Prevalence of ischaemic heart disease at admission to intensive care and its influence on red cell transfusion thresholds: Multicentre Scottish study

Background. Restrictive transfusion triggers are safe for most critically ill patients, but doubts exist for patients with ischaemic heart disease (IHD). We investigated the prevalence of reported IHD at admission to the intensive care unit (ICU) and investigated how this influenced red cell transfusion triggers. We also compared observed practice with the clinicians\u27 responses to clinical scenarios. Methods. We studied 1023 sequential ICU admissions over 100 days to 10 Scottish ICUs. Daily haemoglobin, red cell transfusion, and haemorrhage data were available for 99.4% of 5638 ICU patient days. We recorded if IHD was recorded in clinical records at ICU admission. We grouped admissions as having a non-cardiac primary ICU diagnosis and no documentary evidence of IHD (Group 1, n=697), a non-cardiac primary ICU diagnosis with evidence of IHD (Group 2, n=213), or a cardiac primary ICU admission diagnosis (Group 3, n=113). We examined pre-transfusion haemoglobin concentration (Hb) for transfusion episodes not associated with haemorrhage. Clinical transfusion scenarios were sent to intensivists in the ICUs after data collection, which were designed to explore the clinicians\u27 attitude to transfusion triggers in patients with IHD. Results. Previous myocardial infarction was documented in 159 (16%), cardiac failure in 142 (14%), and angina in 167 (16%). Overall, 28.8% of admissions had ≥1 of these documented. The adjusted mean (SE) pre-transfusion Hb concentrations varied across the groups. These were 74 (2.2) g litre-1 in Group 1, 77 (2.3) g litre-1 in Group 2, and 79 (3.1) g litre-1 in Group 3 (P=0.003 across the groups). There was concordance between observed practice and responses to the scenario similar to Group 1, but discordance for patients with IHD (Groups 2 and 3). In scenario responses, intensivists stated these patients should have significantly higher transfusion triggers than were actually observed (median [IQR] response for both groups: 90 [80-100] g litre-1). Conclusions. About 29% of patients admitted to Scottish ICUs had documented IHD, which was associated with small adjustments to Hb transfusion triggers. In response to scenarios, clinicians believe that patients with IHD require higher transfusion triggers than are observed in practice. © The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved

Other model organisms for sarcomeric muscle diseases.

International audienceModel organisms are vital to our understanding of human muscle biology and disease. The potential of the nematode Caenorhabditis elegans, the fruitfly, Drosophila melanogaster and the zebrafish, Danio rerio, as model genetic organisms for the study of human muscle disease is discussed by examining their muscle biology, muscle genetics and development. The powerful genetic tools available with each organism are outlined. It is concluded that these organisms have already demonstrated potential in facilitating the study of muscle disease and in screening for therapeutic agents

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8- 1.2 ×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL- cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance