Catalytic reactors that convert carbon dioxide into methanol are one of the key technologies in carbon recycling. Various numerical simulations have been conducted to study catalytic reactors, ...including multi-step chemical reactions, flow, reaction heat, heat transfer, and diffusion. However, in most cases, the microstructures of the catalyst bed are treated as a homogeneous body, in which permeability, diffusion coefficient, and thermal conductivity are estimated by simplified estimation formula, making it difficult to evaluate the effects of the differences in pellet shapes. In this study, we developed a macroscopic homogenization model combined with a three-dimensional microstructure in the catalyst bed in order to predict complex phenomena in the reactor. The model validation was also performed with the actual experiments of catalytic reactions. Furthermore, the effects of different pellet shapes on the temperature, flow field, and reaction field in the reactor were compared.
The ELDERCARE-AF trial showed that low-dose edoxaban benefits elderly patients with nonvalvular atrial fibrillation considered ineligible for standard oral anticoagulants due to high bleeding risk, ...but whether this applied to patients with extremely low body weight was unclear.
This was a prespecified subanalysis by body weight (≤45, >45 kg) of the phase 3, multicenter, randomized, double-blind, placebo-controlled, event-driven ELDERCARE-AF trial, which compared low-dose edoxaban (15 mg once daily) with placebo in Japanese patients considered ineligible for oral anticoagulants at the recommended therapeutic strength or the approved doses. The primary efficacy and safety end points were stroke or systemic embolism and major bleeding (International Society on Thrombosis and Hemostasis definition), respectively. The ≤45-kg weight group included 374/984 patients (38.0%), and the >45-kg group included 610/984 patients (62.0%). The stroke or systemic embolism rate was lower with edoxaban than placebo in both weight groups (≤45 kg: hazard ratio HR, 0.36 95% CI, 0.16-0.80; >45 kg: HR, 0.31 95% CI, 0.13-0.73; interaction
=0.82). Major bleeding incidence was numerically higher with edoxaban than placebo (≤45 kg: HR, 3.05 95% CI, 0.84-11.11; >45 kg: HR, 1.40 95% CI, 0.56-3.48), with no interaction with body weight (interaction
=0.33). All-cause mortality was higher in the ≤45-kg group, with no significant difference between treatment groups.
The benefit of edoxaban 15 mg was consistent in elderly patients with atrial fibrillation and extremely low body weight, though clinicians must remain vigilant about the risk of major bleeding, especially gastrointestinal bleeding.
ClinicalTrials.gov. Identifier: NCT02801669.
We have previously reported that atrial endocardial remodeling is induced by atrial fibrillation (AF), and the endocardial dysfunction may be partly responsible for the thrombus formation in the left ...atrium associated with AF. However, the relationship between the endocardial dysfunction and the epidemiologically determined risk factors of AF-related strokes, including aging, hypertension, and diabetes mellitus, is yet to be elucidated.To test the hypothesis that aging, hypertension, and diabetes mellitus individually impair the atrial endocardial function in conjunction with AF, we have analyzed the expression of the tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) in the atrial endocardium in 30-week-old Wister-Kyoto (WKY), 60-week-old WKY, 30-week-old spontaneously hypertensive rats (SHR), and 30-week Goto-Kakizaki (GK) rats during normal sinus rhythm and after rapid atrial pacing at 1200 bpm for 8 hours, using Western blotting and immunohistochemical analysis. Even during sinus rhythm, the TFPI and TM expressions were noted to be remarkably downregulated in the atrial endocardium among 60-week-old WKY rats. In contrast, in SHR rats, only the TFPI expression has significantly decreased, while TM was preserved to the same level of control 30-week-old WKY rats. Rapid atrial pacing significantly reduced the TM and TFPI expression similarly in each model, thereby augmenting the endocardial dysfunction during normal sinus rhythm individually induced by the risk factors themselves prior to AF.Aging and hypertension, both of which are epidemiologically well-known risk factors for strokes in AF, have been associated with a specific atrial endocardial impairment prior to AF that could additionally disturb the antithrombotic function of the atrial endocardium.
Recently, a once-daily dose of edoxaban (15-mg) has been approved for stroke prevention in non-valvular atrial fibrillation (NVAF) patients aged ≥ 80 years, in whom standard oral anticoagulants are ...not recommended because of high bleeding risk (HBR), based on the ELDERCARE-AF trial. However, information regarding the characteristics and clinical outcomes among such patients is limited. Thus, this study aimed to clarify the characteristics and event rates in elderly patients with NVAF and HBR defined by the ELDERCARE-AF criteria. Of the 7406 NVAF outpatients included in the J-RHYTHM Registry, 60 patients with creatinine clearance (CrCl) < 15 mL/min were excluded. The remaining 7346 patients (age, 69.7 ± 9.9 years; men, 70.9%; warfarin use, 78.7%) were divided into three groups: Group 1, aged < 80 years (
n
= 6165); Group 2, aged ≥ 80 years without HBR (
n
= 584); and Group 3, aged ≥ 80 years with HBR (at least one of the followings; CrCl, 15–30 mL/min, history of bleeding, body weight ≤ 45 kg, and antiplatelet use) (
n
= 597, eligible for 15-mg edoxaban). Patients in Group 3 had a higher prevalence of comorbidities, and therefore, both higher thromboembolic and bleeding risk scores than in the other groups. During the 2-year follow-up period, the incidence rates (per 100 person-years) of thromboembolism in Groups 1, 2, and 3 were 0.7, 1.5, and 2.1 (
P
< 0.001), major hemorrhage, 0.8, 1.2, and 2.0 (
P
< 0.001), and all-cause death, 0.8, 2.6, and 4.6 (
P
< 0.001), respectively. Adjusted hazard ratios of Group 3 were 1.64 (95% confidence interval 0.89–3.04,
P
= 0.116) for thromboembolism, 1.53 (0.85–2.72,
P
= 0.154) for major hemorrhage, and 1.84 (1.19–2.85,
P
= 0.006) for all-cause death compared with Group 1. The NVAF Patients aged ≥ 80 years with HBR defined by the ELDERCARE-AF criteria were certainly at a higher adverse event risk, especially for all-cause death.
Clinical trial registration
: The J-RHYTHM Registry is registered in the University Hospital Medicine Information Network (UMIN) Clinical Trials Registry (unique identifier: UMIN000001569)
http://www.umin.ac.jp/ctr/
.
Background: A rapid heart rate (HR) during atrial fibrillation (AF) and atrial flutter (AFL) in left ventricular (LV) dysfunction often impairs cardiac performance. The J-Land study was conducted to ...compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction. Methods and Results: The 200 patients with AF/AFL, HR ≥120beats/min, and LV ejection fraction 25–50% were randomized to receive either landiolol (n=93) or digoxin (n=107). Successful HR control was defined as ≥20% reduction in HR together with HR <110beats/min at 2h after starting intravenous administration of landiolol or digoxin. The dose of landiolol was adjusted in the range of 1–10μg·kg–1·min–1 according to the patient’s condition. The mean HR at baseline was 138.2±15.7 and 138.0±15.0beats/min in the landiolol and digoxin groups, respectively. Successful HR control was achieved in 48.0% of patients treated with landiolol and in 13.9% of patients treated with digoxin (P<0.0001). Serious adverse events were reported in 2 and 3 patients in each group, respectively. Conclusions: Landiolol was more effective for controlling rapid HR than digoxin in AF/AFL patients with LV dysfunction, and could be considered as a therapeutic option in this clinical setting. (Circ J 2013; 77: 908–916)
A 37year old Japanese man experienced severe sore throat. He was infected by the Omicron variant of SARSCoV2. The posterior pharyngeal wall in the left showed closely aggregated multiple milletsized ...white spots with surrounding redness.
Non-linear models by machine learning may identify different risk factors with different weighting in comparison to conventional linear models.
The analyses were performed in 15,933 patients included ...in the Shinken Database (SD) 2004-2014 (n = 22,022) for whom baseline data of blood sampling and ultrasound cardiogram and follow-up data at 2 years were available. Using non-linear models with machine learning software, 118 risk factors and their weighting of risk for all-cause mortality, heart failure (HF), acute coronary syndrome (ACS), ischemic stroke (IS), and intracranial hemorrhage (ICH) were identified, where the top two risk factors were albumin/hemoglobin, left ventricular ejection fraction/history of HF, history of ACS/anti-platelet use, history of IS/deceleration time, and history of ICH/warfarin use. The areas under the curve of the developed models for each event were 0.900, 0.912, 0.879, 0.758, and 0.753, respectively.
Here, we described our experience with the development of models for predicting cardiovascular prognosis by machine learning. Machine learning could identify risk predicting models with good predictive capability and good discrimination of the risk impact.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Atrial fibrosis is a hallmark of atrial structural remodeling leading to the persistence of atrial fibrillation. Although fibroblasts play a major role in atrial fibrosis, their ...source in the adult atrium is unclear. We tested the hypothesis that endothelial cells contribute to fibroblast accumulation through an endothelial–mesenchymal transition in the atrium of patients with atrial fibrillation. Methods and results The study group consisted of patients with atrial fibrillation and valvular disease or atrial septal defect who underwent left atrial appendectomy during cardiac surgery ( n = 38). The amount of fibrotic depositions in the left atrium positively correlated with left atrial dimension. Furthermore, snail and S100A4, indicative of endothelial–mesenchymal transition, were quantified in the left atrium using western blot analysis, which showed statistically significant correlations with left atrial dimension. Immunofluorescence assay of the left atrial tissue identified snail and S100A4 being expressed within the endocardium which is composed of CD31+ cells. The snail-positive endocardium also showed the expression of membrane type 1-matrix metalloproteinase. Immunofluorescence multi-labeling experiments identified that heat shock protein 47, prolyl-4-hydroxylase, and procollagen type 1 co-localized with snail and S100A4 within the endothelial cells of the left atrium, indicating the mesenchymal phenotype to produce collagen. Conclusions In this study, we showed that the endothelial–mesenchymal transition occurs in the atrium of patients with atrial fibrillation. This observation should help in constructing a novel therapeutic approach for preventing atrial structural remodeling.
Background: Edoxaban is a once-daily (QD) oral, direct factor Xa inhibitor in clinical development for the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). The aim of ...this study was to evaluate the safety of edoxaban in Japanese patients with NVAF. Methods and Results: A total of 536 NVAF patients (CHADS2 ≥1) were randomized to receive double-blinded edoxaban 30, 45, or 60mg QD or open-label warfarin (international normalized ratio INR 2.0-3.0 for age <70 years; 1.6-2.6 for age ≥70 years) for 12 weeks. The primary endpoint was the incidence of all bleeding events (major, clinically relevant non-major, and minor bleeds). Patients underwent CT and/or MRI to assess asymptomatic intracranial hemorrhage (ICH). Secondary endpoints included thromboembolic events and pharmacodynamic indices. The mean incidence of all bleeding events for edoxaban 30, 45, and 60mg, and warfarin was 18.5%, 22.4%, 27.7%, and 20.0%, respectively. There were no statistically significant differences among the edoxaban groups and no significant differences from the warfarin group. There were no asymptomatic ICH events in any group. One episode of cerebral infarction was observed in the edoxaban 45-mg group. Subgroup analysis suggested low body weight (≤60kg) was associated with higher bleeding risk. Conclusions: Edoxaban 30, 45, and 60mg QD in patients with NVAF was associated with a numerical increase in all bleeding across the dose range, but this was not statistically significant, nor was any dose compared with warfarin. (Circ J 2012; 76: 1840–1847)
Background:Despite the well-established benefits in patients with nonvalvular atrial fibrillation (NVAF), anticoagulants have been underused in elderly patients. The All Nippon AF In the Elderly ...(ANAFIE) Registry is a multicenter, prospective, observational study with 2-year follow-up of Japanese patients aged ≥75 years with a definitive diagnosis of NVAF, aiming to collect detailed information on clinical status and therapeutic challenges in this patient population.Methods and Results:Patients were enrolled from October 2016 to January 2018. A total of 32,726 patients (57.2% male) were included. The average age, CHADS2score, and creatinine clearance were 81.5±4.8 years (26.2% of patients were aged ≥85 years), 2.9±1.2, and 48.4±21.8 mL/min, respectively. Paroxysmal AF was the most common clinical AF type (42.0%), and most patients (97.2%) had comorbidities. Most patients (91.9%) were receiving anticoagulant therapy; of these, 27.8% and 72.2% were treated with warfarin and direct oral anticoagulants, respectively. The average number of concomitant drugs used was 6.6±3.2, including anticoagulants.Conclusions:The ANAFIE Registry is the largest prospective registry study of elderly Japanese patients with NVAF to date. Baseline data indicate that patients in this age group are treated in a manner similar to their younger counterparts.
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