Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Incidence of obesity in parturients scheduled for caesarean section, intra-operative complications, management and outcome

Objectives: To determine the incidence of obesity in parturients scheduled for Caesarean section, identify intra-operative complications, management and outcome.Design: A prospective observational study.Setting: University of Benin Teaching Hospital, a university-affiliated tertiary centre. Subjects: Parturients scheduled for Caesarean section excluding patients in American Society of Anaesthesiologists (ASA) health status 4 and 5. Results: Three hundred patients were recruited in the study. One hundred and forty eight (49.3%) were non – obese (BMI 30kgm –2). The incidence of obesity was extremely significant

Classification Types Of Postoperative Enterocutaneous Fistula As A Determinant Of Outcome Of Treatment In Ile-Ife, Nigeria

Objective: Post operative enterocutaneous fistula, in this environment, continues to excite interest because it runs a distressing course, and it is often associated with high mortality and morbidity. Determining the classification type best suited to suggest the outcome would be helpful in guiding the management of the condition. Setting: Ife Hospital Unit, Obafemi Awolowo Teaching Hospitals Complex, Ile – Ife. Outcome Measure: To determine the clinical pattern of post operative external enterocutaneous fistula and the classification method that best predict outcome of the condition. Methodology: Consecutive patients with clinical postoperative external enterocutaneous fistula seen between 1994 and 2006 were studied. The case files were retrieved and information on demographic data, type of initial surgery, source of referral, and characteristic of the fistula in terms of effluent per day and type of intestine involved were retrieved and analyzed. Patient with incomplete clinical information were excluded from the study. Result: There were 30 patients aged 17 to 65 years, mean of 33 years ±SD 12.23 years, with male to female ratio of 2:1. Length of hospital stay ranged from 1 to 43 weeks. Majority 28 (93.3%) were referred after primary operation at the lower cadre hospitals. Enterocutaneous fistula followed intestinal resection in 15 cases (50.0%) and was post appendicectomy in 9 cases (30.06%). Three (11.1%) cases each had burst abdomen and Acquired Immunodeficiency Syndrome (AIDS) in 3 cases (11.1%) additionally. Overall mortality was 12 (40 %) was high. Compared with the other classifications considered in the study classification into high and low output highly correlated with the outcome of treatment logistic regression p < 0.006 versus p = 0.123 and p = 0.244 respectively for Sitges – Serra and schein and groups. Conclusion: In this study majority of patients with enterocutaneous fistula were referred from Private and State hospitals set up. This might be a reflection of the generally lower level of technical surgical skills at this level of healthcare facilities. Classification of enterocutaneous fistula into high and low output was still useful in our environment for predicting prognosis and may, therefore, be used to guide management strategies. Keywords: Post operative enterocutaneous fistula, Treatment outcome determinant, Classification.Sahel Medical Journal Vol. 11 (4) 2008: pp. 105-10