Thoracic analgesia plays a key role in management and outcomes of rib fractures and can generally be broken down into oral or parenteral medication administration and regional analgesia. Surgical stabilization of rib fractures (SSRF) may be an underused resource in the management of rib fractures. This study describes recent trends in rib fracture management and outcomes. National Trauma Data Bank datasets from 2008 to 2014 were reviewed. Patients with three or more rib fractures were identified, and the frequencies of epidural analgesia (EA), other regional analgesia, and SSRF were analyzed. Those older than 65 years were more likely to be admitted to the ICU but had shorter ICU length of stay, lower intubation, and need for tracheostomy rates. In addition, those older than 65 years had about 2.5 times higher mortality (6.3% vs 2.6%, P < 0.001). EA was used in only 3 per cent of the population and more commonly in the older than 65 years group (3.7% vs 2.8%, P < 0.001). Regardless of age, SSRF was more commonly performed when compared with the placement of EA (5.8% vs 3%). This difference was even greater in the younger than 65 years group, where 7 per cent underwent SSRF. Utilization of EA remains low nationally. SSRF should be considered not only for chest wall stabilization but also as an analgesic modality in selected patients. A more complete accounting of analgesic care in rib fracture patients is needed to allow a more detailed analysis of analgesia for rib fracture–related pain to elucidate optimal treatment.

The American Cancer Society predicted more than 52 000 new cases of thyroid cancer in 2020, making it the most prevalent endocrine malignancy. Due to the approximately threefold higher incidence of thyroid cancer in women, we hypothesize that androgens and/or androgen receptors play a protective role and that thyroid cancer in men represents an escape from androgen‐mediated cell regulation. The analysis of androgen receptor (AR) expression in patient tissue samples identified a 2.7‐fold reduction in AR expression (p < 0.005) in papillary thyroid cancer compared with matched, normal tissue. An in vitro cell model was developed by stably transfecting AR into 8505C undifferentiated thyroid cancer cells (resulting in clone 84E7). The addition of DHT to the clone 84E7 resulted in AR translocation into the nucleus and a 70% reduction in proliferation, with a shift in the cell cycle toward G1 arrest. RNASeq analysis revealed significant changes in mRNA levels associated with proliferation, cell cycle, and cell cycle regulation. Furthermore, androgen significantly decreased the levels of the G1‐associated cell cycle progression proteins cdc25a CDK6 CDK4 and CDK2 as well as increased the levels of the cell cycle inhibitors, p27 and p21. The data strongly suggest that DHT induces a G1 arrest in androgen‐responsive thyroid cancer cells. Together, these data support our hypothesis that AR/androgen may play a protective, antiproliferative role and are consistent with younger men having a lower incidence of thyroid cancer than women.

There has been a steady increase in the incidence thyroid cancer in the United States, with over 56,000 cases predicted for 2012. The increased aggressiveness of the disease and poorer clinical outcome in men and postmenopausal women may be due to androgen/androgen receptor (AR) related functions. FK506 binding protein 51 (FKBP5) is a member of the immunophilin family and plays a role in steroid receptor function. Further, FKBP5 regulates the NFkB and AKT pathways and is thought to be relevant to the neoplastic process. Immunohistochemical analysis of 38 papillary thyroid cancer (PTC) specimens indicated that androgen receptor is expressed in both normal and cancerous epithelial cells, in both men and women. Analysis of AR expression in thyroid cell lines indicated that the normal thyroid cell line, Nthy-ori 3-1 and PTC cell lines BCPAP and TPC-1 expressed very low levels of AR, as measured by qRT-PCR and western blotting (&gt;1000 fold less than the prostate cancer cell line, LNCaP). In contrast, PTC/anaplastic 8505C cells expressed higher levels of AR protein (approximately one third the level expressed in LNCaP cells). Upon addition of androgen, AR in 8505C translocated into the nucleus (as determined by immunocytochemistry) and upregulated transcription of both AR (∼1.7 fold) and FKBP5 (∼1.8 fold). To more fully understand the function of androgen/AR in thyroid cells, the AR cDNA from pSG5-AR was subcloned into the pcDNA3.1+ expression vector and stably transfected into thyroid cell lines. Primers for qRT-PCR of the endogenous or the transfected gene were designed. The 84E7 clone of transfected 8505C cells expressed 68 fold higher levels of AR mRNA than 8505C and 16 fold higher AR protein expression (∼5 fold higher AR protein expression than LNCaP). Upon addition of DHT to clone 84E7, AR translocated into the nucleus, and increased AR and FKBP5 mRNA expression (∼3 fold and ∼13 fold, respectively). The association between androgens/AR and upregulation of FKBP5 in thyroid cancer cells suggests that FKBP5 may play a role in thyroid cancer etiology and the different clinical presentation and outcomes between young women and men/postmenopausal women. Citation Format: Melanie E. MacEwan, Ken Wong, Ismatun Swati, Suqing Xie, Mohammad Rasul, Olena Ardacheva, Joseph Buchsbaum, Edward Shin, Augustine Moscatello, Stimson Schantz, Raj K. Tiwari, Jan Geliebter. FKBP5 is an androgen-responsive gene in thyroid cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3559. doi:10.1158/1538-7445.AM2013-3559