Sunnybrook Health Sciences Centre

About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Breast cancer. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

Surgically Important Bowel and/or Mesenteric Injury in Blunt Trauma: Accuracy of Multidetector CT for Evaluation

Abstract: Purpose: To determine the accuracy of multidetector computed tomography (CT) in the detection of surgically important blunt bowel and/or mesenteric injury, to identify and describe the most reliable CT features of bowel and/or mesenteric injury, and to evaluate the performance of readers with different levels of expertise. Materials and Methods: Institutional review board approval was obtained for this retrospective case-control study of 96 subjects with laparotomy-confirmed findings: 54 consecutive patients with bowel and/or mesenteric injury (surgically important and unimportant) (32 male patients, 22 female patients; mean age, 40.4 years ± 17.6 [standard deviation]; range, 16–86 years) and 42 matched patients without bowel and/or mesenteric injury (22 male patients, 20 female patients; mean age, 36.8 years ± 20.1; range, 14–84 years) who underwent four-detector CT prior to surgery. A second-year radiology resident, an abdominal imaging fellow, and a staff abdominal radiologist, blinded to patient outco...

Cardiopulmonary bypass, temperature, and central nervous system dysfunction.

Abstract: BACKGROUND Neurological injury is an important cause of morbidity and mortality after cardiac surgery. With the advent of warm heart surgery, the neuroprotective role of hypothermic cardiopulmonary bypass (CPB) has come under increasing scrutiny. Preliminary work by us in the area found no increased risk of neurological morbidity with normothermic CPB in a small group of patients and suggested a possible benefit. The purpose of the present study is to compare the incidence of neurological and neuropsychological dysfunction in a larger number of patients randomized to warm or cold aortocoronary bypass surgery. METHODS AND RESULTS With the approval of the institutional research ethics committee, 201 aortocoronary bypass patients were randomized to normothermic or moderate hypothermic CPB and subjected to neurological and neuropsychological evaluation. These subjects were a subset of patients enrolled in a large multicenter trial comparing warm versus cold heart surgery. The examinations took place preoperatively, 5 days after operation, and a 3-month follow-up. The examination consisted of a clinical neurological examination and a brief neuropsychological test battery. The neuropsychological tests included the Buschke selective reminding procedure, the Wechsler memory scale-revised visual reproduction subtest, the trial making test (parts A and B), the Wechsler adult intelligence scale-revised digit symbol subtest, and the grooved pegboard test. The examiner and subjects were unaware of the CPB temperature allocation (warm, > 34 degrees C; cold, < or = 28 degrees C). Statistical analysis was performed using the SAS statistical software package. Two hundred one patients were enrolled in the study. Of these, 155 patients completed the entire protocol and were included in the final analysis (warm group, n = 78; cold group, n = 77). One patient in the warm group died perioperatively from a massive hemispheric stroke. Another warm group patient was unable to complete neuropsychological evaluation because of a perioperative stroke. Thus, 153 patients completed the entire series of neuropsychological tests. A total of 6 patients (warm group, n = 2; cold group, n = 4; P = NS) suffered from perioperative focal neurological deficits. There was a consistent deterioration in scores from tests of psychomotor speed/coordination (trial making, digit symbol, pegboard) in the early postoperative period, which resolved by the 3-month follow-up. Tests of memory (Buschke, Wechsler memory scale) showed no evidence of patient deterioration in the postoperative period. No difference was seen between the warm and cold groups. CONCLUSIONS In this randomized trial of normothermic versus hypothermic CPB, we found deterioration in scores of tests of psychomotor speed but not of memory in the early postoperative period. We were unable to demonstrate any neuroprotective effect from moderate hypothermia in this patient population.

miRNA-95 Mediates Radioresistance in Tumors by Targeting the Sphingolipid Phosphatase SGPP1

Abstract: Radiation resistance poses a major clinical challenge in cancer treatment, but little is known about how microRNA (miR) may regulate this phenomenon. In this study, we used next-generation sequencing to perform an unbiased comparison of miR expression in PC3 prostate cancer cells rendered resistant to fractionated radiation treatment. One miR candidate found to be upregulated by ionizing radiation was miR-95, the enforced expression of which promoted radiation resistance in a variety of cancer cells. miR-95 overexpression recapitulated an aggressive phenotype including increased cellular proliferation, deregulated G2-M checkpoint following ionizing radiation, and increased invasive potential. Using combined in silico prediction and microarray expression analyses, we identified and validated the sphingolipid phosphatase SGPP1, an antagonist of sphingosine-1-phosphate signaling, as a target of miR-95 that promotes radiation resistance. Consistent with this finding, cell treatment with FTY720, a clinically approved small molecule inhibitor of S1P signaling, sensitized miR-95 overexpressing cells to radiation treatment. In vivo assays extended the significance of these results, showing that miR-95 overexpression increased tumor growth and resistance to radiation treatment in tumor xenografts. Furthermore, reduced tumor necrosis and increased cellular proliferation were seen after radiation treatment of miR-95 overexpressing tumors compared with control tumors. Finally, miR-95 expression was increased in human prostate and breast cancer specimens compared with normal tissue. Together, our work reveals miR-95 expression as a critical determinant of radiation resistance in cancer cells.

Prospective Cost-Effectiveness Analysis of Cetuximab in Metastatic Colorectal Cancer: Evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 Trial

Abstract: The National Cancer Institute of Canada Clinical Trials Group CO.17 study showed that patients with advanced colorectal cancer had improved overall survival when cetuximab, an epidermal growth factor receptor-targeting antibody, was given in addition to best supportive care. We conducted a cost-effectiveness analysis using prospectively collected resource utilization and health utility data for patients in the CO.17 study who received cetuximab plus best supportive care (N = 283) or best supportive care alone (N = 274). Direct medical resource utilization data were collected, including medications, physician visits, toxicity management, blood products, emergency department visits, and hospitalizations. Mean survival times for the study arms were calculated for the entire population and for the subset of patients with wild-type KRAS tumors over an 18- to 19-month period. All costs were presented in 2007 Canadian dollars. One-way and probabilistic sensitivity analysis was used to determine the robustness of the results. Cost-effectiveness acceptability curves were determined. The 95% confidence intervals (CIs) for the incremental cost-effectiveness ratios and the incremental cost-utility ratios were estimated by use of a nonparametric bootstrapping method (with 1000 iterations). For the entire study population, the mean improvement in overall and quality-adjusted survival with cetuximab was 0.12 years and 0.08 quality-adjusted life-years (QALYs), respectively. The incremental cost with cetuximab compared with best supportive care was $23,969. The incremental cost-effectiveness ratio was $199,742 per life-year gained (95% CI = $125,973 to $652,492 per life-year gained) and the incremental cost-utility ratio was $299,613 per QALY gained (95% CI = $187,440 to $898,201 per QALY gained). For patients with wild-type KRAS tumors, the incremental cost with cetuximab was $33,617 and mean gains in overall and quality-adjusted survival were 0.28 years and 0.18 QALYs, respectively. The incremental cost-effectiveness ratio was $120,061 per life-year gained (95% CI = $88,679 to $207,075 per life-year gained) and the incremental cost-utility ratio was $186,761 per QALY gained (95% CI = $130,326 to $334,940 per QALY gained). In a sensitivity analysis, cetuximab cost and patient survival were the only variables that influenced cost-effectiveness. The incremental cost-effectiveness ratio of cetuximab over best supportive care alone in unselected advanced colorectal cancer patients is high and sensitive to drug cost. Incremental cost-effectiveness ratios were lower when the analysis was limited to patients with wild-type KRAS tumors.