The Effects of Hyperglycemia on Early Endothelial Activation and the Initiation of Atherosclerosis.

It is well established that patients with diabetes have an increased risk of developing atherosclerotic cardiovascular disease. The earliest detectable sign of atherosclerosis initiation is endothelial cell activation. Activated endothelial cells express adhesion proteins, P-selectin, E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1, which function to recruit monocytes to the subendothelial layer. This study examines the effect of hyperglycemia on endothelial cell activation and the initiation and progression of atherosclerosis. In vitro studies revealed that exposure of human aortic endothelial cells to elevated (30 mmol/L) glucose concentrations significantly increased the expression of P-selectin, E-selectin, and vascular cell adhesion molecule-1. In vivo studies showed that, before lesion development, 5-week-old hyperglycemic ApoE-/-Ins2+/akita mice had significantly increased expression of these adhesion proteins in the aortic sinus and increased macrophage infiltration, compared with normoglycemic ApoE-/- controls. At 25 weeks of age, ApoE-/-Ins2+/akita mice had significantly larger atherosclerotic plaques than ApoE-/- controls (0.022 ± 0.004 versus 0.007± 0.001 mm3; P < 0.05). Similar endothelial activation was observed in heterozygous ApoE+/-Ins2+/akita mice; however, detectable atherosclerotic lesions did not develop in the absence of dyslipidemia. Lowering blood glucose levels (by 55%) using a sodium-glucose cotransporter 2 inhibitor reduced endothelial activation. Together, these findings support a causative role for hyperglycemia in atherogenesis and highlight the importance of blood glucose regulation in preventing atherosclerotic cardiovascular disease.

Otolaryngology - Head and Neck Surgeon unemployment in Canada: a cross-sectional survey of graduating Otolaryngology - Head and Neck Surgery residents.

OBJECTIVE: Recently graduated Otolaryngology - Head and Neck Surgeons (OTO-HNS) are facing an employment crisis. To date, there has been no systematic evaluation of the factors contributing to this situation, graduating OTO-HNS trainee employment rates, nor the employment concerns of these graduating residents. This investigation sought to empirically evaluate prospective OTO-HNS graduate employment, identify factors contributing to this situation, and provide suggestions going forward. METHODS: A cross-sectional survey of the 2014 graduating cohort of OTO-HNS residents was conducted 6-months prior to graduation, and immediately following residency graduation. Surveyed items focused on the demographics of the graduating cohort, their future training and employment plans, and their concerns relative to the OTO-HNS employment situation. RESULTS: All twenty-nine Canadian medical school graduated OTO-HNS residents completed the initial survey, with 93% responding at the completion of residency. Only 6 (22%) indicated confirmed employment following residency training. 78% indicated that they were pursuing fellowship training. 90% identified the pursuit of fellowship training as a moderately influenced by limited job opportunities. The ability to find and secure full-time employment, losing technical skills if underemployed/unemployed, and being required to consider working in a less-desired city/province were most concerning. 34% of the residents felt that they were appropriately counseled during their residency training about employment. 90% felt that greater efforts should be made to proactively match residency-training positions to forecasted job opportunities. CONCLUSIONS: Canadian OTO-HN Surgeons lack confirmed employment, are choosing to pursue fellowship training to defer employment, and are facing startling levels of under- and unemployment. A multitude of factors have contributed to this situation and immediate action is required to rectify this slowly evolving catastrophe.

Extended Temporal Bone Resection for Squamous Cell Carcinoma.

OBJECTIVE: The aim of this study was to assess the surgical results of a series of patients from this unit who underwent extended temporal bone resection for recurrent squamous cell carcinoma as a salvage procedure. DESIGN: The surgical records of 15 patients were analyzed in detail. Each patient had salvage surgery in the form of an extended temporal bone resection with supraomohyoid block dissection, dural grafting, and free microvascular forearm or scalp rotation flap repair for recurrent squamous cell carcinoma in a radical mastoid cavity. RESULTS: Radical surgery yielded a 47% 5-year survival. Twenty-nine percent of the survivors had temporal lobe involvement that necessitated a partial excision of the temporal lobe of the brain. Histologic evidence of local lymph node involvement in the supraomohyoid neck dissection was present in 13% of cases. Those who died did so in the first postoperative year. All those with poorly differentiated tumors died. The survivors had well or moderately differentiated tumors. CONCLUSIONS: Radiotherapy alone or partial temporal bone resection, most commonly a radical mastoidectomy with or without preoperative or postoperative radiotherapy is used by the majority of otolaryngologists in treating squamous cell carcinoma of the temporal bone. The 5-year survival rate after this treatment remains depressingly low and the prognosis gloomy, particularly for advanced tumors. The findings in this series of extended temporal bone resections as salvage surgery in recurrent disease is encouraging, and radical surgery combined with radiotherapy from the outset may give much better 5-year survival figures in the future than the conventional partial temporal bone resection and radiotherapy. (Otolaryngol Head Neck Surg 1997;116:617-23.).