With FFR as the reference standard, the diagnostic ability of MR perfusion to detect ischemic CAD is high.

OBJECTIVES:  Crohn's disease is now increasingly considered as a disabling disease. Conventionally, the disease is managed by step‐up therapy. In recent years, the top‐down strategy has been proposed and is thought to benefit the patients in whom the condition is likely to rapidly deteriorate toward disabling. However, this strategy has severe adverse effects which have to be weighed against its benefits. The aim of this study is to identify the risk factors that can predict the requirement of top‐down therapy among Chinese patients. METHODS:  We included 207 Chinese patients who had histories of Crohn's disease for ≥5 years, or those who had Crohn's disease for <5 years and at least one criterion of disabling disease. The risk factors related to the 5‐year disabling course and the 2‐year disabling course of Crohn's disease were separately analyzed in the same cohort by logistic regression. RESULTS:  Among the 207 patients, the rate of disabling disease was 80.19% for 5‐year, and 71.01% for 2‐year. The risk factors of age <40 years at diagnosis, steroids requirement for treating acute exacerbation, and presence of perianal disease at diagnosis were significantly associated with a 5‐year disabling course. In the same cohort, the risk factors related to 2‐year disabling course were likewise steroids requirement for treating acute exacerbation and presence of perianal disease at diagnosis. CONCLUSION:  The risk factors associated with disabling Crohn's disease, which entails the requirement of top‐down therapy in Chinese patients, are requirement of steroids for treating acute exacerbation and the presence of perianal disease at diagnosis.

Background Aspects of infant antibiotic exposure and its association with asthma development have been variably explored. We aimed to evaluate comprehensively and simultaneously the impact of dose, timing, and type of infant antibiotic use on the risk of childhood asthma. Methods Singleton, term-birth, non–low-birth-weight, and otherwise healthy children enrolled in the Tennessee Medicaid Program were included. Infant antibiotic use and childhood asthma diagnosis were ascertained from prescription fills and healthcare encounter claims. We examined the association using multivariable logistic regression models. Results Among 152 622 children, 79% had at least 1 antibiotic prescription fill during infancy. Infant antibiotic use was associated with increased odds of childhood asthma in a dose-dependent manner, with a 20% increase in odds (adjusted odds ratio [aOR], 1.20 [95% confidence interval {CI}, 1.19–1.20]) for each additional antibiotic prescription filled. This significant dose-dependent relationship persisted after additionally controlling for timing and type of the antibiotics. Infants who had broad-spectrum-only antibiotic fills had increased odds of developing asthma compared with infants who had narrow-spectrum-only fills (aOR, 1.10 [95% CI, 1.05–1.19]). There was no significant association between timing, formulation, anaerobic coverage, and class of antibiotics and childhood asthma. Conclusions We found a consistent dose-dependent association between antibiotic prescription fills during infancy and subsequent development of childhood asthma. Our study adds important insights into specific aspects of infant antibiotic exposure. Clinical decision making regarding antibiotic stewardship and prevention of adverse effects should be critically assessed prior to use during infancy.

• The accuracy of CCTA with different prospective ECG gating is similar • CCTA with prospective ECG gating is effective to exclude coronary artery disease • The radiation dose of volume mode increases with higher heart rate.

A classical approach to combine independent test statistics is Fisher's combination of $p$-values, which follows the $\chi ^2$ distribution. When the test statistics are dependent, the gamma distribution (GD) is commonly used for the Fisher's combination test (FCT). We propose to use two generalizations of the GD: the generalized and the exponentiated GDs. We study some properties of mis-using the GD for the FCT to combine dependent statistics when one of the two proposed distributions are true. Our results show that both generalizations have better control of type I error rates than the GD, which tends to have inflated type I error rates at more extreme tails. In practice, common model selection criteria (e.g. Akaike information criterion/Bayesian information criterion) can be used to help select a better distribution to use for the FCT. A simple strategy of the two generalizations of the GD in genome-wide association studies is discussed. Applications of the results to genetic pleiotrophic associations are described, where multiple traits are tested for association with a single marker.

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Individuals with monogenic disorders can experience variable phenotypes that are influenced by genetic variation. To investigate this in sickle cell disease (SCD), we performed whole-genome sequencing (WGS) of 722 individuals with hemoglobin HbSS or HbSβ0-thalassemia from Baylor College of Medicine and from the St. Jude Children’s Research Hospital Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study. We developed pipelines to identify genetic variants that modulate sickle hemoglobin polymerization in red blood cells and combined these with pain-associated variants to build a polygenic score (PGS) for acute vaso-occlusive pain (VOP). Overall, we interrogated the α-thalassemia deletion −α3.7 and 133 candidate single-nucleotide polymorphisms (SNPs) across 66 genes for associations with VOP in 327 SCCRIP participants followed longitudinally over 6 years. Twenty-one SNPs in 9 loci were associated with VOP, including 3 (BCL11A, MYB, and the β-like globin gene cluster) that regulate erythrocyte fetal hemoglobin (HbF) levels and 6 (COMT, TBC1D1, KCNJ6, FAAH, NR3C1, and IL1A) that were associated previously with various pain syndromes. An unweighted PGS integrating all 21 SNPs was associated with the VOP event rate (estimate, 0.35; standard error, 0.04; P = 5.9 × 10−14) and VOP event occurrence (estimate, 0.42; standard error, 0.06; P = 4.1 × 10−13). These associations were stronger than those of any single locus. Our findings provide insights into the genetic modulation of VOP in children with SCD. More generally, we demonstrate the utility of WGS for investigating genetic contributions to the variable expression of SCD-associated morbidities.

Introduction Sickle cell anemia (SCA) results in numerous adverse effects on the brain, including neurocognitive dysfunction. Hydroxyurea has been utilized extensively for management of SCA, but its effects on brain function have not been established. Methods We examined prospectively the effects of 1 year of treatment with hydroxyurea on brain function in children with SCA (HbSS/HbSβ0‐thalassemia) by baseline and exit evaluations, including comprehensive neurocognitive testing, transcranial Doppler ultrasound (TCD), and brain MRI (silent cerebral infarcts [SCI], gray matter cerebral blood flow [GM‐CBF], and blood oxygen level‐dependent [BOLD] signal from visual stimulation). Results Nineteen patients with SCA, mean age 12.4 years (range 7.2–17.8), were evaluated. At baseline, subjects had these mean values: full‐scale IQ (FSIQ) 82.8, TCD velocity 133 cm/s, GM‐CBF 64.4 ml/100 g/min, BOLD signal 2.34% increase, and frequency of SCI 47%. After 1 year of hydroxyurea, there were increases in FSIQ (+2, p = .059) and reading passage comprehension (+4, p = .033), a significant decrease in TCD velocity (−11 cm/s, p = .007), and no significant changes in GM‐CBF, BOLD, or SCI frequency. Hemoglobin F (HbF) was associated with passage comprehension, hemoglobin with lower TCD velocity, and lower GM‐CBF with greater working memory. Higher BOLD signal was associated with higher processing speed and lower TCD velocity with higher math fluency. Discussion Improvements in neurocognition and decreased TCD velocity following 1 year of treatment support hydroxyurea use for improving neurocognitive outcomes in SCA. Understanding the mechanisms of benefit, as indicated by relationships of neurocognitive function with HbF, hemoglobin, and CBF, requires further evaluation.