Pediatric cardiac computed tomography angiography: Expert consensus from the Filiale de Cardiologie Pédiatrique et Congénitale (FCPC) and the Société Française d’Imagerie Cardiaque et Vasculaire diagnostique et interventionnelle (SFICV)

This article was designed to provide a pediatric cardiac computed tomography angiography (CCTA) expert panel consensus based on opinions of experts of the Société Française d’Imagerie Cardiaque et Vasculaire diagnostique et interventionnelle (SFICV) and of the Filiale de Cardiologie Pédiatrique Congénitale (FCPC). This expert panel consensus includes recommendations for indications, patient preparation, CTA radiation dose reduction techniques, and post-processing techniques. The consensus was based on data from available literature (original papers, reviews and guidelines) and on opinions of a group of specialists with extensive experience in the use of CT imaging in congenital heart disease. In order to reach high potential and avoid pitfalls, CCTA in children with congenital heart disease requires training and experience. Moreover, pediatric cardiac CCTA protocols should be standardized to acquire optimal images in this population with the lowest radiation dose possible to prevent unnecessary radiation exposure. We also provided a suggested structured report and a list of acquisition protocols and technical parameters in relation to specific vendors.     

颞下颌关节强直动物模型中最大张口度与强直严重程度关系研究

目的　研究主、被动最大张口度（AMMO、PMMO）与颞下颌关节强直严重程度的关系。方法　选取28只健康雄性绵羊随机分为实验组和对照组，每组各14只。实验组绵羊双侧颞下颌关节模拟髁突矢状骨折，其中左侧翼外肌被切断以阻断其功能；对照组绵羊未进行手术。于术前及术后12、24周对所有绵羊体重、AMMO、PMMO、颞下颌关节形态学特点进行测量评估。结果　实验组只有右侧保留翼外肌功能的颞下颌关节发生了骨强直。术后12、24周，实验组绵羊AMMO、PMMO、极限距离均显著低于对照组，差异均有统计学意义（均P < 0.05）。实验组绵羊AMMO和PMMO与骨融合区宽度、长度、面积及钙化程度均呈负相关（均P < 0.05），其中骨融合区面积为主要影响因素（术后12、24周相关系数r分别为-0.94、-0.95）。结论　颞下颌关节强直动物模型中阻断翼外肌功能可阻止骨强直的发生；对于早期髁突矢状骨折，可通过牙合垫或牙合板进行张口训练，进而阻断翼外肌功能。当颞下颌关节发生骨强直时，骨融合区面积越大，张口受限越明显。     

Coronary Artery Lumen Segmentation Using Location–Adaptive Threshold in Coronary Computed Tomographic Angiography: A Proof-of-Concept

ObjectiveTo compare the lumen parameters measured by the location-adaptive threshold method (LATM), in which the inter- and intra-scan attenuation variabilities of coronary computed tomographic angiography (CCTA) were corrected, and the scan-adaptive threshold method (SATM), in which only the inter-scan variability was corrected, with the reference standard measurement by intravascular ultrasonography (IVUS).Materials and MethodsThe Hounsfield unit (HU) values of whole voxels and the centerline in each of the cross-sections of the 22 target coronary artery segments were obtained from 15 patients between March 2009 and June 2010, in addition to the corresponding voxel size. Lumen volume was calculated mathematically as the voxel volume multiplied by the number of voxels with HU within a given range, defined as the lumen for each method, and compared with the IVUS-derived reference standard. Subgroup analysis of the lumen area was performed to investigate the effect of lumen size on the studied methods. Bland-Altman plots were used to evaluate the agreement between the measurements.ResultsLumen volumes measured by SATM was significantly smaller than that measured by IVUS (mean difference, 14.6 mm³; 95% confidence interval [CI], 4.9–24.3 mm³); the lumen volumes measured by LATM and IVUS were not significantly different (mean difference, −0.7 mm³; 95% CI, −9.1–7.7 mm³). The lumen area measured by SATM was significantly smaller than that measured by LATM in the smaller lumen area group (mean of difference, 1.07 mm²; 95% CI, 0.89–1.25 mm²) but not in the larger lumen area group (mean of difference, −0.07 mm²; 95% CI, −0.22–0.08 mm²). In the smaller lumen group, the mean difference was lower in the Bland-Altman plot of IVUS and LATM (0.46 mm²; 95% CI, 0.27–0.65 mm²) than in that of IVUS and SATM (1.53 mm²; 95% CI, 1.27–1.79 mm²).ConclusionSATM underestimated the lumen parameters for computed lumen segmentation in CCTA, and this may be overcome by using LATM.     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Quantile regression and empirical likelihood for the analysis of longitudinal data with monotone missing responses due to dropout,with applications to quality of life measurements from clinical trials

The analysis of quality of life (QoL) data can be challenging due to the skewness of responses and the presence of missing data. In this paper, we propose a new weighted quantile regression method for estimating the conditional quantiles of QoL data with responses missing at random. The proposed method makes use of the correlation information within the same subject from an auxiliary mean regression model to enhance the estimation efficiency and takes into account of missing data mechanism. The asymptotic properties of the proposed estimator have been studied and simulations are also conducted to evaluate the performance of the proposed estimator. The proposed method has also been applied to the analysis of the QoL data from a clinical trial on early breast cancer, which motivated this study.     

Dynamic Indicators That Impact the Outcomes of Thoracic Endovascular Aortic Repair in Complicated Type B Aortic Dissection

PurposeTo investigate dynamic variables obtained from retrospective computed tomography angiography for ability to predict thoracic endovascular aortic repair (TEVAR) outcomes in patients with complicated type B aortic dissection (cTBAD).Materials and MethodsSeventy-nine patients with cTBAD who received TEVAR from March 2009 to June 2018 were retrospectively enrolled. Relative true lumen area (r-TLA) was computed at the level of tracheal bifurcation every 5% of all R-R intervals. Parameters that reflect the state of intimal motion were evaluated, including difference between maximum and minimum r-TLA (D-TLA) and true lumen collapse. The endpoints comprised early (≤ 30 days) and late (> 30 days) outcomes after intervention.ResultsOverall early mortality rate was 13.9% (11/79), and early adverse events rate was 24.1% (19/79). Patients who received TEVAR within 2 days of symptom onset demonstrated the worst outcomes. A longer time of r-TLA < 25% in 1 cardiac cycle (P = .049) and larger D-TLA (P < .001) were correlated to an increased early death. In addition, D-TLA was an independent predictor of early mortality. Area under the curve of D-TLA was 0.849 (95% confidence interval 0.730–0.967) for predicting early mortality and 0.742 (95% CI 0.611–0.873) for predicting early adverse events. Survival and event-free survival rates during follow-up were decreased in the D-TLA > 21.5% group compared with the D-TLA ≤ 21.5% group (all P < .001).ConclusionsLarger D-TLA is correlated with worse postoperative outcomes and might be a crucial parameter for future risk stratification in patients with cTBAD.     

Recipient hypertonic saline infusion prevents cardiac allograft dysfunction

Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.

Normal obstetric ultrasound reduces the risk of Down syndrome in fetuses of older mothers

The objective of this study is to determine whether a normal fetal morphology ultrasound scan in women older than 35 years reduces the risk of aneuploidy. We reviewed the results of amniocentesis and second trimester sonogram in all women older than 35 years from 1991 to 1995. None had prior screening. We excluded fetuses with structural anomalies. We determined the sensitivity and specificity of minor markers in detecting Down syndrome and also determined the reduction in risk of a normal sonogram. Among the 2060 women older than 35 years giving birth during the study period, 16 (0.78%) delivered an infant with Down syndrome. Of the 16 fetuses, two had no prenatal testing or ultrasound, two had invasive testing but no second trimester sonogram, five had a normal sonogram and seven had one or more sonographic markers of Down syndrome. At least 17% of women older than 35 years did not participate in prenatal testing or ultrasound. Ultrasound detected Down syndrome with a sensitivity of 59% (95% confidence interval: 45–72%), a false‐positive rate of 10.6% (9.4–11.8%) and a positive predictor value of 1 in 9. The likelihood of having normal karyotype if the sonogram was normal was 0.46 (0.31–0.61). In women older than 35 years, a normal second trimester sonogram reduces the risk of Down syndrome by more than 50%. At least 17% of women older than 35 years do not participate in prenatal testing or ultrasound.     

Bayesian estimation of a random effects heteroscedastic probit model

Summary Bayesian analysis is given of a random effects binary probit model that allows for heteroscedasticity. Real and simulated examples illustrate the approach and show that ignoring heteroscedasticity when it exists may lead to biased estimates and poor prediction. The computation is carried out by an efficient Markov chain Monte Carlo sampling scheme that generates the parameters in blocks. We use the Bayes factor, cross‐validation of the predictive density, the deviance information criterion and Receiver Operating Characteristic (ROC) curves for model comparison.