Adherence to blood product transfusion guidelines-An observational study of the current transfusion practice in a medical intensive care unit.

BACKGROUND: Blood transfusions though life-saving are not entirely benign. They are the most overused procedure in the hospital and have been under scrutiny by the 'Choosing Wisely campaign'. The strict adoption of restrictive transfusion guidelines could improve patient outcomes while reducing cost. OBJECTIVES: In this study, we evaluate adherence to restrictive transfusion guidelines, along with hospital mortality and length of stay (LOS) in transfusion events with a pre-transfusion haemoglobin (Hb) ≥7 g/dl. Additionally, we evaluated associated costs accrued due to unnecessary transfusions. METHODS: We conducted a retrospective observational study in a 64-bed medical intensive care unit (MICU) of an academic medical centre involving all adult patients (N = 957) requiring packed red blood cell transfusion between January 2015 and December 2015. RESULTS: In total, 3140 units were transfused with a mean pre-transfusion Hb of 6.75 ± 0.86 g/dl. Nine hundred forty-four (30%) transfusion events occurred with a pre-transfusion Hb ≥7 g/dl, and 385 (12.3%) of these occurred in patients without hypotension, tachycardia, use of vasopressors, or coronary artery disease. Forgoing them could have led to a savings of approximately 0.3 million dollars. Transfusion events with pre-transfusion Hb ≥7 g/dl were associated with an increased mortality in patients with acute blood loss (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.11-3.88; p = 0.02) and LOS in patients with chronic blood loss (ß1 .8.26, 95% CI 4.09-12.43; p < 0.01). CONCLUSION: A subset of anaemic patients in the MICU still receive red blood cell transfusions against restrictive guidelines offering hospitals the potential for effective intervention that has both economic and clinical implications.

HES6 promotes prostate cancer aggressiveness independently of Notch signalling.

Notch signalling is implicated in the pathogenesis of a variety of cancers, but its role in prostate cancer is poorly understood. However, selected Notch pathway members are overrepresented in high-grade prostate cancers. We comprehensively profiled Notch pathway components in prostate cells and found prostate cancer-specific up-regulation of NOTCH3 and HES6. Their expression was particularly high in androgen responsive lines. Up- and down-regulating Notch in these cells modulated expression of canonical Notch targets, HES1 and HEY1, which could also be induced by androgen. Surprisingly, androgen treatment also suppressed Notch receptor expression, suggesting that androgens can activate Notch target genes in a receptor-independent manner. Using a Notch-sensitive Recombination signal binding protein for immunoglobulin kappa J region (RBPJ) reporter assay, we found that basal levels of Notch signalling were significantly lower in prostate cancer cells compared to benign cells. Accordingly pharmacological Notch pathway blockade did not inhibit cancer cell growth or viability. In contrast to canonical Notch targets, HES6, a HES family member known to antagonize Notch signalling, was not regulated by Notch signalling, but relied instead on androgen levels, both in cultured cells and in human cancer tissues. When engineered into prostate cancer cells, reduced levels of HES6 resulted in reduced cancer cell invasion and clonogenic growth. By molecular profiling, we identified potential roles for HES6 in regulating hedgehog signalling, apoptosis and cell migration. Our results did not reveal any cell-autonomous roles for canonical Notch signalling in prostate cancer. However, the results do implicate HES6 as a promoter of prostate cancer progression.

Intracerebroventricular injection of orexin-2 receptor antagonist promotes REM sleep.

Orexins are important regulators of sleep-wakefulness (S-W). Rats were intracerebroventricularly (ICV) administered selective orexin-2 receptor antagonist, TCS-OX2-29. There was decreased wakefulness due to a decrease in the average wake episode duration and an increased REM sleep due to an increase in the number of REM episodes, indicating an inhibitory role of the central orexin-2 receptors on REM sleep generation.