RESUMO
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.
RESUMO
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.
