Do vascular surgery patients need a cardiology work-up? A review of pre-operative cardiac clearance guidelines in vascular surgery.

OBJECTIVES: to outline the appropriate pre-operative cardiac work-up for patients who are scheduled for major peripheral vascular surgery. DESIGN: review of the literature. MATERIALS AND METHODS: a review of the literature focusing on studies that have correlated the pre-operative cardiac work-up patients receive to the cardiac morbidity and mortality following vascular surgery. Only studies with level A evidence were included. RESULTS: peri-operative beta blockade has been shown to decrease cardiac complications after vascular surgery in all risk groups. Non-invasive cardiac testing is only necessary for patients in the intermediate/high risk group. Coronary revascularization should only be considered after a positive non-invasive cardiac test. CONCLUSIONS: patients must be risk stratified pre-operatively based on history and physical examination. Low risk patients should receive peri-operative beta blockade only with no further non-invasive testing. On the other hand, intermediate and high risk patients should undergo non-invasive cardiac testing before going to the operating room.     

Somatic activation of beta-catenin bypasses pre-TCR signaling and TCR selection in thymocyte development

Mutation or ablation of T cell factor 1 and lymphocyte enhancer factor 1 indicated involvement of the Wnt pathway in thymocyte development. The central effector of the Wnt pathway is beta-catenin, which undergoes stabilization upon binding of Wnt ligands to frizzled receptors. We report here that conditional stabilization of beta-catenin in immature thymocytes resulted in the generation of single positive T cells that lacked the alpha beta TCR and developed in the absence of pre-TCR signaling and TCR selection. Although active beta-catenin induced differentiation in the absence of TCRs, its action was associated with reduced proliferation and survival when compared to developmental changes induced by the pre-TCR or the alpha beta TCR.     

Serotonergic modulation of suicidal behaviour: integrating preclinical data with clinical practice and psychotherapy

Many studies have provided important information regarding the anatomy, development and functional organization of the 5-HT system and the alterations in this system that are present within the brain of the suicidal patient. There is also a growing interest in genetic factors associated with suicide, since these may lead to the emergence of personality traits that prove to be long-term predictors of suicidal behaviour. This review will focus on presenting the scientific literature on the role of the serotonergic system in suicidal behaviour as well as dysfunctional attitudes and personality traits associated with the suicidal patient. The association of the serotonin transporter gene, the 5-HT2 receptors and its metabolite 5-hydroxyindoleacetic acid with suicidal behaviour and animal models that may capture the complexity of suicidal behaviour will be discussed. Finally, the relationship between neurobiological models and psychotherapeutic interventions for suicide prevention will be considered with a focus on Schema Therapy (an approach that has shown particular promise in the treatment of suicidal individuals with personality disorders), aiming to invite the reader to integrate some aspects of the neurobiology of human suicidal behaviour into a model of suicide that can be used in a clinical encounter.     

Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12Rβ1

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Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation

Somatic loss-of-function mutations in the ten-eleven translocation 2 (TET2) gene occur in a significant proportion of patients with myeloid malignancies. Although there are extensive genetic data implicating TET2 mutations in myeloid transformation, the consequences of Tet2 loss in hematopoietic development have not been delineated. We report here an animal model of conditional Tet2 loss in the hematopoietic compartment that leads to increased stem cell self-renewal in vivo as assessed by competitive transplant assays. Tet2 loss leads to a progressive enlargement of the hematopoietic stem cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis, and extramedullary hematopoiesis. In addition, Tet2(+/-) mice also displayed increased stem cell self-renewal and extramedullary hematopoiesis, suggesting that Tet2 haploinsufficiency contributes to hematopoietic transformation in vivo.     

Ulcerative colitis: patient characteristics may predict 10-yr disease recurrence in a European-wide population-based cohort

OBJECTIVES: Cumulative 10-yr relapse rates in ulcerative colitis (UC) of 70% to almost 100% have been reported in regional studies. The aim of this study was to determine the relapse rate in UC in a European population-based cohort 10 yr after diagnosis and to identify factors that may influence the risk of relapse. METHODS: From 1991 to 1993, 771 patients with UC from seven European countries and Israel were prospectively included in a population-based inception cohort and followed for 10 yr. A relapse was defined as an increase in UC-related symptoms leading to changes in medical treatment or surgery. The cumulative relapse rate, time to first relapse, and number of relapses in the follow-up period were recorded and possible causative factors were investigated. RESULTS: The cumulative relapse rate of patients with at least one relapse was 0.67 (95% CI 0.63-0.71). The time to first relapse showed a greater hazard ratio (HR) (1.2, CI 1.0-1.5) for women and for patients with a high level of education (1.4, CI 1.1-1.8). The number of relapses decreased with age, and current smokers had a lower relapse rate (0.8, CI 0.6-0.9) than nonsmokers. The relapse rate in women was 1.2 (CI 1.1-1.3) times higher than in men. An inverse relation was found between the time to the first relapse and the total number of relapses. CONCLUSION: In 67% of patients, there was at least one relapse. Smoking status, level of education, and possibly female gender were found to influence the risk of relapse.