum median MME per day after introduction of state legislation and a substantial increase in opioid antagonist coprescription. Total knee arthroplasty, younger age, male sex, chronic pain disorders, post-traumatic stress disorder, and prior opioid abuse were correlated with increased opioid prescribing. CONCLUSION: Our findings suggest that state-level legislation is effective in decreasing the MME per day prescribed and increasing opioid antagonist coprescription in the postoperative period for patients undergoing total hip and knee arthroplasties at our institution. These changes may lead to a decrease in opioid-related morbidity and mortality in the patient population undergoing total hip and knee arthroplasties.
RESUMO
Triple negative breast cancer (TNBC) has an unusually low 5-year survival rate linked to higher metastatic rates. Our laboratory recently delineated a role for the alternative RNA splicing (AS) of cytoplasmic polyadenylation element binding protein 2 (CPEB2), via inclusion/exclusion of exon 4, in the metastasis of TNBC. In these studies, the mechanism governing the inclusion/exclusion of exon 4 was examined. Specifically, the RNA trans-factor, SRSF3, was found to be explicitly associated with CPEB2 exon 4. A SRSF3 consensus sequence was identified in exon 4, and mutation of this sequence abolished the association of SRSF3. The expression of SRSF3 was upregulated in TNBC cells upon the acquisition of anoikis resistance correlating with a reduction in the CPEB2A/B ratio. Importantly, downregulation of SRSF3 in these cells by siRNA induced the exclusion of exon 4 in cells increasing the ratio of CPEB2A (exon 4 excluded) to CPEB2B (exon 4 included). Downregulation of SRSF3 also reversed the CPEB2A/B ratio of a wild-type CPEB2 exon 4 minigene and endogenous CPEB2 pre-mRNA, but not a mutant CPEB2 minigene with the SRSF3 RNA cis-element ablated. SRSF3 downregulation ablated the anoikis resistance of TNBC cells, which was "rescued" by ectopic expression of CPEB2B. Finally, analysis of The Cancer Genome Atlas database showed a positive relationship between SRSF3 expression and lower CPEB2A/B ratios in aggressive breast cancers. IMPLICATIONS: These findings demonstrate that SRSF3 modulates CPEB2 AS to induce the expression of the CPEB2B isoform that drives TNBC phenotypes correlating with aggressive human breast cancer. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/17/9/1920/F1.large.jpg.
