BackgroundMammographically dense breast tissue is one of the greatest risk factors for developing breast carcinoma. Despite the strong clinical correlation, breast density has not been causally linked to tumorigenesis, largely because no animal model has existed for studying breast tissue density. Importantly, regions of high breast density are associated with increased stromal collagen. Thus, the influence of the extracellular matrix on breast carcinoma development and the underlying molecular mechanisms are not understood.MethodsTo study the effects of collagen density on mammary tumor formation and progression, we utilized a bi-transgenic tumor model with increased stromal collagen in mouse mammary tissue. Imaging of the tumors and tumor-stromal interface in live tumor tissue was performed with multiphoton laser-scanning microscopy to generate multiphoton excitation and spectrally resolved fluorescent lifetimes of endogenous fluorophores. Second harmonic generation was utilized to image stromal collagen.ResultsHerein we demonstrate that increased stromal collagen in mouse mammary tissue significantly increases tumor formation approximately three-fold (p < 0.00001) and results in a significantly more invasive phenotype with approximately three times more lung metastasis (p < 0.05). Furthermore, the increased invasive phenotype of tumor cells that arose within collagen-dense mammary tissues remains after tumor explants are cultured within reconstituted three-dimensional collagen gels. To better understand this behavior we imaged live tumors using nonlinear optical imaging approaches to demonstrate that local invasion is facilitated by stromal collagen re-organization and that this behavior is significantly increased in collagen-dense tissues. In addition, using multiphoton fluorescence and spectral lifetime imaging we identify a metabolic signature for flavin adenine dinucleotide, with increased fluorescent intensity and lifetime, in invading metastatic cells.ConclusionThis study provides the first data causally linking increased stromal collagen to mammary tumor formation and metastasis, and demonstrates that fundamental differences arise and persist in epithelial tumor cells that progressed within collagen-dense microenvironments. Furthermore, the imaging techniques and signature identified in this work may provide useful diagnostic tools to rapidly assess fresh tissue biopsies.

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For elective non-cardiac surgery, preoperative hyperglycaemia should be given greater consideration in patients without diabetes than in those with diagnosed diabetes.

The simulation assessments yielded reasonably reliable measures of Critical Care Medicine decision-making skills. Despite a wide range of performance, those with more ICU training and experience performed better, providing evidence to support the validity of the scores. Simulation-based assessments may ultimately prove useful to determine readiness to assume decision-making roles in the ICU.

Purpose Given that preoperative hyperglycemia is associated with poor outcomes and many non-diabetic patients have high plasma glucose (PG) levels, the purpose of our study was to estimate the prevalence of undiagnosed diabetes among non-cardiac surgery patients and to identify predictors of hyperglycemia in non-diabetics. MethodsWe included all non-cardiac surgery patients with complete records in the Clinical Database of the Anesthesiology Institute at the Cleveland Clinic during January 2007 to April 2009, and we estimated the prevalence of undiagnosed diabetes and impaired fasting glucose (IFG) among the non-diabetic patients. The mean glucose levels for known diabetics and undiagnosed diabetics were compared using two-tailed Student's t tests, and we assessed the association between PG levels and demographic variables within the non-diabetics. Results Of the 39,434 patients analyzed, 5,511 (14%) were known diabetics. Of the 33,923 known non-diabetics, 3,426 (10 %) were undiagnosed diabetics and another 3,549 (11%) had IFG. Thus, 6,975 patients (21%) of the non-diabetic patients presented with abnormally high glucose. Previously undiagnosed diabetics had higher preoperative glucose levels compared with known diabetics, with a mean ± standard deviation (SD) of 161 ± 48 vs 146 ± 67 mgÁdL -1 (8.9 ± 2.7 vs 8.1 ± 3.7 mmoLÁL -1 ), respectively. The difference remained highly significant after adjusting for body mass index, age, sex, and American Society of Anesthesiologists (ASA) physical status (P \ 0.001). Among non-diabetics, older age, obesity, male sex, and a higher ASA physical status were collectively significant predictors of hyperglycemia, with a c-statistic (95% confidence interval) of 0.67 (0.66-0.68). Conclusion A significant proportion of non-cardiac surgery patients have previously undiagnosed diabetes and pre-diabetes. Previously undiagnosed patients have higher fasting glucose levels compared with diabetic patients. Further studies should be conducted to identify the implications of these findings on patient outcomes. RésuméObjectif E´tant donne´que l'hyperglyce´mie pre´ope´ratoire est associe´e à un mauvais pronostic et que de nombreux Preliminary results were presented at