Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study.

Genetic pleiotropy is abundant across spatially distributed brain characteristics derived from one neuroimaging modality (e.g. structural, functional or diffusion magnetic resonance imaging [MRI]). A better understanding of pleiotropy across modalities could inform us on the integration of brain function, micro- and macrostructure. Here we show extensive genetic overlap across neuroimaging modalities at a locus and gene level in the UK Biobank (N = 34,029) and ABCD Study (N = 8607). When jointly analysing phenotypes derived from structural, functional and diffusion MRI in a genome-wide association study (GWAS) with the Multivariate Omnibus Statistical Test (MOSTest), we boost the discovery of loci and genes beyond previously identified effects for each modality individually. Cross-modality genes are involved in fundamental biological processes and predominantly expressed during prenatal brain development. We additionally boost prediction of psychiatric disorders by conditioning independent GWAS on our multimodal multivariate GWAS. These findings shed light on the shared genetic mechanisms underlying variation in brain morphology, functional connectivity, and tissue composition.

Effect of the "door-to-balloon" time on the results of treatment of patients with ST-segment elevation myocardial infarction, depending on the duration of the pre-hospital delay.

Aim    To analyze the effect of the door-to-balloon time on treatment outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) depending on the duration of pre-hospital delay.Material ad methods    The study used data of the hospital registry of percutaneous coronary interventions (PCI) in STEMI from 2006 through 2017. The analysis included 1333 patients. All patients were divided into two groups. The first group included 574 (43.1%) patients with the time from the pain syndrome onset to admission was ≤120 min. The second group consisted of 759 (56.9 %) patients with the time of pre-hospital delay exceeding 120 min. Results of the treatment were analyzed for each group depending on the door-to-balloon time, ≤60 min or >60 min.Results    In the group of patients with the prehospital delay less than 120 min and the door-to-balloon time ≤60 min vs. patients with the door-to-balloon time >60 min, the following was observed: decreased in-hospital mortality (1.3 % vs. 6.8 %, p=0.001), reduced incidence of major adverse cardiac effects (МАСЕ) (3.2 % vs. 8.3 %, p=0.008), and reduced incidence of the no-reflow phenomenon (3.9 % vs. 9.4 %, p=0.007). Also, immediate angiographic success of PCI was more frequently achieved in these patents (94.5 % vs. 87.5 %, p=0.003). In addition, in the group with the prehospital delay ≤120 min and the door-to-balloon time ≤60 min, a higher ejection fraction was noted at discharge from the hospital (48 [43; 51] % vs. 46 [42; 51] %, р=0.038). Comparison of treatment outcomes between the groups with different door-to-balloon time (≤60 min or >60 min) and a prehospital delay >120 min did not show any significant intergroup differences. According to a multivariate analysis, the door-to-balloon time ≤60 min did not predict in-hospital mortality. There was a strong correlation between the time of prehospital delay and the total time of myocardial ischemia (r=0.87; р<0.001) while the correlation between the door-to-balloon time and the total time of myocardial ischemia was moderate (r=0.41; р<0.001). At the same time, there was no correlation between the time of prehospital delay and the door-to-balloon time.Conclusion    In STEMI patients with a prehospital delay less than 120 min from the pain syndrome onset, a decrease in the door-to-balloon time was associated with better outcome of the hospital treatment. When the duration of prehospital delay was more than 120 min, a decrease in door-to-balloon time did not influence the treatment outcome. The time of prehospital delay strongly correlated with the total time of myocardial ischemia.

The risk score for in-hospital mortality in patients with ST-segment elevation myocardial infarction.

Aim    To develop a scale (score system) for predicting the individual risk of in-hospital death in patients with ST segment elevation acute myocardial infarction (STEMI) with an account of results of percutaneous coronary intervention (PCI).Material and methods    The analysis used data of 1 649 sequential patients with STEMI included into the hospital registry of PCI from 2006 through 2017. To test the model predictability, the original sample was divided into two groups: a training group consisting of 1150 (70 %) patients and a test group consisting of 499 (30 %) patients. The training sample was used for computing an individual score. To this purpose, ß-coefficients of each variable obtained at the last stage of the multivariate logistic regression model were subjected to linear transformation. The scale was verified using the test sample.Results    Seven independent predictors of in-hospital death were determined: age ≥65 years, acute heart failure (Killip class III-IV), total myocardial ischemia time ≥180 min, anterior localization of myocardial infarction, failure of PCI, SYNTAX scale score ≥16, glycemia on admission ≥7.78 mmol/l for patients without a history of diabetes mellitus and ≥14.35 mmol/l for patients with a history of diabetes mellitus. The contribution of each value to the risk of in-hospital death was ranked from 0 to 7. A threshold total score of 10 was determined; a score ≥10 corresponded to a high probability of in-hospital death (18.2 %). In the training sample, the sensitivity was 81 %, the specificity was 80.6 %, and the area under the curve (AUC) was 0.902. In the test sample, the sensitivity was 96.2 %, the specificity was 83.3 %, and the AUC was 0.924.Conclusion    The developed scale has a good predictive accuracy in identifying patients with acute STEMI who have a high risk of fatal outcome at the hospital stage.