Abstract
Ensembl (https://www.ensembl.org) is a freely available genomic resource that has produced high-quality annotations, tools, and services for vertebrates and model organisms for more than two ...decades. In recent years, there has been a dramatic shift in the genomic landscape, with a large increase in the number and phylogenetic breadth of high-quality reference genomes, alongside major advances in the pan-genome representations of higher species. In order to support these efforts and accelerate downstream research, Ensembl continues to focus on scaling for the rapid annotation of new genome assemblies, developing new methods for comparative analysis, and expanding the depth and quality of our genome annotations. This year we have continued our expansion to support global biodiversity research, doubling the number of annotated genomes we support on our Rapid Release site to over 1700, driven by our close collaboration with biodiversity projects such as Darwin Tree of Life. We have also strengthened support for key agricultural species, including the first regulatory builds for farmed animals, and have updated key tools and resources that support the global scientific community, notably the Ensembl Variant Effect Predictor. Ensembl data, software, and tools are freely available.
Graphical Abstract
Graphical Abstract
Summary
In the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial, the use of intravenous iron did not reduce the need for blood ...transfusion or reduce patient complications or length of hospital stay. As part of the trial protocol, serum was collected at randomisation and on the day of surgery. These samples were analysed in a central laboratory for markers of iron deficiency. We performed a secondary analysis to explore the potential interactions between pre‐operative markers of iron deficiency and intervention status on the trial outcome measures. Absolute iron deficiency was defined as ferritin <30 μg.l−1; functional iron deficiency as ferritin 30–100 μg.l−1 or transferrin saturation < 20%; and the remainder as non‐iron deficient. Interactions were estimated using generalised linear models that included different subgroup indicators of baseline iron status. Co‐primary endpoints were blood transfusion or death and number of blood transfusions, from randomisation to 30 days postoperatively. Secondary endpoints included peri‐operative change in haemoglobin, postoperative complications and length of hospital stay. Most patients had iron deficiency (369/452 82%) at randomisation; one‐third had absolute iron deficiency (144/452 32%) and half had functional iron deficiency (225/452 50%). The change in pre‐operative haemoglobin with intravenous iron compared with placebo was greatest in patients with absolute iron deficiency, mean difference 8.9 g.l−1, 95%CI 5.3–12.5; moderate in functional iron deficiency, mean difference 2.8 g.l−1, 95%CI −0.1 to 5.7; and with little change seen in those patients who were non‐iron deficient. Subgroup analyses did not suggest that intravenous iron compared with placebo reduced the likelihood of death or blood transfusion at 30 days differentially across subgroups according to baseline ferritin (p = 0.33 for interaction), transferrin saturation (p = 0.13) or in combination (p = 0.45), or for the number of blood transfusions (p = 0.06, 0.29, and 0.39, respectively). There was no beneficial effect of the use of intravenous iron compared with placebo, regardless of the metrics to diagnose iron deficiency, on postoperative complications or length of hospital stay.
ObjectivesGiven the current excellent early mortality rates for paediatric cardiac surgery, stakeholders believe that this important safety outcome should be supplemented by a wider range of ...measures. Our objectives were to prospectively measure the incidence of morbidities following paediatric cardiac surgery and to evaluate their clinical and health-economic impact over 6 months.DesignThe design was a prospective, multicentre, multidisciplinary mixed methods study.SettingThe setting was 5 of the 10 paediatric cardiac surgery centres in the UK with 21 months recruitment.ParticipantsIncluded were 3090 paediatric cardiac surgeries, of which 666 patients were recruited to an impact substudy.ResultsFamilies and clinicians prioritised:Acute neurological event, unplanned re-intervention, feeding problems, renal replacement therapy, major adverse events, extracorporeal life support, necrotising enterocolitis, postsurgical infection and prolonged pleural effusion or chylothorax.Among 3090 consecutive surgeries, there were 675 (21.8%) with at least one of these morbidities. Independent risk factors for morbidity included neonatal age, complex heart disease and prolonged cardiopulmonary bypass (p<0.001). Among patients with morbidity, 6-month survival was 88.2% (95% CI 85.4 to 90.6) compared with 99.3% (95% CI 98.9 to 99.6) with none of the morbidities (p<0.001). The impact substudy in 340 children with morbidity and 326 control children with no morbidity indicated that morbidity-related impairment in quality of life improved between 6 weeks and 6 months. When compared with children with no morbidities, those with morbidity experienced a median of 13 (95% CI 10.2 to 15.8, p<0.001) fewer days at home by 6 months, and an adjusted incremental cost of £21 292 (95% CI £17 694 to £32 423, p<0.001).ConclusionsEvaluation of postoperative morbidity is more complicated than measuring early mortality. However, tracking morbidity after paediatric cardiac surgery over 6 months offers stakeholders important data that are of value to parents and will be useful in driving future quality improvement.
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