ABSTRACT
Background: Various studies have examined the relationship between preoperative mental health diagnoses (MHDs) and postoperative outcomes in orthopedic shoulder patients. However, few investigations delve into the relationship between a preoperative MHD and postoperative opioid pain control regimens in patients who have undergone rotator cuff repair (RCR), total shoulder arthroplasty (TSA), and reverse TSA (rTSA). We hypothesize that orthopedic shoulder patients with a preoperative MHD will be prescribed more opioids (ie, request more refills) postoperatively than those without a MHD. Methods: An institutional review board-approved retrospective chart review was performed on 438 patients, 18 years or older, who underwent RCR, TSA, or rTSA. Patients were divided into two groups: those diagnosed with depression, anxiety, bipolar disorder, and/or schizophrenia (n = 193), and those with no previous MHD (n = 245). Statistical outcomes were analyzed with the independent t-test, Mann-Whitney U test, one-way Analysis of Variance, and Kruskal-Wallis test. Results: Univariate analysis demonstrated significant differences between the MHD group and non-MHD group in average 90-day postoperative opioid scripts (2.10 vs. 1.55, respectively, P < .001) and median 90-day postoperative morphine milligram equivalents (MMEs) prescribed (225 MME vs. 185.25 MME, respectively, P < .001). Among patients who were opioid naive 90 days preoperatively, significant differences were found in MMEs prescribed between the MHD and non-MHD group (225 MME vs. 150 MME, respectively, P < .001). Further analysis of opioid naive patients with specifically depression compared to patients with an alternate or no MHD diagnosis yielded significant differences in scripts (1.78 vs. 1.33, respectively, P = .031) and MMEs prescribed (225 MME vs. 150 MME, respectively, P < .001). Conclusion: This study found that RCR, TSA, or rTSA patients with a preoperative MHD were prescribed significantly more postoperative MMEs and more opioid scripts (ie, requested more refills) than those without MHD. This is despite preoperative education on postoperative pain expectations and limiting opioid use. Our findings support our hypothesis and emphasize the clinical importance of recognizing mental health disease while navigating postoperative pain control expectations. Given the rising prevalence of mental health disorders nationwide, considering the effect of these comorbidities on postoperative pain in RCR, TSA, and rTSA patients will be essential to enhance preoperative and postoperative counseling and management by orthopedic surgeons. We further recommend a multidisciplinary approach to help manage pain in these patients.
ABSTRACT
BACKGROUND & AIMS: Defining the genetic heterogeneity of intrahepatic biliary epithelial cells (BECs) is challenging, and tools for identifying BEC subpopulations are limited. Here, we characterize the expression of a Sox9EGFP transgene in the liver and demonstrate that green fluorescent protein (GFP) expression levels are associated with distinct cell types. METHODS: Sox9EGFP BAC transgenic mice were assayed by immunofluorescence, flow cytometry, and gene expression profiling to characterize in vivo characteristics of GFP populations. Single BECs from distinct GFP populations were isolated by fluorescence-activated cell sorting, and functional analysis was conducted in organoid forming assays. Intrahepatic ductal epithelium was grown as organoids and treated with a Yes-associated protein (Yap) inhibitor or bile acids to determine upstream regulation of Sox9 in BECs. Sox9EGFP mice were subjected to bile duct ligation, and GFP expression was assessed by immunofluorescence. RESULTS: BECs express low or high levels of GFP, whereas periportal hepatocytes express sublow GFP. Sox9EGFP+ BECs are differentially distributed by duct size and demonstrate distinct gene expression signatures, with enrichment of Cyr61 and Hes1 in GFPhigh BECs. Single Sox9EGFP+ cells form organoids that exhibit heterogeneous survival, growth, and HNF4A activation dependent on culture conditions, suggesting that exogenous signaling impacts BEC heterogeneity. Yap is required to maintain Sox9 expression in biliary organoids, but bile acids are insufficient to induce BEC Yap activity or Sox9 in vivo and in vitro. Sox9EGFP remains restricted to BECs and periportal hepatocytes after bile duct ligation. CONCLUSIONS: Our data demonstrate that Sox9EGFP levels provide readout of Yap activity and delineate BEC heterogeneity, providing a tool for assaying subpopulation-specific cellular function in the liver.
