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We investigated the effects of voluntary exercise after myocardial infarction (MI) on cardiac function, remodeling, and inflammation. Male C57BL/6J mice were divided into the following four groups: sedentary + sham (Sed-Sh), sedentary + MI (Sed-MI), exercise + sham (Ex-Sh), and exercise + MI (Ex-MI). MI induction was performed by ligation of the left coronary artery. Exercise consisting of voluntary wheel running started after the operation and continued for 4 weeks. The Ex-MI mice had significantly increased cardiac function compared with the Sed-MI mice. The Ex-MI mice showed significantly reduced expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10 in the infarcted area of the left ventricle compared with the Sed-MI mice. In the Ex-MI mice, the expression levels of fibrosis-related genes including collagen I and III were decreased compared to the Sed-MI mice, and the expression levels of IL-1β, IL-6, follistatin-like 1, fibroblast growth factor 21, and mitochondrial function-related genes were significantly elevated in skeletal muscle compared with the Sed mice. The plasma levels of IL-6 were also significantly elevated in the Ex-MI group compared with the Sed-MI groups. These findings suggest that voluntary exercise after MI may improve in cardiac remodeling associated with anti-inflammatory effects in the myocardium and myokine production in the skeletal muscles.

We experienced a case of primary percutaneous coronary intervention for ST‐elevation myocardial infarction (STEMI) with coronavirus disease 2019 (COVID‐19) using appropriate infection prevention protocol. However, recanalization was difficult due to severe coagulopathy. Further researches are needed to clarify optimal treatment for STEMI in patients with COVID‐19. [ABSTRACT FROM AUTHOR]

Background: Peak oxygen uptake (peak VO2) and heart rate reserve (HRR) are independent prognostic markers of cardiovascular disease. However, the impact of peak VO2 and HRR on long‐term prognosis after off‐pump coronary artery bypass grafting (OP‐CABG) remains unclear. Hypothesis: To determine the prognostic impact of peak VO2 and HRR in patients after OP‐CABG. Results: We enrolled 327 patients (mean age, 65.1 ± 9.3 years; male, 80%) who underwent OP‐CABG and participated in early phase II cardiac rehabilitation. All participants underwent cardiopulmonary exercise testing (CPET) at the beginning of such rehabilitation. Overall, 48 (14.6%) patients died during the median follow‐up period of 103 months. The non‐survivor had significantly lower levels of peak VO2 (10.6 ± 0.5 vs. 13.7 ± 0.2 ml/kg/min, p <.01) and HRR (24.2 ± 1.8 vs. 32.7 ± 0.8 beats/min, p <.01) than the survivor. In both groups, peak VO2 significantly correlated with HRR (p <.01). Moreover, patients were divided into four groups according to the peak VO2 and HRR levels for predicting total mortality. The low‐peak VO2/low‐HRR group had a significantly higher mortality risk than the other groups (hazards ratio, 5.61; 95% confidence interval, 2.59–12.16; p <.01). After adjusted the confounding factors, peak VO2 and HRR were independently associated with total mortality (both p <.05). Conclusions: HRR is a simple parameter of CPET and an important prognostic marker for the risk stratification of total mortality even in patients with low‐peak VO2 after OP‐CABG. [ABSTRACT FROM AUTHOR]

Background and Aim: Successful Helicobacter pylori eradication has been shown to prevent the development of gastric cancer (GC), but clinical evidence for factors that correlate with GC of previously H. pylori‐infected gastric mucosa (after eradication or natural disappearance) is limited. The purpose of our study was to identify these correlative factors. Methods: We retrospectively examined data from patients with previously H. pylori‐infected gastric mucosa. Data from 168 patients who developed early GC and underwent endoscopic submucosal dissection (Group C) and 835 patients with no history of early GC (Group NC) were compared. We extracted data on gender; age; complications from malignant disease and diabetes mellitus; American Society of Anesthesiologists (ASA) physical status classification; and endoscopic characteristics of atrophy (open type), intestinal metaplasia, and gastric xanthoma (GX). Correlations were determined with multivariate logistic regression analysis and propensity score matching. Results: A significantly higher proportion of patients had GX in Group C than in Group NC. Age, male gender, ASA physical status classification of class III or higher, complications from malignant disease, atrophy (open type), and the presence of intestinal metaplasia and GX were identified as factors that correlated independently with GC (odds ratio = 3.65; 95% confidence interval = 2.37–5.61; P < 0.0001). Propensity score matching demonstrated that the prevalence of GC was also significantly higher in patients who were positive for GX (37.2% vs 18.3%; P < 0.0001). Conclusion: GX was shown to correlate with early GC of previously H. pylori‐infected gastric mucosa. [ABSTRACT FROM AUTHOR]

Aim: We examined the changes in oxidative stress, mitochondrial function and muscle atrophy during aging in mice. Methods: We used 6‐, 12‐ and 24‐month (6 M, 12 M and 24 M)‐old C57BL/6J mice. Skeletal muscles were removed from the lower limb and used for quantitative real‐time polymerase chain reaction, immunoblotting and histological analyses. Results: The muscle weight and myocyte cross‐sectional area were significantly decreased in the 12 M and 24 M mice compared with those of the 6 M mice. The levels of the oxidative stress markers, nicotinamide adenine dinucleotide phosphate oxidase 2, nicotinamide adenine dinucleotide phosphate oxidase 4, mitochondrial 4‐hydroxy‐2‐nonenal and 3‐nitrotyrosine, were significantly higher in the 24 M mice compared with those of the 6 M mice. Furthermore, the 24 M mice had lower levels of mitochondrial markers, peroxisome proliferator‐activated receptor gamma coactivator 1 (PGC)‐α, peroxisome proliferator‐activated receptor gamma coactivator‐1β, sirtuin‐1, adenosine triphosphate synthase mitochondria F1 complex α subunit 1 and mitochondrial cytochrome c oxidase 1. The ubiquitin–proteasome pathway genes muscle ring finger‐1 and atrogin‐1 were significantly upregulated in the 12 M and 24 M mice, and protein synthesis markers (phosphorylated‐Akt and ‐p70 ribosomal S6 kinase) were significantly lower in the 24 M mice compared with the 6 M mice (all P < 0.05). Conclusions: These findings have important implications for the mechanisms that underlie sarcopenia and frailty processes. Geriatr Gerontol Int 2020; 20: 78–84. [ABSTRACT FROM AUTHOR]

Objectives: Follistatin-like 1 (FSTL1) is a glycoprotein secreted by skeletal muscle cells and cardiac myocytes. Previous studies showed that serum FSTL1 concentrations were increased in acute coronary syndrome and chronic heart failure. The aim of this study was to assess the associations among plasma FSTL1 concentration, clinical parameters, and whether FSTL1 concentration could predict cardiovascular events in patients with elective percutaneous coronary intervention (PCI). Methods and results: A consecutive series of 410 patients who underwent elective PCI with drug-eluting stents (DES) were enrolled between August 2004 and December 2006 at Juntendo University hospital. We measured plasma FSTL1 levels prior to elective PCI and assessed the association among FSTL1 levels, clinical parameters, and occurrence of major adverse cardiac or cerebrovascular events (MACCE) defined as cardiac death, nonfatal myocardial infarction, unstable angina, stroke, and hospitalization for heart failure. FSTL1 concentration was positively correlated with high-sensitivity C-reactive protein (hsCRP), serum creatinine, and N-terminal pro b-type natriuretic peptide (all P < 0.01). After excluding patients with creatinine clearance < 60 mL/min and hsCRP ≥ 0.2 mg/dL, the remaining 214 were followed for a median of 5.1 years. Twenty (9.3%) patients experienced MACCE. Receiver operating characteristics curve analysis estimated an FSTL1 cutoff of 41.1 ng/mL to predict MACCE occurrence. Kaplan–Meier analysis found a higher MACCE rate in patients with high (≥ 41.1 ng/mL) than with low (< 41.1 ng/mL) FSTL1 (P < 0.01). Multivariate Cox hazard analysis found that high FSTL1 was an independent predictor of MACCE (hazard ratio 4.54, 95% confidence interval: 1.45–20.07, P < 0.01). Conclusion: High plasma FSTL1 may be a predictor of cardiovascular events in patients who underwent elective PCI with DES, especially with preserved renal function and low hsCRP. [ABSTRACT FROM AUTHOR]

Aim: The Kihon Checklist is a useful screening tool for assessing frailty in older individuals. However, the clinical significance of the Kihon Checklist in cardiac rehabilitation patients remains unclear. The present study aimed to evaluate the relationship between the Kihon Checklist and the clinical parameters in patients who participated in cardiac rehabilitation. Methods: We enrolled 845 consecutive patients (584 men, mean age 71 years) who participated in cardiac rehabilitation at Juntendo University Hospital, Tokyo, Japan, between November 2015 and October 2017. The patients were divided into non‐frailty (n = 287), pre‐frailty (n = 270) and frailty (n = 288) groups according to their Kihon Checklist scores. Cardiopulmonary exercise testing was carried out in 302 patients. Results: The frailty group was older and had a higher prevalence of history of heart failure than the non‐frailty group, although left ventricular ejection fraction did not differ significantly between groups. Nutritional index, trunk and limb muscle mass, lean body weight, and grip strength were significantly lower in the frailty and pre‐frailty groups than those in the non‐frailty group. In the cardiopulmonary exercise test, a stepwise significant decrease in peak oxygen uptake was observed across the three groups (non‐frailty 17.2 ± 3.6, pre‐frailty 16.0 ± 3.4, frailty 14.4 ± 3.5 mL/kg/min, P < 0.01). Multivariate regression analyses showed that the Kihon Checklist score was significantly and independently associated with peak oxygen uptake (r = −0.34, P < 0.0001). Conclusions: The Kihon Checklist, which was associated with frailty and exercise tolerance, could be used as a clinical assessment method for patients who participated in cardiac rehabilitation. Geriatr Gerontol Int 2019; 19: 287–292. [ABSTRACT FROM AUTHOR]

Background: Muscle wasting is a debilitating phenotype associated with chronic heart failure (CHF). We have previously demonstrated that angiotensin II (AII) directly induces muscle wasting in mice through the activation of NADPH oxidase (Nox). In this study, we tested the hypothesis that deficiency of NADPH oxidase 4 (Nox4), a major source of oxidative stress, ameliorates AII-induced muscle wasting through the regulation of redox balance. Methods and Results: Nox4 knockout (KO) and wild-type (WT) mice were used. At baseline, there were no differences in physical characteristics between the WT and KO mice. Saline (vehicle, V) or AII was infused via osmotic minipumps for 4 weeks, after which, the WT + AII mice showed significant increases in Nox activity and NOX4 protein compared with the WT + V mice, as well as decreases in body weight, gastrocnemius muscle weight, and myocyte cross-sectional area. These changes were significantly attenuated in the KO + AII mice (27 ± 1 vs. 31 ± 1 g, 385 ± 3 vs. 438 ± 13mg, and 1,330 ± 30 vs. 2281 ± 150 μm2, respectively, all P < 0.05). The expression levels of phospho-Akt decreased, whereas those of muscle RING Finger-1 (MuRF-1) and MAFbx/atrogin-1 significantly increased in the WT + AII mice compared with the WT + V mice. Furthermore, nuclear factor erythroid-derived 2-like 2 (Nrf2) and the expression levels of Nrf2-regulated genes significantly decreased in the WT + AII mice compared with the WT + V mice. These changes were significantly attenuated in the KO + AII mice (P < 0.05). Conclusion: Nox4 deficiency attenuated AII-induced muscle wasting, partially through the regulation of Nrf2. The Nox4-Nrf2 axis may play an important role in the development of AII-induced muscle wasting. [ABSTRACT FROM AUTHOR]

Objective. We evaluated inflammatory cytokines and chemokine in peripheral blood mononuclear cells (PBMCs) in patients with either acute coronary syndrome (ACS) or stable coronary artery disease (CAD). Methods. We enrolled 20 ACS patients and 50 stable CAD patients without previous history of ACS who underwent cardiac catheterization. Patients with an estimated glomerular filtration rate of ≤30 mL/min/1.73 m2 and C-reactive protein of ≥1.0 mg/dL were excluded. Blood samples were collected from the patients just before catheterization, and PBMCs were isolated from the whole blood. The levels of inflammatory cytokines and chemokine were measured by using real-time quantitative polymerase chain reaction and immunoassays. Results. The expression of tumor necrosis factor alpha (TNF-α), interleukin- (IL-) 6, IL-10, IL-23A, IL-27, and IL-37 was significantly higher in the ACS group than in the CAD group (P<0.05). In contrast, the expression of IL-33 was significantly lower in the ACS group than in the CAD group (P<0.05). The ACS patients had higher plasma levels of TNF-α, IL-6, and IL-10 in the ACS group than in the CAD group. Conclusion. Circulating levels of pro-/anti-inflammatory cytokines, including IL-23A, IL-27, IL-33, and IL-37, may be associated with the pathogenesis of atherosclerosis in ACS patients. [ABSTRACT FROM AUTHOR]

Infection and inflammation suppress the expression and activity of several drug transporters in liver. In the intestine, P-glycoprotein (P-gp/MDR1), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) are important barriers to the absorption of many clinically important drugs. The expression and activity of these proteins were examined under inflammation. Drug transport was determined in jejunum and ileum segments isolated from 1.0 mg/kg, 5.0 mg/kg, and 7.5 mg/kg indomethacin-treated or control rats in diffusion chambers. Transport of laminaran, used as a model compound of (1-3) β-D-glucan, was measured for 120 min in the presence or absence of inhibitors. Reverse transcription-polymerase chain reaction was used to measure mRNA levels. Compared with controls, levels of Mdr1a mRNA were significantly decreased in the jejunum and ileum of 7.5 mg/kg indomethacin-treated rats. Both reductions in the basolateral to apical efflux of laminaran and increases in the apical to basolateral influx of laminaran were observed, resulting in significant increases in the apical to basolateral absorption of laminaran in 7.5 mg/kg indomethacin-treated rats. The inhibitory effect of verapamil on laminaran transport was observed in control rats but not in indomethacin-treated rats. Fluorescein isothiocyanate dextran 40,000 permeability, membrane resistance, and claudin-4 mRNA level were not altered, indicating no change in the paracellular pathway. These results indicate that indomethacin-induced inflammation reduces the intestinal expression and activity of P-gp in rats, which elicits corresponding changes in the intestinal transport of laminaran. Hence, inflammatory diseases may impose variability in drug bioavailability through alterations in the intestinal expression and activity of drug transporters. [ABSTRACT FROM AUTHOR]

Background: We investigated the combined effects of physical activity (PA) and aggressive low-density lipoprotein cholesterol (LDL-C) reduction on the changes in coronary plaque volume (PV) in patients with acute coronary syndrome (ACS) using volumetric intravascular ultrasound (IVUS) analysis. Methods: We retrospectively analyzed data from two different prospective clinical trials that involved 101 ACS patients who underwent percutaneous coronary intervention (PCI) and assessed the non-culprit sites of PCI lesions using IVUS at baseline and at the follow-up. After PCI, all the patients participated in early phase II comprehensive cardiac rehabilitation. Patients were divided into four groups based on whether the average daily step count, measured using a pedometer, was 7000 steps of more and whether the follow-up LDL-C level was <70 mg/dL. At the time of follow-up, we examined the correlation of changes in the PV with LDL-C and PA. Results: The baseline characteristics of the four study groups were comparable. At the follow-up, plaque regression in both the achievement group (PA and LDL-C reduction) was higher than that in the other three groups. In addition, plaque reduction independently correlated with increased PA and reduction in LDL-C level. Conclusions: Combined therapy of intensive PA and achievement of LDL-C target retarded coronary PV in patients with ACS. [ABSTRACT FROM AUTHOR]

Background: Delirium is a common occurrence in patients admitted to the intensive care unit and is related to mortality and morbidity. Malnutrition is a predisposing factor for the development of delirium. Nevertheless, whether the nutritional status on admission anticipates the development of delirium in patients with acute cardiovascular diseases remains unknown. Objective: This study aims to assess the correlation between the nutritional status on admission using the nutritional index and the development of delirium in the coronary intensive care unit. Design: We examined 653 consecutive patients (mean age: 70 ± 14 years) admitted to the coronary intensive care unit of Juntendo University Hospital between January 2015 and December 2016. We evaluated three nutritional indices frequently used to assess the nutritional status, i.e., Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT). We defined delirium as patients with a delirium score >4 using the Intensive Care Delirium Screening Checklist. Results: Delirium was present in 58 patients. All nutritional indices exhibited a tendency for malnutrition in the delirium group compared with the non-delirium group (GNRI, 86.5 ± 9.38 versus 91.6 ± 9.89; PNI, 36.4 ± 6.95 versus 41.6 ± 7.62; CONUT, 5.88 ± 3.00 versus 3.61 ± 2.56; for all, p < 0.001). Furthermore, the maximum delirium score increased progressively from the low- to the high-risk group, as evaluated by each nutritional index (GNRI, PNI, CONUT; for all, p < 0.001). A multivariate analysis revealed that the PNI and CONUT were independent risk factors for the occurrence of delirium. Conclusions: A marked correlation exists between the nutritional index on admission, especially PNI and CONUT, and the development of delirium in patients with acute cardiovascular diseases, suggesting that malnutrition assessment upon admission could help identify patients at high risk of developing delirium. [ABSTRACT FROM AUTHOR]

The European Society of Cardiology (ESC) recommends a 0-h/1-h (0/1-h) algorithm to classify patients with suspected non-ST-segment elevation myocardial infarction (NSTEMI). However, reliable evidence about patients who present early after the onset of symptoms is limited, likely because high-sensitivity cardiac troponin (hs-cTn) values cannot increase sufficiently within that time. This study aimed to evaluate the outcomes in real-world situations that utilized the 0/1-h algorithm. In a prospective, international, multicenter cohort study that enrolled 1638 patients presenting with acute chest pain to the emergency department, we assessed the performance of the 0/1-h algorithm using hs-cTnT and the associated 30-day rates of major adverse cardiac events: death and acute myocardial infarction (AMI). Among 1074 patients, the prevalence of AMI was 16.0%. An approximately 60.1% (n = 645) of patients visited the hospital within 3 h after onset of chest pain (less than 1 h; 18.2% n = 196], less than 2 h; 27.5% n = 295], and less than 3 h; 14.3% n = 154]). Moreover, the prevalence rates of AMI were similar at all times (1 h, 16.8%; 1–2 h, 20.7%; 2–3 h, 18.2%; p =.5). According to the ESC 0/1-h algorithm, the distribution patterns of rule-out, observe, and rule-in groups were similar; however, none of the patients was diagnosed with AMI or cardiac death in the rule-out group. This study revealed the applicability of the 0/1-h algorithm for the management of early presenters. • None of the 30-day major advanced cardiac events was associated with the 0/1-h algorithm for the management of very early presenters. • A distribution patterns of rule-out, observe, and rule-in groups were similar at 1 h, 1–2 h, and 2–3 h after chest pain onset. • Strategies that incorporate a HEART score with the algorithm can be used for clinical implementation. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive unresectable or recurrent/metastatic salivary gland carcinoma., Patients and Methods: This trial was an open-label, single-arm, multicenter phase II study. Patients with histologically confirmed unresectable or recurrent/metastatic salivary gland carcinoma with AR expression were included. The primary endpoint was the overall response rate (ORR) according to RECIST v1.1 by an independent central radiology review in the first 24 response-evaluable (RE) patients who had been observed at least 24 weeks from study initiation (primary RE patients). The efficacy was to be declared when at least 8 of the 24 primary RE patients responded., Results: A total of 31 patients were enrolled. In the first 24 primary RE patients with a median follow-up of 7.4 months, confirmed ORR by independent central radiology review was 25.0% [6/24 patients; 95% confidence interval, 9.8%-46.7%; P = 0.11 (one-sided)], which did not meet the predefined criteria of efficacy. Clinical benefit rate (ORR + rate of stable disease for at least 24 weeks) and median progression-free survival were 50.0% and 7.4 months, respectively. Both median duration of response and overall survival were not reached. Exploratory analyses showed a better ORR of 54.5% (6/11) in patients with AR positivity ≥70% and no history of prior systemic therapy. Grade 3 or higher treatment-emergent adverse events were reported in 35.5% (11/31), which included skin rash, anemia, leukopenia, and cancer pain., Conclusions: Although this study did not meet the predefined efficacy criteria, apalutamide plus goserelin showed clinically meaningful efficacy in a subset of patients with AR-positive salivary gland carcinoma and safety consistent with prior experience in prostate cancer., (©2024 American Association for Cancer Research.)

Purpose: The presence of severely calcified plaque remains problematic in endovascular therapy, and no specific endovascular treatment strategy has been established. Estimating plaque solidity before the procedure may help operators penetrate calcified plaque with a guide wire. The aim of this study was to establish a method of measuring plaque solidity with noncontrast computed tomography (CT)., Methods: This retrospective, single-center study included consecutive patients who, between October 2020 and July 2022, underwent noncontrast 5 mm and 1 mm CTs before endovascular therapy to penetrate calcified plaque with a wire in the common femoral, superficial femoral, and popliteal arteries. Three cross-sectional CT slices were selected. To target a calcified plaque lesion, the operator identified a region of interest, which corresponded to 24×24 pixels, and Hounsfield unit (HU) values of each pixel were displayed on the CT image. The average HU values and the ratio of number of pixels of lower values (130-599 HU) represented plaque solidity. We used the Mann-Whitney-Wilcoxon rank-sum test and the chi-square test to compare the solidity of plaques penetrated and not penetrated by the wire., Results: We evaluated 108 images of 36 calcified plaque lesions (in 19 patients). The wire penetrated 28 lesions (77.8%) successfully. The average HU value was significantly lower in the lesions that the wire penetrated than in the others, in both the 5 mm CT slices (434.7±86.8 HU vs 554.3±112.7 HU, p=0.0174) and 1 mm slices (497.8±103.1 HU vs 593.5±114.5 HU, p=0.0381). The receiver operating curve revealed that 529.9 and 533.9 HU in the 5 and 1 mm slices, respectively, were the highest values at which wires could penetrate. Moreover, at the lesions that were penetrates successfully, the ratio of number of lower HU value pixels was significantly higher both in 5 mm slice CTs (74.7±13.4 vs 61.7±13.1%, p=0.0347) and 1 mm (68.7±11.8 vs 57.1±11.4%, p=0.0174)., Conclusion: The use of noncontrast CT to evaluate plaque solidity was associated with successful wire penetration of calcified lesions in peripheral arteries., Clinical Impact: This study revealed an association between the wire penetration inside calcified plaque and plaque solidity estimated using non-contrasted computed tomography. The mean Hounsfield unit values of three cross-sections in calcified plaques were associated with the successful wire penetration. This wire penetration difficulty is associated with extended procedure time, excessive radiation exposure, usage of extra contrast agents, and increased medical costs. Therefore, estimating calcified plaque solidity before procedure enables us to choose effective and lean procedures. In addition, to predict the success of dilating calcified plaque from the inside is also beneficial when the operator wants to avoid extra scaffold implantation for target lesions.

Purpose: To improve the performance of a denoising convolutional neural network (DnCNN) and to make it applicable to images with inhomogeneous noise, a refinement involving an activation function (AF) and an application of the refined method for inhomogeneous-noise images was examined in combination with parallelized image denoising., Methods: Improvements in the DnCNN were performed by three approaches. One is refinement of the AF of each neural network that constructs the DnCNN. Swish was used in the DnCNN instead of rectifier linear unit. Second, blind noise removal was introduced to the DnCNN in order to adapt spatially variant noises. Third, blind noise removal was applied to parallelized image denoising, referred to herein as ParBID. The ParBID procedure is as follows: (1) adjacent 2D slice images are linearly combined to obtained higher peak SNR (PSNR) images, (2) combined images with different weight coefficients are denoised using the blind DnCNN, and (3) denoised combined images are separated into original position images by algebraic calculation., Results: Experimental studies showed that the PSNR and the structural similarity index (SSIM) were improved by using Swish for all noise levels, from 2.5% to 7.5%, as compared to the conventional DnCNN. It was also shown that a well-trained CNN could remove spatially variant noises superimposed on images. Experimental studies with ParBID showed that the greatest PSNR and SSIM improvements were obtained at the middle slice when three slice images were used for linear image combination. More fine structures of images and image contrast remained when the proposed ParBID procedure was used., Conclusion: Swish can improve the denoising performance of the DnCNN, and the denoising performance and effectiveness were further improved by ParBID.

Purpose: A deep residual learning convolutional neural network (DRL-CNN) was applied to improve image quality and speed up the reconstruction of compressed sensing magnetic resonance imaging. The reconstruction performances of the proposed method was compared with iterative reconstruction methods., Methods: The proposed method adopted a DRL-CNN to learn the residual component between the input and output images (i.e., aliasing artifacts) for image reconstruction. The CNN-based reconstruction was compared with iterative reconstruction methods. To clarify the reconstruction performance of the proposed method, reconstruction experiments using 1D-, 2D-random under-sampling and sampling patterns that mix random and non-random under-sampling were executed. The peak-signal-to-noise ratio (PSNR) and the structural similarity index (SSIM) were examined for various numbers of training images, sampling rates, and numbers of training epochs., Results: The experimental results demonstrated that reconstruction time is drastically reduced to 0.022 s per image compared with that for conventional iterative reconstruction. The PSNR and SSIM were improved as the coherence of the sampling pattern increases. These results indicate that a deep CNN can learn coherent artifacts and is effective especially for cases where the randomness of k-space sampling is rather low. Simulation studies showed that variable density non-random under-sampling was a promising sampling pattern in 1D-random under-sampling of 2D image acquisition., Conclusion: A DRL-CNN can recognize and predict aliasing artifacts with low incoherence. It was demonstrated that reconstruction time is significantly reduced and the improvement in the PSNR and SSIM is higher in 1D-random under-sampling than in 2D. The requirement of incoherence for aliasing artifacts is different from that for iterative reconstruction.

Arterial stiffness contributes to the development of cardiovascular disease (CVD). However, the relationship between the arterial stiffness and exercise tolerance in CVD patients with preserved ejection fraction (pEF) and those with reduced EF (rEF) is unclear. We enrolled 358 patients who participated in cardiac rehabilitation and underwent cardiopulmonary exercise testing at Juntendo University Hospital. After excluding 195 patients who had undergone open heart surgery and 20 patients with mid-range EF, the patients were divided into pEF (n = 99) and rEF (n = 44) groups. Arterial stiffness was assessed using arterial velocity pulse index (AVI) and arterial pressure volume index (API) at rest. The patients in the pEF group were significantly older and had a higher prevalence of coronary artery disease than the rEF group. The pEF group had significantly lower AVI levels and higher API levels than the rEF group. In the pEF group, the peak oxygen uptake (peak VO 2 ) and the anaerobic threshold was significantly higher than those in the rEF group. The peak VO 2 was significantly and negatively correlated with AVI and API in the pEF group (All, P < 0.05), but not in the rEF group. Multivariate linear regression analyses demonstrated that AVI was independently associated with peak VO 2 (β = -0.34, P < 0.05) in the pEF group. In conclusion, AVI may be a useful factor for assessing exercise tolerance, particularly in CVD patients with pEF.

Background and Aim: Successful Helicobacter pylori eradication has been shown to prevent the development of gastric cancer (GC), but clinical evidence for factors that correlate with GC of previously H. pylori -infected gastric mucosa (after eradication or natural disappearance) is limited. The purpose of our study was to identify these correlative factors., Methods: We retrospectively examined data from patients with previously H. pylori -infected gastric mucosa. Data from 168 patients who developed early GC and underwent endoscopic submucosal dissection (Group C) and 835 patients with no history of early GC (Group NC) were compared. We extracted data on gender; age; complications from malignant disease and diabetes mellitus; American Society of Anesthesiologists (ASA) physical status classification; and endoscopic characteristics of atrophy (open type), intestinal metaplasia, and gastric xanthoma (GX). Correlations were determined with multivariate logistic regression analysis and propensity score matching., Results: A significantly higher proportion of patients had GX in Group C than in Group NC. Age, male gender, ASA physical status classification of class III or higher, complications from malignant disease, atrophy (open type), and the presence of intestinal metaplasia and GX were identified as factors that correlated independently with GC (odds ratio = 3.65; 95% confidence interval = 2.37-5.61; P  < 0.0001). Propensity score matching demonstrated that the prevalence of GC was also significantly higher in patients who were positive for GX (37.2% vs 18.3%; P  < 0.0001)., Conclusion: GX was shown to correlate with early GC of previously H. pylori -infected gastric mucosa., (© 2020 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The frailty state consists of not only physical but also psycho-emotional problems, such as cognitive dysfunction and depression as well as social problems. However, few reports have examined the relationship between frailty and anxiety levels in elderly patients undergoing cardiac rehabilitation (CR)., Methods: We analyzed 255 patients (mean age: 74.9 ± 5.8 years, 67% male) who participated in early phase II CR at Juntendo University Hospital. At the beginning of CR, patients carried out self-assessments based on the Kihon Checklist (KCL) and the State Trait Anxiety Inventory Form (STAI). Patients were divided into three groups: frailty group (n = 99, 39%), pre-frailty group (n = 81, 32%), and non-frailty group (n = 75, 29%) according to the KCL. We assessed results from the KCL scores and its relationship with anxiety levels., Results: Among the three groups, there were no significant differences in age, underlying illnesses, or the prevalence of coronary risk factors. Depressive mood domains of the KCL were significantly higher in the frailty and pre-frailty groups than in the non-frailty groups (3.0 ± 1.5 vs. 1.4 ± 1.2 vs. 0.4 ± 0.6; P < 0.01). The state anxiety level was significantly higher in the frailty group than in the non-frailty group (41.6 ± 0.9 vs. 34.9 ± 1.0; P < 0.01). The trait anxiety levels were significantly higher in the frailty group and pre-frailty group than in the non-frailty group (45.5 ± 0.9 vs. 39.2 ± 1.0 vs. 35.1 ± 1.1; P < 0.01). State anxiety and trait anxiety also showed a significantly positive correlations with the KCL scores (r = 0.32 vs. 0.41, P < 0.01)., Conclusions: Frailty scores were positively correlated not only with physical function but also with depression mood and anxiety levels in elderly patients undergoing early phase II CR. These results suggest that assessment of depressive mood and anxiety is also important in elderly patients undergoing early phase II CR., Competing Interests: The authors do not have any conflict of interest to declare concerning the present article., (Copyright 2020, Honzawa et al.)

A 70-year-old woman received H. pylori eradication therapy in March, 201X-12. She was admitted to our department because early gastric cancer was detected on esophagogastroduodenoscopy, and we performed endoscopic submucosal dissection (ESD) in June, 201X-2. The final diagnosis was well-differentiated tubular adenocarcinoma. Afterwards, we performed ESD two times (in November, 201X-1, and in March, 201X), and final diagnoses were both adenocarcinoma of fundic gland type.

A 51-year-old woman had been taking proton pump inhibitor since August 2008. In May, 2016, endoscopic findings showed no atrophy and no intestinal metaplasia in the stomach, and multiple fundic gland polyps were identified in the stomach. A biopsy of a pedunculated polyp measuring 10 millimeters in diameter at the greater curvature of the middle gastric body demonstrated well differentiated tubular adenocarcinoma. In July 2016, we treated this lesion and two other semipedunculated polyps located near the first polyp and also measuring 10 mm in diameter by endoscopic mucosal resection. The final diagnosis of all lesions was a fundic gland polyp with low grade dysplasia and the cutting end was negative.

Objective The detection of early gastric cancer (GC) after Helicobacter pylori eradication is expected to increase in Japan. However, the predictive markers for early GC detected after H. pylori eradication have not been extensively studied. We conducted a retrospective, single-center observational study to investigate the predictive markers for early GC detected after H. pylori eradiation. Methods A total of 421 patients underwent endoscopic submucosal dissection for early GC at NTT West Osaka Hospital between June 2006 and August 2017. Data from patients with GC (Group C; n=70) and without GC (Group NC; n=114) after H. pylori eradication were analyzed. Results The proportion of men was significantly higher in Group C than in Group NC (92.9% vs. 65.8%; p<0.0001). Complications with other malignant diseases were more prevalent in Group C than in Group NC. A significantly greater proportion of patients had gastric xanthoma (GX) in Group C than in Group NC (64.3% vs. 14.9%; p<0.0001). Regarding scores for endoscopic findings related to the risk of GC, the atrophy score, intestinal metaplasia score and total score were significantly higher in Group C than in Group NC. A multivariate logistic regression analysis identified male sex, atrophy (open type), the presence of intestinal metaplasia and GX as independent predictors for early GC detected after H. pylori eradication. An atrophy-matched control analysis also identified GX as an independent predictor. Conclusion GX is a novel predictive marker for early GC detected after H. pylori eradication.

A 60-year-old man visited our department because of watery diarrhea that lasted for several months. On colonoscopy, we diagnosed him as ulcerative colitis. Additionally, a laterally spreading tumor (non-granular type) was discovered in the rectum above the peritoneal reflection (Ra). The patient was initially treated with 5-aminosalicylic acid. Four months later, endoscopic submucosal dissection was performed. Histopathology examination showed a sporadic tubular adenoma. Complete en bloc resection was performed.

A 44-year-old man was administered Niflec ® containing macrogol 4000 as a bowel cleanser for colonoscopic examination. Immediately after ingestion, he experienced oral cavity discomfort and nasal congestion, followed by acute urticaria and presyncope. His systolic blood pressure and peripheral capillary oxygen saturation dropped to 66mmHg and 89%, respectively. Fluid infusion, as well as steroid and epinephrine administration, improved his symptoms. Skin prick tests were then performed using Niflec ® , macrogol 4000, and Actosin ® ointment (containing macrogol 4000), all of which were positive. Therefore, the patient was diagnosed with anaphylactic shock caused by macrogol 4000 included in Niflec ® . Macrogol present in bowel cleansers used for colonoscopy rarely causes anaphylactic shock. However, clinicians need to be mindful of this risk. Prompt and appropriate treatment is needed should this condition occur.

Background: Cardiac rehabilitation (CR) is an established multidisciplinary secondary preventive program. We investigated the effects of CR involving intensive physical activity (PA) on coronary plaque volume and components in patients with acute coronary syndrome (ACS).Methods and Results:We enrolled 32 consecutive patients with ACS in early phase II CR and randomly assigned them to an intensive CR group (n=18; CR participation ≥twice/week, daily PA ≥9,000 steps) or a standard CR group (n=14; CR participation ≥once/2weeks, daily PA ≥6,000 steps). Serial integrated backscatter intravascular ultrasound was performed for non-culprit lesions at baseline and after 8 months. Baseline clinical data were identical between the 2 groups. Unexpectedly, CR participation and PA did not differ significantly between the 2 groups, and there was no significant difference in plaque volume (PV) or components between the 2 groups. Subsequently, we classified the patients into 2 groups according to median PA (7,000 steps). There were significant differences in percent change of PV and of lipid volume between these 2 groups. In addition, these changes were negatively and independently correlated with PA., Conclusions: No significant difference was observed in PV or components between the intensive CR and the standard CR groups. Intensive PA, however, may retard coronary PV and ameliorate lipid component in patients with ACS participating in late phase II CR.

Background: Diabetes mellitus is considered an important risk factor for cardiovascular diseases. High hemoglobin A1c (HbA1c) levels, which indicate poor glycemic control, have been associated with occurrence of cardiovascular diseases. There are few parameters which can predict cardiovascular risk in patients with well-controlled diabetes. Low 1,5-anhydroglucitol (1,5-AG) levels are considered a clinical marker of postprandial hyperglycemia. We hypothesized that low 1,5-AG levels could predict long-term mortality in acute coronary syndrome (ACS) patients with relatively low HbA1c levels., Methods: The present study followed a retrospective observational study design. We enrolled 388 consecutive patients with ACS admitted to the cardiac intensive care unit at the Juntendo University Hospital from January 2011 to December 2013. Levels of 1,5-AG were measured immediately before emergency coronary angiography. Patients with early stent thrombosis, no significant coronary artery stenosis, malignancy, liver cirrhosis, a history of gastrectomy, current steroid treatment, moderately to severely reduced kidney function (estimated glomerular filtration rate < 45 ml/min/1.73 m 2 ; chronic kidney disease stage 3B, 4, and 5), HbA1c levels ≥ 7.0%, and those who received sodium glucose co-transporter 2 inhibitor therapy were excluded., Results: During the 46.9-month mean follow-up period, nine patients (4.5%) died of cardiovascular disease. The 1,5-AG level was significantly lower in the cardiac death group compared with that in the survivor group (12.3 ± 5.3 vs. 19.2 ± 7.7 µg/ml, p < 0.01). Kaplan-Meier survival analysis showed that low 1,5-AG levels were associated with cardiac mortality (p = 0.02). Multivariable Cox regression analysis showed that 1,5-AG levels were an independent predictor of cardiac mortality (hazard ratio 0.76; 95% confidence interval 0.41-0.98; p = 0.03)., Conclusion: Low 1,5-AG levels, which indicate postprandial hyperglycemia, predict long-term cardiac mortality even in ACS patients with HbA1c levels < 7.0%.

Aim: Polyunsaturated fatty acids (PUFAs) take part in various biological events linked to the pathogenesis of venous thromboembolism (VTE), including inflammation, endothelial dysfunction, and hypercoagulability. Several studies have demonstrated the association between PUFAs and the occurrence of VTE. However, the role of PUFAs in the pathogenesis of VTE remains unclear., Methods: We enrolled 45 patients with acute VTE and 37 age-, gender-, and body mass index-matched healthy volunteers to examine their PUFA levels. Serum omega 3 (eicosapentaenoic acid: EPA and docosahexaenoic acid: DHA) and omega 6 (dihomogammalinolenic acid: DGLA and arachidonic acid: AA) fatty acids levels were measured within 24 h of admission., Results: Patients with VTE showed significantly higher AA and lower EPA levels, and lower EPA/AA ratios than the controls. Multivariate analysis revealed that AA was an independent marker for VTE. In addition, we divided the patients based on their median age (58 years old). The younger patients with VTE showed significantly lower EPA/AA levels than their age-matched controls, whereas older patients with VTE showed a significantly higher AA/DGLA levels than the older controls., Conclusions: High serum AA levels and low EPA levels are associated with the development of acute VTE, suggesting that the imbalance of PUFAs may be a potential therapeutic target for preventing acute VTE.

A 62-year-old woman was admitted to our hospital with septic shock due to left submandibular osteomyelitis and cellulitis. Her condition improved following tooth extraction, drainage, and the administration of antibiotics. However, on the 4th day of hospitalization, she went into hemorrhagic shock after defecating a massive tarry stool. Emergency esophagogastroduodenoscopy (EGD) was performed. We found a giant ulcer at the antral greater curvature of the stomach. Computed tomography (CT) revealed that the gastric ulcer had penetrated the pancreas. She had no signs of peritonitis and had a bad general condition. She was therefore managed solely by conservative therapy. She recovered within days.

Aim: Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported to reduce the risk of cardiovascular disease. However, whether omega-3 PUFAs are involved in the pathogenesis of abdominal aortic aneurysms (AAA) remains unclear., Methods: We analyzed 67 consecutive patients admitted for the elective surgical repair of AAA. We investigated the association of serum EPA and DHA levels as well as the EPA/AA ratio with the size of AAA assessed using three-dimensional reconstructed computed tomography images., Results: Mean patient age was 70±9 years and 60 patients were male. Serum EPA and DHA levels were 75.2±35.7 μg/mL and 146.1±48.5 μg/mL, respectively. EPA/AA ratio was 0.44±0.22, which was lower than those in healthy Japanese subject and equivalent to those in Japanese patients with coronary artery disease as previously reported. Mean of the maximum AAA diameter was 56.4±8.9 mm, and serum EPA levels and EPA/AA ratio negatively correlated with it (r=-0.32 and r=-0.32, respectively). Multiple liner regression analysis showed that EPA levels were significant independent factor contributing to the maximum AAA diameter. Furthermore, low serum EPA levels and low EPA/AA ratio were significantly associated with the growth rate of AAA diameter (r=-0.43 and r=-0.33, respectively)., Conclusion: EPA levels in patients with AAA were relatively low. Low serum EPA levels and EPA/AA ratio were associated with the size and growth rate of AAA.

The clinical significance of polyunsaturated fatty acids (PUFAs) in acute decompensated heart failure (ADHF) in various nutritional statuses remains unclear. For this study, we enrolled 267 patients with ADHF admitted to the cardiac intensive care unit at Juntendo University hospital between April 2012 and March 2014. The association between long-term mortality, the geriatric nutritional risk index (GNRI), and levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) was investigated. The median age was 73 (64-82) years, and mortality was 29% (62 patients). The event-free survival rates for all-cause death were higher in patients with high PUFA levels or GNRI than in those with low PUFA levels or GNRI ( p < 0.05 for all). In particular, high DGLA in the low-GNRI group and high DHA or AA in the high-GNRI group were associated with high event-free survival ( p < 0.05 for all). After accounting for confounding variables, DHA, DGLA, and AA, but not EPA, were associated with long-term mortality ( p < 0.01 for all). This study concludes that in patients with ADHF, decreased levels of DHA, DGLA, and AA are independently associated with long-term mortality in the various nutritional statuses., Competing Interests: Hiroyuki Daida has received scholarship funds and lecture fees from Takeda Pharmaceutical Company Ltd. Katsumi Miyauchi and Kazunori Shimada received lecture fees from Mochida Pharmaceutical Company Ltd. and Takeda Pharmaceutical Company Ltd, respectively. The remaining authors have no conflicts of interest to declare.

Aim: To investigate predictive markers for metachronous and synchronous gastric cancer (GC), which can develop after endoscopic submucosal dissection (ESD)., Methods: A total of 352 patients underwent ESD for early GC at NTT West Osaka Hospital between June 2006 and February 2016. Exclusion criteria were as follows: Remnant stomach, unknown Helicobacter pylori status, and endoscopic observation of the whole stomach outside our hospital. We analyzed data from 192 patients comprising 109 patients with solitary GC (Group A) and 83 with metachronous and synchronous GC (Group B). We retrospectively investigated the clinicopathological and endoscopic characteristics, and endoscopic risk score as predictive markers for GC., Results: The median age of Group B [72 years (interquartile range 63-78)] was significantly higher than that of Group A [66 years (interquartile range 61-74), respectively, P = 0.0009]. The prevalence of intestinal metaplasia in Group B tended to be higher than that in Group A (57.8% vs 45.0%, P = 0.08). The prevalence of gastric xanthoma (GX) in Group B was significantly higher than that in Group A (54.2% vs 32.1%, P = 0.003). The atrophy score in Group B was significantly higher than that in Group A ( P = 0.005). Multivariate analysis revealed that higher age and the presence of GX were independently related to metachronous and synchronous GC [OR = 1.04 (1.01-1.08), P = 0.02; and OR = 2.11 (1.14-3.99), P = 0.02, respectively]., Conclusion: The presence of GX is a useful predictive marker for metachronous and synchronous GC., Competing Interests: Conflict-of-interest statement: All authors have no conflict of interest to disclose.

Background: Polyunsaturated fatty acids (PUFAs) have important roles in the pathogenesis of cardiovascular diseases. However, the clinical significance of omega-6 PUFAs in acute cardiovascular disease remains unknown., Methods: We enrolled 417 consecutive patients with acute cardiovascular disease admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We investigated the association between serum PUFA levels and long-term mortality. Blood samples were collected after an overnight fast, within 24 h of admission. We excluded patients who received eicosapentaenoic acid therapy and those with malignancy, end-stage kidney disease, chronic hepatic disease, and connective tissue disease., Results: Overall, 306 patients (mean age: 66.4 ± 15.0 years) were analysed. During the follow-up period of 2.4 ± 1.2 years, 50 patients (16.3%) died. The dihomo-gamma-linolenic acid (DGLA) levels, arachidonic acid (AA) levels, and DGLA/AA ratio were significantly lower in the nonsurvivor group than in the survivor group (DGLA: 23.2 ± 9.8 vs. 31.5 ± 12.0 μg/ml, AA: 151.1 ± 41.6 vs. 173.3 ± 51.6 μg/ml, and DGLA/AA: 0.16 ± 0.05 vs. 0.19 ± 0.06, all p < 0.01). Kaplan-Meier curves showed that survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.01), although omega-3 PUFAs were not associated with prognosis. Furthermore, in patients with acute decompensated heart failure (ADHF), survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.04). However, among patients with acute coronary syndrome, none of the PUFA levels were associated with prognosis. Among patients with ADHF, after controlling for confounding variables, DGLA and DGLA/AA were associated with long-term mortality [DGLA: hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.88-0.99; p = 0.01 and DGLA/AA: HR, 0.87; 95% CI, 0.77-0.97; p < 0.01], whereas AA was not associated with prognosis., Conclusion: Low omega-6 PUFA levels, particularly DGLA, and a low DGLA/AA ratio predict long-term mortality in patients with acute cardiovascular disease and ADHF., Trial Registration: UMIN-CTR; UMIN000007555 .

Background: Risk factors for atrial fibrillation (AF) recurrence in patients who have undergone AF catheter ablation have not been fully clarified. The objective of this study was to assess whether the left atrium (LA) and LA appendage (LAA) volumes, and cardio-metabolic markers such as polyunsaturated fatty acids (PUFAs) levels were associated with AF recurrence., Methods: Seventy-seven consecutive patients with AF (mean age, 59 ± 8 years; male, 81%; paroxysmal AF, 64%) undergoing catheter ablation were enrolled. Using contrast-enhanced cardiac multi-detector computed tomography (MDCT) scan, the LA and LAA volume and orifice area were assessed. Radiofrequency ablation was performed by an irrigation catheter, initially targeting the pulmonary veins with a wide area circumferential ablation., Results: Patients with AF recurrence (36%) exhibited both larger LAA volumes and an LAA orifice area than those without AF recurrence, whereas the LA diameter and LA volumes were not significantly different. Notably, AF recurrence occurred in all patients with a large LAA (≥ 25 mL), and the LAA volume was significantly and negatively associated with docosahexaenoic acid (DHA) levels (β = -0.33, P = 0.003). A multiple regression analysis revealed that the log N-terminal proB-type natriuretic peptide and plasma DHA levels were independent factors for the LAA volume when adjusted for age, AF detected age, left ventricular (LV) ejection fraction, end-systolic LV diameter., Conclusions: These results suggest that the association between LAA volume and low plasma DHA levels may be an important factor for post-ablation AF recurrence., Competing Interests: The other authors report no conflicts of interest.

A woman in her 70s was an outpatient at our hospital. Esophagogastroduodenoscopy revealed a slightly elevated lesion with erosion, 10mm in diameter, located at the greater curvature of the antrum. Helicobacter pylori testing yielded negative results, and there was no atrophy of the gastric mucosa. Biopsy revealed a well-differentiated tubular adenocarcinoma. Complete en bloc resection was performed via endoscopic submucosal dissection, in accordance with the current Japanese guidelines. The gastric adenocarcinoma of the fundic gland type and coexisting with a hyperplastic or fundic gland polyp was negative according to the histological examination.