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- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 3. |
- Christiansen, Colette, et al.
(författare)
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Adipose methylome integrative-omic analyses reveal genetic and dietary metabolic health drivers and insulin resistance classifiers
- 2022
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is considerable evidence for the importance of the DNA methylome in metabolic health, for example, a robust methylation signature has been associated with body mass index (BMI). However, visceral fat (VF) mass accumulation is a greater risk factor for metabolic disease than BMI alone. In this study, we dissect the subcutaneous adipose tissue (SAT) methylome signature relevant to metabolic health by focusing on VF as the major risk factor of metabolic disease. We integrate results with genetic, blood methylation, SAT gene expression, blood metabolomic, dietary intake and metabolic phenotype data to assess and quantify genetic and environmental drivers of the identified signals, as well as their potential functional roles. Methods: Epigenome-wide association analyses were carried out to determine visceral fat mass-associated differentially methylated positions (VF-DMPs) in SAT samples from 538 TwinsUK participants. Validation and replication were performed in 333 individuals from 3 independent cohorts. To assess functional impacts of the VF-DMPs, the association between VF and gene expression was determined at the genes annotated to the VF-DMPs and an association analysis was carried out to determine whether methylation at the VF-DMPs is associated with gene expression. Further epigenetic analyses were carried out to compare methylation levels at the VF-DMPs as the response variables and a range of different metabolic health phenotypes including android:gynoid fat ratio (AGR), lipids, blood metabolomic profiles, insulin resistance, T2D and dietary intake variables. The results from all analyses were integrated to identify signals that exhibit altered SAT function and have strong relevance to metabolic health. Results: We identified 1181 CpG positions in 788 genes to be differentially methylated with VF (VF-DMPs) with significant enrichment in the insulin signalling pathway. Follow-up cross-omic analysis of VF-DMPs integrating genetics, gene expression, metabolomics, diet, and metabolic traits highlighted VF-DMPs located in 9 genes with strong relevance to metabolic disease mechanisms, with replication of signals in FASN, SREBF1, TAGLN2, PC and CFAP410. PC methylation showed evidence for mediating effects of diet on VF. FASN DNA methylation exhibited putative causal effects on VF that were also strongly associated with insulin resistance and methylation levels in FASN better classified insulin resistance (AUC=0.91) than BMI or VF alone. Conclusions: Our findings help characterise the adiposity-associated methylation signature of SAT, with insights for metabolic disease risk.
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