In-hospital Outcome in Octogenarians with Acute Coronary Syndrome Undergoing Emergent Coronary Angiography

金沢大学附属病院臨床試験管理センターVery elderly patients have higher mortality rates than younger patients after acute coronary syndrome (ACS). However, the mechanism by which increasing age contributes to such mortality remains unclear. In addition, the efficacy and safety of invasive coronary procedures for octogenarians with ACS have not been well established. We compared the clinical characteristics and in-hospital outcome of 193 octogenarians (mean age, 83 years) with those of 1,462 younger patients (mean age, 64 years) with ACS who underwent emergent coronary angiography. Octogenarians included a greater number of females, had higher rates of cerebrovascular disease and multivessel disease, a higher Killip class, a higher Forrester class, and lower rates of smoking, diabetes, and hypercholesterolemia than the younger subjects. Interventions, including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG), were performed less frequently in octogenarians than in younger patients (88.0% versus 90.8%). The procedural success rate in octogenarians did not differ from that in younger patients. However, the in-hospital mortality rate for the octogenarians was about three times higher than for the younger patients (19.2% versus 6.9%). Multivariate analysis revealed that the predictors of in-hospital mortality in the octogenarians were a higher Killip class and a higher Forrester class. Octogenarians with ACS had fewer coronary risk factors and a similar success rate for the intervention, but had more greatly impaired hemodynamics and higher in-hospital mortality than the younger patients. Therefore, impaired myocardial reserve may contribute to a large portion of in-hospital deaths in octogenarians with ACS

Percutaneous coronary intervention using new-generation drug-eluting stents versus coronary arterial bypass grafting in stable patients with multi-vessel coronary artery disease: From the CREDO-Kyoto PCI/CABG registry Cohort-3

AIMS: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease. METHODS AND RESULTS: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001). CONCLUSIONS: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Lithium Vapor Chemistry of Hyper-Stoichiometric Lithium Metatitanate Li₂.₁₂(₂)TiO₃+y

Developing a better ceramic breeder (Li-containing oxide) is a key challenge for realizing fuel-self-sufficient fusion reactors. Ceramic breeder pebbles of hyper-stoichiometric lithium metatitanate, Li2+xTiO3+y (Li/Ti > 2), have been developed for a demonstration fusion reactor as high Li density enhances fuel tritium production. Previous studies have reported that Li loss by vaporization at high temperatures was largely enhanced by the increase in Li/Ti ratio and environmental moisture concentration. Minimizing the Li loss is a key issue for sufficient tritium breeding and reduced corrosion of structural steel. However, a suitable environmental parameter for hyper-stoichiometric Li2+xTiO3+y pebbles has not yet been determined because of the unavailability of thermodynamic data. Herein, a solid/gas equilibria for Li2.12(2)TiO3+y was investigated by measuring vapor pressures using atmosphere controllable Knudsen cell high temperature mass spectrometry. The enhanced thermodynamic activities of Li and Li2O in Li2.12(2)TiO3+y in comparison with those in stoichiometric Li2TiO3 were obtained as functions of temperature and oxygen concentration. The equilibrium constants were used to achieve the optimum moisture concentration that can suppress the vapor reactions in a cylindrical breeding zone with inhomogeneous temperature distribution

Unmanned Observation in Autarctica (I) : Development of an Unmanned Observatory and Preliminary Result of Geomagnetic Variatios Recorded at the Observatory

It was planned to set up several unmanned upper atmosphere observatories in the area around Mizuho Station (70°42' S, 44°20' E) in Antarctica during the period of 1976-1978 for the IMS (International Magnetospheric Study). The first unmanned observatory, situated between Mizuho and Syowa Stations in Antarctica, was set up on May 30, 1977 by the wintering party of the 18th Japanese Antarctic Research Expedition. Observation of geomasnetic variations at this observatory was carried out from May 30 to August 23, 1977. The unmanned observatory consists of the following parts. 1. Wind-driven generator Two wind-driven generators (DYNA Technology Co., model 1222H) are used for keeping batteries and instruments warm. Each generator can supply electric power of～200 W on an average when the wind blows continuously at a speed of～10 m/s. 2. Heat insulation boxes Batteries and instruments are put in two heat insulation boxes. The boxes protect the batteries and instruments from low temperature and heavy snow in Antarctica. The wall of these boxes is made of veneer, aluminium plate and styrofoam plate with a thickness of～10 cm. Using thermostats and heaters (200 W for the battery box and 100 W for the instrument box), the temperature inside the boxes can be kept from 0℃ to 10℃ near Mizuho Station throughout the year. 3. Instrumentation Fluxgate type magnetometer Component : H, D, Z components Sensitivity : 10 nT/mm on the chart record Range : ±1250 nT Power consumotion : +18 V/100 mA, -18 V/60 mA Timing : Chronometer (stability 10^8) 4. Recorder The heat pen recorder is used. The data observed at the unmanned observatory are recorded on a chart which is replaced every three and half months. A specification of the recorder is as follows. Available chart width : 250 mm (±1250 nT) Recording speed : 30 mm/h Power consumotion : +18 V/670 mA, -18 V/100 mA 5. Battery Layer-built air cells are used for power supply to the instruments. In this report, results of the environmental test of these facilities in a lowtemperature room are given in detail. Furthermore, magnetic variation data obtained from the unmanned observatory are presented

Q-T peak dispersion in congenital long QT syndrome: Possible marker of mutation of HERG

金沢大学大学院医学系研究科　Congenital long QT syndrome (LQTS) is caused by mutations in various cardiac potassium or sodium channel genes, with 6 different genotypes thus far identified. However, it is unknown whether these genotypes can be differentiated by QT variables. The electrocardiograms obtained from 16 patients with a mutation in KCNQ1 (LQT1), 7 patients with a mutation in HERG (LQT2) and 20 control subjects were analyzed. The corrected QT interval (QTc), Q-T peak interval (QTpc) and dispersion of QTc or QTpc were measured in 6 precordial leads. The corrected interval from T peak to T end (Tpec) was measured in lead V5. The maximum QTc, QTc dispersion, and Tpec were significantly increased in the LQT1 and LQT2 patients than in the controls. However, there were no significant differences in these indices between the LQT1 and LQT2 patients. In contrast, QTpc dispersion was significantly increased in the LQT2 patients (78±25 ms) compared with the LQT1 patients (29±15 ms) and controls (26±19 ms). These results suggest that increased lag of the peak of the T wave in each precordial lead (QTpc dispersion) may be a possible index to differentiate LQTS patients with HERG mutation from those with KCNQ1 mutation