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 & Medicine. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

Differential expression patterns of S100A2, S100A4 and S100A6 during progression of human malignant melanoma

Abstract: Three members of the S100 gene family, S100A2, S100A4 and S100A6, have been suggested to be associated with cancer development and metastasis. To study their involvement in the tumorigenesis of human melanoma, we examined the mRNA expression levels of the 3 genes in 45 melanoma metastases and in 20 benign nevi. Interestingly, whereas none of the metastases expressed S100A2 mRNA, and the expression level was low in 6 cell lines established from primary melanomas, all nevi showed moderate to high expression levels. Our results suggest that loss of S100A2 gene expression may be an early event in melanoma development. A significant correlation was found between the expression of S100A6 in melanoma metastases and both the survival time of the patients and the thickness of the corresponding primary tumors. For the S100A4 gene, however, no relationship was found between gene expression and clinical parameters of melanoma malignancy. The observed differences in expression patterns of the 3 S100 genes suggest distinct roles of their products in melanoma tumorigenesis and/or metastasis, and the results encourage studies to evaluate the potential value of using S100A2 and S100A6 expression levels as markers in the clinical management of melanoma.

Course of Subthreshold Bipolar Disorder in Youth: Diagnostic Progression From Bipolar Disorder Not Otherwise Specified

Abstract: Objective To determine the rate of diagnostic conversion from an operationalized diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I disorder (BP-I) or bipolar II disorder (BP-II) in youth over prospective follow-up and to identify factors associated with conversion. Method Subjects were 140 children and adolescents recruited from clinical referrals or advertisement who met operationalized criteria for BP-NOS at intake and participated in at least one follow-up evaluation (91% of initial cohort). Diagnoses were assessed at follow-up interviews using the Longitudinal Interval Follow-Up Evaluation. The mean duration of follow-up was 5 years and the mean interval between assessments was 8.2 months. Results Diagnostic conversion to BP-I or BP-II occurred in 63 subjects (45%): 32 (23%) to BP-I (nine of whom had initially converted to BP-II) and 31 to only BP-II (22%). Median time from intake to conversion was 58 weeks. First- or second-degree family history of mania or hypomania was the strongest baseline predictor of diagnostic conversion ( p = .006). Over follow-up, conversion was associated with greater intensity of hypomanic symptoms and with greater exposure to specialized, intensive outpatient psychosocial treatments. There was no association between conversion and exposure to treatment with particular medication classes. Conclusions Children and adolescents referred with mood symptoms that meet operationalized criteria for BP-NOS, particularly those with a family history of BP, frequently progress to BP-I or BP-II. Efforts to identify these youth and effectively intervene may have the potential to curtail the progression of mood disorders in this high-risk population.

The Vancouver 3M (Multidisciplinary, Multimodality, But Minimalist) Clinical Pathway Facilitates Safe Next-Day Discharge Home at Low-, Medium-, and High-Volume Transfemoral Transcatheter Aortic Valve Replacement Centers: The 3M TAVR Study.

Abstract: Objectives The authors sought to prospectively determine the safety and efficacy of next-day discharge using the Vancouver 3M (Multidisciplinary, Multimodality, but Minimalist) Clinical Pathway. Background Transfemoral transcatheter aortic valve replacement (TAVR) is an alternative to surgery in high- and intermediate-risk patients; however, hospital stays average at least 6 days in most trials. The Vancouver 3M Clinical Pathway is focused on next-day discharge, made possible by the use of objective screening criteria as well as streamlined peri- and post-procedural management guidelines. Methods Patients were enrolled from 6 low-volume ( 200 TAVR/year) centers in Canada and the United States. The primary outcomes were a composite of all-cause death or stroke by 30 days and the proportion of patients successfully discharged home the day following TAVR. Results Of 1,400 screened patients, 411 were enrolled at 13 centers and received a SAPIEN XT (58.2%) or SAPIEN 3 (41.8%) valve (Edwards Lifesciences, Irvine, California). In centers enrolling exclusively in the study, 55% of screened patients were enrolled. The median age was 84 years (interquartile range: 78 to 87 years) with a median STS score of 4.9% (interquartile range: 3.3% to 6.8%). Next-day discharge home was achieved in 80.1% of patients, and within 48 h in 89.5%. The composite of all-cause mortality or stroke by 30 days occurred in 2.9% (95% confidence interval: 1.7% to 5.1%), with neither component of the primary outcome affected by hospital TAVR volume (p = 0.51). Secondary outcomes at 30 days included major vascular complication 2.4% (n = 10), readmission 9.2% (n = 36), cardiac readmission 5.7% (n = 22), new permanent pacemaker 5.7% (n = 23), and >mild paravalvular regurgitation 3.8% (n = 15). Conclusions Adherence to the Vancouver 3M Clinical Pathway at low-, medium-, and high-volume TAVR centers allows next-day discharge home with excellent safety and efficacy outcomes.

Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial

Abstract: Summary Background In a pilot study, lithium treatment slowed progression of amyotrophic lateral sclerosis (ALS). We aimed to confirm or disprove these findings by assessing the safety and efficacy of lithium in combination with riluzole in patients with ALS. Methods We did a double-blind, placebo-controlled trial with a time-to-event design. Between January and June, 2009, patients with ALS who were taking a stable dose of riluzole for at least 30 days were randomly assigned (1:1) by a centralised computer to receive either lithium or placebo. Patients, caregivers, investigators, and all site study staff with the exception of site pharmacists were masked to treatment assignment. The primary endpoint was the time to an event, defined as a decrease of at least six points on the revised ALS functional rating scale score or death. Interim analyses were planned for when 84 patients had been allocated treatment, 6 months later or after 55 events, and after 100 events. Analysis was by intention to treat. The stopping boundary for futility at the first interim analysis was a p value of at least 0·68. We used a log-rank test to compare the distributions of the time to an event between the lithium and placebo groups. This trial is registered with ClinicalTrials.gov, NCT00818389. Findings At the first interim analysis, 22 of 40 patients in the lithium group had an event compared with 20 of 44 patients in the placebo group (log rank p=0·51). The hazard ratio of reaching the primary endpoint was 1·13 (95% CI 0·61–2·07). The study was stopped at the first interim analysis because criterion for futility was met (p=0·78). The difference in mean decline in the ALS functional rating scale score between the lithium group and the placebo group was 0·15 (95% CI −0·43 to 0·73, p=0·61). There were no major safety concerns. Falls (p=0·04) and back pain (p=0·05) were more common in the lithium group than in the placebo group. Interpretation We found no evidence that lithium in combination with riluzole slows progression of ALS more than riluzole alone. The time-to-event endpoint and use of prespecified interim analyses enabled a clear result to be obtained rapidly. This design should be considered for future trials testing the therapeutic efficacy of drugs that are easily accessible to people with ALS. Funding National Institute of Neurological Disorders and Stroke, ALS Association, and ALS Society of Canada.

Improving clinical outcomes by reducing bleeding in patients with non-ST-elevation acute coronary syndromes

Abstract: Aims Bleeding in patients with coronary artery disease has been linked with adverse outcomes. We examined the incidence and outcomes after bleeding in 20 078 patients with acute coronary syndromes (ACS) enrolled in the OASIS-5 trial who were treated with fondaparinux or the low-molecular weight heparin, enoxaparin. Methods and results Nine hundred and ninety (4.9%) patients developed major bleeding and 423 (2.1%) developed minor bleeding. Fondaparinux compared with enoxaparin reduced fatal bleeding [0.07 vs. 0.22%, relative risk (RR) 0.30, 95% CI: 0.13–0.71], non-fatal major bleeding (2.2 vs. 4.2%, RR 0.52, 95% CI: 0.44–0.61), minor bleeding (1.1 vs. 3.2%, RR 0.34, 95% CI: 0.27–0.42), and need for transfusion (1.8 vs. 3.1%, RR 0.56, 95% CI: 0.47–0.61) during the first 9 days. One of every six deaths during the first 30 days occurred in patients who experienced bleeding. Cox proportional hazards model revealed that major bleeding was associated with about a four-fold increased hazard of death, myocardial infarction, or stroke during the first 30 days and about a three-fold increased hazard during 180 days of follow up. Conclusion Bleeding in patients with ACS is a powerful determinant of fatal and non-fatal outcomes. Reducing the risk of bleeding using a safer anticoagulant strategy during the first 9 days is associated with substantial reductions in morbidity and mortality.