Trans-lesional fractional flow reserve gradient as derived from coronary CT improves patient management: ADVANCE registry

BackgroundThe role of change in fractional flow reserve derived from CT (FFR_CT) across coronary stenoses (ΔFFR_CT) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown.ObjectivesTo investigate the incremental value of ΔFFR_CT in predicting early revascularization and improving efficiency of catheter laboratory utilization.MaterialsPatients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFR_CT was measured 2 ?cm distal to stenosis. ΔFFR_CT was manually measured as the difference of FFR_CT across visible stenosis.ResultsOf 4730 patients (66 ?± ?10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFR_CT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26–1.35]; p ?< ?0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFR_CT. Among the 3 models (model 1: risk factors ?+ ?stenosis type and location ?+ ?CAD-RADS; model 2: model 1 ?+ ?FFR_CT; model 3: model 2 ?+ ?ΔFFR_CT), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86–0.88] vs 0.85 [0.84–0.86]; p ?< ?0.001), with the greatest incremental value for FFR_CT 0.71–0.80. ΔFFR_CT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFR_CT ≤0.8, a diagnostic strategy incorporating ΔFFR_CT >0.13, would potentially reduce ICA by 32.2% (1638–1110, p ?< ?0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%.ConclusionsΔFFR_CT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFR_CT, particularly for those with FFR_CT 0.71–0.80. ΔFFR_CT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization.     

Delayed haemolytic transfusion reaction due to Kidd antibodies

A delayed haemolytic transfusion reaction (DHTR) encompasses a positive direct antiglobulin test (DAT) developed anytime between 24 hours to 28 days after cessation of transfusion, a positive eluate or a newly identified alloantibody in the plasma or serum along with features of haemolysis in the patient. Routinely, it is expected that with the transfusion of one unit of packed red cells in a patient of average height and weight, the haemoglobin level and hematocrit increase by 1 g/dL and 3% respectively. However, in a patient with DHTR, an inadequate rise of post-transfusion haemoglobin (< 1 g/dL) or rapid fall in haemoglobin back to pre-transfusion levels is observed. Kidd antibodies are particularly known to cause DHTR, maybe alone or in unison with other antibodies. Detection of these alloantibodies is consequential in providing good transfusion support to these patients. These events may be difficult to detect as they may present as varied clinical features or immunological nuisances. In this case series, we have presented three cases of DHTR with special emphasis on their clinical presentations, immunohaematological evaluations, laboratory parameters and the role of proper transfusion support in these patients to avoid further complications.     

Dietary patterns and the risk of abnormal blood lipids among young adults: A prospective cohort study

Background and aimsThe extent to which dietary patterns influence the risk of abnormal blood lipids throughout young adulthood remains unclear. The aim was to investigate whether early young adulthood dietary patterns predict the risk of abnormal blood lipids during later young adulthood.Methods and resultsWe used data from a long running birth cohort study in Australia. Western dietary pattern rich in meats, processed foods and high-fat dairy products and prudent pattern rich in fruit, vegetables, fish, nuts, whole grains and low-fat dairy products were derived using principal component analysis at the 21-year follow-up from dietary data obtained using a food frequency questionnaire. After 9-years, fasting blood samples of all participants were collected and their total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterols and triglyceride (TG) levels were measured. Abnormal blood lipids were based on clinical cut-offs for total, LDL and HDL cholesterols, and TG and relative distributions for total:HDL and TG:HDL cholesterols ratios. Log-binomial models were used to estimate risk of each outcome in relation to dietary patterns. Greater adherence to the Western pattern predicted increased risks of high LDL (RR: 1.47; 95%CI: 1.06, 2.03) and TG (1.90; 1.25, 2.86), and high ratios of total:HDL (1.48; 1.00, 2.19) and TG:HDL (1.78; 1.18, 2.70) cholesterols in fully adjusted models. Conversely, a prudent pattern predicted reduced risks of low HDL (0.58; 0.42, 0.78) and high TG (0.66; 0.47, 0.92) and high total:HDL (0.71; 0.51, 0.98) and TG:HDL (0.61; 0.45, 0.84) cholesterols ratios.ConclusionThis is the first prospective study to show greater adherence to unhealthy Western diet predicted increased risks of abnormal blood lipids, whereas healthy prudent diet predicted lower such risks in young adults. Addressing diets in early course may improve cardiovascular health of young adults.     

Eulerian Algorithms for Computing the Forward Finite Time Lyapunov Exponent Without Finite Difference upon the Flow Map

In this paper, effective Eulerian algorithms are introduced for the computation of the forward finite time Lyapunov exponent (FTLE) of smooth flow fields. The advantages of the proposed algorithms mainly manifest in two aspects. First, previous Eulerian approaches for computing the FTLE field are improved so that the Jacobian of the flow map can be obtained by directly solving a corresponding system of partial differential equations, rather than by implementing certain finite difference upon the flow map, which can significantly improve the accuracy of the numerical solution especially near the FTLE ridges. Second, in the proposed algorithms, all computations are done on the fly, that is, all required partial differential equations are solved forward in time, which is practically more natural. The new algorithms still maintain the optimal computational complexity as well as the second order accuracy. Numerical examples demonstrate the effectiveness of the proposed algorithms.     

我国弓形虫Chinese 1优势基因型感染对小鼠脑组织铁代谢影响

目的　探讨我国弓形虫Chinese 1优势基因型感染对宿主脑组织铁代谢及脑损伤的影响。方法　将20只C57BL/6（体质量15～17 g）小鼠随机分为对照组和感染组，每组10只。感染组每只小鼠腹腔注射4 000个弓形虫Chinese 1优势基因型TgCtwh3虫株速殖子，对照组小鼠注射等量无菌PBS，饲养6 d后处死小鼠并取其脑组织。采用电感耦合等离子体质谱法（inductively coupled plasma mass spectrometry, ICP⁃MS）检测小鼠脑组织铁元素水平；采用RNA芯片检测两组小鼠脑组织差异基因数目并对功能基因表达情况进行基因本体论（Gene Ontology, GO）功能富集；采用实时荧光定量PCR（fluorescent quantitative real⁃time PCR, qPCR）技术检测小鼠脑组织中弓形虫表面抗原1（Toxoplasma gondii surface antigen 1，TgSAG1）基因及部分锌铁调控蛋白（Zrt⁃ and Irt⁃like protein, ZIP）家族mRNA表达水平；采用光镜和电镜观察小鼠脑组织海马齿轮回（dentate gyrus, DG）超微结构；采用Western blotting检测谷胱甘肽过氧化物酶4（glutathione peroxidase 4, GPx4）蛋白表达水平；采用硫代巴比妥酸（TBA）法检测丙二醛（malondialdehyde, MDA）水平；采用免疫组化检测血管内皮生长因子（vascular endothelial growth factor, VEGF）蛋白表达光密度（optical density, OD）值。结果　光镜下可见感染组小鼠脑组织海马DG区细胞坏死，电镜下见感染组小鼠脑组织海马区出现胞质空泡化、核皱缩坏死、线粒体嵴断裂消融、自噬小体增加等超微结构变化。与对照组相比，感染组小鼠脑组织中铁元素水平上调[（32.92 ± 0.90） µg/g vs.（37.72 ± 1.10） µg/g；t = 3.397, P < 0.01]；RNA芯片检测感染组小鼠脑组织发现721个基因上调、276个基因下调，差异表达基因在金属离子结合能力上有明显富集。与对照组相比，感染组小鼠脑组织金属元素转运体ZIP2 mRNA表达水平上调（t = 8.659，P < 0.05）、GPx4表达下降[（1.046 ± 0.025） vs. （0.720 ± 0.101）；t = 3.129，P < 0.01]）、MDA水平升高[（4.37 ± 0.33） nmol/mgprot vs.（5.93 ± 0.54） nmol/mgprot；t = 2.451，P < 0.05）]、VEGF蛋白平均OD值上调[（0.348 3 ± 0.017 8） vs. （0.490 6 ± 0.010 5）；t = 6.641，P < 0.01]。结论　Chinese 1优势基因型弓形虫感染后，小鼠脑组织中铁元素蓄积、抗氧化能力下调、氧化应激水平升高，提示弓形虫感染可影响宿主脑组织铁代谢而导致脑损伤。     

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies

PurposeTo assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and MethodsThe VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7–21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.ResultsEight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441–404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%–100%). There were no significant changes in perfusion imaging parameters after TACE.ConclusionsBTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.