Novel 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents.

Liver fibrosis is a critical wound healing response to chronic liver injury such as hepatitis C virus (HCV) infection. If persistent, liver fibrosis can lead to cirrhosis and hepatocellular carcinoma (HCC). The development of new therapies for preventing liver fibrosis and its progression to cancer associated with HCV infection remains a critical challenge. Identification of novel anti-fibrotic compounds will provide opportunities for innovative therapeutic intervention of HCV-mediated liver fibrosis. We designed and synthesized a focused set of 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents. Liver fibrosis assays demonstrated that the compounds 3a and 3c show inhibitory activity towards human hepatic stellate cells (LX2) activation at 10µM. The HCV NS3 and NS5A proteins in HCV subgenome-expressing cells were also significantly reduced in cells treated with 3a and 3c, suggesting the possible inhibitory role of the compounds in HCV translation/replication activities. We have also examined the reactivity of these compounds with medicinally-relevant metal compounds such as platinum and gold. The reactivity of these complexes with metals and during Mass Spectrometry suggests that CS bond cleavage is relatively facile.

The Association of Insurance Status and Complications After Carpal Tunnel Release.

BACKGROUND: Carpal tunnel release (CTR) is one of the most commonly performed procedures in hand surgery. Complications from surgery are a rare but significant patient dissatisfier. The purpose of this study was to determine whether insurance status is independently associated with complications after CTR. METHODS: We retrospectively identified all patients undergoing CTR between 2008 and 2018 using the Indiana Network for Patient Care, a state-wide health information exchange, and built a database that included patient demographics and comorbidities. Patients were followed for 90 days to determine whether a postoperative complication occurred. To minimize dropout, only patients with 1 year of encounters after surgery were included. RESULTS: Of the 26 151 patients who met inclusion criteria, 2662 (10.2%) had Medicare, 7027 (26.9%) had Medicaid, and 16 462 (62.9%) had commercial insurance. Compared with Medicare, Medicaid status (P < .001) and commercial insurance status (P < .001) were independently associated with postoperative CTR complications. The overall complication rate was 2.23%, with infection, wound breakdown, and complex regional pain syndrome being the most common complications. Younger age, alcohol use, diabetes mellitus, hypertension, and depression were also independently associated with complications. CONCLUSIONS: The incidence of complications after CTR is low. Insurance status, patient demographics, and medical comorbidities, however, should be evaluated preoperatively to appropriately risk stratify patients. Furthermore, surgeons can use these data to initiate preventive measures such as working to manage current comorbidities and lifestyle choices, and to optimize insurance coverage.