RESUMO
BACKGROUND: Numerous observational studies have documented a correlation between inflammatory bowel disease (IBD) and an increased risk of dementia. However, the causality of their associations remains elusive. AIM: To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization (MR) method. METHODS: Genetic variants extracted from the large genome-wide association study (GWAS) for IBD (the International IBD Genetics Consortium, n = 34652) were used to identify the causal link between IBD and dementia (FinnGen, n = 306102). The results of the study were validated via another IBD GWAS (United Kingdom Biobank, n = 463372). Moreover, MR egger intercept, MR pleiotropy residual sum and outlier, and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity. Finally, multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia, with the inverse variance wei-ghted approach adopted as the primary analysis. RESULTS: The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS. No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted [odds ratio (OR) = 0.980, 95%CI : 0.942-1.020, P value = 0.325], weighted median (OR = 0.964, 95%CI : 0.914-1.017, P value = 0.180), and MR-Egger (OR = 0.963, 95%CI : 0.867-1.070, P value = 0.492) approaches. Consistent results were observed in validation analyses. Reverse MR analysis also showed no effect of dementia on the development of IBD. Furthermore, MR analysis suggested that IBD and its subtypes did not causally affect all-cause dementia and its four subtypes, including dementia in Alzheimer's disease, vascular dementia, dementia in other diseases classified elsewhere, and unspecified dementia. CONCLUSION: Taken together, our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes. Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.
RESUMO
BACKGROUND: Pulse oximetry screening for critical congenital heart disease (CHD) is inapplicable to high altitude due to the variedly decreased arterial saturations and rare complex CHD. We examined the incidence and spectrum of CHD in newborns using echocardiography at high altitude and followed up their outcomes. METHODS: A total of 1337 babies were studied. Echocardiography was performed in 1002 asymptomatic newborns (3-5â¯days). In the same period, retrospectively studied 394 newborns (≤2â¯days) admitted to the NICU where echocardiograph was performed in 335. In both groups, follow-up was made at 1-3, 6 and 12-18â¯months. RESULTS: The incidence of CHD in asymptomatic newborns was 27.8%, consisting secundum atrial septal defect (ASD) [175 (62.7%)], patent ductus arteriosus (PDA) [61 (21.9%)], ventricular septal defect (VSD) [8 (2.9%)] and multiple defects [35 (12.6%)]. And 19.4% in NICU patients with similar spectrum, except for 2 with complex CHD who died before discharge. By 12-18â¯months of follow-up, 30% of CHD remained open. Thirteen patients developed mild to severe pulmonary arterial hypertension (PAH), and 2 of them died of heart failure. CONCLUSIONS: The incidence of CHD in newborns at high altitude is about 20 times higher than that at low altitude, consisting mostly of simple forms with left to right shunt, with rare complex CHD. By 12-18â¯months, the incidence of CHD is still about 10 times higher than that at low altitude. About 8% patients developed PAH or death. Follow-up must be reinforced in order to provide early intervention and prevent from PAH or death.
