Is Cooled Radiofrequency Genicular Nerve Block and Ablation a Viable Option for the Treatment of Knee Osteoarthritis?

Background The purpose of this study was to determine demographic and psychosocial factors that influence the effectiveness of cooled radiofrequency genicular nerve ablation (C-RFA) and block in patients with chronic knee pain secondary to osteoarthritis (OA). Methods A retrospective review was completed including patients with knee OA who underwent genicular nerve ablation or block or both. Patient information collected included opioid use, psychological comorbidities, smoking history, body mass index, and medical comorbidities. Success was defined using the Osteoarthritis Research Society International criterion of greater than or equal to 50% reported pain relief from the procedure. Patients without a diagnosis of knee OA and patients with ipsilateral total knee arthroplasty were excluded. Patient factors were compared between (1) those that did or did not respond to the initial block and (2) those that did or did not respond to C-RFA. Results Of the 176 subjects that underwent genicular nerve block, 31.8% failed to respond to the procedure. Subjects that failed the initial block were significantly more likely to have psychological comorbidities, smoking history, and diabetes. Of the subjects that proceeded to genicular nerve ablation, 53.7% reported less than 50% pain relief, and 46.3% reported pain relief greater than or equal to 50% at the first follow-up visit. While the presence of psychological comorbidities, smoking, and diabetes were associated with first-stage block failures, these patient factors were not associated with second-stage ablation failures. Conclusions C-RFA may be an effective adjunct therapy as part of a multimodal pain regimen; however, individual patient characteristics must be considered

The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells

Estrogen receptor-? (ER) is expressed in the great majority of breast cancers, and the inhibition of ER action is a key part of breast cancer treatment. The inhibition of ER action is achieved using anti-estrogens, primarily tamoxifen, and with aromatase inhibitors that inhibit estrogen biosynthesis, thereby preventing ER activation. However, resistance to these therapies is common. With the aim of identifying new molecular targets for breast cancer therapy, we have identified the liver receptor homolog-1 (LRH-1) as an estrogen-regulated gene. RNA interference and over-expression studies were used to investigate the role of the LRH-1 in regulating breast cancer growth and to identify the targets of an LRH-1 action. Promoter recruitment was determined using reporter gene and chromatin immunoprecipitation (ChIP) assays. We show that LRH-1 regulates breast cancer cell growth by regulating the ER expression. Reporter gene and in vitro DNA-binding assays identified an LRH-1-binding site in the ER gene promoter, and ChIP assays have demonstrated in vivo binding at this site. We also provide evidence for new LRH-1 variants in breast cancer cells arising from the use of alternative promoters. Previous studies have shown that LRH-1 functions in estrogen biosynthesis by regulating aromatase expression. Our findings extend this by highlighting LRH-1 as a key regulator of the estrogen response in breast cancer cells through the regulation of ER expression. Hence, inhibition of LRH-1 could provide a powerful new approach for the treatment of endocrine-resistant breast cancer